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.

An 84-year-old man underwent transcatheter aortic valve replacement (TAVR) for severe aortic stenosis with heart failure. Paravalvular leak (PVL) of the aortic valve was observed immediately after the operation, and the heart failure was difficult to manage; closure with a vascular plug was attempted, but PVL did not improve. Therefore, four months after TAVR, the decision was made to perform surgical aortic valve replacement (SAVR). The operation was expected to take a long time due to the concomitant mitral valve replacement, ascending aortic valve replacement and pulmonary vein isolation, in addition to SAVR with removal of the TAVR valve, so a rapid deployment valve was used for aortic valve replacement. The patient's postoperative course was good, with no complications. Postoperative echocardiography showed no problems with the replaced aortic or mitral valves. Twenty-six days after surgery, the patient was discharged home, although it took time for rehabilitation due to the long hospital stay after TAVR. More than two years have passed since the surgery, and the patient is currently an outpatient with no symptoms of heart failure. The present report describes the use of a rapid deployment valve for surgical AVR after TAVR with good results.

At present, lifestyle-related diseases are one of the most critical health issues worldwide. It has been reported that lipopolysaccharide derived from a Gram-negative bacteria (IP-PA1) symbiotic with wheat exhibited several advantageous biological effects, such as the reduction of plasma glucose levels in NOD mice and low-density lipoprotein (LDL) levels in WHHL rabbits. In this study, the beneficial effects on plasma glucose and lipids of a tea (SI tea) consisting of IP-PA1 and Salacia (which contains an inhibitor of alpha-glucosidase) were investigated in the KK-Ay/TaJcl type 2 diabetic model mice and in human subjects with premetabolic syndrome in a double-blind, randomized study. SI tea significantly decreased plasma glucose levels in KK-Ay/TaJcl mice. A clinical trial of SI tea was performed with 41 subjects between the ages of 40 and 69, who belonged either to a high plasma glucose group (HG: FPG 100-125 mg/dl) or to a hyperlipidemia group (HL: TG > or = 150 mg/dl, or LDL > or = 120 mg/dl, or HDL < 40 mg/dl). These subjects ingested either Salacia without IP-PA1 (the control) or SI tea. Blood samples were collected at 0, 30, and 60 days after initiating SI tea treatment, and were measured for FPG, HbA1c, TG, LDL, and HDL. These results showed that SI tea reduced FPG and HbA1c more rapidly than the control in the HL group, and also significantly improved LDL and HDL levels in the HG group. Thus, SI tea may be helpful in preventing lifestyle-related diseases.
Animals ; Cholesterol ; Fasting ; Glucose ; Gram-Negative Bacteria ; Humans ; Hyperlipidemias ; Lipoproteins ; Mice ; Mice, Inbred NOD ; Plasma ; Rabbits ; Salacia ; Tea ; Triticum