Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add-on therapy in drug-naïve patients with type 2 diabetes (TRIPLE-AXEL study): A multicentre, randomized, 104-week, open-label, active-controlled trial.

AIM: To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add-on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D). MATERIALS AND METHODS: This multicentre, randomized, 104-week, open-label trial randomized 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104. RESULTS: HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was -2.56% in the TCT group vs. -2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well-tolerated and had fewer adverse events than SAT. CONCLUSIONS: Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.

Renal Protection of Mineralocorticoid Receptor Antagonist, Finerenone, in Diabetic Kidney Disease.

Chronic kidney disease (CKD) is the most common cause of end-stage renal disease in patients with type 2 diabetes mellitus (T2DM). CKD increases the risk of cardiovascular diseases; therefore, its prevention and treatment are important. The prevention of diabetic kidney disease (DKD) can be achieved through intensive glycemic control and blood pressure management. Additionally, DKD treatment aims to reduce albuminuria and improve kidney function. In patients with T2DM, renin-angiotensin-aldosterone system inhibitors, sodium glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists can delay the progression of DKD. Hence, there is a need for novel treatments that can effectively suppress DKD progression. Finerenone is a first-in-class nonsteroidal mineralocorticoid receptor antagonist with clinically proven efficacy in improving albuminuria, estimated glomerular filtration rate, and risk of cardiovascular events in early and advanced DKD. Therefore, finerenone is a promising treatment option to delay DKD progression. This article reviews the mechanism of renal effects and major clinical outcomes of finerenone in DKD.

Site-specific cancer risk in patients with type 2 diabetes: a nationwide population-based cohort study in Korea.

BACKGROUND/AIMS: We aimed to evaluate site-specific cancer risk in diabetic patients and to investigate causal and temporal relationships by analyzing organ-specific cancer risk according to the duration of diabetes. METHODS: Using a database provided by the Korean National Health Insurance Service, we conducted a retrospective, population-based cohort study of adults aged ≥ 30 years from January 2005 to December 2013. To verify the possibility of detection bias or reverse causation, we compared hazard ratios (HRs) for each cancer according to the following duration of diabetes: less than 6 months, 6 months to 3 years, and more than 3 years. RESULTS: The incidence of overall cancer per 1,000 person-years was higher in patients with diabetes than in those without diabetes (20.36 vs. 10.83). The overall cancer risk according to the duration of diabetes was the highest within the first 6 months after diagnosis (HR, 2.03; 95% confidence interval [CI], 1.99 to 2.07), and the HR decreased with the duration of diabetes, ranging from 1.19 (95% CI, 1.18 to 1.21) between 6 months and 3 years to 1.12 (95% CI, 1.11 to 1.13) after 3 years. Both overall cancer risk and HR remained significantly higher in patients with diabetes than in those without diabetes. The risk for prostate cancer was higher in men with diabetes than in those without diabetes (HR, 1.12; 95% CI, 1.10 to 1.14). In women, the risk for endometrial cancer was significantly higher in patients with diabetes than in those without diabetes throughout the duration of diabetes. CONCLUSION: The risk for stomach, colorectum, liver, pancreas, and kidney cancer appeared to be higher in patients with diabetes than in those without diabetes regardless of the sex or duration of diabetes.

Impaired Cortisol and Growth Hormone Counterregulatory Responses among Severe Hypoglycemic Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Elevated levels of cortisol and growth hormone are critical counterregulatory responses to severe hypoglycemia. However, the proportion and clinical characteristics of patients with type 2 diabetes mellitus (DM) who fail to show appropriate cortisol and/or growth hormone secretion in response to severe hypoglycemia have not been investigated. METHODS: We measured plasma cortisol and growth hormone levels in type 2 DM patients with severe hypoglycemia who visited the emergency department between 2006 and 2015. RESULTS: Of 112 hypoglycemic patients, 23 (20.5%) had an impaired cortisol response (<18 µg/dL) and 82 patients (73.2%) had an impaired growth hormone response (<5 ng/mL). Nineteen patients (17.0%) had impaired responses to both cortisol and growth hormone. The patients with impaired responses of cortisol, growth hormone, and both hormones were significantly older and more likely to be female, and had higher admission rates, lower growth hormone levels, and lower adrenocorticotropic hormone levels than the patients with a normal hormonal response. Multivariate logistic regression analysis indicated that an impaired growth hormone response was significantly associated with advanced age, shorter DM duration, a higher admission rate, and a higher body mass index (BMI). An impaired cortisol response was significantly associated with growth hormone levels. Patients with an impaired growth hormone response had higher admission rates than patients with a normal response. CONCLUSION: A considerable number of type 2 DM patients had impaired cortisol and/or growth hormone responses to severe hypoglycemia. Advanced age, shorter DM duration, and higher BMI were independently associated with an abnormal growth hormone response.

Effects of Vildagliptin or Pioglitazone on Glycemic Variability and Oxidative Stress in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A 16-Week, Randomised, Open Label, Pilot Study.

BACKGROUND: Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress. This study aimed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor, vildagliptin, or a thiazolidinedione, pioglitazone, on glycemic variability and oxidative stress in patients with type 2 diabetes. METHODS: In this open label, randomised, active-controlled, pilot trial, individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin (50 mg twice daily, n=17) or pioglitazone (15 mg once daily, n=14) treatment groups for 16 weeks. Glycemic variability was assessed by calculating the mean amplitude of glycemic excursions (MAGE), which was obtained from continuous glucose monitoring. Urinary 8-iso prostaglandin F2α, serum oxidised low density lipoprotein, and high-sensitivity C-reactive protein were used as markers of oxidative stress or inflammation. RESULTS: Both vildagliptin and pioglitazone significantly reduced glycated hemoglobin and mean plasma glucose levels during the 16-week treatment. Vildagliptin also significantly reduced the MAGE (from 93.8±38.0 to 70.8±19.2 mg/dL, P=0.046), and mean standard deviation of 24 hours glucose (from 38±17.3 to 27.7±6.9, P=0.026); however, pioglitazone did not, although the magnitude of decline was similar in both groups. Markers of oxidative stress or inflammation including urinary 8-iso prostaglandin F2α did not change after treatment in both groups. CONCLUSION: In this 16-week treatment trial, vildagliptin, but not pioglitazone, reduced glycemic variability in individuals with type 2 diabetes who was inadequately controlled with metformin monotherapy, although a reduction of oxidative stress markers was not observed.

Effects of thyroid hormone withdrawal on metabolic and cardiovascular parameters during radioactive iodine therapy in differentiated thyroid cancer.

Objective To investigate the cardiometabolic effects of a severe hypothyroid state induced by withdrawal of thyroid hormone replacement before radioactive iodine therapy. Methods Patients with thyroid cancer who were scheduled to receive radioactive iodine ablation were enrolled. Cardiometabolic parameters were measured using blood samples taken immediately before levothyroxine withdrawal, 4 weeks following withdrawal (on radiotherapy day), and 4 weeks following reinstitution of levothyroxine. Results Out of 48 patients (age 49.4 ± 10.5 years; 77.1% [37/48] female), the severe hypothyroid state induced by levothyroxine withdrawal significantly aggravated the majority of lipid parameters, particularly in patients with a greater number of metabolic syndrome components. Fasting plasma glucose levels and homeostatic model assessment values for insulin resistance and ß-cell function significantly decreased following levothyroxine withdrawal. Serum high-sensitivity C-reactive protein, fibrinogen and cystatin C levels significantly decreased, and homocysteine levels increased during the severe hypothyroid state. All of these changes were reversed by levothyroxine reinstitution. Conclusions Severe hypothyroid state induced pronounced changes in cardiometabolic parameters. Further studies should identify the long-term effects of changes in these parameters on cardiovascular morbidity and mortality in relation to thyroid disease.

Effect of Rubus Occidentalis Extract on Metabolic Parameters in Subjects with Prediabetes: A Proof-of-concept, Randomized, Double-blind, Placebo-controlled Clinical Trial.

Rubus occidentalis (RO) has beneficial effects on glucose and lipid profiles in vitro. The aim of the study was to investigate RO extract effect on metabolic parameters in prediabetic patients, adopting a 12-week, randomized, double-blind, placebo-controlled trial. Forty-four patients (age 59.0 ± 8.2 years, 70.5% females, HbA1c 5.8 ± 0.4%) were divided into placebo (n = 13), low-dose RO extract (LRE; n = 14), or high-dose RO extract (HRE; n = 17) groups. Either 900 or 1800 mg per day of RO extract was administered orally. Area under the curve for glucose obtained 2 h after a 75-g oral glucose tolerance test was significantly decreased in the HRE group, compared with the placebo group (-28.1 ± 42.4 vs. +13.4 ± 52.6 mg/dL, p < 0.05). Homoeostasis model assessment-B was increased (+17.11 ± 10.69, +5.24 ± 4.10, and +0.86 ± 6.01 in HRE, LRE, and placebo, respectively, p < 0.05). Serum levels of monocyte chemoattractant protein-1 and oxidized low-density lipoprotein were significantly decreased by treatment in a dose-dependent manner (monocyte chemoattractant protein-1: -35.0 ± 21.2, +8.4 ± 18.1, and +24.2 ± 14.5; oxidized low-density lipoprotein: -19.7 ± 8.5, -13.1 ± 7.2, and -2.2 ± 11.0 in the HRE, LRE, and placebo, respectively, p < 0.05). The results support the beneficial effects of RO extract on the control of glycemia and vascular inflammation in prediabetic patients. (ClinicalTrials.gov: NCT01964703). Copyright © 2016 John Wiley & Sons, Ltd.

Is an Oral Glucose Tolerance Test Still Valid for Diagnosing Diabetes Mellitus?

BACKGROUND: We evaluated the diagnostic rate of diabetes using fasting plasma glucose (FPG), 2-hour plasma glucose (2h PG) after 75 g oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels, and we elucidated the pathophysiologic characteristics and risk factors that give rise to diabetes in patients with prediabetes. METHODS: The data of 236 patients who had the OGTT at Konkuk University Hospital were analyzed. Fasting, 30, and 120 minutes blood glucose levels and insulin levels were measured. The diagnostic rate of diabetes was assessed using FPG, 2h PG, and HbA1c levels. The clinical data and insulin resistance and secretion evaluations were compared using indexes according to the fasting glucose level. RESULTS: Among 236 subjects, 97 (41.1%) were diabetics and 102 (43.2%) were prediabetics. The rate of diabetes diagnosis by one of the individual criteria was 56.7%, 53.6%, and 84.5% for FPG, HbA1c, and 2h PG, respectively. When two criteria were used to diagnose diabetes, 72.2% of the diabetic patients were identified by FPG and HbA1c, while 100% were identified by FPG and 2h PG, and 91.7% were identified by 2h PG and HbA1c. The HbA1c cut-off value for 2h PG ≥200 mg/dL was 6.1%, and the FPG cut-off value was 115 mg/dL. In impaired fasting glucose subjects, the HbA1c level, Matsuda index, and insulinogenic index were associated with risk of occurrence of overt diabetes (P<0.01). CONCLUSION: This study suggests that performing additional OGTT for patients with FPG ≥110 mg/dL or HbA1c ≥6.1% is helpful to reclassify their glucose tolerance status and evaluate their potential for progressing to overt diabetes.

RAS mutations in indeterminate thyroid nodules are predictive of the follicular variant of papillary thyroid carcinoma.

OBJECTIVE: RAS mutations are the most common mutations in thyroid nodules with indeterminate cytology by fine-needle aspiration cytology (FNAC), and are mutually exclusive with BRAF mutations. However, the diagnostic utility of RAS mutation analysis is uncertain. We evaluated the diagnostic utility of RAS mutation analysis in indeterminate thyroid nodules. DESIGN, PATIENTS, AND MEASUREMENTS: A total of 155 thyroid nodules (90 benign and 65 indeterminate) negative for BRAF(V) (600E) mutations on FNAC were analysed for mutations in RAS codon 61 using pyrosequencing methods. We evaluated diagnostic accuracy of RAS mutation for predicting thyroid malignancy based on the surgical pathologic diagnosis. RESULTS: Among the 65 BRAF(V) (600E) -negative indeterminate thyroid nodules identified by FNAC, 25 (38·5%) exhibited point mutations in RAS 61 consisting of 18 NRAS 61 (72%), and 7 HRAS 61 (28%) mutations. In contrast, only five of 90 (5·6%) nodules with benign cytology had RAS mutations. Only two of 25 (8·0%) RAS 61(+) indeterminate nodules exhibited malignant ultrasonographic features. Of the 15 patients with RAS 61(+) -indeterminate nodules who underwent thyroid surgery, 14 (93·3%) were diagnosed as malignant, including 13 follicular variant of papillary thyroid carcinomas (FVPTC), and one follicular thyroid carcinoma (FTC). The average tumour size was 1·79 ± 0·62 cm. Multifocality was seen in 28·6% of cases, with 7·1% exhibiting extrathyroidal extension; no lymph node or distant metastases were evident. Based on the surgical pathologic diagnosis results, preoperative RAS 61 mutation analysis on FNAC exhibited 93·3% sensitivity, 75·0% specificity, 93·3% positive predictive value, 75·0% negative predictive value and 89·5% diagnostic accuracy for predicting malignancies. CONCLUSION: Our results suggest that RAS mutation analysis holds great promise as a preoperative diagnostic tool for predicting FVPTC in cytologically and sonographically indeterminate nodules negative for BRAF mutations.

Efficacy of glimepiride/metformin fixed-dose combination vs metformin uptitration in type 2 diabetic patients inadequately controlled on low-dose metformin monotherapy: A randomized, open label, parallel group, multicenter study in Korea.

AIMS/INTRODUCTION: To compare the efficacy and safety of early combination therapy with glimepiride/metformin to metformin uptitration in reducing glycated hemoglobin (HbA1c) levels in Korean type 2 diabetic patients inadequately controlled on low-dose metformin monotherapy. MATERIALS AND METHODS: In a randomized, open label, parallel group, multicenter study, 209 Korean type 2 diabetic patients (HbA1c 7.0-10.0%, on metformin 500-1,000 mg/day) received glimepiride/metformin fixed-dose combination (G/M FDC) or metformin uptitration treatment (Met UP). The primary end-point was the change in HbA1c from baseline to week 24. RESULTS: G/M FDC therapy provided significantly greater adjusted mean decreases vs Met UP therapy in HbA1c (-1.2 vs -0.8%, P < 0.0001), and fasting plasma glucose (-35.7 vs -18.6 mg/dL, P < 0.0001). A significantly greater proportion of patients with G/M FDC therapy achieved HbA1c < 7% (74.7 vs 46.6%, P < 0.0001) at the end of the study. More patients experienced hypoglycemia with G/M FDC therapy compared with Met UP therapy (41 vs 5.6%, P < 0.0001), but there was no serious hypoglycemia in any group. A modest increase in mean bodyweight occurred in the patients who were treated with G/M FDC therapy (1.0 kg), whereas a slight decrease was observed in the patients who were treated with Met UP therapy (-0.7 kg). CONCLUSION: The present study showed that glimepiride/metformin fixed-dose combination therapy was more effective in glycemic control than metformin uptitration, and was well tolerated in type 2 diabetic patients inadequately controlled by low-dose metformin monotherapy in Korea. This trial was registered with ClinicalTrial.gov (no. NCT00612144).

Improvement in negative bias stress stability of solution-processed amorphous In-Ga-Zn-O thin-film transistors using hydrogen peroxide.

We have investigated the effect of hydrogen peroxide (H2O2) on negative bias stress (NBS) stability of solution-processed amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFTs). The instability of solution-processed a-IGZO TFTs under NBS is attributed to intrinsic oxygen vacancy defects (Vo) and organic chemical-induced defects, such as pores, pin holes, and organic residues. In this respect, we added H2O2 into an indium-gallium-zinc oxide solution to reduce the defects without any degradation of electrical performance. The field-effect mobility and sub-threshold slope of the a-IGZO TFTs were improved from 0.37 cm(2) V(-1) s(-1) and 0.86 V/dec to 0.97 cm(2) V(-1) s(-1) and 0.58 V/dec, respectively. Furthermore, the threshold voltage shift under NBS was dramatically decreased from -3.73 to -0.18 V. These results suggest that H2O2 effectively reduces Vo through strong oxidation and minimizes organic chemical-induced defects by eliminating the organic chemicals at lower temperatures compared to a conventional solution process.

Accelerated formation of metal oxide thin film at 200 °C using oxygen supplied by a nitric acid additive and residual organic suction vacuum annealing for thin-film transistor applications.

Oxide semiconductors have gradually replaced amorphous and polycrystalline silicon for thin-film transistor (TFT) because of their high mobility and large-area uniformity. Especially, the oxide semiconductors have also achieved the low-cost manufacturing using a solution process. However, because the solution-processed oxide semiconductors require a high thermal energy to form the oxide thin film, the additional solution synthesis and annealing process are needed for low-temperature solution process. Because the conventional solution-processed oxide thin films have low oxidation level and high residual organic concentration at low annealing temperature, we propose the novel solution process that includes the nitric acid additive and the vacuum ambient annealing as an oxidizing agent and a residual organic suction, respectively. Therefore, we have successfully developed the simple oxide solution process and the soluble InZnO TFT with high field-effect mobility of 3.38 cm(2)/(V s) at 200 °C.

Hole transport enhancing effects of polar solvents on poly(3,4-ethylenedioxythiophene):poly(styrene sulfonic acid) for organic solar cells.

This study analyzed the properties of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonic acid) (PEDOT:PSS) thin-films prepared by spin-coating solutions made with the polar solvents methanol, acetone, or N,N-dimethylformamide (DMF). A characteristic analysis was carried out for poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C(61)-butyric acid methyl ester (PCBM)-based organic solar cells (OSCs) having these modified PEDOT:PSS thin-films as the hole transport layer. The resistivity of the PEDOT:PSS thin-film obtained from the DMF solution was 4.89 × 10(-3) Ω·cm with a roughness of 3.23 × 10° nm, compared to 3.51 × 10(-1) Ω·cm and 7.72 × 10(-1) nm for a pristine PEDOT:PSS thin-film. The dipole moment increase of the solvent led to the decreased resistivity and the increased roughness and transparency of PEDOT:PSS thin-films on the structural arrangement of the polymers. Highly efficient OSCs with a power conversion efficiency of 3.47% were obtained when DMF-treated PEDOT:PSS thin-film was used as the hole transport layer.

Improved electrical performance of an oxide thin-film transistor having multistacked active layers using a solution process.

Thin-film transistors (TFTs) with multistacked active layers (MSALs) have been studied to improve their electrical performance. The performance enhancement with MSALs has been attributed to higher film density in the effective channel; the density was higher because the porosities of the sublayers were reduced by filling with solution. The proposed TFT with MSALs exhibited an enhanced field-effect mobility of 2.17 cm(2)/(V s) and a threshold voltage shift under positive bias stress of 8.2 V, compared to 1.21 cm(2)/(V s) and 18.1 V, respectively, for the single active layer TFT.

The Association between Midnight Salivary Cortisol and Metabolic Syndrome in Korean Adults.

BACKGROUND: The common characteristics of metabolic syndrome (MetS) and Cushing's syndrome suggest that excess cortisol may be involved in the pathogenesis of MetS. Salivary cortisol measurements are simple and can be surrogates for plasma free cortisol, which is the most biologically active form. We evaluated the association between levels of midnight salivary cortisol and MetS in Korean adults. METHODS: A total of 46 subjects, aged 20 to 70 years, who visited the Health Care Center at Konkuk University Hospital from August 2008 to August 2009 were enrolled. We compared the levels of midnight salivary cortisol in subjects with MetS with those in subjects without MetS. We analyzed the associations between midnight salivary cortisol levels and components of MetS. RESULTS: Midnight salivary cortisol levels were higher in the MetS group (70±42.4 ng/dL, n=12) than that in the group without MetS (48.1±36.8 ng/dL, n=34) (P=0.001). Positive correlations were observed between midnight salivary cortisol levels and waist circumference, fasting blood glucose, and homeostasis model assessment of insulin resistance. The risk for MetS was significantly higher in subjects with midnight salivary cortisol levels ≥100 ng/dL than in those with levels <50 ng/dL (odds ratio, 5.9; 95% confidence interval, 2.35 to 36.4). CONCLUSION: The results showed a positive correlation between midnight salivary cortisol levels and MetS, suggesting that hypercortisolism may be related to MetS.

The BRAF(V600E) mutation is associated with malignant ultrasonographic features in thyroid nodules.

CONTEXT: Several ultrasonographic (US) features of thyroid nodules have been reported to predict malignancy. The BRAF(V600E) mutation is a useful diagnostic marker for differentiating papillary thyroid carcinoma from benign thyroid nodules, especially in BRAF(V600E) -prevalent populations such as in Korea. OBJECTIVE: To evaluate the association of BRAF(V600E) mutation with US features of thyroid nodules in predicting the malignancy of thyroid nodules in Korean patients. DESIGN: A total of 991 thyroid nodules from 823 patients in fine-needle aspiration biopsy (FNAB) specimens were investigated. The relationship between US features and the presence of BRAF(V600E) mutation by pyrosequencing method was prospectively analysed. RESULTS: The BRAF(V600E) mutation was associated with the following US features: solid composition [odds ratio (OR) 20·338; 95% confidence interval (CI): 4·952-83·532; P < 0·001], marked hypoechogenicity (OR 30·744; 95% CI: 15·951-59·255; P < 0·001), irregular margin (OR 9·889; 95% CI: 7·005-13·859; P < 0·001), taller-than-wide shape (OR 6·031; 95% CI: 4·343-8·376; P < 0·001) and the presence of microcalcifications (OR 6·664; 95% CI: 4·604-9·648; P < 0·001). The BRAF(V600E) mutation with malignant US features in FNAB enhanced the diagnostic accuracy compared with cytologic diagnosis alone (94·3%vs 69·7%). CONCLUSION: The BRAF(V600E) mutation is significantly associated with malignant US features, such as solid composition, marked hypoechogenicity, irregular margin, taller-than-wide shape and the presence of microcalcifications. The application of BRAF(V600E) mutation analysis in US-guided FNAB can improve the diagnostic accuracy of thyroid nodules.

Surgical results of thyroid nodules according to a management guideline based on the BRAF(V600E) mutation status.

CONTEXT: In Korea, where PTC comprises about 90-95% of the reported thyroid cancers, the prevalence of BRAF(V600E) mutation in papillary thyroid carcinoma (PTC) is above 80%. OBJECTIVE: We analyzed the surgical result according to a management guideline based on the BRAF(V600E) mutation status of thyroid nodules. DESIGN: A total of 865 thyroid nodules were prospectively analyzed for their cytology and BRAF(V600E) mutation status by pyrosequencing. For the patients who had a diagnosis of atypical cells of undetermined significance (ACUS), we recommended surgery when there was positivity for BRAF(V600E) mutation or the nodules were clinically suspicious. RESULTS: Among 865 cases, 504, 141, 54, 140, 10, and 16 were diagnosed as benign, ACUS, suspicious for malignancy, malignant, suspicious for follicular neoplasm, and nondiagnostic, respectively. None of the 504 benign, 45 (31.9%) of the 141 ACUS, 46 (85.2%) of the 54 suspicious for malignancy, 129 (92.1%) of the 140 malignant, and one (10%) of the 10 suspicious for follicular neoplasm cases showed BRAF(V600E) mutation. Surgery was recommended to all 45 patients with BRAF(V600E) mutation-positive ACUS nodules; among them, 30 patients underwent surgery, 29 had PTC, and one had nodular hyperplasia. All the patients diagnosed as suspicious for malignancy or malignant were advised to undergo an operation, and they turned out to have PTCs regardless of their BRAF(V600E) mutation status. CONCLUSIONS: We found that performing BRAF(V600E) mutation analysis on the fine-needle aspiration biopsy specimens was of great help to make a therapeutic decision for thyroid nodules when the fine-needle aspiration biopsy results were equivocal.