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.

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BACKGROUND: The living arrangement has been suggested as an important factor affecting health. Recent studies have also suggested that there was a risk among elderly persons who were not alone. This study examined whether the detailed living arrangement was associated with a future decline in functional capacity in the elderly, by gender, in a Japanese suburban city. METHODS: A 3-year longitudinal questionnaire survey (baseline: 2011; follow-up: 2014) for aged 65 years or older was conducted in Kurihara city, Japan. Of the respondents in the baseline survey, we analyzed those who scored 13 points (a perfect score which indicates the highest functional capacity; n = 2627) on the Tokyo Metropolitan Institute of Gerontology Index of Competence at the baseline. The exposure was living arrangement at baseline, divided into five categories: "with spouse only," "living alone," "with child and his/her spouse," "with child without his/her spouse," and "with other family/person." The outcome was the decline in functional capacity at the follow-up survey (score decreased to 10 points or less from 13 points). RESULTS: Of the 2627 analyzed population, 1199 (45.6%) were men. The incidence of the decline was 5.8% in men and 5.9% in women. Multivariable logistic regression analyses adjusted for age, educational attainment, and health behavior and condition revealed that in women, the odds ratio of the decline was higher in living with child and his/her spouse (2.41, 95% confidence interval; 1.10-5.28) referring to living with spouse only. When adjusting activities inside and outside the home such as housework additionally, the association was attenuated to marginal significance (2.25, 0.98-5.18). No statistical significance was observed in men. CONCLUSIONS These results suggested that living with child and spouse of a child was associated with the future decline in women's functional capacity.
Activities of Daily Living ; Aged ; Aged, 80 and over ; Female ; Geriatric Assessment ; Humans ; Independent Living ; statistics & numerical data ; Japan ; Longitudinal Studies ; Male ; Self Report

The patient was a 34-year-old woman who had been routinely monitored after receiving a childhood diagnosis of partial anomalous pulmonary venous connection, but unilaterally discontinued follow-up examinations after the age of 18. At 33 years of age, she was admitted to our hospital after a physical examination revealed an abnormal shadow on a chest X-ray. Transthoracic echocardiography detected an atrial septal defect (ASD), and contrast-enhanced computed tomography showed that the right lower pulmonary vein drained to the inferior vena cava. The patient was diagnosed with scimitar syndrome with ASD. Cardiac catheterization showed a pulmonary/systemic flow ratio (Qp/Qs) of 2.48 and a left-to-right shunt rate of 59.7%. Surgical treatment was deemed to be indicated. The right lower pulmonary vein was anastomosed to the anterolateral wall of the right atrium, and an intra-atrial baffle repair was performed from the orifice within the right atrium to the left atrium through the existing ASD using untreated fresh autologous pericardium. Two years after the operation, good blood flow was maintained within the baffle with no stenosis at the anastomotic site. This report describes a rare case of scimitar syndrome with ASD in an adult woman, and provides a review of the existing literature.