Age-related macular degeneration (AMD) is a leading cause of blindness in people over 65 years old. Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for neovascular AMD (nAMD); however, fibrosis remains an unmet medical need due to the lack of effective medications. This study evaluated eight natural products from Celastrus orbiculatus, which has been reported to have anti-inflammatory effects, for their effects on the fibrotic pathological process as well as choroidal neovascularization (CNV). We investigated the half-maximal inhibitory concentration (IC 50) values of these compounds on VEGF and alphasmooth muscle actin (α-SMA, a fibrosis marker) expression-induced by human acute monocytic cell (THP-1) conditioned media in retinal pigment epithelium cells (ARPE-19). Four compounds reduced both VEGF and α-SMA at 10 μM, with three—Celafolin A-1, COFH5645, and COFH543435—showing the highest potency. Intravitreal injections of the compound in a mouse model of CNV induced by laser photocoagulation confirmed its efficacy. Celafolin A-1 significantly reduced α-SMA and VEGF expression and decreased hyper-reflective lesions and CNV areas. Binding affinity measurements using biolayer interferometry identified an interaction between Celafolin A-1 and crystallin alpha B (Cryab), a protein involved in stress responses and fibrosis. Celafolin A-1 reduced the expression levels of Cryab as well as its phosphorylated form at Ser45, indicating that its mechanism involves the regulation of Cryab phosphorylation. Taken together, Celafolin A-1 exhibits dual inhibitory effects on VEGF and fibrosis, suggesting it as a candidate for the treatment of nAMD.

Purpose: The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Materials and Methods: A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire. Results: Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ. Conclusion KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

Background: With the aging population and advancements in medical care worldwide, the number of older patients with end-stage kidney disease continues to rise. This study aimed to identify factors associated with osteoporosis and osteopenia in older patients undergoing incident hemodialysis and assess their impact on mortality. Methods: We analyzed a large multicenter retrospective cohort of patients aged ≥70 years undergoing incident hemodialysis to identify factors associated with osteoporosis using logistic regression analysis and to assess the association of death with osteoporosis and osteopenia using Cox multivariable analysis. Results: Among 710 patients, 39.0% and 19.6% had osteoporosis and osteopenia, respectively. Osteoporosis was significantly associated with female sex, a history of fractures, and the absence of phosphate binder use. During a median follow-up of 36.8 months, 348 participants (58.8%) died. Mortality rates were the highest in the osteoporosis group (79.8%), followed by the osteopenia (77.2%) and normal bone mineral density (BMD) groups (35.2%). Cox regression analysis revealed that even after adjusting for covariates, the osteoporosis group was significantly associated with a higher mortality risk than the normal BMD group. Osteoporosis at the start of hemodialysis was significantly associated with higher mortality. Conclusion We should consider the importance of bone health in patients undergoing incident hemodialysis and pay attention to the use of phosphate binders and fracture prevention.

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: Autosomal dominant giant platelet syndrome (GPS) is characterized by thrombocytopenia, giant platelets, and Döhle-like inclusion bodies in leukocytes.Previous studies suggest relatively preserved platelet structure and function, implicating impaired megakaryocyte fragmentation. This study aimed to identify myosin heavy chain 9 (MYH9) mutations in Korean patients with GPS and to define the associated clinical, molecular and functional characteristics. Methods: After detailed personal and family history taking, peripheral blood smears were reviewed for platelet size, count, and leukocyte inclusions. MYH9 mutations were analyzed in peripheral blood mononuclear cells by direct sequencing of selected exons or complementary DNA (cDNA). Computer-assisted structural modeling was performed to evaluate the functional consequences of identified mutations. Results: Twenty-two affected individuals from six unrelated families were diagnosed with hereditary macrothrombocytopenia consistent with GPS. The median platelet count was 59,000/L, and the mean platelet volume was markedly increased (17.8 fL). Platelets ranged from approximately half to 1.5 times the size of red blood cells.Döhle-like inclusions were observed in 25-33% of leukocytes in four families. Extrahematologic manifestations included hearing impairment (family with Ile1816Val) and renal involvement, ranging from mild proteinuria to chronic renal failure requiring renal transplantation (family with Lys373Asn). Five families harbored MYH9 mutations—Arg1933Ter, Trp33Cys (novel), Lys373Asn, Ile1816Val, and Arg1165Cys—located in exons 40, 1, 10, 37, and 26, respectively; mutations segregated with affected status.Biochemical analysis revealed decreased MYH9 in soluble fractions with increased insoluble pellets; Trp33Cys and Lys373Asn produced aberrant approximately 140 kDa bands in addition to the normal 224 kDa band. Modeling localized Trp33Cys to the proximal myosin head region implicated in actin interaction. Conclusion Five GPS-associated MYH9 mutations were identified, including a novel Trp33Cys variant. Altered MYH9 solubility and disturbed protein–protein interactions may contribute to disease pathogenesis.

This study aimed to develop a predictive model for the early identification of patients at risk of sepsis, using routinely available clinical information and laboratory test results collected during the initial phase of patient care. Methods: This retrospective analysis included electronic medical records of 22,400 adult patients who presented with suspected infection to a tertiary care university hospital in Korea between January 2013 and May 2024. Patients were classified according to Systemic Inflammatory Response Syndrome (score ≥ 2) or Quick Sequential Organ Failure Assessment (score ≥ 2), in combination with sepsis-related International Classification of Diseases, 10th revision codes. Four different machine learning models were trained and validated using five-fold cross-validation. In addition, Shapley additive explanations analysis was performed to interpret the contribution and clinical relevance of key predictive variables. Results: Among the evaluated models, CatBoost demonstrated the strongest predictive performance. Notably, platelet distribution width, alveolar–arterial oxygen difference, procalcitonin, and the arterial/alveolar oxygen ratio consistently emerged as major predictors. Importantly, several variables that did not reach statistical significance in univariate analysis nevertheless contributed substantially to overall model performance, highlighting the importance of complex, multidimensional interactions among clinical factors. Conclusion: These findings indicate that a model based on simple, routinely collected clinical data can achieve high predictive accuracy and strong generalizability. Such a tool may support early clinical decision-making by multidisciplinary teams, including nurses, across diverse real-world care settings. Further prospective studies are warranted to validate its clinical utility and to assess its potential effects on patient outcomes.

Background: Asthma remission has recently emerged as an aspirational treatment goal, yet its definition remains inconsistent across studies and expert groups. The absence of a standardized framework hampers its application in clinical practice and research, particularly in Korea where biologics use is rapidly increasing. This study aimed to establish a consensus definition of clinical remission in severe asthma among Korean experts. Methods: A two-round modified Delphi survey, followed by a focused third round, was conducted among 28 board-certified pulmonologists from the Korean Academy of Tuberculosis and Respiratory Diseases (KATRD). The questionnaire consisted of six domains and 27 items. Responses were analyzed using agreement rates, interquartile ranges, and content validity ratios to determine consensus levels. Results: Consensus was reached on defining clinical remission as a composite of no exacerbations, no systemic corticosteroid use, sustained symptom control (Asthma Control Test ≥20 on at least three occasions over 12 months), and stabilization and optimization of pulmonary function while on maintenance treatment. Experts agreed that pulmonary function should be assessed based on clinical judgment rather than absolute thresholds. Complete remission was additionally defined as fulfilling all clinical remission criteria with normalization of type 2 inflammation (blood eosinophils <300/μL and fractional exhaled nitric oxide <25 ppb). Conclusion This Delphi consensus provides a regionally relevant and pragmatic framework for defining remission in severe asthma. These statements may help guide clinical practice, inform guideline development, and support future research on remission as a treatment goal.

Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Background and Objectives: Circulating microRNAs (miRNAs) have been proposed as potential biomarkers in atrial fibrillation (AF) and heart failure (HF), but their role in patients with AF and heart failure with preserved ejection fraction (HFpEF) remains uncertain. Methods: We measured serum levels of 4 candidate miRNAs (miR-21, miR-146a, miR-146b, and miR-328) using quantitative polymerase chain reaction in 45 patients with persistent AF and HFpEF and five non-AF arrhythmia controls (Healthy). Expression levels were normalized to miR-16 and expressed as fold change (2−ΔCt ). Baseline (V1) and 3–6 months follow-up (V2) samples were analyzed, and comparisons were performed using non-parametric tests. Results: At baseline, none of the 4 miRNAs differed significantly between AF patients and Healthy controls; miR-21, 1.24 ± 0.55 vs. 1.15 ± 0.32 (P = 0.57); miR-146a, 0.66 ± 0.35 vs. 0.65 ± 0.06 (P = 0.71); miR-146b, 0.12 ± 0.07 vs. 0.11 ± 0.01 (P = 0.90); and miR-328, 0.08 ± 0.05 vs. 0.07 ± 0.03 (P = 0.95), all P > 0.5. Baseline comparisons were analyzed using relative expression values (2−ΔCt , normalized to miR-16), while longitudinal changes between V1 and V2 were assessed using fold change (2−ΔΔCt ). No significant longitudinal changes were observed across treatment groups. Conclusions In patients with persistent AF and HFpEF/HF with mildly reduced ejection fraction, circulating miR-21, miR-146a, miR-146b, and miR-328 showed no significant differences compared with the non-AF arrhythmia control group and did not change after 6 months of renin-angiotensin-aldosterone system-targeted therapy. These pilot data suggest that the short-term utility of biomarkers is limited and warrants validation in larger, randomized cohorts.

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.