Keisuke Jimbo

Protein-losing enteropathy (PLE) is a serious complication affecting approximately 5–12% of patients following the Fontan procedure for congenital he

Characteristics of monogenic inflammatory bowel disease in very early-onset cases: a Japanese multicenter registry study

Fecal surrogate markers strongly correlate with endoscopic findings in pediatric onset inflammatory bowel disease: a retrospective study in Japan

Background: Real-world evidence for mirikizumab (MIRI) in pediatric ulcerative colitis (UC) is limited. We evaluate the real-world effectiveness, remission kinetics, and optimization strategies for MIRI in pediatric UC. Methods: This prospective cohort study included Japanese children with UC receiving intravenous MIRI (300 mg at weeks 0, 4, 8), followed by subcutaneous maintenance (200 mg every 4 weeks). Those without clinical remission (CR; Pediatric Ulcerative Colitis Activity Index [PUCAI] < 10 plus intestinal ultrasonographic [IUS] remission) by week 12 underwent prolonged intravenous induction every 4 weeks until week 24. Outcomes included CR, symptomatic remission (SR), ultrasonographic remission (UR), and endoscopic remission (ER). Results: Twenty-eight children were included (median age 13 years; 50% female; median PUCAI 67.5; 67.4% biologics-naive). All remission measures improved by week 12 (P < 0.001). Median time to CR was 10 (interquartile range 4-16) weeks; durable CR occurred in 27/28 (96.4%). From weeks 12 to 52, CR, UR, and ER continued increasing, whereas SR plateaued. Prolonged induction delayed median CR (16 vs 8 weeks) but most patients achieved remission by week 52. On multivariate analysis, prolonged induction was the sole independent predictor of delayed CR, whereas prior biologic exposure was not. Early IUS findings differentiated patients requiring prolonged induction or with prior biologic exposure. No serious adverse events occurred, and MIRI was well tolerated. Conclusions: MIRI can induce and sustain CR in pediatric UC, particularly when early optimization strategies are applied. These findings highlight IUS as a useful surrogate for mucosal healing and support MIRI as a promising, adaptable, and safe therapeutic option in pediatric UC.

Background: Small bowel capsule endoscopy is a valuable modality for evaluating small intestinal lesions in children with inflammatory bowel disease. However, its application for very early-onset inflammatory bowel disease remains insufficiently documented. This study investigated the feasibility and safety of small bowel capsule endoscopy for very early-onset inflammatory bowel disease. Methods: A cohort of patients with very early-onset inflammatory bowel disease who underwent small bowel capsule endoscopy at under 6 years of age between January 2013 and December 2022 at 7 Japanese pediatric centers was included. Their medical records were retrospectively reviewed for actual procedures, safety, and test results. Results: Eighty-two patients (21 with ulcerative colitis, 25 with Crohn’s, 31 with inflammatory bowel disease—unclassified, 4 with monogenic inflammatory bowel disease, and 1 with intestinal Behçet’s disease) were enrolled, and 104 small bowel capsule endoscopies (median age, 3.8 years; median body weight, 13.0 kg) were analyzed. All capsules were deployed endoscopically, mostly using delivery devices (95%). Gastrointestinal patency was assessed in 95% of procedures, most commonly using patency capsules (70%). Abnormal small bowel findings were observed in 42% of patients, with aphthae being the most common (34%), followed by ulcers (18%). No serious complications, including small intestinal retention and perforation, were reported. Conclusions: Small bowel capsule endoscopy for very early-onset inflammatory bowel disease is feasible with diagnostic utility, and it can be performed safely with appropriate evaluation using patency capsules.

Background: Very-early-onset ulcerative colitis (VEO-UC) is a severe form of inflammatory bowel disease that manifests before the age of 6 years. Compared to typical pediatric UC, it is characterized by distinct genetic and immunological factors. This study aimed to investigate the roles of specific human leukocyte antigen (HLA) alleles and maternal microchimerism (MMc) in the pathogenesis of VEO-UC in a Japanese population. Methods: This study included 27 VEO-UC patients, including 4 patients treated with colorectal resection. HLA typing was performed by polymerase chain reaction–sequence-specific oligonucleotide probing (PCR-SSOP) and compared with the Japanese general population. Immunohistochemistry and fluorescence in situ hybridization were used to evaluate MMc in intestinal tissues. Statistical comparisons of HLA were performed against data from the general Japanese population, with Bonferroni corrections applied to handle multiple comparisons. Results: HLA-B52 and HLA-DR15 were more prevalent in cases of VEO-UC than in the general Japanese population, although the statistical significance decreased after the Bonferroni correction. MMc was found in the intestinal tissues of three VEO-UC cases, whereas it was absent in the control UC cases. Maternal HLA concordance with specific alleles associated with VEO-UC was noted in several cases, suggesting maternal immune involvement in the pathogenesis of the disease. Conclusions: VEO-UC seems to share genetic traits with adult UC, such as an association with HLA-B52 and HLA-DR15, and is also affected by maternal immune contributions, as shown by the presence of MMc in the affected tissues. These findings highlight the complex interaction between genetic and immunological factors in the pathogenesis of VEO-UC and underscore the need for further research to develop targeted therapeutic strategies that address these mechanisms.

Background: This study aimed to evaluate the effects of psychosocial and neurodevelopmental disorders on pediatric ulcerative colitis management. Specifically, the relationships between these disorders and disease severity, as well as treatment strategies, were assessed through a single-center, retrospective, observational study. Methods: The study included pediatric patients with ulcerative colitis (UC) under 15 years of age diagnosed by colonoscopy and histological evaluation between January 2022 and May 2024. Data on comorbid functional gastrointestinal disorders and neurodevelopmental disorders were obtained from patients’ electronic medical records, and their effects on disease severity and treatment choices were analyzed. Results: Of the 166 patients with UC, 21.4% had neurodevelopmental disorders, and 17.5% had functional gastrointestinal disorders. Patients with these comorbidities had significantly lower Pediatric Ulcerative Colitis Activity Index scores, with notable differences in parameters such as abdominal pain and stool consistency. In addition, these patients had more extensive disease and higher rates of immunomodulator (66.1%) and biologic use (46.4%) than those without these complications. The prevalence of functional gastrointestinal disorders was higher in patients with autism spectrum disorder, and specialized care at a developmental outpatient clinic was required in 23.2% of cases. Conclusions: Psychosocial and neurodevelopmental disorders are prevalent in children with UC and significantly affect both disease severity and therapeutic approaches. The findings suggest that comprehensive management involving psychosocial interventions and multidisciplinary support is crucial for effectively treating these patients.

Background: Transabdominal ultrasonography and transperineal ultrasonography (TPUS) appear correspond to colonoscopy (CS) for evaluating ulcerative colitis (UC) activity, but their utility in UC diagnosis remains unclear. This research compared the accuracy of TPUS and CS for assessing rectal activity and differentiating noninflammatory bowel disease proctitis from UC in pediatric cases. Methods: The study is a blinded, prospective, and controlled trial. Prospectively, values of fecal calprotectin (FCP) and findings of the TPUS and CS were compared between child cases of UC and non-IBD proctitis. Findings of rectal wall thickening (RWT), rectal wall flow (RWF) on power Doppler, and microvascular signal at wall circumference (MSWC) on monochrome superb microvascular imaging assessed using TPUS were compared with the CS. Results: Thirty patients with Mayo endoscopic subscore (MES) 0 to 1 UC, 57 with MES 2 to 3 UC, and 44 with proctitis were registered. Fecal calprotectin, RWF, and MSWC indicated significant differences among the groups (P < .05). Rectal wall thickening showed no significant difference between MES 0–1 and proctitis (P = .76). Rectal wall thickening and MSWC were independent predictors of endoscopic activity of UC, resulting in a sensitivity and specificity of 100% for RWT ≥4.5 mm and positive MSWC. Fecal calprotectin and RWF were independent predictors for differentiating MES 0 to 1 and proctitis, and FCP and RWT were independent predictors for differentiating MES 2 to 3 and proctitis. Sensitivity and specificity were 77.2% and 80.9%, respectively, for FCP >242.5 μg/g and RWF negative; and they were both 100% for RWT >4.1 mm and MSWC positive. Conclusions: Transperineal ultrasonography with mSMI may enable the evaluation of rectal activity and differentiation of UC from non-IBD proctitis with accuracy comparable to endoscopy.