Intestinal Research最新文献

Background/aims: Diagnosis of intestinal tuberculosis (ITB) is challenging. Histopathology and microbiological examination remain the gold standard, but previous studies show varied diagnostic performance. We aimed to systematically evaluate the accuracy of tests to diagnose ITB in both conventional and novel methods.

Methods: We searched MEDLINE and EMBASE from inception to October 2023. All studies enrolling at least 10 patients with reported information regarding the diagnosis of ITB based on endoscopic biopsy specimens, stool tests, and blood tests were included. We performed a meta-analysis using a random-effects model to estimate the performance of each test.

Results: Of 3,308 abstracts reviewed, 55 studies with 6,072 participants met the inclusion criteria. Endoscopic tissue biopsy for acid-fast bacilli, the presence of caseous granuloma on histopathology, polymerase chain reaction (PCR) for tuberculosis, mycobacterial culture, and Xpert MTB/RIF showed pooled sensitivity of 12% (95% confidence interval [CI], 8%-17%), 18% (95% CI, 12%-27%), 58% (95% CI, 44%-72%), 23% (95% CI, 12%-40%) and 29% (95% CI, 17%-46%), respectively. The liquid medium culture showed higher sensitivity than conventional Lowenstein-Jensen medium (25% [95% CI, 13%-43%] and 6% [95% CI, 3%-13%]). Pooled sensitivity and specificity of stool PCR for TB were 73% (95% CI, 43%-90%) and 95% (95% CI, 79%-99%), respectively. Additionally, the pooled sensitivity and specificity of interferon-gamma release assay (IGRA) were 86% (95% CI, 79%-91%) and 86% (95% CI, 81%-89%).

Conclusions: Endoscopic tissue biopsy samples had limited sensitivity in diagnosing ITB. IGRA showed good accuracy and may be combined with other methods to improve the diagnostic yield. Stool PCR demonstrated a good performance but based on a few studies.

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

Background/aims: Ustekinumab (UST) and infliximab (IFX) are both effective in the treatment of perianal fistulizing Crohn's disease (CD), but limited research has focused on comparing the efficacy of UST versus IFX in this field. This study aimed to compare the effectiveness of UST or IFX in treating perianal fistula of CD patients naive to biological agents in a real-world setting.

Methods: A retrospective cohort study included patients with perianal fistulizing CD treated with UST or IFX was conducted to evaluate the rates of luminal and perianal fistula response and remission at 6 months after treatment.

Results: Ninety-seven patients (49 UST and 48 IFX) were enrolled. Compared to IFX, UST exhibited significantly higher rates of treatment success (89.8% vs. 50.0%, P< 0.001) and intestinal clinical response (85.7% vs. 68.8%, P= 0.048), but no significant differences in fistula remission, fistula response, fistula closure, intestinal clinical remission, endoscopic remission and endoscopic response was observed. Furthermore, multivariate analyses demonstrated complexity of fistula was conversely associated with fistula remission between the UST and IFX groups. Finally, the rates of disease relapse and operation in the IFX group were higher as compared to the UST group during follow-up.

Conclusions: UST may serve as a promising alternative to IFX for the treatment of perianal fistulizing CD.

Crohn's disease is a chronic inflammatory disease of the digestive tract with extraintestinal manifestations, which include skin conditions, arthritis, ocular inflammation, and several autoimmune conditions. Dermatologic manifestations in Crohn's disease complicate the treatment course and prognosis and should be addressed promptly. Here, we report a 20-year-old male with a history of Crohn's disease, presenting with palpable purpura, consistent with Henoch-Schönlein purpura, upon administration of ustekinumab. The immunoglobulin A vasculitis was treated with prednisone and the discontinuation of ustekinumab. Due to the increased usage of biological agents in inflammatory bowel diseases, associations between biologics and vasculitides should be further studied in Crohn's disease patients for alternative treatment strategies and to understand potential adverse effects caused by biologics in Crohn's disease.

Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents-tofacitinib, filgotinib, and upadacitinib-differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

Background/aims: The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response.

Methods: In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled.

Results: Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00-7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13-0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response.

Conclusions: Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence.

Background/aims: Inflammatory bowel disease (IBD) is increasing across the globe, more so in populous countries like India. We aimed to study the disease burden and epidemiological trends of IBD in India and look closer into the disease pattern across the country from 1990 to 2019.

Methods: The burden of IBD was estimated in India using the data from the Global Burden of Disease estimate for 2019, which is a comprehensive worldwide project. The analysis included various parameters like incidence, prevalence, mortality, disability-adjusted life years, years lived with disability, and years of life lost as age-adjusted rates (per 100,000 population). Using modeling, the prediction was also made for 2050 in India.

Results: The age-standardized incidence, prevalence, mortality, and disability rates of IBD in India for 2019 were 2.34, 20.34, 0.40, and 13.04, respectively. These are lower than the global incidence, prevalence, mortality, and disability rates of 4.97, 59.25, 0.54, and 20.15, respectively. The annual rates of change in incidence, prevalence, mortality, and disability rates in India from 1990 to 2019 were 0.05, -0.02, -0.36, and -0.35, respectively. The annual rates of change in incidence and prevalence are higher than the global rate of -0.18 and -0.19, while the annual rates of change in mortality and disability are lower than the global rate of -0.19 and -0.26.

Conclusions: The incidence and prevalence of IBD in India are lower compared to the global population but are increasing at a faster rate than the global population.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis, is a chronic condition marked by immune dysregulation, genetic predisposition, and metabolic disturbances. Emerging evidence highlights the role of lipid metabolism and peroxisome proliferator-activated receptor (PPAR) signaling in modulating immune responses in IBD. PPAR-γ and PPAR-α regulate macrophage polarization, T-cell differentiation, and epithelial barrier integrity, influencing disease severity and progression. Alterations in PPAR activity contribute to metabolic stress and inflammation, linking IBD pathophysiology to immunometabolism. Studies suggest that targeting PPARs may mitigate inflammation through modulation of cytokine production, immune cell function, and gut microbiota interactions. In this review, we focus specifically on CD and explore how PPAR signaling intersects with mesenteric adipose tissue dysfunction and microbial dysbiosis, 2 hallmark features of CD. PPAR agonists, already used in metabolic-inflammatory diseases such as metabolic-associated liver disease, have demonstrated antiinflammatory effects in experimental colitis models. Translating these findings into clinical applications could offer novel treatment strategies for CD. Future research should focus on clinical trials, genetic studies, and microbiota-targeted approaches to elucidate PPAR-driven mechanisms in CD pathogenesis. Understanding the interplay between PPARs, lipid metabolism, and immune responses may lead to innovative therapeutic strategies, improving disease management and patient outcomes.