External Validation of Updated Prediction Models for Neurological Outcomes at 90 Days in Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: Few prediction models for individuals with early-stage out-of-hospital cardiac arrest (OHCA) have undergone external validation. This study aimed to externally validate updated prediction models for OHCA outcomes using a large nationwide dataset. METHODS AND RESULTS: We performed a secondary analysis of the JAAM-OHCA (Comprehensive Registry of In-Hospital Intensive Care for Out-of-Hospital Cardiac Arrest Survival and the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest) registry. Previously developed prediction models for patients with cardiac arrest who achieved the return of spontaneous circulation were updated. External validation was conducted using data from 56 institutions from the JAAM-OHCA registry. The primary outcome was a dichotomized 90-day cerebral performance category score. Two models were updated using the derivation set (n=3337). Model 1 included patient demographics, prehospital information, and the initial rhythm upon hospital admission; Model 2 included information obtained in the hospital immediately after the return of spontaneous circulation. In the validation set (n=4250), Models 1 and 2 exhibited a C-statistic of 0.945 (95% CI, 0.935-0.955) and 0.958 (95% CI, 0.951-0.960), respectively. Both models were well-calibrated to the observed outcomes. The decision curve analysis showed that Model 2 demonstrated higher net benefits at all risk thresholds than Model 1. A web-based calculator was developed to estimate the probability of poor outcomes (https://pcas-prediction.shinyapps.io/90d_lasso/). CONCLUSIONS: The updated models offer valuable information to medical professionals in the prediction of long-term neurological outcomes for patients with OHCA, potentially playing a vital role in clinical decision-making processes.

Nanofiber Hydrogel Drug Delivery System for Prevention of Postsurgical Intestinal Adhesion.

Intestinal adhesion is one of the complications that occurs more frequently after abdominal surgery. Postsurgical intestinal adhesion (PIA) can lead to a series of health problems, including abdominal pain, intestinal obstruction, and female infertility. Currently, hydrogels and nanofibrous films as barriers are often used for preventing PIA formation; however, these kinds of materials have their intrinsic disadvantages. Herein, we developed a dual-structure drug delivery patch consisting of poly lactic-co-glycolic acid (PLGA) nanofibers and a chitosan hydrogel (NHP). PLGA nanofibers loaded with deferoxamine mesylate (DFO) were incorporated into the hydrogel; meanwhile, the hydrogel was loaded with anti-inflammatory drug dexamethasone (DXMS). The rapid degradation of the hydrogel facilitated the release of DXMS at the acute inflammatory stage of the early injury and provided effective anti-inflammatory effects for wound sites. Moreover, PLGA composite nanofibers could provide sustained and stable release of DFO for promoting the peritoneal repair by the angiogenesis effects of DFO. The in vivo results indicated that NHP can effectively prevent PIA formation by restraining inflammation and vascularization, promoting peritoneal repair. Therefore, we believe that our NHP has a great potential application in inhibition of PIA.

Prevalence of and factors influencing Hikikomori in Osaka City, Japan: A population-based cross-sectional study.

OBJECTIVES: Hikikomori is commonly defined as a social condition in which individuals avoid social participation and relationships beyond their family members by confining themselves to a room or their house for 6 months or longer. Hikikomori has been predominantly considered a problem among young people; however, as the population is ageing, hikikomori has also emerged as a social issue among adults. Nevertheless, no comparative studies have examined the differences in the factors associated with hikikomori among teenagers/young adults and middle-aged/older adults. Thus, this phenomenon has not been thoroughly examined, and it remains unclear whether the risk factors vary between teenagers/young adults and middle-aged/older adults. Based on the Japan Cabinet Office's definition of hikikomori, this cross-sectional study evaluated the prevalence and related factors of hikikomori among the working age population (15-64 years), utilising univariate and multivariate analyses. The study also compared differences in the prevalence of and factors related to hikikomori between teenagers/young adults and middle-aged/older adults. METHODS: We distributed self-administered questionnaires to individual participants and their families between 24 December 2020 and 18 January 2021. RESULTS: Data from an anonymised sample of 3,092 individuals (split into two groups of 15-39 and 40-64 years) were subjected to analysis. The results revealed a hikikomori prevalence of 2.3% in the target population; the prevalence rate was 2.12% among individuals aged 15 to 39 years and 2.42% among those aged 40 to 64 years. The analysis demonstrated strong correlations between hikikomori and several factors, including unemployment, truancy, a history of psychiatric consultation or hospitalisation, being male and the absence of ibasho, which is defined as a place where individuals can feel peace, security, acceptance and belonging. The factors associated with hikikomori differed between teenagers/young adults and middle-aged/older adults. CONCLUSION: Our findings, thus, contribute to existing research by providing a comparative analysis of risk factors across different age groups.

Intestinal Bacteria Fluctuating in Early-Stage Colorectal Cancer Carcinogenesis are Associated with Diet in Healthy Adults.

This hospital-based, cross-sectional study aimed to explore the association between diet and fluctuating intestinal bacteria in early-stage colorectal cancer (CRC) (Atopobium parvulum, Actinomyces odontolyticus, Solobacterium moorei, and Bifidobacterium longum). Healthy participants (n = 212) who underwent total colonoscopy at National Cancer Center Hospital (Tokyo, Japan) were divided into two groups according to the relative abundance of bacteria in their feces: those in the top 25% of relative bacterial abundance as cases and the bottom 25% as controls. The participants were divided into three groups (low, medium, and high) according to their intake of food groups associated with CRC. Multivariable logistic regression analysis was conducted to estimate the association between dietary intake and higher relative abundance of bacteria. Dairy products were inversely associated with a higher relative abundance of A. parvulum, A. odontolyticus, and S. moorei, with odds ratios (high vs. low) and 95% confidence interval as follows: 0.16 (0.06-0.44), 0.25 (0.08-0.82), and 0.29 (0.11-0.78), respectively. Additionally, dietary fiber was inversely associated with a higher relative abundance of S.moorei (0.29 [0.11-0.78]). No association was observed between diet and B.longum. In conclusion, healthy adults with a higher intake of dairy products and fiber had lower odds of having a higher relative abundance of CRC-associated microbiota.

Suicide risk among patients with cancer by sex in Japan: A population-based study.

BACKGROUND: In Japan, few studies have examined suicide risk for five-year relative survival rates for cancer sites. Since five-year relative survival rates differ by sex, we aim to examine suicide risk for patients with cancer separately for men and women. METHODS: We estimated the risk of suicide among patients with cancer by sex in Japan compared to the general population, using standardized mortality ratios (SMRs). Patients with cancer diagnosed between January 1, 1985-December 31, 2013 and registered in the Osaka Cancer Registry were followed-up with for up to 10 years. The outcome was suicide death. In addition, cancer sites were classified into three prognosis groups based on five-year relative survival rates: good (> 70%), moderate (40-70%), poor (< 40%). RESULTS: Among 623 995 patients with cancer observed for 2 349 432 person-years, 1210 patients died by suicide (867 men and 343 women). The SMRs were almost equal for men (1.66, 95% CI, 1.55-1.77) and women (1.65, 95% CI, 1.48-1.83). SMRs for cancer prognosis groups were 1.01 (95% CI, 0.84-1.22) for men and 1.47 (95% CI, 1.24-1.73) for women in the good group, 1.53 (95% CI, 1.39-1.68) for men and 1.74 (95% CI, 1.47-2.05) for women in the moderate group, and 2.54 (95% CI, 2.27-2.85) for men and 1.87 (95% CI, 1.43-2.46) for women in the poor group. CONCLUSIONS: In this population, both sexes had higher suicide risk with poor prognosis, but the difference in SMRs between the good and poor groups was smaller for women than men.

Long-term use of anti-cholesterol drugs and cancer risks in a Japanese population.

Several studies have investigated the association between the use of anti-cholesterol drugs and cancer risks, of which results have been inconsistent. This study included 67,768 participants from the Japan Public Health Center-based Prospective Study. The data on anti-cholesterol drug use was collected using three questionnaires of the survey conducted every five years. We divided the participants into three groups according to the duration of the anti-cholesterol drug use. Multivariable-adjusted Cox proportional hazard regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). During the 893,009 person-years of follow-up from the 10-year follow-up survey, 8,775 participants (5,387 men and 3,388 women) were newly diagnosed with cancers. The duration of anti-cholesterol drug use was significantly associated with a decreased risk of liver cancer (HR:0.26, 95% CI 0.11-0.64 in > 5 y group) and with an increased risk of pancreatic cancer (HR:1.59, 95% CI 1.03-2.47 in > 5 y group). Moreover, a different trend was observed between men and women in the association with the risk of lung cancer. This study suggested that long-term use of anti-cholesterol drugs may have associations with a decreased incidence of liver cancer and with an increased incidence of pancreatic cancers.

Adult Height and Risk of Colorectal Cancer: A Pooled Analysis of 10 Population-based Cohort Studies in Japan.

BACKGROUND: While tall stature has been linked to an increase in the risk of colorectal cancer (CRC), its association with cancer in the colorectum and its subsites remains unclear among Asians. METHODS: We conducted a pooled analysis of 10 population-based cohort studies among adults in Japan. Each study estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence associated with adult height were estimated using Cox proportional hazards regression with adjustment of the same set of covariates were then pooled to estimate summary HRs incidence using random-effect models. RESULTS: We identified 9,470 CRC incidences among 390,063 participants during 5,672,930 person-years of follow-up. Men and women with tall stature had a higher risk of CRC and colon cancer. HRs for CRC, colon cancer, and distal colon cancer for the highest versus lowest height categories were 1.23 (95% CI, 1.07-1.40), 1.22 (95% CI, 1.09-1.36), and 1.27 (95% CI, 1.08-1.49), respectively, in men and 1.21 (95% CI, 1.09-1.35), 1.23 (95% CI, 1.08-1.40), and 1.35 (95% CI, 1.003-1.81), respectively, in women. The association with proximal colon cancer and rectal cancer was less evident in both sexes. CONCLUSION: This pooled analysis confirms the link between tall stature and a higher risk of CRC and colon cancer (especially distal colon) among the Japanese and adds evidence to support the use of adult height to identify those at a higher risk of CRC.

Dietary Consumption of Antioxidant Vitamins in Relation to Prostate Cancer Risk in Japanese Men: The Japan Public Health Center-based Prospective Study.

BACKGROUND: Many epidemiological studies have investigated dietary intake of antioxidant vitamins in relation to prostate cancer risk in Western countries, but the results are inconsistent. However, few studies have reported this relationship in Asian countries. METHODS: We investigated the association between intake of vitamins, including lycopene, α-carotene, ß-carotene, vitamin C, vitamin E, with prostate cancer risk in the Japan Public Health Center-based Prospective (JPHC) study. 40,720 men without history of cancer finished the food frequency questionnaire (FFQ) and were included in the study. Hazard ratios (HRs) and 95% confidence intervals (CIs) of prostate cancer risk were calculated according to the quintiles of energy-adjusted intake of vitamins using Cox models. RESULTS: After an average of 15.2 years (617,599 person-years in total) of follow-up, 1,386 cases of prostate cancer were identified, including 944 localized cases and 340 advanced cases. No associations were observed in consumption of antioxidant vitamins, including α-carotene, ß-carotene, vitamin C, and vitamin E, and prostate cancer risk. Although higher lycopene intake was associated with increased risk of prostate cancer (highest vs lowest quintile, HR 1.24; 95% CI, 1.04-1.47; P for trend = 0.01), there was a null association of lycopene intake with risk of prostate cancer detected by subjective symptoms (HR 1.12; 95% CI, 0.79-1.58; P for trend = 0.11). CONCLUSION: Our study suggested no association between antioxidant intake of vitamins and prostate cancer risk.

Combined Vorinostat and Chloroquine Inhibit Sodium-Iodide Symporter Endocytosis and Enhance Radionuclide Uptake In Vivo.

PURPOSE: Patients with aggressive thyroid cancer are frequently failed by the central therapy of ablative radioiodide (RAI) uptake, due to reduced plasma membrane (PM) localization of the sodium/iodide symporter (NIS). We aimed to understand how NIS is endocytosed away from the PM of human thyroid cancer cells, and whether this was druggable in vivo. EXPERIMENTAL DESIGN: Informed by analysis of endocytic gene expression in patients with aggressive thyroid cancer, we used mutagenesis, NanoBiT interaction assays, cell surface biotinylation assays, RAI uptake, and NanoBRET to understand the mechanisms of NIS endocytosis in transformed cell lines and patient-derived human primary thyroid cells. Systemic drug responses were monitored via 99mTc pertechnetate gamma counting and gene expression in BALB/c mice. RESULTS: We identified an acidic dipeptide within the NIS C-terminus that mediates binding to the σ2 subunit of the Adaptor Protein 2 (AP2) heterotetramer. We discovered that the FDA-approved drug chloroquine (CQ) modulates NIS accumulation at the PM in a functional manner that is AP2 dependent. In vivo, CQ treatment of BALB/c mice significantly enhanced thyroidal uptake of 99mTc pertechnetate in combination with the histone deacetylase (HDAC) inhibitor vorinostat/SAHA, accompanied by increased thyroidal NIS mRNA. Bioinformatic analyses validated the clinical relevance of AP2 genes with disease-free survival in RAI-treated DTC, enabling construction of an AP2 gene-related risk score classifier for predicting recurrence. CONCLUSIONS: NIS internalization is specifically druggable in vivo. Our data, therefore, provide new translatable potential for improving RAI therapy using FDA-approved drugs in patients with aggressive thyroid cancer. See related commentary by Lechner and Brent, p. 1220.

Risk of Parkinson's disease-related death in cancer survivors: A population-based study in Japan.

BACKGROUND: The risk of Parkinson's disease (PD)-related death in patients with cancer largely unexplored. METHODS: We analyzed data from the Neoplasms ANd other causes of DEath (NANDE) study, which investigates the causes of death in patients with cancer in Japan. Standardized mortality ratios (SMRs) were calculated to compare the risk of PD-related deaths in patients with cancer to that of the general population. Poisson regression models were employed to estimate the relative risk of PD-related death in the subgroups. RESULTS: The cohort included 548,485 patients with cancer, yielding 2,047,398 person-years at risk from 1995 to 2013. During the study period, 242,250 patients died and 145 deaths were attributable to PD. The SMR for PD-related death was 2.34 (95% confidence interval [CI]: 1.99-2.75). Patients who were diagnosed with cancer before 70 years of age had a high SMR (>5) for PD-related deaths. The SMR of patients with mouth-to-stomach cancers (lip, oral cavity, pharynx, esophagus, and stomach cancers) was 3.72 (95% CI: 2.84-4.86), while that of those with other cancers was 1.93 (95% CI: 1.57-2.37). The multivariate Poisson regression model revealed that patients with mouth-to-stomach cancers were more likely to die of PD than those without (relative risk 2.07, 95 % CI; 1.46-2.93). CONCLUSIONS: Patients with cancer are at a high risk of PD-related death; particularly, mouth-to-stomach cancers and potentially obstructing medication for PD are attributable to a high mortality risk. Careful management, including adequate PD treatment, would benefit cancer survivors with PD and reduce the risk of PD-related death.

Association of anticholinergic drug exposure with the risk of dementia among older adults in Japan: The LIFE Study.

OBJECTIVES: Several studies have investigated that anticholinergic drugs cause cognitive impairment. However, the risk of dementia associated with anticholinergics has not been extensively investigated in the super-aging society of Japan. We conducted this study to assess the association between anticholinergic drugs and the risk of dementia in older adults in Japan. METHODS: This nested case-control study used data from the Longevity Improvement & Fair Evidence Study, which includes claim data in Japan from 2014 to 2020. We included 66,478 cases of diagnosed dementia and 328,919 matched controls aged ≥65 years, matched by age, sex, municipality, and cohort entry year. Primary exposure was the total cumulative anticholinergic drugs prescribed from cohort entry date to event date or matched index date, which was the total standardized daily doses for each patient, calculated by adding the total dose of different types of anticholinergic drugs in each prescription, divided by the World Health Organization-defined daily dose values. Odds ratios for dementia associated with cumulative exposure to anticholinergic drugs were calculated using conditional logistic regression adjusted for confounding variables. RESULTS: The mean (standard deviation) age at index date was 84.3 (6.9), and the percentage of women was 62.1%. From cohort entry date to event date or matched index date, 18.8% of the case patients and 13.7% of the controls were prescribed at least one anticholinergic drug. In the multivariable-adjusted model, individuals with anticholinergic drugs prescribed had significantly higher odds of being diagnosed with dementia (adjusted odds ratio, 1.50 [95% confidence interval, 1.47-1.54]). Among specific types of anticholinergic drugs, a significant increase in risk was observed with the use of antidepressants, antiparkinsonian drugs, antipsychotics, and bladder antimuscarinics in a fully multivariable-adjusted model. CONCLUSIONS: Several types of anticholinergic drugs used by older adults in Japan are associated with an increased risk of dementia. These findings suggest that the underlying risks should be considered alongside the benefits of prescribing anticholinergic drugs to this population.

In-hospital extracorporeal cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest: an analysis by time-dependent propensity score matching using a nationwide database in Japan.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has been proposed as a rescue therapy for patients with refractory cardiac arrest. This study aimed to evaluate the association between ECPR and clinical outcomes among patients with out-of-hospital cardiac arrest (OHCA) using risk-set matching with a time-dependent propensity score. METHODS: This was a secondary analysis of the JAAM-OHCA registry data, a nationwide multicenter prospective study of patients with OHCA, from June 2014 and December 2019, that included adults (≥ 18 years) with OHCA. Initial cardiac rhythm was classified as shockable and non-shockable. Patients who received ECPR were sequentially matched with the control, within the same time (minutes) based on time-dependent propensity scores calculated from potential confounders. The odds ratios with 95% confidence intervals (CI) for 30-day survival and 30-day favorable neurological outcomes were estimated for ECPR cases using a conditional logistic model. RESULTS: Of 57,754 patients in the JAAM-OHCA registry, we selected 1826 patients with an initial shockable rhythm (treated with ECPR, n = 913 and control, n = 913) and a cohort of 740 patients with an initial non-shockable rhythm (treated with ECPR, n = 370 and control, n = 370). In these matched cohorts, the odds ratio for 30-day survival in the ECPR group was 1.76 [95%CI 1.38-2.25] for shockable rhythm and 5.37 [95%CI 2.53-11.43] for non-shockable rhythm, compared to controls. For favorable neurological outcomes, the odds ratio in the ECPR group was 1.11 [95%CI 0.82-1.49] for shockable rhythm and 4.25 [95%CI 1.43-12.63] for non-shockable rhythm, compared to controls. CONCLUSION: ECPR was associated with increased 30-day survival in patients with OHCA with initial shockable and even non-shockable rhythms. Further research is warranted to investigate the reproducibility of the results and who is the best candidate for ECPR.

Heart Disease Mortality in Cancer Survivors: A Population-Based Study in Japan.

BACKGROUND: Data on the risk of cardiovascular-related mortality in patients with cancer are limited. METHODS AND RESULTS: This retrospective cohort study used data from the Osaka Cancer Registry and vital statistics in Japan between 1985 and 2013. The causes of death were investigated, and the risk of fatal heart disease was analyzed. Standardized mortality ratios were calculated to compare the risk of fatal heart disease between patients with cancer and the general population. Fine and Gray competing risk regression models were used to assess the risk of fatal heart disease among patients with cancer. In total, 682 886 patients with cancer were included in the analysis, and 335 635 patients died during the study period. Heart disease was the leading cause of noncancer deaths, with 10 686 deaths. Among the patients who died of heart disease, 5017 had ischemic heart disease, 3598 had heart failure, 356 had hypertensive disease, and 1715 had other heart diseases. The standardized mortality ratio for heart disease was 2.80 (95% CI, 2.74-2.85). The standardized mortality ratio for ischemic heart disease, heart failure, and hypertensive disease were 3.26 (95% CI, 3.17-3.35), 2.69 (95% CI, 2.60-2.78), and 5.97 (95% CI, 5.38-6.63), respectively. The risk of fatal heart disease increased over time after cancer diagnosis. Men were more likely to die of heart disease than women (subdistribution hazard ratio, 1.08 [95% CI, 1.02-1.16]). The risk of fatal heart disease among cancer survivors has decreased in recent years. CONCLUSIONS: Cancer survivors have a higher risk of fatal heart disease than the general population.

Intra-Aortic Balloon Pump among Shockable Out-of-Hospital Cardiac Arrest Patients: A Propensity-Weighted Analysis in a Multicenter, Nationwide Observational Study in Japan (The JAAM-OHCA Registry).

BACKGROUND: The effectiveness of IABP for shockable out-of-hospital cardiac arrest (OHCA) has not been extensively investigated. This study aimed to investigate whether the use of an intra-aortic balloon pump (IABP) for non-traumatic shockable OHCA patients was associated with favorable neurological outcomes. METHODS: From the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry, a nationwide multicenter prospective registry, we enrolled adult patients with non-traumatic and shockable OHCA for whom resuscitation was attempted, and who were transported to participating hospitals between 2014 and 2019. The primary outcome was 1-month survival with favorable neurological outcomes after OHCA. After adopting the propensity score (PS) inverse probability of weighting (IPW), we evaluated the association between IABP and favorable neurological outcomes. RESULTS: Of 57,754 patients in the database, we included a total of 2738 adult non-traumatic shockable patients. In the original cohort, the primary outcome was lower in the IABP group (OR with 95% confidence intervals (CIs)), 0.57 (0.48-0.68), whereas, in the IPW cohort, it was not different between patients with and without IABP (OR, 1.18; 95% CI, 0.91-1.53). CONCLUSION: In adult patients with non-traumatic shockable OHCA, IABP use was not associated with 1-month survival with favorable neurological outcomes.

Annual patterns in the outcomes and post-arrest care for pediatric out-of-hospital cardiac arrest: A nationwide multicenter prospective registry in Japan.

AIM: Out-of-hospital cardiac arrest (OHCA) has a poor prognosis in children; however, the annual patterns of prognosis and treatment have not been fully investigated. METHODS: From the Japanese Association for Acute Medicine OHCA registry, a multicenter prospective observational registry in Japan, we identified pediatric patients (zero to 17 years old) between June 2014 and December 2019. The primary outcome was one-month survival. We investigated the annual patterns in patient characteristics, treatment, and one-month prognosis. RESULTS: During the study period, 1188 patients were eligible for analysis. For all years, the zero-year-old group accounted for a large percentage of the total population (between 30% and 40%). There were significant increases in the rates of bystander-initiated cardiopulmonary resuscitation (CPR; from 50.6% to 62.3%, p = 0.003), dispatcher instructions (from 44.7% to 65.7%, p = 0.001), and adrenaline administration (from 2.4% to 6.9%, p = 0.014) over time, whereas the rate of advanced airway management decreased significantly (from 17.7% to 8.8%, p = 0.003). The odds ratios for one-month survival adjusted for potential resuscitation factors also did not change significantly (from 7.1% to 10.3%, adjusted odds ratio for one-year increment = 0.98, confidence interval: 0.86-1.11). CONCLUSION: Despite an increase in the rate of bystander-initiated CPR and pre-hospital adrenaline administration, there was no significant change in one-month survival.

Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on Emergency Patients Hospitalized With Cardiocerebrovascular Diseases in Osaka Prefecture, Japan　- A Population-Based Study.

BACKGROUND: Little is known about the transport and outcomes of emergency patients with cardiocerebrovascular diseases in Japan before and during the COVID-19 pandemic.Methods and Results: Data were extracted from a population-based registry in Osaka, Japan, from 2019 to 2021. There were almost no differences in the numbers of emergency patients hospitalized with myocardial infarction, stroke, or heart failure or their deaths. However, the number of cases of difficulty obtaining patient acceptance by hospitals increased in 2020 and 2021 compared with 2019. CONCLUSIONS: The numbers of emergency patients hospitalized with cardiocerebrovascular diseases and their deaths in Osaka were not affected by the COVID-19 epidemic.

Dietary Fish and n-3 Polyunsaturated Fatty Acid Consumption, and Renal Cell Carcinoma Risk in Japan: The Japan Public Health Center-Based Prospective Study.

BACKGROUND: Previous epidemiologic studies found inconsistent associations between fish consumption and renal cell carcinoma (RCC). Although the consumption of n-3 polyunsaturated fatty acids (PUFA) was reported to protect against the development of some types of cancer, little is known regarding its association with RCC. METHODS: We investigated the association between fish and n-3 PUFA consumption and RCC risk using the Japan Public Health Center-based Prospective Study. We examined data from 84,063 eligible Japanese participants aged 45 to 74 years who responded to a validated food frequency questionnaire for Cohort I in 1995 and Cohort II in 1998. The participants were followed-up until 2013. HRs and 95% confidence intervals (CI) were estimated using a multivariable-adjusted Cox proportional hazard model, and the exposure level was categorized into quartiles. RESULTS: Among the 1,272,298 person-years of follow-up, 262 cases of newly diagnosed RCC were identified. The multivariate-adjusted HRs for the highest vs. lowest quartile of fish, including shellfish, were (HR = 1.43; 95% CI, 0.98-2.07) and the individual marine n-3 PUFAs were (HR = 1.56; 95% CI, 1.07-2.28; Ptrend = 0.09) for eicosapentenoic acid, (HR = 1.81; 95% CI, 1.27-2.59; Ptrend = 0.01) for docosapentaenoic acid, and (HR = 1.56; 95% CI, 1.07-2.27; Ptrend = 0.09) for docosahexaenoic acid. RCC were further categorized on the basis of diagnosis methods and cancer stage, and the positive correlation did not change substantially. CONCLUSIONS: We demonstrated that high consumption of n-3 PUFA is associated with RCC risk. IMPACT: The positive association between n-3 PUFA and RCC risk was observed in Japanese who consume higher amounts of fish than Western populations.

Association of mesothelioma deaths with neighborhood asbestos exposure due to a large-scale asbestos-cement plant.

A causal relationship between mesothelioma and occupational asbestos exposure is well known, while some studies have shown a relationship to non-occupational exposures. The aim of this study was to quantify the risk of mesothelioma death associated with neighborhood asbestos exposure due to a large-scale asbestos-cement (AC) plant in Amagasaki, Japan, adjusting properly risk factors including occupational exposures. We conducted a nested case-control study in which a fixed population of 143,929 residents who had been living in Amagasaki City between 1975 and 2002 were followed from 2002 to 2015. All 133 cases and 403 matched controls were interviewed about their occupational, domestic, household, and neighborhood asbestos exposures. Odds ratios (ORs) for mesothelioma death associated with the neighborhood exposure were estimated by a conditional logistic-regression model. For quantitative assessments for neighborhood exposure, we adopted cumulative indices for individuals' residential histories at each residence-specific asbestos concentration multiplied by the duration during the potential exposure period of 1957-1975 (crocidolite). We observed an increasing, dose-dependent risk of mesothelioma death associated with neighborhood exposure, demonstrating that ORs in the highest quintile category were 21.4 (95% confidence interval [CI] 5.8-79.2) for all, 23.7 (95% CI 3.8-147.2) for males, and 26.0 (95% CI 2.8-237.5) for females compared to the lowest quintile, respectively. A quantitative assessment for risk of mesothelioma deaths, adjusting for occupational and non-occupational exposures separately, showed a dose-dependent association with neighborhood exposure and no substantial gender differences in magnitude.

Association between meat, fish, and fatty acid intake and incidence of acute myeloid leukemia and myelodysplastic syndrome: the Japan Public Health Center-based Prospective Study.

BACKGROUND: The association between meat, fish, or fatty acid intake and acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) has been investigated in a few studies, and the results were inconsistent. In addition, most studies are mainly based on the United States and European countries, in which the dietary patterns differ from that in Asia. Therefore, the risk of AML/MDS from meat, fish, or fatty acid intake in Asia requires further exploration. The aim of this study was to investigate the association between AML/MDS incidence and meat, fish, or fatty acid intake using the Japan Public Health Center-based prospective study. METHODS: The present study included 93,366 participants who were eligible for analysis and followed up from the 5-year survey date until December 2012. We estimated the impact of their intake on AML/MDS incidence using a Cox proportional hazards model. RESULTS: The study participants were followed up for 1,345,002 person-years. During the follow-up period, we identified 67 AML and 49 MDS cases. An increased intake of processed red meat was significantly associated with the incidence of AML/MDS, with a hazard ratio of 1.63 (95% confidence interval, 1.03-2.57) for the highest versus lowest tertile and a Ptrend of 0.04. Meanwhile, the intake of other foods and fatty acids was not associated with AML/MDS. CONCLUSION: In this Japanese population, processed red meat was associated with an increased incidence of AML/MDS.