Background: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is among the most important multidrug-resistant pathogens causing bloodstream infections (BSIs).Cefotaximase (CTX-M) enzymes are the most common and highly diverse ESBL family in E.coli. CTX-M-15 in group CTX-M-1 and CTX-M-14 in group CTX-M-9 are the most extensively disseminated enzymes. Multidrug-resistant E. coli strains complicate empirical therapy and increase healthcare burden globally and in Korea. We investigated the molecular epidemiology, sequence types (STs), and ESBL genotypes of E. coli bloodstream isolates in Korea and identified clinical risk factors for cefotaxime resistance. Methods: We collected all non-duplicated isolates of E. coli and related clinical information from patients with BSIs at eight sentinel hospitals in the Korean Global Antimicrobial Resistance Surveillance System (Kor-GLASS) collection network during 2017–2021. Duplicate isolates were removed to ensure representativeness of the data. Antimicrobial susceptibility was tested using disk diffusion tests, and multilocus sequence typing and betalactamase genotyping were performed. Results: Among 9,232 E. coli blood isolates, resistance rates to cefotaxime and ceftazidime were 36.4% and 11.4%, respectively. Among the clinical factors, age > 65 yrs (adjusted odds ratio [aOR], 1.36), hospital-origin infection (aOR, 2.55), and admission type (intensive care unit [ICU] vs. general ward; aOR, 1.34) were significant cefotaxime resistance risk factors. ST131 was the most prevalent among cefotaxime-resistant E. coli (64.8%, 2,180/3,363), followed by ST1193 (5.3%, N = 177), and ST69 (5.1%, N = 170).ST131, ST648, ST405, and ST410 cefotaxime-resistant E. coli isolates frequently harbored blaCTX-M-15, whereas ST1193 and ST68 showed a high proportion of blaCTX-M-27 carriers, and most ST457 and ST5150 isolates carried blaCTX-M-55. Conclusions Continuous monitoring of ESBL-producing E. coli is required to prevent further dissemination, guide empirical therapy, inform infection control policies, and ensure early detection of multidrug-resistant clones with the potential for widespread transmission.

Myopia, particularly high myopia, is a significant risk factor for several ocular pathologies including cataract, glaucoma, and retinal detachment. Excessive axial elongation associated with high myopia can induce biomechanical stretching, increasing the risk of serious complications like posterior staphyloma and myopic maculopathy. Global meta-analyses estimate that approximately 10 million people were visually impaired due to myopic maculopathy in 2015, with 3 million being blind. Recent nationwide surveys in South Korea revealed a prevalence of 65.4% for myopia and 6.9% for high myopia in children and adolescents, highlighting the urgent need for effective management. Delaying the onset and slowing the progression of myopia during childhood and adolescence is crucial for reducing the potential lifetime risk of these complications. This consensus statement, prepared by the Korean Myopia Society for the Korean Association for Pediatric Ophthalmology and Strabismus (KAPOS), reviews the current evidence for myopia control interventions and provides management strategies applicable to the South Korean clinical setting. Key interventions covered include lifestyle modifications (outdoor time, near work adjustment), optical methods (myopia-control spectacle lenses, dual-focus soft contact lenses, orthokeratology), and pharmacologic treatment (low-concentration atropine), as well as combination therapies. The statement also addresses patient selection, treatment outcome evaluation using spherical equivalent and axial length changes, and the crucial aspects related to treatment cessation and the rebound effect.

Background and Objectives: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. Methods: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. Results: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). Conclusions There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

Background: Unlike conventional T cells, innate and virtual-memory CD8 T cells in naïve mice acquire their memory phenotypes and functions in the absence of antigenic encounters in a cytokine-dependent manner. The relevant cytokines include interleukin-4 (IL-4), type I interferon, and interleukin-15 (IL-15). Moreover, exogenous IL-4 can also induce de novo generation and/or expansion of the virtual-memory CD8 T cell population. In this study, we investigated whether exogenous IL-4 could enhance the immune response to a viral infection. Results: In vivo administration of IL-4 and an anti-IL-4 antibody complex (IL-4C) increased CXCR3 expression in both memory and naïve phenotype CD8 T cells in the absence of antigenic stimulation, and protected mice from lethal influenza infection. Flow cytometric analysis of lung-infiltrating immune cells on day 5 after virus infection revealed higher numbers of antigen-specific and bystander CD8 T cells in IL-4C-treated mice than in control mice. In particular, the bystander CD8 T cells were a naïve or evident memory phenotypes. Crucially, an anti-CXCR3 blocking antibody abrogated this IL-4C effect, reflecting that the increased accumulation of CD8 T cells in the lungs after IL-4C treatment is dependent on CXCR3. Conclusions These data demonstrate that exogenous IL-4C plays a protective role by enhancing CXCR3-dependent migration of CD8 T cells into influenza-infected lungs.

Background: Influenza A viruses (IAVs) have long posed a threat to humans, occasionally causing significant morbidity and mortality. The initial immune response is triggered by infected epithelial cells, alveolar macrophages and dendritic cells. However, an exaggerated innate immune response can result in severe lung injury and even host mortality. One notable pathology observed in hosts succumbing to severe influenza is the excessive influx of neutrophils and monocytes into the lung. In this study, we investigated a strategy for controlling lung immunopathology following severe influenza infection. Results: To evaluate the impact of innate immunity on influenza-associated lung injury, we employed CB17.SCID and NOD.SCID mice. NOD.SCID mice exhibited slower weight loss and longer survival than CB17.SCID mice following influenza infection. Lung inflammation was reduced in NOD.SCID mice compared to CB17.SCID mice. Bulk RNA sequencing analysis of lung tissue showed significant downregulation of 827 genes, and differentially expressed gene analysis indicated that the cytokine-cytokine receptor interaction pathway was predominantly downregulated in NOD.SCID mice. Interestingly, the expression of the Cxcl14 gene was higher in the lungs of influenza-infected NOD.SCID mice than in CB17.SCID mice. Therefore, we induced overexpression of the Cxcl14 gene in the lung using the adeno-associated virus 9 (AAV9)-vector system for target gene delivery. However, when we administered the AAV9 vector carrying the Cxcl14 gene or a control AAV9 vector to BALB/c mice from both groups, the morbidity and mortality rates remained similar. Both groups exhibited lower morbidity and mortality than the naive group that did not receive the AAV9 vector prior to IAV infection, suggesting that the pre-administration of the AAV9 vector conferred protection against lethal influenza infection, irrespective of Cxcl14 overexpression. Furthermore, we found that pre-inoculation of BALB/c mice with AAV9 attenuated the infiltration of trans-macrophages, neutrophils and monocytes in the lungs following IAV infection. Although there was no difference in lung viral titers between the naive group and the AAV9 pre-inoculated group, pre-inoculation with AAV9 conferred lung injury protection against lethal influenza infection in mice. Conclusions Our study demonstrated that pre-inoculation with AAV9 prior to IAV infection protected mouse lungs from immunopathology by reducing the recruitment of inflammatory cells.

Purpose: We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea. Materials and Methods: We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients). Results: Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance. Conclusion The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

Purpose: Phosphorylated AKT1 (p-AKT1) at Ser473 is a functional isoform of AKT and a key component of the PI3K/mTOR/AKT pathway. This study aimed to evaluate the prognostic significance of p-AKT1 (Ser473) based on the molecular subtypes of breast cancer. Methods: To investigate the prognostic value of p-AKT1 (Ser473), we performed a retrospective chart review of patients with breast cancer. Data on p-AKT1 (Ser473) positivity, hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) expression status, and other clinicopathological factors were obtained. Furthermore, the therapeutic effect of blocking p-AKT1 (Ser473) in breast cancer cells was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis assay, apoptosis protein array, and western blot analysis. Results: A total of 3,044 patients were evaluated, and the median follow-up time was 43 (range: 0–125) months. In patients with HR-positive and HER2-positive disease, the p-AKT1 (Ser473)-positive group had worse disease-free survival (DFS) than the p-AKT1 (Ser473)-negative group (hazard ratio, 1.9; 95% confidence interval, 1.1–3.5; p = 0.024). In the multivariate analysis, p-AKT1 (Ser473) remained a significantly worse prognostic factor in patients with HR-positive/HER2-positive breast cancer (p = 0.03). There was no difference in DFS according to p-AKT1 (Ser473) status among patients with other breast cancer subgroups.In vitro analysis showed that blocking p-AKT1 (Ser473) levels enhanced trastuzumab-induced cell death in HR-positive/HER2-positive and p-AKT1 (Ser473)-positive breast cancer cells. Conclusion p-AKT1 (Ser473) is a prognostic marker for poor outcomes in patients with HRpositive/HER2-positive breast cancer and may have a potential value as a therapeutic target.

Background/Aims: We examined temporal trends in the rate of gout and seropositive rheumatoid arthritis (RA) hospital visits and healthcare costs in Korea. Methods: We conducted a serial cross-sectional analysis of Korean national healthcare claims. We calculated the annual increase in hospital visits (emergency department [ED] visits, outpatient visits, and hospitalizations) and total healthcare costs per visit. Results: From 2010 to 2017, the annual rates of ED visits, outpatient visits, and hospitalizations for gout increased from 6.28 to 21, from 638.38 to 1059.55, and from 12.37 to 15.6 per 100,000 persons, respectively. Before 2013, ED visits for gout were most common in patients over 70 years old, but they were most common in those aged between 30 and 49 years after 2013. The number of patients with ED visits, outpatient visits, and hospitalizations for RA from 2010 to 2017 increased from 1.25 to 1.87, from 219.04 to 307.49 and from 8.44 to 12.32 per 100,000 persons, respectively. However, there was no increase in the prevalence of ED visits for RA in any age group except for those older than 70 years. The cost per ED visit for gout significantly decreased from 496.3 to 273.6 US dollar during the study period. There was no significant change in the cost per ED visit for RA between 2010 and 2017. Conclusions There was a large increase in ED visits for gout during the study period. Further studies are needed to analyze the reason behind increased ED visits for gout and suggest ways on how to improve gout care.

Background and Objectives: Menkes disease (MNK) is a rare X-linked recessive disease, caused by mutations in the copper transporting ATP7A gene that is required for copper homeostasis. MNK patients experience various clinical symptoms including neurological defects that are closely related to the prognosis of MNK patients. Neural stem cells (NSCs) in the hippocampal dentate gyrus (DG) produce new neurons throughout life, and defects in DG neurogenesis are often correlated with cognitive and behavioral problems. However, neurodevelopmental defects in the DG during postnatal period in MNK have not been understood yet. Methods: and Results: Mottled-brindled (Mo Br/y ) mice (MNK mice) and littermate controls were used in this study. In vivo microCT imaging and immunohistochemistry results demonstrate that blood vasculatures in hippocampus are abnormally decreased in MNK mice. Furthermore, postnatal establishment of NSC population and their neurogenesis are severely compromised in the DG of MNK mice. In addition, in vitro analyses using hippocampal neurosphere culture followed by immunocytochemistry and immunoblotting suggest that neurogenesis from MNK NSCs is also significantly compromised, corresponding to defective neurogenic gene expression in MNK derived neurons. Conclusions Our study is the first reports demonstrating that improper expansion of the postnatal NSC population followed by significant reduction of neurogenesis may contribute to neurodevelopmental symptoms in MNK. In conclusion, our results provide new insight into early neurodevelopmental defects in MNK and emphasize the needs for early diagnosis and new therapeutic strategies in the postnatal central nerve system damage of MNK patients.

We surveyed on the infection status of zoonotic trematode metacercariae (ZTM) in freshwater fishes from Soyang-cheon (a branch stream of Mangyeong-gang) in Wanju-gun, Jeollabuk-do, the Republic of Korea. A total of 927 fishes were individually examined with the artificial digestion method during 2013-2015 (462 fish in 15 spp.) and 2018-2019 (465 fish in 25 spp.). Clonorchis sinensis metacercariae were detected in 207 (31.4%) out of 659 fishes in 14 positive fish species (PFS), and their mean intensity was 114 per fish infected (PFI). Metagonimus spp. metacercariae were found in 302 (37.4%) out of 808 fishes in 21 PFS, and their mean intensity was 12 PFI. Centrocestus armatus metacercariae were detected in 222 (59.0%) out of 376 fishes in 12 PFS, and their mean intensity was 383 PFI. Echinostoma spp. metacercariae were found in 139 (22.1%) out of 628 fishes in 10 PFS, and their mean intensity was 7 PFI. Clinostomum complanatum metacercariae were detected in 14 (6.5%) out of 214 fishes in 4 PFS, and their mean intensity was 2.4 PFI. Metorchis orientalis metacercariae were detected in 36 (13.5%) out of 267 fishes in 5 PFS, and their mean intensity was 4.3 PFI. Conclusively, the prevalence and infection intensity of ZTM is generally not so high in fishes from Soyang-cheon. However, those of C. sinensis metacercariae are more or less higher in 2 fish species, Pungtungia herzi and Sarcocheilichthys variegatus wakiyae.