Feasibility of active surveillance in patients with clinically T1b papillary thyroid carcinoma ≤1.5 cm in preoperative ultrasonography: MASTER study.

Objective: Active surveillance (AS) is generally accepted as an alternative to immediate surgery for papillary thyroid carcinoma (PTC) measuring ≤1.0 cm (cT1a) without risk factors. This study investigated the clinicopathologic characteristics of PTCs measuring ≤2.0 cm without cervical lymph node metastasis (cT1N0) by tumor size group to assess the feasibility of AS for PTCs between 1.0 cm and 1.5 cm (cT1b≤1.5). Design: This study enrolled clinically T1N0 patients with preoperative ultrasonography information (n= 935) from a cohort of 1259 patients who underwent lobectomy and were finally diagnosed with PTC from June 2020 to March 2022. Results: The cT1b≤1.5 group (n = 171; 18.3 %) exhibited more lymphatic invasion and occult central lymph node (LN) metastasis with a higher metastatic LN ratio than the cT1a group (n = 719; 76.9 %). However, among patients aged 55 years or older, there were no significant differences in occult central LN metastasis and metastatic LN ratio between the cT1a, cT1b≤1.5, and cT1b>1.5 groups. Multivariate regression analyses revealed that occult central LN metastasis was associated with age, sex, tumor size, extrathyroidal extension, and lymphatic invasion in patients under 55, while in those aged 55 or older, it was associated only with age and lymphatic invasion. Conclusion: For PTC patients aged 55 years or older with cT1b≤1.5, AS could be a viable option due to the absence of a significant relationship between tumor size and occult central LN.

Effect of thyroid-stimulating hormone suppression on quality of life in thyroid lobectomy patients: interim analysis of a multicenter, randomized controlled trial in low- to intermediate-risk thyroid cancer patients (MASTER study).

Purpose: Current clinical practices favor less or no thyroid-stimulating hormone (TSH) suppression for low- to intermediate-risk thyroid cancer patients who receive thyroid lobectomy. The association of TSH suppression on health-related quality of life (HR-QoL) in patients after thyroid lobectomy is not well studied. This study aimed to evaluate the effect of TSH suppression on patient HR-QoL after thyroid lobectomy. Methods: This study included patients enrolled in an ongoing, multicenter, randomized controlled study investigating the effects of TSH suppression. Patients were randomized to either the low-TSH group (TSH target range, 0.3-1.99 µIU/mL) or the high-TSH group (TSH target range, 2.0-7.99 µIU/mL). The HR-QoL, hyperthyroidism symptom, and depression symptom questionnaires performed preoperatively and 2 weeks and 3 months postoperatively were evaluated. Results: Total of 669 patients (low-TSH group, 340; high-TSH group, 329) were included. Although total HR-QoL score changes were not different between the 2 groups, the high-TSH group had a significantly higher score in the physical domain at postoperative 3 months (P = 0.046). The 2 groups did not have significant differences in hyperthyroidism and depression scores. Conclusion: In the short-term postoperative period, the physical HR-QoL scores in thyroid lobectomy patients were better when they did not receive TSH suppression. This study suggests the importance of considering HR-QoL when setting TSH suppression targets in thyroid lobectomy patients.

Clinical impact of coexistent chronic lymphocytic thyroiditis on central lymph node metastasis in low- to intermediate-risk papillary thyroid carcinoma: The MASTER study.

BACKGROUND: The clinicopathological impact of chronic lymphocytic thyroiditis on patients with papillary thyroid carcinoma patients is still controversial. This study aimed to evaluate the clinicopathologic differences and risk factors for central lymph node metastasis based on the presence of coexistent chronic lymphocytic thyroiditis in patients with low- to intermediate-risk papillary thyroid carcinoma. METHODS: The medical records of 1,022 patients with low- to intermediate-risk papillary thyroid carcinoma who underwent lobectomy and central neck dissection between June 2020 and March 2022 were reviewed. Differences in clinicopathological factors were analyzed in patients with papillary thyroid carcinoma with or without chronic lymphocytic thyroiditis. Furthermore, risk factors for central lymph node metastasis in patients with low- to intermediate-risk papillary thyroid carcinoma with or without chronic lymphocytic thyroiditis were evaluated. RESULTS: Among the 1,022 patients with low to intermediate-risk papillary thyroid carcinoma, 102 (10.0%) had coexisting chronic lymphocytic thyroiditis. Female sex (odds ratio = 3.536, P = .001, 95% confidence interval 1.781-8.069), a multifocal tumor (odds ratio = 2.162, P = .001, 95% confidence interval 1.358-3.395), and angiolymphatic invasion (odds ratio = 0.365, P < .001, 95% confidence interval 0.203-0.625) were independent factors associated with patients who had coexisting chronic lymphocytic thyroiditis compared to those without chronic lymphocytic thyroiditis. There were 358 (35%) patients who had central lymph node metastasis. Multivariate analysis showed that younger age (odds ratio = 0.667, P = .013, 95% confidence interval 0.482-0.555), male sex (odds ratio = 0.549, P < .001, 95% confidence interval 0.402-0.751), tumor size >1 cm (odds ratio = 1.454, P = .022, 95% confidence interval 1.053-2.003), extrathyroidal extension (odds ratio = 1.874, P < .001, 95% confidence interval 1.414-2.486), and angiolymphatic invasion (odds ratio = 3.094, P < .001, 95% confidence interval 2.339-4.101) were risk factors for central lymph node metastasis. Angiolymphatic invasion (odds ratio = 11.184, P < .001, 95% confidence interval 3.277-46.199) was identified as the sole independent risk factor for central lymph node metastasis in patients with papillary thyroid carcinoma with coexisting chronic lymphocytic thyroiditis. CONCLUSION: Our data suggest that patients with low to intermediate-risk papillary thyroid carcinoma with coexistent chronic lymphocytic thyroiditis exhibit different clinical features than patients with papillary thyroid carcinoma without chronic lymphocytic thyroiditis. Additionally, the presence of chronic lymphocytic thyroiditis may be considered a potential factor against central lymph node metastasis.

Incidence of Endocrine-Related Dysfunction in Patients Treated with New Immune Checkpoint Inhibitors: A Meta-Analysis and Comprehensive Review.

BACKGRUOUND: This study investigated the incidence of endocrine immune-related adverse events (irAEs) for recently developed immune checkpoint inhibitor (ICI) drugs. METHODS: We collected studies on newly developed ICI drugs using PubMed/Medline, Embase, and Cochrane Library from inception through January 31, 2023. Among ICI drugs, nivolumab, pembrolizumab, and ipilimumab were excluded from the new ICI drugs because many papers on endocrine-related side effects have already been published. RESULTS: A total of 44,595 patients from 177 studies were included in this analysis. The incidence of hypothyroidism was 10.1% (95% confidence interval [CI], 8.9% to 11.4%), thyrotoxicosis was 4.6% (95% CI, 3.8% to 5.7%), hypophysitis was 0.8% (95% CI, 0.5% to 1.1%), adrenal insufficiency was 0.9% (95% CI, 0.7% to 1.1%), and hyperglycemia was 2.3% (95% CI, 1.6% to 3.4%). Hypothyroidism and thyrotoxicosis occurred most frequently with programmed cell death protein-1 (PD-1) inhibitors (13.7% and 7.5%, respectively). The rate of endocrine side effects for the combination of a programmed death-ligand 1 inhibitor (durvalumab) and cytotoxic T lymphocyte-associated antigen 4 inhibitor (tremelimumab) was higher than that of monotherapy. In a meta-analysis, the combination of tremelimumab and durvalumab had a 9- to 10-fold higher risk of pituitary and adrenal-related side effects than durvalumab alone. CONCLUSION: Newly developed PD-1 inhibitors had a high incidence of thyroid-related irAEs, and combined treatment with durvalumab and tremelimumab increased the risk of pituitary- and adrenal-related irAEs. Based on these facts, it is necessary to predict the endocrine side effects corresponding to each ICI drug, diagnose and treat them appropriately, and try to reduce the morbidity and mortality of patients.

Management of Subclinical Hypothyroidism: A Focus on Proven Health Effects in the 2023 Korean Thyroid Association Guidelines.

Subclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) and normal free thyroxine levels. The Korean Thyroid Association recently issued a guideline for managing SCH, which emphasizes Korean-specific TSH diagnostic criteria and highlights the health benefits of levothyroxine (LT4) treatment. A serum TSH level of 6.8 mIU/L is presented as the reference value for diagnosing SCH. SCH can be classified as mild (TSH 6.8 to 10.0 mIU/L) or severe (TSH >10.0 mIU/L), and patients can be categorized as adults (age <70 years) or elderly (age ≥70 years), depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, including a thyroid peroxidase antibody test, preferably 2 to 3 months after the initial assessment. While LT4 treatment is not generally recommended for mild SCH in adults, it is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and it may be considered for those with concurrent dyslipidemia. Conversely, LT4 treatment is generally not recommended for elderly patients, regardless of SCH severity. For those SCH patients who are prescribed LT4 treatment, the dosage should be personalized, and serum TSH levels should be regularly monitored to maintain the optimal LT4 regimen.

Potential impact of obesity on the aggressiveness of low- to intermediate-risk papillary thyroid carcinoma: results from a MASTER cohort study.

PURPOSE: Obesity is associated with an increased risk of papillary thyroid carcinoma (PTC). Evidence of the impact of obesity on PTC aggressiveness is scarce. We aimed to evaluate the association between the body mass index (BMI) and the presence of aggressive features of low- to intermediate-risk PTC in a prospective cohort. METHODS: We prospectively enrolled 1,032 patients with low- to intermediate-risk PTC who underwent lobectomy at 22 hospitals in Korea and divided into three groups according to BMI, as follows: normal/underweight ( < 23 kg/m2), overweight (23-24.9 kg/m2), and obese ( ≥ 25 kg/m2). Clinicopathological features of PTC at diagnosis were evaluated. RESULTS: Obese patients had a higher rate of macro-PTC ( > 1 cm) and greater incidence of extra-thyroidal extension (ETE), vascular invasion, and intermediate-risk tumors than those not classified as obese. Increased BMI was positively associated with the incidence of macro-PTC, ETE, vascular invasion, and intermediate-risk category. After adjusting for age, sex, pathological features, metabolic syndrome, thyroid function test, and smoking habits, obesity was a risk factor for ETE (odds ratio [OR] = 1.7, 95% confidence interval [CI]: 1.2-2.5, p = 0.005) and intermediate-risk PTC (OR = 1.7, 95% CI: 1.1-2.5, p = 0.011) in women. The association between obesity and ETE was significant regardless of whether or not women had metabolic syndrome. There was no significant association between obesity and aggressive PTC features in men. CONCLUSION: BMI at the time of thyroid cancer diagnosis may affect the aggressiveness of low- to intermediate-risk PTC, especially in women.

Long-Term Effectiveness of Quadruple Combination Therapy with Empagliflozin Versus Basal Long-Acting Insulin Therapy in Patients with Type 2 Diabetes: 3-Year Retrospective Observational Study.

INTRODUCTION: Effective blood glucose control remains a constant problem in patients with type 2 diabetes (T2D), even if they are being properly treated with one or more currently available drugs. The present study was designed as a 3-year retrospective observational study to determine whether the use of either empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, or insulin would provide any improvement in the control of the blood glucose levels in patients with T2D who were already being treated with a cocktail of three different oral antidiabetic drugs. METHODS: Adult patients with T2D were enrolled in this study if they exhibited suboptimal glycemic control (HbA1c 7.5-12.0%) despite being continuously treated for at least 3 months with metformin, dipeptidyl-peptidase 4 inhibitor, and glimepiride. Empagliflozin (25 mg/day, n = 154) or basal long-acting insulin (n = 147) was added as a fourth medication to the existing drug regimen. The major outcomes that were monitored in this study included the measurement of HbA1c, fasting plasma glucose (FPG), and general cardiometabolic and blood markers. RESULTS: After the addition of empagliflozin or basal insulin to the existing oral anti-diabetic agent (OAD) regimen, the baseline levels of HbA1c were reduced after month 36 in both the empagliflozin (8.9 ± 1.0% to 7.4 ± 0.8%, P < 0.01) and insulin (9.0 ± 1.4% to 8.0 ± .1.4%, P < 0.05) groups. The HbA1c reduction was higher in the empagliflozin group to the end of the 36-month study period (7.4 ± 0.8% vs. 8.0 ± 1.4%, empagliflozin vs. insulin, P < 0.05). FPG showed a similar trend in the early period but it was not maintained at the end of study. Body weight decreased (P < 0.01) from baseline (70.4 ± 12.3 kg) to month 36 (65.6 ± 11.4 kg) in the empagliflozin group but not the insulin group. At 36 months, the body weight in the empagliflozin group (65.6 ± 11.4 kg) was significantly lower (P < 0.01) than that in the insulin treatment group (70.0 ± 10.9 kg). CONCLUSION: Empagliflozin was shown to perform as well as better than insulin when used as part of a quadruple drug regimen for regulating blood glucose levels in suboptimally controlled patients with T2D. CLINICAL TRIAL NUMBER: NCT05103306 (ClinicalTrials.gov).

Mortality and Severity of Coronavirus Disease 2019 in Patients with Long-Term Glucocorticoid Therapy: A Korean Nationwide Cohort Study.

BACKGRUOUND: The severity of coronavirus disease 2019 (COVID-19) among patients with long-term glucocorticoid treatment (LTGT) has not been established. We aimed to evaluate the association between LTGT and COVID-19 prognosis. METHODS: A Korean nationwide cohort database of COVID-19 patients between January 2019 and September 2021 was used. LTGT was defined as exposure to at least 150 mg of prednisolone (≥5 mg/day and ≥30 days) or equivalent glucocorticoids 180 days before COVID-19 infection. The outcome measurements were mortality, hospitalization, intensive care unit (ICU) admission, length of stay, and mechanical ventilation. RESULTS: Among confirmed patients with COVID-19, the LTGT group (n=12,794) was older and had a higher proportion of comorbidities than the control (n=359,013). The LTGT group showed higher in-hospital, 30-day, and 90-day mortality rates than the control (14.0% vs. 2.3%, 5.9% vs. 1.1%, and 9.9% vs. 1.8%, respectively; all P<0.001). Except for the hospitalization rate, the length of stay, ICU admission, and mechanical ventilation proportions were significantly higher in the LTGT group than in the control (all P<0.001). Overall mortality was higher in the LTGT group than in the control group, and the significance remained in the fully adjusted model (odds ratio [OR], 5.75; 95% confidence interval [CI], 5.31 to 6.23) (adjusted OR, 1.82; 95% CI, 1.67 to 2.00). The LTGT group showed a higher mortality rate than the control within the same comorbidity score category. CONCLUSION: Long-term exposure to glucocorticoids increased the mortality and severity of COVID-19. Prevention and early proactive measures are inevitable in the high-risk LTGT group with many comorbidities.

Grave-to-cradle: human embryonic lineage tracing from the postmortem body.

Curiosity concerning the process of human creation has been around for a long time. Relevant questions seemed to be resolved with the knowledge of how cells divide after fertilization obtained through in vitro fertilization experiments. However, we still do not know how human life is created at the cellular level. Recently, the value of cadavers as a resource from which to obtain "normal" cells and tissues has been established, and human research using postmortem bodies has attracted growing scientific attention. As the human genome can be analyzed at the level of nucleotides through whole-genome sequencing, individual cells in a postmortem body can be traced back to determine what developmental processes have transpired from fertilization. These retrospective lineage tracing studies have answered several unsolved questions on how humans are created. This review covers the methodologies utilized in lineage tracing research in a historical context and the conceptual basis for reconstructing the division history of cells in a retrospective manner using postzygotic somatic variants in postmortem tissue. We further highlight answers that postmortem research could potentially address and discuss issues that wait to be solved in the future.

Preliminary Study of Different Treatment Responses between Bevacizumab, Aflibercept and Dexamethasone Implant According to Renal Function in Diabetic Macular Edema Patients.

Background: The purpose of this study was to investigate the association between responses to intravitreal bevacizumab injection and renal function in diabetic macular edema (DME) patients. Methods: A retrospective study of the medical records of 104 treatment-naïve DME patients who received intravitreal bevacizumab injection (IVBI) was conducted. Based on the estimated glomerular filtration rate (eGFR, mL/min/1.73 m2), the participants were classified into three groups. Intergroup comparisons of the best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) changes were performed after three-monthly consecutive IVBIs. In the groups with decreased renal function, the response to further treatment with a different drug was investigated. Results: A total of 104 participants were included in the study: 60 participants in the preserved renal function group (eGFR ≥ 60), 25 participants in the moderate chronic kidney disease (CKD) group (30 ≤ eGFR < 60), and 19 participants in the severe CKD group (eGFR < 30). After three-monthly consecutive IVBIs, BCVA (p < 0.001) and CST (p < 0.001) were significantly improved only in the preserved renal function group. Following further treatment of patients with decreased renal function, the treatment results were significantly better in those who were switched to aflibercept or dexamethasone implant than in those who were maintained on IVBI. Conclusions: From this preliminary study, we observed that renal function might affect the response to IVBI treatment in patients with DME. In the case of a poor response to initial IVBI treatment for DME in patients with moderate to severe CKD, our study supports switching to the aflibercept or dexamethasone implant.

The Anti-Atherosclerosis Effect of Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, in Apolipoprotein E Knockout Mice.

Interleukin (IL)-1ß plays an important role in atherosclerosis pathogenesis. We aimed to investigate the effect of anakinra, a recombinant human IL-1 receptor antagonist, on the progression of atherosclerosis in apolipoprotein E knockout (ApoE−/−) mice. ApoE−/− mice (8-week male) were treated with saline (control), anakinra 10, 25, and 50 mg/kg, respectively (n = 10 in each group). Mice were fed a standard chow (4 weeks) followed by an atherogenic diet (35kcal% fat, 1.25% cholesterol, 12 weeks). Atheromatous plaques in ApoE−/− mice and the expression of inflammatory genes and signaling pathways in human umbilical vein endothelial cells (HUVECs), rat aortic smooth muscle cells (RAOSMCs), and 3T3-L1 adipocytes were assessed. Anakinra reduced the plaque size of the aortic arch (30.6% and 25.2% at the 25 mg/kg and 50 mg/kg doses, both p < 0.05) and serum triglyceride in ApoE−/− mice and suppressed inflammatory genes (IL-1ß and IL-6) expressions in HUVECs and RAOSMCs (all p < 0.05). In RAOSMCs, anakinra reduced metalloproteinase-9 expression in a dose-dependent manner and inhibited cell migration. Anakinra-treated mice exhibited trends of lower CD68+ macrophage infiltration in visceral fat and monocyte chemoattractant protein-1 expression was reduced in 3T3-L1 adipocytes. Anakinra could be a useful component for complementary treatment with a standard regimen to reduce the residual cardiovascular risk.

Long-term effectiveness and safety of quadruple combination therapy with empagliflozin versus dapagliflozin in patients with type 2 diabetes: 3-year prospective observational study.

AIMS: To investigate the long-term effectiveness and safety of two distinct sodium-glucose co-transporter 2 (SGLT2) inhibitors, empagliflozin and dapagliflozin, in inadequately controlled type 2 diabetes (T2D) despite a combined administration of metformin, glimepiride and dipeptidyl peptidase-4 inhibitor. METHODS: A total of 362 patients with T2D were enrolled for this 3-year open-label, prospective observational study. Empagliflozin (25 mg/day, n = 185) or dapagliflozin (10 mg/day, n = 177) was added to the existing triple drug regimen. HbA1c, fasting plasma glucose (FPG), body weight, and other cardiometabolic variables and adverse events were evaluated. RESULTS: At 3 years, changes in HbA1c and FPG were -1.7% (standard error [SE] 0.10) and -60.0 mg/dL(2.2), and -1.1%(0.12) and -48.1 mg/dL(3.6), for empagliflozin and dapagliflozin group, respectively (P = 0.001 and P = 0.055). Empagliflozin group showed significantly greater body weight reduction (-4.5 kg [SE 0.35] vs. -1.0 kg [SE 0.40], P = 0.024) and had beneficial effects on HDL cholesterol and LDL cholesterol (both P < 0.05). The overall incidence of adverse events, cardiovascular events and mortality did not differ between the two groups. CONCLUSIONS: Quadruple combination therapy with either empagliflozin or dapagliflozin showed a positive long-term effect in the glycemic control and body weight reduction with generally well tolerance. In general, the use of empagliflozin performed better than dapagliflozin. Clinical Trial Number NCT03748810 (ClinicalTrials.gov).

Effect of Dipeptidyl Peptidase-4 Inhibitors on Bone Health in Patients with Type 2 Diabetes Mellitus.

Patients with type 2 diabetes (T2DM) have a higher risk of bone fracture even when bone mineral density (BMD) values are normal. The trabecular bone score (TBS) was recently developed and used for evaluating bone strength in various diseases. We investigated the effect of DPP-4 inhibitors on bone health using TBS in patients with T2DM. This was a single-center, retrospective case-control study of 200 patients with T2DM. Patients were divided into two groups according to whether they were administered a DPP-4 inhibitor (DPP-4 inhibitor group vs. control group). Parameters related to bone health, including BMD, TBS, and serum markers of calcium homeostasis, were assessed at baseline and after one year of treatment. We found TBS values increased in the DPP-4 group and decreased in the control, indicating a significant difference in delta change between them. The BMD increased in both groups, with no significant differences in delta change between the two groups observed. Serum calcium and 25-hydroxy vitamin D3 increased only in the DPP-4 inhibitor group, while other glycemic parameters did not show significant differences between the two groups. Treatment with DPP-4 inhibitors was associated with favorable effects on bone health evaluated by TBS in patients with T2DM.

Metabolic Subtyping of Adrenal Tumors: Prospective Multi-Center Cohort Study in Korea.

BACKGROUND: Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids. METHODS: The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing's syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors. RESULTS: The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6ß-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT. CONCLUSION: The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

RANTES 59029A/G Polymorphisms Associated with Diabetic Compilations in Korean Patients with Type 2 Diabetes for over 15 Years.

BACKGROUND: Polymorphisms in the RANTES gene are known to be associated with several diseases related to insulin resistance. In this study, we investigated the association between RANTES 59029A/G polymorphisms and the prevalence of diabetic complications relative to obesity in Korean patients who had type 2 diabetes (T2D) for over 15 years. METHODS: A single-center, retrospective case-control study was performed. We included 271 patients with a duration of diabetes greater than 15 years. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze RANTES polymorphisms, identifying genotypes as GG, AG, or AA. Obesity was defined using the body mass index with a cutoff value of 25 kg/m2. Both microvascular (retinopathy and nephropathy) and macrovascular (coronary artery disease and cerebrovascular disease) complications were evaluated. RESULTS: The duration of T2D and hemoglobin A1c values at enrollment were 24.4 ± 5.0 years and 7.8 ± 1.6%, respectively, in the non-obese group, and 25.4 ± 6.1 years and 7.7 ± 1.7%, respectively, in the obese group. The prevalence of microvascular complications was significantly higher in the obese group compared with that in the non-obese group (83.5% vs. 72.0%, p = 0.039). Compared to the non-obese group, the obese group showed a higher proportion of the patients with AA or AG genotypes (64.3% vs. 84.5%, p = 0.001). CONCLUSIONS: The A allele of the RANTES gene is associated with obesity and may affect diabetic microvascular complications in patients with T2D for over 15 years.

Polymorphism in the HaeIII single nucleotide polymorphism of the SLC2A1 gene and cardiovascular disease in the early type 2 diabetes mellitus.

INTRODUCTION: SLC2A1 polymorphism may play a role in the smooth muscle cell proliferation and extracellular matrix synthesis in vessels. However, the role of SLC2A1 polymorphism on diabetic cardiovascular disease (CVD) have not yet been identified. In this study, we aimed to investigate the association between SLC2A1 HaeIII polymorphism and CVD in Korean patients with type 2 diabetes mellitus (T2DM) according to disease duration. METHODS: A total of 846 patients with T2DM who visited the Chungbuk National University Hospital were investigated. The HaeIII polymorphism of SLC2A1 gene was determined by real time polymerase chain reaction method. Genotyping results were presented GG, AG, or AA. Subgroup analysis was performed according to duration of T2DM (⩽10, 11-20, >20 years). RESULTS: The AA genotype was significantly associated with higher prevalence of CVD in patients with DM duration less than 10 years (26.3% vs 9.2%, p = 0.014). There was no significant association between SLC2A1 HaeIII polymorphism and other diabetic complications including, retinopathy, nephropathy, neuropathy, cerebrovascular disease, and peripheral artery disease. CONCLUSIONS: The SLC2A1 HaeIII polymorphism was associated with CVD in Korean patients with T2DM with short disease duration.

Cardiovascular Outcomes in Thyroid Cancer Patients Treated With Thyroidectomy: A Meta-analysis.

CONTEXT: Thyroid dysfunction is associated with an increased risk of cardiovascular disease (CVD) in the general population; however, it remains controversial whether differentiated thyroid cancer (DTC) treatment, including thyroidectomy and thyroid-stimulating hormone suppression, further increases the risk of CVD. OBJECTIVE: This study aimed to evaluate the risk of CVD in patients with DTC. METHODS: We performed a review of observational studies on associations between DTC and cardiovascular outcomes, indexed in MEDLINE, Embase, and Web of Science. We excluded studies that evaluated CVD as comorbidity before DTC diagnosis and those that used active surveillance without thyroidectomy as an intervention. Risk estimates were pooled using random- and fixed-effects models when 3 or more studies reported on the outcome of interest. Echocardiographic and hemodynamic parameters were examined. RESULTS: Eighteen studies were included in the quantitative analysis (193 320 cases with DTC and 225 575 healthy controls). DTC was associated with an increased risk of atrial fibrillation (pooled risk ratio [RR] = 1.55 [95% CI: 1.30-1.84]), coronary artery disease (RR = 1.10 [1.00-1.21]), cerebrovascular accidents (RR = 1.15 [1.09-1.20]), and all-cause mortality (RR = 1.95 [1.03-3.69]). DTC was associated with higher diastolic blood pressure (standardized mean difference [SMD], 0.22 [0.01-0.42]), heart rate (0.37 [0.17-0.57]), left ventricular mass index (0.66 [0.45-0.88]), and interventricular septal thickness (0.91 [0.33-1.49]) and lower early to late ventricular filling velocities (-0.42 [-0.79 to -0.05]), but not with ejection fraction. CONCLUSION: Patients with DTC are at an increased risk of atrial fibrillation, CVD, increased heart rate, and left ventricular mass development.

Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Because subclinical hyperthyroidism increases the risk of osteoporosis and fractures, concerns are growing about the long-term skeletal safety of TSH suppression therapy after total thyroidectomy in patients with differentiated thyroid cancer (DTC). OBJECTIVE: We aimed to determine the effect of TSH suppression therapy on bone mineral density (BMD) in DTC patients. METHODS: We searched PubMed, Embase, the Cochrane library, and other sources. Eligible observational studies included DTC patients who underwent TSH suppression therapy and BMD measurement. Two independent reviewers extracted data on the studies' characteristics and outcomes and determined their risk of bias. Data were extracted from each study for postmenopausal/premenopausal women's and men's lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD and summed using a random-effects meta-analysis model. The weighted mean differences with 95% CIs are expressed for the differences in outcome measurements between groups. RESULTS: Seventeen studies (739 patients and 1085 controls) were included for quantitative analysis. In postmenopausal women, TSH suppression therapy showed a significant decrease in LS BMD (-0.03; -0.05, -0.02), and a similar trend was seen in TH. In premenopausal women, TSH suppression therapy significantly increased LS BMD (0.04; 0.02, 0.06) and FN BMD (0.02; 0.01, 0.04). In men, there was no significant association between TSH suppression therapy and BMD at any site compared with the controls. CONCLUSION: Evidence from observational studies suggests that postmenopausal women treated with TSH suppression therapy are at risk for lower BMD. Attention should be paid to long-term skeletal safety in DTC survivors.

Identification of candidate gene variants of monogenic diabetes using targeted panel sequencing in early onset diabetes patients.

INTRODUCTION: Monogenic diabetes is attributed to genetic variations in a single gene. Maturity-onset diabetes of the young (MODY) is the most common phenotype associated with monogenic diabetes, but is frequently misdiagnosed as either type 1 or type 2 diabetes. Increasing our basic understanding of genetic variations in MODY may help to improve the accuracy of providing the correct diagnosis and personalize subsequent treatment regimens in different racial populations. For this reason, this study was designed to identify nucleotide variants in early onset diabetes patients with clinically suspected MODY in a Korean population. RESEARCH DESIGN AND METHODS: Among 2908 Korean patients diagnosed with diabetes, we selected 40 patients who were diagnosed before 30 years old and were clinically suspected of MODY. Genetic testing was performed using a targeted gene sequencing panel that included 30 known monogenic diabetes genes. The pathogenicity of the identified variants was assessed according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG-AMP) guidelines. RESULTS: A total of six rare missense variants (p.Ala544Thr in HNF1A, p.Val601Ile and p.His103Tyr in ABCC8, p.Pro33Ala in PDX1, p.Gly18Glu in INS, and p.Arg164Gln in PAX4) in five distinct MODY genes were identified in five patients. In addition, a variant was identified in mitochondrial DNA at 3243A>G in one patient. The identified variants were either absent or detected at a rare frequency in the 1000 Genomes Project. These variants were classified as uncertain significance using the ACMG-AMP guidelines. CONCLUSION: Using a targeted gene sequencing panel, we identified seven variants in either MODY genes or mitochondrial DNA using a Korean patient population with early onset diabetes who were clinically suspected of MODY. This genetic approach provides the ability to compare distinct populations of racial and ethnic groups to determine whether specific gene is involved in their diagnosis of MODY.