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1. Can Biomarkers Correctly Predict Ventilator-associated Pneumonia in Patients Treated With Targeted Temperature Management After Cardiac Arrest? An Exploratory Study of the Multicenter Randomized Antibiotic (ANTHARTIC) Study

Author: Nicolas Deye, MD, PhD, Amelie Le Gouge, MSc, Bruno François, MD, Camille Chenevier-Gobeaux, MD, PhD, Thomas Daix, MD, Hamid Merdji, MD, PhD, Alain Cariou, MD, PhD, Pierre-François Dequin, MD, PhD, Christophe Guitton, MD, Bruno Mégarbane, MD, PhD, Jacques Callebert, PharmD, PhD, Bruno Giraudeau, PhD, Alexandre Mebazaa, MD, PhD, Nicolas Vodovar, PhD, for the Clinical Research in Intensive Care and Sepsis-TRIal Group for Global Evaluation and Research in SEPsis (TRIGGERSEP) Network and the ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) Study Group, Arnaud Desachy, Christophe Cracco, Laurence Robin, Marie Anne Fally, David Schnell, Olivier Baudin, Charles Lafon, Philippe Petua, Stéphane Rouleau, Cyrille Nowak, Gaétan Plantefeve, Hervé Mentec, Olivier Pajot, Damien Contou, Jo-Anna Tirolien, Constance Vuillard, Cécile Zylberfajn, Nadile Ali, Dieudonne Kilendo, Olivia Chauvel, Elias Karam, Pascal Chevallier, Dorothée Ducoux, Fabrice Raymond, Christophe Gellis, Jean-Pierre Quenot, Thérèse Devaux, Audrey Large, Sébastien Mortreux, Pierre-Emmanuel Charles, Sébastien Prin, Jean-Baptiste Roudaut, Pascal Andreu, Auguste Dargent, Nora Perrot, Audrey Massard, Solenne Villot, Corinne Pernot, Bruno Francois, Thomas Daix, Philippe Vignon, Nicolas Pichon, Celine Gonzalez, Nicolas Rodier, Jean François Mary, Ludmila Baudrillart, Christine Vallejo, Emmanuelle Begot, Claire Mancia, Michelle Nouaille, Cécile Duchiron, Sandrine Naturel, Marie-Anne De Vinzellles, Hélène Beacco, Thierry Boulain, Chantal Brossard, Armelle Mathonnet, Dalila Benzekri-Lefevre, Anne Bretagnol, Isabelle Runge, François Barbier, Grégoire Muller, Mai-Anh Nay, Julie Rossi, Lucie Muller, Sophie Tollec, Alain Cariou, Nathalie Marin, Camille Chenevier-Gobeaux, Michel Arnaout, Omar Ben Hadj Salem, Wulfran Bougouin, Simon Bourcier, Benoit Champigneulle, Matthieu Jamme, Alexis Ferre, Guillaume Geri, Frédéric Pene, Julien Charpentier, Jean-Daniel Chiche, Lucie Guillemet, Jean-Paul Mira, Marine Paul, Nicolas Deye, Bruno Megarbane, Alexandre Mebazaa, Isabelle Malissin, Sebastian Voicu, Nicolas Vodovar, Jacques Callebert, Claire Pernin, Lydia Suarez, Philippe Manivet, Dominique Vodovar, Anthony Checinski, Lamia Kerdjana, Pierre Garcon, Antoine Goury, Catherine Fauvaux, Salamata Agne, Nahima Gueblaoui, Aude Jacob, Loic Chimot, Catherine Huchet, Nadège Lacoste, Pierre-Henri Dessalles, Mélanie Saint-Leger, Yannick Monseau, Marie Heil, Ferhat Meziani, Hamid Merdji, DrKhoury, Samir Chenaf, Christine Kummerlen, Yannick Rabouel, Hayat Allam, Anne Hutt-Clauss, Alexandra Monnier, Pierre-François Dequin, Christine Mabilat, Emmanuelle Rouve, Charlotte Salmon-Gandonnière, Denis Garot, Youen Jouan, Stephan Ehrmann, Antoine Guillon, Laetitia Bodet–Contentin, Emmanuelle Mercier, Julie Mankikian, Stéphane Legriel, MrSébastien Cavelot, Christophe Guitton, Charlotte Garret, Cédric Bretonniere, Laurent Nicolat, Noëlle Brule, and Olivier Zambon
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: IMPORTANCE:. Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated. OBJECTIVES:. To evaluate biomarkers’ impact in helping VAP diagnosis after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS:. This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included. MAIN OUTCOMES AND MEASURES:. The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group. RESULTS:. Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP (n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP (n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C–C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C. CONCLUSIONS AND RELEVANCE:. Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.
Published: 2024
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2. Physiological response to prone positioning in intubated adults with COVID-19 acute respiratory distress syndrome: a retrospective study

Author: Andrea Boffi, Maximilien Ravenel, Ermes Lupieri, Antoine Schneider, Lucas Liaudet, Michel Gonzalez, Jean-Daniel Chiche, and Lise Piquilloud
Subjects: ARDS, COVID-19, Proning, Prone position, Alveolo-arterial gradient, Oxygenation, Diseases of the respiratory system, RC705-779
Abstract: Abstract Background COVID-19 related acute respiratory distress syndrome (ARDS) has specific characteristics compared to ARDS in other populations. Proning is recommended by analogy with other forms of ARDS, but few data are available regarding its physiological effects in this population. This study aimed to assess the effects of proning on oxygenation parameters (PaO2/FiO2 and alveolo-arterial gradient (Aa-gradient)), blood gas analysis, ventilatory ratio (VR), respiratory system compliance (CRS) and estimated dead space fraction (VD/VT HB). We also looked for variables associated with treatment failure. Methods Retrospective monocentric study of intubated COVID-19 ARDS patients managed with an early intubation, low to moderate positive end-expiratory pressure and early proning strategy hospitalized from March 6 to April 30 2020. Blood gas analysis, PaO2/FiO2, Aa-gradient, VR, CRS and VD/VT HB were compared before and at the end of each proning session with paired t-tests or Wilcoxon tests (p
Published: 2022
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3. Body composition and short-term mortality in patients critically ill with acute-on-chronic liver failure

Author: Thomas Mangana del Rio, Sophie-Caroline Sacleux, Julien Vionnet, Philippe Ichaï, Alban Denys, Antoine Schneider, Audrey Coilly, Montserrat Fraga, Alexandre Wetzel, Joachim Koerfer, Jean-Daniel Chiche, Faouzi Saliba, Darius Moradpour, Fabio Becce, and Florent Artru
Subjects: Acute-on-chronic liver failure, Body composition, Cirrhosis, Intensive care medicine, Sarcopenia, Computed tomography, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Body composition is sex dependent and associated with an increased mortality risk in patients with cirrhosis. We evaluated whether it was also associated with short-term mortality in patients critically ill with acute-on-chronic liver failure (ACLF). Patients and methods: We retrospectively included all patients with cirrhosis and ACLF hospitalised in the intensive care unit (ICU) of Lausanne University Hospital between 2010 and 2019 for whom an abdominal computed tomography (CT) scan performed ±7 days from admission was available. Patients from the ICU of Paul Brousse University Hospital admitted between 2017 and 2020 served as an external cohort. All body composition parameters at the third lumbar vertebral level (L3) were quantified using a deep learning-based method. Results: In total, 192 patients from Lausanne were included. Median age was 62 years and 28-day survival rate was 58.2%. In males, variables independently associated with 28-day mortality on days 1 and 3 were Chronic Liver Failure Consortium (CLIF-C) ACLF-lactate and sarcopenia. In females, CLIF-C ACLF-lactate on days 1 and 3 was the only predictor of 28-day survival. We derived two scores combining sarcopenia and the CLIF-C ACLF-lactate score on days 1 and 3, with area under the receiver operating characteristic outperforming the CLIF-C ACLF-lactate score alone in male but not in female patients. Comparable results were found in the external cohort of 58 patients and supported the sex specificity of the performance of the model. Patients with sarcopenia had increased risks of invasive fungal infection and renal replacement therapy. Conclusion: Sarcopenia was associated with 28-day mortality in male but not in female patients critically ill with ACLF. Although screening for sarcopenia could impact the management of male patients, further studies are needed in female cohorts to investigate whether other body composition parameters are associated with outcomes. Impact and implications: Body composition, easily assessed by CT, is altered in patients with cirrhosis and associated with outcome; it has never been investigated in patients critically ill with ACLF. The results of the present study, underlining the benefit of sarcopenia evaluation to improve prognosis prediction in males critically ill with ACLF, are of importance for physicians managing such patients to optimise the decision-making process toward continued treatment, liver transplantation, or limitation of care. In a wider sense, besides the number and course of organ failures, the results recall the weight of the general condition of males with ACLF at admission to ICU. In females critically ill with ACLF, in analyses limited by the sample size, none of the body composition parameters was associated with short-term mortality independently of organ failures; this suggests that the number and course of organ failures are the main determinant of mortality in these patients.
Published: 2023
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4. Simulation study for evaluating an adaptive-randomisation Bayesian hybrid trial design with enrichment

Author: Valentin Vinnat, Jean-Daniel Chiche, Alexandre Demoule, and Sylvie Chevret
Subjects: Response-adaptive randomisation, Marker-based strategy designs, Bayesian designs, Precision medicine, Medicine (General), R5-920
Abstract: Background: As we enter the era of precision medicine, the role of adaptive designs, such as response-adaptive randomisation or enrichment designs in drug discovery and development, has become increasingly important to identify the treatment given to a patient based on one or more biomarkers. Tailoring the ventilation supply technique according to the responsiveness of patients to positive end-expiratory pressure is a suitable setting for such a design. Methods: In the setting of marker-strategy design, we propose a Bayesian response-adaptive randomisation with enrichment design based on group sequential analyses. This design combines the elements of enrichment design and response-adaptive randomisation. Concerning the enrichment strategy, Bayesian treatment-by-subset interaction measures were used to adaptively enrich the patients most likely to benefit from an experimental treatment while controlling the false-positive rate.The operating characteristics of the design were assessed by simulation and compared to those of alternate designs. Results: The results obtained allowed the detection of the superiority of one treatment over another and the presence of a treatment-by-subgroup interaction while keeping the false-positive rate at approximately 5/% and reducing the average number of included patients. In addition, simulation studies identified that the number of interim analyses and the burn-in period may have an impact on the performance of the scheme. Conclusion: The proposed design highlights important objectives of precision medicine, such as determining whether the experimental treatment is superior to another and identifying wheter such an efficacy could depend on patient profile.
Published: 2023
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5. Myeloid-Derived Suppressor-like Cells as a Prognostic Marker in Critically Ill Patients: Insights from Experimental Endotoxemia and Intensive Care Patients

Author: Irene T. Schrijver, Jacobus Herderschee, Charlotte Théroude, Antonios Kritikos, Guus Leijte, Didier Le Roy, Maelick Brochut, Jean-Daniel Chiche, Matthieu Perreau, Giuseppe Pantaleo, Benoit Guery, Matthijs Kox, Peter Pickkers, Thierry Calandra, and Thierry Roger
Subjects: myeloid-derived suppressor cell, biomarker, endotoxemia, critically ill patient, intensive care, sepsis, Cytology, QH573-671
Abstract: Patients admitted to the intensive care unit (ICU) often experience endotoxemia, nosocomial infections and sepsis. Polymorphonuclear and monocytic myeloid-derived suppressor cells (PMN-MDSCs and M-MDSCs) can have an important impact on the development of infectious diseases, but little is known about their potential predictive value in critically ill patients. Here, we used unsupervised flow cytometry analyses to quantify MDSC-like cells in healthy subjects challenged with endotoxin and in critically ill patients admitted to intensive care units and at risk of developing infections. Cells phenotypically similar to PMN-MDSCs and M-MDSCs increased after endotoxin challenge. Similar cells were elevated in patients at ICU admission and normalized at ICU discharge. A subpopulation of M-MDSC-like cells expressing intermediate levels of CD15 (CD15int M-MDSCs) was associated with overall mortality (p = 0.02). Interestingly, the high abundance of PMN-MDSCs and CD15int M-MDSCs was a good predictor of mortality (p = 0.0046 and 0.014), with area under the ROC curve for mortality of 0.70 (95% CI = 0.4–1.0) and 0.86 (0.62–1.0), respectively. Overall, our observations support the idea that MDSCs represent biomarkers for sepsis and that flow cytometry monitoring of MDSCs may be used to risk-stratify ICU patients for targeted therapy.
Published: 2024
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6. Cardiogenic shock due to reverse takotsubo syndrome triggered by multiple sclerosis brainstem lesions: a case report and mini review

Author: Joas Brandner, Henri Lu, Olivier Muller, Elissavet Eskioglou, Jean-Daniel Chiche, Panagiotis Antiochos, and Yaniv Chocron
Subjects: takotsubo syndrome, multiple-sclerosis, takotsubo, reverse takotsubo, inverted takotsubo, cardiogenic shock, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: BackgroundTakotsubo syndrome (TTS) is mainly characterized by chest pain, left ventricular dysfunction, ST-segment deviation on electrocardiogram (ECG) and elevated troponins in the absence of obstructive coronary artery disease. Diagnostic features include left ventricular systolic dysfunction shown on transthoracic echocardiography (TTE) with wall motion abnormalities, generally with the typical “apical ballooning” pattern. In very rare cases, it involves a reverse form which is characterized by basal and mid-ventricular severe hypokinesia or akinesia, and sparing of the apex. TTS is known to be triggered by emotional or physical stressors. Recently, multiple sclerosis (MS) has been described as a potential trigger of TTS, especially when lesions are located in the brainstem.Case summaryWe herein report the case of a 26-year-old woman who developed cardiogenic shock due to reverse TTS in the setting of MS. After being admitted for suspected MS, the patient presented with rapidly deteriorating clinical condition, with acute pulmonary oedema and hemodynamic collapse, requiring mechanical ventilation and aminergic support. TTE found a severely reduced left ventricular ejection fraction (LVEF) of 20%, consistent with reverse TTS (basal and mid ventricular akinesia, apical hyperkinesia). Cardiac magnetic resonance imaging (MRI) performed 4 days later showed myocardial oedema in the mid and basal segments on T2-weighted imaging, with partial recovery of LVEF (46%), confirmed the diagnosis of TTS. In the meantime, the suspicion of MS was also confirmed, based on cerebral MRI and cerebral spinal fluid analyses, with a final diagnosis of reverse TTS induced by MS. High-dose intravenous corticotherapy was initiated. Subsequent evolution was marked by rapid clinical improvement, as well as normalization of LVEF and segmental wall-motion abnormalities.ConclusionOur case is an example of the brain-heart relationship: it shows how neurologic inflammatory diseases can trigger a cardiogenic shock due to TTS, with potentially serious outcomes. It sheds light on the reverse form, which, although rare, has already been described in the setting of acute neurologic disorders. Only a handful of case reports have highlighted MS as a trigger of reverse TTS. Finally, through an updated systematic review, we highlight the unique features of patients with reversed TTS triggered by MS.
Published: 2023
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7. Impact of COVID-19 on the association between pulse oximetry and arterial oxygenation in patients with acute respiratory distress syndrome

Author: Lee S. Nguyen, Marion Helias, Lisa Raia, Estelle Nicolas, Paul Jaubert, Sarah Benghanem, Zakaria Ait Hamou, Pierre Dupland, Julien Charpentier, Frédéric Pène, Alain Cariou, Jean-Paul Mira, Jean-Daniel Chiche, and Mathieu Jozwiak
Subjects: Medicine, Science
Abstract: Abstract Managing patients with acute respiratory distress syndrome (ARDS) requires frequent changes in mechanical ventilator respiratory settings to optimize arterial oxygenation assessed by arterial oxygen partial pressure (PaO2) and saturation (SaO2). Pulse oxymetry (SpO2) has been suggested as a non-invasive surrogate for arterial oxygenation however its accuracy in COVID-19 patients is unknown. In this study, we aimed to investigate the influence of COVID-19 status on the association between SpO2 and arterial oxygenation. We prospectively included patients with ARDS and compared COVID-19 to non-COVID-19 patients, regarding SpO2 and concomitant arterial oxygenation (SaO2 and PaO2) measurements, and their association. Bias was defined as mean difference between SpO2 and SaO2 measurements. Occult hypoxemia was defined as a SpO2 ≥ 92% while concomitant SaO2
Published: 2022
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8. Comparison of Nasopharyngeal and Saliva Swab Nucleic Acid Amplification and Rapid Antigen Testing To Detect Omicron SARS-CoV-2 Variant of Concern: a Prospective Clinical Trial (OMICRON)

Author: Antonios Kritikos, Giorgia Caruana, Catherine Lazor-Blanchet, Michael Currat, Jean-Daniel Chiche, Peter Vollenweider, Pierre-Alexandre Bart, Onya Opota, and Gilbert Greub
Subjects: SARS-CoV-2 diagnosis, Omicron variant, RT-PCR, rapid antigen testing, nasopharyngeal swab, saliva swab, Microbiology, QR1-502
Abstract: ABSTRACT In November 2021, the World Health Organization declared the Omicron variant (B.1.1.519) a variant of concern. Since then, worries have been expressed regarding the ability of usual diagnostic tests to detect the Omicron variant. In addition, some recently published data suggested that the salivary reverse transcription (RT)-PCR might perform better than the current gold standard, nasopharyngeal (NP) RT-PCR. In this study, we aimed to compare the sensitivities of nasopharyngeal and saliva RT-PCR and assess the diagnostic performances of rapid antigen testing (RAT) in nasopharyngeal and saliva samples. We conducted a prospective clinical study among symptomatic health care professionals consulting the occupational health service of our hospital for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening and hospitalized patients in internal medicine/intensive care wards screened for SARS-CoV-2 with COVID-19-compatible symptoms. A composite outcome considering NP PCR and/or saliva PCR was used as a reference standard to define COVID-19 cases. A total of 475 paired NP/saliva specimens have been collected with a positivity rate of 40% (n = 192). NP and salivary RT-PCR exhibited sensitivities of 98% (95% CI, 94 to 99%) and 87% (95% CI, 81 to 91%), respectively, for outpatients (n = 453) and 94% (95% CI, 72 to 99%) and 69% (95% CI, 44 to 86%), respectively, for hospitalized patients (n = 22). Nasopharyngeal rapid antigen testing exhibited much lower diagnostic performances (sensitivity of 66% and 31% for outpatients and inpatients, respectively), while saliva RAT showed a sensitivity of less than 5% in both groups. Nasopharyngeal RT-PCR testing remains the gold standard for SARS-CoV-2 Omicron variant screening. Salivary RT-PCR can be used as an alternative in case of contraindication to perform NP sampling. The use of RAT should be limited to settings where access to molecular diagnostic methods is lacking. IMPORTANCE The Omicron variant of concern spread rapidly since it was first reported in November 2021 and currently accounts for the vast majority of new infections worldwide. Recent reports suggest that saliva sampling might outweigh nasopharyngeal sampling for the diagnosis of the Omicron variant. Nevertheless, data investigating the best diagnostic strategy specifically for the Omicron variant of concern remain scarce. This study fills this gap in current knowledge and elucidates the question of which strategy to use in which patient. It provides a new basis for further improving COVID-19 screening programs and managing patients suspected to have COVID-19.
Published: 2022
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9. Equilibrating SSC guidelines with individualized care

Author: Jean-Louis Vincent, Mervyn Singer, Sharon Einav, Rui Moreno, Julia Wendon, Jean-Louis Teboul, Jan Bakker, Glenn Hernandez, Djillali Annane, Angélique M. E. de Man, Xavier Monnet, V. Marco Ranieri, Olfa Hamzaoui, Jukka Takala, Nicole Juffermans, Jean-Daniel Chiche, Sheila N. Myatra, and Daniel De Backer
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2021
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10. Causes of acute respiratory failure in patients with small-vessel vasculitis admitted to intensive care units: a multicenter retrospective study

Author: Aude Gibelin, Guillaume Dumas, Sandrine Valade, Marc Pineton de Chambrun, François Bagate, Mathilde Neuville, Francis Schneider, Loredana Baboi, Matthieu Groh, Jean-Herlé Raphalen, Jean-Daniel Chiche, Nicolas De Prost, Charles-Edouard Luyt, Claude Guérin, Eric Maury, Etienne de Montmollin, Alexandre Hertig, Antoine Parrot, Raphaël Clere-Jehl, and Muriel Fartoukh
Subjects: Vasculitis, Diffuse alveolar hemorrhage, Intensive care, Acute respiratory failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Rationale Acute respiratory failure (ARF) in patients admitted to the intensive care unit (ICU) with known or de novo small-vessel vasculitis (Svv) may be secondary to the underlying immune disease or to other causes. Early identification of the cause of ARF is essential to initiate the most appropriate treatment in a timely fashion. Methods A retrospective multicenter study in 10 French ICUs from January 2007 to January 2018 to assess the clinical presentation, main causes and outcome of ARF associated with Svv, and to identify variables associated with non-immune etiology of ARF in patients with known Svv. Results During the study period, 121 patients [62 (50–75) years; 62% male; median SAPSII and SOFA scores 39 (27–52) and 6 (4–8), respectively] were analyzed. An immune cause was identified in 67 (55%), and a non-immune cause in 54 (45%) patients. ARF was associated with several causes in 43% (n = 52) of cases. The main immune cause was diffuse alveolar hemorrhage (DAH) (n = 47, 39%), whereas the main non-immune cause was pulmonary infection (n = 35, 29%). The crude 90-day and 1-year mortality were higher in patients with non-immune ARF, as compared with their counterparts (32% and 38% vs. 15% and 20%, respectively; both p = 0.03), but was marginally significantly higher after adjusted analysis in a Cox model (p = 0.053). Among patients with a known Svv (n = 70), immunosuppression [OR 9.41 (1.52–58.3); p = 0.016], and a low vasculitis activity score [0.84 (0.77–0.93)] were independently associated with a non-immune cause, after adjustment for the time from disease onset to ARF, time from respiratory symptoms to ICU admission, and severe renal failure. Conclusions An extensive diagnosis workup is mandatory in ARF revealing or complicating Svv. Non-immune causes are involved in 43% of cases, and their short and mid-term prognosis may be poorer than those of immune ARF. Readily identified predictive factors of a non-immune cause could help avoiding unnecessary immunosuppressive therapies.
Published: 2021
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11. Canakinumab in patients with COVID-19 and type 2 diabetes – A multicentre, randomised, double-blind, placebo-controlled trial

Author: Matthias Hepprich, Jonathan M. Mudry, Claudia Gregoriano, Francois R. Jornayvaz, Sebastian Carballo, Anne Wojtusciszyn, Pierre-Alexandre Bart, Jean-Daniel Chiche, Stefan Fischli, Thomas Baumgartner, Claudia Cavelti-Weder, Dominique L. Braun, Huldrych F. Günthard, Felix Beuschlein, Anna Conen, Emily West, Egon Isenring, Stefan Zechmann, Gabriela Bucklar, Yoann Aubry, Ludovic Dey, Beat Müller, Patrick Hunziker, Philipp Schütz, Marco Cattaneo, and Marc Y. Donath
Subjects: COVID-19, Diabetes, Obesitiy, IL-1beta, Inflammasome, Medicine (General), R5-920
Abstract: Summary: Background: Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1β (IL-1β) blockade using canakinumab improves clinical outcome. Methods: CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m2 hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. Findings: Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74·6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1·08 (95 % CI 0·69-1·69; p = 0·72). During four weeks, in the canakinumab vs placebo group 4 (7·0%) vs 7 (12·3%) participants died, 11 (20·0 %) vs 16 (28·1%) patients were on ICU, 12 (23·5 %) vs 11 (21·6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high-sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11·4%) in each group. Interpretation: In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumab in addition to standard-of-care did not result in a statistically significant improvement of the primary composite outcome. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemic control. Canakinumab was associated with a prolonged reduction of systemic inflammation. Funding: Swiss National Science Foundation grant #198415 and University of Basel. Novartis supplied study medication.
Published: 2022
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12. Response to the first awake prone positioning relates with intubation rate in SARS-CoV-2 patients suffering from acute respiratory failure with moderate to severe hypoxaemia: a retrospective study

Author: Ermes Lupieri, Andrea Boffi, Zied Ltaief, Antoine Schneider, Samia Abed-Maillard, Jean-Daniel Chiche, Mauro Oddo, and Lise Piquilloud
Subjects: Medicine
Abstract: AIMS OF THE STUDY: Awake prone positioning (aPP) in non-intubated patients with severe SARS-CoV-2-related pneumonia improves oxygenation and reduces the intubation rate, but no early predictors for success or failure of the strategy have been described. The main objective of this study was to assess whether response to the first aPP in terms of PaO2/FiO2, alveolar-arterial gradient (Aa-O2), respiratory rate and PaCO2 could predict the need for intubation. As secondary objective, we assessed the effects of aPP on the same parameters for all the sessions considered together. METHODS: Retrospective analysis of consecutive SARS-CoV-2 pneumonia patients suffering from acute respiratory failure with moderate to severe hypoxaemia for whom aPP was performed for at least 45 minutes based on the prescription of the clinician in charge according to predefined criteria. Respiratory rate, blood gases and oxygenation parameters (PaO2/FiO2 and Aa-O2), before and after the first aPP were compared between patients who were subsequently intubated or not. Effects of all the aPP sessions together were also analysed. RESULTS: One hundred and sixty-six patients were admitted for SARS-CoV-2 pneumonia during the study period. Among them, 50 received aPP lasting at least 45 minutes. Because 17 denied consent for data analysis and 2 were excluded because of a “do not intubate order”, 31 patients (for a total of 116 aPP sessions without any severe adverse events reported) were included. Among them, 10 (32.3%) were intubated. Mean age ± standard deviation (SD) was 60 ± 12 years. At ICU admission, respiratory rate was 26 ± 7/minute, median PaO2/FiO2 94 (interquartile range [IQR] 74–116) mm Hg and median Aa-O2 412 (IQR 286–427) mm Hg (markedly increased). Baseline characteristics did not statistically differ between patients who subsequently needed intubation or not. During the first aPP, PaO2/FiO2 increased and Aa-O2 decreased. When comparing patients who later where intubated or not, we observed, in the non intubated group only, a clinically significant decrease in median Aa-O2, from 294 (280–414) to 204 (107–281) mm Hg, corresponding to a 40% (26–56%) reduction, and a PaO2/FiO2 increase, from 103 (84–116) to 162 (138–195), corresponding to an increase of 48% (11–93%). The p value is
Published: 2022
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13. Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis

Author: Maria Julia Ruiz, Gabriel Siracusano, Andréa Cottignies-Calamarte, Daniela Tudor, Fernando Real, Aiwei Zhu, Claudia Pastori, Claude Capron, Arielle R. Rosenberg, Nigel Temperton, Diego Cantoni, Hanqing Liao, Nicola Ternette, Pierre Moine, Mathieu Godement, Guillaume Geri, Jean-Daniel Chiche, Djillali Annane, Elisabeth Cramer Bordé, Lucia Lopalco, and Morgane Bomsel
Subjects: SARS-CoV-2, COVID-19, mucosal immunity, IgA, severe infection, inflammatory cytokine, Immunologic diseases. Allergy, RC581-607
Abstract: The role of the mucosal pulmonary antibody response in coronavirus disease 2019 (COVID-19) outcome remains unclear. Here, we found that in bronchoalveolar lavage (BAL) samples from 48 patients with severe COVID-19-infected with the ancestral Wuhan virus, mucosal IgG and IgA specific for S1, receptor-binding domain (RBD), S2, and nucleocapsid protein (NP) emerged in BAL containing viruses early in infection and persist after virus elimination, with more IgA than IgG for all antigens tested. Furthermore, spike-IgA and spike-IgG immune complexes were detected in BAL, especially when the lung virus has been cleared. BAL IgG and IgA recognized the four main RBD variants. BAL neutralizing titers were higher early in COVID-19 when virus replicates in the lung than later in infection after viral clearance. Patients with fatal COVID-19, in contrast to survivors, developed higher levels of mucosal spike-specific IgA than IgG but lost neutralizing activities over time and had reduced IL-1β in the lung. Altogether, mucosal spike and NP-specific IgG and S1-specific IgA persisting after lung severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance and low pulmonary IL-1β correlate with COVID-19 fatal outcome. Thus, mucosal SARS-CoV-2-specific antibodies may have adverse functions in addition to protective neutralization.HighlightsMucosal pulmonary antibody response in COVID-19 outcome remains unclear. We show that in severe COVID-19 patients, mucosal pulmonary non-neutralizing SARS-CoV-2 IgA persit after viral clearance in the lung. Furthermore, low lung IL-1β correlate with fatal COVID-19. Altogether, mucosal IgA may exert harmful functions beside protective neutralization.
Published: 2022
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14. Low-dose mycophenolate mofetil improves survival in a murine model of Staphylococcus aureus sepsis by increasing bacterial clearance and phagocyte function

Author: Fanny Alby-Laurent, Nadia Belaïdouni, Benoit Blanchet, Christophe Rousseau, Jean-François Llitjos, Sylvia Sanquer, Jean-Paul Mira, Frédéric Pène, Julie Toubiana, and Jean-Daniel Chiche
Subjects: mycophenolate mofetil, sepsis, staphylococcus aureus, NF-κB, toll-like receptor 4, innate immunity, Immunologic diseases. Allergy, RC581-607
Abstract: Regulators of TLRs signaling pathways play an important role in the control of the pro-inflammatory response that contributes to sepsis-induced tissue injury. Mycophenolate mofetil, an immunosuppressive drug inhibiting lymphocyte proliferation, has been reported to be a regulator of TLRs signaling pathways. Whether MMF used at infra-immunosuppressive doses has an impact on survival and on innate immune response in sepsis is unknown.C57BL/6J mice were infected intraperitoneally with 108 CFU Staphylococcus aureus, and treated or not with low-dose of MMF (20mg/kg/day during 4 days). Survival rate and bacterial clearance were compared. Cytokine levels, quantitative and qualitative cellular responses were assessed. S. aureus – infected mice treated with MMF exhibited improved survival compared to non-treated ones (48% vs 10%, p
Published: 2022
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15. Acute Kidney Injury Associated With Lopinavir/Ritonavir Combined Therapy in Patients With COVID-19

Author: Yannick Binois, Hafsah Hachad, Joe-Elie Salem, Julien Charpentier, Bénédicte Lebrun-Vignes, Frédéric Pène, Alain Cariou, Jean-Daniel Chiche, Jean-Paul Mira, and Lee S. Nguyen
Subjects: Diseases of the genitourinary system. Urology, RC870-923
Published: 2020
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16. Assessing the Functional Heterogeneity of Monocytes in Human Septic Shock: a Proof-of-Concept Microfluidic Assay of TNFα Secretion

Author: Jean-François Llitjos, Yacine Bounab, Christophe Rousseau, Sophie Dixneuf, Blandine Rimbault, Jean-Daniel Chiche, Julien Textoris, Frédéric Pène, and Christophe Védrine
Subjects: septic shock, immune suppression, monocyte, microfluidic, tolerance, Immunologic diseases. Allergy, RC581-607
Abstract: ObjectiveThe development of advanced single-cell technologies to decipher inter-cellular heterogeneity has enabled the dynamic assessment of individual cells behavior over time, overcoming the limitation of traditional assays. Here, we evaluated the feasibility of an advanced microfluidic assay combined to fluorescence microscopy to address the behavior of circulating monocytes from septic shock patients.MethodsSeven septic shock patients and ten healthy volunteers were enrolled in the study. Using the proposed microfluidic assay we investigated the production over time of LPS-elicited TNFα by single monocytes encapsulated within droplets. Cellular endocytic activity was assessed by internalization of magnetic nanoparticles. Besides, we assessed HLA-DR membrane expression and LPS-induced TNFα production in monocytes through classical flow cytometry assays.ResultsConsistent with the flow cytometry results, the total number of TNFα molecules secreted by encapsulated single monocytes was significantly decreased in septic shock patients compared to healthy donors. TNFα production was dampened as soon as 30 and 60 minutes after LPS stimulation in monocytes from septic patients. Furthermore, the microfluidic assay revealed heterogeneous individual behavior of monocytes from septic shock patients. Of note, monocytes from both healthy donors and patients exhibited similar phagocytic activities over time.ConclusionThe microfluidic assay highlights the functional heterogeneity of monocytes, and provides in-depth resolution in assessing the hallmark monocyte deactivation encountered in post-septic immunosuppression.
Published: 2021
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17. Formal guidelines: management of acute respiratory distress syndrome

Author: Laurent Papazian, Cécile Aubron, Laurent Brochard, Jean-Daniel Chiche, Alain Combes, Didier Dreyfuss, Jean-Marie Forel, Claude Guérin, Samir Jaber, Armand Mekontso-Dessap, Alain Mercat, Jean-Christophe Richard, Damien Roux, Antoine Vieillard-Baron, and Henri Faure
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Fifteen recommendations and a therapeutic algorithm regarding the management of acute respiratory distress syndrome (ARDS) at the early phase in adults are proposed. The Grade of Recommendation Assessment, Development and Evaluation (GRADE) methodology has been followed. Four recommendations (low tidal volume, plateau pressure limitation, no oscillatory ventilation, and prone position) had a high level of proof (GRADE 1 + or 1 −); four (high positive end-expiratory pressure [PEEP] in moderate and severe ARDS, muscle relaxants, recruitment maneuvers, and venovenous extracorporeal membrane oxygenation [ECMO]) a low level of proof (GRADE 2 + or 2 −); seven (surveillance, tidal volume for non ARDS mechanically ventilated patients, tidal volume limitation in the presence of low plateau pressure, PEEP > 5 cmH2O, high PEEP in the absence of deleterious effect, pressure mode allowing spontaneous ventilation after the acute phase, and nitric oxide) corresponded to a level of proof that did not allow use of the GRADE classification and were expert opinions. Lastly, for three aspects of ARDS management (driving pressure, early spontaneous ventilation, and extracorporeal carbon dioxide removal), the experts concluded that no sound recommendation was possible given current knowledge. The recommendations and the therapeutic algorithm were approved by the experts with strong agreement.
Published: 2019
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18. Methodological challenges in European ethics approvals for a genetic epidemiology study in critically ill patients: the GenOSept experience

Author: Ascanio Tridente, Paul A. H. Holloway, Paula Hutton, Anthony C. Gordon, Gary H. Mills, Geraldine M. Clarke, Jean-Daniel Chiche, Frank Stuber, Christopher Garrard, Charles Hinds, Julian Bion, and The GenOSept National Coordinators, European Society of Intensive Care Medicine
Subjects: GenOSept, Genetic epidemiology, Research ethics, Decision-making, Human genetics, Intensive care, Medical philosophy. Medical ethics, R723-726
Abstract: Abstract Background During the set-up phase of an international study of genetic influences on outcomes from sepsis, we aimed to characterise potential differences in ethics approval processes and outcomes in participating European countries. Methods Between 2005 and 2007 of the FP6-funded international Genetics Of Sepsis and Septic Shock (GenOSept) project, we asked national coordinators to complete a structured survey of research ethic committee (REC) approval structures and processes in their countries, and linked these data to outcomes. Survey findings were reconfirmed or modified in 2017. Results Eighteen countries participated in the study, recruiting 2257 patients from 160 ICUs. National practices differed widely in terms of composition of RECs, procedures and duration of the ethics approval process. Eight (44.4%) countries used a single centralised process for approval, seven (38.9%) required approval by an ethics committee in each participating hospital, and three (16.7%) required both. Outcomes of the application process differed widely between countries because of differences in national legislation, and differed within countries because of interpretation of the ethics of conducting research in patients lacking capacity. The RECs in four countries had no lay representation. The median time from submission to final decision was 1.5 (interquartile range 1–7) months; in nine (50%) approval was received within 1 month; six took over 6 months, and in one 24 months; had all countries been able to match the most efficient approvals processes, an additional 74 months of country or institution-level recruitment would have been available. In three countries, rejection of the application by some local RECs resulted in loss of centres; and one country rejected the application outright. Conclusions The potential benefits of the single application portal offered by the European Clinical Trials Regulation will not be realised without harmonisation of research ethics committee practices as well as national legislation.
Published: 2019
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19. Pulmonary infections prime the development of subsequent ICU-acquired pneumonia in septic shock

Author: Jean-François Llitjos, Aïcha Gassama, Julien Charpentier, Jérôme Lambert, Charles de Roquetaillade, Alain Cariou, Jean-Daniel Chiche, Jean-Paul Mira, Matthieu Jamme, and Frédéric Pène
Subjects: Septic shock, Immunosuppression, Nosocomial infection, Ventilator-acquired pneumonia, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Purpose To investigate the determinants and the prognosis of intensive care unit (ICU)-acquired pneumonia in patients with septic shock. Methods This single-center retrospective study was conducted in a medical ICU in a tertiary care center from January 2008 to December 2016. All consecutive patients diagnosed for septic shock within the first 48 h of ICU admission were included. Patients were classified in three groups: no ICU-acquired infections (no ICU-AI), ICU-acquired pneumonia and non-pulmonary ICU-AI. The determinants of ICU-acquired pneumonia and death were investigated by multivariate competitive risk analysis. Results A total of 1021 patients were admitted for septic shock, and 797 patients were alive in the ICU after 48 h of management. The incidence of a first episode of ICU-AI was 31%, distributed into pulmonary (17%) and non-pulmonary ICU-AI (14%). Patients with septic shock caused by pneumonia were at increased risk of further pulmonary ICU-AI with a cumulated incidence of 34.4%. A pulmonary source of the initial septic shock was an independent risk factor for subsequent ICU-acquired pneumonia (cause-specific hazard 2.33, 95% confidence interval [1.55–3.52], p
Published: 2019
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20. Use of Venovenous Extracorporeal Membrane Oxygenation in Critically-Ill Patients With COVID-19

Author: Mathieu Jozwiak, Jean-Daniel Chiche, Julien Charpentier, Zakaria Ait Hamou, Paul Jaubert, Sarah Benghanem, Pierre Dupland, Ariane Gavaud, Frédéric Péne, Alain Cariou, Jean-Paul Mira, and Lee S. Nguyen
Subjects: acute respiratory distress syndrome—ARDS, COVID-19, extracorporeal membrane oxygenation (ECMO), intensive care unit (ICU), mechanical ventilation, Medicine (General), R5-920
Abstract: Acute respiratory distress syndrome (ARDS) related to Coronavirus disease (COVID-19) is associated with high mortality. It has been suggested that venovenous extracorporeal membrane oxygenation (ECMO) was suitable in this indication, albeit the effects of ECMO on the mechanical respiratory parameters have been scarcely described. In this case-series, we prospectively described the use of venovenous ECMO and its effects on mechanical respiratory parameters in eleven COVID-19 patients with severe ARDS. Implantation of ECMO occurred 6 [3–11] days after the onset of mechanical ventilation. At the time of ECMO implantation, all patients received neuromuscular blocking agents, three (27%) received inhaled nitric oxide and prone positioning was performed in all patients with 4 [3−5] sessions of PP per patient. Under ECMO, the tidal volume was significantly decreased from 6.1 [4.0–6.3] to 3.4 [2.5–3.6] mL/kg of predicted body weight and the positive end-expiratory pressure level was increased by 25 ± 27% whereas the driving pressure and the mechanical power decreased by 33 ± 25% and 71 ± 27%, respectively. The PaO2/FiO2 ratio significantly increased from 68 [58–89] to 168 [137–218] and the oxygenation index significantly decreased from 28 [26–35] to 13 [10–15]. The duration of ECMO was 12 [8–25] days. Nine (82%) patients experienced ECMO-related complications and the main complication was major bleeding requiring blood transfusions. Intensive care unit mortality rate was 55% but no patient died from ECMO-related complications. In COVID-19 patients with severe ARDS, venovenous ECMO allowed ultra-protective ventilation, improved oxygenation and should be considered in highly selected patients with the most severe ARDS.
Published: 2020
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21. Venoarterial Extracorporeal Membrane Oxygenation in High-Risk Pulmonary Embolism: A Case Series and Literature Review

Author: Zied Ltaief, Ermes Lupieri, Jean Bonnemain, Nawfel Ben-Hamouda, Valentina Rancati, Sabine Schmidt Kobbe, Matthias Kirsch, Jean-Daniel Chiche, and Lucas Liaudet
Subjects: pulmonary embolism, cardiac arrest, obstructive cardiogenic shock, cardiopulmonary resuscitation, extra-corporeal cardiopulmonary resuscitation (ecpr), veno-arterial extra-corporeal membrane oxygenation (va-ecmo), Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: High-risk Pulmonary Embolism (PE) has an ominous prognosis and requires emergent reperfusion therapy, primarily systemic thrombolysis (ST). In deteriorating patients or with contraindications to ST, Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) may be life-saving, as supported by several retrospective studies. However, due to the heterogeneous clinical presentation (refractory shock, resuscitated cardiac arrest (CA) or refractory CA), the real impact of VA-ECMO in high-risk PE remains to be fully determined. In this study, we present our centre experience with VA-ECMO for high-risk PE. Method: From 2008 to 2020, we analyzed all consecutive patients treated with VA-ECMO for high-risk PE in our tertiary 35-bed intensive care unit (ICU). Demographic variables, types of reperfusion therapies, indications for VA-ECMO (refractory shock or refractory CA requiring extra-corporeal cardiopulmonary resuscitation, ECPR), hemodynamic variables, initial arterial blood lactate and ICU complications were recorded. The primary outcome was ICU survival, and secondary outcome was hospital survival. Results: Our cohort included 18 patients (9F/9M, median age 57 years old). VA-ECMO was indicated for refractory shock in 7 patients (2 primary and 5 following resuscitated CA) and for refractory CA in 11 patients. Eight patients received anticoagulation only, 9 received ST, and 4 underwent surgical embolectomy. ICU survival was 1/11 (9%) for ECPR vs 3/7 (42%) in patients with refractory shock (p = 0.03, log-rank test). Hospital survival was 0/11 (0%) for ECPR vs 3/7 for refractory shock (p = 0.01, log-rank test). Survivors and Non-survivors had comparable demographic and hemodynamic variables, pulmonary obstruction index, and amounts of administered vasoactive drugs. Pre-ECMO lactate was significantly higher in non-survivors. Massive bleeding was the most frequent complication in survivors and non-survivors, and was the direct cause of death in 3 patients, all treated with ST. Conclusions: VA-ECMO for high-risk PE has very different outcomes depending on the clinical context. Furthermore, VA-ECMO was associated with significant bleeding complications, with more severe consequences following systemic thrombolysis. Future studies on VA-ECMO for high-risk PE should therefore take into account the distinct clinical presentations and should determine the best strategy for reperfusion in such circumstances.
Published: 2022
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22. Sensitivity of Rapid Antigen Testing and RT-PCR Performed on Nasopharyngeal Swabs versus Saliva Samples in COVID-19 Hospitalized Patients: Results of a Prospective Comparative Trial (RESTART)

Author: Antonios Kritikos, Giorgia Caruana, René Brouillet, John-Paul Miroz, Samia Abed-Maillard, Geraldine Stieger, Onya Opota, Antony Croxatto, Peter Vollenweider, Pierre-Alexandre Bart, Jean-Daniel Chiche, and Gilbert Greub
Subjects: SARS-CoV-2 diagnosis, RT-PCR, rapid antigen testing, saliva, viral transport medium, Biology (General), QH301-705.5
Abstract: Saliva sampling could serve as an alternative non-invasive sample for SARS-CoV-2 diagnosis while rapid antigen tests (RATs) might help to mitigate the shortage of reagents sporadically encountered with RT-PCR. Thus, in the RESTART study we compared antigen and RT-PCR testing methods on nasopharyngeal (NP) swabs and salivary samples. We conducted a prospective observational study among COVID-19 hospitalized patients between 10 December 2020 and 1 February 2021. Paired saliva and NP samples were investigated by RT-PCR (Cobas 6800, Roche-Switzerland, Basel, Switzerland) and by two rapid antigen tests: One Step Immunoassay Exdia® COVID-19 Ag (Precision Biosensor, Daejeon, Korea) and Standard Q® COVID-19 Rapid Antigen Test (Roche-Switzerland). A total of 58 paired NP-saliva specimens were collected. A total of 32 of 58 (55%) patients were hospitalized in the intensive care unit, and the median duration of symptoms was 11 days (IQR 5-19). NP and salivary RT-PCR exhibited sensitivity of 98% and 69% respectively, whereas the specificity of these RT-PCRs assays was 100%. The NP RATs exhibited much lower diagnostic performance, with sensitivities of 35% and 41% for the Standard Q® and Exdia® assays, respectively, when a wet-swab approach was used (i.e., when the swab was diluted in the viral transport medium (VTM) before testing). The sensitivity of the dry-swab approach was slightly better (47%). These antigen tests exhibited very low sensitivity (4% and 8%) when applied to salivary swabs. Nasopharyngeal RT-PCR is the most accurate test for COVID-19 diagnosis in hospitalized patients. RT-PCR on salivary samples may be used when nasopharyngeal swabs are contraindicated. RATs are not appropriate for hospitalized patients.
Published: 2021
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23. Derivation and validation of a prognostic model for postoperative risk stratification of critically ill patients with faecal peritonitis

Author: Ascanio Tridente, Julian Bion, Gary H. Mills, Anthony C. Gordon, Geraldine. M. Clarke, Andrew Walden, Paula Hutton, Paul A. H. Holloway, Jean-Daniel Chiche, Frank Stuber, Christopher Garrard, Charles Hinds, and On behalf of the GenOSept and GAinS Investigators
Subjects: Faecal peritonitis, Outcome, Prognostication, GenOSept, GAinS, Sepsis, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Prognostic scores and models of illness severity are useful both clinically and for research. The aim of this study was to develop two prognostic models for the prediction of long-term (6 months) and 28-day mortality of postoperative critically ill patients with faecal peritonitis (FP). Methods Patients admitted to intensive care units with faecal peritonitis and recruited to the European GenOSept study were divided into a derivation and a geographical validation subset; patients subsequently recruited to the UK GAinS study were used for temporal validation. Using all 50 clinical and laboratory variables available on day 1 of critical care admission, Cox proportional hazards regression was fitted to select variables for inclusion in two prognostic models, using stepwise selection and nonparametric bootstrapping sampling techniques. Using Area under the receiver operating characteristic curve (AuROC) analysis, the performance of the models was compared to SOFA and APACHE II. Results Five variables (age, SOFA score, lowest temperature, highest heart rate, haematocrit) were entered into the prognostic models. The discriminatory performance of the 6-month prognostic model yielded an AuROC 0.81 (95% CI 0.76–0.86), 0.73 (95% CI 0.69–0.78) and 0.76 (95% CI 0.69–0.83) for the derivation, geographic and temporal external validation cohorts, respectively. The 28-day prognostic tool yielded an AuROC 0.82 (95% CI 0.77–0.88), 0.75 (95% CI 0.69–0.80) and 0.79 (95% CI 0.71–0.87) for the same cohorts. These AuROCs appeared consistently superior to those obtained with the SOFA and APACHE II scores alone. Conclusions The two prognostic models developed for 6-month and 28-day mortality prediction in critically ill septic patients with FP, in the postoperative phase, enhanced the day one SOFA score’s predictive utility by adding a few key variables: age, lowest recorded temperature, highest recorded heart rate and haematocrit. External validation of their predictive capability in larger cohorts is needed, before introduction of the proposed scores into clinical practice to inform decision making and the design of clinical trials.
Published: 2017
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24. Sepsis inhibits tumor growth in mice with cancer through Toll-like receptor 4-associated enhanced Natural Killer cell activity

Author: Clara Vigneron, Adrien Mirouse, Hamid Merdji, Christophe Rousseau, Clément Cousin, Fanny Alby-Laurent, Jean-Paul Mira, Jean-Daniel Chiche, Jean-François Llitjos, and Frédéric Pène
Subjects: sepsis, cancer, toll-like receptor 4, natural killer, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Sepsis-induced immune dysfunctions are likely to impact on malignant tumor growth. Sequential sepsis-then-cancer models of tumor transplantation in mice recovering from sepsis have shown that the post-septic immunosuppressive environment was able to promote tumor growth. We herein addressed the impact of sepsis on pre-established malignancy in a reverse cancer-then sepsis experimental model. Mice previously inoculated with MCA205 fibrosarcoma cells were subjected to septic challenges by polymicrobial peritonitis induced by cecal ligation and puncture or endotoxinic shock. The anti-tumoral immune response was assessed through the distribution of tumor-infiltrating immune cells, as well as the functions of cytotoxic cells. As compared to sham surgery, polymicrobial sepsis dampened malignant tumor growth in wild-type (WT) mice, but neither in Toll-like receptor 4 (Tlr4)−/- nor in Myd88−/- mice. Similar tumor growth inhibition was observed following a LPS challenge in WT mice, suggesting a regulatory role of Tlr4 in this setting. The low expression of MHC class 1 onto MCA205 cells suggested the involvement of Natural Killer (NK) cells in sepsis-induced tumor inhibition. Septic insults applied to mice with cancer promoted the main anti-tumoral NK functions of IFNγ production and degranulation. The anti-tumoral properties of NK cells obtained from septic mice were exacerbated when cultured with MHC1low MCA205 or YAC-1 cells. These results suggest that sepsis may harbor dual effects on tumor growth depending on the sequential experimental model. When applied in mice with cancer, sepsis prevents tumor growth in a Tlr4-dependent manner by enhancing the anti-tumoral functions of NK cells.
Published: 2019
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25. Study of human RIG-I polymorphisms identifies two variants with an opposite impact on the antiviral immune response.

Author: Julien Pothlichet, Anne Burtey, Andriy V Kubarenko, Gregory Caignard, Brigitte Solhonne, Frédéric Tangy, Meriem Ben-Ali, Lluis Quintana-Murci, Andrea Heinzmann, Jean-Daniel Chiche, Pierre-Olivier Vidalain, Alexander N R Weber, Michel Chignard, and Mustapha Si-Tahar
Subjects: Medicine, Science
Abstract: RIG-I is a pivotal receptor that detects numerous RNA and DNA viruses. Thus, its defectiveness may strongly impair the host antiviral immunity. Remarkably, very little information is available on RIG-I single-nucleotide polymorphisms (SNPs) presenting a functional impact on the host response.Here, we studied all non-synonymous SNPs of RIG-I using biochemical and structural modeling approaches. We identified two important variants: (i) a frameshift mutation (P(229)fs) that generates a truncated, constitutively active receptor and (ii) a serine to isoleucine mutation (S(183)I), which drastically inhibits antiviral signaling and exerts a down-regulatory effect, due to unintended stable complexes of RIG-I with itself and with MAVS, a key downstream adapter protein.Hence, this study characterized P(229)fs and S(183)I SNPs as major functional RIG-I variants and potential genetic determinants of viral susceptibility. This work also demonstrated that serine 183 is a residue that critically regulates RIG-I-induced antiviral signaling.
Published: 2009
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26. Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial

Author: Djillali, ANNANE, Christian, BRUN-BUISSON, Benoit, MISSET, Jean, CHASTRE, François, BRIVET, Julien, BOHE, Carole, SCHWEBEL, Shidasp, SIAMI, Michel, SLAMA, Olivier, LEROY, Gilles, CAPELLIER, Michel, WOLFF, Mohamed, ALI BEN ALI, François, ANTONINI, Jean-François, LORIFERNE, Franck, PETITPAS, Claire, CHARPENTIER, Jean-Michel, CONSTANTIN, Gilles, D'HONNEUR, Bertrand, SOUWEINE, Xavier, FORCEVILLE, Bruno, MEGARBANE, Francois, BAUDIN, Gwenhaël, COLIN, Karim, ASEHNOUNE, Jean-Pierre, QUENOT, Bruno, FRANCOIS, Thierry, BOULAIN, Emmanuelle, MERCIER, Jean, REIGNIER, Roland, AMATHIEU, Fabrice, COOK, Alain, CARIOU, Loic, CHIMOT, Fouad, Fadel, Andrea, Polito, Bernard, Clair, Virginie, Maxime, David, Luis, Tarek, Sharshar, David, Orlikowski, Keyvan, RAZAZI, Nicolas, DE PROST, Guillaume, CARTEAUX, Maité, GARROUSTE ORGEAS, François, Philippart, Alain, Combes, Ania, Nieszkowska, Frederic, Jacobs, Dominique, Prat, Patrick, Lafforgue, Claire, ARA SOMOHANO, Clémence, MINET, Maxime, LUGOSI, Julien, Maizel, Jean Christophe, Navellou, Bruno, Mourvillier, Lila, Bouadma, Jean François, Timsit, Claude Denis, Martin, Julien, Textoris, Sandrine, Wiramus, Clément, BRUN, Benoît, RAGONNET, Ali, Ait-Hssain, Samia, Touati, Jean, Kuba, Vincent, Willems, Pierre, Lahillaire, Mohammed, Lassi, Marion, ANTONA, Alia, MEGHENEM, Marine, DEMESMAY, Eric, Boulet, Olivier, LOUTREL, Romain, DUMONT, Antoine, ROQUILLY, Pierre-Joachim, MAHE, Dominique, DEMEURE dit LATTE, Philippe, CHAMPIN, Jean François, ARNOULD, Raphaël, CINOTTI, Ronan, Le FLOCH, Marc, Clavel, Philippe, Vignon, Nicolas, Pichon, Emmanuelle, BEGOT, Anne-Laure, FEDOU, Catherine, CHAPELLAS, Antoine, GALY, Dalila, Benzekri Lefevre, Armelle, Mathonnet, Anne, Bretagnol, Isabelle, Runge, François, BARBIER, Grégoire, MULLER, Denis, GAROT, Pierre François, DEQUIN, Dominique, PERROTIN, Annick, LEGRAS, Julie, MANKIKIAN, Patrice, TALEC, Stephan, EHRMANN, Aurélie, JORET, Claire, LHOMMET, Emmanuelle, ROUVE, Laetitia, BODET-CONTENTIN, Youenn, JOUAN, Charlotte, SALMONGANDONNIERE, Laurent, MARTIN-LEFEVRE, Matthieu, HENRY-LAGARRIGUE, Aihem, YEHIA, Jean-Baptiste, LASCARROU, Christine, LEBERT, Jean-Claude, LACHERADE, Eric, LEVESQUE, Yen-Lan, NGUYEN, Fabrice, DAVIAUD, Adrien, BOUGLE, Jean Paul, MIRA, Jean Daniel, CHICHE, Frederic, PENE, Tristan, MORICHAU-BEAUCHANT, Guillaume, GERI, Pierre Henri, DESSALLES, Yannick, MONSEAU, Mélanie, SAINT-LEGER, Sandrine, BEDON-CARTE, Laetitia, Bodet-Contentin, Walid, Darwiche, Stephan, Ehrmann, Denis, Garot, Antoine, Guillon, Youenn, Jouan, Annick, Legras, Julie, Mankikian, Emmanuelle, Mercier, Marlene, Morisseau, Yonatan, Perez, Emmanuelle, Rouve, Charlotte, Salmon-Gandonniere, Julie, Helms, Hassene, Rahmani, Alexandra, Monnier, Hamid, Merdji, Raphael, Clere-Jehl, Laure, Stiel, Antoine, Studer, Pascal, Andreu, Jean-Baptiste, Roudaut, Marie, Labruyere, Marine, Jacquier, Francois, Barbier, Dalila, Benzekri, Thierry, Boulain, Sophie, Jacquier, Gregoire, Muller, Mai-Anh, Nai, Sophie, Tollec, Damien, Roux, Jonathan, Messika, Constance, Vuillard, Louis-Marie, Dumont, Laura, Federici, Noemie, Zucman, Marc, Amouretti, Djillali, Annane, Pierre, Moine, Paris, Meng, Rania, Bounab, Muriel-Sarah, Fartoukh, Michel, Djibre, Alexandre, Elabbadi, Marie-Ange, Azais, Konstantinos, Bachoumas, Arthur, Bailly, Remi, Bernardon, Gauthier, Blonz, Luc, Desmedt, Brian, Emonet, Maud, Fiancette, Matthieu, Henry, Jean-Claude, Lacherade, Jean-Baptiste, Lascarrou, Christine, Lebert, Julien, Lorber, Laurent Martin-, Lefevre, Caroline, Pouplet, Isabelle, Vinatier, Aihem, Yehia, Sarah, Benghanem, Julien, Charpentier, Clara, Vigneron, Anne-Laure, Fedou, Claire, Mancia, Emmanuelle, Begot, Thomas, Daix, Antoine, Galy, Celine, Gonzalez, Marine, Goudelin, Bruno, Evrard, Arnaud, Desachy, Julien, Vaidie, Guillaume, Gilbert, Cedric, Darreau, Benoit, Derrien, Marjorie, Saint-Martin, Patrice, Tirot, Mickael, Landais, Nicolas, Chudeau, Jean Christophe, Callahan, Dominique, Vivier, Charlene, Le Moal, Pierre-Yves, Olivier, Remy, Marnai, Francis, Schneider, Nicolas, Sedillot, Xavier, Tchenio, Adrien, Robine, Yves, Poncelin, Remi, Bruyere, Heming, Nicholas, Renault, Alain, Kuperminc, Emmanuelle, Brun-Buisson, Christian, Megarbane, Bruno, Quenot, Jean-Pierre, Siami, Shidasp, Cariou, Alain, Forceville, Xavier, Schwebel, Carole, Leone, Marc, Timsit, Jean-Francois, Misset, Benoît, Benali, Mohamed Ali, Colin, Gwenhael, Souweine, Bertrand, Asehnoune, Karim, Mercier, Emmanuelle, Chimot, Loïc, Charpentier, Claire, François, Bruno, Boulain, Thierry, Petitpas, Frank, Constantin, Jean Michel, Dhonneur, Gilles, Baudin, François, Combes, Alain, Bohé, Julien, Loriferne, Jean-François, Cook, Fabrice, Slama, Michel, Leroy, Olivier, Capellier, Gilles, Dargent, Auguste, Hissem, Tarik, Bounab, Rania, Maxime, Virginie, Moine, Pierre, Bellissant, Eric, and Annane, Djillali
Published: 2024
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27. Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial

Author: Heming, Nicholas, primary, Renault, Alain, additional, Kuperminc, Emmanuelle, additional, Brun-Buisson, Christian, additional, Megarbane, Bruno, additional, Quenot, Jean-Pierre, additional, Siami, Shidasp, additional, Cariou, Alain, additional, Forceville, Xavier, additional, Schwebel, Carole, additional, Leone, Marc, additional, Timsit, Jean-Francois, additional, Misset, Benoît, additional, Benali, Mohamed Ali, additional, Colin, Gwenhael, additional, Souweine, Bertrand, additional, Asehnoune, Karim, additional, Mercier, Emmanuelle, additional, Chimot, Loïc, additional, Charpentier, Claire, additional, François, Bruno, additional, Boulain, Thierry, additional, Petitpas, Frank, additional, Constantin, Jean Michel, additional, Dhonneur, Gilles, additional, Baudin, François, additional, Combes, Alain, additional, Bohé, Julien, additional, Loriferne, Jean-François, additional, Cook, Fabrice, additional, Slama, Michel, additional, Leroy, Olivier, additional, Capellier, Gilles, additional, Dargent, Auguste, additional, Hissem, Tarik, additional, Bounab, Rania, additional, Maxime, Virginie, additional, Moine, Pierre, additional, Bellissant, Eric, additional, Annane, Djillali, additional, Djillali, ANNANE, additional, Christian, BRUN-BUISSON, additional, Benoit, MISSET, additional, Jean, CHASTRE, additional, François, BRIVET, additional, Julien, BOHE, additional, Carole, SCHWEBEL, additional, Shidasp, SIAMI, additional, Michel, SLAMA, additional, Olivier, LEROY, additional, Gilles, CAPELLIER, additional, Michel, WOLFF, additional, Mohamed, ALI BEN ALI, additional, François, ANTONINI, additional, Jean-François, LORIFERNE, additional, Franck, PETITPAS, additional, Claire, CHARPENTIER, additional, Jean-Michel, CONSTANTIN, additional, Gilles, D'HONNEUR, additional, Bertrand, SOUWEINE, additional, Xavier, FORCEVILLE, additional, Bruno, MEGARBANE, additional, Francois, BAUDIN, additional, Gwenhaël, COLIN, additional, Karim, ASEHNOUNE, additional, Jean-Pierre, QUENOT, additional, Bruno, FRANCOIS, additional, Thierry, BOULAIN, additional, Emmanuelle, MERCIER, additional, Jean, REIGNIER, additional, Roland, AMATHIEU, additional, Fabrice, COOK, additional, Alain, CARIOU, additional, Loic, CHIMOT, additional, Fouad, Fadel, additional, Andrea, Polito, additional, Bernard, Clair, additional, Virginie, Maxime, additional, David, Luis, additional, Tarek, Sharshar, additional, David, Orlikowski, additional, Keyvan, RAZAZI, additional, Nicolas, DE PROST, additional, Guillaume, CARTEAUX, additional, Maité, GARROUSTE ORGEAS, additional, François, Philippart, additional, Alain, Combes, additional, Ania, Nieszkowska, additional, Frederic, Jacobs, additional, Dominique, Prat, additional, Patrick, Lafforgue, additional, Claire, ARA SOMOHANO, additional, Clémence, MINET, additional, Maxime, LUGOSI, additional, Julien, Maizel, additional, Jean Christophe, Navellou, additional, Bruno, Mourvillier, additional, Lila, Bouadma, additional, Jean François, Timsit, additional, Claude Denis, Martin, additional, Julien, Textoris, additional, Sandrine, Wiramus, additional, Clément, BRUN, additional, Benoît, RAGONNET, additional, Ali, Ait-Hssain, additional, Samia, Touati, additional, Jean, Kuba, additional, Vincent, Willems, additional, Pierre, Lahillaire, additional, Mohammed, Lassi, additional, Marion, ANTONA, additional, Alia, MEGHENEM, additional, Marine, DEMESMAY, additional, Eric, Boulet, additional, Olivier, LOUTREL, additional, Romain, DUMONT, additional, Antoine, ROQUILLY, additional, Pierre-Joachim, MAHE, additional, Dominique, DEMEURE dit LATTE, additional, Philippe, CHAMPIN, additional, Jean François, ARNOULD, additional, Raphaël, CINOTTI, additional, Ronan, Le FLOCH, additional, Marc, Clavel, additional, Philippe, Vignon, additional, Nicolas, Pichon, additional, Emmanuelle, BEGOT, additional, Anne-Laure, FEDOU, additional, Catherine, CHAPELLAS, additional, Antoine, GALY, additional, Dalila, Benzekri Lefevre, additional, Armelle, Mathonnet, additional, Anne, Bretagnol, additional, Isabelle, Runge, additional, François, BARBIER, additional, Grégoire, MULLER, additional, Denis, GAROT, additional, Pierre François, DEQUIN, additional, Dominique, PERROTIN, additional, Annick, LEGRAS, additional, Julie, MANKIKIAN, additional, Patrice, TALEC, additional, Stephan, EHRMANN, additional, Aurélie, JORET, additional, Claire, LHOMMET, additional, Emmanuelle, ROUVE, additional, Laetitia, BODET-CONTENTIN, additional, Youenn, JOUAN, additional, Charlotte, SALMONGANDONNIERE, additional, Laurent, MARTIN-LEFEVRE, additional, Matthieu, HENRY-LAGARRIGUE, additional, Aihem, YEHIA, additional, Jean-Baptiste, LASCARROU, additional, Christine, LEBERT, additional, Jean-Claude, LACHERADE, additional, Eric, LEVESQUE, additional, Yen-Lan, NGUYEN, additional, Fabrice, DAVIAUD, additional, Adrien, BOUGLE, additional, Jean Paul, MIRA, additional, Jean Daniel, CHICHE, additional, Frederic, PENE, additional, Tristan, MORICHAU-BEAUCHANT, additional, Guillaume, GERI, additional, Pierre Henri, DESSALLES, additional, Yannick, MONSEAU, additional, Mélanie, SAINT-LEGER, additional, Sandrine, BEDON-CARTE, additional, Laetitia, Bodet-Contentin, additional, Walid, Darwiche, additional, Stephan, Ehrmann, additional, Denis, Garot, additional, Antoine, Guillon, additional, Youenn, Jouan, additional, Annick, Legras, additional, Julie, Mankikian, additional, Emmanuelle, Mercier, additional, Marlene, Morisseau, additional, Yonatan, Perez, additional, Emmanuelle, Rouve, additional, Charlotte, Salmon-Gandonniere, additional, Julie, Helms, additional, Hassene, Rahmani, additional, Alexandra, Monnier, additional, Hamid, Merdji, additional, Raphael, Clere-Jehl, additional, Laure, Stiel, additional, Antoine, Studer, additional, Pascal, Andreu, additional, Jean-Baptiste, Roudaut, additional, Marie, Labruyere, additional, Marine, Jacquier, additional, Francois, Barbier, additional, Dalila, Benzekri, additional, Thierry, Boulain, additional, Sophie, Jacquier, additional, Gregoire, Muller, additional, Mai-Anh, Nai, additional, Sophie, Tollec, additional, Damien, Roux, additional, Jonathan, Messika, additional, Constance, Vuillard, additional, Louis-Marie, Dumont, additional, Laura, Federici, additional, Noemie, Zucman, additional, Marc, Amouretti, additional, Djillali, Annane, additional, Pierre, Moine, additional, Paris, Meng, additional, Rania, Bounab, additional, Muriel-Sarah, Fartoukh, additional, Michel, Djibre, additional, Alexandre, Elabbadi, additional, Marie-Ange, Azais, additional, Konstantinos, Bachoumas, additional, Arthur, Bailly, additional, Remi, Bernardon, additional, Gauthier, Blonz, additional, Luc, Desmedt, additional, Brian, Emonet, additional, Maud, Fiancette, additional, Matthieu, Henry, additional, Jean-Claude, Lacherade, additional, Jean-Baptiste, Lascarrou, additional, Christine, Lebert, additional, Julien, Lorber, additional, Laurent Martin-, Lefevre, additional, Caroline, Pouplet, additional, Isabelle, Vinatier, additional, Aihem, Yehia, additional, Sarah, Benghanem, additional, Julien, Charpentier, additional, Clara, Vigneron, additional, Anne-Laure, Fedou, additional, Claire, Mancia, additional, Emmanuelle, Begot, additional, Thomas, Daix, additional, Antoine, Galy, additional, Celine, Gonzalez, additional, Marine, Goudelin, additional, Bruno, Evrard, additional, Arnaud, Desachy, additional, Julien, Vaidie, additional, Guillaume, Gilbert, additional, Cedric, Darreau, additional, Benoit, Derrien, additional, Marjorie, Saint-Martin, additional, Patrice, Tirot, additional, Mickael, Landais, additional, Nicolas, Chudeau, additional, Jean Christophe, Callahan, additional, Dominique, Vivier, additional, Charlene, Le Moal, additional, Pierre-Yves, Olivier, additional, Remy, Marnai, additional, Francis, Schneider, additional, Nicolas, Sedillot, additional, Xavier, Tchenio, additional, Adrien, Robine, additional, Yves, Poncelin, additional, and Remi, Bruyere, additional
Published: 2024
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28. Les agonistes α2-adrénergiques pour l’intensiviste

Author: Lorenzo Gavino, Maité Willaredt, Jean-Daniel Chiche, and Nawfel Ben-Hamouda
Subjects: General Medicine
Published: 2023

29. Delirium in Adults With COVID-19–Related Acute Respiratory Distress Syndrome

Author: Raphael, Bernard-Valnet, Eva, Favre, Adriano, Bernini, Mauro, Oddo, Jean-Daniel, Chiche, Renaud A, Du Pasquier, and Andrea O, Rossetti
Subjects: Adult, Respiratory Distress Syndrome, Intensive Care Units, Critical Illness, Humans, COVID-19, Delirium, Neurology (clinical), Respiration, Artificial, Retrospective Studies
Abstract: Background and ObjectivesNeurologic complications have been associated with COVID-19, including delirium. Such complications have been reported to be frequent among intensive care unit (ICU)-admitted patients. We hypothesized that the rate of neurologic complications would be higher in COVID-19 associated acute respiratory distress syndrome (ARDS) than those who develop ARDS from a different cause.MethodsWe conducted a retrospective cohort study in the adult ICU of Lausanne University Hospital, including all consecutive patients fulfilling the Berlin criteria for ARDS hospitalized between December 2017 and June 2021, stratifying exposure between COVID-19 or not. The primary outcome was delirium onset during ICU stay, defined by the confusion assessment method (CAM-ICU). Exploratory outcomes included development of neurologic complications of the central nervous system (stroke, hemorrhage, and vasculitis), critical illness weakness, and 30- and 180-day all-cause mortality.ResultsThree hundred eleven patients were included in the study (253 with COVID-19 and 58 with other causes) and CAM-ICU could be assessed in 231 (74.3% in COVID-19 vs 74.1% in non-COVID-19). The proportion of patients developing delirium was similar in patients with COVID-19 and controls in univariate comparison (69.1% vs 60.5%,p= 0.246). Yet, patients with COVID-19 had a higher body mass index, lower ICU severity, longer mechanical ventilation, and higher sedation doses (propofol and dexmedetomidine). After adjusting for these factors in a multivariable analysis, the risk of delirium remained comparable across groups (adjusted OR [95% CI]: 0.86 [0.35–2.1]). Similarly, COVID-19–related ARDS had no effect on all-cause mortality at 30 days (adjusted OR: 0.87 [0.39–1.92]) and 180 days (adjusted OR: 0.67 [0.33–1.35]). Finally, neurologic complications affecting the CNS (adjusted OR: 1.15 [0.25–5.29]) and critical illness weakness (adjusted OR: 2.99 [0.97–9.1]) were not higher in the COVID-19 group.DiscussionCompared with other etiologies, patients with COVID-19 did not have higher incidence of delirium and other neurologic complications, after accounting for underlying disease severity in patients with ARDS. Management of COVID-19–associated ARDS needed longer invasive ventilation and higher sedation, which could explain higher rates of delirium in uncontrolled studies.
Published: 2022

30. Modes ventilatoires de base en ventilation mécanique invasive

Author: Arnaud Rey, Ermes Lupieri, Davy Cabrio, Jean Bonnemain, Thierry Fumeaux, Jean-Daniel Chiche, and Lise Piquilloud
Subjects: General Medicine
Published: 2022

31. Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study

Author: Amado-Rodríguez, Laura, Rodríguez-Garcia, Raquel, Bellani, Giacomo, Pham, Tài, Fan, Eddy, Madotto, Fabiana, Laffey, John G, Albaiceta, Guillermo M, Antonio Pesenti, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, DanielF McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Fernando Rios, Frank Van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Sanatorio Las Lomas, San Isidro, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Joris Vermassen, Philippe Meersseman, Helga Ceunen, JonasI Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, MarlusM Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid BinHJAbul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, ShouH Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, ChristianM Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, BorisG Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, FrancescoL Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, DanieleM Combaux, Fabien Grelon, Charlene Le Moal, EliseP Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, RachanaV Rhayakar, Nagarajan Ramakrishnan, VallishK Bhardwaj, HeeraL Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, EimhinS Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, ColinS Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Sara Sher, Anna Rossi, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, RobertoR Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, EttoreR Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, YvesD Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, AsiscloJ Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Hellen M Van Wezel, SergeJ Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, DanielleJ Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, BritÅ Sjøbø, AnneB Guttormsen, Hector H LeonYoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, AnaM Araujo, NunoT Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, IsabelM Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, AhmedS AlJabbary, Edgardo Tabhan, YaseenM Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, JuanC Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, GuillermoM Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, AntonioL RuizAguilar, LuisM Claraco-Vega, Juan Alfonso Soler, Maria Del CarmenLorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, JuanB López-Messa, ManuelP Perez, CesarP Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana Temprano, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, M Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, AntonioG Jimenez, FranciscoP Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, CorcolesG Virgilio, NoeliaN Recio, Richard O Adamsson, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, KarinE Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, SilviaL Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, HervéO Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, OnatO Akyol, SuleymanS Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, ChristopherJ Scott, HelenE Ellis, Stuart Mckechnie, PaulaJ Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, MichaelN Dean, JuliusH Cranshaw, EmmaL Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, PieterD Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, SimonK Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, KatieH McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, DonaldA Irvine, Charing Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, SamanthaJ Hagan, JadeM Cole, Caroline C MacFie, AnnaT Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M BannerGoodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz Mesar, DaleJ Yeatts, Jessica Warren, MichaelJ Lanspa, Russel R Miller, ColinK Grissom, SamuelM Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baro, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, RobertL Owens, Ashley Schomer, Amado-Rodríguez, Laura, Rodríguez-Garcia, Raquel, Bellani, Giacomo, Pham, Tài, Fan, Eddy, Madotto, Fabiana, Laffey, John G, Albaiceta, Guillermo M, Antonio Pesenti, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, DanielF McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Fernando Rios, Frank Van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, DanielF McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Sanatorio Las Lomas, San Isidro, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, JonasI Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, MarlusM Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid BinHJAbul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, ShouH Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, ChristianM Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, BorisG Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, FrancescoL Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, DanieleM Combaux, Fabien Grelon, Charlene Le Moal, EliseP Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, RachanaV Rhayakar, Nagarajan Ramakrishnan, VallishK Bhardwaj, HeeraL Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, EimhinS Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, ColinS Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Sara Sher, Anna Rossi, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, RobertoR Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, EttoreR Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, YvesD Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, AsiscloJ Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M Van Wezel, SergeJ Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, DanielleJ Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, BritÅ Sjøbø, AnneB Guttormsen, Hector H LeonYoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, AnaM Araujo, NunoT Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, IsabelM Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, AhmedS AlJabbary, Edgardo Tabhan, YaseenM Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, JuanC Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, GuillermoM Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, AntonioL RuizAguilar, LuisM Claraco-Vega, Juan Alfonso Soler, Maria Del CarmenLorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, JuanB López-Messa, ManuelP Perez, CesarP Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana Temprano, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, M Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, AntonioG Jimenez, FranciscoP Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, CorcolesG Virgilio, NoeliaN Recio, Richard O Adamsson, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, KarinE Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, SilviaL Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, HervéO Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, OnatO Akyol, SuleymanS Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, ChristopherJ Scott, HelenE Ellis, Stuart Mckechnie, PaulaJ Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, MichaelN Dean, JuliusH Cranshaw, EmmaL Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, PieterD Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, SimonK Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, KatieH McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, DonaldA Irvine, Charing Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, SamanthaJ Hagan, JadeM Cole, Caroline C MacFie, AnnaT Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M BannerGoodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz Mesar, DaleJ Yeatts, Jessica Warren, MichaelJ Lanspa, Russel R Miller, ColinK Grissom, SamuelM Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, RobertL Owens, Ashley Schomer, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, AII - Inflammatory diseases, ACS - Diabetes & metabolism, ACS - Microcirculation, Albaiceta, Guillermo, M, Pesenti, Antonio, Brochard, Laurent, Esteban, Andre, Gattinoni, Luciano, van Haren, Frank, Larsson, Ander, Mcauley, Danielf, Ranieri, Marco, Rubenfeld, Gordon, Taylor Thompson, B., Wrigge, Hermann, Slutsky, Arthur S., Rios, Fernando, Van Haren, Frank, Sottiaux, Thierry, Depuydt, Pieter, Lora, Fredy S., Azevedo, Luciano Cesar, Bugedo, Guillermo, Qiu, Haibo, Gonzalez, Marco, Silesky, Juan, Cerny, Vladimir, Nielsen, Jona, Jibaja, Manuel, Matamis, Dimitrio, Ranero, Jorge Lui, Amin, Pravin, Hashemian, S. 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Subjects: Ventilator-induced lung injury, Cardiogenic pulmonary edema, Driving pressure, Mechanical ventilation, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Settore MED/41 - ANESTESIOLOGIA, Critical Care and Intensive Care Medicine
Abstract: Supported by Centro de Investigación Biomédica en Red (CIBER)‑Enfermedades respiratorias, Madrid, Spain (CB17/06/00021) and Fundación para el Fomento en Asturias de la Investigación Científica aplicada y la tecnología (FICYT, AYUD2021/52014). RRG is the recipient of a grant from Instituto de Salud Carlos III, Madrid, Spain (CM20/00083)., Amado-Rodríguez L., Rodríguez-Garcia R., Bellani G., Pham T., Fan E., Madotto F., Laffey J.G., Albaiceta G.M., Pesenti A., Brochard L., Esteban A., Gattinoni L., van Haren F., Larsson A., McAuley D.F., Ranieri M., Rubenfeld G., Taylor Thompson B., Wrigge H., Slutsky A.S., Rios F., Van Haren F., Sottiaux T., Depuydt P., Lora F.S., Azevedo L.C., Bugedo G., Qiu H., Gonzalez M., Silesky J., Cerny V., Nielsen J., Jibaja M., Wrigge H., Matamis D., Ranero J.L., Amin P., Hashemian S.M., Clarkson K., Kurahashi K., Villagomez A., Zeggwagh A.A., Heunks L.M., Laake J.H., Palo J.E., do Vale Fernandes A., Sandesc D., Arabi Y.M., Bumbasierevic V., Nin N., Lorente J.A., Larsson A., Piquilloud L., Abroug F., McAuley D.F., McNamee L., Hurtado J., Bajwa E., Démpaire G., Sula H., Nunci L., Cani A., Zazu A., Dellera C., Insaurralde C.S., Las Lomas S., Isidro S., Alejandro R.V., Daldin J., Vinzio M., Fernandez R.O., Cardonnet L.P., Bettini L.R., Bisso M.C., Osman E.M., Setten M.G., Lovazzano P., Alvarez J., Villar V., Pozo N.C., Grubissich N., Plotnikow G.A., Vasquez D.N., Ilutovich S., Tiribelli N., Chena A., Pellegrini C.A., Saenz M.G., Estenssoro E., Brizuela M., Gianinetto H., Gomez P.E., Cerrato V.I., Bezzi M.G., Borello S.A., Loiacono F.A., Fernandez A.M., Knowles S., Reynolds C., Inskip D.M., Miller J.J., Kong J., Whitehead C., Bihari S., Seven A., Krstevski A., Rodgers H.J., Millar R.T., McKenna T.E., Bailey I.M., Hanlon G.C., Aneman A., Lynch J.M., Azad R., Neal J., Woods P.W., Roberts B.L., Kol M.R., Wong H.S., Riss K.C., Staudinger T., Wittebole X., Berghe C., Bulpa P.A., Dive A.M., Verstraete R., Lebbinck H., Depuydt P., Vermassen J., Meersseman P., Ceunen H., Rosa J.I., Beraldo D.O., Piras C., Rampinelli A.M., Nassar Jr A.P., Mataloun S., Moock M., Thompson M.M., Gonçalves C.H., Antônio A.C.P., Ascoli A., Biondi R.S., Fontenele D.C., Nobrega D., Sales V.M., BinHJAbul Wahab A.Y., Ismail M., Shindhe S., Laffey J., Beloncle F., Davies K.G., Cirone R., Manoharan V., Ismail M., Goligher E.C., Jassal M., Nishikawa E., Javeed A., Curley G., Rittayamai N., Parotto M., Ferguson N.D., Mehta S., Knoll J., Pronovost A., Canestrini S., Bruhn A.R., Garcia P.H., Aliaga F.A., Farías P.A., Yumha J.S., Ortiz C.A., Salas J.E., Saez A.A., Vega L.D., Labarca E.F., Martinez F.T., Carreño N.G., Lora P., Liu H., Qiu H., Liu L., Tang R., Luo X., An Y., Zhao H., Gao Y., Zhai Z., Ye Z.L., Wang W., Li W., Li Q., Zheng R., Yu W., Shen J., Li X., Yu T., Lu W., Wu Y.Q., Huang X.B., He Z., Lu Y., Han H., Zhang F., Sun R., Wang H.X., Qin S.H., Zhu B.H., Zhao J., Liu J., Li B., Liu J.L., Zhou F.C., Li Q.J., Zhang X.Y., Li-Xin Z., Xin-Hua Q., Jiang L., Gao Y.N., Zhao X.Y., Li Y.Y., Li X.L., Wang C., Yao Q., Yu R., Chen K., Shao H., Qin B., Huang Q.Q., Zhu W.H., Hang A.Y., Hua M.X., Li Y., Xu Y., Di Y.D., Ling L.L., Qin T.H., Wang S.H., Qin J., Han Y., Zhou S., Vargas M.P., Jimenez J.I.S., Rojas M.A.G., SolisQuesada J.E., Ramirez-Alfaro C.M., Máca J., Sklienka P., Gjedsted J., Christiansen A., Nielsen J., Villamagua B.G., Llano I., Burtin P., Buzancais G., Beuret P., Pelletier N., Mortaza S., Mercat A., Chelly J., Jochmans S., Terzi N., Daubin C., Carteaux G., de Prost N., Chiche J.-D., Daviaud F., Fartoukh M., Barberet G., Biehler J., Dellamonica J., Doyen D., Arnal J.-M., Briquet A., Hraiech S., Papazian L., Follin A., Roux D., Messika J., Kalaitzis E., Dangers L., Combes A., Béduneau G., Carpentier D., Zogheib E.H., Dupont H., Ricome S., Santoli F.L., Besset S.L., Michel P., Gelée B., Danin P.-E., Goubaux B., Crova P.J., Phan N.T., Berkelmans F., Badie J.C., Tapponnier R., Gally J., Khebbeb S., Herbrecht J.-E., Schneider F., Declercq P.L.M., Rigaud J.-P., Duranteau J., Harrois A., Chabanne R., Marin J., Bigot C., Thibault S., Ghazi M., Boukhazna M., Zein S.O., Richecoeur J.R., Combaux D.M., Grelon F., Le Moal C., Sauvadet E.P., Robine A., Lemiale V., Reuter D., Dres M., Demoule A., Goldgran-Toledano D., Baboi L., Guérin C., Lohner R., Kraßler J., Schäfer S., Zacharowski K.D., Meybohm P., Reske A.W., Simon P., Hopf H.B.F., Schuetz M., Baltus T., Papanikolaou M.N., Papavasilopoulou T.G., Zacharas G.A., Ourailogloy V., Mouloudi E.K., Massa E.V., Nagy E.O., Stamou E.E., Kiourtzieva E.V., Oikonomou M.A., Avila L.E., Cortez C.A., Citalán J.E., Jog S.A., Sable S.D., Shah B., Gurjar M., Baronia A.K., Memon M., Muthuchellappan R., Ramesh V.J., Shenoy A., Unnikrishnan R., Dixit S.B., Rhayakar R.V., Ramakrishnan N., Bhardwaj V.K., Mahto H.L., Sagar S.V., Palaniswamy V., Ganesan D., Jamaati H., Heidari F., Meaney E.A., Nichol A., Knapman K.M., O’Croinin D., Dunne E.S., Breen D.M., Jaafar R.F., Dwyer R., Amir F., Ajetunmobi O.O., O’Muircheartaigh A.C., Black C.S., Treanor N., Collins D.V., Altaf W., Zani G., Fusari M., Spadaro S., Volta C.A., Graziani R., Brunettini B., Palmese S., Formenti P., Umbrello M., Lombardo A., Pecci E., Botteri M., Savioli M., Protti A., Mattei A., Schiavoni L., Tinnirello A., Todeschini M., Giarratano A., Cortegiani A., Sher S., Rossi A., Antonelli M.M., Montini L.M., Casalena P., Scafetti S., Panarello G., Occhipinti G., Patroniti N., Pozzi M., Biscione R.R., Poli M.M., Raimondi F., Albiero D., Crapelli G., Beck E., Pota V., Schiavone V., Molin A., Tarantino F., Monti G., Frati E., Mirabella L., Cinnella G., Fossali T., Colombo R., Terragni P., Pattarino I., Mojoli F., Braschi A., Borotto E.E., Cracchiolo A.N., Palma D.M., Raponi F., Foti G., Vascotto E.R., Coppadoro A., Brazzi L., Floris L., Iotti G.A., Venti A., Yamaguchi O., Takagi S., Maeyama H.N., Watanabe E., Yamaji Y., Shimizu K., Shiozaki K., Futami S., Ryosuke S., Saito K., Kameyama Y., Ueno K., Izawa M., Okuda N., Suzuki H., Harasawa T., Nasu M., Takada T., Ito F., Nunomiya S., Koyama K., Abe T., Andoh K., Kusumoto K., Hirata A., Takaba A., Kimura H., Matsumoto S., Higashijima U., Honda H., Aoki N., Imai H., Ogino Y., Mizuguchi I., Ichikado K., Nitta K., Mochizuki K., Hashida T., Tanaka H., Nakamura T., Niimi D., Ueda T., Kashiwa Y., Uchiyama A., Sabelnikovs O., Oss P., Haddad Y., Liew K.Y., Ñamendys-Silva S.A., Jarquin-Badiola Y.D., Sanchez-Hurtado L.A., Gomez-Flores S.S., Marin M.C., Lemus J.S., Fierro J.M., Cervantes M.R., Mejia F.J.F., Dector D., Rojas A., Gonzalez D.R., Estrella C.R., Sanchez-Medina J.R., Ramirez-Gutierrez A., George F.G., Aguirre J.S., Buensuseso J.A., Poblano M., Dendane T., Zeggwagh A.A., Balkhi H., Elkhayari M., Samkaoui N., Ezzouine H., Benslama A., Amor M., Maazouzi W., Cimic N., Beck O., Bruns M.M., Schouten J.A., Rinia M., Raaijmakers M., Heunks L.M., Van Wezel H.M., Heines S.J., Strauch U., Buise M.P., Simonis F.D., Schultz M.J., Goodson J.C., Browne T.S., Navarra L., Hunt A., Hutchison R.A., Bailey M.B., Newby L., McArthur C., Kalkoff M., Mcleod A., Casement J., Hacking D.J., Andersen F.H., Dolva M.S., Laake J.H., Barratt-Due A., Noremark K.A.L., Søreide E., Sjøbø B.Å., Guttormsen A.B., LeonYoshido H.H., Aguilar R.Z., Oscanoa F.A.M., Alisasis A.U., Robles J.B., Pasanting-Lim R.A.B., Tan B.C., Andruszkiewicz P., Jakubowska K., Coxo C.M., Alvarez A.M., Oliveira B.S., Montanha G.M., Barros N.C., Pereira C.S., Messias A.M., Monteiro J.M., Araujo A.M., Catorze N.T., Marum S.M., Bouw M.J., Gomes R.M., Brito V.A., Castro S., Estilita J.M., Barros F.M., Serra I.M., Martinho A.M., Tomescu D.R., Marcu A., Bedreag O.H., Papurica M., Corneci D.E., Negoita S.I., Grigoriev E., Gritsan A.I., Gazenkampf A.A., Almekhlafi G., Albarrak M.M., Mustafa G.M., Maghrabi K.A., Salahuddin N., Aisa T.M., AlJabbary A.S., Tabhan E., Trinidad O.A., Al Dorzi H.M., Bumbasirevic V., Jovanovic B., Bolon S., Smith O., Mancebo J., Aguirre-Bermeo H., Lopez-Delgado J.C., Esteve F., Rialp G., Forteza C., De Haro C., Artigas A., Albaiceta G.M., De Cima-Iglesias S., Seoane-Quiroga L., Ceniceros-Barros A., RuizAguilar A.L., Claraco-Vega L.M., Soler J.A., del CarmenLorente M., Hermosa C., Gordo F., PrietoGonzález M., López-Messa J.B., Perez M.P., Perez C.P., Allue R.M., RocheCampo F., Ibañez-Santacruz M., Temprano S., Pintado M.C., De Pablo R., Gómez P.R.A., Ruiz S.R., Moles S.I., Jurado M.T., Arizmendi A., Piacentini E.A., Franco N., Honrubia T., Cheng M.P., Losada E.P., Blanco J., Yuste L.J., Carbayo-Gorriz C., Cazorla-Barranquero F.G., Alonso J.G., Alda R.S., Algaba Á., Navarro G., Cereijo E., Diaz-Rodriguez E., Marcos D.P., Montero L.A., Para L.H., Sanchez R.J., Navalpotro M.A.B., Abad R.D., González R.M., Toribio D.P., Castro A.G., Artiga M.J.D., Penuelas O., Roser T.P., Olga M.F., Curto E.G., Sánchez R.M., Imma V.P., Elisabet G.M., Claverias L., Magret M., Pellicer A.M., Rodriguez L.L., Sánchez-Ballesteros J., González-Salamanca Á., Jimenez A.G., Huerta F.P., Diaz J.C.J.S., Lopez E.B., Moya D.D.L., Alfonso A.A.T., Luis P.S.E., Cesar P.S., Rafael S.I., Virgilio C.G., Recio N.N., Adamsson R.O., Rylander C.C., Holzgraefe B., Broman L.M., Wessbergh J., Persson L., Schiöler F., Kedelv H., Tibblin A.O., Appelberg H., Hedlund L., Helleberg J., Eriksson K.E., Glietsch R., Larsson N., Nygren I., Nunes S.L., Morin A.-K., Kander T., Adolfsson A., Zender H.O., Leemann-Refondini C., Elatrous S., Bouchoucha S., Chouchene I., Ouanes I., Souissi A.B., Kamoun S., Demirkiran O., Aker M., Erbabacan E., Ceylan I., Girgin N.K., Ozcelik M., Ünal N., Meco B.C., Akyol O.O., Derman S.S., Kennedy B., Parhar K., Srinivasa L., McNamee L., McAuley D., Hopkins P., Mellis C., Kakar V., Hadfield D., Vercueil A., Bhowmick K., Humphreys S.K., Ferguson A., Mckee R., Raj A.S., Fawkes D.A., Watt P., Twohey L., Jha R.R., Thomas M., Morton A., Kadaba V., Smith M.J., Hormis A.P., Kannan S.G., Namih M., Reschreiter H., Camsooksai J., Kumar A., Rugonfalvi S., Nutt C., Oneill O., Seasman C., Dempsey G., Scott C.J., Ellis H.E., Mckechnie S., Hutton P.J., Di Tomasso N.N., Vitale M.N., Griffin R.O., Dean M.N., Cranshaw J.H., Willett E.L., Ioannou N., Gillis S., Csabi P., Macfadyen R., Dawson H., Preez P.D., Williams A.J., Boyd O., de Gordoa L.O.-R., Bramall J., Symmonds S., Chau S.K., Wenham T., Szakmany T., Toth-Tarsoly P., McCalman K.H., Alexander P., Stephenson L., Collyer T., Chapman R., Cooper R., Allan R.M., Sim M., Wrathall D.W., Irvine D.A., Zantua C.K.S., Adams J.C., Burtenshaw A.J., Sellors G.P., Welters I.D., Williams K.E., Hessell R.J., Oldroyd M.G., Battle C.E., Pillai S., Kajtor I., Sivashanmugavel M., Okane S.C., Donnelly A., Frigyik A.D., Careless J.P., May M.M., Stewart R., Trinder T.J., Hagan S.J., Cole J.M., MacFie C.C., Dowling A.T., Hurtado J., Nin N., Hurtado J., Nuñez E., Pittini G., Rodriguez R., Imperio M.C., Santos C., França A.G., Ebeid A., Deicas A., Serra C., Uppalapati A., Kamel G., BannerGoodspeed V.M., Beitler J.R., Mukkera S.R., Kulkarni S., Shinn III J.O., Gomaa D., Tainter C., Lee J., Mesar T., Yeatts D.J., Warren J., Lanspa M.J., Miller R.R., Grissom C.K., Brown S.M., Bauer P.R., Gosselin R.J., Kitch B.T., Cohen J.E., Beegle S.H., Choudry S., Gueret R.M., Tulaimat A., Stigler W., Batra H., Huff N.G., Lamb K.D., Oetting T.W., Mohr N.M., Judy C., Saito S., Kheir F.M., Kheir F., Schlichting A.B., Delsing A., Crouch D.R., Elmasri M., Crouch D.R., Ismail D., Dreyer K.R., Blakeman T.C., Baro R.M., Hou P.C., Seethala R., Aisiku I., Henderson G., Frendl G., Hou S.-K., Owens R.L., Schomer A.
Published: 2022

32. In memoriam: Warren M. Zapol

Author: Lorenzo Berra, Konrad J. Falke, Roland C. E. Francis, Jesse D. Roberts, and Jean-Daniel Chiche
Subjects: Critical Care and Intensive Care Medicine
Published: 2022

33. Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19

Author: Aiwei Zhu, Fernando Real, Claude Capron, Arielle R. Rosenberg, Aymeric Silvin, Garett Dunsmore, Jaja Zhu, Andréa Cottoignies-Callamarte, Jean-Marc Massé, Pierre Moine, Simon Bessis, Mathieu Godement, Guillaume Geri, Jean-Daniel Chiche, Silvana Valdebenito, Sandrine Belouzard, Jean Dubuisson, Geoffroy Lorin de la Grandmaison, Sylvie Chevret, Florent Ginhoux, Eliseo A. Eugenin, Djillali Annane, Elisabeth Cramer Bordé, Morgane Bomsel, Institut Cochin [IC UM3 (UMR 8104 / U1016)], Université de Versailles Saint-Quentin-en-Yvelines [UVSQ], Hôpital Ambroise Paré [AP-HP], Hôpital Cochin [AP-HP], Immunologie anti-tumorale et immunothérapie des cancers [ITIC], Institut Gustave Roussy [IGR], Infection et inflammation [2I], The University of Texas Medical Branch [UTMB], Institut Pasteur de Lille, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Hôpital Raymond Poincaré [Garches], Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) [SBIM], Singapore Immunology Network [SIgN], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service d'Hématologie et d'Immunologie [AP-HP Hôpital Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation médicale polyvalente [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], The University of Texas Medical Branch (UTMB), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP), Université de Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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 (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Agency for science, technology and research [Singapore] (A*STAR), ANR-20-COVI-0024,MUCOLUNG,Rôle des cellules pulmonaires infectées par le SRAS-CoV-2 et réponse humoral dans l' évolution du COVID-19: de la physiopathologie au test de médicaments candidats dans les modèles de cellules muqueuses(2020), Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), School of Medicine [Shanghai Jiaotong University], Shanghai Jiaotong University, Accident Compensation Corporation, ACC, Fondation pour la Recherche Médicale, FRM, China Scholarship Council, CSC, The authors thank Professor John F. Martin (University College of London, UK) for fruitful advice and discussion on the role of NRP1 receptor and VEGF in COVID19 and resultant therapeutical implications, and for English editing. The authors greatly acknowledge Karine Bailly and Muriel Andrieu of the Cochin Cytometry and Immunobiology Facility for cytokine analyses, as well as Thomas Guilbert from the Imag’IC facility for instruction on the IXplore Spin Confocal Imaging Microscope System (Olympus) and Livine Duban from Luminex corp for instruction on the Guava easyCyte 12HT base system (Millipore) during the COVID-19 confinement period. We also thank also Dr. Nicolas Chapuis (Hôpital Cochin, Paris, France) and Pr. Nicholas Heming (Hôpital Raymond Poincaré, Garches, France) for helpful discussion., Joint funding by the Agence Nationale de la Recherche (France) and Fondation pour la Recherche Médicale (France): Flash COVID ANR-FRM: ANR-20-COVI-0024. Funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript. AZ was supported by the China Scholarship Council and ACC by the Fondation pour la Recherche Médicale., and REAL, Fernando
Subjects: Blood Platelets, Pharmacology, Platelets, SARS-CoV-2, Macrophages, [SDV]Life Sciences [q-bio], Membrane Proteins, RNA-Binding Proteins, COVID-19, Thrombosis, Cell Biology, [SDV] Life Sciences [q-bio], Lung, Megakaryocytes, Cellular and Molecular Neuroscience, Humans, Molecular Medicine, Molecular Biology
Abstract: SARS-CoV-2, although not being a circulatory virus, spread from the respiratory tract resulting in multiorgan failures and thrombotic complications, the hallmarks of fatal COVID-19. A convergent contributor could be platelets that beyond hemostatic functions can carry infectious viruses. Here, we profiled 52 patients with severe COVID-19 and demonstrated that circulating platelets of 19 out 20 non-survivor patients contain SARS-CoV-2 in robust correlation with fatal outcome. Platelets containing SARS-CoV-2 might originate from bone marrow and lung megakaryocytes (MKs), the platelet precursors, which were found infected by SARS-CoV-2 in COVID-19 autopsies. Accordingly, MKs undergoing shortened differentiation and expressing anti-viral IFITM1 and IFITM3 RNA as a sign of viral sensing were enriched in the circulation of deadly COVID-19. Infected MKs reach the lung concomitant with a specific MK-related cytokine storm rich in VEGF, PDGF and inflammatory molecules, anticipating fatal outcome. Lung macrophages capture SARS-CoV-2-containing platelets in vivo. The virus contained by platelets is infectious as capture of platelets carrying SARS-CoV-2 propagates infection to macrophages in vitro, in a process blocked by an anti-GPIIbIIIa drug. Altogether, platelets containing infectious SARS-CoV-2 alter COVID-19 pathogenesis and provide a powerful fatality marker. Clinical targeting of platelets might prevent viral spread, thrombus formation and exacerbated inflammation at once and increase survival in COVID-19.
Published: 2022

34. [Classic ventilatory modes for invasive mechanical ventilation]

Author: Arnaud, Rey, Ermes, Lupieri, Davy, Cabrio, Jean, Bonnemain, Thierry, Fumeaux, Jean-Daniel, Chiche, and Lise, Piquilloud
Subjects: Humans, Respiration, Artificial, Monitoring, Physiologic
Abstract: Invasive mechanical ventilation is part of the daily practice of the intensivist and anesthetist. The comprehensive knowledge of ventilatory modes is mandatory for managing the ventilated patients. The objective of this article is to explain the characteristics of the barometric and volumetric modes and the differences between controlled, assist-controlled, and assisted ventilation. The most common modes (volume and pressure assist-control, dual modes and pressure support) are described in detail. Parameters that must be set and those that must be monitored in each mode are also described. Finally, suggestions for initial settings are provided in order to offer the reader unfamiliar with mechanical ventilation a practical decision-making aid.La ventilation mécanique invasive est un outil indispensable à la pratique de l’intensiviste et de l’anesthésiste. La connaissance des modes ventilatoires est nécessaire pour la prise en charge des patients ventilés. L’objectif de cet article est, d’une part, de distinguer les caractéristiques des modes barométriques et volumétriques, et de comprendre les différences entre les modes contrôlé, assisté-contrôlé et assisté et, d’autre part, de distinguer les paramètres qui doivent être réglés de ceux qui doivent être monitorés. Les modes les plus utilisés (volume contrôlé, pression contrôlée, modes mixtes et aide inspiratoire) font l’objet d’une description détaillée. Des suggestions de réglages initiaux sont proposées pour ces modes afin d’offrir au lecteur peu familier avec la ventilation mécanique une aide décisionnelle pratique.
Published: 2022

35. Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study

Author: Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andres, Gattinoni, Luciano, Larsson, Anders, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, 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Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, 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Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Pham, T, Pesenti, A, Bellani, G, Rubenfeld, G, Fan, E, Bugedo, G, Lorente, J, Fernandes, A, Van Haren, F, Bruhn, A, Rios, F, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Thompson, B, Wrigge, H, Brochard, L, Laffey, J, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), St. Michael's Hospital, University of Toronto, Groupe de recherche clinique CARMAS, 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, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano [Milano] (UNIMI), University of Milan, San Gerardo Hospital, Sunnybrook Health Sciences Center, Mount Sinai Hospital [Toronto, Canada] (MSH), Pontificia Universidad Católica de Chile (UC), University Hospital of Getafe, CIBER Enfermedades Respiratorias (CIBERES), Universidad Europea de Madrid, Hospital Garcia de Orta (EPE), Canberra Hospital, Medical School [Australian National University - ANU], Australian National University (ANU), University of Canberra, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Göttingen - Georg-August-Universität Göttingen, Uppsala University, Queen's University [Belfast] (QUB), Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC), Università degli Studi di Bologna, Massachusetts General Hospital [Boston], University Hospital Leipzig, Department of Anaesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, 06112, Halle, National University of Ireland [Galway] (NUI Galway), Bayer GlaxoSmithKline, GSK Baxter International Boehringer Ingelheim Wellcome Trust, WT National Institute for Health Research, NIHR Queen's University Belfast, QUB Medical Research Council Canada, MRC European Society of Intensive Care Medicine, ESICM, Support statement: This work was supported by the European Society of Intensive Care Medicine. Funding information for this article has been deposited with the Crossref Funder Registry., Conflict of interest: T. Pham has nothing to disclose. A. Pesenti reports personal fees from Maquet, Novalung/Xenios, Baxter, Gilead and Boehringer Ingelheim, outside the submitted work. G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Getinge, Hamilton, GE Healthcare, Dimar SRL, Intersurgical and Flowmeter SPA, outside the submitted work. G. Rubenfeld has nothing to disclose. E. Fan reports personal fees from ALung Technologies, Getinge and MC3 Cardiopulmonary, grants, personal fees and non-financial support from Fresenius Medical Care, outside the submitted work. G. Bugedo has nothing to disclose. J.A. Lorente has nothing to disclose. A.D. V. Fernandes has nothing to disclose. F. Van Haren has nothing to disclose. A. Bruhn has nothing to disclose. F. Rios has nothing to disclose. A. Esteban has nothing to disclose. L. Gattinoni has nothing to disclose. A. Larsson reports grants from the Swedish Heart and Lung Foundation, during the conduct of the study. D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work, in addition, his institution has received funds from grants from the UK NIHR, Wellcome Trust, Innovate UK, NI HSC R&D Division, NI Chest Heart and Stroke, and MRC, is one of four named inventors on a patent US8962032 covering the use of sialic acid-bearing nanoparticles as anti-inflammatory agents issued to his institution, The Queen’s University of Belfast (http://www.google.com/patents/US8962032), and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. M. Ranieri has nothing to disclose. B.T. Thompson reports personal fees from Bayer, Thetis and Novartis, outside the submitted work. H. Wrigge reports personal fees for consultancy from Dräger Medical, personal fees for advisory board work from Liberate Medical, grants and personal fees for lectures from InfectoPharm, personal fees for lectures from MSD and GE, outside the submitted work. L.J. Brochard reports grants from Medtronic Covidien, grants and non-financial support from Fisher Paykel, non-financial support from Air Liquide, Sentec and Philips, other (patent) from General Electric, outside the submitted work. J.G. Laffey reports grants and personal fees from Baxter, grants and non-financial support from Aerogen and Factor Biosciences, outside the submitted work., LUNG SAFE Investigators and the European Society of Intensive Care Medicine Trials Group: Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J 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I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette 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Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, and UCL - (SLuc) Service de soins intensifs
Subjects: Pulmonary and Respiratory Medicine, ARDS, Unidades de cuidados intensivos, [SDV]Life Sciences [q-bio], medicine.medical_treatment, mechanical ventilation, NO, law.invention, 03 medical and health sciences, Tratamiento médico, 0302 clinical medicine, law, Settore MED/41 - ANESTESIOLOGIA, Insuficiencia respiratoria, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Lung, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Respiration, Incidence (epidemiology), medicine.disease, Intensive care unit, Respiration, Artificial, 3. Good health, Intensive Care Units, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], medicine.anatomical_structure, 030228 respiratory system, Respiratory failure, Heart failure, Anesthesia, Artificial, ards, business, Respiratory Insufficiency, Enfermedad
Abstract: BackgroundCurrent incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).MethodsAn international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.Findings12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.InterpretationMore than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.
Published: 2021

36. Post-cardiac arrest myoclonus and in ICU mortality: insights from the Parisian Registry of Cardiac Arrest (PROCAT)

Author: Eric Azabou, Jean-Daniel Chiche, Alain Cariou, Florence Dumas, Matthieu Jamme, Jean-Paul Mira, Lucie Guillemet, Marine Paul, Frédéric Pène, Hervé Outin, Omar Ben Hadj Salem, and Julien Charpentier
Subjects: Male, Myoclonus, medicine.medical_specialty, Dermatology, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, medicine, Humans, Prospective Studies, Registries, 030212 general & internal medicine, Post cardiac arrest, Prospective cohort study, Aged, Retrospective Studies, Icu mortality, business.industry, Confounding, General Medicine, Odds ratio, Intensive care unit, Cardiopulmonary Resuscitation, Heart Arrest, Intensive Care Units, Psychiatry and Mental health, Emergency medicine, Female, Neurology (clinical), Neurosurgery, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Post-cardiac arrest myoclonus (PCAM) is a frequent finding in resuscitated patients after cardiac arrest (CA), with rather poor prognostic significance. In this study, we evaluated the association of PCAM within intensive care unit (ICU) mortality from a university hospital CA patients’ registry. Clinical data of consecutive CA survivors admitted in the intensive care unit (ICU) between January and December 2016 at the Paris Cochin University Hospital were assessed from the Parisian registry of cardiac arrest (PROCAT) and analyzed. Neurologic outcome was assessed using the Cerebral Performance Categories (CPC) scale at ICU discharge. Prevalence of PCAM and their association with mortality at ICU discharge were computed. One hundred thirty-two (132) patients were included (73.5% males), median age of 66 years. Among them, 37 (28%) developed PCAM during their ICU stay. Only two patients with PCAM survived (5.4%). PCAM was strongly associated with mortality at ICU discharge (odds ratio 17.5 [4.2–123.2]). Sensitivity, specificity, PPV, and NPV of PCAM for prediction of death were 41%, 96%, 95%, and 46%, respectively. PCAM was observed in nearly one-third of CA patients admitted in ICU. Patients with PCAM had a significantly higher likelihood of ICU mortality and a low likelihood of a good outcome. The prognostic value of PCAM seems rather bleak but remains nuanced and merits study in larger-scale prospective studies taking into account confounding factors.
Published: 2021

37. Body composition and short-term mortality in critically ill patients with acute on chronic liver failure

Author: Thomas Mangana del Rio, Sophie-Caroline Sacleux, Julien Vionnet, Philippe Ichaï, Alban Denys, Antoine Schneider, Audrey Coilly, Montserrat Fraga, Alexandre Wetze, Joachim Koerfer, Jean-Daniel Chiche, Faouzi Saliba, Darius Moradpour, Fabio Becce, and Florent Artru
Subjects: Hepatology, Gastroenterology, Internal Medicine, Immunology and Allergy
Published: 2023

38. Impact of Blood Product Transfusions on the Risk of ICU-Acquired Infections in Septic Shock*

Author: Matthieu Jamme, Julien Charpentier, Nathalie Marin, Jean-François Llitjos, Anne François, Edwige Péju, Alain Cariou, Frédéric Pène, Jérôme Lambert, Jean-Paul Mira, and Jean-Daniel Chiche
Subjects: Male, medicine.medical_specialty, Critical Illness, Health Status, Critical Care and Intensive Care Medicine, Tertiary Care Centers, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Blood product, Internal medicine, medicine, Humans, Blood Transfusion, Platelet, Aged, Retrospective Studies, Aged, 80 and over, First episode, Cross Infection, business.industry, Septic shock, Hazard ratio, 030208 emergency & critical care medicine, Retrospective cohort study, Middle Aged, medicine.disease, Shock, Septic, Icu admission, Intensive Care Units, 030228 respiratory system, Female, Fresh frozen plasma, business
Abstract: Objectives Transfusions of blood products are common in critically ill patients and have a potential for immunomodulation. The aim of this study is to address the impact of transfusion of blood products on the susceptibility to ICU-acquired infections in the high-risk patients with septic shock. Design A single-center retrospective study over a 10-year period (2008-2017). Setting A medical ICU of a tertiary-care center. Patients All consecutive patients diagnosed for septic shock within the first 48 hours of ICU admission were included. Patients who were discharged or died within the first 48 hours were excluded. Interventions RBC, platelet, and fresh frozen plasma transfusions collected up to 24 hours prior to the onset of ICU-acquired infection. Measurements and main results During the study period, 1,152 patients were admitted for septic shock, with 893 patients remaining alive in the ICU after 48 hours of management. A first episode of ICU-acquired infection occurred in 28.3% of the 48-hour survivors, with a predominance of pulmonary infections (57%). Patients with ICU-acquired infections were more likely to have received RBC, platelet, and fresh frozen plasma transfusions. In a multivariate Cox cause-specific analysis, transfusions of platelets (cause-specific hazard ratio = 1.55 [1.09-2.20]; p = 0.01) and fresh frozen plasma (cause-specific hazard ratio = 1.38 [0.98-1.92]; p = 0.05) were independently associated with the further occurrence of ICU-acquired infections. Conclusions Transfusions of platelets and fresh frozen plasma account for risk factors of ICU-acquired infections in patients recovering from septic shock. The occurrence of ICU-acquired infections should be considered as a relevant endpoint in future studies addressing the indications of transfusions in critically ill patients.
Published: 2021

39. Sepsis and Cancer: An Interplay of Friends and Foes

Author: Elie Azoulay, Jean-François Llitjos, Djamel Mokart, Jean-Daniel Chiche, Clara Vigneron, Adrien Mirouse, Jean-Paul Mira, and Frédéric Pène
Subjects: Pulmonary and Respiratory Medicine, business.industry, medicine.medical_treatment, Cancer, Immunosuppression, Comorbidity, Critical Care and Intensive Care Medicine, medicine.disease, Bioinformatics, Pathophysiology, Bacterial sepsis, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Immune system, 030228 respiratory system, Risk Factors, Neoplasms, medicine, Humans, Tumor growth, 030212 general & internal medicine, Immune homeostasis, business
Abstract: Sepsis and cancer share a number of pathophysiological features, and both result from the inability of the host's immune system to cope with the initial insult (tissue invasion by pathogens and malignant cell transformation, respectively). The common coexistence of both disorders and the profound related alterations in immune homeostasis raise the question of their mutual impact on each other's course. This translational review aims to discuss the interactions between cancer and sepsis supported by clinical data and the translation to experimental models. The dramatic improvement in cancer has come at a cost of increased risks of life-threatening infectious complications. Investigating the long-term outcomes of sepsis survivors has revealed an unexpected susceptibility to cancer long after discharge from the ICU. Nonetheless, it is noteworthy that an acute septic episode may harbor antitumoral properties under particular circumstances. Relevant double-hit animal models have provided clues to whether and how bacterial sepsis may impact malignant tumor growth. In sequential sepsis-then-cancer models, postseptic mice exhibited accelerated tumor growth. When using reverse cancer-then-sepsis models, bacterial sepsis applied to mice with cancer conversely resulted in inhibition or even regression of tumor growth. Experimental models thus highlight dual effects of sepsis on tumor growth, mostly depending on the sequence of insults, and allow deciphering the immune mechanisms and their relation with microorganisms.
Published: 2020

40. Canakinumabin patients with COVID-19 and type 2 diabetes (CanCovDia) - a multicentric, randomised, double-blind, placebo-controlled phase 3 trial

Author: Matthias Hepprich, Jonathan Mudry, Claudia Gregoriano, Francois R Jornayvaz, Sebastian Carballo, Anne Wojtusciszyn, Pierre-Alexandre Bart, Jean-Daniel Chiche, Stefan Fischli, Thomas Baumgartner, Claudia Cavelti-Weder, Felix Beuschlein, Dominque L Braun, Huldrych F Gunthard, Emily West, Anna Conen, Egon Isenring, Gabriela Bucklar, Yoann Aubry, Ludovic Dey, Beat Muller, Philipp Schutz, Marco Cattaneo, Patrick Hunziker, and Marc Y Donath
Published: 2022

41. Author response for 'COVID‐19 rapidly increases MDSCs and prolongs innate immune dysfunctions'

Author: null Irene T. Schrijver, null Charlotte Théroude, null Nikolaos Antonakos, null Jean Regina, null Didier Le Roy, null Pierre‐Alexandre Bart, null Jean‐Daniel Chiche, null Matthieu Perreau, null Giuseppe Pantaleo, null Thierry Calandra, and null Thierry Roger
Published: 2022

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

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

43. Delirium in Adults With COVID-19-related ARDS: Comparison With Other Etiologies

Author: Raphael, Bernard-Valnet, Eva, Favre, Adriano, Bernini, Mauro, Oddo, Jean-Daniel, Chiche, Renaud A, Du Pasquier, and Andrea, Rossetti
Abstract: Neurological complications have been associated with COVID-19, including deliriumSuch complications have been reported to be frequent among ICU admitted patients. We hypothesized that the rate of neurological complications would be higher in COVID-19 associated acute respiratory distress syndrome (ARDS) than those who develop ARDS from a different cause.We conducted a retrospective cohort study in the adult intensive care unit (ICU) of our hospital, including all consecutive patients fulfilling Berlin criteria for ARDS hospitalized between December 2017 and June 2021, stratifying exposure between COVID-19 or not. The primary outcome was delirium onset during ICU stay, defined by the confusion assessment method (CAM-ICU). Exploratory outcomes included development of neurological complications of the central (stroke, hemmorhage, vasculitis) or critical illness weakness, and 30 and 180 days all-cause mortality.311 patients were included in the study (253 with COVID-19 and 58 with other causes); CAM-ICU was assessed in 231 (74.3% in COVID-19 vs. 74,1% in non-COVID-19). The proportion of patients developing delirium was similar in patients with COVID-19 and controls in univariate comparison(69.1% vs 60.5%
Published: 2022

44. The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study. Rationale and Design

Author: Jean Daniel Chiche, Alistair Nichol, Allen C. Cheng, Zahra Bhimani, Peter Kruger, Genevieve K. O'Neill, Paul J Young, Anthony C. Gordon, Jane Parker, Rachael Parke, Derek C. Angus, Kathryn M Rowan, Sebastiaan J. Hullegie, Anne Turner, Anna McGlothlin, Paul R Mouncey, Roger J. Lewis, John Marshall, Farah Al-Beidh, Steven A R Webb, Kristine Broglio, Srinivas Murthy, Lennie P. G. Derde, Colin McArthur, Alisa Higgins, Edward Litton, Scott M. Berry, Yaseen M. Arabi, Gernot Rohde, Menno de Jong, Herman Goossens, Frank M. Brunkhorst, Marc J.M. Bonten, Cameron Green, Wilma van Bentum-Puijk, Shay McGuinness, Michelle A. Detry, Francois Lamontagne, AII - Infectious diseases, and Medical Microbiology and Infection Prevention
Subjects: community-acquired pneumonia, Respiratory System, Psychological intervention, Disease, law.invention, 0302 clinical medicine, Community-acquired pneumonia, Randomized controlled trial, law, Bayesian adaptive platform trial, Medicine, 030212 general & internal medicine, Viral, Clinical Study Design, Evidence-Based Medicine, Coronavirus disease 2019, master protocol, Bayesian adaptive, Intensive care unit, 3. Good health, Anti-Bacterial Agents, Community-Acquired Infections, Randomized clinical trial, Coronavirus Infections, Human, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Randomization, Point-of-Care Systems, Clinical Sciences, Pneumonia, Viral, Antiviral Agents, 03 medical and health sciences, coronavirus disease 2019, Betacoronavirus, Intensive care, Influenza, Human, Master protocol, Humans, Intensive care medicine, Pandemics, business.industry, SARS-CoV-2, COVID-19, Evidence-based medicine, Pneumonia, medicine.disease, randomized clinical trial, Influenza, 030228 respiratory system, platform trial, Human medicine, business
Abstract: There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia. The trial uses a novel design, entitled “a randomized embedded multifactorial adaptive platform.” The design has five key features: 1) randomization, allowing robust causal inference; 2) embedding of study procedures into routine care processes, facilitating enrollment, trial efficiency, and generalizability; 3) a multifactorial statistical model comparing multiple interventions across multiple patient subgroups; 4) response-adaptive randomization with preferential assignment to those interventions that appear most favorable; and 5) a platform structured to permit continuous, potentially perpetual enrollment beyond the evaluation of the initial treatments. The trial randomizes patients to multiple interventions within four treatment domains: antibiotics, antiviral therapy for influenza, host immunomodulation with extended macrolide therapy, and alternative corticosteroid regimens, representing 240 treatment regimens. The trial generates estimates of superiority, inferiority, and equivalence between regimens on the primary outcome of 90-day mortality, stratified by presence or absence of concomitant shock and proven or suspected influenza infection. The trial will also compare ventilatory and oxygenation strategies, and has capacity to address additional questions rapidly during pandemic respiratory infections. As of January 2020, REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) was approved and enrolling patients in 52 intensive care units in 13 countries on 3 continents. In February, it transitioned into pandemic mode with several design adaptations for coronavirus disease 2019. Lessons learned from the design and conduct of this trial should aid in dissemination of similar platform initiatives in other disease areas. Clinical trial registered with www.clinicaltrials.gov (NCT02735707).
Published: 2020

45. [Monitoring respiratory mechanics in ventilated patients: a bedside approach]

Author: Davy, Cabrio, Arnaud, Rey, Jean, Bonnemain, Jean-Daniel, Chiche, and Lise, Piquilloud
Subjects: Treatment Outcome, Ventilators, Mechanical, Respiratory System, Respiratory Mechanics, Humans, Respiration, Artificial
Abstract: In clinical practice, the term respiratory mechanics usually refers to the concept of compliance and resistance of the respiratory system. In ventilated patients, measurements of compliance and resistance can be performed at the bedside using the ventilator (end- inspiratory and end-expiratory occlusions). Those measurements allow caregivers to monitor pulmonary disorders and evaluate treatment effectiveness. In case of sudden change in compliance or resistance, the variation of flow and pressure curves displayed on the ventilator screen helps to narrow down the differential diagnosis. This article defines what are compliance and resistance and how to calculate and use them at the bedside.Le terme « mécanique respiratoire » se rapporte souvent, en pratique, aux concepts de compliance et résistance du système respiratoire. Chez un patient ventilé, les mesures de compliance et de résistance s’effectuent à l’aide du ventilateur (occlusion télé-inspiratoire et télé-expiratoire). Ces mesures permettent de suivre l’évolution d’une atteinte pulmonaire ou l’efficacité d’un traitement administré. En cas de changement brusque de compliance ou de résistance, l’analyse des variations des courbes affichées sur l’écran du ventilateur permet d’élaborer un diagnostic différentiel rapidement. Cet article de synthèse décrit les concepts de compliance et résistance du système respiratoire, la façon de les calculer et de les utiliser au lit du malade.
Published: 2022

46. Validation of a Protocol for Continuous Hemodiafiltration with Regional Citrate Anticoagulation with Omni®

Author: Livia Whiting, Nathan Axel Bianchi, Karima Alouazen, Olivier Joannes-Boyau, Jean-Daniel Chiche, and Antoine Schneider
Subjects: Nephrology, Renal Dialysis, Creatinine, Humans, Anticoagulants, Urea, Hematology, General Medicine, Citrates, Hemodiafiltration, Acute Kidney Injury, Citric Acid
Abstract: Introduction: Omni® (B Braun, Melsungen, Germany) is able to run continuous renal replacement therapy (CRRT) in continuous veno-venous hemofiltration (CVVH), hemodialysis (CVVHD), and hemodiafiltration (CVVHDF) modes. However, to date, there is no validated protocol to guide the use of Omni® in CVVHDF mode with regional citrate anticoagulation (RCA). Methods: We designed a protocol for CVVHDF-RCA tailored for Omni®. This protocol was tested in patients included in an observational study conducted in our center between January and March 2021. For all study patients, we collected baseline characteristics, laboratory results, CRRT circuit lifespan as well as plasma and effluent samples at 12, 24, 48, and 72 h of CRRT circuit initiation. At each study time point, we computed urea, creatinine, and β2-microglobulin clearance as well as effluent/blood ratios. Data from circuits in CVVHDF-RCA mode are compared with those in standard therapy (CVVHD-RCA) with the same device. Results: We analyzed ten circuits (5 patients) in CVVHDF-RCA mode and 32 (13 patients) in CVVHD-RCA mode. No adverse events related to the therapy were observed. In CVVHDF-RCA mode, median circuit running time was 68 (IQR 8.1) hours versus 46 (IQR 9.0) in CVVHD mode, p = 0.053. Therapy adaptations (dialysate rate and/or blood flow) were required in one (10%) circuit (15.6% in CVVHD mode, p = 0.56). Compared to CVVHD, CVVHDF was able to achieve similar clearance and effluent/blood ratio for urea, creatinine, and β2-microglobulin across the entire duration of circuit lifetime. Conclusion: The proposed protocol for CVVHDF-RCA for Omni® was associated with similar circuit lifetime, number of required adaptations and clearances to standard CVVHD-RCA. It appears to be safe and feasible.
Published: 2021

47. Sarcopenia assessed via computed tomography is associated with short-term outcomes and improves prognostic scores’ performance in critically ill patients with acute on chronic liver failure

Author: Thomas Mangana Del Rio, Fabio Becce, Julien Vionnet, Alban Denys, Antoine Schneider, Alexandre Wetzel, Darius Moradpour, Jean-Daniel Chiche, and Florent Artru
Subjects: Hepatology
Published: 2022

48. Causes of acute respiratory failure in patients with small-vessel vasculitis admitted to intensive care units: a multicenter retrospective study

Author: François Bagate, Matthieu Groh, Etienne de Montmollin, Aude Gibelin, Alexandre Hertig, Loredana Baboi, Guillaume Dumas, Mathilde Neuville, Raphaël Clere-Jehl, Charles-Edouard Luyt, Francis Schneider, Eric Maury, Jean-Herlé Raphalen, Nicolas de Prost, Muriel Fartoukh, Marc Pineton de Chambrun, Sandrine Valade, Claude Guérin, Jean-Daniel Chiche, Antoine Parrot, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (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 (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], CHU Henri Mondor, Hôpital Foch [Suresnes], CHU Necker - Enfants Malades [AP-HP], Service de réanimation médicale polyvalente [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], 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), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], Service d'Anesthésie réanimation [CHU Tenon], Gestionnaire, HAL Sorbonne Université 5, 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], Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Département de Néphrologie [CHU Tenon] (Néphrologie et dialyse), 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)-Sorbonne Université (SU), and Service de Pneumologie, Médecine Intensive et Réanimation - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S)
Subjects: Vasculitis, medicine.medical_specialty, medicine.medical_treatment, Critical Care and Intensive Care Medicine, Acute respiratory failure, [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, Internal medicine, Anesthesiology, Intensive care, medicine, 030212 general & internal medicine, RC86-88.9, Proportional hazards model, business.industry, Diffuse alveolar hemorrhage, Research, Medical emergencies. Critical care. Intensive care. First aid, Immunosuppression, Retrospective cohort study, medicine.disease, Intensive care unit, 3. Good health, 030228 respiratory system, Etiology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract: Rationale Acute respiratory failure (ARF) in patients admitted to the intensive care unit (ICU) with known or de novo small-vessel vasculitis (Svv) may be secondary to the underlying immune disease or to other causes. Early identification of the cause of ARF is essential to initiate the most appropriate treatment in a timely fashion. Methods A retrospective multicenter study in 10 French ICUs from January 2007 to January 2018 to assess the clinical presentation, main causes and outcome of ARF associated with Svv, and to identify variables associated with non-immune etiology of ARF in patients with known Svv. Results During the study period, 121 patients [62 (50–75) years; 62% male; median SAPSII and SOFA scores 39 (27–52) and 6 (4–8), respectively] were analyzed. An immune cause was identified in 67 (55%), and a non-immune cause in 54 (45%) patients. ARF was associated with several causes in 43% (n = 52) of cases. The main immune cause was diffuse alveolar hemorrhage (DAH) (n = 47, 39%), whereas the main non-immune cause was pulmonary infection (n = 35, 29%). The crude 90-day and 1-year mortality were higher in patients with non-immune ARF, as compared with their counterparts (32% and 38% vs. 15% and 20%, respectively; both p = 0.03), but was marginally significantly higher after adjusted analysis in a Cox model (p = 0.053). Among patients with a known Svv (n = 70), immunosuppression [OR 9.41 (1.52–58.3); p = 0.016], and a low vasculitis activity score [0.84 (0.77–0.93)] were independently associated with a non-immune cause, after adjustment for the time from disease onset to ARF, time from respiratory symptoms to ICU admission, and severe renal failure. Conclusions An extensive diagnosis workup is mandatory in ARF revealing or complicating Svv. Non-immune causes are involved in 43% of cases, and their short and mid-term prognosis may be poorer than those of immune ARF. Readily identified predictive factors of a non-immune cause could help avoiding unnecessary immunosuppressive therapies.
Published: 2021

49. Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: Insights from the LUNG SAFE study

Author: Madotto F, Rezoagli E, Pham T, Schmidt M, McNicholas B, Protti A, Panwar R, Bellani G, Fan E, van Haren F, Brochard L, Laffey JG, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Fernando Rios, T Sottiaux, P Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Uhc Mother Theresa, Hektor Sula, Lordian Nunci, Alma Cani, Villa Maria, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E Mckenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Suresh Shindhe, Dk Maizatul Aiman B Pg Hj Ismail, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E Solis-Quesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Miguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tai Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, Pierre-Louis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, Hans-Bernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed 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Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin-Nunomiya Kansuke-Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Dulce M Dector, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra-Rinia, Monique Raaijmakers, Hellen M Van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin Mcarthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L Ruiz-Aguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam-Prieto-González, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran Roche-Campo, Marcos Ibañez-Santacruz, Susana-Temprano, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier-Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel Gonz Á Lez, D Á Cil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Richard O Adamsson, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R JhaMatthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla O'Neill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz De Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C O'Kane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Matt P Wise, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, Jarone Lee, Tomaz Mesar, John O Shinn 3rd, Dina Gomaa, Christopher Tainter, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, LUNG SAFE Investigators and the ESICM Trials Group, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Renaud M Gueret, Aiman Tulaimat, Shazia Choudry, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baron, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Vesna Bumbasirevic, Bojan Jovanovic, Maja Surbatovic, Milic Veljovic, Madotto, F., Rezoagli, E., Pham, T., Schmidt, M., Mcnicholas, B., Protti, A., Panwar, R., Bellani, G., Fan, E., Van Haren, F., Brochard, L., Laffey, J. G., Pesenti, A., Esteban, A., Gattinoni, L., Larsson, A., Mcauley, D. F., Ranieri, M., Rubenfeld, G., Thompson, B. T., Wrigge, H., Slutsky, A. S., Rios, F., Sottiaux, T., Depuydt, P., Lora, F. S., Azevedo, L. C., Bugedo, G., Qiu, H., Gonzalez, M., Silesky, J., Cerny, V., Nielsen, J., Jibaja, M., Matamis, D., Ranero, J. L., Amin, P., Hashemian, S. M., Clarkson, K., Kurahashi, K., Villagomez, A., Zeggwagh, A. A., Heunks, L. M., Laake, J. H., Palo, J. E., Do Vale Fernandes, A., Sandesc, D., Arabi, Y., Bumbasierevic, V., Nin, N., Lorente, J. A., Piquilloud, L., Abroug, F., Mcnamee, L., Hurtado, J., Bajwa, E., Dempaire, G., Theresa, U. M., Sula, H., Nunci, L., Cani, A., Maria, V., Zazu, A., Dellera, C., Insaurralde, C. S., Alejandro, R. V., Daldin, J., Vinzio, M., Fernandez, R. O., Cardonnet, L. P., Bettini, L. R., Bisso, M. C., Osman, E. M., Setten, M. G., Lovazzano, P., Alvarez, J., Villar, V., Pozo, N. C., Grubissich, N., Plotnikow, G. A., Vasquez, D. N., Ilutovich, S., Tiribelli, N., Chena, A., Pellegrini, C. A., Saenz, M. G., Estenssoro, E., Brizuela, M., Gianinetto, H., Gomez, P. E., Cerrato, V. I., Bezzi, M. G., Borello, S. A., Loiacono, F. A., Fernandez, A. M., Knowles, S., Reynolds, C., Inskip, D. M., Miller, J. J., Kong, J., Whitehead, C., Bihari, S., Seven, A., Krstevski, A., Rodgers, H. J., Millar, R. T., Mckenna, T. E., Bailey, I. M., Hanlon, G. C., Aneman, A., Lynch, J. M., Azad, R., Neal, J., Woods, P. W., Roberts, B. L., Kol, M. R., Wong, H. S., Riss, K. C., Staudinger, T., Wittebole, X., Berghe, C., Bulpa, P. A., Dive, A. M., Verstraete, R., Lebbinck, H., Vermassen, J., Meersseman, P., Ceunen, H., Rosa, J. I., Beraldo, D. O., Piras, C., Rampinelli, A. M., Nassar, A. P., Mataloun, S., Moock, M., Thompson, M. M., Goncalves, C. H., Antonio, A. C. P., Ascoli, A., Biondi, R. S., Fontenele, D. C., Nobrega, D., Sales, V. M., Shindhe, S., Pg Hj Ismail, D. M. A. B., Laffey, J., Beloncle, F., Davies, K. G., Cirone, R., Manoharan, V., Ismail, M., Goligher, E. C., Jassal, M., Nishikawa, E., Javeed, A., Curley, G., Rittayamai, N., Parotto, M., Ferguson, N. D., Mehta, S., Knoll, J., Pronovost, A., Canestrini, S., Bruhn, A. R., Garcia, P. H., Aliaga, F. A., Farias, P. A., Yumha, J. S., Ortiz, C. A., Salas, J. E., Saez, A. A., Vega, L. D., Labarca, E. F., Martinez, F. T., Carreno, N. G., Lora, P., Liu, H., Liu, L., Tang, R., Luo, X., An, Y., Zhao, H., Gao, Y., Zhai, Z., Ye, Z. L., Wang, W., Li, W., Li, Q., Zheng, R., Yu, W., Shen, J., Li, X., Yu, T., Lu, W., Wu, Y. Q., Huang, X. B., He, Z., Lu, Y., Han, H., Zhang, F., Sun, R., Wang, H. X., Qin, S. H., Zhu, B. H., Zhao, J., Liu, J., Li, B., Liu, J. L., Zhou, F. C., Li, Q. J., Zhang, X. Y., Li-Xin, Z., Xin-Hua, Q., Jiang, L., Gao, Y. N., Zhao, X. Y., Li, Y. Y., Li, X. L., Wang, C., Yao, Q., Yu, R., Chen, K., Shao, H., Qin, B., Huang, Q. Q., Zhu, W. H., Hang, A. Y., Hua, M. X., Li, Y., Xu, Y., Di, Y. D., Ling, L. L., Qin, T. H., Wang, S. H., Qin, J., Han, Y., Zhou, S., Vargas, M. P., Silesky Jimenez, J. I., Gonzalez Rojas, M. A., Solis-Quesada, J. E., Ramirez-Alfaro, C. M., Maca, J., Sklienka, P., Gjedsted, J., Christiansen, A., Villamagua, B. G., Llano, M., Burtin, P., Buzancais, G., Beuret, P., Pelletier, N., Mortaza, S., Mercat, A., Chelly, J., Jochmans, S., Terzi, N., Daubin, C., Carteaux, G., De Prost, N., Chiche, J. -D., Daviaud, F., Fartoukh, M., Barberet, G., Biehler, J., Dellamonica, J., Doyen, D., Arnal, J. -M., Briquet, A., Hraiech, S., Papazian, L., Follin, A., Roux, D., Messika, J., Kalaitzis, E., Dangers, L., Combes, A., Au, S. -M., Beduneau, G., Carpentier, D., Zogheib, E. H., Dupont, H., Ricome, S., Santoli, F. L., Besset, S. L., Michel, P., Gelee, B., Danin, P. -E., Goubaux, B., Crova, P. J., Phan, N. T., Berkelmans, F., Badie, J. C., Tapponnier, R., Gally, J., Khebbeb, S., Herbrecht, J. -E., Schneider, F., Declercq, P. -L. M., Rigaud, J. -P., Duranteau, J., Harrois, A., Chabanne, R., Marin, J., Bigot, C., Thibault, S., Ghazi, M., Boukhazna, M., Zein, S. O., Richecoeur, J. R., Combaux, D. M., Grelon, F., Le Moal, C., Sauvadet, E. P., Robine, A., Lemiale, V., Reuter, D., Dres, M., Demoule, A., Goldgran-Toledano, D., Baboi, L., Guerin, C., Lohner, R., Krassler, J., Schafer, S., Zacharowski, K. D., Meybohm, P., Reske, A. W., Simon, P., Hopf, H. -B. F., Schuetz, M., Baltus, T., Papanikolaou, M. N., Papavasilopoulou, T. G., Zacharas, G. A., Ourailogloy, V., Mouloudi, E. K., Massa, E. V., Nagy, E. O., Stamou, E. E., Kiourtzieva, E. V., Oikonomou, M. A., Avila, L. E., Cortez, C. A., Citalan, J. E., Jog, S. A., Sable, S. D., Shah, B., Gurjar, M., Baronia, A. K., Memon, M., Muthuchellappan, R., Ramesh, V. J., Shenoy, A., Unnikrishnan, R., Dixit, S. B., Rhayakar, R. V., Ramakrishnan, N., Bhardwaj, V. K., Mahto, H. L., Sagar, S. V., Palaniswamy, V., Ganesan, D., Jamaati, H., Heidari, F., Meaney, E. A., Nichol, A., Knapman, K. M., O'Croinin, D., Dunne, E. S., Breen, D. M., Clarkson, K. P., Jaafar, R. F., Dwyer, R., Amir, F., Ajetunmobi, O. O., O'Muircheartaigh, A. C., Black, C. S., Treanor, N., Collins, D. V., Altaf, W., Zani, G., Fusari, M., Spadaro, S., Volta, C. A., Graziani, R., Brunettini, B., Palmese, S., Formenti, P., Umbrello, M., Lombardo, A., Pecci, E., Botteri, M., Savioli, M., Mattei, A., Schiavoni, L., Tinnirello, A., Todeschini, M., Giarratano, A., Cortegiani, A., Sher, S., Rossi, A., Antonelli, M. M., Montini, L. M., Casalena, P., Scafetti, S., Panarello, G., Occhipinti, G., Patroniti, N., Pozzi, M., Biscione, R. R., Poli, M. M., Raimondi, F., Albiero, D., Crapelli, G., Beck, E., Pota, V., Schiavone, V., Molin, A., Tarantino, F., Monti, G., Frati, E., Mirabella, L., Cinnella, G., Fossali, T., Colombo, R., Pattarino, P. T. I., Mojoli, F., Braschi, A., Borotto, E. E., Cracchiolo, A. N., Palma, D. M., Raponi, F., Foti, G., Vascotto, E. R., Coppadoro, A., Brazzi, L., Floris, L., Iotti, G. A., Venti, A., Yamaguchi, O., Takagi, S., Maeyama, H. N., Watanabe, E., Yamaji, Y., Shimizu, K., Shiozaki, K., Futami, S., Ryosuke, S., Saito, K., Kameyama, Y., Ueno, K., Izawa, M., Okuda, N., Suzuki, H., Harasawa, T., Nasu, M., Takada, T., Ito, F., Shin-Nunomiya, Andoh, K., Kusumoto, K., Hirata, A., Takaba, A., Kimura, H., Kansuke-Koyama, Abe, T., Honda, H., Aoki, N., Imai, H., Ogino, Y., Mizuguchi, I., Ichikado, K., Nitta, K., Mochizuki, K., Hashida, T., Tanaka, H., Nakamura, T., Niimi, D., Ueda, T., Kashiwa, Y., Uchiyama, A., Sabelnikovs, O., Oss, P., Haddad, Y., Liew, K. Y., Namendys-Silva, S. A., Jarquin-Badiola, Y. D., Sanchez-Hurtado, L. A., Gomez-Flores, S. S., Marin, M. C., Villagomez, A. J., Lemus, J. S., Fierro, J. M., Cervantes, M. R., Mejia, F. J. F., Dector, D., Dector, D. M., Gonzalez, D. R., Estrella, C. R., Sanchez-Medina, J. R., Ramirez-Gutierrez, A., George, F. G., Aguirre, J. S., Buensuseso, J. A., Poblano, M., Dendane, T., Balkhi, H., Elkhayari, M., Samkaoui, N., Ezzouine, H., Amor, A. B. M., Maazouzi, W., Cimic, N., Beck, O., Bruns, M. M., Schouten, J. A., Myra-Rinia, Van Wezel, H. M., Heines, S. J., Strauch, U., Buise, M. P., Simonis, F. D., Schultz, M. J., Goodson, J. C., Browne, T. S., Raaijmakers, M., Hunt, A., Hutchison, R. A., Bailey, M. B., Newby, L., Mcarthur, C., Kalkoff, M., Mcleod, A., Casement, J., Hacking, D. J., Andersen, F. H., Dolva, M. S., Barratt-Due, A., Noremark, K. A. L., Soreide, E., Sjobo, B. A., Guttormsen, A. B., Leon Yoshido, H. H., Aguilar, R. Z., Montes Oscanoa, F. A., Alisasis, A. U., Robles, J. B., Pasanting-Lim, R. A. B., Tan, B. C., Andruszkiewicz, P., Jakubowska, K., Coxo, C. M., Alvarez, A. M., Oliveira, B. S., Montanha, G. M., Barros, N. C., Pereira, C. S., Messias, A. M., Monteiro, J. M., Araujo, A. M., Catorze, N. T., Marum, S. M., Bouw, M. J., Gomes, R. M., Brito, V. A., Castro, S., Estilita, J. M., Barros, F. M., Serra, I. M., Martinho, A. M., Tomescu, D. R., Marcu, A., Bedreag, O. H., Papurica, M., Corneci, D. E., Negoita, S. I., Grigoriev, E., Gritsan, A. I., Gazenkampf, A. A., Almekhlafi, G., Albarrak, M. M., Mustafa, G. M., Maghrabi, K. A., Salahuddin, N., Aisa, T. M., Al Jabbary, A. S., Tabhan, E., Arabi, Y. M., Trinidad, O. A., Al Dorzi, H. M., Tabhan, E. E., Bolon, S., Smith, O., Mancebo, J., Aguirre-Bermeo, H., Lopez-Delgado, J. C., Esteve, F., Rialp, G., Forteza, C., De Haro, C., Artigas, A., Albaiceta, G. M., De Cima-Iglesias, S., Seoane-Quiroga, L., Ceniceros-Barros, A., Ruiz-Aguilar, A. L., Claraco-Vega, L. M., Soler, J. A., Del Carmen Lorente, M., Hermosa, C., Gordo, F., Miryam-Prieto-Gonzalez, Perez, M. P., Perez, C. P., Allue, R. M., Roche-Campo, F., Ibanez-Santacruz, M., Susana-Temprano, De Pablo, R., Gomez, P. R. A., Ruiz, S. R., Moles, S. I., Jurado, Mª. T., Arizmendi, A., Piacentini, E. A., Franco, N., Honrubia, T., Cheng, M. P., Losada, E. P., Javier-Blanco, Pintado, M. C., Cazorla-Barranquero, F. G., Alonso, J. G., Alda, R. S., Algaba, A., Navarro, G., Cereijo, E., Diaz-Rodriguez, E., Marcos, D. P., Montero, L. A., Para, L. H., Sanchez, R. J., Navalpotro, M. A. B., Abad, R. D., Gonz A Lez, R. M., Toribio, D. A. C. P., Castro, A. G., Artiga, M. J. D., Penuelas, O., Roser, T. P., Olga, M. F., Curto, E. G., Sanchez, R. M., Imma, V. P., Elisabet, G. M., Claverias, L., Magret, M., Pellicer, A. M., Rodriguez, L. L., Sanchez-Ballesteros, J., Gonzalez-Salamanca, A., Jimenez, A. G., Huerta, F. P., Sotillo Diaz, J. C. J., Lopez, E. B., Llinares Moya, D. D., Tallet Alfonso, A. A., Luis, P. S. E., Cesar, P. S., Rafael, S. I., Virgilio, C. G., Recio, N. N., Adamsson, R. O., Rylander, C. C., Holzgraefe, B., Broman, L. M., Wessbergh, J., Persson, L., Schioler, F., Kedelv, H., Tibblin, A. O., Appelberg, H., Hedlund, L., Helleberg, J., Eriksson, K. E., Glietsch, R., Larsson, N., Nygren, I., Nunes, S. L., Morin, A. -K., Kander, T., Adolfsson, A., Zender, H. O., Leemann-Refondini, C., Elatrous, S., Bouchoucha, S., Chouchene, I., Ouanes, I., Souissi, A. B., Kamoun, S., Demirkiran, O., Aker, M., Erbabacan, E., Ceylan, I., Girgin, N. K., Ozcelik, M., Unal, N., Meco, B. C., Akyol, O. O., Derman, S. S., Kennedy, B., Parhar, K., Srinivasa, L., Hopkins, P., Mellis, C., Kakar, V., Hadfield, D., Vercueil, A., Bhowmick, K., Humphreys, S. K., Ferguson, A., Mckee, R., Raj, A. S., Fawkes, D. A., Watt, P., Twohey, L., Jhamatthew Thomas, R. R., Morton, A., Kadaba, V., Smith, M. J., Hormis, A. P., Kannan, S. G., Namih, M., Reschreiter, H., Camsooksai, J., Kumar, A., Rugonfalvi, S., Nutt, C., O'Neill, O., Seasman, C., Dempsey, G., Scott, C. J., Ellis, H. E., Mckechnie, S., Hutton, P. J., Di Tomasso, N. N., Vitale, M. N., Griffin, R. O., Dean, M. N., Cranshaw, J. H., Willett, E. L., Ioannou, N., Gillis, S., Csabi, P., Macfadyen, R., Dawson, H., Preez, P. D., Williams, A. J., Boyd, O., De Gordoa, L. O. -R., Bramall, J., Symmonds, S., Chau, S. K., Wenham, T., Szakmany, T., Toth-Tarsoly, P., Mccalman, K. H., Alexander, P., Stephenson, L., Collyer, T., Chapman, R., Cooper, R., Allan, R. M., Sim, M., Wrathall, D. W., Irvine, D. A., Zantua, K. S., Adams, J. C., Burtenshaw, A. J., Sellors, G. P., Welters, I. D., Williams, K. E., Hessell, R. J., Oldroyd, M. G., Battle, C. E., Pillai, S., Kajtor, I., Sivashanmugavel, M., O'Kane, S. C., Donnelly, A., Frigyik, A. D., Careless, J. P., May, M. M., Stewart, R., Trinder, T. J., Hagan, S. J., Wise, M. P., Cole, J. M., Macfie, C. C., Dowling, A. T., Nunez, E., Pittini, G., Rodriguez, R., Imperio, M. C., Santos, C., Franca, A. G., Ebeid, A., Deicas, A., Serra, C., Uppalapati, A., Kamel, G., Banner-Goodspeed, V. M., Beitler, J. R., Mukkera, S. R., Kulkarni, S., Lee, J., Mesar, T., Shinn, J. O., Gomaa, D., Tainter, C., Yeatts, D. J., Warren, J., Lanspa, M. J., Miller, R. R., Grissom, C. K., Brown, S. M., Bauer, P. R., Gosselin, R. J., Kitch, B. T., Cohen, J. E., Beegle, S. H., Gueret, R. M., Tulaimat, A., Choudry, S., Stigler, W., Batra, H., Huff, N. G., Lamb, K. D., Oetting, T. W., Mohr, N. M., Judy, C., Saito, S., Kheir, F. M., Kheir, F., Schlichting, A. B., Delsing, A., Crouch, D. R., Elmasri, M., Ismail, D., Dreyer, K. R., Blakeman, T. C., Baron, R. M., Grijalba, C. Q., Hou, P. C., Seethala, R., Aisiku, I., Henderson, G., Frendl, G., Hou, S. -K., Owens, R. L., Schomer, A., Bumbasirevic, V., Jovanovic, B., Surbatovic, M., Veljovic, M., UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, UCL - (SLuc) Service de soins intensifs, Graduate School, Intensive Care Medicine, ACS - Heart failure & arrhythmias, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Madotto, F, Rezoagli, E, Pham, T, Schmidt, M, Mcnicholas, B, Protti, A, Panwar, R, Bellani, G, Fan, E, Van Haren, F, Brochard, L, Laffey, J, Pesenti, A, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Rubenfeld, G, Thompson, B, Wrigge, H, Slutsky, A, Rios, F, Sottiaux, T, Depuydt, P, Lora, F, Azevedo, L, Bugedo, G, Qiu, H, Gonzalez, M, Silesky, J, Cerny, V, Nielsen, J, Jibaja, M, Matamis, D, Ranero, J, Amin, P, Hashemian, S, Clarkson, K, Kurahashi, K, Villagomez, A, Zeggwagh, A, Heunks, L, Laake, J, Palo, J, Do Vale Fernandes, A, Sandesc, D, Arabi, Y, Bumbasierevic, V, Nin, N, Lorente, J, Piquilloud, L, Abroug, F, Mcnamee, L, Hurtado, J, Bajwa, E, Dempaire, G, Theresa, U, Sula, H, Nunci, L, Cani, A, Maria, V, Zazu, A, Dellera, C, Insaurralde, C, Alejandro, R, Daldin, J, Vinzio, M, Fernandez, R, Cardonnet, L, Bettini, L, Bisso, M, Osman, E, Setten, M, Lovazzano, P, Alvarez, J, Villar, V, Pozo, N, Grubissich, N, Plotnikow, G, Vasquez, D, Ilutovich, S, Tiribelli, N, Chena, A, Pellegrini, C, Saenz, M, Estenssoro, E, Brizuela, M, Gianinetto, H, Gomez, P, Cerrato, V, Bezzi, M, Borello, S, Loiacono, F, Fernandez, A, Knowles, S, Reynolds, C, Inskip, D, Miller, J, Kong, J, Whitehead, C, Bihari, S, Seven, A, Krstevski, A, Rodgers, H, Millar, R, Mckenna, T, Bailey, I, Hanlon, G, Aneman, A, Lynch, J, Azad, R, Neal, J, Woods, P, Roberts, B, Kol, M, Wong, H, Riss, K, Staudinger, T, Wittebole, X, Berghe, C, Bulpa, P, Dive, A, Verstraete, R, Lebbinck, H, Vermassen, J, Meersseman, P, Ceunen, H, Rosa, J, Beraldo, D, Piras, C, Rampinelli, A, Nassar, A, Mataloun, S, Moock, M, Thompson, M, Goncalves, C, Antonio, A, Ascoli, A, Biondi, R, Fontenele, D, Nobrega, D, Sales, V, Shindhe, S, Pg Hj Ismail, D, Beloncle, F, Davies, K, Cirone, R, Manoharan, V, Ismail, M, Goligher, E, Jassal, M, Nishikawa, E, Javeed, A, Curley, G, Rittayamai, N, Parotto, M, Ferguson, N, Mehta, S, Knoll, J, Pronovost, A, Canestrini, S, Bruhn, A, Garcia, P, Aliaga, F, Farias, P, Yumha, J, Ortiz, C, Salas, J, Saez, A, Vega, L, Labarca, E, Martinez, F, Carreno, N, Lora, P, Liu, H, Liu, L, Tang, R, Luo, X, An, Y, Zhao, H, Gao, Y, Zhai, Z, Ye, Z, Wang, W, Li, W, Li, Q, Zheng, R, Yu, W, Shen, J, Li, X, Yu, T, Lu, W, Wu, Y, Huang, X, He, Z, Lu, Y, Han, H, Zhang, F, Sun, R, Wang, H, Qin, S, Zhu, B, Zhao, J, Liu, J, Li, B, Zhou, F, Zhang, X, Li-Xin, Z, Xin-Hua, Q, Jiang, L, Zhao, X, Li, Y, Wang, C, Yao, Q, Yu, R, Chen, K, Shao, H, Qin, B, Huang, Q, Zhu, W, Hang, A, Hua, M, Xu, Y, Di, Y, Ling, L, Qin, T, Wang, S, Qin, J, Han, Y, Zhou, S, Vargas, M, Silesky Jimenez, J, Gonzalez Rojas, M, Solis-Quesada, J, Ramirez-Alfaro, C, Maca, J, Sklienka, P, Gjedsted, J, Christiansen, A, Villamagua, B, Llano, M, Burtin, P, Buzancais, G, Beuret, P, Pelletier, N, Mortaza, S, Mercat, A, Chelly, J, Jochmans, S, Terzi, N, Daubin, C, Carteaux, G, De Prost, N, Chiche, J, Daviaud, F, Fartoukh, M, Barberet, G, Biehler, J, Dellamonica, J, Doyen, D, Arnal, J, Briquet, A, Hraiech, S, Papazian, L, Follin, A, Roux, D, Messika, J, Kalaitzis, E, Dangers, L, Combes, A, Au, S, Beduneau, G, Carpentier, D, Zogheib, E, Dupont, H, Ricome, S, Santoli, F, Besset, S, Michel, P, Gelee, B, Danin, P, Goubaux, B, Crova, P, Phan, N, Berkelmans, F, Badie, J, Tapponnier, R, Gally, J, Khebbeb, S, Herbrecht, J, Schneider, F, Declercq, P, Rigaud, J, Duranteau, J, Harrois, A, Chabanne, R, Marin, J, Bigot, C, Thibault, S, Ghazi, M, Boukhazna, M, Zein, S, Richecoeur, J, Combaux, D, Grelon, F, Le Moal, C, Sauvadet, E, Robine, A, Lemiale, V, Reuter, D, Dres, M, Demoule, A, Goldgran-Toledano, D, Baboi, L, Guerin, C, Lohner, R, Krassler, J, Schafer, S, Zacharowski, K, Meybohm, P, Reske, A, Simon, P, Hopf, H, Schuetz, M, Baltus, T, Papanikolaou, M, Papavasilopoulou, T, Zacharas, G, Ourailogloy, V, Mouloudi, E, Massa, E, Nagy, E, Stamou, E, Kiourtzieva, E, Oikonomou, M, Avila, L, Cortez, C, Citalan, J, Jog, S, Sable, S, Shah, B, Gurjar, M, Baronia, A, Memon, M, Muthuchellappan, R, Ramesh, V, Shenoy, A, Unnikrishnan, R, Dixit, S, Rhayakar, R, Ramakrishnan, N, Bhardwaj, V, Mahto, H, Sagar, S, Palaniswamy, V, Ganesan, D, Jamaati, H, Heidari, F, Meaney, E, Nichol, A, Knapman, K, O'Croinin, D, Dunne, E, Breen, D, Jaafar, R, Dwyer, R, Amir, F, Ajetunmobi, O, O'Muircheartaigh, A, Black, C, Treanor, N, Collins, D, Altaf, W, Zani, G, Fusari, M, Spadaro, S, Volta, C, Graziani, R, Brunettini, B, Palmese, S, Formenti, P, Umbrello, M, Lombardo, A, Pecci, E, Botteri, M, Savioli, M, Mattei, A, Schiavoni, L, Tinnirello, A, Todeschini, M, Giarratano, A, Cortegiani, A, Sher, S, Rossi, A, Antonelli, M, Montini, L, Casalena, P, Scafetti, S, 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Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam-Prieto-González, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran Roche-Campo, Marcos Ibañez-Santacruz, Susana-Temprano, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier-Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel Gonz Á Lez, D Á Cil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Richard O Adamsson, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R JhaMatthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla O'Neill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz De Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C O'Kane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Matt P Wise, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, Jarone Lee, Tomaz Mesar, John O Shinn 3rd, Dina Gomaa, Christopher Tainter, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Madotto F, Rezoagli E, Pham T, Schmidt M, McNicholas B, Protti A, Panwar R, Bellani G, Fan E, van Haren F, Brochard L, Laffey JG, and LUNG SAFE Investigators and the ESICM Trials Group, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Renaud M Gueret, Aiman Tulaimat, Shazia Choudry, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baron, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Vesna Bumbasirevic, Bojan Jovanovic, Maja Surbatovic, Milic Veljovic
Subjects: ARDS, medicine.medical_treatment, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Hyperoxemia, Hypoxemia, law.invention, 0302 clinical medicine, law, Fraction of inspired oxygen, Oxygen therapy, Prevalence, Medicine, Hypoxia, Acute respiratory distress syndrome, Hyperoxia, Invasive mechanical ventilation, Mortality, Respiratory Distress Syndrome, Hyperbaric Oxygenation, Respiration, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Intensive care unit, Intensive Care Units, Anesthesia, Artificial, medicine.symptom, Human, Artificial ventilation, Intensive Care Unit, NO, 03 medical and health sciences, Intensive care, Settore MED/41 - ANESTESIOLOGIA, Humans, business.industry, Research, Respiratory Distress Syndrome, Adult, lcsh:RC86-88.9, medicine.disease, Respiration, Artificial, respiratory tract diseases, Oxygen, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030228 respiratory system, business
Abstract: Background Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55–100 mmHg) patients (P = 0.47). Conclusions Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073
Published: 2020

50. Pulmonary infections prime the development of subsequent ICU-acquired pneumonia in septic shock

Author: Jérôme Lambert, Matthieu Jamme, Charles de Roquetaillade, Jean-Paul Mira, Frédéric Pène, Jean-Daniel Chiche, Alain Cariou, Julien Charpentier, Aïcha Gassama, and Jean-François Llitjos
Subjects: medicine.medical_specialty, health care facilities, manpower, and services, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, Nosocomial infection, law, Septic shock, medicine, Risk factor, First episode, Proportional hazards model, business.industry, Incidence (epidemiology), Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, Retrospective cohort study, lcsh:RC86-88.9, medicine.disease, Intensive care unit, Pneumonia, 030228 respiratory system, Emergency medicine, Ventilator-acquired pneumonia, business, Immunosuppression
Abstract: Purpose To investigate the determinants and the prognosis of intensive care unit (ICU)-acquired pneumonia in patients with septic shock. Methods This single-center retrospective study was conducted in a medical ICU in a tertiary care center from January 2008 to December 2016. All consecutive patients diagnosed for septic shock within the first 48 h of ICU admission were included. Patients were classified in three groups: no ICU-acquired infections (no ICU-AI), ICU-acquired pneumonia and non-pulmonary ICU-AI. The determinants of ICU-acquired pneumonia and death were investigated by multivariate competitive risk analysis. Results A total of 1021 patients were admitted for septic shock, and 797 patients were alive in the ICU after 48 h of management. The incidence of a first episode of ICU-AI was 31%, distributed into pulmonary (17%) and non-pulmonary ICU-AI (14%). Patients with septic shock caused by pneumonia were at increased risk of further pulmonary ICU-AI with a cumulated incidence of 34.4%. A pulmonary source of the initial septic shock was an independent risk factor for subsequent ICU-acquired pneumonia (cause-specific hazard 2.33, 95% confidence interval [1.55–3.52], p
Published: 2019

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