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Background: Bradycardia and dysautonomia observed during SARS-Cov2 infection suggests involvement of the autonomic nervous system (ANS). Limited data exists on ANS dysregulation and its association with outcomes in patients with acute respiratory distress syndrome (ARDS) related to COVID-19 (C-ARDS) or other etiologies (NC-ARDS)., Objectives: We aimed to explore sympathovagal balance, assessed by heart rate variability (HRV), and its clinical prognostic value in C-ARDS compared with NC-ARDS., Methods: A single-center, prospective case-control study was conducted. Consecutive patients meeting ARDS criteria between 2020 and 2022 were included. HRV was assessed using 1-hour electrographic tracing during a stable, daytime period., Results: Twenty-four patients with C-ARDS and 19 with NC-ARDS were included. Age, sex and ARDS severity were similar between groups. The median heart rate was markedly lower in the C-ARDS group than in the NC-ARDS group (60 [53-72] versus 101 [91-112] bpm, p<.001). Most of HRV parameters were significantly increased in patients with C-ARDS. HRV correlated with heart rate only in patients with C-ARDS. A positive correlation was found between the low-to high-frequency ratio (LF/HF) and length of intensive care unit stay (r = 0.576, p<.001)., Conclusion: This study confirmed that C-ARDS was associated with marked bradycardia and severe ANS impairment, suggesting a sympathovagal imbalance with vagal overtone. Poor outcomes appeared to be more related to sympathetic rather than parasympathetic hyperactivation., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To assess the compliance with French guidelines for the prevention of central venous catheter (CVC)-related infections in two university hospitals., Methods: An observational audit was conducted in 7 wards using a digital tool., Results: The prerequisite of hand hygiene (HH) were respected by 90% of health-care worker; 86% performed HH prior to equipment preparation and 59% repeated it prior to infusion. Wearing gloves when necessary and rinsing were respected in 46.7% and 75.6% of the observations., Conclusion: Findings showed an acceptable level of adherence to recommended practices for CVC management. However, barriers of unrespect evidence-based recommendations need to be investigated in depth., (© 2024. The Author(s).)

Background: The first aim of this study was to evaluate the capacity of electrical impedance tomography (EIT) to identify the effect of PEEP on regional ventilation distribution and the regional risk of collapse, overdistention, hypoventilation, and pendelluft in mechanically ventilated patients. The second aim was to evaluate the feasibility of EIT for estimating airway opening pressure (AOP)., Methods: The EIT signal was recorded both during baseline cyclic ventilation and slow insufflation for one breath for 9 subjects with moderate-to-severe ARDS. From these data, the AOP and volumes insufflated to lung regions with or without the risk of either collapse, overdistention, hypoventilation, or pendelluft were assessed at 3 PEEP levels (5, 10, and 15 cm H 2 O). PEEP levels were compared by Friedman analysis of variance and the AOP measured by EIT evaluated using an F-test and the Bland and Altman method., Results: The volume for which there was no specific risk significantly decreased at the highest PEEP from 55 ± 31% tidal volume (V T ) at PEEP 5 or 82 ± 18% V T at PEEP 10 to 10 ± 30% V T at PEEP 15 ( P = .038 between PEEP 5 vs PEEP 15; P = .01 between PEEP 10 vs PEEP 15). The volume associated with overdistention significantly increased with increasing PEEP, whereas that associated with atelectrauma significantly decreased. Pendelluft significantly decreased with increasing PEEP: V T of 8.9 ± 18.6%, 3.6 ± 7.0%, and 3.2 ± 7.1% for PEEP 5, PEEP 10, and PEEP 15, respectively. The center of ventilation tended to increase in the dependent direction with higher PEEP. The AOPs assessed by EIT and from the pressure-volume curve were in good agreement (bias 0.48 cm H 2 O)., Conclusions: Our results suggest that EIT could aid clinicians in making personalized and reasoned choices in setting the PEEP for subjects with ARDS., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Background: Clinical guidelines recommend systematic follow-up of patients surviving invasive meningococcal disease (IMD) to assess sequelae. However, little is known about survivors and family caregivers' experiences of the follow-up care. Study sought to explore IMD survivors' and their family caregivers' experiences after hospitalization for IMD and to identify unmet needs., Methods: Semi-structured interviews were conducted with patients and family caregivers, identified through hospitals database. Interviews were audiotaped, transcribed and subject to a thematic analysis. NVivo software was used for data management and analysis., Results: Eight IMD survivors and 14 family caregivers were interviewed. Three themes were identified from the data: (1) perception of patient and family caregiver on follow-up after IMD and role of healthcare professionals; (2) access to care and support; (3) relationship with healthcare professionals. Although most were satisfied with follow-up care after IMD, suggestions for improving the healthcare pathway were made relating information on potential sequelae and follow-up care, coordination, and access to psychological support., Conclusions: This study confirms the need for more structured follow-up care for patients suffering from IMD and their families which is currently limited and focused on physical recovery. Optimal follow-up should aim to provide sufficient information, emotional support and logistical support for patient and family caregivers., Trial Registration: Ethics Committee of University of Lyon, France (ref: 2022-06-23-002)., (© 2024. The Author(s).)

Objectives: Severe thrombotic antiphospholipid syndrome (APS) frequently affects the kidney, heart, and central nervous system. The precise frequency, clinical picture, differential diagnoses, and outcome of APS-related hematological involvement are lacking, especially in patients requiring ICU admission. This study aimed to describe the hematological manifestations associated with critically ill thrombotic APS patients and catastrophic antiphospholipid syndrome., Methods: This French, national, multicenter, retrospective study, conducted, from January 2000 to September 2018, included all APS patients admitted to 24 participating centers' ICUs with any new thrombotic manifestation. The prevalence of hematological manifestations and their associated outcomes were studied., Results: One hundred and thirty-four patients, female 72%, median [IQR] age 45 [34-56] years, with 152 episodes were included. Anemia was present in 95% of episodes and thrombocytopenia in 93%. The lowest values for hemoglobin and platelets were 7.1 [6.3-8.8] g/dL and 38 [21-60] g/L, respectively. The lowest platelet count below 20 g/L was significantly associated with a higher in-ICU mortality rate (50%, p < 0.0001). A thrombotic microangiopathy syndrome (TMA) syndrome was seen in 16 patients (12%) and was associated with higher in-hospital mortality (p = 0.05). Median ADAMTS-13 levels were 44% [27-74]. Anti-ADAMTS13 antibodies were tested in 11 patients and found negative in all. A suspicion of heparin-induced thrombocytopenia (HIT) was raised in 66 patients but only four patients were classified as definite HIT. Disseminated intravascular coagulation (DIC) was seen in 51% of patients., Conclusion: Thrombocytopenia is very frequent in severe APS patients and may be related to TMA, HIT, or DIC. Deciphering the mechanisms of thrombocytopenia is decisive in CAPS patients. Key Points • Thrombocytopenia is the hallmark laboratory finding in CAPS. • A complete thrombotic microangiopathy pattern is infrequent in CAPS patients. • Alternate diagnoses of CAPS, especially heparin-induced thrombocytopenia, need to be adequately investigated., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Carbon dioxide rebreathing (CO 2 rebreathing) significantly influences respiratory drive and the work of breathing during BiPAP ventilation. We analyzed CO 2 movement during BiPAP ventilation to find a method of real time detection of CO 2 rebreathing without the need of CO 2 concentration measurement sampled from the circuit (method expensive and not routinely used). Observational study during routine care in 15 bed university hospital ICU. At 18 patients who required BiPAP ventilation, intubated or during noninvasive ventilation, during weaning period airflow, pressure and CO 2 concentration signals were registered on both sides of venting port and 17 respiratory parameters were measured or calculated for each of 4747 respiratory cycles analyzed. Based on CO 2 movement (expiration-inspiration sequences) 3 types of cycle were identified, type I and II do not induce rebreathing but type III does. To test differences between the 3 types ANOVA, t-tests, and canonical discriminant analysis (CDA) were used. Then a multilayer perceptron (MLP) network, a type of artificial neural network, using the above parameters (excluding CO 2 concentration) was applied to automatically identify the three types of respiratory cycles. Of the 4747 respiratory cycles, 1849 were type I, 1545 type II, and 1353 type III. ANOVA and t-tests showed significant differences between the types of respiratory cycles. CDA confirmed a correct apportionment of 93.9% of the cycles; notably, of 97.9% of type III. MLP automatically classified the respiratory cycles into the three types with 98.8% accuracy. Three types of respiratory cycles could be distinguished based on CO 2 movement during BiPAP ventilation. Artificial neural networks can be used to automatically detect respiratory cycle type III, the only inducing CO 2 rebreathing., (© 2024. The Author(s).)

Background: POINCARE-2 trial aimed to assess the effectiveness of a strategy designed to tackle fluid overload through daily weighing and subsequent administration of treatments in critically ill patients. Even in highly standardized care settings, such as intensive care units, effectiveness of such a complex intervention depends on its actual efficacy but also on the extent of its implementation. Using a process evaluation, we aimed to provide understanding of the implementation, context, and mechanisms of change of POINCARE-2 strategy during the trial, to gain insight on its effectiveness and inform the decision regarding the dissemination of the intervention., Methods: We conducted a mixed-method process evaluation following the Medical Research Council guideline. Both quantitative data derived from the trial, and qualitative data from semi-structured interviews with professionals were used to explain implementation, mechanisms of change of the POINCARE-2 strategy, as well as contextual factors potentially influencing implementation of the strategy., Results: Score of actual exposure to the strategy ranged from 29.1 to 68.2% during the control period, and from 61.9 to 92.3% during the intervention period, suggesting both potential contamination and suboptimal fidelity to the strategy. Lack of appropriate weighing devices, lack of human resources dedicated to research, pre-trial rooted prescription habits, and anticipated knowledge of the strategy have been identified as the main barriers to optimal implementation of the strategy in the trial context., Conclusions: Both contamination and suboptimal fidelity to POINCARE-2 strategy raised concerns about a potential bias towards the null of intention-to-treat (ITT) analyses. However, optimal fidelity seemed reachable. Consequently, a clinical strategy should not be rejected solely on the basis of the negativity of ITT analyses' results. Our findings showed that, even in highly standardized care conditions, the implementation of clinical strategies may be hindered by numerous contextual factors, which demonstrates the critical importance of assessing the viability of an intervention, prior to any evaluation of its effectiveness., Trial Registration: Number NCT02765009., (© 2024. The Author(s).)

Background: Cytomegalovirus (CMV) infection in patients with cellular immune deficiencies is associated with significant morbidity and mortality. However, data on CMV end-organ disease (CMV-EOD) in critically ill, immunocompromised patients are scarce. Our objective here was to describe the clinical characteristics and outcomes of CMV-EOD in this population., Methods: We conducted a multicenter, international, retrospective, observational study in adults who had CMV-EOD and were admitted to any of 18 intensive care units (ICUs) in France, Israel, and Spain in January 2010-December 2021. Patients with AIDS were excluded. We collected the clinical characteristics and outcomes of each patient. Survivors and non-survivors were compared, and multivariate analysis was performed to identify risk factors for hospital mortality., Results: We studied 185 patients, including 80 (43.2%) with hematologic malignancies, 55 (29.7%) with solid organ transplantation, 31 (16.8%) on immunosuppressants, 16 (8.6%) with solid malignancies, and 3 (1.6%) with primary immunodeficiencies. The most common CMV-EOD was pneumonia (n = 115, [62.2%] including 55 [47.8%] with a respiratory co-pathogen), followed by CMV gastrointestinal disease (n = 64 [34.6%]). More than one organ was involved in 16 (8.8%) patients. Histopathological evidence was obtained for 10/115 (8.7%) patients with pneumonia and 43/64 (67.2%) with GI disease. Other opportunistic infections were diagnosed in 69 (37.3%) patients. Hospital mortality was 61.4% overall and was significantly higher in the group with hematologic malignancies (75% vs. 51%, P = 0.001). Factors independently associated with higher hospital mortality were hematologic malignancy with active graft-versus-host disease (OR 5.02; 95% CI 1.15-27.30), CMV pneumonia (OR 2.57; 95% CI 1.13-6.03), lymphocytes < 0.30 × 10 9 /L at diagnosis of CMV-EOD (OR 2.40; 95% CI 1.05-5.69), worse SOFA score at ICU admission (OR 1.18; 95% CI 1.04-1.35), and older age (OR 1.04; 95% CI 1.01-1.07)., Conclusions: Mortality was high in critically ill, immunocompromised patients with CMV-EOD and varied considerably with the cause of immunodeficiency and organ involved by CMV. Three of the four independent risk factors identified here are also known to be associated with higher mortality in the absence of CMV-EOD. CMV pneumonia was rarely proven by histopathology and was the most severe CMV-EOD., (© 2024. The Author(s).)

Background: Critical-illness survivors may experience post-traumatic stress disorder (PTSD) and quality-of-life impairments. Resilience may protect against psychological trauma but has not been adequately studied after critical illness. We assessed resilience and its associations with PTSD and quality of life, and also identified factors associated with greater resilience., Methods: This prospective, multicentre, study in patients recruited at 41 French ICUs was done in parallel with the NUTRIREA-3 trial in patients given mechanical ventilation and vasoactive amines for shock. Three months to one year after intensive-care-unit admission, survivors completed the Connor-Davidson Resilience Scale (CD-RISC-25), Impact of Event-Revised scale for PTSD symptoms (IES-R), SF-36 quality-of-life scale, Multidimensional Scale of Perceived Social Support (MSPSS), and Brief Illness Perception Questionnaire (B-IPQ)., Results: Of the 382 included patients, 203 (53.1%) had normal or high resilience (CD-RISC-25 ≥ 68). Of these resilient patients, 26 (12.8%) had moderate to severe PTSD symptoms (IES-R ≥ 24) vs. 45 (25.4%) patients with low resilience (p = 0.002). Resilient patients had higher SF-36 scores. Factors independently associated with higher CD-RISC-25 scores were higher MSPSS score indicating stronger social support (OR, 1.027; 95%CI 1.008-1.047; p = 0.005) and lower B-IPQ scores indicating a more threatening perception of the illness (OR, 0.973; 95%CI 0.950-0.996; p = 0.02)., Conclusions: Resilient patients had a lower prevalence of PTSD symptoms and higher quality of life scores, compared to patients with low resilience. Higher scores for social support and illness perception were independently associated with greater resilience. Thus, our findings suggest that interventions to strengthen social support and improve illness perception may help to improve resilience. Such interventions should be evaluated in trials with PTSD mitigation and quality-of-life improvement as the target outcomes., (© 2024. The Author(s).)

The recent SarsCov2 pandemic has disrupted healthcare system notably impacting intensive care units (ICU). In severe cases, the immune system is dysregulated, associating signs of hyperinflammation and immunosuppression. In the present work, we investigated, using a joint modeling approach, whether the trajectories of cellular immunological parameters were associated with survival of COVID-19 ICU patients. This study is based on the REA-IMMUNO-COVID cohort including 538 COVID-19 patients admitted to ICU between March 2020 and May 2022. Measurements of monocyte HLA-DR expression (mHLA-DR), counts of neutrophils, of total lymphocytes, and of CD4+ and CD8+ subsets were performed five times during the first month after ICU admission. Univariate joint models combining survival at day 28 (D28), hospital discharge and longitudinal analysis of those biomarkers' kinetics with mixed-effects models were performed prior to the building of a multivariate joint model. We showed that a higher mHLA-DR value was associated with a lower risk of death. Predicted mHLA-DR nadir cutoff value that maximized the Youden index was 5414 Ab/C and led to an AUC = 0.70 confidence interval (95%CI) = [0.65; 0.75] regarding association with D28 mortality while dynamic predictions using mHLA-DR kinetics until D7, D12 and D20 showed AUCs of 0.82 [0.77; 0.87], 0.81 [0.75; 0.87] and 0.84 [0.75; 0.93]. Therefore, the final joint model provided adequate discrimination performances at D28 after collection of biomarker samples until D7, which improved as more samples were collected. After severe COVID-19, decreased mHLA-DR expression is associated with a greater risk of death at D28 independently of usual clinical confounders., (© 2024 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented., Results: To analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30-6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09-4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72-13.57), p = 0.001)., Conclusions: By using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches., (© 2024. The Author(s).)

Background: The efficacy and safety of cefiderocol in ICU patients with difficult-to-treat resistance (DTR) non-fermenting Gram-negative bacteria (Nf-GNB) are not as well-established. Consequently, we conducted a cohort study to compare Cefiderocol with the Best Available Therapy (BAT) in ICU patients., Methods: We included adult patients from 9 different ICUs, including a burn ICU unit, from 2019 to 2023 treated with Cefiderocol for DTR Nf-GNB isolated from the blood or lungs. We matched each patient at a 1:2 ratio based on the same DTR Nf-GBN isolated pathogen, and when possible, within the same type of ICU (burn unit or not). The primary endpoint of the study was the clinical cure at 15 days, with secondary endpoints including clinical cure at 30 days, relapse, and in-ICU mortality. For each outcome, adjusted odds ratios were estimated using bidirectional stepwise regression in a final model, which included 13 preselected confounders., Results: We included 27 patients with cefiderocol, matched with 54 patients receiving the BAT. Four patients were not exactly matched on the type of ICU unit. Characteristics were comparable between groups, mostly male with a Charlson Comorbidity Index of 3 [1-5], and 28% had immunosuppression. Cefiderocol patients were most likely to have higher number of antibiotic lines. The main DTR Nf-GNB identified was Pseudomonas aeruginosa (81.5%), followed by Acinetobater baumanii (14.8%) and Stenotrophomonas maltophilia (3.7%). Pneumonia was the identified infection in 21 (78.8%) patients in the Cefiderocol group and in 51 (94.4%) patients in the BAT group (p = 0.054). Clinical cure at 15 and 30-day and the in-ICU mortality was comparable between groups, however relapse was higher in the cefiderocol group (8-29.6% vs. 4-7.4%;aOR 10.06[1.96;51.53]) CONCLUSION: Cefiderocol did not show an improvement in clinical cure or mortality rates compared to BAT in the treatment of DTR Nf-GNB, but it was associated with a higher relapse rate., (© 2024. The Author(s).)

Rationale: Apart from hypoxic hepatitis (HH), the hepatic consequences of out-of-hospital cardiac arrest (OHCA) have been little studied. This cohort study aimed to investigate the characteristics of liver dysfunction resulting from OHCA and its association with outcomes., Methods: Among the conventional static liver function tests used to define acute liver failure (ALF), we determined which one correlated more closely with the reference indocyanine green (ICG) clearance test in a series of OHCA patients from the CYRUS trial (NCT01595958). Subsequently, we assessed whether ALF, in addition to HH (i.e., acute liver injury), was an independent risk factor for death in a large cohort of OHCA patients admitted to two intensive care units between 2007 and 2017., Results: ICG clearance, available for 22 patients, was impaired in 17 (77.3%) cases. Prothrombin time (PT) ratio was the only static liver function test that correlated significantly (r = -0.66, p < 0.01) with ICG clearance and was therefore used to define ALF, with the usual cutoff of < 50%. Of the 418 patients included in the analysis (sex ratio: 1.4; median age: 64 [53-75] years; non-shockable rhythm: 73%), 67 (16.0%) presented with ALF, and 61 (14.6%) had HH at admission. On day 28, 337 (80.6%) patients died. Following multivariate analysis, ALF at admission, OHCA occurring at home, absence of bystander, non-cardiac cause of OHCA, low-flow duration ≥ 20 min, and SOFA score excluding liver subscore at admission were independently associated with day 28 mortality., Conclusions: ALF occurred frequently after OHCA and, unlike HH, was independently associated with day 28 mortality., 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 Elsevier B.V. All rights reserved.)

Sepsis triggers a complex response marked by the simultaneous presence of proinflammatory and immunosuppressive elements, disrupting the mechanisms intended to maintain homeostasis. While the NLRP3 inflammasome has been demonstrated to contribute to the inflammatory side, its connection with delayed sepsis-induced immunosuppression remains unexplored. The present objective was to concomitantly and prospectively assess NLRP3 activation (IL-1β, IL-18, and soluble receptors) and features of immune failure (IL-10, mHLA-DR, myeloid-derived suppressor cells) in septic patients. To validate our findings, we conducted a transcriptomic analysis of mRNA of NLRP3-related genes (IL-18R1, IL-1R2) on an additional cohort of 107 patients. Two distinct endotypes were identified. One cluster displayed moderate inflammation rapidly returning to normal values, while the other exhibited a higher inflammatory response persisting until day 28, which was associated with persistent marked immunosuppression and higher 28-d mortality. Identifying endotypes with different pro/anti-inflammatory trajectories could hold important clinical implications for the management of sepsis., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Due to aging population and increasing part of immunocompromised patients, a raise in life-threatening organ damage related to VZV can be expected. Two retrospective studies were already conducted on VZV in ICU but focused on specific organ injury. Patients with high-risk of VZV disease still must be identified. The objective of this study was to report the clinical features and outcome of all life-threatening VZV manifestations requiring intensive care unit (ICU) admission. This retrospective cohort study was conducted in 26 French ICUs and included all adult patients with any life-threatening VZV-related event requiring ICU admission or occurring in ICU between 2010 and 2019., Results: One-hundred nineteen patients were included with a median SOFA score of 6. One hundred eight patients (90.8%) were admitted in ICU for VZV disease, leaving 11 (9.2%) with VZV disease occurring in ICU. Sixty-one patients (51.3%) were immunocompromised. Encephalitis was the most prominent organ involvement (55.5%), followed by pneumonia (44.5%) and hepatitis (9.2%). Fifty-four patients (45.4%) received norepinephrine, 72 (60.5% of the total cohort) needed invasive mechanical ventilation, and 31 (26.3%) received renal-replacement therapy. In-hospital mortality was 36.1% and was significantly associated with three independent risk factors by multivariable logistic regression: immunosuppression, VZV disease occurring in ICU and alcohol abuse. Hierarchical clustering on principal components revealed five phenotypically distinct clusters of patients: VZV-related pneumonia, mild encephalitis, severe encephalitis in solid organ transplant recipients, encephalitis in other immunocompromised hosts and VZV disease occurring in ICU. In-hospital mortality was highly different across phenotypes, ranging from zero to 75% (p < 0.001)., Conclusion: Overall, severe VZV manifestations are associated with high mortality in the ICU, which appears to be driven by immunosuppression status rather than any specific organ involvement. Deciphering the clinical phenotypes may help clinicians identify high-risk patients and assess prognosis., (© 2024. The Author(s).)

This retrospective study aimed to compare the mortality and burden of respiratory syncytial virus (RSV group), SARS-CoV-2 (COVID-19 group), non-H1N1 (Seasonal influenza group) and H1N1 influenza (H1N1 group) in adult patients admitted to intensive care unit (ICU) with respiratory failure. A total of 807 patients were included. Mortality was compared between the four following groups: RSV, COVID-19, seasonal influenza, and H1N1 groups. Patients in the RSV group had significantly more comorbidities than the other patients. At admission, patients in the COVID-19 group were significantly less severe than the others according to the simplified acute physiology score-2 (SAPS-II) and sepsis-related organ failure assessment (SOFA) scores. Using competing risk regression, COVID-19 (sHR = 1.61; 95% CI 1.10; 2.36) and H1N1 (sHR = 1.87; 95% CI 1.20; 2.93) were associated with a statistically significant higher mortality while seasonal influenza was not (sHR = 0.93; 95% CI 0.65; 1.31), when compared to RSV. Despite occurring in more severe patients, RSV and seasonal influenza group appear to be associated with a more favorable outcome than COVID-19 and H1N1 groups., (© 2024. The Author(s).)

Purpose: The effect of renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in comatose patients with severe AKI., Methods: We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72 h and/or blood urea nitrogen higher than 112 mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140 mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale [RASS] < - 3), irrespective of sedation, at randomization. A multi-state model was built, defining five mutually exclusive states: death, coma (RASS < - 3), incomplete awakening (RASS [- 3; - 2]), awakening (RASS [- 1; + 1] two consecutive days), and agitation (RASS >  + 1). Primary outcome was the transition from coma to awakening during 28 days after randomization., Results: A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio [HR] = 0.36 [0.17-0.78]; p = 0.010). Time spent awake was 10.11 days [8.11-12.15] and 7.63 days [5.57-9.64] in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results., Conclusion: In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: Psychological resilience (the ability to thrive in adversity) may protect against mental-health symptoms in healthcare professionals during coronavirus disease (COVID-19) waves. Objectives: To identify determinants of resilience in ICU staff members. Methods: In this cross-sectional survey in 21 French ICUs, staff members completed the 10-item Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Impact of Event Scale-Revised (for post-traumatic stress disorder [PTSD]). Factors independently associated with resilience were identified. Measurements and Main Results: The response rate was 73.1% (950 of 1,300). The median 10-item Connor-Davidson Resilience Scale score was 29 (interquartile range, 25-32). Symptoms of anxiety, depression, and PTSD were present in 61%, 39%, and 36% of staff members, respectively. Distress associated with the COVID-19 infodemic was correlated with symptoms of depression and PTSD. More resilient respondents less often had symptoms of anxiety, depression, and PTSD. Greater resilience was independently associated with male sex, having provided intensive care during the early waves, having managed more than 50 patients with COVID-19, and, compared with earlier waves, working longer hours, having greater motivation, and more often involving families in end-of-life decisions. Independent risk factors for lower resilience were having managed more than 10 patients who died of COVID-19, having felt frightened or isolated, and greater distress from the COVID-19 infodemic. Conclusions: This study identifies modifiable determinants of resilience among ICU staff members. Longitudinal studies are needed to determine whether prior resilience decreases the risk of mental ill health during subsequent challenges. Hospital and ICU managers, for whom preserving mental well-being among staff members is a key duty, should pay careful attention to resilience.

The transmission risk of SARS-CoV-2 within hospitals can exceed that in the general community because of more frequent close proximity interactions (CPIs). However, epidemic risk across wards is still poorly described. We measured CPIs directly using wearable sensors given to all present in a clinical ward over a 36-h period, across 15 wards in three hospitals in April-June 2020. Data were collected from 2114 participants and combined with a simple transmission model describing the arrival of a single index case to the ward to estimate the risk of an outbreak. Estimated epidemic risk ranged four-fold, from 0.12 secondary infections per day in an adult emergency to 0.49 per day in general paediatrics. The risk presented by an index case in a patient varied 20-fold across wards. Using simulation, we assessed the potential impact on outbreak risk of targeting the most connected individuals for prevention. We found that targeting those with the highest cumulative contact hours was most impactful (20% reduction for 5% of the population targeted), and on average resources were better spent targeting patients. This study reveals patterns of interactions between individuals in hospital during a pandemic and opens new routes for research into airborne nosocomial risk., (© 2024. The Author(s).)

Invasive fusariosis can be life-threatening, especially in immunocompromised patients who require intensive care unit (ICU) admission. We conducted a multicenter retrospective study to describe clinical and biologic characteristics, patient outcomes, and factors associated with death and response to antifungal therapy. We identified 55 patients with invasive fusariosis from 16 ICUs in France during 2002----2020. The mortality rate was high (56%). Fusariosis-related pneumonia occurred in 76% of patients, often leading to acute respiratory failure. Factors associated with death included elevated sequential organ failure assessment score at ICU admission or history of allogeneic hematopoietic stem cell transplantation or hematologic malignancies. Neither voriconazole treatment nor disseminated fusariosis were strongly associated with response to therapy. Invasive fusariosis can lead to multiorgan failure and is associated with high mortality rates in ICUs. Clinicians should closely monitor ICU patients with a history of hematologic malignancies or stem cell transplantation because of higher risk for death.

Background: Inhaled sedation during invasive mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) has received increasing attention. However, inhaled sedation devices increase dead-space ventilation and an undesirable effect is the increase in minute ventilation needed to maintain CO 2 removal. A consequence of raising minute ventilation is an increase in mechanical power (MP) that can promote lung injury. However, the effect of inhaled sedation devices on MP remains unknown., Methods: We conducted a bench study to assess and compare the effects of three devices delivering inhaled sevoflurane currently available in ICU (AnaConDa-50 mL (ANA-50), AnaConDa-100 mL (ANA-100), and MIRUS) on MP by using a test lung model set with three compliances (20, 40, and 60 mL/cmH 2 O). We simulated lung-protective ventilation using a low tidal volume and two levels of positive end-expiratory pressure (5 and 15 cmH 2 O) under ambient temperature and dry conditions. Following the insertion of the devices, either the respiratory rate or tidal volume was increased in 15%-steps until end-tidal CO 2 (EtCO 2 ) returned to the baseline value. MP was calculated at baseline and after EtCO 2 correction using a simplified equation., Results: Following device insertion, the EtCO 2 increase was significantly greater with MIRUS (+ 78 ± 13%) and ANA-100 (+ 100 ± 11%) than with ANA-50 (+ 49 ± 7%). After normalizing EtCO 2 by adjusting minute ventilation, MP significantly increased by more than 50% with all inhaled sedation devices compared to controls. The lowest increase in MP was observed with ANA-50 (p < 0.05 versus ANA-100 and MIRUS). The Costa index, another parameter assessing the mechanical energy delivered to the lungs, calculated as driving pressure × 4 + respiratory rate, significantly increased by more than 20% in all experimental conditions. Additional experiments performed under body temperature, ambient pressure, and gas saturated with water vapor conditions, confirmed the main results with an increase in MP > 50% with all devices after normalizing EtCO 2 by adjusting minute ventilation., Conclusion: Inhaled sedation devices substantially increased MP in this bench model of protective ventilation, which might limit their benefits in ARDS., (© 2024. The Author(s).)

Key Messages: In this study including 391 critically ill patients with nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not associated with a reduced hazard of death at Day 28 or a greater likelihood of clinical cure at Day 14. No over-risk of AKI was observed in patients receiving combination therapy., Background: The benefits and harms of combination antimicrobial therapy remain controversial in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria., Methods: We included all patients in the prospective multicenter OutcomeRea database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium and treated with initial adequate single-drug or combination therapy. The primary endpoint was Day-28 all-cause mortality. Secondary endpoints were clinical cure rate at Day 14 and a composite outcome of death or treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of combination therapy on the study endpoints were investigated through inverse probability of treatment-weighted regression and multivariable regression models. Subgroups analyses were performed according to the resistance phenotype of the causative pathogens (multidrug-resistant or not), the pivotal (carbapenems or others) and companion (aminoglycosides/polymyxins or others) drug classes, the duration of combination therapy (< 3 or ≥ 3 days), the SOFA score value at pneumonia onset (< 7 or ≥ 7 points), and in patients with pneumonia due to non-fermenting Gram-negative bacteria, pneumonia-related bloodstream infection, or septic shock., Results: Among the 391 included patients, 151 (38.6%) received single-drug therapy and 240 (61.4%) received combination therapy. VAP (overall, 67.3%), vHAP (16.4%) and HAP (16.4%) were equally distributed in the two groups. All-cause mortality rates at Day 28 (overall, 31.2%), clinical cure rate at Day 14 (43.7%) and the rate of death or AKI at Day 7 (41.2%) did not significantly differ between the groups. In inverse probability of treatment-weighted analyses, combination therapy was not independently associated with the likelihood of all-cause death at Day 28 (adjusted odd ratio [aOR], 1.14; 95% confidence interval [CI] 0.73-1.77; P = 0.56), clinical cure at Day 14 (aOR, 0.79; 95% CI 0.53-1.20; P = 0.27) or death or AKI at Day 7 (aOR, 1.07; 95% CI 0.71-1.63; P = 0.73). Multivariable regression models and subgroup analyses provided similar results., Conclusions: Initial combination therapy exerts no independent impact on Day-28 mortality, clinical cure rate at Day 14, and the hazard of death or AKI at Day 7 in critically ill patients with mono-bacterial HAP, vHAP or VAP due to Gram-negative bacteria., (© 2024. The Author(s).)

Objective: Unplanned invasive mechanical ventilation (IMV) is associated with high mortality in lung cancer patients. We aimed to identify factors associated with weaning from IMV, intensive care unit (ICU) survival and 1-year survival in lung cancer patients requiring unplanned IMV., Design: Retrospective observational study (2007-2017)., Setting: University-affiliated ICU., Patients: Lung cancer patients requiring unplanned IMV., Intervention: None., Main Variables of Interest: Weaning from IMV, ICU and 1-year survival., Results: Of the 136 patients included in the analysis (age 64 (9) years, male 110 (81%), metastatic disease 97 (62%)), 52 (38%) were weaned from IMV, 51 (38%) were discharged from ICU and 22 (16%) were alive at 1year. The main indication for intubation was acute respiratory failure. In multivariate analysis, PaO 2 /FiO 2 >175mmHg at ICU admission and intubation before ICU admission were associated with successful weaning from IMV while intubation for cardiac arrest was associated with weaning failure. Same factors were associated with ICU survival. Absence of metastasis at ICU admission and lung resection surgery were independently associated with 1-year survival., Conclusions: A significant proportion of patients with lung cancer treated with unplanned IMV could be weaned from IMV and survived to ICU discharge, especially in the absence of severe hypoxemia at ICU admission. The low one-year survival was mostly driven by metastatic status., (Copyright © 2023 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Sepsis is a life-threatening organ dysfunction caused by a dysregulated response to infection. In this context, the aberrant activation of the NLRP3 inflammasome has been documented mostly through the measurement of increased plasmatic concentrations of IL-1β and IL-18. At the cellular level, contradictory results have been published. However, no study has comprehensively monitored NLRP3 inflammasome activation at the basal level and after ex vivo reactivation of whole blood monocytes and neutrophils focusing on ICU patients with bacterial and viral sepsis, including a longitudinal analysis. Thus, we conducted a prospective longitudinal study, examining NLRP3 inflammasome functionality in COVID-19 ICU patients ( n = 15) and bacterial septic shock patients ( n = 17) during the first week of ICU hospitalization, compared with healthy donors. Using two whole-blood flow cytometry assays, we detected ASC speck-positive monocytes (i.e., monocytes presenting the polymerization of ASC proteins) and activated caspase-1 in polymorphonuclear cells as read-outs, both at baseline and following nigericin stimulation, a drug that forms pores and activates the NLRP3 inflammasome. Our findings showed that, at baseline and regardless of the type of infection, patients exhibited reduced ASC speck-positive monocytes and decreased activated caspase-1 in PMN compared to healthy volunteers. This decrease was prominent at day 0. Following nigericin stimulation, this reduction was also observed and persisted throughout the first week of hospitalization, irrespective of the cellular population or parameter being considered. Notably, at day 0, this diminished activation and response to stimulation of NLRP3 was associated with a higher 28-day mortality rate. Consequently, our observations highlighted a concurrent decline in both basal expression and ex vivo activation of the NLRP3 inflammasome in circulating myeloid cells from patients with bacterial and viral sepsis in association with increased mortality.

Background: In immunocompromised patients with acute respiratory failure (ARF), the clinical significance of respiratory virus detection in the nasopharynx remains uncertain., Research Question: Is viral detection in nasopharyngeal swabs associated with causes and outcomes of ARF in immunocompromised patients?, Study Design and Methods: This preplanned post hoc analysis of a randomized controlled trial enrolled immunocompromised patients admitted to 32 ICUs for ARF between May 2016 and December 2017. Nasopharyngeal swabs sampled at inclusion were assessed for 23 respiratory pathogens using multiplex polymerase chain reaction (PCR) assay. Causes of ARF were established by managing physicians and were reviewed by three expert investigators masked to the multiplex PCR assay results. Associations between virus detection in nasopharyngeal swabs, causes of ARF, and composite outcome of day 28 mortality, invasive mechanical ventilation (IMV), or both were assessed., Results: Among the 510 sampled patients, the multiplex PCR assay results were positive in 103 patients (20.2%), and a virus was detected in 102 samples: rhinoviruses or enteroviruses in 35.5%, coronaviruses in 10.9%, and flu-like viruses (influenza virus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus) in 52.7%. The cause of ARF varied significantly according to the results of the multiplex PCR assay, especially the proportion of viral pneumonia: 50.0% with flu-like viruses, 14.0% with other viruses, and 3.6% when no virus was detected (P < .001). No difference was found in the composite outcome of day 28 mortality, IMV, or both according to positive assay findings (54.9% vs 54.7%; P = .965). In a pre-established subgroup analysis, flu-like virus detection was associated with a higher rate of day 28 mortality, IMV, or both among recipients of allogeneic hematopoietic stem cell transplantation compared with those without detected virus., Interpretation: In immunocompromised patients with ARF, the results of nasopharyngeal multiplex PCR assays are not associated with IMV or mortality. A final diagnosis of viral pneumonia is retained in one-third of patients with positive assay results and in one-half of the patients with a flu-like virus., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J. L. reports receiving personal fees from Qiagen and Abbott Rapid Diagnostics SAS. V. L. received support for article research from Assistance Publique - Hôpitaux de Paris and is treasurer of the GRRR-OH research group, which has received fees from Pfizer, Fisher-Paykel, Gilead, Astellas, Sanofi, and Alexion. F. B. reports personal fees from Merck Sharp and Dohme and BioMérieux outside the submitted work. A. D. reports grants from the French Ministry of Health; grants and personal fees from Philips, Fisher & Paykel, Respinor, and Lungpacer; personal fees from Baxter, Getinge, Gilead, and Lowenstein; and nonfinancial support from Fisher & Paykel outside the submitted work. E. A. has received fees for lectures from MSD, Pfizer, and Alexion; his institution and research group have received support from Baxter, Jazz Pharmaceuticals, Fisher & Paykel, Gilead, Alexion, and Ablynx; and he received support for article research from Assistance Publique - Hôpitaux de Paris. None declared (A. M., M. B., S. M.-D., L. F., S. J., K. K., A. K., L. A., N. B., A.-S. M., E. C., F. P., M. S., D. M.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Intention-to-treat analyses of POINCARE-2 trial led to inconclusive results regarding the effect of a conservative fluid balance strategy on mortality in critically ill patients. The present as-treated analysis aimed to assess the effectiveness of actual exposure to POINCARE-2 strategy on 60-day mortality in critically ill patients., Methods: POINCARE‑2 was a stepped wedge randomized controlled trial. Eligible patients were ≥ 18 years old, under mechanical ventilation and had an expected length of stay in ICU > 24 h. POINCARE-2 strategy consisted of daily weighing over 14 days, and subsequent restriction of fluid intake, administration of diuretics, and/or ultrafiltration. We computed a score of exposure to the strategy based on deviations from the strategy algorithm. We considered patients with a score ≥ 75 as exposed to the strategy. We used logistic regression adjusted for confounders (ALR) or for an instrumental variable (IVLR). We handled missing data using multiple imputations., Results: A total of 1361 patients were included. Overall, 24.8% of patients in the control group and 69.4% of patients in the strategy group had a score of exposure ≥ 75. Exposure to the POINCARE-2 strategy was not associated with 60-day all-cause mortality (ALR: OR 1.2, 95% CI 0.85-1.55; IVLR: OR 1.0, 95% CI 0.76-1.33)., Conclusion: Actual exposure to POINCARE-2 conservative strategy was not associated with reduced mortality in critically ill patients. Trial registration POINCARE-2 trial is registered at ClinicalTrials.gov (NCT02765009). Registered 29 April 2016., (© 2023. The Author(s).)

Background: COVID-19-related acute respiratory distress syndrome (ARDS) is associated with a high mortality rate and longer mechanical ventilation. We aimed to assess the effectiveness of ventilation with ultra-low tidal volume (ULTV) compared with low tidal volume (LTV) in patients with COVID-19-related ARDS., Methods: This study was a multicentre, open-label, parallel-group, randomised trial conducted in ten intensive care units in France. Eligible participants were aged 18 years or older, received invasive mechanical ventilation for COVID-19 (confirmed by RT-PCR), had ARDS according to the Berlin definition, a partial pressure of arterial oxygen to inspiratory oxygen fraction (PaO 2 /FiO 2 ) ratio of 150 mm Hg or less, a tidal volume (V T ) of 6·0 mL/kg predicted bodyweight or less, and received continuous intravenous sedation. Patients were randomly assigned (1:1) using randomisation blocks to receive ULTV (intervention group) aiming for V T of 4·0 mL/kg predicted bodyweight or LTV (control group) aiming for V T 6·0 mL/kg predicted bodyweight. Participants, investigators, and outcome assessors were not masked to group assignment. The primary outcome was a ranked composite score based on all-cause mortality at day 90 as the first criterion and ventilator-free days among patients alive at day 60 as the second criterion. Effect size was computed with the unmatched win ratio, on the basis of pairwise prioritised comparison of primary outcome components between every patient in the ULTV group and every patient in the LTV group. The unmatched win ratio was calculated as the ratio of the number of pairs with more favourable outcome in the ULTV group over the number of pairs with less favourable outcome in the ULTV group. Primary analysis was done in the modified intention-to-treat population, which included all participants who were randomly assigned and not lost to follow-up. This trial is registered with ClinicalTrials.gov, NCT04349618., Findings: Between April 15, 2020, and April 13, 2021, 220 patients were included and five (2%) were excluded. 215 patients were randomly assigned (106 [49%] to the ULTV group and 109 [51%] to the LTV group). 58 (27%) patients were female and 157 (73%) were male. The median age was 68 years (IQR 60-74). 214 patients completed follow-up (one lost to follow-up in the ULTV group) and were included in the modified intention-to-treat analysis. The primary outcome was not significantly different between groups (unmatched win ratio in the ULTV group 0·85 [95% CI 0·60 to 1·19]; p=0·38). 46 (44%) of 105 patients in the ULTV group and 43 (39%) of 109 in the LTV group died by day 90 (absolute difference 4% [-9 to 18]; p=0·52). The rate of severe respiratory acidosis in the first 28 days was higher in the ULTV group than in the LTV group (35 [33%] vs 14 [13%]; absolute difference 20% [95% CI 9 to 31]; p=0·0004)., Interpretation: In patients with moderate-to-severe COVID-19-related ARDS, there was no significant difference with ULTV compared with LTV in the composite score based on mortality and ventilator-free days among patients alive at day 60. These findings do not support the systematic use of ULTV in patients with COVID-19-related ARDS., Funding: French Ministry of Solidarity and Health and Hospices Civils de Lyon., Competing Interests: Declaration of interests J-CR received a grant from Hamilton Medical for an unrelated experimental study, and from Hospices Civils De Lyon to conduct the present study. Congress attendance fees for J-CR were covered by GILEAD. NT reports personal fees from Pfizer outside of the submitted work. HY received a grant from the French Ministry of Health to conduct the study. GR and MMe report congress attendance fees covered by Pfizer. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Severe Legionnaires' disease (LD) can lead to multi-organ failure or death in 10%-30% of patients. Although hyper-inflammation and immunoparalysis are well described in sepsis and are associated with high disease severity, little is known about the immune response in LD. This study aimed to evaluate the immune status of patients with LD and its association with disease severity., Methods: A total of 92 hospitalized LD patients were included; 19 plasmatic cytokines and pulmonary Legionella DNA load were measured in 84 patients on the day of inclusion (day 0, D0). Immune functional assays (IFAs) were performed from whole blood samples collected at D2 and stimulated with concanavalin A [conA, n = 19 patients and n = 21 healthy volunteers (HV)] or lipopolysaccharide (LPS, n = 14 patients and n = 9 HV). A total of 19 cytokines (conA stimulation) and TNF-α (LPS stimulation) were quantified from the supernatants. The Sequential Organ Failure Assessment (SOFA) severity score was recorded at D0 and the mechanical ventilation (MV) status was recorded at D0 and D8., Results: Among the 84 patients, a higher secretion of plasmatic MCP-1, MIP1-β, IL-6, IL-8, IFN-γ, TNF-α, and IL-17 was observed in the patients with D0 and D8 MV. Multiparametric analysis showed that these seven cytokines were positively associated with the SOFA score. Upon conA stimulation, LD patients had a lower secretion capacity for 16 of the 19 quantified cytokines and a higher release of IL-18 and MCP-1 compared to HV. IL-18 secretion was higher in D0 and D8 MV patients. TNF-α secretion, measured after ex vivo LPS stimulation, was significantly reduced in LD patients and was associated with D8 MV status., Discussion: The present findings describe a hyper-inflammatory phase at the initial phase of Legionella pneumonia that is more pronounced in patients with severe LD. These patients also present an immunoparalysis for a large number of cytokines, except IL-18 whose secretion is increased. An assessment of the immune response may be relevant to identify patients eligible for future innovative host-directed therapies., 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., (Copyright © 2023 Allam, Mouton, Testaert, Ginevra, Fessy, Ibranosyan, Descours, Beraud, Guillemot, Chapalain, Albert-Vega, Richard, Argaud, Friggeri, Labeye, Jamilloux, Freymond, Venet, Lina, Doublet, Ader, Trouillet-Assant and Jarraud.)

Background: Acute respiratory failure (ARF) is the leading cause of ICU admission. Viruses are increasingly recognized as a cause of pneumonia in immunocompromised patients, but epidemiologic data are scarce. We used the Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie's database (2003-2017, 72 intensive care units) to describe the spectrum of critically ill immunocompromised patients with virus-detected ARF and to report their outcomes. Then, patients with virus-detected ARF were matched based on clinical characteristics and severity (1:3 ratio) with patients with ARF from other origins., Results: Of the 4038 immunocompromised patients in the whole cohort, 370 (9.2%) had a diagnosis of virus-detected ARF and were included in the study. Influenza was the most common virus (59%), followed by respiratory syncytial virus (14%), with significant seasonal variation. An associated bacterial infection was identified in 79 patients (21%) and an invasive pulmonary aspergillosis in 23 patients (6%). The crude in-hospital mortality rate was 37.8%. Factors associated with mortality were: neutropenia (OR = 1.74, 95% confidence interval, CI [1.05-2.89]), poor performance status (OR = 1.84, CI [1.12-3.03]), and the need for invasive mechanical ventilation on the day of admission (OR = 1.97, CI [1.14-3.40]). The type of virus was not associated with mortality. After matching, patients with virus-detected ARF had lower mortality (OR = 0.77, CI [0.60-0.98]) than patients with ARF from other causes. This result was mostly driven by influenza-like viruses, namely, respiratory syncytial virus, parainfluenza virus, and human metapneumovirus (OR = 0.54, CI [0.33-0.88])., Conclusions: In immunocompromised patients with virus-detected ARF, mortality is high, whatever the species, mainly influenced by clinical severity and poor general status. However, compared to non-viral ARF, in-hospital mortality was lower, especially for patients with detected viruses other than influenza., (© 2023. La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF).)

Background: Cardiac arrest is the most life-threatening complication of attempted suicide by hanging. However, data are scarce on its characteristics and outcome predictors., Methods: This retrospective observational multicentre study in 31 hospitals included consecutive adults admitted after cardiac arrest induced by suicidal hanging. Factors associated with in-hospital mortality were identified by multivariate logistic regression with multiple imputations for missing data and adjusted to the temporal trends over the study period., Results: Of 450 patients (350 men, median age, 43 [34-52] years), 305 (68%) had a psychiatric history, and 31 (6.9%) attempted hanging while hospitalized. The median time from unhanging to cardiopulmonary resuscitation was 0 [0-5] min, and the median time to return of spontaneous circulation (ROSC) was 20 [10-30] min. Seventy-nine (18%) patients survived to hospital discharge. Three variables were independently associated with higher in-hospital mortality: time from collapse or unhanging to ROSC>20 min (odds ratio [OR], 4.71; 95% confidence intervals [95%CIs], 2.02-10.96; p = 0.0004); glycaemia >1.4 g/L at admission (OR, 6.38; 95%CI, 2.60-15.66; p < 0.0001); and lactate >3.5 mmol/L at admission (OR, 6.08; 95%CI, 1.71-21.06; p = 0.005). A Glasgow Coma Scale (GCS) score of >5 at admission was associated with lower in-hospital mortality (OR, 0.009; 95%CI, 0.02-0.37; p = 0.0009)., Conclusion: In patients with hanging-induced cardiac arrest, time from collapse or unhanging to return of spontaneous circulation, glycaemia, arterial lactate, and coma depth at admission were independently associated with survival to hospital discharge. Knowledge of these risk factors may help guide treatment decisions in these patients at high risk of hospital mortality., 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., (Copyright © 2023 Salvetti, Schnell, Pichon, Schenck, Cronier, Perbet, Lascarrou, Guitton, Lesieur, Argaud, Colin, Cholley, Quenot, Merdji, Geeraerts, Piagnerelli, Jacq, Paul, Chelly, de Charentenay, Deye, Danguy des Déserts, Thiery, Simon, Das, Jacobs, Cerf, Mayaux, Beuret, Ouchenir, Lafarge, Sauneuf, Daubin, Cariou, Silva and Legriel.)

Background: Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP), a nosocomial pneumonia that is not related to invasive mechanical ventilation (IMV), has been less studied than ventilator-associated pneumonia, and never in the context of patients in an ICU for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD), a common cause of ICU admission. This study aimed to determine the factors associated with NV-ICU-AP occurrence and assess the association between NV-ICU-AP and the outcomes of these patients., Methods: Data were extracted from the French ICU database, OutcomeRea™. Using survival analyses with competing risk management, we sought the factors associated with the occurrence of NV-ICU-AP. Then we assessed the association between NV-ICU-AP and mortality, intubation rates, and length of stay in the ICU., Results: Of the 844 COPD exacerbations managed in ICUs without immediate IMV, NV-ICU-AP occurred in 42 patients (5%) with an incidence density of 10.8 per 1,000 patient-days. In multivariate analysis, prescription of antibiotics at ICU admission (sHR, 0.45 [0.23; 0.86], p = 0.02) and no decrease in consciousness (sHR, 0.35 [0.16; 0.76]; p < 0.01) were associated with a lower risk of NV-ICU-AP. After adjusting for confounders, NV-ICU-AP was associated with increased 28-day mortality (HR = 3.03 [1.36; 6.73]; p < 0.01), an increased risk of intubation (csHR, 5.00 [2.54; 9.85]; p < 0.01) and with a 10-day increase in ICU length of stay (p < 0.01)., Conclusion: We found that NV-ICU-AP incidence reached 10.8/1000 patient-days and was associated with increased risks of intubation, 28-day mortality, and longer stay for patients admitted with AECOPD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

In sepsis, personalized immunotherapy is being evaluated as a means of restoring immune function in the most severely affected patients. Biomarkers play a crucial role in this process, as there are no clear clinical indicators of immune dysfunction. Functional testing is considered a gold standard for assessing immune function, but this approach faces analytical challenges in terms of clinical implementation. The use of technician-dependent, time-consuming, home-made protocols often leads to poor standardization. This study represents the first beta testing of a fully automated interferon-γ release assay (IGRA) for monitoring the functionality of antigen-independent T lymphocytes. We observed a significant decrease in IFN-γ release capacity, which was associated with typical alterations in immunological cellular parameters (such as low mHLA-DR expression and decreased CD8 T lymphocyte count), in 22 patients with septic shock. Since the test is performed using whole blood and requires no technician intervention, with results available within 4 h, it may offer new possibilities for monitoring patients with immune alterations in routine clinical conditions. Further investigations in larger cohorts of patients are now needed to validate its clinical potential., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Both AIDS-defining and non-AIDS-defining cancers (ADC/NADC) predispose people living with HIV (PLHIV) to critical illnesses. The objective of this multicentre study was to investigate the prognostic impact of ADC and NADC in PLHIV admitted to the intensive care unit (ICU)., Methods: All PLHIV admitted over the 2015-2020 period in 12 university-affiliated ICUs in France were included in the study cohort. The effect of ADC and NADC on in-hospital mortality (primary study endpoint) was measured through logistic regression with augmented backward elimination of potential independent variables. The association between ADC/NADC and treatment limitation decision (TLD) during the ICU stay (secondary study endpoint) was analysed. One-year mortality in patients discharged alive from the index hospital admission (exploratory study endpoint) was compared between those with ADC, NADC or no cancer., Results: Amongst the 939 included PLHIV (median age, 52 [43-59] years; combination antiretroviral therapy, 74.4%), 97 (10.3%) and 106 (11.3%) presented with an active NADC (mostly lung and intestinal neoplasms) and an active ADC (predominantly AIDS-defining non-Hodgkin lymphoma), respectively. Inaugural admissions were common. Bacterial sepsis and non-infectious neoplasm-related complications accounted for most of admissions in these subgroups. Hospital mortality was 12.4% in patients without cancer, 30.2% in ADC patients and 45.4% in NADC patients (P < 0.0001). NADC (adjusted odds ratio [aOR], 7.00; 95% confidence interval [CI], 4.07-12.05) and ADC (aOR, 3.11; 95% CI 1.76-5.51) were independently associated with in-hospital death after adjustment on severity and frailty markers. The prevalence of TLD was 8.0% in patients without cancer, 17.9% in ADC patients and 33.0% in NADC patients (P < 0.0001)-organ failures and non-neoplastic comorbidities were less often considered in patients with cancer. One-year mortality in survivors of the index hospital admission was 7.8% in patients without cancer, 17.0% in ADC patients and 33.3% in NADC patients (P < 0.0001)., Conclusions: NADC and ADC are equally prevalent, stand as a leading argument for TLD, and strongly predict in-hospital death in the current population of PLHIV requiring ICU admission., (© 2023. La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF).)

Background: The immuno-receptor Triggering Expressed on Myeloid cells-1 (TREM-1) is activated during bacterial infectious diseases, where it amplifies the inflammatory response. Small studies suggest that TREM-1 could be involved in viral infections, including COVID-19. We here aim to decipher whether plasma concentration of the soluble form of TREM-1 (sTREM-1) could predict the outcome of hospitalized COVID-19 patients., Methods: We conducted a multicentre prospective observational study in 3 university hospitals in France. Consecutive hospitalized patients with confirmed infection with SARS-CoV-2 were enrolled. Plasma concentration of sTREM-1 was measured on admission and then at days 4, 6, 8, 14, 21, and 28 in patients admitted into an ICU (ICU cohort: ICUC) or 3 times a week for patients hospitalized in a medical ward (Conventional Cohort: ConvC). Clinical and biological data were prospectively recorded and patients were followed-up for 90 days. For medical ward patients, the outcome was deemed complicated in case of requirement of increased oxygen supply > 5 L/min, transfer to an ICU, or death. For Intensive Care Unit (ICU) patients, complicated outcome was defined by death in the ICU., Results: Plasma concentration of sTREM-1 at inclusion was higher in ICU patients (n = 269) than in medical ward patients (n = 562) (224 pg/mL (IQR 144-320) vs 147 pg/mL (76-249), p < 0.0001), and higher in patients with a complicated outcome in both cohorts: 178 (94-300) vs 135 pg/mL (70-220), p < 0.0001 in the ward patients, and 342 (288-532) vs 206 pg/mL (134-291), p < 0.0001 in the ICU patients. Elevated sTREM-1 baseline concentration was an independent predictor of complicated outcomes (Hazard Ratio (HR) = 1.5 (1.1-2.1), p = 0.02 in ward patients; HR = 3.8 (1.8-8.0), p = 0.0003 in ICU patients). An sTREM-1 plasma concentration of 224 pg/mL had a sensitivity of 42%, and a specificity of 76% in the ConvC for complicated outcome. In the ICUC, a 287 pg/mL cutoff had a sensitivity of 78%, and a specificity of 74% for death. The sTREM-1 concentrations increased over time in the ConvC patients with a complicated outcome (p = 0.017), but not in the ICUC patients., Conclusions: In COVID-19 patients, plasma concentration of sTREM-1 is an independent predictor of the outcome, although its positive and negative likelihood ratio are not good enough to guide clinical decision as a standalone marker., (© 2023. The Author(s).)

Background: The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets., Methods: The pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2-0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0-1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed., Findings: Of 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference -1·5%, 95% CI -5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0-14·0) in the low group and 9·0 days (5·0-17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p<0·001), diarrhoea (0·83, 0·73 to 0·94; p=0·004), bowel ischaemia (0·50, 0·26 to 0·95; p=0·030), and liver dysfunction (0·92, 0·86-0·99; p=0·032)., Interpretation: Compared with standard calorie and protein targets, early calorie and protein restriction did not decrease mortality but was associated with faster recovery and fewer complications., Funding: French Ministry of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Community-acquired bacterial meningitis is a rare but severe central nervous system infection that may be associated with cerebrovascular complications (CVC). Our objective is to assess the prevalence of CVC in patients with community-acquired bacterial meningitis and to determine the first-48 h factors associated with CVC., Methods: We analyzed data from the prospective multicenter cohort study (COMBAT) including, between February 2013 and July 2015, adults with community-acquired bacterial meningitis. CVC were defined by the presence of clinical or radiological signs (on cerebral CT or MRI) of focal clinical symptom. Factors associated with CVC were identified by multivariate logistic regression., Results: CVC occurred in 128 (25.3%) of the 506 patients in the COMBAT cohort (78 (29.4%) of the 265 pneumococcal meningitis, 17 (15.3%) of the 111 meningococcal meningitis, and 29 (24.8%) of the 117 meningitis caused by other bacteria). The proportion of patients receiving adjunctive dexamethasone was not statistically different between patients with and without CVC (p = 0.84). In the multivariate analysis, advanced age (OR = 1.01 [1.00-1.03], p = 0.03), altered mental status at admission (OR = 2.23 [1.21-4.10], p = 0.01) and seizure during the first 48 h from admission (OR = 1.90 [1.01-3.52], p = 0.04) were independently associated with CVC., Conclusions: CVC were frequent during community-acquired bacterial meningitis and associated with advanced age, altered mental status and seizures occurring within 48 h from admission but not with adjunctive corticosteroids., (© 2023. The Author(s).)

Objectives: Our aim was to describe changes in the management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) by ICUs and patient outcomes., Design: We extracted data from the OutcomeRea database concerning patients admitted for AECOPD between 1997 and 2018. We analyzed trends in the use of ventilatory support, corticosteroid therapy, antibiotic therapy, and patient survival., Setting: ICUs at 32 French sites., Patients: One thousand eight hundred sixteen patients in the database had a diagnosis of AECOPD., Interventions: None., Measurements and Main Results: Over time, there was a reduction in the prescription of corticosteroids and antibiotics. In a time-series analysis, these changes in practice were not linked with ICU mortality. The proportion of patients treated with invasive mechanical ventilation (IMV) also gradually declined (from 51% between 1997 and 2002 to 35% between 2013 and 2018) with an association between decrease in IMV use and reduction in ICU mortality in a time series analysis. Rates of noninvasive ventilation (NIV) failure decreased with an increase in NIV use to support weaning from IMV. There was a reduction in the median ICU length of stay (from 8 d in 1997-2002 to 4 d in 2013-2018) and in the median total duration of hospitalization (from 23 d in 1997-2002 to 14 d in 2013-2018). We observed an improvement in prognosis, with decreases in overall hospital mortality (from 24% between 1997 and 2002 to 15% between 2013 and 2018), ICU mortality (from 14% between 1997 and 2002 to 10% between 2013 and 2018), and 90-day mortality (from 41% between 1997 and 2002 to 22% between 2013 and 2018)., Conclusions: The length of stay and mortality of patients with AECOPD admitted to ICUs has decreased over the last 20 years, with a wider use of NIV and a reduction in antibiotic and corticosteroid prescriptions., Competing Interests: Dr. Terzi received funding from Pfizer for attending meetings and/or travel. Dr. Hong Tuan Ha disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: The spontaneous breathing trial (SBT) is the final step of weaning from invasive mechanical ventilation. An SBT is aimed at predicting work of breathing (WOB) after extubation and, most importantly, a patient's eligibility for extubation. The optimal SBT modality remains debated. A high-flow oxygen (HFO) has been tested during SBT in clinical study only, which is why no definite conclusion can be drawn on its physiologic effects on the endotracheal tube. Our objective was to assess, on a bench, inspiratory tidal volume (V T ), total PEEP, and WOB across 3 different SBT modalities: T-piece, 40 L/min HFO, and 60 L/min HFO., Methods: A test lung model was set with 3 conditions of resistance and linear compliance, 3 inspiratory efforts (low, normal, and high), each at 2 breathing frequencies (low and high for 20 and 30 breaths/min, respectively). Pairwise comparisons and a quasi-Poisson generalized linear model that compared SBT modalities were performed., Results: Inspiratory V T , total PEEP, and WOB differed from one SBT modality to another. Inspiratory V T remained higher with the T-piece than in the HFO independent of the mechanical condition, effort intensity, and breathing frequency ( P < .001 in each comparison). WOB adjusted by the inspiratory V T was significantly lower during SBT performed with an HFO than when performed with the T-piece ( P < .001 in each comparison). The total PEEP was significantly higher in the HFO at 60 L/min than in the other modalities ( P < .001). The end points were significantly influenced by breathing frequency, effort intensity, and mechanical condition., Conclusions: With the same effort intensity and breathing frequency, inspiratory V T was higher in the T-piece than in the other modalities. Compared with the T-piece, WOB was significantly lower in the HFO condition and higher flow was a benefit. Based on the results of the present study, the HFO as an SBT modality would seem to require clinical testing., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2023 by Daedalus Enterprises.)

Background and Objectives: To report the prevalence of acute encephalopathy and outcomes in patients with severe coronavirus disease 2019 (COVID-19) and to identify determinants of 90-day outcomes., Methods: Data from adults with severe COVID-19 and acute encephalopathy were prospectively collected for patients requiring intensive care unit management in 31 university or university-affiliated intensive care units in 6 countries (France, United States, Colombia, Spain, Mexico, and Brazil) between March and September of 2020. Acute encephalopathy was defined, as recently recommended, as subsyndromal delirium or delirium or as a comatose state in case of severely decreased level of consciousness. Logistic multivariable regression was performed to identify factors associated with 90-day outcomes. A Glasgow Outcome Scale-Extended (GOS-E) score of 1-4 was considered a poor outcome (indicating death, vegetative state, or severe disability)., Results: Of 4,060 patients admitted with COVID-19, 374 (9.2%) experienced acute encephalopathy at or before the intensive care unit (ICU) admission. A total of 199/345 (57.7%) patients had a poor outcome at 90-day follow-up as evaluated by the GOS-E (29 patients were lost to follow-up). On multivariable analysis, age older than 70 years (odds ratio [OR] 4.01, 95% CI 2.25-7.15), presumed fatal comorbidity (OR 3.98, 95% CI 1.68-9.44), Glasgow coma scale score <9 before/at ICU admission (OR 2.20, 95% CI 1.22-3.98), vasopressor/inotrope support during ICU stay (OR 3.91, 95% CI 1.97-7.76), renal replacement therapy during ICU stay (OR 2.31, 95% CI 1.21-4.50), and CNS ischemic or hemorrhagic complications as acute encephalopathy etiology (OR 3.22, 95% CI 1.41-7.82) were independently associated with higher odds of poor 90-day outcome. Status epilepticus, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome were associated with lower odds of poor 90-day outcome (OR 0.15, 95% CI 0.03-0.83)., Discussion: In this observational study, we found a low prevalence of acute encephalopathy at ICU admission in patients with COVID-19. More than half of patients with COVID-19 presenting with acute encephalopathy had poor outcomes as evaluated by GOS-E. Determinants of poor 90-day outcome were dominated by older age, comorbidities, degree of impairment of consciousness before/at ICU admission, association with other organ failures, and acute encephalopathy etiology., Trial Registration Information: The study is registered with ClinicalTrials.gov, number NCT04320472., (© 2023 American Academy of Neurology.)

Purpose: We aimed to characterize the outcomes of patients with severe meningoencephalitis requiring intensive care., Methods: We conducted a prospective multicenter international cohort study (2017-2020) in 68 centers across 7 countries. Eligible patients were adults admitted to the intensive care unit (ICU) with meningoencephalitis, defined by an acute onset of encephalopathy (Glasgow coma scale (GCS) score [Formula: see text] 13), a cerebrospinal fluid pleocytosis [Formula: see text] 5 cells/mm 3 , and at least two of the following criteria: fever, seizures, focal neurological deficit, abnormal neuroimaging, and/or electroencephalogram. The primary endpoint was poor functional outcome at 3 months, defined by a score of three to six on the modified Rankin scale. Multivariable analyses stratified on centers investigated ICU admission variables associated with the primary endpoint., Results: Among 599 patients enrolled, 589 (98.3%) completed the 3-month follow-up and were included. Overall, 591 etiologies were identified in those patients which were categorized into five groups: acute bacterial meningitis (n = 247, 41.9%); infectious encephalitis of viral, subacute bacterial, or fungal/parasitic origin (n = 140, 23.7%); autoimmune encephalitis (n = 38, 6.4%); neoplastic/toxic encephalitis (n = 11, 1.9%); and encephalitis of unknown origin (n = 155, 26.2%). Overall, 298 patients (50.5%, 95% CI 46.6-54.6%) had a poor functional outcome, including 152 deaths (25.8%). Variables independently associated with a poor functional outcome were age > 60 years (OR 1.75, 95% CI 1.22-2.51), immunodepression (OR 1.98, 95% CI 1.27-3.08), time between hospital and ICU admission > 1 day (OR 2.02, 95% CI 1.44-2.99), a motor component on the GCS [Formula: see text] 3 (OR 2.23, 95% CI 1.49-3.45), hemiparesis/hemiplegia (OR 2.48, 95% CI 1.47-4.18), respiratory failure (OR 1.76, 95% CI 1.05-2.94), and cardiovascular failure (OR 1.72, 95% CI 1.07-2.75). In contrast, administration of a third-generation cephalosporin (OR 0.54, 95% CI 0.37-0.78) and acyclovir (OR 0.55, 95% CI 0.38-0.80) on ICU admission were protective., Conclusion: Meningoencephalitis is a severe neurologic syndrome associated with high mortality and disability rates at 3 months. Actionable factors for which improvement could be made include time from hospital to ICU admission, early antimicrobial therapy, and detection of respiratory and cardiovascular complications at admission., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections. Few data are available regarding neutropenic patients with NSTIs. Our objectives were to describe the characteristics and management of neutropenic patients with NSTIs in intensive care units (ICUs). We conducted a retrospective multicentre cohort study in 18 ICUs between 2011 and 2021. Patients admitted with NSTIs and concomitant neutropenia at diagnosis were included and compared to non-neutropenic patients with NSTIs. The relationship between therapeutic interventions and outcomes was assessed using Cox regression and propensity score matching., Results: 76 neutropenic patients were included and compared to 165 non-neutropenic patients. Neutropenic patients were younger (54 ± 14 vs 60 ± 13 years, p = 0.002) and had less lower limb (44.7% vs 70.9%, p < 0.001) and more abdomino-perineal NSTIs (43.4% vs 18.8%, p < 0.001). Enterobacterales and non-fermenting gram-negative bacteria were the most frequently isolated microorganisms in neutropenic patients. In-hospital mortality was significantly higher in neutropenic than in non-neutropenic patients (57.9% vs 28.5%, p < 0.001). Granulocyte colony-stimulating factor (G-CSF) administration was associated with a lower risk of in-hospital mortality in univariable Cox (hazard ratio (HR) = 0.43 95% confidence interval (CI) [0.23-0.82], p = 0.010) and multivariable Cox (adjusted HR = 0.46 95% CI [0.22-0.94], p = 0.033) analyses and after overlap propensity score weighting (odds ratio = 0.25 95% CI [0.09; 0.68], p = 0.006)., Conclusions: Critically ill neutropenic patients with NSTIs present different clinical and microbiological characteristics and are associated with a higher hospital mortality than non-neutropenic patients. G-CSF administration was associated with hospital survival., (© 2023. The Author(s).)

Introduction: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a frequent cause of intensive care unit (ICU) admission. However, data are scarce and conflicting regarding the impact of systemic corticosteroid treatment in critically ill patients with acute exacerbation of COPD. The aim of the study was to assess the impact of systemic corticosteroids on the occurrence of death or need for continuous invasive mechanical ventilation at day 28 after ICU admission., Methods: In the OutcomeReaTM prospective French national ICU database, we assessed the impact of corticosteroids at admission (daily dose ≥ 0.5 mg/kg of prednisone or equivalent during the first 24 hours ICU stay) on a composite outcome (death or invasive mechanical ventilation) using an inverse probability treatment weighting., Results: Between January 1, 1997 and December 31, 2018, 391 out of 1,247 patients with acute exacerbations of COPDs received corticosteroids at ICU admission. Corticosteroids improved the main composite endpoint (OR = 0.70 [0.49; 0.99], p = 0.044. However, for the subgroup of most severe COPD patients, this did not occur (OR = 1.12 [0.53; 2.36], p = 0. 770). There was no significant impact of corticosteroids on rates of non-invasive ventilation failure, length of ICU or hospital stay, mortality or on the duration of mechanical ventilation. Patients on corticosteroids had the same prevalence of nosocomial infections as those without corticosteroids, but more glycaemic disorders., Conclusion: Using systemic corticosteroids for acute exacerbation of COPD at ICU admission had a positive effect on a composite outcome defined by death or need for invasive mechanical ventilation at day 28., Competing Interests: NT is supported by Pfizer for attending meetings and/or travel. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare that they have no competing interests., (Copyright: © 2023 Galerneau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale: Nurse-to-nurse familiarity at work should strengthen the components of teamwork and enhance its efficiency. However, its impact on patient outcomes in critical care remains poorly investigated. Objectives: To explore the role of nurse-to-nurse familiarity on inpatient deaths during ICU stay. Methods: This was a retrospective observational study in eight adult academic ICUs between January 1, 2011 and December 31, 2016. Measurements and Main Results: Nurse-to-nurse familiarity was measured across day and night 12-hour daily shifts as the mean number of previous collaborations between each nursing team member during previous shifts within the given ICU (suboptimal if <50). Primary outcome was a shift with at least one inpatient death, excluding death of patients with a decision to forego life-sustaining therapy. A multiple modified Poisson regression was computed to identify the determinants of mortality per shift, taking into account ICU, patient characteristics, patient-to-nurse and patient-to-assistant nurse ratios, nurse experience length, and workload. A total of 43,479 patients were admitted, of whom 3,311 (8%) died. The adjusted model showed a lower risk of a shift with mortality when nurse-to-nurse familiarity increased in the shift (relative risk, 0.90; 95% confidence interval per 10 shifts, 0.82-0.98; P  = 0.012). Low nurse-to-nurse familiarity during the shift combined with suboptimal patient-to-nurse and patient-to-assistant nurse ratios (suboptimal if >2.5 and >4, respectively) were associated with increased risk of shift with mortality (relative risk, 1.84; 95% confidence interval, 1.15-2.96; P  < 0.001). Conclusions: Shifts with low nurse-to-nurse familiarity were associated with an increased risk of patient deaths.

Intra-Abdominal Candidiasis (IAC) is frequent and associated with high mortality in intensive care unit (ICU) patients. Antifungal treatments may be overused due to a lack of diagnostic tools to rule out IAC. Serum 1,3-Beta-D-Glucan (BDG) concentrations are used to diagnose Candida infections, its concentration in peritoneal fluid (PF) may help to confirm or invalidate the diagnosis of IAC. We performed a non-interventional, prospective, multicenter study, at the Hospices Civils de Lyon, France, in seven ICU located in three different hospitals from December 2017 to June 2018. IAC was defined as the isolation of Candida in a sample collected from the intra-abdominal cavity under sterile conditions in patients displaying clinical evidence of intra-abdominal infection. Among the 113 included patients, 135 PF samples corresponding to 135 intra-abdominal infection episodes were collected and BDG concentrations were assessed. IAC accounted for 28 (20.7%) of the intra-abdominal infections. Antifungals were administered empirically to 70 (61.9%) patients; among them, 23 (32.9%) had an IAC. The median [IQR] BDG value was significantly higher in IAC (8100 [3000;15000] pg/mL) than in non-IAC samples (1961 [332;10650] pg/mL). BDG concentrations were higher in PF with Fecaloid aspect and in case of positive bacterial culture. For a BDG threshold of 125 pg/mL, the negative predictive value to assess IAC was 100%. In conclusion, low BDG PF concentrations could be used to rule out IAC. https://clinicaltrials.gov/ct2/show/NCT03469401., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)