Metabolically healthy obesity and risks of cardiovascular disease and all-cause mortality, a matched cohort study: the Shizuoka study.

BACKGROUND: Metabolically healthy obesity is not always a benign condition. It is associated with an increased incidence of cardiovascular disease and all-cause mortality. We investigated the prognostic significance of metabolically healthy obesity by comparing clinical profile-matched metabolically healthy obesity and non-obesity groups. METHODS: We analyzed a health insurance dataset with annual health checkup data from Japan. The analyzed data included 168,699 individuals aged <65 years. Obesity was defined as ≥25 kg/m2 body mass index. Metabolically healthy was defined as ≤1 metabolic risk factor (high blood pressure, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, or high hemoglobin A1c). Incidence rates of stroke, myocardial infarction, and all-cause mortality identified from the insurance data were compared between metabolically healthy obesity and non-obesity groups (n = 8644 each) using a log-rank test. RESULTS: The stroke (obesity: 9.2 per 10,000 person-years; non-obesity: 10.5; log-rank test p = 0.595), myocardial infarction (obesity: 3.7; non-obesity: 3.1; p = 0.613), and all-cause mortality (obesity: 26.6; non-obesity: 23.2; p = 0.304) incidence rates did not differ significantly between the metabolically healthy obesity and non-obesity groups, even when the abdominal obesity was considered in the analysis. The lack of association was also observed in the comparison between the metabolically unhealthy obesity and non-obesity groups (n = 10,965 each). The population with metabolically healthy obesity reported negligibly worse metabolic profiles than the population with non-obesity at the 5.6-year follow-up. CONCLUSION: Obesity, when accompanied by a healthy metabolic profile, did not increase the risk of cardiovascular outcomes and all-cause mortality.

Additive association of blood pressure and short stature with stroke incidence in 450,000 Japanese adults: the Shizuoka study.

Short stature was suggested to be a risk factor for cardiovascular events. Because short stature increases central blood pressure, this study aimed to investigate a longitudinal association between short stature, blood pressure, and incidence of cardiovascular disease by the analysis of insurance-based real-world dataset. We analyzed data from 463,844 adults aged 40 or older with a mean age of 66.7 enrolled in National Health Insurance, excluding individuals who experienced a stroke or myocardial infarction, or required long-term care. Data from annual health checkups were used to obtain baseline clinical information. Comorbidities and incidences of stroke and myocardial infarction were obtained from the insurance data. During a 5.5-year follow-up period, we observed 11,027 cases of stroke. Adults of a short stature exhibited a higher incidence rate in both men (≤155 cm: 99.7, >175 cm: 24.4) and women (≤140 cm: 85.9, >160 cm: 13.7). Although those in the short stature group had higher blood pressure, and often took antihypertensive drugs, the inverse association between height and stroke incidence was independent of these factors (hazard ratio for 5 cm shorter in height; men: 1.06 [1.03-1.09], women: 1.11 [1.06-1.13]). Short stature and blood pressure showed additive association with stoke incidence (log-rank p < 0.001). No significant association was observed with myocardial infarction (men: 1.01 [0.95-1.06], women: 1.06 [0.98-1.14]). In a longitudinal analysis of a large general Japanese population, short stature was linked to an increased risk of stroke in both genders in any blood pressure range.

[Optimal search conditions for identification of patients with chronic myeloid leukemia from Japanese National Health Insurance data].

This study investigated which conditions could be used to identify patients with chronic myeloid leukemia (CML) from a National Health Insurance claims dataset. During April 2012 and September 2018, 1,789,462 employees were enrolled in the dataset for Shizuoka Prefecture residents. The number of patients with the ICD-10 code for CML was 761. Among them, 246 who had been prescribed a tyrosine kinase inhibitor were considered as having true CML. The positive predictive value was calculated as 32.3% when CML was identified by ICD-10 code alone. Combination of ICD-10 code with prescribed drugs was required to accurately identify patients with CML from the insurance database.

Risk factors for glioblastoma in adults in Japan: an exploratory cohort study based on the Shizuoka Kokuho Database, the Shizuoka study.

PURPOSE: To elucidate the risk factors associated with the onset of glioblastoma (GBM) utilizing a comprehensive administrative claims database from a major governmental district in Japan. METHODS: Using the Shizuoka Kokuho Database (SKDB) for the period from April 2012 to September 2021, we conducted a retrospective analysis of 1,465,353 participants, identifying GBM cases using specific Japanese disease codes in conjunction with associated treatments. Risk factors were assessed using both univariable and multivariable Cox proportional hazards models. RESULTS: Within the cohort, 182 participants (0.012%) received a GBM diagnosis during the study period, resulting in an incidence rate of 2.1 per 100,000 person-years. The multivariable analysis revealed that older age, male sex, and peripheral vascular disease (PVD) significantly influenced the risk of GBM onset. No clear link was found between allergic conditions and GBM risk, in contrast to some previous research. CONCLUSION: Employing a robust health insurance database, this study revealed significant associations between GBM and factors such as age, male sex, and PVD within the Japanese population. It provides key insights into GBM epidemiology and underscores the potential of health insurance databases for large-scale oncological research.

Risk factors, treatment and survival rates of late-onset acquired haemophilia A: A cohort study from the Shizuoka Kokuho Database.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare disease. The risk factors have yet to be studied. AIM: We aimed to identify risk factors for late-onset AHA in Japan. METHODS: A population-based cohort study was conducted using data from the Shizuoka Kokuho Database. The study population was defined as individuals aged ≥60 years. Cause-specific Cox regression analysis was performed to calculate hazard ratios. RESULTS: Of 1,160,934 registrants, there were 34 patients with newly diagnosed AHA. The mean follow-up period was 5.6 years, and the incidence of AHA was 5.21 per million person-years. Myocardial infarction, diabetes mellitus, solid tumors, antimicrobial agents, phenytoin and anti-dementia drugs, which showed significant differences in the univariate analysis, were excluded from the multivariable analysis because of the small number of cases. Multivariable regression analysis showed that the presence of Alzheimer's disease (hazard ratio [HR]:4.28, 95% confidence interval [CI]:1.67-10.97) and rheumatic disease (HR:4.65, 95% CI:1.79-12.12) increased the risk of AHA development. CONCLUSION: We found that comorbid Alzheimer's disease is a risk factor of AHA incidence in the general population. Our findings provide insight into the etiology of AHA, and the proof of the coexistence of Alzheimer's disease may support the recent notion that Alzheimer disease is an autoimmune disease.

Practical Total Syntheses of Acromelic Acids A and B.

Practical total syntheses of acromelic acids A (1) and B (2), which were scarce natural products isolated from toxic mushroom by Shirahama and Matsumoto, were accomplished in 13 (36% total yield) and 17 steps (6.9% total yield), respectively, from 2,6-dichloropyridine (8). Beginning with regioselective transformation of symmetric 8 by either ortho-lithiation or bromination, nitroalkenes 15 and 16 were provided. Stereoselective construction of the vicinal stereocenters at the C-3, 4 positions of 1 and 2 was performed by a Ni-catalyzed asymmetric conjugate addition of α-ketoesters to the nitroalkenes. Construction of the pyrrolidine ring was accomplished in a single operation via a sequence consisting of reduction of the nitro group, intramolecular condensation with the ketone, and reduction of the resulting ketimine.

Acquired factor X deficiency developed four years after autologous transplantation in a patient with multiple myeloma associated with systemic AL amyloidosis.

We describe a case of acquired factor X deficiency after high-dose melphalan with autologous stem cell transplantation (HDM/ASCT) for multiple myeloma (MM) with systemic AL amyloidosis. A 68-year-old woman with renal amyloidosis was diagnosed as having MM in 2007. She achieved a partial response after VAD (vincristine, adriamycin, dexamethasone) therapy and HDM/ASCT. In December 2011, coagulation tests revealed a prolonged prothrombin time (PT) of 17.6 sec and she was administered vitamin K. In January 2012, she received low anterior resection with colostomy for rectal cancer. She received fresh frozen plasma (FFP) infusion but the perioperative bleeding tendency persisted. In February 2012, she was referred from surgery for colostomy closure. She showed no progression of MM and had prolonged PT, corrected by mixing with normal plasma. Factor X activity was markedly decreased. She was diagnosed as having an acquired factor X deficiency and was given FFP infusion for colostomy closure. Although acquired factor X deficiency after HDM/ASCT for MM with systemic AL amyloidosis is rare, we should be aware of the possibility of this disease in MM patients with a bleeding tendency.

Practical total syntheses of acromelic acids A and B.

Practical total syntheses of acromelic acids A (1) and B (2), which have potent neuro-excitatory activity, were accomplished in 13 (36% total yield) and 17 steps (6.9% total yield), respectively, from 2,6-dichloropyridine (8). Regioselective transformation of symmetric 8 provided nitroalkenes 15 and 16. The pyrrolidine ring was efficiently constructed by Ni-catalyzed asymmetric conjugate addition followed by intramolecular reductive amination.

JmjC-domain containing histone demethylase 1B-mediated p15(Ink4b) suppression promotes the proliferation of leukemic progenitor cells through modulation of cell cycle progression in acute myeloid leukemia.

The histone demethylase JHDM1B has been implicated in cell cycle regulation and tumorigenesis. In addition, it has been reported that JHDM1B is highly expressed in various human tumors, including leukemias. However, it is not clearly understood how JHDM1B contributes to acute myeloid leukemia (AML) cell proliferation. In this study, we investigated the cellular and molecular function of JHDM1B in AML cells. In AML cell lines and AML-derived ALDH(hi) (high aldehyde dehydrogenase activity)/CD34(+) cells, the levels of JHDM1B mRNA were significantly higher than in normal ALDH(hi) /CD34(+) cells. Reduction of JHDM1B expression in AML cells inhibited cell proliferation compared to control cells, through induction of G1 cell cycle arrest, an increase in the p15(Ink4b) mRNA and protein expression. JHDM1B mRNA was overexpressed in all 133 AML clinical specimens tested (n = 22, 57, 34, and 20 for M1, 2, 4, and 5 subtypes respectively). Compared to normal ALDH(hi) /CD34(+) cells, JHDM1B gene expression was 1.57- to 1.87-fold higher in AML-derived ALDH(hi) /CD34(+) cells. Moreover, the JHDM1B protein was more strongly expressed in AML-derived ALDH(hi) /CD34(+) cells from compared to normal ALDH(hi) /CD34(+) cells. In addition, depletion of JHDM1B reduced colony formation of AML-derived ALDH(hi) /CD34(+) cells due to induction of p15(Ink4b) expression through direct binding to p15(Ink4b) promoter and loss of demethylation of H3K36me2. In summary, we found that JHDM1B mRNA is predominantly expressed in AML-derived ALDH(hi) /CD34(+) cells, and that aberrant expression of JHDM1B induces AML cell proliferation through modulation of cell cycle progression. Thus, inhibition of JHDM1B expression represents an attractive target for AML therapy.