Intestinal Research最新文献

Background/aims: Timely detection with highly accurate biomarkers would be helpful in effectively managing colorectal cancer (CRC). We aim to investigate the accuracy of 3 emerging biomarkers-miR-21, miR-24, and miR-145-in detecting synchronous metastases in CRC.

Methods: We recruited newly diagnosed CRC patients with extensive investigations to determine cancer staging and metastatic status. The expression levels of miR-21, miR-24, and miR-145 in tumor biopsy were measured using reverse transcription quantitative polymerase chain reaction. Multivariate and receiver operating characteristic analyses were conducted to evaluate the association and performance of these miRNAs in identifying various metastases.

Results: Out of the 63 Indonesian patients involved, 37 (58.7%) were diagnosed with localized CRC, whereas the remaining 26 (41.3%) were identified as having metastases: 31.7% liver, 14.3% lung, 3.2% bone, and 4.8% other metastases. There was a significant downregulation of miR-24 expression in metastatic CRC patients compared to those without metastases (0.024 [4.680] vs. 12.900 [42.376], P< 0.01). Overexpression of miR-21 was identified as an independent risk factor of synchronous metastasis (odds ratio [OR], 1.016; 95% confidence interval [CI], 1.003-1.030; P< 0.05), particularly lung (OR, 1.011; 95% CI, 1.002-1.020; P< 0.05) and bone (OR, 1.022; 95% CI, 1.001-1.043; P< 0.05) metastases. No association was found between miR-145 expression and metastatic status. The miR-21/24 ratio accurately identified synchronous metastases irrespective of organ site, with an area under the curve (95% CI) of 0.833 (0.722-0.944) and positive predictive value of 94.4%.

Conclusions: Alteration of miR-21 and miR-24 expression levels was associated with a high incidence of synchronous metastases in Indonesian CRC. The mir-21/24 ratio demonstrated significant potential as a biomarker for detecting synchronous metastases in CRC.

The rising incidence of ulcerative colitis (UC) globally highlights the necessity for treatment strategies that extend beyond symptom control to include inducing and maintaining remission, achieving biochemical and endoscopic remission, and restoring quality of life. Janus kinase inhibitors, such as filgotinib (FIL), show promise in treating UC. This review consolidates evidence on FIL in treating UC from the SELECTION and SELECTIONLTE trials, and real-world studies. Overall, FIL demonstrated rapid symptom relief (e.g., improved rectal bleeding and stool frequency) within 7 days and durable efficacy (e.g., clinical remission, Mayo Clinic Score response) up to 4 years. Improvements in health-related quality of life (HRQoL) and reduced corticosteroid dependency were also observed. The 200 mg dose generally elicited greater efficacy responses than the 100 mg dose, and hence may potentially be a more suitable choice for optimizing treatment outcomes. Although FIL may be an effective long-term treatment option regardless of prior biologic experience, biologic-naive patients may experience greater sustained clinical improvements. Safety outcomes indicated that FIL was well tolerated with no unexpected safety signals in SELECTION and SELECTIONLTE. These findings support FIL's potential as a robust therapeutic option for UC, due to its acceptable safety profile and benefits across clinical and HRQoL outcomes.

Background/aims: The gender-specific impact of inflammatory bowel disease (IBD) on women in low- and middle-income countries remains underexplored. We aimed to assess the effects of IBD on different domains of women's health.

Methods: A cross-sectional study was conducted in women with IBD at a tertiary care center in North India. Women with IBD were interviewed using a structured questionnaire assessing menstrual, reproductive, sexual, mental, social, and financial health, and healthcare access.

Results: Two hundred and two women (median age, 41 years; ulcerative colitis [n = 155, 76.7%]) were enrolled. Anemia was present in 161 women (79.7%), with a median hemoglobin of 10.5 g/dL. Among menstruating women (n = 138), 69 (50%) had irregular cycles, and 39 (28.3%) experienced IBD exacerbations during menstruation. Sexual dysfunction was reported in 82.5% (n = 137/166). Pregnancy-related concerns were common (n= 120, 59.4%), mainly due to risk of heritability and safety of IBD medication. Ten women (4.9%) attributed pregnancy loss to disease activity. Cervical cancer screening (3.0%) and human papillomavirus vaccination (4.0%) rates were low. The median SICC-IBD (social impact of chronic conditions in IBD) score was 0.6. Forty-three women (21.3%) reported difficulties in finding a partner due to IBD. Limited access to IBD specialists (n = 150, 74.3%) and medications (n = 164, 81.2%) were reported in hometown. Fifty-five women (27.2%) relied on loans to manage treatment expenses.

Conclusions: IBD affects women across physical, reproductive, social, and financial domains. Culturally sensitive, multidisciplinary care models are essential to address these unmet needs.

In real-world clinical practice, 3 Janus kinase (JAK) inhibitors-tofacitinib, filgotinib, and upadacitinib-are now available for the treatment of ulcerative colitis. Emerging real-world evidence highlights distinct efficacy and safety profiles among these agents, largely attributed to differences in JAK selectivity and dosing strategies. Notably, data are accumulating on differential efficacy, predictors of therapeutic response, and outcomes in patients who switch between JAK inhibitors, contributing to a clearer understanding of the optimal positioning of each agent. Regarding safety, particular attention has been given to risks such as herpes zoster infection and drug-induced acne, underscoring the importance of appropriate patient education and individualized risk assessment. This review summarizes clinical trials and current real-world data on tofacitinib, filgotinib, and upadacitinib in ulcerative colitis, and discusses strategies for optimizing their clinical application.

Background/aims: The real-world management of acute severe ulcerative colitis (ASUC) varies considerably across regions and healthcare settings. This study aimed to evaluate current management practices for ASUC among gastroenterologists in India.

Methods: A structured, web-based survey covering 5 thematic domains (provider and institutional characteristics, clinical workload and initial management, diagnostic practices, infectious work-up, and strategies for rescue therapy) was disseminated via email. Responses were analyzed using descriptive statistics.

Results: A total of 228 responses were received from across India's 5 geographic zones. The majority of respondents were affiliated with either corporate hospitals (n = 76, 33.3%) or teaching hospitals (n = 68, 29.8%). The majority (n = 135, 59.2%) reported managing up to 10 ASUC cases annually. The Truelove and Witts criteria were the most commonly used for diagnosis (n = 169, 74.1%). Nutritional assessment was performed by 89 respondents (39.0%). Biopsies for cytomegalovirus during index sigmoidoscopy were obtained by 75 (32.9%). Intravenous hydrocortisone was the preferred steroid (n = 188, 82.5%). Low molecular weight heparin for thromboprophylaxis was never prescribed by 62 respondents (27.2%). Oxford criteria were most frequently used to assess steroid response (n = 150, 65.8%). More than half of the respondents (n = 125, 54.8%) reported that fewer than 50% of patients accepted rescue therapy. Rescue therapy was initiated on or after day 5 by 153 respondents (67.1%). Early involvement of colorectal surgeons was reported by 66 (28.9%). A majority (n = 200, 87.7%) were associated with low-volume centers for ileal pouch-anal anastomosis, performing < 5 procedures per year.

Conclusions: This nationwide survey reveals considerable heterogeneity in ASUC management in India. Standardizing care through patient and healthcare provider education and context-specific guidelines is imperative.

Background/aims: The development of antinuclear antibodies (ANAs) during infliximab treatment has been observed in previous clinical trials. To evaluate the clinical significance of ANA seroconversion and its potential association with the formation of antibodies against infliximab.

Methods: This retrospective study included 130 Crohn's disease patients undergoing infliximab therapy. ANA titers were measured at baseline and after 6 months of treatment. Inverse probability of treatment weighting was applied to control for confounding variables.

Results: Among the 111 patients with negative baseline ANA, 36 (32.4%) developed ANA positivity after 6 months of infliximab treatment. After adjustment with inverse probability of treatment weighting, a significantly higher proportion of patients in the ANA non-seroconversion group achieved endoscopic remission at 6 months compared to those with ANA seroconversion (64.5% vs. 35.5%: adjusted odds ratio [aOR], 3.61; 95% confidence interval [CI], 1.30-10.02; P= 0.014). At 18 months, patients in the non-seroconversion group also exhibited higher rates of both endoscopic response (57.5% vs. 42.3%: aOR, 3.38; 95% CI, 1.15-9.96; P= 0.027) and endoscopic remission (60.0% vs. 40.1%: aOR, 2.91; 95% CI, 1.06-8.01; P= 0.039) compared to the seroconversion group. Additionally, patients who developed ANA seroconversion had a higher rate of detectable antibodies against infliximab at both 6 and 18 months. A multivariable analysis identified female sex, older age at diagnosis, and lower serum albumin levels as independent predictors of ANA seroconversion at 6 months.

Conclusions: ANA non-seroconversion at 6 months was associated with higher rates of endoscopic remission and a lower likelihood of developing antibodies against infliximab.

Background/aims: Guidelines recommend that steroid treatment for ulcerative colitis (UC) is tapered or withdrawn within 3 months of initiation, and thiopurine treatment or advanced therapy is administered for steroid-dependent UC. This study aimed to clarify real-world treatment patterns and outcomes in patients with steroid-dependent UC in Japan.

Methods: A retrospective analysis of JMDC (Japan Medical Data Center) claims data was conducted to identify patients with a new UC diagnosis between June 2010 and September 2019. Index dates were the UC treatment start date (initiation of any UC treatment), steroid dependence/resistance confirmation date (identification of steroid-dependent UC), and treatment intensification date (initiation of thiopurine treatment/advanced therapy).

Results: Of 5,602 patients with newly diagnosed UC, 986 (17.6%) initiated steroids within 12 months (85.4% [842/986] received 5-aminosalicylic acid at the UC treatment start date). Of these 986 patients, 429 (43.5%) were classified as steroid-dependent (steroid dependence/resistance confirmation date). Of these 429 patients, 128 (29.8%) initiated thiopurine treatment and 75 (17.5%) initiated advanced therapy (treatment intensification date); 226 (52.7%) continued with steroids only. Across these groups, 3-6% discontinued steroids within 3 months of initiation. Hospitalization due to UC in the 12 months after the treatment intensification date occurred in 24.2% (31/128) and 18.7% (14/75) of patients who initiated thiopurine and advanced therapy, respectively.

Conclusions: Over half of patients with steroid-dependent UC continued steroid treatment only. Steroid discontinuation within 3 months of initiation was low, irrespective of whether thiopurines or advanced therapy were initiated. Management of patients with steroid-dependent UC in Japan requires further treatment optimization toward guideline adherence.

Background/aims: To assess, post hoc, tofacitinib safety/effectiveness in patients with ulcerative colitis (UC), stratified by age, using data from a 60-week post-marketing surveillance (PMS) study in Japan.

Methods: All patients with UC receiving tofacitinib in Japan were enrolled in a large PMS study. Incidence proportions of adverse events (AEs), incidence rates (IRs; unique patients with events/100 patient-years of exposure) of clinically important AEs, reasons for discontinuation, and partial Mayo score clinical remission, stratified by age ( ≥ 65 and < 65 years), were evaluated.

Results: The analysis included 212 older ( ≥ 65 years) and 1,770 younger ( < 65 years) patients. Demographics and baseline disease characteristics were generally similar between groups; however, more older versus younger patients had cardiovascular disease (23.1% vs. 4.6%). Incidence proportions of AEs were comparable between groups, but IRs (95% confidence intervals) in older versus younger patients were numerically higher for herpes zoster (9.81 [5.72-15.71] vs. 5.44 [4.28-6.82]), and higher for serious infections (4.45 [1.92-8.76] vs. 1.14 [0.65-1.85]). More older versus younger patients discontinued due to AEs (28.6% vs. 17.6%); more younger versus older patients discontinued due to insufficient clinical responses (50.3% vs. 35.2%). Clinical remission rates through 60 weeks were generally similar between groups.

Conclusions: Older patients had higher IRs of herpes zoster and serious infection than younger patients, although tofacitinib effectiveness was similar between age groups. Discontinuation due to AEs was more common in older patients. Despite the smaller sample size of older versus younger patients, a focused evaluation of older patients is of benefit.

The incidence and prevalence of elderly-onset inflammatory bowel disease (EO-IBD) are increasing worldwide. The rising incidence of EO-IBD in Asia is driven by rapid industrialization and an aging population. Older patients often have multiple comorbidities and polypharmacy, which make diagnosis and management of the disease more challenging. Additionally, Asian patients with EO-IBD exhibit unique clinical characteristics, including frequent ileal involvement. Differences in phenotype between patients with EO-IBD in Western and Asian countries may explain subsequent disparities in the natural history of these patients. Although EO-IBD often manifests with a mild clinical course at diagnosis, it poses distinct diagnostic and therapeutic challenges. Understanding these characteristics is essential for optimizing patient care and for optimizing patient outcomes. In this review, we explore the epidemiology, disease burden, and clinical characteristics of EO-IBD in Asia, as well as the therapeutic approaches for treating the disease.