In mid-2022, as the wave of pediatric coronavirus disease 2019 (COVID-19) cases escalated in South Korea, a public-private partnership was made to establish a Pediatric COVID-19 Module Clinic (PMC). We describe the utilization of the first prototype children’s modular clinic in Korea University Anam Hospital functioning as the COVID-19 PMC. Between August 1 and September 30, 2022, a total of 766 children visited COVID-19 PMC. Daily number of patient visits to the COVID-19 PMC ranged between 10 and 47 in August; and less than 13 patients per day in September 2022. Not only the model provided timely care for the COVID-19 pediatric patients, but it also enabled safe and efficacious care for the non-COVID-19 patients in the main hospital building while minimizing exposure risk to severe acute respiratory syndrome coronavirus 2 transmission. Current description highlights the importance of spatial measures for mitigating in-hospital transmission of COVID-19, in specifically on pediatric care.

Background: While the association of congenital heart disease (CHD) and growth retardation (GR) is known, data remain limited. This study investigated the incidence of GR and its neonatal risk factors in patients with CHD using nationwide population-based claims data.Method: The study population was extracted from Korean National Health Insurance Service claims data from January 2002 to December 2020. We included patients diagnosed with CHD under one year of age. GR was defined as an idiopathic growth hormone deficiency or short stature on the claims data. We investigated the neonatal risk factors for GR. Results: The number of patients diagnosed with CHD within the first year of birth was 133,739. Of these, 2,921 newborns were diagnosed with GR. The cumulative incidence of GR was 4.8% at 19 years of age for individuals diagnosed with CHD at infancy. In the multivariable analysis, the significant risk factors for GR were preterm birth, small for gestational age, low birth weight, respiratory distress, bronchopulmonary dysplasia, bacterial sepsis, necrotizing enterocolitis, feeding problems and cardiac procedure. Conclusion Several neonatal conditions were significant risk factors for GR in CHD patients, and appropriate monitoring and treatment programs are required in CHD neonates with these factors. Considering this study is limited to claims data, further studies are warranted, including genetic and environmental factors affecting GR in CHD patients.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Purpose: Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors. Materials and Methods: We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1–mouse model for in vivo experiments to confirm our findings. Results: In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3β serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion. Conclusion Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken toget

PURPOSE: The soluble programmed death-ligand 1 (sPDL1) has immunosuppressive activity and is a candidate biomarker for immuno-oncology drug development. In this study, we measured sPDL1 at pre- and post-chemotherapy and at disease progression to uncover the dynamics of sPDL1 during treatment in biliary tract cancer (BTC) patients. MATERIALS AND METHODS: From 90 BTC patients (training cohort, 53; validation cohort, 37) who were candidates for palliative first-line chemotherapy, blood was collected at pre- and post-chemotherapy (at the time of best response) and at disease progression. The sPDL1 levels were measured using an enzyme-linked immunosorbent assay. Responses to chemotherapy, overall survival (OS), and other prognostic factors including the neutrophil-lymphocyte ratio (NLR) were analyzed. RESULTS: The OS of all patients was 11.5 months (confidence interval [CI], 9.7 to 16.2). The best response was complete response in seven (7.8%), partial response in 20 (22.2%), stable disease in 52 (57.8%), and disease progression (PD) in 11 patients (12.2%). Patients with high pre-chemotherapy sPDL1 (≥ 1.30 ng/mL) showed worse OS than patients with low prechemotherapy sPDL1 (9.1 months vs. 12.5 months, p=0.003). In multivariate analyses, high pre-chemotherapy sPDL1 (hazard ratio [HR], 1.96; 95% CI, 1.2 to 3.9; p=0.011) and high pre-chemotherapy NLR (HR, 1.82; 95% CI, 1.1 to 3.0; p=0.020) were independent poor prognostic factors for OS. At the time of PD, sPDL1 was increased significantly compared with pre-chemotherapy sPDL1 (1.59 ng/mL vs. 0.72 ng/mL, p=0.003). CONCLUSION: The sPDL1 at pre-chemotherapy confers the prognostic value for OS in BTC patients under palliative chemotherapy. The dynamics of sPDL1 during chemotherapy correlate with disease burden and have prognostic value.
Biliary Tract Neoplasms ; Biomarkers ; Cohort Studies ; Disease Progression ; Drug Therapy ; Enzyme-Linked Immunosorbent Assay ; Humans ; Multivariate Analysis ; Prognosis

PURPOSE: The DNA damage response (DDR) is a multi-complex network of signaling pathways involved in DNA damage repair, cell cycle checkpoints, and apoptosis. In the case of biliary tract cancer (BTC), the strategy of DDR targeting has not been evaluated, even though many patients have DNA repair pathway alterations. The purpose of this study was to test the DDR-targeting strategy in BTC using an ataxia-telangiectasia and Rad3-related (ATR) inhibitor. MATERIALS AND METHODS: A total of nine human BTC cell lines were used for evaluating anti-tumor effect of AZD6738 (ATR inhibitor) alone or combination with cytotoxic chemotherapeutic agents through MTT assay, colony-forming assays, cell cycle analyses, and comet assays. We established SNU478-mouse model for in vivo experiments to confirm our findings. RESULTS: Among nine human BTC cell lines, SNU478 and SNU869 were the most sensitive to AZD6738, and showed low expression of both ataxia-telangiectasia mutated (ATM) and p53. AZD6738 blocked p-Chk1 and p-glycoprotein and increased γH2AX, a marker of DNA damage, in sensitive cells. AZD6738 significantly increased apoptosis, G2/M arrest and p21, and decreased CDC2. Combinations of AZD6738 and cytotoxic chemotherapeutic agents exerted synergistic effects in colony-forming assays, cell cycle analyses, and comet assays. In our mouse models, AZD6738 monotherapy decreased tumor growth and the combination with cisplatin showed more potent effects on growth inhibition, decreased Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling than monotherapy with each drug. CONCLUSION: In BTC, DDR targeting strategy using ATR inhibitor demonstrated promising antitumor activity alone or in combination with cytotoxic chemotherapeutic agents. This supports further clinical development of DDR targeting strategy in BTC.
Animals ; Apoptosis ; Ataxia Telangiectasia ; Biliary Tract Neoplasms ; Biliary Tract ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line ; Cisplatin ; Comet Assay ; DNA Damage ; DNA Repair ; DNA ; Humans ; Mice ; P-Glycoprotein

PURPOSE: Jab1 is a coactivator of c-Jun that enhances the transcriptional function of c-Jun. Jab1 is frequently overexpressed in various cancers and is associatedwith poor prognosis of cancer patients. Thus, Jab1 could be a potential therapeutic target in cancer. However, the role of Jab1 in biliary tract cancer (BTC) has not been studied. MATERIALS AND METHODS: We performed in vitro and in vivo experiments to evaluate the therapeutic potential ofJab1 inhibition in BTC. RESULTS: Among 8 BTC cell lines, many showed higher Jab1 expression levels. In addition, Jab1 silencing by siRNA increased p27 expression levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti-proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti-proliferative and anti-migratory effects of cisplatin by increasing DNA damage. Interestingly,Jab1 knockdown increased PTEN protein half-life, resulting in increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and p27 expression. CONCLUSION: Jab1 knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest. In addition, Jab1 silencing potentiated the anti-proliferative effects of cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in BTC that is worthy of further investigations.
Animals ; Biliary Tract Neoplasms ; Biliary Tract ; Cell Line ; Cisplatin ; DNA Damage ; G1 Phase Cell Cycle Checkpoints ; Half-Life ; Heterografts ; Humans ; In Vitro Techniques ; Mice ; Phosphorylation ; Prognosis ; PTEN Phosphohydrolase ; RNA, Small Interfering ; Transfection

PURPOSE: KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo. MATERIALS AND METHODS: The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects. RESULTS: KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho-Src and proliferative-signaling molecules were down-regulated in KX-01-sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01-induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01-sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model. CONCLUSION: KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.
Aneuploidy ; Animals ; Breast Neoplasms ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line ; Fluorescent Antibody Technique ; Heterografts ; In Vitro Techniques ; Mice ; Microtubules ; Mitosis* ; src-Family Kinases* ; Triple Negative Breast Neoplasms ; Tubulin ; Wound Healing

Ethnically specific data on genetic variation are crucial for understanding human biology and for clinical interpretation of variant pathogenicity. We analyzed data obtained by deep sequencing 1303 Korean whole exomes; the data were generated by three independent whole exome sequencing projects (named the KOEX study). The primary focus of this study was to comprehensively analyze the variant statistics, investigate secondary findings that may have clinical actionability, and identify loci that should be cautiously interpreted for pathogenicity. A total of 495 729 unique variants were identified at exonic regions, including 169 380 nonsynonymous variants and 4356 frameshift insertion/deletions. Among these, 76 607 were novel coding variants. On average, each individual had 7136 nonsynonymous single-nucleotide variants and 74 frameshift insertion/deletions. We classified 13 pathogenic and 13 likely pathogenic variants in 56 genes that may have clinical actionability according to the guidelines of the American College of Medical Genetics and Genomics, and the Association for Molecular Pathology. The carrier frequency of these 26 variants was 2.46% (95% confidence interval 1.73–3.46). To identify loci that require cautious interpretation in clinical sequencing, we identified 18 genes that are prone to sequencing errors, and 671 genes that are highly polymorphic and carry excess nonsynonymous variants. The catalog of identified variants, its annotation and frequency information are publicly available (https://koex.snu.ac.kr). These findings should be useful resources for investigating ethnically specific characteristics in human health and disease.
Biology ; Clinical Coding ; Exome ; Exons ; Genetic Variation ; Genetics, Medical ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Pathology, Molecular ; Virulence