Dupilumab is increasingly used for the treatment of eosinophilic esophagitis (EoE), yet its infectious safety profile in real-world clinical practice remains incompletely defined. Given the immunomodulatory effects of IL-4/IL-13 pathway inhibition, understanding infection risk relative to conventional therapies, such as proton pump inhibitors (PPIs) and swallowed TCS, is clinically important. Using the TriNetX Research USA network, we conducted three retrospective propensity-matched cohort analyses among adults with EoE initiating (1) dupilumab vs. PPIs, (2) dupilumab vs. topical steroids, (3) dupilumab vs. combined PPI/topical steroid therapy, and (4) dupilumab vs. no treatment. Patients receiving other systemic immunosuppressive biologics were excluded. One-to-one matching was adjusted for demographics and comorbidities associated with infection risk. Infectious outcomes ≥ 30 days post-index were noted. Relative risks and Kaplan–Meier analyses were performed. After propensity matching, cohorts included 3053 pairs (dupilumab v. PPI), 2143 pairs (dupilumab v. topical steroids), 3973 pairs (dupilumab v. combined therapy), and 2329 pairs (dupilumab vs. no treatment). Infection rates were similar between dupilumab and PPIs or topical steroids alone across all outcomes. Compared with combined PPI/topical steroid therapy, dupilumab was associated with lower rates of COVID-19 (10.3 vs. 12.6

Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections in the US, and recurrence remains a major clinical challenge, as standard-of-care antibiotics fail to prevent recurrence in up to one-third of cases. Fecal microbiota, live-jslm (RBL) is the first single-dose, microbiota-based product approved by the US Food and Drug Administration and Health Canada for the prevention of recurrent CDI (rCDI) following standard-of-care antibiotics. The RBL clinical development program is the largest to date for any microbiota-based product, encompassing seven studies and enrolling over 1700 participants to evaluate the safety and efficacy of RBL in preventing rCDI. Although the RBL development program consistently evaluated both efficacy and safety outcomes across all studies, this review summarizes the study designs, with a primary focus on the efficacy outcomes. The program consists of randomized controlled trials, open-label cohorts, retrospective analyses, and real-world data, each contributing unique insights across different patient populations and treatment settings. All studies enrolled adults aged ≥ 18 years with rCDI who received antibiotics for their enrolling CDI episode before RBL administration. Most studies administered RBL rectally, except for an open-label study and a retrospective study, which evaluated colonoscopic administration of RBL. Treatment success was evaluated at 8 weeks, and sustained clinical response was evaluated at 6 or 24 months after RBL and/or placebo administration, depending on the study design. Overall, the study designs for all seven studies were consistent, with slight differences between number of CDI episodes (specifically, 2 studies allowed enrollment after the first CDI recurrence), blinding, controls, and administration routes. Efficacy data of RBL reported across all studies consistently demonstrated RBL is efficacious for the prevention of rCDI in a broad adult population. ClinicalTrials.gov. NCT01925417; NCT02299570; NCT02589847; NCT03244644; NCT03931941; NCT05831189. Antibiotics used to treat bacterial infections can also damage good bacteria in the gut (dysbiosis). When these good bacteria are damaged, a bacterium called Clostridioides difficile can overgrow and release toxins that harm the colon. This can cause severe diarrhea and may become life-threatening. Antibiotics used to treat C. difficile infection contribute to dysbiosis and increase the chance the infection will return. Microbiota-based products are treatments comprising a wide variety of gut microbes. They help restore the natural balance of bacteria in the gut and have been shown to prevent C. difficile infection from returning. RBL, also known as REBYOTA® or fecal microbiota, live-jslm, is one of these microbiota-based products developed to prevent recurrent C. difficile infection in adults. The RBL clinical development program is currently the largest group of studies for any microbiota-based product. More than 1700 people have taken part in these studies to test the safety of RBL and its efficacy in preventing recurrent C. difficile infections. This review summarizes all the RBL studies and results seen so far. Across the different studies, which were similar in design and included a wide range of adult participants, RBL consistently helped prevent C. difficile infections from returning. Overall, the evidence shows RBL is effective for many adults at risk of recurrent C. difficile infection.

Background and aims Gastrointestinal (GI) histiocytosis is an uncommon and heterogeneous finding that may represent reactive, infectious, medication-related, or neoplastic processes. Because lesions are often identified incidentally on biopsy, their true frequency, etiologic spectrum, and optimal diagnostic approach remain poorly defined. We aimed to characterize GI histiocytosis using a large institutional cohort and contextualize findings using a review of published adult cases. Methods We performed a retrospective case series of adult patients at the Cleveland Clinic Foundation with histiocytic involvement of the GI tract identified on pathology specimens between 2007 and 2022, along with a systematic review of adult cases published on PubMed from 2002 to 2022. Extracted data included demographics, presenting symptoms, indications for endoscopy, anatomic distribution, endoscopic findings, associated conditions, and available immunohistochemical and molecular results. Results The institutional cohort included 108 patients (mean age 63.7 years; 60.2% female), of whom 35% were asymptomatic. Involvement spanned the esophagus to rectum, most commonly affecting the stomach. Endoscopic findings ranged from normal mucosa to polyps, nodules, and ulcerations. Nearly half of cases lacked definitive etiologic classification. Conclusions GI histiocytosis may be more common than previously appreciated but frequently remains incompletely evaluated in routine clinical practice. Integrating clinical context with targeted histologic assessment and selective molecular testing may help distinguish incidental reactive findings from clinically significant histiocytic disorders.

Background: Recurrent Clostridioides difficile infection (rCDI) occurs in up to 35% of patients with CDI, and further recurrence is common. Fecal microbiota, live-jslm (RBL) is safe and effective for preventing rCDI in adults following antibiotic treatment for rCDI when administered rectally. There is clinical interest in alternative routes of administration. Objectives: CDI-SCOPE assessed the safety and clinical effectiveness of RBL when administered via colonoscopy to adults with rCDI. Design: Single-arm, exploratory phase IIIb trial conducted at 12 sites in the United States. Methods: Eligible adults with rCDI received one administration of RBL consisting of one 150-mL dose of RBL, delivered via colonoscopy to the right side of the colon. The primary endpoint assessed RBL-related treatment-emergent adverse events (TEAEs) within 8 weeks of RBL administration or until confirmed treatment failure. Secondary endpoints included treatment success (absence of CDI recurrence for 8 weeks following RBL administration), physician experience administering RBL via colonoscopy, and physician perception of participant benefit. Results: Of 54 participants screened, 41 were enrolled and received RBL via colonoscopy; 39 participants completed the 8-week visit. Five TEAEs in four participants (9.8%) were assessed as related to RBL, all of which were gastrointestinal and mild in severity. Overall, 18 participants (43.9%) experienced 33 TEAEs within 8 weeks, most of which were of mild (25/33; 75.8%) or moderate (5/33; 15.2%) severity. No TEAEs led to intensive care unit admission or death. Overall, 39 participants (95.1%) experienced treatment success; 2 participants (4.9%) withdrew consent and had an indeterminate outcome. Among physicians, 90.2% of investigators indicated a “positive” or “very positive” experience administering RBL by colonoscopy. All physicians assessed participant benefit as “much” or “very much” improved. Conclusion: This single-arm study suggests RBL administered via colonoscopy is practical, safe, and effective for preventing CDI recurrence following antibiotic treatment in adults. Trial registration: ClinicalTrials.gov: NCT05831189.

BACKGROUND:The aim of this study was to evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA)-the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the US Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment. METHODS:PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered within 24-72 hours of antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success and sustained clinical response, at 8 weeks and 6 months after RBL administration, respectively. RESULTS:Overall, 793 participants were enrolled, of whom 697 received RBL. TEAEs through 8 weeks after administration were reported by 47.3% of participants; most events were mild or moderate gastrointestinal disorders. Serious TEAEs were reported by 3.9% of participants. The treatment success rate at 8 weeks was 73.8%; in participants who achieved treatment success, the sustained clinical response rate at 6 months was 91.0%. Safety and efficacy rates were similar across demographic and baseline characteristic subgroups. CONCLUSIONS:RBL was safe and efficacious in participants with rCDI and common comorbidities. This is the largest microbiota-based live biotherapeutic study to date, and findings support use of RBL to prevent rCDI in a broad patient population. CLINICAL TRIALS REGISTRATION:NCT03931941.

Background:Fecal microbiota, live-jslm (RBL) is a microbiota-based product for the prevention of recurrent Clostridioides difficile infection (rCDI) in adults following antibiotic treatment. The safety and clinical effectiveness of RBL administered via colonoscopy in adults with rCDI were evaluated in CDI-SCOPE. An 8-week analysis showed 9.8% of participants had RBL-related treatment-emergent adverse events (TEAEs; primary endpoint) and 95.1% experienced treatment success (no CDI recurrence). Objectives:To evaluate long-term safety and clinical effectiveness of RBL through 6 months of follow-up in CDI-SCOPE. Design:Single-arm exploratory phase IIIb trial conducted at 12 sites in the United States. Methods:Eligible adults with rCDI received a single 150-mL dose of RBL to the right colon via colonoscopy. The primary endpoint was RBL-related TEAEs through 8 weeks after RBL administration or confirmed treatment failure. Secondary endpoints included safety up to 6 months after RBL administration. Exploratory analyses included assessment of further CDI episodes. Results:Of the 41 participants enrolled, 39 completed trial assessments through 6 months. From 8 weeks through 6 months after RBL administration, 36 TEAEs in 15 participants (36.6%) were reported, one of which (irritable bowel syndrome) was RBL-related; most TEAEs (97.2%) were of mild or moderate severity. Over the 6-month trial period, 23 participants (56.1%) experienced 69 TEAEs; 94.2% were of mild or moderate severity. Serious TEAEs occurred in three participants (7.3%), none of which were related to RBL or its administration, and no TEAEs led to discontinuation or death. Overall, 38 participants (92.7%) did not experience further CDI episodes, 1 (2.4%) did between 8 weeks and 6 months, and 2 (4.9%) had an indeterminate outcome due to trial withdrawal before 8 weeks. Conclusion:RBL administered via colonoscopy was safe and effective for preventing CDI recurrence in adults with rCDI in CDI-SCOPE. Trial registration:ClinicalTrials.gov: NCT05831189.

Background: Recurrent Clostridioides difficile infection (rCDI) occurs in up to 35% of patients with CDI, and further recurrence is common. Fecal microbiota, live-jslm (RBL) is safe and effective for preventing rCDI in adults following antibiotic treatment for rCDI when administered rectally. There is clinical interest in alternative routes of administration. Objectives: CDI-SCOPE assessed the safety and clinical effectiveness of RBL when administered via colonoscopy to adults with rCDI. Design: Single-arm, exploratory phase IIIb trial conducted at 12 sites in the United States. Methods: Eligible adults with rCDI received one administration of RBL consisting of one 150-mL dose of RBL, delivered via colonoscopy to the right side of the colon. The primary endpoint assessed RBL-related treatment-emergent adverse events (TEAEs) within 8 weeks of RBL administration or until confirmed treatment failure. Secondary endpoints included treatment success (absence of CDI recurrence for 8 weeks following RBL administration), physician experience administering RBL via colonoscopy, and physician perception of participant benefit. Results: Of 54 participants screened, 41 were enrolled and received RBL via colonoscopy; 39 participants completed the 8-week visit. Five TEAEs in four participants (9.8%) were assessed as related to RBL, all of which were gastrointestinal and mild in severity. Overall, 18 participants (43.9%) experienced 33 TEAEs within 8 weeks, most of which were of mild (25/33; 75.8%) or moderate (5/33; 15.2%) severity. No TEAEs led to intensive care unit admission or death. Overall, 39 participants (95.1%) experienced treatment success; 2 participants (4.9%) withdrew consent and had an indeterminate outcome. Among physicians, 90.2% of investigators indicated a “positive” or “very positive” experience administering RBL by colonoscopy. All physicians assessed participant benefit as “much” or “very much” improved. Conclusion: This single-arm study suggests RBL administered via colonoscopy is practical, safe, and effective for preventing CDI recurrence following antibiotic treatment in adults. Trial registration: ClinicalTrials.gov: NCT05831189.

Clostridioides difficile infection is the most common healthcare-associated infection in the United States, with potential life-threatening complications and significant impact in the costs of care. Antibiotic stewardship as well as discontinuation of chronic acid suppressive therapy are key for its prevention and treatment. Effective infection management requires appropriate interpretation of diagnostic tests, as well as the use of vancomycin and fidaxomicin as first-line treatment. Novel treatments as Bezlotoxumab, fecal microbiota transplant and live biotherapeutic products are proven effective in recurrent C. difficile infection and addresses dysbiosis.

Background and Aims The COVID-19 pandemic has highlighted the importance of telemedicine in improving healthcare access and reducing costs. This study aimed to assess order compliance in the virtual versus in-person setting for the initial evaluation of abdominal pain (AP) prior to and during the pandemic. Methods A retrospective evaluation of virtual and in-person outpatient gastroenterology visits for AP were identified through natural language processing from January 2019 through September 2021 at the Cleveland Clinic main campus and regional hospitals in Ohio. We assessed the number and type of orders placed for patients and measured compliance through order completion. This study received Institutional Review Board approval (IRB 21-514). Results Among 20,356 patients at their initial visit, 79% had orders placed, of which 40% had pandemic in-person visits, 13% had pandemic virtual visits, and 47% had pre-pandemic in-person visits. Patients seen virtually were 65.1% less likely to complete orders compared to patients seen in-person (p < 0.001) during the pandemic. Patients seen in a pandemic virtual setting were 71.0% less likely to complete imaging orders (p < 0.001), 82.6% less likely to complete procedure orders (p < 0.001), and 60.5% less likely to complete lab orders (p < 0.001). Conclusion Compared with in-person visits, patients seen virtually for their first presentation of AP were less likely to complete labs, imaging, and endoscopic evaluations. In-person visits were more successful with patient order completion during the pandemic. These findings highlight that virtual visits for AP, despite convenience, may compromise care delivery and warrant additional care coordination to achieve compliance with medical recommendations.

IntroductionObesity has a known association with certain types of malignancy, and we aimed to determine whether bariatric surgery has a protective effect against de novo obesity-associated cancer development in adult patients.MethodsWe performed a multi-center retrospective cohort studying utilizing TriNetX national database. Patients were identified utilizing ICD-10-CM coding, and propensity score matching was performed. We compared patients with obesity who underwent bariatric surgery to patients with obesity who did not undergo bariatric surgery.ResultsWe initially identified 60,285 patients in the bariatric surgery group and 1,570,440 patients in nonsurgical control group. After propensity score matching, we included 55,789 patients in each patient cohort. The cumulative incidence of de novo obesity-associated cancers at 10 years was 4.0% (2206 patients) in the bariatric surgery group and 8.9% (4,960 patients) in the nonsurgical control group (HR 0.482 [95% CI 0.459-0.507]). The bariatric surgery group had lower incidence proportions for de novo breast cancer (HR 0.753 [CI 0.678-0.836]), colon cancer (HR 0.638 [CI 0.541-0.752]), liver cancer (HR 0.370 [CI 0.345-0.396]), ovarian cancer (HR 0.654 [CI 0.531-0.806]), and endometrial cancer (HR 0.448 [CI 0.362-0.556]) when compared to the nonsurgical control group.ConclusionWe noted that bariatric surgery is associated with a significantly lower cumulative incidence of de novo obesity-associated cancer compared to a nonsurgical matched control group. Incidence proportions of de novo breast, colon, liver, ovarian, and endometrial cancer were significantly lower in adult patients with obesity in the bariatric surgery group compared to the nonsurgical group.

Introduction: Gastrointestinal histiocytosis can be a diagnostic challenge as there are many possible etiologies and the incidence of most of these diseases is quite rare. We sought to review the causes of GI histiocytosis and evaluate the significance of this finding. Methods: A search of Cleveland Clinic Foundation (CCF) adult patients was conducted for pathology of histiocytes in the GI tract over the last 15 years. This search collected patient demographics (e.g., age, sex, race), presenting symptom(s), indication for endoscopy, site(s) of GI involvement, and endoscopic findings. This search also included related medical conditions such Langerhans cell histiocytosis, Erdheim-Chester disease, or Rosai-Dorfman disease as well as BRAF, MAP kinase, and ALK gene mutations. A literature review was also performed by searching the keywords “gastrointestinal,” “histiocyte,” and “histiocytosis,” for articles published in the last 20 years. The same data was collected for the literature review as the CCF patients. Results: The search for CCF patients with GI histiocytosis yielded 108 cases, while the literature review yielded 26 cases. Demographic data is available in Table 1. Most patients were asymptomatic, including 38 (35.19%) CCF patients and 10 (38.46%) literature review patients. The leading symptom was abdominal pain, affecting 26 (24.07%) CCF patients and 4 (15.38%) literature review patients. The top reason endoscopy was performed was due to signs and symptoms, as was the case for 70 patients (61.95%) at the Cleveland Clinic and 14 patients (53.85%) from the literature review. The most common site of involvement for CCF patients was the stomach in 62 cases (54.39%). However, the most common site of involvement for literature review patients was the large intestine in 15 cases (51.72%). Conclusion: The most common etiology for CCF cases was xanthomas or xanthelasma, occurring in 32 (29.63%) patients. In 53 (49.07%) of the cases, the etiology was unknown and could not be determined based on the information available. This was in stark contrast to the literature review, with 21 of the 26 cases (80.77%) due to Langerhans cell histiocytosis. This study demonstrates that careful review of the history as well as detailed workup including endoscopy and genetic testing can help diagnose the cause of gastrointestinal histiocytosis. Table 1. - Patient Demographics Cleveland Clinic (n = 108) Literature Review (n = 26) Female (n [%]) 65 (60.19%) 18 (69.23%) Male (n [%]) 43 (39.81%) 8 (30.77%) White (n [%]) 71 (65.74%) 2 (7.69%) Black (n [%]) 30 (27.52%) 0 Asian (n [%]) 3 (2.78%) 4 (15.38%) Multiracial (n [%]) 1 (0.93%) 0 Race not available (n [%]) 3 (2.78%) 20 (76.92%) Age, years (mean ± SD) 63.74 ± 15.61 54.50 ± 15.50

Introduction: Artificial intelligence (AI) chatbots are becoming increasingly popular and likely to become frequently used by patients inquiring about health-related concerns. ChatGPT was introduced in November 2022 and recently updated to version 4. We sought to assess the accuracy of answers and references provided by ChatGPT4.0 to questions on irritable bowel syndrome (IBS), a diagnosis frequently queried online. Methods: After reviewing the most frequently searched terms related to IBS on Google Trends, we formulated 15 questions on the topic. We entered each question into ChatGPT-4.0 in a separate chat log, asking the model to supply references for each generated answer. Accuracy of the AI's responses and provided references were then assessed by 3 independent gastroenterologists. Answers were evaluated using 2 grading systems: an overall grade (accurate vs inaccurate) and a granular grade (100% accurate, 100% inaccurate, accurate with missing information, partly inaccurate). References were graded as suitable, unsuitable (existent but unrelated to answer), or nonexistent. We used free-marginal Fleiss kappa coefficients (κ) to quantify inter-rater agreement pre(κpre) and post(κpost) consensus discussions, which served to rectify any grading discrepancies. When disagreement persisted, the most stringent evaluation was accepted as the definitive grade (Table 1). Results: Overall assessment showed 80% of AI answers were accurate and 20% inaccurate (κpre=0.82 [95% confidence interval CI 0.58-1.00], κpost=1.00 [95%CI, 1.00-1.00]). Granular grading showed 53% of answers were accurate, 33% partially inaccurate, 13% correct but incomplete and 0% completely inaccurate (κpre=0.38 [95%CI 0.14-0.62], κpost=0.88 [95%CI 0.72-1.00]). Provided references were suitable for 33% of answers, unsuitable for 53%, and nonexistent for 13% of answers (κpre=0.53 [95%CI, 0.27-0.79]/κpost=1.00 [95%CI, 1.00-1.00]) (Figure 1). Conclusion: While overall accuracy was high at 80%, ChatGPT-4.0 still missed some details or provided outdated information. However, no fully inaccurate information was given, making this model a potential safe source for general guidance on common IBS queries. The model remains problematic for medical professionals when it comes to literature research and referencing as ChatGPT failed to provide a satisfying number of suitable references. These findings underscore the need for enhancing AI's precision and references validity in health-related information dissemination.Figure 1.: Visual Comparison of Reviewers' Assessments of ChatGPT-4.0 Responses to IBS Queries: A Clustered Column Chart. Table 1. - Questions posed to ChatGPT-4.0 and reviewers' evaluation of responses IBS Questions Granular Grade Overall Grade References Grade 1. What are the symptoms of IBS? Provide references Partly Inaccurate Accurate Suitable 2. What causes IBS? Provide references Accurate Accurate Suitable 3. Is IBS a serious condition? Provide references Partly Inaccurate Accurate Suitable 4. How is IBS diagnosed? Provide references Partly Inaccurate Inaccurate Unsuitable 5. What are the treatment options for IBS? Provide references Accurate with Missing Information Accurate Nonexistent 6. What foods should I avoid if I have IBS? Provide references Accurate Accurate Suitable 7. Are there any natural remedies for IBS? Provide references Accurate Accurate Unsuitable 8. Can probiotics help with IBS? Provide references Accurate Accurate Unsuitable 9. What support resources are available for people with IBS? Provide references Accurate with Missing Information Accurate Unsuitable 10. Can Cannabinoids (CBD) improve IBS symptoms? Provide references Partly Inaccurate Inaccurate Unsuitable 11. What causes IBS flare-ups? Provide references Accurate Accurate Unsuitable 12. Why do people with IBS pass gas so much? Provide references Accurate Accurate Unsuitable 13. Is there a test for IBS? Provide references Partly Inaccurate Inaccurate Suitable 14. How to cure IBS permanently? Provide references Accurate Accurate Unsuitable 15. How to manage IBS during pregnancy? Provide references Accurate Accurate Nonexistent