Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Objectives: . Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by recurrent epistaxis, telangiectasia, and visceral arteriovenous malformations (AVMs). Activin A receptor-like type 1 (ACVRL1/ALK1) and endoglin (ENG) are the principal genes whose mutations cause HHT. No multicenter study has yet investigated correlations between genetic variations and clinical outcomes in Korean HHT patients. Methods: . Seventy-two members from 40 families suspected to have HHT based on symptoms were genetically screened for pathogenic variants of ACVRL1 and ENG. Patients with genetically diagnosed HHT were also evaluated. Results: . In the HHT genetic screening, 42 patients from 24 of the 40 families had genetic variants that met the pathogenic criteria (pathogenic very strong, pathogenic strong, pathogenic moderate, or pathogenic supporting) based on the American College of Medical Genetics and Genomics Standards and Guidelines for either ENG or ACVRL1: 26 from 12 families (50%) for ENG, and 16 from 12 families (50%) for ACVRL1. Diagnostic screening of 42 genetically positive HHT patients based on the Curaçao criteria revealed that 24 patients (57%) were classified as having definite HHT, 17 (41%) as having probable HHT, and 1 (2%) as unlikely to have HHT. Epistaxis was the most common clinical presentation (38/42, 90%), followed by visceral AVMs (24/42, 57%) and telangiectasia (21/42, 50%). Five patients (12%) did not have a family history of HHT clinical symptoms. Conclusion . Only approximately half of patients with ACVRL1 or ENG genetic variants could be clinically diagnosed as having definite HHT, suggesting that genetic screening is important to confirm the diagnosis.

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Background: Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). Methods: From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. Results: In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9± 14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, –1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. Conclusion This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

PURPOSE: Mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with epileptic encephalopathy and severe cognitive impairment. We aim to characterize the association between this gene and treatment efficacy. METHODS: We retrospectively analyzed 10 patients who were treated at Severance Children's Hospital for epileptic encephalopathy who were subsequently diagnosed with a CDKL5 mutation using next-generation sequencing. RESULTS: Electroencephalography (EEG) results showed generalized pattern abnormalities in 60% (6/10) of patients with CDKL5 mutations. We analyzed the effects of three treatments, namely antiepileptic drugs (AEDs), ketogenic diet (KD), and steroids. A more than 50% reduction in seizures was observed in 12% (1/8) of patients treated with clobazam. KD treatment proved ineffective in most cases. In addition, a more than 50% reduction in seizures was observed in 57% (4/7) of patients treated with steroids. EEG analysis of patients treated effectively with steroids revealed that 75% (3/4) showed hypsarrhythmia and 25% (1/4) showed focal epileptiform. CONCLUSION In this study, as in other studies, AEDs and KD did not effectively control seizures in most patients with a CDKL5 mutation. However, steroid therapy reduced the frequency of seizures in patients who also exhibited hypsarrhythmia. This suggests that steroid treatment is helpful in cases of hypsarrhythmia with CDKL5 mutations.

PURPOSE: In Korea, the incidence of breast cancer peaks in the fifth decade, which is younger than that observed in the Western world. We conducted this study to compare the clinical characteristics and prognostic factors of breast cancer in women < 35 and ≥35 years old.METHODS: The medical records of 969 patients treated for breast cancer at the Gil Medical Center from 2008 through 2012 were reviewed. Tumor characteristics, surgical methods, and adjuvant therapies were compared in two groups.RESULTS: Number of childbirths, family history, the proportion of postmenopausal women were lower among those aged < 35 years. However, tumor size, number of metastatic lymph nodes, and surgical procedures were similar in two groups. The rate of triple negative status in younger patients was higher than in older patients. Adjuvant chemotherapy was effective in patients positive for hormone receptors and no lymph nodal invasion, and it was effective in patients negative for hormone receptors and lymph nodal invasion in patients aged >35 years old. Postoperative radiotherapy was statistically effective in patients aged < 35 and ≥35 years old that underwent breast-conserving surgery. Pregnancy were significantly associated with survival in younger patients. While lymph node stage, presence of progesterone receptor, and triple negative status were significantly associated with survival on older patients.CONCLUSION: The prognostic factors of breast cancer in patients younger than 35 years old were pregnancy. Triple negative status rate was higher in younger patients than in older patients. Adjuvant therapy had similar effects in patients aged < 35 or ≥35 years old.
Breast Neoplasms ; Breast ; Chemotherapy, Adjuvant ; Female ; Humans ; Incidence ; Korea ; Lymph Nodes ; Mastectomy, Segmental ; Medical Records ; Parturition ; Pregnancy ; Prognosis ; Radiotherapy ; Receptors, Progesterone ; Western World ; Young Adult

PURPOSE: The aim of this study is to examine the SCN1A variants in Korean patients with Dravet syndrome. METHODS: We conducted a retrospective study of clinically confirmed thirty-nine patients with Dravet syndrome who visit our hospital from January 2007 to May 2015. We analyzed the SCN1A variants by direct sequencing. We analyzed and classified SCN1A variants according to ACMG/AMP (American College of Medical Genetics and Genomics and the Association for Molecular Pathology) guideline. RESULTS: A total thirty-nine patients (female 22, male 17) were included. Among them, twenty patients (51.2%) with Dravet syndrome had pathogenic or likely pathogenic SCN1A mutations including fifteen truncating mutations (12 nonsense and 3 splice region mutations), 5 missense mutations. The remained variants in nineteen patients with Dravet syndrome classified into ten variants of unknown significances, and 9 benign variants. In our study, truncation mutations are located whole span of SCN1A protein, while half of missense mutations are located at higher density on pore loop (S5-S6) regions. CONCLUSION: Unlike previous known study, lower positive rate of SCN1A mutation of Dravet syndrome was revealed in our study. The importance of parental test (trio test) and other additional tests have been emphasized.
Epilepsies, Myoclonic* ; Genetics, Medical ; Genomics ; Humans ; Male ; Mutation, Missense ; Parents ; Retrospective Studies