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Background Breastfeeding is said to prevent overweight and obesity in childhood but the evidence about its long-term impact on body size into adolescence and adulthood is scarce. We sought to examine the association between feeding types and subsequent physical size at the ages of 3, 6, 12, and 22 years. Methods The Ibaraki Children's Cohort (IBACHIL) Study, which began in 1992, involved a cohort of 4,592 Japanese children from 87 communities of a single prefecture whose parents answered health questionnaires about their child's health and life habits at the age of 3 years. Follow-up questionnaires were distributed to the same cohort when they were 6, 12, and 22 years old. Self-reported height and weight, body mass index (BMI), and overweight status at ages of 3 (n = 4,290), 6 (n = 1,999; proportion of participants analyzed = 47%), 12 (n = 2,227; 52%), and 22 (n = 1,459; 34%) years were compared according to feeding type (breastfeeding, formula feeding, and mixed feeding) during infancy. Results At the age of 3 years, multivariable adjusted-mean weight and prevalence of overweight were less for breastfed children than those formula-fed in both boys (weight: 14.6 kg vs 14.7 kg, P = 0.07, overweight: 6.3% vs 9.3%, P = 0.03) and in girls (14.0 kg vs 14.2 kg, P = 0.01 and 10.4% vs 13.6%, P = 0.06). However, there were no statistically significant differences in weight, BMI, and overweight at the ages of 6, 12, and 22 years according to feeding type. Conclusions Breastfeeding may prevent overweight in childhood, but its impact is not significant in adolescence and adulthood.

Aims The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an ‘Add-on’ to incorporate CKD measures into these algorithms, using a validated approach. Methods In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP. We validated C-statistics and net reclassification improvement (NRI), accounting for competing risk of non-CVD death, in 5,997 719 participants from 34 different datasets. Results In the target population of SCORE2 and SCORE2-OP without diabetes, the CKD Add-on (eGFR only) and CKD Add-on (eGFR + ACR) improved C-statistic by 0.006 (95%CI 0.004–0.008) and 0.016 (0.010–0.023), respectively, for SCORE2 and 0.012 (0.009–0.015) and 0.024 (0.014–0.035), respectively, for SCORE2-OP. Similar results were seen when we included individuals with diabetes and tested the CKD Add-on (eGFR + dipstick). In 57 485 European participants with CKD, SCORE2 or SCORE2-OP with a CKD Add-on showed a significant NRI [e.g. 0.100 (0.062–0.138) for SCORE2] compared to the qualitative approach in the ESC guideline. Conclusion Our Add-ons with CKD measures improved CVD risk prediction beyond SCORE2 and SCORE2-OP. This approach will help clinicians and patients with CKD refine risk prediction and further personalize preventive therapies for CVD.

Small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC) are both classified as lung neuroendocrine carcinoma (NEC). It has recently been reported that the special AT-rich sequence-binding protein 2 (STAB2), known as a colorectal cancer marker, is also expressed in NECs occurring in various organs including the lung. However, few studies have examined any differences of SATB2 immunopositivity between SCLC and LCNEC. We investigated SATB2 expression in 45 SCLC and 14 LCNEC cases using immunohistochemistry as well as the expression of caudal-type homeobox 2 (CDX2) and keratin (KRT) 20. The LCNEC cases were more frequently positive for SATB2 (ten out of 14, 71%) than the SCLC ones (seventeen out of 45, 38%) with a statistically significance (P = 0.035). Furthermore, two LCNEC cases were positive for CDX2 while no positive findings were observed for any SCLC cases, the difference of which, however, was not statistically significant (P = 0.053). KRT20 was negative in all LCNEC and SCLC cases. These results require our attention when we use SATB2 and CDX2 as colorectal cancer markers because their expression in pulmonary NECs can lead to a misdiagnosis that the tumor is of metastatic colorectal adenocarcinoma, especially when the patient has a past history of colorectal cancer. Analyzing the relationship between the demographic/clinical variables and the SATB2 expression in the SCLC cases, just high Brinkman index (≥ 600) was significantly related to the positivity of SATB2 (P = 0.017), which is interesting considering the strong relationship between SCLC and smoking.

Historically, a right bundle branch block has been considered a benign finding in asymptomatic individuals. However, this conclusion is based on a few old studies with small sample sizes. We examined the association between a complete right bundle branch block (CRBBB) and subsequent cardiovascular mortality in the general population in Japan. In this large community-based cohort study, data of 90,022 individuals (mean age, 58.5 ± 10.2 years; 66.2% women) who participated in annual community-based health check-ups were assessed. Subjects were followed up from 1993 to the end of 2016. Cox proportional hazards’ models and log-rank tests were used for the data analysis. CRBBB was documented in 1,344 participants (1.5%). Among all included participants, CRBBB was associated with an increased risk of cardiovascular mortality after adjustment for all potential confounders (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.06–1.38). The increased risk of cardiovascular mortality was particularly evident in women aged

AIM: To examine the association between long-term exposure to suspended particulate matter (SPM) and cardiovascular mortality in Japan after controlling for known major confounding factors among a large middle and elderly cohort study in Ibaraki Prefecture, Japan. METHODS: We followed 91,808 residents (men 34%) who undertook a national health check-up at age 40-79 years for 17 years (1993-2010). Two different exposure indices were adopted: baseline SPM concentration (in the year 1990) and average SPM concentration for the first (average of 1990 and 1995) and the second half (average of 2005 to 2009) of the study period. Sex-specific adjusted risk ratios (RRs) for cardiovascular mortality were calculated using general mixed Poisson regression models after adjusting the age, BMI, history of diabetes mellitus and hypertension, creatinine, glutamic pyruvic transaminase, total cholesterol, high-density lipoprotein cholesterol, smoking, alcohol, and temperature. The variation between seven medical administration areas was also taken into account as a random effect. RESULTS: Baseline SPM concentration was associated with an increased risk of mortality from all cardiovascular diseases, coronary artery disease, and stroke. The adjusted RRs (95% confidence interval [CI]) per 10 µg/m3 increase in SPM concentration for all cardiovascular mortality were 1.147 (1.014-1.300) for men and 1.097 (0.985-1.222) for women. The point estimate of RR was highest for non-hemorrhagic stroke in men (1.248 [0.991-1.571]), although CI overlapped the unity. The RRs seemed slightly lower in the second half than in the first half, though the CIs widened in the second half. CONCLUSION: Our results suggest that long-term exposure to SPM is associated with an increased risk of all cardiovascular mortality for men in Ibaraki, Japan.

Aim: The association between atrial fibrillation (AF) and risk of stroke mortality among men and women without traditional cerebrocardiovascular risk factors (TCVRFs) is unclear. This study aimed to determine whether AF was a risk factor for stroke and total cardiovascular disease mortality among individuals without TCVRFs. Methods: A total of 90,629 Japanese subjects from the Ibaraki Prefectural Health Study aged 40–79 years, with and without TCVRFs, were studied from 1993 to 2013. Hazard ratios (HRs) were calculated using the Cox proportional hazard regression model stratified by sex and the presence of TCVRFs. Covariates were age, systolic blood pressure, anti-hypertensive medication use, and serum total cholesterol levels. A standard 12-lead electrocardiogram at rest was used to screen AF. Cause-specific mortality was classified according to the International Classification of Disease code. Results: Compared with participants without AF, multivariable-adjusted hazard ratios (with 95% confidence intervals) for stroke mortality among participants without TCVRFs were 4.3 (1.1–17.8) and 15.0 (5.5–40.8) for men and women with AF, respectively. HRs for total cardiovascular disease mortality were 6.2 (2.8–14.2) for men and 10.7 (4.8–24.1) for women. For participants with TCVRFs, multivariable-adjusted HRs for stroke mortality were 3.1 (2.2–4.6) and 4.3 (2.6–7.3), whereas HRs for total cardiovascular disease mortality were 2.9 (2.2–3.8) and 3.5 (2.4–5.1) for men and women, respectively. Conclusions: AF was found to be an independent risk factor for stroke and total cardiovascular mortality even in individuals without other TCVRFs.

Potassium iodide (KI), initially derived from seaweed in the early 19th century, is used for treating sporotrichosis in dermatological practice. KI has also been used to treat several noninfectious inflammatory skin diseases. However, the mechanisms underlying the improvement in such skin diseases remain unknown, and KI is not used widely. Thus, although KI is an old drug, physicians may not prescribe it frequently because they lack knowledge about it. Although KI is very inexpensive and causes few side effects, it has been superseded by new powerful and expensive drugs, such as biological agents. We applied 3% KI topically to areas of inflammation induced by SDS in mice. The levels of IL-1 and TNF-α gene expression were reduced, whereas that of IL-10 gene expression was increased. Small interfering RNA that was designed to reduce IL-10 gene expression levels was injected into the same mice, and the anti-inflammatory effects of KI were not observed. Thus, the pharmacologic action of KI is based on its anti-inflammatory effects caused by the increase in IL-10 levels. This information would increase dermatologists' awareness of KI as an efficacious and cost-effective treatment.

Background It is uncertain whether health counselling after community-based health checkups for high-risk individuals of lifestyle-related disease enhances their referral to physicians. Methods We performed a clustered randomized controlled trial of untreated high-risk individuals aged 40 to 74 years who were screened from the annual health checkup in 2014 and 2015 under the national health insurance in 43 municipalities around Japan, assigning 21 intervention and 22 usual care municipalities. The high-risk conditions were severe forms of hypertension, diabetes, dyslipidemia (for men), and proteinuria. For the intervention group, the theory-based health counselling was performed to enhance referrals to physicians, while each municipality performed its own standard counselling for the usual care group. Data on clinical visits and risk factors were collected systematically and anonymously from the databases of health insurance qualification, health insurance claims, and annual health checkups. Hypotheses are that the cumulative proportion of seeing physicians (clinical visits) is higher in the intervention than the usual care groups, and that those in the intervention group have lower cumulative incidence of composite outcomes associated with lifestyle-related diseases. Results The numbers of subjects for the analyses were 8,977 in the intervention group and 6,733 in the usual care group. Among them, 6,758 had hypertension, 2,147 had diabetes, 2,861 had dyslipidemia, and 1,221 had proteinuria in the intervention group, with corresponding numbers of 4,833, 1,517, 2,262, and 845, respectively, in the usual care group. There were no material differences in mean levels and proportions of major cardiovascular risk factors between the two groups. Conclusions We expect to provide scientific evidence on the effectiveness of health counselling.

Background The gold standard for diagnosis of cutaneous sporotrichosis involves the isolation of the fungus, Sporothrix, by a culture test. Generally, the sampling for the culture test is performed at the same time as skin biopsy under local anaesthesia. However, the culture test may occasionally return a false negative result. Objective The aim of our study was to investigate the diagnostic value of a molecular method for diagnosing cutaneous sporotrichosis from formalin-fixed and paraffin-embedded (FFPE) tissues. Methods Over a 30-year period, we collected 52 cases of cutaneous sporotrichosis from biopsied specimens that had been positively diagnosed by a culture test. A nested PCR specific for Sporothrix detection was applied using FFPE tissue as template. The results were compared with control samples from 79 patients diagnosed with other cutaneous diseases according to histopathological, clinical findings and a cutler test. Results Of the 52 patients who were tested positive on the culture test, all cutaneous diseases were detected by PCR. Of the 59 patients in the control group, 58 tested negative by PCR. Under our conditions, the calculated sensitivity of this method was 100%, the specificity was 98.7% and the kappa coefficient was 0.984 (95% CI: 0.953-1.000). Conclusions The specific PCR assay used appears to be a useful tool for the prompt and accurate diagnosis of sporotrichosis. Using this method, it would be possible to diagnose cutaneous sporotrichosis for patients who were suspected of cutaneous sporotrichosis but tested negative on culturing, and for pathologically suspected cutaneous sporotrichosis patients for whom the culture test was not undertaken.

In right-handed patients with idiopathic rapid eye movement sleep behavior disorder (IRBD) or Parkinson's disease (PD), dopamine transporter (DAT) single-photon emission computed tomography (SPECT) shows a predominant nigrostriatal deficit in the left striatum. To confirm this hypothesis, we longitudinally investigated whether the nigrostriatal function is asymmetric in Japanese patients with IRBD.In 91 polysomnography-confirmed IRBD patients, which included 87 right-handed IRBD patients who underwent 33 repeat DAT-SPECT scans, we retrospectively examined the striatal dopaminergic terminals in each hemisphere using DAT-SPECT. We calculated the values of interhemispheric laterality index for the right and left sides.The proportion of IRBD patients with lower SBR in the striatum was different between the left (n = 60, 69.0%) and right (n = 27, 31.0%) hemispheres. In the repeat DAT-SPECT scan (n = 33), the rate of decline in the striatum was greater on the left than on the right side, and the proportion of patients with lower decline rates in the left striatum (n = 25, 73.5%) was greater than the that in the right striatum (n = 3, 8.8%). The proportion of lower SBR side at baseline did not predict the development of PD or DLB.Right-handed IRBD patients have asymmetric nigrostriatal dopaminergic function, as evidenced by the faster estimated rate of decline for the left striatum than the right striatum. The left-right hemispheric striatal predominance of the nigrostriatal deficit in the right-handed prodromal PD or DLB patients represents a difference in the early pathological process of the disease.

Aim Diabetes mellitus and hypertriglyceridemia may adversely interact with the development of ischemic cardiovascular disease, but epidemiological evidence on this issue is scarce. We hypothesized that the impact of hypertriglyceridemia on ischemic cardiovascular disease (ischemic heart disease and ischemic stroke) would differ according to the presence or absence of diabetes mellitus and tested our a priori hypothesis under a large population-based prospective study. Methods A total of 90,468 men and women aged 40-79 years in 1993 were enrolled in the Ibaraki Prefectural Health Study (IPHS), a community-based cohort study of Japanese. The participants' serum triglyceride levels (mostly nonfasting) were measured every 5 years, and the participants were followed up for mortality from ischemic cardiovascular disease through 2016. Hazard ratios (95% confidence intervals) were calculated according to 5-year updated triglyceride levels (＜100, 100-149, 150-199, 200-299, and ≥ 300 mg/dl). Results During 1,795,877 person-years, there were 3,323 deaths from ischemic cardiovascular diseases (1,968 ischemic heart diseases and 1,355 ischemic strokes). We found no association between triglyceride levels and the risk of mortality from ischemic cardiovascular disease after adjustment for known cardiovascular risk factors. However, when stratified by the presence or absence of diabetes mellitus, excess mortality from ischemic cardiovascular disease appeared among participants with diabetes mellitus with triglyceride levels of ≥ 300 mg/dl. Further adjustment for high-density lipoprotein-cholesterol attenuated the association toward being statistically nonsignificant. Conclusion The impact of high serum triglyceride levels on the risk of ischemic cardiovascular disease mortality was confined to participants with diabetes mellitus.

IMPORTANCE Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions.OBJECTIVE To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR).DESIGN, SETTING, AND PARTICIPANTS Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540).EXPOSURES Demographic and clinical factors.MAIN OUTCOMES AND MEASURES Incident eGFR of less than 60 mL/min/1.73 m(2).RESULTS Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A(1c), and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25.CONCLUSIONS AND RELEVANCE Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

Introduction: Those who are considered to be low risk in short term such as 10 year risk actually have high risk of cardiovascular disease for the remaining lifespan at younger age. Absolute risk of Lifetime risk (LTR) is more useful and understandable for lay audience compared with short term risk or relative risk. CKD (Chronic Kidney Disease) is global burden of cardiovascular disease (CVD) and hypertension is damaging complication of CKD for CVD. To date, there have been no reports of LTR with the outcome of CVD death based on CKD in Asian population. Hypothesis: We sought to estimate LTR of CVD death stratified by the status of CKD and hypertension. Methods: We used data from EPOCH-JAPAN (Evidence for Cardiovascular Prevention From Observational Cohorts in Japan) which is designed to pool data from nationwide and regional cohort studies in Japan. Modified Kaplan-Meier approach was used to estimate the remaining lifetime risk of cardiovascular death at each index age starting from 40 years according to CKD stratified by Hypertension. Participants were classified into four groups, which were those without CKD and hypertension (CKD-/HT-), those with CKD but without hypertension (CKD+/HT-), those without CKD but with hypertension (CKD-/HT+), and those with both CKD and hypertension (CKD+/HT+). Results: A total of 44,582 participants from 8 cohorts was included in the analysis. Mean follow-up period was 14.9 years with 662,488 person years and total CVD death was 1,035 in men and 1,160 in women. The LTRs at the index age of 40 years increased in groups with CKD and/or HT as follows: 12.6% (95% confidence interval: 9.4 - 14.5%) in CKD-/HT- group, 20.6% (11.4 - 25.9%) in CKD+/HT- group, 23.2% (19.9 - 25.2%) in CKD-/HT+ group, and 27.9% (21.7 - 32.9%) in CKD+/HT+ group for men; 11.3%(8.9 - 13.2%), 17.4%(13.2 - 20.4%) , 17.8%(15.3 - 19.8%) , and 22.7%(19.5 - 25.2%) for women. Conclusions: We observed that complication of CKD and hypertension are collectively responsible for lifetime risk due to CVD death. Management of blood pressure from an early age is important to reduce CVD mortality in CKD patients.

Objectives Adiposity rebound (AR) refers to an increase in body mass index (BMI) after a nadir. Early AR, in which AR occurs earlier than five years old, is a risk factor for future obesity and metabolic syndrome, but has not been widely studied in very-low-birth-weight infants (VLBWIs). Methods The subjects were VLBWIs born in Dokkyo Medical University NICU from January 2008 to December 2010. Height and weight measured at birth and at intervals until seven years old were obtained from medical records. The lowest BMI after one year of age was used for the age of AR. The subjects were divided into those with early and normal AR ( Results There were 38 early AR cases and 62 normal AR cases, giving a prevalence of early AR similar to that in infants with normal birth weight. BMI percentile at age seven years was significantly higher in early AR cases than in normal AR cases (44.6 [IQR: 21.0–79.2] vs. 14.4 [IQR: 3.8–40.8] kg/m2). Changes in BMI were also significantly higher in early AR cases (p=0.024 by ANOVA). Conclusions Early AR in VLBWIs is a predictor of future obesity.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): H20–Junkankitou [Seishuu]–Ippan–013; H23–Junkankitou [Seishuu]–Ippan–005; H26-Junkankitou [Seisaku]-Ippan-001; H29–Junkankitou–Ippan–003 and 20FA1002 OnBehalf EPOCH-JAPAN Introduction Absolute risk of Lifetime risk (LTR) is useful estimate for risk communication compared with short term risk or relative risk especially for young people. Proteinuria is leading cause of end-stage kidney disease (ESKD) and independent risk factor for cardiovascular disease (CVD). Although nonproteinuric renal disease is global burden of ESKD, it has been poorly focused. To date, there have been no reports of impact of proteinuria and low eGFR on LTR with the outcome of CVD death in Asian population. Purpose We aimed to estimate LTR of CVD death stratified by the status of proteinuria and low eGFR. Methods We used modified Kaplan-Meier approach to estimate the remaining lifetime risk of cardiovascular death based on EPOCH-JAPAN(Evidence for Cardiovascular Prevention From Observational Cohorts in Japan) database. LTR was estimated at each index age starting from 40 years for those with proteinuria and without proteinuria stratified by low eGFR, which is defined as eGFR Results A total of 47,292 participants from 9 cohorts was included in the analysis. Mean follow-up period was 14.6 years with 690,463 person years and total CVD death was 1,075 in men and 1,193 in women. The LTRs at the index age of 40 years were as follows: 17.7% (95% confidence interval: 15.4 – 19.0%) in Proteinuria (-)/Low eGFR (-) group, 26.2% (20.2 – 31.1%) in Proteinuria (-)/low eGFR (+) group, 24.5% (15.1 – 29.3%) in Proteinuria (+) group for men; 15.3%(13.7 – 16.5%), 29.9%(14.7 – 46.8%) , 28.3%(19.4 – 34.7%) for women. Conclusions We observed that those without proteinuria with low eGFR have equivalently high LTR with those with proteinuria. These results indicate that even in the absence of proteinuria, low eGFR has high impact on LTR. Lifestyle modification from young age is necessary to prevent from renal dysfunction.

Objectives This study aimed to compare the short-term outcomes of transcatheter and surgical aortic valve replacements (TAVR and SAVR) in high-, intermediate-, and low-preoperative risk patients. Methods A total of 454 patients who underwent TAVR or SAVR were included. Patients were categorized into high-, intermediate-, and low-risk according to the Society of Thoracic Surgery-Predicted Risk of Mortality score and clinical outcomes were compared between TAVR and SAVR groups. Results TAVR was less invasive, with less bleeding and transfusion (p p p p = 0.003) and pressure gradient (p p p p Conclusions TAVR was superior to SAVR in the sense of less invasiveness and valvular function. However, the indication of TAVR in low-risk patients should be carefully discussed, because paravalvular leakage was a risk factor for short-term mortality.

In Japan, heart disease and cerebrovascular disease were the second and fourth leading cause of death, respectively in 2014. Hematocrit, the ratio of the red blood cells to the total volume of blood is known to play a role in cardiovascular diseases. However, the relationship between elevated hematocrit and the risk of cardiovascular disease based on sex has not been examined in Asian countries. We analyzed data from the Ibaraki Prefectural Health Study, a community-based large cohort study, which included 87,533 individuals, aged 40 to 79 years living in 38 municipalities of the Ibaraki Prefecture, who had completed an annual health checkup in 1993, and were followed until 2013. The hematocrit levels of the subjects were categorized into 5 quintiles (Q1-Q5), and hazard ratios for cause-specific mortality were calculated using the Cox proportional hazards regression models. Age and other cardiovascular risk factors were the covariates in the study. During the follow-up for a mean of 17.9 years, 1,207 deaths (615 men and 592 women) due to acute myocardial infarction (AMI) were reported in this population. The p values for the trend in the Q3-Q5 groups were 0.661 for men and 0.020 for women. Additionally, these values were significant in younger (40 to 59 years) women but not in older (60 to 79 years) women. This study is the first one to demonstrate an association between high hematocrit level and risk of AMI mortality in younger Japanese women, but not in men and older women.

Background. The role of central sensitization in refractory pain-related diseases has not yet been clarified. Methods. We performed a multicenter case-controlled study including 551 patients with various neurological, psychological, and pain disorders and 5,188 healthy controls to investigate the impact of central sensitization in these patients. Symptoms related to central sensitization syndrome (CSS) were assessed by the Central Sensitization Inventory (CSI) parts A and B. Patients were categorized into 5 groups based on CSI-A scores from subclinical to extreme. The Brief Pain Inventory (BPI), addressing pain severity and pain interference with daily activities, and the Patient Health Questionnaire (PHQ)-9, assessing depressive symptoms, were also administered. Results. CSI-A scores and CSI-B disease numbers were significantly greater in patients than in controls ( p < 0.001 ). Medium effect sizes (r = 0.37) for CSI-A scores and large effect sizes (r = 0.64) for CSI-B disease numbers were found between patients and control groups. Compared with the CSI-A subclinical group, the CSI-A mild, moderate, severe, and extreme groups had significantly higher BPI pain interference and severity scores, PHQ-9 scores, and CSS-related disease numbers based on ANCOVA. Greater CSI-B numbers resulted in higher CSI-A scores ( p < 0.001 ) and a higher odds ratio ( p for trend

AIM: Lifetime risk (LTR) indicates the absolute risk of disease during the remainder of an individual's lifetime. We aimed to assess the LTRs for coronary heart disease (CHD) mortality associated with blood pressure (BP) and total cholesterol levels in an Asian population using a meta-analysis of individual participant data because no previous studies have assessed this risk. METHODS: We analyzed data from 105,432 Japanese participants in 13 cohorts. Apart from grade 1 and 2-3 hypertension groups, we defined "normal BP" as systolic/diastolic BP ＜130/＜80 mmHg and "high BP" as 130-139/80-89 mmHg. The sex-specific LTR was estimated while considering the competing risk of death. RESULTS: During the mean follow-up period of 15 years (1,553,735 person-years), 889 CHD deaths were recorded. The 10-year risk of CHD mortality at index age 35 years was ≤ 0.11%, but the corresponding LTR was ≥ 1.84%. The LTR of CHD at index age 35 years steeply increased with an increase in BP of participants with high total cholesterol levels [≥ 5.7 mmol/L (220 mg/dL)]. This risk was 7.73%/5.77% (95% confidence interval: 3.53%-10.28%/3.83%-7.25%) in men/women with grade 2-3 hypertension and high total cholesterol levels. In normal and high BP groups, the absolute differences in LTRs between the low and high total cholesterol groups were ≤ 0.25% in men and ≤ 0.40% in women. CONCLUSIONS: High total cholesterol levels contributed to an elevated LTR of CHD mortality in hypertensive individuals. These findings could help guide high-risk young individuals toward initiating lifestyle changes or treatments. ispartof: JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS vol:28 issue:1 pages:6-24 ispartof: location:Japan status: published

Background/Introduction The right bundle branch block (RBBB) has been considered a benign finding in asymptomatic individuals. However, this concept based on a few, old, small sample size studies. Recently, the importance of the right ventricular dysfunction was focused on cardiovascular prognosis in clinical cardiology. Purpose To determine the prognostic value of RBBB in community-based health checkups cohort with a large sample size in recent years in Japan. Methods We assessed 88,089 individuals (mean age, 58.3±10.2 years; 66.1% women) who participated in annual community-based health checkups. Exclusion criteria were current or previous history of heart disease, stroke, and intraventricular block such as left bundle branch block other than RBBB. We followed them from 1993 to 2016. The primary endpoint was cardiovascular death, or all-cause death. The Cox regression model was assessed in each gender. The variables included in the multivariate analyses were age, body mass index, systolic blood pressure, hypertension, total cholesterol level, high-density lipoprotein cholesterol level, treated-hyperlipidemia, hyperglycemia, treated-diabetes, estimated glomerular filtration rate (eGFR), current smoking, and drinking habit. Results The prevalence of RBBB was higher in men than women (723/29,863 2.4% in men vs. 581/58,204 1.0% in women, P In women, RBBB was associated with significantly increased cardiovascular mortality with multivariate-adjusted hazard ratios (HR) of 1.26 [95% confidence interval (CI), 1.03–1.54]. Then, we divided them into younger or elder groups according to the cut-off age of 65-year-old. In women ≤65-year-old, RBBB related to greater cardiovascular mortality with multivariate-adjusted HR of 1.89 [95% CI, 1.27–2.80]. However, in women >65-year-old, RBBB did not show the prognostic significance. In men, RBBB did not reach the significant results in all participants, however, men >65-year-old with RBBB showed the significant poor prognosis with HR of 1.26 [95% CI, 1.04–1.53]. Conclusions In this cohort study, contrary to common perception, RBBB was associated with increased cardiovascular mortality in women, especially younger women ≤65-year-old, and elderly men. To the extent we know, the present study is the largest and long-term follow-up study showing that the significance of RBBB differs depending on sex and age. Especially in young women who usually are less prone to show wide QRS, RBBB might represent the pathological abnormality. Although the pathophysiological effect of the RBBB on the cardiovascular outcome needs further investigation in the future, clinicians should alert the RBBB in young women and elder men even if they have no symptoms and evaluate the heart abnormality and follow them up carefully. Funding Acknowledgement Type of funding source: None

ObjectivesThere have been no longitudinal surveys on the changes in 25-hydroxyvitamin D [25(OH)D] while considering hemodilution factors among pregnant Japanese women. Therefore, we examined 25(OH)D levels as well as red blood cell count (RBC), hemoglobin (Hb), and Hematocrit (Hct) at the three trimesters among pregnant Japanese women to determine the distribution of serum 25(OH)D levels and the influence of hemodilution.DesignThis was a longitudinal study.SettingThe study was conducted at Ibaraki Seinan Medical Center Hospital in Japan.ParticipantsThe participants comprised 50 women in the first trimester with singleton pregnancies and without any complications.Outcome measuresParticipants were recruited from June to August 2018, and followed up till their postpartum period. Blood samples were collected at the first, second, and third trimesters, i.e., at 4-15, 16-27, and 28-39 weeks, respectively. 25(OH)D levels, RBC, Hb, and Hct were analyzed across the three trimesters.ResultsComparing the first, second, and third trimesters, 25(OH)D, RBC, and Hb were significantly declined in the second and third trimesters (p < 0.001). According to Spearman's correlation coefficient with 25(OH)D and RCB, Hb, Hct, significant correlations were found between 25(OH)D and Hb (p < 0.001), as well as Hct (p < 0.001) in the third trimester.ConclusionsThe present study had two major findings. First, it showed that the vitamin D status of most pregnant Japanese women were considered as vitamin D deficient. Second, the maternal serum 25(OH)D levels, RBC, Hb, and Hct of the pregnant women declined in the second and third trimesters. Thus we propose to have routine screening of vitamin D status of pregnant women, especially in the second trimester.

Few studies have reported on the increase in cervical cancer incidence in Japan. We aimed to determine the relevant trends in the metropolitan regions of Japan and to identify the population with the highest risk, based on histological subtype, cancer stage, and diagnostic processes. Using population-based data (2009&ndash, 2013), we identified 2110 women, aged &ge, 20 years, with cervical cancer. We estimated the age-standardized and age-specific incidence rates of cervical cancer for the study period based on the 1985 national model population. The average annual percent change (AAPC) and 95% confidence interval (CI) were calculated using the joinpoint regression analysis. We stratified the analyses based on histological subtypes, stage, and diagnostic process via cancer screening. The increase in the overall age-standardized incidence was not significant. However, the increase was significant for women aged 30&ndash, 39 years (AAPC 20.0%/year, 95% CI: 9.9&ndash, 31.1), which was attributable to the increase in the incidence of the squamous cell carcinoma (SCC) subtype (AAPC 23.1%/year, 95% CI: 10.7&ndash, 36.8). Among younger women, aged &lt, 50 years, further stratification showed an increase in the undiagnosed early-stage SCC subtype via cancer screening. In Japan, the incidence of HPV-related cervical cancer has been increasing in undiagnosed younger women.

Objective To examine the association between the risk of postpartum hemorrhage (PPH) and poor uterine contractility, which is suggested by the characteristics of labor. Methods This case-control study used cases recorded in the Japan Perinatal Registry database during the period 2013-2016. After exclusion of women with specified known risk factors for PPH, we enrolled 174 082 primiparas who had a full-term live singleton vaginal birth. Participants were classified into four classes according to the diagnosis of abnormal labor patterns and use of uterotonics. χ2 tests were used to compare PPH cases with controls, and odds ratios (OR) were calculated by univariate and multivariate analyses. Results Among the enrolled women, 10 508 (6.0%) had PPH. Abnormal labor patterns were significantly associated with an increased risk of PPH. Compared with women without any abnormal labor patterns who had not used uterotonics, women with abnormal labor patterns were at a significantly increased risk for PPH regardless of whether they had used uterotonics (adjusted OR 1.23, 95% confidence interval [CI] 1.10-1.37) or not (adjusted OR 1.30, 95% CI 1.23-1.37). Conclusion Our study suggests that among low-risk women with PPH, poor uterine contractility in labor could be a significant predisposing risk factor for PPH.

We hypothesized that, in migraine patients, central sensitization (CS) could be associated with comorbid restless legs syndrome (RLS). We conducted a case–control study including 186 migraine patients and 186 age- and sex-matched healthy controls. Symptoms related to CS syndrome were assessed by the Central Sensitization Inventory (CSI). Individuals with CSI Part A (CSI-A) scores ≥ 40 were defined as having CS. For patients with migraine, the Brief Pain Inventory (BPI) and Patient Health Questionnaire (PHQ)-9 were administered. In the patient group, RLS and migraine were diagnosed through face-to-face interviews. Among migraine patients, 26 (14.0%) suffered from chronic migraine. The mean disease duration was 23.7 ± 11.8 years. Migraine patients showed a higher rate of CS (21.0% vs. 8.6%) than healthy controls, with an adjusted odds ratio (AOR) of 3.039 (95% confidence interval (CI) 1.560–5.992; p = 0.001). Migraine patients in the CS group had higher rates of smoking, chronic migraine and RLS and higher BPI and PHQ-9 scores than migraine patients in the non-CS group. The use of acute and preventive treatment for migraine did not significantly differ between the CS and non-CS groups. Multivariable analysis identified the presence of RLS (AOR, 28.471; 95% CI 6.438–125.918; p

The association of gestational hypertension (GH) with future hypertension in Japanese women is unclear. Hence, this study aimed to examine the association between GH and the risk of future hypertension in middle-aged-to-older Japanese women. A case-control study was performed, including 62 hypertensive women (case) and 75 nonhypertensive women (control). GH during the first pregnancy was diagnosed on the basis of the Maternal and Child Health Handbook record. Hypertensive women were recruited from outpatients in the hospital and residents who completed an annual health check-up in a community. Hypertension was defined as blood pressure with systolic blood pressure &ge, 140 mmHg and/or diastolic blood pressure &ge, 90 mmHg, or taking antihypertensive medications. The average age (SD) of the cases and controls at the time of recruitment was 63.1 (8.4) and 57.7 (9.4), respectively. The multivariable-adjusted odds ratio of GH for hypertension in middle-aged-to-older women was 4.2 (95% confidence interval, 1.0&ndash, 17.5) after adjustment for potential confounding factors such as age and body-mass index (BMI) upon recruitment, prepregnancy BMI, and age at first delivery. In conclusion, GH can be an independent risk factor for future hypertension among Japanese women.

Background Postpartum hemorrhage (PPH) is a major cause of maternal mortality. Even seemingly low-risk women may suddenly develop postpartum hemorrhage, and these cases are often unpredictable and threatens maternal life. We hypothesized that innate poor uterine contractility may be a risk factor of PPH. In this study, we examined the association between the innate poor uterine contractility, suggested by the characteristics of labor and PPH in obstetrically low-risk women.Methods We used the Japan Perinatal Registry database of the Japan Society of Obstetrics and Gynecology registered in 2013–2016. With exclusion of women with well-known risk factors for PPH (maternal basal disease of hematologic disease, uterine leiomyoma, pregnancy by assisted reproductive technology, placenta abruption, placenta accrete, low-lying placenta, hypertensive disorders of pregnancy, macrosomia, polyhydramnios, or epidural analgesia), we analyzed 174,082 primiparous women who had one live singleton birth via vaginal delivery in cephalic presentation at 37 weeks’ gestation. Information about abnormal labor patterns (hypotonic uterine dysfunction, prolonged labor, and arrest of labor) diagnosed by obstetricians were also used in this study. In order to focus on innate maternal poor uterine contractility, we classified subjects into four classes according to whether they were diagnosed with abnormal labor patterns and whether they had used uterotonics, and Odds ratios and their 95% CI were calculated as well.Results Among the enrolled women, 10,508 (6.0%) had PPH. Abnormal labor patterns, including hypotonic uterine dysfunction (adjusted OR 1.28, 95% CI 1.22 to 1.34), prolonged labor (adjusted OR 1.41, 95% CI 1.30 to 1.52) and arrest of labor (adjusted OR 2.02, 95% CI 1.78 to 2.29) were significantly associated with an increased risk of PPH. Compared to women who were not diagnosed any abnormal labor patterns and did not use any uterotonics, women who were diagnosed with abnormal labor patterns were at a significantly increased risk for PPH regardless of whether they had used uterotonics(adjusted OR 1.23, 95% CI 1.10 to 1.37) or not (adjusted OR 1.30, 95% CI 1.23 to 1.37).Conclusion Our study suggests that innate poor uterine contractility is a significant predisposing risk factor in otherwise low-risk women.Trial Registration: This study is retrospectively registered.