High WHSC1L1 Expression Reduces Survival Rates in Operated Breast Cancer Patients with Decreased CD8+ T Cells: Machine Learning Approach.

Nuclear receptor-binding SET domain protein (NSD), a histone methyltransferase, is known to play an important role in cancer pathogenesis. The WHSC1L1 (Wolf-Hirschhorn syndrome candidate 1-like 1) gene, encoding NSD3, is highly expressed in breast cancer, but its role in the development of breast cancer is still unknown. The purpose of this study was to analyze the survival rates and immune responses of breast cancer patients with high WHSC1L1 expression and to validate the results using gradient boosting machine (GBM) in breast cancer. We investigated the clinicopathologic parameters, proportions of immune cells, pathway networks and in vitro drug responses according to WHSC1L1 expression in 456, 1500 and 776 breast cancer patients from the Hanyang University Guri Hospital, METABRIC and TCGA, respectively. High WHSC1L1 expression was associated with poor prognosis, decreased CD8+ T cells and high CD274 expression (encoding PD-L1). In the pathway networks, WHSC1L1 was indirectly linked to the regulation of the lymphocyte apoptotic process. The GBM model with WHSC1L1 showed improved prognostic performance compared with the model without WHSC1L1. We found that VX-11e, CZC24832, LY2109761, oxaliplatin and erlotinib were effective in inhibiting breast cancer cell lines with high WHSC1L1 expression. High WHSC1L1 expression could play potential roles in the progression of breast cancer and targeting WHSC1L1 could be a potential strategy for the treatment of breast cancer.

Cardiovascular safety of evogliptin in patients with type 2 diabetes: A nationwide cohort study.

AIM: To assess whether the use of evogliptin, a novel dipeptidyl peptidase-4 inhibitor (DPP-4i), was associated with an increased risk of cardiovascular events compared with glimepiride in patients with type 2 diabetes (T2D). METHODS: We conducted a population-based cohort study using South Korea's nationwide healthcare database from 1 January 2014 to 31 December 2018. We identified a base cohort of patients with T2D who newly initiated metformin monotherapy, from which we identified a study cohort of patients who either added or switched to glimepiride or DPP-4is (including evogliptin). Patients were followed up from initiation of DPP-4is or glimepiride until the earliest of either outcome occurrence or 31 December 2018. Our primary outcome was hospitalization or an emergency visit for cardiovascular events, a composite endpoint comprised of cerebrovascular events, heart failure, myocardial infarction, transient ischaemic attack, angina pectoris and revascularization procedures; secondary outcomes were the individual components of the primary outcome. A multivariable Cox proportional hazards model was used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the risk of study outcomes associated with evogliptin compared with glimepiride. RESULTS: Our base and study cohorts had 317,307 and 128,788 patients, respectively, of which 100,038 were DPP-4i users (2946 were evogliptin users) and 28,750 were glimepiride users within the study cohort. The median follow-up was 195 days for evogliptin and 113 days for glimepiride users. Compared with glimepiride, evogliptin was associated with a reduced risk of the primary outcome (aHR 0.67, 95% CI 0.48-0.95) and cerebrovascular events (aHR 0.41, 95% CI 0.22-0.78) but showed non-significant associations for myocardial infarction (aHR 0.63, 95% CI 0.27-1.46), heart failure (aHR 0.35, 95% CI 0.09-1.47), transient ischaemic attack (aHR 0.23, 95% CI 0.03-1.72) and angina pectoris (aHR 1.35, 95% CI 0.82-2.21). CONCLUSIONS: Findings from this population-based cohort study provide novel real-world evidence that the use of evogliptin, compared with glimepiride, did not increase the risk of cardiovascular events, including cerebrovascular events, myocardial infarction, heart failure, transient ischaemic attack and angina pectoris.

Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology.

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

Changes in Thyroid Peroxidase and Thyroglobulin Antibodies Might Be Associated with Graves' Disease Relapse after Antithyroid Drug Therapy.

BACKGROUND: Graves' disease (GD) is an autoimmune thyroid disorder caused by antibodies stimulating the thyrotropin (TSH) receptor. TSH receptor antibody (TRAb) measurement is useful for predicting GD relapse after antithyroid drug (ATD) treatment. However, the association of other thyroid autoantibodies with GD relapse remains obscure. METHODS: This retrospective study enrolled patients with GD who were initially treated with ATD. TRAb, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured at the initial diagnosis and at the time of ATD discontinuation. RESULTS: A total of 55 patients were enrolled. The mean age was 49.7 years, and 39 patients (70.9%) were female. Antibody positivity at diagnosis was 90.9%, 69.1%, and 61.9% for TRAb, TPOAb, TgAb, respectively. Median ATD treatment period was 15.1 months. At the time of ATD withdrawal, TRAb titers decreased uniformly overall. Conversely, TPOAb and TgAb showed various changes. After withdrawal of ATD, 19 patients (34.5%) experienced relapse. No clinical features or laboratory results were significantly related to relapse in the overall patient group. However, in the TPOAb positive group at diagnosis, increasing titer of TPOAb or TgAb after ATD treatment was significantly and independently related to relapse free survival (TPOAb: hazard ratio [HR], 17.99; 95% confidence interval [CI], 1.66 to 195.43; P=0.02) (TgAb: HR, 5.73; 95% CI, 1.21 to 27.26; P=0.03). CONCLUSION: Changes in TPOAb or TgAb titers during treatment might be useful for predicting relapse after ATD treatment in patients with positive TPOAb at diagnosis.

Changes in standardized mortality rates from thyroid cancer in Korea between 1985 and 2015: Analysis of Korean national data.

BACKGROUND: The incidence of thyroid cancer has increased very rapidly in Korea; however, most previous studies suggested that the mortality rate for thyroid cancer remained stable. The objective of the current study was to evaluate recent changes in standardized thyroid cancer mortality using data from Statistics Korea. METHODS: Population and mortality data from 1985 through 2015 were obtained from Statistics Korea. Age-standardized mortality rates (ASMRs) from thyroid cancer per 100,000 population were calculated based on the World Health Organization standard population. RESULTS: In Korea, the ASMRs from thyroid cancer increased from 0.17 (95% confidence interval [CI], 0.17-0.18) per 100,000 in 1985 to 0.85 (95% CI, 0.83-0.86) per 100,000 in 2004, which was the highest among all countries. Subsequently, the ASMRs continuously decreased to 0.42 (95% CI, 0.41-0.43) per 100,000 between 2004 and 2015. The estimated annual percent change (APC) from 1985 to 2004 was 7.94 (95% CI, 6.43-9.46), and the corresponding value from 2004 to 2015 was -4.10 (95% CI, -5.76 to -2.40). Changes in the ASMRs reflected similar patterns in men (1985-2003: APC, 8.51; 2003-2015: APC, -4.32) and women (1985-2004: APC, 7.62; 2004-2015: APC, -4.38) and were also observed in older patients (aged ≥ 55 years). CONCLUSIONS: Thyroid cancer mortality in Korea increased until 2004 and then continuously decreased until 2015. Increases in the early diagnosis of thyroid cancer, changes in exposure to risk factors, and standardization in diagnosis and treatment may be associated with the decrease in thyroid cancer mortality in Korea. Cancer 2017; 123:4808-14. © 2017 American Cancer Society.

Efficacy and safety of adding evogliptin versus sitagliptin for metformin-treated patients with type 2 diabetes: A 24-week randomized, controlled trial with open label extension.

AIMS: This trial consisted of a 24-week multicentre, randomized, double-blind, double-dummy, active-controlled study and a 52-week open label extension study to assess the efficacy and safety of evogliptin, a novel dipeptidyl peptidase-4 inhibitor, compared to sitagliptin in patients with type 2 diabetes who have inadequate glycaemic control with metformin alone. METHODS: Adult patients with type 2 diabetes mellitus (N = 222) with HbA1c 6.5% to 11% who were receiving stable doses of metformin (≥1000 mg/d) were randomized 1:1 to add-on evogliptin 5 mg (N = 112) or sitagliptin 100 mg (N = 110) once daily for 24 weeks. The primary efficacy analysis consisted of a comparison of the change from baseline HbA1c at week 24. Non-inferiority was concluded if the upper limit of the 2-sided 95% confidence interval for the HbA1c difference between treatments was <0.35%. RESULTS: Mean changes in HbA1c following addition of evogliptin or sitagliptin were -0.59% and -0.65%, respectively. The between-group difference was 0.06% (2-sided 95% confidence interval, -0.10 to 0.22), demonstrating non-inferiority. After the 52-week treatment, evogliptin caused a persistently decreased level of HbA1c (-0.44% ± 0.65%, P < .0001). In general, both treatments were well tolerated, with incidences and types of adverse events comparable between the two groups. Hypoglycaemic events, mostly mild, were reported in 0.9% of patients treated with evogliptin and in 2.8% of patients treated with sitagliptin for 24 weeks. CONCLUSIONS: Evogliptin 5 mg added to metformin therapy effectively improved glycaemic control and was non-inferior to sitagliptin and well tolerated in patients with type 2 diabetes mellitus that was inadequately controlled by metformin alone.

Partial Androgen Insensitivity Syndrome Presenting with Gynecomastia.

Gynecomastia is a benign enlargement of the male breast caused by the proliferation of glandular breast tissue. Determining the various causes of gynecomastia such as physiological causes, drugs, systemic diseases, and endocrine disorders is important. Androgen insensitivity syndrome (AIS) is a rare endocrine disorder presenting with gynecomastia and is a disorder of male sexual differentiation caused by mutations within the androgen receptor gene. All individuals with AIS have the 46 XY karyotype, although AIS phenotypes can be classified as mild, partial or complete and can differ among both males and females including ambiguous genitalia or infertility in males. We experienced a case of partial AIS presenting with gynecomastia and identified the androgen receptor gene mutation.

A case of acute suppurative thyroiditis with thyrotoxicosis in an elderly patient.

Acute suppurative thyroiditis (AST) is a rare condition, as the thyroid gland is relatively resistant to infection. Thyroid function tests are usually normal in AST. A few cases of AST associated with thyrotoxicosis have been reported in adults. We report a case of AST that was associated with thyrotoxicosis in a 70-year-old woman. We diagnosed AST with thyroid ultrasonography and fine needle aspiration of pus. The patient improved after surgical intervention and had no anatomical abnormality. Fine needle aspiration is the best method for the difficult task of differentiating malignancy and subacute thyroiditis from AST with thyrotoxicosis. Earlier diagnosis and proper treatment for AST might improve the outcome.

Clinical efficacy of sentinel lymph node biopsy using methylene blue dye in clinically node-negative papillary thyroid carcinoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has recently been used to detect occult lymph node metastases. The aim of this study was to assess the feasibility and clinical efficacy of SLNB in the treatment of clinically node-negative papillary thyroid carcinoma. METHODS: A total of 114 consecutive patients with clinically node-negative papillary thyroid carcinoma were enrolled and underwent SLNB. After injection of 1% methylene blue around the tumors, blue-stained sentinel lymph nodes (SLN) were collected from the central compartments. All the patients underwent total thyroidectomy with bilateral central compartment neck dissection after SLNB. RESULTS: SLN were identified in 84 (73.7%) of the 114 patients. Of these 84 patients, 24 (28.6%) had metastases in the SLN. Among the 60 patients who had no metastases in their SLN in frozen biopsy samples, seven had metastatic foci in their SLN in the permanent biopsy samples and six had metastases in their non-SLN samples. Central compartment lymph node metastases were detected in 11 of the 30 patients in whom SLN were not identified. Thus, the sensitivity, specificity, and positive and negative predictive values of SLNB were 64.9, 100, 100, and 78.3%, respectively. The false-positive and false-negative rates were 0 and 35.1%, respectively. The detection of SLN led to no major complications. CONCLUSIONS: SLNB using methylene blue in papillary thyroid carcinoma is a safe and technically feasible procedure. However, it is of limited use in the management of clinically node-negative papillary thyroid carcinoma because of low sensitivity and a high false-negative rate.

[Outbreak of hepatitis by Orientia tsutsugamushi in the early years of the new millenium].

BACKGROUND/AIMS: Orientia -tsutsugamushi infection is an acute febrile disease due to the accidental transmission through human skin of forest dwelling vector Leptotrombidium larva. The authors observed liver dysfunctions in patients diagnosed with tsutsugamushi disease (Scrub typhus) in the past 3 years and report the data in the hope of bringing attention to this disease in the differential diagnosis of autumn-season hepatitis, especially of non-A, non-B and non-C hepatitis. METHODS: Medical records of 22 patients diagnosed with tsutsugamushi disease by the hemagglutinin method between October 2000 and November 2002 were reviewed. RESULTS: Female gender was dominant in the ratio of 3.4:1. Mean age was 56.4 +/- 2.6. Admission was between 23rd September and 15th November with the peak between mid October and early November. Fever, being the most common symptom, was observed in 21 cases, myalgia in 13, arthralgia in 12, chills in 6, and skin rash in 6. An incubation period of 7-9 days was most common (10 cases), 13-15 days (4), 10-12 days (3), within 3 days (3), and 4-6 days (2). Average ALT, AST and GGTP were increased to 93.2 +/- 17.3 IU/L (18 +/- 345 IU/L), 92.5 +/- 11.7 IU/L (34-255 IU/L) and 132.2 +/- 14.5 IU/L (19-251 IU/L), respectively, but total bilirubin was normal. All the patients improved with doxycycline therapy. CONCLUSIONS: Since it usually shows liver dysfunction, it is important to take Orientia tsutsugamushi into consideration in differential diagnosis of autumn-season, febrile hepatic disease.