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.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

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.

Abrupt vessel closure (AVC) is a complication of percutaneous coronary intervention (PCI) and is defined as the sudden cessation of forward coronary blood flow due to a variety of mechanisms. The incidence of AVC has markedly decreased from approximately 3.0% in the early era to about 0.3% today. Nevertheless, cardiovascular interventionists must remain prepared to manage AVC effectively, given its significant impact on clinical outcomes.AVC can arise from several mechanisms, including dissection, intramural hematoma, intracoronary thrombosis, air embolism, vasospasm, and no-reflow. The clinical impact of AVC varies depending on the extent of myocardium affected, ranging from asymptomatic events or transient ischemic chest pain to cardiogenic shock or cardiac arrest. Both a general approach for stabilizing hemodynamic consequences and an etiology-specific management strategy are essential. Hasty decision-making may worsen the situation, whereas a structured approach—focused on hemodynamic stabilization, logical diagnostic processes, and targeted interventions—can improve outcomes. In this narrative review, we describe the mechanisms underlying each etiology, outline mechanism-specific management strategies, and discuss general approaches to managing patients with AVC through logical diagnostic and treatment processes. We hope this review offers valuable insights into this uncommon but significant complication and enhances readers’ skills in managing AVC more effectively during PCI.

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 and Objectives: Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min). Methods: XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints. Results: XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year. Conclusions XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.