Search Results (2,441)

Background and Objectives: Early risk stratification remains challenging in patients undergoing left ventricular assist device (LVAD) implantation. Red cell distribution width (RDW) and serum albumin reflect systemic stress and nutritional reserve; their ratio (RDW-to-albumin ratio, RAR) may provide a simple preoperative index. We evaluated whether preoperative RAR is associated with early mortality after LVAD implantation. Materials and Methods: We conducted a retrospective cohort study of LVAD recipients (2019–2025). RAR was calculated as RDW (%) divided by albumin (g/dL) from preoperative blood tests obtained 24–48 h before surgery. The primary endpoint was in-hospital mortality. The secondary endpoint was 90-day survival. In-hospital mortality was analyzed using logistic regression with parsimonious adjustment for INTERMACS high-risk status (profiles 1–2 vs. 3–7); penalized regression was used to reduce small-sample bias. Discrimination was assessed using receiver operating characteristic (ROC) analysis. Ninety-day survival was evaluated using Cox proportional hazards models. Results: Forty-seven patients were included (37 survivors; 10 in-hospital deaths). Higher RAR was associated with increased odds of in-hospital mortality and remained significant after adjustment for INTERMACS high-risk status (OR 1.68, 95% CI 1.04–2.90). INTERMACS high-risk status was strongly associated with in-hospital mortality (OR 17.89, 95% CI 3.19–138.07). RAR demonstrated good discrimination for in-hospital mortality (AUC 0.801, 95% CI 0.648–0.955). For 90-day survival, RAR showed a borderline association in unadjusted analysis (HR 1.28, 95% CI 0.98–1.68) and was not significant after adjustment (HR 1.20, 95% CI 0.89–1.63). Conclusions: In this small single-center cohort, preoperative RAR was independently associated with in-hospital mortality after LVAD implantation. These findings should be considered hypothesis-generating and require external validation. Full article

Introduction: Idiopathic pulmonary fibrosis (IPF) is associated with high morbidity and mortality and a substantial burden of comorbidities, which may influence prognosis and survival. This study aimed to evaluate the burden of comorbidity in patients with IPF receiving antifibrotic therapy using the Charlson, TORVAN, and GAP indices and to analyse their relationships and prognostic impact on survival. Methods: Retrospective observational study including patients with IPF diagnosed according to ATS/ERS/JRS/ALAT criteria. Patients receiving antifibrotic therapy between June 2010 and September 2025 were included. Baseline comorbidities were recorded, and the Charlson, TORVAN, and GAP indices were calculated. Associations between indices were assessed using chi-square tests and kappa statistics. Survival was analysed using Kaplan–Meier curves and compared with the log-rank test. Cox proportional hazards regression and model comparison metrics (Harrell’s C-index and Akaike Information Criterion) were also performed to assess the independent prognostic value of each index. Results: Seventy-two patients were included (76.7% male; mean age 73.8 ± 7.4 years). Pirfenidone was prescribed in 63.9% and nintedanib in 36.1%. The most frequent comorbidities were gastro-oesophageal reflux disease (62.5%), arterial hypertension (57.5%), pulmonary hypertension (32.9%), diabetes mellitus (24.7%), and non-metastatic solid tumours (17.6%), including lung cancer. Survival differed significantly according to GAP stage (p = 0.020) and Charlson categories (p = 0.006). The TORVAN stage was associated with the GAP stage (p < 0.001; kappa = 0.246), whereas the Charlson index showed no association with GAP or TORVAN. Conclusions: In this cohort of patients with IPF receiving antifibrotic therapy, both the GAP and Charlson indices were associated with survival. These findings suggest that combining disease-specific and comorbidity indices may provide a more comprehensive prognostic assessment, although further validation in larger cohorts is required. Full article

Background: Adenoid cystic carcinoma (ACC) demonstrates marked clinical heterogeneity that is inadequately explained by conventional histopathologic and staging systems alone. Recent studies have identified two molecular subtypes based on transcriptomic profiling and MYC/TP63 expression (ACC I: MYC-high/TP63-low; ACC II: MYC-low/TP63-high) with potential prognostic significance. However, the magnitude and consistency of their survival impact remain uncertain. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Embase, and PubMed Central were searched through January 2026 for studies reporting overall survival in ACC stratified by MYC/TP63 molecular subtype. Hazard ratios (HRs) were pooled using random-effects models. Heterogeneity, subgroup analyses by classification method, sensitivity analyses, cumulative meta-analysis, influence diagnostics, and publication bias assessment were performed. Results: Five independent cohorts from two publications comprising 247 patients (90 ACC I, 157 ACC II) were included. ACC I was associated with significantly worse overall survival compared with ACC II, with a pooled HR of 3.88 (95% CI: 2.55–5.90; p < 0.001). No statistical heterogeneity was observed (I² = 0%). Prognostic separation was consistent across RNA sequencing and immunohistochemistry-based classification methods. Conclusions: Transcriptomic and MYC/TP63-based molecular subtyping provides strong and reproducible prognostic stratification in ACC. ACC I tumors confer an approximately four-fold higher mortality risk compared with ACC II tumors. Incorporation of molecular subtype into routine diagnostic and clinical decision-making may improve risk stratification, surveillance strategies, and future trial design in ACC. Full article

Background: Liver cirrhosis, particularly in its decompensated stages, is associated with high short-term mortality among hospitalized patients. Although the prognostic value of the Child–Pugh classification is well established, its independent impact on survival in real-world tertiary emergency settings requires further evaluation. This study aimed to assess the prognostic role of Child–Pugh stage and other clinical factors on short- and mid-term survival in hospitalized cirrhotic patients over a 10-year period. Methods: We conducted a retrospective cohort study including 2831 patients hospitalized for liver cirrhosis between 2015 and 2025. Among them, 631 patients with complete Child–Pugh staging were included in the survival analysis. Survival time was defined as the interval between the first hospitalization and the last recorded discharge or in-hospital death. Survival differences were assessed using Kaplan–Meier curves and log-rank tests, while independent predictors of mortality were identified using multivariate Cox proportional hazards regression. A complementary logistic regression model was used to evaluate predictors of mortality as a binary outcome. Results: Among the 631 staged patients, 13.5% were classified as Child–Pugh A, 31.9% as Child–Pugh B and 54.7% as Child–Pugh C. In-hospital mortality increased significantly across stages (1.2%, 9.0% and 46.7%, respectively; p < 0.001). One-year survival was 98.7% for Child–Pugh A, 83.6% for Child–Pugh B and 40.7% for Child–Pugh C (log-rank p < 0.001). In multivariate Coxregression analysis, the strongest predictor of mortality was mixed cirrhosis type (HR = 8.58, 95% CI: 4.81–15.32, p < 0.001). Child–Pugh C was also independently associated with a markedly increased mortality risk compared with Child–Pugh A (HR = 25.11, 95% CI: 3.44–183.29, p = 0.002). Alcohol-related etiology (HR = 1.81, 95% CI: 1.09–3.01, p = 0.023) and age (HR = 1.18 per SD increase, 95% CI: 1.00–1.39, p = 0.050) were additionalindependent predictors. The Cox model demonstrated good discrimination (C-statistic ≈ 0.80). In the logistic regression model, mixed cirrhosis type (OR = 13.28, p < 0.001) and Child–Pugh stage (OR = 8.66, p < 0.001) were the strongest predictors of mortality, while ascites showed an inverse association after adjustment (OR = 0.62, p = 0.036). The logistic model showed excellent discrimination (AUC = 0.865). Conclusions: Child–Pugh stage remains a strong and independent predictor of survival in hospitalized patients with decompensated cirrhosis. The marked survival gradient across stages, particularly the substantially reduced survival observed in Child–Pugh C patients, highlights thecontinued clinical utility of this simple classification for early risk stratification intertiary emergency hospital settings. Full article

Background: High-grade soft tissue sarcomas (STSs) are heterogeneous tumours lacking robust prognostic or predictive biomarkers. Regnase-1, an immune RNase, enhances antitumour immunity by limiting immunosuppressive tumour microenvironment (TME) components (e.g., myeloid-derived suppressor cells (MDSCs)), but remains unexplored in STS. As CD68⁺ tumour-associated macrophages (TAMs) drive TME suppression and poor prognosis in non-translocation-driven STS, we evaluated Regnase-1 and CD68⁺ TAMs to assess Regnase-1 as an indicator of an immunologically activated TME. Methods: Immunohistochemistry scoring of Regnase-1 and CD68⁺ TAMs was performed in 91 patients. Overall survival (OS) was assessed by Kaplan–Meier and Cox regression, and findings were validated in an independent “The Cancer Genome Atlas” Sarcoma (TCGA-SARC) cohort (n = 212). Results: In UPS, Regnase-1-high predicted longer OS (17.0 months vs. not reached; p = 0.0247) and lower mortality (univariate hazard ratio (HR) = 0.3; p = 0.0343; multivariate HR = 0.4; p = 0.0413), but not after radiotherapy. CD68⁺ TAM-high predicted shorter OS (13.0 months vs. not reached; p = 0.0274) and higher mortality (HR = 2.0, 95% CI 1.1–3.7; p = 0.0325). Both Regnase-1 effects were reproduced in TCGA-SARC. Regnase-1-high tumours showed inflammatory/interferon enrichment, reduced TGF-β signalling, and SERPINE1 upregulation. Conclusions: Regnase-1 marked a pro-inflammatory TME and favourable outcome in UPS, but this effect may reverse upon radiotherapy. Full article

Inhalation injury (II) exacerbates burn mortality via obstructive fibrin casts. We evaluated a protocol combining scheduled flexible bronchoscopy (FOB) with nebulized heparin and N-acetylcysteine (NAC). This single-center, randomized controlled trial enrolled 76 mechanically ventilated adult burn patients with bronchoscopically confirmed II. The intervention (n = 38) comprised a 7-day protocol of scheduled FOB with alternating nebulized heparin (5000 IU) and 20% NAC every 4 h. Controls (n = 38) received standard care with on-demand FOB. Primary outcomes were 28-day mortality and day-7 Lung Injury Score (LIS). Unadjusted 28-day mortality was lower in the intervention group (57.9% vs. 81.6%; p = 0.025), alongside a decreased median day-7 LIS (1.0 vs. 1.38; p = 0.021). Respiratory mechanics improved significantly, demonstrating reduced driving pressure and increased static compliance (p < 0.001). However, in multivariable Cox regression, baseline injury severity independently predicted mortality, while the intervention indicated a non-significant hazard reduction trend (aHR = 0.66, 95% CI: 0.36–1.23). No systemic anticoagulation occurred. In conclusion, scheduled FOB with nebulized heparin and NAC improves respiratory mechanics and attenuates lung injury in II. Although unadjusted mortality decreased, baseline severity remains the primary mortality driver, suggesting this protocol is a physiologically beneficial adjunct requiring further multicenter validation. Trial registration: Thai Clinical Trials Registry, TCTR20260408001 (retrospectively registered). Full article

Background: Body mass index (BMI) is a common nutritional marker, but admission-only measurements present limitations. Early dynamic BMI changes may better reflect metabolic stress and fluid balance. However, the clinical significance of early BMI trajectory during critical illness remains poorly understood. This study evaluated the impact of early BMI trajectory on mortality and ventilator weaning in critically ill patients. Methods: This retrospective cohort study included 1355 adult patients (ICU stay ≥ 7 days) admitted to the medical ICU between 2019 and 2025. BMI trajectory was defined as the percentage change from admission to day 7 and was categorized into three groups: decrease (>5% reduction), stable (±5%), and increase (>5% gain). Multivariable Cox proportional hazard and logistic regression analyses were performed to evaluate the association between BMI trajectory and clinical outcomes. Results: Of the 1355 patients, 15.9%, 57.7%, and 26.4% were in the decrease, stable, and increase groups, respectively. The increase group demonstrated significantly higher hospital mortality (52.5%) than the decrease (41.9%) and stable (40.0%) groups (p = 0.001). Multivariable analysis revealed that an increasing BMI trajectory was independently associated with higher hospital mortality (HR 1.25, 95% CI 1.05–1.48). A decreasing BMI trajectory strongly predicted successful ventilator weaning (OR 2.76, 95% CI 1.81–4.21). Conclusions: Early BMI trajectory significantly predicted ICU outcomes. Increasing and decreasing BMI were associated with higher mortality and improved ventilator weaning, respectively. These findings suggest that BMI trajectory may be a simple surrogate marker of metabolic stress, nutritional status, and fluid balance during early critical illness. Full article

Introduction: Recent research underscores the risks of maintaining a positive calcium balance in hemodialysis (HD) patients. This study aims to evaluate outcomes based on the calcium levels of HD patients, specifically those with hypocalcemia. Methods: In this retrospective cohort study, data from 71,101 HD patients were analyzed and classified into six groups based on calcium levels: severe hypocalcemia (<7.5 mg/dL, n = 1078), moderate hypocalcemia (7.5–7.99 mg/dL, n = 4000), mild hypocalcemia (8.0–8.39 mg/dL, n = 9846), lower-normal calcium (8.4–9.29 mg/dL, n = 38,697), upper-normal calcium (9.3–10.19 mg/dL, n = 14,505), and hypercalcemia (≥10.2 mg/dL, n = 1975). Results: The numbers of deaths, CVE, and fracture at the end point of the follow-up were recorded: 401 (37.2%), 189 (23.2%), and 224 (20.8%) in the severe hypocalcemia group, respectively; 1523 (38.1%), 663 (22.8%), and 802 (20.1%) in the moderate hypocalcemia group, respectively; 3985 (40.5%), 1618 (22.9%), and 2054 (20.9%) in the mild hypocalcemia group, respectively; 17,067 (44.1%), 6948 (24.9%), and 8676 (22.4%) in the lower-normal calcium group, respectively; 6904 (47.6%), 2967 (27.3%), and 3471 (23.9%) in the upper-normal calcium group, respectively; and 1074 (54.4%), 457 (30.0%), and 473 (23.9%) in the hypercalcemia group, respectively. The 5-year patient survival rates for the severe hypocalcemia, moderate hypocalcemia, mild hypocalcemia, lower-normal calcium, upper-normal calcium, and hypercalcemia groups were 73.9%, 70.0%, 68.8%, 66.4%, 66.1%, and 62.8%, respectively. The 5-year cardiovascular event-free survival rates for the severe hypocalcemia, moderate hypocalcemia, mild hypocalcemia, lower-normal calcium, upper-normal calcium, and hypercalcemia groups were 78.2%, 79.0%, 78.2%, 76.2%, 75.3%, and 72.6%, respectively. The hazard ratios (HRs) for the all-cause mortality (HR: 0.94, 95% CI: 0.84–1.05) and cardiovascular events (HR: 0.98, 95% CI: 0.84–1.15) of the severe hypocalcemia group were consistently not higher than those of the lower-normal calcium group even after thorough adjustments were made for various clinical variables. Multivariable Cox regression analyses revealed that the HRs for all-cause mortality and cardiovascular events of the mild hypocalcemia groups were lower than those of the lower-normal calcium group. Serum calcium levels were not associated with increased risk of fracture. Conclusions: Patients with various degrees of hypocalcemia, including severe hypocalcemia, were not associated with increased mortality and cardiovascular event rates. We suggest that symptoms and clinical presentation should be prioritized rather than simply targeting the normalization of calcium levels in hypocalcemia correction. Full article

Introduction: The relationship between epilepsy and alcohol use is complex and clinically significant. Alcohol acts as a neurochemical modulator capable of lowering the seizure threshold during both intoxication and withdrawal, while chronic misuse may contribute to epileptogenesis through neuronal injury, metabolic stress, and neurotransmitter dysregulation. However, the long-term impact of alcohol use on mortality among people with epilepsy (PWE) remains insufficiently characterized. The purpose of this study was to assess all-cause mortality risk among individuals with epilepsy based on alcohol use history, stratified by race/ethnicity. Methods: Data from the 2008–2018 National Health Interview Survey (NHIS) were linked to mortality outcomes on 31 December 2019 from the National Death Index (NDI) for U.S. adults aged 18 years and older. PWE and alcohol use were determined using self-reported data. Survival probabilities were estimated using weighted Kaplan–Meier methods, and hazard ratios were calculated using Cox proportional hazards models adjusted for demographic and clinical covariates. Results: Our results indicated that among PWE, alcohol use was associated with increased all-cause mortality. The unadjusted hazard ratio (HR) for alcohol use among individuals with epilepsy was 1.30, increasing to 1.40 after multivariable adjustment. In contrast, alcohol use alone without epilepsy was not associated with elevated mortality risk after adjustment. When stratified by race, the combined effect of epilepsy and alcohol use was significantly associated with increased mortality among Black individuals but not White individuals. Conclusions: In this nationally representative cohort, the combined presence of epilepsy and alcohol use was associated with higher all-cause mortality compared with alcohol use alone. Racial differences were observed, underscoring the need for integrated clinical care and further research into genetic, biological, and social determinants influencing epilepsy outcomes. Full article

Background: Evidence regarding potential agent-specific differences among β-blockers in heart failure with mildly reduced ejection fraction (HFmrEF) remains limited. Objective: The present study sought to investigate the association of metoprolol versus carvedilol prescribed at hospital discharge with 30-month all-cause mortality and HF-related rehospitalization, and to explore potential effect modification by atrial fibrillation (AF). Methods: Consecutive patients hospitalized with HFmrEF between 2016 and 2022 were included. Exposure was β-blocker therapy at discharge (metoprolol succinate or carvedilol). Outcomes were analyzed using Kaplan–Meier estimates, multivariable Cox regression and propensity score matching. Results: Among 2109 patients discharged alive, 1625 (77.5%) received β-blockers (metoprolol n = 1033; carvedilol n = 283). Carvedilol recipients were younger (median 72 vs. 76 years) and more frequently had prior heart failure (44.2% vs. 33.2%). Thirty-month mortality occurred in 25.5% of metoprolol-treated and 31.8% of carvedilol-treated patients (unadjusted hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61–0.98; p = 0.031). This association was observed in patients without AF, but not in those with AF. After multivariable adjustments, the association remained directionally similar (adjusted HR 0.76, 95% CI 0.58–1.00). In the matched cohort (n = 246 per group), metoprolol was still associated with lower mortality (HR 0.65, 95% CI 0.46–0.93; p = 0.017). By contrast, HF-related rehospitalization did not differ significantly between the two groups. Conclusions: In this observational HFmrEF cohort, treatment with metoprolol at index hospital discharge was associated with lower 30-month mortality compared with carvedilol. Given the observational study design in line with the higher burden of comorbidities in patients discharged on carvedilol, further prospective studies are needed to clarify the impact of different β-blocker types in heart failure patients. Full article

Background/Objectives: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Identifying reliable biomarkers that reflect the underlying immune pathophysiology of sepsis and support early risk stratification remains a major clinical priority. This prospective study aimed to evaluate the prognostic value of interleukin-6 (IL-6) measured at ICU admission in patients with sepsis and septic shock. Methods: This prospective observational study included adult patients with sepsis and septic shock admitted to the Intensive Care Unit (ICU) of the Clinical Hospital of Infectious Diseases Constanța between 2021 and 2025. Receiver operating characteristic (ROC) curve analysis with DeLong comparisons, Kaplan–Meier survival analysis, and Cox proportional hazards regression modeling were performed to assess the association between baseline IL-6 levels, in-hospital mortality, and time to death. Results: Among the analyzed biomarkers, IL-6 demonstrated the highest discriminatory performance for in-hospital mortality (AUC = 0.956; 95% CI: 0.893–0.987; p < 0.0001). The optimal cut-off value (>135.14 pg/mL) yielded a sensitivity of 87.65% and specificity of 92.86% (Youden index = 0.805). However, despite this excellent discrimination between survivors and non-survivors, baseline IL-6 levels were not significantly associated with time-to-death in Cox proportional hazards regression analysis. Conclusions: Admission IL-6 showed excellent discriminatory performance for mortality risk stratification but was not associated with survival duration in time-to-event analyses. These findings suggest that IL-6 should be interpreted primarily as an early risk stratification biomarker rather than a predictor of survival duration in patients with sepsis. Full article

Background: The combined prognostic value of the fibrinogen-to-albumin ratio (FAR) and uric acid-to-albumin ratio (UAR) in acute kidney injury patients undergoing continuous renal replacement therapy remains unclear. Methods: This retrospective cohort study utilized the MIMIC-IV database. Adult patients with AKI receiving CRRT were included and stratified into four groups based on optimal FAR and UAR cut-offs. Multivariable Cox proportional hazards regression and restricted cubic spline analyses were employed to examine associations with 30-, 90-, and 360-day all-cause mortality. Results: Patients with high FAR/high UAR had the poorest survival (log-rank p < 0.001). After multivariable adjustment, high FAR/high UAR was associated with higher 30-day (HR = 2.17, 95%CI: 1.61–2.92) and 360-day mortality (HR = 1.50, 95%CI: 1.18–1.90) vs. low FAR/low UAR. The association was stronger in patients with an SOFA score >12 or vasopressin use (interaction p < 0.05). Conclusions: In critically ill AKI patients undergoing CRRT, the combined assessment of the FAR and UAR is associated with elevated mortality risk. These readily obtainable composite markers may support risk stratification in clinical practice. Full article

Despite the widespread use of Aloe vera extracts, their developmental toxicity in aquatic organisms remains poorly understood. This study investigated the effects of a commercial Aloe vera extract on zebrafish embryogenesis, focusing on developmental, morphological, behavioural, and oxidative stress-related endpoints. The 96 h-LC₅₀ was determined to be 0.03%. Embryos at 2 h post-fertilization (hpf) were exposed for 96 h to 0.0004% (LC₁₀) and 0.03% (LC₅₀). Exposure to 0.0004% caused no significant effects compared to controls. In contrast, exposure to 0.03% significantly increased mortality, reduced heart rate, impaired locomotion, and induced multiple malformations. Biochemical analyses revealed alterations in redox-associated biomarkers, characterized by unchanged ROS levels and mitochondrial activity, increased antioxidant enzyme activities (SOD, GPx, GR), and a decreased GSH:GSSG ratio. Lipid peroxidation levels were reduced, while a significant increase in DNA double-strand breaks (DSBs) was observed. Additionally, Nrf2 protein expression was upregulated at 0.03%. Together, these findings suggest concentration-dependent developmental toxicity correlated with alterations in redox homeostasis and genomic stability during early zebrafish development. This study provides new insight into the developmental hazard potential of a commercial Aloe vera extract in an aquatic vertebrate model. Full article

Background: Heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) are common in the growing population of elderly patients, yet little evidence specifically targeting this population exists. The purpose of this study is to analyze the effect of SGLT2 inhibition in this cohort. Methods: A single-center, real-world observational study was performed. Patients aged >75 with HFrEF and CKD and theoretical indication for sodium–glucose cotransporter 2 (SGLT2) inhibitors were enrolled. Results: A total of 173 patients were included, with a mean age of 84.7 years, mean left ventricle ejection fraction of 29.5% and estimated glomerular filtration rate of 45.9 mL/min/1.73 m². During a median follow-up of 39 months, 73 (42.2%) deaths from any cause and 95 (53.3%) major clinical events (composite of mortality and heart failure admission) were recorded. Multivariate Cox proportional hazards regression analyses were performed to identify associated variables, and SGLT2 inhibition showed to be a protective factor for the mortality endpoint (hazard ratio 0.324 [0.117–0.894]). Male sex was shown to be a risk factor for both endpoints, diabetes mellitus for the mortality endpoint and diuretic use for the major clinical event endpoints. Conclusions: In a real-world study, treatment with SGLT2 inhibitors in elderly patients with HFrEF and CKD was associated with a lower rate of all-cause mortality. Full article

This study evaluates deterministic flood fatality models using a harmonised dataset of river and flash flood events in Europe (1980–2024). The objective is to quantify differences across data sources and critically assess the applicability of commonly used prediction models for hydrological floods, with particular emphasis on flash floods, which remain poorly represented in existing methodologies. The analysis integrates large-scale databases on flood fatalities (HANZE, EM-DAT) with detailed event-based studies containing hazard and other indicators, enabling a combined evaluation from different sources. Three model groups are assessed by comparing predicted and observed fatalities: Damage–Fatality, Depth–Fatality, and Depth–Velocity–Fatality approaches. Results confirm discrepancy between exposure and mortality: river floods dominate in terms of affected population (87%) and economic losses (71%), whereas flash floods account for nearly half of all fatalities despite affecting only 13% of people. All evaluated models show significant limitations for prediction of flash floods fatalities; single-parameter approaches perform poorly, while multi-parameter models remain highly sensitive to uncertain hydraulic inputs. The study demonstrates that current methods are not transferable to flash flood conditions and highlights the need for integrated, multi-variable approaches supported by consistent and high-quality datasets. The main contributions of the study are the first systematic validation of widely used models against historical river and flash flood events, revealing their uncertainties, and a comprehensive assessment of their robustness and sensitivity to key input indicators. Full article