Hiroyuki Baba

Multidisciplinary genomic evaluation is increasingly recognized for its diagnostic and therapeutic implications in adults with suspected inborn errors of immunity (IEI) presenting with rheumatic and musculoskeletal disease (RMD) phenotypes. We retrospectively analyzed 50 adults with suspected IEI who underwent genetic testing and were pre-classified into immunodeficiency (ID), autoinflammatory disorders (AID), and non-ID/AID groups. Genetic findings, clinical classification, treatment modifications, and exploratory machine learning analyses were evaluated. A final genetic diagnosis consistent with IEI was identified in 15 patients (30.0%), with the highest yield in the non-ID/AID group (44.4%). Variants were most frequently associated with autoinflammatory diseases (40.0%). Four patients, all initially classified as non-ID/AID, were reclassified based on genetic findings and IUIS classification. Treatment was modified in 12 patients, including eight genetically diagnosed patients and three genotype-driven interventions. Two patients died from disease-related complications. Machine learning analyses provided heterogeneous feature contributions across groups. These findings highlight the utility of multidisciplinary genomic evaluation for refining diagnoses in challenging adult patients.

Nuclear factor-κB (NF-κB) plays a central role in inflammatory responses, while its physiological functions are essential for cell survival and proliferation. Currently, drugs targeting NF-κB inhibition have not yet been applied in clinical practice. We investigated the physiological effect of a novel NF-kB inhibitory compound, 1H-pyrazolo[3,4-d]pyrimidin-4-amine derivative (INH #1) on three inflammatory animal models. The pharmacokinetics was measured by LC-MS/MS analysis. Acute hepatitis was induced by administrating LPS and D-(+)-galactosamine hydrochloride followed by the analysis of survival time and inflammatory mediators. Collagen-induced arthritis (CIA) was induced by immunization with type II collagen (CII), and serum-transfer arthritis (STA) was caused by injecting K/BxN mice serum. Clinical and histological scores were evaluated in both arthritis models. Immune cell subset analysis, CII-induced IFN-γ production and proliferation, and measurement of anti-CII IgG antibodies were performed in the CIA model. In the acute hepatitis model, INH #1 suppressed TNF-α production and prevented early death in a dose-dependent manner. INH #1 significantly attenuated arthritis scores and joint inflammation in both arthritis models. Additionally, in the CIA model, dendritic cells in the regional lymph nodes were decreased in the treated mice, and antigen-induced IFN-γ production and cell proliferation in splenocytes were inhibited, while the titers of anti-CII IgG antibodies were comparable regardless of the treatment. Here, we revealed that INH #1 exerted anti-inflammatory effects in vivo via inhibition of inflammatory mediators and suppression of cellular immune responses. This compound could be a novel candidate for inhibition of NF-κB in certain inflammatory diseases. Significance Statement A novel NF-κB inhibitory compound, 1H-pyrazolo[3,4-d]pyrimidin-4-amine derivative (INH #1) that retains physiologically essential NF-κB bioactivity, suppressed inflammation in three different mouse models; the acute hepatitis model, the collagen-induced arthritis model, and the K/BxN serum-transfer arthritis model. These results suggest that this compound could be a novel and potent anti-inflammatory agent.

To identify differences in effectiveness and safety of a treat-to-target (T2T) strategy comparing late-onset MTX-naïve RA patients ≥75 or < 75 years of age: LORA ≥ 75 vs.s LORA < 75. Treatment was adjusted to target low disease activity with conventional synthetic DMARDs, followed by biological DMARDs (bDMARDs) in LORA ≥ 75 (n = 98, mean age 80.0 years) and LORA < 75 (n = 99) with moderate-to-high disease activity. Achievement of simplified disease activity index (SDAI) remission at week 156 by non-responder imputation analysis was evaluated as a primary outcome. LORA ≥ 75 had more comorbidities than LORA < 75, but SDAI and ACPA-positivity were similar at baseline. Of the LORA ≥ 75, 70.4% started MTX and 34.1% and 37.1% received a bDMARD at week 52 and 156, respectively (very similar to the LORA < 75). Glucocorticoid use was more frequent in the LORA ≥ 75 than in the LORA < 75. Comorbidities/adverse events more frequently contributed to the reasons for non-adherence to T2T in the LORA ≥ 75 than in the LORA < 75. At week 156, 32.7% of the LORA ≥ 75 and 66.7% of the LORA < 75 achieved SDAI remission (p < 0.001). The cumulative incidence of serious adverse events (SAEs) over 156 weeks was 42.8% in the LORA ≥ 75 and 22.1% in the LORA < 75. Multivariable analysis indicated an increased risk of SDAI non-remission at week 156 in the LORA ≥ 75 (odds ratio 2.82, 95% CI 1.29–6.14) after adjusting for comorbidities at baseline, non-adherence to T2T, and SAEs. It was more difficult to achieve remission in the LORA ≥ 75 than in the LORA < 75 due to both poor treatment responses and safety issues.

Deployment of electric vehicles (EVs) has been accelerated in many countries. However, for further deployment of EVs and their contribution to electrical power systems, various new services need to be implemented related to EVs and their charging, called “Place of Use” (PoU) services. The combined menu of the charging services has been proposed which bundles EV charging fees with home electricity bills. Settlement will be needed for such combined menu. This paper proposes the combined menu of EV charging with settlement of electricity. Technical feasibility of the settlement has been tested by EV charging testbed with the IoT-HUB technology. IoT-HUB is the virtual infrastructure which interconnects various connected devices and application by using “drivers” for each device. This paper also proposes a forecast method of EV charging demand for the settlement after the charging starts. The proposed method has reduced the forecast error of total charged energy compared to the simple method, but some of the forecast error has remained because of the variability of the charging time at the final step of state of charge.

Heterotopic mesenteric ossification (HMO) is a rare disease that results in intra-abdominal ossification of unknown origin. An 88-year-old man developed an intestinal obstruction 2 weeks after undergoing an operation for a ruptured abdominal aortic aneurysm, resulting in intestinal obstructions those did not improved concervatively. During relaparotomy performed 30 days after the first operation, hard adhesions of the small intestine and mesentery were found; these adhesions were difficult to separate without damaging the serosa of the small intestine. We removed 240cm of the small intestine and performed a jejuno-ileo anastomosis. Microscopically, trabecular bone tissue had increased irregularly in the fat tissue of the nodules with fibrosis, which were partially lined with osteoblasts. Accordingly, we histopathologically diagnosed the patient as having HMO. The patient was treated with NSAIDs and cimetidine to prevent the recurrence of HMO. No signs of recurrence have occurred as of one year after the second operation.