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Abstract In this pilot study, we assessed the role of autophagy in Crohn’s Disease (CD), particularly in patients with a stenosing phenotype. Through the analysis of biopsied specimens from 36 patients, including 11 controls and 25 CD patients, categorized into inflammatory and stenosing groups, we identified a significant reduction in the autophagosomal marker Lc3b-II in patients with active inflammation and stenosis. This was paralleled by an increase in oxidative stress markers, including sNOX2-dp and H2O2, and a decrease in the antioxidant capacity measured by HBA, suggesting an imbalance in autophagy and oxidative stress mechanisms. Additionally, our findings show a correlation between autophagy markers and oxidative stress levels, indicating that autophagy dysfunction may play a pivotal role in CD and in the progression of a stenosing disease phenotype, by failing to eliminate detrimental molecules and pathogenic bacteria, thereby promoting fibrosis. This study is the first to demonstrate in vivo autophagy inhibition in stenosing CD patients and suggests that stimulating autophagic processes could offer a new avenue for the prevention and treatment of intestinal fibrosis in CD. Our results highlight the importance of exploring the interactions between autophagy, the fibrotic process, and the inflammatory cascade, opening avenues for potential therapeutic interventions in CD management.

Helicobacter pylori (Hp) infection can be diagnosed by invasive and noninvasive methods, and, among the former, Rapid Urease Tests (RUTs) are an important option. Accuracy and rapidity of results are fundamental for RUTs. The aim of the study is to prospectively evaluate the sensitivity, specificity and time to positivity of a new-generation ultra-rapid urease test (iNatal duo test) for Hp detection and compare the results with other available RUTs [CLO Test (Campylobacter-Like Organism Test), CP Test (Campylobacter pylori Test) and Pronto Dry]. Gastric biopsies were taken in consecutive patients undergoing upper endoscopy: two in the antrum and two in the body for histology, and one in the antrum and one in the body for each RUT. RUTs were read at 1, 5, 15, 30 and 60 min, 3 h and 24 h after biopsy insertion into the reagent. Histology was considered as “gold standard”. The performance of the tests was evaluated in patients not taking proton pump inhibitors (PPI) (n = 924) by calculation of sensitivity, specificity and positive and negative predictive value. Agreement rate (κ) for every RUT and histology was calculated and compared. The performance of the iNatal duo test was also tested in a subgroup of patients taking PPI (n = 198). Hp was positive in 225/924 patients (24.3%) not taking PPIs and in 56/198 (28.3%) who were taking PPIs. The iNatal duo test was more sensitive than the other RUTs for detecting Hp at every time point. The sensitivity at 5 min was 96.2% in patients not taking PPIs and 92.2% in patients taking PPIs. κ with histology was higher for the iNatal duo test than any other RUT (at 30 min: iNatal duo 0.99, CLO 0.60, CP 0.78, Pronto 0.85, at 15 min: iNatal duo 0.99, CLO 0.46, CP 0.63, Pronto 0.71). In a prospective study, the iNatal duo test demonstrated high accuracy and rapidity for Hp detection, both in patients with and without PPI therapy. This new generation of ultra-rapid urease test could be useful for the rapid and correct management of patients undergoing upper GI endoscopy for suspected Hp infection.

The role of endoscopic evaluation in ulcerative colitis (UC) is well recognized, but a universally accepted gold standard for endoscopic activity evaluation is still lacking, and many scores have been proposed to this purpose. Among these, the Mayo Endoscopic Score (MES) and the Ulcerative Colitis Endoscopic Index (UCEIS) are currently the most used in trials and clinical practice. The aim of the study is to evaluate feasibility and performance of MES and UCEIS among expert endoscopists with no specific expertise in inflammatory bowel diseases (IBD), in a single hospital center. Two minutes video recordings, from colonoscopy of 12 UC patients, were observed and scored, according to MES and UCEIS, by seven hospital gastroenterologists with experience in digestive endoscopy and no particular expertise in IBD. Knowledge and utilization of the two scores were investigated. Inter-observer agreement and agreement with an IBD-expert gastroenterologist of the same center (central reader), and correlation between the two scores, was calculated. Among the endoscopists, MES was much more known and currently used than UCEIS. Both the scores displayed a similar good performance. Agreement with central reader was moderate for MES and UCEIS, and interobserver agreement was good, for both MES and UCEIS. Correlation between the two scores was very good both for central reader and for the hospital endoscopists. This single center study confirmed potential feasibility and usefulness of MES and UCEIS for assessment of endoscopic activity in UC patients in a real-life setting.

Probiotics are microorganisms that confer benefits to the host, and, for this reason, they have been proposed in several pathologic states. Specifically, probiotic bacteria have been investigated as a therapeutic option in ulcerative colitis (UC) patients, but clinical results are dishomogeneous. In particular, many probiotic species with different therapeutic schemes have been proposed, but no study has investigated probiotics in monotherapy in adequate trials for the induction of remission. Lactobacillus rhamnosus GG (LGG) is the more intensively studied probiotic and it has ideal characteristics for utilization in UC patients. The aim of the present study is to investigate the clinical efficacy and safety of LGG administration in an open trial, delivered in monotherapy at two different doses, in UC patients with mild–moderate disease. The UC patients with mild–moderate disease activity (Partial Mayo score ≥ 2) despite treatment with oral mesalamine were included. The patients stopped oral mesalamine and were followed up for one month, then were randomized to receive LGG supplement at dose of 1.2 or 2.4 × 1010 CFU/day for one month. At the end of the study, the clinical activity was evaluated and compared to that at the study entrance (efficacy). Adverse events were recorded (safety). The primary end-point was clinical improvement (reduction in the Partial Mayo score) and no serious adverse events, while the secondary end-points were the evaluation of different efficacies and safeties between the two doses of LGG. The patients with disease flares dropped out of the study and went back to standard therapy. The efficacy data were analyzed in an intention-to-treat (ITT) and per-protocol (PP) analysis. Out of the 76 patients included in the study, 75 started the probiotic therapy (n = 38 and 37 per group). In the ITT analysis, 32/76 (42%) responded to treatment, 21/76 (28%) remained stable, and 23/76 (30%) had a worsening of their clinical condition; 55 (72%) completed the treatment and were analyzed in a PP analysis: 32/55 (58%) had a clinical response, 21 (38%) remained stable, and 2 (4%) had a light worsening of their clinical condition (p < 0.0001). Overall, 37% of the patients had a disease remission. No severe adverse event was recorded, and only one patient stopped therapy due to obstinate constipation. No difference in the clinical efficacy and safety has been recorded between groups treated with different doses of LGG. The present prospective clinical trial demonstrates, for the first time, that LGG in monotherapy is safe and effective for the induction of remission in UC patients with mild–moderate disease activity (ClinicalTrials.gov identifier: NCT04102852).