Relationship Between Results of Pathological Evaluation of Endomyocardial Biopsy and Echocardiographic Indices in Patients With Non-Ischemic Cardiomyopathy.

Background: Endomyocardial biopsy (EMB) is a useful modality in diagnosing the origin of cardiomyopathy and the condition of the impaired myocardium. However, the usefulness of obtaining an EMB from the right and left ventricles (RV and LV, respectively), and its associations with echocardiographic parameters, have not been explored. Methods and Results: Ninety-five consecutive patients with non-ischemic cardiomyopathy excluding myocarditis who underwent EMB between July 2017 and May 2019 were studied. Seventy-nine RV and 93 LV biopsy specimens were pathologically analyzed. The relationships among echocardiographic data before EMB and pathologically measured cardiomyocyte diameter (CMD) and interstitial fibrosis (IF) were evaluated. CMD in both LV and RV specimens correlated with echocardiographic LV morphology, but only CMD in the LV was significantly correlated with cardiac function evaluation, including LV ejection fraction, E' and E/E'. In contrast, there were no significant correlations between IF in either the LV or RV and any echocardiographic parameters measured. Furthermore, CMD of both ventricles was significantly correlated with B-type natriuretic peptide (BNP) concentration at EMB, whereas IF of the LV was barely related and IF of the RV was not significantly correlated with BNP concentrations. Conclusions: Pathologically evaluated CMD of EMB specimens of the LV may be more related to functional parameters for heart failure status and LV geometry on echocardiographic examination, than IF.

Development and Validation of a Novel Score to Predict Mortality in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: CRISTEN.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, severe mucocutaneous adverse reactions. Severity prediction at early onset is urgently required for treatment. However, previous prediction scores have been based on data of blood tests. OBJECTIVE: This study aimed to present a novel score that predicts mortality in patients with SJS/TEN in the early stages based on only clinical information. METHODS: We retrospectively evaluated 382 patients with SJS/TEN in a development study. A clinical risk score for TEN (CRISTEN) was created according to the association of potential risk factors with death. We calculated the sum of these risk factors using CRISTEN, and this was validated in a multinational survey of 416 patients and was compared with previous scoring systems. RESULTS: The significant risk factors for death in SJS/TEN comprised 10 items, including patients' age of ≥65 years, ≥10% body surface area involvement, the use of antibiotics as culprit drugs, the use of systemic corticosteroid therapy before the onset, and mucosal damage affecting the ocular, buccal, and genital mucosa. Renal impairment, diabetes, cardiovascular disease, malignant neoplasm, and bacterial infection were included as underlying diseases. The CRISTEN model showed good discrimination (area under the curve [AUC] = 0.884) and calibration. In the validation study, the AUC was 0.827, which was statistically comparable to those of previous systems. CONCLUSION: A scoring system based on only clinical information was developed to predict mortality in SJS/TEN and was validated in an independent multinational study. CRISTEN may predict individual survival probabilities and direct the management and therapy of patients with SJS/TEN.

Association of adipocytokines and adipocytokine ratios with cardiovascular risk factors in Japanese preadolescents.

OBJECTIVES: Asians are particularly susceptible to obesity-associated disorders and rapid progression of obesity from childhood to adulthood. Data on the association between adipocytokine parameters, particularly adipocytokine ratios, and cardiovascular risk factors in childhood remain limited. Herein, we assessed the association of resistin, adiponectin, and leptin levels and leptin/adiponectin and resistin/adiponectin ratios with selected cardiovascular risk factors and the influence of unhealthy weight on such associations in children aged 9-10 years. METHODS: We included 380 children aged 9-10 years from three public elementary schools in Japan. RESULTS: The body mass index (BMI) was significantly higher in male preadolescents than in female adolescents (median 16.5 kg/m2 vs. 16.2 kg/m2, p=0.032). No differences in height, weight, waist circumference (WC), waist/height ratio (W/Hr), total cholesterol and high-density lipoprotein cholesterol levels, or atherosclerosis index (AI) were observed between the sexes. Of the adipocytokine levels and ratios analyzed, only the leptin level and leptin/adiponectin ratio (L/Ar) were strongly and significantly positively correlated with the cardiovascular risk factors WC, W/Hr, and BMI (all p<0.05). The AI was not strongly correlated with any adipocytokine levels or ratios. Apart from the strong positive correlation between the L/Ar and W/Hr, no other significant associations were observed between any of the adipocytokine levels or ratios and the selected cardiovascular risk factors. CONCLUSIONS: Our findings confirmed the value of adipocytokine ratios in risk assessment in pediatric populations, with leptin levels and leptin/adiponectin ratios strongly correlating with risk factors in children aged 9-10 years.

Diagnostic accuracy of a deep learning model using YOLOv5 for detecting developmental dysplasia of the hip on radiography images.

Developmental dysplasia of the hip (DDH) is a cluster of hip development disorders and one of the most common hip diseases in infants. Hip radiography is a convenient diagnostic tool for DDH, but its diagnostic accuracy is dependent on the interpreter's level of experience. The aim of this study was to develop a deep learning model for detecting DDH. Patients younger than 12 months who underwent hip radiography between June 2009 and November 2021 were selected. Using their radiography images, transfer learning was performed to develop a deep learning model using the "You Only Look Once" v5 (YOLOv5) and single shot multi-box detector (SSD). A total of 305 anteroposterior hip radiography images (205 normal and 100 DDH hip images) were collected. Of these, 30 normal and 17 DDH hip images were used as the test dataset. The sensitivity and the specificity of our best YOLOv5 model (YOLOv5l) were 0.94 (95% confidence interval [CI] 0.73-1.00) and 0.96 (95% CI 0.89-0.99), respectively. This model also outperformed the SSD model. This is the first study to establish a model for detecting DDH using YOLOv5. Our deep learning model provides good diagnostic performance for DDH. We believe our model is a useful diagnostic assistant tool.

Lip Seal Strength and Tongue Pressure among Japanese Male Workers: Comparison of Different Age Groups.

Lip seal strength and tongue pressure are related to sarcopenia in older adults and are directly linked to the quality of life of workers after retirement. This study examined lip seal strength and tongue pressure among Japanese male workers by age. A self-administered questionnaire survey including alcohol consumption and smoking was conducted on 454 male workers. Height, weight, lip seal strength, and tongue pressure were also measured and then stratified by age (20s, 30s, 40s, 50s, and 60s and over). The mean (25th, 75th percentiles) lip seal strength and tongue pressure for all workers were 13.7 N (11.6, 16.4) and 41.7 kPa (35.2, 48.2), respectively. Both lip seal strength and tongue pressure were lowest in the 20s, at 12.1 N (9.6, 14.0) and 40.6 kPa (33.4, 47.6), respectively. The multiple regression analysis adjusted for smoking showed a significant positive association between lip seal strength and BMI for the 20s, 50s, and 60s and over, and a significant positive association between tongue pressure and BMI for the 30s, 40s, 50s, and 60s and over. To maintain oral health in older adults, it may be useful to measure workers' lip seal strength and tongue pressure and intervene at an earlier stage.

Epidemiology of Developmental Dysplasia of the Hip: Analysis of Japanese National Database.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a cluster of hip development disorders that affects infants. The incidence of DDH-related dislocation (DDH-dislocation) is reportedly 0.1-0.3%; however, the nationwide incidence of DDH-dislocation in Japan has not been previously reported. The primary aim of this study was to report the nationwide incidence of DDH-dislocation in Japan using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), and to examine its regional variation across Japan. METHODS: This was a retrospective birth cohort study using the NDB. Data on patients born between 2011 and 2013 and assigned DDH-dislocation-related disease codes during 2011-2018 were extracted. Among these, patients who underwent treatment for DDH-dislocation between 2011 and 2018 were defined as patients with DDH-dislocation. RESULTS: Across the 2011, 2012, and 2013 birth cohorts, 2,367 patients were diagnosed with DDH-dislocation, yielding the nationwide incidence of 0.076%. Region-specific incidence rates were almost similar across Japan. Secondary analyses revealed that 273 (11.5%) patients were diagnosed at the age of ≥1 year. The effect of birth during the cold months on the incidence of DDH-dislocation was significant (relative risk [RR] = 1.89, 95% confidence interval [CI]: 1.75-2.06). The risk of DDH-dislocation among girls was approximately seven times higher than that among boys. CONCLUSION: This is the first study to report the nationwide incidence of DDH-dislocation in Japan, which was estimated at 0.076%. The regional variation was trivial and unlikely to be clinically significant. Thus, the incidence rates were approximately equal across all regions in Japan.

Impact of the state of emergency on trends in the care of three major diseases at Showa University Hospital, Japan: a retrospective and descriptive study.

Introduction: This study aimed to examine the trends in patient consultations for three major diseases (cancer, heart disease, and stroke) at Showa University Hospital, Japan during the state of emergency for the Coronavirus 2019 (COVID-19) pandemic. Methods: The present study was a retrospective and descriptive study of Showa University Hospital in Tokyo, Japan. Subjects were patients who had received medical treatment at Showa University Hospital and were diagnosed from 2017 to 2020. To examine the impact of the state of emergency, the number visits to hospital by the top three causes of death or other diseases were summarised from 21 weeks of data, from week 8 to week 28, for each year. Results: Compared to the average of the previous 3 years, a comparison of the three periods before and after the state of emergency showed a V-shaped curve in 2020, with a large drop in the number of cancer patients during the state of emergency, both from within Tokyo and from outside the city. Conclusions: This study showed a long-term decrease in cancer patient visits to Showa University Hospital since the beginning of the COVID-19 pandemic compared to the previous 3 years. It is also possible that medical care that would have been available may not have been provided due to the state of emergency, so it is necessary to follow up patients while keeping a close eye on measures other than infectious diseases.

Optimal Breast Density Characterization Using a Three-Dimensional Automated Breast Densitometry System.

Dense breasts are a risk factor for breast cancer. Assessment of breast density is important and radiologist-dependent. We objectively measured mammographic density using the three-dimensional automatic mammographic density measurement device Volpara™ and examined the criteria for combined use of ultrasonography (US). Of 1227 patients who underwent primary breast cancer surgery between January 2019 and April 2021 at our hospital, 441 were included. A case series study was conducted based on patient age, diagnostic accuracy, effects of mammography (MMG) combined with US, size of invasion, and calcifications. The mean density of both breasts according to the Volpara Density Grade (VDG) was 0-3.4% in 2 patients, 3.5-7.4% in 55 patients, 7.5-15.4% in 173 patients, and ≥15.5% in 211 patients. Breast density tended to be higher in younger patients. Diagnostic accuracy of MMG tended to decrease with increasing breast density. US detection rates were not associated with VDG on MMG and were favorable at all densities. The risk of a non-detected result was high in patients without malignant suspicious calcifications. Supplementary use of US for patients without suspicious calcifications on MMG and high breast density, particularly ≥25.5%, could improve the breast cancer detection rate.

Quantification of bromide ion in biological samples using headspace gas chromatography-mass spectrometry.

OBJECTIVES: In this study, we aimed to establish a method for quantifying bromide ions (Br- ) in blood and urine using gas chromatograph-mass spectrometer (GC-MS) equipped with a headspace sampler, for biological monitoring of workers exposed to methyl bromide. METHODS: Samples were mixed with dimethyl sulfate, and Br- ions were detected using GC-MS with a headspace sampler. The validity of the proposed method was evaluated based on most of the US FDA guidance. The values obtained were compared with reference values by analysis using SeronormTM Trace Elements Whole Blood L-1 RUO. RESULTS: The calibration curve showed good linearity in the Br- concentration range of 0.1-20.0 mg/L, and the coefficient of determination R2 value was >.999. Intraday and interday accuracy values were 99.3%-103.1% and 97.4%-101.8%, respectively. The measured and reference values of Seronorm were concordant. Herein, eight urine and serum samples of workers were analyzed; the samples' Br- concentrations were known. The correlation coefficients of urine and serum samples were 0.97 and 0.96, respectively, and results were consistent. CONCLUSIONS: This study established a simple and rapid method for the determination of Br- concentration in biological samples using GC-MS with a headspace sampler. Moreover, it can be used for biological monitoring of occupational exposure to methyl bromide and for the determination of Br- concentration in a wide range of biological samples.

Predictors of resignation and sick leave after cancer diagnosis among Japanese breast cancer survivors: a cross-sectional study.

BACKGROUND: In Japan, 55.5% of breast cancer survivors (BCSs) are of working age, so various perspectives regarding return to work (RTW) after cancer diagnosis need to be considered. Therefore, this study aimed to clarify the risk factors for resignation and taking sick leave (SL) among BCSs in continued employment at the time of diagnosis. METHODS: A web-based retrospective cross-sectional survey was conducted on BCSs using data from a 2018 Japanese national research project (Endo-Han) commissioned by the Ministry of Health, Labour and Welfare of Japan. The subjects were women aged 18-69 years who had been diagnosed with breast cancer for the first time at least 1 year previously. The risk factors for resignation and taking SL after breast cancer diagnosis, including age at diagnosis, education level, cancer stage, surgery, chemotherapy, radiotherapy, employment status, and occupational type, were then analyzed using a logistic regression model. RESULTS: In total, 40 (14.9%) of 269 BCSs quit their jobs at least 1 year after being diagnosed with breast cancer. The results of the multivariable analysis indicated that lower education level (odds ratio [OR]: 3.802; 95% confidence interval [CI]: 1.233-11.729), taking SL (OR: 2.514; 95%CI: 1.202-5.261), and younger age at diagnosis (OR: 0.470; 95%CI: 0.221-0.998) were predictors of resignation. Of 229 patients who continued working, SL was taken by 72 (31.4%). In addition, undergoing surgery was found to be a predictor of taking SL (OR: 8.311; 95%CI: 1.007-68.621). CONCLUSIONS: In total, 40 (14.9%) of 269 BCSs quit their jobs at least 1 year after being diagnosed with breast cancer. The results of this study indicated that younger age, lower education level, and taking SL were predictors of resignation after breast cancer diagnosis.

Eating quickly is associated with a low aspartate aminotransferase to alanine aminotransferase ratio in middle-aged adults: a large-scale cross-sectional survey in Japan.

BACKGROUND: An elevated alanine aminotransferase (ALT) and a low aspartate aminotransferase (AST) to ALT ratio (AST/ALT ratio) suggest nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, increasing the risk of liver cirrhosis and hepatocellular carcinoma. In addition, eating quickly has been found to be associated with outcomes such as obesity. This study sought to investigate the relationship between eating quickly and an elevated ALT or a low AST/ALT ratio in Japanese middle-aged adults. METHODS: The present study included 283,073 adults aged 40-64 years who had annual health checkups in Japan from April 2013 to March 2014. The data of serum parameters and lifestyle factors, including eating speed, were analyzed. An elevated ALT was defined as > 40 U/L, and a low AST/ALT ratio was defined as < 1. Logistic regression analysis was performed to calculate the odds ratios (ORs) and the 95% confidence intervals (CIs) for an elevated ALT and a low AST/ALT ratio. RESULTS: Significantly increased ORs for an elevated ALT were observed in men (OR: 1.45, 95% CI: 1.41-1.49) and women (OR: 1.34, 95% CI: 1.25-1.43). Moreover, eating quickly significantly increased the ORs for a low AST/ALT ratio in men (OR: 1.53, 95% CI: 1.50-1.56) and women (OR: 1.36, 95% CI: 1.31-1.41). When the analysis was limited to those with ALT ≤40 U/L, eating quickly had significantly increased ORs for a low AST/ ALT ratio, regardless of sex. CONCLUSIONS: Eating quickly was significantly associated with an elevated ALT and a low AST/ALT ratio. In addition, eating quickly was significantly associated with a low AST/ALT ratio even for those without ALT elevation. This study suggested that modification of eating speed may contribute to reducing the risk for an elevated ALT and a low AST/ALT ratio.

The nationwide epidemiological survey of Stevens-Johnson syndrome and toxic epidermal necrolysis in Japan, 2016-2018.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs). The first national epidemiological survey of SJS/TEN was carried out in 2008. We conducted a new survey to identify changes from the previous survey. OBJECTIVE: The present survey aimed to estimate the number of SJS/TEN patients in Japan between 2016 and 2018 (primary survey) and to clarify clinical epidemiological profiles (secondary survey). METHODS: A primary survey asking for numbers of SJS/TEN patients during the study period was sent to 1205 institutions nationwide. A secondary survey was sent to institutions reporting SJS/TEN patients, seeking detailed information. RESULTS: Yearly prevalence per million was 2.5 for SJS and 1 for TEN. The secondary survey allowed analysis of 315 SJS cases and 174 TEN cases from 160 institutions. Mean age was 53.9 years in SJS, and 61.8 years in TEN. Mortality rate was 4.1 % for SJS and 29.9 % for TEN. In TEN, mean age and mortality rates had increased from the previous survey. The ratio of expected to observed mortality calculated by SCORTEN score was lowest with high-dose steroid therapy (0.40), followed by steroid pulse therapy (0.52). CONCLUSION: The present findings suggest that the mortality rate of TEN has increased because of increases in mean ages of patients and patients with malignant neoplasm as underlying disease. When comparing the ratio of expected mortality to actual mortality, high-dose steroid therapy achieved the greatest reduction in mortality.

Clustering of Lifestyle Factors and Its Association with Low Back Pain: A Cross-Sectional Study of Over 400,000 Japanese Adults.

PURPOSE: Although many studies have indicated the association between low back pain (LBP) and lifestyle factors, the combined effect of lifestyle factors on LBP has not been adequately investigated. We aimed to investigate the association between a cluster of unhealthy lifestyle behaviors and LBP using a large cohort of Japanese adults. METHODS: We included 419,003 adults aged over 20 years who underwent an annual health checkup between April 2013 and March 2014 in Japan. Information on the following lifestyle factors was collected using the standardized questionnaire: smoking, alcohol intake, exercise, physical activity, walking speed, weight control, eating habits, and sleep. Each factor was evaluated as a dichotomous variable (1: health risk, 0: no health risk). A lifestyle risk score was calculated by summing the score of each lifestyle factor (range: 0-12) and was categorized into three groups (low, moderate, high). LBP was defined as self-reported LBP under treatment. Logistic regression analysis was conducted to calculate the odds ratio (OR) and 95% confidence interval (CI) for LBP. RESULTS: In multivariable logistic regression analysis, the OR for LBP was significantly higher in the moderate-risk score group (adjusted OR: 1.33 [95% CI: 1.23-1.44] in men; 1.40 [95% CI: 1.27-1.54] in women) and the high-risk score group (adjusted OR: 1.54 [95% CI: 1.43-1.67] in men; 1.83 [95% CI: 1.64-2.03] in women) than in the low-risk score group. A trend of higher risk of LBP associated with higher lifestyle risk score was observed in both sexes (p for trend < 0.001). These results were similar even in subgroup analysis by age and body mass index (BMI). CONCLUSION: Clustering of unhealthy lifestyles was associated with increased risk of LBP regardless of age and BMI. These results may provide implications for better prevention and management of LBP, considering modifiable lifestyle factors.

Seven-day services in surgery and the "weekend effect" at a Japanese teaching hospital: a retrospective cohort study.

BACKGROUND: Hospitals deliver 24-h, 7-day care on a 5-day workweek model, as fewer resources are available on weekends. In prior studies, poorer outcomes have been observed with weekend admission or surgery. The purpose of this study was to investigate the effect of 7-day service at a hospital, including outpatient consultations, diagnostic examinations and elective surgeries, on the likelihood of the "weekend effect" in surgery. METHODS: This was a retrospective cohort study of patients who underwent surgery between April 2014 and October 2016 at an academic medical centre in Tokyo, Japan. The main outcome measure was 30-day in-hospital mortality from the index surgery. The characteristics of the participants were compared using the Mann-Whitney U test or the chi-squared test as appropriate. Logistic regression was used to test for differences in the mortality rate between the two groups, and propensity score adjustments were made. RESULTS: A total of 7442 surgeries were identified, of which, 1386 (19%) took place on the weekend. Of the 947 emergency surgeries, 25% (235) were performed on the weekend. The mortality following emergency weekday surgery was 21‰ (15/712), compared with 55‰ (13/235) following weekend surgery. Of the 6495 elective surgeries, 18% (1151) were performed on the weekend. The mortality following elective weekday surgery was 2.3‰ (12/5344), compared with 0.87‰ (1/1151) following weekend surgery. After adjustment, weekend surgeries were associated with an increased risk of death, especially in the emergency setting (emergency odds ratio: 2.7, 95% confidence interval: 1.2-6.5 vs. elective odds ratio: 0.4, 95% confidence interval: 0.05-3.2). CONCLUSIONS: Patients undergoing emergency surgery on the weekend had higher 30-day mortality, but showed no difference in elective surgery mortality. These findings have potential implications for health administrators and policy makers who may try to restructure the hospital workweek or consider weekend elective surgery.

Longevity-associated mitochondrial DNA 5178 C/A polymorphism modifies effect of aging on renal function in male Japanese health checkup examinees: an exploratory cross-sectional study.

BACKGROUND: Mitochondrial DNA 5178 (Mt5178) C/A polymorphism is reportedly associated with longevity in the Japanese population. The objective of this study was to investigate whether Mt5178 C/A polymorphism influences the effect of physiological aging on renal function in male Japanese health checkup examinees. METHODS: A total of 404 male subjects (mean age ± SD, 53.9 ± 7.8 years; range, 29-76 years) were selected from among individuals visiting the hospital for regular medical checkups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and aging on renal function was then conducted. Renal function was evaluated by estimated glomerular filtration rate (eGFR). Subjects were divided into three age groups (< 50, 50-59, ≥ 60 years). RESULTS: In simple linear regression analysis, a significant negative association between aging and eGFR was observed in both Mt5178C and Mt5178A genotypic men (P < 0.001 and P = 0.003, respectively). However, in multiple linear regression analysis, a significant effect of aging on reduced eGFR was observed only in Mt5178C genotypic men (P < 0.001). Logistic regression analysis showed that, in the case of reduced eGFR defined as < 75 mL/min/1.73 m2, reduced eGFR was dependent on aging in both Mt5178C and Mt5178A genotypic men (P for trend < 0.001 and P for trend = 0.002, respectively). After adjusting for smoking status and alcohol consumption, reduced eGFR was also dependent on aging in both Mt5178C and Mt5178A genotypic men (P for trend < 0.001 and P for trend = 0.014, respectively). However, in reduced eGFR defined as < 90 mL/min/1.73 m2, reduced eGFR was dependent on aging only in Mt5178C genotypic men (P for trend < 0.001). CONCLUSIONS: This cross-sectional study suggests that Mt5178 C/A polymorphism modulates the effects of physiological aging on kidney function in Japanese men.

NADH Dehydrogenase Subunit-2 237 Leu/Met Polymorphism Influences the Association of Coffee Consumption with Serum Chloride Levels in Male Japanese Health Checkup Examinees: An Exploratory Cross-Sectional Analysis.

BACKGROUND: Nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism has been shown to modify the association of coffee consumption with the risk of hypertension, dyslipidemia, and abnormal glucose tolerance, and low serum chloride levels have been shown to be associated with all-cause and cardiovascular disease mortality. Therefore, the purpose of the present study was to investigate whether ND2-237 Leu/Met polymorphism influences the association of coffee consumption with serum chloride levels in male Japanese health checkup examinees. METHODS: From among individuals visiting the hospital for a regular medical checkup, 402 men (mean age ± standard deviation, 53.9 ± 7.8 years) were selected for inclusion in the study. After ND2-237 Leu/Met genotyping, we conducted an exploratory cross-sectional study to examine the combined association of ND2-237 Leu/Met polymorphism and coffee consumption with serum electrolyte levels. RESULTS: After adjusting for age, body mass index, habitual smoking, alcohol consumption, green tea consumption, and antihypertensive medication, coffee consumption significantly increased serum chloride levels (p for trend = 0.001) in men with the ND2-237Leu genotype. After these adjustments, the odds ratios (ORs) for low levels of serum chloride, defined as <100 mEq/L, were found to be dependent on coffee consumption (p for trend = 0.001). In addition, the OR for low levels of serum chloride was significantly lower in men with the ND2-237Leu genotype who consumed ≥4 compared with <1 cup of coffee per day (OR = 0.096, 95% confidence interval = 0.010⁻0.934; p = 0.044). However, neither serum chloride levels nor risk of low levels of serum chloride appeared to be dependent on coffee consumption. CONCLUSIONS: The results suggest that ND2-237 Leu/Met polymorphism modifies the association of coffee consumption with serum chloride levels in middle-aged Japanese men.

Mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on elevated levels of serum liver enzymes in male Japanese health check-up examinees: an exploratory cross-sectional study.

BACKGROUND: Longevity-associated mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia, and abnormal glucose tolerance. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees. METHODS: A total of 421 male subjects (mean age ± SD, 54.1 ± 7.7 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on elevated levels of serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and serum gamma-glutamyl transpeptidase (GGT) was then conducted. RESULTS: For men with Mt5178C, after adjustment for age, body mass index, alcohol consumption, habitual smoking, green tea consumption, antihypertensive treatment, and antidiabetic treatment, elevated levels of serum AST, as defined as ≥30 U/L; those of serum ALT, as defined as ≥25 U/L; or those of serum GGT, as defined as ≥60 or >51 U/L, may depend on coffee consumption (P for trend = 0.013, P for trend <0.001, P for trend = 0.002, and P for trend <0.001, respectively). On the other hand, no significant joint effects of Mt5178A genotype and coffee consumption on elevated levels of serum liver enzymes were observed. CONCLUSIONS: The present results suggest that Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees.

Dietary patterns and serum gamma-glutamyl transferase in Japanese men and women.

BACKGROUND: Although specific foods and nutrients have been examined as potential determinants of serum gamma-glutamyl transferase (GGT) concentrations, the relationship between dietary patterns and GGT remains unknown. The present cross-sectional study aimed to determine relationships between dietary patterns and GGT concentrations, and the effects of lifestyle factors on GGT. METHODS: Relationships between dietary patterns and GGT were analyzed in 9803 Japanese individuals (3723 men and 6080 women age 40-69 years) without a history of liver diseases or elevated serum aminotransferase. We examined major dietary patterns by factor analysis of 46 items determined from a validated, short food frequency questionnaire. RESULTS: We defined dietary patterns as healthy, Western, seafood, bread, and dessert. The healthy pattern was inversely related to GGT in men (odds ratio [OR] for highest vs lowest quartile, 0.72; 95% confidence interval [CI], 0.57-0.92; P < 0.01 for trend) and women (OR 0.82; 95% CI, 0.66-1.0; P = 0.05 for trend), whereas the seafood pattern was positively related to GGT in men (OR 1.27; 95% CI, 1.01-1.61; P = 0.03 for trend) and women (OR 1.21; 95% CI, 0.98-1.49; P = 0.05 for trend). Male-specific inverse associations with GGT were found for bread and dessert patterns (OR 0.63; 95% CI, 0.50-0.80 and OR 0.53; 95% CI, 0.41-0.68, respectively; P < 0.01 for both trends). Seafood or bread patterns and alcohol consumption significantly interacted with GGT in men (P = 0.03 and <0.01 for interaction, respectively) and between the dessert pattern and body mass index or smoking habit in women (P = 0.03 and <0.01, respectively, for interaction). CONCLUSIONS: Dietary patterns may be important determinants of GGT, and their possible clinical implications warrant further investigation.

Longevity-associated mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters in Japanese men: an exploratory cross-sectional analysis.

BACKGROUND: Mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism reportedly modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia and abnormal glucose tolerance. The objective of this analysis was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on erythrocytic parameters in male Japanese health check-up examinees. METHODS: A total of 436 men (mean age ± standard deviation, 54.1 ± 7.8 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, an exploratory cross-sectional analysis assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on red blood cell counts, hematocrit and hemoglobin was conducted. RESULTS: For Mt5178C genotypic men, after adjustment for age, body mass index, alcohol consumption, habitual smoking and green tea consumption, coffee consumption significantly decreased red blood cell counts (P for trend = 0.022) and hemoglobin (P for trend = 0.035). The risk of anemia, defined as hemoglobin of <14 g/dL, after the aforementioned adjustment, appeared to depend on coffee consumption (P for trend = 0.078), and the adjusted odds ratio for anemia was significantly higher in men who consumed ≥4 cups of coffee per day than in those who consumed <1 cup per day (odds ratio = 3.771, 95% confidence interval: 1.088 to 13.06, P = 0.036). For Mt5178A genotypic men, coffee consumption possibly reduced the risk of anemia (P for trend = 0.049). However, after the aforementioned adjustment, the statistical significance disappeared (P for trend = 0.137). CONCLUSIONS: This exploratory cross-sectional analysis suggests that Mt5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters and the risk of anemia in male Japanese health check-up examinees.

NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modifies effects of cigarette smoking on risk of elevated levels of serum liver enzyme in male Japanese health check-up examinees: a cross-sectional study.

BACKGROUND: NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism reportedly influences the effects of cigarette smoking on respiratory function, risk of dyslipidemia, serum non-high-density lipoprotein cholesterol levels, hematological parameters and intraocular pressure. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of cigarette smoking on serum liver enzyme levels in male Japanese health check-up examinees. METHODS: A total of 421 male subjects (mean age ± SD, 54.1 ± 7.7 years) were selected from among individuals visiting the hospital for regular medical check-ups. After ND2-237 Leu/Met genotyping, a cross-sectional study assessing the combined effects of ND2-237 Leu/Met polymorphism and cigarette smoking on serum aspartate aminotransferase levels, serum alanine aminotransferase (ALT) levels and serum gamma-glutamyltransferase (GGT) levels was then conducted. RESULTS: No statistically significant differences in serum liver enzyme levels among the three smoking status groups (never- or ex-smokers, 1-20 cigarettes smoked per day and >20 cigarettes smoked per day) by ND2-237 Leu/Met genotype were observed. However, for men with ND2-237Met, cigarette smoking significantly increased the risk of elevated levels of serum ALT (>30 U/L) or serum GGT (≥60 U/L or >51 U/L) (P for trend = 0.031, P for trend = 0.007 and P for trend = 0.004, respectively). After adjustment for age, body mass index, alcohol consumption, coffee consumption, antihypertensive treatment and antidiabetic treatment, a significant association between cigarette smoking and risk of elevated levels of serum ALT (>30 U/L) or serum GGT (≥60 U/L or >51 U/L) was also observed (P for trend = 0.032, P for trend = 0.019 and P for trend = 0.009, respectively). Surprisingly, for men with ND2-237Leu, cigarette smoking significantly decreased the risk of elevated levels of serum ALT (>30 U/L or ≥25 U/L) (P for trend = 0.026 and P for trend = 0.003, respectively). CONCLUSIONS: Cigarette smoking appears to increase the risk of elevated levels of serum ALT or serum GGT in ND2-237Met genotypic men, but to decrease the risk of elevated levels of serum ALT in ND2-237Leu genotypic men.