Intestinal Research最新文献

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.

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.

Background/aims: Crohn's disease (CD) leads to bowel damage and disability if suboptimally treated. We investigated firstyear treatment decisions and real-world use of biologics in patients with CD in Japan.

Methods: In this retrospective observational study (2010-2021) from the JMDC claims database, patients with a new diagnosis of CD (no CD claims record within 12 months before index) who received ≥ 1 pre-defined treatment were grouped by use of biologics and systemic corticosteroids (SCS) within the first year of diagnosis.

Results: Of 823 patients included, 470 (57.1%) were prescribed biologics and 353 (42.9%) were not; 77.6% were male, 75.7% had adult-onset CD, and median age was 24 years. Patients prescribed biologics were younger (median: 23 years vs. 28 years) and more had perianal lesions (43.0% vs. 22.9%) than those not prescribed biologics; 64.9% (95% confidence interval, 60.4%-69.2%) received a top-down treatment approach (no SCS before biologics). Factors significantly associated with a top-down treatment approach were male sex, perianal lesions, no use of immunomodulators, and use of anti-tumor necrosis factor therapies. The proportion of patients receiving SCS before biologics (step-up approach) increased after 2018, with a shift from prednisolone to budesonide from 2016. Persistence with first biologics decreased over time, with no differences between biologic types.

Conclusions: Use of biologics for treatment of CD within the first year of diagnosis in Japan has remained stable over the past decade. However, there was a shift to a step-up treatment approach, with an increase in use of SCS before biologics over time.

Background/aims: The incidence of perianal lesions (PL) in children with Crohn's disease (CD) is higher in East Asia than in Western countries. Early intervention for PL is essential to prevent sphincter dysfunction and ostomy placement. In this study, we aimed to investigate the clinical features, treatment, and consequences of pediatric CD with PL.

Methods: We retrospectively reviewed a cohort of children diagnosed with CD from 2010 to 2020 at a Japanese children's hospital. Demographics, treatments, and outcomes were evaluated and compared among subgroups.

Results: Among 112 pediatric patients with CD, 36 (32.1%) had experienced PL during the observational period. The median ages at diagnosis and follow-up periods were 131 and 70 months, respectively. Six (85.7%) patients in the very early-onset (VEO) group (CD diagnosed before 6 years old) and 24 (82.8%) in the older age group had PL upon diagnosis of CD (P= 0.851). Biologics were given to 94.4% of patients: infliximab (67.7%), adalimumab (58.8%), ustekinumab (44.1%), risankizumab (11.8%), and vedolizumab (5.9%). Biologics were introduced within 1 year in 89.5% and 40.0% of patients diagnosed in 2016-2020 and 2010-2016, respectively (P= 0.002). Seton was frequently used in the older age group (87.5 vs. 42.9%, P= 0.190). Ostomy was frequently required in the VEO group (42.9% vs. 0.0%, P= 0.006).

Conclusions: Patients with VEO-CD and PL had a notably high risk of ostomy placement. The earlier introduction of biologics and surgical interventions reduced corticosteroids use and ostomy placement in pediatric CD patients with PL.

Background/aims: Both endoscopic resection (ER) and transanal surgery (TAS) are minimally invasive treatment options that allow organ preservation in early rectal tumors. We conducted a meta-analysis to compare treatment outcomes between the 2 treatments.

Methods: We searched all relevant studies published until January 2024 that examined the comparative outcomes between ER and TAS for rectal tumors, including adenoma, adenocarcinoma, and neuroendocrine tumor (NET). TAS included transanal excision, transanal endoscopic microsurgery, and transanal minimally invasive surgery.

Results: Seventeen studies with a total of 1,569 patients were included in this meta-analysis. For adenoma/adenocarcinoma, the R0 resection rate did not differ between ER and TAS (risk ratio [RR], 0.99; 95% confidence interval [CI], 0.94-1.03). For NET, the R0 resection rate was lower in the ER group than in the TAS group (RR, 0.76; 95% CI, 0.68-0.84) and the procedure time for ER was shorter than that for TAS. For both adenoma/adenocarcinoma and NET, ER and TAS did not differ in terms of complication rates, additional surgery, and recurrence.

Conclusions: ER and TAS showed similar treatment outcomes for adenoma/adenocarcinoma. Considering that TAS typically incurs higher costs than ER, ER may be favored in the treatment of rectal adenoma/adenocarcinoma. For rectal NET, TAS showed a superior R0 resection rate than ER. However, given that TAS requires a long procedure time, expensive equipment, and complex manipulations, TAS may be considered selectively for large NETs with suspected deep tumorous infiltration.

Background/aims: Data from Asia regarding the short-term and long-term outcomes for acute severe ulcerative colitis (ASUC) are limited. We assessed the outcomes of ASUC, identified the risk factors for colectomy, and compared colectomy rates between the pre-biologics and post-biologics eras in Taiwan.

Methods: The patients with an ASUC diagnosis between January 2013 and March 2022 at 5 tertiary medical centers were retrospectively analyzed.

Results: In total, 98 patients were enrolled, with 68.4% diagnosed in the post-biologics era. In 78.6% of the ASUC patients initially received intravenous steroid therapy, for which the success rate was 74.1%. As for rescue therapy, 15 patients (93.8%) received biologics and 1 (6.3%) received cyclosporin. Biologics rescue therapy had a 93.3% success rate. One (1%) mortality due to septic shock occurred. The colectomy rate for index ASUC admission was 11.2%. Patients receiving colectomy were predominantly male (P= 0.012) and at older age (P= 0.016). Higher C-reactive protein (P= 0.035), lower albumin (P= 0.017), and hemoglobin (P= 0.023) levels were associated with colectomy risk. During a median follow-up of 24 months, 13 patients (15.1%) had recurrent ASUC and 23.1% of patients received colectomy. The accumulated colectomy rate at 3 years did not differ between the pre- and post-biologics eras (16.1% vs. 13.4%, P= 0.270).

Conclusions: This is the first Asian study on ASUC to compare colectomy rates between the prebiologics and post-biologics eras, revealing no significant difference. The recurrent ASUC had a higher colectomy rate than the index ASUC.