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.

OBJECTIVES: Increasing bone mineral density (BMD) to reduce fracture risk is a primary goal of osteoporosis treatment. This prospective, observational study evaluates the effects of monthly minodronate (MIN; 50 mg) with or without eldecalcitol (ELD) addition in osteoporosis patients with rheumatoid arthritis (RA) during 18 months. METHODS: The cohort was prospectively and randomly split into the MIN monotherapy group (14 cases) and MIN plus ELD group (combination group; 14 cases) due to no reports on the effectiveness and safety of MIN therapy in relation to ELD addition for comparisons of serum tartrate-resistant acid phosphatase (TRACP)-5b, bone alkaline phosphatase (BAP), and BMD of the lumbar 1–4 vertebrae (L-BMD), bilateral total hips (H-BMD; the mean value of the right and left hips), and bilateral femoral necks (FN-BMD) at baseline and at 6, 12, and 18 months of treatment. RESULTS: Baseline values were comparable between the groups apart from a tendency for higher TRACP5b in the combination group. Seven of 14 patients in the combination group had received previous bisphosphonate treatment. BAP was significantly more reduced in the monotherapy group at 6 months, with no other remarkable differences for TRACP5b, L-BMD, H-BMD, or FN-BMD during the observation period. CONCLUSIONS The above findings suggest that regardless of ELD addition, MIN potentially improves BMD during 18 months in osteoporosis patients with RA.

OBJECTIVES: The aim of this study was to examine the efficacy, safety, and adherence of ibandronate (IBN) treatment with or without vitamin D supplementation for 3 years in Japanese women with postmenopausal osteoporosis. METHODS: This prospective investigation included 27 patients treated with IBN alone (monotherapy group) and 29 patients receiving IBN and alfacalcidol (ALF) (combination group). Bone metabolism and bone mineral density (BMD) were measured before and at 18, 24, 30, and 36 months of therapy. Treatment discontinuation and fracture occurrence were assessed as well. RESULTS: Lumbar 1–4 BMD (L-BMD) was significantly increased in the monotherapy and combination groups by 3.9% and 7.2%, respectively, at 36 months, with significant gains in total hip BMD (H-BMD) of 3.7% and 4.9%, respectively. There were significant differences in L-BMD improvement between the groups at 18, 24, and 30 months (P < 0.05) and at 36 months (P < 0.01). Compared with pretreatment levels, the percentage changes of L-BMD and H-BMD were significant at all time points in the combination group and at all points apart from L-BMD at 36 months in the monotherapy group. In the monotherapy group, 14 patients dropped out during 3 years and 2 vertebral fractures occurred during the first year. In the combination group, 16 cases dropped out during 3 years and 1 nonvertebral fracture was noted during the first year. CONCLUSIONS: Our findings suggest that combination therapy of IBN and vitamin D is superior to monotherapy with regard to L-BMD improvements for 3 years, with both groups showing comparable safety and adherence to treatment.
Asian Continental Ancestry Group ; Bone Density ; Compliance ; Female ; Hip ; Humans ; Metabolism ; Osteoporosis ; Osteoporosis, Postmenopausal ; Prospective Studies ; Vitamin D

OBJECTIVES: The aim of this study was to examine the discontinuation and occurrence of fracture during denosumab treatment in Japanese women with primary osteoporosis or rheumatoid arthritis (RA) with osteoporosis. METHODS: This retrospective study included 143 patients with primary osteoporosis and 96 patients with RA and osteoporosis who were treated with denosumab. Treatment discontinuation, fracture occurrence, lumbar spine (L1–4) bone mineral density (LS-BMD), and bilateral total hip BMD (TH-BMD) were examined before and at 1 and 2 years after treatment commencement. RESULTS: In the primary osteoporosis group, 32 cases dropped out and no fractures occurred from 0 to 1 year. Eighteen cases were lost to follow-up and no fractures were noted from 1 to 2 years. In the RA with osteoporosis group, 7 cases dropped out and no fracture occurred from 0 to 1 year. Twenty-one cases were lost to follow-up and 2 nonvertebral fractures were noted from 1 to 2 years. In this group, 13 cases dropped out from 1 to 2 years and 16 cases dropped out during the 2-year study period due to economic reasons. LS-BMD and TH-BMD values increased continuously for 2 years of treatment in both primary osteoporosis and RA with osteoporosis groups. CONCLUSIONS: These results suggest that during denosumab therapy, the discontinuation rate is expected to remain low during 2 years of treatment in primary osteoporotic patients. In RA patients with osteoporosis, however, the discontinuation rate may increase due to economic reasons from 1 to 2 years of therapy.
Arthritis, Rheumatoid* ; Asian Continental Ancestry Group* ; Bone Density ; Compliance* ; Denosumab* ; Female ; Hip ; Humans ; Lost to Follow-Up ; Osteoporosis* ; Retrospective Studies ; Spine

The UBE woven 150cc WYK graft is a non-sealed graft that became available commercially in January 2005, and does not need to be preclotted before implantation. Subjects in this study comprised 50 patients with abdominal aortic aneurysms or common iliac arterial aneurysms, who received prosthetic Y grafts in our institution. Subjects were divided into 2 groups: the U group (n=26), with implantation of the UBE graft, and the I group (n=24) who received implantation of an INTERGARD^TM woven Y graft. Intraoperative bleeding, inflammatory response and duration of postoperative hospitalization were evaluated in each group. Significant differences were noted between C-reactive protein levels, frequency of recurrence of fever and duration of postoperative hospitalization. No differences were noted between intraoperative bleeding and time. The UBE woven 150cc WYK graft, compared with the INTERGARD^TM woven Y graft, required no extra time for implantation and appeared to offer advantages such reduced immunoreaction after surgery. However, follow-up for sufficient late-phase evaluation of the grafts is required.

Median sternotomy is commonly used for suture fixation of a myocardial lead. Instead of this conventional technique, we used the technique of resecting the 5th costal cartilage through a small horizontal skin incision at the left 5th sternocostal junction in 33 patients, between 1980 and 2001. Here we describe this procedure, as well as the outcome of patients who underwent this myocardial lead fixation procedure. A skin incision of about 6 to 8cm was made in the left 5th intercostal space. Approximately 5cm of the 5th costal cartilage was resected through the skin incision. Then, a myocardial lead was sutured on to the anterior wall of the right ventricle. The generator was generally placed in the upper subcutaneous space of abdomen. Additional costal cartilages were removed in 7 patients in whom a larger operating field could not be obtained initially. The electrode was sutured to the right ventricular wall in 28 patients, right atrial wall in 6 patients, and the left ventricular wall in 5 patients. The mean operation time was 150min and mean bleeding during operation was 82ml. Long-term results (258 months at the longest, at the time of writing) showed that all the patients did well, except for one adult who suffered cerebral infarction, and one child with pacing failure. Based on these findings, we believe that this procedure is minimally invasive method, and is good for fixation of a myocardial lead.

We studied cardiac function and outcome long after aortic valve replacement using a 19mm bileaflet valve. The subjects consisted of 10 of 12 patients living 10 or more years after the operation and 7 of 8 living 5-9 years after the operation. We measured the left ventricular ejection fraction (LVEF), %fraction shortening (%FS), left ventricular diastolic dimension (LVDd), systolic dimension (LVDs), PWT, IVST, and LV-aortic pressure gradient (PG) of in 6 patients each in 10 more years after the operation (Group I) and 5-9 years after the operation (Group II) who underwent ultrasonography, and calculated the left ventricular mass index (LVMI). No statistically significant differences were seen in either parameter in either group. Prognosis was 1 cardiac 2 cancer deaths each in 10 or more years after the operation group. The cumulative survival rate was in 85.7% post operative 5-9 years and 72.7% in 10 years. Although cardiac function was maintained in both groups, more observation is needed from now on because the pressure difference or LVMI may increase.