Background/Aims: This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension. Methods: The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension. Results: The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events. Conclusions This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.

Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 588.6 → 264.4 for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625–160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.
Animals ; Calibration ; Carcinoma, Hepatocellular ; Cell Line ; Chromatography, Liquid ; Dermatitis, Atopic ; Gaucher Disease ; Humans ; Mass Screening ; Mass Spectrometry ; Metabolism ; Methods ; Mice

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
Academies and Institutes ; Asian Continental Ancestry Group ; DNA ; Humans ; Korea ; Methods ; Paraffin ; Point Mutation ; Precision Medicine ; Prevalence

OBJECTIVE: We used data from the 2010 to 2012 Korean National Health and Nutrition Examination Surveys to investigate whether the age at menopause is related to age at last delivery. METHODS: This was a cross-sectional study of the data for 714 women who became menopausal within the 3 years preceding the Korean National Health and Nutrition Examination Survey. RESULTS: Smoking, exercise, drink, educational level, and income were adjusted in model 1, and the mean ages at menopause were 50.5±0.3, 51.2±0.2, 51.2±0.3, and 50.2±0.4 years for women with <25, ≥25 and <30, ≥30 and <35, ≥35 years age at last delivery, respectively (P=0.049). Smoking, exercise, drink, educational level, income, age at first delivery, age at last delivery, and gravidity were adjusted in model 2, and the respective mean ages at menopause were 50.5±0.5, 50.7±0.4, 50.3±0.4, and 49.2±0.5 years (P=0.03). In both models, older age at last delivery showed higher age at menopause compared with women with younger age at last delivery. CONCLUSION: Korean women with older age at last delivery were associated with younger age at menopause. Increased number of pregnancies was related to older age at menopause.
Cross-Sectional Studies ; Female ; Gravidity ; Humans ; Korea* ; Menopause* ; Nutrition Surveys* ; Pregnancy ; Smoke ; Smoking

PURPOSE: In this retrospective study, we compared the incidence of leptomeningeal carcinomatosis or dural metastasis (LMCDM) in patients who received whole brain radiotherapy (WBRT), partial radiotherapy (PRT), or no radiotherapy (RT) following resection of brain metastases from breast cancer. MATERIALS AND METHODS: Fifty-one patients with breast cancer underwent surgical resection for newly diagnosed brain metastases in two institutions between March 2001 and March 2015. Among these, 34 received postoperative WBRT (n=24) or PRT (n=10) and 17 did not. RESULTS: With a median follow-up of 12.4 months (range, 2.3 to 83.6 months), 22/51 patients developed LMCDM at a median of 8.6 months (range, 4.8 to 51.2 months) after surgery. The 18-months LMCDM-free survival (LMCDM-FS) rates were 77.5%, 30.0%, and 13.6%, in the WBRT, PRT, and no RT groups, respectively (p=0.013). The presence of a tumor adjacent to cerebrospinal fluid flow and no systemic treatment after treatment for brain metastases were also associated with poor LMCDM-FS rate. Multivariate analysis showed that WBRT compared to PRT (p=0.009) and systemic treatment (p < 0.001) were independently associated with reduced incidence of LMCDM. CONCLUSION: WBRT improved LMCDM-FS rate after resection of brain metastases compared to PRT in breast cancer patients.
Brain* ; Breast Neoplasms* ; Breast* ; Cerebrospinal Fluid ; Follow-Up Studies ; Humans ; Incidence ; Meningeal Carcinomatosis* ; Multivariate Analysis ; Neoplasm Metastasis* ; Radiotherapy* ; Retrospective Studies

PURPOSE: In this retrospective study, we compared the incidence of leptomeningeal carcinomatosis or dural metastasis (LMCDM) in patients who received whole brain radiotherapy (WBRT), partial radiotherapy (PRT), or no radiotherapy (RT) following resection of brain metastases from breast cancer. MATERIALS AND METHODS: Fifty-one patients with breast cancer underwent surgical resection for newly diagnosed brain metastases in two institutions between March 2001 and March 2015. Among these, 34 received postoperative WBRT (n=24) or PRT (n=10) and 17 did not. RESULTS: With a median follow-up of 12.4 months (range, 2.3 to 83.6 months), 22/51 patients developed LMCDM at a median of 8.6 months (range, 4.8 to 51.2 months) after surgery. The 18-months LMCDM-free survival (LMCDM-FS) rates were 77.5%, 30.0%, and 13.6%, in the WBRT, PRT, and no RT groups, respectively (p=0.013). The presence of a tumor adjacent to cerebrospinal fluid flow and no systemic treatment after treatment for brain metastases were also associated with poor LMCDM-FS rate. Multivariate analysis showed that WBRT compared to PRT (p=0.009) and systemic treatment (p < 0.001) were independently associated with reduced incidence of LMCDM. CONCLUSION: WBRT improved LMCDM-FS rate after resection of brain metastases compared to PRT in breast cancer patients.
Brain* ; Breast Neoplasms* ; Breast* ; Cerebrospinal Fluid ; Follow-Up Studies ; Humans ; Incidence ; Meningeal Carcinomatosis* ; Multivariate Analysis ; Neoplasm Metastasis* ; Radiotherapy* ; Retrospective Studies

OBJECTIVE: Although guideline recommends beta blockers (BBs) as first line antianginal agent and calcium channel blockers (CCBs) as alternatives after percutaneous coronary intervention (PCI), the prescription patterns in real practice are not in accordance with the guideline. We aimed to investigate the prescribing patterns of primary antianginal drug and relating factors in patients who underwent PCI. METHODS: Patients who have undergone PCI without myocardial infarction (MI) from November 2012 to June 2014 and followed up at least one year in a tertiary teaching hospital were included. Prescribing patterns of primary antianginal drug before, at the time of, and one year after PCI were described. Factors affecting drug selection, and their relationship with incidence of clinical outcomes defined as MI and repeated PCI, unscheduled admission or visit related with heart problem were analyzed with multivariate logistic regression. RESULTS: A total of 506 patients were included and as primary antianginal drugs, BB, CCB, and both were prescribed in 32.2%, 24.5%, and 17.8% of patients, respectively. Also, neither BB nor CCB was prescribed at the time of PCI in 25.5% of patients. Compared with BB, CCBs were more likely prescribed in patients who had hypertension (Odds Ratio, OR 2.18, 95% confidence interval, CI 1.16-4.07), use of same class before PCI (OR 7.18, 3.37-15.2) and concomitant angiotensin receptor blocker (ARB) use (OR, 1.92, 95% CI 1.10-3.33). Incidence of clinical outcomes were not significantly greater in patients who prescribed CCB compared with BB at the time of PCI (aOR 1.32, CI 0.65-2.68). CONCLUSION: This study demonstrated that half of the patients who underwent PCI were prescribed BB. CCB were favored in patients with hypertension, use of same class before PCI, and concomitant ARB use. Significant difference in clinical outcome was not observed between BB and CCB selection as primary antianginal drug.
Angiotensins ; Calcium Channel Blockers* ; Calcium Channels* ; Calcium* ; Heart ; Hospitals, Teaching ; Humans ; Hypertension ; Incidence ; Logistic Models ; Myocardial Infarction ; Percutaneous Coronary Intervention* ; Prescriptions*

We aimed to assess one-year persistence with antihypertensive therapy (AHT) among newly treated uncomplicated hypertensive patients in Korea and to evaluate the effect of initial therapeutic classes on persistence. We retrospectively analyzed a random sample of 20% of newly treated uncomplicated hypertensive patients (n = 45,787) in 2012 from the National Health Insurance claims database. This group was classified into six cohorts based on initial AHT class. We then measured treatment persistence, allowing a prescription gap of 60 days. Adherence to AHT was assessed with the medication possession ratio. Calcium channel blockers (CCB, 43.7%) and angiotensin receptor blockers (ARB, 40.3%) were most commonly prescribed as initial monotherapy. Overall, 62.1% and 42.0% were persistent with any AHT and initial class at one year, respectively, and 64.2% were adherent to antihypertensive treatment. Compared with ARBs, the risk of AHT discontinuation was significantly increased with initial use of thiazide diuretics (hazard ratio [HR], 3.16; 95% confidence interval [CI] 2.96-3.74) and beta blockers (HR, 1.86; CI, 1.77-1.95) and was minimally increased with CCBs (HR, 1.12; CI, 1.08-1.15). In conclusion, persistence and adherence to AHT are suboptimal, but the differences are meaningful in persistence and adherence between initial AHT classes.
Adolescent ; Adrenergic beta-Antagonists/therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Antihypertensive Agents/classification/*therapeutic use ; Calcium Channel Blockers/therapeutic use ; Cohort Studies ; Female ; Humans ; Hypertension/*drug therapy ; Male ; Medication Adherence ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Sodium Chloride Symporter Inhibitors/therapeutic use ; Young Adult

PURPOSE: To report a case of secondary pigmentary glaucoma after implantable contact lens (ICL) implantation successfully treated with trabeculectomy without ICL removal. CASE SUMMARY: A 29-year-old woman presented with refractory intraocular pressure (IOP) increase in both eyes. IOP was 22 mm Hg in the right eye and 39 mm Hg in the left eye. The patient received posterior chamber phakic intraocular lens implantation in both eyes 22 months prior. Slit lamp examination revealed patent iridotomy sites in both eyes. Gonioscopy revealed open angles with 4-degree pigment deposits on the trabecular meshwork in both eyes. Ultrasound biomicroscopy examination confirmed contact between ICL and the posterior surface of the iris. In spite of well tolerated medical therapy and selective laser trabeculoplasty, IOP was 46 mm Hg in her left eye. Trabeculectomy was performed in her left eye without ICL removal. At 6 months postoperative, IOP measured 6 mm Hg without any anti-glaucoma medication and bleb was maintained in good condition in the left eye. CONCLUSIONS: The results from this case study indicate that ICL implantation can lead to secondary pigmentary glaucoma and trabeculectomy without ICL removal may help to decrease the IOP.
Blister ; Eye ; Female ; Glaucoma, Open-Angle ; Gonioscopy ; Humans ; Intraocular Pressure ; Iris ; Lenses, Intraocular ; Microscopy, Acoustic ; Phakic Intraocular Lenses ; Trabecular Meshwork ; Trabeculectomy

PURPOSE: The purpose of this study was to know whether ultrasonography is proper diagnostic tool for decision of treatment method or not, as compared the efficacy of US in allowing identifying fracture patterns of nasal bone with that of CT. MATERIALS AND METHODS: Fifty patients with nasal trauma were investigated prospectively by CT and US. According to CT and ultrasonographic findings, each case of nasal bone injury were rated as grade 1 (nasal injury but not fracture), grade 2 (simple fracture without displacement), grade 3 (unilateral simple fracture with displacement), grade 4 (bilateral simple fractures with displacement), and grade 5 (bilateral comminuted fractures with depression). Assessment for ultrasonographic method were defined as overestimations or underestimation according to whether the nasal fracture had been assigned a higher or lower grade at the review of the findings of CT. The correlation between the results of CT and ultrasonography were measured. RESULTS: In ultrasonographic estimation of grade of 50 cases of nasal bone injuries, there were correctly graded in 42 cases, overestimated in 5 cases, underestimated in 3 cases. In allowing accurate grading of nasal bone injury, images of nasal ultrasonography correlated closely with those of CT (r = 0.796). CONCLUSION: Nasal ultrasonography is a reliable method that allows appropriate grading of nasal bone injury and would be a useful first line imaging method in providing the detail necessary for proper management of patients with mild simple nasal bone injury.
Fractures, Comminuted ; Humans ; Nasal Bone ; Prospective Studies