Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

Immune checkpoint inhibitors (ICIs) have expanded therapeutic options for advanced malignancies, offering new hope for conditions once deemed untreatable. However, the advent of ICIs has introduced a spectrum of immune-related adverse events (irAEs), including leukocytoclastic vasculitis (LCV), a rare but significant complication. This case report describes development of LCV after treatment with nivolumab and ipilimumab in a 70-year-old man with malignant melanoma, highlighting the diagnostic and management challenges of such irAEs. Despite extensive investigation, conventional pathology failed to identify the immune complexes typically associated with LCV. The clinical presentation, alongside a detailed medical history and the exclusion of infections, medications, and autoimmune diseases, was crucial in establishing a diagnosis. Ulcer resolution following discontinuation of ICI therapy and initiation of steroids further support the conclusion that LCV was an irAE in this patient. This case underscores the need for vigilant monitoring for irAEs for the variable onset after ICI therapy and the importance of thorough history-taking to guide diagnosis and treatment. With ICIs becoming increasingly prevalent in oncology, the incidence of ICI-induced ulcers like LCV is expected to rise, necessitating heightened awareness and multidisciplinary approaches to patient care.

Background   Since the Alma Ata Declaration in 1978, Community Health Volunteers (CHVs) have become critical assets to assist tuberculosis (TB) control programs in low and middle-income countries, such as in case finding and treatment support activities. Yet community-based tuberculosis control programs (CBTBC) are faced with numerous challenges, including recruitment and retaining of CHVs. While the possible effect of financial incentives has been extensively discussed, other motivational factors have received less attention. Objective   This study sought to explore on potential motivations for entering, remaining, and exiting volunteer work among CHVs working in a CBTBC project run by an NGO, Japan Anti-Tuberculosis Association (JATA), in urban townships of Yangon, Myanmar.Methods   A semi-structured questionnaire was administered to CHVs who were working for a JATA CBTBC project in Yangon, Myanmar. The questionnaire consisted of closed- and open-ended questions asking about demographic characteristics, their experiences, and their motivations for entering, remaining and exiting volunteer work. Functional theory of motivation was used as a conceptual framework for analysis.Results   A total of 69 volunteers participated in the survey, representing 69% of all CHVs for JATA CBTBC (69/100). From the questionnaire, we found that altruism, self-empowerment, and psychological job satisfaction mainly influenced CHVs’ motivation to enter and remain in volunteer work. Expectations for financial incentives were less important. Being busy with housework and other work priorities could motivate them to temporarily exist volunteer work, while ill-health and old age potentially triggered permanent exit. Conclusions   CHVs working in JATA CBTBC were motivated mainly by altruism, self-empowerment, and psychological job satisfaction - however, their volunteer work must be systematically supported so as to avoid unnecessary burden on CHVs. Further qualitative study would extend the evidences of the potential factors which might contribute to sustaining CHV participation.

Background/Aims: Bispectral index (BIS) monitors process and display electroencephalographic data are used to assess the depth of anesthesia. This study retrospectively evaluated the usefulness of BIS monitoring during endoscopic ultrasonography (EUS). Methods: This study included 725 consecutive patients who underwent EUS under sedation with propofol. BIS monitoring was used in 364 patients and was not used in 361. The following parameters were evaluated: (1) median dose of propofol; (2) respiratory and circulatory depression; (3) occurrence of body movements; (4) awakening score >8 at the time; and (5) awakening score 2 hours after leaving the endoscopy room. Results: The BIS group received a significantly lower median dose of propofol than the non-BIS group (159.2 mg vs. 167.5 mg; p=0.015) in all age groups. For patients aged ≥75 years, the reduction in heart rate was significantly lower in the BIS group than in the non-BIS group (1.2% vs. 9.1%; p=0.023). Moreover, the occurrence of body movements was markedly lower in the BIS group than in the non-BIS group (8.5% vs. 39.4%; p<0.001). Conclusions During EUS examination, BIS monitoring is useful for maintaining a constant depth of anesthesia, especially in patients 75 years of age or older.