Background and Objectives: The objective of this study was to estimate the supply and demand for cardiologists in Korea and provide evidence for healthcare policy to ensure a stable and adequate workforce for optimal cardiovascular disease management. Methods: Past trends of inflow and outflow of cardiologists were used to make crude projections, which were then adjusted based on demands of services to obtain final projections. Inflow of cardiologists was estimated using second-order polynomial regression and demand for cardiology care was estimated using linear regression. Results: There were 1,139 active cardiologists who were under the age of 65 in clinical practice in Korea. The estimated number of cardiologists from 2022 to 2040 showed that the number of cardiologists would peak at 1,344 in 2032 and gradually decrease thereafter. We also estimated an increase of 947,811 cases of heart-related procedures annually from 2023 to 2032. The number of heart-related procedures per cardiologist would increase 1.4 times from 12,964 in 2023 to 17,862 in 2032. The estimated number of emergency patients per cardiologist under 50 years old would almost double from 544 in 2022 to 987 in 2032. Conclusions We expect significant shortage of cardiologists in Korea within the next 10 years. The number of emergency patients per cardiologist will increase by nearly 50%, leading to high individual workload for cardiologists. To prevent this imbalance between supply and demand, an organized and collective approach by the specialty of cardiology is imperative to produce a balanced workforce.

BACKGROUND: In humans, after fertilization, the zygote divides into two 2n diploid daughter blastomeres. During this division, DNA is replicated, and the remaining mutually exclusive genetic mutations in the genome of each cell are called post-zygotic variants. Using these somatic mutations, developmental lineages can be reconstructed. How these two blastomeres are contributing to the entire body is not yet identified. This study aims to evaluate the cellular contribution of two blastomeres of 2-cell embryos to the entire body in humans using post-zygotic variants based on whole genome sequencing. METHODS: Tissues from different anatomical areas were obtained from five donated cadavers for use in single-cell clonal expansion and bulk target sequencing. After conducting whole genome sequencing, computational analysis was applied to find the early embryonic mutations of each clone. We developed our in-house bioinformatics pipeline, and filtered variants using strict criteria, composed of mapping quality, base quality scores, depth, soft-clipped reads, and manual inspection, resulting in the construction of embryological phylogenetic cellular trees. RESULTS: Using our in-house pipeline for variant filtering, we could extract accurate true positive variants, and construct the embryological phylogenetic trees for each cadaver. We found that two daughter blastomeres, L1 and L2 (lineage 1 and 2, respectively), derived from the zygote, distribute unequally to the whole body at the clonal level. From bulk target sequencing data, we validated asymmetric contribution by means of the variant allele frequency of L1 and L2. The asymmetric contribution of L1 and L2 varied from person to person. CONCLUSION We confirmed that there is asymmetric contribution of two daughter blastomeres from the first division of the zygote across the whole human body.

Background/Aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Cardiovascular disease (CVD) remains the leading cause of morbidity, mortality, and health care costs in South Korea. The prevalence of preventable and treatable risk factors for CVD such as obesity, hypercholesterolemia, and smoking has continued to increase, despite improvements management of hypertension. Active leadership, participation, and support of professional organizations and medical institutions in national cardiovascular registries and regional treatment network have proven to be effective models to reduce the global burden of CVD in the Europe and North America. Regional treatment network systems for ST-segment elevation myocardial infarction have established to coordinate percutaneous coronary intervention (PCI) treatment centers, non-PCI treatment centers, and emergency centers especially across the Europe. The Act on the Prevention and Management of Cardio-cerebrovascular Disease was enacted in South Korea in 2017 to establish the legal frameworks and a comprehensive plan for the prevention and management CVD and risk factors. To fully achieve the goal of a NationalHealth Plan for Cardiovascular Disease, it is necessary to embark on a nationwide registry project and to promote the regional acute treatment accessibility which can therefore play a key role in achieving the objectives of the 2017 Act. In this regard, the Korean Society of Cardiology advocates a national project for health promotion and cardiovascular prevention to improve cardiovascular outcomes, which includes the expansion and establishment of regional cardiocerebrovascular centers (CCVCs) and new local CCVCs.

Cardiovascular disease (CVD) remains the leading cause of morbidity, mortality, and health care costs in South Korea. The prevalence of preventable and treatable risk factors for CVD such as obesity, hypercholesterolemia, and smoking has continued to increase, despite improvements management of hypertension. Active leadership, participation, and support of professional organizations and medical institutions in national cardiovascular registries and regional treatment network have proven to be effective models to reduce the global burden of CVD in the Europe and North America. Regional treatment network systems for ST-segment elevation myocardial infarction have established to coordinate percutaneous coronary intervention (PCI) treatment centers, non-PCI treatment centers, and emergency centers especially across the Europe. The Act on the Prevention and Management of Cardio-cerebrovascular Disease was enacted in South Korea in 2017 to establish the legal frameworks and a comprehensive plan for the prevention and management CVD and risk factors. To fully achieve the goal of a NationalHealth Plan for Cardiovascular Disease, it is necessary to embark on a nationwide registry project and to promote the regional acute treatment accessibility which can therefore play a key role in achieving the objectives of the 2017 Act. In this regard, the Korean Society of Cardiology advocates a national project for health promotion and cardiovascular prevention to improve cardiovascular outcomes, which includes the expansion and establishment of regional cardiocerebrovascular centers (CCVCs) and new local CCVCs.

PURPOSE: Transducin-like enhancer of split 1 (TLE1) is a member of the TLE family of transcriptional co-repressors that control the transcription of a wide range of genes. We investigated the prognostic significance of TLE1 protein expression in breast cancers by using immunohistochemistry and explored the relationship of TLE1 with clinicopathological parameters. METHODS: Immunohistochemistry was performed on 456 cases of breast cancer tiled on tissue microarrays. The relationship between TLE1 expression in normal breast specimens and ductal carcinoma in situ (DCIS) was also analyzed. RESULTS: TLE1 was highly expressed in 57 of 456 (12.5%) carcinoma samples. TLE1 was more frequently expressed in DCIS and invasive breast cancers than in normal breast tissue (p=0.002). High expression of TLE1 significantly correlated with negative lymph node (LN) metastasis (p=0.007), high histologic grade (p<0.001), estrogen receptor negativity (p<0.001), progesterone receptor negativity (p<0.001), human epidermal growth factor receptor 2 (HER2) positivity (p<0.001), and high Ki-67 proliferation index (p<0.001). Based on intrinsic subtypes, high TLE1 expression was strongly associated with HER2+ and triple-negative breast cancers (TNBC) (p<0.001). Survival analysis demonstrated no significant association between TLE1 expression and disease-free survival (DFS) (p=0.167) or overall survival (OS) (p=0.286). In subgroup analyses, no correlation was found between TLE1 expression and DFS or OS according to LN status or intrinsic subtype. CONCLUSION: High TLE1 expression is significantly associated with the HER2+ and TNBC subtypes. This is the first study documenting immunohistochemical expression of TLE1 in invasive breast cancer and its association with clinicopathological parameters, prognosis, and intrinsic subtype.
Breast Neoplasms* ; Breast* ; Carcinoma, Intraductal, Noninfiltrating ; Co-Repressor Proteins ; Disease-Free Survival ; Estrogens ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Triple Negative Breast Neoplasms

A 64-year-old woman was admitted with vertebral osteomyelitis and polyarthritis (both knees and the right shoulder). She had had no health problems before these conditions developed. Joint culture grew methicillin-resistant Staphylococcus aureus. During hospitalization, hematuria, proteinuria, azotemia, and decreased C3 were reported. The renal biopsy showed mesangial proliferative glomerulonephritis with C3 and IgA co-dominant deposits on immunofluorescence staining. Following incision and drainage of the right shoulder and right knee, and intravenous vancomycin for 15 weeks, the C-reactive protein, proteinuria, hematuria, and C3 level all normalized. Here, we report a case of Staphylococcus-associated glomerulonephritis with a brief review of the literature.
Arthritis ; Azotemia ; Biopsy ; C-Reactive Protein ; Drainage ; Female ; Fluorescent Antibody Technique ; Glomerulonephritis* ; Hematuria ; Hospitalization ; Humans ; Immunoglobulin A ; Joints ; Knee ; Methicillin-Resistant Staphylococcus aureus ; Middle Aged ; Osteomyelitis ; Proteinuria ; Shoulder ; Vancomycin

PURPOSE: The enhancer of zeste homologue 2 (EZH2) is a catalytic subunit of the polycomb repressive complex 2, a highly conserved histone methyltransferase. EZH2 overexpression has been implicated in various malignancies, including breast cancer, where is associated with poor outcomes. This study aims to clarify nuclear EZH2 expression levels in breast cancers using immunohistochemistry (IHC) and correlate these findings with clinicopathologic variables, including prognostic significance. METHODS: IHC was performed on tissue microarrays of 432 invasive ductal carcinoma (IDC) tumors. Associations between EZH2 expression, clinicopathologic characteristics, and molecular subtype were retrospectively analyzed. The relationship between EZH2 protein expression in normal breast tissue and ductal carcinoma in situ (DCIS) was also assessed. RESULTS: High EZH2 expression was demonstrated in 215 of 432 tumors (49.8%). EZH2 was more frequently expressed in DCIS and IDC than in normal breast tissue (p=0.001). High EZH2 expression significantly correlated with high histologic grade (p<0.001), large tumor size (p=0.014), advanced pathologic stage (p=0.006), negative estrogen receptor status (p<0.001), positive human epidermal growth factor receptor 2 (HER2) status (p<0.001), high Ki-67 staining index (p<0.001), positive cytokeratin 5/6 status (p=0.003), positive epidermal growth factor receptor status (p<0.001), and positive p53 status (p<0.001). Based on molecular subtypes, high EZH2 expression was significantly associated with HER2-negative luminal B, HER2-positive luminal B, and HER2 type and triple-negative basal cancers (p<0.001). In patients with luminal A, there was a significant trend toward shorter overall survival for those with tumors having high EZH2 expression compared to those with tumors having low EZH2 expression (p=0.045). CONCLUSION: EZH2 is frequently upregulated in breast malignancies, and it may play an important role in cancer development and progression. Furthermore, EZH2 may be a prognostic marker, especially in patients with luminal A cancer.
Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Catalytic Domain ; Estrogens ; Histones ; Humans ; Immunohistochemistry ; Keratins ; Phenobarbital* ; Polycomb Repressive Complex 2 ; Prognosis ; Receptor, Epidermal Growth Factor ; Retrospective Studies

PURPOSE: The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis. METHODS: PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas. RESULTS: High PD-L1 expression was demonstrated in 63 of 465 tumors (13.5%). High PD-L1 expression was significantly associated with high histologic grade (p<0.001), negative lymph nodes (p=0.011), early pathologic stage (p=0.025), high tumor-infiltrating lymphocyte (TIL) (p<0.001) counts, negative estrogen receptor (p<0.001) and progesterone receptor (p=0.002) expression, positive human epidermal growth factor receptor 2 (HER2) (p=0.003), cytokeratin 5/6 (p=0.011), epidermal growth factor receptor (p<0.001), and p53 (p<0.001) expression, and high Ki-67 proliferating index (p<0.001). Based on intrinsic subtypes, high PD-L1 expression and high TIL counts were significantly associated with the HER2 and triple-negative basal type (p<0.001). PD-L1 expression was significantly associated with better disease-free survival (DFS) (p=0.041) and overall survival (OS) (p=0.026) in the univariate analysis, but not in the multivariate analysis. Higher TIL levels was an independent prognostic factor for decreased disease progression (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.284–4.445; p=0.006) and overall death (HR, 3.666; 95% CI, 1.561–8.607; p=0.003). CONCLUSION: PD-L1 protein expression in breast cancer is associated with better DFS and OS, but is not an independent prognostic factor. High PD-L1 expression was significantly associated with high TIL levels. This finding has important implications for antibody therapies targeting the PD-1/PD-L1 signaling mechanism in breast cancer.
Breast Neoplasms* ; Breast* ; Disease Progression ; Disease-Free Survival ; Estrogens ; Humans ; Immunohistochemistry ; Keratins ; Lymph Nodes ; Lymphocytes, Tumor-Infiltrating* ; Multivariate Analysis ; Prognosis* ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone