BACKGROUND: Mirikizumab is a selective anti-IL-23 monoclonal antibody approved for moderate-to-severe ulcerative colitis (UC). Evidence regarding its efficacy mostly derives from registration trials, as real-world data i...BACKGROUND: Mirikizumab is a selective anti-IL-23 monoclonal antibody approved for moderate-to-severe ulcerative colitis (UC). Evidence regarding its efficacy mostly derives from registration trials, as real-world data in multi-refractory populations remain limited. METHODS: We conducted an observational study including UC patients treated with mirikizumab. Clinical activity was assessed using the partial Mayo (pMayo) score at baseline, Week12 (W12), and Week24 (W24). Urgency, biomarkers, endoscopic activity and safety were evaluated. Steroid-free clinical remission (SFCR) was defined as pMayo≤1 without corticosteroids; clinical response as ≥3-point or ≥30% reduction. Changes over time were analyzed using paired non-parametric tests; logistic regression identified predictors of remission. RESULTS: One-hundred-twenty-three highly treatment-expierenced patients were included (median 3 prior advanced therapies, IQR 2-4). Most patients (89.0%) continued extended IV induction after W12. SFCR was achieved in 25.2% (31/123) at W12 and 31.3% (30/96) at W24, while clinical response occurred in 70.7% and 67.7%, respectively. Bowel urgency improved at W12 and W24 (p<0.001). Adverse events occurred in 20.3% of patients; the colectomy rate was 4.9%. Higher baseline pMayo and prior JAKi exposure were associated with lower remission. CONCLUSION: Mirikizumab showed encouraging effectiveness and safety in multirefractory UC. Prior JAKi exposure emerged as a potential negative predictor of remission; this hypothesis-generating signal warrants validation.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of obesity in adults and are now gaining attention in pediatric populations facing a dramatic rise of obesity prevalence and related co...Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of obesity in adults and are now gaining attention in pediatric populations facing a dramatic rise of obesity prevalence and related comorbidities. In addition to weight loss, their role extends to cardiometabolic effects and improvements of kidney function. Liraglutide and semaglutide have demonstrated clinically meaningful efficacy in adolescents, leading to FDA and EMA approvals for patients ≥12 years. Ongoing trials are being conducted to combine GLP-1 analogues with other effective molecules or with bariatric surgery. Current evidence on safety most frequently highlights gastrointestinal adverse events, with no consistent impact on growth or pubertal development reported to date. Psychosocial dimensions, including stigma, mental health risks, and potential disordered eating, together with economic barriers and disparities in access, require careful consideration and efforts to be overcome. Implementing intensive lifestyle interventions is mandatory, including nutritional education, physical activity promotion, and family-based behavioral strategies, to support long-term weight management and address the broader determinants of health. Preliminary studies suggest complementary roles for GLP-1RAs alongside metabolic bariatric surgery in selected high-risk patients. Long-term data on safety and multidisciplinary approaches are required to define the optimal integration of pharmacotherapy into comprehensive, family-centered pediatric obesity care models.
BACKGROUND: Oral vancomycin therapy (OVT) induces histological remission in children with ulcerative colitis (UC) showing primary sclerosing cholangitis (PSC)-associated features (proximally dominant or patchy inflammati...BACKGROUND: Oral vancomycin therapy (OVT) induces histological remission in children with ulcerative colitis (UC) showing primary sclerosing cholangitis (PSC)-associated features (proximally dominant or patchy inflammation, backwash ileitis, or rectal sparing). However, predictors of response and optimal treatment duration remain unclear. AIM: To evaluate segmental colonoscopy outcomes across various OVT durations. METHODS: Children with active UC receiving OVT for ≥3 months were retrospectively identified. Pre-post-OVT colonoscopies were available for 38 children, 4 had repeated examination after relapsing and re-commencing OVT, totaling 42 colonoscopy pairs. RESULTS: Pre-OVT colonoscopies showed 19 proximally dominant inflammation (more severe gradient proximal to hepatic flexure), 18 pancolitis with backwash ileitis or rectal sparing, 3 patchy colitis, and 2 distal colitis. Within 5.7 (IQR 3.5-7.5) months after OVT, follow-up colonoscopy showed mucosal healing (Mayo 0) in 27/42. Pan-colonic histological remission was achieved in 23/42, more frequently in proximally dominant colitis than in other UC types (aOR 7.50, 95% CI 1.22-46.3). Remission rate was higher after ≥4 months of therapy compared with shorter durations (aOR 7.12, 95% CI 1.14-44.7). CONCLUSIONS: Over half of post‑OVT colonoscopies showed pan‑colonic histological remission, particularly in proximally dominant UC. Treating for ≥4 months further improved outcomes, helping identify which patients may benefit from OVT.
BACKGROUND: Primary risk assessment for liver fibrosis involves the Fibrosis-4 (FIB-4) index, a non-invasive test (NIT) reported to have suboptimal accuracy with lower prevalence of fibrosis, particularly at younger ages...BACKGROUND: Primary risk assessment for liver fibrosis involves the Fibrosis-4 (FIB-4) index, a non-invasive test (NIT) reported to have suboptimal accuracy with lower prevalence of fibrosis, particularly at younger ages. The LiverRisk score (LRS) is a NIT developed for general-population prediction of liver fibrosis and liver-related outcomes. AIMS: This retrospective study compared in a general-population cohort the accuracy by age groups of the LRS vs. FIB-4 for classification of LSM ≥8 and ≥10 kPa. METHODS: Analysis was conducted of the National Health and Nutrition Examination Survey (NHANES) 2017-2023 cycles. Accuracy of the LRS vs. FIB-4 for classification of LSM ≥8 kPa and ≥10 kPa was evaluated as area-under-the-curve (AUC), overall, by three age groups, and by metabolic risk factors. RESULTS: The study included N = 12,050 participants. For LSM ≥8 kPa (n = 1310), AUC (95% confidence interval) for the LRS ranged from 0.662 (0.614-0.710) at ages 18-34 to 0.711 (0.689-0.731) at ages 35-64, and for FIB-4 from 0.510 (0.462-0.559) to 0.591 (0.567-0.614) (respectively). The LRS also demonstrated improved accuracy vs. FIB-4 for LSM ≥10 kPa (n = 724) in the age groups assessed. CONCLUSION: In this general-population cohort, the LRS demonstrated greater accuracy vs. FIB-4 for LSM ≥8 and ≥10 kPa, particularly at younger ages.
Guilabert L, Maisonneuve P, Deli C
… +11 more, Bellafante D, Apadula L, Marengon I, Vanella G, Tacelli M, Dell'Anna G, Petrone MC, Mariani A, de-Madaria E, Arcidiacono PG, Capurso G
BACKGROUND: Chronic pancreatitis (CP) is a heterogeneous disease in which etiology influences presentation; however, idiopathic forms remain poorly characterized, and conventional approaches may not capture their complex...BACKGROUND: Chronic pancreatitis (CP) is a heterogeneous disease in which etiology influences presentation; however, idiopathic forms remain poorly characterized, and conventional approaches may not capture their complexity. AIMS: This study aimed to compare clinical features at diagnosis across etiologies, using unsupervised Multiple Correspondence Analysis (MCA)-based clustering to define distinct groups, focusing on idiopathic subtype. METHODS: A retrospective analysis of a prospectively maintained database of CP patients was performed. Demographics, clinical characteristics, and imaging features categorized based on the TIGAR-O classification were compared. MCA was performed to explore the underlying structure of a series of categorical variables related to CP. RESULTS: 282 patients were included. Toxic was the leading etiology (47.2%), followed by idiopathic (18.8%). Genetic patients were younger and leaner, whereas the toxic group had more men, pulmonary disease and calcifications; idiopathic cases were more often painless and incidentally diagnosed. MCA identified six clusters. Autoimmune and obstructive etiologies formed distinct clusters, while early-onset idiopathic cases (≤ 35 years) mapped near the genetic group, late-onset cases (> 35 years) were positioned between the genetic and the toxic and were characterized by painless incidental presentation. CONCLUSION: Early-onset idiopathic CP clustered near genetic CP, suggesting unidentified genetic components, whereas late-onset idiopathic CP resembled toxic CP and was characterized by painless presentation.
BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), early integration of simultaneous care plays a key role in maintaining function, improving treatment tolerance, and aligning care with patient preferences. AIMS: Th...BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), early integration of simultaneous care plays a key role in maintaining function, improving treatment tolerance, and aligning care with patient preferences. AIMS: This national survey, promoted by the Italian Association for the Study of the Pancreas (AISP), assessed current practices, barriers, and facilitators related to supportive and simultaneous care in Italian centers managing pancreatic cancer. METHODS: Between April and July 2024, a 19-item cross-sectional online survey, including a clinical vignette, was distributed to healthcare professionals involved in PDAC care. The questionnaire explored screening, counseling, and referral practices for nutrition, physical activity, and psycho-oncological support, as well as the organization of simultaneous care pathways. The vignette evaluated regret of omission and commission regarding multimodal prehabilitation (0-100 scale). RESULTS: Overall, 191 professionals responded (94.7% physicians; 65% AISP members). Although most acknowledged the value of simultaneous care, implementation was inconsistent: 70% routinely provided nutritional advice, but only 20% screened for physical activity or psychological distress. Younger clinicians showed greater awareness and readiness to integrate supportive care. Main barriers were limited funding (22%), insufficient knowledge (21%), and lack of dedicated specialists (19%). Key facilitators included supportive care experts within teams (30%) and structured training (27%). Regret of omission (median 60) exceeded regret of commission (median 10). CONCLUSIONS: Standardized simultaneous care pathways, structured education, and dedicated personnel are urgently needed to improve pancreatic cancer care in Italy.
BACKGROUND AND AIMS: Statins have been proposed as hepatoprotective agents in chronic liver disease (CLD); however, evidence from existing systematic reviews-including observational studies and clinical trials-is inconsi...BACKGROUND AND AIMS: Statins have been proposed as hepatoprotective agents in chronic liver disease (CLD); however, evidence from existing systematic reviews-including observational studies and clinical trials-is inconsistent and affected by substantial overlap. We conducted an umbrella review to synthesize the available evidence on the associations between statin use and hepatological outcomes in CLD patients, while addressing study overlap. DESIGN: PubMed, EMBASE, and Cochrane Library were searched up to September 2025 for systematic reviews of statin therapy in CLD. Methodological quality was evaluated using AMSTAR-2. Study overlap was assessed using corrected covered area (CCA) and minimized via hierarchical exclusion prioritizing methodological quality, comprehensiveness, and recency. Random-effects meta-analyses with bias assessments were conducted. RESULTS: Of 850 records screened, 17 systematic reviews (229 unique studies; 10,515,877 participants from 34 countries) were included after overlap adjustment (CCA = 5.79%). Statin therapy was associated with 46% reduction in hepatocellular carcinoma (HCC) risk (HR 0.54, 95% CI 0.48-0.59; I² = 46.7%) and 46% reduction in hepatic decompensation (HR 0.54, 95% CI 0.49-0.59; I² = 0.1%); these estimates derive predominantly from observational studies and should be interpreted as associations rather than causal effects. Geographic heterogeneity was observed: Asian populations showed stronger benefits (HCC HR 0.49, 95% CI 0.45-0.53; I² = 0%) compared with Western populations (HCC HR 0.71, 95% CI 0.52-0.96; I² = 95.7%; p = 0.003). Statin use also associated with reduced all-cause mortality (HR 0.65, 95% CI 0.52-0.81), though with substantial heterogeneity (I² = 80%). In contrast, available RCT-based evidence does not consistently confirm these associations for decompensation or mortality outcomes. CONCLUSIONS: Statin use is consistently associated with reduced HCC risk and hepatic decompensation in CLD patients, particularly in Asian populations, though these findings derive predominantly from observational evidence subject to potential confounding. These associations support the continued use of statins in patients with CLD and cardiovascular indications where these are otherwise indicated, with potential additive hepatoprotective effects. These results underscore the urgent need for adequately powered randomized trials to clarify the boundaries of safety and efficacy in this high-risk population.
Scaldaferri F, Di Vincenzo F, Falco GM
… +57 more, Lazzaro FG, Aloi M, Alivernini S, Scolieri P, Balestrieri P, Basile M, Cela E, Bianchi L, Biancone L, Bosello SL, Calabrese E, Caldarola G, Cammarota G, Capacci A, Chimenti MS, Cicala M, Cicchetti A, Conti F, Corsano B, Dattola A, De Angelis P, De Simone C, Picchianti-Diamanti A, Di Brino E, Dori N, Faggiani R, Festa S, Fiore D, Fiorino G, Galluzzo M, Laterza L, Lopetuso L, Mensurati M, Monteleone G, Natalello G, Ortolan A, Pagnanelli G, Pani M, Papa A, Pellacani G, Persechino S, Pica R, Potenza C, Pugliese D, Refolo P, Richetta A, Rumi F, Sacchini D, Giacomelli R, Sebastiani G, Spagnolo AG, Talamonti M, Zampaletta C, Petrangolini T, Peris K, D'Agostino MA, Gasbarrini A
BACKGROUND: Advanced therapies (ADTs) have transformed the management of chronic immune-mediated inflammatory diseases (IMIDs) across gastroenterology, dermatology, and rheumatology. Their growing use pressures universal...BACKGROUND: Advanced therapies (ADTs) have transformed the management of chronic immune-mediated inflammatory diseases (IMIDs) across gastroenterology, dermatology, and rheumatology. Their growing use pressures universal, regionalized systems such as the Italian National Health System, challenging sustainability, equitable access, and integration of innovation. To address these challenges, an interdisciplinary Italian consortium (Latium Net) developed consensus-based recommendations on sustainability and innovation in IMIDs care. METHODS: Three-phases: (1) targeted literature review; (2) round-table discussions involving clinicians, pharmacists, administrators, and patient-representatives, then a modified Delphi survey with iterative voting and refinement; (3) final discussion and approval (consensus: ≥80% agreement on a 5-point Likert-scale). RESULTS: After three Delphi-rounds, 31 of 37 preliminary statements achieved consensus. Recommendations addressed: cross-stakeholder responsibilities within a regional system; sustainability indicators (biosimilar uptake, persistence, hospitalization rates, PROs/PREMs, direct and indirect costs); criteria for innovation and timely drug availability; and multidisciplinary management for complex IMID patients. Emphasis was placed on biosimilar adoption in biologic-naïve patients, harmonized data collection, and mitigating regional inequalities in access to therapies, key issues in the decentralized Italian SSN. CONCLUSIONS: This consensus provides a pragmatic multidisciplinary framework to guide sustainable, innovative ADT use in IMIDs, supporting equitable access, optimized resource allocation, and long-term healthcare sustainability within regionalized health systems.
Burgess D, Collins T, Landorf E
… +12 more, Ashley-Jones S, Marks K, Brown S, Andrews A, Herbison K, King S, Liew M, Allworth S, Cram H, McGrath K, Roberts A, Pursey KM
Chronic liver disease (CLD) in children is associated with high risk of malnutrition, micronutrient deficiencies, growth failure, and poor post-transplant outcomes. Although international 2019 guidelines exist, variabili...Chronic liver disease (CLD) in children is associated with high risk of malnutrition, micronutrient deficiencies, growth failure, and poor post-transplant outcomes. Although international 2019 guidelines exist, variability in practice across Australia and New Zealand (ANZ) highlights the need for locally relevant, updated nutritional guidance. This study aimed to conduct a rapid review of recent evidence (2018-2025) on the nutritional management of paediatric CLD and develop updated consensus statements to inform a best practice nutrition pathway for ANZ. A rapid review was conducted in accordance with PRISMA guidelines. Evidence tables were developed and appraised using National Health Medical Research Council (NHMRC) guidelines. Consensus statements were derived from the evidence tables, and voted on by all AuSPEN group members. Consensus was reached at 80% agreement. Of 1260 records screened, 67 full-text articles were included in the review, resulting in 19 evidence-informed consensus statements. Key areas included: proactive use of enteral and parenteral nutrition; cautious use of medium chain triglyceride (MCT) in context of potential essential fatty acid (EFA) deficiency; use of mid upper arm circumference (MUAC) and subjective global nutritional assessment (SGNA) for assessment; monitoring of sarcopenia; targeted support during post-transplant recovery and transition to adult care. Emerging topics included sarcopenia measurement and rehabilitation, and advancements in optimal nutrition management. This rapid review highlights both alignment with and advances upon 2019 international guidelines. The consensus statements provide a framework for best practice nutritional care of children with CLD across ANZ.
BACKGROUND AND AIMS: Recent data suggest a role for the gut microbiome in the development of hepatocellular carcinoma. We investigated associations of gut microbiome abundances and concentrations of circulating bacteria-...BACKGROUND AND AIMS: Recent data suggest a role for the gut microbiome in the development of hepatocellular carcinoma. We investigated associations of gut microbiome abundances and concentrations of circulating bacteria-associated metabolites with hepatocellular carcinoma using Mendelian randomisation. METHODS: Two-sample Mendelian randomisation was conducted using summary statistics from release 11 of FinnGen (609 cases and 473,046 controls) and The North American Hepatocellular Cancer Epidemiology Consortium (1872 cases and 2907 controls). Inverse variance-weighted analyses were performed as well as several sensitivity analyses. RESULTS: In the FinnGen analyses, acetoacetate, ascorbate and asparagine were nominally associated with decreased risk. Alanine, hippuric acid and taurocholic acid were nominally associated with increased risk. The Barnesiella, Catenibacterium, Enterorhabdus and Eubacterium oxidoreducens genera were nominally associated with increased risk. Escherichia-Shigella was nominally associated with decreased risk. In the North American Hepatocellular Cancer Epidemiology Consortium analyses, the circulating bacteria-associated metabolites taurochenodeoxycholic acid and threonate were nominally associated with decreased risk. Five genera were nominally associated with increased risk; Eubacterium rectale group, Hungatella, Sellimonas and the unknown genus 1000005472. CONCLUSION: These results, based on genetically predicted gut microbiome characteristics and circulating gut bacteria-related metabolite concentrations, suggest a putative causal role in hepatic carcinogenesis.
AIMS: To evaluate the feasibility and efficacy of Laparoscopy-Assisted mesenteric vein access for portal vein recanalization-transjugular intrahepatic portosystemic shunt (LAmTIPS) in patients with symptomatic portal hyp...AIMS: To evaluate the feasibility and efficacy of Laparoscopy-Assisted mesenteric vein access for portal vein recanalization-transjugular intrahepatic portosystemic shunt (LAmTIPS) in patients with symptomatic portal hypertension and Cavernous Transformation. METHODS: A total of five patients (5 male, mean age: 41.4 years; range, 15-63 years) with chronic portal vein thrombosis (PVT) complicated by cavernous transformation of the portal vein (CTPV) were included in this study. Transjugular intrahepatic portosystemic shunt (TIPS) could not be accomplished via the conventional splenic vein-guided or intrahepatic portal vein-guided approaches in these cases, primarily attributed to intrahepatic portal vein occlusion and splenic vein thrombosis with cavernous transformation. Consequently, LAmTIPS was performed in all the 5 cases. RESULTS: LAmTIPS was successful in all patients at first attempt (4 cases via conventional laparoscopy, 1 case via robot-assisted laparoscopy). No immediate complication was observed following the procedures. Follow-up imaging with computed tomography (CT) scan and Doppler ultrasound revealed patent TIPS and portal venous vasculature in all patients. CONCLUSION: LAmTIPS is a feasible approach for patients with chronic PVT complicated by CTPV.
Gaudio AD, Calabrese E, Balestrieri P
… +15 more, Pugliese D, Fiorino G, Vincenzo FD, Marafini I, Baldaro F, Cuccia G, Cascella F, Colella A, Parisio L, Murgiano M, Laterza L, Gasbarrini A, Papa A, Lopetuso LR, Scaldaferri F
BACKGROUND: Vedolizumab has demonstrated efficacy in randomized trials on postoperative Crohn's disease; however, real-world data on both prophylaxis and treatment of recurrence are limited. METHODS: In this retrospectiv...BACKGROUND: Vedolizumab has demonstrated efficacy in randomized trials on postoperative Crohn's disease; however, real-world data on both prophylaxis and treatment of recurrence are limited. METHODS: In this retrospective multicenter study, patients with Crohn's disease treated with vedolizumab after ileocolonic resection (2018-2024) were included. Patients were stratified into a prophylaxis cohort and a recurrence-treatment cohort. Severe endoscopic recurrence (Rutgeerts ≥i3) at 6-12 months was the primary endpoint in the prophylaxis cohort. Endoscopic response (≥1-point Rutgeerts reduction) at a follow-up colonoscopy within 2 years, was evaluated in the treatment cohort. Treatment failure was defined as discontinuation of vedolizumab due to any reason. Treatment persistence was analyzed using Kaplan-Meier and multivariable Cox regression models. RESULTS: A total of 108 patients were included; 50 received vedolizumab as postoperative prophylaxis. Severe endoscopic recurrence occurred in 22% of prophylaxis patients. Prior intestinal resection (OR 5.24, 95% CI 1.03-26.61; p = 0.046) and younger age at surgery (OR 0.93, 95% CI 0.87-0.99; p = 0.042) were independently associated with severe recurrence. In the recurrence cohort (n = 58), endoscopic response was 44.8%. Overall VDZ failure occurred in 31.5%. Prophylactic use was independently associated with reduced failure (HR 0.17, 95% CI 0.05-0.53; p = 0.002). CONCLUSIONS: Vedolizumab showed sustained effectiveness for postoperative prophylaxis and more modest effectiveness in established recurrence.