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RATIONALE: The use of noninvasive ventilation (NIV) as an early weaning/extubation technique from mechanical ventilation remains controversial. OBJECTIVES: To investigate NIV effectiveness as an early weaning/extubation technique in difficult-to-wean patients with chronic hypercapnic respiratory failure (CHRF). METHODS: In 13 intensive care units, 208 patients with CHRF intubated for acute respiratory failure (ARF) who failed a first spontaneous breathing trial were randomly assigned to three groups: conventional invasive weaning group (n = 69), extubation followed by standard oxygen therapy (n = 70), or NIV (n = 69). NIV was permitted as rescue therapy for both non-NIV groups if postextubation ARF occurred. Primary endpoint was reintubation within 7 days after extubation. Secondary endpoints were: occurrence of postextubation ARF or death within 7 days after extubation, use of rescue postextubation NIV, weaning time, and patient outcomes. MEASUREMENTS AND MAIN RESULTS: Reintubation rates were 30, 37, and 32% for invasive weaning, oxygen-therapy, and NIV groups, respectively (P = 0.654). Weaning failure rates, including postextubation ARF, were 54, 71, and 33%, respectively (P < 0.001). Rescue NIV success rates for invasive and oxygen-therapy groups were 45 and 58%, respectively (P = 0.386). By design, intubation duration was 1.5 days longer for the invasive group than in the two others. Apart from a longer weaning time in NIV than in invasive group (2.5 vs. 1.5 d; P = 0.033), no significant outcome difference was observed between groups. CONCLUSIONS: No difference was found in the reintubation rate between the three weaning strategies. NIV decreases the intubation duration and may improve the weaning results in difficult-to-wean patients with CHRF by reducing the risk of postextubation ARF. The benefit of rescue NIV in these patients deserves confirmation. [ABSTRACT FROM AUTHOR]

Context: The need for lung protection is universally accepted, but the optimal level of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) or acute respiratory distress syndrome remains debated.Objective: To compare the effect on outcome of a strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation to one aimed at minimizing alveolar distension in patients with ALI.Design, Setting, and Patients: A multicenter randomized controlled trial of 767 adults (mean [SD] age, 59.9 [15.4] years) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005.Intervention: Tidal volume was set at 6 mL/kg of predicted body weight in both strategies. Patients were randomly assigned to a moderate PEEP strategy (5-9 cm H(2)O) (minimal distension strategy; n = 382) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O (increased recruitment strategy; n = 385).Main Outcome Measures: The primary end point was mortality at 28 days. Secondary end points were hospital mortality at 60 days, ventilator-free days, and organ failure-free days at 28 days.Results: The 28-day mortality rate in the minimal distension group was 31.2% (n = 119) vs 27.8% (n = 107) in the increased recruitment group (relative risk, 1.12 [95% confidence interval, 0.90-1.40]; P = .31). The hospital mortality rate in the minimal distension group was 39.0% (n = 149) vs 35.4% (n = 136) in the increased recruitment group (relative risk, 1.10 [95% confidence interval, 0.92-1.32]; P = .30). The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days (7 [interquartile range {IQR}, 0-19] vs 3 [IQR, 0-17]; P = .04) and organ failure-free days (6 [IQR, 0-18] vs 2 [IQR, 0-16]; P = .04). This strategy also was associated with higher compliance values, better oxygenation, less use of adjunctive therapies, and larger fluid requirements.Conclusions: A strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality. However, it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure.Trial Registration: clinicaltrials.gov Identifier: NCT00188058. [ABSTRACT FROM AUTHOR]

Background: Limited data are available on long-term respiratory disabilities in patients following acute COVID-19., Patients and Methods: This prospective, monocentric, observational cohort study included patients admitted to our hospital with acute COVID-19 between 12 March and 24 April 2020. Clinical, functional and radiological data were collected up to 28 months after hospital discharge., Results: Among 715 patients hospitalised for COVID-19, 493 (69.0%) were discharged alive. We could access complete medical records for 268 out of 493 patients (54.4%); 138 out of 268 (51.5%) exhibited persistent respiratory symptoms and agreed with the data collection and follow-up. Patients were predominantly male (64.5%), with a mean±sd age of 58.9±15.3 years. At the last follow-up, the leading symptoms were asthenia (31.5%), dyspnoea (29.8%) and neuropsychological symptoms (17.7%). Lung function improved up to the last visit. Mean diffusing capacity of the lung for carbon monoxide ( D LCO ) was 77.8% of predicted value, total lung capacity (TLC) was 83.5% and O 2 desaturation during exercise (O 2 desaturation) was 2.3%. While D LCO improved over the entire period, TLC improved in the early phase and O 2 desaturation in the late phase. Except for those with lung comorbidities, only one patient presented with minor functional and chest radiological alterations at 28 months., Conclusion: Patients with acute COVID-19 discharged alive showed improved clinical symptoms, lung function parameters and radiological signs up to 28 months post-infection. Persistent symptoms consisted mainly of asthenia and dyspnoea, with lung function returning to normal. One patient without prior respiratory issues exhibited moderate pulmonary fibrosis., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2024.)

Background: Acute exacerbations of COPD (AECOPD) are common and significantly contribute to mortality in patients with COPD. Prognostic scores can assist clinicians in making tailored decisions to manage AECOPD. In the current study, we therefore aimed to evaluate the performance of the Noninvasive Ventilation Outcomes (NIVO) score, originally designed to assess in-ICU mortality, in predicting 1 year mortality and NIV failure in AECOPD., Methods: This retrospective study analyzed data from patients hospitalized for AECOPD requiring mechanical ventilation between January 1st, 2018, and December 31st, 2022. Mortality was assessed at the end of ICU stay and 1 year after admission, while NIV failure was defined as intubation or death without intubation., Results: Among 302 ICU admissions of COPD patients, 190 patients with AECOPD requiring mechanical ventilation were included. Of these, 44 (23%) died in the ICU, 62 out of 184 (34%) failed NIV, and 78 (41%) died within 1 year of admission. Patients who died in ICU or experienced NIV failure had more severe COPD and more impaired blood gas parameters at admission. The NIVO score demonstrated an AUC of 0.68 in predicting 1-year mortality and an AUC of 0.85 in predicting NIV failure. A NIVO score over 7 was associated with higher 1-year mortality and NIV failure (HR of 4.4 [1.8-10.9] and 41.6 [5.6-307.9], respectively)., Conclusion: Beyond predicting in-ICU mortality, the NIVO-score is a reliable tool in predicting 1-year mortality and NIV failure in AECOPD., (© 2024. The Author(s).)

Purpose: The aim of this study was to compare the effect of a pressure-controlled strategy allowing non-synchronised unassisted spontaneous ventilation (PC-SV) to a conventional volume assist-control strategy (ACV) on the outcome of patients with acute respiratory distress syndrome (ARDS)., Methods: Open-label randomised clinical trial in 22 intensive care units (ICU) in France. Seven hundred adults with moderate or severe ARDS (PaO 2 /FiO 2  < 200 mmHg) were enrolled from February 2013 to October 2018. Patients were randomly assigned to PC-SV (n = 348) or ACV (n = 352) with similar objectives of tidal volume (6 mL/kg predicted body weight) and positive end-expiratory pressure (PEEP). Paralysis was stopped after 24 h and sedation adapted to favour patients' spontaneous ventilation. The primary endpoint was in-hospital death from any cause at day 60., Results: Hospital mortality [34.6% vs 33.5%, p = 0.77, risk ratio (RR) = 1.03 (95% confidence interval [CI] 0.84-1.27)], 28-day mortality, as well as the number of ventilator-free days and organ failure-free days at day 28 did not differ between PC-SV and ACV groups. Patients in the PC-SV group received significantly less sedation and neuro-muscular blocking agents than in the ACV group. A lower proportion of patients required adjunctive therapy of hypoxemia (including prone positioning) in the PC-SV group than in the ACV group [33.1% vs 41.3%, p = 0.03, RR = 0.80 (95% CI 0.66-0.98)]. The incidences of pneumothorax and refractory hypoxemia did not differ between the groups., Conclusions: A strategy based on PC-SV mode that favours spontaneous ventilation reduced the need for sedation and adjunctive therapies of hypoxemia but did not significantly reduce mortality compared to ACV with similar tidal volume and PEEP levels., (© 2024. The Author(s).)

Introduction: The monitoring of unfractionated heparin (UFH) by anti-factor Xa activity (AXA) is commonly used to ensure effective anticoagulation and prevent bleeding risk. However, in patients previously treated with an anti-Xa direct oral anticoagulant (DOAC) switching to UFH therapy, there is a risk of interference that may lead to inappropriate anticoagulation. The first objective of this study was to validate DOAC-Remove to remove DOAC for measuring UFH specific AXA. The second objective was to assess the length of DOAC interference on UFH monitoring and to identify potential predictive factors., Materials and Methods: This monocentric retrospective study included all patients admitted from April 2019 to April 2021 previously treated with anti-Xa DOAC, and for whom an interference on UFH monitoring was suspected. Interference was defined as a difference in the AXA measured before and after using DOAC-Remove >2.8-fold standard deviation of the method., Results: Removal with DOAC-Remove was specific of DOAC (apixaban n = 42, rivaroxaban n = 41, UFH n = 20) and sufficient to avoid interference on UFH AXA measurement. The exact interference length was 6.0 days [IQR 3.0-11.0] for apixaban (n = 26) and 4.5 days [IQR 2.0-5.8] for rivaroxaban (n = 20). Among the 89 patients sorted based on an interference length ≤ or >3 days, 74 (83.1%) presented an interference greater than 3 days. Correlations were observed with age for apixaban and creatinine for rivaroxaban., Conclusions: Our results suggest that DOAC-Remove could be of high interest in patients receiving UFH previously treated with an anti-Xa DOAC even if DOAC was stopped for more than 3 days., (© 2024 John Wiley & Sons Ltd.)

Background: Hypoxic ischemic brain injury (HIBI) induced by cardiac arrest (CA) seems to predominate in cortical areas and to a lesser extent in the brainstem. These regions play key roles in modulating the activity of the autonomic nervous system (ANS), that can be assessed through analyses of heart rate variability (HRV). The objective was to evaluate the prognostic value of various HRV parameters to predict neurological outcome after CA., Methods: Retrospective monocentric study assessing the prognostic value of HRV markers and their association with HIBI severity. Patients admitted for CA who underwent EEG for persistent coma after CA were included. HRV markers were computed from 5 min signal of the ECG lead of the EEG recording. HRV indices were calculated in the time-, frequency-, and non-linear domains. Frequency-domain analyses differentiated very low frequency (VLF 0.003-0.04 Hz), low frequency (LF 0.04-0.15 Hz), high frequency (HF 0.15-0.4 Hz), and LF/HF ratio. HRV indices were compared to other prognostic markers: pupillary light reflex, EEG, N20 on somatosensory evoked potentials (SSEP) and biomarkers (neuron specific enolase-NSE). Neurological outcome at 3 months was defined as unfavorable in case of best CPC 3-4-5., Results: Between 2007 and 2021, 199 patients were included. Patients were predominantly male (64%), with a median age of 60 [48.9-71.7] years. 76% were out-of-hospital CA, and 30% had an initial shockable rhythm. Neurological outcome was unfavorable in 73%. Compared to poor outcome, patients with a good outcome had higher VLF (0.21 vs 0.09 ms 2 /Hz, p < 0.01), LF (0.07 vs 0.04 ms 2 /Hz, p = 0.003), and higher LF/HF ratio (2.01 vs 1.01, p = 0.008). Several non-linear domain indices were also higher in the good outcome group, such as SD2 (15.1 vs 10.2, p = 0.016) and DFA α1 (1.03 vs 0.78, p = 0.002). These indices also differed depending on the severity of EEG pattern and abolition of pupillary light reflex. These time-frequency and non-linear domains HRV parameters were predictive of poor neurological outcome, with high specificity despite a low sensitivity., Conclusion: In comatose patients after CA, some HRV markers appear to be associated with unfavorable outcome, EEG severity and PLR abolition, although the sensitivity of these HRV markers remains limited., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

COVID-19 and infectious diseases have been included in strategic development goals (SDG) of United Nations (UN). The SARS-CoV-2 pandemic has unveiled complex pathophysiological mechanisms underpinning COVID-19, notably inducing a systemic acquired vascular hemopathy characterized by endothelial dysfunction and intussusceptive angiogenesis, a rapid vascular remodeling process identified as a hallmark in severe COVID-19 cases affecting pulmonary and cardiac tissues. Stem cell migration have been proposed as significant regulators of this neoangiogenic process. In a monocentric cross-sectional study, through spectral flow cytometry analysis of peripheral blood mononuclear cells, we identified a distinct stem cell subpopulation mobilized in critical COVID-19. Indeed, by an unsupervised analysis generating a UMAP representation we highlighted eleven different clusters in critical and non-critical COVID-19 patients. Only one cluster was significantly associated to critical COVID-19 compared to non-critical patients. This cluster expressed the markers: CD45dim, CD34+, CD117+, CD147+, and CD143+, and were negative for CD133. Higher level of expression of hemangioblast markers CD143 were found in critical COVID-19 patients. This population, indicative of hemangioblast-like cells, suggests a key role in COVID-19-related neoangiogenesis, potentially driving the severe vascular complications observed. Our findings underscore the need for further investigation into the contributions of adult stem cells in COVID-19 pathology, offering new insights into therapeutic targets and interventions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Disclosure: J.-L.D. reports grants and nonfinancial research support from ALung, nonfinancial research support from General Electric Healthcare, and personal fees and nonfinancial research support from Xenios/Novalung (Fresenius Medical Care), all outside the submitted work. D.M.S. reports personal fees from Carmat and Léo Pharma all outside the submitted work. The other authors have no conflicts of interest to report.

Background: Ageing leads to altered immune responses, resulting in higher susceptibility to certain infections in the elderly. Immune ageing is a heterogeneous process also associated with inflammaging, a low-grade chronic inflammation. Altered cytotoxic T cell responses and cytokine storm have previously been described in severe COVID-19 cases, however the parameters responsible for such immune response failures are not well known. The aim of our study was to characterize CD8 + T cells and cytokines associated with ageing, in a cohort of patients aged over 70 years stratified by COVID-19 severity., Results: One hundred and four patients were included in the study. We found that, in older people, COVID-19 severity was associated with (i) higher level of GM-CSF, CXCL10 (IP-10), VEGF, IL-1β, CCL2 (MCP-1) and the neutrophil to lymphocyte ratio (NLR), (ii) increased terminally differentiated CD8 + T cells, and (ii) decreased early precursors CD8 + T stem cell-like memory cells (TSCM) and CD27 + CD28 + . The cytokines mentioned above were found at higher concentrations in the COVID-19 + older cohort compared to a younger cohort in which they were not associated with disease severity., Conclusions: Our results highlight the particular importance of the myeloid lineage in COVID-19 severity among older people. As GM-CSF and CXCL10 were not associated with COVID-19 severity in younger patients, they may represent disease severity specific markers of ageing and should be considered in older people care., (© 2024. The Author(s).)

Camera traps became the main observational method of a myriad of species over large areas. Data sets from camera traps can be used to describe the patterns and monitor the occupancy, abundance, and richness of wildlife, essential information for conservation in times of rapid climate and land-cover changes. Habitat loss and poaching are responsible for historical population losses of mammals in the Atlantic Forest biodiversity hotspot, especially for medium to large-sized species. Here we present a data set from camera trap surveys of medium to large-sized native mammals (>1 kg) across the Atlantic Forest. We compiled data from 5380 ground-level camera trap deployments in 3046 locations, from 2004 to 2020, resulting in 43,068 records of 58 species. These data add to existing data sets of mammals in the Atlantic Forest by including dates of camera operation needed for analyses dealing with imperfect detection. We also included, when available, information on important predictors of detection, namely the camera brand and model, use of bait, and obstruction of camera viewshed that can be measured from example pictures at each camera location. Besides its application in studies on the patterns and mechanisms behind occupancy, relative abundance, richness, and detection, the data set presented here can be used to study species' daily activity patterns, activity levels, and spatiotemporal interactions between species. Moreover, data can be used combined with other data sources in the multiple and expanding uses of integrated population modeling. An R script is available to view summaries of the data set. We expect that this data set will be used to advance the knowledge of mammal assemblages and to inform evidence-based solutions for the conservation of the Atlantic Forest. The data are not copyright restricted; please cite this paper when using the data., (© 2024 The Ecological Society of America.)

Background: The STROMA-CoV-2 study was a French phase 2b, multicenter, double-blind, randomized, placebo-controlled clinical trial that did not identify a significant efficacy of umbilical cord-derived mesenchymal stromal cells in patients with SARS-CoV-2-induced acute respiratory distress syndrome. Safety on day 28 was found to be good. The aim of our extended study was to assess the 6- and 12-month safety of UC-MSCs administration in the STROMA-CoV-2 cohort., Methods: A detailed multi-domain assessment was conducted at 6 and 12 months following hospital discharge focusing on adverse events, lung computed tomography-scan, pulmonary and muscular functional status, and quality of life in the STROMA-CoV-2 cohort including SARS-CoV-2-related early (< 96 h) mild-to-severe acute respiratory distress syndrome., Results: Between April 2020 and October 2020, 47 patients were enrolled, of whom 19 completed a 1-year follow-up. There were no significant differences in any endpoints or adverse effects between the UC-MSCs and placebo groups at the 6- and 12-month assessments. Ground-glass opacities persisted at 1 year in 5 patients (26.3%). Furthermore, diffusing capacity for carbon monoxide remained altered over 1 year, although no patient required oxygen or non-invasive ventilatory support. Quality of life revealed declines in mental, emotional and physical health throughout the follow-up period, and the six-minute walking distance remained slightly impaired at the 1-year patient assessment., Conclusions: This study suggests a favorable safety profile for the use of intravenous UC-MSCs in the context of the first French wave of SARS-CoV-2-related moderate-to-severe acute respiratory distress syndrome, with no adverse effects observed at 1 year., (© 2024. The Author(s).)

Objective: To investigate autonomic nervous system activity measured by brain-heart interactions in comatose patients after cardiac arrest in relation to the severity and prognosis of hypoxic-ischemic brain injury., Methods: Strength and complexity of bidirectional interactions between EEG frequency bands (delta, theta, and alpha) and ECG heart rate variability frequency bands (low frequency, LF and high frequency, HF) were computed using a synthetic data generation model. Primary outcome was the severity of brain injury, assessed by (i) standardized qualitative EEG classification, (ii) somatosensory evoked potentials (N20), and (iii) neuron-specific enolase levels. Secondary outcome was the 3-month neurological status, assessed by the Cerebral Performance Category score [good (1-2) vs. poor outcome (3-4-5)]., Results: Between January 2007 and July 2021, 181 patients were admitted to ICU for a resuscitated cardiac arrest. Poor neurological outcome was observed in 134 patients (74%). Qualitative EEG patterns suggesting high severity were associated with decreased LF/HF. Severity of EEG changes were proportional to higher absolute values of brain-to-heart coupling strength (p < 0.02 for all brain-to-heart frequencies) and lower values of alpha-to-HF complexity (p = 0.049). Brain-to-heart coupling strength was significantly higher in patients with bilateral absent N20 and correlated with neuron-specific enolase levels at Day 3. This aberrant brain-to-heart coupling (increased strength and decreased complexity) was also associated with 3-month poor neurological outcome., Interpretation: Our results suggest that autonomic dysfunctions may well represent hypoxic-ischemic brain injury post cardiac arrest pathophysiology. These results open avenues for integrative monitoring of autonomic functioning in critical care patients., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Purpose: There is a growing interest in the quality of work life (QWL) of healthcare professionals and staff well-being. We decided to measure the perceived QWL of ICU physicians and the factors that could influence their perception. Methods: We performed a survey coordinated and executed by the French Trade Union of Intensive Care Physicians (SMR). QWL was assessed using the French version of the Work-Related Quality of Life (WRQoL) scale, perceived stress using the French version of 10 item-Perceived Stress Scale (PSS-10) and group functioning using the French version of the Reflexivity Scale, the Social Support at Work Questionnaire (QSSP-P). Results: 308 French-speaking ICU physicians participated. 40% perceived low WRQoL, mainly due to low general well-being, low satisfaction with working conditions and low possibility of managing the articulation between their private and professional lives. Decreased QWL was associated with being a woman (p = .002), having children (p = .022) and enduring many monthly shifts (p = .022). Conclusions: This work highlights the fact that ICU physicians feel a significant imbalance between the demands of their profession and the resources at their disposal. Communication and exchanges within a team and quality of social support appear to be positive elements to maintain and/or develop within our structures., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article: N. Terzi reports personal fees from Pfizer outside the submitted work. None of the other authors have any competing interests to disclose.

Background: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent clinical symptoms following COVID-19., Objective: To correlate biomarkers of endothelial dysfunction with persistent clinical symptoms and pulmonary function defects at distance from COVID-19., Methods: Consecutive patients with long COVID-19 suspicion were enrolled. A panel of endothelial biomarkers was measured in each patient during clinical evaluation and pulmonary function test (PFT)., Results: The study included 137 PASC patients, mostly male (68%), with a median age of 55 years. A total of 194 PFTs were performed between months 3 and 24 after an episode of SARS-CoV-2 infection. We compared biomarkers evaluated in PASC patients with 20 healthy volunteers (HVs) and acute hospitalized COVID-19 patients (n = 88). The study found that angiogenesis-related biomarkers and von Willebrand factor (VWF) levels were increased in PASC patients compared to HVs without increased inflammatory or platelet activation markers. Moreover, VEGF-A and VWF were associated with persistent lung CT scan lesions and impaired diffusing capacity of the lungs for carbon monoxide (DLCO) measurement. By employing a Cox proportional hazards model adjusted for age, sex, and body mass index, we further confirmed the accuracy of VEGF-A and VWF. Following adjustment, VEGF-A emerged as the most significant predictive factor associated with persistent lung CT scan lesions and impaired DLCO measurement., Conclusion: VEGF-A is a relevant predictive factor for DLCO impairment and radiological sequelae in PASC. Beyond being a biomarker, we hypothesize that the persistence of angiogenic disorders may contribute to long COVID symptoms., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Recently, the tiger-cat species complex was split into Leopardus tigrinus and Leopardus guttulus, along with other proposed schemes. We performed a detailed analysis integrating ecological modeling, biogeography, and phenotype of the four originally recognized subspecies-tigrinus, oncilla, pardinoides, guttulus-and presented a new multidimensional niche depiction of the species. Species distribution models used > 1400 records from museums and photographs, all checked for species accuracy. Morphological data were obtained from institutional/personal archives. Spotting patterns were established by integrating museum and photographic/camera-trap records. Principal component analysis showed three clearly distinct groups, with the Central American specimens (oncilla) clustering entirely within those of the Andes, namely the pardinoides group of the cloud forests of the southern Central-American and Andean mountain chains (clouded tiger-cat); the tigrinus group of the savannas of the Guiana Shield and central/northeastern Brazil (savanna tiger-cat); and the guttulus group in the lowland forests of the Atlantic Forest domain (Atlantic Forest tiger-cat). This scheme is supported by recent genetic analyses. All species displayed different spotting patterns, with some significant differences in body measurements/proportions. The new distribution presented alarming reductions from the historic range of - 50.4% to - 68.2%. This multidimensional approach revealed a new species of the elusive and threatened tiger-cat complex., (© 2024. The Author(s).)

Background: Epinephrine increases the chances of return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA), especially when the initial rhythm is non-shockable. However, this drug could also worsen the post-resuscitation syndrome (PRS). We assessed the association between epinephrine use during cardiopulmonary resuscitation (CPR) and subsequent intensive care unit (ICU) mortality in patients with ROSC after non-shockable OHCA., Methods: We used data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (capturing OHCA data located in the Greater Paris area, France) between May 2011 and December 2021. All adults with ROSC after medical, cardiac and non-cardiac causes, non-shockable OHCA admitted to an ICU were included. The mode of death in the ICU was categorized as cardiocirculatory, neurological, or other., Results: Of the 2,792 patients analyzed, there were 242 (8.7%) survivors at hospital discharge, 1,004 (35.9%) deaths from cardiocirculatory causes, 1,233 (44.2%) deaths from neurological causes, and 313 (11.2%) deaths from other etiologies. The cardiocirculatory death group received more epinephrine (4.6 ± 3.8 mg versus 1.7 ± 2.8 mg, 3.2 ± 2.6 mg, and 3.5 ± 3.6 mg for survivors, neurological deaths, and other deaths, respectively; p < 0.001). The proportion of cardiocirculatory death increased linearly (R 2  = 0.92, p < 0.001) with cumulative epinephrine doses during CPR (17.7% in subjects who did not receive epinephrine and 62.5% in those who received > 10 mg). In multivariable analysis, a cumulative dose of epinephrine was strongly associated with cardiocirculatory death (adjusted odds ratio of 3.45, 95% CI [2.01-5.92] for 1 mg of epinephrine; 12.28, 95% CI [7.52-20.06] for 2-5 mg; and 23.71, 95% CI [11.02-50.97] for > 5 mg; reference 0 mg; population reference: alive at hospital discharge), even after adjustment on duration of resuscitation. The other modes of death (neurological and other causes) were also associated with epinephrine use, but to a lesser extent., Conclusions: In non-shockable OHCA with ROSC, the dose of epinephrine used during CPR is strongly associated with early cardiocirculatory death. Further clinical studies aimed at limiting the dose of epinephrine during CPR seem warranted. Moreover, strategies for the prevention and management of PRS should take this dose of epinephrine into consideration for future trials., (© 2023. The Author(s).)

Background: Despite advances in asthma treatments, severe asthma exacerbation (SAE) remains a life-threatening condition in adults, and there is a lack of data derived from adult patients admitted to intensive care units (ICUs) for SAE. The current study investigated changes in adult patient characteristics, management, and outcomes of SAE over a 20-year period in 40 ICUs in the greater Paris area., Methods: In this retrospective observational study, admissions to 40 ICUs in the greater Paris area for SAE from January 1, 1997, to December 31, 2016 were analyzed. The primary outcome was the proportion of ICU admissions for SAE during 5-year periods. Secondary outcomes were ICU and hospital mortality, and the use of mechanical ventilation and catecholamine. Multivariate analysis was performed to assess factors associated with ICU mortality., Results: A total of 7049 admissions for SAE were recorded. For each 5-year period, the proportion decreased over time, with SAE accounting for 2.84% of total ICU admissions ( n =2841) between 1997 and 2001, 1.76% ( n =1717) between 2002 and 2006, 1.05% ( n =965) between 2007 and 2011, and 1.05% ( n =1526) between 2012 and 2016. The median age was 46 years (interquartile range [IQR]: 32-59 years), 55.41% were female, the median Simplified Acute Physiology Score II was 20 (IQR: 13-28), and 19.76% had mechanical ventilation. The use of mechanical ventilation remained infrequent throughout the 20-year period, whereas the use of catecholamine decreased. ICU and hospital mortality rates decreased. Factors associated with ICU mortality were renal replacement therapy, catecholamine, cardiac arrest, pneumothorax, acute respiratory distress syndrome, sepsis, and invasive mechanical ventilation (IMV). Non-survivors were older, had more severe symptoms, and were more likely to have received IMV., Conclusion: ICU admission for SAE remains uncommon, and the proportion of cases decreased over time. Despite a slight increase in symptom severity during a 20-year period, ICU and hospital mortality decreased. Patients requiring IMV had a higher mortality rate., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: Restoring plasma arginine levels through enteral administration of L-citrulline in critically ill patients may improve outcomes. We aimed to evaluate whether enteral L-citrulline administration reduced organ dysfunction based on the Sequential Organ Failure Assessment (SOFA) score and affected selected immune parameters in mechanically ventilated medical intensive care unit (ICU) patients., Methods: A randomized, double-blind, multicenter clinical trial of enteral administration of L-citrulline versus placebo for critically ill adult patients under invasive mechanical ventilation without sepsis or septic shock was conducted in four ICUs in France between September 2016 and February 2019. Patients were randomly assigned to receive enteral L-citrulline (5 g) every 12 h for 5 days or isonitrogenous, isocaloric placebo. The primary outcome was the SOFA score on day 7. Secondary outcomes included SOFA score improvement (defined as a decrease in total SOFA score by 2 points or more between day 1 and day 7), secondary infection acquisition, ICU length of stay, plasma amino acid levels, and immune biomarkers on day 3 and day 7 (HLA-DR expression on monocytes and interleukin-6)., Results: Of 120 randomized patients (mean age, 60 ± 17 years; 44 [36.7%] women; ICU stay 10 days [IQR, 7-16]; incidence of secondary infections 25 patients (20.8%)), 60 were allocated to L-citrulline and 60 were allocated to placebo. Overall, there was no significant difference in organ dysfunction as assessed by the SOFA score on day 7 after enrollment (4 [IQR, 2-6] in the L-citrulline group vs. 4 [IQR, 2-7] in the placebo group; Mann‒Whitney U test, p = 0.9). Plasma arginine was significantly increased on day 3 in the treatment group, while immune parameters remained unaffected., Conclusion: Among mechanically ventilated ICU patients without sepsis or septic shock, enteral L-citrulline administration did not result in a significant difference in SOFA score on day 7 compared to placebo., Trial Registration: ClinicalTrials.gov Identifier NCT02864017 (date of registration: 11 August 2016)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Long-term outcomes of patients with severe stroke remain poorly documented. We aimed to characterize one-year outcomes of patients with stroke requiring mechanical ventilation in the intensive care unit (ICU)., Methods: We conducted a prospective multicenter cohort study in 33 ICUs in France (2017-2019) on patients with consecutive strokes requiring mechanical ventilation for at least 24 hours. Outcomes were collected via telephone interviews by an independent research assistant. The primary end point was poor functional outcome, defined by a modified Rankin Scale score of 4 to 6 at 1 year. Multivariable mixed models investigated variables associated with the primary end point. Secondary end points included quality of life, activities of daily living, and anxiety and depression in 1-year survivors., Results: Among the 364 patients included, 244 patients (66.5% [95% CI, 61.7%-71.3%]) had a poor functional outcome, including 190 deaths (52.2%). After adjustment for non-neurological organ failure, age ≥70 years (odds ratio [OR], 2.38 [95% CI, 1.26-4.49]), Charlson comorbidity index ≥2 (OR, 2.01 [95% CI, 1.16-3.49]), a score on the Glasgow Coma Scale <8 at ICU admission (OR, 3.43 [95% CI, 1.98-5.96]), stroke subtype (intracerebral hemorrhage: OR, 2.44 [95% CI, 1.29-4.63] versus ischemic stroke: OR, 2.06 [95% CI, 1.06-4.00] versus subarachnoid hemorrhage: reference) remained independently associated with poor functional outcome. In contrast, a time between stroke diagnosis and initiation of mechanical ventilation >1 day was protective (OR, 0.56 [95% CI, 0.33-0.94]). A sensitivity analysis conducted after exclusion of patients with early decisions of withholding/withdrawal of care yielded similar results. We observed persistent physical and psychological problems at 1 year in >50% of survivors., Conclusions: In patients with severe stroke requiring mechanical ventilation, several ICU admission variables may inform caregivers, patients, and their families on post-ICU trajectories and functional outcomes. The burden of persistent sequelae at 1 year reinforces the need for a personalized, multi-disciplinary, prolonged follow-up of these patients after ICU discharge., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03335995., Competing Interests: Disclosures Dr Sonneville reports grants from the French Ministry of Health, outside the submitted work. Dr Mazighi reports compensation from Novo Nordisk for consultant services; compensation from Boerhinger-Ingelheim for consultant services; and compensation from Acticor Biotech for consultant services. Dr Cortier reports employment by Foch. Dr Geri reports compensation from BARD for consultant services. Dr Demoule reports compensation from Agence Européenne Informatique for other services; compensation from Fisher and Paykel Healthcare Limited for other services; compensation from Baxter Healthcare for other services; compensation from Lowenstein for other services; compensation from Getinge for other services; travel support from Lowenstein; compensation from AstraZeneca for other services; compensation from Lungpacer for other services; compensation from Liberate Medical for other services; compensation from Respinor for other services; and compensation from Mindray DS USA Inc. for other services. Dr Timsit reports grants from Merck; compensation from BD Biosciences for consultant services; and grants from Pfizer. The other authors report no conflicts.

Background: While the short-term prognosis of cardiac arrest patients - nearly 250,000 new cases per year in Europe - has been extensively studied, less is known regarding the mid and long-term outcome of survivors., Objective: The aim of the DESAC study is to describe mid- and long-term survival rate and functional status of cardiac arrest survivors, and to assess the influence of pre and intra hospital therapeutic strategies on these two outcomes., Methods: Between Jul 2015 and Oct 2018, adult patients over 18 years who were discharged alive from any intensive care units (public and private hospitals) in the Ile-de-France area (Paris and suburbs, France) after a non-traumatic cardiac arrest were screened for participation in this multicentric study. Survivors were included after they signed (or the proxies) an informed consent before discharge during initial hospitalisation. We calculated that including 600 patients in total would allow an 80% power to demonstrate a 2 years survival rate difference of 10% between patients who did and those who did not receive therapeutic hypothermia after resuscitation. Pre- and in-hospital data related to the circumstances surrounding the event and to the therapeutic interventions (such as cardio-pulmonary resuscitation, defibrillation, emergent coronary revascularization, neuroprotective therapeutics) were collected. After discharge, patients were interviewed at 3 months, 6 months and every year thereafter for a minimum follow-up of 26 months and a maximum follow-up of 48 months. Information on vital status, occurrence of cardiovascular events, medications and a comprehensive assessment of the functional status (qualitive of life as assessed by the Short-Form General Health Survey (SF36) scale, activities of daily living (ADL) scale, neurological Cerebral Performance Categories (CPC) and Overall Performance Categories (OPC) scales, socio-professional activities) were collected at follow-up interviews., Discussion: The DESAC study should provide important information regarding several dimensions of the mid and long-term prognosis of cardiac arrest survivors and on the benefit (and potentially harm) of early therapeutic strategies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Antoine Vieillard-Baron declares being member of a research advisory board for Air Liquide Company. Alain Cariou received fees from Bard for lectures and conferences]., (© 2023 The Authors.)

Background: Coronavirus disease 2019 (COVID-19) is associated with an inflammatory cytokine burst and a prothrombotic coagulopathy. Platelets may contribute to microthrombosis, and constitute a therapeutic target in COVID-19 therapy., Aim: To assess if platelet activation influences mortality in COVID-19., Methods: We explored two cohorts of patients with COVID-19. Cohort A included 208 ambulatory and hospitalized patients with varying clinical severities and non-COVID patients as controls, in whom plasma concentrations of the soluble platelet activation biomarkers CD40 ligand (sCD40L) and P-selectin (sP-sel) were quantified within the first 48hours following hospitalization. Cohort B was a multicentre cohort of 2878 patients initially admitted to a medical ward. In both cohorts, the primary outcome was in-hospital mortality., Results: In cohort A, median circulating concentrations of sCD40L and sP-sel were only increased in the 89 critical patients compared with non-COVID controls: sP-sel 40,059 (interquartile range 26,876-54,678)pg/mL; sCD40L 1914 (interquartile range 1410-2367)pg/mL (P<0.001 for both). A strong association existed between sP-sel concentration and in-hospital mortality (Kaplan-Meier log-rank P=0.004). However, in a Cox model considering biomarkers of immunothrombosis, sP-sel was no longer associated with mortality, in contrast to coagulopathy evaluated with D-dimer concentration (hazard ratio 4.86, 95% confidence interval 1.64-12.50). Moreover, in cohort B, a Cox model adjusted for co-morbidities suggested that prehospitalization antiplatelet agents had no significant impact on in-hospital mortality (hazard ratio 1.05, 95% CI 0.80-1.37; P=0.73)., Conclusions: Although we observed an association between excessive biomarkers of platelet activation and in-hospital mortality, our findings rather suggest that coagulopathy is more central in driving disease progression, which may explain why prehospitalization antiplatelet drugs were not a protective factor against mortality in our multicentre cohort., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Coagulopathy is one of the main triggers of severity and worsening of Coronavirus disease 2019 (COVID-19) particularly in critically ill patients. D-dimer has been widely used to detect COVID-19 coagulation disorders and has been correlated with outcomes such as disease severity and in-hospital mortality. Involvement of other fibrin degradation products, particularly fibrin monomers (FM), remains an ongoing question., Methods: We performed a monocentric study of adult patients with COVID-19, who were admitted either in the medical ward (MW) or in the intensive care unit (ICU) and who had FM measurements performed on them during the first wave of COVID-19 outbreak. We analyzed the positivity of FM levels (FM > 7 µg/mL) to assess the ability of FM monitoring during the first days of hospitalization to predict COVID-19 outcomes., Results: In our cohort, 935 FM measurements were performed in 246 patients during their first 9 days of hospitalization. During patient follow-up, the FM levels were higher in patients admitted directly to the ICU than in those admitted to the MW. Moreover, we observed significantly increased levels of FM in patients when the data were stratified for in-hospital mortality. At hospital admission, only 27 (11%) patients displayed a positive value for FM; this subgroup did not differ from other patients in terms of severity (indicated by ICU referral at admission) or in-hospital mortality. When analyzing FM positivity in the first 9 days of hospitalization, we found that 37% of patients had positive FM at least once during hospitalization and these patients had increased in-hospital mortality ( p  = 0.001). Thus, we used non-adjusted Kaplan-Meier curves for in-hospital mortality according to FM positivity during hospitalization and we observed a statistically significant difference for in-hospital mortality (hazard ratio = 1.48, 95% CI: 1.25-1.76, p  < 0.001). However, we compared the AUC of FM positivity associated with a ratio of D-dimer >70% and found that this combined receiver operating characteristic (ROC) curve was superior to the FM positivity ROC curve alone., Conclusion: Monitoring of FM positivity in hospitalized patients with COVID-19 could be a reliable and helpful tool to predict the worsening condition and mortality of COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Smadja, Gendron, Philippe, Diehl, Ochat, Bory, Beauvais, Mareau, Jannot and Chocron.)

COVID-19 and infectious diseases have been included in strategic development goals (SDG) of United Nations (UN). Severe form of COVID-19 has been described as an endothelial disease. In order to better evaluate Covid-19 endotheliopathy, we characterized several subsets of circulating endothelial extracellular vesicles (EVs) at hospital admission among a cohort of 60 patients whose severity of COVID-19 was classified at the time of inclusion. Degree of COVID-19 severity was determined upon inclusion and categorized as moderate to severe in 40 patients and critical in 20 patients. We measured citrated plasma EVs expressing endothelial membrane markers. Endothelial EVs were defined as harboring VE-cadherin (CD144+), PECAM-1 (CD31 + CD41-) or E-selectin (CD62E+). An increase in CD62E + EV levels on admission to the hospital was significantly associated with critical disease. Moreover, Kaplan-Meier survival curves for CD62E + EV level showed that level ≥ 88,053 EVs/μL at admission was a significant predictor of in hospital mortality (p = 0.004). Moreover, CD62E + EV level ≥ 88,053 EV/μL was significantly associated with higher in-hospital mortality (OR 6.98, 95% CI 2.1-26.4, p = 0.002) in a univariate logistic regression model, while after adjustment to BMI CD62E + EV level ≥ 88,053 EV/μL was always significantly associated with higher in-hospital mortality (OR 5.1, 95% CI 1.4-20.0, p = 0.01). The present findings highlight the potential interest of detecting EVs expressing E-selectin (CD62) to discriminate Covid-19 patients at the time of hospital admission and identify individuals with higher risk of fatal outcome., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: Malnutrition following intensive care unit (ICU) stay is frequent and could be especially prominent in critically ill Coronavirus Disease 2019 (COVID-19) patients as they present prolonged inflammatory state and long length stay. We aimed to determine the prevalence of malnutrition in critically ill COVID-19 patients both at the acute and recovery phases of infection., Methods: We conducted a prospective observational study including critically ill COVID-19 patients requiring invasive mechanical ventilation discharged alive from a medical ICU of a university hospital. We collected demographic, anthropometric and ICU stay data (SAPS2, recourse to organ support and daily energy intake). Nutritional status and nutritional support were collected at one month after ICU discharge (M1) by phone interview and at 3 months after ICU discharge (M3) during a specialized and dedicated consultation conducted by a dietitian. Malnutrition diagnosis was based on weight loss and body mass index (BMI) criteria following the Global Leadership Initiative on Malnutrition. Primary outcome was the prevalence of malnutrition at M3 and secondary outcomes were the evolution of nutritional status from ICU admission to M3 and factors associated with malnutrition at M3., Results: From march 13th to may 15th, 2020, 38 patients were discharged alive from the ICU, median [IQR] age 66 [59-72] years, BMI 27.8 [25.5-30.7] kg/m 2 and SAPS2 47 [35-55]. Thirty-three (86%) patients were followed up to M3. Prevalence of malnutrition increased during the ICU stay, from 18% at ICU admission to 79% at ICU discharge and then decreased to 71% at M1 and 53% at M3. Severe malnutrition prevailed at ICU discharge with a prevalence of 55% decreasing 32% at M3. At M3, the only factors associated with malnutrition in univariate analysis were the length of invasive mechanical ventilation and length of ICU stay (28 [18-44] vs. 13 [11-24] days, P = 0.011 and 32 [22-48] vs. 17 [11-21] days, P = 0.006, respectively), while no ICU preadmission and admission factors, nor energy and protein intakes distinguished the two groups. Only 35% of undernourished patients at M3 had benefited from a nutritional support., Conclusion: Malnutrition is frequent, protracted and probably underrecognized among critically ill Covid-19 patients requiring invasive mechanical ventilation with more than half patients still being undernourished three months after ICU discharge. A particular attention should be paid to the nutritional status of these patients not only during their ICU stay but also following ICU discharge., Competing Interests: Conflicts of interest The authors declare no conflict of interest in relation to this work., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Thrombosis is a hallmark of severe COVID-19. Alpha-1-antitrypsin (AAT), an inflammation-inducible serpin with anti-inflammatory, tissue protective and anticoagulant properties may be involved in severe COVID-19 pathophysiology including thrombosis onset. In this study, we examined AAT ability to predict occurrence of thrombosis and in-hospital mortality during COVID-19. To do so, we performed a monocentric cross-sectional study of 137 hospitalized patients with COVID-19 of whom 56 (41%) were critically ill and 33 (22.4%) suffered from thrombosis during hospitalization. We measured AAT and IL-6 plasma levels in all patients and phenotyped AAT in a subset of patients with or without thrombosis paired for age, sex and COVID-19 severity. We observed that AAT levels at admission were higher in both non-survivors and thrombosis patients than in survivors and non-thrombosis patients. AAT: IL-6 ratio was lower in non-survivors and thrombosis patients. In a logistic regression multivariable analysis model adjusted on age, BMI and D-dimer levels, a higher AAT: IL-6 was a protective factor of both in-hospital mortality (Odds ratio, OR: 0.07 95%CI [0.02-0.25], p < 0.001) and thrombosis (OR 0.36 95%CI [0.14-0.82], p = 0.02). AAT phenotyping did not show a higher proportion of AAT abnormal variants in thrombosis patients.Our findings suggest an insufficient production of AAT regarding inflammation intensity during severe COVID-19. AAT appeared as a powerful predictive marker of severity, mortality and thrombosis mirroring the imbalance between harmful inflammation and protective counter-balancing mechanism in COVID-19. Restoring the balance between AAT and inflammation could offer therapeutic opportunities in severe COVID-19., (Copyright © 2022. Published by Elsevier B.V.)

Objective:  D-dimer measurement is a safe tool to exclude pulmonary embolism (PE), but its specificity decreases in coronavirus disease 2019 (COVID-19) patients. Our aim was to derive a new algorithm with a specific D-dimer threshold for COVID-19 patients., Methods:  We conducted a French multicenter, retrospective cohort study among 774 COVID-19 patients with suspected PE. D-dimer threshold adjusted to extent of lung damage found on computed tomography (CT) was derived in a patient set ( n  = 337), and its safety assessed in an independent validation set ( n  = 337)., Results:  According to receiver operating characteristic curves, in the derivation set, D-dimer safely excluded PE, with one false negative, when using a 900 ng/mL threshold when lung damage extent was <50% and 1,700 ng/mL when lung damage extent was ≥50%. In the derivation set, the algorithm sensitivity was 98.2% (95% confidence interval [CI]: 94.7-100.0) and its specificity 28.4% (95% CI: 24.1-32.3). The negative likelihood ratio (NLR) was 0.06 (95% CI: 0.01-0.44) and the area under the curve (AUC) was 0.63 (95% CI: 0.60-0.67). In the validation set, sensitivity and specificity were 96.7% (95% CI: 88.7-99.6) and 39.2% (95% CI: 32.2-46.1), respectively. The NLR was 0.08 (95% CI; 0.02-0.33), and the AUC did not differ from that of the derivation set (0.68, 95% CI: 0.64-0.72, p  = 0.097). Using the Co-LEAD algorithm, 76 among 250 (30.4%) COVID-19 patients with suspected PE could have been managed without CT pulmonary angiography (CTPA) and 88 patients would have required two CTs., Conclusion:  The Co-LEAD algorithm could safely exclude PE, and could reduce the use of CTPA in COVID-19 patients. Further prospective studies need to validate this strategy., Competing Interests: T.M. reports personal fees and nonfinancial support from Bayer Healthcare SAS, personal fees and nonfinancial support from Incyte Biosciences, France, nonfinancial support from Alexion Pharma, France, nonfinancial support from Abbott, France, nonfinancial support from Amgen SAS, nonfinancial support from Boehringer Ingelheim, France, nonfinancial support from Bristol-Myers Squibb, no-financial support from MSD France, outside the submitted work; F.C. reports grants from Pfizer, personal fees from Bayer, other from Boehringer; grants, personal fees, and other from BMS; personal fees and other from Astra-Zeneca, other from GSK, personal fees from LEO-Pharma, other from Actelion, outside the submitted work; S.S. reports grants from LEO-Pharma, personal fees from Bayer, personal fees from BMS Pfizer, outside the submitted work; N.G. reports personal fees and nonfinancial support from Boehringer Ingelheim, personal fees and nonfinancial support from Bayer, personal fees from Bristol-Myers Squibb/Pfizer, personal fees from LEO-Pharma, personal fees from Aspen, outside the submitted work; O.S. reports grants, personal fees, and nonfinancial support from Bayer; grants, personal fees, and nonfinancial support from BMS; personal fees and nonfinancial support from Sanofi Aventis; personal fees and nonfinancial support from Boston Scientifics; personal fees from Pfizer; grants, personal fees, and nonfinancial support from MSD; grants and personal fees from Boehringer Ingelheim; grants from Daiichi Sankyo; personal fees from Chiesi; personal fees and nonfinancial support from BTG, outside the submitted work; L.K. reports personal fees from Bristol-Myers Squibb/Pfizer, outside the submitted work; M.A.S. reports personal fees and nonfinancial support from Bristol-Myers Squibb/Pfizer, personal fees and nonfinancial support from Bayer SA, grants, personal fees, and nonfinancial support from Leo-Pharma, personal fees from Aspen, outside the submitted work; R.C. reports personal fees from Aspen, outside the submitted work; D.M.S. reports grants from Boehringer Ingelheim, personal fees from Bayer, personal fees from Bristol-Myers Squibb/Pfizer, personal fees from Leo-Pharma, personal fees from Aspen, personal fees from Carmat, outside the submitted work; E.M. reports personal fees and nonfinancial support from Bayer, personal fees from Bristol-Myers Squibb/Pfizer, personal fees from Novartis, outside the submitted work; . N.M. reports grants and personal fees from Bayer Healthcare, grants and personal fees from BMS Pfizer, personal fees from Astra-Zeneca, personal fees from Terumo, grants and personal fees from Abbott, outside the submitted work; L.F. reports personal fees from Janssen, personal fees from Sanofi, personal fees from General Electrics, nonfinancial support from Guerbet, grants from Invectys, nonfinancial support from Philips, nonfinancial support from Ariana Pharma, nonfinancial support from Evolucare, outside the submitted work. All the other authors have nothing to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Although sepsis is a life-threatening condition, its heterogeneous presentation likely explains the negative results of most trials on adjunctive therapy. This study in patients with sepsis aimed to identify subgroups with similar immune profiles and their clinical and outcome correlates., Methods: A secondary analysis used data of a prospective multicenter cohort that included patients with early assessment of sepsis. They were described using Predisposition, Insult, Response, Organ failure sepsis (PIRO) staging system. Thirty-eight circulating biomarkers (27 proteins, 11 mRNAs) were assessed at sepsis diagnosis, and their patterns were determined through principal component analysis (PCA). Hierarchical clustering was used to group the patients and k-means algorithm was applied to assess the internal validity of the clusters., Results: Two hundred and three patients were assessed, of median age 64.5 [52.0-77.0] years and SAPS2 score 55 [49-61] points. Five main patterns of biomarkers and six clusters of patients (including 42%, 21%, 17%, 9%, 5% and 5% of the patients) were evidenced. Clusters were distinguished according to the certainty of the causal infection, inflammation, use of organ support, pro- and anti-inflammatory activity, and adaptive profile markers., Conclusions: In this cohort of patients with suspected sepsis, we individualized clusters which may be described with criteria used to stage sepsis. As these clusters are based on the patterns of circulating biomarkers, whether they might help to predict treatment responsiveness should be addressed in further studies., Trial Registration: The CAPTAIN study was registered on clinicaltrials.gov on June 22, 2011, # NCT01378169., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Virginie Moucadel, PhD, is employed by bioMérieux SA, a private company specialized in in vitro diagnostics. The authors declare no other potential conflicts of interest in relation with the subject of the present manuscript.

Extracorporeal carbon dioxide removal (ECCO 2 R) is a form of extracorporeal life support (ECLS) largely aimed at removing carbon dioxide in patients with acute hypoxemic or acute hypercapnic respiratory failure, so as to minimize respiratory acidosis, allowing more lung protective ventilatory settings which should decrease ventilator-induced lung injury. ECCO 2 R is increasingly being used despite the lack of high-quality evidence, while complications associated with the technique remain an issue of concern. This review explains the physiological basis underlying the use of ECCO 2 R, reviews the evidence regarding indications and contraindications, patient management and complications, and addresses organizational and ethical considerations. The indications and the risk-to-benefit ratio of this technique should now be carefully evaluated using structured national or international registries and large randomized trials., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)