Acute respiratory distress syndrome (ARDS) exhibits significant clinical heterogeneity, with inflammatory subphenotypes (hypoinflammatory and hyperinflammatory) representing a key axis for precision medicine. The role of the pulmonary microbiome in these subphenotypes remains poorly understood. This retrospective study enrolled 159 ARDS patients. Using a validated machine-learning classifier, patients were stratified into hypoinflammatory (n=92) and hyperinflammatory (n=67) groups. Bronchoalveolar lavage fluid (BALF) was analyzed by metagenomic next-generation sequencing (mNGS) and conventional microbiological testing (CMT). Clinical characteristics, pathogen profiles, and pulmonary microbiome composition were compared between groups. Patients in the hyperinflammatory phenotype had more severe disease, with significantly higher in-hospital mortality (65.7
Organ shortages remain a critical global challenge, and extracorporeal membrane oxygenation (ECMO) has emerged as a potential strategy to preserve organ perfusion and expand the donation after brain death (DBD) donor pool. In regions where donation after circulatory death (DCD) is not legally permitted, maximizing DBD donor utilization carries particular clinical and policy importance. However, evidence regarding organ-specific recovery rates and post-transplant graft outcomes in ECMO-supported DBD donors remains limited and heterogeneous. We conducted a two-center retrospective cohort study of all consecutive brain-dead organ donors managed at two tertiary referral centers between January 2012 and June 2025. Donors were stratified by ECMO exposure prior to organ procurement. Primary outcomes were organ-specific recovery rates and the number of organs recovered per donor. Kaplan–Meier analysis with log-rank testing was used to evaluate post-transplant recipient survival stratified by donor ECMO exposure and organ type. Of 210 donors (ECMO n=25, non-ECMO n=185), baseline demographics and cause of brain death were broadly comparable, although ECMO donors more frequently had antecedent cardiac arrest (76.0
Patients requiring prolonged mechanical ventilation (PMV) after tracheostomy represent a severely deconditioned population with high mortality and substantial healthcare burden. Weaning outcomes vary widely across centers, and evidence supporting standardized protocol in dedicated rehabilitation settings remains limited. We conducted a prospective, single-arm interventional trial at a specialized weaning unit (SWU) of a tertiary rehabilitation hospital. From January 2025 to October 2025, consecutive tracheostomized PMV patients were enrolled and managed with a standardized stepwise weaning protocol integrating spontaneous breathing trials, high-flow oxygen therapy, and noninvasive ventilator. The primary outcome was the 60-day weaning success rate, which was tested against a pre-specified historical benchmark (p₀ = 65 https://jianghongying.shinyapps.io/Weaning-for-PMV/ . A standardized weaning protocol delivered in a dedicated rehabilitation unit was associated with a 60-day weaning success rate that exceeded a pre-specified historical benchmark in PMV patients. The individualized calculated weaning score identifies clinical phenotypes for individualized decision-making; the accompanying web-based calculator is provided as an exploratory research tool and warrants external validation before any routine clinical application. ClinicalTrials.gov, NCT06642714.
Lung-protective ventilation (LPV) reduces mortality in ARDS, but adherence remains incomplete and women and shorter patients disproportionately receive tidal volumes above predicted-body-weight (PBW)-based targets. The relative associations of recorded sex and body height with this disparity remain uncertain. Retrospective single-centre cohort study (January 2013 to December 2023, RWTH Aachen University Hospital surgical ICU). Adults (≥ 18 years) with Berlin-definition ARDS receiving mechanical ventilation for ≥ 72 h were included. Patient-level adherence to lung-protective targets was described, and repeated-measure PBW-normalised tidal volume and mechanical power were analysed with linear mixed-effects models containing a patient-level random intercept and fixed effects for recorded sex, centred recorded height, age, BMI, SAPS II, SOFA, ARDS aetiology, linear relative ICU day and the lowest same-day PaO₂/FiO₂ ratio. Among 798 adults (263 women [33.0
Sepsis remains a major cause of morbidity and mortality, yet current strategies for identifying susceptible individuals provide limited discriminatory performance. Although serum uric acid (SUA) and gout have been implicated in inflammatory and immune dysregulation, the associations of clinical urate phenotypes with incident sepsis risk and prognosis remain incompletely understood. A prospective cohort analysis was conducted using UK Biobank data including 466,611 participants, in which clinical urate phenotypes (normal uric acid, asymptomatic HUA, and gout) were evaluated as primary exposures, with SUA quartiles and separate HUA and gout status analyses used as alternative exposure definitions, using multivariable Cox proportional hazards models, restricted cubic spline analyses, subgroup analyses, and sensitivity analyses including Fine-Gray competing-risk models. During a median follow-up of 14.53 years, 16,210 incident sepsis cases were identified. Compared with the normal uric acid group, asymptomatic HUA and gout were associated with higher sepsis risk after full adjustment, with HRs of 1.31 (95
Abstract Background Sepsis-associated acute kidney injury (SA-AKI) frequently progresses to acute kidney disease (AKD) and is linked to poor outcomes. We evaluated whether combining biomarkers reflecting complementary pathophysiological domains—histone H3.1 nucleosomes (cellular injury), midregional pro-adrenomedullin (MR-proADM; endothelial dysfunction), and kinetic estimated glomerular filtration rate (kinetic eGFR; dynamic renal function)—improves prediction of AKD and renal recovery. Methods This secondary analysis of the multicentre randomized SISPCT trial included 690 patients with sepsis after exclusion of patients with pre-existing renal replacement therapy or missing AKI data. Biomarkers and kinetic eGFR were assessed at baseline, day 2, and day 7. Multivariable logistic regression models adjusted for age, sex, and non-renal SOFA score were used to assess associations with AKD. Predictive performance was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). Calibration for the combined models for each day was evaluated using bootstrap-corrected calibration plots. Clinical utility was assessed using decision curve analysis with fivefold cross-validation. Results AKD occurred in 196 patients (28.4%). At baseline, only MR-proADM was independently associated with AKD (adjusted OR 1.17, 95% CI 1.08–1.28; p < 0.001), whereas H3.1 and kinetic eGFR were not. At day 2 and day 7, only changes in kinetic eGFR were independently associated with AKD (both p < 0.001). Discriminative performance increased over time, with AUCs for the combined model of 0.65 at baseline, 0.70 at day 2, and 0.76 at day 7. At later time points, kinetic eGFR consistently showed the highest discriminative performance based on the point estimates of the AUC. An overall good calibration performance was shown. Decision curve analysis demonstrated only modest and inconsistent additional clinical net benefit of the combined model compared with kinetic eGFR alone. AKD was associated with increased 90-day mortality (55% vs. 24%; risk ratio 2.3, 95% CI 1.9–2.9). Biomarkers showed limited and inconsistent performance for prediction of renal recovery. Conclusions In patients with sepsis, MR-proADM at baseline and dynamic changes in kinetic eGFR during the first week were independently associated with AKD, whereas histone H3.1 nucleosomes provided limited predictive value. Although multimarker models seemed to modestly improve baseline discrimination, this advantage was not sustained over time and added little clinical benefit beyond kinetic eGFR. These findings highlight the value of dynamic renal function assessment for risk stratification of SA-AKI progression to AKD. Trial registration ClinicalTrials.gov Identifier: NCT00832039.
Abstract Background Prognostic assessment at continuous kidney replacement therapy (CKRT) initiation remains challenging in ICU practice. CKRT recipients are heterogeneous; most have acute kidney injury (AKI), whereas a clinically important subset has end-stage kidney disease (ESKD). We evaluated whether pre-CKRT urine output in AKI and dialysis vintage in ESKD were associated with short-term prognosis after CKRT initiation. Methods We conducted a single-center retrospective cohort study of consecutive adults who started CKRT in a combined medical–surgical ICU between 2012 and 2021. Patients were classified at CKRT initiation as ESKD, oliguric AKI, or non-oliguric AKI. ESKD was defined as maintenance hemodialysis or peritoneal dialysis before ICU admission. Among patients with AKI, oliguric and non-oliguric AKI were defined as pre-CKRT urine output <0.5 and ≥0.5 mL/kg/h, respectively. The primary outcome was time to all-cause death within 90 days after CKRT initiation. We used Cox proportional hazards models adjusted for prespecified covariates measured at CKRT initiation. Within ESKD, we modeled dialysis vintage as a continuous variable using Cox models adjusted for APACHE II score and sepsis. Results Among 560 patients, 66 had ESKD, 305 had oliguric AKI, and 189 had non-oliguric AKI. Documented death within 90 days occurred in 236 patients (42.1%). Using ESKD as the reference, oliguric AKI was not associated with a different hazard of death within 90 days (adjusted hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.58–1.29), whereas non-oliguric AKI was associated with a lower hazard (adjusted HR, 0.63; 95% CI 0.41–0.99). Among patients with ESKD, longer dialysis vintage was associated with a higher hazard of death within 90 days (adjusted HR per 1-year increase, 1.07; 95% CI 1.02–1.11). Conclusions In ICU patients starting CKRT, pre-CKRT urine output in AKI and dialysis vintage in ESKD were associated with short-term prognosis. Non-oliguric AKI was associated with a lower adjusted hazard of death than ESKD, and longer dialysis vintage was associated with a higher hazard of death within ESKD. These findings require external validation in contemporary multicenter cohorts.
The ROX index (the ratio of peripheral oxygen saturation to the fraction of inspired oxygen, divided by respiratory rate) has been validated to predict high-flow nasal cannula (HFNC) failure, but whether acting on ROX to guide the timing of intubation improves patient outcomes is unknown. We estimated the per-protocol effect of ROX-guided strategies versus usual care on mortality after HFNC initiation. We emulated target trials using Medical Information Mart for Intensive Care IV (MIMIC-IV) electronic health record data. Adults initiated on HFNC within 7 days of intensive care unit (ICU) admission were eligible. Strategies were usual care or intubation within 2 h after ROX first fell below 3.85, 4.88, or time-varying thresholds (2.85 for hours 1–5, 3.47 for hours 6–11, and 3.85 from hour 12). We used clone-censor-weighting with pooled logistic regression, adjusted for baseline and time-varying covariates, to estimate 30-day mortality. We included 1,651 adults (median age, 66 years; women, 41
To describe the age-stratified clinical characteristics, ICU management, and in-hospital outcomes of adults admitted to Japanese ICUs with aspiration pneumonia. Multicenter, retrospective, observational cohort study. Multiple ICUs participated in the Japanese Intensive Care Patient Database (JIPAD), a nationwide registry of the Japanese Society of Intensive Care Medicine, from 2015 to 2023. Adults ≥ 18 years admitted to ICUs with a primary diagnosis of aspiration pneumonia. Among 3,906 eligible ICU admissions (median age, 76 years [IQR, 68–83]; 75.5
Tachycardia is common in sepsis and is associated with poor outcomes. β-blockers have been used for heart rate (HR) control, but comparative evidence between short- and long-acting agents remains limited. The aim of this study was to compare the efficacy and safety of intravenous landiolol and a bisoprolol transdermal patch in patients with sepsis-related tachycardia. This multicenter retrospective cohort study included adult patients with sepsis-related tachycardia (HR ≥ 100 bpm) treated with landiolol or a bisoprolol transdermal patch at intensive care units (ICUs) participating in a Japanese ICU database, from January 2014 to March 2026. Propensity score matching (PSM) at a 1:1 ratio was performed to adjust for baseline differences between groups. The primary outcome was the proportion of patients who achieved HR control (60–94 bpm) at 24 h. The secondary outcomes included in-hospital mortality, bradycardia incidence, the proportion requiring increased norepinephrine-equivalent doses at 24 h, and trends in HR and mean arterial pressure (MAP) over 24 h. After PSM, data from 950 patients were analyzed (n = 475 in each group). HR control at 24 h did not differ between the two groups (landiolol: 56
Abstract Background Adults who survive critical illness requiring mechanical ventilation frequently experience prolonged physical, psychological, and social difficulties following discharge, yet access to structured recovery support remains variable. This study explored how ICU survivors and staff perceived the acceptability of a remote multicomponent rehabilitation programme versus standard care following discharge from critical care. Methods A theory-informed qualitative interview study was conducted, guided by the Theoretical Framework of Acceptability. ICU survivors who received either remote multicomponent rehabilitation or standard care, alongside staff involved in delivery, were purposively sampled from a pragmatic UK trial (iRehab) across 24 hospital sites. Semi-structured interviews were audio-recorded, transcribed verbatim, and analysed using framework analysis. Thirty-five ICU survivors and six staff members participated in interviews conducted between January 2023 and June 2025. Results Eight inter-related themes captured the factors shaping acceptability during recovery after ICU discharge. Participants who received remote multicomponent rehabilitation generally found it acceptable, as it provided structure, continuity, and support for confidence-building and self-management. In contrast, standard care was often experienced as lacking coordination and follow-up, leaving individuals to navigate recovery with limited support. However, acceptability was not experienced in the same way by all participants. Digital delivery and optional components, such as peer support, were valued by many but not by everyone, depending on readiness, context, and capability. Conclusions Remote multicomponent rehabilitation was valued for its structure, continuity, and support, while standard care was often experienced as lacking these features. Acceptability of support was shaped by how well it aligned with survivors’ needs and contexts. These findings support the integration of structured, flexible rehabilitation pathways into post-ICU care. Trial registration ISRCTN11266403; registered 26 July 2022.
Intensive care unit-acquired weakness (ICUAW) is frequent in critically ill adults and is associated with adverse outcomes, but early recognition is difficult because standard diagnosis relies on volitional strength testing. In this prospective multicentre cohort study across 16 tertiary ICUs in southwest China, adults expected to remain in the ICU for ≥ 3 days underwent quadriceps ultrasound and routine clinical assessment within 24 h of admission. ICUAW was defined by the first evaluable Medical Research Council (MRC) score during ICU stay. We developed and compared nine algorithms in a development cohort (n = 858) and performed temporal external validation in a later cohort (n = 345). ICUAW occurred in 579/858 (67.5
Surgical site infection (SSI) is a major cause of postoperative morbidity. Surgical antibiotic prophylaxis (SAP), defined as the pre-incision administration of an antimicrobial agent targeting likely organisms in clean or clean-contaminated procedures without active infection at the operative site, is a cornerstone of prevention in surgery. However, critically ill patients represent a distinct population with profound susceptibility to infection. Data on SSI incidence and SAP practices in patients undergoing surgery during an intensive care unit (ICU) stay remain scarce. Retrospective multicenter cohort study in five French ICUs (March 2022–March 2023). Adult patients (≥18 years) with an ICU stay ≥ 48 h who underwent surgery during their ICU stay were included. Primary outcome was SSI incidence after surgery. Generalized estimating equations (GEE) with a prespecified adjustment set were used to estimate the adjusted association between antimicrobial spectrum and SSI, accounting for clustering within centers. 338 patients were included (median age 56 years, IQR 35 – 67; 72
Physical restraint remains common in the intensive care unit (ICU), but it is increasingly questioned following recent high‑quality evidence, particularly the R2D2‑ICU trial, which challenges the assumption that reducing restraint inherently improves short‑term neurological outcomes. Epidemiological data reveal significant variability in the prevalence of restraint use, which is influenced by a complex interplay of patient characteristics, caregiver factors, and systemic elements. The evidence on its effectiveness for mainly preventing the pulling out of tubes is questionable. However, its association with a range of negative physical, neurological, and psychological outcomes. It also imposes a heavy burden of moral distress on caregivers, who are tasked with balancing patient safety against the imperative to minimize harm. Successful minimization of restraint use requires multicomponent approaches. Moving toward restraint minimization requires a paradigm shift from viewing physical restraint as a standard safety tool to recognizing it as a potentially harmful intervention of last resort. Future evaluations should adopt the triadic outcomes framework outlined here, assessing neurological and psychological outcomes, family satisfaction, and caregiver moral burden to guide ethically sound, sustainable ICU practice.
Prone positioning (PP) and inhaled nitric oxide (iNO) are widely utilized rescue therapies for severe hypoxemia during invasive mechanical ventilation. However, their combined effects on regional ventilation–perfusion (V/Q) matching remain incompletely characterized. This study utilized single-plane saline-contrast electrical impedance tomography (EIT) to achieve real-time bedside visualization and evaluate the relative spatial mechanisms of these interventions in patients with COVID-19-related ARDS. We conducted a prospective sequential physiological study in mechanically ventilated patients with moderate-to-severe COVID-19-related acute respiratory distress syndrome (ARDS). Relative regional ventilation, perfusion, and V/Q matching distributions were monitored across four predefined, fixed sequential conditions: supine position ventilation (SPV), SPV with iNO (20 ppm for 1 h; SPV + iNO), prone position ventilation after stabilization (PPV), and PPV with an additional 1 h of iNO (PPV + iNO). Primary analyses focused on prespecified within-patient contrasts, supplemented by exploratory difference-in-differences (DiD) analyses to evaluate position-dependent vascular responses. Twenty-eight patients completed all study phases. Hemodynamics and conventional respiratory mechanics remained remarkably stable across all four conditions. Systemic oxygenation improved progressively; both SPV + iNO and PPV significantly increased PaO2 and PaO2/FiO2 compared to SPV alone, while the addition of iNO during PPV (PPV + iNO) yielded further oxygenation improvements and reduced FiO2 requirements. Within the EIT-assessed thoracic slice, SPV + iNO produced the most widespread V/Q improvements, significantly reducing the global non-perfused fraction (−7.28
Osmotherapy is frequently used in neurocritical care to manage cerebral edema and intracranial hypertension. However, its association with subsequent new-onset acute kidney injury (AKI), and whether early serum sodium or chloride burden materially attenuates this association, remain uncertain. We conducted a retrospective cohort study using MIMIC-IV version 3.1. Adult first-ICU neurocritical care patients were analyzed with a 48-h landmark design. The primary risk set included patients who were alive, remained in the ICU, and were AKI-free at 48 h after ICU admission. The primary exposure was any osmotherapy, defined as mannitol or hypertonic saline administered within the first 48 ICU hours, compared with no osmotherapy. The primary outcome was incident AKI after the 48-h landmark through ICU day 7 or ICU discharge. Multivariable regression was used as the main adjusted model; propensity-score weighting, overlap weighting, doubly robust models, and modified Poisson regression were used as complementary estimators. Sodium/chloride burden analyses were conducted in the lab-complete subset. The final 48-h landmark cohort included 2,756 adult neurocritical care patients, of whom 624 (22.6
Delirium is common in the intensive care unit and associated with adverse outcomes. However, bedside indicators that flag patients at high risk for delirium the following day are lacking. Although physical restraint has been linked to delirium, many prior studies relied on cross-sectional, same-day assessments that cannot exclude reverse causation. This study aimed to evaluate whether cumulative previous-day physical restraint duration was a bedside signal for following-day delirium. We conducted a single-center retrospective observational cohort study using patient-days (00:00–24:00 h) as the unit of analysis, with the exposure and covariates derived from more granular, time-stamped nursing records aggregated into calendar-day units. The exposure was cumulative physical restraint duration on the previous day, reported per 8-h increase. The outcome was incident delirium on the following day, defined as an Intensive Care Delirium Screening Checklist (ICDSC) score ≥ 4. The primary analysis was restricted to patient-days without previous-day delirium (ICDSC 0–3). We fitted a generalized linear mixed model with a random intercept for each patient. The restraint duration was modeled using a natural cubic spline (degrees of freedom = 3). Of 1,482 patient-days from 281 patients, 263 patient-days were excluded due to coma. The primary analysis included 729 patient-days from 247 patients without previous-day delirium (115 incident delirium events, 15.8
Sepsis-induced myocardial injury (SIMI) contributes substantially to sepsis mortality. We investigated whether low-dose esmolol is associated with improved autophagy-related homeostasis and restored PI3K/Akt phosphorylation in SIMI. Human peripheral blood transcriptomic datasets (GSE28750, GSE232753, GSE134347, and GSE185263) and a rat septic myocardial dataset (GSE125042) were analyzed. Sprague–Dawley rats underwent cecal ligation and puncture (CLP) and received low-dose (5 mg·kg⁻1·h⁻1) or high-dose (15 mg·kg⁻1·h⁻1) esmolol infusion starting at 4h post-CLP. Autophagy was modulated with rapamycin, 3-methyladenine (3-MA), or chloroquine (CQ). Conscious hemodynamic monitoring, serial echocardiography, survival analysis, sepsis severity scoring, cardiac troponin I (cTnI) measurement, chamber-specific transmission electron microscopy, LC3/p62 co-localization, and TFEB subcellular localization were assessed. The unified endpoint was 18 h post-CLP. Bioinformatics analyses identified Akt1 and mTOR as hub genes and highlighted PI3K/Akt signaling as a candidate pathway associated with SIMI and esmolol response. Low AKT1 expression was associated with poorer survival in septic patients and showed moderate prognostic performance (AUC = 0.750). Rat myocardial transcriptomic data showed no transcriptional suppression of PI3K/mTOR components during sepsis. Sepsis suppressed PI3K/Akt phosphorylation, with p62 and LC3-II accumulation and TFEB cytoplasmic retention. Low-dose esmolol reduced tachycardia by 15–20
