Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS), with plasma levels largely unaffected by lifestyle modification or conventional lipid-lowering therapy. Although international guidelines increasingly recognize Lp(a) as a risk-enhancing factor, in many Asian populations thresholds for high Lp(a) and treatment strategies remain undefined.This Korean position paper, developed by the Lp(a) Task Force of the Korean Society of Lipid and Atherosclerosis, presents an evidence-based summary of the pathophysiology, clinical relevance, and therapeutic landscape surrounding Lp(a), with a focus on Koreanspecific data. It reviews the genetic architecture of Lp(a), ethnic variability in concentrations, and its mechanistic roles in inflammation, thrombosis, and calcification. Based on large Korean cohorts, a 3-tiered classification is proposed of normal (<30 mg/dL), borderline high (30–49 mg/dL), and high (≥50 mg/dL), harmonizing global thresholds with local data. The document also highlights the limitations of current Lp(a) assays in Korea, and calls for standardized, isoform-insensitive testing. Novel therapeutics, including antisense oligonucleotides, small interfering RNAs, and small molecular inhibitors, have shown promising Lp(a)-lowering effects, with multiple phase 3 trials currently ongoing, or in planning. Given the unmet clinical need, the paper recommends incorporating Lp(a) into cardiovascular risk assessment, and calls for Korean-specific longitudinal studies, national screening strategies, and participation in clinical trials. These efforts will help clarify Lp(a)-associated risk in Korean patients and guide the adoption of future targeted therapies.

Chronic liver diseases, including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and hepatocellular carcinoma (HCC), account for approximately two million deaths globally each year. Despite increasing insight into their pathophysiology, substantial heterogeneity in disease progression, and therapeutic response underscores the need for precision hepatology. MicroRNAs (miRNAs), a class of small noncoding RNAs of approximately 20–22 nucleotides, have emerged as promising molecular tools owing to their abundant hepatic expression, dynamic regulation across disease stages, and high stability in biological fluids. In this review, we examine the roles of miRNAs across three pillars of precision medicine in liver disease. First, circulating miRNA panels enable noninvasive diagnosis of metabolic dysfunction-associated steatohepatitis, significant liver fibrosis, and early-stage HCC, offering a practical alternative to liver biopsy. Second, miRNAs serve as prognostic biomarkers capable of stratifying patients according to fibrosis progression and risk of HCC recurrence. Third, miRNA-based therapeutics―including mimics and antagomirs delivered via lipid nanoparticles or exosomes―have demonstrated promising efficacy in preclinical models. Broader clinical implementation will require standardized protocols, validated quantification platforms, and international regulatory consensus, all of which will be essential for establishing miRNAs as practical tools in precision hepatology.

Background and Objectives: Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Recent advances in PAH-specific drugs have improved its outcomes, although the healthcare burden of novel therapeutics may lead to a discrepancy in outcomes between developing and developed countries. We analyzed how the epidemiology and clinical features of PAH has changed through the rapidly advancing healthcare infrastructure in South Korea. Methods: PAH was defined according to a newly devised 3-component algorithm. Using a nationwide health insurance claims database, we delineated annual trends in the prevalence, incidence, medication prescription pattern, and 5-year survival of PAH in Korea. Cumulative survival and potential predictors of mortality were also assessed among 2,151 incident PAH cases. Results: Between 2002 or 2004 and 2018, the prevalence and incidence of PAH increased 75-fold (0.4 to 29.9 per million people) and 12-fold (0.5 to 6.3 per million person-years), respectively. The proportion of patients on combination PAH-specific drug therapy has also steadily increased up to 29.0% in 2018. Among 2,151 incident PAH cases (median [interquartile range] age, 50 [37–62] years; 67.2% female), the 5-year survival rate and median survival duration were 71.8% and 13.1 years, respectively. Independent predictors of mortality were age, sex, etiology of PAH, diabetes, dyslipidemia, and chronic kidney disease. Conclusions This nationwide study delineated that the prevalence and incidence of PAH have grown rapidly in Korea since the early 2000s. The use of combination therapy has also increased, and the 5-year survival rate of PAH in Korea was similar to those in western countries.

Background/Aims: Standard triple therapy (STT; proton pump inhibitor [PPI]+clarithromycin+amoxicillin) used for Helicobacter pylori (H. pylori) eradication has shown low treatment success rates in recent years, which is most likely attributable to increased clarithromycin resistance. In this study, we compared treatment success rates of tailored therapy (TT) using real-time polymerase chain reaction (RT-PCR) and empirical STT. Methods: This retrospective study included 650 patients with H. pylori infection, who visited Eunpyeong St. Mary’s Hospital in Korea; 343 patients received TT based on RT-PCR assays, and 307 patients received STT. Eradication success was defined as a negative 13C-urea breath test result 4~8 weeks after treatment completion. Patients who failed first-line therapy and those with clarithromycin resistance received bismuth-containing quadruple therapy (BQT; PPI+bismuth+metronidazole+tetracycline). Results: Intention-to-treat analysis showed that H. pylori eradication rates were higher in patients who received RT-PCR–based TT than in those who were treated using empirical STT (80.5% [190/236] vs. 70.4% [216/307], P=0.069). Per-protocol (PP) analysis showed similar results (84.4% [190/225] vs. 74.7% [216/289], P=0.007). PP analysis showed that 7-day TT treatment was associated with a higher eradication rate than that observed with 10- to 14-day STT (85.2% [178/209] vs. 73.8% [59/80], P=0.029). The clarithromycin resistance rate was 27.9% (87/312). The eradication success rate was 89.2% (74/83) in patients with clarithromycin resistance, who received BQT as first-line therapy. Conclusions The treatment success rate was higher in patients who received 7-day RT-PCR–based TT than in those who were administered 10- to 14-day empirical treatment.

Purpose: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. Materials and Methods: Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). Results: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. Conclusion The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Purpose: Next-generation sequencing (NGS) can facilitate precision medicine approaches in metastatic colorectal cancer (mCRC) patients. We investigated the molecular profiling of Korean mCRC patients under the K-MASTER project which was initiated in June 2017 as a nationwide precision medicine oncology clinical trial platform which used NGS assay to screen actionable mutations. Materials and Methods: As of 22 January 2020, total of 994 mCRC patients were registered in K-MASTER project. Targeted sequencing was performed using three platforms which were composed of the K-MASTER cancer panel v1.1 and the SNUH FIRST Cancer Panel v3.01. If tumor tissue was not available, cell-free DNA was extracted and the targeted sequencing was performed by Axen Cancer Panel as a liquid biopsy. Results: In 994 mCRC patients, we found 1,564 clinically meaningful pathogenic variants which mutated in 71 genes. Anti-EGFR therapy candidates were 467 patients (47.0%) and BRAF V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), HER2 amplifications (n=10, 1.0%) could be incorporated with recently approved drugs. The patients with high tumor mutation burden (n=101, 12.7%) and DNA damaging response and repair defect pathway alteration (n=42, 4.2%) could be enrolled clinical trials with immune checkpoint inhibitors. There were more colorectal cancer molecular alterations such as PIK3CA, KRAS G12C, atypical BRAF, and HER2 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors. Conclusion K-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.

Purpose: We investigated the effects of cold water immersion (CWI) treatment during half-time break on performance related physiological indices during second half soccer match. Methods: Twenty-two collegiate soccer players participated in the study. Subjects undertook 3 minutes head out seated with whole body immersion at 19 o C to 21 o C. Total four venous blood samples were collected and analyzed for markers of ionic regulations and inflammatory (interleukin [IL]-1b, IL-6, IL-8, IL-10, tumor necrosis factor-α , and vascular endothelial growth factor) and immune functions (immunoglobulin [Ig] G, IgG2, IgG2, IgG3, IgG4, IgA, and IgM). Results: Partial oxygen concentration and %SO 2 level was lowered in CWI. Hemoglobin and hematocrit values were not significantly different between experimental groups. While there was no notable effect was shown in Na ＋ and Ca 2＋ , K ＋ concentration was higher in CWI during second half match. There were no effects in any of inflammatory and/or anti-inflammatory cytokines and Ig. Conclusion These results suggest that CWI during half time break exert positively affects in buffering capacity and promote oxygen delivery to the actively recruited skeletal muscle, possibly results in improve soccer performance during second half match.

OBJECTIVES: The purpose of this study was to compare aripiprazole versus bupropion augmentation therapy in older adult patients with major depressive disorder unresponsive to selective serotonin reuptake inhibitors(SSRIs).METHODS: This is a post-hoc analysis of a 6-week, randomized prospective open-label multi-center study in thirty older adult patients with major depressive disorder. Participants were randomized to receive aripiprazole(N=16, 2.5–10mg/day) or bupropion(N=14, 150–300mg/day) for 6 weeks. Montgomery Asberg Depression Rating Scale (MADRS), 17-item Hamilton Depression Rating scale(HAM-D17), Iowa Fatigue Scale, Drug-Induced Extrapyramidal Symptoms Scale, Psychotropic-Related Sexual Dysfunction Questionnaire scores, and Clinical Global Impression-Severity (CGI-S) were obtained at baseline and after one, two, four, and six weeks. Changes on individual items of HAM-D17 were assessed as well as on composite scales(anxiety, insomnia and drive), and on four core subscales that capture core depression symptoms.RESULTS: There was a significantly greater decrease in MADRS scores in aripiprazole group compared to bupropion group at 4(p<0.05) and 6(p<0.05) weeks. There were significantly higher response rate at week 4(p<0.05) and 6(p<0.05) and remission rate at week 6 in aripiprazole group compared to bupropion group. Individual HAM-D17 items showing significantly greater change with adjunctive aripiprazole than bupropion: insomnia, late(ES=0.81 vs. −0.24, p=0.043), psychomotor retardation(ES=1.30 vs. 0.66, p=0.024), general somatic symptoms(ES=1.24 vs. 0.00, p=0.01). On three composite scales, adjunctive aripiprazole was significantly more effective than bupropion with respect to mean change for drive(p=0.005).CONCLUSION: Results of this study suggested that aripiprazole augmentation have superior efficacy in treating general and core symptoms of depression in older adult patients. Aripiprazole augmentation is associated with greater improvement in specific symptoms of depression such as psychomotor retardation, general somatic symptoms and drive.
Adult ; Aripiprazole ; Bupropion ; Depression ; Depressive Disorder, Major ; Fatigue ; Humans ; Iowa ; Prospective Studies ; Serotonin ; Sleep Initiation and Maintenance Disorders ; Weights and Measures

We aim to investigate the effect of fronto-temporal transcranial direct current stimulation (tDCS) on the interactions among functional networks and its association with psychotic symptoms. In this pilot study, we will determine possible candidate functional networks and an adequate sample size for future research. Seven schizophrenia patients with treatment-refractory auditory hallucinations underwent tDCS twice daily for 5 days. Resting-state fMRI data and measures of the severity of psychotic symptoms were acquired at baseline and after completion of the tDCS sessions. At baseline, decreased functional network interaction was negatively correlated with increased hallucinatory behavior. After tDCS, the previously reduced functional network connectivity significantly increased. Our results showed that fronto-temporal tDCS could possibly remediate aberrant hallucination-related functional network interactions in patients with schizophrenia.
Hallucinations ; Humans ; Magnetic Resonance Imaging ; Neuroimaging ; Pilot Projects ; Sample Size ; Schizophrenia ; Transcranial Direct Current Stimulation