Importance Anemia is a prevalent condition among patients with traumatic brain injury (TBI); however, the optimal hemoglobin (Hb) threshold to initiate red blood cell transfusion (RBCT) is not well defined. Objective To assess which of 2 different Hb thresholds for guiding RBCT in patients with anemia and TBI is associated with a more favorable neurological outcome. Design, Setting, and Participants This was a preplanned secondary analysis of the Transfusion Strategies in Acute Brain Injured Patients multicentric randomized clinical trial, conducted in 72 intensive care units across 22 countries between September 1, 2017, and December 31, 2022. Follow-up was completed June 30, 2023. Only patients with TBI were included in the present analysis, conducted from February to May 2025. Interventions Liberal (transfusion at Hb <9 g/dL [to convert to g/L, multiply by 10.0]) vs restrictive (transfusion at Hb <7 g/dL) RBCT strategy over a maximum of 28 days. Main Outcome and Measures The primary outcome was the occurrence of unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score of 1 to 5 (overall range, 1-8, with higher scores indicating more favorable outcome) at 180 days. In addition, 14 prespecified serious adverse events, including infection and cerebral ischemia, were assessed. Data were analyzed using both the intention-to-treat and per-protocol principles. Results Of 486 patients who presented with TBI (mean [SD] age, 46.8 [17.6] years; 347 [71.4%] male), 475 were included in the primary outcome analysis: 236 were randomized to the liberal transfusion strategy group and 239 to the restrictive transfusion strategy group. Both groups had similar baseline characteristics. In total, 534 RBCTs were administered in the liberal transfusion strategy group, compared with 246 RBCTs in the restrictive group. At 180 days after randomization, 138 patients (58.5%) in the liberal group had unfavorable neurological outcome compared with 161 patients (67.4%) in the restrictive group (relative risk [RR], 0.86 [95% CI, 0.75-1.00]; P = .047; fragility index = 1). There were no significant differences in the occurrence of secondary outcomes (eg, 28-day mortality: 42 of 240 [17.5%] vs 51 of 244 [20.9%]; RR, 0.84 [95% CI, 0.58-1.21]; P = .34) or serious adverse events (eg, RR, 1.13 [95% CI, 0.88-1.43]; P = .34 for infection and RR, 0.87 [95% CI, 0.40-1.90]; P = .72 for cerebral ischemia). After adjustment for several confounders, being randomized to the liberal group was associated with a lower observed probability of unfavorable neurological outcome (odds ratio, 0.60 [95% CI, 0.38-0.94]; P = .03). Conclusions and Relevance In this secondary analysis of a multicenter randomized clinical trial, a liberal RBCT strategy was associated with a lower risk than a restrictive RBCT strategy of unfavorable neurological outcome at 180 days among patients with TBI. These findings should be interpreted with caution in light of the inherent uncertainty of the estimate. Trial Registration ClinicalTrials.gov Identifier: NCT02968654

The anticipated "tripledemic" during the 2023-2024 season-in which simultaneous epidemics of SARS‑CoV‑2, influenza, and respiratory syncytial virus were projected-ultimately fell short of early forecasts. Nevertheless, each virus remains a significant public health concern in its own right. This article reviews the microbiology, diagnosis, and treatment of these three pathogens (including the role of immunomodulatory therapies), as well as key considerations for hospital infection prevention in the care of critically ill patients. The piece highlights the clinical indistinguishability of these viral infections and acknowledges the evolving public health discourse surrounding the role of vaccination in preventing disease.

Optimal dosing of vancomycin in critically ill patients receiving renal replacement therapy (RRT) is uncertain due to high pharmacokinetic variability. We aimed to develop individualised vancomycin dosing recommendations that optimise efficacy while minimising toxicity. Prospective, international, pharmacokinetic study enrolling critically ill patients treated with vancomycin and various RRT modalities. A population pharmacokinetic model was developed, externally validated and applied to perform Monte Carlo dosing simulations. We calculated the probability of each dosing regimen to achieve the efficacy target against methicillin-resistant Staphylococcus aureus (ratio of the area under the concentration–time curve to the minimum inhibitory concentration (AUC0-24 h/MIC) ≥ 400) without exceeding the toxicity threshold (AUC0-24 h ≥ 700 mg.h/L). We enrolled 65 critically ill patients from 6 countries receiving continuous RRT (50.8

The use of [18F]FDG PET/CT for detection of infectious and inflammatory foci in patients admitted to the intensive care unit (ICU) has gained interest as previous retrospective studies have shown promising results. [18F]FDG PET/CT in these studies was predominantly performed in patients with prolonged organ failure. These patients often acquire an immune dysregulated state, resulting in infectious complications impairing organ recovery. Early detection of infectious or inflammatory foci in this population may improve outcomes and reduce health care costs. We aim to explore the value of [18F]FDG PET in comparison to contrast-enhanced CT (ceCT) for the detection of infectious and inflammatory foci in patients with persistent critical illness. In addition, we will assess the influence of imaging findings on therapy changes after the scans and the relation between circulating biomarkers and [18F]FDG PET/CT findings. Methods: This study protocol describes a prospective, dual-center, international, head-to-head diagnostic comparison observational cohort study. Patients admitted to the ICU for at least 7 d with organ failure and persistently increased inflammatory parameters are eligible for inclusion. After inclusion, [18F]FDG PET/CT and ceCT will be performed simultaneously between day 8 and day 15 of ICU admission. For the primary endpoint, masked and standardized assessment of the scans will be ensured by exchanging the scans cross-over between both institutions. Primary outcome will be the incidence of findings for both imaging modalities, categorizing the results as PET-positive/CT-positive, PET-negative/CT-positive, PET-positive/CT-negative, or PET-negative/CT-negative. Direct clinical availability of the scans will allow for integration into decision-making. Therapy changes within 48 h after imaging will be recorded. Additionally, a questionnaire on the expected therapy plan and known or suspected foci is completed by the attending physician before the imaging procedure to better assess the impact of imaging on decision-making. Blood samples are taken on the day of inclusion and imaging. Conclusion: This first large prospective study will explore the application of [18F]FDG PET/CT compared with ceCT to image infectious and inflammatory foci in persistent critically ill patients. This study may help define the role of [18F]FDG PET/CT imaging in the ICU environment, supporting clinicians with an additional diagnostic tool for patient management.

2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) is a hybrid imaging tool increasingly recognized for its effectiveness in evaluating inflammatory and infectious diseases. An emerging application of [18F]FDG PET/CT is the detection of infectious and inflammatory foci in critically ill patients within the intensive care unit (ICU). We performed a systematic review and a diagnostic accuracy meta-analysis to assess the value of [18F]FDG PET/CT in this setting. A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, and the Cochrane Library databases, covering studies published up to May 2025. Pooled estimates of sensitivity, specificity, positive and negative likelihood ratios (LR + and LR-), and diagnostic odds ratios (DOR) along with their 95

La mobilisation précoce et l’activité physique des patients admis en soins intensifs font partie des moyens préventifs de la fonte musculaire et du déconditionnement qui apparaissent dès les premiers jours d’admission. De multiples moyens de mobilisation adaptés permettent une activation musculaire au cours des premiers jours qui suivent l’admission en soins aigus, avec des technologies qui permettent de prolonger ou mimer une activité musculaire. Dès que la participation du patient est possible, l’initiation d’une activation physique progressive des muscles périphériques et respiratoires montre des effets physiologiques et cliniques bénéfiques. Des protocoles de mobilisation multidisciplinaires sont fortement indiqués afin d’assurer la réalisation systématique et sécuritaire des approches précoces de mobilisation. Le dosage adéquat de l’activité physique en réanimation reste encore à investiguer, toutefois des approches qui considèrent le ressenti des patients permettraient d’individualiser le temps, la durée et la nature des activités.

Background & Aims Medical nutrition therapy (MNT) is fundamental for ICU patients. This post-hoc subgroup analysis of the prospective observational EuroPN survey aimed to assess MNT in the participating Belgian ICUs. Methods MNT practices in 9 Belgian ICUs (148 patients) were compared to 77 ICUs (1172 patients) from 11 European countries during the first 15 days for patients staying ≥5 days in ICU - and with the 2019 ESPEN guideline on clinical nutrition in ICU (<70 % of estimated energy expenditure in week 1 and up to 1.3 g/kg/d protein). Additionally, overfeeding was evaluated in the Belgian cohort. Results The Belgian cohort had longer median ICU and hospital length of stay, higher emergency room admission rates and delayed MNT initiation compared to overall (EN: day 2.5 [2.0;4.0] vs 2.0 [2.0;4.0] and PN: day 5.0 [3.0,7.0] vs 2.0 [2.0,4.0]). They received more often EN than PN. In week 1 overfeeding was on average present in 30 % (energy) and 15 % (protein) of observation days. Conclusion Similar to overall, the Belgian subgroup received a daily average moderate caloric and low protein intake. The gradual intake increase aligned with ESPEN guidelines, though temporary overfeeding occurred in about one third of the patients.

BACKGROUND:Electrical impedance tomography (EIT) is a noninvasive method for visualization and quantification of regional ventilation. The objective of this study was to assess regional variations in ventilation across different positions in healthy subjects. METHODS:Regional differences in ventilation were compared between the right and left lateral decubitus positions, as well as between the supine, semi-sitting, and prone positions. EIT was performed using a PulmoVista 500 (Dräger Medical, Lübeck, Germany). RESULTS:During lateral decubitus, ventilation significantly increased in the dependent lung. In the right lung, ventilation was 42.5 ± 11.4% in the left lateral decubitus compared with 65.2 ± 12.8% in the right lateral decubitus (P < .001). In the left lung, ventilation was 56.6 ± 11.6% in left lateral decubitus versus 34.4 ± 13.0% in right lateral decubitus (P < .001). These changes were mainly observed in the ventral dependent quadrants. In the supine, semi-sitting, and prone positions, no global differences in ventilation distribution were observed. However, ventilation slightly increased in the left ventral quadrant (supine < prone, P = .03) and decreased in the right dorsal quadrant (supine > prone, P = .03). These subtle variations likely reflect the physiological characteristics of healthy individuals. CONCLUSIONS:EIT demonstrated a clear redistribution of ventilation toward the dependent lung in lateral decubitus positions. In contrast, only minimal regional ventilation changes were observed among supine, semi-sitting, and prone positions in healthy subjects. These findings support the utility of EIT in assessing position-related ventilation shifts and underscore the need for further research in patients with impaired pulmonary function.

Purpose: The American Clinical Neurophysiology Society has provided a set of recommendations on the use of critical care EEG monitoring (CEEG). However, these recommendations have not been prospectively validated. We aimed to assess the adherence to the American Clinical Neurophysiology Society recommendations for obtaining CEEG for different indications and the yield of obtained CEEG according to these different indications. Methods: This was a multicenter prospective observational study of critically ill adult patients between April 01, 2022, and June 22, 2022, in two academic medical centers and a large teaching hospital. Indications for CEEG, according to the American Clinical Neurophysiology Society recommendations, were determined based on clinical data at the time of discharge from the intensive care unit. The use of CEEG and detection of electrographic seizures were retrieved from the EEG databases. Results: A total of 600 patients were enrolled in this study. The primary admission diagnoses were medical (49%), surgical (30%), or neurologic/neurosurgical (21%). Approximately 60% of patients had an altered mental status. A few (6%) patients had a preceding clinical seizure, and 1% had generalized convulsive status epilepticus. Indications were identified in 226 admissions. Of these patients, 88 (39%) underwent CEEG. In addition, 12 patients underwent CEEG without clear indications. Of the 100 patients, 33 (33%) had electrographic seizures. Adherence to recommendations and yields was highest for refractory status epilepticus, altered mental status after any clinical seizure, and acute brain injury. Adherence and yield varied the most and were inversely correlated in the group of patients without acute brain injury, suggesting that additional clinical factors may have contributed to patient selection. Conclusions: Patients meeting American Clinical Neurophysiology Society indications and receiving CEEG had a high seizure risk. Emerging CEEG programs should focus on epilepsy-related and neurologic diagnosis. Although recommendations effectively identify groups of patients with a high seizure risk, additional clinical factors might further help select candidates in the low-risk group.

Introduction: Cytomegalovirus (CMV) DNAemia has been described in critically ill patients, including patients with severe acute respiratory syndrome-coronavirus2 (SARS-CoV-2) infection. Our objective is to evaluate the prevalence and clinical impact of CMV DNAemia among patients undergoing invasive mechanical ventilation (IMV) for severe SARS-CoV-2 infection and to explore the association between CMV DNAemia levels and clinical outcomes. Methods: In this retrospective monocentric study, we included patients admitted in a tertiary ICU for severe COVID-19 and who required IMV. We aimed to compare clinical and demographic variables between patients with and without CMV DNAemia. Univariate and Cox regression analyses were performed to identify factors associated with CMV DNAemia. Results: During the study period, CMV blood DNAemia occurred in 30/135 patients (22%). Patients with CMV blood DNAemia had longer ICU and hospital length of stay, as well as longer duration of IMV, and were more likely to have received dexamethasone. However, there was no significant difference in ICU mortality between patients with and without CMV DNAemia (64.8% vs. 56.7%, p = 0.42). The Cox regression analysis showed that dexamethasone was the only factor independently associated with CMV blood DNAemia (HR 4.23 [1.006–17.792], p = 0.049). Conclusions: In patients with severe SARS-CoV-2 pneumonia requiring IMV, CMV DNAemia is common and associated with prolonged ventilation and increased LOS but not with increased mortality.

Optimal dosing of meropenem and piperacillin/tazobactam in critically ill patients receiving renal replacement therapy (RRT) is uncertain due to variable pharmacokinetics. We aimed to develop generalisable optimised dosing recommendations for these antibiotics. Prospective, multinational pharmacokinetic study including patients requiring various forms of RRT. Independent population PK models were developed, externally validated and applied to perform Monte Carlo dosing simulations using Monolix and Simulx. We calculated the probability that these dosing regimens achieved standard and high therapeutic unbound antibiotic concentrations over 100

BACKGROUND:Mortality is high both during intensive care unit (ICU) stay and in the year following discharge, yet factors influencing long-term survival remain poorly defined. We hypothesized that pre-existing chronic conditions may be more strongly associated with post-ICU survival than acute illness severity or admission diagnosis. METHODS:This is a post-hoc analysis of the prospective, observational, multicenter FROG-ICU cohort, which included all consecutive patients admitted to 21 French ICUs and followed for one year after discharge. ICU survivors with complete data on admission severity scores (Sequential Organ Failure Assessment [SOFA], Simplified Acute Physiology Score II [SAPS-II]), comorbidities (Charlson Comorbidity Index [CCI]), and cardiovascular/renal biomarkers at discharge (n = 1400) were included. Associations with one-year mortality were assessed using Cox models. Discriminatory performance was evaluated with time-dependent area under the receiver operating characteristic curve (AUC). RESULTS:Among 1548 ICU survivors, 1400 were analyzed (median age 61 years, 63 % male). Admission diagnoses included acute respiratory failure (19 %), septic shock (24 %), and neurologic conditions (16 %). The CCI was the strongest predictor of mortality at day 7 (AUC 0.70 [95 % Confidence Interval [CI], 0.64-0.77]), at 3 weeks (AUC 0.75 [0.69-0.78]), and remained high over one year, outperforming SAPS-II (0.63 [0.54-0.72]) and SOFA (0.61 [0.53-0.68]). Although cardiovascular (NT-proBNP, bio-ADM) and kidney (pNGAL) biomarkers had comparable short-term discriminatory value, CCI performed better for long-term outcomes across different admission diagnoses. CONCLUSION:In this analysis, pre-existing chronic conditions were primary drivers of short- and long-term survival after ICU discharge, exceeding prognostic value of acute illness severity at admission. CLINICAL TRIAL REGISTRATION:French and European Outcome Registry in Intensive Care Units (FROG-ICU) study: ClinicalTrials.govNCT01367093. Registered 3 June 2011.

AIMS:The beta-lactam antibiotic temocillin is increasingly used to treat extended-spectrum beta-lactamase (ESBL-producing) strains; however, its protein binding is complex. This study aims to predict unbound temocillin concentrations in various participant groups to determine its impact on the probability of target attainment (PTA) and to improve dosing recommendations. METHODS:The plasma pharmacokinetics were analysed using non-linear mixed-effects modelling. Data from individuals in four groups: healthy volunteers (HV), urinary tract infection patients (UTI), ventriculitis patients and sepsis-ICU patients were included. Simulations were performed to compare the PTA for different dosing regimens and participant-groups. RESULTS:A two-compartment protein-binding model best fitted the 1085 concentrations (543 unbound, 542 total). Temocillin clearance was influenced by creatinine clearance, serum albumin (ALB) and C-reactive protein (CRP). For 2 g q8h intermittent infusion, the PTAs at an MIC of 16 mg/L were 2.3%, 39.5%, 10.0% and 72.5%, for HV, UTI, ventriculitis and sepsis-ICU patients, respectively. The effects of the covariates on the PTA were simulated for two example patients with intermittent infusion: the PTAs at an MIC of 8 mg/L for a sepsis-ICU patient (CRP 300 mg/L, albumin 15 g/L) and a mild-UTI patient (CRP 30 mg/L, albumin 35 g/L) were 94.3% and 62.4%, respectively. Continuous infusion consistently outperformed intermittent infusion in achieving the desired pharmacodynamic target (time above MIC). CONCLUSIONS:Our study underscores the significant variation in temocillin clearance and unbound fractions among different participant groups, challenging the efficacy of traditional 2 g q12h dosing. For patients with enhanced renal function and lower inflammation, continuous infusion emerges as a more effective strategy to achieve optimal target attainment.

Purpose: Evaluate the safety profile of expanded allogeneic adipose-derived mesenchymal stem cell (eASC) for the treatment of severe community-acquired bacterial pneumonia (CABP). Materials and methods: Randomized, multicenter, double-blind, placebo-controlled, phase 1b/2a trial. Patients with severe CABP were enrolled to receive intravenous infusions of Cx611 or placebo. The primary objective was safety including hypersensitivity reactions, thromboembolic events, and immunological responses to Cx611. The secondary endpoints included the clinical cure rate, ventilation-free days, and overall survival (Day 90). Results: Eighty-three patients were randomized and received infusions (Cx611: n = 42]; placebo: n = 41]. The mean age was similar (Cx611: 61.1 [11.2] years; placebo: 63.4 [10.4] years). The number of AEs and treatmentemergent AEs were similar (243; 184 and 2; 1) in Cx611 and placebo respectively. Hypersensitivity reactions or thromboembolic events were similar (Cx611: n = 9; placebo: n = 12). Each study arm had similar anti-HLA antibody/DSA levels at Day 90. The clinical cure rate (Cx611: 86.7%; placebo: 93.8%), mean number of ventilator-free days (Cx611: 12.2 [10.29] days; placebo: 15.4 [10.75] days), and overall survival (Cx611: 71.5%; placebo: 77.0%) did not differ between study arms. Conclusion: Cx611 was well tolerated in severe CABP. These data provide insights for future stem cell clinical study designs, endpoints and sample size calculation. Trial registration: NCT03158727 (retrospectively registered: May 09, 2017). Full study protocol: https://clinicaltrials.gov/ProvidedDocs/27/NCT03158727/Prot_000.pdf

BACKGROUND:Cerebral ventriculitis might be caused by Gram-negative bacteria, including ESBL producers. Temocillin may be a useful treatment option in this scenario; however, no consistent data are available regarding its penetration into the CSF. OBJECTIVES:To describe the population pharmacokinetics of temocillin in plasma and CSF and to determine the probability for different simulated dosing regimens to achieve pharmacokinetic/pharmacodynamic (PK/PD) targets in the CSF. METHODS:Ten post-neurosurgical critically ill adult patients requiring continuous drainage of CSF were included in this monocentric, prospective, open-label, non-randomized study. They received 2 g loading dose temocillin over 30 min IV infusion, followed by a 6 g continuous infusion over 24 h. Total and unbound concentrations were measured in plasma (n = 88 and 86) and CSF (n = 88 and 88) samples and used to build a population PK model. Monte Carlo simulations were performed to estimate the PTA at 100% Css>MIC (steady state concentration above the MIC) in CSF. RESULTS:All patients were infected with Enterobacterales with temocillin MICs ≤8 mg/L. The median (min-max) temocillin penetration in CSF was 12.1% (4.3-25.5) at steady state. Temocillin unbound plasma pharmacokinetics were best described by a one-compartment model. PTA for the applied dosing regimen was >90% for bacteria with MIC ≤ 4 mg/L. CONCLUSIONS:The currently approved dose of 6 g by continuous infusion may be adequate for the treatment of ventriculitis by Enterobacterales with MIC ≤ 4 mg/L if considering 100% Css>MIC as the PK/PD target to reach. Higher maintenance doses could help covering higher MICs, but their safety would need to be assessed.