Ken Sugimoto

Background/Aims: Fecal calprotectin (FC) reliably reflects both clinical and endoscopic disease activity in inflammatory bowel disease (IBD) and helps differentiate IBD from irritable bowel syndrome (IBS). The aim of this study was to determine the diagnostic utility of FC using the colloidal gold agglutination (CGA) method in distinguishing active-phase IBD from IBS in both children and adults. Methods: This prospective, multicenter, observational study was conducted across eight participating institutions. The primary goal was to validate the discriminatory ability and reference values of FC using the CGA method between patients with IBD in the active phase and those with IBS. Results: A total of 285 patients were analyzed, including 205 with ulcerative colitis (UC), 24 with Crohn’s disease, and 56 with IBS. In the receiver operating characteristic (ROC) curve analysis, FC demonstrated very high specificity (98%) for differentiating patients with active-phase IBD from those with IBS when a cutoff value of 500 µg/g was applied.With respect to endoscopic evaluation, the correlation between FC and cumulative endoscopic scores, which were calculated by summing segmental scores across the colon, was stronger in pediatric patients with UC (MES, rs = 0.48; cumulative MES, rs = 0.65) than in adult patients (MES, rₛ = 0.65; cumulative MES, rₛ = 0.69).Conclusion: FC measured using the CGA method proved to be a reliable and clinically meaningful biomarker for differentiating active IBD from IBS in adults and active UC from IBS in children. Comprehensive evaluation with cumulative endoscopic scores can be useful for understanding disease activity in pediatric patients with UC.

Gastric squamous metaplasia is a rare condition whose clinical significance and malignant potential remain unclear. Most reported cases are located in the

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. 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. 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. 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]).

Effect of Low-Dose Vonoprazan on Hepatic Cytochrome P450 Activity By 13C-Aminopyrine Breath Test in Healthy Subjects - Article abstract #953332

Background/Objectives: Artificial intelligence (AI)-assisted endoscopy has shown high sensitivity for early gastric cancer detection; however, false-positive diagnoses remain a clinical challenge. This study aimed to evaluate the real-world diagnostic performance of a commercially available AI system and to identify factors associated with false-positive diagnoses, focusing on repeated AI evaluations and confidence stratification. Methods: This single-center retrospective study included 47 patients with 89 localized gastric lesions evaluated between March 2024 and March 2025. Endoscopic examinations were performed under white-light, non-magnified observation with repeated AI assessments of each lesion. The rates of “Consider biopsy” (B) judgments were calculated. Lesions with a B judgment rate of ≥50% were defined as AI-positive and classified into four AI confidence categories. Diagnostic performance was assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Factors associated with false-positive diagnoses were analyzed using penalized logistic regression. Results: The AI system demonstrated a sensitivity of 97.6% and an NPV of 95.7%, with a specificity of 45.8%. Pathology-positive rates decreased stepwise across the four AI confidence categories (p < 0.001). Among AI-positive lesions, low regional reproducibility, lesion size ≥ 30 mm, scar, and erosion were independently associated with false-positive diagnoses. In analyses restricted to non-neoplastic lesions, lesion size ≥ 30 mm remained significantly associated with false-positive diagnosis. Conclusions: In real-world clinical practice, a commercially available AI system provides high sensitivity for early gastric cancer detection. Incorporating confidence stratification and regional reproducibility into clinical decision-making may enhance the effective use of AI-assisted endoscopic diagnosis beyond binary interpretations.

Background: The growing number of ulcerative colitis (UC) treatments has complicated the selection process. We hypothesized that the degree of epithelial neutrophilic infiltration, which is a hallmark of interleukin-23 (IL-23) pathway activation, could guide personalized therapy. Methods: This single-center, prospective study included 42 patients with active UC who were treated between July 2024 and September 2025. The study was registered (NCT 06626165) on 20 July 2024. Prior to treatment, all patients underwent colonoscopy with biopsy. Using a refined subclassification of the Geboes histopathology score, patients were stratified into two groups based on the percentage of crypts with neutrophilic infiltration: Grade ≥ 3.2 and Grade < 3.2. The primary outcome was clinical remission at four weeks. The secondary outcome was endoscopic remission at six months. Results: Of the 42 patients, 22 were classified as Grade ≥ 3.2, and 20 were classified as Grade < 3.2. Baseline clinical and endoscopic characteristics were similar between the two groups. All 22 patients in the Grade ≥ 3.2 group treated with mirikizumab achieved clinical remission within four weeks. Nineteen (86%) of the twenty-two patients achieved endoscopic remission within six months. All 20 patients in the Grade < 3.2 group who received vedolizumab (16) or upadacitinib (4) achieved clinical remission within the same timeframe. Both treatment strategies led to a statistically significant reduction in the inflammatory biomarker leucine-rich alpha-2-glycoprotein (LRG) (p < 0.001). Conclusions: Our findings suggest that UC patients with advanced epithelial neutrophil infiltration (Geboes Grade ≥ 3.2) may have a disease that is predominantly driven by the IL-23 pathway, making them potential candidates for selective IL-23p19 inhibitors. This histopathology-driven approach appears to be a useful strategy for tailoring treatment to patients with active UC, though further validation is required.

Background: Ferroptosis is a key mechanism of tubular cell death in acute kidney injury (AKI), particularly in folic acid– and glycerol-induced models. Dipeptidyl peptidase 4 (DPP4) and sodium–glucose co-transporter 2 (SGLT2) inhibitors exhibit renoprotective effects beyond glucose lowering, and emerging evidence suggests both may suppress ferroptosis. We hypothesized that teneligliptin (TG) and empagliflozin (EMPA) protect tubular cells from ferroptosis-mediated injury by reducing lipid peroxidation. Methods: HK-2 cells were pretreated with inhibitors of apoptosis (z-VAD-FMK), necroptosis (necrostatin-1s) or ferroptosis (ferrostatin-1) and then exposed to folic acid or myoglobin. The effects of TG on erastin-, folic acid– and myoglobin-induced injury and of EMPA on erastin- and myoglobin-induced injury were evaluated using cell viability and lipid peroxidation assays. In vivo, TG was tested in folic acid– and glycerol-induced AKI models and EMPA in the glycerol-induced AKI model. Renal function, tubular injury, inflammation and glutathione peroxidase 4 (GPX4) expression were assessed. Localization of DPP4, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), NOX4 and megalin in the kidney was analysed by immunostaining. Results: Ferrostatin-1, but not z-VAD-FMK or necrostatin-1s, prevented folic acid– and myoglobin-induced cell death in vitro. Both TG and EMPA significantly reduced erastin-induced cell death and lipid peroxidation. TG also attenuated cell death and lipid peroxidation in folic acid– and myoglobin-induced injury. EMPA improved viability and reduced lipid peroxidation in the myoglobin model. In vivo, TG improved renal function, reduced tubular damage and inflammation and preserved GPX4 expression. EMPA showed similar protective effects in rhabdomyolysis-associated AKI. DPP4 co-localized with NOX4 but showed no co-localization with NOX1. TG treatment disrupted the co-localization of NOX4 with DPP4. Conclusion: TG and EMPA attenuate tubular cell death and kidney injury in ferroptosis-mediated AKI models, potentially through the reduction of lipid peroxidation. These findings highlight ferroptosis suppression as a potential mechanism underlying their renoprotective effects in AKI prevention.

Background: The goal of treatment for Crohn’s disease (CD) is to achieve mucosal or transmural healing, and biomarker measurements are useful in monitoring disease activity and guiding treatment. This study aimed to investigate the utility of a new urinary biomarker, prostaglandin E-major urinary metabolite (PGE-MUM), in assessing CD activity. Methods: The study involved 87 patients with CD who underwent endoscopic examination and measurements of 4 biomarkers: Prostaglandin E-major urinary metabolite, fecal calprotectin (FC), leucine-rich α2 glycoprotein (LRG), and C-reactive protein (CRP). Endoscopic activity was assessed by the Simple Endoscopic Score for Crohn’s Disease (SES-CD). Correlations between the CD activity index (CDAI) and SES-CD with the 4 biomarkers were analyzed, and receiver-operating characteristic (ROC) analyses were performed to predict SES-CD ≧ 3. Results: All 4 biomarkers showed significant correlations with both CDAI and SES-CD. The cutoff (area under the curve [AUC]) values for predicting SES-CD ≥ 3 were as follows: PGE-MUM, 25.2 µg/g Cr (0.800); FC, 257 mg/kg (0.816); LRG, 11.8 µg/mL (0.748); and CRP, 0.22 mg/dL (0.656). Subgroup analysis revealed significant correlations between PGE-MUM and SES-CD in both the L1 (small intestine only) and L2 + L3 (including large intestine) groups, with correlation coefficients of 0.654 and 0.586, respectively. In the L1 group, ROC analysis revealed that, among the 4 biomarkers, PGE-MUM had the highest AUC for predicting SES-CD ≥ 3, with a cutoff (AUC) of 33.1 µg/g Cr (0.861). Conclusions: PGE-MUM is a biomarker that can reflect endoscopic activity in patients with CD and may be particularly useful in small intestinal lesions.

Ustekinumab is prescribed for the treatment of patients with steroid-resistant moderate to severe Crohn’s disease. We investigated its clinical outcome in patients with small and large intestinal lesions. Patients who were newly administered ustekinumab between March 2014 and December 2020 at Hamamatsu University Hospital were included in the study. The primary endpoint was Crohn’s disease activity index score at baseline and weeks 8, 24, and 48 after the initiation of treatment, and secondary endpoints were albumin, hemoglobin, and C-reactive protein at these time points. Ustekinumab treatment retention was examined in both groups; the 2 groups were compared using the Friedman test, Mann–Whitney U test, or Fisher exact test. Overall, Crohn’s disease activity index scores improved between baseline and 48 weeks, but the difference was not significant. However, there was a significant improvement between baseline and 48 weeks in patients with lesions in the small intestine only. Overall, patients showed significant improvement in albumin levels between baseline and 48 weeks but not in C-reactive protein or hemoglobin levels. When limited to patients with lesions in the small intestine, albumin and hemoglobin levels showed significant improvement. Both types showed high rates of treatment retention, although there was no significant difference. Ustekinumab appears to be a safe and effective treatment option that may be particularly effective in patients with lesions in the small intestine only.

Anti-tumor necrosis factor (TNF) -α antibodies, including infliximab (IFX), adalimumab (ADA), and golimumab, which were the first biologic therapeutic agents, have a crucial position in advanced therapy for ulcerative colitis (UC). We aimed to investigate serum albumin (Alb) change as a prognostic factor for the therapeutic effect of ADA in UC. Thirty-four patients with UC treated with ADA were enrolled in this study and were divided into failure and non-failure groups. Biological data, such as Alb were compared between the two groups. Thirteen patients showed failure within six months. Examination of the biological data showed a significant difference between the two groups only in the week 2/week 0 Alb ratio. In receiver-operating characteristic (ROC) curve analysis to predict failure, the cut-off value of week 2/week 0 Alb ratio was 1.00, and the area under the curve was 0.868 (95% confidence interval: 0.738–0.999). In addition, in the sub-group analysis of only clinically active patients, the week 2/week 0 Alb ratio of the non-failure group was significantly higher than that of the failure group, and the cut-off-value in ROC analysis was 1.00. Week 2/week 0 Alb ratio ≤ 1 predicts failure within six months of ADA for UC.