Background The use of extracorporeal Membrane Oxygenation (ECMO) increases for patients with refractory cardiac and/or respiratory failure. To ensure broader access to this life-saving therapy, regional ECMO networks have been developed worldwide, enabling the transfer of patients supported with ECMO to specialized referral centers. At the University Hospital of Martinique, a Mobile Circulatory Support Unit provides 24 h/7 coverage for inter-hospital aeromedical transport of patients receiving ECMO across the French Departments of the America and to mainland France. This study aimed to describe the characteristics, transport modalities, and transport-related adverse events of patients undergoing ECMO-supported aeromedical transfer within this regional mobile ECMO network, as well as their short-term and in-hospital outcomes. Methods We conducted a retrospective, observational, single-centre study including patients who underwent ECMO-supported aeromedical transfer coordinated by the Mobile Circulatory Support Unit and Emergency Medical Service between January 2010 and December 2021. We collected data on patient characteristics, ECMO configuration and indication, transport modalities, transport-related adverse events, and short-term and in-hospital outcomes. Results Of the 520 patients supported with ECMO during the study period, only the 126 who underwent aeromedical evacuation were included in the analysis, including 87 intra-Caribbean and 39 transatlantic transfers. Patients were predominantly male (61.1%), with a mean age of 43 [29.25-56] years, and at least one comorbidity present in 60.3% of cases. Veno-venous ECMO was predominantly used for intra-Caribbean transfers (80.5%), mainly for acute respiratory distress syndrome, whereas veno-arterial ECMO for refractory cardiogenic shock predominated in transatlantic transfers (87.2%). In-transfer complications occurred in 18.3% of cases and were mainly related to hemodynamic instability, with one transport-related death reported. Overall in-hospital mortality was 54.7%, with no significant difference between intra-Caribbean and transatlantic patients. Conclusion Aeromedical transport of critically-ill patients under ECMO support appears feasible and relatively safe in our experience, with a low incidence of serious adverse events. The high in-hospital mortality reflects the acute cardiac and/or pulmonary failure, as well as the burden of comorbidities in this population. Prospective studies using standardized adverse-event collection are needed to more accurately evaluate transport-related risks and longer-term outcomes in this high-risk population.
Background Although guidelines recommend light sedation with propofol or dexmedetomidine in mechanically ventilated patients, appropriate management with monotherapy is often challenging. Whether combined sedation reduces dose-dependent adverse effects of each agent or causes additive harm remains unclear. We investigated short-term outcomes associated with early sedation practice patterns in mechanically ventilated patients with bacterial pneumonia. Methods Using the Japanese Diagnosis Procedure Combination database, we identified adult intensive care unit patients with bacterial pneumonia requiring mechanical ventilation between April 2018 and March 2023 and classified them into combined sedation, propofol-based sedation, and dexmedetomidine-based sedation groups. The composite outcome included in-hospital death and functional decline at discharge. Propensity-score matching-weight analyses adjusted for measured confounders. Results Among 3,302 eligible patients, 1,135 (34.4%) were classified into the combined-sedation group, 1,067 (32.3%) into the propofol-based sedation group, and 1,100 (33.3%) into the dexmedetomidine-based sedation group. Combined sedation was not associated with a lower risk of the composite outcome compared with propofol-based sedation (26.3 % vs. 30.0 %; risk difference [RD] −3.7 %; 95% confidence interval [CI] −8.0 to 0.7) but was associated with a lower risk of the composite outcome compared with dexmedetomidine-based sedation (26.3 % vs. 33.1 %; RD − 6.7%; 95% CI − 11.2 to −2.3). In-hospital mortality was lower with combined sedation than propofol-based (22.4% vs. 26.7%; RD, −4.2%; 95% CI, −8.5 to −0.03) or dexmedetomidine-based (22.4% vs. 30.1%; RD, −7.7%; 95% CI, −12.1 to −3.3) sedation, although the comparison with propofol-based sedation was not robust in sensitivity analyses and was not supported by 28-day or 90-day in-hospital mortality. The in-hospital mortality difference between combined sedation and dexmedetomidine-based sedation was consistent across sensitivity analyses and 28-day and 90-day in-hospital mortality. Functional decline at discharge did not differ among groups. Tracheostomy was more frequent with combined sedation than with both comparators, whereas 28-day ventilator-free days did not differ. Conclusions Combined sedation was not associated with a lower risk of the composite outcome of in-hospital death and functional decline at discharge, compared with propofol-based sedation; however, a lower risk was observed compared with dexmedetomidine-based sedation.
Objective This randomized, open-label, non-inferiority trial aimed to compare the safety and efficacy of cipepofol vs. a dexmedetomidine plus propofol regimen for sedating intensive care unit (ICU) patients requiring mechanical ventilation (MV). Methods This single-center study randomly assigned Chinese adult patients to cipepofol or dexmedetomidine/propofol groups (1:1 ratio). Cipepofol was infused intravenously at a loading dose of 0.1 mg/kg (over 4 min ± 30 s) and an initial maintenance dose of 0.3 mg/kg/h, which was adjusted within the range 0.06–0.8 mg/kg/h to produce sedation in the range of 0 to -4 on the Richmond Agitation-Sedation Scale. Propofol and dexmedetomidine were infused intravenously at initial dosages of 0.3 mg/kg/h and 0.2 μg/kg/h, respectively (neither drug required a loading dose). When the maximum dexmedetomidine dose (0.7 μg/kg/h) was insufficient to achieve the target sedation depth or intolerance developed, the propofol dose was modified within the range 0.3–4.0 mg/kg/h. The primary endpoint was sedation success rate, and the non-inferiority margin was set as 10%. Results Of 72 patients enrolled for the intention-to-treat (ITT) analysis, 71 patients were included in the full analysis set/per-protocol set (FAS/PPS). The sedation success rates for the cipepofol and dexmedetomidine/propofol groups were 100% and 97.2%, respectively, in the ITT analysis and 100% for both in the FAS/PPS. Non-inferiority was established, and the lower limit of the 95% confidence interval (CI) for the inter-group difference was -1.34% for the ITT analysis and -9.64% for the FAS/PPS. There were no differences between groups in sedation compliance rate, extubation and recovery times, MV duration, or length of ICU stay (all P>0.05). Cipepofol was associated with lower incidences of treatment-emergent adverse events (TEAEs; 33.3% vs. 66.7%) and drug-related TEAEs (30.6% vs. 63.9%) than dexmedetomidine/propofol (all P < 0.05). Notably, hypotension incidence was lower in the cipepofol group than in the dexmedetomidine/propofol group (30.6% vs. 61.1%, P = 0.017). Conclusion Cipepofol was not inferior to dexmedetomidine/propofol for >24-h sedation in Chinese adult patients receiving MV in the ICU. Furthermore, cipepofol elicited fewer hypotensive events than dexmedetomidine/propofol. Large-scale, multicenter studies are warranted to confirm our findings.
Background:The ability of perfusion index (PI) for predicting fluid responsiveness has been extensively studied with conflicting results. This meta-analysis evaluated the value of variation of PI (ΔPI) for predicting fluid responsiveness in adult patients undergoing preload challenge tests. Methods:PubMed, Embase, and Cochrane Library were searched up to 20th July 2026. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operator characteristic curve (AUROC) were calculated. Q test and I2 statistics were used for study heterogeneity and publication bias was assessed by Deeks' funnel plot asymmetry test. Subgroup analysis was performed for the potential causes of heterogeneity arising from varied patient characteristics. Results:Overall, nine studies including 492 preload challenge tests were administered to 419 patients in this review, of whom 52% were fluid responsive. The cutoff values of ΔPI were increased between 1.024% and 33% or decreased between -7% and -40%. Pooled sensitivity and specificity were 0.79 (95% CI: 0.71-0.85) and 0.82 (95% CI: 0.75-0.87), respectively. DOR was 17 (95% CI: 10-30) and AUROC was 0.88 (95% CI: 0.85-0.90), indicating good diagnostic accuracy. Heterogeneity was low (I 2 = 28.95%, P = 0.124). Subgroup analysis showed that ΔPI performed consistently across ICU and operating room settings, regardless of preload challenge type, PI device, or ventilation status. Conclusions:Our meta-analysis suggests that ΔPI may serve as a promising adjunct non-invasive marker for predicting fluid responsiveness during preload challenge tests, but the current evidence base remains limited, heterogeneous, and at risk of bias.
Sepsis is a life-threatening syndrome characterized by a heterogeneous host response to infection that remains a major cause of mortality worldwide. Current clinical scoring systems capture organ dysfunction but fail to reflect the underlying biological diversity, limiting their utility for patient stratification and targeted therapy. This review provides a comprehensive overview of molecular biomarker approaches used to predict sepsis course and prognosis in adult patients, covering genetic, transcriptomic, proteomic, and integrative strategies up to May 2026. Here, we summarize findings from genetic association studies, along with analyses based on polygenic risk scores to aggregate genetic effects, Mendelian randomization, and rare-variant sequencing approaches. We also review transcriptomic and proteomic strategies for endotyping, and diagnostic and prognostic discrimination. Lastly, we discuss how multi-omics integration is emerging as a promising framework to assist in distinguishing causal therapeutic targets from non-causal biomarkers. We also address the challenges that still constrain clinical translation towards precision medicine.
Background: Critically ill patients frequently develop intestinal dysbiosis, leading to gastrointestinal (GI) symptoms and infectious complications. No network meta-analysis (NMA) has compared the relative effectiveness of prebiotics, probiotics, and synbiotics for reducing the risk of GI symptoms in critically ill patients. Objective: This study aimed to evaluate their comparative effects in preventing GI symptoms and improving clinical outcomes. Methods: MEDLINE, CENTRAL, and Web of Science were searched through June 2025. Eligible randomized controlled trials enrolled critically ill adults and compared prebiotics, probiotics, or synbiotics with controls (placebo or usual care). The primary outcome was GI symptom incidence. Secondary outcomes included mortality, intensive care unit (ICU) length of stay, mechanical ventilation duration, infectious complications, and adverse events. A frequentist random-effects NMA was conducted. Treatment rankings were exploratory, and certainty of evidence was not formally assessed. Results: Thirty-three randomized controlled trials involving 5,073 patients were included in the analysis of GI symptoms. Compared with control, synbiotics significantly reduced the risk of GI symptoms (risk ratio [RR] 0.52; 95% confidence interval [CI]: 0.35 to 0.77), as did prebiotics (RR 0.66; 95% CI: 0.49 to 0.87). Probiotics produced a similar directional effect, but the difference was not statistically significant (RR 0.81; 95% CI: 0.60 to 1.10). No significant differences were found between the active interventions. Subgroup analyses suggested differences according to the ICU population. Among medical intensive care patients, prebiotics were associated with a lower risk of GI symptoms than control, whereas probiotics and synbiotics were associated with a lower risk among surgical intensive care patients. Conclusions: Synbiotics and prebiotics were associated with a significantly lower risk of gastrointestinal symptoms in critically ill patients, whereas probiotics showed a similar but statistically nonsignificant effect. No active intervention was significantly superior to another. The findings suggest that the relative benefits of these interventions may differ between medical and surgical intensive care populations. Nevertheless, the results should be interpreted cautiously because certainty of evidence was not formally assessed.PROSPERO registration number: CRD420251015729; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251015729
Background:Candidiasis remains a major global health challenge, with rising incidence and antifungal resistance complicating management. This multicenter survey aimed to describe diagnostic and therapeutic management practices of ICU physicians in France for high-risk invasive candidiasis cases, using randomized clinical case simulations distributed to French ICU physicians via email and academic congresses. Results:A total of 75 physicians completed 283 cases. Overall, clinical suspicion justified diagnostic investigation in 72.1% of cases. Key factors associated with the decision to test for invasive candidiasis included post-abdominal surgery (OR = 3.92; p = 0.002), central venous catheter (OR = 2.28; p = 0.04), parenteral nutrition (OR = 2; p = 0.027), prolonged antibiotic exposure (OR = 1.90; p = 0.041), and physician experience >10 years (OR = 2.79; p = 0.014). Echinocandins were the preferred first-line treatment (88.2%; n = 120/136). Their use was guided by clinical guidelines (78.3%), pharmacokinetic/pharmacodynamic profile (38.3%), SOFA score (29.2%), patient status (25.8%), and immunosuppression (20%). De-escalation to azoles upon documented mycological susceptibility occurred in 87.5% of cases initially treated with an echinocandin and 60.0% of cases initiated on amphotericin B, primarily after 5 days of treatment (51.2%; n = 64). Conclusions:Patient severity, immunosuppression, and catheter presence were the main factors guiding antifungal treatment decisions Management of confirmed invasive candidiasis was largely consensual among respondents, whereas empirical treatment decisions were heterogeneous. While conclusions are primarily reflective of practice patterns within specialized university hospital centers, the INSPIRE survey highlights the need for enhanced training, broader access to rapid diagnostics, and improved decision-support systems to better harmonize clinical practices.
Background:Prior corticosteroid use is linked to influenza-associated pulmonary aspergillosis (IAPA) in critically ill patients, yet the dose-response relationship remains unclear. Methods:In this multicenter emulated target trial across 48 ICUs in Central China (January 2023-June 2025), we included critically ill, non-neutropenic adults with influenza. Using inverse probability of treatment weighting (IPTW) and restricted cubic splines, we modeled the dose-response association between pre-ICU corticosteroid exposure and IAPA, identifying risk thresholds via segmented regression. Effect modification by pre-specified patient characteristics was further assessed. Results:Among 2763 patients (74.2% exposed to corticosteroids; median dose 35 mg dexamethasone-equivalent), 191 (6.9%) developed IAPA during their ICU stay. Pre-ICU corticosteroid exposure was independently associated with IAPA (weighted HR = 2.11; 95% CI 1.25-3.56). A non-linear, J-shaped dose-response relationship was identified (P < 0.001). Risk increased continuously, with a 50% increase at 43.4 mg and doubling at 51.4 mg, followed by a steep inflection point at 63.7 mg (95% CI 62.8-64.7). Higher SOFA scores (>7) significantly amplified per-dose risk (P < 0.001), lowering thresholds to 35.2 mg for 50% increase and 39.5 mg for doubling. Conclusions:Pre-ICU corticosteroid exposure is associated with a nonlinear, dose-dependent increase in IAPA risk. Cumulative doses approaching 40-50 mg warrant heightened vigilance, particularly in severely ill patients. These findings support individualized, dose-aware corticosteroid stewardship in severe influenza.
Background:No gold standard currently exists to evaluate fluid status during continuous renal replacement therapy (CRRT). We aimed to describe systemic venous congestion by using venous excess ultrasound (VExUS) and pulmonary congestion by lung ultrasound (LUS) in critically ill patients with acute kidney injury (AKI) who received CRRT. Methods:This was a single-centre prospective cohort study. Adult patients with AKI undergoing CRRT underwent serial ultrasound assessments on Day 1 and 3 by two independent operators. VExUS score and its individual components, including an inferior vena cava (IVC) diameter (≥2 cm), hepatic vein, portal vein, as well as intrarenal vein Doppler flow patterns, and 6-zone lung ultrasound (LUS) scores (ranged from 0 to 20 points), were collected. An exploratory modified VExUS (mVExUS) grading was derived by incorporating an IVC distensibility index (<18%) or collapsibility index (<50%). Venous congestion was defined as VExUS or mVExUS Grade ≥2. The primary descriptive outcome was the prevalence of venous congestion and serial LUS score changes. The principal clinical endpoint was the association between ultrasound parameters and 90-day mortality (NCT06254703). Results:Among 100 enrolled patients (median age 66 years, male 58%), baseline venous congestion was documented in 20% by VExUS score and 35% by mVExUS scores. The median LUS score was 4 (interquartile range 1-9). Baseline VExUS Grade 2-3 (Log rank p = 0.049) and mVExUS Grade 2-3 (Log rank p = 0.01) were associated with lower 90-day survival. In time-updated Cox models after adjustment for baseline Sequential Organ Failure Assessment score, hepatic vein Doppler Grade 2-3 (adjusted hazard ratio (aHR) 1.78; 95% confidence interval (CI) 1.05-3.01, p = 0.01) and higher LUS scores (aHR 1.04; 95% CI 1.001-1.08, p = 0.04) were independently associated with 90-day mortality. Unchanged or worsening LUS scores between Day 1 and Day 3 were associated with a significantly higher cumulative fluid balance compared to improved scores (p = 0.01). Conclusion:Systemic and pulmonary congestion assessed by multiorgan point-of-care ultrasound was associated with increased 90-day mortality in AKI patients receiving CRRT. Future studies should explore the utility of these tools in guiding individualised fluid management during CRRT.
Background:Public awareness of sepsis is essential for early recognition of warning signs and timely healthcare seeking behavior, but data from resource-limited settings remain scarce. Methods:We evaluated sepsis knowledge in Brazil using cross-sectional surveys conducted in 2014, 2017, and 2026. Standardized questionnaires were administered through face-to-face interviews using random sampling stratified by age, sex, and geographic region. Adequate basic knowledge was defined as having heard the term sepsis and correctly identifying it as a severe host response to infection. In 2026, we additionally assessed knowledge of sepsis time-dependent nature and long-term disability after sepsis. Multivariable logistic regression identified factors associated with knowledge. Results:A total of 6,312 participants were interviewed (2014: n = 2,126; 2017: n = 2,100; 2026: n = 2,086). Adequate basic knowledge increased from 2.6% in 2014 to 5.8% in 2017 (OR 2.25, 95% CI 1.63-3.16; p < 0.001) and 10.3% in 2026 (OR 3.45, 95% CI 2.54-4.75; p < 0.001). In 2026, 70.0% of participants acknowledged that earlier diagnosis and treatment improve survival. Awareness of long-term disabilities was lower (24.4%). Higher educational attainment was the strongest determinant of knowledge across all domains. Younger age, male sex, residence outside state capitals, and lower household income were independently associated with lower knowledge. Conclusion:Public awareness of sepsis in Brazil has improved substantially over the past decade, suggesting a positive impact of national and international awareness initiatives. Nevertheless, important knowledge gaps persist, and awareness continues to be strongly influenced by socioeconomic factors, highlighting the need for continued efforts to improve sepsis awareness and promote equitable access to health information.
Background:Acute kidney injury (AKI) is prevalent in critically ill patients, contributing to high morbidity, mortality, and healthcare costs. Early detection and differentiation between transient and persistent AKI are critical for guiding timely interventions. This study evaluates the NephroCheck® score, based on Tissue inhibitor of metalloproteinases-2 (TIMP-2) and Insulin-like growth factor-binding protein 7 (IGFBP7) biomarkers. The primary objective was to assess its ability to predict AKI risk and AKI subtype within the first seven days of Intensive Care Unit (ICU) admission. Secondary objectives included evaluating its association with the need for renal replacement therapy (RRT) and overall ICU outcomes in a heterogeneous critical care population. Methods:This prospective, multicenter observational study included 455 ICU patients from five hospitals in Barcelona, Spain. Biomarker analysis was conducted on urine samples collected at admission, and AKI was classified according to the kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patients were grouped by TIMP-2·IGFBP7 values and AKI subtypes. Data was analyzed using Stata version 18.0 (StataCorp, College Station, TX). Results:AKI occurred in 51% of patients; with 29% transient and 71% persistent. High TIMP-2·IGFBP7 (TIMP-2·IGFBP7 > 2.0) levels were significantly associated with AKI (OR 19.44; 95% CI [2.57-146.5], p = 0.004), persistent AKI (OR 4.3; 95% CI [1.61-11.41], p = 0.003), and RRT requirements (OR 3.93; 95% CI [1.34-11.47], p = 0.012). Patients with high TIMP-2·IGFBP7 had longer ICU stays, more severe AKI, increased RRT duration, and higher mortality rates. TIMP-2·IGFBP7 values correlated positively with ICU and in-hospital mortality and reduced 90-day survival. Conclusion:TIMP-2·IGFBP7 showed modest performance for early AKI detection, identifying RRT requirements and risk stratification in critically ill patients. While moderately effective for predicting outcomes, its role in differentiating transient from persistent AKI remains inconsistent. Further research is warranted to optimize TIMP-2·IGFBP7 guided interventions and explore its application in diverse AKI etiologies.
Background:Ventilator-associated pneumonia (VAP) remains an important complication in mechanically ventilated patients in intensive care units (ICUs). Early subglottic microleakage may precede overt infection but remains difficult to detect at the bedside. Airway tracers and biochemical biomarkers have been proposed as bedside tools for detecting upstream microleakage and predicting downstream VAP, but their diagnostic value remains uncertain because studies differ in sampling matrices, thresholds, reference standards, and endpoints. Methods:Six databases were systematically searched from inception to 1 March 2026. Studies evaluating airway tracers or biomarkers in critically ill adults receiving invasive mechanical ventilation or with artificial airways were included under a dual-endpoint framework, comprising upstream microleakage or aspiration-related event detection and downstream VAP prediction. Study data were extracted, and risk of bias was assessed using the QUADAS-2 tool. For markers with sufficient clinical and methodological comparability, quantitative analyses included bivariate random-effects pooling, variance decomposition, stepwise sensitivity analyses, and Bayes' theorem-based post-test probability projection. Results:Sixteen studies were included. Blue-dye-based visual methods were summarized descriptively because the available studies represented distinct aspiration paradigms and did not meet the criteria for quantitative pooling. FEES-validated tracheostomy studies reported relatively high sensitivity for swallowing-related transglottic aspiration, whereas enteral-tracer or reflux-aspiration monitoring studies were limited by surrogate reference standards and/or low visual detectability for continuous, low-volume microleakage. One mechanically ventilated enteral-feeding cohort was retained as narrative evidence only because it did not provide a direct 2 × 2 diagnostic accuracy comparison of visual blue-dye detection against the microsphere reference standard. For VAP prediction, airway α-amylase showed a pooled sensitivity of 78.1%, specificity of 70.3%, and an area under the curve of 0.811. Conclusions:Current airway tracers and biomarkers do not appear suitable as standalone diagnostic triggers for VAP. However, airway α-amylase may have potential as a negative-predictive screening tool. Future research should standardize volumetric airway sampling and prospectively validate clinically actionable rule-out algorithms to support early antimicrobial de-escalation.
Background:Whether or not a direct tracheostomy without any prior weaning attempt is beneficial in patients intubated for Guillain-Barré syndrome (GBS) remains to be determined. Our objective was to determine whether direct tracheostomy results in earlier or later ventilator weaning compared to standard weaning. Methods:Multicenter, retrospective cohort study including all patients intubated for GBS over a 10-year period (2014-2023). We compared patients having undergone direct tracheostomy without any prior weaning attempt with those having undergone standard weaning (spontaneous-breathing trial or extubation attempt). We also compared direct tracheostomy with tracheostomy after weaning failure. The primary outcome was the proportion of patients alive and free from mechanical ventilation 28 days after weaning initiation. Results:Overall, 221 patients (45%) underwent direct tracheostomy and 273 (55%) standard weaning. Compared to patients with standard weaning, those with direct tracheostomy were less likely to be alive and free from mechanical ventilation at day 28 (43% vs. 83%, p < 0.001). Using G-computation to estimate the marginal causal effect of the weaning strategy, standard weaning was more effective than direct tracheostomy in reducing the risk of remaining under mechanical ventilation at day 28: -39.5% [95% Confidence Interval, -47.3% to -31.5%]. Even when compared to patients having undergone tracheostomy after weaning failure, those with direct tracheostomy were less likely to be alive and free from mechanical ventilation 28 days after the tracheostomy procedure. Interpretation:A direct tracheostomy without any prior weaning attempt might significantly delay the ventilator weaning process in patients intubated for GBS. Clinical Trial Registration:NCT07022028.
Background:While intensive care unit (ICU) capacity remains constrained, the number of older patients receiving resource-demanding ICU treatment continues to rise. Yet, long-term outcomes and post-critical illness frailty trajectories remain poorly characterized. We examined long-term mortality and frailty trajectories, and their associations with clinical characteristics and ICU treatment intensity. Methods:In this prospective, observational study across five Norwegian hospitals representing all health regions, we included patients aged ≥65 years who required invasive mechanical ventilation for ≥24 h. Frailty was assessed using the Clinical Frailty Scale (CFS) at baseline and at 3 and 12 months, categorized as robust (CFS 1-3), prefrail (CFS 4) and frail (CFS ≥ 5). Multiple regression models were used to examine associations between frailty trajectories and mortality, with baseline frailty, clinical characteristics and potentially modifiable aspects of ICU treatment. Results:346 patients were included. Mean age was 74 years (± 6), and 98 % lived at home before admission. The median ICU length of stay was 8 (IQR 9) days. Total mortality was 52 %, with most deaths occurring before hospital discharge. In the survivors, the prevalence of frailty increased from 23 % (79/346) at baseline, to 47 % (81/174) at three months. Between the three- and 12- month follow-up, CFS scores remained unchanged in 71 % (108/153), improved in 19 % (29/153) and deteriorated in 10 % (15/153). By 12 months 86 % (132/153) had returned home, though 32 % (49/153) required home care compared to 10 % pre-admission. Baseline CFS showed the strongest association with 12-month mortality (Risk Ratio 1.46, p < 0.001). Age (Risk Ratio 1.22, p < 0.001) and SOFA score on the first day after intubation (Risk Ratio 1.14, p < 0.01) were also significant predictors, whereas comorbidity was not. Conclusions:In elderly ICU-patients long-term frailty is deranged, and baseline CFS is closely associated with mortality. However, a small group of patients had a transitory decline in frailty at three months follow-up and then improved. Intervention studies targeting modifiable factors associated with long-term functional decline and mortality are warranted. Trial registration:ClinicalTrials.gov (NCT06012942).
CAR T-cell therapy carries significant risks, including ICANS. There is limited data on ICANS presentation and outcomes in patients admitted to ICU and it is still challenging to predict those who will have severe ICANS. This is a pre-planned substudy of an international, multicenter, observational cohort study of 241 CAR T-cell recipients for hematological malignancies, admitted to the ICU, focusing on those who developed ICANS. We aimed for a detailed description of symptoms and hierarchical clustering analysis was used to identify distinct patterns of neurological symptom presentation. ICANS was identified in 100 patients (41.5%), median age of 61 years. Most patients (93%) had non-Hodgkin lymphoma. Severe ICANS occurred in 38% of patients, associated with longer duration of symptoms (p = 0.02). On the whole cohort, the median duration of neurological symptoms was 5 (IQR 1-8) days and was also longer for patients with isolated ICANS (median of 16 days (IQR 11-24, p = 0.001)). Hierarchical clustering revealed four distinct clusters with minimal symptom overlap: Cluster 1: Mild or no symptoms, primarily confusion (11.2%); Cluster 2: High incidence of confusion (78.9%) and drowsiness (47.4%), with significant risks of seizures (42.1%) and coma (21.1%); Cluster 3: Predominantly tremor (75%) and attention deficit (37.5%); Cluster 4: High incidence of aphasia (70.3%), dysgraphia (37.8%), and disorientation (27%). The clustering of neurological symptoms was statistically significant (p < 0.001). This study provides a detailed characterization of ICANS, highlighting distinct patterns of neurological symptoms. These findings could inform clinicians, particularly regarding the risk and timing of ICU admission.
Acute kidney injury (AKI) is a common and harmful syndrome associated with sepsis. It is difficult to predict and has an adverse impact on both short- and long-term prognosis. Two urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2), and insulin-like growth factor-binding protein 7 (IGFBP7) have been validated for predicting moderate and severe AKI and improving the recognition of organ failure in critically ill patients with sepsis. We aimed to evaluate the performance of these markers for predicting sepsis-related AKI and its evolution in a cohort of patients admitted to the Emergency Department with infectious disease and high risk of sepsis. This single-centre, prospective, observational study included adult patients presenting to the Emergency Department (ED) with suspected infection. Patients were included in the study if they had a National Early Warning Score 2 (NEWS 2) of 3 or higher. Three blood samples were drawn during the first 24 h, and we defined AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition. The first urine sample during ED stay was collected for urinary [TIMP-2]•[ IGFBP7] determination. Higher admission levels of urinary [TIMP-2]•[IGFBP7] were associated with the development of AKI moderate-severe within 24 h (adjusted Odds Ratio 1.24; 95% Confidence Interval 1.07-1.43; p < 0.01). The biomarker showed only modest overall discrimination (AUC 0.67). Still, predefined cut-offs revealed complementary diagnostic roles: low values (<0.3) may help exclude AKI with a negative predictive value of 0.86, whereas the highest values (>2.0) increase its likelihood. Creatinine trajectories and inflammatory profiles were largely similar across groups, except for elevations in IL-10 and IL-1RN in high-risk patients. In conclusion, urinary [TIMP-2]•[IGFBP7] measured on presentation to the ED had only moderate discrimination for sepsis-associated AKI. However, values (<0.3 units) could help to rule out the risk of developing AKI, while values >2.0 indicated high risk.
