Search Results (239)

Background: Secondary hepatic dysfunction is a frequent yet often under-recognized complication in critically ill children. It commonly arises as a consequence of systemic processes—particularly sepsis, hypoperfusion, hypoxia, and multiorgan dysfunction—rather than primary hepatobiliary disease. This study aimed to determine the incidence, clinical characteristics, and prognostic significance of secondary hepatic dysfunction in a pediatric intensive care unit (PICU) cohort, and to evaluate its relationship with PRISM III and PELOD-2 scores. Methods: This retrospective study included patients hospitalized in a tertiary PICU between January 2022 and December 2024. Children with pre-existing liver disease or primary acute liver failure were excluded. Hepatic dysfunction was defined by elevations in age-adjusted biochemical markers. Demographic variables, clinical interventions, laboratory values, and outcomes were recorded. Mortality risk and prolonged PICU stay (>7 days) were analyzed in relation to hepatic dysfunction, PRISM III, and PELOD-2 scores. Results: Among 567 PICU admissions, 50 patients (8.8%) met criteria for secondary hepatic dysfunction. The cohort had a median age of 57.5 months and 66% were male. Hepatocellular injury predominated (96%), while cholestatic patterns were less common (4%). Overall mortality was 22%. Mortality was significantly associated with sepsis (p = 0.04), mechanical ventilation (p < 0.01), and inotropic support (p < 0.01). Both PRISM III and PELOD-2 scores were higher in non-survivors on day 1 and day 7 (p ≤ 0.01). ALT ≥ 2 × ULN and total bilirubin > 2 mg/dL were not independently predictive of mortality. Conclusions: Secondary hepatic dysfunction is relatively common in critically ill children and is associated with adverse clinical outcomes. Its prognostic relevance appears to extend beyond conventional severity scores, particularly with respect to morbidity-related outcomes such as prolonged PICU stay, suggesting that routine hepatic assessment may contribute to early risk stratification in the PICU setting. Full article

Background/Objectives: There are multiple decision nodes, during and after subtotal colectomy for ulcerative colitis (UC), regarding the management of the rectal stump. Intra-operatively, the surgeon must decide on the closure technique and positioning of the retained stump, while post-operatively, clinicians often face the challenge of managing diversion proctitis, as well as determining an appropriate endoscopic surveillance strategy, given the increased risk of cancer. This narrative review aims to summarise the evidence relating to these key decision points in rectal stump management. Methods: A narrative review of the literature was performed. Relevant studies were identified through a search of Ovid Medline and Embase. Inclusion criteria were adult population and diagnosis of UC. Cohort studies, review articles, and guidelines were eligible for inclusion. The references were grouped according to the subject of interest and reported accordingly. Results: Intra-peritoneal closure has been shown to have higher pelvic sepsis rates (5–25%), whereas subcutaneous placement results in higher rates of wound infections (up to 15%). A mucous fistula has been shown to have the lowest overall complication rate. Microscopic findings compatible with diversion proctitis develop in most patients, with incidence ranging from 71.4% to 100%. However, only a minority of these patients (30–40%) develop symptoms. Suggested treatments for diversion proctitis include topical mesalamine, corticosteroids, or short-chain fatty acids. The overall risk of rectal stump neoplasia in patients with UC after subtotal colectomy is as low as 0.7%, with prior colorectal neoplasia being a major risk factor. No universal standardised guidance exists regarding endoscopic surveillance in this patient population. Conclusions: This narrative review has appraised the latest evidence on three crucial stages of rectal stump management in UC. There is still uncertainty about the optimal surgical management of the stump, with different complication profiles. Medical management of diversion proctitis remains a major unmet need, and there are no randomised trials addressing this issue. There are no universally accepted guidelines on endoscopic surveillance of the rectal stump. Full article

Introduction: Patients with extremely elevated IL-6 levels remain poorly characterized, and no specific plasma concentration has been established to reliably predict mortality or guide immunomodulatory interventions. We hypothesized that extreme hypercytokinemia is associated with increased mortality in sepsis. The primary objective was to identify, in patients with hyperinflammatory endotype, an IL-6 threshold associated with a significantly elevated risk of death. Methods: We conducted a retrospective, single-center observational study based on a historical cohort of adult patients with consecutive activation of the in-hospital sepsis code, a prospective and standardized institutional care pathway, at Vall d’Hebron University Hospital between July 2018 and December 2024. Patients fulfilling Sepsis-2 diagnostic criteria and criteria for severe sepsis or septic shock were eligible. Plasma interleukin-6 (IL-6) levels were routinely determined in all patients. The analysis included patients with complete clinical and laboratory data available in the study database. To identify the IL-6 threshold associated with critical risk of death, a cumulative conditional relative frequency analysis was performed. A quantile-based analysis was conducted using predefined intervals of 1000 pg/mL and 15,000 pg/mL. A multivariable logistic regression analysis was conducted to identify clinical and laboratory parameters independently associated with IL-6 > 15,000 pg/mL and outcome. Results are presented as odds ratios (ORs). Survival differences were assessed using Kaplan–Meier analysis. Results: Overall mortality was 31% in the 1669 patients analyzed. Median IL-6 concentration was 772 pg/mL (IQR: 164–8750 pg/mL) with significantly higher levels in non-survivors (2137 pg/mL, IQR: 267–34,758). A critical IL-6 cutoff of 14,930 pg/mL was identified, which was rounded to 15,000 pg/mL for clinical applicability. IL-6 > 15,000 pg/mL was associated with increased mortality (OR 2.22, 95% CI: 1.12–5.36). Kaplan–Meier analysis revealed significantly reduced survival in patients above this IL-6 threshold (p < 0.0001). Conclusions: In this cohort of patients with severe sepsis or septic shock, plasma IL-6 levels > 15,000 pg/mL defined a critical threshold beyond which mortality risk exceeded survival probability. Critical hypercytokinemia may serve as a clinically relevant biomarker to identify patients with sepsis and multiorgan dysfunction who could benefit from precision immunomodulatory therapies. Full article

Background: Sepsis is a life-threatening condition characterized by a dysregulated host response to infection. Hemadsorption therapies remove inflammatory mediators and are used as adjunctive treatment in selected patients. Although increased immature granulocyte (IG) levels correlate with inflammatory severity, changes in IG levels after hemadsorption therapy have not been previously evaluated. Methods: This retrospective observational study included patients with sepsis who received hemadsorption therapy in intensive care units between January 2021 and July 2025. Sepsis was diagnosed according to the Surviving Sepsis Campaign 2021 guidelines, and hemadsorption was initiated for persistent hemodynamic instability despite standard therapy. Treatment was performed using a Jafron HA330 cartridge for at least three 6 h sessions. IG count and percentage, inflammatory parameters, lactate levels, and organ dysfunction scores were recorded before and after therapy. ICU mortality was the primary outcome. Statistical analyses included paired comparisons, multivariable logistic regression, and ROC curve analysis. Results: Among 887 patients with sepsis, 196 met the inclusion criteria. The ICU mortality rate was 43.9%, and the median time between pre- and post-treatment measurements was 4 days (IQR: 3–5). After hemadsorption therapy, IG count, IG%, inflammatory parameters, lactate levels, SOFA scores, and vasopressor requirements decreased (all p-values < 0.001). IG parameters were higher in non-survivors. Post-treatment IG# (AUC 0.880) and IG% (AUC 0.812) showed good discriminative performance. Conclusions: Hemadsorption therapy was associated with reductions in IG parameters and inflammatory indicators in sepsis. These findings support IG parameters as complementary measures of immune and inflammatory dynamics during hemadsorption therapy. Accordingly, this study should be regarded as a hypothesis-generating investigation describing associations of IG dynamics in septic patients undergoing hemadsorption, rather than demonstrating treatment efficacy or causal effects. Full article

Background and Objectives: Early recognition of life-threatening organ dysfunction is central to modern sepsis frameworks. We systematically reviewed the prognostic performance and clinical utility of the Neonatal Sequential Organ Failure Assessment (nSOFA) for mortality and major morbidity in NICU populations. The search identified 939 records across databases; after screening and full-text assessment, 16 studies met the inclusion criteria. Methods: Following PRISMA guidance, we searched major databases (2019–2025) for observational or interventional studies reporting discrimination or risk stratification using nSOFA in neonates. Populations included suspected/proven infection and condition-specific cohorts. Heterogeneity in timing, thresholds, and outcomes precluded meta-analysis. Results: A cumulative sample exceeding 25,000 neonates was identified across late- and early-onset infection, all-NICU admissions, necrotizing enterocolitis, respiratory distress, and very preterm screening cohorts. Across settings and timepoints, nSOFA demonstrated consistent, good-to-excellent mortality discrimination, with reported AUROCs ≥ 0.80 and upper ranges near 0.90–0.92; serial scoring within the first 6–12 h generally improved risk classification. Disease-specific applications (NEC, early-onset infection) showed similar discrimination for death or composite adverse outcomes. Conclusions: Evidence from diverse NICU contexts indicates that nSOFA is a pragmatic, EHR-ready organ dysfunction score with robust discrimination for mortality and serious morbidity, supporting routine, serial use for risk stratification and standardized endpoints in neonatal sepsis pathways, aligned with contemporary organ dysfunction–based pediatric criteria. Full article

Background and Objectives: Acute and obstructive pyelonephritis (AOP) management, despite advancements in diagnostic imaging and antimicrobial therapy, is characterized by delayed recognition and increasing antimicrobial resistance. This review aimed to summarize current evidence regarding the clinical characteristics, microbiological spectrum, biomarkers, and imaging findings associated with AOP. Materials and Methods: A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251162736). Literature searches were performed across the PubMed, Scopus, and Web of Science databases for articles published between January 2014 and 31 March 2025 using the term “acute obstructive pyelonephritis”. Inclusion criteria comprised original full-text English-language studies, published in the last 10 years and conducted in adults, reporting clinical, laboratory, microbiological, and imaging characteristics. Exclusion criteria are letters to the editor, expert opinions, case reports, conference or meeting abstracts, reviews, and redundant publications; having unclear or incomplete data; and being performed on cell cultures or on mammals. The quality of included studies was assessed using the Newcastle–Ottawa Scale. Results: Twenty-three studies met the inclusion criteria. AOP predominantly affected elderly patients with comorbidities, especially diabetes mellitus and urinary tract obstruction. Predictors of septic shock included thrombocytopenia, hypoalbuminemia, elevated procalcitonin (>1.12 µg/L), presepsin, and a neutrophil-to-lymphocyte ratio ≥ 8.7. Escherichia coli remained the leading pathogen (60–95%) with extended-spectrum β-lactamase (ESBL) rates between 20 and 70%, followed by Klebsiella pneumoniae. CT demonstrated 71–100% sensitivity for detecting obstructive complications, confirming its superiority over ultrasound, while MRI provided comparable diagnostic accuracy in selected cases. Source control through double-J stenting or percutaneous drainage significantly improved survival. Conclusions: AOP requires prompt recognition and early decompression to prevent sepsis-related mortality. Biomarkers such as procalcitonin, presepsin, and neutrophil to lymphocyte ratio enhance risk stratification, while CT remains the gold-standard imaging modality. The increasing prevalence of ESBL-producing pathogens underscores the need for antimicrobial stewardship and individualized therapeutic strategies guided by local resistance data. Full article

Background/Objectives: Sepsis detection remains challenging due to clinical heterogeneity and limitations of traditional scoring systems. This study developed and validated a hospital-wide machine learning model for sepsis detection using retrospectively developed data from prospectively expert-validated cases, aiming to improve diagnostic accuracy beyond conventional approaches. Methods: This retrospective cohort study analysed 218,715 hospital episodes (2014–2018) at a tertiary care centre. Sepsis cases (n = 11,864, 5.42%) were prospectively validated in real-time by a Multidisciplinary Sepsis Unit using modified Sepsis-2 criteria with organ dysfunction. The model integrated structured data (26.95%) and unstructured clinical notes (73.04%) extracted via natural language processing from 2829 variables, selecting 230 relevant predictors. Thirty models including random forests, support vector machines, neural networks, and gradient boosting were developed and evaluated. The dataset was randomly split (5/7 training, 2/7 testing) with preserved patient-level independence. Results: The BiAlert Sepsis model (random forest + Sepsis-2 ensemble) achieved an AUC-ROC of 0.95, sensitivity of 0.93, and specificity of 0.84, significantly outperforming traditional approaches. Compared to the best rule-based method (Sepsis-2 + qSOFA, AUC-ROC 0.90), BiAlert reduced false positives by 39.6% (13.10% vs. 21.70%, p < 0.01). Novel predictors included eosinopenia and hypoalbuminemia, while traditional variables (MAP, GCS, platelets) showed minimal univariate association. The model received European Medicines Agency approval as a medical device in June 2024. Conclusions: This hospital-wide machine learning model, trained on prospectively expert-validated cases and integrating extensive NLP-derived features, demonstrates superior sepsis detection performance compared to conventional scoring systems. External validation and prospective clinical impact studies are needed before widespread implementation. Full article

Bleeding and thromboembolism are among the leading causes of mortality worldwide. Thrombosis encompasses both arterial forms—primarily associated with atherosclerosis and leading to heart attacks or strokes—and venous forms. Microvascular thrombosis typically arises in the context of sepsis or systemic inflammation, and it became particularly prominent during the COVID-19 pandemic, substantially contributing to increased mortality. Given this burden, the rapid development of new therapies using advanced techniques and materials to prevent and treat these conditions is essential. This review summarizes recent advances in the design of antithrombotic polymers, discussing mechanisms of action, surface-modification strategies, and current clinical and preclinical applications. It also outlines criteria for evaluating hemocompatibility, describes in vitro and in vivo testing methods, and highlights key barriers to translating these materials into clinical practice. The review concludes by identifying promising directions for future research, including multifunctional approaches that combine antifouling properties, controlled drug release, and bioresistance strategies with the greatest potential to reduce thromboembolic complications associated with medical materials. It further evaluates the progress made to date in combating thrombotic diseases and identifies remaining gaps in the development and clinical implementation of new antithrombotic materials. Full article

Background/Objectives: Emergency Medical Services (EMSs) frequently provide the first medical contact for sepsis patients, but recognition is challenging. This study thus aimed to determine how often EMSs suspect sepsis and to evaluate the diagnostic accuracy of the quick Sequential Organ Failure Assessment (qSOFA), the Prehospital Early Sepsis Detection (PRESEP) score, and the Modified Early Warning Score (MEWS). Methods: A retrospective observational study of all EMS transports to one emergency department during a one-month period in 2023 was conducted. Prehospital vital signs, EMS working diagnoses, and final in-hospital diagnoses were abstracted. Scores were calculated post hoc. The primary outcome was the diagnostic accuracy of the EMSs’ working diagnosis of “suspected sepsis.” Secondary outcomes included the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of qSOFA, PRESEP, and MEWS. Results: Among 786 EMS encounters, 597 met the inclusion criteria. Twelve patients (2.0%) were ultimately diagnosed with sepsis. EMSs explicitly suspected sepsis in three of them (25.0%; sensitivity 16.7%, specificity 99.8%). Retrospective application of scores yielded markedly higher sensitivity: qSOFA 83.3%, PRESEP 91.7%, and MEWS 83.3%. Specificities were 74.2% for qSOFA, 41.2% for PRESEP, and 77.6% for MEWS. The AUCs were 0.838 for qSOFA, 0.695 for PRESEP, and 0.863 for MEWS, with MEWS significantly outperforming PRESEP (p = 0.0215). Conclusions: EMS personnel rarely labeled patients with sepsis, recognizing 3 of 12 cases (25%). Retrospective use of scoring systems based on routine vital signs substantially improved diagnostic accuracy, with MEWS performing best overall. Structured screening tools should be prospectively validated and potentially implemented in EMS. Full article

Background: Acute kidney injury (AKI) is a frequent and clinically relevant complication in cancer patients, with highly variable incidence. AKI increases morbidity and mortality, prolongs hospitalization, and may limit access to oncologic therapies. This study evaluated the incidence, risk factors, and outcomes of AKI in hospitalized cancer patients. Methods: We retrospectively analyzed patients admitted between 1 January 2016 and 31 December 2019. Individuals with cancer were identified and categorized into three groups: hematologic malignancies, solid cancers with metastases, and solid cancers without metastases. Demographic, clinical, and laboratory data were collected, and AKI was defined and staged according to KDIGO criteria, evaluating serum creatinine changes. Results: Among 56,390 hospitalized patients, 6723 (11.9%) had a cancer diagnosis. AKI incidence was significantly higher in cancer versus non-cancer patients (30.1% vs. 19.6%). Hematologic cancers showed the highest incidence (39.3%). Among hematologic patients, ICU admission, sepsis, and diabetes were strongly associated with AKI. In non-metastatic solid cancers, more conventional factors—including female sex, older age, sepsis, and ICU admission—were significant predictors. In contrast, in metastatic solid cancers, traditional AKI risk factors did not correlate with increased AKI occurrence. In cancer patients overall, AKI per se did not increase mortality risk; however, stage 3 AKI was associated with significantly higher mortality (HR 1.37, 95% CI 1.13–1.66, p < 0.001). Conclusions: AKI is common in hospitalized cancer patients, with specific patterns and heterogeneous risk factors and impact on outcomes. Implementation of tailored preventive strategies and early recognition are necessary to mitigate progression and improve clinical trajectories. Full article

Sepsis remains a leading cause of global mortality, and early management in the emergency department (ED) is a key determinant of clinical outcomes. Among the earliest physiological derangements in sepsis are abnormalities in coagulation, which represent not merely laboratory disturbances but fundamental reflections of dysregulated host response, endothelial injury, and evolving microvascular thrombosis. Sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC) form a dynamic continuum that frequently begins before shock is clinically apparent. Despite their prognostic value and pathophysiologic significance, these abnormalities are often underrecognized in the ED, where coagulation tests are still commonly interpreted through the narrow lens of bleeding risk rather than as markers of systemic thromboinflammation. This narrative review synthesizes current understanding of the mechanisms linking sepsis, endothelial dysfunction, and coagulation abnormalities; outlines the distinction between SIC and overt DIC; and highlights why early identification of coagulopathy in the ED is essential. We discuss practical bedside approaches, including recommended laboratory testing, pattern recognition, and application of validated scores such as the SIC and ISTH DIC criteria. System-level strategies, such as embedding coagulation testing into sepsis bundles, automating score calculation, and enhancing communication between the ED and ICU teams, are explored as avenues to improve early detection. Evidence suggests that ED recognition of SIC/DIC may refine risk stratification, guide triage decisions, and identify patients who may benefit from targeted anticoagulant strategies once stabilized. Ultimately, recognizing coagulation disorders in the ED reframes sepsis not solely as a hemodynamic crisis but as a complex, thromboinflammatory syndrome in which early intervention may alter trajectory and improve outcomes. Full article

Accurate post-mortem diagnosis of sepsis remains a critical challenge in forensic pathology, as conventional morphological findings often lack specificity. Circulating microRNAs (miRNAs) have been proposed as stable molecular biomarkers, yet their diagnostic value in cadaveric samples is still unclear. This exploratory study investigated the expression of three candidate miRNAs (miR-122-5p, miR-125b-5p, and miR-27a-3p) in post-mortem peripheral whole blood to assess their association with sepsis-related death versus non-infective controls. Out of 58 cases, 45 met quality-control criteria (26 sepsis-related deaths and 19 controls). miRNA expression was quantified by qRT-PCR, normalized to miR-320, and analyzed using ΔCt values. Group differences were evaluated using linear regression models with adjustment for age, sex, and post-mortem interval, with Benjamini–Hochberg correction for multiple testing. In adjusted models, miR-125b-5p and miR-27a-3p showed evidence of association with sepsis status, whereas miR-122-5p did not. These results support the feasibility of miRNA quantification in post-mortem samples and motivate validation in larger, independent cohorts and within multimodal post-mortem diagnostic frameworks. Full article

Background/Objective: Early hemodynamic instability in sepsis arises from endothelial dysfunction and vasoplegia before capillary leakage and organ failure occur. Albumin administration guided by serum concentration or shock criteria has not improved outcomes. This review synthesized evidence supporting an early, physiology-guided framework for albumin and norepinephrine use in pre-δ vasoplegic sepsis. Methods: A narrative synthesis of experimental and clinical studies examined endothelial injury, sepsis phenotypes, hemodynamic monitoring, biochemical markers, and intravascular albumin mass. Evidence from phenotype cohorts was integrated to construct a physiology-based therapeutic framework. Results: The δ phenotype consistently emerged as a vasoplegic, hyperinflammatory endotype with hypoalbuminemia, elevated lactate, and the highest mortality. Studies showed 20–25% of patients with community-acquired sepsis exhibit early vasoplegia, with low systemic vascular resistance and high cardiac output. Mass-balance analyses showed intravascular albumin mass declines early in sepsis, correlate inversely with fluid balance, and predict mortality. These findings suggest early low-dose norepinephrine may stabilize perfusion pressure, while albumin use should follow intravascular albumin mass trajectories. A dynamic exclusion concept proposes withholding albumin during capillary leak and reintroducing it when intravascular albumin mass stabilizes. Conclusions: Albumin therapy in sepsis should shift from late concentration-based to early physiology-guided endothelial protection. Monitoring intravascular albumin mass, lactate, and fluid balance may guide targeted norepinephrine and albumin use before δ-type endothelial failure occurs. This framework needs phenotype-stratified validation. Full article

Sepsis is defined as a dysregulated host response to an infection, leading to life-threatening organ dysfunction. While sepsis is most commonly the result of a bacterial infection, it may also be caused by viral pathogens. The aim of this study was to describe differences in organ dysfunction patterns and inflammatory markers between bacterial and viral sepsis. In this prospective multicenter cohort study, adults meeting SEPSIS-3 criteria were recruited from four Austrian ICUs between 1 August 2021 and 1 April 2024, excluding those who were immunocompromised within the preceding 12 months. Ninety patients were enrolled, of whom 57 had bacterial and 33 viral sepsis. Inflammatory markers, including IL-6 and PCT, were higher at ICU admission in bacterial sepsis. Adjusted linear regression confirmed bacterial etiology as the only significant predictor of higher 48 h peak IL-6 and PCT values. Patients with viral sepsis typically fulfilled SEPSIS-3 criteria through respiratory and cardiovascular SOFA components, while other organ dysfunctions were less frequent. Significant differences in the phenotype of bacterial and viral sepsis were observed, characterized by distinct inflammatory profiles and differing patterns of organ dysfunction. These findings may support the improved differentiation of bacterial and viral etiologies in sepsis. Full article

Background/Objectives: Postoperative organ complications following open thoracoabdominal aortic aneurysm (TAAA) repair pose significant challenges during the early postoperative period, where prompt detection is crucial for improving patient outcomes. Sepsis is often a central factor in these complications. This study investigates the perioperative dynamics of soluble urokinase plasminogen activator receptor (suPAR) plasma levels in TAAA patients undergoing elective surgical repair and evaluates its diagnostic potential for early detection of postoperative sepsis. Methods: In this retrospective, single-center study, 28 patients (mean age 52.6 ± 13.4 years; 67.9% male) underwent elective open TAAA repair between 2022 and 2024. Blood samples were collected at five perioperative time points, and suPAR levels were measured using ELISA. The primary endpoint was the onset of postoperative sepsis, with secondary endpoints including other organ complications. The predictive performance of suPAR levels was evaluated using Receiver Operator Characteristics (ROC) analysis. Results: Postoperative sepsis developed in 7 of 28 patients (25%), with the diagnostic criteria met at a mean of 9.7 ± 6.9 days. Baseline suPAR levels did not differ between groups; however, from 12 h after surgery, the sepsis group exhibited significantly higher serum concentrations (14.43 ng/mL vs. 7.23 ng/mL; p = 0.004), a difference that persisted throughout the first 24 h. At 24 h, suPAR had the highest predictive accuracy for sepsis, with an AUC of 0.90, 90% sensitivity, and 86% specificity at a 9 ng/mL cut-off (p < 0.001). Conclusions: Elevated suPAR levels in the early postoperative period are strongly associated with the later onset of sepsis. Early monitoring may enable timely intervention, potentially improving outcomes in this high-risk patient population. Full article