Purpose: BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants. Materials and Methods: Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity. Results: A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w. Conclusion We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.

Background: A substantial cardiovascular disease risk remains even after optimal statin therapy. Comparative predictiveness of major lipid and lipoprotein parameters for cardiovascular events in patients with type 2 diabetes mellitus (T2DM) who are treated with statins is not well documented. Methods: From the Korean Nationwide Cohort, 11,900 patients with T2DM (≥40 years of age) without a history of cardiovascular disease and receiving moderate- or high-intensity statins were included. The primary outcome was the first occurrence of major adverse cardiovascular events (MACE) including ischemic heart disease, ischemic stroke, and cardiovascular death. The risk of MACE was estimated according to on-statin levels of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), highdensity lipoprotein cholesterol (HDL-C), and non-HDL-C. Results: MACE occurred in 712 patients during a median follow-up period of 37.9 months (interquartile range, 21.7 to 54.9). Among patients achieving LDL-C levels less than 100 mg/dL, the hazard ratios for MACE per 1-standard deviation change in ontreatment values were 1.25 (95% confidence interval [CI], 1.07 to 1.47) for LDL-C, 1.31 (95% CI, 1.09 to 1.57) for non-HDL-C, 1.05 (95% CI, 0.91 to 1.21) for TG, and 1.16 (95% CI, 0.98 to 1.37) for HDL-C, after adjusting for potential confounders and lipid parameters mutually. The predictive ability of on-statin LDL-C and non-HDL-C for MACE was prominent in patients at high cardiovascular risk or those with LDL-C ≥70 mg/dL. Conclusion On-statin LDL-C and non-HDL-C levels are better predictors of the first cardiovascular event than TG or HDL-C in patients with T2DM.

Background: The weight-adjusted waist index (WWI) reflected body compositional changes with aging. This study was to investigate the association of WWI with abdominal fat and muscle mass in a diverse race/ethnic population. Methods: Computed tomography (CT) data from 1,946 participants for abdominal fat and muscle areas from the Multi-Ethnic Study of Atherosclerosis (785 Whites, 252 Asians, 406 African American, and 503 Hispanics) were used. Among them, 595 participants underwent repeated CT. The WWI was calculated as waist circumference (cm) divided by the square root of body weight (kg). The associations of WWI with abdominal fat and muscle measures were examined, and longitudinal changes in abdominal composition measures were compared. Results: In all race/ethnic groups, WWI was positively correlated with total abdominal fat area (TFA), subcutaneous fat area, and visceral fat area, but negatively correlated with total abdominal muscle area (TMA) and abdominal muscle radiodensity (P<0.001 for all). WWI showed a linear increase with aging regardless of race and there were no significant differences in the WWI distribution between Whites, Asians, and African Americans. In longitudinal analyses, over 38.6 months of follow-up, all abdominal fat measures increased but muscle measures decreased, along with increase in WWI. The more the WWI increased, the more the TFA increased and the more the TMA decreased. Conclusion WWI showed positive associations with abdominal fat mass and negative associations with abdominal muscle mass, which likely reflects the abdominal compositional changes with aging in a multi-ethnic population.

Objective: We aimed to investigate the association between statin use and the risk of major osteoporotic fractures in patients with metabolic syndrome (MetS). Methods: A nested case-control study was performed in patients with MetS (≥50 years) who had no history of osteoporotic fracture using the Korean National Health Insurance ServiceHealth Screening Cohort. This study included 17,041 patients diagnosed with new-onset osteoporotic fractures and controls matched in a 1:1 ratio by age, sex, body mass index, cohort entry date, and follow-up duration. Conditional logistic regression analysis was used to evaluate covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: During a 4-year follow-up period, the risk of major osteoporotic fractures was significantly reduced by 9% (OR, 0.91; 95% CI, 0.85–0.97) in statin users compared with that in non-users. Among subtypes of major osteoporotic fracture, a risk reduction with statin therapy was significant for vertebral fracture (OR, 0.86; 95% CI, 0.79–0.94) but not for non-vertebral fracture (OR, 0.97; 95% CI, 0.88–1.06). Longer duration (OR, 0.97; 95% CI, 0.96–0.99, per 1-year increase) and higher cumulative dose (OR, 0.97; 95% CI, 0.95–0.99, per 365 defined daily doses) of statins were negatively associated with the risk of major osteoporotic fracture. Conclusion This study supports the hypothesis that statin therapy has a beneficial effect on major osteoporotic fractures, especially vertebral fractures, in patients with MetS.

Background/Aims: Chest pain in patients with obstructive coronary artery disease (OCAD) is affected by several social factors. The gender-based differences in chest pain among Koreans have yet to be investigated. Methods: The study consecutively enrolled 1,549 patients (male/female, 514/1,035; 61 ± 11 years old) with suspected angina. The predictive factors for OCAD based on gender were evaluated. Results: Men experienced more squeezing type pain on the left side of chest, while women demonstrated more dull quality pain in the retrosternal and epigastric area. After adjustment for risk factors, pain in the retrosternal area (odds ratio [OR], 1.491; 95% confidence interval [CI], 1.178 to 1.887) and aggravation by exercise (OR, 2.235; 95% CI, 1.745 to 2.861) were positively associated with OCAD. In men, shorter duration (OR, 1.581; 95% CI, 1.086 to 2.303) and dyspnea (OR, 1.610; 95% CI, 1.040 to 2.490) increased the probability for OCAD, while left-sided chest pain suggested a low probability for OCAD (OR, 0.590; 95% CI, 0.388 to 0.897). In women, aggravation by emotional stress (OR, 0.348; 95% CI, 0.162 to 0.746) and dizziness (OR, 0.457; 95% CI, 0.246 to 0.849) decreased the probability for OCAD. Conclusions This is the first study to focus on gender differences in chest pain among Koreans with angina. Symptoms with high probability for OCAD were different between sexes. Our findings suggest that patient’s medical history in pretest assessment for OCAD should be individualized considering gender.

Background: Prognosis of patients with diverse chronic diseases is reportedly associated with 25-hydroxyvitamin D levels. In this study, we investigated the potential role of 25-hydroxyvitamin D3 (25[OH]D3) levels in improving the predictive power of conventional prognostic models for patients with liver cirrhosis. Methods: We investigated clinical findings, including serum 25(OH)D3 levels at admission, of 155 patients with cirrhosis who were followed up for a median of 16.9 months. Results: Median 25(OH)D3 levels were significantly different among patients exhibiting Child-Pugh grades A, B, and C. Mortality, including urgent transplantation, was significantly associated with 25(OH)D3 levels in univariate analysis. Severe vitamin-D deficiency (serum 25[OH]D3 level < 5.0 ng/mL) was significantly related to increased mortality, even after adjusting for Child-Pugh and Model for End-stage Liver Disease (MELD) scores. In particular, the presence of severe vitamin D deficiency clearly defined a subgroup with significantly poorer survival among patients with Child-Pugh scores of 5–10 or MELD scores ≤ 20. A new combination model of MELD score and severe vitamin D deficiency showed significantly more accurate predictive power for short- and long-term mortality than MELD scores alone. Additionally, serum 25(OH)D3 levels and new model scores were significantly associated with the development of spontaneous bacterial peritonitis, overt encephalopathy, and acute kidney injury. Conclusion Serum 25(OH)D3 level is an independent prognostic factor for patients with liver cirrhosis and has a differential impact on disease outcomes according to MELD and Child-Pugh scores.

Recently, sarcopenia has garnered renewed interest. Sarcopenia is a disease characterized by decreased skeletal muscle mass and strength/function, which can impair the quality of life and increase physical disability, adverse metabolic effects, and mortality. Imaging tools for evaluating and diagnosing sarcopenia have developed rapidly. Radiologists should be aware of sarcopenia and its clinical implications. We review current knowledge about sarcopenia, its pathophysiological impact, and advantages and disadvantages of methods for evaluation of sarcopenia focusing on body composition imaging modalities such as whole-body dual-energy X-ray absorptiometry, CT, and MRI. Controversial issues are discussed, including the lack of consensus and standardization of the disease definition, imaging modality, measurement methods, and diagnostic cutoff points.
Absorptiometry, Photon ; Body Composition ; Consensus ; Magnetic Resonance Imaging ; Mortality ; Muscle, Skeletal ; Quality of Life ; Sarcopenia

Entecavir (Baraclude(R), Bristol-Myers Squibb) is a potent and selective antiviral agent that has demonstrated efficacy in patients with chronic hepatitis B. The most frequent adverse events attributed to entecavir include increased alanine aminotransferase, upper respiratory tract infection, headache, abdominal pain, cough, pyrexia, fatigue, and diarrhea. Although quite a few randomized double-blind studies including ones investigating adverse events along with these general symptoms have been reported, few cases of cutaneous adverse events have been described in detail. We demonstrate a case of granulomatous drug eruption as a cutaneous adverse event induced by entecavir.
Abdominal Pain ; Alanine Transaminase ; Cough ; Diarrhea ; Double-Blind Method ; Drug Eruptions* ; Fatigue ; Fever ; Guanine ; Headache ; Hepatitis B, Chronic ; Humans ; Respiratory Tract Infections

Disseminated superficial porokeratosis (DSP) is an autosomal dominant specific disorder of keratinization. Clinically, the lesions show a sharply demarcated and hyperkeratotic plaque with central atrophy, with a predilection for the extensor surface of the extremities. Unusual cases of DSP accompanied by severe pruritus have been reported as "eruptive pruritic papular porokeratosis" or "inflammatory DSP." Histopathologically, inflammatory DSP is characterized by the presence of cornoid lamella with a dense infiltration of lymphocytes in the perivascular area of the upper dermis. Here we report a case of inflammatory DSP in an 80-year-old man with choledocholithiasis.
Aged, 80 and over ; Atrophy ; Choledocholithiasis ; Dermis ; Extremities ; Humans ; Keratins ; Lymphocytes ; Porokeratosis ; Pruritus

BACKGROUND: Scabies is a contagious parasitic infestation, which causes an allergic reaction to mites. Despite a decrease in the prevalence of scabies, there is still a significantly great infestation rate among the elderly. OBJECTIVE: The purpose of the study is to evaluate the clinical aspects of scabies patients in the last 6 years. METHODS: A total of 133 out-patients, who were diagnosed as scabies in the department of dermatology from January, 2006 to December, 2011, were analyzed retrospectively. RESULTS: Scabies patients accounted for 0.28% of all new patients (133/47,249). The ratio of male to female was 0.60 to 1. The mean age of the patients was 48.4 years old. Of the participating patients, 35.3% were over 65 years old. There was no seasonal variation in the occurrence. The most common cutaneous lesions were pruritic papule and burrow. The most common suspected routes of infection were hospitalization infection (54.9%), and occupational infection in the hospital or residential home for the elderly (23.3%). The mean time to be required to diagnose scabies was 78.8 days. The mean time to diagnose scabies in people who work in the hospital or residential home for the elderly was 58.0 days. CONCLUSION: The study provides useful data on the prevalence and characteristics of scabies.
Aged ; Dermatology ; Female ; Hospitalization ; Humans ; Hypersensitivity ; Male ; Mites ; Outpatients ; Prevalence ; Scabies ; Seasons