Search Results (561)

Background/Objectives: Hemodynamic disturbances in sepsis and septic shock arise from the vasoactive effects of inflammatory mediators involved in the immune response. Relaxin-1 is a pleiotropic hormone associated with inflammation, angiogenesis, tissue repair, and vasodilation. This study aimed to investigate the changes in relaxin-1 levels in septic shock and to evaluate their association with mortality. Methods: This prospective observational study was conducted in a Level II intensive care unit. Demographic characteristics, vital signs, APACHE II and SOFA scores, comorbidities, and routine laboratory parameters were recorded at admission and at 48 h. Serum relaxin-1 levels were measured at both time points and analyzed in relation to survival status. Binary logistic regression was additionally performed to evaluate variables associated with mortality in a multivariable framework. Results: A total of 48 patients with sepsis and septic shock were included (54.2% female; mean age 73.4 ± 14.7 years). Overall mortality was 33.3%. Relaxin-1 levels significantly increased from baseline (11.25 ± 4.85 pg/mL) to 48 h (12.64 ± 4.81 pg/mL) (p = 0.047). Baseline relaxin-1 levels were significantly higher in non-survivors compared to survivors (14.62 ± 4.47 pg/mL vs. 11.65 ± 4.73 pg/mL, p = 0.043). Conclusions: Elevated Relaxin-1 levels were associated with mortality in patients with sepsis and septic shock. The observed increase in Relaxin-1 during early follow-up suggests a potential link with the underlying pathophysiological processes. Although Relaxin-1 was associated with mortality, its independent prognostic value could not be established in multivariable analysis due to the limited sample size. Larger, adequately powered multicenter studies are required to confirm these findings. Full article

Background/Objectives: Acute respiratory failure (ARF) encompasses heterogeneous etiologies, and early bedside prognostication remains challenging. Cytokines and chemokines may capture underlying biological severity and identify high-risk patients. We evaluated whether admission cytokine/chemokine profiles add incremental prognostic value over clinical risk factors in unselected ARF patients. Methods: This prospective, single-center cohort study enrolled adult patients admitted to medical ICUs with ARF requiring high-intensity respiratory support. Plasma samples were collected within 24 h of ARF diagnosis, and 19 cytokines/chemokines were measured using multiplex immunoassays. The primary outcome was ICU mortality. Univariate and multivariable logistic regression models assessed associations between biomarkers and mortality, with discrimination evaluated by the area under the receiver operating characteristic curve (AUC). Results: Among 41 patients, 15 (37%) died in the ICU. Non-survivors had higher rates of immunosuppression (80% vs. 38%, p = 0.010) and hematologic malignancy (67% vs. 31%, p = 0.026). CXCL10 (IP-10), IL-18, and CCL2 (MCP-1) were significantly higher in non-survivors, and IL-1Ra showed a marked numerical increase with a significant univariable association with ICU mortality, despite comparable severity scores and oxygenation indices at admission. A clinical core model (SOFA, immunosuppression, hematologic malignancy) achieved an AUC of 0.74 (95% CI 0.58–0.90); adding cytokines improved discrimination modestly (AUC 0.76–0.80). In highest-quartile survival analyses, IL-1Ra (p = 0.002), CXCL10 (p = 0.005), and CCL2 (p = 0.009) demonstrated significant survival separation. Conclusions: At ICU admission, CXCL10 (IP-10), IL-18, CCL2 (MCP-1), and IL-1Ra showed exploratory associations with ICU mortality and were prioritized as candidate inflammatory biomarkers. These findings require validation in larger multicenter cohorts. Full article

Background/Objectives: Adipokines are candidate biomarkers in critical illness due to their roles in immunity and metabolism, both profoundly altered in sepsis. Omentin-1, vaspin, and chemerin have been studied in selected septic cohorts, but not concurrently in a heterogeneous ICU population including both septic and non-septic patients. Methods: Prospective observational cohort of 200 consecutive ICU patients with 28-day follow-up. Biomarkers were measured by ELISA within 24 h of admission. Analyses included Mann–Whitney U tests, Spearman correlations, ROC curves, and logistic regression with APACHE II and SOFA as comparators. Results: Vaspin was significantly higher in septic versus non-septic patients (406.4 [190.0–799.6] vs. 275.8 [101.8–559.8] pg/mL; p = 0.009). Omentin-1 was elevated in 28-day non-survivors (34.4 [22.5–56.1] vs. 25.1 [15.0–48.4] ng/mL; p = 0.037; AUROC 0.599), but lost significance after APACHE II adjustment (p = 0.295). Chemerin trended lower in non-survivors (p = 0.099); in septic patients, it correlated inversely with SOFA (r = −0.43) and lactate (r = −0.40), both p < 0.001. IL-6 and IL-10 were higher in non-survivors; IL-10 predicted 28-day mortality (AUROC 0.783), comparable to APACHE II (0.785). Conclusions: Vaspin distinguishes sepsis in mixed ICU populations. Omentin-1 shows a severity-driven association with mortality that does not survive APACHE II adjustment (AUROC 0.599, poor standalone discrimination), while chemerin inversely tracks hypoperfusion markers in septic patients, suggesting a potential counter-regulatory role requiring mechanistic confirmation. Individually, these adipokines do not add prognostic value beyond established severity scores, but their biological orthogonality to classical cytokines warrants exploration in multi-marker panel studies. Full article

Background/Objectives: Patients with prolonged or chronic critical illness (PCI/CCI) represent a subgroup characterized by extended stays in an intensive care unit (ICU), persistent organ dysfunction, and increased susceptibility to recurrent sepsis episodes. Current sepsis prognostic tools have not been specifically tailored for this high-risk population. This study aimed to develop and validate a prognostic nomogram for predicting mortality in septic ICU patients with PCI/CCI. Methods: Data were obtained from the Russian Intensive Care Dataset (RICD). Eligible patients had confirmed sepsis episodes according to Sepsis-3 criteria. The cohort was randomly split into training and testing sets in a 7:3 ratio. Multivariable Cox regression identified predictors of mortality, which were incorporated into a prognostic nomogram. Predictive accuracy was assessed using Harrell’s C-index, and horizon-specific area under the receiver operating characteristic curve (AUROC). Results: A total of 336 septic patients were analyzed, with an overall ICU mortality of 14.0%. Median ICU length of stay was 44 days, and median time to sepsis onset was 10 days. Recurrent sepsis episodes occurred in 28.6% of patients. In multivariable analysis, four predictors of mortality were identified: age, SOFA score at sepsis onset, type 2 diabetes mellitus, and time to sepsis onset. The nomogram demonstrated a C-index of 0.787 (95% confidence interval [CI] 0.669; 0.890) in the training set and one of 0.715 (95% CI 0.584; 0.836) in the testing set. In the testing set, the horizon-specific AUROCs were 0.898, 0.741, and 0.703 for 14-, 28-, and 42-day survival prediction, respectively. Conclusions: The prognostic nomogram, specifically tailored for PCI/CCI septic patients, demonstrated a testing-set C-index of 0.715, with higher 14-day predictive performance, whereas predictive accuracy decreased at later time points. Prospective multicenter validation is necessary before clinical implementation. Full article

Background: Vasoplegic shock (VS) in critically ill patients without microbiological evidence of infection poses a major clinical challenge in intensive care units (ICUs). Extracorporeal cytokine hemadsorption using the oXiris^® membrane—a high-permeability polyacrylonitrile-based (AN69-ST) filter with adsorptive properties against inflammatory mediators—has emerged as a potential adjunct to restore haemodynamic stability. Evidence supporting its use remains limited, particularly regarding timing of initiation and downstream mortality biomarkers. Methods: We conducted a single-centre prospective observational study at the ICU of Istanbul Prof. Dr. Cemil Taşcıoğlu City Hospital between October 2022 and January 2023. Adults aged ≥18 years with VS (CRP ≥ 100 mg/L, procalcitonin [PCT] < 2 μg/L, no positive microbiological culture) requiring continuous renal replacement therapy (CRRT) with the oXiris^® membrane were enrolled (n = 34), of whom 30 completed the study period without microbiological exclusion and comprised the final analysis cohort. Pre- and post-treatment (72 h) clinical and cytokine parameters were compared. The association of VS resolution and 7-day mortality with timing of oXiris^® initiation, cytokine levels, and treatment duration was assessed. This study was conducted and reported in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement. Results: Significant changes were observed across all principal haemodynamic and inflammatory parameters at 72 h of oXiris^® treatment, including mean arterial pressure (MAP: 50.8 ± 6.3 to 69.3 ± 17 mmHg, p < 0.001), SOFA score (8.33 ± 2.29 to 4.9 ± 3.22, p < 0.001), IL-6 (767.3 ± 1205.7 to 294.4 ± 686.3 pg/mL, p < 0.001), IL-1β, TNF-α, CRP, lactate, and creatinine. VS resolved in 24/30 patients (80%). Younger age was associated with VS resolution (57.8 ± 19.7 vs. 76.6 ± 13.9 years; p = 0.021). Initiation of oXiris^® within 8 h was associated with significantly shorter VS resolution time (52.5 ± 23.9 vs. 85.9 ± 48.2 h; p = 0.045). Seven-day mortality was 20% (n = 6) and hospital mortality was 50% (n = 15). Post-treatment IL-1β (856.7 ± 548.5 vs. 1086.9 ± 353.6 pg/mL; p = 0.044) and TNF-α (111.0 ± 70.0 vs. 145.4 ± 47.8 pg/mL; p = 0.011) at 72 h were significantly higher in hospital non-survivors, representing exploratory prognostic associations. Conclusions: Changes in haemodynamic and inflammatory parameters were observed during oXiris^®-based CRRT treatment in critically ill patients with non-septic VS. Early initiation (≤8 h) was associated with shorter VS resolution time in this exploratory, uncontrolled analysis. Residual IL-1β and TNF-α at 72 h were associated with hospital mortality in exploratory analyses and may represent hypothesis-generating prognostic signals requiring prospective validation. Randomised controlled trials are warranted to confirm these findings and define optimal timing strategies. Full article

Background: This study investigated whether lactate dehydrogenase (LDH) levels measured at ICU admission predict early in-hospital mortality among critically ill medical patients in a single-center retrospective cohort study conducted in Turkey. Specifically, we aimed to (i) determine an optimal LDH threshold; (ii) examine the temporal trajectory of discriminatory performance over 72 h; and (iii) assess LDH as an independent predictor beyond established severity scores. Methods: In this single-center retrospective cohort study, 681 adults admitted to a medical ICU between January 2015 and January 2025 were analyzed. Serial LDH measurements were obtained at 0, 24, 48, and 72 h after ICU admission. This study was approved by the Institutional Ethics Committee (Decision No.: 2025/99). ROC analysis was performed under a predefined sensitivity constraint (≥0.70), and time-to-event outcomes were examined using Kaplan–Meier methods and Cox proportional hazards regression. Determinants of maximum LDH were assessed using a GLM with Gamma distribution and log link. Results: The 28-day mortality rate was 39.1%. ROC analysis identified an optimal 24-h LDH cut-off of approximately 275 U/L (AUC = 0.650; sensitivity = 0.70). Discriminatory performance improved progressively over time (AUC of 0.632 at baseline to 0.690 at 72 h), suggesting that serial measurements may capture evolving prognostic information more effectively than single-time-point measurements. Kaplan–Meier analyses demonstrated a stepwise decline in survival with increasing LDH across all categorization approaches (all log-rank p < 0.001). In multivariable Cox models, log-transformed maximum LDH within the first 72 h was the strongest independent predictor of mortality (HR = 2.2–2.6; p < 0.001), demonstrating larger effect sizes than APACHE II, SOFA, and age in fully adjusted models. GLM analysis indicated that male sex was associated with approximately 33% lower expected maximum LDH. Conclusions: Admission LDH is an independently predictive and readily obtainable prognostic biomarker for early in-hospital mortality in critically ill medical patients. LDH may complement established ICU risk assessment tools, and its integration into clinical workflows as a triage adjunct warrants further evaluation in prospective multicenter studies. Full article

Background/Objectives: Acute-on-chronic liver failure (ACLF) is characterized by multiple organ failure and short-term mortality, and hepatic encephalopathy (HE) is its frequent complication. We investigated whether the severity of HE upon admission in patients with alcohol-related ACLF at the intensive care unit (ICU) was associated with short-term mortality. Methods: In total, 100 patients with alcohol-related ACLF and HE admitted in ICU were enrolled in the study. Laboratory biomarkers, total hospital length of stay (LOS), ICU length of stay, acute kidney injury (AKI), Acute Physiology and Chronic Health Evaluation II score, CLIF-C organ failure and Sequential Organ Failure Assessment score were tested in relation to the mortality risk. HE was assessed and divided into groups using the West Haven criteria. Results: Total hospital LOS, 7-day and 28-day mortality were significantly higher in the higher-grade HE group (p = 0.035, p = 0.031, p = 0.002, respectively). CLIF-C OF, SOFA, and APACHE II scores were significantly higher in the higher-grade HE group (p < 0.001). Kaplan–Meier survival analysis demonstrated reduced survival in patients with higher-grade HE (log-rank p < 0.001). In Cox regression analyses, AKI was associated with short-term mortality in both HE groups. Total hospital LOS and ICU length of stay were also associated with mortality, but were interpreted as post-baseline markers of clinical trajectory rather than baseline prognostic predictors. Conclusions: In patients with alcohol-related ACLF and HE, higher-grade HE was associated with poorer short-term survival. AKI and higher CLIF-C OF, SOFA and APACHE II scores were associated with poor outcomes, supporting their clinical relevance for mortality risk stratification in this population. LOS-related findings should be interpreted as markers of clinical trajectory rather than baseline prognostic predictors. Full article

Background: Short-term mortality stratification in sepsis remains clinically challenging, particularly because outcome is influenced by acute inflammation, coagulation abnormalities, organ dysfunction, and baseline comorbidity burden. This study evaluated the clinical performance of the BIO-S and BIO-SC composite bioscores for 28-day mortality stratification in adults with sepsis and septic shock. Methods: We conducted a prospective observational monocentric cohort study including 572 adult patients admitted between January 2022 and December 2024. BIO-S integrated procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), International Normalized Ratio (INR), and Sequential Organ Failure Assessment (SOFA) score, while BIO-SC extended this model by adding the Charlson Comorbidity Index (CCI). Prognostic performance was assessed using receiver operating characteristic (ROC) curve analysis, DeLong comparisons, bootstrap validation, calibration analysis, Kaplan–Meier survival curves, and Cox proportional hazards models. Results: The cohort included 418 patients with sepsis and 154 patients with septic shock. Overall 28-day mortality was 31.5% and was significantly higher in septic shock than in sepsis, 77.9% versus 14.4%, p < 0.001. BIO-S and BIO-SC showed strong discriminatory ability for 28-day mortality, with areas under the curve (AUCs) of 0.889 and 0.897, respectively. BIO-SC had the highest AUC, although the difference between BIO-SC and BIO-S was not statistically significant by the DeLong test, p = 0.328. At the optimal thresholds, BIO-S showed 97.8% sensitivity and 69.4% specificity, while BIO-SC showed 89.4% sensitivity and 77.8% specificity. Both bioscores stratified observed mortality across predefined risk categories and remained significantly associated with 28-day mortality in adjusted Cox models. Conclusions: BIO-S and BIO-SC showed clinically relevant performance for 28-day mortality stratification in adults with sepsis and septic shock. BIO-SC provided a numerically higher AUC and slightly better calibration, suggesting that comorbidity burden may improve prognostic characterization, although further independent multicenter validation is needed before broader clinical implementation. Full article

Background/Objectives: Urinary tract infections (UTIs) in older adults are common and potentially life-threatening conditions that often present with atypical symptoms. Early identification of prognostic factors is essential to improve clinical outcomes and reduce mortality in this vulnerable population. Methods: This retrospective, multicenter study included patients aged ≥65 years who were hospitalized with a diagnosis of UTI between January 2019 and December 2023. Diagnoses were established by infectious disease specialists based on clinical findings and microbiological confirmation in accordance with international guidelines. Only patients with urine cultures showing ≥100,000 CFU/mL bacterial growth were included. Demographic, clinical, laboratory, and microbiological data were analyzed. Multivariable logistic regression was used to identify independent predictors of in-hospital mortality. Results: A total of 1175 patients (median age: 75 years; 51.1% male) were included. The in-hospital mortality rate was 14.6%, and 25.6% required intensive care unit (ICU) admission. Multidrug-resistant (MDR) bacteria were detected in 63.6% of isolates, and bacteremia was present in 24.3% of cases. In multivariable analysis, MDR/ESBL positivity (OR: 2.09, 95% CI: 1.24–3.50, p = 0.005), bacteremia (OR: 2.10, 95% CI: 1.32–3.35, p = 0.002), and SOFA score (OR: 1.53, 95% CI: 1.42–1.65, p < 0.001) were independently associated with in-hospital mortality. Age and altered mental status were also significant predictors, while CRP and procalcitonin lost significance after adjustment. Conclusions: UTIs in elderly patients are associated with substantial morbidity and mortality. Multidrug-resistant pathogens, bacteremia, and disease severity play a central role in determining outcomes. Early identification of high-risk patients using clinical severity scores and microbiological data may improve risk stratification and guide timely, targeted therapeutic interventions. Full article

Background: Sepsis, a life-threatening organ dysfunction caused by dysregulated host responses to infection, frequently involves impaired macrophage efferocytosis that leads to apoptotic cell accumulation, secondary necrosis, and persistent inflammation. Early prognostic stratification remains challenging, as current biomarkers lack sufficient specificity and sensitivity, underscoring the urgent need for novel prognosis-related indicators. Methods: We integrated bulk transcriptomic data from a discovery cohort (GSE205672) and an independent validation cohort (GSE133822) with single-cell RNA-seq profiles of early- and late-stage sepsis (GSE167363, GSE175453). WGCNA and five consensus machine-learning algorithms were combined to screen core efferocytosis-associated genes, and expression was validated via qPCR in PBMCs from sepsis patients and CLP-induced septic mice. Results: ADAP2 was identified as the core gene achieving strict consensus across all five algorithms, with early upregulation and late depletion in sepsis, predominant expression in monocytes/macrophages—particularly M1-like and IFN-responsive subsets—and a significant correlation with efferocytosis scores and immune cell infiltration. Its expression was negatively correlated with sepsis severity (SOFA score) and showed a trend toward worse survival in patients with low ADAP2 levels. Conclusions: This multi-dimensional transcriptomic study establishes ADAP2 as a candidate biomarker with potential prognostic value in sepsis, closely linked to macrophage efferocytosis. These findings may aid early risk stratification and inform macrophage-directed immunotherapies, although prospective validation and functional studies are required. Full article

Endogenous candidiasis remains an underrecognized yet clinically relevant complication in non-neutropenic critically ill patients. This study examines Candida spp. infections in the intensive care unit (ICU) within a patient-safety and risk-management framework, focusing on the identification of patients at highest risk and the development of an early diagnostic and therapeutic strategy. The target population comprises long-stay ICU patients requiring prolonged mechanical ventilation who develop multiple organ dysfunction syndrome (MODS) associated with immunoparalysis, typically reflected by a Sequential Organ Failure Assessment (SOFA) score ≥ 5. In this population, Candida spp. colonization may evolve into multifocal candidiasis and subsequently invasive or disseminated disease. Notably, candidemia often represents a late manifestation and therefore lacks sensitivity as an early diagnostic marker. Drawing on a series of clinical investigations conducted from 1978 to the early 2000s, the authors developed a standardized diagnostic–therapeutic algorithm based on systematic surveillance cultures, identification of multifocal Candida spp. colonization, and early initiation of antifungal therapy. Implementation of this strategy, together with progressive individualization of antifungal treatment, was associated with a marked reduction in attributable mortality related to candidiasis in ICU patients. These findings support the concept of Candida spp. infection as a sentinel indicator of systemic immune dysfunction and physiological fragility in critical illness. Integrating risk-based surveillance with early targeted therapy may substantially improve outcomes and reinforce patient-safety strategies in the ICU. Full article

Background: Sepsis and septic shock are associated with high mortality in intensive care units (ICUs), with a substantial risk persisting after ICU discharge. However, it remains unclear whether inflammatory biomarkers retain their prognostic value at the time of ICU discharge. This study aimed to evaluate whether discharge inflammatory biomarkers—including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-mean platelet volume ratio (PLT/MPV), and C-reactive protein-to-albumin ratio (CAR)—remain predictive of short- and long-term mortality in patients with sepsis and septic shock. Methods: In this single-center, retrospective cohort study, adult patients with sepsis or septic shock discharged from a tertiary ICU specializing in chest diseases between January 2013 and January 2015 were included. Sepsis and septic shock were retrospectively re-classified according to Sepsis-3 criteria. Inflammatory biomarkers measured at ICU admission and discharge, along with clinical variables and disease severity scores (APACHE II and SOFA), were recorded. Patients were followed for 28-day, 6-month, and 2-year mortality. The prognostic performance of biomarkers was assessed using receiver operating characteristic (ROC) analysis, and optimal cut-off values were determined. Independent predictors of mortality were evaluated using Cox proportional hazards regression analysis. Results: A total of 461 patients were included. In total, 291 (63.1%) had sepsis without shock and 170 (36.9%) had septic shock. The overall male proportion was 62%, with a median age of 65 (IQR 54–74) years in the sepsis group and 70 (63–79) years in the septic shock group. Mortality rates were significantly higher in patients with septic shock compared to those with sepsis at 28 days (24% vs. 10%, p < 0.001), 6 months (44% vs. 27%, p < 0.001), and 2 years (71% vs. 57%, p = 0.003). In unadjusted survivor/non-survivor comparisons, elevated discharge NLR and CAR were associated with early post-ICU mortality. However, in multivariable Cox regression, discharge NLR, but not discharge CAR, remained independently associated with 28-day and 6-month mortality. On ROC analysis, discharge NLR showed moderate discriminative performance for 28-day mortality (AUC 0.67, 95% CI 0.60–0.74), as did discharge CAR (AUC 0.68, 95% CI 0.60–0.76), although CAR did not retain independent prognostic significance after adjustment. An NLR value ≥ 5 was identified as an independent predictor of 28-day mortality (HR 2.44; 95% CI 1.24–4.80; p = 0.010) and was also significantly associated with 6-month mortality (HR 2.02; 95% CI 1.18–3.45; p = 0.011), although its predictive value decreased over longer follow-up periods (HR 1.37; 95% CI 0.93–2.01; p = 0.11 at 2 years). Conclusions: Inflammatory biomarkers measured at ICU discharge, particularly NLR, remain predictive of short-term mortality in patients with sepsis and septic shock, but their prognostic value diminishes over time. Assessment of inflammatory status at ICU discharge may provide a practical tool for early post-ICU risk stratification and may support clinical decisions regarding intensified outpatient surveillance and follow-up scheduling in this vulnerable population. Full article

Background: Chronic critical illness (CCI) following acute brain injury involves persistent immune dysfunction, yet its genetic determinants remain unclear. We investigated whether the rate of T-cell receptor excision circle (TREC) depletion—a proposed marker of adaptive homeostatic resilience—is associated with the burden of rare damaging genetic variants. Methods: Whole-exome sequencing (WES) was performed on a cohort of 84 patients (64 with traumatic brain injury, 20 with stroke). In a longitudinal sub-cohort (n = 27), patients were stratified into quartiles (Q1–Q4) based on the slope of their TREC trajectories. “Qualifying variants” (QVs) were defined using strict rarity (gnomAD allele frequency ≤ 0.001) and pathogenicity criteria. Gene-level burden (collapsing) analysis and permutation-based statistical testing (10,000 iterations) were employed to evaluate genetic enrichment in the extreme quartiles. Results: While baseline TREC levels were strictly age dependent (p < 0.0001), the rate of change (TREC slope) was age independent. Rapid TREC decline (Q1) correlated with significantly higher final SOFA scores (p = 0.001) and neutrophil-to-lymphocyte ratios (p = 0.020). Rare variant burden analysis revealed that Q1 patients were significantly more likely to harbor QVs in immune-related genes compared to the Q4 recovery group (odds ratio = 8.25; permutation p = 0.016). Patients with rapid decline were enriched for QVs in putative core “housekeeping” pathways essential for T-cell maintenance and DNA repair (e.g., ERCC3, FANCM), whereas variants in recovering patients were restricted to peripheral effector or structural pathways. Conclusions: Our findings suggest, as a conceptual framework, that an individual’s ability to maintain T-cell homeostasis during critical illness is influenced by their underlying genetic buffering capacity. We propose a hypothetical “two-hit” framework where physiological stress unmasks pre-existing fragilities in core homeostatic pathways—potentially reflecting a state of functional haploinsufficiency under extreme proliferative demand—leading to accelerated immune exhaustion. These results position the TREC slope as a dynamic, age-independent biomarker of genomic resilience in the ICU. All findings are exploratory and hypothesis generating. Full article

Background: Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, remains a leading cause of death worldwide. Its diagnostic criteria have evolved from Sepsis-1 (SIRS) to Sepsis-3 (SOFA). The recent introduction of the SOFA-2 score, an update to the original SOFA, warrants validation in specific patient populations and against other established scoring systems. This study aims to compare the performance of SIRS, NEWS2, SOFA, and the newly proposed SOFA-2 in the classification agreement and prognostic performance for sepsis in a cohort of patients with suspected infection. Methods: This retrospective study enrolled adults with suspected infection admitted to a tertiary emergency center (January 2024–February 2025). SIRS, NEWS2, SOFA, and SOFA-2 scores were calculated from admission data. Patients were stratified using established thresholds (SIRS ≥ 2, NEWS2 ≥ 5, SOFA ≥ 2, SOFA-2 ≥ 2). Concordance with Sepsis-3 (SOFA ≥ 2) and prognostic accuracy for 28-day mortality were evaluated using AUROC analysis. Score distributions and organ dysfunction patterns were compared. Results: Of 562 screened patients, 516 were included. For sepsis classification agreement, SOFA-2 showed excellent agreement with SOFA (kappa = 0.923) and higher specificity than SIRS and SOFA. For 28-day mortality prediction, SOFA-2 showed the numerically highest AUC (0.863, 95% CI: 0.830–0.892), demonstrating slightly better discrimination than SOFA (AUC:0.854, 95% CI: 0.820–0.883). Pairwise DeLong tests indicated no significant differences between SOFA-2 and SOFA (p = 0.160). At optimal cutoffs, SOFA-2 demonstrated higher specificity (89.08% vs. SOFA 78.59% vs. NEWS2 76.87% vs. SIRS 41.33%), while SOFA showed higher sensitivity (81.63% vs. SOFA-2 73.47%). Increasing SOFA-2 scores strongly correlated with higher in-hospital mortality and longer ICU stay (both p < 0.001). SOFA-2 reclassified respiratory and cardiovascular dysfunction with higher thresholds and greater granularity than SOFA. Conclusions: Based on our dataset, SOFA-2 demonstrates high diagnostic alignment with Sepsis-3 classification and higher specificity for mortality prediction, with slightly better discrimination compared to SOFA, NEWS2, and SIRS. While its slightly lower sensitivity may limit early risk stratification in some patients, its strong prognostic performance supports its utility for risk stratification. Multicenter studies are warranted to determine its role in future sepsis definitions. Full article

Background: Stroke is the most common neurological disorder in adults and a leading cause of mortality and disability. Intracerebral hemorrhage (ICH), although less frequent than ischemic stroke, is associated with higher morbidity and mortality and often requires ICU admission. Predicting mortality remains challenging due to disease heterogeneity. Objectives: This study evaluated the prognostic value of the modified Nutrition Risk in Critically Ill (mNUTRIC) and Controlling Nutritional Status (CONUT) scores, along with conventional severity scores (GCS, APACHE II, SOFA), in ICU patients with ICH. Methods: This retrospective cohort study included 347 ICU patients with ICH admitted between January 2019 and June 2025. Patients were stratified by survival status and nutritional and conventional severity scores were analyzed. Subgroup analysis was performed in patients with GCS ≤ 12 and APACHE II ≥ 17 (n = 96). Multivariate logistic regression and receiver operating characteristic (ROC) analyses assessed predictive performance. Results: ICU mortality was 24.2%. Deceased patients had lower GCS and higher APACHE II, SOFA, mNUTRIC, and CONUT scores (p < 0.001). Subgroup analysis showed higher mortality in patients with elevated mNUTRIC and CONUT scores (p = 0.038 and p = 0.005). Multivariate analysis identified GCS (OR = 0.675, p < 0.001) and CONUT (OR = 1.174, p = 0.040) as independent predictors; mNUTRIC was not significant. ROC analysis demonstrated good discrimination (AUC 0.818 for mNUTRIC and 0.81 for CONUT), with mNUTRIC being more specific and CONUT more sensitive. Optimal cut-off values were >3 for mNUTRIC and >4 for CONUT. Conclusions: Both mNUTRIC and CONUT scores are associated with mortality in ICU patients with ICH, with CONUT showing independent prognostic value. Their combined use may aid clinical decision-making. Full article