AIM:to assess the effectiveness and safety of Risankizumab (RZB) in a large, nationwide real-world cohort of Crohn's disease (CD) patients. METHODS:We conducted a multicentre, retrospective observational cohort of adults initiating RZB with assessments at weeks 12, 26, and 52. Co-primary endpoints were (i) week-12 steroid-free clinical remission (SFCR) (HBI <5 in the absence of systemic corticosteroids or budesonide) and (ii) week-52 endoscopic remission (SES-CD 0-2 or Rutgeerts i0-i1 post-operatively). The main effectiveness analysis was as-observed; a preplanned sensitivity analysis included patients expected to reach week-52 before database lock and applied non-responder imputation. RESULTS:We included 520 patients, 45.0% failed ≥3 and 54.8% were ustekinumab-exposed. At week 12, clinical response was 76.5% and 60.8% achieved SFCR. By week 52, SFCR was 65.6%; endoscopic remission occurred in 37.5%, while radiologic remission and transmural healing were 24.6% and 9.8%, respectively. Ustekinumab-naïve patients showed significantly superior early clinical outcomes (week-12 SFCR: 69.8% vs 53.3%) and a higher rate of endoscopic remission at week 52 (56.5% vs 28.6%) compared with ustekinumab-exposed patients. Notably, week-52 effectiveness was comparable between patients with 2 and those with ≥3 prior failures. Extra-intestinal manifestations decreased over time, while perianal disease improved modestly. In the sensitivity cohort (N = 213), SFCR was 47% at week-52. Risankizumab was well-tolerated with no new safety signals identified. CONCLUSIONS:In a large, refractory, real-world CD population, RZB induced rapid and sustained favorable clinical, endoscopic, and radiologic outcomes. Importantly, one-year effectiveness was similar in patients with 2, and ≥3 prior failures, supporting RZB as a valuable option for a refractory population.

Objective To evaluate the effectiveness and safety of mirikizumab in patients with ulcerative colitis in clinical practice.Methods We conducted a retrospective, multicenter cohort study across five Italian inflammatory bowel disease centers. Patients initiating mirikizumab between November 2024 and May 2025 were included. The primary endpoint was steroid-free clinical remission (SFCR) at 12 weeks, defined as the absence of rectal bleeding and near-normal stool frequency without corticosteroids. Secondary outcomes included clinical response (≥30% improvement in stool frequency and rectal bleeding), biochemical response (normalisation of fecal calprotectin (FCP) and C-reactive protein (CRP)), and safety (any adverse events). Follow-up at 24 weeks was assessed when available. Subgroup analyses were performed according to prior exposure to biologics (including ustekinumab) and induction regimen.Results A total of 95 patients were included (mean age 49.9±16.9 years; 50.5% male); 12.6% were biologic naïve and 17 (17.9%) received extended induction. At week 12, 43.2% of patients (41/95) achieved SFCR, 61.1% (58/95) clinical response, and 32/95 (33.7%) biochemical remission. SFCR rates were similar between biologic-naïve and biologic-experienced patients (42.6% vs 43.8%, p=0.906). SFCR rates were 36.2% and 88.2% in patients receiving extended and standard induction, respectively (p=0.002). At week 24, prior ustekinumab exposure was associated with numerically lower SFCR, although this difference was not statistically significant (38.5% vs 73.7%; OR=0.22, 95% CI 0.05 to 1.01, p=0.052). Changes in biomarkers were not statistically significant at week 12 (CRP Δ−0.08 mg/dL, p=0.464; FCP Δ−249 µg/g, p=0.127). Three patients discontinued treatment due to lack of efficacy. No adverse events were observed.Conclusion Mirikizumab demonstrated meaningful clinical effectiveness and a favourable safety profile in a real-world setting, including in biologic-experienced patients.

BACKGROUND:Proton pump inhibitors (PPIs) are widely used for upper gastrointestinal symptoms but are frequently prescribed inappropriately and often continued without clear indications. Deprescribing PPIs can be challenging due to symptom recurrence or rebound acid hypersecretion. The mucosal protective agent Poliprotect, a natural formulation with barrier, antioxidant, and anti-inflammatory properties, has shown non-inferiority to omeprazole in non-erosive heartburn and epigastric pain syndrome (EPS) without affecting intestinal microbiota. AIM:To evaluate the role of Poliprotect formulation (neoBianacid) in maintaining symptom control after PPI withdrawal in patients with endoscopy-negative heartburn (HRTB) and EPS. METHODS:This post hoc analysis used data from a multicenter, double-blind RCT including 125 endoscopy-negative patients (80 with HRTB, 45 with EPS) treated with omeprazole 20 mg/day for 4 weeks, followed by 4 weeks of on-demand Poliprotect after PPI discontinuation. Outcomes included symptom severity (VAS), responder rate (≥ 50% VAS reduction), use of rescue medication, quality of life (GIQLI), gastrointestinal symptoms (GSRS), treatment satisfaction, and safety. RESULTS:At the end of deprescription, mean VAS scores remained stable, and 69.5% of PPI responders (65.8%, HRTB, and 76.2%, EPS) maintained symptom control. Additionally, 31% of PPI non-responders (33.3%, HRTB, and 27.3%, EPS) became responders with Poliprotect. Rescue antacid use and quality of life scores were not significantly changed. No adverse events were reported during the deprescribing phase. CONCLUSIONS:On-demand Poliprotect was associated with maintenance of symptom control after PPI withdrawal and outcome improvement in approximately one-third of PPI non-responders. Poliprotect appears to be a safe, well-tolerated, and promising strategy to support PPI discontinuation in endoscopy-negative heartburn and EPS patients. TRIAL REGISTRATION:Clinicaltrial.gov (NCT03238534) and EudraCT Database (2015-005216-15).

The biliary tract, long considered a sterile environment, is now recognized to harbor a resident microbiota with important implications for health and disease. This review aims to summarize current knowledge on the composition and function of the biliary microbiota in physiological conditions, and its alterations in pathological states such as infection and lithiasis, with a particular focus on antimicrobial resistance. In healthy individuals, the biliary microbiota appears to be shaped by bile acids and gut-bile axis interactions, playing a role in local immune modulation. In disease, microbial dysbiosis contributes to conditions such as acute cholecystitis, cholangitis, and gallstone formation, with distinct microbial signatures linked to specific stone types. Common biliary pathogens, including E. coli, Enterococcus spp., Pseudomonas spp., and K. pneumoniae, often exhibit concerning resistance patterns, impacting therapeutic strategies. Emerging evidence highlights the interplay between intestinal and biliary microbiota, suggesting potential diagnostic and prognostic applications. Understanding these dynamics opens new avenues for microbiota-informed antibiotic stewardship, targeted microbiota modulation, and precision medicine approaches. Further research, particularly culture-independent and longitudinal studies, is crucial to fully elucidate the clinical significance of the biliary microbiota and to integrate microbiota profiling into patient management strategies.

Background Frailty is a multidimensional syndrome associated with poor outcomes and increased vulnerability, yet its assessment in inflammatory bowel diseases (IBD) remains challenging due to the absence of disease-specific tools. Aims This study aimed to develop and validate the IBD Frailty Score, a tailored instrument for evaluating frailty in patients with Crohn disease (CD) and ulcerative colitis (UC). Methods In the development phase, 28 categorical items were included in the IBD Frailty Score. This tool was tested in an exploratory cohort of 121 IBD outpatients and later validated in a prospective multicenter cohort of 512 patients across four tertiary centers. Predictive factors of frailty were identified through univariate and multivariate analyses. Results The IBD Frailty Score was feasible, with an average administration time of ∼2 minutes. It correlated positively with the Fried Frailty Phenotype, IBD Disability Index, and Charlson Comorbidity Index and showed good reproducibility (rho = 0.78) and strong diagnostic accuracy (AUC = 0.79). A cut-off score of 4 reliably distinguished fit from frail patients. Increasing age, polypharmacy, history of extraintestinal manifestations, and higher disease activity were independent risk factors for frailty. Conclusions The IBD Frailty Score is the first validated, disease-specific tool for assessing frailty in IBD. It is practical, reproducible, and correlates well with established measures.

BACKGROUND & AIMS:Persistent symptoms, despite proton pump inhibitor therapy, are common in patients with gastroesophageal reflux disease. The Lyon Consensus 2.0 provides an objective diagnostic framework, but factors associated with proton pump inhibitor nonresponse across gastroesophageal reflux disease phenotypes remain incompletely defined. The aim of this study was to assess the association between anxiety severity and proton pump inhibitor response across gastroesophageal reflux disease phenotypes defined by the Lyon 2.0 classification. METHODS:We analyzed 204 consecutive patients undergoing off-therapy pH impedance monitoring and anxiety assessment using the Hamilton Anxiety Rating Scale. Patients were classified according to Lyon 2.0 criteria. Multivariable logistic regression and receiver operating characteristic analyses were performed. RESULTS:Proton pump inhibitor response rates progressively declined from conclusive gastroesophageal reflux disease (70.2%) to inconclusive gastroesophageal reflux disease with supportive evidence (53.3%), inconclusive gastroesophageal reflux disease without supportive evidence (31.6%), and no gastroesophageal reflux disease (30.8%) (P < .001). Nonresponders showed significantly higher anxiety scores than responders (20.9 ± 9.8 vs 13.4 ± 6.3; P < .001). Anxiety was significantly associated with proton pump inhibitor nonresponse in patients with inconclusive gastroesophageal reflux disease with supportive evidence (odds ratio, 1.14 per 1-point Hamilton Anxiety Rating Scale increase; P = .004) and in patients with no gastroesophageal reflux disease (odds ratio, 1.22; P < .001), but not in patients with conclusive gastroesophageal reflux disease. Increasing anxiety severity was associated with a marked reduction in response rates (59.0% mild, 20.5% moderate, 7.7% severe; P < .001). The Hamilton Anxiety Rating Scale demonstrated good discrimination for proton pump inhibitor nonresponse (area under the curve = 0.73 overall), with highest performance observed in patients with no gastroesophageal reflux disease (area under the curve = 0.78). CONCLUSIONS:Anxiety is significantly associated with proton pump inhibitor refractoriness, particularly in patients with no gastroesophageal reflux disease. Integrating anxiety evaluation into the diagnostic framework may contribute in both optimizing therapeutic strategies and reducing inappropriate proton pump inhibitor use, although its role in managing treatment strategies requires confirmation in prospective studies.

INTRODUCTION:Acid exposure time (AET) is the reference metric quantifying esophageal acid burden, yet patients with pathological AET may fail to respond to proton pump inhibitor (PPI) therapy. Given the logarithmic nature of pH, AET does not account for the exponential increase in hydrogen ion (H + ) concentration at lower pH values. Aim: To quantify acid burden using total integrated acidity exposure (TIAE), a dose-based metric integrating H + load over time, and to assess whether TIAE improves prediction of PPI response compared with conventional AET. METHODS:Impedance-pH data were retrospectively evaluated. TIAE was calculated by integrating H + concentration (10 -pH ) at 1 second resolution across all acid reflux episodes. Diagnostic performance for PPI response was assessed using Receiver operating characteristic analysis, multivariable logistic regression and decision curve analysis. RESULTS:Among 174 patients (97 PPI responders, 77 nonresponders), responders exhibited higher TIAE than nonresponders and controls ( P < 0.0001). TIAE showed superior discrimination for PPI response compared with AET (area under the receiver operating characteristic curve 0.78 vs 0.64). In multivariable models, TIAE independently predicted response both as a dichotomized and continuous variable, whereas continuous AET was not independently associated. TIAE correlated more strongly with mean nocturnal baseline impedance than AET (ρ = -0.49 vs -0.26). Decision curve analysis demonstrated greater net clinical benefit for models incorporating TIAE across clinically relevant threshold probabilities. In patients with inconclusive AET (4%-6%), TIAE accurately segregated responders from nonresponders. Very low pH (pH < 2) greatly affected TIAE value and showed the strongest association with treatment response. DISCUSSION:Quantifying H + load provides a physiologically grounded assessment of esophageal acid burden and improves prediction of PPI response.

Obesity is a multifactorial disease linked to chronic inflammation, metabolic disorders, and gut microbiota dysbiosis. Bariatric surgery (BS) and endoscopic sleeve gastroplasty (ESG) are effective for sustained weight loss and comorbidity improvement but may cause gastrointestinal and nutritional complications. This narrative review, informed by a structured literature search, synthesizes evidence on gastrointestinal side effects, gut microbiota alterations, and nutritional management after BS and ESG. Literature searches in PubMed and Scopus, without time limits, included English full-text articles on postoperative symptoms, microbiota changes, and nutritional outcomes. Bariatric procedures (e.g., Roux-en-Y gastric bypass, sleeve gastrectomy) and ESG are associated with adverse events such as dumping syndrome, GERD, nausea, and micronutrient deficiencies. Surgery induces profound shifts in gut microbiota composition and diversity, contributing to improved metabolic regulation. ESG, though less invasive, produces comparable microbial changes with a favorable safety profile. Nutritional management-progressive diet protocols and supplementation-is critical for preventing deficiencies and sustaining outcomes. Mediterranean-style diets appear more sustainable than high-protein regimens. Study heterogeneity, small cohorts, and limited long-term ESG follow-up reduce generalizability. Multidisciplinary care integrating surgical or endoscopic approaches with personalized nutrition and microbiota modulation is essential to optimize outcomes in obesity management.