Background: Barrier healing is an emerging therapeutic target in inflammatory bowel disease (IBD), though its assessment remains challenging. We evaluated automated advanced imaging for real-time barrier assessment, its correlation with epithelial/vascular barrier markers, and ability to predict adverse outcomes. Methods: IBD patients and healthy controls undergoing endoscopic assessment were prospectively enrolled. The intestinal barrier was evaluated using ultra-high-magnification endocytoscopy and probe-based confocal laser endomicroscopy. Targeted biopsies were obtained from inflamed and non-inflamed segments. Epithelial and vascular barriers were assessed through automated multiplex immunofluorescence for Claudin-2, ZO-1, E-cadherin, PV-1, and CD31. Gene expression profiling was performed in epithelial and lamina propria compartments. Artificial intelligence (AI)-based analysis was employed for automated evaluation of barrier features captured by advanced imaging. Results: In total, 103 patients were included (38 ulcerative colitis [UC], 54 Crohn’s disease [CD], 11 healthy controls). Advanced imaging revealed barrier healing in 21% (8/38) of UC and 30% (16/54) of CD patients. In UC, Claudin-2 moderately correlated with abnormal crypt architecture (ρ = 0.49), goblet cell depletion (ρ = 0.5), and overall endocytoscopy activity (ρ = 0.49). In CD, PV-1 moderately correlated with altered blood flow (ρ = 0.41) and vessel architecture (ρ = 0.40). An integrated assessment of advanced imaging, combined with Claudin-2 and PV-1 expression, effectively predicted adverse outcomes in UC and CD, respectively. AI tools accurately classified epithelial and vascular barrier features captured by advanced imaging. Finally, gene expression confirmed upregulation of Claudin-2 and PV-1 in IBD. Conclusion: Automated advanced imaging enables real-time barrier assessment in IBD and correlates with markers of epithelial and vascular barrier impairment. AI integration can enhance standardization toward broader clinical applicability.

A wide range of advanced therapies has become available in recent years for the treatment of moderate-to-severe inflammatory bowel disease (IBD). Among these, monoclonal antibodies targeting the interleukin 23 p19 subunit (anti-IL23p19) have emerged as a promising therapeutic class. Pivotal Phase 3 trials have demonstrated their favourable clinical efficacy and safety in both Crohn’s disease (CD) and ulcerative colitis (UC). Three such agents, Risankizumab, Mirikizumab and Guselkumab, have now been approved in CD and UC. For gastroenterologists, the ability to rationally select among these options to personalise treatment and maximise patient benefit is critical. Key factors to consider when selecting an anti-IL23p19 agent include patient preference regarding mode of administration, IBD phenotype, presence of co-existing extra-intestinal manifestations, concomitant immune mediated diseases and previous advanced-therapy exposure. Our review summarises the current clinical evidence on anti-IL23p19 therapies and provides practical guidance on their use in IBD clinical management, including dosing strategies, choice of dose in CD and UC and clinical positioning across patients. Finally, anti-IL23p19 inhibition may represent a future first-line therapy option for moderate-to-severe IBD, particularly in patients with concomitant IL-23 driven co-morbidities such as psoriasis. Its use in combination with other advanced therapies in selected patients is being explored to enhance therapeutic efficacy and improve long-term outcomes. Further real-world studies are needed to assess its effectiveness and benefits in complex disease phenotypes, including perianal fistulizing Crohn’s disease.

Small bowel capsule endoscopy (SBCE) has emerged in the past two decades as the cornerstone for assessing small bowel disorders, and its use is supported by several guidelines. However, there are several limitations, such as the considerable time required for gastroenterologists to review these videos and reach a diagnosis. To address these limitations, researchers have explored the integration of artificial intelligence in the interpretation of these videos. In our review, we explore the evolving and emerging role of artificial intelligence in SBCE and examine the latest advancements and ongoing studies in these areas, aiming at overcoming current limitations.

Background: The fecal immunochemical test (FIT) is widely implemented as a first‐line tool in organized colorectal cancer (CRC) screening programs, including Italy. Following a positive FIT, colonoscopy is recommended. Computer‐aided detection (CADe) systems have the potential to enhance adenoma detection, particularly in FIT‐positive populations where identifying advanced adenomas is critical for cancer prevention. This study evaluated the diagnostic performance of CADe‐assisted colonoscopy versus standard colonoscopy (SC) in a FIT‐based screening cohort. Methods: In this multicenter, randomized controlled trial, patients with a positive FIT result were randomized to undergo either CADe‐assisted or standard colonoscopy. The primary endpoint was the advanced adenoma detection rate (AADR). Secondary endpoints included overall adenoma detection rate (ADR), adenomas per colonoscopy (APC), and mean withdrawal time (WT). Results: Of 1077 patients enrolled, 68 were excluded due to inadequate bowel preparation, leaving 1009 patients for analysis (CADe: n = 506; SC: n = 503). AADR was comparable between the groups (21.3% vs. 20.5%, p = 0.794). However, CADe significantly improved ADR (67.6% vs. 59.8%, p = 0.012) and APC (1.82 ± 2.12 vs. 1.34 ± 1.81, p < 0.001). Mean WT was longer in the CADe group (17.10 ± 8.28 min vs. 16.13 ± 8.28 min, p = 0.016). Conclusions: In a FIT‐based organized CRC screening setting, CADe did not enhance detection of AADR with a modest increase in withdrawal time. NCT04441580.

Background and Aims: Despite major therapeutic advances, many patients with inflammatory bowel disease (IBD) continue to experience inadequate treatment response, progressive disease, and irreversible complications requiring surgery. Current management is constrained by a biological efficacy ceiling and lack of agents directly targeting key drivers of fibrosis and barrier dysfunction. This systematic review synthesizes current knowledge on tumor necrosis factor-like cytokine 1A (TL1A) and death-domain receptor 3 (DR3) signaling pathways, critically evaluates the therapeutic potential of TL1A-targeted interventions, and explores future directions for precision medicine applications in IBD care. Methods: A comprehensive systematic search of PubMed, EMBASE, Cochrane library, Web of Science, and ClinicalTrials.gov was conducted according to PRISMA guidelines. Three independent reviewers screened preclinical and clinical studies using Rayyan software. Study selection, data extraction, and quality assessment were performed in duplicate. Eligible studies underwent narrative thematic synthesis. Results: Of 250 studies identified, 63 met inclusion criteria. Preclinical data consistently demonstrate TL1A-DR3 signaling drives inflammation, fibrosis, and barrier dysfunction. Phase 2 clinical trials showed anti-TL1A monoclonal antibodies (Tulisokibart, Afimkibart, Duvakitug) achieved clinical remission/response rates between 26% and 66% in patients with moderate-to-severe IBD at 12-14 weeks, with favorable safety profiles. Emerging themes include extended dosing intervals, therapeutic benefit in treatment-refractory populations, potential anti-fibrotic effects, and opportunities for biomarker-guided patient stratification. Conclusion: TL1A inhibitors represent a promising novel therapeutic class with dual anti-inflammatory and anti-fibrotic properties, addressing critical unmet clinical needs in IBD. These agents hold the potential to become cornerstone therapies in the evolving landscape of precision medicine for IBD care.

Adequate bowel preparation is essential for high-quality colonoscopy but remains challenging in hospitalized patients, and comparative data on preparation volume are limited. To compare the efficacy, tolerability, and safety of very low-volume (1-liter [1L]), low-volume (2-liter [2L]), and high-volume (4-liter [4L]) polyethylene glycol (PEG) regimens for inpatient colonoscopy preparation. Multicenter, randomized controlled, endoscopist-blinded trial. (EudraCT: 2019-002799-15; ClinicalTrials.gov: NCT04708366). Community and academic hospitals in Italy. Hospitalized adults undergoing elective colonoscopy. Patients were randomly assigned (1:1:1) to split-dose 1L PEG-ascorbate, 2L PEG-ascorbate, or 4L PEG. Primary end point was adequate bowel cleansing (Boston Bowel Preparation Scale [BBPS] score ≥6 with all segments ≥2). Secondary end points included high-quality cleansing (BBPS score, 8 to 9), high-quality right-colon cleansing (BBPS score, 3), and willingness to repeat. Among 665 randomly assigned patients (1L, n = 228; 2L, n = 218; 4L, n = 219), adequate overall cleansing occurred in 82.0%, 78.0%, and 78.5% (absolute difference between the 1L and 2L groups [Δ1L-2L], 4.0 percentage points [95% CI, -3.4 to 11.4 percentage points]; absolute difference between the 1L and 4L groups [Δ1L-4L], 3.5 percentage points [CI, -3.9 to 10.9 percentage points]). High-quality overall cleansing occurred in 46.9%, 35.3%, and 37.4% (Δ1L-2L, 11.6 percentage points [CI, 2.5 to 20.5 percentage points]; Δ1L-4L, 9.5 percentage points [CI, 0.3 to 18.5 percentage points]). High-quality right-colon cleansing occurred in 40.6%, 29.5%, and 31.6% (Δ1L-2L, 11.2 percentage points [CI, 2.1 to 20.0 percentage points]; Δ1L-4L, 9.0 percentage points [CI, 0.0 to 17.9 percentage points]). Tolerability was good across regimens, with the highest willingness to repeat in the 1L group (84.2%), despite more frequent vomiting and thirst. Patients requiring urgent colonoscopy for active gastrointestinal bleeding and those with severe/unstable comorbid conditions were excluded. In hospitalized adults undergoing elective colonoscopy, 1L PEG-ascorbate yielded higher rates of high-quality cleansing, including right colon, than 2L PEG-ascorbate and 4L PEG, with similar rates of adequate cleansing and high willingness to repeat. Norgine Srl.