BackgroundAcute kidney injury (AKI) is frequent in patients supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO), largely due to the severity of cardiogenic shock and multiorgan failure. Renal replacement therapy (RRT) can be delivered either via an indwelling catheter (parallel system, PS) or through direct connection to the ECMO circuit (integrated system, IS). Their respective safety profiles, particularly regarding infectious, hemorrhagic, and circuit-related complications, remain insufficiently characterized.MethodsWe conducted a single-center retrospective analysis of prospectively collected data from consecutive adults who received RRT for ≥24 h while on VA-ECMO between 2006 and 2019. Complications occurring during the concomitant ECMO-RRT period were compared between IS and PS configurations.ResultsEighty patients (84 procedures: 42 IS, 42 PS) were included. Infectious complications occurred in 31% of IS procedures and 45.2% of PS procedures, with earlier onset in the PS group (3 vs 5 days; p = 0.048). However, in multivariable analysis, IS was not independently associated with reduced infection risk (OR 0.67 [0.27-1.70]; p = 0.421). Hemorrhagic events (54.8% IS vs 59.5% PS) and circuit dysfunctions, including filter clotting, were comparable between groups.ConclusionIn VA-ECMO patients requiring RRT, integrated and parallel configurations demonstrate similar safety profiles with no significant differences in infectious, hemorrhagic, or circuit-related complications. These findings support selecting the RRT configuration based primarily on local expertise and technical feasibility rather than expected differences in complication risk.

Acute ischemic stroke is a medical emergency in which treatment relies on achieving cerebral reperfusion as early as possible. Therapeutic strategies target the ischemic penumbra, where neuronal injury remains potentially reversible during the first few hours after symptom onset. Reperfusion is achieved through intravenous thrombolysis (IVT), combined or not, with mechanical thrombectomy (MT). The selection of eligible patients is based on clinical criteria (NIHSS score, time from symptom onset) and imaging findings (MRI or CT perfusion imaging). IVT involves the administration of a thrombolytic agent (alteplase or tenecteplase), with intracranial hemorrhage being the primary complication. Patients with proximal occlusion of the anterior circulation or involvement of the posterior circulation may also benefit from MT. MT can be performed under general anesthesia (GA) or local anesthesia with procedural sedation (PS), each with specific advantages and limitations. GA is recommended in certain high-risk situations (impaired consciousness, posterior circulation stroke, respiratory instability, etc.); however, current evidence does not clearly favor GA over PS in other settings. Perioperative management is complex and requires specialized multidisciplinary teams, with the primary goals of avoiding arterial hypotension and preventing secondary brain insults.

Candidemia displays significant clinical heterogeneity in critically ill patients. This study aimed to identify distinct clinical phenotypes and to assess their association with 90-day mortality. We conducted a multicenter retrospective cohort study of 492 intensive care unit (ICU) patients with candidemia from 16 French ICUs (2015–2023). We performed a factor analysis of mixed data (FAMD) incorporating both categorical and continuous baseline variables, followed by hierarchical clustering on principal components (HCPC). Survival analysis was performed with Kaplan–Meier curves and Cox proportional hazards models. Overall, 90-day mortality for the 492 patients (median age: 64 years, 69.1

Background Candida spp. is frequently isolated in critically ill patients with peritonitis. Guidelines recommend empirical antifungal therapy in high-risk cases, but the clinical significance of Candida spp. isolation in peritoneal fluid and the benefit of early antifungal therapy remain uncertain. Methods We conducted a retrospective multicenter cohort study including all consecutive adults admitted with peritonitis to the ICUs of four hospitals in Western France between 2020 and 2022. Risk factors for Candida spp. isolation in peritoneal fluid were assessed using multivariate logistic regression. Outcomes were compared according to Candida spp. isolation in peritoneal fluid and, among affected patients, according to early antifungal therapy. Survival up to day-90 after peritonitis onset were compared using Inverse Probability Treatment-weighted Cox proportional hazards models. Results Among 378 patients, Candida spp. was isolated in 81 (21.4%). Independent risk factors included antimicrobial therapy within the last 3 months (adjusted OR 2.15, 95% CI 1.20–3.81; p = 0.009), malnutrition (adjusted OR 1.84, 95% CI 1.10–3.14; p = 0.022), upper gastrointestinal origin (adjusted OR 2.04, 95% CI 1.20–3.44; p = 0.008) and diffuse peritonitis (adjusted OR 1.75, 95% CI 1.01–3.13; p = 0.049). Candida spp. isolation in peritoneal fluid was not associated with 90-day mortality (weighted HR 1.00, 95% CI 0.62–1.59; p = 0.991) and clinical courses were similar between groups. Among patients with Candida spp. in peritoneal fluid isolation, early antifungal therapy was not associated with 90-day mortality (weighted HR 1.37, 95% CI 0.58–3.22; p = 0.470) or clinical outcomes. Conclusions In ICU patients with peritonitis, Candida spp. isolation in peritoneal fluid was not associated with 90-day mortality, and early antifungal therapy did not improve 90-day survival among patient with isolated Candida spp. in peritoneal fluid.

INTRODUCTION:Peritonitis is a frequent cause of sepsis in the intensive care unit (ICU) and is characterized by substantial microbiological variability, including multidrug-resistant organisms (MDROs). METHOD:We conducted a retrospective, multicenter cohort study including ICU patients diagnosed with intra-abdominal infection across 4 hospitals 2020-2022). The primary objective was to describe clinico-biological features, and microbiological characteristics according to the setting of the peritonitis (Community peritonitis (CP), early nosocomial peritonitis (ENP), or late nosocomial peritonitis (LNP)). Additionally, we analyzed 90-day survival using Kaplan-Meier curves and multivariable Cox regression. RESULTS:Among the 392 patients included in the study period, 195 experienced a CP, 88 an ENP, and 109 an LNP. Extended-spectrum beta-lactamase-producing bacteria were identified in 24 patients (6.1%), and carbapenem-resistant bacteria in 5 patients (1.3%). MDRO rates differed significantly: carbapenem-resistant bacteria were more frequent in LNP patients (3.7% vs. 0.0% in CP and 0.5% in ENP; p = 0.03), and cephalosporinase-producing bacteria were more common in nosocomial settings (40.4% in LNP vs. 19.0% in CP; p < 0.001). Ninety-day mortality was 34.7% overall and did not differ across settings (p = 0.345). Age and SAPS II were independently associated with mortality. Finally, appropriate empirical antimicrobial therapy was not associated with improved 90-day survival (p = 0.128). CONCLUSION:Through this large cohort study of ICU patients with peritonitis, we observed a low prevalence of MDRO. Our findings challenge the relevance of broad-spectrum empirical therapy in low-MDRO regions and underscore the need for tailored antimicrobial stewardship strategies.

We report the case of a 58-year-old farmer who developed multiple intracerebral aneurysms due to Scedosporium boydii, complicated by two episodes ofsubarachnoid hemorrhage occurring two months after a penetrating head injury. The rapidly catastrophic clinical course, the time required for accurate identification of the pathogen, and the lack of scientific consensus regarding the role of endovascular intervention represented a major challenge for our team. Collaboration with a national reference center, combined with the securing of the aneurysms and the initiation of appropriate antifungal therapy, ultimately led to a favorable outcome.

The role of Enterococcus spp. and the need for specific anti-Enterococcus therapy in Intensive Care Unit (ICU) patients with peritonitis remain debated. We conducted a retrospective multicentre cohort study including all consecutive adults admitted to the ICUs of four hospitals in western France with peritonitis between 2020 and 2022. Outcomes were compared according to Enterococcus spp. isolation and, among Enterococcus-positive cases, according to early administration (< 48 h) of active antimicrobial therapy. Propensity-weighted Cox models were used to estimate 90-day survival. Among 392 patients, Enterococcus spp. were isolated in 161 (41.1

BACKGROUND:The management of COVID-19-associated invasive aspergillosis (CAPA) is still debated while cases continue to occur, and more and more frequently in vulnerable populations, stressing the importance of obtaining data on the treatment of this disease. Only small cohort studies and case reports have yet discussed this essential issue, and the data obtained are insufficient to make conclusions with confidence. RESEARCH QUESTION:Is antifungal treatment associated with lower 60-day mortality in patients with probable or proven CAPA? STUDY DESIGN AND METHODS:This study assessed the association of antifungal treatment with 60-day mortality for probable/proven CAPA cases from a French multicenter study and all consecutive CAPA cases (after 2020) from ICUs of 5 major European centers. Patients were compared according to antifungal treatment. Survival analysis was conducted by using Cox regression analysis and inverse probability of treatment weighting based on a propensity score. RESULTS:In total, 259 patients with CAPA were included, 237 (91.5%) receiving antifungals for CAPA (215 [90.7%] of whom received azole antifungal drugs). Baseline characteristics were similar between patients who received antifungals and those who did not. Age (hazard ratio [HR], 1.02; 95% CI, 1.00-1.04; P = .048), immunosuppressive treatment (HR, 2.08; 95% CI, 1.12-3.41; P < .001), and remdesivir administration (HR, 1.96; 95% CI, 1.12-3.41; P = .018) were independently associated with increased 60-day mortality according to Cox regression analysis in the raw population. Male sex (HR, 0.61; 95% CI, 0.40-0.95; P = .024) and antifungal treatment (HR, 0.31; 95% CI, 0.17-0.59; P < .001) were associated with lower 60-day mortality. Cox-weighted regression showed lower 60-day mortality for patients receiving antifungals (weighted HR, 0.28; 95% CI, 0.13-0.58; P < .001. INTERPRETATION:Our results show that antifungal treatment was associated with lower 60-day mortality in patients with CAPA. The high mortality rate observed in CAPA in immunocompromised patients and improved outcome for treated patients should encourage clinicians to actively screen for CAPA to enable rapid diagnosis and targeted treatment.

Aneurysmal subarachnoid hemorrhage (aSAH) remains a severe condition with high morbidity and mortality. Evidence on sex-related differences in outcomes and complication profiles is inconsistent. We assessed the association between sex and 90-day functional outcome and ICU complications in aSAH patients requiring intensive care. We performed a retrospective secondary analysis of the ATLANREA cohort (NCT02426255), a prospective multicenter ICU registry in western France. Adult patients (≥ 18 years) admitted with aSAH between January 1, 2013, and December 31, 2022, requiring orotracheal intubation within 24 h and for ≥ 24 h, were included. The primary outcome was favourable neurological status at day 90 (Glasgow Outcome Scale–Extended [GOS-E] > 4). A prespecified baseline multivariable logistic model included sex, age, WFNS grade, collapsed Fisher grade and mydriasis. Age subgroup analyses (≤ 42, 43–50, > 50 years) were prespecified as exploratory and complemented by a formal sex × age interaction test. Among 865 patients, 540 (62.4

IntroductionTechniques for measuring digestive motility are becoming increasingly precise and enable therapeutic interventions. However, while most of these interventions require general anesthesia, there is limited data on the impact of anesthetic agents on these measurements, and no standardized anesthesia protocol currently exists to guide such procedures. Our working group carried out two Delphi processes involving experts in neurogastroenterology and anesthesiology to reach a consensus on which drugs affect these measurements and to establish an anesthesia protocol.MethodTwo expert groups were formed, comprising 13 neurogastroenterology experts from the French Neuro-Gastroenterology Group (GFNG) and 15 full- or associate professors in anesthesia and intensive care. The first Delphi process involved the neurogastroenterologists and aimed to identify which anesthetic drugs influenced digestive pressure measurements. The second Delphi process, involving anesthetists, sought to develop an anesthesia protocol. Each expert indicated their level of agreement with each statement using a 6-point Likert scale. A statement was endorsed when at least 80% of experts agreed with it. The strength of evidence for each statement was evaluated using the GRADE system.ResultsThe Delphi process with neurogastroenterologists was conducted over three rounds and ultimately resulted in 91 amendments. The second Delphi process with anesthetists took place over two rounds and included 28 amendments, leading to the development of an anesthesia protocol.ConclusionTo our knowledge, this work is the first to establish an expert consensus on anesthetic agents that can affect digestive motility measurements and to propose an anesthesia protocol that accounts for the needs of neurogastroenterologists.

INTRODUCTION:Subarachnoid haemorrhage (SAH) is relatively frequent, accounting for 5% of strokes and affects a young population. Arterial vasospasm is a frequent complication of SAH, with an estimated incidence as high as 70%. Vasospasm is responsible for cerebral ischaemia which in turn is potentially responsible for severe morbidity (neurological deficit, neuropsychiatric disorders), poor quality of life (institutionalisation, inability to return to work) and increased mortality. Treatment with intravenous milrinone, an arterial vasodilator, has been proposed, but no randomised controlled study exists. We hypothesised that an intravenous infusion of milrinone would improve the neurological recovery of patients with vasospasm following aneurysmal SAH at 3 months. METHODS AND ANALYSIS:The MiVAR (Milrinone Infusion for VAsospam treatment in subarachnoid hemoRrhage) study is an investigator-initiated, phase III multicentre, randomised placebo-controlled, double-blinded, superiority trial evaluating the effect of intravenous milrinone versus placebo (saline), in patients with cerebral vasospasm following aneurysmal SAH. Patients will be included within 6 hours of the confirmation of vasospasm diagnosis by a CT angiography and randomised to receive either milrinone (initial bolus of 0.1 mg/kg over 30 min-max 10 mg-followed by a continuous infusion at 1 µg/kg/min rate for at least 48 hours) or placebo. Milrinone (or placebo) could be increased to 1.5 µg/kg/min. The dose is adapted according to the clinical and/or transcranial Doppler response. 360 patients are expected to be included. The primary endpoint is the proportion of patients with a good neurological outcome at 3 months, defined as a modified Rankin score ≤2, obtained through a centralised standardised telephone interview (done by a unique trained team). The study started in August 2020, and the expected final follow-up is the last quarter of 2025. Analyses of the intention-to-treat and per-protocol populations are planned. ETHICS AND DISSEMINATION:The MiVAR trial protocol has been approved by an ethics committee (Comité de Protection des Personnes Ouest V), by the Agence Nationale de Sécurité du Médicament (ANSM, Number 160 828A-21, approval date 26 December 2019) and by the 'Commission Nationale Informatique et Liberté' (CNIL, decision DR-2020-076, approval date 21 February 2020). The study will be conducted according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The MiVAR study will be the first multicentre randomised study to evaluate the efficacy of intravenous milrinone in improving the neurological outcomes at 3 months in patients with vasospasm following aneurysmal SAH. TRIAL REGISTRATION NUMBERS:NCT04362527, EudractCT number 2019-002145-37.

Background: With more than 60 million new cases around the world each year, traumatic brain injury (TBI) causes substantial mortality and morbidity. Managing TBI is a major human, social, and economic concern. In the last 20 years, there has been an increase in clinical trials in neurocritical care, leading mostly to negative results. The evaluation of neurological outcomes, predominantly as primary outcomes, using clinical scales (Glasgow Outcome Scale) has limitations that could explain these results. Moreover, patient-centered outcomes are seldom reported despite their recognized clinical relevance. Objective: The aim of this project is to establish a core outcome set (COS) for patients with moderate-to-severe TBI in randomized control trials in neurocritical care research. MethodsThis study will follow five distinct steps: (1) systematic review to identify outcomes that have been reported in trials; (2) semistructured interviews with patients and their families to identify their priorities after TBI and explore potential patient-centered outcomes; (3) health care stakeholder focus groups with clinicians, researchers, and policy makers to describe potential outcomes; (4) an eDelphi survey with stakeholder groups to make a list of previously identified core outcomes; and (5) a consensus workshop to establish a COS for moderate-to-severe TBI clinical trials. Results: The systematic review was published in August 2024. Regarding Step 2, 30 semistructured interviews of patients and relatives were performed from July 2021 to December 2023, and analyses were completed in October 2024. Step 3 is currently under development, and Step 4 is planned for the end of 2025. Step 5 is expected to occur during fall/winter 2026. Conclusions: Establishing a COS, to be consistently measured and reported in TBI trials in neurocritical care will ensure rigorous reporting, avoid bias, and improve the integrity, transparency, and usability of clinical research. The French context of the study is the main limitation, but we are seeking international collaboration on the project. The results of each step of the project will be disseminated through abstracts, publications, and patient associations. ConclusionsEstablishing a COS, to be consistently measured and reported in TBI trials in neurocritical care will ensure rigorous reporting, avoid bias, and improve the integrity, transparency, and usability of clinical research. The French context of the study is the main limitation, but we are seeking international collaboration on the project. The results of each step of the project will be disseminated through abstracts, publications, and patient associations. International Registered Report Identifier (IRRID)DERR1-10.2196/54525

Despite optimal antimicrobial therapy, the treatment failure rate of hospital-acquired pneumonia (HAP) routinely reaches 40

Measuring reliable intracranial pressure (ICP) is critical for patients with acute brain injuries. The aim of this study was to evaluate zero drift of the intraparenchymal strain gauge Pressio transducer (Sophysa, Orsay, France) in clinical conditions. A prospective observational multicenter study was conducted in four French intensive care units of university hospitals. Patients with acute brain injuries were included if they needed ICP measurement using the Pressio transducer. The zero drift was measured at the explantation of the sensor. ICP-related adverse events were also collected. Between January 1, 2018, and March 31, 2020, 235 patients were included in this study for a monitoring time of 2,180 days. The zero drift assessment was determined in 223 transducers (95

BACKGROUND:Acute respiratory distress syndrome (ARDS), a common condition among intensive care patients, is characterized by severe hypoxemia that may lead to acute brain injury. Although prone positioning has emerged as a lifesaving strategy in the management of ARDS, its effects on cerebral oxygenation remain insufficiently explored. OBJECTIVE:To evaluate the evolution of cerebral oxygenation during prone positioning in patients with ARDS. METHODS:This prospective, single-center study was done in the intensive care unit of a community hospital. Consecutive patients with moderate or severe ARDS were prospectively enrolled during a 12-month period. Cerebral oxygenation was assessed by near-infrared spectroscopy before and during an 18-hour period of prone positioning. Continuous variables were compared before and during prone positioning using the Wilcoxon signed rank test. Correlations were assessed using the Spearman rank test. RESULTS:Ten patients were included in the study, with 2 patients exiting at hours 6 and 12 after the start of prone positioning because of hemodynamic instability. Evidence of oxygenation improvement during prone positioning was indicated by an increase in regional cerebral oxygen saturation (rSo2) and the ratio of Pao2 to fraction of inspired oxygen (Fio2). The rSo2/Fio2 ratio was significantly increased from hour 3 to 12 (P = .049 at hour 3, P = .02 at hour 8, and P = .02 at hour 12). Also, rSo2 was significantly correlated with oxygen delivery (ρ = 0.811, P < .001) and cardiac index (ρ = 0.463, P < .001). CONCLUSION:Prone positioning in patients with ARDS seems to be associated with improved cerebral oxygenation based on rSo2/Fio2 ratio.

Introduction Virtual Reality (VR) is playing an increasingly important role in the medical field environment, whether for pain management or healthcare professionals’ training. The use of a VR device during a stay in Intensive Care Unit (ICU) could contribute to early rehabilitation’s management. Evaluation of the acceptability of such VR device on patients and healthcare professionals in these departments is the first step before considering integrating it, in order to ascertain the intention to use this device, but also to assess the possible obstacles to its use. Method We performed an acceptability study including patients and healthcare professionals from the ICUs of the University Hospital of Rennes, France. They answered a questionnaire based on the UTAUT 2 model, after a brief presentation of the VR device created to promote mental imagery early in ICU. Main judgment criterion was evaluating the acceptability via intention-to-use of this VR tool. Secondary objectives were to identify items influencing intention to use a VR tool in the healthcare professionals and patient populations. Results Sixty-eight healthcare professionals and fifty patients completed the questionnaire. We found a positive evaluation and a favorable intention to use the device in both populations. The main factors influencing intention to use were “perception of use” and “hedonic motivation” in both populations. Healthcare professionals attached importance to social influence, while patients prioritized “perceived ease of use”. Discussion Our results are in line with the literature on the a priori acceptability and intention to use virtual reality. However, this is the first study of virtual reality for early rehabilitation in ICU. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was submitted to the Ethics Committee of the University Hospital of Rennes, France, which issued a favorable opinion on 19th December 2020 (Opinion 20.161). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes

Objective Unfractionated heparin (UFH) is a widely used therapy in intensive care units (ICUs) and is associated with an increased risk of serious adverse events or death if the therapeutic target is not reached quickly. Adjusting UFH dosage is challenging, and no reliable algorithms exist for predicting anti-Xa levels in ICUs. This study aimed to develop and evaluate machine learning algorithms to predict anti-Xa levels during UFH therapy, helping clinicians optimize dosing. Methods This single-center retrospective cohort study was conducted using Rennes University Hospital's clinical data warehouse from December 21, 2019 to November 22, 2021. Critically ill patients ≥ 18 years on UFH, without other anticoagulants and complete data, were included. Anti-Xa levels were classified as infra-therapeutic (<0.3), therapeutic (0.3–0.7), or supra-therapeutic (>0.7). Models incorporated UFH rate, bolus, prior anti-Xa, kidney function, inflammation, volemic state, extracorporeal membrane oxygenation, and bilirubinemia. Performance was assessed using the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), sensitivity, and specificity. Results A total of 3790 anti-Xa intervals, corresponding to 211 patients, were included in the study. Out of several machine learning algorithms, random forest achieved the best results with an AUROC score of 0.80 [0.77;0.83], an AUPRC score of 0.61 [0.58;0.65], sensitivity of 0.56 [0.53;0.59] and specificity of 0.82 [0.82;0.82]. Conclusion In this cohort study, machine learning-based prediction models achieved good performance for predicting anti-Xa results during UFH therapy in an ICU setting. Further validation with prospective multicenter data is needed in order to confirm the model's generalizability and support its integration into clinical practice to assist clinicians in selecting the optimal heparin dose.