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.

Background: To investigate the fracture risks associated with anti-diabetic drugs in older women with type 2 diabetes mellitus (T2DM), who are particularly susceptible to skeletal fragility. Methods: Using data from the Korean National Health Insurance Service, this nested case-control study included 10,104 older women with T2DM and osteoporotic fractures (aged 66.5±3.4 years) matched in a 1:3 ratio with controls by birthdate, Charlson Comorbidity Index, and cohort entry date. We analyzed the odds of major osteoporotic fracture (MOF), vertebral fracture (VF), and non-VF (NVF) in users of sulfonylurea, thiazolidinedione (TZD), dipeptidyl peptidase-4 inhibitor, and sodium-glucose cotransporter 2 inhibitor (SGLT2i), compared to metformin (Met)-only users using multivariable logistic regression. Results: During a follow-up period of 3.8±2.8 years, TZD users had a higher risk of MOF than Met-only users (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.19-1.53; P<0.001). Risks of VF and NVF were also increased in the TZD group (OR, 1.21; 95% CI 1.03-1.42; P=0.022 and OR, 1.32; 95% CI 1.14-1.52; P<0.001, respectively). No significant differences were observed in other drug groups. The increased risk of VF and NVF in the TZD group were particularly pronounced in patients with normal or osteopenic bone mineral density (BMD) and in those with normal body mass index (BMI), respectively. Conclusions In older women with T2DM, TZD use was associated with increased VF and NVF risks, particularly among those with normal or osteopenic BMD and normal BMI. SGLT2i showed no increased risk, but further large-scale studies are needed to confirm its skeletal safety.

Background: s/Aims: Phase angle (PhA), as measured by bioelectrical impedance analysis, provides insights into hydration and nutritional status, making it a prognostic indicator of frailty. While low preoperative PhA has been linked to postoperative complications in cancer patients, its predictive value in individuals undergoing pancreaticoduodenectomy (PD) has not been thoroughly investigated.This study aims to evaluate the clinical utility of preoperative PhA in predicting postoperative complications for patients undergoing PD. Methods: Among 41 patients who underwent PD at Seoul National University Hospital between September and December 2024, 35 were included in the analysis after excluding 6 patients who had concomitant blood vessel or other organ resections. Patients were divided into low (Comprehensive Complication Index [CCI] ≤ 20) and high (CCI > 20) complication groups based on the CCI, derived from the Clavien–Dindo classification. The differences in PhA between the two groups were analyzed, and logistic regression was performed to assess the relationship between PhA and CCI. Results: The mean PhA was significantly lower in the high-CCI group compared to the low-CCI group (5.7° vs. 6.7°, p = 0.025). Multivariate logistic regression analysis indicated that PhA (odds ratio: 0.17; 95% confidence interval: 0.04–0.68; p = 0.012) was an independent predictor of high CCI. A low preoperative PhA was associated with an increased risk of postoperative complications following PD. Conclusions Preoperative PhA may serve as a valuable predictive indicator of postoperative complications after PD, enabling the identification of patients who could benefit from preoperative prehabilitation, including nutritional support.

Background: Despite widespread vaccination efforts against severe acute respiratory syndrome coronavirus 2, variants with increased transmissibility or immune evasion continue to emerge, posing a considerable challenge. Understanding the immunological factors associated with coronavirus disease (COVID-19) progression is essential for improving patient management and treatment strategies. We explored the dynamic changes in the peripheral white blood cell (WBC) profile, including T lymphocyte subsets, to assess their potential as predictors of disease severity and progression. Methods: Two hundred fifty-eight patients hospitalized for confirmed COVID-19 were classified into four sub-cohorts based on changes in disease severity over 7 days. WBC parameters, including absolute neutrophil, total lymphocyte, and T cell subset counts, and the neutrophil-to-lymphocyte ratio (NLR) were assessed at admission and after 7 days. Results: Patients with persistent mild-to-moderate illness exhibited a marked increase in the lymphocyte count and a decrease in the NLR over time. In contrast, patients with sustained severe-to-critical illness showed an increasing WBC count without a corresponding increase in the lymphocyte count, in addition to a marked elevation in the NLR. Patients whose condition improved from severe-to-critical to mild-to-moderate illness showed increased cluster of differentiation (CD)3+ and CD4+ T cell counts and an elevated CD4/CD8 ratio, whereas the NLR did not significantly change. Conclusions The early-phase dynamics of T cell subsets may serve as a useful biomarker of disease severity and recovery in patients with COVID-19. Monitoring these immunological changes may help support clinical decision-making and inform the timing of therapeutic interventions.

Objective: To evaluate the diagnostic performance of the “probable hepatocellular carcinoma (HCC)” category in the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) v2022 guidelines. Materials and Methods: This multicenter retrospective study included patients at risk of HCC who underwent gadoxetic acid-enhanced MRI between January 2015 and June 2018; a subgroup of these patients also underwent liver CT. Eligible patients had at least one non-cystic lesion (≥10 mm) with a reference standard. Four radiologists interpreted the images independently and the results were pooled. The performance of “definite HCC” and “probable HCC” together and “probable HCC” alone were compared between v2018 and v2022. Results: A total of 2,237 patients (1,666 men; mean age, 59 ± 11 years) with 2,445 lesions were included. In v2022, 1.5% (143/9,780) of the lesions were additionally categorized as “probable HCC” by four reviewers on MRI; among these, 104 lesions were not HCCs. Focal nodular hyperplasia (FNH) or FNH-like nodules constituted 90.4% (94/104) of the false positives. When “definite HCC” and “probable HCC” were combined, v2022 showed higher sensitivity (83.7% [5,670/6,776] vs. 83.1% [5,631/6,776]) but lower specificity (77.1% [2,316/3,004] vs. 80.6% [2,420/3,004]) than v2018 (P < 0.001). For “probable HCC” alone, v2022 showed a lower positive predictive value (PPV) than v2018 (64.1% [373/582] vs. 76.1% [334/439], P < 0.001). In v2022, lesions with non-rim arterial-phase hyperenhancement (APHE) showed a lower PPV than those without APHE (42.3% [91/215] vs. 76.8% [282/367], P < 0.001). In the CT subgroup (n = 1,590), 1.6% (99/6,360) of the lesions were reassessed as “probable HCC,” and its PPV was 83.8% (83/99) in v2022 whereas no lesions were classified as “probable HCC” under v2018. Conclusion The revised “probable HCC” category in the KLCA-NCC v2022 aligns with updates in the diagnostic flow, demonstrating acceptable performance on MRI and CT. Notably, FNH or FNH-like nodules can be misclassified as “probable HCC” when MRI is used.

Microglia are the resident immune cells of the brain; they respond rapidly to inflammatory stimuli and contribute to the progression of neurodegenerative diseases. Receptor-interacting protein kinase 3 (RIPK3) is known to mediate pro-inflammatory signaling and necroptosis, a form of regulated necrotic cell death. However, the role of RIPK3 in microglial activation remains unclear. This study aimed to investigate the role of RIPK3 in both in vitro and in vivo models of neuroinflammation and necroptosis using a selective RIPK3 inhibitor, GSK872. In lipopolysaccharide (LPS)-injected mice, GSK872 attenuated microglial activation, decreased the expression of pro-inflammatory mediators, and reduced the phosphorylation of RIPK3 and mixed lineage kinase domain-like protein (MLKL). In BV2 microglial cells, GSK872 suppressed the production of inflammatory mediators under both inflammatory and necroptotic conditions induced by LPS or LPS/Z-VAD. In particular, GSK872 reduced necroptosis-associated cell death and the release of HMGB1 and IL-1 in LPS/Z-VAD-treated cells. Detailed mechanistic studies revealed that GSK872 inhibits the c-Jun N-terminal kinase (JNK) pathway, while pharmacological inhibition of JNK using SP600125 recapitulates the effects of GSK872 on inflammatory and necroptotic markers. These results indicate that JNK plays a critical role in mediating the effects of GSK872. Notably, IL-1 released during necroptosis appears to contribute modestly to the phosphorylation of JNK and MLKL, indicating a potential feedback mechanism that reinforces necroptotic signaling. Our findings provide compelling evidence that the inhibition of RIPK3 by GSK872 alleviates neuroinflammatory responses and necroptotic cell death by modulating JNK signaling in activated microglia, offering a promising therapeutic strategy for neurodegenerative diseases.

Purpose: This study analyzed nationwide trends in lung cancer surgery in South Korea over 14 years, focusing on surgical volume, patient demographics, surgical approaches, and outcomes. Materials and Methods: We performed a retrospective cohort study using nationwide health insurance claims data (124,334 cases) and robotic surgery data (1,740 cases) provided by the manufacturer. Patients who underwent lung cancer surgery between 2010 and 2023 were included. Annual trends were assessed using the annual percentage change (APC), and logistic as well as linear regression models were used to identify predictors of mortality and prolonged hospital stay. Results: The annual surgical volume increased from 4,557 in 2010 to 14,184 in 2023 (APC, 8.86%; p < 0.001). Video-assisted thoracoscopic surgery (VATS) became the predominant approach, rising from 52.9% to 94.8% (APC, 4.11%; p < 0.001). Sub-lobar resections increased, with wedge resections growing from 9.0% to 18.5% (APC, 5.72%; p < 0.001) and segmentectomies from 3.0% to 17.9% (APC, 14.63%; p < 0.001). The proportion of female patients increased from 32.0% to 44.7% (APC, 2.39%; p < 0.001), while patients aged 70-79 years increased from 26.3% to 32.3% (APC, 1.60%; p < 0.001) and those aged ≥ 80 years from 2.0% to 6.2% (APC, 9.63%; p < 0.001). The median hospital stay decreased from 13 to 7 days (APC, –4.34%; p < 0.001), and 30-day mortality declined from 2.45% to 0.76% (APC, –8.32%; p < 0.001). Conclusion Lung cancer surgery in Korea has increased substantially, with a notable shift toward minimally invasive and lung-sparing techniques that have improved outcomes. However, persistent disparities underscore the need for a national surgical registry.

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.

Purpose: This study aimed to assess the efficacy and safety of first-line modified FOLFIRINOX in patients with advanced urachal cancer. Materials and Methods: The ULTIMA trial (NCT04611724) is a single-arm, open-label, multicenter phase II study evaluating modified FOLFIRINOX (oxaliplatin 85 mg/m2 over 2 hours, irinotecan 150 mg/m2 over 1.5 hours, leucovorin 400 mg/m2 over 2 hours, and 5-fluorouracil 2,400 mg/m2 over 46 hours) plus prophylactic pegteograstim in patients with recurrent or metastatic urachal cancer every 2 weeks for up to 12 cycles, or until disease progression or unacceptable toxicity. The primary endpoint was the overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the incidence of febrile neutropenia. Results: Between April 2021 and November 2023, 21 patients with advanced urachal cancer were enrolled across five cancer centers. The median age was 50 years (range, 28 to 68 years), with 15 male patients. The most common metastatic site was the lung (47.6%), followed by lymph nodes (38.1%) and peritoneal seeding (33.3%). Two patients and 11 patients achieved a complete and partial response, respectively, yielding an ORR of 61.9%. The study met its primary endpoint in the first stage. With a median follow-up of 23.3 months, the median PFS was 9.3 months (95% confidence interval [CI], 6.7 to 11.9), and the median OS was 19.7 months (95% CI, 14.3 to 25.1). The treatment regimen was well tolerated, with no unexpected adverse events, and no instances of febrile neutropenia or grade 4 adverse events. Conclusion In this preliminary analysis of the ULTIMA trial, Modified FOLFIRINOX demonstrated a promising ORR and PFS in patients with advanced urachal cancer. Completing the full study is essential to confirm the potential role of this regimen in the management of advanced urachal cancer.