1.Muscle Loss Driven by Extracellular Signal-Regulated Kinase Suppression via β-Adrenergic Activation in High-Normal Catecholamine Status
Jieun LEE ; Ju Yeon KWAK ; Ho Yeop LEE ; Ji Sun MOON ; Hyo Ju JANG ; Ha Thi NGA ; Thi Linh NGUYEN ; Alfin Mohammad ABDILLAH ; Junglyun KIM ; Sihwan KIM ; Yong Ryoul YANG ; Jeong Eun LEE ; Hyon-Seung YI
Endocrinology and Metabolism 2026;41(2):319-332
Background:
Catecholamines play a crucial role in muscle biogenesis, but their persistent elevation is linked to muscle wasting, which is poorly understood. This study aimed to investigate the association between catecholamine levels and age-related muscle loss.
Methods:
This retrospective study evaluated the plasma levels of two catecholamines, metanephrine and normetanephrine, and the clinical characteristics of 830 patients with adrenal incidentaloma on computed tomography (CT). Cross-sectional CT data at the L3 lumbar vertebrae were used to measure muscle areas. In vitro studies on C2C12 myotubes were conducted to examine β-adrenergic receptor signaling pathways and their role in myogenesis.
Results:
Men had significantly higher mean metanephrine levels of 0.17 nmol/L and normetanephrine levels of 0.63 nmol/L than women (P<0.05). Total abdominal muscle area was negatively correlated with catecholamine levels in both men and women, with the strongest negative correlation between normetanephrine levels and total abdominal muscle area in men (r=–0.31, P<0.001). Similarly, the strongest negative correlation between visceral fat area and metanephrine was observed in men (r=–0.25, P=0.004). Clenbuterol, a β-adrenergic receptor agonist, inhibited myogenesis, including myotube formation by extracellular signal-regulated kinase (ERK) suppression in C2C12 myoblasts. Conversely, β-blockers increased myogenesis via increasing ERK phosphorylation in C2C12 cells. These findings suggest that β-adrenergic modulation influences skeletal muscle differentiation, with ERK phosphorylation.
Conclusion
Catecholamine levels are associated with age, sex, muscle mass, and fat mass. Monitoring catecholamine levels, particularly in older men and in individuals with reduced muscle mass, may help manage age-related muscle loss and lead to individualized treatment strategies.
2.Acute Heart Failure Across the Ejection Fraction Spectrum: Phenotypes, Management, and Outcomes From Nationwide KorHF III Registry
Huijin LEE ; Eung Ju KIM ; Seong Woo HAN ; Seong-Mi PARK ; Hyung-Seop KIM ; Myung-Chan CHO ; Hyo-Suk AHN ; Mi-Seung SHIN ; Seok-Jae HWANG ; Jin-Ok JEONG ; Dong Heon YANG ; Junho HYUN ; Jin Oh CHOI ; Hae-Young LEE ; Byung-Su YOO ; Seok-Min KANG ; Dong-Ju CHOI ; Hyun-Jai CHO ;
International Journal of Heart Failure 2026;8(1):43-55
Background and Objectives:
Clinical characteristics and outcomes in acute heart failure (AHF) vary by phenotype. We assessed phenotype-specific features, treatment patterns, and outcomes in a nationwide Korean cohort.
Methods:
The Korean Heart Failure III registry prospectively enrolled 7,351 AHF admissions at 47 hospitals. Among 6,777 patients with available left ventricular ejection fraction (EF), phenotypes were defined as heart failure with reduced EF (HFrEF, ≤40%), mildly reduced EF (HFmrEF,41–49%), or preserved EF (HFpEF, ≥50%). The primary endpoint was a 12-month composite of all-cause death or heart transplantation, evaluated from index admission and, among hospital survivors, from discharge. We used inverse probability weighting (multinomial generalized boosted models with stabilized, trimmed weights) and weighted Cox proportional-hazards models to estimate hazard ratios (HRs).
Results:
Phenotype distribution was 58.9% HFrEF, 13.6% HFmrEF, and 27.5% HFpEF. Crude 12-month composite rates from index admission were 13.4% (HFrEF), 12.7% (HFmrEF), and 16.8% (HFpEF). After weighting, from index admission, HFmrEF (HR, 0.892; 95% confidence interval [CI], 0.731–1.088) and HFpEF (HR, 1.101; 95% CI, 0.939–1.291) did not differ from HFrEF; from discharge, HFpEF had modestly higher risk (HR, 1.207; 95% CI, 1.008–1.445) whereas HFmrEF did not (HR, 1.039; 95% CI, 0.844–1.279). Hyponatremia and chronic kidney disease were consistent adverse markers, while angiotensin-converting enzyme inhibitor/ angiotensin II receptor blocker use at discharge was protective.
Conclusions
Across the EF spectrum, phenotypes showed distinct profiles and risk. Postdischarge risk was modestly higher in HFpEF, supporting phenotype-tailored care and systematic discharge optimization in Korean patients with AHF.
3.Exosomes from Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells Protect Lung Epithelium and Attenuate Fibrosis
Sangryul CHA ; Jooyeon LEE ; Jimin JANG ; Yeongcheol KIM ; Dahee HAN ; Seok-Ho HONG ; Seung-Jin KIM ; Dae-Hee LEE ; Chung Hyeun MA ; Han Pil LEE ; Se-Ran YANG
International Journal of Stem Cells 2026;19(1):66-82
Idiopathic pulmonary fibrosis (IPF) is characterized by maladaptive epithelial–mesenchymal crosstalk and progressive extracellular matrix accumulation, whereas currently available antifibrotic agents merely decelerate functional decline.This study investigated whether exosomes derived from human mesenchymal stem cells derived from embryonic stem cells (ESC-MSCs) restore epithelial stress responses and attenuate fibrotic remodeling. Human IPF lung transcriptomes were integrated with a bleomycin-induced murine model analyzed by RNA sequencing and protein signaling, together with cigarette smoke extract-induced injury in A549 epithelial cells. ESC-MSCs-derived exosomes exhibited typical morphology and size distribution, enrichment of tetraspanins, and absence of endoplasmic reticulum contamination, consistent with high-purity preparations. Across human IPF and bleomycin-injured lungs, transcriptomic profiling revealed prominent enrichment of extracellular matrix and cytoskeletal gene programs, whereas mitogen-activated protein kinase (MAPK) and Smad families displayed only modest alterations at the mRNA level. In vivo administration of exosomes during the fibrotic remodeling phase, via either intravenous or intratracheal delivery, resulted in improved body weight, reduced lung weight-to-body weight ratios, and decreased collagen deposition and Ashcroft scores. These structural and functional improvements were accompanied by suppression of profibrotic and mesenchymal markers and selective attenuation of activator protein-1 (AP-1) activity. In epithelial injury models, ESC-MSCs-derived exosomes enhanced cell viability, restored redox homeostasis, and constrained stress-induced mesenchymal gene expression and MAPK phosphorylation in both co-treatment and post-treatment settings. Collectively, these data support an epithelial-centered mechanism in which ESC-MSCs-derived exosomes re-establish oxidative balance and selectively restrict AP-1-driven stress signaling, thereby secondarily limiting extracellular matrix accumulation and fibrotic remodeling.
4.Germline Mutations Related to Complete Remission After Neoadjuvant Chemotherapy in Patients With Triple-negative Breast Cancer
Jee Hyun AHN ; Ji Soo PARK ; Dongju WON ; Seung-Tae LEE ; Suk Jun LEE ; Seung Hye YANG ; Jee Ye KIM ; Seho PARK ; Seung Il KIM ; Byeong-Woo PARK ; Min Hwan KIM ; Gun Min KIM ; Joohyuk SOHN ; Hyung Seok PARK
Journal of Breast Cancer 2026;29(2):118-127
Purpose:
Triple-negative breast cancer (TNBC) is a frequent phenotype of BRCA-mutanttumors. Tumors with BRCAness may show characteristics of BRCA-mutant tumors and respond to similar treatments. Next-generation sequencing is an efficient and cost-effective method for simultaneously sequencing multiple cancer susceptibility genes, surpassing conventional Sanger testing.
Methods:
A total of 148 women with TNBC were recruited from December 2015 to November 2018, as part of a sub-analysis based on the PEARLY trial data. Of them, 103 patients received neoadjuvant chemotherapy (NCT). The targeted genes related to hereditary cancers were sequenced using the 65-gene germline next-generation sequencing (gNGS) panel pathogenic and likely pathogenic variants (P&LPs) were determined by Sanger sequencing. We examined the occurrence of pathologic complete remission (ypCR) in patients with P&LPs.
Results:
The patients’ median age was 47 years (range, 27–69 years). Twenty (13.7%) of 148 patients had P&LP in six genes, including BARD1 (n = 2), BRCA1 (n = 9), BRCA2 (n = 5), CHEK2 (n = 1), RAD51C (n = 1), and RAD51D (n = 2). Among the 103 patients with NCT, 43 (41.7%) achieved ypCR (P&LPs; 9 individuals vs. non-variants; 34 individuals). Among the 103 patients with NCT, 14 (9.3%) had P&LPs. Nine of 14 patients with P&LPs, including BARD1 (n = 2), BRCA1 (n = 4), BRCA2 (n = 1), RAD51C (n = 1), and RAD51D (n = 1), achieved ypCR, showing a trend toward statistical significance (p = 0.066).
Conclusion
Germline P&LP mutations in TNBC patients can be detected by gNGS. This panel test can identify BRCA and BRCAness mutations that may predict ypCR in TNBC.
5.Ethnic Heterogeneity in Reproductive Risk Factors for Breast Cancer, With a Focus on Asian Populations:A Meta-analysis
Youjin HONG ; Soseul SUNG ; Woojin LIM ; Sungji MOON ; Kwang-Pil KO ; Jung Eun LEE ; Inah KIM ; Sun Ha JEE ; Sun-Seog KWEON ; Min-Ho SHIN ; Sangmin PARK ; Seung-Ho RYU ; Sun Young YANG ; Jeongseon KIM ; Sang-Wook YI ; Sue K. PARK
Journal of Cancer Prevention 2026;31(1):20-27
suggest that some reproductive factors associated with BC differ across ethnicities and time trends, perhaps due to the prevalence of reproductive factors and the baseline hazard of BC.
6.Nationwide Survey on Endoscopic Submucosal Dissection for Early Gastric Cancer in Korea: Results From the Korean College of Helicobacter and Upper Gastrointestinal Research (KCHUGR) 2023 Survey
Jae Yong PARK ; Jeong Hoon LEE ; Tae-Se KIM ; Da Hyun JUNG ; Bong Eun LEE ; Yonghoon CHOI ; Wan-Sik LEE ; Young-Il KIM ; Sun Hyung KANG ; Hyunsoo CHUNG ; Su Jin KIM ; Joon Sung KIM ; Donghoon KANG ; Su Youn NAM ; Seung Han KIM ; Hyo-Joon YANG ; Hyun LIM ; Jin LEE ; Seon-Young PARK ; Seung-Woo LEE ; Sun Moon KIM ; Sam Ryong JEE ; Dae Young CHEUNG ; Chung Hyun TAE ; Seokin KANG ; Sung Chul PARK ; Seung In SEO ; Cheol Min SHIN ; Kee Don CHOI ; Jong Yeul LEE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2026;26(1):50-59
Objectives:
Endoscopic submucosal dissection (ESD) has become a standard minimally invasive treatment for selected patients with early gastric cancer (EGC). This study presents the first nationwide survey of patients with EGC treated with ESD in 2023, conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research.
Methods:
Data were retrospectively collected from participating referral centers across Korea using a standardized case report form covering patient characteristics, tumor features, procedural details, histopathological findings, and clinical outcomes. Descriptive and comparative analyses were conducted to summarize nationwide ESD practice patterns and outcomes.
Results:
Data from 5460 ESD cases from 5250 patients across 27 institutions were analyzed. The mean age was 67.4 years, with 74.1% males. Multiple synchronous lesions were identified in 3.7%. Most lesions were located in the lower third of the stomach (64.0%), and differentiated-type adenocarcinomas accounted for 87.8%. The en bloc and complete resection rates were 99.2% and 91.4%, respectively. Curative resection was achieved in 80.5%, whereas local non-curative resection (L-NCR) and surgical non-curative resection (S-NCR) were identified in 2.8% and 16.7%, respectively. Additional surgery was performed more frequently in patients with S-NCR than in those with L-NCR (59.3% vs. 24.7%). The bleeding and perforation rates were 3.6% and 0.9%, respectively, and were mostly managed conservatively or endoscopically. The median length of hospitalization was 4.0 days.
Conclusions
This first nationwide survey provides a comprehensive overview of the current practice of EGC treatment using ESD in Korea, demonstrating high technical success and safety, and establishing a baseline dataset for future longitudinal research.
7.The Recommendation of the Neuropathic Pain Special Interesting Group of the International Association for the Study of Pain: A Comparison of Systematic Reviews and Meta-analyses between 2015 and 2025
Kyomin CHOI ; Kyung Min KIM ; Byung-Su KIM ; Hee-Jin KIM ; Seung Woo KIM ; Kyoungwon BAIK ; Jin Myoung SEOK ; Jun-Sang SUNWOO ; In-Uk SONG ; Ho Geol WOO ; Eek-Sung LEE ; Jin-Man JUNG ; Yun Ho CHOI ; Kwang Ik YANG ;
Journal of the Korean Neurological Association 2026;44(1):1-7
Neuropathic pain markedly impairs quality of life and imposes a substantial socioeconomic burden, while available treatments often provide only partial relief and are limited by safety concerns. The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG-IASP) first published pharmacologic recommendations in 2007, followed by a major update in 2015 and a new guideline in 2025. This narrative review specifically compares the 2015 and 2025 NeuPSIG-IASP guidelines, outlining key methodological changes and therapeutic shifts. The 2025 guideline is based on a larger, more rigorous meta-analysis, maintains α2δ-ligands (adds mirogabalin), serotonin-noradrenaline reuptake inhibitors, and tricyclic antidepressants as first-line drugs, downgrades tramadol into the opioid third-line group. It also introduces high-frequency motor-cortex repetitive transcranial magnetic stimulation as a weakly recommended third-line option and discusses implications for Korean clinical practice.
8.Arteriovenous fistulas are associated with superior outcomes in very elderly hemodialysis patients: a nationwide cohort study
Hyung Duk KIM ; Do Hyoung KIM ; Hyangkyoung KIM ; Hyung-Seok LEE ; Seung Boo YANG ; Seok Joon SHIN ; Hoon Suk PARK ;
The Korean Journal of Internal Medicine 2026;41(1):152-162
Background/Aims:
The optimal vascular access strategy for very elderly patients initiating hemodialysis (HD) remains unclear. Arteriovenous fistulas (AVFs) offer long-term benefits but may be limited due to vascular aging. This study evaluated vascular access outcomes in patients aged ≥ 80 years.
Methods:
We conducted a retrospective cohort study using data from the Korean National Health Insurance Service between 2008 and 2019. Patients aged ≥ 80 years who initiated HD with a newly created AVF or arteriovenous graft (AVG) were included. Primary outcomes were primary, assisted primary, and secondary patency. The secondary outcome was all-cause mortality. Outcomes were compared using Kaplan–Meier analysis and multivariable Cox regression.
Results:
Among 8,487 patients, 5,124 (60.4%) received AVFs (AVF group) and 3,363 (39.6%) received AVGs (AVG group). AVFs were associated with significantly lower rates of patency loss across all definitions. The adjusted hazard ratios (HRs) for AVG vs. AVF were 1.76 (95% confidence interval [CI], 1.67–1.86) for primary patency loss, 1.90 (95% CI, 1.77–2.03) for assisted primary, and 3.18 (95% CI, 2.81–3.61) for secondary patency loss. All-cause mortality was also higher in the AVG group (adjusted HR, 1.24; 95% CI, 1.17–1.30).
Conclusions
In this large-scale study, AVF use was associated with superior patency and lower mortality compared with AVG in patients aged ≥ 80 years. These findings suggest that AVF remains a beneficial option for appropriately selected elderly patients and that age alone should not be a primary barrier to its creation.
9.Gestational Age and Neurodevelopmental Outcomes in Preterm Children at Early Preschool Age: A Longitudinal Multidomain Logistic Modeling Study
Ji Na YANG ; Ye Kyeng SEO ; Dong Hyun KIM ; Nam Hun HEO ; Soo A KIM ; Jun Hwan SONG ; Seung Soo KIM
Annals of Child Neurology 2026;34(2):109-119
Purpose:
Preterm birth remains a leading cause of long-term neurodevelopmental impairment, yet early evaluations frequently underestimate subsequent deficits. This study examined longitudinal neurodevelopmental trajectories across gestational age groups and identified predictors of developmental delay.
Methods:
A retrospective cohort of 532 preterm children, stratified by gestational age, was followed from the neonatal period to early preschool age. Neurodevelopment was assessed using the Korean version of the Bayley Scales of Infant and Toddler Development, Third Edition at 8–12 months (n=481), 13–24 months (n=118), and 25–42 months (n=100). Longitudinal trajectories were analyzed using general linear models, and predictors of developmental delay were identified through multivariable logistic regression.
Results:
During the first year, motor scores differed significantly across gestational age groups, with extremely preterm infants showing the lowest values. By the third to fourth years of life, cognitive and language scores diverged markedly, with extremely preterm children exhibiting the steepest decline and additional deficits in motor and adaptive behavior domains. Lower gestational age remained an independent predictor of both cognitive and language delay at early preschool age, while no independent predictors were identified for motor, social-emotional, or adaptive behavior outcomes.
Conclusion
Neurodevelopmental outcomes in preterm children follow dynamic, domain-specific trajectories influenced by gestational age and developmental timing. Motor delays are most evident in infancy, whereas cognitive and language impairments emerge by early preschool age. Gestational age remains a consistent predictor of later delay, emphasizing the need for longitudinal, gestational age–stratified monitoring and early, targeted intervention.
10.Nationwide Survey on Endoscopic Submucosal Dissection for Early Gastric Cancer in Korea: Results From the Korean College of Helicobacter and Upper Gastrointestinal Research (KCHUGR) 2023 Survey
Jae Yong PARK ; Jeong Hoon LEE ; Tae-Se KIM ; Da Hyun JUNG ; Bong Eun LEE ; Yonghoon CHOI ; Wan-Sik LEE ; Young-Il KIM ; Sun Hyung KANG ; Hyunsoo CHUNG ; Su Jin KIM ; Joon Sung KIM ; Donghoon KANG ; Su Youn NAM ; Seung Han KIM ; Hyo-Joon YANG ; Hyun LIM ; Jin LEE ; Seon-Young PARK ; Seung-Woo LEE ; Sun Moon KIM ; Sam Ryong JEE ; Dae Young CHEUNG ; Chung Hyun TAE ; Seokin KANG ; Sung Chul PARK ; Seung In SEO ; Cheol Min SHIN ; Kee Don CHOI ; Jong Yeul LEE ;
Journal of Gastric Cancer 2026;26(2):169-183
Purpose:
Endoscopic submucosal dissection (ESD) has become a standard minimally invasive treatment for selected patients with early gastric cancer (EGC). This study presents the first nationwide survey of patients with EGC treated with ESD in 2023, conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research.
Materials and Methods:
Data were retrospectively collected from participating referral centers across Korea using a standardized case report form covering patient characteristics, tumor features, procedural details, histopathological findings, and clinical outcomes.Descriptive and comparative analyses were conducted to summarize nationwide ESD practice patterns and outcomes.
Results:
Data from 5,460 ESD cases from 5,250 patients across 27 institutions were analyzed. The mean age was 67.4 years, with 74.1% males. Multiple synchronous lesions were identified in 3.7%. Most lesions were located in the lower third of the stomach (64.0%), and differentiated-type adenocarcinomas accounted for 87.8%. The en bloc and complete resection rates were 99.2% and 91.4%, respectively. Curative resection was achieved in 80.5%, whereas local non-curative resection (L-NCR) and surgical non-curative resection (S-NCR) were identified in 2.8% and 16.7%, respectively. Additional surgery was performed more frequently in patients with S-NCR than in those with L-NCR (59.3% vs. 24.7%). The bleeding and perforation rates were 3.6% and 0.9%, respectively, and were mostly managed conservatively or endoscopically. The median length of hospitalization was 4.0 days.
Conclusions
This first nationwide survey provides a comprehensive overview of the current practice of EGC treatment using ESD in Korea, demonstrating high technical success and safety, and establishing a baseline dataset for future longitudinal research.

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