This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

Purpose: This study evaluated the feasibility of radical nephrectomy and thrombectomy without cardiopulmonary bypass (CPB) in patients with renal cell carcinoma (RCC) and level IV venous tumor thrombus, compared with CPB-assisted surgery. Materials and Methods: This retrospective cohort study analyzed patients with RCC and level IV venous tumor thrombus who underwent surgery at a single center between 2014 and 2020. Feasibility of non-CPB surgery was assessed by comparing perioperative safety-related outcomes, overall survival (OS), and progression-free survival (PFS) between the non-CPB and CPB groups. Perioperative outcomes included operative time, blood loss, severe complications (Clavien-Dindo classification grade ≥III), intensive care unit (ICU) stay, and mortality. Kaplan-Meier analysis and generalized Wilcoxon tests were used to compare survival outcomes. Results: A total of 16 patients met eligibility criteria: 5 underwent surgery without CPB, and 11 underwent CPB-assisted surgery. Median operative time was similar between the CPB and non-CPB groups (490 minutes vs. 480 minutes, p=0.650). Compared with the CPB group, blood loss was lower in the non-CPB group (4000 mL vs. 1080 mL, p=0.333). Severe complications occurred in 36.4% of CPB patients and 0% of non-CPB patients (p=0.245). ICU stay was comparable between the non-CPB and CPB groups (2 days vs. 3 days, p=0.356). OS did not differ significantly between groups (p=0.180), whereas PFS was longer in the non-CPB group (p=0.041). Conclusions Radical nephrectomy and thrombectomy without CPB appears feasible and may be associated with lower perioperative morbidity and blood loss without compromising oncologic outcomes. Non-CPB surgery should be considered in selected patients with level IV venous tumor thrombus when technically feasible.

Background: The pulse wave transit time (PWTT) increases with decreased vascular tone resulting from sympathetic blockade caused by regional anesthesia. It oscillates, exhibiting variability due to the interaction between the autonomic nervous and cardiovascular systems. We hypothesized that interscalene brachial plexus block (ISBPB) placement increases the PWTT and reduces the low-frequency power of PWTT variability (LF). Methods: Fifty-six patients receiving an ISBPB were analyzed. The PWTT was defined as the difference in milliseconds (ms) between the R peak of the electrocardiogram and the peak of the second-derivative photoplethysmographic waveform. The LF was calculated by integrating from 0.04 to 0.15 Hz on the power spectrum obtained from fast Fourier transform. The two variables were collected during the 5 min before the end of acclimatization (baseline), between 5 and 10 min after block needle insertion, and between 15 and 20 min after block needle insertion. Results: The PWTT increased significantly (P < 0.001) from baseline (mean [SD]: 155.3 [16.7] ms) to 5–10 min post-needle insertion (166.9 [15.4] ms) (mean difference [MD]: 11.6, 95% CI [9.2–14.0], P < 0.001) and 15–20 min post-needle insertion (165.6 [16.1] ms) (MD: 10.3, 95% CI [7.3–13.2], P < 0.001). The natural log-transformed LF (lnLF) decreased significantly (P < 0.01) from baseline (1.539 [0.560] ln[ms2/Hz]) to 5–10 min post-needle insertion (1.341 [0.617] ln[ms2/Hz]) (MD: –0.198, 95% CI [–0.356 to –0.040], P < 0.01) and 15–20 min post-needle insertion (1.396 [0.548] ln[ms2/Hz]) (MD: –0.144, 95% CI [–0.274 to –0.013], P = 0.03). Conclusions The post-ISBPB decrease in lnLF and increase in PWTT may be attributable to ISBPB-induced sympathectomy.

Objective: This study aimed to evaluate reproductive outcomes according to the timing of testicular sperm retrieval. Methods: The study included 282 infertile couples divided into three groups: group A (freeze-thawed testicular sperm extraction [TESE] sperm, n=233), group B (fresh TESE sperm collected 1 day before ovum pickup, n=22), and group C (fresh TESE sperm collected on the same day as ovum pickup, n=27). The indications for TESE were surgically uncorrectable azoospermia or ejaculation failure, often accompanied by medical comorbidities such as diabetes mellitus and spinal cord injury. The outcome parameters assessed were fertilization rates, embryo quality, and clinical pregnancy rates. Results: The mean paternal age was 36.8±5.7 years, and the mean maternal age was 32.6±3.5 years. The mean duration of infertility was 2.9±1.8 years. The fertilization rates were 70.7%, 78.9%, and 73.0% for groups A, B, and C, respectively (p=0.047). The percentages of good-quality embryos were 68.2%, 65.3%, and 48.4%, respectively (p=0.007); specifically, the percentage of good-quality embryos was significantly lower in group C compared with the other two groups. Clinical pregnancy rates per transfer were similar at 51.1%, 50.0%, and 48.1% (p=0.958), with no differences observed in miscarriage rates. Conclusion Testicular sperm retrieval can be safely performed 1 day before ovum pickup, resulting in favorable fertility outcomes.

Background: and Purpose Whole-exome sequencing (WES) is a valuable tool for identifying causative mutations in adult moyamoya disease (MMD), thereby advancing our understanding of the genetic mechanisms underlying this condition. Here, we conducted the first WESbased association study aimed at identifying genetic modifiers implicated in MMD. Methods: This WES study involved 160 patients with MMD and 189 controls from a multicenter hospital-based biobank, and evaluated combined annotation-dependent depletion (CADD) scores. Mutant-allele frequencies were compared in 369,121 individuals derived from the UK Biobank (UKB) WES. Mutant-allele risk scores (MARSs) were created based on WESidentified mutations. Gene-based association analyses and pooled analyses in East-Asian populations were further performed. Results: Fourteen mutations reached the genome-wide significance criterion (p<5×10-8 ), among which the p.R4810K mutation in the ring finger protein 213 gene (RNF213) showed the strongest significance (odds ratio=117.4, p=8.54×10-24 ). Notably, two mutations—p.G576S (alpha-glucosidase [GAA]) and p.D54N (charged multivesicular body protein 6 [CHMP6])— exhibited high CADD scores of 32 and 25, respectively, whereas the RNF213 p.R4810K mutation demonstrated a moderate deleteriousness score of 10.63. Fourteen mutations exhibited significant differences in allele frequencies between patients and UKB controlled data (p<1×10-8 ).The MARS9 model (incorporating nine missense mutations) showed better predictability for MMD (90.89%). The analysis of gene-based associations revealed four candidate genes: GAA, RNF213, CHMP6, and CARD14 (p=5×10-19 to 4×10-7 ). The subsequent pooled analyses validated four mutations in East Asian populations: p.V1195M, p.D1331G, p.S2334N, and p.R4810K (p<3×10-8 ). Conclusions This pioneering study has corroborated the significance of p.R4810K and identified several causative mutations predisposing patients to MMD, which helps to improve the understanding of its polygenetic nature.

Heart failure (HF) prevalence and associated socio-economic costs have risen rapidly in Korea, creating urgent demand for a national, standardized prospective registry to support quality monitoring, outcome comparison, and real-world evidence. Standardized data definitions are essential for valid comparisons across studies and healthcare settings. We created a unified national HF cohort by integrating the two largest Korean registries, KorAHF (2011–2014;n=5,625) and KorHF III (2018–2023; n=7,351), yielding 12,976 hospitalized HF patients. Because heterogeneous variable definitions impeded direct comparisons, we implemented a harmonization pipeline across demographic, clinical, imaging, biomarker, therapeutic, and outcome domains, aligned with international standards and reinforced by systematic data quality checks.A multidisciplinary panel then conducted a structured decision process to produce the Korean HF Standard Dataset, a tiered and interoperable variable set spanning six domains: demographics, presentation at admission, in-hospital events and comorbidities, discharge status, outpatient follow-up, and readmission events. This integrated platform and standardized variables enable precise identification of HF patient phenotypes and prognostic factors, establishing an evidence-based foundation for disease management. This supports an analysis of temporal changes in treatment patterns and outcomes, generates data to inform future clinical practice guidelines, and provides a practical basis for planning large, continuous, prospective HF registries. Furthermore, it also facilitates pragmatic, registry-based randomized clinical trials and unmet-needs assessments that can guide national health policy. Establishing a foundation for future linkage with national health databases, this platform will allow for enhanced accuracy, comparability, and representativeness, powering quality improvement initiatives and population-level monitoring of Korea’s growing HF burden.

Background and Objectives: Heart failure (HF) imposes a significant global burden, yet awareness and implementation of guideline-directed management remain suboptimal. This study evaluated HF awareness, diagnostic patterns, and therapeutic strategies among physicians in Korea. Methods: A nationwide online survey was conducted from July to August 2019, targeting primary care physicians (PCPs; n=8,000) and hospital-based cardiology specialists (n=1,339) across Korea. The questionnaire comprised 23 items covering baseline characteristics, perceptions of HF prognosis, diagnostic approaches, and treatment practices. Results: A total of 543 physicians responded (209 PCPs and 334 cardiology specialists). While the majority correctly defined HF, a substantial proportion underestimated the lifetime risk and poor prognosis. Cardiology specialists were more likely than PCPs to use objective diagnostic tools, including echocardiography (97% vs. 61%, p<0.001) and natriuretic peptide testing (90% vs. 57%, p<0.001). Among PCPs, 29% reported diagnosing HF based on symptoms and physical findings without objective testing, and 27% reported referring patients to general hospitals for diagnostic evaluation. Prescription rates for guideline-directed medical therapies, including renin-angiotensin system blockers and beta-blockers, were consistently higher among cardiology specialists.PCPs more frequently cited advanced age as a barrier to prescribing evidence-based medications. Conclusions Physicians’ awareness and clinical practices regarding HF in Korea remain suboptimal. Given the growing burden, high mortality, and substantial costs of HF, early detection, appropriate diagnostic evaluation, and timely referral are essential. Targeted education and system-level strategies to improve guideline implementation, particularly in primary care settings, are warranted.

In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.

Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. Results: Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). Conclusion Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.