BACKGROUND & AIMS:With the advent of agents targeting distinct inflammatory pathways, therapeutic sequencing after anti-tumor necrosis factor alpha (TNF-α) failure in ulcerative colitis (UC) represents a major challenge. We compared the real-world effectiveness and safety of vedolizumab, ustekinumab, and Janus kinase inhibitors (JAKis) in anti-TNF-α-exposed patients. METHODS:In this retrospective, multicenter European study, adults with UC initiating second-line vedolizumab, ustekinumab, or a JAKi after anti-TNF-α were evaluated. Baseline confounding was addressed by applying energy balancing weights (EBWs). Effectiveness outcomes included probability of steroid-free clinical remission (SFCR) and biochemical SFCR at 12 months, analyzed using EBW-weighted Royston-Parmar survival models to derive adjusted time-averaged hazard ratios (aHRs). Adverse event (AE) rates were compared using EBW-weighted Poisson regression. RESULTS:A total of 596 patients were included (301 vedolizumab, 149 ustekinumab, 146 JAKi); 54.7% were male, with a mean age of 43.9 ± 15.5 years. Clinical activity, endoscopic scores, and biomarker levels were broadly comparable across treatment groups. Infliximab was the most common prior anti-TNF-α (74.8%), and secondary failure was the predominant discontinuation reason (47.3%). Compared with vedolizumab, both ustekinumab and JAKi showed significantly higher probability of SFCR (aHR, 1.54; 95% confidence interval [CI], 1.09-2.07; and aHR, 1.66; 95% CI, 1.07-2.53, respectively) and biochemical SFCR (aHR, 2.26; 95% CI, 1.48-3.28 and 3.37; 95% CI, 2.01-5.36, respectively) at 12 months, with no differences between them. JAKi recipients experienced an approximately 4-fold higher incidence of AEs, compared with both vedolizumab and ustekinumab, with no differences between ustekinumab and vedolizumab. CONCLUSIONS:Ustekinumab and JAKi were more effective than vedolizumab in inducing steroid-free and biochemical remission following anti-TNF-α failure. Safety concerns with JAKi warrant careful patient selection in clinical practice. CLINICALTRIALS:gov, Number: NCT06691061.

BACKGROUND AND AIMS:Upadacitinib is an oral selective JAK1 inhibitor approved for moderate-to-severe Crohn's disease (CD), but real-world prospective multicentre data in advanced therapy-experienced (AT-experienced) patients are limited. The UPGRADE-CD study evaluated its effectiveness and safety. METHODS:In this prospective, multicentre, observational study across 38 Italian centres, we enrolled consecutive AT-experienced CD patients initiating upadacitinib. Effectiveness was assessed at weeks 12 and 24, including clinical response (HBI reduction ≥ 3) and remission (HBI ≤ 4), steroid-free counterparts, biomarker normalisation, resolution of extraintestinal manifestations (EIMs) and endoscopic outcomes. Safety was assessed in all patients receiving ≥ 1 dose. RESULTS:A total of 391 patients were included in the safety analysis and 323 in the efficacy analysis; 48% had failed more than two advanced therapies. Clinical remission reached 51.2% at Week 12 and 54.7% at Week 24 (p = 0.07). Steroid-free clinical response rose from 53.8% to 63.5% (p = 0.09). Active EIMs, present in 39.9% at baseline, resolved completely in 65.7% by Week 24. Higher baseline HBI was the strongest predictor of failure to achieve remission. Discontinuation by Week 24 was 11.3%, mainly from treatment failure (7.2%) and adverse events (3.1%). No major cardiovascular, thromboembolic events or malignancies occurred. CONCLUSIONS:Upadacitinib was effective and well-tolerated in AT-experienced CD, including patients with active EIMs, with induction benefit maintained through 6 months without novel safety signals.

Ulcerative colitis is a chronic inflammatory bowel disease with rising global prevalence. Despite therapeutic advances including biologic agents targeting tumor necrosis factor-alpha, integrins, and interleukin pathways, alongside Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators, substantial unmet needs persist in moderate to severe disease. Current advanced therapies achieve clinical response rates of only 30-60% in trials, with approximately 20% of patients requiring hospitalization and 7% undergoing colectomy within five years of diagnosis. The therapeutic pipeline for moderate to severe ulcerative colitis currently encompasses over 100 investigational agents in Phase II and III clinical development. Emerging mechanisms include next-generation Janus kinase and tyrosine kinase 2 inhibitors with enhanced selectivity, novel cell trafficking modulators, advanced tumor necrosis factor-alpha inhibition strategies, and selective interleukin-23 pathway antagonists. Tumor necrosis factor-like ligand 1A pathway inhibitors demonstrate particularly robust efficacy in early trials, with clinical remission rates exceeding 25% compared to less than 2% for placebo. Additional promising approaches target immune checkpoint pathways, receptor-interacting protein kinase 1, and intracellular signaling cascades. innovative combination therapy approaches demonstrated to achieve superior response rates compared to monotherapy. The convergence of novel therapeutic targets, gut-selective compounds minimizing systemic immunosuppression, and biomarker-guided therapy selection represents a paradigm shift toward precision medicine. These advances hold genuine promise for transforming moderate to severe ulcerative colitis management.

BACKGROUND & AIMS:Controlled real-world evidence on nonmedical switching from reference ustekinumab to biosimilars in Crohn's disease (CD) is limited. We compared 6-month outcomes after switching versus continued reference treatment. METHODS:In this prospective observational cohort at 18 Italian centers, adults with CD in clinical remission (Harvey-Bradshaw Index <5), steroid-free for ≥8 months of reference ustekinumab, underwent a procurement-driven switch to 1 of 3 approved biosimilars or continued reference treatment. The expanded clinical-success endpoint required clinical remission without systemic corticosteroids, anti-interleukin-12/23 discontinuation, inflammatory bowel disease-related hospitalization, or intestinal surgery. The protocol-specified noninferiority margin was -15%. RESULTS:Among 462 patients, 337 switched and 125 continued reference ustekinumab; only 4 (0.9%) received every-4-week dosing. Expanded clinical success occurred in 306 of 332 switched patients (92.2%) and 114 of 123 controls (92.7%; risk difference, -0.5%, 95% CI -5.9 to 4.9), meeting the noninferiority criterion. Results were consistent for the protocol-defined three-component composite and after propensity-score weighting. Biosimilar persistence was 93.7%; switch-back occurred in 1.2%. Two adverse events were reported after switching. CONCLUSIONS:In clinically stable CD, observed 6-month effectiveness and safety after procurement-driven ustekinumab biosimilar switching were similar to continued reference treatment. Longer-term studies, particularly in patients receiving every-4-week dosing, are needed.

Crohn’s disease (CD) is a chronic, relapsing inflammatory disorder often resistant to therapies. While upadacitinib (UPA) has shown promise in registration trials, real-world data are scarce. UPGRADE-CD study, promoted by IG-IBD, was designed to assess UPA effectiveness and safety in refractory CD. This is a preliminary analysis of a prospective, multicenter, observational study enrolling consecutive adults patients with refractory CD from Italian referral centers. Patients were treated with UPA and evaluated with standardized clinical (Harvey-Bradshaw Index, HBI), endoscopic (Simple Endoscopic Score for Crohn’s Disease, SES-CD), and biochemical [C-Reactive Protein (CRP), fecal calprotectin] parameters at baseline, 3, and 6 months; 12-month follow-up data collection is still ongoing. Primary endpoints: clinical response (HBI decrease ≥3), clinical remission (HBI < 5), and their steroid-free equivalents. Secondary endpoints were endoscopic improvement (≥50% SES-CD reduction or ≥ 2-point drop if baseline SES-CD = 4) and endoscopic remission (SES-CD ≤ ssss2). Dropouts were counted as non-responders from discontinuation onward, and missing data excluded. Analyses were performed using R software. Overall, 309 patients were included. Demographics characteristics are reported in Table 1. Clinical response rates remained high at 3 and 6 months (58.3% and 62.1%, p < 0.001). Clinical remission showed similar proportions (54.7%, 57.5% p < 0.001). Steroid-free clinical response was achieved in 52.5% at 3 months and 51.1% at 6 months, whereas steroid-free clinical remission rates were 47.9% and 46.6% at 3 and 6 months, respectively. Endoscopic improvement increased over time from 20.0% at 3 months to 43.5% at 6 months (p < 0.001), with endoscopic remission occurring in 40.1% of patients at 6 months (p < 0.01). Mean fecal calprotectin remained above normal but trended lower (from 986.7± 1619.9 at baseline to 362.0 ± 743.3 at 6 months, p < 0.001). Mean CRP levels declined significantly over time (from 62.3±197.4 mg/L at baseline to 17.1±37.2 mg/L at 6 months, p < 0.001). UPA was discontinued in 18 patients by month 3 and 21 patients by 6 months due to inefficacy or adverse events (6/18 and 7/21 at 3 and 6 months, respectively). In this preliminary real-world analysis, UPA induced high clinical and steroid-free remission rates and improved endoscopic outcomes over 6 months in refractory CD, with a favorable safety profile and low discontinuation rates. Extended follow-up will clarify long-term effectiveness and safety. Conflict of interest: Barberio, Brigida: Brigida Barberio: has served as speaker for Abbvie, Agave, Alfasigma, AGpharma, Johnson & Johnson, Eli Lilly, MSD, Pfizer, Procise, Sofar, Takeda, Unifarco. BB has served as consultant for Abbvie, Eli Lilly, ohnson & Johnson. Scaldaferri, Franco: Consultancy fee/board for Janseen, Takeda, Pfizer, MSD, Sandoz, Galapagos, Celltrion, Ferring, Abbvie, Lilly, Alfasigma, Abivax Bezzio, Cristina: Personal Fees: I received consulting/advisory board/lecture fees from Alfa Sigma, AbbVie, Celltrion, Eli Lilly, Ferring, Gilead, Johnson & Johnson MSD, Pfizer and Takeda Dragoni, Gabriele: Grant: ECCO Grant 2020 ECCO/AOCC Travel Grant 2021 ECCO IIS Registry Grant 2023 ECCO/IBUS Research Grant 2023 Personal Fees: - Speaker’s fees from: 2020: Novartis 2022: Janssen 2023: Alfasigma, Janssen, Pfizer, and Takeda 2024: Ferring, Johnson & Johnson, Eli Lilly, Pfizer, and Takeda 2025: Abbvie, Alfasigma, Ferring, Eli Lilly, LionHealth, Pfizer, Takeda - Advisory board fees from: 2023: Celltrion Healthcare and Pfizer 2024: AbbVie 2025: AbbVie, Johnson & Johnson Viola, Anna: No conflict of interest Todeschini, Alessia: The author has served as a consultant and/or received lecture fees from Abbvie, Alfasigma, Celltrion, Johnson & Johnson, Ely Lilly, Ferring, Lion Health,Takeda. Principi, Maria Beatrice: No conflict of interest Onali, Sara: Consultant/lecture fees to: Abbvie, Alfasigma, MSD, Takeda, J & J, Galapagos, Pfizer, Eli Lilly D’Amico, Ferdinando: Grant: ECCO fellowship grant 2020 ECCO grant 2021 Personal Fees: F D’Amico has served as a speaker for Abbvie, Alfasigma, Ferring, Lilly, Sandoz, Janssen, Fresenius Kabi, Galapagos, Giuliani, MSD, Pfizer, Takeda, Tillotts, and Omega Pharma he also served as an advisory board member for Abbvie, AnaptysBio, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Takeda, and Nestlè. Viganò, Chiara: Consultancy and lecture fees from: AbbVie, Galapagos, Janssen-Cilag, Johnson & Johnson, Pfizer, Takeda, Celltrion, Alfasigma, Eli Lilly and research grant from Celltrion and Pfizer. Cappello, Maria: None Mocci, Giammarco: No conflict of interest Viscido, Angelo: none Bodini, Giorgia: No conflict of interest Ribaldone, Davide Giuseppe: Davide Giuseppe Ribaldone declares the following paid consultancies, lecture fees for the past two years: Johnson & Johnson, Takeda, Celltrion, Alfasigma, Pfizer, Eli Lilly, Abbvie, Sandoz Marafini, Irene: Irene Marafini served as advisory board member for Abbvie, Eli Lilly, Galapagos and received speaker honoraria from Abbvie and Eli Lilly Pugliese, Daniela: Consultant/Lectures fees from: AbbVie, Takeda, Johnson, Pfizer, Alfasigma, MSD, Lilly, Celltrion. Massari, Alessandro: No conflict of interest Saibeni, Simone: Consultancy, lecture fees, and advisory board for AbbVie, Alfasigma, Arena, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, Johnson & Johnson, MSD, Pfizer, and Takeda. Pastorelli, Luca: Luca Pastorelli served as consultant for Giuliani, received lecture fees and/or advisory board fees from Abbvie, Takeda, Ferring, Pfizer, Sandoz, Janssen, Johnson & Johnson, Galapagos, Arena, Eli-Lilly Rizzello, Fernando: No conflict of interest Bergna, Irene Maria Bambina: None Gravina, Antonietta Gerarda: Gravina AG has conducted training activities [e.g. educational continuing medical activities (ECM), preceptorship] for Pfizer, Galapagos Biopharma, and AbbVie. Desideri, Federico: No conflict of interest Merli, Manuela: No conflict of interest Bertani, Lorenzo: No conflict of interest Spagnuolo, Rocco: no Imperatore, Nicola: None to declare Ferracane, Concetta: nothing to declare Quadarella, Alessandro: I have no conflict of interest. Di Luna, Imma: No conflict of interest Tortorella, Vincenza: Nessuno Mazzuoli, Silvia: No conflict of interest Felice, Carla: Advisory board for AbbVie, MSD, J & J. Balestrieri, Paola: Advisory board for Alfasigma- Janssen- Abbvie- Takeda- Eli Lilly Balducci, Daniele: none Aratari, Annalisa: Consultant or Advisory board member (in the last two years) for Takeda,Abbvie,Pfizer,Galapagos De Barba, Caterina: No conflict of interest Zingone, Fabiana: No conflict of interest Savarino, Edoardo Vincenzo: Personal Fees: Takeda, Abbvie, MSD, Janssen, Sofar

BACKGROUND:Spirituality may influence coping and quality of life in inflammatory bowel disease (IBD), yet spiritual needs are rarely assessed systematically in routine care. The Spiritual Needs Questionnaire - Extended Version (SpNQ-EV) and the Interpretation of Illness Questionnaire (IIQ) explore spiritual needs and illness meanings but require cross-cultural adaptation and content validation for use in the Italian IBD context. METHODS:This protocol describes a qualitative questionnaire validation study using think-aloud cognitive interviews. Purposive sampling with planned heterogeneity and saturation-based stopping will be used to recruit adult IBD patients and healthcare professionals from two Italian IBD outpatient centers. Participants will complete the Italian versions of the questionnaires while verbalizing their thoughts, followed by retrospective probing guided by Tourangeau's cognitive model and a brief debriefing. Interviews will be audio-recorded, anonymized, and analyzed item-by-item in a matrix using predefined problem codes complemented by inductive coding. Inter-coder reliability will be assessed on a subset of transcripts; AI-assisted coding will be explored using de-identified text under human oversight. RESULTS:As this manuscript represents a research protocol, no empirical results have been generated at this stage. This protocol describes a structured approach to evaluating the content validity of two questionnaires, emphasizing transparency in translation, cognitive testing, and item-revision decision rules. The combined use of concurrent think-aloud and retrospective probing will enable observation of real-time cognitive processes and clarification of ambiguous responses. The inclusion of both patients and healthcare professionals will provide complementary perspectives. The exploratory use of AI-assisted coding may offer efficiencies for segment classification in large item-by-item matrices. CONCLUSIONS:Rigorously adapted and content-validated Italian versions of the SpNQ-EV and IIQ may support both research and clinical practice by providing a shared language for exploring existential and spiritual dimensions of living with IBD, supporting future psychometric validation and implementation of spiritual and interpretation of illness assessment.

BACKGROUND:Primary intestinal B-cell (IBCL) and T-cell (ITCL) lymphomas are rare and poorly characterized entities. AIM:To compare clinical features and survival outcomes of IBCL and ITCL. METHODS:We conducted a multicentre, retrospective study including patients diagnosed with primary intestinal lymphoma between 2001 and 2024. Clinical and laboratory variables were analysed using univariate and multivariate logistic regression. Discriminatory accuracy was assessed through ROC analysis. Overall survival was estimated with Kaplan-Meier curves. RESULTS:Ninety-four patients (41 IBCL and 53 ITCL) were included. IBCL were more frequently diagnosed at Lugano stage I (90% vs 5.7%; p<0.01) and showed markedly lower lactate dehydrogenase and β2-microglobulin levels compared with ITCL (p<0.01). Coeliac disease (CD) was strongly associated with ITCL (p<0.01). In multivariable analysis, CD and biomarker levels independently differentiated IBCL from ITCL, with excellent model discrimination (AUROC 0.95). Median follow-up was 56 months for IBCL and 12 months for ITCL. IBCL demonstrated significantly greater survival (HR 0.21; log-rank p=0.01). CONCLUSIONS:IBCL and ITCL exhibit distinct clinical and prognostic profiles, with IBCL showing more favourable clinical profile and better survival. Tailored diagnostic and therapeutic approaches that reflect the divergent behaviour of these lymphomas are urgently needed.

Inflammatory bowel diseases, comprising Crohn’s disease and ulcerative colitis, represent chronic inflammatory disorders with rising global incidence, underscoring the pivotal role of modifiable environmental factors in disease pathogenesis. Diet and intestinal microbiota have emerged as critical bidirectional therapeutic targets through complex interactions with host immune responses. Epidemiological evidence demonstrates that healthy and high fiber diets reduce disease risk, while ultra-processed foods and inflammatory dietary patterns increase susceptibility. Therapeutic nutritional interventions, including exclusive enteral nutrition, the Crohn’s Disease Exclusion Diet combined with partial enteral nutrition, and the Mediterranean diet can induce and maintain clinical remission while promoting favorable microbiome modifications characterized by the enrichment of butyrate-producing taxa such as Faecalibacterium prausnitzii and Roseburia species, alongside a reduction in pathogenic Proteobacteria. Micronutrient deficiencies affect up to 78% of patients through malabsorption, chronic blood losses, dietary restrictions, and drug–nutrient interactions. Nutritional status significantly impacts surgical outcomes, with preoperative malnutrition and sarcopenia associated with increased postoperative complications, and it reciprocally influences biologic therapy response. Integration of personalized, microbiome-informed dietary strategies as complementary components of comprehensive treatment plans represents a promising therapeutic frontier, requiring multidisciplinary collaboration, rigorous clinical trials with standardized microbiome analyses, and precision nutrition algorithms accounting for disease phenotype, baseline microbial composition, and individual patient characteristics to optimize outcomes and improve quality of life.

Dermatitis herpetiformis (DH) shares a pathophysiological basis with celiac disease (CD), but its epidemiology remains poorly defined. This systematic review and meta-analysis estimated the prevalence of DH among CD patients. Following the PRISMA 2020 guidelines, PubMed, Embase, Web of Science, and Scopus were searched. Observational studies with extractable DH data in CD patients were pooled using a random-effects model, with subgroup and meta-regression analyses. The risk of bias was assessed using the JBI Checklist. Of 7271 records, 24 studies published between 1996 and 2023, comprising 73,905 patients with celiac disease and 2203 DH cases (crude prevalence: 3.0%), met the inclusion criteria. Pooled DH prevalence in CD was 6.8% (95% CI: 5.0-9.3). When restricting the analysis to nonselected populations, the pooled prevalence was 6.7% (95% CI: 4.7-9.6). Prevalence was lower in pediatric CD (2.6%, 1.4-4.5) than in adults (8.6%, 5.8-12.6). Gender-specific prevalence, based on 5 of the 24 studies and not directly comparable with the overall estimate, was 12.9% (7.0-22.7) in males and 9.6% (3.7-22.9) in females. Sensitivity analyses yielded comparable estimates across all models (range: 6%-9%), indicating that the results were consistent across different methodological assumptions and not driven by specific study characteristics. Given the very high heterogeneity (I2 = 98.9%), the pooled estimate should be interpreted as an average across diverse settings rather than a single generalizable figure. These findings emphasize the need for standardized diagnostic approaches and more consistent reporting in clinical settings. TRIAL REGISTRATION: PROSPERO (CRD42023444060).

Background and aimsValidated biomarkers of biologic response in Crohn’s disease (CD) are lacking. We assessed whether serum microRNAs (miRNAs) track disease activity and predict outcomes during biologic induction in CD.MethodsThirty-nine adults with active CD initiating infliximab (n = 20) or vedolizumab (n = 19) and 10 controls were studied at a single centre. Serum was sampled at the first and fourth infusions. Six target miRNAs were qPCR-quantified and normalised to the geometric mean of miR-93-5p and miR-425-5p. Harvey–Bradshaw Index, C-reactive protein, faecal calprotectin and Simple Endoscopic Score for CD were recorded at baseline, post-induction and 12 months. Four pre-specified analysis families were tested with false discovery rate (FDR) correction for multiple testing. This was a single-centre, exploratory, hypothesis-generating study.ResultsmiR-21-5p and miR-146b-5p were significantly reduced in CD versus controls (q < 0.05). Baseline miR-146b-5p inversely predicted post-induction CRP independently of baseline disease severity (partial r = −0.46, p = 0.010), supporting it as a candidate severity-independent predictor of biochemical response. Post-induction miR-424-5p strongly tracked concurrent inflammation (faecal calprotectin: Spearman ρ = +0.52, q = 0.004; CRP: ρ = +0.44, q = 0.030), these associations remained significant after adjustment for baseline disease severity, after leave-one-out removal of single patients, and under single-reference normalisation. An exploratory post-hoc analysis linked treatment-induced miR-106a-5p upregulation to penetrating (Montreal B3) disease (permutation p = 0.019).ConclusionSerum miRNAs offer novel predictive (baseline miR-146b-5p and miR-106a-5p) and concurrent (post-induction miR-424-5p) biomarker signals during biologic induction in CD, providing information complementary to faecal calprotectin. Prospective independent validation is warranted before clinical translation.

Purpose of reviewTraditional approaches to irritable bowel syndrome with diarrhea (IBS-D) relied on extensive exclusionary testing and empiric symptom management. Recent advances in understanding neuroimmune pathophysiology, refined diagnostic algorithms, emergence of novel biomarkers, and clarification of comparative treatment efficacy through systematic reviews necessitate evaluation of whether accumulated evidence warrants substantive changes to contemporary diagnostic and therapeutic practice in IBS-D management.Recent findingsDiagnostic paradigms have shifted toward symptom-based approaches utilizing judicious testing informed by alarm features, with emerging biomarkers including neutrophil-to-albumin ratio, microRNA-148, and bile acid malabsorption markers showing promise. Therapeutically, tricyclic antidepressants demonstrate robust efficacy as neuromodulators, while selective serotonin reuptake inhibitors show limited benefit. Emerging neuroimmune therapies targeting mast cell activation, including histamine receptor antagonists, represent promising avenues. Low FODMAP and Mediterranean diets demonstrate substantial efficacy, while brain-gut behavioral therapies achieve clinically meaningful improvements in refractory populations through accessible delivery modalities.SummaryContemporary evidence supports fundamental practice shifts from exclusionary testing toward targeted investigation of treatable mimics and from empiric management toward mechanism-based multimodal interventions integrating neuromodulators, dietary modifications, and behavioral therapies. Optimal outcomes require individualized treatment selection informed by symptom phenotype and comorbidity profiles, ideally delivered through integrated care models combining gastroenterology, dietetic, and behavioral expertise.

Short bowel syndrome (SBS) is the leading cause of chronic intestinal failure in adults, arising when the residual small bowel can no longer absorb the macronutrients, water and electrolytes needed to sustain health without intravenous supplementation. Its management is, at its core, a nutritional problem. This review synthesises current evidence and guideline recommendations on the two pillars of that management: dietary (oral/enteral) therapy and parenteral nutritional support. We frame both around the two variables that dominate clinical behaviour, namely residual intestinal anatomy and the phase of intestinal adaptation, and translate them into anatomy-tailored dietary strategies, rational fluid and electrolyte replacement, micronutrient surveillance, and the composition, delivery and complications of (home) parenteral nutrition. We also position the pharmacological adjuncts, culminating in glucagon-like peptide-2 (GLP-2) analogues, within a stepwise strategy to reduce parenteral-support dependence. The goal throughout is a practical, physiology-anchored approach that maximises enteral autonomy and quality of life while preventing the metabolic, hepatic and catheter-related complications of long-term intravenous feeding.

Introduction: Since the publication of the first European Society for the Study of Coeliac Disease (ESsCD) guidelines in 2019, substantial advances have been made in understanding the management and complex disease courses of coeliac disease (CeD) in adults. These 2025 updated guidelines aim to integrate new evidence, refine management strategies, and promote a personalised and multidisciplinary approach to care. Methods: The ESsCD convened a multidisciplinary panel of experts to revise the 2019 guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) framework. Evidence was appraised and graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Statements and recommendations were draughted within working groups and finalised through a structured Delphi consensus process. Results: The updated guidelines are presented in two parts. Part 1, which has already been published, addresses the diagnostic approach to CeD in adults, whereas Part 2 focuses on disease management, structured follow-up, and the evaluation and treatment of persistent symptoms despite a gluten-free diet or refractory disease. New or expanded sections include guidance on the safe inclusion of oats, use of low-FODMAP diets in patients with persistent symptoms, management of exocrine pancreatic insufficiency, recognition of functional asplenia and related vaccination recommendations, and stratified bone-health screening. The guidelines also discuss nutritional and psychosocial support, digital models of care, and structured transition from paediatric to adult services. Updated therapeutic strategies for refractory CeD are provided, including immunosuppressive and novel pharmacologic options. Conclusions: These updated guidelines offer a comprehensive, evidence-based framework for the management and follow-up of adults with CeD. By integrating recent scientific advances with pragmatic, patient-centred recommendations, they seek to optimise clinical outcomes, quality of life, and long-term health in individuals with CeD.

Primary intestinal lymphangiectasia (PIL; Waldmann’s disease, ORPHA 90362) is a rare protein-losing enteropathy in which dilated intestinal lacteals leak chyle into the gut lumen. Cross-sectional imaging and lymphoscintigraphy have historically dominated assessment, while transabdominal B-mode intestinal ultrasound (IUS)—a cornerstone modality for inflammatory bowel disease—has remained almost unmapped in PIL. We conducted a PRISMA-ScR scoping review (Open Science Framework preregistration gfbc9) of all primary studies reporting transabdominal B-mode IUS in PIL, searching three bibliographic platforms (PubMed/MEDLINE, Ovid Multifile, Scopus) supplemented by forward and backward citation chasing. Studies using only extra-intestinal ultrasound, endoscopic ultrasound, those describing secondary lymphangiectasia or focal lymphangioma, and those using ultrasound only as procedural guidance for lymphangiography were excluded at full-text stage. Fifteen primary studies, published 1986–2026 across thirteen countries, met eligibility (nine paediatric, six adult). All fifteen reported per-patient B-mode IUS findings extractable for synthesis. A consistent sonographic signature emerged: diffuse, regular, slightly hypoechoic small-bowel-wall thickening with preserved five-layer stratification and prominent valvulae conniventes; dilated fluid-filled loops with reduced peristalsis; oedematous mesentery, variable ascites; and characteristically absent mesenteric lymphadenopathy (with two notable exceptions framed only as a research hypothesis). Diagnostic accuracy as a screening tool has been evaluated only in one study (n = 20: accuracy 80

OBJECTIVES:Autoimmune gastritis (AIG) has been poorly described in childhood. We sought to identify the patterns of manifestations of pediatric AIG at onset and to describe its laboratory, clinical, and histopathological features. METHODS:This was a retrospective, longitudinal, multicenter, cohort study enrolling histologically proven AIG patients with an onset in the pediatric age (<18 years old). We retrieved laboratory and clinical data at the time of onset and at last follow-up when available. Differences between Helicobacter pylori-exposed versus H. pylori-naïve, and anti-parietal cell antibody (PCA)-positive versus PCA-negative patients were investigated. RESULTS:Overall, 51 pediatric AIG patients (median age: 13 years, interquartile range: 11-16; F:M ratio 1.7:1) were included. Most patients were diagnosed with the overt type of AIG (47; 92.1%), while four (7.8%) were still in the potential phase. Atopic dermatitis (9.8%), rhinitis (7.8%), and asthma (5.9%) were common comorbidities, suggesting a link with T helper 2 (Th2) disorders. Two patients (3.9%) were found to have had previous or concurrent eosinophilic esophagitis, and five (9.8%) had eosinophilic gastritis. Notably, four patients (7.8%) presented with collagenous gastritis. On histological examination, the majority of patients were negative for H. pylori infection, except for 1 case out of 51 (2.0%) who had an active infection. CONCLUSIONS:AIG may affect pediatric patients and lead to complications in this population. At presentation, the disease may exhibit histologic patterns attributed to collagenous and/or eosinophilic gastritis. Moreover, a possible association between AIG and Th2 disorders has been observed, warranting further research.

Postoperative recurrence (POR) remains a significant challenge in Crohn's disease (CD) management despite therapeutic advances. Contemporary data show ileocecal resection rates of 18.7%, 28.0%, and 39.5% at one, five, and ten years after diagnosis, with endoscopic recurrence occurring in 22.4-53% of patients within 18-36 months postoperatively. Current understanding of POR pathophysiology includes microbiota dysbiosis, mesenteric inflammation, immune dysregulation, and genetic factors, particularly NOD2 variants. Key risk factors comprehend smoking, penetrating or perianal disease, prior surgeries, and extensive small bowel involvement. The Rutgeerts score remains the endoscopic gold standard for assessing recurrence, though it has never been validated and modifications addressing modern anastomotic techniques have been proposed. Non-invasive monitoring strategies using fecal calprotectin, intestinal ultrasound, and magnetic resonance enterography demonstrate promising diagnostic performance and may reduce the burden of routine endoscopy. Anti-TNF agents and Vedolizumab show superior efficacy in preventing endoscopic recurrence compared to conventional therapies, while other advanced therapies like anti-JAKs, risankizumab and ustekinumab demonstrate potential benefit in postoperative prophylaxis. Management approaches have evolved toward risk-stratified strategies balancing systematic prophylaxis against endoscopy-driven therapy. While medical prophylaxis remains first-line for high-risk patients, the expanding therapeutic armamentarium and improved understanding of pathophysiologic mechanisms enable increasingly personalized postoperative care. Further research is needed to validate risk assessment tools, optimize timing and selection of prophylactic therapies, and define the role of emerging agents in reducing long-term disease burden.