Paola Cesaro

Introduction Inflammatory bowel disease (IBD) is a chronic relapsing condition associated with substantial psychological burden, including elevated anxiety, depression, and perceived stress. Psychological distress is consistently linked to poorer quality of life (QoL), yet the mechanisms underlying this relationship remain incompletely understood. In particular, whether distress affects QoL directly or indirectly through disease symptomatology is still debated. Most mediation studies assume a single temporal ordering, although alternative specifications are often equally plausible. This study compares temporal mediation models to evaluate how temporal assumptions influence conclusions on this relationship in IBD. Objectives To investigate the mediating role of disease symptomatology in the association between psychological distress and QoL in patients with IBD, comparing alternative temporal mediation models and evaluating the robustness of findings under different missing-data imputation strategies. Methods A longitudinal cohort of 102 patients with IBD was assessed at baseline (T0) and four-month follow-up (T1). Psychological distress was measured with the Depression Anxiety Stress Scale-21 (DASS-21), disease symptomatology with the patient-reported IBD-Control symptom score, and QoL with the EQ-5D-5L. Baron and Kenny’s mediation framework was applied to three alternative specifications: (1) a fully cross-sectional model, all variables at T0; (2) a fully prospective model, distress at T0 and symptomatology/QoL at T1; and (3) a partially prospective model, distress and symptomatology at T0 and QoL at T1. Mediation paths (a, b, c, c’) were estimated for each specification. About 20% of follow-up observations were missing; missing data were handled via predictive mean matching and missForest multiple imputation. As both approaches produced comparable estimates, missForest was retained for the final analyses due to its lower computational burden. Results The fully cross-sectional model supported partial mediation of IBD symptoms on the relation distress-quality of life: path a) distress is significantly correlated with IBD symptoms (mediator) ; path b) IBD symptom significantly correlated with QoL, while path c’) a direct effect of distress on QoL remained after accounting for the mediator. The fully prospective specification also identified significant indirect pathways; however, the direct effect of distress on QoL reversed direction, suggesting an unstable mediation structure under this temporal assumption. In contrast, the partially prospective model, linking baseline distress and symptomatology with follow-up QoL, showed significant effects for all mediation paths in the expected direction, providing the most coherent evidence for partial mediation. Results were highly consistent between complete-case and imputed datasets, indicating robustness to the handling of missing follow-up data. Conclusions Among the temporal specifications examined, the model linking baseline distress to concurrent symptomatology and subsequent QoL at four-month follow-up provided the most coherent mediation pattern. These findings suggest that psychological distress rapidly influences patients’ perceived symptom burden, which subsequently contributes to poorer QoL over time, while a direct effect of distress on QoL also persists. More broadly, this study shows that mediation results may depend substantially on the temporal specification adopted. Explicitly comparing plausible temporal models should be considered good practice when applying the Baron and Kenny framework to longitudinal observational data, improving the robustness and interpretability of mediation analyses beyond the specific clinical context of IBD.

Colorectal cancer (CRC) remains a major global health burden, and early detection through population-based screening programs significantly reduces both incidence and mortality. Although gut microbiome-based biomarkers have emerged as promising non-invasive tools for CRC detection, limited evidence is available regarding patient acceptance and compliance with microbiome-based screening studies, factors that may influence their future implementation in clinical practice. We conducted a preliminary analysis of an ongoing multicenter, prospective observational study designed to develop a gut microbiome-based diagnostic tool for CRC and advanced colorectal adenomas in fecal immunochemical test (FIT)-positive individuals. The primary objective of this preliminary analysis was to evaluate patient acceptance and compliance with participation in a microbiome-based study within an organized CRC screening setting. Secondary objectives included describing the clinical, endoscopic, and histopathological characteristics of the enrolled cohort. FIT-positive individuals referred for screening colonoscopy at participating Italian centers were screened for eligibility, underwent colonoscopy, and were invited to provide a stool sample for microbiome analysis. A total of 315 individuals were screened, of whom 212 (67%) were enrolled. Among eligible patients, 90% agreed to enroll after receiving study information. Overall, 200 (94%) of enrolled individuals completed the required study activities, including stool sample collection and colonoscopy, indicating high compliance with study procedures. Colonoscopy was performed in 209 patients (99% of enrolled patients). CRC was detected in 7 patients (3%), and advanced colorectal adenomas in 39 (18%), while 86 (41%) colonoscopies were negative. The positive predictive value of FIT was 3.35% for CRC and 18.66% for advanced adenomas. In our preliminary analysis, patient acceptance and compliance with microbiome-based sampling were high among FIT-positive individuals undergoing CRC screening. These findings support the feasibility of conducting microbiome-based studies within organized screening programs. Analyses aimed at developing and validating the microbiome-based diagnostic tool are currently ongoing and are beyond the scope of the present report.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed worldwide for their analgesic, antipyretic, and anti-inflammatory properties. However, their long-term use is associated with substantial gastrointestinal (GI) toxicity. Although upper GI injury has traditionally received greater attention, NSAID-induced enteropathy is now increasingly recognized as a common yet underdiagnosed condition. Advances in small-bowel imaging, particularly capsule endoscopy, have demonstrated that mucosal injury of the small intestine occurs in up to 70–80% of chronic NSAID users and may also develop after short-term exposure in otherwise healthy individuals, often without overt clinical symptoms. When symptoms do occur, NSAID-induced enteropathy is characterized by non-specific clinical manifestations and may lead to severe complications in approximately 1% of cases. The pathogenesis of NSAID-induced enteropathy is multifactorial and more complex than that underlying upper GI damage. It involves prostaglandin depletion, increased intestinal permeability, bile acid-mediated toxicity, enterohepatic recirculation of NSAIDs, and, importantly, interactions with the gut microbiota. Concomitant therapies, particularly proton pump inhibitors, may further aggravate small-bowel injury by promoting intestinal dysbiosis. Growing evidence supports a relevant contributory role for the gut microbiota as both a mediator and a modulator of NSAID-induced toxicity, affecting epithelial barrier function, oxidative stress, immune responses, and bile acid metabolism. This review provides an overview of current knowledge of NSAID-induced enteropathy, with a particular emphasis on the microbiota-driven mechanisms underlying mucosal injury. By integrating emerging microbiota-targeted therapeutic approaches, we propose a management algorithm that may help modify disease progression in a condition that remains frequently overlooked in clinical practice.

Early rectal cancer represents a challenging setting in which accurate locoregional staging is essential to guide appropriate treatment. Current diagnostic strategies primarily include magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). However, both modalities show significant limitations in early-stage disease, particularly in T staging. This diagnostic gap impacts therapeutic decision-making, particularly in patients with lesions suggestive of deep submucosal invasion. In these cases, endoscopic submucosal dissection (ESD) may be insufficient to achieve adequate vertical negative margins, whereas radical surgery is associated with considerable morbidity and potential impairment of quality of life. In this gray zone, endoscopic intermuscular dissection (EID) has recently emerged as a novel therapeutic approach designed to overcome the limitations of standard endoscopic resection. By enabling dissection within the deeper intermuscular plane, it can achieve curative resections while preserving rectal wall integrity. This narrative review aims to explore the current diagnostic gaps in early rectal cancer and to define the potential role of EID within the current therapeutic algorithm.

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.

Malignancy-related gastrointestinal bleeding (GIB) remains a significant clinical challenge, contributing substantially to morbidity, mortality, and healthcare utilization in patients with cancer. Up to 10% of individuals with advanced malignancies develop GIB during their disease, and these episodes are frequently characterized by a high risk of rebleeding and poor long-term hemostatic control. Tumor-associated bleeding typically arises from friable, infiltrative, and highly vascular lesions that respond suboptimally to conventional endoscopic techniques such as thermal coagulation or mechanical clipping. These limitations underscore the need for improved diagnostic accuracy and more reliable therapeutic options. Recent advances in imaging modalities, including contrast-enhanced CT studies, have enhanced the ability to localize and characterize bleeding sources in complex oncologic cases. Parallel developments in endoscopic hemostasis—such as over-the-scope clips and contact-free coagulation devices—have expanded the therapeutic armamentarium for managing malignant bleeding. Clinically, topical hemostatic powders—particularly TC-325—represent a highly effective option for achieving rapid endoscopic hemostasis, supported by the strongest comparative evidence and the highest rates of immediate bleeding control among currently available technologies. In this review, we synthesize contemporary diagnostic approaches to GIB and place particular emphasis on the evolving and emerging therapeutic strategies for malignancy-related bleeding. We also highlight innovative technologies that are reshaping clinical practice and improving management options in this challenging clinical domain.

Artificial intelligence (AI) has revolutionized medical image analysis. Several neural network (NN) architectures were developed and applied across the last decade, becoming essential for automated diagnosis and clinical applications. AI based on NNs has become increasingly integrated into gastroenterology, offering new opportunities for automated lesion detection and workflow optimization. Small-bowel capsule endoscopy (SBCE) has benefited substantially from these advances, addressing long-standing challenges such as time-consuming video review and variability among readers. This systematic review and meta-analysis evaluated neural network-based models for lesion detection in SBCE, assessing pooled diagnostic accuracy and the impact of AI on reading time. A total of 44 primary studies were included: 36 validation studies for accuracy and 9 clinical studies for reading time. All NN architectures demonstrated high diagnostic performance, with a pooled accuracy of 95.3% (95% CI: 94.1–96.5%). More recent architectures, including transformer-based and capsule networks, outperformed classical convolutional neural networks (CNNs). AI assistance significantly reduced SBCE reading time, with a pooled mean reduction of 84% compared to standard review. These findings highlight the strong potential of AI to enhance SBCE efficiency and diagnostic reliability.

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.

INTRODUCTION: Mucosal exposure devices (MEDs) and computer-aided detection (CADe) systems may both improve adenoma detection through distinct mechanisms: expanding mucosal visualization and highlighting lesions, respectively. This study investigated the efficacy of combining CADe-assisted colonoscopy with a MED compared with CADe-assisted colonoscopy alone. METHODS: This international, multicenter, prospective, nonrandomized, single-arm study (NTC05220345) was conducted at 3 centers that also participated in the previous DISCOVERY II randomized controlled trial, comparing CADe-assisted with conventional colonoscopy. Eligible participants were patients referred for diagnostic, nonfecal immunochemical test screening, or surveillance colonoscopy and underwent CADe-assisted colonoscopy (DISCOVERY, PENTAX Medical) with a MED using an integrated inflatable balloon (G-EYE, SMART Medical Systems). The primary outcome was adenoma detection rate (ADR); secondary outcomes included sessile serrated lesion detection rate and withdrawal time without interventions. Outcomes were compared with historical controls of the CADe-arm of the DISCOVERY II study. RESULTS: Of 196 enrolled participants, 182 were included in the final analysis and compared with 250 participants from the historical CADe-arm. ADR was 47.3% in the CADe + MED-group vs 38.4% in the CADe-group ( P = .066; absolute difference: 8.9%, 95% confidence interval: 0.6–18.3). Mixed-effects logistic regression model adjusting for clustering and confounders calculated an odds ratio of 1.16 (95% confidence interval: 0.74–1.81). Median withdrawal time was slightly longer with CADe + MED compared with CADe-only (10.0 vs 9.2 minutes, P = 0.004), whereas sessile serrated lesion detection rate was not significantly different (12.6% vs 18.4%, P = 0.11). DISCUSSION: In this study using historical controls, CADe-assisted colonoscopy combined with a MED did not significantly increase ADR compared with CADe alone, suggesting limited synergistic benefit.

Clostridioides difficile infection (CDI) is a major complication in inflammatory bowel disease (IBD), due to coexistence of altered microbiota, chronic inflammation, and immune dysregulation. This narrative review summarizes recent evidence on the epidemiology, pathogenesis, risk factors, diagnosis, and management of CDI in IBD. Overall, IBD patients have a four- to five-fold higher risk of CDI than the general population and face more severe courses, higher rates of hospitalization, colectomy, recurrence, and mortality. Pathogenesis involves profound dysbiosis with loss of butyrate-producing Firmicutes and Bacteroidetes, bile acid imbalance that promotes spore germination, and enhanced toxin effects on an already inflamed mucosa. Major risk factors include active colonic disease, broad-spectrum antibiotic exposure, prolonged hospitalization, and corticosteroid or combined immunosuppressive therapy. Diagnosis requires careful integration of stool assays with clinical evaluation, supported by endoscopy or imaging when needed, to distinguish infection from IBD flares. Recommended first-line treatments are fidaxomicin or oral vancomycin, reserving fecal microbiota transplantation for recurrent or high-risk cases. Optimal IBD control is essential to reduce both primary and recurrent infection. CDI and IBD share a mutual pathogenic interplay in which microbial, immune, and therapeutic factors from each condition drive and magnify the other. Early recognition, guideline-based antibiotic therapy, judicious use of immunosuppression, and microbiota-based preventive strategies are crucial to improve patient outcomes and limit recurrence, thus reducing healthcare costs.