Aplastic anemia, mental retardation, and dwarfism (AMeD) syndrome, also known as aldehyde degradation deficiency (ADD) syndrome, is an autosomal recessive disorder caused by mutations in the ALDH2 and ADH5 genes, leading to decreased activity of the aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 5 (ADH5) enzymes, subsequently triggering enhanced cellular levels of formaldehyde and diverse multisystem manifestations. Herein, we present the case of a 7-year-old girl with AMeD syndrome, characterized by pancytopenia, developmental delay, microcephaly, epilepsy, and myelodysplastic syndrome. Whole-exome sequencing revealed compound heterozygous variants (c.832G＞C and c.678delA) in the ADH5 gene and a heterozygous pathogenic variant (c.1510G＞A) in the ALDH2 gene. This case underscores the complexity of AMeD syndrome, emphasizing the importance of genetic testing to ensure diagnosis and aid in the development of potential targeted therapeutic approaches.

Aplastic anemia, mental retardation, and dwarfism (AMeD) syndrome, also known as aldehyde degradation deficiency (ADD) syndrome, is an autosomal recessive disorder caused by mutations in the ALDH2 and ADH5 genes, leading to decreased activity of the aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 5 (ADH5) enzymes, subsequently triggering enhanced cellular levels of formaldehyde and diverse multisystem manifestations. Herein, we present the case of a 7-year-old girl with AMeD syndrome, characterized by pancytopenia, developmental delay, microcephaly, epilepsy, and myelodysplastic syndrome. Whole-exome sequencing revealed compound heterozygous variants (c.832G＞C and c.678delA) in the ADH5 gene and a heterozygous pathogenic variant (c.1510G＞A) in the ALDH2 gene. This case underscores the complexity of AMeD syndrome, emphasizing the importance of genetic testing to ensure diagnosis and aid in the development of potential targeted therapeutic approaches.

Aplastic anemia, mental retardation, and dwarfism (AMeD) syndrome, also known as aldehyde degradation deficiency (ADD) syndrome, is an autosomal recessive disorder caused by mutations in the ALDH2 and ADH5 genes, leading to decreased activity of the aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 5 (ADH5) enzymes, subsequently triggering enhanced cellular levels of formaldehyde and diverse multisystem manifestations. Herein, we present the case of a 7-year-old girl with AMeD syndrome, characterized by pancytopenia, developmental delay, microcephaly, epilepsy, and myelodysplastic syndrome. Whole-exome sequencing revealed compound heterozygous variants (c.832G＞C and c.678delA) in the ADH5 gene and a heterozygous pathogenic variant (c.1510G＞A) in the ALDH2 gene. This case underscores the complexity of AMeD syndrome, emphasizing the importance of genetic testing to ensure diagnosis and aid in the development of potential targeted therapeutic approaches.

Aplastic anemia, mental retardation, and dwarfism (AMeD) syndrome, also known as aldehyde degradation deficiency (ADD) syndrome, is an autosomal recessive disorder caused by mutations in the ALDH2 and ADH5 genes, leading to decreased activity of the aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 5 (ADH5) enzymes, subsequently triggering enhanced cellular levels of formaldehyde and diverse multisystem manifestations. Herein, we present the case of a 7-year-old girl with AMeD syndrome, characterized by pancytopenia, developmental delay, microcephaly, epilepsy, and myelodysplastic syndrome. Whole-exome sequencing revealed compound heterozygous variants (c.832G＞C and c.678delA) in the ADH5 gene and a heterozygous pathogenic variant (c.1510G＞A) in the ALDH2 gene. This case underscores the complexity of AMeD syndrome, emphasizing the importance of genetic testing to ensure diagnosis and aid in the development of potential targeted therapeutic approaches.

Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Background: Brugada syndrome (BrS) and arrhythmogenic cardiomyopathy (ACM) are inherited cardiac diseases that may predispose to ventricular arrhythmia. Although overlapping features between BrS and ACM have been demonstrated previously, it remains to be determined whether genetic testing for ACM-related genes is needed in BrS probands.MethodBased on a single-center, retrospective registry of BrS, we aimed to verify genetic profiles of BrS using a next-generation sequencing panel, and further analyzed genetic testing of ACM-related variants in Brugada phenotypes. Results: Among a total of 119 Brugada phenotypes, 114 patients (95.8%) were male and the mean age of onset was 43.6 years. Genetic variants were identified in 25 of the 42 patients who underwent genetic testing. Fifteen patients had BrS-related genotypes, including SCN5A in 6 patients, and non-SCN5A genes in 9 patients (SCN10A, HCN4, SCN3B, and KCNE3). Nineteen patients underwent additional genetic testing with cardiomyopathy panel, which revealed ACM-related genotypes (2 PKP2, 1 DSG2, 1 TMEM43, 1 JUP, and 1 DSP) present in 6 patients (31.5%). None of the patients had structural or electrocardiographic features that fulfilled the diagnostic criteria for ACM. Conclusions In clinical setting, ACM-related genes were identified in a significant proportion of Brugada phenotypes, supporting the argument that genetic testing of ACM overlapping is needed. Follow-up imaging studies should be considered to monitor if the disease progresses to ACM.

During the coronavirus disease 2019 (COVID-19) pandemic, conclusively evaluating possible associations between COVID-19 vaccines and potential adverse events was of critical importance. The National Academy of Medicine of Korea established the COVID-19 Vaccine Safety Research Center (CoVaSC) with support from the Korea Disease Control and Prevention Agency to investigate the scientific relationship between COVID-19 vaccines and suspected adverse events. Although determining whether the COVID-19 vaccine was responsible for any suspected adverse event necessitated a systematic approach, traditional causal inference theories, such as Hill's criteria, encountered certain limitations and criticisms. To facilitate a systematic and evidence-based evaluation, the United States Institute of Medicine, at the request of the Centers for Disease Control and Prevention, offered a detailed causality assessment framework in 2012, which was updated in the recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) in 2024.This framework, based on a weight-of-evidence approach, allows the independent evaluation of both epidemiological and mechanistic evidence, culminating in a comprehensive conclusion about causality. Epidemiological evidence derived from population studies is categorized into four levels—high, moderate, limited, or insufficient—while mechanistic evidence, primarily from biological and clinical studies in animals and individuals, is classified as strong, intermediate, weak, or lacking. The committee then synthesizes these two types of evidence to draw a conclusion about the causal relationship, which can be described as “convincingly supports” (“evidence established” in the 2024 NASEM report), “favors acceptance,” “favors rejection,” or “inadequate to accept or reject.” The CoVaSC has established an independent committee to conduct causality assessments using the weightof-evidence framework, specifically for evaluating the causality of adverse events associated with COVID-19 vaccines. The aim of this study is to provide an overview of the weight-ofevidence framework and to detail the considerations involved in its practical application in the CoVaSC.

Objective: : The primary treatment goal of current endovascular thrombectomy (EVT) for emergent large-vessel occlusion (ELVO) is complete recanalization after a single maneuver, referred to as the ‘first-pass effect’ (FPE). Hence, we aimed to identify the predictive factors of FPE and assess its effect on clinical outcomes in patients with ELVO of the anterior circulation. Methods: : Among the 129 patients who participated, 110 eligible patients with proximal ELVO (intracranial internal carotid artery and proximal middle cerebral artery) who achieved successful recanalization after EVT were retrospectively reviewed. A comparative analysis between patients who achieved FPE and all others (defined as a non-FPE group) was performed regarding baseline characteristics, clinical variables, and clinical outcomes. Multivariate logistic regression analyses were subsequently conducted for potential predictive factors with p<0.10 in the univariate analysis to determine the independent predictive factors of FPE. Results: : FPE was achieved in 31 of the 110 patients (28.2%). The FPE group had a significantly higher level of functional independence at 90 days than did the non-FPE group (80.6% vs. 50.6%, p=0.002). Pretreatment intravenous thrombolysis (IVT) (odds ratio [OR], 3.179; 95% confidence interval [CI], 1.025–9.861; p=0.045), door-to-puncture (DTP) interval (OR, 0.959; 95% CI, 0.932–0.987; p=0.004), and the use of balloon guiding catheter (BGC) (OR, 3.591; 95% CI, 1.231–10.469; p=0.019) were independent predictive factors of FPE. Conclusion : In conclusion, pretreatment IVT, use of BGC, and a shorter DTP interval were positively associated with FPE, increasing the chance of acquiring better clinical outcomes.

In response to the increase in the prevalence of chronic kidney disease (CKD) in Korea, the growth of patients requiring renal replacement therapy and the subsequent increase in medical costs, the rapid expansion of patients with end-stage kidney disease (ESKD), and the decrease in patients receiving home therapy, including peritoneal dialysis, the Korean Society of Nephrology has proclaimed the new policy, Kidney Health Plan 2033 (KHP 2033). KHP 2033 would serve as a milestone to bridge the current issues to a future solution by directing the prevention and progression of CKD and ESKD, particularly diabetic kidney disease, and increasing the proportion of home therapy, thereby reducing the socioeconomic burden of kidney disease and improving the quality of life. Here, we provide the background for the necessity of KHP 2033, as well as the contents of KHP 2033, and enlighten the Korean Society of Nephrology’s future goals. Together with patients, healthcare providers, academic societies, and national policymakers, we need to move forward with goal-oriented drive and leadership to achieve these goals.

The COVID-19 Vaccine Safety Research Committee (CoVaSC) was established in November 2021 to address the growing need for independent, in-depth scientific evidence on adverse events (AEs) following coronavirus disease 2019 (COVID-19) vaccination. This initiative was requested by the Korea Disease Control and Prevention Agency and led by the National Academy of Medicine of Korea. In September 2022, the COVID-19 Vaccine Safety Research Center was established, strengthening CoVaSC’s initiatives. The center has conducted various studies on the safety of COVID-19 vaccines. During CoVaSC’s second research year, from September 29, 2022 to July 19, 2023, the center was restructured into 4 departments: Epidemiological Research, Clinical Research, Communication & Education, and International Cooperation & Policy Research. Its main activities include (1) managing CoVaSC and the COVID-19 Vaccine Safety Research Center, (2) surveying domestic and international trends in AE causality investigation, (3) assessing AEs following COVID-19 vaccination, (4) fostering international collaboration and policy research, and (5) organizing regular fora and training sessions for the public and clinicians. Causality assessments have been conducted for 27 diseases, and independent research has been conducted after organizing ad hoc committees comprising both epidemiologists and clinical experts on each AE of interest. The research process included protocol development, data analysis, interpretation of results, and causality assessment. These research outcomes have been shared transparently with the public and healthcare experts through various fora. The COVID-19 Vaccine Safety Research Center plans to continue strengthening and expanding its research activities to provide reliable, high-quality safety information to the public.