Purpose: The chromodomain helicase DNA-binding (CHD) protein family comprises adenosine triphosphate-dependent chromatin remodelers that regulate chromatin structure and gene expression. Pathogenic CHD2 variants are associated with neurodevelopmental phenotypes, but these genotype–phenotype correlations remain unclear. This study aimed to delineate the clinical and genetic features of patients with CHD2-related disorders and to explore the associated genotype–phenotype relationships. Methods: Among 22 patients with pathogenic or likely pathogenic CHD2 variants identified using a customized 172-gene neurodevelopmental and epilepsy panel, 19 with sufficient clinical data were included. Demographic, clinical, neuroimaging, electroencephalographic, and genetic data were retrospectively reviewed. Results: Eighteen pathogenic or likely pathogenic variants were identified, including eight novel variants: nine nonsense (50.0%), five splice-site (27.8%), two missense (11.1%), and two exon deletions (11.1%). All patients had epilepsy, with a median age of seizure onset of 2.33 years. Comorbidities included global developmental delay (89.5%), intellectual disability (82.0%), and neuropsychiatric symptoms (47.4%). Seizure types were heterogeneous, with a predominance of generalized-onset seizures, and 13 patients (68.4%) achieved seizure freedom. Marked phenotypic variability was observed: two unrelated patients with the same truncating variant had different developmental and seizure-related profiles, a symptomatic child with an inherited exon 5 deletion contrasted with her asymptomatic father, and a patient with an exon 17–29 deletion exhibited relatively mild features. Conclusion Epilepsy was a consistent manifestation in this study and was accompanied by diverse developmental and neurobehavioral features, with substantial genotype–phenotype discordance. Further research on genotype–phenotype correlation is warranted.

Objective: This study aims to compare the incidence of active tuberculosis (TB) among Korean patients with rheumatoid arthritis (RA) initiating treatment with tumor necrosis factor inhibitors (TNFi) or tofacitinib. Methods: Using the Korean National Health Insurance database, we conducted a nationwide, retrospective cohort study of RA patients who started TNFi or tofacitinib therapy between 2015 and 2018. We calculated the incidence rates of active TB based on the treatment type and results from latent tuberculosis infection (LTBI) screening tests. A multivariable Cox proportional hazards model was employed to evaluate the risk of active TB in RA patients beginning TNFi or tofacitinib treatment. Results: Among 3,382 RA patients (596 on tofacitinib and 2,786 on TNFi), LTBI screening was predominantly conducted using the IGRA (interferon-gamma release assays) test. Of these patients, 624 (18.5%) with a positive LTBI test received prophylactic treatment. No cases of active TB occurred in tofacitinib users, while 32 cases were observed in TNFi users. The adjusted hazard ratio for active TB in LTBI-positive patients was 5.47 (95% confidence interval 2.74 to 10.92) compared to LTBI-negative patients.In subgroup analyses, TB incidence was significantly higher among individuals aged over 65 years. Conclusion Despite LTBI treatment, active TB remains prevalent among RA patients on TNFi therapy and in those with positive LTBI tests.

Atopic dermatitis is the most common chronic inflammatory skin disease in children and adolescents. The Korean Academy of Pediatric Allergy and Respiratory Disease published the Atopic Dermatitis Treatment Guideline in 2008, which has been helpful in atopic dermatitis treatment until now. Various reports on the development and effectiveness of new drugs have suggested that there is a need to develop and revise old treatment guidelines. Part 1 aimed to provide evidence-based recommendations for skin care management and topical treatment for atopic dermatitis. Part 2 focuses on systemic treatment, novel therapeutics, and adjuvant therapy. The goal of this guideline is intended to assist front-line doctors treating pediatric and adolescent atopic dermatitis patients make safer, more effective, and more rational decisions regarding systemic treatment, novel therapeutics, and adjuvant therapy by providing evidence-based recommendations with a clear level of evidence and benefit regarding treatment.

Atopic dermatitis is the most common chronic inflammatory skin disease in children and adolescents. The Korean Academy of Pediatric Allergy and Respiratory Disease published the Atopic Dermatitis Treatment Guideline in 2008, which has been helpful in atopic dermatitis treatment until now. Various reports on the development and effectiveness of new drugs have suggested that there is a need to develop and revise old treatment guidelines. Part 1 aimed to provide evidence-based recommendations for skin care management and topical treatment for atopic dermatitis. Part 2 focuses on systemic treatment, novel therapeutics, and adjuvant therapy. The goal of this guideline is intended to assist front-line doctors treating pediatric and adolescent atopic dermatitis patients make safer, more effective, and more rational decisions regarding systemic treatment, novel therapeutics, and adjuvant therapy by providing evidence-based recommendations with a clear level of evidence and benefit regarding treatment.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Background/Aims: This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV). Methods: Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified. Results: Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (p<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (p<0.05). Conclusions This study elucidated the optimal tacrolimus trough level and highlighted the impact of IPV on the CKD and ESRD development post-LT.

The applicability of the Phoenix criteria and Phoenix Sepsis Score in higher-resource pediatric intensive care units (PICUs) outside the United States requires further validation. A retrospective cohort study analyzed electronic health records of 1,304 PICU admissions under 18 years old with suspected infection between February 2017 and December 2023. The score was calculated using two methods: 24-hour assessment, based on worst sub-scores within 24 hours of admission, and prompt assessment, using values closest to admission within 6 hours before or after. Based on the 24-hour assessment, in-hospital mortality was 8.3% for sepsis and 10.3% for septic shock. The score demonstrated an area under the precision-recall curve of 0.42 (95% confidence interval, 0.31–0.55) for in-hospital mortality. Results were consistent across both assessment methods. The Phoenix criteria and the Phoenix Sepsis Score are reliable predictors of mortality outcomes. Further investigation in diverse clinical settings is warranted.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.