Increasing survivors of anthracycline-related cardiomyopathy with breast cancer in trastuzumab era: thirty-one-year trends in a Japanese Community.

BACKGROUND: Trastuzumab has improved breast cancer (BC) prognosis and reduced anthracycline use. However, the characteristic changes of anthracycline-related cardiomyopathy (ARCM) in patients with BC remain unclear. We aimed to update our understanding of ARCM in the trastuzumab era. METHODS: This retrospective observational cohort study included 2959 patients with BC treated with anthracyclines at three regional cancer centers in Niigata City between 1990 and 2020. Seventy-five patients (2.5%) developed ARCM and were categorized into two groups: pre- 2007 (early phase) and post-2007 (late phase), corresponding to before and during the trastuzumab era in Japan. RESULTS: ARCM incidence peaked at 6% in the 1990s, then decreased and stabilized at 2% until the 2010s. Survivors of anthracycline-treated BC increased more rapidly in the late phase, with four times as many patients with ARCM compared to the end of the early phase (26 and six, respectively). Although the rate of change in accumulation from the early phase to the late phase was slight in the anthracycline-treated BC group, it was more pronounced in the ARCM group (P < 0.001). Mean anthracycline use in the late phase was significantly lower than in the early phase (307 vs. 525 mg/m2, P < 0.001). Five-year survival rates in the late phase tended to be higher than early phase (45% and 28%, respectively. P = 0.058). Human epidermal growth factor receptor type 2 (HER2) positivity with trastuzumab therapy in the late phase was an independent predictor for mortality within 10 years (hazard ratio = 0.24, 95% confidence interval: 0.10-0.56; P = 0.001). CONCLUSIONS: HER2-positive patients with ARCM receiving trastuzumab therapy had a better prognosis than HER2-positive and HER2-negative patients with ARCM not receiving trastuzumab therapy, and this trend has been increasing in the trastuzumab era. These findings highlight the importance of HER2-targeted treatments in improving prognosis for BC patients with ARCM.

Characteristics of back pain in patients with adolescent idiopathic scoliosis: Considerations in candidates for corrective surgery.

BACKGROUND: Previous studies have demonstrated that the point prevalence of back pain ranges from 12 % to 33 % and that the lifetime prevalence of back pain ranges from 28 % to 51 % in adolescents. However, few studies on back pain in patients with Adolescent idiopathic scoliosis (AIS) have been conducted, and these studies had significant limitations, including a lack of comparative controls and detailed information about scoliotic deformity or pain location. This study aimed to determine whether adolescents with AIS experience back pain in specific regions. METHODS: This retrospective case-control study included 189 female adolescents with AIS who underwent corrective fusion from 2008 to 2020. Questionnaires on back pain and health-related quality of life (HRQOL) using the Scoliosis Research Society Outcomes Instrument-22 (SRS-22) were conducted preoperatively. The control group included 2909 general female adolescents. RESULTS: The mean Cobb angles in the main thoracic and thoracolumbar/lumbar curves were 51.4 ± 15.3° and 40.4 ± 12.9°. Back pain characteristics included higher point prevalence (25.9 %) and lifetime prevalence (64.6 %) compared to healthy controls. Adolescents with back pain showed lower scores in the pain and mental health domains of the SRS-22. Adolescents with major thoracic AIS showed more back pain in the upper and middle right back compared to adolescents with major thoracolumbar/lumbar AIS. CONCLUSION: The point and lifetime prevalence of back pain were definitely higher in patients with AIS, which affected their HRQOL. There was a relationship between pain around the right scapula and the right major thoracic curve with a rib hump deformity.

Impact of Body Mass Index on Obesity-Related Cancer and Cardiovascular Disease Mortality; The Japan Collaborative Cohort Study.

AIM: We aimed to examine the association of obesity-related cancer and cardiovascular disease (CVD) with body mass index (BMI) and the estimated population attributable fraction in lean Asians. METHODS: We studied 102,535 participants aged 40-79 years without histories of cancer or CVD at baseline between 1988 and 2009. The cause-specific hazard ratios (csHRs) of BMI categories (＜18.5, 18.5-20.9, 21.0-22.9 [reference], 23.0-24.9, 25.0-27.4, and ≥ 27.5 kg/m2) were estimated for each endpoint. The events considered were mortalities from obesity-related cancer (esophageal, colorectal, liver, pancreatic, kidney, female breast, and endometrial cancer) and those from CVD (coronary heart disease and stroke). Population attributable fractions (PAFs) were calculated for these endpoints. RESULTS: During a 19.2-year median follow-up, 2906 died from obesity-related cancer and 4532 died from CVD. The multivariable-adjusted csHRs (95% confidence interval) of higher BMI categories (25-27.4 and ≥ 27.5 kg/m2) for obesity-related cancer mortality were 0.93 (0.78, 1.10) and 1.18 (0.92, 1.50) in men and 1.25 (1.04, 1.50) and 1.48 (1.19, 1.84) in women, respectively. The corresponding csHRs for CVD mortality were 1.27 (1.10, 1.46) and 1.59 (1.30, 1.95) in men and 1.10 (0.95, 1.28) and 1.44 (1.21, 1.72) in women, respectively. The PAF of a BMI ≥ 25 kg/m2 for obesity-related cancer was -0.2% in men and 6.7% in women and that for CVD was 5.0% in men and 4.5% in women. CONCLUSION: A BMI ≥ 25 kg/m2 is associated with an increased risk of obesity-related cancer in women and CVD in both sexes.

Relationship Between Heart Rate at Discharge and Long-Term Outcomes of Surgically Treated Patients With Type A Acute Aortic Dissections.

BACKGROUND: Resting heart rate (HR) at discharge is an important predictor of mortality after acute myocardial infarction. However, in patients with Stanford type A acute aortic dissections (TA-AADs), the relationship between HR and long-term outcomes is unclear. Therefore, this relationship was investigated in the present study.Methods and Results:Surgically treated consecutive patients with TA-AAD (n=721) were retrospectively categorized according to HR quartiles, recorded within 24 h before discharge (<70, 70-77, 78-83, and ≥84 beats/min). The study endpoints included aortic aneurysm-related deaths, sudden deaths, aortic surgeries, and hospitalizations for recurrence of acute aortic dissections. The mean (±SD) patient age was 65.8±13.0 years. During a median observation period of 5.8 years (interquartile range 3.9-8.5 years), 17.2% of patients (n=124) experienced late aortic events. Late aortic surgery was performed in 14.0% of patients. After adjusting for potential confounders, including ß-blocker use, HR at discharge remained an independent predictor of long-term aortic outcomes. Patients with discharge HR ≥84 beats/min had a higher risk (hazard ratio 1.86; 95% confidence interval 1.06-3.25; P=0.029) of long-term aortic events than those with HR <70 beats/min; the cumulative survival rates were similar among the groups (log-rank, P=0.905). CONCLUSIONS: In surgically treated patients with TA-AAD, HR at discharge independently predicted long-term aortic outcomes. Consequently, HR in patients with TA-AAD should be optimized before discharge, particularly if the HR is ≥84 beats/min.

Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity: a prospective observational study.

BACKGROUND: Cisplatin is a potent chemotherapeutic agent used to treat a variety of solid tumors. One of the major side effects of cisplatin is dose-limiting nephrotoxicity. We recently demonstrated that the renal uptake of cisplatin and resultant cisplatin-induced nephrotoxicity are mediated in part by megalin, an endocytic receptor in proximal tubule epithelial cells (PTECs). We also developed sandwich enzyme-linked immunosorbent assays to measure the megalin ectodomain (A-megalin) and full-length megalin (C-megalin) in urine using monoclonal antibodies against the amino- and carboxyl-termini of megalin, respectively. The present study examined the correlation of urinary megalin level with cisplatin-induced nephrotoxicity and its utility as a biomarker in patients with thoracic cancer. METHODS: This prospective observational study involved 45 chemotherapy-naïve patients scheduled to receive chemotherapy with ≥60 mg/m2 cisplatin for histologically diagnosed small cell lung cancer, non-small cell lung cancer, or malignant pleural mesothelioma. Before and after the first course of chemotherapy, we measured urinary A- and C-megalin and other markers of PTEC injury, such as N-acetyl-ß-D-glucosaminidase, α1-microglobulin, ß2-microglobulin, neutrophil gelatinase-associated lipocalin, and liver-type fatty acid-binding protein, and compared the values with the change in the estimated glomerular filtration rate (eGFR) and clinical risk factors for renal impairment. RESULTS: A negative correlation was found between baseline urinary A-megalin levels and change in eGFR (r = - 0.458, P = 0.002). According to Kaplan-Meier survival curves, eGFR decline was associated with the baseline urinary A-megalin quartile (P = 0.038). In addition, according to the hazard ratios (HRs) for eGFR decline > 10 mL/min/1.73 m2 calculated using a Cox proportional hazard model, the highest quartile had a significantly higher risk of eGFR decline compared with the lowest quartile (HR 7.243; 95% confidence interval 1.545-33.962). Other baseline urinary markers showed no correlation with eGFR decline. CONCLUSIONS: This is the first report demonstrating that prechemotherapy urinary A-megalin levels are correlated with the development of cisplatin-induced nephrotoxicity. This finding has clinical implications for the identification of patients at risk for cisplatin-induced nephrotoxicity and the development of possible prophylactic therapies.

Correction to: Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

n the original publication, in a title of Table 2.

Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

BACKGROUND: The number of cancer patients in Japan is estimated to rise to 3.5 million by 2025. The disease burden may be further complicated by comorbidities caused by cardiovascular disease (CVD). Predicting the number of cancer patients with CVD can help anticipate future resource needs. METHODS: We used statistics derived from the Niigata Cancer Center CVD Study (2015) as well as population estimates from the National Cancer Center's Cancer Registry and Statistics survey of 2017 for convenience. We simply multiplied the projected number of cancer patients through the year 2039 by the CVD prevalence in 2015, with patients classified by sex, age, and cancer type to estimate the number of cancer patients with CVD. RESULTS: The total number of Japanese cancer patients with CVD was 253,000 in 2015 and is predicted to increase rapidly by 30,000 in 2020 and peak at 313,000 in 2030-2034. Men will dominate the CVD population at 2.5-fold the number of women. The growth rate of the population with both cancer and CVD will be greater than that of the cancer-only population (1.23 vs 1.18, P < 0.001), and will comprise notably high proportions of patients with prostatic, breast, and uterine cancers (1.80, 1.57, and 1.66, P < 0.001, respectively). CONCLUSION: Future cancer patients will be older and more likely to have CVD. Although men will continue to dominate this population, the increase in the number of women will be pronounced. Cancer care providers should be trained to recognize CVD and provide any necessary interventions concurrently with cancer therapy.

Alcohol consumption and mortality from aortic disease among Japanese men: The Japan Collaborative Cohort study.

BACKGROUND AND AIMS: Only a few population-based prospective studies have examined the association between alcohol consumption and abdominal aortic aneurysm, and the results are inconsistent. Moreover, no evidence exists for aortic dissection. We examined the effect of alcohol consumption on risk of mortality from aortic diseases. METHODS: A total of 34,720 men from the Japan Collaborative Cohort study, aged 40-79 years, without history of cardiovascular disease and cancer at baseline 1988 and 1990 were followed up until the end of 2009 for their mortality and its underlying cause. Hazard ratios of mortality from aortic diseases were estimated according to alcohol consumption categories of never-drinkers, ex-drinkers, regular drinkers of ≤30 g, and >30 g ethanol per day. RESULTS: During the median 17.9-year follow-up period, 45 men died of aortic dissection and 41 men died of abdominal aortic aneurysm. Light to moderate drinkers of ≤30 g ethanol per day had lower risk of mortality from total aortic disease and aortic dissection compared to never-drinkers. The respective multivariable hazard ratios (95% confidence intervals) were 0.46 (0.28-0.76) for total aortic disease and 0.16 (0.05-0.50) for aortic dissection. Heavy drinkers of >30 g ethanol per day did not have reduced risk of mortality from total aortic disease, albeit had risk variation between aortic dissection and abdominal aortic aneurysm. CONCLUSIONS: Light to moderate alcohol consumption was associated with reduced mortality from aortic disease among Japanese men.

Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in both AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis.

The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues. A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens. In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log10%amyloid). The results of sex-, age-, and Log10%amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and the deposition pattern in the glomerulus was nodular. Nodular deposition in extraglomerular mesangium leads to renal impairment in AA group. There are significant differences between AA and AL amyloidosis with regard to the renal function, especially in terms of Ccr, eGFR and urinary protein, even after Log10%amyloid was adjusted; showing that these inter-group differences in renal function would not be depend on the amount of renal amyloid deposits. These differences could be explained by the difference in distribution and morphological pattern of amyloid deposition in the renal tissue.

Similarities and differences between coronary heart disease and stroke in the associations with cardiovascular risk factors: The Japan Collaborative Cohort Study.

BACKGROUND AND AIMS: Coronary heart disease (CHD) and stroke have common risk factors, but some of these differ in the magnitude or direction of associations between CHD and stroke. We assessed whether the impact of each risk factor differed between CHD and stroke mortality in Asians. METHODS: In total, 104 910 subjects aged 40-79 years without histories of cancer, CHD and stroke at baseline were followed between 1988 and 2009. Competing-risks analysis was used to test for differences in the associations of each risk factor with two endpoints (CHD and stroke). Population attributable fractions (PAFs) were also calculated for these endpoints to estimate the population impact of each risk factor. RESULTS: During a median 19.1-year follow-up, 1554 died from CHD and 3163 from stroke. The association of hypertension with CHD was similar to that with stroke in terms of the magnitude and direction (multivariable-adjusted hazard ratio for CHD: 1.63 vs. stroke: 1.73 in men and 1.70 vs. 1.66 in women). Conversely, the magnitude of these associations differed for smoking (CHD: 1.95 vs. stroke: 1.23 in men and 2.45 vs. 1.35 in women) and diabetes (1.49 vs. 1.09 in men and 2.08 vs. 1.39 in women). The highest PAF for CHD was caused by smoking in men and by hypertension in women; that for stroke was caused by hypertension in both sexes. CONCLUSIONS: Hypertension associations and PAFs were consistent between CHD and stroke, but not for other risk factors. These findings may be useful to optimize public health intervention strategies.

Effects of Biologic Agents in Patients with Rheumatoid Arthritis and Amyloidosis Treated with Hemodialysis.

Objective Our objective was to examine the safety and effects of therapy with biologics on the prognosis of rheumatoid arthritis (RA) patients with reactive amyloid A (AA) amyloidosis on hemodialysis (HD). Methods Twenty-eight patients with an established diagnosis of reactive AA amyloidosis participated in the study. The survival was calculated from the date of HD initiation until the time of death, or up to end of June 2015 for the patients who were still alive. HD initiation was according to the program of HD initiation for systemic amyloidosis patients associated with RA. Results Ten patients had been treated with biologics before HD initiation for a mean of 28.2 months (biologic group), while 18 had not (non-biologic group). HD was initiated in patients with similar characteristics except for the tender joint count, swollen joint count, and disease activity score (DAS)28-C-reactive protein (CRP). History of biologics showed that etanercept was frequently used for 8 patients as the first biologic. There was no significant difference in the mortality rate according to a Kaplan-Meier analysis (p=0.939) and or associated risk of death in an age-adjusted Cox proportional hazards model (p=0.758) between both groups. Infections were significantly more frequent causes of death in the biologic group than in the non-biologic group (p=0.021). However, treatment with biologics improved the DAS28-CRP score (p=0.004). Conclusion Under the limited conditions of AA amyloidosis treated with HD, the use of biologics might affect infection and thus may not improve the prognosis. Strict infection control is necessary for the use of biologics with HD to improve the prognosis.

Serum Albumin Levels and Economic Status in Japanese Older Adults.

BACKGROUND: Low serum albumin levels are associated with aging and medical conditions such as cancer, liver dysfunction, inflammation, and malnutrition and might be an independent predictor of long-term mortality in healthy older populations. We tested the hypothesis that economic status is associated with serum albumin levels and explained by nutritional and health status in Japanese older adults. DESIGN: We performed a cross-sectional analysis using data from the Japan Gerontological Evaluation study (JAGES). The study participants were 6528 functionally independent residents (3189 men and 3339 women) aged ≥65 years living in four municipalities in Aichi prefecture. We used household income as an indicator of economic status. Multiple linear regression was used to compare serum albumin levels in relation to household income, which was classified as low, middle, and high. Additionally, mediation by nutritional and health-related factors was analyzed in multivariable models. RESULTS: With the middle-income group as reference, participants with low incomes had a significantly lower serum albumin level, even after adjustment for sex, age, residential area, education, marital status, and household structure. The estimated mean difference was -0.17 g/L (95% confidence interval, -0.33 to -0.01 g/L). The relation between serum albumin level and low income became statistically insignificant when "body mass index", "consumption of meat or fish", "self-rated health", "presence of medical conditions", "hyperlipidemia", or "respiratory disease "was included in the model. CONCLUSION: Serum albumin levels were lower in Japanese older adults with low economic status. The decrease in albumin levels appears to be mediated by nutrition and health-related factors with low household incomes. Future studies are needed to reveal the existence of other pathways.

Television viewing time and mortality from stroke and coronary artery disease among Japanese men and women -- the Japan Collaborative Cohort Study.

BACKGROUND: No study has examined the association between television (TV) viewing time and mortality from stroke and coronary artery disease (CAD) in Japanese. METHODS AND RESULTS: A total of 35,959 men and 49,940 women aged 40-79 years without a history of cardiovascular disease (CVD) and cancer were followed from 1988-1990 until 2009. During 19.2 median years of follow-up, there were 2,553 deaths from stroke, 1,206 from CAD and 5,835 from total CVD. Compared with viewing TV for <2 h/day, mortality from stroke, CAD and total CVD were higher for ≥6 h/day of TV viewing. The multivariable hazard ratios (HRs) for ≥6 h/day of TV viewing were 1.15 (95% confidence interval: 0.96-1.37) for stroke, 1.33 (1.03-1.72) for CAD and 1.19 (1.06-1.34) for total CVD. The corresponding HRs for each 1-h/day increment in TV viewing time were 1.01 (0.99-1.04), 1.04 (1.01-1.08) and 1.02 (1.01-1.04), respectively. The excess risk of mortality from CAD and total CVD was somewhat attenuated after further adjustment for potential mediators such as history of hypertension and diabetes: the multivariable HRs for ≥6 h/day of TV viewing were 1.24 (0.96-1.61) and 1.14 (1.02-1.28). The corresponding HRs for each 1-h/day increment in TV viewing time were 1.03 (1.00-1.07) and 1.01 (1.00-1.03). CONCLUSIONS: Prolonged TV viewing was associated with a small but significant increase in mortality from CAD and total CVD in Japanese.

Benefits of a 12-week lifestyle modification program including diet and combined aerobic and resistance exercise on albuminuria in diabetic and non-diabetic Japanese populations.

BACKGROUND: Albuminuria is a biomarker for chronic kidney disease and an independent predictor of cardiovascular and all-cause mortality. A recent meta-analysis concluded that these risks increase with urinary albumin concentration, even when below the microalbuminuria threshold. Thus, minimizing urinary albumin may be a valuable therapeutic goal regardless of disease status. METHODS: We investigated the benefits and safety of a 12-week lifestyle modification program including diet and combined aerobic and resistance exercise for reducing albuminuria in 295 normoalbuminuric or microalbuminuric Japanese adults, including 30 with type 2 diabetes mellitus (T2DM), 104 with metabolic syndrome (MS), and 145 with hypertension (HT). RESULTS: In the study population, the urinary albumin:creatinine ratio (UACR) was reduced significantly (ΔUACR -3.8 ± 16.8 mg/g, P < 0.001) with no change in estimated glomerular filtration rate (eGFR) (ΔeGFR -0.4 ± 7.4 mL/min/1.73 m(2), P = 0.343). The reduction in UACR was associated with decreased fasting plasma glucose (P < 0.05). The UACR was also reduced in the T2DM, MS, and HT groups with no change in eGFR. Reduced UACR was associated with decreased fasting plasma glucose in the MS group and decreased systolic blood pressure in the HT group. The UACR was also reduced in 46 subjects using renin-angiotensin system inhibitors with no change in eGFR. CONCLUSIONS: Our 12-week lifestyle modification program reduced UACR, maintained eGFR, and improved multiple fitness findings in Japanese subjects including T2DM, MS, and HT patients.

Real-time polymerase chain reaction analysis of MDM2 and CDK4 expression using total RNA from core-needle biopsies is useful for diagnosing adipocytic tumors.

BACKGROUND: Diagnosing adipocytic tumors can be challenging because it is often difficult to morphologically distinguish between benign, intermediate and malignant adipocytic tumors, and other sarcomas that are histologically similar. Recently, a number of tumor-specific chromosome translocations and associated fusion genes have been identified in adipocytic tumors and atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL), which have a supernumerary ring and/or giant chromosome marker with amplified sequences of the MDM2 and CDK4 genes. The purpose of this study was to investigate whether quantitative real-time polymerase chain reaction (PCR) could be used to amplify MDM2 and CDK4 from total RNA samples obtained from core-needle biopsy sections for the diagnosis of ALT/WDL. METHODS: A series of lipoma (n = 124) and ALT/WDL (n = 44) cases were analyzed for cytogenetic analysis and lipoma fusion genes, as well as for MDM2 and CDK4 expression by real-time PCR. Moreover, the expression of MDM2 and CDK4 in whole tissue sections was compared with that in core-needle biopsy sections of the same tumor in order to determine whether real-time PCR could be used to distinguish ALT/WDL from lipoma at the preoperative stage. RESULTS: In whole tissue sections, the medians for MDM2 and CDK4 expression in ALT/WDL were higher than those in the lipomas (P < 0.05). Moreover, karyotype subdivisions with rings and/or giant chromosomes had higher MDM2 and CDK4 expression levels compared to karyotypes with 12q13-15 rearrangements, other abnormal karyotypes, and normal karyotypes (P < 0.05). On the other hand, MDM2 and CDK4 expression levels in core-needle biopsy sections were similar to those in whole-tissue sections (MDM2: P = 0.6, CDK4: P = 0.8, Wilcoxon signed-rank test). CONCLUSION: Quantitative real-time PCR of total RNA can be used to evaluate the MDM2 and CDK4 expression levels in core-needle biopsies and may be useful for distinguishing ALT/WDL from adipocytic tumors. Thus, total RNA from core-needle biopsy sections may have potential as a routine diagnostic tool for other tumors where gene overexpression is a feature of the tumor.

Is the association between healthy lifestyle behaviors and cardiovascular mortality modified by overweight status? The Japan Collaborative Cohort Study.

OBJECTIVE: To examine the modifying effects of overweight status on the association of healthy lifestyle behaviors with cardiovascular mortality in the Japanese population. METHODS: A community-based, prospective cohort of 18,730 men and 24,216 women aged 40-79 years without a history of cardiovascular disease (CVD) or cancer at baseline (1988-1990) was followed until 2009. Healthy lifestyle behaviors included intake of fruits, fish, and milk; exercise; avoidance of smoking; moderate alcohol intake; and moderate sleep duration. RESULTS: During the median of 19.3 years of follow-up, there were 2412 deaths from total CVD. Inverse associations between healthy lifestyle scores and mortality from stroke, total CVD, and coronary heart disease (CHD) were observed for non-overweight and overweight (body mass index ≥25 kg/m2) individuals, although the association was weaker for overweight individuals. The multivariable hazard ratios (HRs, 95% confidence interval) of mortality from total CVD for the highest (6-7) versus the lowest (0-2) scores were 0.44 (0.37-0.54) for non-overweight and 0.56 (0.39-0.81) for overweight individuals. Especially for CHD mortality, such association was more evident for non-overweight compared to that for overweight individuals. CONCLUSIONS: Our findings suggest that lifestyle modification may be beneficial in the prevention of cardiovascular mortality for persons who are and are not overweight.

Influence of municipal- and individual-level socioeconomic conditions on mortality in Japan.

BACKGROUND: The health effect of area socioeconomic conditions has been evident especially in Western countries; however, limited research has focused on the effect of municipal-level socioeconomic conditions, especially in Asia. PURPOSE: Multilevel research using data from the Japan Collaborative Cohort Study, a large cohort study followed from 1990 to 2006, was conducted to examine individual as well as municipal socioeconomic conditions on risk of death, adjusting for each other. METHOD: We included 24,460 men and 32,649 women aged 40 to 65 years at baseline in 35 municipalities as our study population. Primary predictors were municipal socioeconomic conditions (proportion of college graduates, per capita income, unemployment rate, and proportion of households receiving public assistance) and individual socioeconomic conditions (education level and occupation). RESULTS: Among men, the multilevel logistic estimate (standard errors) of proportion of college graduates and unemployment rate for mortality from cardiovascular disease were -0.399 (0.094) and -0.343 (0.122), respectively. Among women, the multilevel logistic estimate (standard errors) of proportion of college graduates and per capita annual income for mortality from injuries were -0.386 (0.171) and -1.069 (0.407). Individual education level and occupation were associated with all-cause mortality, in particular, mortality from cardiovascular disease or injuries. Interactions between individual education level and indicators of municipal socioeconomic conditions were observed for mortality from cancer and cardiovascular disease among men and mortality from injuries among women. CONCLUSION: Municipal and individual socioeconomic conditions were independently and interactively associated with premature death; this suggests that reducing social inequalities in health demands a focus on municipal conditions in addition to those of individuals.

Distribution of amyloid deposits in the kidneys of a patient with reactive amyloidosis associated with rheumatoid arthritis.

BACKGROUND: We previously reported that the amount of amyloid A (AA) amyloid deposited in renal biopsy specimens was highly correlated with parameters of renal function. However, the distribution of amyloid deposits throughout the kidneys of these patients, and the degree of renal abnormality, remained unclear. Therefore, we describe the features of reactive amyloidosis associated with rheumatoid arthritis (RA) in an autopsied patient. CASE PRESENTATION: The present report case is a 50-year-old female with RA and reactive amyloidosis. She was diagnosed as RA in 1978. Diagnosis of AA amylodosis was made by renal biopsy in 1991 for the reason of proteinuria. Because of the pancreatitis, she was died in 2006 and autopsy was performed. Renal tissues from autopsy specimens were evaluated for their proportions of amyloid-positive areas. A total of 6 specimens (three tissue blocks from each kidney obtained at autopsy) were evaluated in this study. The size of each block was approximately 20 mm × 20 mm. One section of whole tissue was photographed in each case. The borders of the amyloid-positive areas in each specimen were traced in each photograph, excluding any tissue-free spaces. The total amyloid-positive area was measured, and the percentage area of amyloid per whole-tissue section (percent (%) area of amyloid deposition) was calculated. The distribution of amyloid deposits in the kidneys was examined. The significance of differences in the mean percent (%) area of amyloid deposition between the right and left sides and among three long-axis levels (upper, middle and lower) were analyzed by two-way analysis of variance (ANOVA) at a significance level of p <0.05. CONCLUSION: The area of amyloid deposition in these samples was about 7-11%, and the degree of variability among them seemed to be small. It also shows a comparison of amyloid deposition between the right and left sides and between the long axis samples for quadruplicate determinations; no significant differences were evident, and thus the percent (%) area of amyloid deposition throughout the whole kidneys appeared to be uniform in this patient.

Body mass index and weight change during adulthood are associated with increased mortality from liver cancer: the JACC Study.

BACKGROUND: We investigated the association of baseline body mass index (BMI) and weight change since age 20 years with liver cancer mortality among Japanese. METHODS: The data were obtained from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). A total of 31 018 Japanese men and 41 455 Japanese women aged 40 to 79 years who had no history of cancer were followed from 1988 through 2009. RESULTS: During a median 19-year follow-up, 527 deaths from liver cancer (338 men, 189 women) were documented. There was no association between baseline BMI and liver cancer mortality among men or men with history of liver disease. Men without history of liver disease had multivariable hazard ratios (HR) of 1.95 (95%CI, 1.07-3.54) for BMI less than 18.5 kg/m(2) and 1.65 (1.05-2.60) for BMI of 25 kg/m(2) or higher, as compared with a BMI of 21.0 to 22.9 kg/m(2). BMI was positively associated with liver cancer mortality among women and women with history of liver disease. Weight change since age 20 years was positively associated with liver cancer mortality among women regardless of history of liver disease. Women with history of liver disease had a multivariable HRs of 1.96 (1.05-3.66) for weight gain of 5.0 to 9.9 kg and 2.31 (1.18-4.49) for weight gain of 10 kg or more, as compared with weight change of -4.9 to 4.9 kg. CONCLUSIONS: Both underweight (BMI <18.5 kg/m(2)) and overweight (BMI ≥25 kg/m(2)) among men without history of liver disease, and weight gain after age 20 (weight change ≥5 kg) among women with history of liver disease, were associated with increased mortality from liver cancer.

Cohort profile of the Japan Collaborative Cohort Study at final follow-up.

The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) was established in the late 1980s to evaluate the risk impact of lifestyle factors and levels of serum components on human health. During the 20-year follow-up period, the results of the study have been published in almost 200 original articles in peer-reviewed English-language journals. However, continued follow-up of the study subjects became difficult because of the retirements of principal researchers, city mergers throughout Japan in the year 2000, and reduced funding. Thus, we decided to terminate the JACC Study follow-up at the end of 2009. As a final point of interest, we reviewed the population registry information of survivors. A total of 207 (0.19%) subjects were ineligible, leaving 110 585 eligible participants (46 395 men and 64 190 women). Moreover, errors in coding date of birth and sex were found in 356 (0.32%) and 59 (0.05%) cases, respectively, during routine follow-up and final review. Although such errors were unexpected, their impact is believed to be negligible because of the small numbers relative to the large total study population. Here, we describe the final cohort profile at the end of the JACC Study along with selected characteristics of the participants and their status at the final follow-up. Although follow-up of the JACC Study participants is finished, we will continue to analyze and publish study results.