Background:In patients with septic shock as well as in the critically ill, the impact of hypothermia and core temperature changes during the first 24 h on mortality remains uncertain. In this post-hoc analysis of the SEPSISPAM trial, we investigated the association between hypothermia at inclusion, hypothermia trajectories and 90-day mortality in patients with septic shock. Methods:This post-hoc analysis of the SEPSISPAM trial included patients with septic shock enrolled within 6 h of vasopressors initiation. Core temperature was assessed every 2 h during the first 24 h. Hypothermia was defined by a temperature <36 °C. Mortality was assessed at day 90. Results:We included 691 patients from the SEPSISPAM trial, of whom 103 (14.9%) presented with hypothermia at inclusion. After adjustment for confounding factors, as compared with patients without hypothermia at inclusion, patients with hypothermia at inclusion had a higher mortality (HR 1.92, 95% CI [1.38-2.67], p < 0.001). Three groups of patients were identified according to the evolution of their core temperature: "without hypothermia" (86.6%), i.e., patients without any hypothermia during the first 24 h; "transient hypothermia" (10%), i.e., patients with hypothermia at inclusion and becoming normothermic during the first 24 h, and "persistent hypothermia" (3.4%), i.e., patients with sustained hypothermia both at inclusion and during the first 24 h. Compared with patients without hypothermia, the "persistent hypothermia" group had the highest mortality rate at day 90 (78.3%, HR 2.83 [1.62-4.95], p < 0.0001). Mortality at day 90 increased according to temperature trajectories, being highest in patients with persistent hypothermia (78%), followed by those with transient hypothermia (49%), and lowest in patients without hypothermia (40%). Conclusion:In patients with septic shock, hypothermia at inclusion and persistence of hypothermia during the first 24 h were associated with higher mortality at day 90. Mortality increased according to the course of hypothermia during the first 24 h, being highest in patients with persistent hypothermia, followed by those with transient hypothermia, and lowest in patients who never developed hypothermia.

BACKGROUND:Sepsis is a dysregulated host response to infection resulting in life-threatening organ failure. Although immune dysregulation is central to the sepsis definition, immunomodulation trials enrol participants based on clinical severity, not the extent of dysregulation, which could contribute to treatment heterogeneity. A pragmatic way to quantify immune dysregulation could improve prognostication, help to evaluate treatment responses, and identify individuals most likely to benefit from immunomodulation. We aimed to construct a parsimonious machine-learning tool that defines and quantifies immune dysregulation, thereby supporting biologically informed immunomodulation. METHODS:In this multicohort analysis and reanalysis of a randomised controlled trial, the primary objective was to derive and validate a categorical and continuous immune dysregulation score that is independent of clinical presentation or outcome. We measured 35 plasma biomarkers reflecting key host response domains in individuals with community-acquired pneumonia (CAP) across different care settings (emergency department, general ward, and intensive care unit) and disease severities using data from three independent cohorts. We applied unsupervised trajectory inference analysis to identify an immune dysregulation gradient captured as discrete immune dysregulation stages (Dysregulated Immune Profile [DIP]) and a continuous score (cDIP; 0-1). We developed two parsimonious machine-learning models to predict the DIP stages and cDIP scores based on 35 biomarkers, and validated their ability to capture immune dysregulation and predict clinical outcomes in five independent cohorts. On the basis of our hypothesis that only individuals with severe immune dysregulation benefit from immunomodulation, we carried out a post-hoc analysis of a randomised trial evaluating hydrocortisone in severe CAP (CAPE COD trial, NCT02517489), assessing treatment effects across DIP stages and the cDIP continuum, and how hydrocortisone influenced dysregulation trajectories over time. FINDINGS:We organised 398 participants with CAP along a continuum of immune dysregulation from mild to severe on the basis of 35 plasma biomarkers, yielding three dysregulation stages (DIP1-3) and a continuous score (cDIP). Clinical severity proved to be an inadequate proxy for immune dysregulation. A three-biomarker machine-learning framework (procalcitonin, soluble TREM-1, and IL-6) accurately predicted the degree of dysregulation derived from 35 biomarkers (DIP stage accuracy 91·2%; cDIP root mean square error 0·056). Although the framework was not designed for outcome prediction, increased immune dysregulation-reflected in DIP and cDIP-was associated with a gradual rise in mortality (cDIP odds ratio [OR] 1·26 [95% CI 1·13-1·40] per 10% increase, p<0·0001) and secondary infections (OR 1·50 [1·22-1·93] per 10% increase, p=0·0005), independent of clinical severity. The three-biomarker tool was validated in five external cohorts of varying infections, severities, and care settings (n=1191). Reanalysis of the CAPE COD trial showed that hydrocortisone conferred a survival benefit only in participants classified as severely dysregulated by our model (30-day mortality: DIP3 OR 0·25 [0·05-0·85], p=0·042; cDIP ≥0·63 OR 0·21 [0·10-0·72], p=0·011), accompanied by faster immune recovery (time × treatment interaction, p<0·0001). No such effect modification was observed when stratifying participants by clinical severity. INTERPRETATION:We have provided a publicly available three-biomarker framework to determine the extent of host response dysregulation with potential value for precision-guided immunomodulatory therapy. FUNDING:EU Horizon 2020.

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.

Community-acquired pneumonia, particularly in its severe forms (sCAP), remains a major public health problem due to its frequency, immediate and delayed complications, and the cost of treatment. Although rare, resistant pathogens could make it increasingly difficult to choose an empirical antibiotic treatment. Rapid molecular microbiological diagnostic techniques could help guide this choice, but their role needs to be better evaluated and their cost may be an obstacle to their widespread use. The duration of treatment tends to be decreasing, but could be guided by clinical progression and possibly biomarkers. As a disorder of dysregulated systemic inflammation, sCAP is potentially eligible for immunomodulatory treatment. Three recent high-powered randomized trials on corticosteroids have yielded conflicting results. There is a need to better define which patients are likely to benefit, perhaps those with a marked inflammatory syndrome, and in any case not those with influenza. Some macrolides also have a potential immunomodulatory effect. Other treatments are currently being investigated. Supportive care, particularly respiratory support, remains essential. It is not specific to sCAP and must be tailored to the severity of the patient's condition.

BACKGROUND:Although largely used, the place of extracorporeal renal replacement therapy (RRT) in acute kidney injury (AKI) in intensive care unit (ICU) patients has yet to be clarified. The French Intensive Care Society (Société de Réanimation de Langue Française, SRLF) and the French Pediatric Group of Intensive Care and Emergency (Groupe Francophone de Réanimation et d'Urgence Pédiatrique, GFRUP) organized a consensus conference in November 2024. METHODS:A committee, without any conflict of interest (CoI) on the subject, defined seven generic questions and drew up a list of sub questions according to the population, intervention, comparison and outcomes (PICO) model. An independent work group reviewed literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Eighteen experts in the field from both societies proposed their own answers in a public session and answered questions from the jury (a panel of 14 critical-care medicine physicians and a nurse) and the public. The jury then met for 48 h to write out and vote on its recommendations. RESULTS:The panel provided 45 statements addressing seven questions. In patients, adults or children, admitted to the ICU with AKI (1) What are the indications for RRT, when should it be initiated, and within what timeframe? (2) What are the advantages/disadvantages of the different RRT modalities in ICU, and based on what criteria should they be chosen? (3) Which dose of dialysis should be prescribed for ICU patients? (4) How to prescribe, adjust and monitor each RRT technique? (5) Which vascular access technique should be preferred (insertion site, catheter type and length)? (6) How to prevent circuit thrombosis? (7) What are the criteria to consider weaning from RRT and how can it be achieved? CONCLUSIONS:These recommendations should optimize the prescription and use of RRT during AKI in ICUs for both adult and pediatric patients.

Background Despite several randomised controlled trials (RCTs) on the use of adjuvant treatment with corticosteroids in patients with community-acquired pneumonia (CAP), the effect of this intervention on mortality remains controversial. We aimed to evaluate heterogeneity of treatment effect (HTE) of adjuvant treatment with corticosteroids on 30-day mortality in patients with CAP. Methods In this individual patient data meta-analysis, we included RCTs published before July 1, 2024, comparing adjuvant treatment with corticosteroids versus placebo in patients hospitalised with CAP. The primary endpoint was 30-day all-cause mortality, collected across all trials, and analyses followed the intention-to-treat principle. We analysed HTE using risk and effect modelling. For risk modelling, patients were classified as having less severe or severe CAP based on the pneumonia severity index (PSI), comparing PSI class I-III versus class IV-V. For effect modelling, we trained a corticosteroid-effect model on six trials and externally validated it using data from two trials, received after model preregistration. This model classified patients into two groups: no predicted benefit and predicted benefit from adjuvant treatment with corticosteroids. The literature search was registered on PROSPERO, CRD42022380746. Findings We included eight RCTs with 3224 patients. Across all eight trials, 246 (76%) patients died within 30 days (106 [66%] of 1618 in the corticosteroid group vs 140 [87%] of 1606 in the placebo group; odds ratio [OR] 072 [95% CI 056-094], p=0017). The corticosteroid-effect model, which selected C-reactive protein (CRP), showed significant HTE during external validation in the two most recent trials. In these trials, 154 (114%) of 1355 patients died within 30 days (88 [131%] of 671 in the placebo group vs 66 [96%] of 684 in the corticosteroid group; OR 071 [95% CI 050-099], p=0044). Among patients predicted to have no benefit (CRP <= 204 mg/L, n=725), no significant effect was observed (OR 098 [95% CI 063-150]), whereas for those with predicted benefit (CRP >204 mg/L, n=630), 39 (130%) of 301 patients died in the placebo group compared with 20 (61%) of 329 in the corticosteroid group (043 [025-076], p(interaction)=0026). No significant HTE was found between less severe CAP (PSI class I-III, n=229) and severe CAP (PSI class IV-V, n=1126). Corticosteroid therapy significantly increased hyperglycaemia risk (44 [128%] of 344 in the placebo group vs 84 [248%] of 339 in the corticosteroid group; OR 250 [95% CI 163-383], p<00001) and hospital re-admission risk (30 [37%] of 814 in the placebo group vs 57 [70%] of 819 in the corticosteroid group; 195 [124-307], p=00038). Interpretation Overall, adjuvant therapy with corticosteroids significantly reduces 30-day mortality in patients hospitalised with CAP. The treatment effect varied significantly among subgroups based on CRP concentrations, with a substantial mortality reduction observed only in patients with high baseline CRP. Copyright (c) 2025 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Multiplex polymerase chain reaction (mPCR) testing has the potential to rapidly and accurately identify causative microorganisms in patients with community-acquired pneumonia (CAP). Its use in a management strategy, along with biomarkers, may reduce antibiotic exposure and improve clinical outcomes. The MULTI-CAP trial was a multicenter (n = 20), parallel-group, superiority, open-label, randomized trial. Subjects were non-immunocompromised adult patients (≥ 18 years) admitted to the intensive care unit (ICU) for CAP and randomly assigned in a 1:1 ratio. In the intervention group, the microbiological diagnosis combined a broad-spectrum respiratory mPCR and conventional microbiological investigations. An algorithm for early discontinuation or de-escalation of antibiotics was applied, based on mPCR results and serum procalcitonin. In the control group, only conventional microbiological investigations were performed. In both groups, antibiotic discontinuation was considered on Day 3 and day after day until Day 7, based on procalcitonin values and kinetics. The primary endpoint was defined as the number of days alive without any antibiotic from the time of enrollment to Day 28. From October 4, 2018, to March 3, 2022, 406 patients were randomized, and 385 were evaluable in the intention-to-treat analysis. The median number of days alive without antibiotics on Day 28 was 19.0 (0.0; 24.0) days in the intervention group and 19.0 (7.0; 22.0) days in the control group (difference, 0.0 (95

Despite a fairly large number of comparative trials (which are, however, very heterogeneous), the role of corticosteroids in the adjuvant treatment of community-acquired pneumonia remains controversial. Nevertheless, recent randomized trials with adequate power in intensive care unit patients, albeit with conflicting results, have contributed to clarifying our understanding of this issue. More accurate phenotyping of patients likely to benefit from corticosteroid treatment must now be performed. In COVID-19 pneumonia, their benefit is not in question. For certain specific pathogens, including viral pathogens, their indications must be refined. They are still not recommended for influenza. They appear generally safe for short-term use in select populations.

Legionnaires' disease, caused by L. pneumophila, can cause severe pneumonia that can progress to acute respiratory distress syndrome (ARDS), requiring intensive care. There are also extra-pulmonary complications, particularly renal, the mechanism, characteristics, risk factors and prognosis of which remain poorly described. Here, we describe the prevalence of associated renal involvement in a multicenter cohort of patients admitted to the ICU with severe legionellosis. Secondary objectives include identifying the risk factors associated with the onset of acute kidney injury (AKI) and studying its impact on the severity of Legionnaires' disease and patient prognosis. Multicenter retrospective cohort study in 39 intensive care centers in France between January 2012 and January 2024. Inclusion criteria were a diagnosis of Legionella pneumonia requiring invasive mechanical ventilation. Exclusion criteria were pre-existing chronic kidney failure. Data were collected from anonymized medical records, covering patient demographics, comorbidities, initial severity data, legionellosis-related data, blood and urine biology data, and follow-up data related to renal impairment. 561 patients were included. The mean age was 61 years, with 73% men. The main comorbidities were smoking, alcohol abuse, obesity and arterial hypertension. Biantibiotherapy was administered in 87% of cases. Patients’ severity was high, with a mean SOFA at D1 of 7.9, 69% severe ARDS and 81% septic shock. The prevalence of AKI was 74% during ICU stay, with 44% requiring renal replacement therapy. Rhabdomyolysis (15%), hematuria (52%) and tubular proteinuria (mean 1.74 g/L) were frequently encountered. Rhabdomyolysis was an independent risk factor for AKI and use of RRT: aOR 3.72 [1.25; 11.02], P = 0.018 and aOR 3.69 [1.74; 7.82], P = 0.001, respectively. Use of EER was associated with significant excess mortality: aOR 2.49 [1.27; 4.87], P = 0.008, pLog-rank <0.001. Renal histology showed predominantly acute tubular necrosis lesions. The prevalence of AKI appears higher in our population than for ARDS of all causes, with a high frequency of rhabdomyolysis, proteinuria and haematuria, in favour of kidney involvement specific to legionellosis. A history of chronic kidney disease, patients' initial severity and rhabdomyolysis were independently associated with the onset of AKI and the need for RRT. AKI and, especially, recourse to RRT were associated with a significant excess in mortality, whereas anti-legionella bi-antibiotic therapy was a protective factor.

IMPORTANCE:. Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated. OBJECTIVES:. To evaluate biomarkers’ impact in helping VAP diagnosis after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS:. This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included. MAIN OUTCOMES AND MEASURES:. The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group. RESULTS:. Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP (n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP (n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C–C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C. CONCLUSIONS AND RELEVANCE:. Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.

Purpose: The purpose of this study was to assess the predictive performance of pulse oximetry (SpO2) to rule out hypoxaemia and hyperoxia in critically ill patients.Methods: SpO2, arterial oxygenation (SaO2), and arterial partial pressure of oxygen (PaO2) were prospec-tively and simultaneously measured every 6 h during the first 24 h of intensive care unit admission in a multicentre cohort of critically ill patients suffering acute circulatory failure. Likelihood ratios associated with different cutoff values of SpO2 to rule out hypoxaemia (SaO2 < 90% or PaO2 < 60 mmHg) or hyperoxia (SaO2 > 95% or PaO2 > 100 mmHg) and post-test probabilities were calculated. Mean bias between SpO2 and SaO2 and agreement interval were calculated. Area under the receiver operating characteristics associated with SpO2 to predict different threshold values of SaO2 and PaO2 were calculated. Results: Five hundred seventy-one patients (mean [standard deviation] Simplified Acute Physiology Score II: 58.7 [20.1]; mechanically ventilated 75.6%) with 2643 available SaO2 and PaO2 samples and corresponding 2643 SpO2 values were analysed. Mean bias between SpO2 and SaO2 was 1.1%, and its agreement interval ranged from-8.2 to +11.1%. SpO2 cutoff values of 88%, 90%, and 92% left the pos-sibility that 8%-13% of patients had hypoxaemia. SpO2 < 95% left the possibility that 31% of patients had hyperoxia. All calculated areas under the receiver operating characteristics showed a lower limit of their 95% confidence interval below 0.85Conclusion: In this cohort of patients with circulatory failure, SpO2 had poor discriminative ability to rule out hypoxaemia and hyperoxia. Overconfidence upon SpO2 monitoring may be dangerous.(c) 2022 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.