PURPOSE:Thiopurines remain an effective treatment for maintaining remission in inflammatory bowel disease (IBD), yet their use is often limited by thiopurine-induced leukopenia (TIL), a potentially life-threatening adverse effect. We aimed to investigate pharmacogenetic associations with TIL in patients with IBD. MATERIALS AND METHODS:We retrospectively analyzed 218 thiopurine-treated patients from two independent IBD cohorts with whole-exome sequencing. Pharmacogenetic subgroups were defined using Clinical Pharmacogenetics Implementation Consortium star allele-based molecular phenotypes or genotype-based classifications. Genetic associations with TIL, defined as white blood cell count ≤3000/µL, were analyzed using Andersen-Gill models adjusted for clinical covariates. RESULTS:NUDT15 intermediate metabolizers [hazard ratio (HR) 5.21, p<0.001], poor metabolizers (HR 6.42, p<0.001), and IL6 heterozygotes (HR 4.35, p<0.001) showed reproducible, independent associations with increased TIL risk. Incorporating IL6 into the traditional TPMT/NUDT15 model significantly improved sensitivity (p=0.0156) and negative predictive value (p=0.046). CONCLUSION:Our findings confirm the central role of NUDT15 in TIL susceptibility and identify IL6 as a novel, independent contributor in Korean patients with IBD. Incorporating IL6 into existing pre-emptive pharmacogenetic testing may support safer thiopurine therapy.

Background/Aims: Intestinal Beh & ccedil;et's disease (BD) is a manifestation of BD involving the gastrointestinal tract. Although fecal calprotectin (FC) is a useful inflammatory marker, its role in intestinal BD is unclear. Methods: We retrospectively analyzed 78 patients with intestinal BD to evaluate correlations between FC levels and the Disease Activity Index for Intestinal Beh & ccedil;et's Disease (DAIBD), C-reactive protein (CRP), and erythrocyte sedimentation rate. FC and CRP levels were compared between patients in endoscopic remission and those with active disease. Receiver operating characteristic (ROC) curve analysis was used to evaluate FC's ability to predict endoscopic activity and ulcer size. Results: FC levels significantly correlated with DAIBD scores (r= 0.253, P= 0.025) and CRP (r= 0.227, P= 0.046). Patients with endoscopically active disease had higher FC (1,124 +/- 1,957 mu g/g vs. 367 +/- 1,208 mu g/g; P< 0.001) and CRP levels (16.0 +/- 23.7 mg/L vs. 14.4 +/- 46.5 mg/L; P= 0.027) than those in remission. Patients with larger ulcers ( >= 30 mm) had higher FC levels than those with smaller ulcers (2,212 +/- 2,609 mu g/g vs. 962 +/- 1,822 mu g/g; P= 0.034). An FC cutoff level of 176 mu g/g discriminated active endoscopic disease (sensitivity 59.3%, specificity 83.3%), with an area under the ROC curve (AUC) of 0.724 (95% confidence interval, 0.605-0.843; P= 0.002), outperforming CRP (AUC, 0.657). Conclusions: FC levels correlated with DAIBD scores and endoscopic inflammation in intestinal BD. FC outperformed CRP in detecting endoscopic activity, supporting its use in disease management.

Background:Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic and relapsing condition with complex pathogenesis and limited therapeutic options. The efficacy of CU104, a novel blocker of endothelial dysfunction, in IBD models is poorly understood. Moreover, its precise cellular or molecular mechanisms in colitis remain unknown. Methods:To evaluate the therapeutic potential of CU104, we tested CU104 in two colitis models: dinitrobenzene sulfonic acid (DNBS)-induced colitis in wild-type mice and dextran sodium sulfate (DSS)-challenged colitis in IL-10 knockout mice. Additionally, we used Caco-2, HCT-116, and HT-29 cells to assess CU104 effects on intestinal barrier function (FITC-dextran permeability and TEER), inflammatory signaling (reporter assays), actin dynamics, and gene expression (gene expression profiling and immune assays). Results:CU104 demonstrated potent suppressive effects on innate immune responses, intestinal and vascular barrier dysfunctions, and immune cell recruitment in these colitis models. Furthermore, CU104 inhibited the activation of the transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells and interferon regulatory factor, as well as the ezrin/radixin/moesin (ERM) signaling pathway, both in vitro and in vivo, by modulating actin dynamics. Consistent with these findings, CU104 improved the functions of vascular and intestinal barriers and regulated immune cell recruitment during inflammation. Conclusions:Collectively, our findings demonstrate that CU104 can regulate actin dynamics and inflammatory signaling pathways, highlighting potential therapeutic targets for IBD.

INTRODUCTION:Although sigmoid volvulus is a potentially life-threatening condition in elderly patients, its prognostic factors are not well-known. This study aimed to evaluate clinical outcomes and identify prognostic factors in patients with sigmoid volvulus. METHODS:This retrospective cohort study included 96 patients diagnosed with sigmoid volvulus by abdominal CT between January 2005 and January 2023 at two tertiary referral centers. After patients who underwent emergent surgery, refused endoscopic treatment, or experienced spontaneous decompression were excluded, 75 patients were analyzed. Logistic regression identified factors linked to endoscopic decompression failure, while Cox regression analyzed recurrence factors. RESULTS:Among the 75 patients who underwent endoscopic decompression, 60 (80%) showed improvement, whereas 15 (20%) did not. In the logistic regression analysis, younger (≤ 65 years) age (odds ratio [OR], 10.21; 95% confidence interval [CI], 2.21-47.09) and larger (≥ 85 mm) maximum cross-sectional diameter of distended colon (OR, 5.06; 95% CI, 1.12-22.87) were associated with failure of initial endoscopic treatment. Among the 60 patients who initially improved with endoscopic treatment, cumulative recurrence rates were 30% at 1 year and 36.7% at 3 years. In the Cox regression analysis, a larger (≥ 85 mm) maximum cross-sectional diameter of distended colon (hazard ratio [HR], 3.27; 95% CI, 1.25-8.59) and a greater (≥ 230 mm) longitudinal axis length of spiraled colon (HR, 5.18; 95% CI, 1.67-16.05) at diagnosis were related to volvulus recurrence. CONCLUSIONS:Younger age (≤ 65 years) and severe colonic dilatation (≥ 85 mm) were associated with endoscopic decompression failure, while severe colonic dilatation (≥ 85 mm) and marked longitudinal elongation (≥ 230 mm) were independently related to recurrence. These findings may guide early surgical consultation for high-risk sigmoid volvulus patients and subsequent resection planning after successful decompression.

Background/Aims:Guidelines for further diagnostic evaluation in patients with isolated terminal ileitis have not been established. Although computed tomography enterography (CTE) is an established modality for small bowel evaluation, its diagnostic value in this setting remains unclear. This study aimed to evaluate the diagnostic utility of CTE in patients with isolated terminal ileitis identified during ileocolonoscopy and to identify patient subgroups most likely to benefit from additional CTE evaluation. Methods:We retrospectively reviewed the medical records of 98 patients who were diagnosed with terminal ileitis without colonic abnormalities during ileocolonoscopy at a tertiary referral center between October 2005 and July 2021. A positive CTE finding was defined as the presence of a lesion in the proximal small bowel beyond the terminal ileum. Independent predictors of positive CTE findings were evaluated using logistic regression analysis. Results:The mean patient age was 43.8 years, and 59.2% were male. Positive CTE findings were identified in 48 patients (49.0%). The most common final diagnosis among these patients was Crohn's disease (n=36, 75.0%). Multivariate analysis revealed that an elevated erythrocyte sedimentation rate (>10 mm/hr) (odds ratio [OR], 3.057; p=0.040), older age (>60 years) (OR, 7.392; p=0.002), and mucosal erythema in the terminal ileum on ileocolonoscopy (OR, 12.078; p=0.030) were independent predictors of positive CTE findings. Conclusions:Approximately half of patients with isolated terminal ileitis had positive CTE findings, with Crohn's disease being the most frequent final diagnosis. CTE may be particularly useful in patients with elevated erythrocyte sedimentation rate (>10 mm/hr), age >60 years, or mucosal erythema in the terminal ileum.

BACKGROUND AND AIM:The incidence of ulcerative colitis (UC) has been increasing in Asia. Comprehensive data on the long-term course of moderate-to-severe UC remain scarce. This study investigated the clinical outcomes and factors associated with a disabling disease course in Korean patients with moderate-to-severe UC. METHODS:The moderate-to-severe ulcerative colitis in Korea study was a prospective, multicenter, hospital-based inception cohort study that enrolled patients with newly diagnosed moderate-to-severe UC between August 2014 and February 2017. Clinical outcomes and factors associated with a disabling disease course were evaluated over 5 years. RESULTS:Among 353 patients included, the median follow-up duration was 4.9 (interquartile range, 2.1-5.0) years, and 214 patients (60.6%) completed the 5-year follow-up. At 5 years, the cumulative rates of outcomes were clinical relapses, 62.9%; proximal disease extension, 29.5%; and UC-related hospitalization, 22.4%. Colectomy was required in two patients (0.6%), without mortality. A disabling disease course occurred in 171 patients (48.4%), with cumulative probabilities of 41.0%, 51.1%, and 53.9% at 12, 36, and 60 months, respectively. Elevated baseline white blood cell count was independently associated with a disabling disease course (adjusted hazard ratio: 1.06; 95% confidence interval: 1.00-1.12; p = 0.035). Five distinct partial Mayo score-based disease trajectory clusters were identified, demonstrating clear prognostic separation. CONCLUSIONS:While Korean patients with moderate-to-severe UC showed a benign structural disease course with minimal colectomy rates, approximately half experienced a disabling disease course. The identified disease trajectories provide a novel framework for risk stratification and personalized management.

Despite the advances in biological and small-molecule therapies, a substantial proportion of patients with inflammatory bowel disease (IBD) experience multiple treatment failures, constituting difficult-to-treat IBD with remission rates plateauing at 30-50%. Advanced combination therapy (ACT), defined as the concomitant use of two advanced therapies with distinct mechanisms of action, has become a strategy to overcome this therapeutic ceiling. This review aims to synthesize the rationale, clinical evidence, safety profile, and practical implementation strategies of ACT in IBD. A narrative review of randomized controlled trials (RCTs), meta-analyses, and real-world observational studies evaluating ACT in IBD was performed, focusing on the mechanistic rationale, efficacy outcomes, safety data, and clinical application strategies. ACT is supported by pharmacokinetic synergy (reduced immunogenicity and improved drug exposure) and pharmacodynamic complementarity (simultaneous blockade of multiple inflammatory pathways). Proof-of-concept RCTs, including VEGA and EXPLORER, along with meta-analyses, revealed higher clinical and endoscopic remission rates with ACT than with monotherapy in refractory populations. The safety profiles are generally comparable to monotherapy, but regimen-specific heterogeneity exists. Although vedolizumab- or ustekinumab-based combinations show favorable long-term safety, regimens including natalizumab or JAK inhibitors warrant caution and close monitoring. Detailed clinical strategies include induction-bridge approaches with JAK inhibitors, safety-anchor strategies with gut-selective agents, mechanistic complementarity strategies for treatment failures, and double-indication strategies for extraintestinal manifestations. ACT is a promising rescue strategy for D2T IBD with encouraging efficacy and acceptable safety. Future research should focus on large-scale RCTs and biomarker-driven strategies to optimize patient selection and treatment protocols for ACT.

Purpose To identify long-term and late symptoms associated with impaired health-related quality of life (HRQoL) in Korean colorectal cancer (CRC) survivors, particularly those linked to worse HRQoL relative to the general population. Methods In this prospective cohort study, HRQoL and symptoms were assessed using the EORTC QLQ-C30, -CR29, -CIPN20, and -ELD14, EQ-5D, and EQ-VAS among 186 CRC survivors enrolled since October 2016 (derivation cohort, MKCCS-1) and 128 additional survivors (validation cohort, MKCCS-2) at a single tertiary cancer center in Korea. Exploratory factor analysis was used to identify clinically relevant symptom domains. HRQoL was subsequently compared with that of an age- and sex-matched general-population cohort (KNHANES-V) to identify specific survivorship symptoms associated with poorer perceived health status. Results After propensity-score matching, CRC survivors had lower mean EQ-5D index scores than the general population (0.823 vs. 0.881; p < 0.001). Abdominal pain, frequent bowel movements, sore perianal skin, fecal incontinence, and peripheral numbness were associated with HRQoL below the general-population mean EQ-VAS; decreased sexual interest and erectile dysfunction were additionally associated with lower HRQoL among men. Fourteen clinically relevant symptom items were grouped into four domains: abdominal/defecatory problems, peripheral neuropathy, voiding problems, and sexual problems (Cronbach’s α = 0.767; KMO = 0.718; p < 0.001). Conclusion Specific gastrointestinal, neuropathic, and sexual symptoms were associated with impaired HRQoL in Korean CRC survivors. These findings identify clinically actionable targets for symptom-focused assessment and supportive care in colorectal cancer survivorship.

Background/Aims:This final long-term extension (LTE) analysis assessed the long-term efficacy and safety of ustekinumab (UST) in the Asian patient subpopulation of the UNITI/IM-UNITI study. Methods:Patients completing safety and efficacy evaluations at Week 44 of the maintenance study were eligible to participate in the LTE and continued their UST treatment. Unblinding occurred after Week 44 analyses were completed, and patients still receiving placebo were discontinued; no placebo data were reported beyond Week 44 in this report. Efficacy assessments were performed every 12 weeks (q12w) until unblinding and at dosing visits thereafter through Week 252. Safety events (per 100 patient-years [PY]) were assessed through Week 272. Results:Sixty-three Asian patients entered the LTE. At Week 44, clinical response/clinical remission rates in the UST 90 mg subcutaneous (SC) q12w and every 8 weeks (q8w) arms were 75.0%/58.3% and 61.5%/53.8%, respectively. At Week 252, clinical response/clinical remission rates in the UST 90 mg SC q12w and q8w arms were 58.3%/41.7% and 23.1%/15.4%, respectively. Normalized C-reactive protein levels were maintained over 252 weeks of UST treatment. Among patients who entered the LTE, the number of treatment-emergent adverse events and serious infections in the UST 90 mg SC combined group was 267.2/100 PY and 4.5/100 PY, respectively. Conclusions:Maintenance therapy with UST 90 mg SC was well tolerated and efficacious in maintaining clinical remission and response rates through 5 years in Asian patients with Crohn's disease, consistent with the global population. (ClinicalTrials.gov Identifier: UNITI-1 [NCT01369329], UNITI-2 [NCT01369342], and IM UNITI [NCT01369355]).

This retrospective study aimed to propose and validate a simple magnetic resonance enterography (MRE)-based assessment of Crohn disease (CD) activity based on the most inflamed bowel segment. A total of 252 adult patients who underwent MRE for suspected or known CD were included. Three abdominal radiologists assessed the simplified Magnetic Resonance Index of Activity (sMARIA) score using MRE. The Maximal Segmental Score was defined as the largest segmental sMARIA among 6 evaluated bowel segments in a patient. The global sMARIA was obtained from the sum of each segmental sMARIA score. Correlation analysis was performed between global sMARIA and Maximal Segmental Score. For patients with endoscopic results, correlation analysis was performed between the simple endoscopic score for CD (SES-CD) and maximal segmental score. The diagnostic performance of the maximal segmental score to predict endoscopic remission (SES-CD <3) was evaluated using the receiver operating characteristic curve analysis. Global sMARIA and Maximal Segmental Score correlated strongly (ρ = 0.954, 95% confidence interval: 0.941-0.964). In 77 patients with endoscopic results, global sMARIA (ρ = 0.685) and Maximal Segmental Scores (ρ = 0.634) moderately correlated with SES-CD without significant difference between 2 scores (P = .17). The area under the receiver operating characteristic curve to predict endoscopic remission was 0.850 for global sMARIA and 0.843 for Maximal Segmental Score without significant difference between them (P = .73). The Maximal Segmental Score based on the evaluation of the most inflamed bowel segment can be a simple practical MRE-based index to represent overall disease activity and predict endoscopic remission in CD.

Purpose: The incidence of inflammatory bowel disease (IBD) is rapidly increasing in newly industrialized Asian countries. However, nationwide epidemiological shifts, especially age-specific trends and urbanization effects, remain unclear in Korea. This study aimed to define recent secular trends in IBD incidence by age and residential area using the Korean National Health Insurance database. Materials and Methods: We conducted a nationwide, population-based study using claims data from the National Health Insurance Service from 2004 to 2015. IBD cases were defined by a combination of diagnostic codes for Crohn's disease (CD) or ulcerative colitis (UC) and relevant prescription records. Age-standardized incidence rates (ASRs) were calculated, and joinpoint regression was used to estimate annual percent changes (APCs). Standardized incidence ratios (SIRs) compared incidence between metropolitan and non-metropolitan areas. Results: A total of 15241 CD and 39028 UC patients were identified. ASRs for both CD and UC steadily increased during the study period, with APCs of 6.8% [95% confidence interval (CI): 5.8-7.8] for CD and 3.2% (95% CI: 2.6-3.8) for UC. CD incidence was highest among adolescents aged 15-19 years. For UC, the peak age of onset shifted from 55-69 years in 2004 to 20-39 years by 2015. The most dramatic rise in UC incidence occurred in the 10-19 age group. Metropolitan areas had higher incidence rates than nonmetropolitan areas for both diseases. Conclusion: The epidemiology of IBD in Korea is rapidly evolving, with increasing incidence, younger onset, and an urban-rural divide. Targeted strategies for adolescents and urban populations are needed.

Background/Aims:The exact cause of ulcerative colitis (UC) remains unclear but likely involves an immune response to an unidentified component of gut microbiota. The use of antibiotics in treating acute severe UC (ASUC) remains controversial. This study aimed to assess the benefits of adding antibiotics to corticosteroids for managing ASUC. Methods:This retrospective study included patients with ASUC who met the Truelove and Witts diagnostic criteria at admission and received intravenous (IV) corticosteroids, with or without adjunctive antibiotics. Key outcomes included the need for medical and surgical rescue therapy during hospitalization and UC-related re-hospitalization rates at 1 week, 3 months, and 1 year. Propensity score matching (PSM) was employed to minimize selection bias in evaluating the impact of adjunctive antibiotics on clinical outcomes. Results:Of the 386 screened patients, 222 met the inclusion criteria: 75 (33.8%) received IV corticosteroids alone, while 147 (66.2%) received IV corticosteroids combined with antibiotics. After PSM (60 patients per group), the addition of antibiotics showed no significant effect on the need for medical rescue therapy during hospitalization, re-hospitalization, or clinical response based on the partial Mayo score after 1 week of hospitalization (68.3% vs. 60.0%; P= 0.341). Similarly, no significant differences were observed in the need for medical rescue therapy, re-hospitalization, or UC-related surgery rates at 3 months or 1 year (P> 0.05). Conclusions:In patients with ASUC, treatment outcomes did not significantly differ between those receiving IV corticosteroids alone and those receiving a combination of IV corticosteroids and antibiotics, suggesting that adjunctive antibiotic use may offer no added clinical benefits.

Background/Aims: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is increasing in East Asia. Most known susceptibility loci, identified primarily in Europeans, remain insufficient to explain clinical heterogeneity in Asians. We performed whole-exome sequencing in Korean IBD patients to identify population-specific variants influencing age at diagnosis.Methods: We analyzed 341 Korean IBD patients (192 CD, 149 UC) from three cohorts. Case-control analysis with external controls was confounded by platform heterogeneity, so we used a within-case Cox proportional hazards model instead. Variants were prioritized using a dual-threshold strategy. Gene-level analysis identified subtype-specific pathways, and disease progression was assessed in patients with longitudinal data (n = 206).Results: We identified 12 novel rare variants (minor allele frequency < 0.01 in gnomAD) predominantly observed in East Asian populations. One variant in GSG1 (rs146166808) reached genome-wide significance (p = 3.39 × 10-8); carriers showed accelerated disease onset and increased risk of aggressive progression (OR = 12.52, p = 0.050). Subtype-specific analyses identified two variants for CD (GSG1, CYP2D6) and five for UC (including IGLL1). Gene-level analysis revealed distinct genetic architectures: CD showed enrichment for axon guidance pathways (p = 0.000065), whereas UC showed enrichment for calcium signaling and tissue maintenance pathways (p = 0.00068).Conclusions: We identified population-specific rare variants influencing disease onset and progression in Korean IBD. Distinct genetic architectures underlying CD and UC provide insight into IBD heterogeneity and potential therapeutic targets in this population.

Lynch syndrome (LS) is a hereditary cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes, most notably associated with colorectal cancer. Although LS patients face high risk of CRC, risk can vary even among those with the same pathogenic MMR germline mutations. We suggest a functional assay platform for assessing mutation risk using patient-derived organoid (PDOs). We measured organoid response to the cytotoxic effects of a methylating agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) based on DNA damage-induced apoptosis. When normal (non-LS) colon organoids were used, treatment with MNNG and four passages of organoid culture led to decreased total growth (organoid area), but there was no significant change in number. To increase the effect of MNNG and induce apoptosis in normal colon organoids, we added O6BG (an MGMT inhibitor) and an ATR inhibitor. The cytotoxic effects of combined treatment with MNNG, O6BG and ATR inhibitor on non-LS-PDOs were significantly higher than in PDOs of LS patients. To detect the difference at an earlier phase, we examined DNA damage response by analyzing γH2AX expression after treatment with MNNG and O6BG for 24 h. Then, we found higher expression of γH2AX in non-LS-PDOs than in PDOs of LS patients, suggesting continued cell survival with mutation accumulation in LS-PDOs. In conclusion, treatment with MNNG and O6BG using PDOs and measurement of resulting DNA damage response could be used as a preclinical platform for risk stratification in LS patients.

Upadacitinib is an oral Janus kinase inhibitor approved for the treatment of moderate-to-severe Crohn’s disease (CD). This post hoc analysis reports the efficacy and safety of upadacitinib for CD in patients in East Asia enrolled in the phase 3 clinical trials. In two induction studies (U-EXCEL [NCT03345849], U-EXCEED [NCT03345836]), adults with moderately to severely active CD were randomized 2:1 to once-daily upadacitinib 45 mg or placebo for 12 weeks. In the 52-week U-ENDURE maintenance study (NCT03345823), patients with clinical response to upadacitinib induction therapy were rerandomized 1:1:1 to once-daily upadacitinib 15 mg, upadacitinib 30 mg, or placebo. Data from patients in East Asia were evaluated. In the induction studies, achievement of clinical and endoscopic outcomes occurred at higher rates with upadacitinib vs placebo at week 12 among the 204 patients in East Asia. Clinical remission per CD Activity Index (CDAI) and endoscopic response were achieved by 50.7

Purpose: The aim of this study was to identify at diagnosis factors predictive for subsequent 5-year disabling course and to validate previously proposed clinical predictors in Korea patients with CD. Methods: We analyzed a nationwide retrospective cohort from 32 Korean hospitals. Patients who underwent abdominal surgery within 1 month of diagnosis, received immunomodulators or biologics within 6 months, or had less than 5 years of follow-up were excluded. Disabling CD was defined as hospitalization for flare or complications, requirement for immunomodulators or biologics, intestinal resection, or perianal surgery within 5 years. Results: . A total of 814 patients were enrolled and the rate of disabling CD during subsequent 5-years after diagnosis was 89.4%. An age below 40 years (Odds ratio [OR]: 5.4, 95% confidence interval [CI]: 3.258-8.877), the initial requirement for corticosteroids uses (OR: 2.4, 95% CI: 1.132-4.879), and jejunal involvement (OR: 2.3, 95% CI: 1.043-4.857) were independently associated with disabling CD. Meanwhile, presence of perianal disease, which was significant predictor in previous study, was not related with disabling CD. Based on those three predictors, the positive predictive value of the risk factors for disabling disease was 0.62 (zero risk factor), 0.90 (one risk factor), 0.96 (two risk factors), and 1.00 (three risk factors). Conclusion: Predictors for subsequent 5-year disabling course are an age below 40 years, the initial requirement for corticosteroids, and jejunal involvement in Korean patients with CD. Further prospective validation of these parameters is warranted.

Background/Aims : Familial adenomatous polyposis (FAP), a hereditary colorectal cancer syndrome caused by APC gene mutations, is characterized by the development of numerous colorectal polyps and cancer at young age. To determine an effective chemopreventive strategy, we investigated the combined effects of varying doses of niclosamide and metformin in ApcMin/+ mice.Methods : ApcMin/+ mice were treated with metformin, niclosamide, or their combination at three doses (50, 100, and 200 mg/kg) for 16 weeks. The polyp burden was analyzed, and drug interactions were assessed by using the Bliss independence model to evaluate pharmacodynamic synergy and a physiologically based pharmacokinetic (PBPK) model to quantify the contribution of known pharmacokinetic interactions.Results : Low-dose metformin (50 mg/kg), niclosamide (50 mg/kg), and their combination showed no significant effects on the total polyp numbers compared with those in the control group. Higher doses (100 and 200 mg/kg) of both agents and their combination significantly reduced the total polyp numbers. The Bliss independence model showed a significant additive effect at the 100 mg/kg combination dose, whereas at the 200 mg/kg combination dose, an antagonistic interaction was observed. PBPK modeling predicted that coadministration of niclosamide increased exposure to metformin. Notably, the predicted metformin plasma Cmax remained within a safe therapeutic window at the 100 mg/kg combination dose but exceeded a safety threshold at 200 mg/kg.Conclusions : By integrating in vivo efficacy testing with quantitative modeling, our study identified the 100 mg/kg combination of niclosamide and metformin as the optimal dose for chemoprevention in a murine FAP model, providing a strong rationale for future clinical translation in FAP management.

While the prevalence of ulcerative colitis (UC) is continuously increasing in Asia, published data related to the real-world use of 5-aminosalicylic acid (5-ASA) for this population are sparse. Using Korean national health insurance claims data between 2008 and 2019, distributions of the average daily dose of 5-ASA and mode of administration in the population with UC were analyzed. Treatment outcomes were evaluated through proportions of patients with insufficient response (other treatments added to or switched from 5-ASA), hospitalization, or surgery. The analysis included data from 11,338 patients (mean age, 42.15 years; 59.53

Background/Aims:Few studies have compared the outcomes of catheter angiography and colonoscopy after positive computed tomography angiography (CTA) results in patients with severe lower gastrointestinal bleeding. This study aimed to evaluate differences in clinical outcomes between these approaches. Methods:We analyzed data from 254 patients with positive CTA results of the lower gastrointestinal tract at Severance Hospital, South Korea (2014-2024). Clinical outcomes were compared between the catheter angiography group (n=108) and the colonoscopy group (n=146), and the predictive risk factors for rebleeding were examined. Results:There were no significant differences in the confirmation yield (59.3% vs 47.9%), therapeutic yield (64.8% vs 56.2%), and mean hospitalization duration (20.1 days vs 21.3 days) between groups. However, the mean time to procedure (12.3 hours vs 19.2 hours) and rebleeding rate (36.1% vs 48.6%) were lower in the catheter angiography group. Logistic regression revealed that time to procedure predicted higher confirmation and therapeutic yields. Multivariate Cox regression showed that risk factors for rebleeding included receiving >5 units of packed red blood cells (hazard ratio [HR], 1.711; 95% confidence interval [CI], 1.025 to 2.857, p=0.040) and undergoing colonoscopy instead of catheter angiography (HR, 1.922; 95% CI, 1.242 to 2.974, p=0.003). Conclusions:Following a positive CTA result, colonoscopy (compared to catheter angiography) and the need for more than 5 units of packed red blood cell transfusion were significant risk factors for rebleeding.