Background: Transthyretin amyloidosis, a protein-misfolding disorder characterized by systemic amyloid deposition, can be classified as wild-type transthyretin amyloidosis (ATTRwt) or hereditary transthyretin amyloidosis (ATTRv), depending on the presence of transthyretin (TTR) gene variants. We examined the genetic distribution of TTR variants in Korean patients diagnosed with ATTRv. Methods: We retrospectively reviewed 801 participants who underwent TTR analysis at Samsung Medical Center from 2012 to 2024. The participants were categorized into two groups: in-house probands or relatives, and externally referred probands or relatives. Results: Pathogenic or likely pathogenic TTR variants were detected in 36 of 165 in-house probands (21.8%), among which D38A was the most frequent variant (50.0%; 18/36), followed by M13dup and E89K (8.3% each). Among referred probands, D38A was predominant (54.5%; 12/22), followed by M13dup (22.7%; 5/22). Cardiac amyloid involvement was the most common manifestation, observed in 97.2% (35/36) of in-house probands with ATTRv, followed by peripheral nervous system (PNS; 94.4%) and autonomic nervous system (ANS; 88.9%) involvement. In contrast, ANS involvement was most prevalent among in-house relatives who underwent organ evaluation (61.5%; 24/39), followed by cardiac (52.1%; 25/48) and PNS (48.7%; 19/39) involvement. Five of the eight in-house relatives harboring M13dup (62.5%) showed organ involvement, primarily in the ANS, supporting the pathogenicity of this variant. Conclusions This study provides the largest single-institution dataset of Korean patients with ATTRv, incorporating systematic organ assessments. The predominance of the unique TTR variants D38A and M13dup delineates a distinct genetic landscape that may facilitate accurate and timely diagnosis of ATTRv in the Korean population.

Although venous invasion (VI) is associated with distant metastasis and observed in >50% of pT2–4 colorectal cancers (CRCs), the role of VI in pT1 CRCs is not well-defined. Methods: Thirty-four surgically resected pT1 CRCs were reevaluated for 2-dimensional (2D) VI using hematoxylin and eosin (H&E)–stained slides with additional elastic and desmin immunohistochemical staining (cohort A). Additionally, 27 pT1 CRCs without knowing VI status were selected for 3-dimensional (3D) VI evaluation only (cohort B). All 61 cases (cohorts A and B) were studied in 3D using tissue clearing. Results: VI was detected more commonly in 3D (17/34, 50.0%) than in 2D H&E slide evaluation (9/34, 26.5%, p = .047). When VI was identified in 3D (27/61, 44.3%), the most common phase was that of intraluminal growth (22/27, 81.5%), followed by intravasation (7/27, 25.9%) and extravasation (5/27, 18.5%). E-cadherin expression was characterized in 3D in foci of VI and varied in each phase of invasion. Conclusions: All three phases were observed in VI of pT1 CRCs. The extravasation of neoplastic cells from foci of VI in pT1 CRC suggests that VI could be a route of intratumoral spreading in a subset of pT1 CRCs.

Purpose: Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs. Materials and Methods: This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from nine patients with at least one MSI-high (MSI-H) tumor. Results: Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09%-0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA, in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively. Conclusion Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.

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.

Limited data exist regarding the real-world practices and clinical outcomes in patients with ischemic heart failure with reduced left ventricular ejection fractions (LVEFs).Using nationwide registry data from South Korea, we aimed to investigate long-term outcomes and clinical practices, especially implantable cardioverter defibrillators (ICDs) implantation, in patients with reduced LVEFs at least 40 days after acute myocardial infarction (AMI). Of 13,056 patients with AMI between 2011 and 2015, we analyzed 350 (median age, 66 years [interquartile range, 56-75]) who had LVEFs <40% on follow-up transthoracic echocardiogram 40 days after the index event. The primary outcome was cardiac-cause mortality at 3 years. Secondary outcomes comprised major cardiovascular events as well as outcomes defined by the use of ICDs, cardiac resynchronization therapy defibrillators (CRT-Ds), and electrophysiology studies. Among 350 patients, 39 (11.1%) died from cardiac causes during 3 years of follow-up. Eleven (3.1%) were hospitalized for ventricular tachycardia. The rate of ICD or CRT-D implantation up to 3 years was 5.7% (20/350). Cox time-to-event analysis revealed older age, LVEF <30%, diabetes mellitus, and previous MI or revascularization as positively associated with cardiac death, whereas the use of statins and body weight <67 kg were negatively associated. This nationwide Korean registry demonstrated that only 5.7% of patients who had reduced LVEFs after 40 days of AMI underwent ICD implantations over 3 years. Considering the high mortality, concerted efforts are needed to improve clinical outcomes for patients who may have been candidates for ICD implantation.

OBJECTIVES: Chronic inflammation has been implicated in the development of hypertension in numerous previous studies. However, evidence regarding the association between hematological inflammatory indices derived from complete blood count tests and the long-term risk of hypertension remains limited. Therefore, this study aimed to investigate the association between various hematological inflammatory indices and the risk of incident hypertension in a large cohort study. METHODS: We analyzed data from a large Korean cohort (n=128,241). The incident risk of hypertension was evaluated according to quartiles of the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammatory response index (SIRI) using Cox proportional hazards models. Additional analyses were conducted for high-sensitivity C-reactive protein (hsCRP) levels and stratified by gender. RESULTS: During a median follow-up of 6.8 years, 18,503 participants (14.4%) developed hypertension. Higher quartiles of SII, SIRI, and NLR were significantly associated with an increased risk of incident hypertension in both genders. PLR showed a clearer positive association in women, whereas MLR demonstrated only marginal associations. These patterns were consistent with the associations observed for hsCRP. CONCLUSIONS These findings suggest that elevated hematological inflammatory indices above certain thresholds are associated with an increased risk of hypertension, even among young and generally healthy individuals.

Background: Identifying the risks related to the complications of electrical cardioversion (ECV) can alert the determinaton of rhythm control in patients with atrial fibrillation (AF). Methods: We retrospectively reviewed 1,058 patients who underwent ECV for persistent or long-standing persistent AF/atrial flutter (AFL) from multiple centers. Patients were classified into the no-complication (1,023 patients) and complication (35 patients) groups based on the following major complications: stroke and/or systemic embolism (SSE), myocardial infarction, major bleeding, implantation of cardiac implantable electronic devices, ventricular tachycardia/fibrillation, and death at 1 year follow-up after ECV. Results: Compared with the no-complication group, the complication group exhibited a higher proportion of female patients (37% vs. 22%), as well as a higher proportion of patients with older age (67 ± 11 vs. 61 ± 10 years), diabetes mellitus (DM) (49% vs. 24%), heart failure (HF) (49% vs. 30%), SSE (23% vs. 9%), high CHA 2 DS 2 -VASc (CV) score (3.6 ± 1.8 vs.2.2 ± 1.4), low left ventricular ejection fraction (LVEF) (50 ± 16% vs. 58 ± 21%), and high left atrial volume index (LAVI) (51 ± 26 vs. 40 ± 20 mL/m 2 ). Class I and III antiarrhythmics were less prescribed in the complication group than in the no-complication group (57% vs.76%). Univariate analysis for complications revealed age (≥ 65 years), female sex, DM, HF, SSE, LVEF (< 50%), LAVI (≥ 40 mL/m 2 ), CV score (≥ 3), bradycardia on Holter (< 60/min), and no antiarrhythmics as risk factors. Among these, multivariate analysis revealed clinical significance of female sex and SSE. Conclusion Female sex and a history of SSE were the most important risk factors of complications in patients with persistent or long-standing persistent AF/AFL who underwent ECV.

This study explores the development, roles, and key initiatives of the Regional Environmental Health Centers in Korea, detailing their evolution through four distinct phases and their impact on environmental health policy and local governance. It chronicles the establishment and transformation of these centers from their inception in May 2007, through four developmental stages. Originally named Environmental Disease Research Centers, they were subsequently renamed Environmental Health Centers following legislative changes. The analysis includes the expansion in the number of centers, the transfer of responsibilities to local governments, and the launch of significant projects such as the Korean Children’s Environmental Health Study (Ko-CHENS ). During the initial phase (May 2007–February 2009), the 10 centers concentrated on research-driven activities, shifting from a media-centered to a receptor-centered approach. In the second phase, prompted by the enactment of the Environmental Health Act, six additional centers were established, broadening their scope to address national environmental health issues. The third phase introduced Ko-CHENS, a 20-year national cohort project designed to influence environmental health policy by integrating research findings into policy frameworks. The fourth phase marked a decentralization of authority, empowering local governments and redefining the centers' roles to focus on regional environmental health challenges. The Regional Environmental Health Centers have significantly evolved and now play a crucial role in addressing local environmental health issues and supporting local government policies. Their capacity to adapt and respond to region-specific challenges is essential for the effective implementation of environmental health policies, reflecting geographical, socioeconomic, and demographic differences.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.