Predictive factors of lymph node metastasis in papillary thyroid cancer.

This study aimed to evaluate factors that predict lymph node metastasis (LNM) in papillary thyroid cancer (PTC). This retrospective cross-sectional study compared the demographic, clinical, and ultrasonographic findings of patients with PTC with and without LNM. Subgroup analysis was conducted for micro-PTCs (<1 cm). Among total (n = 512; mean age, 47.3 ± 12.7 years) and micro-PTC patients (n = 312), 35.7% and 19.6% had LNM, respectively. Younger age, male sex, tumor size, bilaterality, and suspicious ultrasound features of the tumor were associated with LNM. In multiple logistic regression analysis, among all patients, age, tumor size, and extrathyroidal extension were independent risk factors for LNM (all p<0.05). In the micro-PTC subgroup, age, extrathyroidal extension, bilaterality of tumor, and presence of autoimmune thyroid disease were independent risk and protective factors for LNM (all p<0.05). In the receiver operating characteristic analysis, the accuracy of the multivariable logistic regression model for predicting LNM among all patients and micro-PTC was acceptable (area under the curve = 0.729 and 0.733, respectively). Age, sex, tumor size, and extrathyroidal extension can assist in predicting LNM in PTC patients. Additionally, the bilaterality of tumors and presence of autoimmune thyroid disease can assist in predicting LNM in micro-PTCs.

Association between the Diabetes Drug Cost and Cardiovascular Events and Death in Korea: A National Health Insurance Service Database Analysis.

BACKGRUOUND: This study aimed to investigate the long-term effects of diabetes drug costs on cardiovascular (CV) events and death. METHODS: This retrospective observational study used data from 2009 to 2018 from the National Health Insurance in Korea. Among the patients with type 2 diabetes, those taking antidiabetic drugs and who did not have CV events until 2009 were included. Patients were divided into quartiles (Q1 [lowest]-4 [highest]) according to the 2009 diabetes drug cost. In addition, the 10-year incidences of CV events (non-fatal myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization) and CV death (death due to CV events) were analyzed. RESULTS: A total of 441,914 participants were enrolled (median age, 60 years; men, 57%). CV events and death occurred in 28.1% and 8.36% of the patients, respectively. The 10-year incidences of CV events and deaths increased from Q1 to 4. After adjusting for sex, age, income, type of diabetes drugs, comorbidities, and smoking and drinking status, the risk of CV events significantly increased according to the sequential order of the cost quartiles. In contrast, the risk of CV death showed a U-shaped pattern, which was the lowest in Q3 (hazard ratio [HR], 0.953; 95% confidence interval [CI], 0.913 to 0.995) and the highest in Q4 (HR, 1.266; 95% CI, 1.213 to 1.321). CONCLUSION: Diabetes drug expenditure affects 10-year CV events and mortality. Therefore, affording an appropriate diabetes drug cost at a similar risk of CV is an independent protective factor against CV death.

The sex-specific effects of blood lead, mercury, and cadmium levels on hepatic steatosis and fibrosis: Korean nationwide cross-sectional study.

AIM: The potential effects of heavy metals on non-alcoholic fatty liver disease (NAFLD) remain unknown. We investigated the sex-specific relationships of blood lead (BPb), mercury (BHg), and cadmium (BCd) levels with hepatic steatosis (HS) and fibrosis (HF). METHOD: We included 4420 participants from the 2016-2017 Korea National Health and Nutrition Examination Survey. High-risk alcoholics and patients with chronic hepatitis B or C infections or liver cirrhosis were excluded. We calculated the hepatic steatosis index (HSI) and fibrosis-4 index (FIB-4) values; we defined the presence of HS and HF as an HSI ≥ 36 and FIB-4 score >2.67, respectively. We adjusted for age, smoking and alcohol consumption statuses, hypertension, obesity, diabetes, hypertriglyceridemia, and BPb, BHg, and BCd levels. RESULT: In males (n = 1860), the HSI was correlated negatively with the BPb level and positively with the BHg level (both p < 0.01). The FIB-4 score was correlated positively with the BPb and BCd levels (both p < 0.01). In females (n = 2560), the HSI and FIB-4 score were correlated positively with the BPb, BHg, and BCd levels (all p < 0.01). After adjustments, the BHg level increased the risk of HS in both males (OR = 1.065, p = 0.003) and females (OR = 1.061, p = 0.048), and the BCd level increased the risk of HF in females (OR = 1.668, p = 0.012). CONCLUSION: Blood heavy metal levels were generally correlated positively with the HSI and FIB4 score, more so in females than males. The BHg level was associated with HS in males and females, and the BCd level was associated with HF in females. Further studies on NAFLD progression according to heavy metal status and sex are warranted.

Risk factors affecting amputation in diabetic foot.

BACKGROUND: A diabetic foot is the most common cause of non-traumatic lower extremity amputations (LEA). The study seeks to assess the risk factors of amputation in patients with diabetic foot ulcers (DFU). METHODS: The study was conducted on 351 patients with DFUs from January 2010 to December 2018. Their demographic characteristics, disease history, laboratory data, ankle-brachial index, Wagner classification, osteomyelitis, sarcopenia index, and ulcer sizes were considered as variables to predict outcome. A chi-square test and multivariate logistic regression analysis were performed to test the relationship of the data gathered. Additionally, the subjects were divided into two groups based on their amputation surgery. RESULTS: Out of the 351 subjects, 170 required LEA. The mean age of the subjects was 61 years and the mean duration of diabetes was 15 years; there was no significant difference between the two groups in terms of these averages. Osteomyelitis (hazard ratio [HR], 6.164; 95% confidence interval [CI], 3.561-10.671), lesion on percutaneous transluminal angioplasty (HR, 2.494; 95% CI, 1.087-5.721), estimated glomerular filtration rate (eGFR; HR, 0.99; 95% CI, 0.981-0.999), ulcer size (HR, 1.247; 95% CI, 1.107-1.405), and forefoot ulcer location (HR, 2.475; 95% CI, 0.224-0.73) were associated with risk of amputation. CONCLUSION: Osteomyelitis, peripheral artery disease, chronic kidney disease, ulcer size, and forefoot ulcer location were risk factors for amputation in diabetic foot patients. Further investigation would contribute to the establishment of a diabetic foot risk stratification system for Koreans, allowing for optimal individualized treatment.

Sex-specific effects of blood cadmium on thyroid hormones and thyroid function status: Korean nationwide cross-sectional study.

Previous studies on blood cadmium (BCd) and changes in thyroid hormone levels are controversial. We investigated whether thyroid hormone levels and thyroid function status were associated with BCd according to sex in the Korean population. Our study included 1972 participants based on the 2013 Korea National Health and Nutrition Examination Survey (KNHANES) data. Participants whose thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels were altered physiologically or medically were excluded. Changes in TSH, fT4, and anti-thyroid peroxidase antibody (TPOAb) in men and women were analyzed by different characteristics: age, body mass index (BMI), smoking status, drinking status, BCd, and urine iodine-to-creatinine ratio (UI/Cre). Thyroid function status was classified as hypothyroidism, euthyroidism, and hyperthyroidism as defined by TSH and fT4 levels. Among the total participants, there was a negative correlation between BCd and fT4 (r=-0.067, p = 0.003). In men (n = 1057), fT4 levels decreased with increasing BCd quartile (p-for-trend = 0.002). After adjustment for age, BMI, smoking status, UI/Cre, and TPOAb, the association between BCd and hypothyroidism was significant in men (odds ratio = 1.813, p = 0.032) but not in women. These results suggest that cadmium accumulation is closely associated with thyroid dysfunction, and there is a difference in metabolic capacity according to sex.

Serum cystatin C is associated with subclinical atherosclerosis in patients with type 2 diabetes: A retrospective study.

BACKGROUND: The aim of this study was to investigate the association between the serum cystatin C level and cardiovascular disease risk in patients with type 2 diabetes mellitus. METHODS: We studied 523 patients with type 2 diabetes mellitus and calculated estimated 10-year risk of atherosclerotic cardiovascular disease (%). Subclinical atherosclerosis was defined as brachial-ankle pulse wave velocity ⩾1700 ms, indicating the presence of arterial stiffness. RESULTS: Cystatin C level was significantly higher in the subclinical atherosclerosis group (brachial-ankle pulse wave velocity ⩾ 1700 ms) than in the non-subclinical atherosclerosis group (brachial-ankle pulse wave velocity < 1700 ms) (7.54 ± 3.15 mg/L vs 10.04 ± 5.12 mg/L, p < 0.001). Subclinical atherosclerosis was mainly determined by age, duration of diabetes and cystatin C level, but not by serum creatinine, 10-year risk of atherosclerotic cardiovascular disease score and estimated glomerular filtration rate in the multiple linear regression analysis. In addition, an increase in cystatin C level was independently associated with the risk of subclinical atherosclerosis after adjusting for age, sex, duration of diabetes, smoking, hypertension, 10-year risk of atherosclerotic cardiovascular disease risk score, serum creatinine level, total cholesterol, high-density lipoprotein cholesterol and haemoglobin A1c (odds ratio = 1.200, 95% confidence interval: 1.04-1.38, p = 0.011). CONCLUSION: Serum cystatin C level was significantly associated with subclinical atherosclerosis. This result suggests that an increase in cystatin C level could be a valuable surrogate marker for the risk of cardiovascular disease in patients with type 2 diabetes mellitus.

A Novel Index Using Soluble CD36 Is Associated with the Prevalence of Type 2 Diabetes Mellitus: Comparison Study with Triglyceride-Glucose Index.

BACKGROUND: Plasma soluble cluster determinant 36 (sCD36) level is closely related with insulin resistance and atherosclerosis, but little is known whether it could be a surrogate for estimating risk of developing diabetes or not. To address this, we evaluated association between sCD36 index, the product of sCD36 and fasting plasma glucose (FPG), and the prevalence of type 2 diabetes mellitus (T2DM), and then compared with triglyceride-glucose (TyG) index which has been suggested simple index for insulin resistance. METHODS: This was cross-sectional study, and participants were classified as normal glucose tolerance (NGT), prediabetes, and T2DM according to glucose tolerance. The formula of TyG index was 'ln [FPG (mg/dL)×triglyceride (mg/dL)/2],' and the sCD36 index was 'ln [sCD36 (pg/mL)×FPG (mg/dL)/2].' RESULTS: One hundred and fifty-five subjects (mean age, 55.2 years) were enrolled, and patients with T2DM were 75. Both indexes were significantly increased in prediabetes and T2DM rather than NGT, and sCD36 index was positively correlated with both glycosylated hemoglobin and homeostasis model assessment of insulin resistance (r=0.767 and r=0.453, respectively; P<0.05) and negatively with homeostasis model assessment estimate of ß-cell function (r=-0.317). The odds ratio (OR) of sCD36 index for T2DM was 4.39 (95% confidential interval, 1.51 to 12.77) after adjusting age, gender, blood pressure, smoking, alcohol, non-high density lipoprotein cholesterol and high-sensitivity C-reactive protein. However, OR of TyG index did not remained significance after adjustment. CONCLUSION: sCD36 index has an independent association with the risk of T2DM, and showed better correlation than TyG index. These results suggest sCD36 index might be useful surrogate marker for the risk of diabetes.

The Relationship between Metformin and Cancer in Patients with Type 2 Diabetes.

BACKGROUND: Recently, several studies reported that the cancer incidence in type 2 diabetes patients is higher than in the general population. Although a number of risks are shared between cancer and diabetes patients, there have been few studies of its correlation. We evaluated the influences of several factors including low density lipoprotein cholesterol (LDL-C), albuminuria and use of metformin on the risk of cancer in patients with type 2 diabetes. METHODS: We enrolled 1,320 patients with at least 5 years of follow-up and 73 patients were diagnosed with cancer during this period. The associations of the risk factors with cancer incidence were evaluated by multiple regression analysis. The subjects were placed into two subgroups based on metformin dosage (<1,000 mg/day, ≥1,000 mg/day) and we compared cancer incidence using analysis of covariance. RESULTS: LDL-C and albuminuria were not significantly correlated with cancer risk. In contrast, metformin showed a reverse correlation with cancer risk (P=0.006; relative risk, 0.574). In the metformin nonadministration group, smoking, male gender, and high triglyceride levels tended to be contributing factors without statistical significance. Cancer occurence was lower in the low dose metformin group (less than 1,000 mg/day) (P=0.00). CONCLUSION: These results suggest that the administration of low dose metformin in patients with type 2 diabetes may be associated with a reduced risk of cancer.

Ginsenoside Rd inhibits the expressions of iNOS and COX-2 by suppressing NF-κB in LPS-stimulated RAW264.7 cells and mouse liver.

Ginsenoside Rd is a primary constituent of the ginseng rhizome and has been shown to participate in the regulation of diabetes and in tumor formation. Reports also show that ginsenoside Rd exerts anti-oxidative effects by activating anti-oxidant enzymes. Treatment with ginsenoside Rd decreased nitric oxide and prostaglandin E2 (PGE2) in lipopolysaccharides (LPS)-challenged RAW264.7 cells and in ICR mouse livers (5 mg/kg LPS; LPS + ginsenoside Rd [2, 10, and 50 mg/kg]). Furthermore, these decreases were associated with the down-regulations of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 and of nuclear factor (NF)-κB activity in vitro and in vivo. Our results indicate that ginsenoside Rd treatment decreases; 1) nitric oxide production (40% inhibition); 2) PGE2 synthesis (69% to 93% inhibition); 3) NF-κB activity; and 4) the NF-κB-regulated expressions of iNOS and COX-2. Taken together, our results suggest that the anti-inflammatory effects of ginsenoside Rd are due to the down-regulation of NF-κB and the consequent expressional suppressions of iNOS and COX-2.

Inhibition of fatty acid translocase cluster determinant 36 (CD36), stimulated by hyperglycemia, prevents glucotoxicity in INS-1 cells.

The purpose of the present study was to determine whether exposure of pancreatic islets to glucotoxic conditions changes fatty acid translocase cluster determinant 36 (CD36) and examine the role of CD36 on the induction of glucotoxicity. We measured the changes of CD36 and insulin secretion in high glucose (30 mM) exposed INS-1 cells and CD36 suppressed INS-1 cells by transfection of CD36 siRNA. The intracellular peroxide level of INS-1 cells increased in the high glucose media compared to normal glucose (5.6mM) media. The mRNA levels of insulin and PDX-1, as well as glucose stimulated insulin secretion (GSIS) were decreased in INS-1 cells exposed to high glucose media compared to normal glucose media, while CD36 and palmitate uptake were significantly elevated with exposure to high glucose media for 12h. The inhibition of CD36 reversed the decreased GSIS and intracellular peroxide level in INS-1 cells. These results suggest that high glucose may exacerbate glucotoxicity via increasing fatty acid influx by elevation of CD36 expression, and that CD36 may be a possible target molecule for preventing glucotoxicity in pancreatic beta-cells.

Clinical characteristics of ectopic thyroid in Korea.

BACKGROUND: Ectopic thyroid is a rare entity and can occur at any location in the midline position. A role for the ectopic thyroid in the pathogenesis of hypothyroidism and nongoitrous cretinism has been emphasized. OBJECTIVE: To assess the clinical characteristics of an ectopic thyroid by analyzing 49 cases reported in Korea. DESIGN: This study was a retrospective review of 19 cases who were diagnosed by thyroid scan at our institutions together with 30 cases reported in the Korean medical literature, found using KoreaMed. MAIN OUTCOMES: Most cases of ectopic thyroid were diagnosed in patients aged between 1 and 29 years; it was more common in females (43 patients). A lingual thyroid was found in 23 patients, a sublingual thyroid in 17 patients, combined type in 7 patients, a prelaryngeal thyroid in 1 patient, and an intratracheal thyroid in 1 patient. Only four cases had the thyroid gland in the normal position. The chief complaints at presentation were palpable mass in 20 patients, growth retardation in 10 patients, and a lump sensation in the throat in 6 patients. Twenty-six of 42 patients (61.9%) had hypothyroidism, and 16 patients (38.1%) had euthyroidism. As for the treatment modalities, 18 of 26 patients with hypothyroidism and 4 of 16 patients with normal thyroid function received thyroid hormone medication; 3 of 26 patients with hypothyroidism and 8 of 16 patients with euthyroidism underwent resection of the ectopic thyroid. CONCLUSION: Our study suggests that radionuclide thyroid scanning and function testing may be useful not only for the diagnosis of an ectopic thyroid but also before deciding on the therapeutic modality; patients should be followed up to detect changes in thyroid function and malignant transformation.

Follicle-stimulating hormone receptor gene polymorphism and ovarian responses to controlled ovarian hyperstimulation for IVF-ET.

This study was performed to investigate the association between FSH receptor (FSHR) gene polymorphism at position 680 and the outcomes of controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) in Korean women. Two hundred and sixty-three patients under 40 years of age who underwent IVF-ET procedures were included in this study. Patients with polycystic ovary syndrome, endometriosis, or a previous history of ovarian surgery were excluded. Following extraction of genomic DNA, the FSHR polymorphism at position 680 was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The FSHR genotype distribution was 41.8% for Asn/Asn, 45.6% for Asn/Ser, and 12.5% for Ser/Ser FSHR genotype groups. Although there was no difference among the three genotype groups in terms of the age and infertility diagnosis of study subjects, the basal levels of FSH (day 3) were significantly different [5.7 +/- 0.3 IU/l (mean+/-SEM), 6.0 +/- 0.3 IU/l, and 8.2 +/- 0.9 IU/l for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively. The Ser/Ser group tended to require a higher dose of gonadotropins for COH, and tended to show lower serum estradiol levels at the time of hCG administration than the other two groups, though these differences did not reach statistical significance. The numbers of oocytes retrieved tended to be different for the three groups (9.6 +/- 0.6, 10.2 +/- 0.6, and 7.9 +/- 0.8 for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively). Clinical pregnancy rate was significantly higher in Asn/Asn, compared to the others (45.7 vs. 30.5%, P=0.013). The homozygous Ser/Ser genotype of FSHR polymorphism at position 680 may be associated with a reduced ovarian response to COH for IVF-ET, while Asn/Asn genotypes showed a higher pregnancy rate.

Increased expression of focal adhesion kinase in thyroid cancer: immunohistochemical study.

Focal adhesion kinase (FAK) is a tyrosine kinase that is found in cellular structures called focal adhesions. FAK appears to be a key element in signal transduction pathways involved in cell adhesion and locomotion. FAK is overexpressed in various tumors, including tumors derived from regions of the head and neck, colon, breast, prostate, and liver. In this study, we investigated immunohistochemically whether FAK expression was increased in thyroid cancers. FAK staining was not seen in any of the 20 normal thyroid tissues or the 6 nodular hyperplasia specimens. In contrast, FAK staining was observed in all of 17 papillary carcinomas, 9 follicular carcinomas, 8 medullary carcinomas, and 2 anaplastic carcinomas. Nine of 17 follicular adenomas showed FAK immunoreactivity. FAK was not expressed in normal tissue and nodular hyperplasia, but was expressed in some of the follicular adenoma, and all of the follicular, papillary, medullary and anaplastic thyroid carcinoma. This result indicates that the up-regulation of FAK may play a role in the development of thyroid carcinogenesis.

Immunohistochemical expression of COX-2 in thyroid nodules.

BACKGROUND: Recent evidence indicates that elevated COX-2 expression is associated with the carcinogenesis of numerous neoplasms. In this study, we investigated COX-2 expression in various thyroid specimens in order to elucidate its physiological role in pathologic conditions, and to evaluate the efficiency of COX-2 protein expression as a molecular marker of malignancy in the thyroid gland. METHODS: COX-2 expression was studied immunohistochemically in 19 papillary carcinomas, 8 follicular carcinomas, 14 follicular adenomas, 2 Hürthle cell carcinomas, 4 Hürthle cell adenomas, 8 nodular hyperplasias, 3 Graves' diseases, 3 Hashimoto's thyroiditis, 2 medullary carcinomas, 1 anaplastic carcinoma, and 20 normal thyroid tissues. RESULTS: COX-2 staining was not seen in any of the normal thyroid, Graves' disease, or nodular hyperplasia specimens. In contrast, COX-2 staining was observed in all of papillary carcinomas, Hashimoto's thyroiditis, Hürthle cell carcinomas, and Hürthle cell adenomas tissues. Moreover, 7 of 8 follicular carcinomas and 11 of 14 follicular adenomas showed COX-2 staining. CONCLUSION: These results indicate that COX-2 is not useful as a marker of malignancy. Since COX-2 expression was evident in follicular adenomas and in papillary and follicular carcinomas. Thus, the enzyme may be involved in the early process of thyroid tumorigenesis.