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Background: The effects of myocarditis after mRNA COVID-19 vaccination (mCV) on myocardial tissue, and the association between cardiomyocyte injury and clinical presentation, are not fully understood., Methods and Results: We retrospectively registered patients clinically diagnosed with myocarditis after the first or second mCV who underwent endomyocardial biopsy or autopsy from 42 participating centers in Japan. We investigated the histological features and their association with clinical presentation based on cardiomyocyte injury. Forty patients who underwent endomyocardial biopsy were included in the study. Of these, 19 (47.5%) showed mild lymphocytic infiltration and interstitial edema without cardiomyocyte injury. The remaining 21 (52.5%) patients showed cardiomyocyte injury accompanied by infiltrating inflammatory cells: 11 with lymphocytic infiltration, 7 with eosinophilic infiltration, and 3 with myocarditis with both lymphocyte and eosinophil infiltration. Compared with patients without cardiomyocyte injury, those with cardiomyocyte injury were clinically characterized by older age, a balanced sex distribution, less frequent chest pain, and a lower left ventricular ejection fraction. Fifteen of 21 (71.4%) patients with cardiomyocyte injury developed fulminant myocarditis, with 13 (86.7%) requiring mechanical circulatory support; in contrast, none of those without cardiomyocyte injury developed fulminant myocarditis (P<0.001)., Conclusions: Our histological examination of patients with myocarditis after mCV revealed varying degrees of cardiomyocyte injury, ranging from pronounced to absent, along with various types of myocarditis. Cardiomyocyte injury was strongly associated with the severity of myocarditis.

Through strengthened biobank governance, broad consent has been widely accepted as a means to replace donors' discretion based on the information of individual research protocols. Trust and other ethical and social notions, such as reciprocity and solidarity, are key concepts that support biobank governance. The types of allowed broad consent are several; however, they remain unclear, and whether these ethical and social notions are associated with public attitudes toward the consent model is not fully understood. This quantitative study examined two hypotheses: narrower and limited broad consent are more accepted by the public, and acceptance rates for broad consent increase with established measures related to biobank governance. This analysis supported both hypotheses, implying that the limited type of broad consent should be considered an important option, and that a specific type of governance is critical in promoting trust, reciprocity, and solidarity between biobanks and the public., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Brain death has been used to decide whether to keep sustained care and treatment. It can facilitate tissue, organ, and body donation for several purposes, such as transplantation and medical education and research. In Japan, brain death has strict diagnostic criteria and family consent is crucial, but it has been a challenging concept for the public since its introduction, including knowledge and communication issues., Objective: We analyzed data across YouTube and Twitter in Japan to uncover actors and assess the quality of brain death communication, providing recommendations to communicate new medical technologies., Methods: Using the keyword "" (brain death), we collected recent data from YouTube and Twitter, classifying the data into 5 dimensions: time, individuality (type of users), place, activity, and relations (hyperlinks). We employed a scale to evaluate brain death information quality. We divided YouTube videos into 3 groups and assessed their differences through statistical analysis. We also provided a text-based analysis of brain death-related narratives., Results: Most videos (20/61, 33%) were uploaded in 2019, while 10,892 tweets peaked between July 3 and 9, 2023, and June 12 and 18, 2023. Videos about brain death were mostly uploaded by citizens (18/61, 27%), followed by media (13/61, 20%) and unknown actors (10/61, 15%). On the other hand, most identified users in a random sample of 100 tweets were citizens (73/100, 73%), and the top 10 retweeted and liked tweets were also mostly authored by citizens (75/100, 75%). No specific information on location was uncovered. Information videos contained guides for accreditation of the National Nursing Exam and religious points of view, while misinformation videos mostly contained promotions by spirituality actors and webtoon artists. Some tweets involved heart transplantation and patient narratives. Most hyperlinks pointed to YouTube and Twitter., Conclusions: Brain death has become a common topic in everyday life, with some actors disseminating high-quality information, others disseminating no medical information, and others disseminating misinformation. Recommendations include partnering with interested actors, discussing medical information in detail, and teaching people to recognize pseudoscience., (©Xanat Vargas Meza, Masanori Oikawa. Originally published in JMIR Formative Research (https://formative.jmir.org), 18.09.2024.)

This study analyzes the role of education in the outcomes of the reform of the Japanese annual health checkup program. In April 2008, the annual checkup was redesigned to address concerns about metabolic syndrome. As the checkup is mandatory only for salaried workers, their participation rate is significantly higher than other workers; thus, they were most affected by the reform. Using institutional information, a difference-in-differences estimation was conducted with salaried workers as the treatment group and self-employed workers as the control group. We found that the reform caused significant changes in health behaviors and outcomes only among university graduates who were at a relatively high risk of metabolic syndrome. This highly educated group increased their physical activity, brought energy intake close to an ideal level, and achieved significant weight loss and BMI reduction to levels that minimize all-cause mortality among middle-aged Japanese. A secondary analysis implies that the difference in cognitive functioning test scores may be a critical factor in explaining the heterogeneous responses to the reform, suggesting that thoroughly well-articulated recommendations for healthy behaviors are needed in order to improve reform uptake., (© 2023. The Author(s).)

Introduction: The aim of the study was to explore the association between urate-lowering agents and reduced response to erythropoietin-stimulating agents in patients suffering from chronic kidney disease G5., Methods: We conducted a cross-sectional, multicenter study in Japan between April and June 2013, enrolling patients aged 20 years or older with an estimated glomerular filtration rate of ≤15 mL/min/1.73 m2. Exclusion criteria encompassed patients with a history of hemodialysis, peritoneal dialysis, or organ transplantation. The patients were categorized into four groups based on the use of urate-lowering drugs: high-dose allopurinol (&gt;50 mg/day), low-dose allopurinol (≤50 mg/day), febuxostat, and no-treatment groups. We used a multivariable logistic regression model, adjusted for covariates, to determine the odds ratio (OR) for erythropoietin hyporesponsiveness, defined by an erythropoietin resistance index (ERI) of ≥10, associated with urate-lowering drugs., Results: A total of 542 patients were included in the analysis, with 105, 36, 165, and 236 patients in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The median and quartiles of ERIs were 6.3 (0, 12.2), 3.8 (0, 11.2), 3.4 (0, 9.8), and 4.8 (0, 11.2) in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The multivariate regression model showed a statistically significant association between the high-dose allopurinol group and erythropoietin hyporesponsiveness, compared to the no-treatment group (OR = 1.98, 95% confidence interval: 1.10-3.57)., Conclusions: Our study suggests that the use of high-dose allopurinol exceeding the optimal dose may lead to hyporesponsiveness to erythropoiesis-stimulating agents., (© 2024 S. Karger AG, Basel.)

Tracheal washing fluid was collected from 170 foals at 28 and 35 d old from February to July in a foaling season on horse-breeding farms with sporadic rhodococcosis in Japan and was investigated by quantitative culture. The history of the 170 foals followed up for the next few months. The proportion of R. equi-positive foals at 28 and 35 d old was significantly increased according to the birth month. Furthermore, the mean number of R. equi in the tracheal washing fluid of each month group increased according to their birth month with the rise in outside temperature. During the follow-up observation, 9/30 foals (30.0 %) born in February showed the first clinical signs at 56 ± 8 d old, 21/61 foals (34.4 %) born in March showed the signs at 37 ± 3 d old, 15/49 foals (30.6 %) born in April showed the signs at 39 ± 2 d old, and 7/30 foals (23.3 %) born in May showed signs at 44 ± 3 d old. Two sick foals (6.7 %) born in February, 19 sick foals (31.1 %) born in March, 15 sick foals (30.6 %) born in April, and 6 sick foals (20.0 %) born in May showed a positive culture of R. equi at 28 or 35 d old. The present study revealed that birth month is associated with the initial colonization of R. equi in the trachea of newborn foals on farms with sporadic rhodococcosis in Japan. Therefore, birth month might be a risk factor for developing R. equi pneumonia in foals., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Japan is facing a rapid increase in the number of reported child maltreatment cases. Child maltreatment has long-term consequences for the victims, and unemployment rate is considered a strong predictor of it. However, only few studies have analyzed the causal relation between child maltreatment and the unemployment rate-particularly the effects of the latter on the former-in Japan., Methods: Using prefecture-level longitudinal data from 2005 to 2016, we employed a fixed effects instrumental variable estimation. The estimation included a weighted average of the national unemployment rate across industries by industrial structures in 2005 as an instrument to identify the causal effects., Results: The average local unemployment rate changed by approximately 50% from the peak to the bottom in the sample period. A 50% increase in local unemployment rates increased the number of reported child neglect cases and child deaths by 80% and 70% (statistically significant at the 5% level), respectively. Further, it increased cases of death due to external causes, unintentional injuries, and unintentional drowning by 146%, 217%, and 315% (statistically significant at the 5% level), respectively., Conclusion: The local unemployment rate is a risk factor for child maltreatment, resulting in children's death, especially as a result of unintentional drowning-the common cause of death due to child neglect. When the local unemployment rates rise, governments should allocate more financial and human resources for preventive measures to combat child deaths caused by neglect., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Asian Working Group for Sarcopenia 2019 (AWGS 2019) is the gold standard diagnostic criteria for sarcopenia in Asian populations. The calf circumference (CalF), the strength, assistance in walking, rising from a chair, climbing stairs, and falls (SARC-F) and the SARC-CalF questionnaires for sarcopenia screening have been used by AWGS 2019. The aim of this study was to assess accuracy of these three sarcopenia screening tools in patients with interstitial lung disease., Methods: In this cross-sectional study, stable patients with interstitial lung disease were enrolled. The SARC-F, SARC-CalF, and CalF, used in patients with interstitial lung disease, were compared to the diagnostic criteria proposed by AWGS 2019. The accuracy of screening tools was compared using sensitivity and specificity. Moreover, areas under the receiver operating characteristic curves (AUC) were computed., Results: Seventy eight patients were analyzed, and sarcopenia was identified in 25 (32.1%) patients with interstitial lung disease by the AWGS 2019 criteria. The sensitivity of the CalF was highest (96%) of the three screening tools, while the specificity was 60%. The sensitivity of SARC-F and SARC-CalF were 24% and 68%, while the specificity were 92% and 66%, respectively. The AUCs of CalF, SARC-F, and SARC-CalF in all patients were 0.78, 0.58, and 0.67, respectively., Conclusions: The CalF is most suitable for screening sarcopenia in patients with interstitial lung disease, while SARC-F and SARC-CalF are not., (© 2022. The Author(s).)

Aim: We aimed to evaluate the significance of the cardio-ankle vascular index (CAVI) to predict stroke in patients with heart failure (HF)., Methods: This was a prospective observational study, which recruited clinical data from a total of 557 patients who had been hospitalized for HF and undergone CAVI. According to the receiver operating characteristic curve analysis, the accurate cut-off value of CAVI in predicting post-discharge stroke was 9.64. We divided the patients into two groups: the high-CAVI group (HF patients with CAVI ≥ 9.64, n=111, 19.9%) and the low-CAVI group (HF patients with CAVI ＜9.64, n=446, 80.1%). We compared the patients' characteristics and post-discharge prognosis. The primary endpoint was stroke., Results: The high-CAVI group was older (73.0 vs. 65.5 years old, P＜0.001). Male sex (73.9% vs. 61.4%, P=0.015), coronary artery disease (47.7% vs. 36.1%, P=0.024), and diabetes mellitus (54.1% vs. 37.4%, P=0.001) were more prevalent in the high-CAVI group. In contrast, there was no difference in left ventricular ejection fraction, and prevalence of hypertension and dyslipidemia. The Kaplan-Meier analysis demonstrated that post-discharge stroke rate was higher in the high-CAVI group than in the low-CAVI group (log-rank P=0.005). In multivariate Cox proportional hazard analysis, high CAVI was found to be an independent predictor of stroke, with an adjusted hazard ratio of 3.599, compared to low CAVI., Conclusion: CAVI independently predicts stroke in patients with HF.

A growing body of evidence suggests that mitral regurgitation (MR) is associated with higher mortality in heart failure patients with reduced ejection fraction. However, prognostic impact of MR on heart failure patients with preserved ejection fraction (HFpEF) has not been fully examined. The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese hospitalized HFpEF patients with LVEF ≥ 50%. Severe valvular heart disease was excluded from this cohort. We divided the consecutive 341 patients into two groups based on the severity of MR at discharge: no or mild MR group (n = 317) and moderate MR group (n = 24). Compared with no or mild MR group, moderate MR group showed larger left ventricular end-diastolic diameter (52 [48-59] vs. 46 [42-50] mm, P < 0.001), left ventricular systolic diameter (35 [30-37] vs. 29 [26-34] mm, P = 0.006), left atrial diameter (49 [46-56] vs. 45 [40-50] mm, P < 0.001), and higher tricuspid regurgitation peak gradient (33 [25-40] vs. 27 [21-33] mmHg, P = 0.012). In contrast, levels of plasma B-type natriuretic peptide and left ventricular ejection fraction were comparable between the two groups. In the follow-up period (median 738 days), there were 57 all-cause deaths. In the Kaplan-Meier analysis, all-cause mortality was higher in moderate MR group than in no or mild MR group (log-rank P = 0.023). In the Cox proportional hazard analysis, moderate MR at discharge was a predictor of all-cause mortality (hazard ratio 2.256, 95% confidence interval 1.035-4.917, P = 0.041). Moderate MR at discharge is associated with adverse prognosis in hospitalized patients with HFpEF.

Introduction: Hyponatremia predicts adverse prognosis in patients with heart failure in particular with reduced ejection fraction. In contrast, it has recently been reported that hyponatremia on admission is not a predictor of post-discharge mortality in patients with heart failure with preserved ejection fraction. We investigated the prognostic impact of hyponatremia at discharge in patients with heart failure with preserved ejection fraction and its clinical characteristics., Methods and Results: The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese patients hospitalised with heart failure with preserved ejection fraction and left ventricular ejection fraction of 50% or greater. Five hundred consecutive patients were enrolled in this analysis. We divided the patients into two groups based on their sodium serum levels at discharge: hyponatremia group (sodium <135 mEq/L, n =50, 10.0%) and control group (sodium ⩾135 mEq/L, n =450, 90.0%). This present analysis had two primary endpoints: all-cause death and all-cause death or rehospitalisation for heart failure. At discharge, the hyponatremia group had lower systolic blood pressure (110.0 mmHg vs. 114.5 mmHg, P =0.014) and higher levels of urea nitrogen (31.9 mg/dL vs. 24.2 mg/dL, P =0.032). In the Kaplan-Meier analysis, more patients in the hyponatremia group reached the primary endpoints than those in the control group (log rank <0.01, respectively). In the Cox proportional hazard analysis, hyponatremia at discharge was a predictor of the two endpoints (all-cause death, hazard ratio 2.708, 95% confidence interval 1.557-4.708, P<0.001; all-cause death or rehospitalisation for heart failure, hazard ratio 1.829, 95% confidence interval 1.203-2.780, P =0.005)., Conclusions: Hyponatremia at discharge is associated with adverse prognosis in hospitalised patients with heart failure with preserved ejection fraction.

The restless legs syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move the legs or arms for relief of uncomfortable or unpleasant sensations. Prevalence and prognostic impact of RLS on patients with heart failure (HF) remain unclear. We aimed to investigate the clinical characteristics and prognostic impact of RLS on HF patients.Consecutive 338 HF patients were evaluated for RLS and divided into two groups on the basis of presence of RLS: HF patients with RLS (RLS group, n = 29) and HF patients without RLS (non-RLS group, n = 309). We compared clinical characteristics, parameters of laboratory data and echocardiography, and rate of follow-up cardiac events including worsening HF and cardiac death between the two groups. Compared with the non-RLS group, the RLS group had higher prevalence of anemia (65.5% versus 40.8%, P = 0.010), higher usage of inotropic agents (31.0% versus 15.2%, P = 0.028), higher levels of B-type natriuretic peptide (570.8 versus 215.8 pg/mL, P = 0.018), and lower levels of left ventricular ejection fraction (40.4% versus 48.4%, P = 0.019). By contrast, age, gender, prevalence of other co-morbidities and medications were comparable between the groups. In the Kaplan-Meier analysis, the cardiac event rate was significantly higher in the RLS group than in the non-RLS group (log-rank P = 0.034). In the Cox proportional hazard analysis, RLS was a predictor for cardiac events in HF patients (hazard ratio: 1.783, 95% confidence interval: 1.038-3.063).RLS is associated with adverse prognosis in HF patients.

A useful biomarker for detecting cardiac amyloidosis (CA) has not been fully established. We aimed to investigate the utility of several biomarkers to detect CA in patients with amyloid light-chain (AL) amyloidosis.We examined the plasma levels of B-type natriuretic peptide (BNP), N-terminal fragment of the pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), serum amyloid A, and the difference between kappa and lambda free light chain (dFLC) between CA patients (n = 30, 47.6%) and non-CA patients (n = 33, 52.4%). Levels of BNP were significantly higher in the CA group compared to the non-CA group (1200.0 versus 224.0 pg/mL, P = 0.001). From the ROC analysis, the sensitivity and specificity of BNP for detecting CA (with a cut-off value of 412 pg/mL) were 83% and 70%, respectively, and the area under the receiver operating curve was 0.75 (95% CI 0.61-0.90, P < 0.001) in all AL amyloidosis patients (n = 63). In contrast, other markers such as NT-proBNP, hs-cTnT, serum amyloid A, and dFLC were not useful for detecting CA in AL amyloidosis patients. Additionally, in the Cox proportional hazard analysis, BNP was a predictor of all-cause mortality (hazard ratio 3.266, 95% confidence interval 1.498-7.119, P = 0.003).BNP is a useful biomarker for detecting cardiac involvement and predicting prognosis in AL amyloidosis patients.

Objective Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease that leads to right-sided heart failure with electrocardiographic abnormalities. There are only a few reports about the effects of balloon pulmonary angioplasty for CTEPH on the electrocardiographic criteria of right ventricular hypertrophy. To determine the effect of balloon angioplasty on electrocardiography in patients with CTEPH. Methods We evaluated electrocardiograms in 19 patients (mean age, 64±10 years) who underwent balloon pulmonary angioplasty. Results We compared the hemodynamic parameters after balloon pulmonary angioplasty. The mean pulmonary artery pressure was decreased (p<0.001), and the cardiac index was increased (p=0.025) after balloon pulmonary angioplasty. The level of brain natriuretic peptide was decreased (p=0.001) after balloon pulmonary angioplasty (p<0.001). We applied 15 criteria for right ventricular hypertrophy to the patients, according to the American Heart Association recommendations of the electrocardiogram, after balloon pulmonary angioplasty. Among the criteria, the numbers of patients who met the criteria of deep S in V 6 (p=0.005) and max R in V 1, 2 +max S in I, aV L -S in V 1 (p=0.046) were significantly decreased after balloon pulmonary angioplasty. The mean numbers regarding the right ventricular hypertrophic criteria in each patient were significantly decreased after balloon pulmonary angioplasty (4.8±2.6 to 3.1±2.5, p=0.003). Conclusion In addition to improvement in hemodynamics, improvement in right ventricular hypertrophy was also observed using the electrocardiographic criteria in patients with CTEPH after balloon pulmonary angioplasty, suggesting that we should pay more attention to these changes.

The clinical scenario, which is based on systolic blood pressure (SBP) upon admission, is useful for classifying and determining initial treatment for acute heart failure (HF). However, the prognostic significance of SBP following the initial treatment is unclear.The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, and prospective registration of consecutive Japanese patients hospitalized with HF with preserved ejection fraction (HFpEF) and left ventricular ejection fraction ≥ 50%. We divided 525 patients into three groups based on their SBP on the day following hospitalization: high (SBP > 140 mmHg, n = 72, 13.7%); normal (100 ≤ SBP ≤ 140 mmHg, n = 379, 72.2%); and low (SBP < 100 mmHg, n = 74, 14.1%) groups. This analysis had two primary endpoints: (1) all-cause death and (2) all-cause death or rehospitalization for HF. In the Kaplan-Meier analysis, both of the endpoints were the highest in the low group (Log-Rank < 0.05, respectively). Compared to the normal and high groups, the low group demonstrated a higher prevalence of atrial fibrillation (67.1%, 63.9%, and 47.8%, P = 0.026) and the lowest left ventricular outflow tract velocity time integral determined by echocardiography (16.4 cm, 19.4 cm, and 23.3 cm, P = 0.001). In the multivariable Cox proportional hazard analysis, low SBP on the day following hospitalization was an independent predictor of all-cause death (hazard ratio 1.868, 95% confidence interval 1.024-3.407, P = 0.042) and the composite endpoint (hazard ratio 1.660, 95% confidence interval 1.103-2.500, P = 0.015).Classification based on SBP on the day following initial treatment predicts post-discharge prognosis in hospitalized patients with HFpEF.

Background: Heart failure (HF) and cancer (CA) are becoming increasingly prevalent as the population ages. We aimed to evaluate prior history and occurrence of CA and its prognostic impact on HF., Methods and results: Consecutive hospitalized HF patients (n=2,103) were divided into 2 groups according to prior history of CA: non-prior-CA group (n=1,828) and prior-CA group (n=275). Compared with the non-prior-CA group, the prior-CA group were older, and had higher prevalence of chronic kidney disease, anemia, and atrial fibrillation (P<0.05). In contrast, sex, other comorbidities, levels of natriuretic peptide and ejection fraction were comparable between groups. We focused on newly diagnosed CA after discharge for HF. In the follow-up period (median 623 days), 114 (6.2%) patients in the non-prior-CA and 17 (6.2%) patients in the prior-CA groups were newly diagnosed as having CA. Additionally, 83 (3.9%) CA-related patient deaths occurred (median 776 days). In the Kaplan-Meier analysis (median 1,037 days), not only all-cause death but also cardiac event rate was significantly higher in the prior-CA group than in the non-prior-CA group (log-rank P<0.01). In the Cox proportional hazard analysis, CA history was a predictor of cardiac event rate (HR 1.450, 95% CI 1.134-1.822), as well as all-cause death (HR 2.483, 95% CI 2.034-3.030)., Conclusions: Prior-CA history was associated with high cardiac event and mortality rates. CA is notable comorbidity in HF patients.

Several case series have suggested that rituximab is efficacious in adult patients with minimal change disease. We herein report a case of disseminated intravascular coagulation-like reaction after rituximab infusion in a patient with nephrotic syndrome. A 58-year-old Japanese man with minimal change disease diagnosed 15 years earlier was started on rituximab to prevent relapse of nephrotic syndrome when he presented to our clinic with low albuminemia, massive proteinuria, and leg edema. Eleven days after rituximab infusion, he presented with abdominal pain, appetite loss, and tarry stool. A laboratory examination revealed severe thrombocytopenia and coagulopathy, and upper gastrointestinal endoscopy revealed multiple hemorrhagic ulcers in his esophagus and stomach. The patient died two days later. Physicians should consider disseminated intravascular coagulation-like reaction when encountering cases with thrombocytopenia after rituximab infusion for any disease.

Aims: It has been reported that circulating soluble neprilysin (sNEP), which catalyses the degradation of several vasodilator peptides such as natriuretic peptides, predicts prognosis in heart failure patients with reduced ejection fraction. Hypoxia-induced decrease in NEP expression in lungs has been reported. However, the associations between sNEP and haemodynamic parameters, as well as the prognostic impact of sNEP in pulmonary hypertension (PH), remain unclear. We aimed to clarify the relationships between sNEP and natriuretic peptide, haemodynamics (e.g. parameters of echocardiography and right heart catheter) or prognosis in PH patients., Methods and Results: First, we examined the associations between sNEP levels and natriuretic peptide, echocardiography, or right heart catheter in PH patients (mean pulmonary artery pressure ≥ 25 mmHg and pulmonary artery wedge pressure ≤ 15 mm Hg on the basis of right heart catheterization, n = 79). Next, we followed up the patients for all-cause mortality. Laboratory data revealed no significant correlations between sNEP and B-type natriuretic peptide (R = 0.022, P = 0.872), N-terminal proBNP (R = -0.018, P = 0.872), and high-sensitivity troponin I (R = 0.206, P = 0.107). Regarding the parameters of echocardiography and right heart catheter, there were no significant correlations between sNEP and left ventricular ejection fraction (R = -0.036, P = 0.764), right ventricular fractional area change (R = -0.259, P = 0.064), tricuspid valve pressure gradient (R = -0.037, P = 0.767), and any of the right heart catheter parameters. In the Kaplan-Meier analysis (mean follow-up, 1284 days, log-rank P = 0.531), all-cause mortality rates were comparable between the higher NEP group (sNEP ≥ median levels of 1.45 ng/mL, n = 39) and the lower NEP group (sNEP < 1.45 ng/mL, n = 40). In the Cox proportional hazard analysis, sNEP was not a predictor of all-cause mortality (hazard ratio 0.902, 95% CI 0.674-1.207, P = 0.487) in PH patients., Conclusions: Circulating sNEP does not correlate with natriuretic peptide, haemodynamic parameters, or prognosis in patients with PH., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Objective: An association of the programmed cell death-1 (PD-1) and its ligand PD-L1 with various types of malignant tumors has been established. This study aimed to investigate the role of the PD-L1/PD-1 pathway in oral squamous cell carcinoma (OSCC) and oral epithelial precursor lesions (OEPL)., Materials and Methods: We examined 106 OSCC and 79 OEPL specimens for PD-L1 and PD-1 expression by immunohistochemistry. The results were compared with clinicopathological features of OSCC patients., Results: In OSCC and OEPL specimens, PD-L1 expression was detected predominantly in epithelial or carcinoma cells, whereas PD-1 expression was found mainly in infiltrating or stromal lymphocytes. Seventy-two OSCC (67.9%) and 21 OEPL (26.6%) specimens were positive for PD-L1, and 73 OSCC (68.9%) and 23 OEPL (29.2%) specimens were positive for PD-1. PD-L1 and PD-1 expression levels were significantly different between OEPL and OSCC specimens (P < 0.001). There were significant positive correlations between PD-L1 and PD-1 expression in OEPL and OSCC specimens (P < 0.001). PD-L1 and PD-1 immunoreactivity was significantly associated with tumor size (P < 0.05). PD-L1 and PD-1 immunoreactivity in cases with advanced TNM staging was significantly higher than that in low staging cases (P < 0.01). There were significant correlations between PD-L1 and PD-1 expression in OSCC specimens and pathological variables such as stromal lymphocytic reaction (P < 0.05) and invasion depth (P < 0.01)., Conclusion: PD-L1 and PD-1 immunohistochemical status may be related to carcinogenesis, tumor progression, and prognosis in oral epithelial lesions. Agents targeting PD-1 and PD-L1 might be useful for OSCC treatment., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Atrial septal defect is the third most common type of congenital heart disease. Surgical closure was the standard treatment for atrial septal defects before transcatheter closure was approved as minimally invasive treatment in Japan in 2006. In our hospital, this procedure has been performed since 2015., Objective: To evaluate the safety and effectiveness of transcatheter closure of atrial septal defects in our hospital., Methods: Thirty patients (mean age 57.0 ± 19.7 years, 11 males), who underwent transcatheter closure of atrial septal defect between September 2015 and February 2018 at the Fukushima Medical University Hospital, were enrolled. All procedures were performed under general anesthesia with angiographic and transesophageal echocardiographic guidance. Safety and effectiveness were evaluated by the procedural results and complications., Results: All 30 patients successfully underwent transcatheter closure of atrial septal defects and no patient developed complications. New York Heart Association functional class was improved, and the right ventricular area and right atrium area were decreased, postoperatively., Conclusion: Transcatheter closure is a safe and effective treatment for atrial septal defects, and thus could be an alternative option to open heart surgery.

Background The Get With the Guidelines-Heart Failure ( GWTG - HF ) risk score was developed using American Heart Association GWTG - HF program data and predicts in-hospital mortality in patients with acute heart failure (HF). We aimed to clarify the prognostic impacts of the GWTG - HF risk score in patients with HF after discharge. Methods and Results We examined the GWTG - HF score in 1452 patients with HF, who were admitted to our hospital and discharged after treatment, by calculating 7 predetermined variables. We divided all subjects into 3 groups according to the GWTG - HF risk score (low, moderate, and high score groups). The plasma B-type natriuretic peptide level significantly increased with increasing GWTG - HF risk score severity (median values of B-type natriuretic peptide: 167.0 in low, 260.7 in moderate, and 418.2 pg/mL in high score groups). We followed up all subjects after discharge, and there were 347 (23.9%) all-cause deaths and 407 (28.0%) cardiac events in follow-up periods. A Kaplan-Meier survival curve demonstrated that event rates of all-cause death and cardiovascular events, including worsening HF and cardiac death, significantly increased with increasing GWTG - HF risk score severity in all subjects, and also in 749 patients with HF with preserved ejection fraction (ejection fraction ≥50%) and 703 patients with HF with reduced ejection fraction (ejection fraction <50%) patients. The multivariable Cox proportional hazard regression analysis demonstrated that the GWTG - HF risk score was one of the significant predictors of all-cause mortality and cardiac events (all-cause mortality: hazard ratio, 1.537, 95% confidence interval, 1.172-2.023; cardiac events: hazard ratio, 1.584, 95% confidence interval, 1.344-1.860, per 10-point increase of GWTG - HF score). Conclusions The GWTG - HF risk score is a useful multivariable score model for several years after hospitalization in patients with HF in a Japanese population.

Background: Zinc is an essential cofactor for energy transfer and physiological heart function, has antioxidant properties, and is involved in multiple signaling pathways. We aimed to investigate the associations between serum zinc levels with prognosis, as well as underlying cardiac function and exercise capacity, in patients with heart failure (HF)., Methods and Results: We measured serum zinc levels in 968 consecutive hospitalized patients with decompensated HF, who were divided into 3 groups based on serum zinc levels (µg/dL): first (zinc ≥75, n = 323), second (62≤ zinc <75, n = 322), and third (zinc <62, n = 323) tertiles. We examined cardiac function and exercise capacity and followed up on all patients. Although cardiac function did not differ among the 3 groups, peak oxygen consumption was significantly lower in the third tertile than in the first and second tertiles (peak oxygen consumption, 14.2 vs 15.9 and 15.2 mL/kg/min, P = .010). In the Kaplan-Meier analysis (mean duration of follow-up 1103 days), cardiac and all-cause mortality was highest in the third tertile compared with the first and second tertiles. In the Cox proportional hazard analysis, serum zinc level was a predictor of cardiac and all-cause mortality. In the subgroup analysis, there were no interactions concerning associations between serum zinc levels with prognosis and other important variables, including age, gender, comorbidities, medications, other micronutrient levels, B-type natriuretic peptide, and left ventricular ejection fraction. The associations between zinc levels with mortality were consistent in all subgroups., Conclusion: Decreased serum zinc levels are associated with high mortality, accompanied by impaired exercise capacity., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Recent evidence suggests that human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is a separate HNSCC subgroup with distinct epidemiology, histopathological characteristics, therapeutic response to chemotherapy and radiation, and clinical outcome. This study aimed to investigate the role of HPV infection in oral squamous cell carcinoma (OSCC) and the correlation between HPV infection, tumor suppressor protein p16 expression, and clinicopathological features in Japanese patients., Methods: In total, 174 OSCC specimens were examined for p16 levels by immunohistochemistry, and p16-positive OSCCs were analyzed for HPV DNA by in situ hybridization (ISH) and HPV genotypes by real-time PCR. The results were evaluated for the association with clinicopathological characteristics of OSCC patients., Results: Twenty-four OSCC samples were found positive for p16 expression; all of them were well-differentiated tumors. P16 immunoreactivity was significantly associated with the invasion depth and tended to correlate with sex, site in the oral cavity, stromal reaction, TNM stage, and survival. HPV DNA was detected in 13 of 24 (54%) p16-positive OSCC by real-time PCR; HPV 16, 18, and other high-risk genotypes were the most prevalent. However, ISH failed to detect HPV DNA in p16-positive OSCCs., Conclusion: P16 immunoreactivity and HPV genotyping by real-time PCR may be useful markers of HPV infection in OSCC. However, although HPV-related OSCC showed good outcomes, HPV infection may have a minor role in oral oncogenesis in Japanese patients., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We constructed a new car-borne survey system called Radi-Probe with a portable germanium gamma-ray spectrometer onboard a cargo truck, to identify radionuclides and quantify surface contamination from the accident at Fukushima Dai-ichi Nuclear Power Station. The system can quickly survey a large area and obtain ambient dose equivalent rates and gamma-ray energy spectra with good energy resolution. We also developed a new calibration method for the system to deal with an actual nuclear disaster, and quantitative surface deposition densities of radionuclides, such as (134)Cs and (137)Cs, and kerma rates of each radionuclide can be calculated. We carried out car-borne survey over northeastern and eastern Japan (Tohoku and Kanto regions of Honshu) from 25 September through 7 October 2012. We discuss results of the distribution of ambient dose equivalent rate H(∗)(10), (134)Cs and (137)Cs surface deposition densities, spatial variation of (134)Cs/(137)Cs ratio, and the relationship between surface deposition densities of (134)Cs/(137)Cs and H(∗)(10). The ratio of (134)Cs/(137)Cs was nearly constant within our measurement precision, with average 1.06 ± 0.04 in northeastern and eastern Japan (decay-corrected to 11 March, 2011), although small variations from the average were observed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To report the ophthalmic relief activities conducted by Iwate Medical University after the Great East Japan Earthquake of March 11, 2011., Subjects and Methods: A retrospective review was conducted of the medical records of patients who visited emergency ophthalmic clinics opened at Yamada-cho, Otsuchi-cho and Rikuzentakada-shi from March 30, 2011 to June 30, 2011., Results: We provided ophthalmic medical care for 14 days at Yamada-cho and Otsuchi-cho, and for 9 days at Rikuzentakada-shi. During this period, 1371 new patients (total of 2015 patients) visited the clinics. The main motives were a desire for prescription of medication, treatment of ocular symptoms and correction of refractive error and presbyopia. The major diseases were cataract, pseudophakia, refractive error, presbyopia and conjunctivitis. Only a few patients had a foreign body in the eye or ocular trauma. Among the 207 patients with contact lenses, 24 patients were wearing them beyond their replacement date, and contact lens care was insufficient in 35 patients. Among 179 patients with glaucoma who were checked for intraocular pressure, 61 patients had an IOP greater than 21 mmHg., Conclusions: Although many patients sought eye drops for chronic eye diseases and correction of refractive error and presbyopia, patients with ocular injuries were few. It is important to prepare for whatever needs patients in emergency circumstances may present.

Background: Management of renal cell carcinoma (RCC) with tumor thrombus extending to the renal vein and inferior vena cava (IVC) is challenging. The aim of this study was to evaluate the benefit of surgical management in such patients., Methods: From February 1995 to February 2013, 520 patients were treated for RCC at Hirosaki University Hospital, Hirosaki, Japan. The RCC patients with tumor thrombus extending to the renal vein (n = 42) and IVC (n = 43) were included in this study. The records of these 85 patients were retrospectively reviewed to assess the relevant clinical and pathological variables and survival. Prognostic factors were identified by multivariate analysis. The benefit of surgical management was evaluated using propensity score matching to compare overall survival between patients who received surgical management and those who did not., Results: RCC was confirmed by pathological examination of surgical or biopsy specimens in 74 of the 85 patients (87%). Sixty-five patients (76%) received surgical management (radical nephrectomy with thrombectomy). Distant metastasis was identified in 45 patients (53%). The proportion of patients with tumor thrombus level 0 (renal vein only), I, II, III, and IV was 49%, 13%, 18%, 14%, and 5%, respectively. The estimated 5-year overall survival rate was 70% in patients with thrombus extending to the renal vein and 23% in patients with thrombus extending to the IVC. Multivariate analysis identified thrombus extending to the IVC, presence of distant metastasis, surgical management, serum albumin concentration, serum choline esterase concentration, neutrophil-lymphocyte ratio, and Carlson comorbidity index as independent prognostic factors. In propensity score-matched patients, overall survival was significantly longer in those who received surgical management than those who did not., Conclusions: Surgical management may improve the prognosis of RCC patients with thrombus extending to the renal vein and IVC.

Although the number of elderly patients requiring dialysis has increased, data regarding the prognosis of elderly patients undergoing hemodialysis are limited. In the present study, prognosis in Japanese hemodialysis patients aged ≥80 years was evaluated. From January 1988 to July 2013, 1144 consecutive patients with end-stage renal disease required renal replacement therapy at our institution; of these, 141 were aged ≥80 years. These patients' charts were retrospectively reviewed for relevant clinical variables and survival time. The life expectancies table from the National Vital Statistics database was used, and prognostic factors were assessed by multivariate analysis. In total, 107 deaths (76%) were recorded during the study period. The median survival time and estimated life-shortening period in the patients were 2.6 years and -5.3 years, respectively. Eastern Cooperative Oncology Group Performance Status and hemoglobin level were revealed as prognostic factors in the multivariate analysis. Estimates of prognosis and prognostic factors may provide useful information for physicians as well as elderly patients with end-stage kidney disease.

The purpose of this report is to describe the results of epidemiological surveys of racing-related fractures in Thoroughbred horses in Japan. In the period 1987-2000, a total of 10,203 fractures were diagnosed in 556,705 runners, resulting in an overall incidence of 1.83%. The annual incidence of fractures in flat racing during the 14-year period fluctuated between 1.44% and 2.19%. The majority of fractures affected the forelimbs. We found significant effects of track condition on injury incidence. The incidence of fractures decreased as track conditions on turf became softer and increased as track conditions on dirt became muddier. Because of the general trend for the incidence of fractures to vary with track condition, we examined the relationship between track conditions and racing times for winning horses in 4117 races and for 50,564 overall runners for the period 1990-1994 on two tracks. For turf courses, racing times became longer as track conditions became softer. In contrast, for dirt courses, racing time tended to become shorter in muddier conditions. The variation in the incidence of fracture with track condition might be due to the corresponding difference in racing time.

Background: We wanted to investigate the clinical usefulness of determining the pretreatment levels of multiple serum tumor markers in predicting lymph node status and the prognosis for patients with cervical carcinoma., Methods: The preoperative serum levels of squamous cell carcinoma antigen (SCC), cancer antigens CA125 and CA19-9 were assayed simultaneously in 103 patients with stages IB to IIB cervical SCC undergoing radical hysterectomy. The cut-off values of SCC, CA125, and CA19-9 in this study were 1.5 ng/ml, 35 U/ml, and 37 U/ml, respectively. The relation between preoperative tumor marker levels and histopathologic prognostic factors including lymph node metastasis and patient survival was studied., Results: Preoperative serum SCC, CA125, and CA19-9 levels were significantly related to the FIGO stage. In addition, serum SCC and CA125 levels were significantly related to tumor diameter, depth of cervical stromal invasion, lymph-vascular space invasion, and lymph node metastasis. We subsequently created a double-tumor-marker (DTM) index, which incorporated the number of positive markers of SCC and CA125. The DTM index was strongly related to the number of positive pelvic lymph nodes (p = 0.0002) and to the site of positive nodes (none vs. pelvic only vs. common iliac/paraaortic) (p = 0.0005). Probability of lymph node metastasis according to the DTM index = 0, 1, and 2 was 6/48 (12.5%), 14/45 (31.1%), and 8/10 (80.0%), respectively. The rate of common iliac/paraaortic node metastasis according to the DTM index = 0, 1, and 2 was 1/48 (2.1%), 2/45 (4.4%), and 3/10 (30.0%), respectively. By logistic regression analysis, it was shown that the DTM index and tumor diameter were independently related to lymph node metastasis. Using multivariate Cox regression analysis including singly determined serum SCC and CA125 levels, clinical stage (IB/IIA vs. IIB), tumor diameter ( 4 cm), parametrial invasion, lymph node metastasis, and the DTM index, the DTM index was found to be the most important prognostic factor (p = 0.0005). However, when the sites of positive nodes were included in the multivariate analysis, only the sites of positive nodes (p = 0.0008) and parametrial invasion (p = 0.041) showed independent prognostic significance., Conclusion: Combination assay of pretreatment serum SCC and CA125 levels seems to be useful in estimating lymph node status and the prognosis for patients with cervical SCC in a preoperative setting.

Background/aims: Recently, the Japanese Classification on Cancer of the Biliary Tract was revised and adopted the new comprehensive staging that is similar to UICC's TNM classification. We should be paying close attention to the significance of newly defined extensive factors of carcinomas on the long-term prognosis., Methodology: The surgical outcome for 99 patients who underwent resected middle (Bm) and lower (Bi) bile duct carcinomas was reviewed in order to evaluate the suitability of the surgical procedures employed for their treatment, namely, standard pancreatoduodenectomy for Bi carcinoma and bile duct resection with D2 lymph node dissection for Bm carcinoma., Results: The overall 5-year cumulative survival rate (operative death excluded) of Bm and Bi carcinoma patients was 37.4% and the 5-year survival rate of the patients in whom surgical curability (curA) was accomplished was 51.6%. Recently, a new prognostic factor, "t-category", which indicates the degree of pericholedochal neoplastic invasion was proposed in the 4th edition of the Japanese General Rules for Surgical and Pathological Studies on Cancer of the Biliary Tract. The 10-year survival rates by t-category were 49.1% (t1), 19.7% (t2), and 0% (t3 and t4) respectively. For Bm carcinoma, the patients undergoing bile duct resection under the condition of curA showed excellent prognoses. For Bi carcinoma, the patients fulfilling particular histological criteria, i.e., those concerning the histological depth of neoplastic invasion (m, fm, panc1a), duodenal involvement (du0, du1), vascular invasion (pv0), pericholedochal neoplastic invasion (t1), lymph node metastasis (n0), and comprehensive stage I, had good postoperative outcomes. Taking into account the fact that the metastatic rate of paragastric lymph nodes was 1.3%, the cases of panc0,1 should be operated by pylorus-preserving pancreatoduodenectomy. The overall 5-year survival rates including far-advanced cases were 39.9% in Bm carcinoma patients and 36.9% in Bi carcinoma patients. However, these postoperative outcomes are far from satisfactory., Conclusions: Therefore, we concluded that pancreatoduodenectomy and pylorus-preserving pancreatoduodenectomy with extended D3 lymphadenectomy combined with systematic multimodal therapy are indicated in each and every case of Bm and Bi carcinoma.