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.

OBJECTIVE: To analyze patient characteristics of cancer rehabilitation and outcomes at our hospital. METHODS: This retrospective study analyzed 580 patients, who underwent cancer rehabilitation at our hospital and rehabilitation outcome after therapy were investigated. The relationship between the initial Barthel index and discharge outcomes was investigated, with a special focus on cancer patients with bone metastasis. The Barthel index and performance status (Eastern Cooperative Oncology Group) before and after rehabilitation were analyzed, and threshold value of home discharge was calculated from a receiver operating characteristic curve (ROC). General criteria for home discharge from our hospital included independence in performing basic activities of daily living such as bathing, feeding, and toileting or availability of home support from a family member/caregiver. RESULTS: The outcomes after rehabilitation among all the patients were as follows: discharge home 59%, death 13%, and others 27%. Statistical differences were observed between the initial and final values of the Barthel index in patients with bone metastasis, who could be discharged home (p=0.012). ROC analysis of the initial Barthel index for predicting home discharge revealed a threshold value of 60, sensitivity of 0.76, and specificity of 0.72. CONCLUSION: The patients with bone metastasis had a lower rate of home discharge and a higher rate of mortality than all the study patients who underwent cancer rehabilitation at our hospital. It is proposed that at the time of initiation of rehabilitation for patients with bone metastasis, an initial Barthel index lower than 60 might predict a worse outcome than home discharge.
Activities of Daily Living ; Asian Continental Ancestry Group* ; Baths ; Humans ; Mortality ; Neoplasm Metastasis* ; Rehabilitation ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Treatment Outcome

Cardiac patient simulators are commonly used in Japanese educational institutions; however, most institutions have not established concrete learning objectives or strategies for mastering physical examination of the circulatory system, including cardiac auscultation. In this study, we propose clear learning objectives and strategies for simulator practice for fifth-year medical students who have passed the objective structured clinical examination, and explored their educational effectiveness.
1)The subjects were fifth-year medical students (n=94) at the University of Miyazaki. Learning objectives were the mastery of the sequential physical examination and the ability to distinguish 6 cardiac findings, including normal status. The subjects were evaluated with a checklist before and after lectures and simulator practice.
2)The mean score (maximum score=14) significantly increased from before simulator practice (2.2±0.9) to after simulator practice (11.4±1.5; p<0.001). There was no difference in scores after practice among the cardiac diseases.
3)Before practice more than 50% of subjects could use a stethoscope on only right positions and could indicate only the maximum point of a cardiac murmur; in contrast, after practice more than 90% of the subjects could sequentially describe physical findings and accurately predict cardiac diseases.
4)In a questionnaire administered after practice, 83% of the subjects answered that all physicians should acquire proficiency in cardiac auscultation regardless of their specialty.
Simulator practice with clear learning objectives may help improve clinical examination skills when both time and human resources are limited. The reevaluation of the program's continuing educational effectiveness and the establishment of an iterative learning program will be needed.