RATIONALE:Patients with severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-related diffuse alveolar hemorrhage (DAH) face high mortality. In the PEXIVAS trial, plasma exchange (PLEX) did not reduce death or end-stage kidney disease, but only 9% had severe DAH. OBJECTIVES:This study aimed to assess whether PLEX lowers mortality in patients with severe DAH. METHODS:We emulated a target trial using retrospective data from a national multicenter cohort of patients with severe AAV-related DAH. The primary endpoint was 30-day mortality after intensive care unit (ICU) admission, analyzed using a Cox model adjusted for prespecified confounders. MEASUREMENTS AND MAIN RESULTS:We included 184 patients (median age 66 [53-75] years; 51% female; 51% with granulomatosis with polyangiitis; 53% MPO (Myeloperoxydase)-ANCA positive). Of these, 144 (78.3%) received PLEX, and 40 (21.7%) did not. Baseline characteristics were similar, except for more severe renal impairment (creatinine 357 vs 171 µmol/L, P = .01) and more frequent cyclophosphamide use (77% vs 55%, P = .01) in the PLEX group. Severity at ICU admission (median Simplified Acute Physiology Score II score: 42) and mechanical ventilation needs (54%) were comparable between groups. At 30 days, overall survival was 85%. No significant difference in mortality was observed between the PLEX and no-PLEX groups: 30-day survival was 85% (95% CI, 81-90) with PLEX vs 88% (95% CI, 77-96) without (hazard ratio, 1.23; 95% CI, 0.57-3.89). Secondary outcomes were also similar. CONCLUSIONS:In this emulated target trial, PLEX did not reduce 30-day mortality in patients with severe AAV-related DAH.

Importance:The effect of wrist-strap physical restraints on outcomes in patients receiving mechanical ventilation in the intensive care unit (ICU) remains uncertain. Objective:To investigate the effect of a low-use wrist-strap physical restraint strategy in critically ill patients receiving invasive mechanical ventilation. Design, Setting, and Participants:Open-label randomized clinical trial conducted across 10 ICUs in France. Between January 5, 2021, and January 2, 2024, 405 adult patients who had initiated invasive mechanical ventilation within the previous 6 hours and were expected to require ventilation for at least 48 hours were enrolled. Follow-up was completed on May 17, 2024. Statistical analysis was conducted from June 1, 2025, to December 15, 2025. Interventions:Patients were randomized to undergo either a restrictive, low-use physical restraint strategy (wrist straps avoided unless necessary because of severe agitation, defined as a Richmond Agitation-Sedation Scale score of ≥3 [on a scale from -5 (unresponsive) to 4 (combative)]; n = 201) or a liberal, high-use strategy (wrist straps applied systematically and reassessed daily; n = 204). Discontinuation of restraints was allowed in patients who were awake or extubated without delirium (measured via the Confusion Assessment Method for the ICU). Main Outcomes and Measures:The primary outcome was the number of days alive without coma or delirium during the first 14 days after randomization. Secondary outcomes included incidence of self-extubation and day-90 mortality. Results:Among 396 patients with available primary outcome data, the median (IQR) age was 65 (56-73) years, 245 (62%) were male, and the median (IQR) Sequential Organ Failure Assessment score was 7 (4-10). The mean days alive without coma or delirium were 6.67 days (95% CI, 5.69-7.65) in the low-use strategy group and 6.30 days (95% CI, 5.35-7.24) in the high-use strategy group (adjusted mean difference, 0.37 days [95% CI, -0.71 to 1.46]; P = .51). Self-extubation occurred in 18 patients (9.2%) in the low-use strategy group and 17 (8.5%) in the high-use strategy group, and day-90 mortality was 37.2% and 41.0%, respectively. Conclusions and Relevance:In this randomized clinical trial, among adult patients receiving mechanical ventilation in the ICU, a low-use wrist-strap physical restraint strategy compared with a high-use strategy did not reduce days free of delirium or coma at 14 days. Trial Registration:ClinicalTrials.gov Identifier: NCT04273360.

Abstract Background Suspected invasive pulmonary aspergillosis (IPA) is increasingly treated in intensive care, including in patients without classical immunosuppression. Whether current research definitions (EORTC/MSGERC, FUNDICU) classify treated cases and predict mortality is unclear. Methods We retrospectively included adults in 48 French intensive care units who received systemic antifungal therapy for suspected IPA (January 2022-July 2024). Patients were categorized as having modified EORTC/MSGERC probable IPA, FUNDICU probable IPA, or unclassified. Ninety-day mortality was analyzed using multivariable Cox regression; heterogeneity was explored with unsupervised clustering. Results Among 371 treated patients, 217 (58%) met modified EORTC, 83 (22%) met FUNDICU, and 71 (19%) were unclassified. Overall, 90-day mortality was 62% and survival did not differ by category (63%, 63%, 58%; log-rank p=0.24). In adjusted analyses, IPA categorization was not associated with mortality (FUNDICU vs EORTC: adjusted hazard ratio (aHR)=0.86, 95% CI 0.62-1.20; unclassified vs EORTC: aHR=0.89, 0.62-1.30). Age (aHR 1.03/year, 1.02-1.05), SOFA (1.06/point, 1.03-1.10), and frailty (1.17/point, 1.07-1.30) independently predicted 90-day mortality. Exploratory clustering identified six phenotypes with 90-day mortality ranging from 40% to 80%. Conclusions Nearly one in five intensive care patients treated for suspected IPA were not classifiable by EORTC/MSGERC or FUNDICU definitions. Mortality was more strongly associated with age, frailty and acute severity than with classification category, supporting ICU-focused diagnostic frameworks and risk stratification; these associations should be read in light of the treatment-based design and do not establish that the definitions lack diagnostic value.

The beneficial effects of prophylactic noninvasive ventilation (NIV) after extubation in patients without hypercapnia are uncertain. Our objective was to assess the effects of prophylactic NIV on reintubation among patients without hypercapnia at the time of extubation. Post hoc analysis of two multicenter clinical trials including high-risk patients (i.e., patients older than 65 years or with underlying cardiac/respiratory disease). Our analysis focused on the 829 patients without hypercapnia (PaCO2 ≤ 45 mmHg), the day of extubation who received NIV alternating high-flow nasal cannula (HFNC) oxygen or HFNC alone after extubation. The primary outcome was the proportion of patients who required reintubation within seven days following extubation. We used G-computation to robustly estimate the marginal causal effect of treatment on the risk of reintubation. After extubation, 540 patients (65

Infection are the leading cause of intensive care unit (ICU) admission, yet conventional microbiological methods frequently fail to identify the causative pathogen. Metagenomic next-generation sequencing (mNGS) is an emerging, unbiased, pan-pathogen diagnostic tool. However, its real-world microbiological and clinical impact in the ICU remains poorly characterized. This study aimed to assess the microbiological yield and clinical impact of mNGS when implemented in routine ICU practice. This retrospective multicenter study was conducted across ten tertiary-care ICUs in the Greater Paris area between January 2018 and April 2024. All patients for whom an mNGS analysis was requested by clinicians from a microbiological sample were included. Any additional pathogens identified by mNGS were independently classified as causative, possibly causative, or non-causative by two reviewers. The independent reviewers also categorised therapeutic changes attributable to mNGS as escalation, de-escalation, discontinuation, or other decision support. Discrepancies were adjudicated by a third reviewer. A total of 144 mNGS analyses were performed in 132 critically ill patients (median age 55 years), 31

Patients with severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-related diffuse alveolar hemorrhage (DAH) face high mortality. In the PEXIVAS trial, plasma exchange (PLEX) did not reduce death or end-stage kidney disease, but only 9% had severe DAH. This study aimed to assess whether PLEX lowers mortality in patients with severe DAH. We emulated a target trial using retrospective data from a national multicenter cohort of patients with severe AAV-related DAH. The primary endpoint was 30-day mortality after ICU admission, analyzed using a Cox model adjusted for prespecified confounders. We included 184 patients (median age 66 [53–75] years; 51% female; 51% with granulomatosis with polyangiitis; 53% MPO-ANCA positive). Of these, 144 (78.3%) received PLEX and 40 (21.7%) did not. Baseline characteristics were similar, except for more severe renal impairment (creatinine 357 vs. 171 µmol/L, P = 0.01) and more frequent cyclophosphamide use (77% vs. 55%, P = 0.01) in the PLEX group. Severity at ICU admission (median SAPS II score: 42) and mechanical ventilation needs (54%) were comparable between groups. At 30 days, overall survival was 85%. No significant difference in mortality was observed between the PLEX and no-PLEX groups: 30-day survival was 85% (95% CI 81–90) with PLEX vs. 88% (95% CI 77–96) without (HR 1.23; 95% CI 0.57–3.89). Secondary outcomes were also similar. In this emulated target trial, PLEX did not reduce 30-day mortality in patients with severe AAV-related DAH.

BACKGROUND:The aim of the DESAC study (Devenir des Survivants d'Arrets Cardiaques) was to describe the survival rate and neurological status of out-of-hospital (out-of-hospital cardiac arrest) survivors, and to assess the influence of prehospital and intrahospital factors. METHODS:Between July 2015 and October 2018, consecutive nontraumatic out-of-hospital cardiac arrest patients aged over 18 years discharged alive from 33 intensive care units in Paris and the suburbs (France) were included. Their neurological status was assessed every 6 months using the Cerebral Performance Category (CPC) scale. Prognostic factors associated with a favorable neurological outcome at 24 months (CPC category of 1 or 2) were assessed by covariate-adjusted logistic regression. Trajectories of CPC level over time were derived using a linear mixed model in survivors with at least 3 repeated assessments. RESULTS:Out of 593 survivors, 525 were followed up for 24 months (mean age, 58.1±15.3 years, 79% males), and 449 of 525 (86%) had a favorable neurological outcome. Initial shockable rhythm (adjusted odds ratio, 3.33 [95% CI, 1.57-7.07]) and previous practice of sport (adjusted odds ratio, 3.13 [95% CI, 1.21-8.12]) were associated with favorable outcome, whereas factors with reduced odds ratio were older age (adjusted odds ratio per 10 years, 0.53 [95% CI, 0.41-0.69]) and prior percutaneous coronary intervention (adjusted odds ratio, 0.38 [95% CI, 0.17-0.85]). Therapeutic hypothermia or acute coronary interventions were not related to prognosis (P>0.05). Overall, among the 514 patients with at least 3 repeated assessments, 5 distinct CPC trajectories (2 reflecting early death were combined) were derived: 64% remained in CPC1, 13.4% in CPC2, 11% improved from CPC2 to CPC1, and 11.6% died either early or lately (>3 months) during follow-up. CONCLUSIONS:This multicentric prospective study indicates that 86% of out-of-hospital cardiac arrest survivors had a favorable neurological outcome at 24 months. Pre-event and intraevent factors (including previous practice of sport and shockable rhythm), but not in-hospital management (therapeutic hypothermia or acute coronary interventions), were associated with a favorable outcome. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02494414.

Background:Whether or not a direct tracheostomy without any prior weaning attempt is beneficial in patients intubated for Guillain-Barré syndrome (GBS) remains to be determined. Our objective was to determine whether direct tracheostomy results in earlier or later ventilator weaning compared to standard weaning. Methods:Multicenter, retrospective cohort study including all patients intubated for GBS over a 10-year period (2014-2023). We compared patients having undergone direct tracheostomy without any prior weaning attempt with those having undergone standard weaning (spontaneous-breathing trial or extubation attempt). We also compared direct tracheostomy with tracheostomy after weaning failure. The primary outcome was the proportion of patients alive and free from mechanical ventilation 28 days after weaning initiation. Results:Overall, 221 patients (45%) underwent direct tracheostomy and 273 (55%) standard weaning. Compared to patients with standard weaning, those with direct tracheostomy were less likely to be alive and free from mechanical ventilation at day 28 (43% vs. 83%, p < 0.001). Using G-computation to estimate the marginal causal effect of the weaning strategy, standard weaning was more effective than direct tracheostomy in reducing the risk of remaining under mechanical ventilation at day 28: -39.5% [95% Confidence Interval, -47.3% to -31.5%]. Even when compared to patients having undergone tracheostomy after weaning failure, those with direct tracheostomy were less likely to be alive and free from mechanical ventilation 28 days after the tracheostomy procedure. Interpretation:A direct tracheostomy without any prior weaning attempt might significantly delay the ventilator weaning process in patients intubated for GBS. Clinical Trial Registration:NCT07022028.

BackgroundSevere COVID-19 is associated with dysregulated immune responses. Immune responses heterogeneity was previously reported during the first waves of the pandemic. We aimed to characterise mucosal transcriptomic profiles in critically-ill patients during the Omicron era.MethodsThis prospective multicentre study included 94 critically-ill COVID-19 patients between May 2022 and August 2023. Upper respiratory tract mucosal transcriptomes were obtained from nasopharyngeal swabs and clustered based on KEGG cytokine-cytokine receptor interaction pathways using an unsupervised algorithm. Differential transcript expression, cell population abundance and gene set enrichment analyses were performed.ResultsHere we show that in 56 critically ill COVID-19 patients, transcriptomic clustering reveals two distinct COVID-19 Immune Transcriptomic Respiratory Profiles (CITRP), including CITRP-1 and CITRP-2, characterised by differential expression of cytokine and immune response pathways. Patients in the CITRP-2 group display a more pronounced immune and inflammatory response, involving specific innate immune pathways, neutrophil degranulation and T-helper 2 cytokines (e.g., IL-1, IL-4 and IL-13), and a significantly higher proportion of neutrophils than patients in the CITRP-1 group. No significant differences are observed between the two transcriptomic clusters in clinical, biological and virological characteristics at ICU admission or in patient outcomes.ConclusionsThis study highlights the heterogeneity of the immune response in critically-ill COVID-19 patients in the Omicron era, identifies two endotypes from the analysis of upper airway mucosal transcriptomics. Our findings suggest the existence of two distinct pathogenic mechanisms and the detrimental role of neutrophil and Th2 helper cell-mediated inflammation in a subset of patients with severe disease. They support the need for personalised treatment strategies targeting neutrophil-mediated lung damage and/or specific cytokine production in a subset of critically-ill COVID-19 patients.

BACKGROUND:Data are needed on the effect of oxygen delivered through a high-flow nasal cannula, as compared with standard oxygen therapy, on intubation and mortality in patients with acute hypoxemic respiratory failure. METHODS:In this multicenter, open-label trial, we randomly assigned patients who had acute hypoxemic respiratory failure to receive high-flow-oxygen or standard-oxygen therapy. All the patients had a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 or less, a respiratory rate of more than 25 breaths per minute, and pulmonary infiltrate on chest imaging. The primary outcome was death by day 28. RESULTS:A total of 1116 patients underwent randomization. Of these patients, 1110 (556 in the high-flow-oxygen group and 554 in the standard-oxygen group) were included in the analysis. Mortality at day 28 was 14.6% (in 81 of 556 patients) in the high-flow-oxygen group and 14.6% (in 81 of 554 patients) in the standard-oxygen group (difference, -0.05 percentage points; 95% confidence interval [CI], -4.21 to 4.10; P = 0.98). The incidence of intubation by day 28 was 42.4% (in 236 of 556 patients) in the high-flow-oxygen group and 48.4% (in 268 of 554 patients) in the standard-oxygen group (difference, -5.93 percentage points; 95% CI, -11.78 to -0.08). Serious adverse events (cardiac arrest or pneumothorax) occurred during spontaneous breathing in 13 patients (2.3%) in the high-flow-oxygen group and in 6 patients (1.1%) in the standard-oxygen group. CONCLUSIONS:Among patients with acute hypoxemic respiratory failure, the use of oxygen delivered through a high-flow nasal cannula did not significantly reduce mortality at day 28. (Funded by the French Ministry of Health and Fisher and Paykel Healthcare; SOHO ClinicalTrials.gov number, NCT04468126.).

The clinical presentation of critically ill patients with coronavirus disease 2019 (COVID-19) has evolved significantly with the emergence of the Omicron variant. Current intensive care unit (ICU) admissions involve patients with diverse comorbidities and immune statuses, highlighting the need to redefine homogeneous phenotypic subgroups within this population. This study aimed to characterize distinct clinical phenotypes among critically ill patients with COVID-19 and acute respiratory failure. This multicenter prospective substudy of the SEVARVIR cohort included adult patients from 39 French ICUs between December 2021 and October 2024 with acute respiratory failure and infected with the Omicron variant. Clustering analysis was conducted using Kohonen’s self-organizing maps (SOMs) and validated with ClinTrajan, two unsupervised clustering methods, to identify homogeneous patient phenotypes. During the study period, 777 patients with Omicron infection were included, and 7 distinct clinical clusters were identified. Clusters 1 and 2 included patients with metabolic and cardiovascular comorbidities. Cluster 3 featured younger, mildly ill patients with isolated chronic respiratory failure, while cluster 4 comprised older male patients with isolated respiratory failure. Cluster 5 included patients with isolated hematologic malignancies, cluster 6 patients with multiorgan failure, and cluster 7 organ transplant recipients, with high severity scores and impaired renal function. ICU management varied substantially across clusters. Patients in clusters 5 and 7 had the highest requirements for organ support, with frequent use of invasive mechanical ventilation, vasopressors (cluster 6), and renal replacement therapy (cluster 7). Dexamethasone and tocilizumab were most commonly prescribed in cluster 4 (91.3

BACKGROUND:Cryptococcus causes life-threatening opportunistic infections in immunocompromised hosts. Data on the most severe cases requiring ICU admission remain limited. METHODS:We conducted a retrospective, multicenter study of patients admitted to 30 French ICUs for severe cryptococcosis between 2000 and 2022. RESULTS:Among 151 patients included, 56.9% were patients with HIV. Cases in patients without HIV became increasingly prevalent over time (51.3% in 2012-2022 vs. 32.4% before 2012); 82.5% were receiving immunosuppressive therapy. Central nervous system infection was predominant (91.1%), followed by lung infection (39.7%). Fungemia occurred in 59.8% patients, and 75.2% had disseminated infection. Neurological failure was the leading organ impairment at admission (75.5%) followed by respiratory failure (47.7%), acute kiney injury (41.7%) and shock (24.5%). The median SOFA score was 4 [2-7]. Invasive mechanical ventilation, vasopressors and renal replacement therapy were required in 54.9%, 34.4% and 18.5% of patients, respectively. At day 90, 94% of patients requiring mechanical ventilation and vasopressors were deceased, compared to 38.7% with invasive ventilation alone and 17.2% without any organ support (p<0.001). Overall, 90-day mortality reached 49.6%. SOFA score (HR 1.04 [1.02-1.06]), admission between 2000 and 2012 (HR 2.30 [1.36-3.89]), disseminated infection (HR 2.32 [1.15-4.67]) and initiation of antifungal therapy before ICU admission (HR 0.38 [0.22-0.63]) were independently associated with 90-day mortality, whereas HIV serostatus was not (HR 0.93 [0.47-1.84]). CONCLUSION:Severe cryptococcosis requiring ICU admission affects an increasing number of patients without HIV and is associated with high, though declining, mortality. Early diagnosis and treatment are mandatory to improve prognosis.

Introduction Legionnaires' disease (LD) can cause severe pneumonia requiring intensive care and frequently associated with multiorgan failure. The mechanisms and prognosis of kidney complications in LD remain poorly characterized. We aimed to describe the incidence, clinical characteristics, and prognosis of AKI in critically ill patients with LD and identify factors associated with AKI, in a multicenter cohort. Methods This multicenter retrospective cohort study was conducted in 39 ICUs in France between 2012 and 2024. Inclusion criteria were a diagnosis of LD requiring invasive mechanical ventilation. Results 561 patients were included. Patients exhibited high severity, with a mean SOFA score on D1 of 7.9; 69% with severe ARDS and 81% with septic shock. The incidence of AKI was 74% in ICU, with 44% requiring renal replacement therapy (RRT). Rhabdomyolysis (16%), hematuria (52%) and proteinuria (mean 1.49 g/L) were commonly observed. Rhabdomyolysis was an independent risk factor for AKI and RRT requirement: aOR 3.99 [1.59-10.00], p=0.003 and aOR 4.07 [2.17-7.63], p<0.001, respectively. RRT requirement was associated with significantly increased mortality: aOR 2.49 [1.27-4.87], p=0.008 at D28, pLog-rank<0.001. In an exploratory analysis, dual anti-Legionella antibiotic therapy, administered in 87% of cases, was independently associated with lower day-28 mortality (aOR 0.27 [95% CI 0.13–0.58], p=0.001). Conclusion AKI appears highly incident in patients with severe LD, with a high frequency of rhabdomyolysis and proteinuria, suggesting marked kidney involvement. Rhabdomyolysis was independently associated with AKI onset and RRT requirement. AKI was associated with significantly increased mortality, whereas anti-legionella dual therapy was protective.

Clinical practice guidelines recommend prophylactic noninvasive ventilation (NIV) after extubation in high-risk patients. The effects of high-flow nasal cannula (HFNC) oxygen during breaks from NIV after extubation have been poorly explored. Our objective was to assess whether HFNC rather than standard oxygen during breaks from NIV may prevent extubation failure. Observational study based on two multicenter clinical trials including patients at high-risk of extubation failure (> 65 years or with underlying cardiac or respiratory disease). We included the 1077 patients who received prophylactic NIV after extubation, alternating with HFNC (NIV/HFNC) or standard oxygen (NIV/O2). The primary outcome was the proportion of patients who failed extubation (reintubation or death within the seven days following extubation). We used G-computation to estimate the causal effect of HFNC on the risk of extubation failure, while accounting for confounding factors. After extubation, 655 patients (61

BACKGROUND:Invasive meningococcal disease (IMD) is traditionally associated with younger populations, but its impact on older adults is rising. We aimed to describe the clinical characteristics and outcomes of critically ill older patients with IMD and identify risk factors for in-hospital mortality. METHODS:We conducted an ancillary analysis of the French nationwide multicenter RETRO-MENINGO cohort (2016-2024). All adults admitted to 102 ICUs with microbiologically confirmed IMD were included and stratified by age (≥65 vs. <65 years). The primary outcome was all-cause in-hospital mortality. Multivariable logistic regression identified factors independently associated with death. RESULTS:Among 654 patients, 114 (17%) were aged ≥65 years, of whom only 0.9% were reported as vaccinated. Compared to younger adults, older patients presented more frequently with hemodynamic failure and less often with classic purpura or meningeal symptoms. Serogroup W predominated in the older group, while serogroup B was more common in younger patients. Older adults required more organ support and had significantly higher in-hospital mortality (28.1%, n=32/114 vs. 9.6%, n=52/540 p<0.001). After adjustment, age ≥65 years remained independently associated with in-hospital mortality (aOR 2.99; 95% CI 1.57-5.72; p<0.001), while administration of a third-generation cephalosporin before ICU admission was protective (aOR 0.45; 95% CI, 0.24-0.84; p=0.01). CONCLUSIONS:Critically ill older adults with IMD exhibit atypical clinical features, a high prevalence of serogroup W, and nearly triple the in-hospital mortality of younger patients. These findings emphasize the need for high clinical suspicion, rapid antibiotic therapy, and potential expansion of vaccination strategies to include older populations.

QuestionDoes a restrictive (low-use) wrist-strap physical restraint strategy, compared with a liberal (high-use) strategy, reduce coma or delirium in adult patients receiving mechanical ventilation in the intensive care unit?FindingsIn this randomized clinical trial of 405 adults receiving invasive mechanical ventilation, the number of days alive without coma or delirium during the first 14 days after randomization did not differ between the low- and high-use restraint strategies (6.67 vs 6.30 days). Delirium; self-extubation; day-90 mortality; and 90-day functional, cognitive, and psychological outcomes were similar between groups.MeaningIn adult patients receiving mechanical ventilation in the intensive care unit, a low-use wrist-strap physical restraint strategy did not improve coma- or delirium-free days. ImportanceThe effect of wrist-strap physical restraints on outcomes in patients receiving mechanical ventilation in the intensive care unit (ICU) remains uncertain.ObjectiveTo investigate the effect of a low-use wrist-strap physical restraint strategy in critically ill patients receiving invasive mechanical ventilation.Design, Setting, and ParticipantsOpen-label randomized clinical trial conducted across 10 ICUs in France. Between January 5, 2021, and January 2, 2024, 405 adult patients who had initiated invasive mechanical ventilation within the previous 6 hours and were expected to require ventilation for at least 48 hours were enrolled. Follow-up was completed on May 17, 2024. Statistical analysis was conducted from June 1, 2025, to December 15, 2025.InterventionsPatients were randomized to undergo either a restrictive, low-use physical restraint strategy (wrist straps avoided unless necessary because of severe agitation, defined as a Richmond Agitation-Sedation Scale score of >= 3 [on a scale from -5 (unresponsive) to 4 (combative)]; n = 201) or a liberal, high-use strategy (wrist straps applied systematically and reassessed daily; n = 204). Discontinuation of restraints was allowed in patients who were awake or extubated without delirium (measured via the Confusion Assessment Method for the ICU).Main Outcomes and MeasuresThe primary outcome was the number of days alive without coma or delirium during the first 14 days after randomization. Secondary outcomes included incidence of self-extubation and day-90 mortality.ResultsAmong 396 patients with available primary outcome data, the median (IQR) age was 65 (56-73) years, 245 (62%) were male, and the median (IQR) Sequential Organ Failure Assessment score was 7 (4-10). The mean days alive without coma or delirium were 6.67 days (95% CI, 5.69-7.65) in the low-use strategy group and 6.30 days (95% CI, 5.35-7.24) in the high-use strategy group (adjusted mean difference, 0.37 days [95% CI, -0.71 to 1.46]; P = .51). Self-extubation occurred in 18 patients (9.2%) in the low-use strategy group and 17 (8.5%) in the high-use strategy group, and day-90 mortality was 37.2% and 41.0%, respectively.Conclusions and RelevanceIn this randomized clinical trial, among adult patients receiving mechanical ventilation in the ICU, a low-use wrist-strap physical restraint strategy compared with a high-use strategy did not reduce days free of delirium or coma at 14 days.Trial RegistrationClinicalTrials.gov Identifier: NCT04273360 This randomized clinical trial examines the effect of a low-use vs high-use physical restraint strategy in critically ill patients receiving invasive mechanical ventilation in the intensive care unit.

Invasive meningococcal disease (IMD) is a rare but potentially fatal infection caused by Neisseria meningitidis. In adults requiring admission to intensive care unit (ICU), IMD typically presents with two distinct clinical presentations: neurological (meningitis) and hemodynamic (sepsis). These presentations are often conflated, despite the differences in pathophysiology and outcome. RETRO-MENINGO is a nationwide, multicentre, retrospective cohort study conducted in 102 French ICUs between January 1, 2016, and December 31, 2024. Adults (≥ 18 years) admitted to the ICU with a microbiologically confirmed IMD were categorised as having either a neurological or a hemodynamic presentation according to the main reason for ICU admission. The primary outcome was day-60 mortality in each presentation. Of 654 patients (median age 33 years [IQR 21–56]; 63.5