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BACKGROUND: Budesonide is accepted as first-choice therapy for microscopic colitis (MC); however, symptoms often recur and some patients may be dependent, intolerant, or even fail budesonide. We performed a systematic review and meta-analysis to determine the effectiveness of non-budesonide therapies (thiopurines, bismuth subsalicylate [BSS], bile acid sequestrants [BAS], loperamide and biologics) for MC suggested by international guidelines.METHODS: We searched the CENTRAL, MEDLINE, and EMBASE databases from their inception to 18 April 2023 for the above-mentioned therapeutics in MC. We pooled the response and remission rates by medication using a random-effects model.RESULTS: Twenty-five studies comprising 1475 patients were included in the meta-analysis. Treatment with BSS showed the highest response rate of 75% (95% confidence interval [CI] 0.65-0.83; I2 = 70.12%), with 50% achieving remission of symptoms (95% CI 0.35-0.65; I2 = 71.06%). Treatment with tumor necrosis factor (TNF) inhibitors (infliximab and adalimumab) demonstrated a response rate of 73% (95% CI 0.63-0.83; I2 = 0.00%), with a remission rate of 44% (95% CI 0.32-0.56; I2 = 0.00%). The response rate for those treated with vedolizumab was similar; 73% responded to treatment (95% CI 0.57-0.87; I2 = 35.93%), with a remission rate of 56% (95% CI 0.36-0.75; I2 = 46.30%). Loperamide was associated with response and remission rates of 62% (95% CI 0.43-0.80; I2 = 92.99%) and 14% (95% CI 0.07-0.25), respectively, whereas BAS use was associated with response and remission rates of 60% (95% CI 0.51-0.68; I2 = 61.65%) and 29% (95% CI 0.12-0.55), respectively. Finally, the outcomes for thiopurine use were 49% (95% CI 0.27-0.71; I2 = 81.45%) and 38% (95% CI 0.23-0.54; I2 = 50.05%), respectively DISCUSSION: The present systematic review and meta-analysis provides rates of effectiveness of non-budesonide therapies for MC based on available data in the field. Studies in the meta-analysis showed a la

BACKGROUND & AIMS: Studies evaluating reproductive outcomes among male patients with inflammatory bowel disease (IBD) are limited. We evaluated use of IBD medications and association with semen parameters, a proxy of male fertility, and adverse pregnancy outcomes (early pregnancy loss [EPL], preterm birth [PB], congenital malformations [CM]).METHODS: We searched Medline, Embase, Scopus, and Web of Science (PROSPERO CRD42020197098) from inception to April 2022 for studies reporting semen parameters and adverse pregnancy outcomes among male patients exposed to biologics, thiopurine, or methotrexate. Standardized mean difference, prevalence, and odds ratios (ORs) of outcomes were pooled and analyzed using a random effects model.RESULTS: Ten studies reporting semen parameters (268 patients with IBD) and 16 studies reporting adverse pregnancy outcomes (over 25,000 patients with IBD) were included. Biologic, thiopurine, or methotrexate use were not associated with decreased sperm count, motility, or abnormal morphology compared with nonexposed patients. The prevalence of adverse pregnancy outcomes with paternal biologic (5%), thiopurine (6%), or methotrexate (6%) exposure was comparable to nonexposed patients (5%). Biologic use was not associated with risk of EPL (OR, 1.26; I2 = 0%; P = .12), PB (OR, 1.10; I2 = 0%; P = .17), or CM (OR, 1.03; I2 = 0%; P = .69). Thiopurine use was not associated with risk of EPL (OR, 1.31; I2 = 19%; P = .17), PB (OR, 1.05; I2 = 0%; P = .20), or CM (OR, 1.07; I2 = 7%; P = .34). Methotrexate use was not associated with risk of PB (OR, 1.06; I2 = 0%; P = .62) or CM (OR, 1.03; I2 = 0%; P = .81).CONCLUSIONS: Biologic, thiopurine, or methotrexate use among male patients with IBD are not associated with impairments in fertility or with increased odds of adverse pregnancy outcomes.

Microscopic colitis is an inflammatory bowel disease divided into two subtypes: collagenous colitis and lymphocytic colitis. With an increasing incidence of microscopic colitis exceeding those of ulcerative and Crohn's disease among elderly people in some countries, microscopic colitis is a debilitating life experience. Therefore, physicians should be familiar with its clinical features and management strategies because the disease deserves the same attention as the classical inflammatory bowel diseases. Here, state-of-the-art knowledge of microscopic colitis is provided from a global perspective with reference to etiopathology and how to establish the diagnosis with the overall aim to create awareness and improve rational management in clinical practice. The immune system and a dysregulated immune response seem to play a key role combined with risk factors (e.g. cigarette smoking) in genetically predisposed individuals. The symptoms are characterized by recurrent or chronic nonbloody, watery diarrhea, urgency, weight loss, and a female preponderance. As biomarkers are absent, the diagnosis relies on colonoscopy with a histological assessment of biopsy specimens from all parts of the colon. Although the disease is not associated with a risk of colorectal cancer, a recent nationwide, population-based cohort study found an increased risk of lymphoma and lung cancer. Budesonide is the first-line therapy for management, whereas immunomodulatory drugs (including biologics) and drugs with antidiarrheal properties may be indicated in those failing, dependent, or intolerant to budesonide. In microscopic colitis induced by checkpoint inhibitors, a drug class used increasingly for a wide range of malignancies, a more aggressive therapeutic approach with biologics introduced early seems reasonable. However, particular attention needs to be drawn to the existence of incomplete forms of microscopic colitis with the risk of being overlooked in routine clinical settings.

The gut microbiome has increasingly been recognized as a critical and central factor in inflammatory bowel disease (IBD). Here, we review specific microorganisms that have been suggested to play a role in the pathogenesis of IBD and the current state of fecal microbial transplants as a therapeutic strategy in IBD. We discuss specific nutritional and dietary interventions in IBD and their effects on gut microbiota composition. Finally, we examine the role and mechanisms of the gut microbiome in mediating colitis-associated colon cancer.

Background: Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of diarrhea and colitis of ICIs alone and in combination with chemotherapy or tyrosine kinase inhibitors (TKIs), histopathological findings, and management. Methods: Two separate studies, including meta-analyses, were performed. Key inclusion criteria were for Study I) phase I-IV trials, and data on diarrhea and/or colitis; for Study II) studies describing histopathologic and endoscopic findings and/or biologic treatment for ICI-induced colitis. Results: The incidence of anti-PD-1/PD-L1 antibody-induced diarrhea and colitis was 10% and 2%, respectively, with no clinically relevant differences between the compounds. The CTLA-4 inhibitor, ipilimumab, induced diarrhea and colitis in 33% and 7% of patients, respectively, whereas the incidence of diarrhea and colitis following ipilimumab combined with nivolumab was 21%-37% and 4%-8%, depending on regimen. The incidence of all-grade diarrhea following ICIs combined with chemotherapy or TKIs was high (17%-56%), whereas only 0.5% of patients developed severe (≥grade 3) colitis. The main patterns of histopathologic presentation after PD-1/CTLA-4 inhibitor mono- or combination therapy were acute and chronic active colitis and microscopic colitis-like. Infliximab and vedolizumab were equally effective against ICI-induced colitis. Conclusion: Expanding treatment options include combinations of ICIs and chemotherapy/TKI with a high incidence of diarrhea and a low incidence of colitis; thus, a potential risk of overtreatment with corticosteroids exists. We suggest a more tailored approach, particularly for the management of low-grade diarrhea. Prospective clinical trials are needed to refine management.

BACKGROUND: Immune-related adverse events due to immune checkpoint inhibitors (ICIs) are not always effectively treated using glucocorticoids and it may negatively affect the antitumor efficacy of ICIs. Interventional studies of alternatives to glucocorticoids are lacking. We examined whether interleukin-6 blockade by tocilizumab reduced ICI-induced colitis and arthritis. PATIENTS AND METHODS: Patients with solid cancer experiencing Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade >1 ICI-induced colitis/diarrhea (n=9), arthritis (n=9), or both (n=2) were recruited and treated with tocilizumab (8 mg/kg) every 4 weeks until worsening or unacceptable toxicity. Patients were not allowed to receive systemic glucocorticoids and other immunosuppressive drugs within the 14-day screening period. The primary endpoint was clinical improvement of colitis and arthritis, defined as ≥1 grade CTCAE reduction within 8 weeks. Secondary endpoints were improvements and glucocorticoid-free remission at week 24; safety; radiologic, endoscopic, and histological changes; and changes in plasma concentrations of C reactive protein, cytokines (IL-6, IL-8, and IL-17), and YKL-40. RESULTS: Nineteen patients were available for efficacy analysis; one patient was excluded due to pancreatic insufficiency-induced diarrhea. Patients received treatment with pembrolizumab (n=10) or nivolumab (n=4) as monotherapy or ipilimumab and nivolumab (n=5) combined. Seven patients had been initially treated with glucocorticoids, and two of them also received infliximab. Ten patients continued ICI therapy during tocilizumab treatment. The primary endpoint was achieved in 15 of 19 (79%) patients. Additional one patient had ≥1 grade reduction at week 10, and another patient had stabilized symptoms. At week 24, ongoing improvement without glucocorticoids (n=12), including complete remission (n=10), was noted. Five patients had grades 3-4 treatment-related adverse events, which were manageable a

The pathogenesis of inflammatory bowel diseases (IBD) involves genetic predisposition, environmental factors, and a broadly dysregulated intestinal immune response to the commensal intestinal microflora. The interface between genetic predisposition and environmental factors is reflected in the epigenetic regulation at the transcriptional level. Treatment targets now involve mucosal and histological healing, but the future might additionally include normalization of intestinal cellular functions also at the molecular level, for example comprising complete restoration of phenotypic, genotypic, and epigenetic states. Recent developments in patient-derived epithelial intestinal stem cell (ISC) organoid technologies have opened exciting new therapeutic opportunities to potentially attain molecular healing by combining stem cell therapy with molecular manipulations using (epi)drugs and/or CRISPR/Cas9 genome editing. Here, we are the first to discuss the possibility for phenotypic, genotypic, and epigenetic restoration via molecular manipulations and stem cell therapy in IBD from a clinical perspective.