Citations

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet their benefits remain limited to a subset of patients, underscoring the need for more reliable biomarkers and novel therapeutic strategies. The gut microbiome has emerged as a critical modulator of systemic immunity and a promising determinant of ICI response. Evidence links specific microbial features, taxa, and bioactive metabolites to enhanced antitumor immunity, whereas disruptions, such as antibiotic exposure, are associated with poorer outcomes. Advances in sequencing and multi-omics technologies have provided more profound insights into microbiome-immune crosstalk, though methodological heterogeneity continues to challenge reproducibility. Translational studies demonstrate that microbiome-based intervention, including fecal microbiota transplantation (FMT), biotics supplementation, and engineered microbial strains, can enhance ICI efficacy or mitigate immune-related toxicities. Despite encouraging early clinical signals, broader implementation requires methodological rigor, standardized protocols, and innovative trial designs that account for host and environmental factors. For clinicians, the most immediate strategies involve prudent antibiotic stewardship and patient enrollment in microbiome-focused clinical trials. Overall, the gut microbiome is a promising biomarker and a therapeutic target, representing a new frontier for personalizing immunotherapy and improving patient outcomes in oncology.

Abstract Background Patients with moderate-to-severe inflammatory bowel disease (IBD) often require immunosuppressive therapy to achieve and maintain remission; however, the impact of these medications on influenza risk and the severity of influenza-related complications remains inadequately characterized. Methods Using the TriNetX U.S. Analytics Network, adults (≥ 18 years) with Crohn’s disease or ulcerative colitis during the 2022–2023 influenza season were identified. Patients were stratified by disease activity into two cohorts: (1) moderate-to-severe/active IBD, defined by elevated inflammatory markers, initiation of corticosteroids or a new biologic or small-molecule agent, or documented IBD-related symptoms or complications within the prior six months; and (2) mild/inactive IBD, defined by the absence of these features and no recent immunosuppressive therapy. Propensity score matching (1:1) was used to balance baseline characteristics, and Cox proportional hazards models were applied to estimate hazard ratios for influenza-related outcomes. Results After propensity score matching, each group had 22,784 patients. The incidence of influenza diagnosis was significantly higher in the moderate-to-severe/active IBD group (HR 1.41; 95% CI, 1.30–1.52). Hospitalization rates were also increased (HR 2.05; 95% CI, 1.89–2.23), as were influenza-related complications (HR 1.36; 95% CI, 1.23–1.51). ICU admissions (HR 1.51; 95% CI, 1.33–1.72) and mechanical ventilation (HR 1.68; 95% CI, 1.32–2.13) were both more frequent in the moderate-to-severe/active IBD group. Use of antiviral medications was higher among those in this cohort (HR 1.60; 95% CI, 1.22–2.10), and overall mortality was modestly increased (HR 1.17; 95% CI, 1.02–1.35). Subgroup analysis revealed the highest risk among patients on corticosteroids, followed by JAK inhibitors and anti–IL-23 agents. Conclusion Patients with moderate-to-severe/active IBD had more severe influenza-related outcomes compared with mild/inactive controls. Improving vaccine uptake and prompt evaluation of upper respiratory symptoms during influenza seasons are key to reducing influenza-related risks in immunosuppressed patients with IBD.

Lay Summary In this study we evaluated the effectiveness of vedolizumab (anti-integrin) vs ustekinumab/risankizumab (anti-interleukin) therapy for isolated small-bowel Crohn’s disease using a real-world, multicenter national database. We found that anti-interleukin therapy was more effective for inducing steroid-free remission and reducing hospitalizations.

ABSTRACT Introduction Chronic pouchitis is a major therapeutic challenge in patients with ulcerative colitis following ileal pouch‐anal anastomosis. Methods We conducted a real‐world, propensity‐matched cohort study of 856 patients from a healthcare database to compare ustekinumab and vedolizumab. Results Ustekinumab was associated with significantly lower relapse rates (aHR = 0.69; p < 0.001), longer time to relapse, reduced hospitalisation and decreased need for steroids or antibiotics. No differences were observed in surgery rates or therapy switching. Conclusion Our findings suggest that ustekinumab may offer advantages over vedolizumab in the management of chronic pouchitis.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at increased risk of herpes zoster and should receive the recombinant herpes zoster vaccine (RZV). We sought to assess the immunogenicity and safety of RZV series in patients receiving anti-tumor necrosis factor (TNF) therapy compared with those receiving vedolizumab. METHODS: This single-center prospective study enrolled patients with IBD on vedolizumab or anti-TNF monotherapy receiving RZV. Primary outcome assessed cell-mediated immunity (CMI) differences between groups postvaccination. Secondary outcomes included humoral response, sustained immunity, and safety monitoring for adverse events and IBD flares. Assessments occurred at baseline, 30, 240, and 425 days postvaccination. Statistical analyses included nonparametric Mann-Whitney U tests for between-group comparisons and Wilcoxon signed-rank tests for within-group changes, with significance set at P < 0.05. RESULTS: Thirty-three patients enrolled (16 vedolizumab, 17 anti-TNF). CMI responses increased postvaccination in both groups (median 56 cells/million [interquartile range {IQR} 21–102] vs 33 cells/million [IQR 11–73]; P = 0.13), with no significant difference between treatment groups. Both groups showed strong antibody responses to vaccination (preimmunization median: 349.9 mIU/mL [IQR 276.8–402.5] vs 90-day median: 605.0 mIU/mL [IQR 525.6–641.0]; P < 0.001). CMI responses remained elevated at both day 240 and 425 assessments. Antibody levels remained elevated through day 425 (549.1 mIU/mL, IQR 516.1–585.6), substantially higher than prevaccination levels. No IBD flares occurred; most adverse events were mild and transient. DISCUSSION: RZV demonstrated robust immunogenicity and favorable safety profile in patients with IBD receiving either vedolizumab or anti-TNF therapy. Both cellular and humoral immune responses persisted through 425 days postvaccination.

Abstract Background Prior studies have examined small intestinal dysplasia and cancer in Crohn’s disease; however, there is limited information on ulcerative colitis (UC). We describe characteristics of small intestinal dysplasia and cancer in patients with UC. In this study, we aimed to identify common characteristics between patients with UC that were diagnosed with small intestinal malignancy. Methods Electronic medical records were reviewed for 3 tertiary referral centers to identify patients with a diagnosis of UC and small intestinal dysplasia or cancer between 2010 and 2023. Data collection included demographics, family history of gastrointestinal malignancy, UC diagnosis date, duration and location of disease, prior UC medical treatment or surgery, diagnosis of primary sclerosing cholangitis (PSC), PSC-related complications, and details of cancer or dysplasia. Descriptive statistics were performed. Results Thirty-five patients (60% male, mean age of diagnosis 39.3 ± 21.5 years old) were identified with UC and subsequent small intestinal dysplasia or cancer. Most had pancolitis (74.3%) or pancolitis with backwash ileitis (8.57%). Half underwent surgery for their UC, and half of these had the cancer or dysplasia found at the time of surgery. Ileal dysplasia was found in 2 patients (5.71%), duodenal adenocarcinoma in 2 (5.71%), ileal adenocarcinoma 2 (5.71%), duodenal carcinoid in 4 (11.4%), ileal carcinoid in 24 (68.6%), other duodenal neuroendocrine tumor in 1 (2.86%). Primary sclerosing cholangitis was diagnosed in 5 patients (14%), and 3 required liver transplants. Conclusions Small intestinal dysplasia and cancer are rare in this population. Most patients with small intestinal cancer or dysplasia were male, Caucasian, and had a history of extensive colitis. Ileal carcinoid had the highest incidence. Gastroenterologists should be aware of this finding in patients with UC.

Background and Goals: Ulcerative colitis (UC) readmissions to the hospital pose a burden to patients and health care systems. Preventing readmissions is important for the quality of care and quality of life of patients with UC. We aimed to identify the incidence of 30 and 90-day readmissions and its predictors in patients with UC. Study: Retrospective review of the 2018 National Readmission Database (NRD) of adult patients readmitted after an index admission (IA) of UC. ICD-10CM/PCS codes were used to identify patients with UC, other comorbidities, and procedures. We identified the most common causes for readmission and independent risk factors for readmission were identified using Cox regression analysis. Results: The 30 and 90-day readmission rates for UC in 2018 were 16.6% and 28.3%. In-hospital mortality and mean length of stay were higher in patients readmitted within both 30 and 90 days. Independent predictors of 30-day readmission were higher Charlson Comorbidity Index (CCI), undergoing ileostomy, increasing length of stay, malnutrition and opioid use disorder at IA. In the 90-day readmission cohort, independent predictors were CCI score of 2 or ≥3, developing shock, admission to large bed size hospitals, undergoing colectomy, increasing length of stay and opioid use disorder at IA. The number one readmission cause at 30 and 90 days was sepsis of unspecified organism. Conclusion: Readmission is associated with higher mortality and is associated with risk factors such as malnutrition, undergoing ileostomy during IA and opioid use disorder. Readmissions in UC continue to pose a high burden to patients and our health care system.

Abstract Background Patients with inflammatory bowel disease (IBD) are at increased risk of herpes zoster (HZ) infection due to innate immune abnormalities and use of immunosuppressive therapy. The recombinant zoster vaccine (RZV) is recommended, but its efficacy in preventing recurrent HZ among patients with IBD is not well established. Methods Using data from the TriNetX Linked Network, we conducted a retrospective cohort study of adults (≥18 years) with IBD and a prior uncomplicated HZ episode. Patients with IBD who received RZV were propensity score-matched 1:1 with those who did not. The primary outcome was subsequent HZ complications. Secondary outcomes included subtypes of HZ complications and recurrent uncomplicated HZ. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated via Cox proportional hazards models. Results After matching, 1260 vaccinated and 1260 unvaccinated patients with IBD were included. Compared to the unvaccinated cohort, patients receiving RZV had a significantly reduced incidence of HZ complications (7.4% vs. 14.5%; HR, 0.75; 95% CI, 0.58–0.97; P = .028). Postherpetic neuralgia was notably decreased (5.8% vs. 12.5%; HR, 0.66; P = .010), and no central nervous system involvement occurred among vaccinated patients. Protective effects were more pronounced in patients with ulcerative colitis, females, and those not receiving immunosuppressive therapy. Conclusions RZV substantially lowers the risk of HZ complications in patients with IBD, offering significant clinical benefits to those at high risk due to immunosuppression. These findings underscore the importance of RZV as part of preventive care strategies in patients with IBD.

Patients with inflammatory bowel disease (IBD) often consider their gastroenterologist to be the primary provider of care. To improve the care delivered to patients with IBD, health maintenance issues need to be addressed by the gastroenterology team. In particular, documentation and recommendation for vaccinations are crucial because more than 70% of patients with IBD will at some time be on immune-modifying therapies that may increase the risk for infections, many of which are preventable with vaccinations. Health maintenance recommendations addressed in this guideline include the safety and appropriate timing of vaccinations, screening for osteoporosis, cervical cancer, melanoma and non-melanoma skin cancer and screening for depression, anxiety, and need for smoking cessation. To accomplish these health maintenance goals, coordination among the primary care provider, gastroenterology team, and other specialists is necessary.