Taoka Hospital

Since comprehensive data on the pathogenic variants of ABCG5 and ABCG8 and clinical features in sitosterolemia remain limited, we aimed to compile a catalog through an extensive literature search of case reports from 2002 to 2024, as well as an evaluation of variants reported in review articles. We compiled 155 cases of sitosterolemia from 133 families with nonsynonymous variants in ABCG5 and ABCG8, along with data on clinical information from case reports. Pathogenic variants were defined either as 1) protein-truncating variants, 2) classified as pathogenic or likely pathogenic variants according to the ACMG guidelines, or 3) serum sitosterol level of the case was measured at ≥ 1 mg/dL. Xanthoma was observed in 69.2% of patients, ischemic heart disease in 14.2%, and hematologic abnormalities in 57.9%. Fifty-three variants in ABCG5 and 52 in ABCG8 were evaluated for their pathogenicity, in which 33 in ABCG5 and 29 in ABCG8 were protein-truncating variants. Additionally, based on the ACMG criteria and serum sitosterol levels, 50 variants in ABCG5 and 51 variants in ABCG8 were finally classified as pathogenic. Among them, the frequently observed R446X and R389H in ABCG5 were highly prevalent in East Asians, while W361X and S107X in ABCG8 were predominantly found in Europeans. We provided the largest catalog of clinical features and pathogenic variants of ABCG5 and ABCG8 in the world. This study may help clarify the pathogenicity of variants in ABCG5 and ABCG8 and provide a valuable reference for the genetic diagnosis of sitosterolemia.

Because monocyte chemoattractant protein-1 (MCP-1) and high-sensitivity C-reactive protein (hs-CRP) are crucial biomarkers in the early stages of atherosclerosis, we examined the association of their serum levels with all-cause and cause-specific deaths in a healthy population. Between 2004 and 2007, 568 participants (64% women, mean age 64.4 years) underwent health check-ups from which their serum MCP-1 and hs-CRP levels were categorized as high or low based on the median values of each biomarker. We analyzed all-cause deaths using Kaplan-Meier curves and used a multivariable Cox regression model to calculate hazard ratios for all-cause, cardiovascular disease (CVD), and cancer deaths both individually and in combination. During a median follow-up of 17.9 years, 140 deaths occurred: 43 from CVD and stroke, and 33 from cancer. The cumulative all-cause mortality rate was higher in participants with both high serum MCP-1 and hs-CRP levels than in those with lower levels. The adjusted hazard ratios for combined high serum MCP-1 and hs-CRP levels vs. low levels were 1.86 (95% confidence interval (CI): 1.09-3.17) for all-cause, 3.24 (95% CI: 1.07-9.82) for CVD and stroke, and 3.28 (95% CI: 1.06-10.18) for cancer deaths. Combined serum MCP-1 and hs-CRP levels could predict all-cause and cause-specific mortality rates in the general population.

Objective: To compare the effectiveness of "semiocclusive dressing (SOD)" treatment using plastic wrap or low-adherent absorbent wound dressings with that of occlusive dressing (OD) treatment for National Pressure Injury Advisory Panel stage III/IV pressure injuries in the inflammatory phase. Approach: This 12-week, open-label, randomized controlled trial was conducted at one hospital and three care facilities. Seventy-seven participants were enrolled; 40 comprised the SOD group and 37 comprised the OD group. The primary outcome was the surface area reduction. Secondary outcomes included the Bates-Jensen Wound Assessment Tool (BWAT) score reductions, incidence of adverse events, and material cost. This trial met the recommendations of the CONSORT 2010 statement. Results: The surface area reduction of the SOD group was greater than that of the OD group throughout the study period. The significant interaction was revealed between treatment and time course (p < 0.0001). The 95% confidence interval of the difference at 12 weeks was 3.4 to 21.9. The median BWAT score reduction of the SOD group at 12 weeks was 23, and that of the OD group was 18.5 (p = 0.0077). The incidence of adverse events was comparable between groups. The OD treatment cost was 3.0 times higher than the SOD treatment cost (p = 0.0012). Innovation: Because the SOD does not completely occlude the wound, excess exudate drains from the wound. Therefore, SOD can treat the wound with abundant exudate effectively and safely. Conclusion: SOD treatment is more effective and less expensive than OD treatment for stage III/IV pressure injuries. Clinical Trial Registration: UMIN Clinical Trials Registry [UMIN000023412]. Registered on July 31, 2016.

Background and AimsOzanimod is a once-daily, oral, selective sphingosine 1-phosphate receptor 1 and 5 modulator. The objective of the randomized, phase 2/3 J-True North study (NCT03915769) was to assess the efficacy and safety of ozanimod in Japanese patients with moderately to severely active ulcerative colitis.MethodsIn the 12-week induction period (IP), patients were randomized 1:1:1 to receive placebo, ozanimod 0.46 mg, or ozanimod 0.92 mg. Patients who completed the IP with a clinical response at week (w) 12 were eligible to enter a 40-week maintenance period where they received the same treatment as they did in the IP. The primary endpoint was clinical response (complete Mayo score) at w12; clinical and mucosal secondary endpoints were assessed at w12 and w52.ResultsOf 198 patients randomized, 176 completed the IP. Of these patients, 97 entered and 77 completed the maintenance period. A significantly higher proportion of patients receiving ozanimod achieved clinical response at w12 versus placebo (ozanimod 0.46 mg: 52.9%, P = .0158; ozanimod 0.92 mg: 61.5%, P = .0006; vs placebo: 32.3%). Similar results were observed in the secondary endpoints where patients receiving ozanimod achieved higher rates of clinical remission, endoscopic improvement, and mucosal healing at w12 than those receiving placebo. Efficacy was maintained at w52 for all endpoints. Both doses of ozanimod were well tolerated, with no unexpected safety signals.ConclusionThis large-scale clinical trial demonstrated the efficacy and safety of once-daily oral ozanimod in Japanese patients with moderately to severely active ulcerative colitis. This is the first time that the efficacy and safety of ozanimod were verified in a large number of patients in Asia.

The global surge in antimicrobial resistance (AMR) highlights the critical need for the development of innovative therapies and the appropriate use of antimicrobial agents. Our research focused on preventing, managing, and mitigating the adverse effects of treatments for infection with methicillin-resistant Staphylococcus aureus. In this review, we present our investigations utilizing medical big data. The first study aimed to elucidate the relationship between renal outcome and survival following the onset of vancomycin-associated nephrotoxicity (VAN). An initial analysis using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database revealed elevated mortality rates among patients with VAN compared with those without VAN, forming the basis for further investigation. A subsequent, more rigorous, retrospective analysis using electronic medical records confirmed that poor survival outcomes were significantly associated with non-recovery from VAN, particularly when progression to acute kidney injury of stage ≥2 occurred. Therefore, preventing progression to severe VAN is critical for enhancing survival outcomes. The second study investigated the relationship between statin use and daptomycin-related musculoskeletal adverse events. By employing a mixed-method approach combining meta-analysis with disproportionality analysis of the FAERS data, a significant association between statin therapy and daptomycin-related rhabdomyolysis was identified. This highlights the importance of cautious statin and daptomycin use, with careful consideration of potential safety risks. Each medical big-data database possesses unique characteristics that require careful consideration during analysis. The accurate interpretation of medical big data, coupled with its integration with complementary methodologies, will produce more robust and reliable research outcomes across diverse fields.

Gastric cancer (GC) has a high prevalence in Asian countries, and there is an unmet need for non-invasive and efficient GC screening methods. This study evaluated the diagnostic efficacy of GASTROClear, a panel of blood serum miRNAs for the detection of GC, in a Japanese population. We conducted a pilot cohort study, comprising 103 patients with GC and 122 healthy controls. Serum samples were prospectively collected from study participants at two Japanese hospitals using a predefined blood-processing protocol. The diagnostic performance of GASTROClear was analyzed using a receiver operating characteristic curve and cutoff. By applying a logistic regression algorithm, we evaluated the diagnostic efficacy of novel combinations of GC diagnostic biomarker panels, consisting of GASTROClear and alternative serum markers (anti-Helicobacter pylori [Hp] antibody and pepsinogen). Most patients had Stage I (58%) GC and were asymptomatic (59%). The area under the curve (AUC) value for the detection of GC using GASTROClear was 0.80, with 70.9% sensitivity and 75.2% specificity. GASTROClear performed equally well within the subgroups based on age, sex, symptoms, Hp status, and tumor characteristics. We improved the diagnostic performance of GASTROClear by combining it with an anti-Hp antibody and pepsinogen. This yielded an AUC value of 0.88, with the highest specificity (86.9%) at a fixed sensitivity (70.9%). GASTROClear demonstrated competent diagnostic efficacy for GC in the detection of GC in our Japanese cohort, even in the early stages of cancer and asymptomatic cases. Its combination with existing serum markers may contribute to efficient risk stratification to detect GC.