INTRODUCTION:Arterial stiffness, typically measured by pulse wave velocity (PWV), is a recognized biomarker of cardiovascular (CV) risk and mortality. Our study assesses the predictive value of arterial stiffness measured by estimated pulse wave velocity (ePWV) for fatal and nonfatal outcomes in a general rural adult population. METHODS:This prospective observational cohort study was conducted within the ENAH project, which initially included 3,305 adults, with 2,232 participants followed up over a median of 11.3 years. Baseline demographic, clinical, and laboratory data, including blood pressure, anthropometry, and biochemical analyses of blood and urine, were collected using standardized protocols. The primary outcome was all-cause mortality, while secondary outcomes comprised nonfatal CV, cerebrovascular, and renal events, analyzed using Kaplan-Meier survival curves and multivariable regression models. RESULTS:In this cohort of 1,175 adults followed for a mean of 11.3 years, 263 participants died (22.4%), and 171 (14.5%) experienced a nonfatal event (myocardial infarction, atrial fibrillation, heart failure, stroke, transient ischemic attack, or dialysis). Kaplan-Meier analysis showed lower survival in participants with ePWV of >10 m/s compared to those with ePWV of <10 m/s (hazard ratio [HR] = 12.8, 95% CI 9.9-16.6, p < 0.001). Similarly, event-free survival was lower for nonfatal outcomes in the higher ePWV group (HR = 1.50, 95% CI 1.0-2.1, p = 0.008). In multivariable analysis for mortality, male sex and ePWV remained significant predictors (HR 1.75, 95% CI 1.18-2.61, p = 0.006; HR 1.81, 95% CI 1.08-3.04, p = 0.030). No independent predictors were found for nonfatal outcomes. However, for the composite endpoint, both male sex (HR = 1.54, 95% CI 1.14-2.08, p = 0.006) and ePWV (HR = 1.94, 95% CI 1.50-2.51, p < 0.001) were associated with increased risk. CONCLUSION:ePWV was an independent predictor of overall mortality as well as composite fatal and nonfatal outcomes. These findings suggest that this simple measure of arterial stiffness may be useful in clinical practice, particularly in rural settings where direct measurements are not available.

Background/Objectives: Hepatocellular carcinoma (HCC) is a major cause of cancer-related morbidity and mortality, with incidence expected to increase. Liver transplantation is the most definitive curative option for early HCC, but many patients present beyond accepted transplant criteria, including the Milan criteria. Downstaging aims to reduce tumor burden and enable transplantation without compromising long-term outcomes. Methods: We reviewed the literature on liver transplantation, immune checkpoint inhibitors, immunotherapy-locoregional therapy combinations, and immune-related adverse events in HCC. Results: Immunotherapy-based strategies are emerging as downstaging approaches in selected patients. In advanced HCC, immune checkpoint inhibitor combinations have improved objective response rates compared with tyrosine kinase inhibitors, reaching approximately 20-36% in pivotal phase III trials. In the downstaging setting, early data suggest that immune checkpoint inhibitors, particularly with locoregional therapies, can achieve sufficient tumor regression to permit transplantation in patients initially beyond criteria. The ImmunoXXL trial reported successful downstaging and transplantation in all 16 patients treated with atezolizumab-bevacizumab, with 62.5% complete pathological responses, 2-year recurrence-free survival of 90%, and overall survival of 94%. The VITALITY study achieved successful downstaging in 75.6% of patients beyond Milan criteria, with 36.7% undergoing transplantation and 3-year post-transplant survival of 85%. However, pre-transplant immune checkpoint inhibitor exposure carries a clinically relevant risk of acute allograft rejection, reported in approximately 16-28% of transplanted patients. Conclusions: Immunotherapy-based downstaging before liver transplantation is promising but remains non-standard. Its use should be restricted to carefully selected patients within multidisciplinary protocols, as evidence remains limited by small cohorts, heterogeneous regimens, uncertain washout intervals, and rejection risk.

INTRODUCTION:Body mass index (BMI) is commonly used to estimate obesity-related risk, but it does not reflect fat distribution. A Body Shape Index (ABSI), which captures central adiposity independently of BMI, may offer better prognostic value. We compared ABSI and BMI as predictors of all-cause and cardiovascular (CV) mortality in a general rural population. METHODS:This prospective analysis included 820 participants from the ENAH (Endemic Nephropathy in Croatia - Epidemiology, Diagnostics and Etiopathogenesis) cohort with complete baseline anthropometric data. BMI and ABSI were calculated at baseline and expressed as z-scores. Participants were followed for a median of 9.7 years. Associations with all-cause mortality, CV mortality, and a composite non-fatal outcome were examined using multivariable Cox regression. Discriminative ability was assessed by receiver operating characteristic analysis. RESULTS:Higher ABSI was independently associated with increased all-cause mortality (hazard ratio per 1-SD increase 1.15, 95% confidence interval 1.01-1.32) and CV mortality (1.27, 1.04-1.55), whereas BMI showed no significant association with either outcome. Mortality risk increased across ABSI tertiles but not BMI tertiles. ABSI demonstrated better discrimination for all-cause and CV mortality than BMI, while neither index predicted non-fatal outcomes. CONCLUSION:ABSI outperformed BMI in predicting all-cause and CV mortality. Measures of central adiposity such as ABSI may improve mortality risk stratification beyond BMI alone.

Uvod: Svrbež je čest simptom povezan s različitim medicinskim stanjima koji ozbiljno utječe na kvalitetu života (KŽ) te negativno utječe na raspoloženje, kvalitetu spavanja, radnu sposobnost i društveno funkcioniranje. 5-D ljestvica za procjenu svrbeža jednostavan je upitnik koji se može primijeniti na različite bolesti za procjenu svrbeža. Slični alati nisu dostupni na hrvatskom jeziku. Cilj ovog istraživanja bio je prevesti i kulturno adaptirati hrvatsku verziju 5-D ljestvice svrbeža za primjenu u hrvatskom govornom području. Materijali i metode: Elman i suradnici razvili su 5-D ljestvicu svrbeža za englesko govorno područje. Obuhvaća pet kategorija – stupanj, trajanje, tijek, smanjenu sposobnost i raspodjelu, a temelji se na pitanjima s višestrukim odgovorima. Tijekom prevođenja i adaptacije upitnika pridržavali smo se protokola, tj. smjernica Souse i suradnika. Rezultati: Većina riječi prevedena je izravno bez modifikacija. Nekoliko riječi zahtijevalo je prilagodbu kako bi se ljestvica uskladila s jezičnim i kulturnim kontekstom hrvatskog jezika; naziv ‘scale’ (mjerilo) zamijenjen je s ‘ljestvica’; ‘direction’ (smjer) promijenjen je u ‘tijek’; ‘disability’ (invalidnost) zamijenjeno je s ‘nesposobnost’, ‘thighs’ (natkoljenice) zamijenjeno je s ‘bedra’; ‘lower legs’ (donje noge) zamijenjeno je s ‘potkoljenice’. Konačna verzija hrvatskog prijevoda 5-D ljestvice svrbeža nosi naziv „Ljestvica za procjenu svrbeža u 5 koraka“. Zaključak: Ljestvica za procjenu svrbeža u 5 koraka višedimenzijski je alat za procjenu svrbeža primjenjiv na različite populacije. Ljestvica je prevedena na hrvatski jezik i prilagođena uporabom standardnog postupka prijevoda / povratnog prijevoda. Hrvatska verzija ljestvice potencijalno može biti koristan alat za procjenu svrbeža u kliničkim studijama i praksi.

BACKGROUND & AIMS:Patients with alcohol-related decompensated advanced chronic liver disease and ongoing non-acute decompensation remain at substantial risk of short-term progression to hospitalization-requiring acute decompensation. Early identification of high-risk patients remains challenging. We evaluated whether the red cell distribution width-to-platelet ratio predicts short-term acute decompensation in this vulnerable population. METHODS:In this prospective multicentre study, 260 patients with alcohol-related decompensated advanced chronic liver disease and ongoing non-acute decompensation were enrolled in a derivation cohort and followed for 3 months. The primary outcome was progression to hospitalization-requiring acute decompensation. Predictive performance was assessed using receiver operating characteristic analysis, bootstrap internal validation, Cox regression, and external validation in an independent cohort of 75 patients. RESULTS:During follow-up, 100 patients (38.5%) progressed to acute decompensation. The red cell distribution width-to-platelet ratio showed the highest discriminative performance among all evaluated non-invasive tests (AUC 0.888). The optimal threshold was 0.159, yielding 90.0% sensitivity, 78.1% specificity, and 92.6% negative predictive value. Higher values remained independently associated with acute decompensation (adjusted HR 1.040 per 0.01 increase; 95% CI 1.021-1.060; p < 0.001). External validation confirmed robust performance (AUC 0.836; negative predictive value 95.3%). CONCLUSIONS:The red cell distribution width-to-platelet ratio is a simple, inexpensive biomarker that predicts short-term acute decompensation and may support early outpatient risk stratification.

Inflammatory Bowel Disease (IBD) is characterized by mucosal injury in the gastrointestinal (GI) tract. During an abnormal immune response in the GI tract, excessive secretion of immune-cell proteases occurs. Neutrophils are the first responders, infiltrating into the inflamed interstitial matrix, where type III collagen accumulates. We aimed to develop a biomarker that reflects early inflammation before clinical symptoms arise; allowing us to intervene and prevent cumulative damage. A competitive enzyme-linked immunosorbent assay targeting a human neutrophil elastase degraded neo-epitope fragment of type III collagen (C3-HNE) was developed and assessed in serum samples from DSS-treated rats and a clinical cohort (n = 91, UC and CD). Moreover, C3M, an MMP- mediated type III collagen degradation marker, was tested for comparison. The DSS-treated rats had elevated C3-HNE levels on day 4, while C3M increased on days 10 and 14, compared to the non-DSS treated group. Percentage change analysis showed that C3-HNE rapidly peaked (day 1), while C3M displayed a sustained elevation over time. Serum C3-HNE concentrations increased in patients with IBD, including those in remission, compared to healthy donors, possibly indicating subclinical inflammation. This biomarker may reflect initial mucosal injury and could provide early detection of inflammation for patients in remission, monitoring flare episodes.

BACKGROUND:Colonization with multidrug-resistant organisms (MDROs) is frequently observed in critically ill patients with liver cirrhosis admitted to intensive care units (ICUs). However, whether colonization directly leads to infections or adversely impacts clinical outcomes remains unclear. Clarifying this relationship may help determine the prognostic significance of colonization in these patients. AIM:To evaluate the clinical relevance of MDRO colonization and infection at ICU admission in patients with cirrhosis. METHODS:This retrospective single-center cohort study included 107 ICU admissions of patients with liver cirrhosis at a tertiary care center (2018-2024). Colonization was assessed by rectal and nasal/pharyngeal swabs within 48 hours of ICU admission. Outcomes analyzed included MDRO infection during ICU stay, concordance between colonizing and infecting strains, organ support requirements, and 28-day transplant free survival. Multivariable logistic regression and Kaplan-Meier analyses were used to evaluate predictors of infection and mortality. RESULTS:Nearly one-third (29.9%) of patients were colonized with MDROs on admission, more commonly in the acute-on-chronic liver failure phenotype than those with acute decompensation (34.5 vs 10.0%, P = 0.033). Although infections were established in the majority (85%) of cases, of which 17.6% due to MDROs, colonization alone did not independently predict these infections [odds ratio (OR) = 2.18, P = 0.383] nor influenced short-term mortality (OR = 1.14, P = 0.813). However, once MDRO infection occurred, an 82% concordance was observed between colonizing and infecting strains. MDRO infections, unlike colonization, significantly increased the need for organ-support interventions, including mechanical ventilation and vasopressor therapy and prolonged ICU stays. Only severity of organ dysfunction, quantified by the Sequential Organ Failure Assessment score, independently predicted 28-day mortality (OR = 1.38, P = 0.024). CONCLUSION:MDRO colonization at ICU admission is frequent among critically ill patients with cirrhosis, particularly those with acute-on-chronic liver failure. While colonization alone does not predict infection or early mortality, its clinical value emerges in guiding empirical antibiotic treatment once infection is suspected. Ultimately, short-term survival appears to be more strongly influenced by the severity of organ failure than by either MDRO colonization or infection.

BACKGROUND & AIMS:The Epi-IBD cohort is a population-based inception cohort of patients with inflammatory bowel disease from 22 European centers. The aim was to assess the 10-year disease course of patients with Crohn's disease (CD) and how regional differences in treatment strategies impact the disease course. METHODS:Patients were followed prospectively from the time of diagnosis, with uniform collection data. Associations between outcomes and covariates were analyzed by multivariable Cox regressions in a propensity score-matched sub-population to address time to first intestinal resection. RESULTS:A total of 547 patients with CD were recruited (Eastern Europe: 139 [25.4%]; Western Europe: 408 [74.6%]). Ten-year cumulative rate of advanced therapy use was higher in Western (42%) compared with Eastern Europe (27%) (P < .05). The median period until initiation of advanced treatment was shorter in Western Europe (10 vs 46 months; P < .001). Despite these differences, the need for surgery remained comparable in Eastern and Western Europe, with a 10-year rate of 24% (P = .9). A similar comparability was observed for disease progression from uncomplicated disease to complicated disease (10-year rate: 20%; P = .07) and hospitalization (10-year rate: 41%; P = .5). Use of advanced therapy, stricturing or penetrating disease at diagnosis, progression of disease behavior, and former smoking were all associated with an increased risk of intestinal resection (all P < .05). CONCLUSIONS:Despite earlier and more frequent use of advanced therapies in Western Europe, no differences in disease outcomes were observed between Western and Eastern European patients. Ten years after diagnosis, 1 in 5 patients with uncomplicated disease at diagnosis progressed to complicated disease, and 1 in 4 needed surgery.

Abstract Background The Epi-IBD cohort is a prospective European population-based cohort of 1,508 patients diagnosed in 2010 and 2011 with inflammatory bowel disease (IBD) according to Copenhagen criteria in centres across 17 European countries. The study aims to describe treatment strategies, disease course and prognosis of IBD unclassified (IBDU) across Europe. Methods Patients with IBDU were defined as not fulfilling the Copenhagen diagnostic criteria of Crohn’s disease (CD) or ulcerative colitis (UC), but still required IBD related treatment and monitoring. They were followed prospectively from the time of diagnosis until December 31st, 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org. Patients with IBDU were categorised as CD-like, UC-like or mixed CD-UC based on disease location and continuity of the affected bowel segments at diagnosis. Results In total, 129 IBDU patients aged ≥15 years from 22 centres were included. They comprised 8.5% (N=129/1,508) of the total cohort. The disease location was reported in Table 1 where 4 patients had unknown disease location at baseline. At diagnosis, 16% (N=25/129) were CD-like, 52% (N=62/129) were UC-like and 32% (N=42/129) were mixed CD-UC.During the 10-year follow-up, 32% (N=41/129) were re-classified as either CD (N=16) or UC (N=25). The crude 1-, 5-, and 10-year rates for re-classification of diagnosis were 19%, 26% and 32%. The time to initiation of therapies and the distribution of therapies according to re-classification of IBDU diagnosis at baseline are presented in Figure 1 A-B . Advanced therapies were used in 13% (N=17/129) of patients over the 10-year follow-up, and was initiated after a median period of 1.9 years (inter-quartile range 0.9-8.1). An intestinal resection was required in 7% (N=9/129). After 1, 5, and 10 years, 9%, 19% and 26% of the patients diagnosed with IBDU at baseline, respectively, required hospitalisation. Conclusion After 10 years of follow-up, a third of patients initially diagnosed with IBDU were re-classified as either CD or UC. The disease course was in general mild with a low number of patients requiring advanced therapy, intestinal resection, and hospitalization. However, patients who were re-classified as CD or UC were more frequently treated with medical therapies.

INTRODUCTION:A proper sample size calculation enables to conduct adequately powered randomized controlled trials (RCTs) and to provide a valid assessment of a specific clinical question. AREAS COVERED:In the current manuscript, we tried to provide the reader with an easy guide on the principles of sample size calculation in RCTs, tailored specifically to the context of gastroenterology and hepatology. The basics of sample size calculation were commented with a description of some of the main methods, including the calculation of the non-inferiority margin for non-inferiority RCTs and the calculation of the minimum clinically important difference (MCID). Some examples from the gastroenterology literature were also provided. EXPERT OPINION:Collaborating with a biostatistician can provide valuable insights into the nuances of sample size calculation and study design. However, it is crucial that the clinicians understand the basics of calculating sample size, so they could provide valuable input in designing the study from a clinical point of view.

Background Endoscopic retrograde cholangiopancreatography (ERCP) still has a relatively high complication rate, underscoring the importance of high-quality training. Despite existing guidelines, real-world data on training conditions remain limited. This pan-European survey aims to systematically explore the perceptions surrounding ERCP training. Methods A survey was distributed through the friends of United European Gastroenterology (UEG) Young Talent Group network to physicians working in a UEG member or associated states who regularly performed ERCPs. Results Of 1035 respondents from 35 countries, 649 were eligible for analysis: 228 trainees, 225 trainers, and 196 individuals who regularly performed ERCP but were neither trainees nor trainers. The mean age was 43 years, with 72.1% identifying as male, 27.6% as female, and 0.3% as non-binary. The majority (80.1%) agreed that a structured training regimen is desirable. However, only 13.7% of trainees and 28.4% of trainers reported having such a structured program in their institutions. Most respondents (79.7%) supported the concept of concentrating training in centers meeting specific quality metrics, with 64.1% suggesting a threshold of 200 annual ERCPs as a prerequisite. This threshold revealed that 36.4% of trainees pursued training in lower-volume centers performing <200 ERCPs annually. As many as 70.1% of trainees performed <50 annual ERCPs, whereas only 5.0% of trainers performed <50 ERCPs annually. A low individual trainee caseload (<50 ERCPs annually) was more common in lower-volume centers than in higher-volume centers (82.9% vs. 63.4%). Conclusions The first pan-European survey investigating ERCP training conditions reveals strong support for structured training and the concentration of training efforts within centers meeting specific quality metrics. Furthermore, this survey exposes the low availability of structured training programs with many trainees practicing at lower-volume centers and 71% of all trainees having little hands-on exposure. These data should motivate to standardize ERCP training conditions further and ultimately improve patient care throughout Europe.

Background: Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events. Carotid-femoral PWV is considered the gold standard for the estimation of arterial stiffness. cfPWV is a demanding, time consuming and expensive method, and an estimated PWV (ePWV) has been suggested as an alternative method when cfPWV is not available. Our aim was to analyze the predictive role of ePWV for CV and all-cause mortality in the general population. Methods: In a stratified random sample of 1086 subjects from the general Croatian adult population (EH-UH study) (men 42.4%, average age 53 ± 16), subjects were followed for 17 years. ePWV was calculated using the following formula: ePWV = 9.587 − 0.402 × age + 4.560 × 10−3 × age2 − 2.621 × 10−5 × age2 × MBP + 3.176 × 10−3 × age × MBP − 1.832 × 10−2 × MBP. MBP= (DBP) + 0.4(SBP − DBP). Results: At the end of the follow-up period, there were 228 deaths (CV, stroke, cancer, dementia and degenerative diseases, COLD, and others 43.4%, 10.5%, 28.5%, 5.2%, 3.1%, 9.3%, respectively). In the third ePWV tercile, we observed more deaths due to CV disease than to cancer (20.5% vs. 51.04%). In a Cox regression analysis, for each increase in ePWV of 1 m/s, there was a 14% increase risk for CV death. In the subgroup of subjects with higher CV risk, we found ePWV to be a significant predictor of CV deaths (ePWV (m/s) CI 1.108; p < 0.029; HR 3.03, 95% CI 1.118–8.211). Conclusions: In subjects with high CV risk, ePWV was a significant and independent predictor of CV mortality.