Mitsuyoshi Suzuki

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: Preschool-aged children can have difficulty adhering to infection control measures and were affected during the Omicron wave of the coronavirus disease 2019 (COVID-19) pandemic. However, the impacts of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination on viral load in this age group remain poorly understood. This study aimed to investigate the relationship between previous SARS-CoV-2 infection, COVID-19 vaccination, and viral load or clinical severity in preschool-aged children infected during the Omicron variant epidemic in Japan. Methods: This prospective observational study investigated 107 children aged 1–75 months who were diagnosed with COVID-19 between May and September 2023. Rapid antigen (Ag) tests were performed on days 1 and 5 or 6, and results were visually graded into four categories (–, ±, 1+, or 2+). Ag results were validated against quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) cycle threshold (Ct) values. Clinical parameters, including vaccination status, previous infection, age, maximum body temperature, and fever duration, were analyzed using multivariate regression models. Results: Higher Ag loads (1+/2+) were more frequently observed in younger children who had not experienced prior infection or full vaccination. Prior infection and vaccination were independently linked to lower Ag loads and reduced maximum body temperature. Many unvaccinated and infection-naïve children continued to show elevated Ag levels on day 5 or 6, corresponding to Ct values suggestive of potential infectivity. Conclusions: Prior SARS-CoV-2 infection and vaccination were linked to lower viral loads and milder febrile responses among preschool-aged children. These findings enhance our understanding of infection dynamics in this age group and may inform future discussions on public health strategies in pediatric settings.

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.