Background: Copy number variations (CNVs) play an important role in human genetic disorders. Detection of exon-level CNVs is crucial for accurate clinical diagnosis. The CytoScan XON Array, a high-resolution microarray, was recently developed to detect exonic CNVs of various genes. Methods: We evaluated the clinical performance of the CytoScan XON Array using 59 patient samples with previously identified CNVs, confirmed via methods including multiple ligation-dependent probe amplification (MLPA), gene-dose PCR, and mRNA assay. Concordance between CytoScan XON and orthogonal methods was evaluated in target regions, and diagnostic utility was compared with that of genome sequencing (GS)-based CNV calling tools through analysis of false-positive CNVs in non-target genomic regions. Results: For target regions, the CytoScan XON Array achieved concordance rates of 89.8% and 92.5% at the exon and gene levels, respectively, for all CNV calls. Concordance was higher for multi-exon CNVs (100%) than that for single-exon CNVs (82.6%, P = 0.03). For non-target regions, false-positive CNV calls were reduced to fewer than 0.01 per gene per person through filtering strategies. The array exhibited false-positive detection rates within dosage-sensitive genes comparable with those of GS-based tools. Conclusions The CytoScan XON Array, a reliable tool for detecting exon-level CNVs in target regions, can serve as a complementary approach to GS-based CNV calling tools for genome-wide CNV screening with high resolution. However, its performance for single-exon CNVs requires further optimization. Cross-validation with GS-based CNV calling tools is recommended to improve diagnostic accuracy.

This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13–1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84–1.11), 1.10 (0.96–1.27), 1.24 (1.06–1.45), 1.37 (1.12–1.66), and 1.99 (1.42–2.79), respectively (p for trend < 0.001). Conclusion In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Background: Epidermal growth factor receptor (EGFR) gene mutation testing is crucial for the administration of tyrosine kinase inhibitors to treat non–small cell lung cancer. In addition to traditional tissue-based tests, liquid biopsies using plasma are increasingly utilized, particularly for detecting T790M mutations. This study compared tissue- and plasma-based EGFR testing methods. Methods: A total of 248 patients were tested for EGFR mutations using tissue and plasma samples from 2018 to 2023 at Pusan National University Yangsan Hospital. Tissue tests were performed using PANAmutyper, and plasma tests were performed using the Cobas EGFR Mutation Test v2. Results: All 248 patients underwent tissue-based EGFR testing, and 245 (98.8%) showed positive results. Of the 408 plasma tests, 237 (58.1%) were positive. For the T790M mutation, tissue biopsies were performed 87 times in 69 patients, and 30 positive cases (38.6%) were detected. Plasma testing for the T790M mutation was conducted 333 times in 207 patients, yielding 62 positive results (18.6%). Of these, 57 (27.5%) were confirmed to have the mutation via plasma testing. Combined tissue and plasma tests for the T790M mutation were positive in nine patients (13.4%), while 17 (25.4%) were positive in tissue only and 12 (17.9%) in plasma only. This mutation was not detected in 28 patients (43.3%). Conclusions Although the tissue- and plasma-based tests showed a sensitivity of 37.3% and 32.8%, respectively, combined testing increased the detection rate to 56.7%. Thus, neither test demonstrated superiority, rather, they were complementary.

Background: Epidermal growth factor receptor (EGFR) gene mutation testing is crucial for the administration of tyrosine kinase inhibitors to treat non–small cell lung cancer. In addition to traditional tissue-based tests, liquid biopsies using plasma are increasingly utilized, particularly for detecting T790M mutations. This study compared tissue- and plasma-based EGFR testing methods. Methods: A total of 248 patients were tested for EGFR mutations using tissue and plasma samples from 2018 to 2023 at Pusan National University Yangsan Hospital. Tissue tests were performed using PANAmutyper, and plasma tests were performed using the Cobas EGFR Mutation Test v2. Results: All 248 patients underwent tissue-based EGFR testing, and 245 (98.8%) showed positive results. Of the 408 plasma tests, 237 (58.1%) were positive. For the T790M mutation, tissue biopsies were performed 87 times in 69 patients, and 30 positive cases (38.6%) were detected. Plasma testing for the T790M mutation was conducted 333 times in 207 patients, yielding 62 positive results (18.6%). Of these, 57 (27.5%) were confirmed to have the mutation via plasma testing. Combined tissue and plasma tests for the T790M mutation were positive in nine patients (13.4%), while 17 (25.4%) were positive in tissue only and 12 (17.9%) in plasma only. This mutation was not detected in 28 patients (43.3%). Conclusions Although the tissue- and plasma-based tests showed a sensitivity of 37.3% and 32.8%, respectively, combined testing increased the detection rate to 56.7%. Thus, neither test demonstrated superiority, rather, they were complementary.

Background: Epidermal growth factor receptor (EGFR) gene mutation testing is crucial for the administration of tyrosine kinase inhibitors to treat non–small cell lung cancer. In addition to traditional tissue-based tests, liquid biopsies using plasma are increasingly utilized, particularly for detecting T790M mutations. This study compared tissue- and plasma-based EGFR testing methods. Methods: A total of 248 patients were tested for EGFR mutations using tissue and plasma samples from 2018 to 2023 at Pusan National University Yangsan Hospital. Tissue tests were performed using PANAmutyper, and plasma tests were performed using the Cobas EGFR Mutation Test v2. Results: All 248 patients underwent tissue-based EGFR testing, and 245 (98.8%) showed positive results. Of the 408 plasma tests, 237 (58.1%) were positive. For the T790M mutation, tissue biopsies were performed 87 times in 69 patients, and 30 positive cases (38.6%) were detected. Plasma testing for the T790M mutation was conducted 333 times in 207 patients, yielding 62 positive results (18.6%). Of these, 57 (27.5%) were confirmed to have the mutation via plasma testing. Combined tissue and plasma tests for the T790M mutation were positive in nine patients (13.4%), while 17 (25.4%) were positive in tissue only and 12 (17.9%) in plasma only. This mutation was not detected in 28 patients (43.3%). Conclusions Although the tissue- and plasma-based tests showed a sensitivity of 37.3% and 32.8%, respectively, combined testing increased the detection rate to 56.7%. Thus, neither test demonstrated superiority, rather, they were complementary.

Early mortality following hemodialysis initiation hinders survival improvement in older patients. This study aimed to develop a clinical risk model for predicting 6-month mortality after dialysis initiation in older Korean hemodialysis patients. Methods: We analyzed data from incident hemodialysis patients aged >70 years from the Korean Society of Geriatric Nephrology (KSGN) database. A prediction model was developed using multivariate logistic regression analysis and externally validated with independent datasets. Results: Among 1,751 incident hemodialysis patients, the 6-month mortality rate was 15.5%. Using multivariate logistic analysis, we constructed the KSGN score as an independent risk factor for 6-month mortality, and its components and score are as follows: old age at dialysis initiation (≥85 years, score 2); hypertension and renovascular disease as a primary etiology of end-stage kidney disease (ESKD) (score 1); malignancy history (yes, score 1); low serum albumin (<3.5 g/dL, score 1); hypertension treatment (yes, score –1); prepared vascular access on maintenance dialysis (arteriovenous fistula/arteriovenous graft, score –3). In the development cohort, the area under the curve (AUC) for the KSGN score was significantly higher than the Alberta Wick’s score (0.707 vs. 0.683, p = 0.001). In the validation cohort, the KSGN score’s performance was comparable to existing models. Conclusion: The KSGN score may be a valuable tool for predicting early mortality after dialysis initiation in older patients with ESKD, aiding in decision-making and management regarding dialysis initiation.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. Methods: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. Results: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. Conclusion This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively.Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques.There has been a decrease in intravenous thrombolysis rates, from 12% in 2017–2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for noncardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.