Hashimoto Thyroiditis and Mortality in Patients with Differentiated Thyroid Cancer: The National Epidemiologic Survey of Thyroid Cancer in Korea and Meta-Analysis.

BACKGRUOUND: Many studies have shown that Hashimoto's thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC. METHODS: This study included two types of research. RESULTS: retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies. RESULTS: Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT. CONCLUSION: This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.

Association between environmental cadmium exposure and increased mortality in the U.S. National Health and Nutrition Examination Survey (1999-2018).

BACKGROUND: Cadmium (Cd) is toxic to human health and increases overall mortality. In this study, we investigated the association between Cd exposure and all-cause, cardiovascular (CVD), and cancer mortality in the general population and the mediating effect of smoking on these association. METHODS: We used data from U.S. National Health and Nutrition Examination Survey for 1999-2018. To evaluate the hazard ratio (HR) for mortality, a multiple Cox regression analysis was conducted by adjusting for age, sex, race/ethnicity, body mass index, smoking, alcohol, hypertension, diabetes, hyperlipidemia, and history of CVD and cancer. A causal mediation analysis was performed to estimate the effects of smoking. RESULTS: Among the 31,637 subjects, 5452 (12.3%) died. Blood Cd concentrations were significantly associated with all-cause (HR 1.473, 95% confidence interval [CI] 1.403-1.546, p < 0.001), CVD (HR 1.445, 95% CI 1.344-1.554, p < 0.001), and cancer (HR 1.496, 95% CI 1.406-1.592, p < 0.001) mortality. Urinary Cd concentrations were also significantly associated with them. Using feature selection via machine learning, the importance of Cd in all-cause and cancer mortality was second only to age. The association between Cd concentrations and all-cause mortality was significant in both ever-smokers and never-smokers. The mediating effect of smoking was estimated at 32%, whereas a large proportion (68%) remained a direct effect of Cd. In a subgroup analysis of subjects with cancer history, blood Cd concentrations were significantly associated with cancer-related deaths in those with a history of breast, gastrointestinal, and skin cancers. CONCLUSION: High Cd exposure is an important risk factor for all-cause, CVD, and cancer mortality among the general population. Cd exposure increased the risk of death even in never-smokers, and its effects unrelated to smoking were substantial, suggesting the importance of regulating other sources of Cd exposure such as food and water. IMPACT STATEMENT: Using national large-scale data, we found that low-level environmental exposure to cadmium significantly increased the risk of all-cause, cardiovascular, and cancer mortality in the general population even after adjusting for several risk factors. Although smoking is a major source of cadmium exposure, cadmium was nevertheless significantly associated with all-cause mortality in never-smokers, and the mediating effect of smoking on this association was only 32%. Hence, other sources of cadmium exposure such as food and water may be important.

Smoking and passive smoking increases mortality through mediation effect of cadmium exposure in the United States.

Cigarette smoking is one of the leading causes of preventable and premature death worldwide. Even worse, many people are generally exposed to passive smoking, which leads to several respiratory diseases and related mortalities. Considering, more than 7000 compounds are included in cigarettes, their combustion results intoxicants that have deleterious effects on health. However, there is a lack of research analyzing the effects of smoking and passive smoking on all-cause and disease-specific mortality through its chemical compounds including heavy metals. Thus, this study aimed to evaluate the effect of smoking and passive smoking on all-cause and disease-specific mortality mediated by cadmium, one of the representative smoking-related heavy metals using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 in the United States. We found that current smoking and passive smoking was related to increased risk of all-cause, CVD-related, and cancer-related mortality. Notably, passive smoking showed a synergistic effect with smoking status on the risk of mortality. In particular, current smokers with passive smoking had the highest risk of all-cause and disease-specific deaths. In addition, the accumulation of cadmium in the blood due to smoking and passive smoking mediates the increased risk of all-cause mortality. Further studies are needed to monitor and treat cadmium toxicity to improve smoking-related mortality rates.

A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice. METHODS: In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled. RESULTS: Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42. CONCLUSION: Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.

Framingham Risk Score Assessment in Subjects with Pre-diabetes and Diabetes: A Cross-Sectional Study in Korea.

BACKGROUND: This study aimed to evaluate cardiovascular risk in subjects with pre-diabetes and diabetes in Korea. METHODS: In this pan-Korean, non-interventional, cross-sectional study, data were collected from medical records of 10 hospitals between November 2013 and June 2014. Subjects (aged ≥40 years) with medical records of dysglycemia and documentation of total cholesterol level, high-density lipoprotein cholesterol level, systolic blood pressure, and smoking status in the past 6 months were included. The primary endpoint was to determine the Framingham risk score (FRS). The relationships between FRS and cardiovascular risk factors, glycated hemoglobin, and insulin usage were determined by multiple linear regression analyses. RESULTS: Data from 1,537 subjects with pre-diabetes (n=1,025) and diabetes (n=512) were analyzed. The mean FRS (mean±standard deviation) in subjects with pre-diabetes/diabetes was 13.72±8.77. FRS was higher in subjects with diabetes than pre-diabetes (P<0.001). FRS in men with pre-diabetes was comparable to that in women with diabetes (13.80±7.37 vs. 13.35±7.13). FRS was elevated in subjects who consumed alcohol (2.66, P=0.033) and with obesity-class II (6.10, P=0.015) among subjects with diabetes (n=199), and was elevated in patients with left ventricular hypertrophy (11.10, P=0.005), those who consumed alcohol (3.06, P=0.000), were pre-obese (3.21, P=0.002), or were obesity-class I (2.89, P=0.002) among subjects with pre-diabetes (n=306) in comparison to subjects without these coexisting risk factors. CONCLUSION: Overall, Korean subjects with pre-diabetes and diabetes have an increased cardiovascular risk, which is significantly higher in those subjects with diabetes than with pre-diabetes. The present data can be used to develop measures to prevent and manage cardiovascular complications in Koreans with impaired glucose metabolism.

Association of nocturia and cardiovascular disease: Data from the National Health and Nutrition Examination Survey.

AIMS: To investigate the association of nocturia with the prevalence of cardiovascular disease (CVD) using the National Health and Nutrition Examination Survey (NHANES) data. METHODS: Among the 40 790 individuals who participated in NHANES from 2005 to 2012, 14 114 adults were analyzed in this study. A participant was considered to have nocturia if they have two or more voiding episodes nightly. In addition, participants with nocturia more than four times in a day were considered to have severe nocturia. A multivariate logistic regression analysis with adjustment for confounding variables, including age, sex, race, body mass index (BMI), smoking status, alcohol consumption, sleeping time, dyslipidemia, hypertension, and diabetes mellitus was performed with 1:1 propensity score matching (PSM). RESULTS: Nocturia occurred in 4610 individuals (32.7%). The prevalence of CVD was significantly higher in men, older individuals, those with higher BMI, smokers, and those with diabetes, hypertension, and hyperlipidemia. There was also a significantly higher prevalence of nocturia in the participants with CVD. Multivariate analysis showed that odds ratios (ORs) of mild and severe nocturia for CVD were 1.23 (95% confidence interval [CI]: 1.08-1.39) and 1.74 (95% CI: 1.39-2.17), respectively. After 1:1 PSM, the ORs of mild and severe nocturia were 1.27 (95% CI: 1.10-1.48) and 1.73 (95% CI: 1.33-2.26), respectively, showing statistical significance. CONCLUSION: Data from the NHANES indicate that CVD was significantly associated with the prevalence of nocturia, after taking major confounding factors into account. Furthermore, the risk for CVD increases with increasing nocturia severity.

Z-score of the log-transformed A Body Shape Index predicts low muscle mass in population with abdominal obesity: The U.S. and Korea National Health and Nutrition Examination Survey.

BACKGROUND AND OBJECTIVE: Sarcopenic obesity is associated with a higher risk of cardiometabolic disease and mortality than either sarcopenia or obesity alone. However, no study has investigated body shape indices for the assessment of sarcopenia in obese populations. Thus, this study aimed to evaluate the accuracy of body shape indices to assess sarcopenia in nationally representative populations with abdominal obesity. METHODS: Data from the U.S. National Health and Nutrition Examination Survey (U.S. NHANES) 1999-2006 and Korea NHANES (KNHANES) 2008-2011 were assessed. The association between Body Shape Index and sarcopenia was analyzed using a receiver operating characteristic curve. The Z-score of the log-transformed A Body Shape Index (LBSIZ) cut-off value was defined as that with the highest score of the Youden's index. Changes in odds ratios (OR) for sarcopenia were investigated using restricted cubic spline (RCS) plots. RESULTS: This study included 8,013 American and 4,859 Korean adults with abdominal obesity. The overall area under the curve (AUC) of LBSIZ for sarcopenia was 0.816 (95% CI: 0.794-0.838) in U.S. NHANES and 0.822 (95% CI: 0.799-0.844) in KNHANES, which was higher than that of the body roundness index, conicity index, and waist to height ratio (p with DeLong's test <0.001). The cut-off values for the LBSIZ were 1.05 (sensitivity, 88.0%; specificity, 81.5%) for American men, 0.45 (sensitivity, 77.1%; specificity, 70.6%) for American women, 1.15 (sensitivity, 77.5%; specificity, 77.1%) for Korean men and 0.95 (sensitivity, 74.3%; specificity, 69.3%) for Korean women in the development groups. Comparable results were verified in validation groups. The RCS plot indicated that ORs for sarcopenia rapidly increased with an increase in the LBSIZ cut-off value. CONCLUSION: The increased LBSIZ could function as a reliable and cost-effective screening tool for assessing low muscle mass in populations with abdominal obesity.

Effect of body shape on the development of cardiovascular disease in individuals with metabolically healthy obesity.

Studies about the effects of metabolically healthy obesity on cardiovascular disease (CVD) have yielded conflicting results. These heterogeneous results could be due to the limited usefulness of BMI in measuring general adiposity, as body mass index (BMI) does not accurately reflect body composition. This study aimed to evaluate the effect of body shape on CVD outcomes across different obesity phenotypes, and to provide an explanation for the heterogeneous effects of metabolically healthy obese (MHO) phenotype on CVD.We analyzed data from the Korean Genome and Epidemiology Study, a population-based cohort study conducted between 2001 and 2012. We divided the participants into 4 groups: metabolically healthy non-obese (MHNO), MHO, metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). To assess body shape, we calculated the z-score of the log-transformed a body shape index (LBSIZ). We computed Pearson correlation coefficients to examine the association of LBSIZ with muscle mass index, percentage of total fat mass (%Total FM), and percentage of abdominal fat mass (%Abdominal FM). We also used Cox proportional hazards regression to evaluate the effect of LBSIZ on CVD events according to the obesity phenotypes.A total of 9460 participants were assessed in this study. The incidence of CVD was 8.53 cases per 1000 person-year. LBSIZ showed strong positive correlation with %Total FM and %Abdominal FM, but negative correlation with muscle mass index. In Cox regression, MHO individuals did not show increased risk of CVD compared with MHNO individuals (hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.96-1.73). However, MHO individuals in the 3rd (HR, 2.40; 95% CI, 1.28-4.51) and 4th (HR, 3.67; 95% CI, 1.99-6.74) quarters of LBSIZ showed significantly higher risk of CVD compared with MHNO individuals in the 1st quarter of LBSIZ. Moreover, LBSIZ showed a linear relationship with CVD among MHO individuals.While the MHO individuals showed similar CVD risk to the MHNO individuals, CVD risk increases with LBSIZ among the MHO individuals. LBSIZ appears to be a useful measure for CVD risk assessment in clinical practice and epidemiologic studies, especially for MHO patients.

Associations between Hashimoto Thyroiditis and Clinical Outcomes of Papillary Thyroid Cancer: A Meta-Analysis of Observational Studies.

BACKGROUND: Epidemiological studies have suggested an association between Hashimoto thyroiditis (HT) and papillary thyroid cancer (PTC) development. Other studies, however, have reported a protective role of HT against PTC progression. Through this updated meta-analysis, we aimed to clarify the effects of HT on the progression of PTC. METHODS: We searched citation databases, including PubMed and Embase, for relevant studies from inception to September 2017. From these studies, we calculated the pooled odds ratios (ORs) of clinicopathologic features and the relative risk (RR) of PTC recurrence with 95% confidence intervals (CIs) using the Mantel-Haenszel method. Additionally, the Higgins I² statistic was used to test for heterogeneity. RESULTS: The meta-analysis included 71 published studies with 44,034 participants, among whom 11,132 had HT. We observed negative associations between PTC with comorbid HT and extrathyroidal extension (OR, 0.74; 95% CI, 0.68 to 0.81), lymph node metastasis (OR, 0.82; 95% CI, 0.72 to 0.94), distant metastasis (OR, 0.49; 95% CI, 0.32 to 0.76), and recurrence (RR, 0.50; 95% CI, 0.41 to 0.61). CONCLUSION: In this meta-analysis, PTC patients with HT appeared to exhibit more favorable clinicopathologic characteristics and a better prognosis than those without HT.

Association between diabetes mellitus and hearing impairment in American and Korean populations.

AIMS: The aim of this study was to evaluate ethnic- and sex-specific associations between DM and hearing impairment. METHODS: For this cross-sectional study using National Health and Nutrition Examination Survey in the U.S. and Korea, the total number of eligible participants included was 7081 in the U.S. and 15,704 in Korea. Hearing impairment was defined as a pure tone threshold level ≥ 25 dB. Multivariate logistic regression analysis was conducted, adjusting for age, sex, race/ethnicity, socioeconomic status, body mass index, noise exposure, smoking, hypertension, and dyslipidemia. RESULTS: The association between DM and hearing impairment was found to be sex-specific. The multivariate adjusted ORs of high-frequency impairment were 0.843 (95% CI, 0.524-1.356) in American men, and 1.073 (95% CI, 0.835-1.379) in Korean men, while the ORs in women from U.S. and Korea were 1.911 (95% CI, 1.244-2.935) and 1.421 (95% CI, 1.103-1.830), respectively. A subgroup analysis of each race/ethnicity among the U.S. adults showed similar results. In contrast to high-frequency impairment, there was no significant association between low-frequency impairment and DM in both men and women. CONCLUSION: Our results suggest that DM is associated with hearing impairment in only women, irrespective of race/ethnicity groups.

Association of Z-Score of the Log-Transformed A Body Shape Index with Cardiovascular Disease in People Who Are Obese but Metabolically Healthy: The Korea National Health and Nutrition Examination Survey 2007-2010.

BACKGROUND: We aimed at evaluating the effect of the z-score of the log-transformed A Body Shape Index (LBSIZ) on cardiovascular disease (CVD) outcomes according to obesity phenotype. METHODS: Data were collected from the Korea National Health and Nutrition Examination Survey conducted from 2007 to 2010. Obesity was defined as a body mass index above 25 kg/m2 and metabolic abnormality was defined as the presence of two or more metabolic risk factors of the Adult Treatment Panel III definition. The participants were classified by obesity and metabolic healthy status: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Each group was further classified into three groups based on the tertile of LBSIZ. A multivariate logistic regression analysis with adjustment for age, sex, smoking status, income, education level, physical activities, alcohol, and energy intake was conducted to evaluate the odds ratio (OR) for CVD events. RESULTS: In the multivariate logistic regression model, MHO participants who are within the third tertile of LBSIZ had a significantly higher OR for CVD events, whereas those who are within the first and second tertile of LBSIZ were not at high risk of developing CVDs compared to MHNO participants who are within the first tertile of LBSIZ. In addition, a similar increase in the OR was observed in MUNO or MUO participants. CONCLUSION: LBSIZ had the lowest risk for CVDs in the first tertile of LBSIZ and a linear relationship with all its tertiles in MHO, MUNO, and MUO participants.

The influence of physical activity on risk of cardiovascular disease in people who are obese but metabolically healthy.

The metabolic outcomes of metabolically healthy obesity (MHO) remain controversial. The aim of the present study was to determine the effect of physical activity on the cardiovascular disease (CVD) outcomes of MHO. The study included participants who were followed for 10 years and recruited from the Korean Genome and Epidemiology Study (KoGES), a population-based cohort study. Participants with previously recorded CVDs or cancer, or who had received steroids or anticoagulants at baseline were excluded. A total of 8144 participants (3,942 men and 4,202 women) fulfilled inclusion criteria. In a multivariate Cox regression model adjusted for age and sex, MHO participants were not at elevated risk of CVD compared with their metabolically healthy non-obese (MHNO) counterparts (HR, 1.28; 95% CI, 0.96-1.71), although both the non-obese (HR, 1.50; 95% CI, 1.19-1.90) and obese (HR, 1.85; 95% CI, 1.48-2.30) participants with metabolic abnormalities were at elevated risk. However, in the subgroup analysis by physical activity, physically inactive MHO participants had a significantly higher HR for CVD events compared to active MHNO participants (HR, 1.54; 95% CI, 1.03-2.30), while active MHO participants were not at elevated risk (HR, 1.15; 95% CI, 0.70-1.89). Physically inactive MHO participants had significantly increased risk of CVD compared to physically active MHNO participants whereas physically active MHO participants did not.

Anti-Proliferative Effects of Rutin on OLETF Rat Vascular Smooth Muscle Cells Stimulated by Glucose Variability.

PURPOSE: Proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in atherosclerosis. Rutin is a major representative of the flavonol subclass of flavonoids and has various pharmacological activities. Currently, data are lacking regarding its effects on VSMC proliferation induced by intermittent hyperglycemia. Here, we demonstrate the effects of rutin on VSMC proliferation and migration according to fluctuating glucose levels. MATERIALS AND METHODS: Primary cultures of male Otsuka Long-Evans Tokushima Fatty (OLETF) rat VSMCs were obtained from enzymatically dissociated rat thoracic aortas. VSMCs were incubated for 72 h with alternating normal (5.5 mmol/L) and high (25.0 mmol/L) glucose media every 12 h. Proliferation and migration of VSMCs, the proliferative molecular pathway [including p44/42 mitogen-activated protein kinases (MAPK), mitogen-activated protein kinase kinase 1/2 (MEK1/2), p38 MAPK, phosphoinositide 3-kinase (PI3K), c-Jun N-terminal protein kinase (JNK), nuclear factor kappa B (NF-κB), and Akt], the migratory pathway (big MAPK 1, BMK1), reactive oxygen species (ROS), and apoptotic pathway were analyzed. RESULTS: We found enhanced proliferation and migration of VSMCs when cells were incubated in intermittent high glucose conditions, compared to normal glucose. These effects were lowered upon rutin treatment. Intermittent treatment with high glucose for 72 h increased the expression of phospho-p44/42 MAPK (extracellular signal regulated kinase 1/2, ERK1/2), phospho-MEK1/2, phospho-PI3K, phospho-NF-κB, phospho-BMK1, and ROS, compared to treatment with normal glucose. These effects were suppressed by rutin. Phospho-p38 MAPK, phospho-Akt, JNK, and apoptotic pathways [B-cell lymphoma (Bcl)-xL, Bcl-2, phospho-Bad, and caspase-3] were not affected by fluctuations in glucose levels. CONCLUSION: Fluctuating glucose levels increased proliferation and migration of OLETF rat VSMCs via MAPK (ERK1/2), BMK1, PI3K, and NF-κB pathways. These effects were inhibited by the antioxidant rutin.

Risk score for postoperative complications in thoracic surgery.

BACKGROUND: Risk scoring system for thoracic surgery patients have not been widely used, as of recently. We tried to forge a risk scoring system that predicts the risk of postoperative complications in patients undergoing major thoracic surgery. We used a prolonged ICU stay as a representative of postoperative complications and tested various possible risk factors for its relation. METHODS: Data from all patients who underwent major lung and esophageal cancer surgeries, between 2005 and 2007 in our hospital, were collected retrospectively (n = 858). Multiple logistic regression analysis was performed with various possible risk factors to build the risk scoring system for prolonged ICU stay (> 3 days). RESULTS: A total of 9% of patients exhibited more than 3 days of ICU stay. Age, operation name, preoperative lung injury, no epidural analgesia, and predicted post operative forced expiratory volume in 1 second (ppoFEV1) were the risk factors for prolonged ICU stay, by multivariable analysis (P < 0.05). Risk score, p was derived from the formula: logit(p/[1-p]) = -5.39 + 0.06 × age + 1.12 × operation name(2) + 1.52 × operation name(3) + 1.32 × operation name(4) + 1.56 × operation name(5) + 1.30 × preoperative lung injury + 0.72 × no epidural analgesia - 0.02 × ppoFEV1 [Age in years, operation name(2): pneumonectomy, operation name(3): esophageal cancer operation, operation name(4): completion pneumonectomy, operation name(5): extended operation, preoperative lung injury(+), epidural analgesia(-), ppoFEV1 in %]. CONCLUSIONS: Age, operation name, preoperative lung injury, epidural analgesia, and ppoFEV1 can predict postoperative morbidity in thoracic surgery patients.