Purpose: This study aimed to evaluate the role of hepatic resection in patients with objective responses after combined transarterial chemoembolization (TACE) and radiotherapy (RT) for hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI). Materials and Methods: We retrospectively reviewed the patients treated with combined TACE and RT for HCC with MVI between 2010 and 2015. Some of the patients with objective responses underwent hepatic resection or liver transplantation; to investigate the impact of surgery, patients with objective responses who did not undergo surgery were selected as the control group. Survival outcomes were compared using a propensity score–based stabilized inverse probability of treatment weighting method. Results: Out of the 170 patients with objective responses after combined TACE and RT, 41 patients underwent surgery, including eight liver transplantations. The unweighted surgery group was younger and had a higher proportion of solitary tumors and unilateral vascular involvement. After adjustment, the 3-year overall survival (OS) rates were 61.0% and 28.6% in the surgery and non-surgery groups, respectively. The most important prognostic factor for OS was surgery (adjusted Cox hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.17 to 0.46; p < 0.001). Complete response after TACE and RT (vs. partial response) was also a significant prognostic factor for OS (adjusted HR, 0.41; 95% CI, 0.27 to 0.61; p < 0.001). There was no surgical mortality. Four patients (9.8%) required additional surgery due to bleeding or graft failure. Conclusion Hepatic resection was significantly associated with improved OS in patients who showed objective responses after receiving combined TACE and RT for HCC with MVI.

Background/Aims: Cardiovascular disease remains a major cause of mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study evaluated the association between subclinical carotid atherosclerosis (SCA) and MASLD or MASLD and increased alcohol intake (MetALD) in asymptomatic individuals. Methods: This cross-sectional study included 56,889 adults undergoing health check-ups in South Korea. Hepatic steatosis was diagnosed by ultrasound, and SCA was defined by carotid plaques or increased intima-media thickness. Liver fibrosis was evaluated using the fibrosis-4 index and elastography. Results: SCA was identified in 13.5%. MASLD and MetALD were significantly associated with SCA in models adjusted for demographic and lifestyle factors (adjusted odds ratio [aOR], 1.26;95% confidence interval [CI], 1.19 to 1.33; aOR, 1.43; 95% CI, 1.30 to 1.58; respectively, p<0.001for both). However, these associations attenuated and lost statistical significance when metabolic risk factors were further adjusted. The risk of SCA increased with greater hepatic steatosis and liver fibrosis severity. In patients with MASLD, aORs were 1.70 (hepatic steatosis index >36),1.23 (fibrosis-4 index ≥1.3), and 1.78 (liver stiffness measurement ≥5.6 kPa), compared to indi-viduals without MASLD. Similar trends were observed in the MetALD group. Additionally, hyper-tension and clustering of ≥3 cardiometabolic risk factors were significantly associated with SCA inthe MASLD group, supporting the role of metabolic burden in SCA development. Conclusions MASLD and MetALD were associated with increased SCA risk, particularly in individuals with hepatic steatosis and fibrosis. These findings suggest that metabolic burden and liver disease severity jointly contribute to subclinical atherosclerosis risk.

Background/Aims: Although metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) represent the updated nomenclature and diagnostic criteria for nonalcoholic fatty liver disease, studies comparing the prognostic implications of these conditions remain limited. This meta-analysis aimed to quantify the associations among MAFLD, MASLD, and long-term clinical outcomes. Methods: A comprehensive literature search was performed to identify cohort studies that assessed the association of MASLD and MAFLD with all-cause mortality, cause-specific (cardiovascular and cancer-related) mortality, and the incidence of cardiovascular disease in the PubMed, Embase, Web of Science, CINAHL, and CENTRAL databases from inception through October 31, 2024. Pooled hazard ratios (HRs) were calculated for relevant outcomes. Results: We identified 18 cohort studies, comprising 10,653,666 patients with MAFLD from 13 studies and 3,202,447 patients with MASLD from nine studies. MAFLD was significantly associated with an increased risk of overall mortality (pooled HR [95% confidence interval], 1.30 [1.16 to 1.47]) and cardiovascular mortality (1.31 [1.08 to 1.60]; both p<0.01), but not with cancer-related mortality (1.10 [0.97 to 1.24]; p=0.130). Conversely, MASLD was associated with a higher risk for all mortality outcomes: overall mortality (1.34 [1.12 to 1.61]), cardiovascular mortality (1.17 [1.07 to 1.27]), and cancer-related mortality (1.24 [1.19 to 1.29]; all p<0.01). The risk of cardiovascular disease was increased in patients with both MAFLD (1.48 [1.31 to 1.66]) and MASLD (1.33 [1.21 to 1.46]; both p<0.001). Conclusions MAFLD and MASLD were both associated with increased risks of mortality and cardiovascular outcomes. Notably, a significant association with cancer-related mortality was observed for MASLD, but not for MAFLD.

Background/Aims: Various expanded criteria (EC) for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) have been proposed to avoid the narrow nature of the Milan criteria (MC). To investigate which EC predicts more favorable outcomes in terms of overall survival (OS) and recurrence-free survival (RFS), we conducted a network meta-analysis (NMA). Methods: A database search was conducted on PubMed, Embase, and the Cochrane Library, to identify studies comparing OS and RFS between patients within the MC and those exceeding the MC but within the EC. Hazard ratios (HRs) were pooled using a random-effects NMA and validated in an in-house cohort of 1,008 LT recipients. Results: Among 22,466 articles identified, 35 studies with 45 pairwise comparisons were included in the NMA along with 8 different EC. The University of California San Francisco (HR, 1.43; 95% CI, 1.19–1.71), Up-to-Seven (HR, 1.50; 95% CI, 1.15–1.97), and Hangzhou criteria (HR, 1.69; 95% CI, 1.11–2.57) showed inferior OS to the MC. The MC ranked highest for both OS and RFS, followed by Metroticket 2.0 for OS and the Asan criteria for RFS. In the validation cohort, both Metroticket 2.0 and AFP model yielded more favorable HCC-specific mortality than other EC. Conclusions Several EC, of which those of Metroticket 2.0 were the best, yielded comparable outcomes to the MC. AFP-based EC such as Metroticket 2.0 and AFP model appeared to be useful in both the NMA and the validation cohort, suggesting a potential role in identifying selected low-risk patients beyond the MC.

Heart failure (HF) is a major cause of mortality and morbidity in South Korea, imposing substantial physical, emotional, and financial burdens on patients and society. Despite the high burden of symptom and complex care needs of HF patients, palliative care and hospice services remain underutilized in South Korea due to cultural, institutional, and knowledge-related barriers. This position statement from the Korean Society of Heart Failure emphasizes the need for integrating palliative and hospice care into HF management to improve quality of life and support holistic care for patients and their families. By clarifying the role of palliative care in HF and proposing practical referral criteria, this position statement aims to bridge the gap between HF and palliative care services in South Korea, ultimately improving patient-centered outcomes and aligning treatment with the goals and values of HF patients.

Purpose: Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). Materials and Methods: In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Results: Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Conclusion Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

Background/Aims: Tenofovir disoproxil fumarate (TDF) is known to have a lipid-lowering effect. This is in contrast to tenofovir alafenamide (TAF), which has a lipid-neutral effect. Therefore, concerns have been raised as to whether these differences affect long-term cardiovascular risk. Here, we aimed to evaluate the long-term risk of cardiovascular events in chronic hepatitis B (CHB) patients treated with TAF or TDF. Methods: We retrospectively analyzed 4,124 treatment-naïve CHB patients treated with TDF (n=3,186) or TAF (n=938) between 2012 and 2022. The primary outcome was a composite endpoint of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, and hospitalization for unstable angina or heart failure. Serial changes in lipid profiles between two treatments were also explored. Results: The median age of the patients was 50.6 years, and 60.6% of the patients were male. At baseline, 486 (11.8%) and 637 (15.4%) of the patients had dyslipidemia and fatty liver, respectively. A total of 42 MACE occurred, with an annual incidence of 0.2%/100 person-years (PYs). At 1, 3, and 5 years, the cumulative risk of MACE was 0.4%, 0.8%, and 1.2% in patients treated with TDF, and 0.2%, 0.7%, and 0.7% in patients treated with TAF, respectively (p=0.538). No significant differences in the risk of MACE were observed between TDF and TAF. A multivariable analysis found that current smoker and a history of cardiovascular events were risk factors associated with an increased risk of MACE. Conclusions Patients treated with TAF had comparable risks of cardiovascular outcomes, defined as MACE, as patients treated with TDF.

Background: The mechanism and medical treatment target for degenerative aortic valve disease, including aortic stenosis, is not well studied. In this study, we investigated the effect of clonal hematopoiesis of indeterminate potential (CHIP) on the development of aortic valve sclerosis (AVS), a calcified aortic valve without significant stenosis. Methods: Participants with AVS (valves ≥ 2 mm thick, high echogenicity, and a peak trans-aortic velocity of < 2.5 m/sec) and an age- and sex-matched control group were enrolled.Twenty-four CHIP genes with common variants in cardiovascular disease were used to generate a next-generation sequencing panel. The primary endpoint was the CHIP detection rate between the AVS and control groups. Inverse-probability treatment weighting (IPTW) analysis was performed to adjust for differences in baseline characteristics. Results: From April 2020 to April 2022, 187 participants (125 with AVS and 62 controls) were enrolled; the mean age was 72.6 ± 8.5 yrs, and 54.5% were male. An average of 1.3CHIP variants was observed. CHIP detection, defined by a variant allele frequency (VAF) of≥ 0.5%, was similar between the groups. However, the AVS group had larger CHIP clones:49 (39.2%) participants had a VAF of ≥ 1% (vs. 13 [21.0%] in the control group; P = 0.020), and 25 (20.0%) had a VAF of ≥ 2% (vs. 4 [6.5%]; P = 0.028). AVS is independently associated with a VAF of ≥ 1% (adjusted odds ratio: 2.44, 95% confidence interval: 1.11–5.36; P = 0.027). This trend was concordant and clearer in the IPTW cohort. Conclusions Participants with AVS more commonly had larger CHIP clones than age- and sex-matched controls. Further studies are warranted to identify causality between AVS and CHIP.

Background/Aims: The programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway has not been fully evaluated in inflammatory bowel disease. We evaluated PD-1/PD-L1 levels in patients with ulcerative colitis (UC) and their significance in tonsil-derived mesenchymal stem cells (TMSCs) treatment. Methods: Using acute and chronic murine colitis model, we measured the PD-1 and PD-L1 levels in inflamed colonic tissues pre- and post-treatment with TMSCs. We also measured PD-1 and PD-L1 levels in colonic tissues from UC patients, compared to normal controls. Results: In the analysis using human colonic tissues, a significant increase in the levels of PD-1 and PD-L1 was observed in the colonic mucosa of patients with UC compared with normal controls (p < 0.001 and p = 0.005, respectively). When comparing the maximal disease extent, PD-L1 levels were highest in patients with proctitis (38.5 ± 46.7), followed by left-side colitis (17.5 ± 23.1) and extensive colitis (5.2 ± 8.2) (p < 0.001). In the chronic colitis model, the level of PD-L1 was decreased (p = 0.040) and the level of PD-1 increased more than in normal controls (p = 0.047). After treatment with TMSC, significant improvements were observed in body weight, disease activity index, and colon length recovery. Additionally, the levels of PD-1 and PD-L1 were recovered; PD-L1 significantly increased (p = 0.031), while the level of PD-1 decreased (p = 0.310). Conclusions The altered expression of PD-1 and PD-L1 in colonic mucosa may be a possible mechanism of UC, and T-MSC-derived PD-L1 could help suppress colitis.

Purpose: Robotic single-site plus one-port myomectomy (RSOM) was designed to reduce the number of incision sites for greater cosmetic satisfaction of patients while retaining the benefits of conventional robotic multi-site myomectomy (CRM). Robotic single-site plus two-port myomectomy (RSTM) eliminated one port relative to conventional CRM, and RSOM achieved the same advantage with respect to RSTM. This study aimed to compare RSOM with RSTM in terms of their respective methodologies and surgical outcomes. Materials and Methods: The medical records of 230 patients who had undergone RSOM and 146 patients who had undergone RSTM were reviewed. The groups’ surgical outcomes were compared using propensity score matching (PSM) analysis. Results: In the total data, RSOM had a shorter operative time (135.1±57.4 min vs. 149.9±46.2 min, p=0.009) and a shorter hospital stay (5.2±0.5 days vs. 5.4±0.7 days, p=0.033) relative to RSTM. The PSM analysis showed that there were no statistically significant intergroup differences in the patients’ baseline characteristics. Regarding the surgical outcomes, the RSOM group showed shorter operative time (129.2±49.3 min vs. 148.7±46.3 min, p=0.001) compared to the RSTM group. Conclusion Compared with RSTM, RSOM was associated with shorter operative time. Additionally, more detailed comparative and prospective studies are needed to evaluate RSOM relative to RSTM.