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1. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial

Author: Nicolas de Prost, Saber Barbar, Stéphane Gaudry, Jean-Pierre Quenot, Christophe Vinsonneau, Laurent Argaud, Eric Boulet, Didier Thevenin, Didier Dreyfuss, Marion Beuzelin, Adrien Robine, Cyril Cadoz, Steven Grangé, Béatrice La Combe, Dimitri Titeca-Beauport, Julien Mayaux, Julio Badie, Saad Nseir, Guillaume Chevrel, Karim Asehnoune, Florent Poirson, Kada Klouche, Sébastien Moschietto, Guillaume Louis, Guillaume Thiery, Marc Leone, David Hajage, Pascal Andreu, Elisabeth Coupez, Bertrand Pons, Said Lebbah, Jean-Damien Ricard, Jean-Marie Forel, Laurent Martin-Lefevre, Julien Bohé, Guillaume Geri, Sébastien Besset, Karim Lakhal, Nicolas Chudeau, Alain Combes, Bertrand Rozec, Nadia Aissaoui, Guillaume Lacave, Jean Reignier, CarMeN, laboratoire, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de Pharmacoépidémiologie de l'AP-HP (Cephepi), 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Laboratoire Informatique, Image et Interaction - EA 2118 (L3I), La Rochelle Université (ULR), Centre Hospitalier Henri Duffaut (Avignon), CHU Amiens-Picardie, Université de Bretagne Sud - Lorient (UBS Lorient), Université de Bretagne Sud (UBS), Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Henri Mondor, Laboratoire Sciences Analytiques, Bioanalytiques, et Miniaturisation (LSABM), Chimie-Biologie-Innovation (UMR 8231) (CBI), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier de Dieppe, CH Belfort-Montbéliard, Centre Hospitalier Sud Francilien, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Le Mans (CH Le Mans), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier de Lens, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Géomécanique, Matériaux et Structures (GEOMAS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre Hospitalier de Versailles André Mignot (CHV), Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Ambroise Paré [AP-HP], 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 Universitaire de Saint-Etienne (CHU de Saint-Etienne), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Louis Mourier - AP-HP [Colombes], 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, Programme Hospitalier de Recherche Clinique., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Université de La Rochelle (ULR), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Laboratoire de Tribologie et Dynamique des Systèmes (LTDS), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Centre Hospitalier Fleyriat [Bourg en Bresse], Centre Hospitalier Sud Francilien [Corbeil-Essonnes] (CH Sud Francilien), Centre Hospitalier de Béthune Beuvry (CH Béthune Beuvry), Hôpital Nord [CHU - APHM], GH Carnelle Portes de l'Oise, Hôpital Lapeyronie [Montpellier] (CHU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord
Subjects: medicine.medical_specialty, MESH: Acute Kidney Injury, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, 030204 cardiovascular system & hematology, urologic and male genital diseases, MESH: Severity of Illnes Index, 03 medical and health sciences, MESH: Aged, 80 and over, 0302 clinical medicine, Oliguria, Intensive care, Internal medicine, Medicine, MESH: Time-to-Treatment, 030212 general & internal medicine, Renal replacement therapy, education, Blood urea nitrogen, MESH: Aged, education.field_of_study, MESH: Humans, MESH: Middle Aged, business.industry, Hazard ratio, Acute kidney injury, General Medicine, medicine.disease, MESH: Male, MESH: Prospective Studies, 3. Good health, [SDV] Life Sciences [q-bio], MESH: France, MESH: Intensive Care Units, medicine.symptom, MESH: Renal Remplacement Therapy, business, MESH: Female, Kidney disease
Abstract: International audience; BACKGROUND: Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy. METHODS: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed. FINDINGS: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups. INTERPRETATION: In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm. FUNDING: Programme Hospitalier de Recherche Clinique.
Published: 2021

2. Occurrence of Invasive Pulmonary Fungal Infections in Patients with Severe COVID-19 Admitted to the ICU

Author: Sophie Demeret, Alexandre Lampros, Antoine Monsel, Corentin Poignon, Arnaud Fekkar, Anne-Geneviève Marcelin, Jean-Michel Constantin, Julien Mayaux, Marion Blaize, Charles-Edouard Luyt, Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service de Neurophysiologie [CHU Pitié-Salpêtrière], Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pulmonary Fungal Infections, Coronavirus disease 2019 (COVID-19), viruses, Disease, Critical Care and Intensive Care Medicine, medicine.disease_cause, Aspergillosis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, aspergillosis, In patient, 030212 general & internal medicine, Significant risk, Coronavirus, SARS-CoV-2, business.industry, fungal infection, aspergillus, COVID-19, virus diseases, Retrospective cohort study, medicine.disease, 3. Good health, 030228 respiratory system, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business
Abstract: International audience; Rationale:Whether severe coronavirus disease (COVID-19) is a significant risk factor for the development of invasive fungal superinfections is of great medical interest and remains, for now, an open question.Objectives: We aim to assess the occurrence of invasive fungal respiratory superinfections in patients with severe COVID-19.Methods: We conducted the study on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related pneumonia admitted to five ICUs in France who had respiratory and serum sampling performed for specific screening of fungal complications.Measurements and Main Results: The study population included a total of 145 patients; the median age was 55 years old. Most of them were male (n = 104; 72%), were overweight (n = 99; 68%), and had hypertension (n = 83; 57%) and diabetes (n = 46; 32%). Few patients presented preexisting host risk factors for invasive fungal infection (n = 20; 14%). Their global severity was high; all patients were on invasive mechanical ventilation, and half (n = 73, 54%) were on extracorporeal membrane oxygenation support. Mycological analysis included 2,815 mycological tests (culture, galactomannan, β-glucan, and PCR) performed on 475 respiratory samples and 532 sera. A probable/putative invasive pulmonary mold infection was diagnosed in 7 (4.8%) patients and linked to high mortality. Multivariate analysis indicates a significantly higher risk for solid organ transplant recipients (odds ratio, = 4.66; interquartile range, 1.98–7.34; P = 0.004). False-positive fungal test and clinically irrelevant colonization, which did not require the initiation of antifungal treatment, was observed in 25 patients (17.2%).Conclusions: In patients with no underlying immunosuppression, severe SARS-CoV-2–related pneumonia seems at low risk of invasive fungal secondary infection, especially aspergillosis.
Published: 2021

3. In-Hospital Mortality-Associated Factors in Patients With Thrombotic Antiphospholipid Syndrome Requiring ICU Admission

Author: Matthieu Jamme, Aude Gibelin, Auguste Dargent, Alain Combes, Rémi Coudroy, Marc Pineton de Chambrun, Jérôme Devaquet, Frédéric Pène, François-Michel Beloncle, Jean-Herlé Raphalen, Nicolas de Prost, Jérémie Lemarié, Pierre Trouiller, Elie Azoulay, Amélie Couteau-Chardon, Vincent Degos, Yacine Tandjaoui-Lambiotte, Julien Mayaux, Stanislas Ledochowski, Stanislas Faguer, Charles-Edouard Luyt, Samuel Gaugain, Zahir Amoura, Damien Contou, Steven Grangé, Romaric Larcher, Laurent Argaud, and Alexis Mathian
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, Hazard ratio, Organ dysfunction, Retrospective cohort study, Critical Care and Intensive Care Medicine, Catastrophic antiphospholipid syndrome, medicine.disease, Intensive care unit, Thrombosis, 3. Good health, law.invention, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Antiphospholipid syndrome, law, Internal medicine, medicine, 030212 general & internal medicine, Simplified Acute Physiology Score, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: Background The antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by thrombotic events that can require ICU admission because of organ dysfunction related to macrovascular and/or microvascular thrombosis. Critically ill patients with thrombosis and APS were studied to gain insight into their prognoses and in-hospital mortality-associated factors. Methods This French national, multicenter, retrospective study included all patients with APS and any new thrombotic manifestations admitted to 24 ICUs (January 2000-September 2018). Results During the study period, 134 patients (male/female ratio, 0.4) with 152 APS episodes were admitted to the ICU (mean age at admission, 46.0 ± 15.1 years). In-hospital mortality of their 134 last episodes was 35 of 134 (26.1%). The Cox multivariable model retained certain factors (hazard ratio [95% CI]: age ≥ 40 years, 11.4 [3.1-41.5], P Conclusions In-ICU anticoagulation was the only APS-specific treatment independently associated with survival for all patients. Double therapy was independently associated with better survival of patients with definite/probable catastrophic APS. In these patients, further studies are needed to determine the role of triple therapy.
Published: 2020

4. Sepsis and Septic Shock in Patients With Malignancies: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study*

Author: Stéphanie Pons, Jean-Jacques Tudesq, Adrien Mirouse, Martine Nyunga, Fabrice Bruneel, Magali Bisbal, Achille Kouatchet, Yannick Hourmant, Dominique Benoit, Elie Azoulay, Matthieu Legrand, Virginie Lemiale, Anne-Pascale Meert, Frédéric Pène, Michael Darmon, Djamel Mokart, Lara Zafrani, Julien Mayaux, and Edith Borcoman
Subjects: Male, medicine.medical_specialty, Time Factors, Critical Illness, medicine.medical_treatment, Population, Hematopoietic stem cell transplantation, Neutropenia, Critical Care and Intensive Care Medicine, law.invention, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Interquartile range, law, Neoplasms, Internal medicine, medicine, Humans, Hospital Mortality, education, Aged, education.field_of_study, business.industry, Septic shock, 030208 emergency & critical care medicine, Odds ratio, Middle Aged, medicine.disease, Respiration, Artificial, Shock, Septic, Intensive care unit, Europe, Survival Rate, Intensive Care Units, 030228 respiratory system, Hematologic Neoplasms, Female, business
Abstract: Objectives: Cancer affects up to 20% of critically ill patients, and sepsis is one of the leading reasons for ICU admission in this setting. Early signals suggested that survival might be increasing in this population. However, confirmation studies have been lacking. The goal of this study was to assess trends in survival rates over time in cancer patients admitted to the ICU for sepsis or septic shock over the last 2 decades. Data Source: Seven European ICUs. Study Selection: A hierarchical model taking into account the year of admission and the source dataset as random variables was used to identify risk factors for day 30 mortality. Data Extraction: Data from cancer patients admitted to ICUs for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Reanimation Onco-Hematologique database (1994-2015). Data Synthesis: Overall, 2,062 patients (62% men, median [interquartile range] age 59 yr [48-67 yr]) were included in the study. Underlying malignancies were solid tumors (n = 362; 17.6%) or hematologic malignancies (n = 1,700; 82.4%), including acute leukemia (n = 591; 28.7%), non-Hodgkin lymphoma (n = 461; 22.3%), and myeloma (n = 244; 11.8%). Two-hundred fifty patients (12%) underwent allogeneic hematopoietic stem cell transplantation and 640 (31.0%) were neutropenic at ICU admission. Day 30 mortality was 39.9% (823 deaths). The year of ICU admission was associated with significant decrease in day 30 mortality over time (odds ratio, 0.96; 95% CI, 0.93-0.98; p = 0.001). Mechanical ventilation (odds ratio, 3.25; 95% CI, 2.52-4.19; p < 0.01) and vasopressors use (odds ratio, 1.42; 95% CI, 1.10-1.83; p < 0.01) were independently associated with day 30 mortality, whereas underlying malignancy, allogeneic hematopoietic stem cell transplantation, and neutropenia were not. Conclusions: Survival in critically ill oncology and hematology patients with sepsis improved significantly over time. As outcomes improve, clinicians should consider updating admission policies and goals of care in this population.
Published: 2020

5. Proportional assist ventilation relieves clinically significant dyspnea in critically ill ventilated patients

Author: Côme Bureau, Maxens Decavèle, Sébastien Campion, Marie-Cécile Nierat, Julien Mayaux, Elise Morawiec, Mathieu Raux, Thomas Similowski, Alexandre Demoule, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Gestionnaire, Hal Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158)
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, genetic structures, RC86-88.9, Physiology, Research, Medical emergencies. Critical care. Intensive care. First aid, Critical Care and Intensive Care Medicine, Clinical study, 03 medical and health sciences, 0302 clinical medicine, Mechanical ventilation, Dyspnea, 030228 respiratory system, 030225 pediatrics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, circulatory and respiratory physiology
Abstract: Introduction Dyspnea is common and often severe symptom in mechanically ventilated patients. Proportional assist ventilation (PAV) is an assist ventilatory mode that adjusts the level of assistance to the activity of respiratory muscles. We hypothesized that PAV reduce dyspnea compared to pressure support ventilation (PSV). Patients and methods Mechanically ventilated patients with clinically significant dyspnea were included. Dyspnea intensity was assessed by the Dyspnea—Visual Analog Scale (D-VAS) and the Intensive Care-Respiratory Distress Observation Scale (IC-RDOS) at inclusion (PSV-Baseline), after personalization of ventilator settings in order to minimize dyspnea (PSV-Personalization), and after switch to PAV. Respiratory drive was assessed by record of electromyographic activity of inspiratory muscles, the proportion of asynchrony was analyzed. Results Thirty-four patients were included (73% males, median age of 66 [57–77] years). The D-VAS score was lower with PSV-Personalization (37 mm [20‒55]) and PAV (31 mm [14‒45]) than with PSV-Baseline (62 mm [28‒76]) (p p p Conclusion In mechanically ventilated patients exhibiting clinically significant dyspnea with PSV, personalization of PSV settings and PAV results in not different decreased dyspnea and activity of muscles to a similar degree, even though PAV was able to reduce asynchrony more effectively.
Published: 2021

6. Beneficial Effects of Non-Invasive Ventilation After Extubation in Obese or Overweight Patients : A Post-Hoc Analysis of a Randomized Clinical Trial

Author: Arnaud W. Thille, Rémi Coudroy, Mai-Anh Nay, Arnaud Gacouin, Maxens Decavèle, Romain Sonneville, François Beloncle, Christophe Girault, Laurence Dangers, Alexandre Lautrette, Quentin Levrat, Anahita Rouzé, Emmanuel Vivier, Jean-Baptiste Lascarrou, Jean-Damien Ricard, Armand Mekontso-Dessap, Guillaume Barberet, Christine Lebert, Stephan Ehrmann, Alexandre Massri, Jeremy Bourenne, Gael Pradel, Pierre Bailly, Nicolas Terzi, Jean Dellamonica, Guillaume Lacave, René Robert, Jean-Pierre Frat, Stéphanie Ragot, Florence Boissier, Delphine Chatellier, Céline Deletage, Carole Guignon, Florent Joly, Morgane Olivry, Anne Veinstein, Dalila Benzekri-Lefevre, Thierry Boulain, Grégoire Muller, Yves Le Tulzo, Jean-Marc Tadié, Adel Maamar, Suela Demiri, Julien Mayaux, Alexandre Demoule, Lila Bouadma, Claire Dupuis, Pierre Asfar, Marc Pierrot, Gaëtan Béduneau, Déborah Boyer, Benjamin Delmas, Bérénice Puech, Konstantinos Bachoumas, Edouard Soum, Séverin Cabasson, Marie-Anne Hoppe, Saad Nseir, Olivier Pouly, Gaël Bourdin, Sylvène Rosselli, Anthony Le Meur, Charlotte Garret, Maelle Martin, Guillaume Berquier, Abirami Thiagarajah, Guillaume Carteaux, Keyvan Razazi, Antoine Poidevin, Anne-Florence Dureau, Marie-Ange Azais, Gwenhaël Colin, Emmanuelle Mercier, Marlène Morisseau, Caroline Sabatier, Walter Picard, Marc Gainnier, Thi-My-Hue Nguyen, Gwenaël Prat, Carole Schwebel, Matthieu Buscot, Service de Médecine Intensive Réanimation [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pulmonary and Respiratory Medicine, business.industry, Airway Extubation, Overweight, Critical Care and Intensive Care Medicine, Intensive care unit, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 3. Good health, law.invention, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Randomized controlled trial, law, Intensive care, Anesthesia, Post-hoc analysis, Breathing, medicine, 030212 general & internal medicine, medicine.symptom, Underweight, business, ComputingMilieux_MISCELLANEOUS
Abstract: RATIONALE Whereas non-invasive ventilation (NIV) may prevent reintubation in patients at high-risk of extubation failure in intensive care units (ICUs), this oxygenation strategy has not been specifically assessed in obese patients. OBJECTIVES We hypothesized that NIV may decrease the risk of reintubation in obese patients compared with high-flow nasal oxygen (HFNO). METHODS Post-hoc analysis of a multicenter, randomized, controlled trial (not pre-specified) comparing NIV alternating with HFNO versus HFNO alone after extubation, with the aim of assessing NIV effects according to patient body-mass index (BMI). MEASUREMENTS AND MAIN RESULTS Among 623 patients at high-risk of extubation failure, 206 (33%) were obese (BMI≥30 kg/m2), 204 (33%) were overweight (25≤BMI
Published: 2021

7. Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial

Author: Florence Ader, Maude Bouscambert-Duchamp, Maya Hites, Nathan Peiffer-Smadja, Julien Poissy, Drifa Belhadi, Alpha Diallo, Minh-Patrick Lê, Gilles Peytavin, Thérèse Staub, Richard Greil, Jérémie Guedj, Jose-Artur Paiva, Dominique Costagliola, Yazdan Yazdanpanah, Charles Burdet, France Mentré, Alexander Egle, Michael Joannidis, Bernd Lamprecht, Antoine Altdorfer, Leila Belkhir, Vincent Fraipont, Gil Verschelden, Jérôme Aboab, Hafid Ait-Oufella, Claire Andrejak, Pascal Andreu, Laurent Argaud, Firouzé Bani-Sadr, François Benezit, Mathieu Blot, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, David Bougon, Kevin Bouiller, Fanny Bounes-Vardon, David Boutoille, Alexandre Boyer, Cédric Bruel, André Cabié, Emmanuel Canet, Charles Cazanave, Cyrille Chabartier, Catherine Chirouze, Raphaël Clere-Jehl, Johan Courjon, Flora Crockett, François Danion, Agathe Delbove, Jean Dellamonica, Félix Djossou, Clément Dubost, Alexandre Duvignaud, Olivier Epaulard, Loïc Epelboin, Murielle Fartoukh, Karine Faure, Emmanuel Faure, Tristan Ferry, Cécile Ficko, Samy Figueiredo, Benjamin Gaborit, Rostane Gaci, Amandine Gagneux-Brunon, Sébastien Gallien, Denis Garot, Guillaume Geri, Sébastien Gibot, François Goehringer, Marie Gousseff, Didier Gruson, Yves Hansmann, Olivier Hinschberger, Stéphane Jaureguiberry, Vanessa Jeanmichel, Solen Kerneis, Antoine Kimmoun, Kada Klouche, Marie Lachâtre, Karine Lacombe, Fabrice Laine, Jean-Philippe Lanoix, Odile Launay, Bruno Laviolle, Vincent Le Moing, Jérôme Le Pavec, Yves Le Tulzo, Paul Le Turnier, David Lebeaux, Benjamin Lefevre, Sylvie Leroy, François-Xavier Lescure, Henry Lessire, Benjamin Leveau, Paul Loubet, Alain Makinson, Denis Malvy, Charles-Hugo Marquette, Guillaume Martin-Blondel, Martin Martinot, Julien Mayaux, Armand Mekontso-Dessap, Ferhat Meziani, Jean-Paul Mira, Jean-Michel Molina, Xavier Monnet, Joy Mootien, Bruno Mourvillier, Marlène Murris-Espin, Jean-Christophe Navellou, Saad Nseir, Walid Oulehri, Thomas Perpoint, Gilles Pialoux, Benoît Pilmis, Vincent Piriou, Lionel Piroth, Valérie Pourcher, Jean-Pierre Quenot, François Raffi, Jean Reignier, Matthieu Revest, Jean-Christophe Richard, Béatrice Riu-Poulenc, Céline Robert, Pierre-Alexandre Roger, Claire Roger, Elisabeth Rouveix-Nordon, Yvon Ruch, Nadia Saidani, Naomi Sayre, Eric Senneville, Albert Sotto, Francois Stefan, Charles Tacquard, Nicolas Terzi, Julien Textoris, Guillaume Thiery, Jean-François Timsit, Violaine Tolsma, Jean-Marie Turmel, Florent Valour, Florent Wallet, Guilhem Wattecamps, Yoann Zerbib, Marc Berna, Jean Reuter, Sandra Braz, Joao-Miguel Ferreira Ribeiro, José-Artur Paiva, Roberto Roncon-Albuquerque, Alexandre Gaymard, Bruno Lina, Sarah Tubiana, Sandrine Couffin-Cadièrgues, Hélène Esperou, Aline Dechanet, Christelle Delmas, Claire Fougerou, Noémie Mercier, Marion Noret, Juliette Saillard, Priyanka Velou, 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), Internal Medicine, Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB), 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, Imperial College London, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), ANRS - Maladies infectieuses émergentes (ANRS - MIE), Institut National de la Santé et de la Recherche Médicale (INSERM), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Universidade do Porto = University of Porto, 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)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, and UCL - (SLuc) Service de médecine interne générale
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, 030204 cardiovascular system & hematology, Antiviral Agents, law.invention, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Internal medicine, Humans, Medicine, media_common.cataloged_instance, 030212 general & internal medicine, European union, education, Contraindication, ComputingMilieux_MISCELLANEOUS, Aged, media_common, Mechanical ventilation, education.field_of_study, Alanine, business.industry, COVID-19, Standard of Care, Odds ratio, Articles, Middle Aged, Respiration, Artificial, Adenosine Monophosphate, COVID-19 Drug Treatment, 3. Good health, Europe, Hospitalization, Oxygen, Clinical trial, Infectious Diseases, Clinical research, Female, business
Abstract: Summary Background The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. Methods DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948. Findings Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77–1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome). Interpretation No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support. Funding European Union Commission, French Ministry of Health, Domaine d'interet majeur One Health Ile-de-France, REACTing, Fonds Erasme-COVID-Universite Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Translation For the French translation of the abstract see Supplementary Materials section.
Published: 2021

8. Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients

Author: Manon Chauvin, Martin Larsen, Bibiana Quirant, Paul Quentric, Karim Dorgham, Luca Royer, Hélène Vallet, Amelie Guihot, Béhazine Combadière, Christophe Combadière, Jaume Barallat, Julien Mayaux, Charles-Edouard Luyt, Alexis Mathian, Zahir Amoura, Jacques Boddaert, Fernando Armestar, Guy Gorochov, Eva Martinez-Caceres, Delphine Sauce, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut d’Investigació Germans Trias i Pujol = Germans Trias i Pujol Research Institute (IGTP), Universitat Autònoma de Barcelona (UAB), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Service de Médecine Gériatrique [CHU Pitié-Salpêtrière], Service d'Immunologie [CHU Pitié-Salpétrière], Centre d'Immunologie et de Maladies Infectieuses (CIMI), CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre de Gériatrie [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), HAL-SU, Gestionnaire, and Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière]
Subjects: Exacerbation, [SDV]Life Sciences [q-bio], clinical outcome, Disease, medicine.disease_cause, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, chemistry.chemical_compound, Cellular and Infection Microbiology, 0302 clinical medicine, immune system diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Coronavirus, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Clinical outcome, Neopterin, Brief Research Report, QR1-502, 3. Good health, Death, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Biomarker (medicine), biomarker, [SDV.IMM]Life Sciences [q-bio]/Immunology, Microbiology (medical), Critical Illness, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Population, Microbiology, 03 medical and health sciences, death, medicine, Humans, education, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, 030304 developmental biology, Innate immune system, business.industry, SARS-CoV-2, COVID-19, Biomarker, chemistry, neopterin, business, 030217 neurology & neurosurgery
Abstract: HighlightsInnate immune activation during Covid-19 infection is associated with pernicious clinical outcome.BackgroundCoronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity.MethodsWe measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death.ResultsSevere and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity.ConclusionWe propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.
Published: 2021

9. COVID-19–related Respiratory Failure and Lymphopenia Do Not Seem Associated with Pneumocystosis

Author: Marion Blaize, Charles Edouard Luyt, Arnaud Fekkar, Julien Mayaux, Alexandre Lampros, Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumocystis carinii, Critical Care and Intensive Care Medicine, Broncho-alveolar lavage, 03 medical and health sciences, 0302 clinical medicine, Lymphopenia, Correspondence, Pneumocystosis, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Coinfection, SARS-CoV-2, 030306 microbiology, business.industry, Pneumonia, Pneumocystis, COVID-19, medicine.disease, 3. Good health, Respiratory failure, Immunology, Respiratory Insufficiency, business
Abstract: International audience
Published: 2020

10. Diaphragm dysfunction, lung aeration loss and weaning-induced pulmonary oedema in difficult-to-wean patients

Author: Alexandre Demoule, Elise Morawiec, Julien Mayaux, Thomas Similowski, Martin Dres, Julie Delemazure, Emmanuel Rozenberg, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), and dres, martin
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Diaphragm, Critical Care and Intensive Care Medicine, Spontaneous breathing trial, Pulmonary oedema, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Anesthesiology, medicine, Weaning, Pulmonary wedge pressure, Lung, Lung ultrasound, business.industry, RC86-88.9, Research, 030208 emergency & critical care medicine, Medical emergencies. Critical care. Intensive care. First aid, Difficult weaning, 3. Good health, Diaphragm (structural system), [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030228 respiratory system, Weaning failure, Cardiology, business
Abstract: Background Diaphragm dysfunction and weaning-induced pulmonary oedema are commonly involved during weaning failure, but their physiological interactions have been poorly reported. Our hypothesis was that diaphragm dysfunction is not particularly associated with weaning-induced pulmonary oedema. Methods It was a single-centre and physiological study conducted in patients who had failed a first spontaneous breathing trial and who underwent a second trial. The diaphragm function was evaluated by measuring the tracheal pressure generated in response to a bilateral magnetic phrenic nerves stimulations. Weaning-induced pulmonary oedema was diagnosed in case of failure of the spontaneous breathing trial if patients exhibited signs of plasma concentration or echocardiographic diagnosis of pulmonary artery occlusion pressure elevation. Results Fifty-three patients were included and 31/53 (58%) failed the spontaneous breathing trial, including 24/31 (77%) patients with weaning-induced pulmonary oedema. Diaphragm dysfunction was present in 33/53 (62%) patients. Diaphragm dysfunction or weaning-induced pulmonary oedema were present in 26/31 (84%) of the patients who failed the spontaneous breathing trial. Weaning-induced pulmonary oedema occurred in 20/33 (61%) patients with a diaphragm dysfunction and in 4/20 (20%) patients without (p = 0.005). Conclusion Weaning-induced pulmonary oedema was three times more frequent in case of diaphragm dysfunction. Even in case of diaphragm dysfunction, physicians might be encouraged to investigate the presence of weaning-induced pulmonary oedema during weaning failure.
Published: 2021

11. COVID-19 ARDS is characterized by higher extravascular lung water than non-COVID-19 ARDS: the PiCCOVID study

Author: Xavier Monnet, Francesca Moretto, Rui Shi, Vincent Bonny, Christopher Lai, Rosanna Vaschetto, Jean-Louis Teboul, Alexandra Beurton, Martin Dres, Julien Mayaux, Tài Pham, Nello De Vita, dres, martin, Hôpital Bicêtre, Pôle des Cardiopathies Congénitales du Nouveau-Né à L'adulte - Centre Constitutif Cardiopathies Congénitales Complexes M3C, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie-Lannelongue, Inserm U999, Université Paris-Saclay, Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Henri Mondor, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University Hospital 'Maggiore della Carità' [Novara, Italy], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Saclay, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Gestionnaire, Hal Sorbonne Université, Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi del Piemonte Orientale - Amedeo Avogadro (UPO), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Male, ARDS, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Thermodilution, Pulmonary Edema, 030204 cardiovascular system & hematology, Lung injury, Critical Care and Intensive Care Medicine, Severity of Illness Index, Capillary Permeability, 03 medical and health sciences, Mechanical ventilation, 0302 clinical medicine, Hemodynamic monitoring, Internal medicine, Intensive care, medicine, Extracorporeal membrane oxygenation, Humans, 030212 general & internal medicine, Transpulmonary thermodilution, Diffuse alveolar damage, Lung, Monitoring, Physiologic, Respiratory Distress Syndrome, RC86-88.9, SARS-CoV-2, business.industry, Research, Hemodynamics, COVID-19, Medical emergencies. Critical care. Intensive care. First aid, Oxygenation, Middle Aged, Prognosis, medicine.disease, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Extravascular Lung Water, Cardiology, business
Abstract: Background In acute respiratory distress syndrome (ARDS), extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) measured by transpulmonary thermodilution reflect the degree of lung injury. Whether EVLWi and PVPI are different between non-COVID-19 ARDS and the ARDS due to COVID-19 has never been reported. We aimed at comparing EVLWi, PVPI, respiratory mechanics and hemodynamics in patients with COVID-19 ARDS vs. ARDS of other origin. Methods Between March and October 2020, in an observational study conducted in intensive care units from three university hospitals, 60 patients with COVID-19-related ARDS monitored by transpulmonary thermodilution were compared to the 60 consecutive non-COVID-19 ARDS admitted immediately before the COVID-19 outbreak between December 2018 and February 2020. Results Driving pressure was similar between patients with COVID-19 and non-COVID-19 ARDS, at baseline as well as during the study period. Compared to patients without COVID-19, those with COVID-19 exhibited higher EVLWi, both at the baseline (17 (14–21) vs. 15 (11–19) mL/kg, respectively, p = 0.03) and at the time of its maximal value (24 (18–27) vs. 21 (15–24) mL/kg, respectively, p = 0.01). Similar results were observed for PVPI. In COVID-19 patients, the worst ratio between arterial oxygen partial pressure over oxygen inspired fraction was lower (81 (70–109) vs. 100 (80–124) mmHg, respectively, p = 0.02) and prone positioning and extracorporeal membrane oxygenation (ECMO) were more frequently used than in patients without COVID-19. COVID-19 patients had lower maximal lactate level and maximal norepinephrine dose than patients without COVID-19. Day-60 mortality was similar between groups (57% vs. 65%, respectively, p = 0.45). The maximal value of EVLWi and PVPI remained independently associated with outcome in the whole cohort. Conclusion Compared to ARDS patients without COVID-19, patients with COVID-19 had similar lung mechanics, but higher EVLWi and PVPI values from the beginning of the disease. This was associated with worse oxygenation and with more requirement of prone positioning and ECMO. This is compatible with the specific lung inflammation and severe diffuse alveolar damage related to COVID-19. By contrast, patients with COVID-19 had fewer hemodynamic derangement. Eventually, mortality was similar between groups. Trial registration number and date of registration ClinicalTrials.gov (NCT04337983). Registered 30 March 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04337983.
Published: 2021

12. Distinct cytokine profiles associated with COVID-19 severity and mortality

Author: Christophe Parizot, Matthieu Schmidt, Hans Yssel, Alexis Mathian, Mehmet Gökkaya, Loïc Le Guennec, Christophe Combadière, Karim Dorgham, Claudia Traidl-Hoffmann, Guillaume Voiriot, Amélie Guihot, Sophie Demeret, Sonia Burrel, Guy Gorochov, Delphine Sauce, Elyes Ben Salah, Paul Quentric, Stéphane Marot, Avidan U. Neumann, Zahir Amoura, Charles-Edouard Luyt, Anne-Geneviève Marcelin, Alexandra Beurton, Béhazine Combadière, Julien Mayaux, Centre d'Immunologie et de Maladies Infectieuses (CIMI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, principal component analysis, medicine.medical_treatment, SAPS-II, simplified acute physiology score, Gastroenterology, Severity of Illness Index, 0302 clinical medicine, Immunology and Allergy, 030212 general & internal medicine, Respiratory system, Simplified Acute Physiology Score, ComputingMilieux_MISCELLANEOUS, COVID-19, coronavirus disease 2019, TNF, tumor necrosis factor, Covid-19, Mortality, Principal Component Analysis, Respiratory Severity, Serum Cytokines, Type-i Ifns, Middle Aged, ALQ, above upper limit of quantification, 3. Good health, Cytokine, SAPS II, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Adult, medicine.medical_specialty, Immunology, type-I IFNs, Ag, antigen, serum cytokines, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, Article, Proinflammatory cytokine, 03 medical and health sciences, Internal medicine, Severity of illness, medicine, Extracorporeal membrane oxygenation, Humans, IFN, interferon, ddc:610, fCC, cytokine combination function, MVS, mechanical ventilatory support, Aged, PCA, principal component analysis, business.industry, SARS-CoV-2, COVID-19, respiratory severity, mortality, Respiration, Artificial, IL, interleukin, 030104 developmental biology, Relative risk, business, ECMO, extracorporeal membrane oxygenation
Abstract: Background Markedly elevated levels of pro-inflammatory cytokines and defective type-I interferon responses were reported in COVID-19 patients. Objective This study aimed to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. Methods Cytokine concentrations and SARS-CoV-2 antigen were measured at hospital admission in serum of symptomatic COVID-19 patients (N=115), classified at hospitalization into three respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS) and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N=86). Results At time of hospitalization, ECMO patients presented a dominant pro-inflammatory response with elevated levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8 and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-β was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at one month was associated with higher levels of pro-inflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (Risk Ratio 24.3, p, Graphical abstract, Capsule SummaryDistinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality in different oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.
Published: 2021

13. Optimal combination of early biomarkers for infection and sepsis diagnosis in the emergency department: The BIPS study

Author: Steven Volant, Laetitia Velly, Gentiane Monsel, Jean-Marc Cavaillon, Julien Mayaux, Catherine Fitting, Daniel Aiham Ghazali, Pierre Hausfater, Florian Salipante, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Accueil des Urgences [CHU Pitié-Salpêtrière] (SAU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics, Institut Pasteur [Paris] (IP), Cytokines et Inflammation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, BIO-RAD, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), BIOSFAST [CHU Pitié-Salpêtrière] (GRC 14), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Groupe de recherche clinique Biomarqueurs d’urgence et de réanimation (GRC 14 - BIOSFAST), Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and The study was supported by Institut Pasteur and a special grant from BioRad
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030106 microbiology, Gastroenterology, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, CD64, business.industry, Area under the curve, Emergency department, MERTK, medicine.disease, 3. Good health, Infectious Diseases, Area Under Curve, Cohort, Biomarker (medicine), Emergency Service, Hospital, business, Biomarkers
Abstract: International audience; Objective: : To define the best combination of biomarkers for the diagnosis of infection and sepsis in the emergency room. Methods: : In this prospective study, consecutive patients with a suspicion of infection in the emergency room were included. Eighteen different biomarkers measured in plasma, and twelve biomarkers measured on monocytes, neutrophils, B and T-lymphocytes were studied and the best combinations determined by a gradient tree boosting approach. Results: : Overall, 291 patients were included and analysed, 148 with bacterial infection, and 47 with viral infection. The best biomarker combination which first allowed the diagnosis of bacterial infection, included HLA-DR (human leukocyte antigen DR) on monocytes, MerTk (Myeloid-epithelial-reproductive tyrosine kinase) on neutrophils and plasma metaloproteinase-8 (MMP8) with an area under the curve (AUC) = 0.94 [95% confidence interval (IC95): 0.91;0.97]. Among patients in whom a bacterial infection was excluded, the combination of CD64 expression, and CD24 on neutrophils and CX3CR1 on monocytes ended to an AUC = 0.98 [0.96;1] to define those with a viral infection. Conclusion: : In a convenient cohort of patients admitted with a suspicion of infection, two different combinations of plasma and cell surface biomarkers were performant to identify bacterial and viral infection.
Published: 2021

14. Vascular access for renal replacement therapy among 459 critically ill patients: a pragmatic analysis of the randomized AKIKI trial

Author: Alexandre Boyer, Nicolas Lerolle, Guillaume Thiery, Anne Bretagnol, Saad Nseir, Guillaume Chevrel, Julien Maizel, Jean-Damien Ricard, Jean-Marie Forel, Laurent Martin-Lefevre, Alexandre Lautrette, Hodane Yonis, Philippe Markowicz, Eric Boulet, David Hajage, Florence Tubach, Bertrand Pons, Bruno Mégarbane, Frédérique Schortgen, Said Lebbah, Nicolas de Prost, Didier Dreyfuss, Julien Mayaux, Stéphane Gaudry, Marina Thirion, Dorothée Carpentier, Nicolas Benichou, 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), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), 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), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre d'investigation clinique Paris Est (CIC Paris-Est), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre Hospitalier René Dubos [Pontoise], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Sud Francilien, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Rouen, Normandie Université (NU), CHU Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Régional d'Orléans (CHRO), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Lille, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Victor Dupouy, Hôpital Nord [CHU - APHM], Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Intercommunal de Cornouaille (CHIC), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Louis Mourier - AP-HP [Colombes], Service de Réanimation Médico-Chirurgicale [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Gestionnaire, Hal Sorbonne Université, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CH Evry-Corbeil, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Lariboisière-Fernand-Widal [APHP], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Intensive care, medicine, Cumulative incidence, 030212 general & internal medicine, Renal replacement therapy, Prospective cohort study, Mechanical ventilation, Catheter, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Acute kidney injury, 030208 emergency & critical care medicine, lcsh:RC86-88.9, medicine.disease, Intensive care unit, 3. Good health, Surgery, [SDV] Life Sciences [q-bio], Critical care, Vascular access, business
Abstract: BackgroundVascular access for renal replacement therapy (RRT) is routine question in the intensive care unit. Randomized trials comparing jugular and femoral sites have shown similar rate of nosocomial events and catheter dysfunction. However, recent prospective observational data on RRT catheters use are scarce. We aimed to assess the site of RRT catheter, the reasons for catheter replacement, and the complications according to site in a large population of critically ill patients with acute kidney injury.Patients and methodsWe performed an ancillary study of the AKIKI study, a pragmatic randomized controlled trial, in which patients with severe acute kidney injury (KDIGO 3 classification) with invasive mechanical ventilation, catecholamine infusion or both were randomly assigned to either an early or a delayed RRT initiation strategy. The present study involved all patients who underwent at least one RRT session. Number of RRT catheters, insertion sites, factors potentially associated with the choice of insertion site, duration of catheter use, reason for catheter replacement, and complications were prospectively collected.ResultsAmong the 619 patients included in AKIKI, 462 received RRT and 459 were finally included, with 598 RRT catheters. Femoral site was chosen preferentially (n = 319, 53%), followed by jugular (n = 256, 43%) and subclavian (n = 23, 4%). In multivariate analysis, continuous RRT modality was significantly associated with femoral site (OR = 2.33 (95% CI (1.34–4.07),p = 0.003) and higher weight with jugular site [88.9 vs 83.2 kg, OR = 0.99 (95% CI 0.98–1.00),p = 0.03]. Investigator site was also significantly associated with the choice of insertion site (p = 0.03). Cumulative incidence of catheter replacement did not differ between jugular and femoral site [sHR 0.90 (95% CI 0.64—1.25),p = 0.67]. Catheter dysfunction was the main reason for replacement (n = 47), followed by suspected infection (n = 29) which was actually seldom proven (n = 4). No mechanical complication (pneumothorax or hemothorax) occurred.ConclusionFemoral site was preferentially used in this prospective study of RRT catheters in 31 French intensive care units. The choice of insertion site depended on investigating center habits, weight, RRT modality. A high incidence of catheter infection suspicion led to undue replacement.
Published: 2021

15. Survival of amyotrophic lateral sclerosis patients after admission to the intensive care unit for acute respiratory failure: an observational cohort study

Author: Jésus Gonzalez-Bermejo, C. Llontop, Thomas Similowski, Martin Dres, Julie Delemazure, Julien Mayaux, Jérôme Lambert, François Salachas, Capucine Morélot-Panzini, Gaëlle Bruneteau, and Alexandre Demoule
Subjects: Male, Advance care planning, medicine.medical_specialty, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, Tracheostomy, 0302 clinical medicine, law, medicine, Humans, Acute respiratory failure, Amyotrophic lateral sclerosis, Lung cancer, Aged, Retrospective Studies, Respiratory Distress Syndrome, business.industry, Amyotrophic Lateral Sclerosis, 030208 emergency & critical care medicine, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, Intensive care unit, Survival Rate, Intensive Care Units, Respiratory acidosis, 030228 respiratory system, Emergency medicine, Female, business, Cohort study
Abstract: Purpose Amyotrophic lateral sclerosis (ALS) entails a risk of acute respiratory failure (ARF). The decision to admit such patients to the intensive care unit (ICU) is difficult given the inexorable prognosis of ALS. To fuel this discussion, this study describes the ICU and post-ICU survival of ALS-related ARF. Material and methods Retrospective cohort analysis over 10 years (university hospital setting, ALS reference center). Results Of 90 patients (66 men, median age: 67 [IQR 59–71], median interval since ALS diagnosis: 26.5 months [14–53], ALSFRS-R: 19 [12−30], bulbar signs 73%), 48 were managed by noninvasive ventilation (NIV) only, 7 were already tracheotomized upon admission, 12 were tracheotomized during the ICU stay (advance care planning project), 18 were already intubated before admission, 5 received oxygen and physiotherapy only. Median ICU stay was 4 days [ [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] ] with 20% mortality. Median hospital stay was 10 days [5–22] with 33% mortality. The 3-month and one year mortality wer 46% and 71%. Hospital mortality was higher in patients with more severe respiratory acidosis and higher simplified acute physiology scores on admission. Conclusions The prognosis of ALS-related ARF requiring ICU admission resembles that of ARF complicating other conditions with high short-term mortality (e.g. lung cancer).
Published: 2019

16. Trachéotomie en réanimation

Author: Erwan L'Her, Hervé Quintard, Jean-Louis Trouillet, Eric Cesareo, François Ravat, Max Guillot, Charles-Edouard Luyt, François Blot, Alexandre Demoule, Julien Amour, Gilles Capellier, Yazine Mahjoub, Olivier Collange, Julien Mayaux, Jean-Luc Diehl, Fouad Belafia, Pierre-Grégoire Guinot, Sébastien Vergez, Jean-Michel Constantin, and Franck Jegoux
Subjects: 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030228 respiratory system, 030208 emergency & critical care medicine
Abstract: Resume La tracheotomie est une procedure courrament realisee en reanimation, mais avec de tres grandes disparites selon les equipes, aussi bien en termes de frequence que de modalite (percutanee ou chirurgicale). Les etudes concernant la tracheotomie en reanimation sont tres heterogenes et parfois meme contradictoires. Notre objectif etait de mener une analyse systematique des donnees publiees pour formuler des recommandations concernant la tracheotomie en reanimation chez le patient adulte et hors contexte d'urgence. Les recommandations ont ete produites a l’aide de la methode GRADE par un groupe de seize experts et de deux coordonnateurs issu de la Societe de reanimation de langue francaise et de la Societe francaise d’anesthesie et de reanimation et avec la participation de la Societe francaise de medecine d’urgence et de la Societe francaise d’ORL. Cinq champs ont ete definis : (1) indications et contre-indications, (2) techniques de mise en place, (3) modalites pratiques de realisation, (4) management des patients tracheotomises et (5) decanulation en reanimation. Le groupe d'expert a formule 8 recommandations formalisees, 10 avis d'experts et a elabore 3 protocoles de soins. Parmi les 8 recommandations formalisees , 2 ont un niveau de preuve eleve (Grade 1+/−), et 6 un niveau de preuve faible (Grade 2+/−). L'ensemble des recomandations, avis d'expert et protocoles de soins a obtenu un accord fort.
Published: 2018

17. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

Author: Mathieu Vautier, Florence Tubach, Marion Licois, Estelle Henry, Marie-Alexandra Alyanakian, Julien Poissy, Solaya Chalal, Anne Gysembergh-Houal, Stéphanie Alary, Sophie Diemunsch, Jonathan London, Camille Petit-Hoang, Ruben Benainous, Catherine Metzger, Olivier Benveniste, Hala Semri, Charléne Jouve, Robin Dhote, johann Cailhol, Elise Morawiec, Kristina Beziriganyan, Mathieu Oberlin, Paul Legendre, Hélène François, Claire Davoine, F Louni, Myriam Virlouvet, Stéphane Renaud, Christiane Verny, Bertrand Guidet, Bob Heger, Lara Zafrani, Pierre-Louis Tharaux, Mandy Nizard, Adrien Contejean, Segolene Toquet, Ulrich Clarac, Sylviane Ravato, Gaëtan Deslée, Frédéric De Blay, Christian Richard, Raphaël Porcher, Malikhone Chansombat, Marie Lachatre, Ines Ben-Mabrouk, Matthieu Uzzan, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Fanny Charbonnier, Pierre-Grégoire Guinot, Alexandre Demoule, Nicolas Champtiaux, Nicolas Belaube, Jean-Pierre Riveline, Kamil Chitour, Joseph Emmerich, Arthur Neuschwander, Mickael Henriques, Anne Hutt, Arthur Pavot, Anne Rachline, Elena Fois, Audrey Phibel, Xavier Monnet, Jean-Charles Duclos-Vallée, Félix Ackermann, Maria Pereira, Anne Sophie Korganow, Elodie Drouet, Tabassome Simon, Morgane Faure, Anne Pattyn, Aida Zahrate-Ghoul, Karine Martin, Jean-Jacques Tudesq, Gladys Aratus, Kévin Cardet, Julien Pottecher, Eric Demonsant, Arsène Mekinian, Rémy Gauzit, Julie Smati, Robin Deleris, Jean-Simon Rech, Boris Bienvenu, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Alexis Régent, François Weill, Lalia Djaghout, Anne Tréhan, Isabelle Lehir, Elena Kiouris, Sophie Renet, Yasmina Mekid, Vanessa Rathouin, David Montani, Annick Tibi, Anne Blanchard, Fanette Denies, Nathalie Menage, Guillaume Becker, Valérie Camara-Clayette, Loic Kassegne, Nathalie Chavarot, Aurélie Clan Hew Wai, Jeremy Arzoine, Louise Bondeelle, Mohamad Zaidan, S Lariven, Laurent Cylly, Edouard Flamarion, Chaouki Bouras, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Marie hélène Pari, Lionel Galicier, Valérie Dejean, Delphine Feyeux, Naima Sguiouar, Anne Bergeron, Laurence Annonay, Anouk Walter-Petrich, Camille Knosp, Laurence Drouard, Thiziri Sadaoui, Julie Delemazure, Antoine Parrot, Carole Burger, Laurence Berard, Nicolas Gambier, Eric Marquis, Isabelle Madeleine, Gwenaël Lorillon, Matthieu Resche-Rigon, Yves Hansmann, Claire Rouzaud, Hélène Gros, Sophie Caillat-Zucman, Bernard Cholley, Celine Wilpotte, Chistophe Willekens, Lydia Suarez, Syllia Belazouz, Valérie Pourchet-Martinez, Dhiaa Meriem Hai, Olivier Collange, Paul Jaubert, Marie-Thérèse Tremorin, Nathalie Marin, Diane Le Pluart, Madona Sakkal, Juliette Djadi-Prat, Alexandre Morel, Agathe Bounhiol, Xavier Jaïs, Nicolas Meyer, Vixra Keo, Michaël Darmont, Benedicte Giroux-Leprieur, Anatole Harrois, Anne Adda, Yaël Amara, Fanny Pommeret, Antony Canellas, Matheus Vieira, Clotilde Le Tiec Le Tiec, Corinne Pernot, Bernard Goichot, Céline Louapre, Roza Rahli, Anne Jacolot, Anne Daguenel-Nguyen, Marie Dubert, Anaïs Razurel, Aurelie Sautereau, Mitja Jevnikar, Pierre Faye, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Florence Patin, Kahina Cheref, Mélanie Dehais, Paul Michel Mertes, Caroline Morbieu, Valérie Paquet, Dominique Roulot, Giovanna Melica, Pauline Jouany, Frédéric Schlemmer, Blandine Lehmann, Pascal Martel, Tomas Urbina, Yazdan Yazdanpanah, Veronique Joly, Damien Bergerot, Claire Courtin, Benjamin Fournier, Guillaume Grailles, Asmaa Mamoune, Caroline Gaudefroy, Charlotte Kaeuffer, Bruno Crestani, Thinhinane Bariz, C Rioux, Karine Celli Lebras, Sophie Granville, Marion Bouhris, Hugues Cordel, Jean-Marie Michot, Mohamed Belloul, Nadège Lemarié, Philippe Dieudé, Sylvie Le Gac, Matthieu Mahévas, Pascal Richette, Anaïs Codorniu, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Vincent Castelain, Aude Rigolet, Valentin Greigert, Gaelle Leroux, Simon Valayer, Eliane Bertrand, Eric Vicaut, Stéphane Brin, Jacques-Eric Gottenberg, Olivier Clovet, Marc Bardou, Muriel Fartoukh, Valentina Isernia, Ada Clarke, Bao Phung, Grégoire Martin de Frémont, Jeanne Meunier, Gonçalo Boleto, David Lebeaux, Hassan Tarhini, Asmaa Mabrouki, Pascaline Choinier, Etienne Canouï, Eric D'Ortenzio, Constance Guillaud, Corine Nyanou, Alexandre Moores, Linda Gimeno, Victoire De Lastours, F-Xavier Lescure, Claire Montlahuc, Sophie Georgin-Lavialle, A Soria, Xavier Mariette, Sophie Ismael, Prissile Bakouboula, Olivier Lambotte, Jérémie Zerbit, Aude Jacob, Z Julia, Nathalie Dournon, Marthe Rigal, Mireille Adda, Nathan Ebstein, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Hélène Lafoeste, Coralie Bloch Queyrat, Sabrina Brahmi, Catherine Le Bourlout, Nicolas Noel, Emmanuelle Guillot, Hakim Tayebi, Sandrine Briois, Anne-Lise Pouliquen, Lakhdar Mameri, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Lelia Escaut, Clément Jourdaine, Cédric Pierron, Marc Garnier, Yves Cohen, Abdellatif Tazi, Maxence Decavele, Paul Henri Grisot, Patrice Cacoub, Laure Allanic, Amira Benattia, Martin Siguier, Luca Semerano, Jean-Sébastien Hulot, Jean-Jacques Mourad, Sara Sambin, Miguel Alejandro Vasquez-Ibarra, Nabil Raked, Christine Lemagner, Martin Dres, Clara Campos-Vega, Tali-Anne Szwebel, Benjamin Chaigne, Emmanuel Andrès, Gabriel Steg, Frédéric Blanc, Isabelle Peigney, Catherine Fauvaux, Côme Bureau, Samira Saleh-Mghir, Julie Jambon, Pierre Dupland, Anne Lise Jegu, Mamadou Salif Cisse, Damien Roux, Moez Jallouli, Philippe Blanche, Sébastien Cavelot, Sophie Ohlmann-Caillard, Louise-Laure Mariani, Adrien Michon, Alain Wynckel, Saskia Flamand, Safaa Nemlaghi, Benjamin G. Chousterman, Geoffroy Volle, Cécile Kedzia, Fanny Domont, Lee S. Nguyen, Férial Berbour, Pierre Diemunsch, Celine Dupré, Etienne Lengliné, Claire Tantet, Gaël Leprun, Sara Virolle, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Mathilde Le Marchand, Vincent Poindron, Victor Lancon, Ruxandra Burlacu, Guillaume Lefèvre, Kamyl Baghli, Emilia Stan, Yann Nguyen, Olivier Sanchez, Olivier Sitbon, Loren Soyez-Herkert, Fanny Defrancq, Véronique Vigna, Aurélien Guffroy, Martine Meunier, Pierre Mora, Léa Resmini, Liem Binh Luong Nguyen, Jean-Luc Diehl, Johanna Oziel, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Marie Matignon, Mourad Djadel, Yasmine Messaoudi, Hassan Joumaa, Isabelle Dusanter, Sarah Benghanem, Julien Mayaux, Marc Michel, Claire Pernin, Antoine Gros, Nassim Mahtal, Philippe Benoit, Cloé Comarmond, Laurence Lecomte, Patricia Senet, Sebastien Abad, Jérôme Pacanowski, Céline Leplay, Claire Aguilar, Cédric Sublon, Jesuthasan Denis, Régis Peffault de Latour, Gabrielle Archer, Alain Fourreau, Emmanuelle Blin, Lise Bernard, Alexandra Beurton, Alexandre Buffet, Pierre Le Guen, Clairelyne Dupin, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Alexandre Bourgoin, Agnes Maurer, Eric Noll, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Carine Karachi, Samy Figueiredo, Hakim Meddah, Greggory Ducrocq, Jeanne Goupil de Bouille, Awa Ndiaye, Jessica Krause le Garrec, Maxime Dougados, Yasmina Ferfar, Damien Vimpere, Olivier Olivier, Annabelle Stoclin, Jean-Louis Teboul, Ridha Belilita, Serge Bureau, Naura Gamany, Emeline Colomba, Baptiste Duceau, Philippe Ravaud, Corinne Guerin, Florence Morin, Pélagie Thibaut, Younes Keroumi, Julie Chas, Elisabeth Coupez, Laetitia Languille, Mathias Cornic, Jean-Michel Molina, Caroline Pradon, Alison Klasen, Zakaria Ait Hamou, Armand Mekontso-Dessaps, Yurdagul Uzunhan, Samir Hamiria, Anne Godier, Elsa Feredj, Nessima Yelles, Jean-Benoit Arlet, Christine Broissand, Belkacem Asselate, Jaouad Benhida, Julien Le Marec, Nawal Derridj, Laurène Deconinck, A. Dossier, Eric Oksenhendler, Eva Chatron, Lucie Aunay, Candice Estellat, Julie Fillon, Marie Antignac, Jade Ghosn, Ilias Koumis, David Schmitz, Domitille Molinari, Soraya Fellahi, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Vincent Provitolo, Marie Lecronier, Dimitri Fremont, Pierrick Le Borgne, Emmanuel Weiss, Faouzi Saliba, Stéphan Pavy, Geoffrey Rossi, Chloe McAvoy, Eric Mariotte, Dorothee Vallois, Sabrine Ouamri, Pierre Tissieres, Luc Mouthon, Blandine Denis, Celine Comparon, Emmanuelle Sacco, Frédéric Pène, Marjolaine Morgand, Vasco Honsel, Laure Choupeaux, Bruno Mourvillier, Ewa Kozaliewicz, Marie-Hélène Legros, Isabelle Debrix, Gabriel Nisand, Julien Chabert, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Marine Livrozet, Lucie Biard, Elodie Perrodeau, Brigitte Sabatier, Raphael Borie, Rosa Da Silva, Nathalie Costedoat-Chalumeau, Emmanuel Chatelus, Jean-Christophe Corvol, Nathalie De Castro, David Boutboul, Benjamin Planquette, Anne Claire Desbois, François Danion, Brigitte Ranque, Amélie Cransac, Marine Nadal, Coralie Gernez, Yacine Boudali, Claire Madelaine, Georgina Maalouf, Jonathan Marey, Sophie Bayer, Antoine Fayol, Souad Benarab, Luc Haudebourg, Sophie Bulifon, Claire Pacheco, Philippe Durand, Olivier Hermine, Fanny Alby-Laurent, Geoffroy Liégeon, Axelle Fuentes, Jean-Daniel Lelievre, Gilles Garcia, Céline Verstuyft Verstuyft, Marie-Aude Penet, Constance Delaugerre, Nicolas Carlier, Aurélie Durel Maurisse, Gilles Pialoux, Zeina Louis, Marion Parisey, Pascal Lim, Gaelle Clavere, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Adrien Joseph, Hilario Nunes, Hanane Fodil, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Isabelle Brindele, Robin Charreteur, Elie Azoulay, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Marie Gilbert, Matthieu Lemoine, Abolfazl Mohebbi, Mathilde Noaillon, Amina Kebir, Virginie Zarrouk, Cécile Yelnik, Benjamin Terrier, Solène Fabre, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Oriane Puéchal, Pernelle Vauboin, Caroline Hauw-Berlemont, Gabriel Baron, Paul Vermes, Yvon Ruch, Dominique Dautel, Tassadit Hadjam, Anne-Marie Roques, Jean-Philippe Bastard, Younes El Amine, Damien Sène, Alaki Thiemele, Catherine Boussard, Vincent Fallet, Timothee Bironne, Damien Vanhoye, Guillaume Geri, Amine Ghembaza, Bertrand Dunogue, Nadia Anguel, Laure Berton, Caroline Semaille, Thomas Volpe, Jacques Cadranel, Thomas Gorget, Julien Saussereau, Elodie Issorat, Sami Kolta, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Porcher, Raphaël
Subjects: Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Hazard ratio, Articles, Middle Aged, Intensive care unit, Hospitals, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Treatment Outcome, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, medicine.drug, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, Population, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, education, Critical Care Outcomes, Aged, Mechanical ventilation, Anakinra, SARS-CoV-2, business.industry, Comment, COVID-19, Bayes Theorem, Pneumonia, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Clinical trial, Interleukin 1 Receptor Antagonist Protein, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, Interleukin-1
Abstract: International audience; Background: Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods: In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual.Findings: Between April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2·5%, 90% credible interval [CrI] -17·1 to 12·0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61·2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54·5% (median posterior HR 0·97; 90% CrI 0·62 to 1·52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usual care group (p=0·45).Interpretation: Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.Funding: The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation.
Published: 2021
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18. Poor outcome associated with mucormycosis in critically ill hematological patients: results of a multicenter study

Author: Sandrine Valade, Fabrice Bruneel, Frédéric Pène, Elie Azoulay, Julien Mayaux, Matthieu Jestin, Martin Murgier, Michael Darmon, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Soins Intensifs [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Bone marrow transplantation, medicine.medical_treatment, Neutropenia, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, Hematological malignancies, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Intensive care, medicine, Mucormycosis, Intensive care unit, 030212 general & internal medicine, Renal replacement therapy, Outcome, 0303 health sciences, 030306 microbiology, business.industry, Research, Mortality rate, lcsh:Medical emergencies. Critical care. Intensive care. First aid, lcsh:RC86-88.9, medicine.disease, 3. Good health, Transplantation, SOFA score, business
Abstract: Background Mucormycosis is an emerging fungal infection that may lead to multi-organ failure, especially in patients with hematological malignancies (HM). We performed a retrospective, cohort study, in five intensive care units (ICU) to assess the outcome of critically ill patients with HM and mucormycosis between 2002 and 2018. The secondary objective was to identify prognostic factors in this setting. Results Twenty-six patients were included with a median age of 38 years [IQR, 26–57]). Acute leukemia was the most frequent underlying disease (50%). Nine patients (35%) underwent allogeneic stem cell transplantation (SCT). Nineteen patients (73%) had neutropenia and 16 (62%) had received steroids. The main reason for admission was acute respiratory failure (n = 14, 54%) followed by shock (n = 5 19%). The median SOFA score at admission was 7 [5–8]. According to EORTC/MSG criteria, mucormycosis was "proven" in 14 patients (54%), "probable" in 5 (19%) and “possible” in 7 (27%) in whom diagnosis was made by qPCR. Rhizopus and Mucor were the most frequent documented species. Seven patients (27%) had concurrent Aspergillus infection. Mucormycosis was diagnosed 1 day [−4 to + 6] after ICU admission. Sixteen patients (62%) had pulmonary involvement and ten (38%) rhino-cerebral involvement. Infection was disseminated in eight patients (31%). Twenty-two patients (85%) were treated with liposomal amphotericin B; 12 (46%) received antifungal combination including posaconazole in 7. Eight patients (31%) underwent curative surgery. Twenty-one patients (81%) required invasive mechanical ventilation (IMV), 18 (69%) vasopressors, and 9 (35%) renal replacement therapy. ICU and hospital mortality rates were 77% and 88%, respectively. The median overall survival was 9 days [3–22]. IMV was strongly associated with ICU mortality (p Conclusions Mucormycosis is associated with a high mortality rate in patients with HM, especially in allogeneic SCT recipients. Benefit of ICU management in these patients should be assessed before admission and strategies aiming to improve these patients’ outcome are urgently needed.
Published: 2021

19. Clinical features and outcome of patients with primary central nervous system lymphoma admitted to the intensive care unit: a French national expert center experience

Author: Caroline Houillier, Isabelle Rivals, Nicolas Gatulle, Charles-Edouard Luyt, Maxens Decavèle, Nicolas Weiss, Thomas Similowski, Aliénor Dreyfus, Julie Delemazure, Khê Hoang-Xuan, Elise Morawiec, Julien Mayaux, Sophie Demeret, Alexandre Demoule, Sylvain Choquet, Martin Dres, Gestionnaire, HAL Sorbonne Université 5, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Institut de neurosciences translationnelles de Paris (NeurATRIS - IHU-A-ICM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Central Nervous System, medicine.medical_specialty, Neurology, Lymphoma, medicine.medical_treatment, Aspiration pneumonia, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Neuro-oncology, medicine, Humans, Intensive care medicine, Hospital Mortality, 030212 general & internal medicine, Primary central nervous system lymphoma, Retrospective Studies, Mechanical ventilation, Coma, Original Communication, business.industry, Prognosis, medicine.disease, Triage, Intensive care unit, 3. Good health, Hospitalization, Intensive Care Units, Critical care, Emergency medicine, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Cohort study
Abstract: Introduction To describe the reasons for intensive care unit (ICU) admission and to evaluate the outcomes and prognostic factors of patients with primary central nervous system lymphoma (PCNSL) admitted to the ICU. Patients and methods Retrospective observational cohort study of 101 PCNSL patients admitted to 3 ICUs over a two-decade period. Results Acute respiratory failure, mainly secondary to aspiration pneumonia and Pneumocystis jirovecii pneumonia, was the leading reason for ICU admission (33%). Aspiration pneumonia was more common in patients with brainstem tumor (67% vs. 0%, p
Published: 2021

20. Pharmacokinetics and pharmacodynamics of hydroxychloroquine in hospitalized patients with COVID-19

Author: Noël Zahr, Valérie Pourcher, Julien Mayaux, Joe-Elie Salem, Estelle Gandjbakhch, Yves Allenbach, Guillaume Hékimian, Saïk Urien, Alexandre Bleibtreu, Olivier Benveniste, Olivier Paccoud, Alain Combes, Christian Funck-Brentano, Benoit Llopis, David Saadoun, Patrice Cacoub, Bruno Pinna, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Pharmacologie Clinique [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service de Cardiologie [CHU Pitié-Salpêtrière], Service de Réanimation Médicale [CHU Pitié-Salpétrière], Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], HAL-SU, Gestionnaire, Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], and Garnier, Sophie
Subjects: Adult, Male, medicine.medical_specialty, 030226 pharmacology & pharmacy, High-performance liquid chromatography, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Intensive care, medicine, Humans, Pharmacology (medical), Retrospective Studies, Volume of distribution, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, business.industry, Clinical Pharmacology, Hydroxychloroquine, Middle Aged, Confidence interval, COVID-19 Drug Treatment, 3. Good health, Bioavailability, Hospitalization, [SDV] Life Sciences [q-bio], Pharmacodynamics, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, business, Covid-19, medicine.drug
Abstract: Summary Background Hydroxychloroquine (HCQ) dosage required to reach circulating levels that inhibit SARS-Cov-2 are extrapolated from pharmacokinetic data in non-COVID-19 patients. Methods We performed a population-pharmacokinetic analysis from 104 consecutive COVID-19 hospitalized patients (31 in intensive care units, 73 in medical wards, n = 149 samples). Plasma HCQ concentration were measured using high performance liquid chromatography with fluorometric detection. Modelling used Monolix-2019R2. Results HCQ doses ranged from 200 to 800 mg/day administered for 1 to 11 days and median HCQ plasma concentration was 151 ng/mL. Among the tested covariates, only bodyweight influenced elimination oral clearance (CL) and apparent volume of distribution (Vd). CL/F (F for unknown bioavailability) and Vd/F (relative standard-error, %) estimates were 45.9 L/h (21.2) and 6690 L (16.1). The derived elimination half-life (t1/2) was 102 h. These parameters in COVID-19 differed from those reported in patients with lupus, where CL/F, Vd/F and t1/2 are reported to be 68 L/h, 2440 L and 19.5 h, respectively. Within 72 h of HCQ initiation, only 16/104 (15.4%) COVID-19 patients had HCQ plasma levels above the in vitro half maximal effective concentration of HCQ against SARS-CoV-2 (240 ng/mL). HCQ did not influence inflammation status (assessed by C-reactive protein) or SARS-CoV-2 viral clearance (assessed by real-time reverse transcription-PCR nasopharyngeal swabs). Conclusion The interindividual variability of HCQ pharmacokinetic parameters in severe COVID-19 patients was important and differed from that previously reported in non-COVID-19 patients. Loading doses of 1600 mg HCQ followed by 600 mg daily doses are needed to reach concentrations relevant to SARS-CoV-2 inhibition within 72 hours in ≥ 60% (95% confidence interval: 49.5–69.0%) of COVID-19 patients.
Published: 2021

21. Randomised trial of first-line bronchial artery embolisation for non-severe haemoptysis of mild abundance

Author: Benjamin Planquette, Vincent Labbe, Tabassome Simon, Alexandra Rousseau, Jacques Cadranel, Antoine Khalil, Emmanuel Bergot, Gérard Zalcman, Guy Meyer, Philippe Cluzel, Vincent Jounieaux, Alexandre Demoule, Muriel Fartoukh, Aude Gibelin, Olivier Sanchez, THOMAS SIMILOWSKI, Claire Andrejak, Valérie Chabbert, Michel Djibré, Sophie Tuffet, Cendrine Godet, Sandrine Pontier-Marchandise, Julien Mayaux, Marc Sapoval, Vincent Le Pennec, Clarisse Blayau, Guillaume Voiriot, Alexandre Duguet, Hélène Prodanovik, Guillaume Briend, Anne Roche, Costantino Del Giudice, Olivier Pellerin, Marie-Pierre Revel, Patrick Courtheoux, Jean Claude Meurice, Elise Antone, Alexandre Remond, Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), CHU Pitié-Salpêtrière [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Unité de Recherche Clinique de l’Est Parisien [CHU Saint-Antoine] (URC-EST), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Picardie Jules Verne (UPJV), Service de pneumologie [Toulouse], CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Service d'Anesthésie réanimation [CHU Tenon], Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Service de Radiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Radiologie [CHU Caen], Service de Radiologie [CHU Tenon], Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service de Radiothérapie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP]
Subjects: Adult, Pulmonary and Respiratory Medicine, Hemoptysis, medicine.medical_specialty, Standard of care, First line, Bronchial Arteries, Imaging/CT MRI etc, Pulmonary Vasculature, 030218 nuclear medicine & medical imaging, Diseases of the respiratory system, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Bronchoscopy, medicine.artery, medicine, Humans, Adverse effect, Trial registration, Retrospective Studies, RC705-779, medicine.diagnostic_test, Adult patients, business.industry, Embolization, Therapeutic, 3. Good health, Surgery, Treatment Outcome, 030228 respiratory system, Medicine, business, Bronchial artery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Massive Haemoptysis
Abstract: BackgroundWhereas first-line bronchial artery embolisation (BAE) is considered standard of care for the management of severe haemoptysis, it is unknown whether this approach is warranted for non-severe haemoptysis.Research questionTo assess the efficacy on bleeding control and the safety of first-line BAE in non-severe haemoptysis of mild abundance.Study design and methodsThis multicentre, randomised controlled open-label trial enrolled adult patients without major comorbid condition and having mild haemoptysis (onset ResultsBleeding recurrence at day 30 after randomisation (primary outcome) occurred in 4 (11.8%) of 34 patients in the BAE strategy and 17 (44.7%) of 38 patients in the medical strategy (difference −33%; 95% CI −13.8% to −52.1%, p=0.002). The 90-day bleeding recurrence-free survival rates were 91.2% (95% CI 75.1% to 97.1%) and 60.2% (95% CI 42.9% to 73.8%), respectively (HR=0.19, 95% CI 0.05 to 0.67, p=0.01). No death occurred during follow-up and no bleeding recurrence needed surgery.Four adverse events (one major with systemic emboli) occurred during hospitalisation, all in the BAE strategy (11.8% vs 0%; difference 11.8%, 95% CI 0.9 to 22.6, p=0.045); all eventually resolved.ConclusionIn non-severe haemoptysis of mild abundance, BAE associated with medical therapy had a superior efficacy for preventing bleeding recurrences at 30 and 90 days, as compared with medical therapy alone. However, it was associated with a higher rate of adverse events.Trial registration numberNCT01278199
Published: 2020

22. IgA dominates the early neutralizing antibody response to SARS-CoV-2

Author: Pierre Charneau, Jean Marc Lacorte, Laetitia Claër, Olivier Schwartz, Amélie Guihot, Cary Gunn, Rick Hockett, Pascale Ghillani, Hans Yssel, Alexis Mathian, Jehane Fadlallah, Timothée Bruel, Karim Dorgham, Paul Quentric, François Anna, Makoto Miyara, Salma Fourati, Charles Edouard Luyt, Guy Gorochov, Delphine Sterlin, Hervé Devilliers, Sasi Mudumba, Alexandra Beurton, Julien Mayaux, Zahir Amoura, Christophe Parizot, Audrey Mohr, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, Institut Pasteur [Paris], Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris]-TheraVectys, Service de Médecine Interne (SOC 1 et SOC 2) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-TheraVectys, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), ANR-20-COVI-0025,iCovid,Immunopathologie du COVID-19 à l'Assistance Publique Hôpitaux de Paris(2020), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Saliva, Time Factors, viruses, Antibodies, Viral, Immunoglobulin E, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunity, Humans, Medicine, Longitudinal Studies, Neutralizing antibody, Research Articles, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, biology, SARS-CoV-2, business.industry, Case-control study, COVID-19, General Medicine, Antibodies, Neutralizing, Primary and secondary antibodies, STM r-articles, Immunity, Humoral, Immunoglobulin A, 3. Good health, Coronavirus, Immunoglobulin M, Case-Control Studies, Immunoglobulin G, 030220 oncology & carcinogenesis, Host-Pathogen Interactions, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Antibody, business, Bronchoalveolar Lavage Fluid, Biomarkers, Research Article
Abstract: Early specific antibody responses against SARS-CoV-2 include IgG, IgM, and IgA, but IgA may neutralize virus and control infection to a larger extent., Early action of IgA Humoral immune responses play a critical role in protecting individuals against SARS-CoV-2 infection, particularly through the activity of neutralizing antibodies. Sterlin et al. measured humoral immune responses in the serum, saliva, and bronchoalveolar lavage fluid of SARS-CoV-2–infected patients who experienced a range of COVID-19 disease severity. IgA antibodies dominated the early SARS-CoV-2–specific antibody response compared with IgG and IgM concentrations in these fluids and was associated with expansion of IgA plasmablasts with mucosal homing characteristics. IgA serum concentrations peaked 3 weeks after symptom onset but persisted for several more weeks in saliva, and serum IgA was more potent than IgG in neutralizing SARS-CoV-2. These findings highlight the potential role of IgA during early SARS-CoV-2 infection., Humoral immune responses are typically characterized by primary IgM antibody responses followed by secondary antibody responses associated with immune memory and composed of IgG, IgA, and IgE. Here, we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of SARS-CoV-2–specific neutralizing antibodies in the serum, saliva, and bronchoalveolar fluid of 159 patients with COVID-19. Early SARS-CoV-2–specific humoral responses were dominated by IgA antibodies. Peripheral expansion of IgA plasmablasts with mucosal homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. The virus-specific antibody responses included IgG, IgM, and IgA, but IgA contributed to virus neutralization to a greater extent compared with IgG. Specific IgA serum concentrations decreased notably 1 month after the onset of symptoms, but neutralizing IgA remained detectable in saliva for a longer time (days 49 to 73 post-symptoms). These results represent a critical observation given the emerging information as to the types of antibodies associated with optimal protection against reinfection and whether vaccine regimens should consider targeting a potent but potentially short-lived IgA response.
Published: 2020

23. Performance of serum apolipoprotein-A1 as a sentinel of Covid-19

Author: Sepideh Akhavan, Marika Rudler, Dominique Bonnefont-Rousselot, Julien Mayaux, Bruno Fautrel, Clemence Franc, Yves Allenbach, Mehdi Sakka, Chantal Housset, Olivier Lucidarme, Vincent Calvez, Thierry Poynard, Frédérique Gandjbakhch, Jean Marc Lacorte, Olivier Deckmyn, Mathieu Vautier, F. Drane, Patrice Cacoub, Yen Ngo, Dominique Thabut, J.M. Castille, David Saadoun, Valentina Peta, Olivier Benveniste, Vlad Ratziu, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), BioPredictive [Paris], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Service de virologie [CHU Pitié-Salpêtrière], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Radiologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Viral Diseases, Epidemiology, [SDV]Life Sciences [q-bio], Biochemistry, Geographical locations, law.invention, Medical Conditions, 0302 clinical medicine, law, Medicine and Health Sciences, Virus Testing, 0303 health sciences, education.field_of_study, Multidisciplinary, biology, medicine.diagnostic_test, Liver Diseases, Haptoglobin, Middle Aged, Intensive care unit, Hospitals, 3. Good health, Europe, [SDV] Life Sciences [q-bio], Intensive Care Units, Infectious Diseases, 030220 oncology & carcinogenesis, Medicine, Female, 030211 gastroenterology & hepatology, Apolipoprotein A1, France, Coronavirus Infections, Research Article, Adult, medicine.medical_specialty, Science, Pneumonia, Viral, Population, Gastroenterology and Hepatology, Betacoronavirus, 03 medical and health sciences, Diagnostic Medicine, Internal medicine, medicine, Humans, European Union, education, Pandemics, Aged, Retrospective Studies, 030304 developmental biology, Plasma Proteins, Haptoglobins, Apolipoprotein A-I, SARS-CoV-2, business.industry, Biology and Life Sciences, Proteins, COVID-19, Covid 19, Retrospective cohort study, medicine.disease, United States, Health Care, Pneumonia, Health Care Facilities, Medical Risk Factors, Relative risk, biology.protein, Observational study, People and places, business, Liver function tests, Biomarkers
Abstract: BackgroundSince 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19.MethodsWe compared the daily mean serum apolipoprotein-A1 during the first 30 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (183,112 sera) and in France (18,316 sera) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (respectively 234,881 and 26,056 sera). We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population.ResultsThe mean serum apolipoprotein-A1 levels in these populations began decreasing in January 2020, compared to the same 30 weeks in 2019. This decrease was highly correlated to and in parallel with the daily increase in confirmed Covid-19 cases in the following 30 weeks, in both France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-A1 at the 1.25 g/L cutoff had a sensitivity of 90.6% (95%CI84.2-95.1) and a specificity of 96.1% (95.7-96.6%) for the diagnosis of Covid-19. The area under the characteristics curve was 0.978 (0.957-0.988), and outperformed haptoglobin and liver function tests. The adjusted risk ratio for survival without transfer to intensive care unit was 5.61 (95%CI 1.02-31.0;P=0.04).ConclusionApolipoprotein-A1 could be both a sentinel of the pandemic in existing routine surveillance of the general population with no new blood sample, as well as a candidate predictor of suspected Covid-19 in multivariate analysis in cases with a negative virological test. NCT01927133, CER-2020-14.Key PointsQuestionDoes serum apolipoprotein-A1 decrease could be a very early biomarker of SARS-CoV-2 pandemic?FindingsDuring the 30 weeks of 2020 we observed in two large cohorts of patients at risk of liver fibrosis a highly significant decrease of serum apolipoprotein-A1, not observed in previous years. This decrease was highly correlated to and in parallel with the daily increase in confirmed Covid-19 cases, including the recovery period.MeaningApolipoprotein-A1 could be used as a sentinel of the pandemic in existing routine surveillance of the general population.
Published: 2020

24. Respiratory Mechanics and Outcomes in Immunocompromised Patients With ARDS

Author: Alexandre Demoule, Massimo Antonelli, Peter Schellongowski, Peter Pickkers, Marcio Soares, Tine Meyhoff, Jordi Rello, Philippe R. Bauer, Andry van de Louw, Virgine Lemiale, David Grimaldi, Ignacio Martin-Loeches, Martin Balik, Sangeeta Mehta, Achille Kouatchet, Andreas Barratt-Due, Miia Valkonen, Jean Reignier, Victoria Metaxa, Anne-Sophie Moreau, Gaston Burghi, Djamel Mokart, Julien Mayaux, Michael Darmon, Elie Azoulay, Karin Amrein, Thomas Staundinger, Gottfried Heinz, Gürkan Sengölge, Christian Zauner, Peter Jaksch, Fabio S. Taccone, Anne Pascale Meert, Dominique Benoît, Ulysses V.A. Silva, Ana Paula Pierre de Moraes, Thiago Lishoa, Jorge Salluh, William Viana, Guilliana Moralez, Thiago Domingos Correa, Umesh Shah, Thomas Karvunidis, Balik Martin, Katerina Russinova, Anders Perner, Tine Sylvest Meyhoff, Nielsen Jonas, Ramin Brandt Bukan, Ann M. Moeller, Lene B. Nielsen, Amélie Seguin, Akli Chermak, Nicolas Terzi, Isabelle Vinatier, Florent Wallet, Kada Klouche, Laura Platon, Benjamin Gaborit, François Barbier, Frederic Pène, Antoine Rabbat, Virginie Lemiale, Martine N'Yunga, Christophe Girault, Caroline Lemaitre, Elise Artaud-Macari, F. Bruneel, Anne Sophie Moreau, Anne Kuitunen, Brian Marsh, Mater Misericordia, Aisling Mc Mahon, Gilda Cinnella, Antonella Cotoia, Ospedali Riuniti, Lucas Montini, Angélique Spoelstra de Man, Precious Pearl Landburg, Dennis Bergmans, Pleun Hemelaar, Thomas Kaufmann, Andreas Barrat-Due, Pål Klepstad, Belen Encina, Gabriel Moreno, Llorenç Socias Crespi, Emilio Rodriguez-Ruiz, Andry Van De Louw, Philippe Bauer, Yadav Hemang, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Medizinische Universität Wien = Medical University of Vienna, Radboud University Medical Centre [Nijmegen, The Netherlands], University of Copenhagen = Københavns Universitet (KU), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Mayo Clinic [Rochester], Penn State Health Milton S. Hershey Medical Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université libre de Bruxelles (ULB), Trinity College Dublin, Charles Darwin University, University of Toronto, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Oslo University Hospital [Oslo], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Service d'anesthésie et réanimation chirurgicale [Nantes], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), King's College Hospital (KCH), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pulmonary and Respiratory Medicine, ARDS, medicine.medical_specialty, MESH: Respiratory Distress Syndrome, medicine.medical_treatment, Population, Respiratory physiology, Neutropenia, Critical Care and Intensive Care Medicine, Acute respiratory failure, MESH: Tidal Volume, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Prognosis, 03 medical and health sciences, MESH: Positive-Pressure Respiration, 0302 clinical medicine, Diagnosis, medicine, MESH: Immunocompromised Host, Renal replacement therapy, education, Immunocompromised, Tidal volume, Outcome, MESH: Aged, education.field_of_study, MESH: Humans, MESH: Middle Aged, business.industry, Mortality rate, 030208 emergency & critical care medicine, MESH: Follow-Up Studies, Plateau pressure, medicine.disease, MESH: Male, MESH: Prospective Studies, 3. Good health, 030228 respiratory system, Emergency medicine, Driving pressure, Etiology, MESH: Respiratory Mechanics, Cardiology and Cardiovascular Medicine, business, MESH: Female
Abstract: International audience; Background: In view of the high mortality rate of immunocompromised patients with ARDS, it is important to identify targets for improvement.Research question: This study investigated factors associated with mortality in this specific ARDS population, including factors related to respiratory mechanics (plateau pressure [Pplat,rs], compliance [Crs], and driving pressure [ΔPrs]).Study design and methods: This study consisted of a predefined secondary analysis of the EFRAIM data. Overall, 789 of 1,611 patients met the Berlin criteria for ARDS, and Pplat,rs, ΔPrs, and Crs were available for 494 patients. A hierarchical model was used to assess factors at ARDS onset independently associated with hospital mortality.Results: Hospital mortality was 56.3%. After adjustment, variables independently associated with hospital mortality included ARDS of undetermined etiology (OR, 1.66; 95% CI, 1.01-2.72), need for vasopressors (OR, 1.91; 95% CI, 1.27-2.88), and need for renal replacement therapy (OR, 2.02; 95% CI, 1.37-2.97). ARDS severity according to the Berlin definition, neutropenia on admission, and the type of underlying disease were not significantly associated with mortality. Before adjustment, higher Pplat,rs, higher ΔPrs, and lower Crs were associated with higher mortality. Addition of each of these individual variables to the final hierarchical model revealed a significant association with mortality: ΔPrs (OR, 1.08; 95% CI, 1.05-1.12), Pplat,rs (OR, 1.07; 95% CI, 1.04-1.11), and Crs (OR, 0.97; 95% CI, 0.95-0.98). Tidal volume was not associated with mortality.Interpretation: In immunocompromised patients with ARDS, respiratory mechanics provide additional prognostic information to predictors of hospital mortality. Studies designed to define lung-protective ventilation guided by these physiological variables may be warranted in this specific population.
Published: 2020

25. Pressure-Support Ventilation vs T-Piece During Spontaneous Breathing Trials Before Extubation Among Patients at High Risk of Extubation Failure

Author: Alexandre Massri, Christine Lebert, Claire Dupuis, Carole Guignon, Konstantinos Bachoumas, Saad Nseir, Morgane Olivry, Maelle Martin, Keyvan Razazi, Alexandre Lautrette, Jean-Marc Tadié, Laurence Dangers, G. Barberet, Carole Schwebel, Pierre Bailly, Jean-Damien Ricard, Jeremy Bourenne, Maxens Decavèle, Guillaume Lacave, Thierry Boulain, Caroline Sabatier, Séverin Cabasson, Nicolas Terzi, Olivier Pouly, Thi-My-Hue Nguyen, Gael Bourdin, Matthieu Buscot, Florence Boissier, Suela Demiri, Arnaud Gacouin, Quentin Levrat, Charlotte Garret, Antoine Poidevin, Jean Dellamonica, René Robert, Gael Pradel, Anne-Florence Dureau, Dalila Benzekri-Lefevre, Rémi Coudroy, Benjamin Delmas, Abirami Thiagarajah, Romain Sonneville, Anahita Rouzé, Emmanuelle Mercier, Déborah Boyer, Christophe Girault, Lila Bouadma, Grégoire Muller, Marie-Ange Azais, Walter Picard, Emmanuel Vivier, Sylvène Rosselli, Mai-Anh Nay, Céline Deletage, Julien Mayaux, Adel Maamar, Anthony Le Meur, Pierre Asfar, Marie-Anne Hoppe, François Beloncle, Anne Veinstein, Guillaume Berquier, Alexandre Demoule, Marlène Morisseau, Marc Pierrot, Stéphanie Ragot, Edouard Soum, Gwenhael Colin, Gwenaël Prat, Bérénice Puech, Stephan Ehrmann, Florent Joly, Arnaud W. Thille, Delphine Chatellier, Jean-Pierre Frat, Jean-Baptiste Lascarrou, Marc Gainnier, Gaetan Beduneau, Armand Mekontso-Dessap, Guillaume Carteaux, Yves Le Tulzo, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional d'Orléans (CHRO), CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Rouen, Normandie Université (NU), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Saint Joseph - Saint Luc [Lyon], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Louis Mourier - AP-HP [Colombes], CHU Henri Mondor [Créteil], Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), 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), Centre hospitalier de Pau, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Henri Mondor d'Aurillac, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Grenoble, CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Pulmonary and Respiratory Medicine, airway extubation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Pressure support ventilation, Airway Extubation, mechanical ventilation, Critical Care and Intensive Care Medicine, law.invention, Spontaneous breathing trial, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Interquartile range, law, Multicenter trial, Post-hoc analysis, medicine, 030212 general & internal medicine, Mechanical ventilation, business.industry, 3. Good health, 030228 respiratory system, Anesthesia, ICU, ventilator weaning, Cardiology and Cardiovascular Medicine, business
Abstract: Background Spontaneous breathing trial (SBT) using a T-piece remains the most frequently performed trial before extubation in ICUs. Research Question We aimed at determining whether initial SBT using pressure-support ventilation (PSV) could increase successful extubation rates among patients at high risk of extubation failure. Study Design and Methods Post hoc analysis of a multicenter trial focusing on reintubation in patients at high-risk of extubation failure. The initial SBT was performed using PSV or T-piece according to the physician/center decision. The primary outcome was the proportion of patients successfully extubated 72 hours after initial SBT, that is, extubated after initial SBT and not reintubated within the following 72 hours. Results Among the 641 patients included in the original study, initial SBT was performed using PSV (7.0 cm H2O in median without positive end-expiratory pressure) in 243 patients (38%) and using a T-piece in 398 patients (62%). The proportion of patients successfully extubated 72 hours after initial SBT was 67% (162/243) using PSV and 56% (223/398) using T-piece (absolute difference 10.6%; 95% CI, 2.8 to 28.1; P = .0076). The proportion of patients extubated after initial SBT was 77% (186/283) using PSV and 63% (249/398) using T-piece (P = .0002), whereas reintubation rates within the following 72 hours did not significantly differ (13% vs 10%, respectively; P = .4259). Performing an initial SBT using PSV was independently associated with successful extubation (adjusted OR, 1.60; 95% CI, 1.30 to 2.18; P = .0061). Interpretation In patients at high risk of extubation failure in the ICU, performing an initial SBT using PSV may hasten extubation without an increased risk of reintubation.
Published: 2020

26. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study

Author: Alexandra Beurton, Abdelmalek Abdelkrim, Nicolas Bréchot, Alexandre Elabbadi, Juliette Chommeloux, Martin De Sarcus, Thomas Urbina, Elodie Baron, Thibaut Schoell, Paris Meng, Charlotte Du Fayet De La Tour, Sofica Marin, Victoria Lepere, Elise Morawiec, Eric Maury, Bertrand Guidet, Pierre Romain Delmotte, Enora Berti, Pierre Bay, Alain Combes, Hafid Ait Oufella, Muriel Fartoukh, Jean Luc Baudel, Samia Abbas, David Levy, Matthieu Turpin, David Hajage, Cossimo D'Alessandro, Pascal Leprince, Corinne Vezinet, Charles Edouard Luyt, Robin Deleris, Martin Dres, Jean Michel Constantin, Alexandre Demoule, Marc Pineton de Chambrun, Mona Assefi, Guillaume Hékimian, Cyrielle Desnos, Pierre Demondion, Guillaume Voiriot, Bao Long Nguyen, Arthur James, Harold Bonvallot, Safaa Nemlaghi, Nathalie Nardonne, Julien Mayaux, Vincent Bonny, Guillaume Lebreton, Cyril Quemeneur, Sara Virolle, Emmanuelle Guerin, Matthieu Schmidt, Aude Gibelin, Julien Le Marec, Charles Juvin, Guillaume Savary, Jean Remi Lavillegrand, Antoine Monsel, Jeremy Arzoine, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Réanimation Médicale [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Réanimation et USC Médico-Chirurgicale [CHU Tenon], CHU Tenon [AP-HP], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Pneumologie, Médecine Intensive et Réanimation - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Service de Réanimation et USC Médico-Chirurgicale = Médecine intensive réanimation [CHU Tenon], Service de Médecine Intensive et Réanimation - R3S [CHU Pitié-Salpêtrière], and Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158)
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, ARDS, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Pneumonia, Viral, Context (language use), Betacoronavirus, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Intensive care, medicine, Extracorporeal membrane oxygenation, Humans, 030212 general & internal medicine, Pandemics, Survival rate, Retrospective Studies, Respiratory Distress Syndrome, SARS-CoV-2, Proportional hazards model, business.industry, COVID-19, Retrospective cohort study, Middle Aged, medicine.disease, Survival Rate, Intensive Care Units, surgical procedures, operative, 030228 respiratory system, Respiratory failure, Emergency medicine, Female, France, Coronavirus Infections, business
Abstract: Summary Background Patients with COVID-19 who develop severe acute respiratory distress syndrome (ARDS) can have symptoms that rapidly evolve to profound hypoxaemia and death. The efficacy of extracorporeal membrane oxygenation (ECMO) for patients with severe ARDS in the context of COVID-19 is unclear. We aimed to establish the clinical characteristics and outcomes of patients with respiratory failure and COVID-19 treated with ECMO. Methods This retrospective cohort study was done in the Paris–Sorbonne University Hospital Network, comprising five intensive care units (ICUs) and included patients who received ECMO for COVID-19 associated ARDS. Patient demographics and daily pre-ECMO and on-ECMO data and outcomes were collected. Possible outcomes over time were categorised into four different states (states 1–4): on ECMO, in the ICU and weaned off ECMO, alive and out of ICU, or death. Daily probabilities of occupation in each state and of transitions between these states until day 90 post-ECMO onset were estimated with use of a multi-state Cox model stratified for each possible transition. Follow-up was right-censored on July 10, 2020. Findings From March 8 to May 2, 2020, 492 patients with COVID-19 were treated in our ICUs. Complete day-60 follow-up was available for 83 patients (median age 49 [IQR 41–56] years and 61 [73%] men) who received ECMO. Pre-ECMO, 78 (94%) patients had been prone-positioned; their median driving pressure was 18 (IQR 16–21) cm H2O and PaO2/FiO2 was 60 (54–68) mm Hg. At 60 days post-ECMO initiation, the estimated probabilities of occupation in each state were 6% (95% CI 3–14) for state 1, 18% (11–28) for state 2, 45% (35–56) for state 3, and 31% (22–42) for state 4. 35 (42%) patients had major bleeding and four (5%) had a haemorrhagic stroke. 30 patients died. Interpretation The estimated 60-day survival of ECMO-rescued patients with COVID-19 was similar to that of studies published in the past 2 years on ECMO for severe ARDS. If another COVID-19 outbreak occurs, ECMO should be considered for patients developing refractory respiratory failure despite optimised care. Funding None.
Published: 2020

27. One-year survival of patients with high-grade glioma discharged alive from the intensive care unit

Author: Isabelle Rivals, Khê Hoang-Xuan, Martin Dres, Sophie Demeret, Nicolas Weiss, Ahmed Idbaih, Elise Morawiec, Julien Mayaux, Nicolas Gatulle, Maxens Decavèle, Alexandre Demoule, and Thomas Similowski
Subjects: medicine.medical_specialty, Critical Care, One-year survival, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Intensive care, Glioma, Internal medicine, medicine, Humans, Intensive care unit, 030212 general & internal medicine, Hospital Mortality, Retrospective Studies, Original Communication, Performance status, business.industry, Mortality rate, Anticancer therapy, Cancer, Odds ratio, medicine.disease, Malignant brain tumors, Patient Discharge, Intensive Care Units, Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study
Abstract: Introduction Only limited data are available regarding the long-term prognosis of patients with high-grade glioma discharged alive from the intensive care unit. We sought to quantify 1-year mortality and evaluate the association between mortality and (1) functional status, and (2) management of anticancer therapy in patients with high-grade glioma discharged alive from the intensive care unit. Patients and methods Retrospective observational cohort study of patients with high-grade glioma admitted to two intensive care units between January 2009 and June 2018. Functional status was assessed by the Karnofsky Performance Status. Anticancer therapy after discharge was classified as (1) continued (unchanged), (2) modified (changed or stopped), or (3) initiated (for newly diagnosed disease). Results Ninety-one high-grade glioma patients (73% of whom had glioblastoma) were included and 78 (86%) of these patients were discharged alive from the intensive care unit. Anticancer therapy was continued, modified, and initiated in 41%, 42%, and 17% of patients, respectively. Corticosteroid therapy at the time of ICU admission [odds ratio (OR) 0.07] and cancer progression (OR 0.09) was independently associated with continuation of anticancer therapy. The mortality rate 1 year after ICU admission was 73%. On multivariate analysis, continuation of anticancer therapy (OR 0.18) and Karnofsky performance status on admission (OR 0.90) were independently associated with lower 1-year mortality. Conclusion The presence of high-grade glioma is not sufficient to justify refusal of intensive care unit admission. Performance status and continuation of anticancer therapy are associated with higher survival after intensive care unit discharge. Previous presentation Preliminary results were presented at the most recent congress of the French Intensive Care Society, Paris, 2019. Electronic supplementary material The online version of this article (10.1007/s00415-020-10191-0) contains supplementary material, which is available to authorized users.
Published: 2020

28. Long-Term Disabilities of Survivors of Out-of-Hospital Cardiac Arrest

Author: Anne Peskine, Alain Cariou, David Hajage, Nicolas Deye, Emmanuel Guérot, Martin Dres, Romain Sonneville, Alexandre Lafourcade, Vincent Navarro, Hélène Robert, Philippe Azouvi, Tarek Sharshar, Eleonore Bayen, Charles-Edouard Luyt, Guillaume Hékimian, Nicolas Bréchot, Mathieu Schmidt, Alain Combes, Alexandre Demoule, Julien Mayaux, Pascale Pradat-Diehl, Eléonore Bayen, Damien Galanaud, Nathalie Marin, Julien Charpentier, Jean-Paul Mira, Olivier Vignaud, Jean-Luc Diehl, Jean-Yves Fagon, Bruno Mégarbane, Jean-Pierre Guichard, Nathalie Kubis, Alain Yelnik, Lila Bouadma, Jean-François Timsit, Isabelle Klein, Robert Carlier, Florence Colle, Service de médecine physique et de réadaptation [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de réanimation médicale polyvalente [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Pharmacoépidémiologie de l'AP-HP (Cephepi), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Raymond Poincaré [AP-HP], Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Service de Médecine Physique et de Réadaptation [CHU Pitié-Salpêtrière] (MPR)
Subjects: Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, SF-36, [SDV]Life Sciences [q-bio], Population, cardiac arrest, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Medicine, education, Depression (differential diagnoses), Coma, education.field_of_study, Mini–Mental State Examination, medicine.diagnostic_test, business.industry, Glasgow Coma Scale, 3. Good health, disability, Anxiety, prognosis, medicine.symptom, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Background Long-term outcomes of awakened survivors of out-of-hospital cardiac arrest (OHCA) are poorly known. Research Question What are the month (M) 18 outcomes of survivors of out-of-hospital cardiac arrest (OHCA) who awakened during the first 2 weeks’ post-OHCA and their poor-outcome risk factors? Study Design and Methods All OHCA survivors with a Glasgow Coma Scale score ≥12 during the first 2 weeks’ post-OHCA were enrolled in six ICUs and followed up at M3, M6, M12, and M18. The primary outcome measure was Glasgow Outcome Scale-Extended (GOS-E) score at M18. Secondary outcome measures included evaluation at M18 of neurologic, behavioral, and cognitive disabilities; health-related quality of life (HR-QOL), anxiety and depression; and poor-outcome risk factors (GOS-E score ≤ 6). Results Among the 139 included patients, 98 were assessable for the primary outcome measure. At M18, 64 (65%) had full recovery or minor disabilities (GOS-E score > 6), 18 (18%) had moderate disabilities but were autonomous for daily-life activities (GOS-E score = 6), 12 (12%) had poor autonomy (GOS-E score 1), and four had died. Percentages of patients with GOS-E scores > 6 increased significantly over the 18-month study period. At M18, no patients had major neurologic disabilities, 20% had cognitive disabilities, 32% had anxiety symptoms, 25% had depression symptoms, and their HR-QOL was impaired compared with a sex- and age-matched population. Low-flow time, Sequential Organ Failure Assessment score at admission, coma duration > 3 days after cardiac arrest, and mechanical ventilation on days 3 and 7 were associated with poor functional outcome. Interpretation Among patients who awoke (Glasgow Coma Scale score ≥12) in the 14 days following OHCA, 35% had moderate to severe disabilities or had died at M18. Interestingly, patients improved until M18 post-OHCA. Risk factors associated with poor functional outcome were low-flow time, clinical severity at ICU admission, prolonged coma duration, and mechanical ventilation. Clinical Trial Registration ClinicalTrials.gov ; No.: NCT02292147; URL: www.clinicaltrials.gov .
Published: 2020

29. Impact of early ICU admission for critically ill cancer patients: Post-hoc analysis of a prospective multicenter multinational dataset

Author: René López, Elie Azoulay, Yannick Hourmant, Julien Mayaux, Anne Renault, Anne-Pascale Meert, Michael Darmon, Dominique Benoit, Virginie Lemiale, Christine Lebert, Djamel Mokart, Achille Kouatchet, Fabrice Bruneel, and Frédéric Pène
Subjects: medicine.medical_specialty, Soins intensifs réanimation, health care facilities, manpower, and services, Critical Illness, Critical Care and Intensive Care Medicine, Early admission, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Neoplasms, Post-hoc analysis, Outcome assessment (health care), Medicine, Humans, Intensive care medicine, Hospital Mortality, Prospective Studies, Mortality, Retrospective Studies, Time-to-treatment, business.industry, Confounding, 030208 emergency & critical care medicine, Intensive care unit, Triage, Intensive Care Units, 030228 respiratory system, Propensity score matching, Emergency medicine, Cohort, SOFA score, business
Abstract: Objectives: Early intensive care unit (ICU) admission, in Critically Ill Cancer Patients (CICP), is believed to have contributed to the prognostic improvement of critically ill cancer patients. The primary objective of this study was to assess the association between early ICU admission and hospital mortality in CICP. Design: Retrospective analysis of a prospective multicenter dataset. Early admission was defined as admission in the ICU < 24 h of hospital admission. We assessed the association between early ICU admission and hospital mortality in CICP via survival analysis and propensity score matching. Results: Of the 1011patients in our cohort, 1005 had data available regarding ICU admission timing and were included. Overall, early ICU admission occurred in 455 patients (45.3%). Crude hospital mortality in patients with early and delayed ICU admission was 33.6% (n = 153) vs. 43.1% (n = 237), respectively (P = 0.02). After adjustment for confounders, early compared to late ICU admission was not associated with hospital mortality (HR 0.92; 95%CI 0.76–1.11). After propensity score matching, hospital mortality did not differ between patients with early (35.2%) and late (40.6%) ICU admission (P = 0.13). In the matched cohort, early ICU admission was not associated with mortality after adjustment on SOFA score (HR 0.89; 95%CI 0.71–1.12). Similar results were obtained after adjustment for center effect. Conclusion: In this cohort, early ICU admission was not associated with a better outcome after adjustment for confounder and center effect. The uncertainty with regard to the beneficial effect of early ICU on hospital mortality suggests the need for an interventional study., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020

30. Usefulness of Parasternal Intercostal Muscle Ultrasound during Weaning from Mechanical Ventilation

Author: Alexandre Demoule, Elise Morawiec, Julien Mayaux, Thomas Similowski, Martin Dres, Laurent Brochard, Bruno-Pierre Dubé, Stefannie Vorona, Ewan C. Goligher, Suela Demiri, dres, martin, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), St. Michael's Hospital, Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], University of Toronto, Mount Sinai Hospital [Toronto, Canada] (MSH), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, medicine.medical_specialty, Weakness, Intraclass correlation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Diaphragm, Intercostal Muscles, Spontaneous breathing trial, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Humans, Ultrasonography, Interventional, Mechanical ventilation, business.industry, Ultrasound, 030208 emergency & critical care medicine, Respiration, Artificial, Diaphragm (structural system), [SDV] Life Sciences [q-bio], Anesthesiology and Pain Medicine, medicine.anatomical_structure, 030228 respiratory system, Parasternal line, Cardiology, Female, medicine.symptom, business, Ventilator Weaning, Intercostal muscle
Abstract: Background The assessment of diaphragm function with diaphragm ultrasound seems to bring important clinical information to describe diaphragm work and weakness. When the diaphragm is weak, extradiaphragmatic muscles may play an important role, but whether ultrasound can also assess their activity and function is unknown. This study aimed to (1) evaluate the feasibility of measuring the thickening of the parasternal intercostal and investigate the responsiveness of this muscle to assisted ventilation; and (2) evaluate whether a combined evaluation of the parasternal and the diaphragm could predict failure of a spontaneous breathing trial. Methods First, an exploratory evaluation of the parasternal in 23 healthy subjects. Second, the responsiveness of parasternal to several pressure support levels were studied in 16 patients. Last, parasternal activity was compared in presence or absence of diaphragm dysfunction (assessed by magnetic stimulation of the phrenic nerves and ultrasound) and in case of success/failure of a spontaneous breathing trial in 54 patients. Results The parasternal was easily accessible in all patients. The interobserver reproducibility was good (intraclass correlation coefficient, 0.77 (95% CI, 0.53 to 0.89). There was a progressive decrease in parasternal muscle thickening fraction with increasing levels of pressure support (Spearman ρ = −0.61 [95% CI, −0.74 to −0.44]; P < 0.0001) and an inverse correlation between parasternal muscle thickening fraction and the pressure generating capacity of the diaphragm (Spearman ρ = −0.79 [95% CI, −0.87 to −0.66]; P < 0.0001). The parasternal muscle thickening fraction was higher in patients with diaphragm dysfunction: 17% (10 to 25) versus 5% (3 to 8), P < 0.0001. The pressure generating capacity of the diaphragm, the diaphragm thickening fraction and the parasternal thickening fraction similarly predicted failure or the spontaneous breathing trial. Conclusions Ultrasound assessment of the parasternal intercostal muscle is feasible in the intensive care unit and provides novel information regarding the respiratory capacity load balance. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Published: 2020

31. Outcomes in 886 Critically Ill Patients After Near-Hanging Injury

Author: Candice Belony, Guillaume Schnell, Caroline Durant, Gwenaëlle Jacq, Pascal Beuret, Emmanuelle Noel, Olivier Lesieur, Sébastien Perbet, Lucie Biard, Christophe Guitton, Nicolas Deye, Thomas Geeraerts, Pauline Moriss, Pierrick Cronier, Nicolas Girard, Charles Cerf, Cédric Daubin, Charlene Leparq, Guillaume Thiery, Elie Azoulay, Alexis Soummer, Pierre Kalfon, Jean Pierre Quenot, Michael Darmon, Quentin de Roux, Gwenhael Colin, Julien Mayaux, Adriaan Prisacariu, Cécile Carre, Abdelkader Ouchenir, Michael Piagnerelli, Laurent Argaud, François Vincent, Maleka Schenck, Vincent Das, Alain Cariou, Marc Danguy Des Déserts, Matthieu Resche-Rigon, Jonathan Chelly, Auguste Dargent, Sébastien Cavelot, Charlotte Martin, Stein Silva, Thibaut Baudic, Thomas Rossignol, Philippe Vignon, Marie Salvetti, Alexandre Demoule, Marc A. Simon, Bruno Mégarbane, Hamid Merdji, Bertrand Sauneuf, Frédéric Jacobs, Louise de Charentenay, Martin Cour, Delphine Bachelet, Bernard Cholley, Marine Paul, Ferhat Meziani, Nicolas Mongardon, Segolene Couraud, Stéphane Legriel, Nicolas Pichon, Jean-Baptiste Lascarrou, Centre Hospitalier de Versailles André Mignot (CHV), Groupe Hospitalier du Havre, Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, AfterROSC Network Group [Paris], Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Hôtel-Dieu de Nantes - Centre Hospitalier Universitaire de Nantes (Hôpital Hôtel-Dieu de Nantes - CHU de Nantes), Centre Hospitalier Le Mans (CH Le Mans), Hopital saint louis (LA ROCHELLE - Hôpital Saint Louis), CH La Rochelle, Hospices Civils de Lyon (HCL), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, 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), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anesthésie-réanimation, hôpital Purpan, CHU Toulouse [Toulouse], Intensive Care Unit, Groupe Hospitalier Sud Ile de France, 270 avenue Marc Jacquet, 77000, Melun, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital d'Instruction des Armées Clermont Tonnerre, Service de Santé des Armées, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU bobigny, Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Foch [Suresnes], Hôpital de la Pitié-Salpêtrière, Centre Hospitalier de Roanne, Hôpital Louis Pasteur [Chartres], Centre Hospitalier Public du Cotentin (CHPC), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Henri Mondor, Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 12/17, FUNDING/SUPPORT: This study was supported by the Délégation à la Recherche Clinique et à l’Innovation de Versailles, the non-profit publicly funded research agency for the Versailles Hospital, Versailles, France [Grant 12/17]., CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CH Centre Hospitalier Public du Cotentin (CHPC), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CCSD, Accord Elsevier, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and CHU Henri Mondor [Créteil]
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Multivariate analysis, near-hanging, medicine.medical_treatment, Critical Illness, [SDV]Life Sciences [q-bio], Suicide, Attempted, coma, Critical Care and Intensive Care Medicine, cardiopulmonary resuscitation, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Belgium, Interquartile range, Medicine, Humans, Glasgow Coma Scale, 030212 general & internal medicine, Cardiopulmonary resuscitation, Hospital Mortality, Retrospective Studies, Coma, business.industry, Glasgow Outcome Scale, Retrospective cohort study, Prognosis, Survival Analysis, Patient Discharge, 3. Good health, Heart Arrest, [SDV] Life Sciences [q-bio], Functional Status, 030228 respiratory system, SAPS II, Emergency medicine, ICU, outcome, CPR, Female, France, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Background: Near-hanging experiences are life-threatening events about which few data are available. Research Question: What are the outcomes and early predictors of hospital mortality in critically ill patients who have undergone a near-hanging experience? Study Design and Methods: Adult patients who were resuscitated successfully after suicidal near-hanging injury admitted to 31 university or university-affiliated ICUs in France and Belgium between 1992 and 2014 were studied retrospectively. Patients were identified by searching the hospital databases for International Statistical Classification of Diseases and Related Health Problems, 9th and 10th revisions, codes and hospital charts for hanging. Logistic multivariate regression was performed to identify factors associated vital and functional outcomes at hospital discharge as the primary end points. Secondary outcomes were evaluation of temporal trends and identification of predictors of hospital mortality. Results: Of the 886 patients (181 women and 705 men; median age, 43 years; interquartile range, 34-52 years), 266 (30.0%) had attempted suicide previously, 600 (67.7%) had a diagnosed mental illness, and 55 (6.2%) attempted hanging while hospitalized. Median time from hanging awareness to unhanging was 0 min (interquartile range [IQR], 0-0; range, 0-82 min). Median Glasgow Coma Scale score was 3 (IQR, 3-5) at ICU admission. Hanging induced cardiac arrest in 450 of 886 patients (50.8%). Overall, 497 of 886 patients (56.1%) were alive at hospital discharge, including 479 of 497 patients (96.4%) with a favorable neurocognitive outcome (defined as a Glasgow Outcome Scale score of 4 or 5). By multivariate analysis, factors associated with hospital mortality were hanging-induced cardiac arrest (OR, 19.50; 95% CI, 7.21-60.90; P < .00001) and findings at ICU admission of glycemia level > 1.4 g/L (OR, 4.34; 95% CI, 1.82-10.81; P = .0007) and of lactate level > 3.5 mmol/L (OR, 9.98; 95% CI, 4.17-25.36; P < .00001). Interpretation: The findings from this large multicenter retrospective cohort emphasize the very high mortality after hanging injury chiefly because of hanging-induced cardiac arrest. However, patients who survive near-hanging experiences achieve excellent neurocognitive recovery. Studies of early neuroprotective strategies for patients who have undergone near-hanging experiences are warranted. Trial Registry: ClinicalTrials.gov; No.: NCT04096976; URL: www.clinicaltrials.gov
Published: 2020

32. ICU-acquired weakness, diaphragm dysfunction and long-term outcomes of critically ill patients

Author: Alexandre Demoule, Bruno-Pierre Dubé, Clément Saccheri, Thomas Similowski, Martin Dres, Julie Delemazure, Elise Morawiec, Julien Mayaux, Sorbonne Université (SU), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), dres, martin, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), and Gestionnaire, Hal Sorbonne Université
Subjects: Quality of life, Weakness, medicine.medical_specialty, Survival, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV]Life Sciences [q-bio], medicine.medical_treatment, Critical Care and Intensive Care Medicine, Diaphragm dysfunction, law.invention, Spontaneous breathing trial, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Limb muscle weakness, Mortality, Survival rate, Survival analysis, Mechanical ventilation, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Intensive care unit, Diaphragm (structural system), [SDV] Life Sciences [q-bio], 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, Cohort study
Abstract: Background Intensive care unit (ICU)-acquired weakness and diaphragm dysfunction are frequent conditions, both associated with poor prognosis in critically ill patients. While it is well established that ICU-acquired weakness severely impairs long-term prognosis, the association of diaphragm dysfunction with this outcome has never been reported. This study investigated whether diaphragm dysfunction is associated with negative long-term outcomes and whether the coexistence of diaphragm dysfunction and ICU-acquired weakness has a particular association with 2-year survival and health-related quality of life (HRQOL). Methods This study is an ancillary study derived from an observational cohort study. Patients under mechanical ventilation were enrolled at the time of their first spontaneous breathing trial. Diaphragm dysfunction was defined by tracheal pressure generated by phrenic nerve stimulation 2O and ICU-acquired weakness was defined by Medical Research Council (MRC) score Results Sixty-nine of the 76 patients enrolled in the original study were included in the survival analysis and 40 were interviewed. Overall 2-year survival was 67% (46/69): 64% (29/45) in patients with diaphragm dysfunction, 71% (17/24) in patients without diaphragm dysfunction, 46% (11/24) in patients with ICU-acquired weakness and 76% (34/45) in patients without ICU-acquired weakness. Patients with concomitant diaphragm dysfunction and ICU-acquired weakness had a poorer outcome with a 2-year survival rate of 36% (5/14) compared to patients without diaphragm function and ICU-acquired weakness [79% (11/14) (p Conclusions ICU-acquired weakness but not diaphragm dysfunction was associated with a poor 2-year survival of critically ill patients.
Published: 2020

33. Functional outcomes in adults with tuberculous meningitis admitted to the ICU: a multicenter cohort study

Author: Etienne de Montmollin, Keyvan Razazi, Vincent Dubée, Stéphane Gaudry, Guillaume Voiriot, Romain Sonneville, Adeline Morisot, Eric Mariotte, Bruno Mourvillier, Eric Boulet, Mathilde Neuville, Frédéric Pène, Julien Mayaux, Lila Bouadma, Emmanuel Guerot, Stéphane Ruckly, Emmanuel Canet, Damien Contou, Marie Cantier, Bruno Mégarbane, Jean-François Timsit, and Michel Wolff
Subjects: Adult, Brain Infarction, Male, Paris, medicine.medical_specialty, Critical Care and Intensive Care Medicine, Statistics, Nonparametric, Tuberculous meningitis, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Modified Rankin Scale, Intensive care, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Retrospective Studies, business.industry, Proportional hazards model, Research, Hazard ratio, Glasgow Coma Scale, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Odds ratio, lcsh:RC86-88.9, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Functional outcomes, Patient Outcome Assessment, Intensive Care Units, Tuberculosis, Meningeal, Female, Steroids, business, 030217 neurology & neurosurgery, Hydrocephalus, Cohort study
Abstract: Background Tuberculous meningitis (TBM) is a devastating infection in tuberculosis endemic areas with limited access to intensive care. Functional outcomes of severe adult TBM patients admitted to the ICU in nonendemic areas are not known. Methods We conducted a retrospective multicenter cohort study (2004–2016) of consecutive TBM patients admitted to 12 ICUs in the Paris area, France. Clinical, biological, and brain magnetic resonance imaging (MRI) findings at admission associated with a poor functional outcome (i.e., a score of 3–6 on the modified Rankin scale (mRS) at 90 days) were identified by logistic regression. Factors associated with 1-year mortality were investigated by Cox proportional hazards modeling. Results We studied 90 patients, of whom 61 (68%) had a score on the Glasgow Coma Scale ≤ 10 at presentation and 63 (70%) required invasive mechanical ventilation. Brain MRI revealed infarction and hydrocephalus in 38/75 (51%) and 25/75 (33%) cases, respectively. A poor functional outcome was observed in 55 (61%) patients and was independently associated with older age (adjusted odds ratio (aOR) 1.03, 95% CI 1.0–1.07), cerebrospinal fluid protein level ≥ 2 g/L (aOR 5.31, 95% CI 1.67–16.85), and hydrocephalus on brain MRI (aOR 17.2, 95% CI 2.57–115.14). By contrast, adjunctive steroids were protective (aOR 0.13, 95% CI 0.03–0.56). The multivariable adjusted hazard ratio of adjunctive steroids for 1-year mortality (47%, 95% CI 37%–59%) was 0.23 (95% CI 0.11–0.44). Among survivors at 1 year, functional independence (mRS of 0–2) was observed in 27/37 (73%, 95% CI 59%–87%) cases. Conclusions A poor functional outcome in adult TBM patients admitted to the ICU in a nonendemic area is observed in 60% of cases and is independently associated with elevated cerebrospinal fluid protein level and hydrocephalus. Our data also suggest a protective effect of adjunctive steroids, with reduced disability and mortality, irrespective of immune status and severity of disease at presentation. One-year follow-up revealed functional independence in most survivors. Electronic supplementary material The online version of this article (10.1186/s13054-018-2140-8) contains supplementary material, which is available to authorized users.
Published: 2018

34. Severe diffuse alveolar hemorrhage related to autoimmune disease: a multicenter study

Author: Alexandre Demoule, Eric Mariotte, Etienne de Montmollin, Matthieu Resche-Rigon, David Saadoun, Guillaume Geri, Jacques Cadranel, Nicolas de Prost, Naïke Bigé, Mathilde Neuville, Julien Mayaux, Adrien Mirouse, Vincent Audigier, Mathieu Vautier, Antoine Parrot, Patrice Cacoub, Nicolas Bréchot, Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], CHU Tenon [AP-HP], CEDRIC. Méthodes statistiques de data-mining et apprentissage (CEDRIC - MSDMA), Centre d'études et de recherche en informatique et communications (CEDRIC), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise (ENSIIE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise (ENSIIE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service de réanimation médicale polyvalente [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Réanimation Médicale [CHU Pitié-Salpétrière], Service de réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de médecine interne [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Service de biostatistiques et information médicale [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise (ENSIIE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise (ENSIIE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM), HESAM Université (HESAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise (ENSIIE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière]
Subjects: Male, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Critical Care and Intensive Care Medicine, law.invention, 0302 clinical medicine, law, Antiphospholipid syndrome, Medicine, 030212 general & internal medicine, Diffuse alveolar hemorrhage, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Middle Aged, Intensive care unit, 3. Good health, Anti-MBG-associated vasculitis, Intensive Care Units, Cryoglobulinemia, SAPS II, Rituximab, Female, France, medicine.drug, Adult, medicine.medical_specialty, IgA-associated vasculitis, Hemorrhage, mechanical ventilation, Autoimmune Diseases, 03 medical and health sciences, Systemic lupus erythematosus, Internal medicine, Humans, Plasma exchange, Renal replacement therapy, Aged, Retrospective Studies, 030203 arthritis & rheumatology, Mechanical ventilation, business.industry, Research, lcsh:RC86-88.9, medicine.disease, Pulmonary Alveoli, ICU, ICU, mechanical ventilation, Complication, business, ANCA-associated vasculitis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Diffuse alveolar hemorrhage (DAH) occurs during the course of autoimmune disease and may be life threatening. The objective was to assess characteristics and prognosis factors of DAH who required intensive care unit (ICU) admission in patients with autoimmune diseases. Methods French multicenter retrospective study including patients presenting DAH related to autoimmune diseases requiring ICU admission from 2000 to 2016. Results One hundred four patients (54% of men) with median age of 56 [32–68] years were included with 79 (76%) systemic vasculitis and 25 (24%) connective tissue disorders. All patients received steroids, and 72 (69%), 12 (11.5%), and 57 (55%) patients had cyclophosphamide, rituximab, and plasma exchanges, respectively. During ICU stay, 52 (50%), 36 (35%), and 55 (53%) patients required mechanical ventilation, vasopressor use, and renal replacement therapy, respectively. Factors associated with mechanical ventilation weaning were age (HR [95%CI] 0.97 [0.96–0.99] per 10 years, p p = 0.04), and time from dyspnea onset to ICU admission (0.99 [0.99–1] per day, p = 0.03). ICU mortality was 15%. Factors associated with alive status at ICU discharge were chronic cardiac failure (HR [95%CI] 0.37 [0.15–0.94], p = 0.04), antiphospholipid syndrome-related DAH (3.17 [1.89–5.32], p p = 0.007), and oxygen flow at ICU admission (0.95 [0.91–0.99] per liter/min, p = 0.04). Conclusion DAH in autoimmune diseases is a life-threatening complication which requires mechanical ventilation in half of the cases admitted to ICU.
Published: 2019

35. Treating hepatic encephalopathy in cirrhotic patients admitted to ICU with sodium phenylbutyrate: a preliminary study

Author: Simona Tripon, Dominique Thabut, Marika Rudler, Françoise Imbert‐Bismut, Helga Junot, Marion Lodey, Maxime Mallet, Nicolas Weiss, Hélène Brisson, Denis Monneret, Julien Mayaux, and Elsa Guiller
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Time Factors, Sodium, chemistry.chemical_element, Gastroenterology, law.invention, Excretion, 03 medical and health sciences, chemistry.chemical_compound, Patient Admission, 0302 clinical medicine, Randomized controlled trial, Ammonia, law, Internal medicine, medicine, Humans, Hyperammonemia, Pharmacology (medical), In patient, Hospital Mortality, Prospective Studies, Glycerol phenylbutyrate, Hepatic encephalopathy, Aged, Pharmacology, business.industry, Sodium phenylbutyrate, Middle Aged, medicine.disease, Phenylbutyrates, Patient Discharge, Intensive Care Units, Treatment Outcome, chemistry, Case-Control Studies, Hepatic Encephalopathy, 030220 oncology & carcinogenesis, Urea, Female, 030211 gastroenterology & hepatology, business, Biomarkers, Preliminary Data, medicine.drug
Abstract: Hepatic encephalopathy (HE) influences short-term and long-term prognoses. Recently, glycerol phenylbutyrate (PB), that lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion, has shown that it was effective in preventing the occurrence of HE in RCT. The aim was to assess the benefits of sodium PB in cirrhotic patients admitted to ICU for overt HE, in terms of ammonia levels decrease, neurological improvement, and survival. Cirrhotic patients who presented with overt HE, ammonia levels >100 μmol/L, and did not display any contra-indication were included. Sodium PB was administered at 200 mg/kg/day. Control group included historical controls treated by standard therapy, matched for age, sex, MELD score, and severity of HE. Eighteen patients were included and treated with sodium PB (age: 59 [45-68], male gender: 15 [83%], Child-Pugh B: 8 [44%], Child-Pugh C: 10 [56%], and MELD score: 16 [13-23]). Ammonia levels significantly decreased in the PB as compared to the control group from inclusion to 12 h and from inclusion to 48 h (P = 0.0201 and P = 0.0230, respectively). The proportion of patients displaying neurological improvement was only higher in the PB-treated group as compared to controls at ICU discharge (15 [83%] vs. 9 [50%], P = 0.0339). ICU discharge survival was significantly higher in patients treated with PB (17 [94%] vs. 9 [50%], P = 0.0017). In cirrhotic patients with overt HE, sodium PB could be effective in reducing ammonia levels and might be effective in improving neurological status and ICU discharge survival. More extensive data, especially a RCT, are mandatory.
Published: 2018

36. Impact of earplugs and eye mask on sleep in critically ill patients: a prospective randomized study

Author: Sophie Lavault, Thomas Similowski, Serge Carreira, Isabelle Arnulf, Elise Morawiec, Julien Mayaux, Alexandre Demoule, Olivier Pallanca, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pathologies du sommeil [CHU Pitié-Salpêtrière], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), HAL-SU, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Letter, Light, [SDV]Life Sciences [q-bio], Polysomnography, Critical Care and Intensive Care Medicine, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Prospective randomized study, Ear Protective Devices, Prospective Studies, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, Masks, Eye mask, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Middle Aged, Intensive care unit, 3. Good health, Intensive Care Units, Female, Sleep (system call), medicine.symptom, Eye Protective Devices, Earplugs, Paris, medicine.medical_specialty, Critical Illness, 03 medical and health sciences, Intensive care, medicine, Humans, Aged, Critically ill, business.industry, Delirium, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Surgery, 030228 respiratory system, Physical therapy, Sleep Deprivation, Noise, business, Sleep, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Poor sleep is common in intensive care unit (ICU) patients, where environmental factors contribute to reduce and fragment sleep. The objective of this study was to evaluate the impact of earplugs and eye mask on sleep architecture in ICU patients. Methods A single-center randomized controlled trial of 64 ICU patients was conducted from July 2012 to December 2013. Patients were randomly assigned to sleep with or without earplugs and an eye mask from inclusion until ICU discharge. Polysomnography was performed on the first day and night following inclusion. The primary outcome was the proportion of stage N3 sleep over total sleep time. Secondary outcomes were other descriptors of sleep and major outcome variables. Results In the intervention group, nine (30%) patients did not wear earplugs all night long. The proportion of N3 sleep was 21 [7–28]% in the intervention group and 11 [3–23]% in the control group (p = 0.09). The duration of N3 sleep was higher among the patients in the intervention group who wore earplugs all night long than in the control group (74 [32–106] vs. 31 [7–76] minutes, p = 0.039). The number of prolonged awakenings was smaller in the intervention group (21 [19–26] vs. 31 [21–47] in the control group, p = 0.02). No significant difference was observed between the two groups in terms of clinical outcome variables. Conclusions Earplugs and eye mask reduce long awakenings and increase N3 duration when they are well tolerated. Trial registration ClinicalTrials.gov, NCT02292134. Registered on 21 Nov 2013.
Published: 2017

37. Cuff Leak Test for the Diagnosis of Post-Extubation Stridor: A Multicenter Evaluation Study

Author: Sandrine Valade, Lucas Strasbach, Sybille Merceron, Asael Berger, Julien Mayaux, Stéphane Legriel, Ferhat Meziani, Michael Darmon, Benjamin Planquette, and David Schnell
Subjects: Adult, Male, Leak, medicine.medical_specialty, Time Factors, Stridor, Endotracheal intubation, Critical Care and Intensive Care Medicine, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Prospective Studies, Aged, Diagnostic Equipment, Respiratory Sounds, business.industry, Critically ill, Reproducibility of Results, 030208 emergency & critical care medicine, Middle Aged, Respiration, Artificial, Respiratory Function Tests, Surgery, Test (assessment), Intensive Care Units, 030228 respiratory system, Anesthesia, Cuff, Airway Extubation, Female, medicine.symptom, business
Abstract: Background: Cuff leak test was developed to predict the occurrence of post-extubation stridor (PES). This study evaluated the diagnostic performance of this test in unselected critically ill patients. Methods: Multicenter prospective study including unselected ventilated patients at the time of their first planned extubation. The diagnostic performance of 4 different cuff leak tests was assessed. Results: Post-extubation stridor occurred in 34 (9.4%) of 362 included patients. Compared to patients without PES, patients with PES required more frequently reintubation (6 [17.6%] vs 26 [7.9%], P = .041), prolonged duration of ventilation (6 [3-13] vs 5 [2-9] days, P = .029), and longer intensive care unit (ICU) stay (12 [6-17.5] vs 7.5 [4-13] days, P = .018). However, ICU mortality was similar in both groups (1 [2.9%] vs 23 [7.0%], P = .61). The 4 cuff leak tests display poor diagnostic accuracy: sensitivities ranging from 27% to 46%, specificities from 70% to 88%, positive predictive values from 14% to 19%, and negative predictive values from 92% to 93%. Conclusion: Post-extubation stridor occurs in less than 10% of unselected critically ill patients. The several cuff leak tests display limited diagnostic performance for the detection of PES. Given the high rate of false positives, routine cuff leak test may expose to undue prolonged mechanical ventilation.
Published: 2017

38. Antimicrobial strategy for severe community-acquired legionnaires’ disease: a multicentre retrospective observational study

Author: Jérôme Cecchini, Romain Sonneville, Martial Tchir, Nicolas de Prost, Martial Thyrault, Samuel Tuffet, Armand Mekontso Dessap, Florence Boissier, Damien Roux, Christian Brun-Buisson, Achille Kouatchet, Julien Mayaux, Muriel Fartoukh, Eric Maury, and Sebastien Jochmans
Subjects: Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Combination therapy, 030106 microbiology, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Risk Factors, Internal medicine, Pneumonia, Bacterial, medicine, Clinical endpoint, Humans, Pharmacology (medical), 030212 general & internal medicine, Aged, Retrospective Studies, Aged, 80 and over, Pharmacology, Proportional hazards model, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Anti-Bacterial Agents, Community-Acquired Infections, Hospitalization, Intensive Care Units, Regimen, Pneumonia, Infectious Diseases, Propensity score matching, Drug Therapy, Combination, Female, Legionnaires' Disease, business, Fluoroquinolones
Abstract: Background: Legionnaires' disease (LD) is an important cause of community-acquired pneumonia with high mortality rates in the most severe cases. Objectives: To evaluate the effect of antimicrobial strategy on ICU mortality. Methods: Retrospective, observational study including patients admitted to 10 ICUs for severe community-acquired LD over a 10 year period (2005-15) and receiving an active therapy within 48 h of admission . Patients were stratified according to the antibiotic strategy administered: (i) fluoroquinolone-based versus non-fluoroquinolone-based therapy; and (ii) monotherapy versus combination therapy. The primary endpoint was in-ICU mortality. A multivariable Cox model and propensity score analyses were used. Results: Two hundred and eleven patients with severe LD were included. A fluoroquinolone-based and a combination therapy were administered to 159 (75%) and 123 (58%) patients, respectively. One hundred and forty-six patients (69%) developed acute respiratory distress syndrome and 54 (26%) died in the ICU. In-ICU mortality was lower in the fluoroquinolone-based than in the non-fluoroquinolone-based group (21% versus 39%, P = 0.01), and in the combination therapy than in the monotherapy group (20% versus 34%, P = 0.02). In multivariable analysis, a fluoroquinolone-based therapy, but not a combination therapy, was associated with a reduced risk of mortality [HR = 0.41, 95% CI 0.19-0.89; P = 0.02]. Conclusions: Patients with severe LD receiving a fluoroquinolone-based antimicrobial regimen in the early course of management had a lower in-ICU mortality, which persisted after adjusting for significant covariates.
Published: 2017

39. Corrective effect of diaphragm pacing on the decrease in cardiac output induced by positive pressure mechanical ventilation in anesthetized sheep

Author: Julie Delemazure, Jérôme Cecchini, Romain Persichini, Hicham Masmoudi, Thomas Similowski, Jalal Assouad, Martin Dres, Julien Mayaux, and Alexandre Demoule
Subjects: Pulmonary and Respiratory Medicine, Cardiac output, Physiology, medicine.medical_treatment, Diaphragm, Positive pressure, Blood Pressure, 030204 cardiovascular system & hematology, Positive-Pressure Respiration, Electrocardiography, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Anesthesia, Cardiac Output, Mechanical ventilation, Sheep, business.industry, Respiration, General Neuroscience, Pulmonary artery catheter, Electrodes, Implanted, Diaphragm (structural system), Phrenic Nerve, Diaphragm pacing, 030228 respiratory system, Breathing, Female, business, Venous return curve
Abstract: Positive pressure ventilation (PPV) is a fundamental life support measure, but it decreases cardiac output (CO). Diaphragmatic contractions produce negative intrathoracic and positive abdominal pressures, promoting splanchnic venous return. We hypothesized that: 1) diaphragm pacing alone could produce adequate ventilation without decreasing CO; 2) diaphragm pacing on top of PPV could improve CO. Of 11 anesthetized and mechanically ventilated ewes (39.6 ± 5.9 kg), 3 were discarded from analysis because of hemodynamic instability during the experiment, and 8 retained for analysis. Phrenic stimulation electrodes were inserted in the diaphragm (implanted phrenic nerve stimulation, iPS). CO was measured by the thermodilution technique (pulmonary artery catheter). CO during end-expiratory apnea served as reference. Median CO was 9.77 [6.25–11.25] l min−1 during end-expiratory apnea, 8.25 [5.06–9.25] l min−1 during “PPV” (−15%) (p
Published: 2017

40. Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient

Author: Alexandre Demoule, Julien Mayaux, Anne-Geneviève Marcelin, Marion Blaize, Renaud Piarroux, Alexandre Lampros, Cécile Nabet, Marc Thellier, and Arnaud Fekkar
Subjects: Male, Pediatrics, Epidemiology, Expedited, medicine.medical_treatment, coronavirus, lcsh:Medicine, Disease, medicine.disease_cause, Aspergillosis, intensive care unit, law.invention, 0302 clinical medicine, law, aspergillosis, 030212 general & internal medicine, Coronavirus, Intensive care unit, Infectious Diseases, Aspergillus, coronavirus disease, Immunocompetence, Coronavirus Infections, severe acute respiratory syndrome coronavirus 2, Microbiology (medical), medicine.medical_specialty, Pneumonia, Viral, 030231 tropical medicine, macromolecular substances, mechanical ventilation, lcsh:Infectious and parasitic diseases, Betacoronavirus, 03 medical and health sciences, Research Letter, Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient, medicine, Humans, viruses, lcsh:RC109-216, fungal superinfection, Pandemics, Aged, SARS, Mechanical ventilation, business.industry, SARS-CoV-2, lcsh:R, COVID-19, medicine.disease, zoonoses, Pneumonia, Pulmonary Aspergillosis, fungi, business, Complication
Abstract: Invasive pulmonary aspergillosis is a complication in critically ill patients with acute respiratory distress syndrome, especially those with severe influenza pneumonia. We report a fatal case of invasive pulmonary aspergillosis in an immunocompetent patient in France who had severe coronavirus disease–associated pneumonia.
Published: 2020

41. Oseltamivir Resistance in Severe Influenza A(H1N1)pdm09 Pneumonia and Acute Respiratory Distress Syndrome: A French Multicenter Observational Cohort Study

Author: Guillaume Voiriot, Sylvie Behillil, Thomas Chicheportiche, Romain Sonneville, Yacine Tandjaoui-Lambiotte, Damien Roux, Armand Mekontso Dessap, Slim Fourati, Nicolas de Prost, Faten May, Julien Mayaux, Sylvie van der Werf, Vincent Enouf, Laurent Guérin, Alexis Ferré, Eric Maury, Charles-Edouard Luyt, Jean-François Georger, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médico-Chirurgicale [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service de Réanimation Médico-Chirurgicale [Hôpital Louis Mourier], Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Intercommunal de Villeneuve-Saint-Georges (CHIV), Service de Réanimation et USC Médico-Chirurgicale = Médecine intensive réanimation [CHU Tenon], CHU Tenon [AP-HP], Génétique moléculaire des virus à ARN ((U-Pasteur_ 2 / UMR_3569)), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Réanimation et USC Médico-Chirurgicale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), and CHU Saint-Antoine [AP-HP]
Subjects: Microbiology (medical), Adult, Oseltamivir, medicine.medical_specialty, viruses, [SDV]Life Sciences [q-bio], Neuraminidase, Acute respiratory distress, Severe influenza, medicine.disease_cause, Antiviral Agents, Virus, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Influenza A Virus, H1N1 Subtype, Internal medicine, Drug Resistance, Viral, Influenza, Human, Influenza A virus, medicine, Influenza A Virus, Humans, H1N1 Subtype, 030212 general & internal medicine, Viral, 0303 health sciences, Respiratory Distress Syndrome, biology, 030306 microbiology, business.industry, virus diseases, Pneumonia, medicine.disease, 3. Good health, respiratory tract diseases, Infectious Diseases, chemistry, biology.protein, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study
Abstract: In a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%. Patients infected with the H275Y mutant virus had higher day 28 mortality than others (80% vs 12%; P = .011).
Published: 2019

42. Non-Carbapenem Antibiotics to Treat Severe Extended-Spectrum-β- Lactamase-Producing Enterobacteriaceae Infections in Intensive Care Unit Patients

Author: Guillaume Hékimian, Sébastien Besset, Florent Huang, Charles-Edouard Luyt, Alexandra Aubry, Morgane Faure, Jean Chastre, Helga Junot, Matthieu Schmidt, Isabelle Bonnet, Julien Mayaux, Nicolas Bréchot, Alain Combes, Service de Réanimation Médicale [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Bactériologie et d'Hygiène Hospitalière [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Gestionnaire, Hal Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre d'Immunologie et des Maladies Infectieuses (CIMI)
Subjects: Male, 0301 basic medicine, Carbapenem, Antibiotics, Antimicrobial stewardship, law.invention, 0302 clinical medicine, Recurrence, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, polycyclic compounds, Pharmacology (medical), Treatment Failure, 030212 general & internal medicine, Mortality rate, Enterobacteriaceae Infections, General Medicine, Middle Aged, Clostridium difficile, Intensive care unit, Anti-Bacterial Agents, 3. Good health, Intensive Care Units, Infectious Diseases, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, medicine.drug, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, Critical Illness, Secondary infection, 030106 microbiology, beta-Lactamases, 03 medical and health sciences, Enterobacteriaceae, Extended-spectrum β-lactamase, Carbapenem-sparing agent, Internal medicine, medicine, Humans, Aged, Retrospective Studies, business.industry, Retrospective cohort study, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, Survival Analysis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, bacteria, business
Abstract: International audience; OBJECTIVES: The aim of this study was to evaluate the use of non-carbapenem antibiotics to treat severe extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) infections in intensive care unit (ICU) patients.METHODS: This retrospective observational study conducted in two ICUs compared the outcomes of patients with ESBL-E infections administered a carbapenem or a non-carbapenem antibiotic as their definitive treatment. The primary outcome was treatment failure within 30 days, a composite endpoint of ESBL-E infection recurrence and 30-day mortality. Secondary outcomes included 30-day and in-hospital mortality rates, ESBL-E infection recurrence and infection(s) due to other pathogen(s).RESULTS: Among 107 patients included in the study, 67 received a carbapenem and 40 received a non-carbapenem antibiotic as their definitive treatment. Clinical characteristics of the two groups were similar. Comparing patients given a non-carbapenem antibiotic with those administered a carbapenem, they had similar 30-day treatment failure (43% vs. 61%, respectively; P = 0.06) and ESBL-E infection recurrence rates (25% vs. 22%; P = 0.8), but the former had lower 30-day mortality (23% vs. 45%; P = 0.02) and in-hospital mortality rates (23% vs. 49%; P = 0.005). Secondary infection rates caused by other pathogen(s), including Clostridium difficile, were comparable. Outcomes were comparable regardless of whether or not patients received an empirical carbapenem.CONCLUSION: For ICU patients with severe ESBL-E infections, treatment with a non-carbapenem antibiotic was not associated with poorer outcomes compared with a carbapenem antibiotic.
Published: 2019

43. Long-term health-related quality of life of critically ill patients with haematological malignancies : a prospective observational multicenter study

Author: Damien Contou, Christine Lebert, Franck Ehooman, François Vincent, Alexandre Demoule, Michael Darmon, Fabrice Bruneel, Anne-Pascale Meert, Frédéric Pène, Martine Nyunga, Achille Kouatchet, Elie Azoulay, Pierre Perez, Julien Mayaux, Lara Zafrani, Djamel Mokart, Virginie Lemiale, Nicolas de Prost, Rebecca Hamidfar, Dominique Benoit, Antoine Rabbat, and Lucie Biard
Subjects: medicine.medical_specialty, IMPACT, Population, SURVEY SF-36, Anxiety, INTENSIVE-CARE, Critical Care and Intensive Care Medicine, law.invention, SOFA SCORE, 03 medical and health sciences, 0302 clinical medicine, POSTTRAUMATIC-STRESS-DISORDER, Quality of life, law, Intensive care, Anesthesiology, Internal medicine, Medicine and Health Sciences, Medicine, Intensive care unit, education, Depression (differential diagnoses), education.field_of_study, OUTCOMES, HOSPITAL DISCHARGE, business.industry, Depression, Research, Mortality rate, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Haematological malignancy, CANCER, humanities, EVENT SCALE, 030228 respiratory system, Post-traumatic syndrome disorder, Economie, SOFA score, CRITICAL ILLNESS, business, Long-term health-related quality of life
Abstract: Background: Although outcomes of critically ill patients with haematological malignancies (HMs) have been fully investigated in terms of organ failure and mortality, data are scarce on health-related quality of life (HRQOL) in this population. We aim to assess post-intensive care unit (ICU) burden and HRQOL of critically ill patients with HMs and to identify risk factors for quality-of-life (QOL) impairment. Results: In total, 1011 patients with HMs who required ICU admission in 17 ICUs in France and Belgium were included in the study; 278 and 117 patients were evaluated for QOL at 3 months and 1 year, respectively, after ICU discharge. HRQOL was determined by applying the interview form of the Short Form 36 (SF-36) questionnaire. Psychological distress symptoms were evaluated using the Hospital Anxiety Depression Score (HADS) and the Impact of Event Scale (IES). In-hospital mortality rates at 3 months and 1 year were, respectively, 39.1, 50.7 and 57.2%, respectively. At 3 months, median [IQR] physical and mental component summary scores (PCS and MCS) (SF-36) were 37 [28–46] and 51 [45–58], respectively. PCS was lower in ICU patients with HMs when compared to general ICU septic patients (52 [5–13], p = 0.00001). The median combined HAD score was 8 [5–13], and the median IES score was 8 [3–16]. However, recovery during the first year after ICU discharge was not consistent in all dimensions of HRQOL. Three months after ICU discharge, the maximum daily Sequential Organ Failure Assessment score and status of the underlying malignancy at ICU admission were significantly associated with MCS impairment (− 0.54 points [95% CI − 0.99; − 0.1], p = 0.018 and − 4.83 points [95% CI − 8.44; − 1.22], p = 0.009, respectively). Conclusion: HRQOL is strongly impaired in critically ill patients with HMs at 3 months and 1 year after ICU discharge. Organ failure and disease status are strongly associated with QOL. The kinetic evaluation of QOL at 3 months and 1 year offers the opportunity to focus on QOL aspects that may be improved by therapeutic interventions during the first year after ICU discharge., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

44. The Artificial Kidney Initiation in Kidney Injury 2 (AKIKI2): study protocol for a randomized controlled trial

Author: Béatrice La Combe, Guillaume Thiery, Guillaume Lacave, Julio Badie, Julien Mayaux, Guillaume Louis, Dimitri Titeca-Beauport, Nicolas Chudeau, Didier Thevenin, Nadia Aissaoui, Jean Reignier, Jean Marie Forel, Eric Boulet, Marc Leone, Laurent Argaud, Karim Asehnoune, Adrien Robine, Elisabeth Coupez, Bertrand Pons, Laurent Martin-Lefevre, Sébastien Besset, Guillaume Geri, Jean Pierre Quenot, Marion Beuzelin, Nicolas de Prost, Steven Grangé, Florent Poirson, Saber Barbar, Karim Lakhal, David Hajage, Stéphane Gaudry, Julien Bohé, Christophe Vinsonneau, Alain Combes, Didier Dreyfuss, Jean-Damien Ricard, Saad Nseir, Guillaume Chevrel, Kada Klouche, Sébastien Moschietto, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Service de Néphrologie-Dialyse-Transplantation [CHU Amiens-Picardie], CHU Amiens-Picardie, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Service de réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Réanimation Médico-Chirurgicale [Hôpital Louis Mourier], Hôpital Louis Mourier - AP-HP [Colombes], Centre hospitalier de Dieppe, Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), Hôpital les oudaries, Service de Réanimation Médicale Sud, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre hospitalier Marc Jacquet (Melun), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de soins intensifs [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Urgence respiratoire et réanimation médicale, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service d'anesthésie et réanimation chirurgicale [Nantes], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunologie - Immunopathologie - Immunothérapeutique (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), 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), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital avicenne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Service de Biostatistique Santé Publique et Information Médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-CHU Saint Louis [APHP], Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical ICU, Avenue Albert Raymond, Saint-Priest en Jarez 42270, France, Saint-Etienne University Hospital, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Tribologie et Dynamique des Systèmes (LTDS), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne-Centre National de la Recherche Scientifique (CNRS), Institut de géologie, Université Scientifique et Médicale de Grenoble, CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Ecologie et Evolution des Microorganismes (EEM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Time Factors, Hyperkalemia, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), 030204 cardiovascular system & hematology, Kidney, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, law.invention, Time-to-Treatment, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, Randomized controlled trial, law, Oliguria, medicine, Humans, Multicenter Studies as Topic, Pharmacology (medical), 030212 general & internal medicine, Renal replacement therapy, Prospective Studies, Treatment outcome, Randomized Controlled Trials as Topic, Mechanical ventilation, lcsh:R5-920, business.industry, Acute kidney injury, Recovery of Function, Interim analysis, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, Critical care, Anesthesia, Anuria, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, medicine.symptom, business, lcsh:Medicine (General), Kidneys, Artificial
Abstract: Background The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed “standard”) with another in which RRT is further delayed for a longer period (termed “delayed strategy”). Methods/design This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation. Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l). The primary outcome will be the number of RRT-free days at day 28. One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects. Discussion The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019. Trial registration ClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018.
Published: 2019

45. Candidemia in critically ill immunocompromised patients: report of a retrospective multicenter cohort study

Author: Imène Rezine, Julien Mayaux, Etienne Ghrenassia, Alexandre Demoule, Elie Azoulay, Laure Calvet, Michael Darmon, Lionel Kerhuel, Djamel Mokart, Audrey De Jong, Université Paris Diderot - Paris 7 (UPD7), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, 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), Hôpital Robert Debré, MORNET, Dominique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Population, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, Solid, 0302 clinical medicine, Hematological malignancy, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Anesthesiology, medicine, Blood culture, Intensive care unit, education, Candida, education.field_of_study, Tumor, medicine.diagnostic_test, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, Retrospective cohort study, Shock, lcsh:RC86-88.9, 3. Good health, Transplantation, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Immune defect, Fluconazole, medicine.drug, Cohort study
Abstract: Background Immunocompromised critically ill patients constitute a population with the high risk of candidemia. This retrospective study aimed to assess the outcome of immunocompromised critically ill patients with candidemia. Secondary objectives were to describe clinical phenotypes of these patients, Candida ecology, and factors associated with mortality. Results Overall, 121 patients were included in this study. Median delay from candidemia to first antifungal therapy was 3 days, in line with the observed delay of blood culture positivity. Candia albicans was the main Candida specie identified (54%), and susceptibility of Candida to fluconazole and echinocandins was of, respectively, 70% and 92%. Hospital mortality was of 60%. After adjustment for confounders, severity as assessed by the need for vasopressors (HR 1.8, CI95% 1.1–3.1), need for mechanical ventilation (HR 2.0, CI95% 1.1–3.8) and allogenic stem cell transplantation (HR 2.5, CI95% 1.1–6.0) were independently associated with poor outcome. Candida specie, susceptibility and treatment strategies were not associated with outcome. Conclusions Candidemia in immunocompromised critically ill patients is associated with a grim outcome. Despite the high prevalence of Candida non-albicans species, neither C. species nor its susceptibility was associated with outcome. Conversely, severity and preexisting allogeneic stem cell transplantation were independently associated with poor outcome. Despite antifungal prophylaxis and use of preemptive antifungal therapy in neutropenic patients, antifungal therapy was initiated three days after symptoms onset suggesting needs for specific strategies aiming to reduce this delay. Electronic supplementary material The online version of this article (10.1186/s13613-019-0539-2) contains supplementary material, which is available to authorized users.
Published: 2019

46. Effect of High-Flow Nasal Oxygen vs Standard Oxygen on 28-Day Mortality in Immunocompromised Patients With Acute Respiratory Failure: The HIGH Randomized Clinical Trial

Author: Christine Lebert, Loay Kontar, Achille Kouatchet, Lilia Berrahil-Meksen, Naïke Bigé, Julien Mayaux, Saad Nseir, Kada Klouche, Samir Jaber, Djamel Mokart, Laurent Papazian, Nicolas Terzi, Elie Azoulay, Jean Reignier, Jean-Michel Constantin, Alexandre Demoule, Laurent Argaud, Alexandre Lautrette, Michael Darmon, Martine Nyunga, Christophe Girault, Lila Bouadma, Guillaume Louis, Igor Théodose, Johanna Oziel, Pierre Perez, Vincent Peigne, François Barbier, Virginie Lemiale, Frédéric Pène, Fabrice Bruneel, Sylvie Chevret, Florent Wallet, and Jean-Herlé Raphalen
Subjects: Adult, Male, Respiratory rate, Critical Care, medicine.medical_treatment, Critical Illness, High-Frequency Ventilation, Nose, law.invention, 03 medical and health sciences, Immunocompromised Host, 0302 clinical medicine, Randomized controlled trial, law, Intensive care, Oxygen therapy, medicine, Humans, 030212 general & internal medicine, Original Investigation, Aged, Mechanical ventilation, Noninvasive Ventilation, Respiratory distress, business.industry, Oxygen Inhalation Therapy, General Medicine, Middle Aged, Intensive care unit, Survival Analysis, 3. Good health, Oxygen, 030228 respiratory system, Anesthesia, SOFA score, Female, business, Respiratory Insufficiency
Abstract: IMPORTANCE: High-flow nasal oxygen therapy is increasingly used for acute hypoxemic respiratory failure (AHRF). OBJECTIVE: To determine whether high-flow oxygen therapy decreases mortality among immunocompromised patients with AHRF compared with standard oxygen therapy. DESIGN, SETTING, AND PARTICIPANTS: The HIGH randomized clinical trial enrolled 776 adult immunocompromised patients with AHRF (Pao(2) 30/min or labored breathing or respiratory distress, and need for oxygen ≥6 L/min) at 32 intensive care units (ICUs) in France between May 19, 2016, and December 31, 2017. INTERVENTIONS: Patients were randomized 1:1 to continuous high-flow oxygen therapy (n = 388) or to standard oxygen therapy (n = 388). MAIN OUTCOMES AND MEASURES: The primary outcome was day-28 mortality. Secondary outcomes included intubation and mechanical ventilation by day 28, Pao(2):Fio(2) ratio over the 3 days after intubation, respiratory rate, ICU and hospital lengths of stay, ICU-acquired infections, and patient comfort and dyspnea. RESULTS: Of 778 randomized patients (median age, 64 [IQR, 54-71] years; 259 [33.3%] women), 776 (99.7%) completed the trial. At randomization, median respiratory rate was 33/min (IQR, 28-39) vs 32 (IQR, 27-38) and Pao(2):Fio(2) was 136 (IQR, 96-187) vs 128 (IQR, 92-164) in the intervention and control groups, respectively. Median SOFA score was 6 (IQR, 4-8) in both groups. Mortality on day 28 was not significantly different between groups (35.6% vs 36.1%; difference, −0.5% [95% CI, −7.3% to +6.3%]; hazard ratio, 0.98 [95% CI, 0.77 to 1.24]; P = .94). Intubation rate was not significantly different between groups (38.7% vs 43.8%; difference, −5.1% [95% CI, −12.3% to +2.0%]). Compared with controls, patients randomized to high-flow oxygen therapy had a higher Pao(2):Fio(2) (150 vs 119; difference, 19.5 [95% CI, 4.4 to 34.6]) and lower respiratory rate after 6 hours (25/min vs 26/min; difference, −1.8/min [95% CI, −3.2 to −0.2]). No significant difference was observed in ICU length of stay (8 vs 6 days; difference, 0.6 [95% CI, −1.0 to +2.2]), ICU-acquired infections (10.0% vs 10.6%; difference, −0.6% [95% CI, −4.6 to +4.1]), hospital length of stay (24 vs 27 days; difference, −2 days [95% CI, −7.3 to +3.3]), or patient comfort and dyspnea scores. CONCLUSIONS AND RELEVANCE: Among critically ill immunocompromised patients with acute respiratory failure, high-flow oxygen therapy did not significantly decrease day-28 mortality compared with standard oxygen therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02739451.
Published: 2018

47. Granulocyte colony-stimulating factor and respiratory status of critically ill neutropenic patients with hematologic malignancies

Author: Frédéric Pène, Antoine Rabbat, Dominique Benoit, Michael Darmon, Elie Azoulay, Christine Lebert, François Vincent, Anne-Pascale Meert, Fabrice Bruneel, Pierre Perez, Achille Kouatchet, Xavier Mignard, Lara Zafrani, Lucie Biard, Rebecca Hamidfar, Virginie Lemiale, Martine Nyunga, Julien Mayaux, and Djamel Mokart
Subjects: Male, Cancer Research, medicine.medical_specialty, Neutropenia, medicine.medical_treatment, Critical Illness, law.invention, 03 medical and health sciences, Leukocyte Count, 0302 clinical medicine, law, Internal medicine, Granulocyte Colony-Stimulating Factor, Medicine, Humans, Respiratory system, Propensity Score, Aged, Chemotherapy, Respiratory Distress Syndrome, business.industry, Respiration, Hematology, Middle Aged, medicine.disease, Intensive care unit, Granulocyte colony-stimulating factor, Respiratory Function Tests, Intensive Care Units, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Propensity score matching, Observational study, Female, business, Febrile neutropenia, 030215 immunology
Abstract: In patients with hematologic malignancies, respiratory status may deteriorate during neutropenia recovery. This multicenter, observational study aims to evaluate granulocyte colony-stimulating factor (G-CSF) impact on respiratory status in critically ill neutropenic patients. Among 1011 critically ill patients with hematologic malignancies, 288 were neutropenic and included in this study. 201 (70%) did not receive G-CSF at day 1 or 2. After propensity score matching for the probability of receiving G-CSF at day 1 or 2, there was no association between G-CSF and respiratory deterioration at day 14 (OR =1.19; 95%CI (0.57-2.51); p = .64). Additional sensitivity analysis in patients admitted for acute respiratory failure showed similar results (OR =1.34; 95%CI (0.5-3.59); p = .57). Among patients who recovered from neutropenia, 75% experienced respiratory deterioration during neutropenia recovery. This study confirms that neutropenia recovery is a situation at risk of respiratory deterioration. However, whether G-CSF is an aggravating factor cannot be supported by our results.
Published: 2018

48. Multidrug-resistant bacteria transmitted through high-density EEG in ICU

Author: Emilie Lafeuille, S. Demeret, Catherine Lafaye, Hélène Brisson, Nicolas Weiss, Frédéric Faugeras, Sandrine Lefebvre, Florence Brossier, Nicolas Bréchot, Jérôme Robert, Benjamin Rohaut, Marion Quirins, Jocelyne Leconte, Mélanie Valente, Julien Mayaux, Julie Bourmaleau, Lionel Naccache, Marika Rudler, and Francis Bolgert
Subjects: Adult, Male, medicine.medical_specialty, Klebsiella pneumoniae, Clinical Neurology, beta-Lactamases, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, In patient, Intensive care medicine, Brain function, Neurologically impaired, Aged, biology, business.industry, 030208 emergency & critical care medicine, Drug Resistance, Microbial, Electroencephalography, General Medicine, High density eeg, Bacterial Infections, Middle Aged, biology.organism_classification, Acinetobacter baumannii, Multiple drug resistance, Intensive Care Units, Multidrug resistant bacteria, Neurology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Purpose Prevention of multidrug resistant (MDR) bacterial contamination remains a major challenge in ICUs. Many hospital outbreaks involving MDR transmitted through environmental contamination have been reported. Bedside high-density EEG allow for dynamic cognitive evaluation in brain-injured patients and is used more and more frequently in clinical practice to evaluate brain function and predict outcome in severely neurologically impaired patients. Unfortunately, the material used for this procedure is not entirely disposable. Method We performed a systematic analysis of MDR bacterial contamination in patients contaminated in our ICU using specific bacteriological methods. Results We report a proven case of cross-contamination of an extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae strain, and a possible case of cross-contamination of a carbapenem-resistant Acinetobacter baumannii strain. Conclusion Cross-contamination of MDR bacteria is possible through high-density EEG material. However, appropriate procedures can decrease this risk.
Published: 2016
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49. Acyclovir for Mechanically Ventilated Patients With Herpes Simplex Virus Oropharyngeal Reactivation

Author: Jean-Paul Mira, Jeremy Bourenne, Qin Lu, Christine Penot-Ragon, Thomas Rimmelé, Jean-Marie Forel, David Hajage, Mamadou Hassimiou Diallo, Jean-François Timsit, Julien Mayaux, Jean-Yves Lefrant, Marc Clavel, Elisabeth Coupez, Jean Chastre, Sophie Cayot-Constantin, Michel Wolff, Jean-Pierre Bedos, Caroline Hauw-Berlemont, Carole Schwebel, Alain Combes, Charles-Edouard Luyt, Samir Jaber, and Laurent Papazian
Subjects: Male, medicine.medical_specialty, Randomization, medicine.medical_treatment, Acyclovir, Oropharynx, Placebo, Antiviral Agents, 01 natural sciences, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Intensive care, Internal Medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, 0101 mathematics, Adverse effect, Aged, Mechanical ventilation, business.industry, 010102 general mathematics, Herpes Simplex, Pharyngeal Diseases, Middle Aged, Respiration, Artificial, Intensive care unit, 3. Good health, Treatment Outcome, Female, Virus Activation, France, Respiratory Insufficiency, business
Abstract: Importance The role of herpes simplex virus (HSV) reactivation on morbidity and mortality in patients in the intensive care unit requiring mechanical ventilation remains unknown. Objective To determine whether preemptive treatment with intravenous acyclovir reduces the duration of mechanical ventilation in patients with HSV oropharyngeal reactivation. Design, Setting, and Participants A double-blind, placebo-controlled randomized clinical trial was conducted in 16 intensive care units in France. Participants included 239 adults (age, >18 years) who received mechanical ventilation for at least 96 hours and continued to receive mechanical ventilation for 48 hours or more, with HSV oropharyngeal reactivation. Patients were enrolled between February 2, 2014, and February 22, 2018. Interventions Participants were randomized to receive intravenous acyclovir, 5 mg/kg, 3 times daily for 14 days or a matching placebo. Main Outcomes and Measures The primary end point was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included mortality at 60 days. Main analyses were conducted on an intention-to-treat basis. Results Of 239 patients enrolled and randomized, 1 patient withdrew consent, leaving 238 patients, with 119 patients in both the acyclovir and placebo (control) groups (median [IQR] age, 61 [50-70] years; 76 [32%] women) available for primary outcome measurement. On day 60, the median (IQR) numbers of ventilator-free days were 35 (0-53) for acyclovir recipients and 36 (0-50]) for controls (P = .17 for between-group comparison). Among secondary outcomes, 26 patients (22%) and 39 patients (33%) had died at day 60 (risk difference, 0.11, 95% CI, –0.004 to 0.22,P = .06). The adverse event frequency was similar for both groups (28% in the acyclovir group and 23% in the placebo group,P = .40), particularly acute renal failure post randomization affecting 3 acyclovir recipients (3%) and 2 controls (2%). Four patients (3%) in the acyclovir group vs none in the placebo group stopped the study drug for treatment-related adverse events. Conclusions and Relevance In patients receiving mechanical ventilation for 96 hours or more with HSV reactivation in the throat, use of acyclovir, 5 mg/kg, 3 times daily for 14 days, did not increase the number of ventilator-free days at day 60, compared with placebo. These findings do not appear to support routine preemptive use of acyclovir in this setting. Trial Registration ClinicalTrials.gov identifier:NCT02152358
Published: 2020

50. A Multivariable Prediction Model for Pneumocystis jirovecii Pneumonia in Hematology Patients with Acute Respiratory Failure

Author: Antoine Rabbat, Michael Darmon, Laurent Argaud, Djamel Mokart, Pierre Perez, François Vincent, Sylvie Chevret, Kada Klouche, Martine Nyunga, Julien Mayaux, Antoine Roux, Elie Azoulay, Fabrice Bruneel, Achille Kouatchet, Virginie Lemiale, and Frédéric Pène
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Time to treatment, Critical Care and Intensive Care Medicine, Pneumocystis carinii, Risk Assessment, Sensitivity and Specificity, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, parasitic diseases, Medicine, Humans, Acute respiratory failure, 030212 general & internal medicine, Prospective Studies, Respiratory system, Lung, Physical Examination, Aged, Hematology, business.industry, Incidence (epidemiology), Pneumonia, Pneumocystis, Pneumocystis jirovecii Pneumonia, Reproducibility of Results, Middle Aged, medicine.disease, Transplantation, Radiography, Leukemia, 030228 respiratory system, Hematologic Neoplasms, Acute Disease, Female, business, Respiratory Insufficiency
Abstract: The incidence of Pneumocystis jirovecii pneumonia (PjP) is rising. Longer time to treatment is associated with higher mortality.To develop a multivariable risk prediction model for PjP diagnosis.In a prospective multicenter cohort of ICU patients with hematological malignancies and acute respiratory failure, factors associated with documented PjP were identified. The risk prediction model was tested in an independent prospective multicenter cohort. We assessed discrimination (by areas under the receiver operating characteristic curves [AUCs]) and goodness of fit (by Hosmer-Lemeshow statistics). Model performance was assessed using 30 sets of imputed data sets.Among the 1,330 patients, 134 of 1,092 (12.3%; 95% confidence interval [CI], 10.4-14.4%) had proven PjP in the derivation cohort, as did 15 of 238 (6.3%, 95% CI, 3.6-10.2%) in the validation cohort. The model included age, lymphoproliferative disease, anti-Pneumocystis prophylaxis, the number of days between respiratory symptom onset and ICU admission, shock, chest radiograph pattern, and pleural effusion. The median (interquartile range) score was 3.5 (1.5-5.0) (range, -3.5 to 8.5) in the derivation cohort and 1.0 (0-2.0) (range, -3.5 to 6.0) in the validation cohort. The best threshold was defined on the validation sample as 3, allowing us to reach 86.7% sensitivity and 67.7% specificity for PjP, with a negative predictive value of 97.9% in the case of 10% prevalence. The score had good calibration (goodness of fit, -0.75) and discrimination in the derivation cohort (mean AUC, 0.80; 95% CI, 0.76-0.84) and validation cohort (mean AUC, 0.83; 95% CI, 0.72-0.93).The PjP score for hematology patients with acute respiratory failure can be computed at admission, based on readily available variables. Potential clinical benefits of using this score deserve assessment.
Published: 2018

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