Cohort Studies ; Coinfection ; Hepatitis B virus ; HIV Infections ; HIV ; Humans ; Immunization, Secondary ; Korea ; Parturition ; Prevalence ; Vaccination

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

The guidelines for chronic obstructive pulmonary disease (COPD) treatment are important for the management of the disease. However, studies regarding the treatment adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have been scarce in Korea. Therefore, to examine the adherence to the GOLD guidelines, we examined the patterns of prescribed medication in COPD patients from 2011 to 2018. Patients were classified as having been appropriately and inappropriately treated (overtreatment or undertreatment) for the GOLD group. Appropriate medical therapy was defined as using the first choice or alternative choice drug recommended in the GOLD guidelines. Inappropriate therapy was classified as overtreatment or undertreatment in accordance with the categorization in the GOLD guidelines. According to treatment of 2011 GOLD guidelines, there was inappropriate treatment in 52.3% in group A, 47.3% in group B, 56.3% in group C, and 17.8% in group D. According to treatment of 2017 GOLD guidelines, there was inappropriate treatment in 66.7% in group A, 45.3% in group B, 14.3% in group C, and 24.0% in group D. The common type of inappropriate COPD treatment is overtreatment, with inhaled corticosteroid (ICS) containing regimens. In conclusions, adherence to the GOLD guideline by the pulmonologist in clinical practice is still low in Korea. Therefore, we need better strategies to both optimize the use of the guidelines and adhere to the guidelines as well.
Humans ; Korea* ; Lung Diseases ; Medical Overuse ; Pulmonary Disease, Chronic Obstructive*

BACKGROUND: Mycobacterium bovis Bacille Calmette-Guérin (BCG) osteitis, a rare complication of BCG vaccination, has not been well investigated in Korea. This study aimed to evaluate the clinical characteristics of BCG osteitis during the recent 10 years in Korea. METHODS: Children diagnosed with BCG osteitis at the Seoul National University Children's Hospital from January 2007 to March 2018 were included. M. bovis BCG was confirmed by multiplex polymerase chain reaction (PCR) in the affected bone. BCG immunization status and clinical information were reviewed retrospectively. RESULTS: Twenty-one patients were diagnosed with BCG osteitis and their median symptom onset from BCG vaccination was 13.8 months (range, 6.0–32.5). Sixteen children (76.2%) received Tokyo-172 vaccine by percutaneous multiple puncture method, while four (19.0%) and one (4.8%) received intradermal Tokyo-172 and Danish strain, respectively. Common presenting symptoms were swelling (76.2%), limited movement of the affected site (63.2%), and pain (61.9%) while fever was only accompanied in 19.0%. Femur (33.3%) and the tarsal bones (23.8%) were the most frequently involved sites; and demarcated osteolytic lesions (63.1%) and cortical breakages (42.1%) were observed on plain radiographs. Surgical drainage was performed in 90.5%, and 33.3% of them required repeated surgical interventions due to persistent symptoms. Antituberculosis medications were administered for a median duration of 12 months (range, 12–31). Most patients recovered without evident sequelae. CONCLUSION: Highly suspecting BCG osteitis based on clinical manifestations is important for prompt management. A comprehensive national surveillance system is needed to understand the exact incidence of serious adverse reactions following BCG vaccination and establish safe vaccination policy in Korea.
Child ; Drainage ; Femur ; Fever ; Humans ; Immunization* ; Incidence ; Korea* ; Methods ; Multiplex Polymerase Chain Reaction ; Mycobacterium bovis* ; Mycobacterium* ; Osteitis* ; Punctures ; Retrospective Studies ; Seoul ; Tarsal Bones ; Vaccination

Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the “Stroke Statistics in Korea” project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.
Adult ; Aged ; Alcohol Drinking ; Ambulances ; Atrial Fibrillation ; Cerebral Hemorrhage ; Emergency Medical Services ; Emergency Service, Hospital ; Epidemiology ; Female ; Hemorrhage ; Hope ; Humans ; Hypertension ; Incidence ; Korea ; Male ; Mortality ; Prevalence ; Reperfusion ; Risk Factors ; Smoke ; Smoking ; Stroke ; Subarachnoid Hemorrhage ; Writing

OBJECTIVE: The benefits of targeted temperature management (TTM) for resuscitated out of hospital cardiac arrest (OHCA) with an initial non-shockable rhythm are still unclear. This study examined whether TTM reduces the mortality and improves the neurological outcomes of OHCA with a non-shockable initial rhythm. METHODS: This study analyzed the clinical outcome of 401 resuscitated patients with an initial non-shockable rhythm among a total of 1,616 OHCA patients who were registered in Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance. The impact of TTM was investigated after accounting for the patients' propensity for TTM. The primary outcome was a 30-day in-hospital course with a neurologically favorable outcome defined by a cerebral performance categories scale ≤2. RESULTS: TTM was performed in 89 patients (22%) with an initial non-shockable rhythm. Patients who has received TTM had a tendency to be younger, more likely to be female, and more likely to undergo percutaneous coronary intervention. The clinical outcome of the patients in the initial non-shockable rhythm treated by TTM was superior to those without TTM (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.27–0.46). Further analysis after propensity score matching or inverse probability of treatment weighting (IPTW) showed consistent findings (propensity score matching: HR, 0.32; 95% CI, 0.22–0.45; IPTW: HR, 0.40; 95% CI, 0.31–0.52; P<0.001, all). CONCLUSION: In this nationwide OHCA registry, TTM was related to an approximately three-fold better 30-day neurologically favorable survival of resuscitated patients with TTM treatment than patients without TTM in the initial non-shockable rhythm.
Cardiopulmonary Resuscitation ; Epidemiological Monitoring ; Female ; Heart Arrest ; Humans ; Hypothermia, Induced ; Mortality ; Out-of-Hospital Cardiac Arrest ; Percutaneous Coronary Intervention ; Prognosis ; Propensity Score

BACKGROUND: Kabuki syndrome is a rare genetic disorder characterized by distinct dysmorphic facial features, growth deficiency, intellectual disabilities, unusual dermatoglyphic patterns, and skeletal abnormalities. The incidence of hip dislocation in Kabuki syndrome ranges from 18% to 62%. We reviewed the outcomes of management of hip dislocations in patients with Kabuki syndrome with special attention to the diagnostic processes for hip dislocation and Kabuki syndrome. METHODS: Among 30 patients with mutation-confirmed Kabuki syndrome, we selected six patients who had hip dislocations and reviewed their medical records and plain radiographs. The modes of presentation and diagnostic processes for both hip dislocations and Kabuki syndrome were investigated. The management and treatment outcomes of hip dislocations in patients with Kabuki syndrome were evaluated. RESULTS: The average age of patients at the time of diagnosis of hip dislocation was 7.7 months (range, 1 week to 22 months). None of the patients were diagnosed as having Kabuki syndrome at that time. Two patients were treated with a Pavlik harness; one, with closed reduction; two, with open reduction and later pelvic and/or femoral osteotomies; and one, with open reduction combined with pelvic osteotomy. The patients were followed up for 5.8 years on average (range, 2.0 to 10.5 years). The radiologic outcome was graded as Severin IA or IB for three patients who were older than 6 years at the latest follow-up (mean age, 9.9 years; range, 7.8 to 12.4 years). In the remaining three patients younger than 6 years (mean age, 3.8 years; range, 2.7 to 5.3 years), the lateral center edge angle was more than 15°. The clinical diagnosis of Kabuki syndrome was made during follow-up after hip dislocation treatment and confirmed by mutational analysis at a mean age of 4.7 years. The mean interval between the diagnosis of hip dislocation and Kabuki syndrome was 4.0 years. CONCLUSIONS: The management of hip dislocation by conservative or surgical method showed successful results. Awareness of Kabuki syndrome could lead to an early diagnosis of this rare disease in patients with hip dislocation and allow for early detection of other underlying conditions and multidisciplinary management.
Dermatoglyphics ; Diagnosis ; Early Diagnosis ; Follow-Up Studies ; Hip Dislocation ; Hip ; Humans ; Incidence ; Intellectual Disability ; Medical Records ; Methods ; Osteotomy ; Rare Diseases

BACKGROUND AND PURPOSE: The clinical implications of echocardiography findings for long-term outcomes in atrial fibrillation (AF)-related stroke patients are unknown. METHODS: This was a substudy of the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION), which is a multicenter-based cohort comprising prospective stroke registries from 11 tertiary centers. Stroke survivors who underwent two-dimensional transthoracic echocardiography during hospitalization were enrolled. Echocardiography markers included the left-ventricle (LV) ejection fraction (LVEF), the left atrium diameter, and the ratio of the peak transmitral filling velocity to the mean mitral annular velocity during early diastole (E/e′ ratio). LVEF was categorized into normal (≥55%), mildly decreased (>40% and <55%), and severely decreased (≤40%). The E/e′ ratio associated with the LV filling pressure was categorized into normal (<8), borderline (≥8 and <15), and elevated (≥15). Kaplan-Meier and Cox regression analyses were performed for recurrent stroke, major adverse cardiac events, and all-cause death. RESULTS: This study finally included 1,947 patients. Over a median follow-up of 1.65 years (interquartile range, 0.42–2.87 years), the rates of recurrent stroke, major adverse cardiac events, and all-cause death were 35.1, 10.8, and 69.6 cases per 1,000 person-years, respectively. Multivariable analyses demonstrated that severely decreased LVEF was associated with a higher risks of major adverse cardiac events [hazard ratio (HR), 3.91; 95% confidence interval (CI), 1.58–9.69] and all-cause death (HR, 1.95; 95% CI, 1.23–3.10). The multivariable fractional polynomial plot indicated that recurrent stroke might be associated with a lower LVEF. CONCLUSIONS: Severe LV systolic dysfunction could be a determinant of long-term outcomes in AF-related stroke.
Atrial Fibrillation ; Cohort Studies ; Diastole ; Echocardiography ; Follow-Up Studies ; Heart Atria ; Hospitalization ; Humans ; Prospective Studies ; Registries ; Stroke ; Survivors

OBJECTIVE: Declines in naming ability and semantic memory are well-known features of early Alzheimer's disease (AD). We developed a new screening algorithm for AD using two brief language tests : the Categorical Fluency Test (CFT) and 15-item Boston Naming Test (BNT15). METHODS: We administered the CFT, BNT15, and Mini-Mental State Examination (MMSE) to 150 AD patients with a Clinical Dementia Rating of 0.5 or 1 and to their age- and gender-matched cognitively normal controls. We developed a composite score for screening AD (LANGuage Composite score, LANG-C) that comprised demographic characteristics, BNT15 subindices, and CFT subindices. We compared the diagnostic accuracies of the LANG-C and MMSE using receiver operating curve analysis. RESULTS: The LANG-C was calculated using the logit of test scores weighted by their coefficients from forward stepwise logistic regression models : logit (case)=12.608−0.107×age+1.111×gender+0.089×education−0.314×HS(1st)−0.362×HS(2nd)+0.455×perseveration+1.329×HFCR(2nd)−0.489×MFCR(1st)−0.565×LFCR(3rd). The area under the curve of the LANG-C for diagnosing AD was good (0.894, 95% confidence interval=0.853–0.926 ; sensitivity=0.787, specificity=0.840), although it was smaller than that of the MMSE. CONCLUSION: The LANG-C, which is easy to automate using PC or smart devices and to deliver widely via internet, can be a good alternative for screening AD to MMSE.
Alzheimer Disease ; Dementia ; Humans ; Internet ; Language Tests ; Logistic Models ; Mass Screening ; Memory ; Semantics

BACKGROUND: Little is known about epigenetic silencing of genes by promoter hypermethylation in renal cell carcinoma (RCC). The aim of this study was to identify prognostic methylation markers in surgically treated clear cell RCC (ccRCC). METHODS: Methylation patterns were assayed using the Infinium HumanMethylation450 BeadChip array on pairs of ccRCC and normal tissue from 12 patients. Using quantitative PSQ analysis, tumor-specific hypermethylated genes were validated in 25 independent cohorts and their clinical relevance was also verified in 152 independent cohorts. RESULTS: Using genome-wide methylation array, Zinc finger protein 278 (ZNF278), Family with sequence similarity 155 member A (FAM155A) and Dipeptidyl peptidase 6 (DPP6) were selected for tumor-specific hypermethylated genes in primary ccRCC. The promoter methylation of these genes occurred more frequently in ccRCC than normal kidney in independent validation cohort. The hypermethylation of three genes were associated with advanced tumor stage and high grade tumor in ccRCC. During median follow-up of 39.2 (interquartile range, 15.4–79.1) months, 22 (14.5%) patients experienced distant metastasis. Multivariate analysis identified the methylation status of these three genes, either alone, or in a combined risk score as an independent predictor of distant metastasis. CONCLUSION: The promoter methylation of ZNF278, FAM155A and DPP6 genes are associated with aggressive tumor phenotype and early development of distant metastasis in patients with surgically treated ccRCC. These potential methylation markers, either alone, or in combination, could provide novel targets for development of individualized therapeutic and prevention regimens.
Carcinoma, Renal Cell ; Cohort Studies ; Disease-Free Survival ; Epigenomics ; Follow-Up Studies ; Humans ; Kidney ; Methylation ; Multivariate Analysis ; Neoplasm Metastasis ; Phenotype ; Zinc Fingers