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.

Purpose: Despite the global paradigm emphasizing earlier and more aggressive intervention for youth-onset type 2 diabetes mellitus (T2DM), metformin and insulin are the only drugs approved for Korean adolescents. We investigated the incidence of complications, changes in glycemic control during the transition period, the effect of second-line antidiabetic agents on glycemic control in young adults with youth-onset T2DM. Methods: Eighty-four patients diagnosed with T2DM at Seoul National University Children's Hospital between January 2001 and July 2023, before age 18 (47 males; mean age, 14 years) with available glycated hemoglobin (HbA1c) data from at least 2 distinct ages between 19 and 22 years old were retrospectively enrolled. Results: At the last follow-up (mean age, 24.9 years; median follow-up, 9.6 years), complications were found in 33.7% (nephropathy, 25.3%; eye disease, 20.6%), and 83% required insulin or second-line agents. During the transition period, HbA1c levels decreased from 8.2% at age 19 to 7.7% at age 22 (P<0.01), with greater improvements in females, those diagnosed before age 15, and those with HbA1c levels ≥7% at age 19. HbA1c level decreased significantly at 1 year after the addition of second-line medications (P=0.03) and at the last visit (P=0.03) compared with baseline. Conclusion Glycemic control improved during the transition period among youth-onset T2DM patients. Given the high incidence of complications and the beneficial effects of second-line agents on glycemic control, there is an urgent need to expand the range of approved second-line agents, along with broader insurance coverage in adolescence.

Purpose: We aimed to compare broad-spectrum antibiotic use between hospice and nonhospice patients with cancer at the end of life using nationwide data from Korea. Methods: In this retrospective cohort study, we analyzed the Korean National Health Insurance Service data of adult patients with cancer who died between 2018 and 2021. Hospice users were defined as patients who received inpatient, home-based, or consultation-based hospice care before death. We applied propensity score matching (1:2) to balance the baseline characteristics of the hospice and non-hospice groups. Broad-spectrum antibiotic use, including anti-pseudomonal penicillins, anti-pseudomonal cephalosporins, carbapenems, and glycopeptides, was assessed during the last 3 months of life using prescription proportions and days of therapy per 1,000 patient-days. Results: After matching, 38,102 hospice and 75,736 non-hospice users were analyzed. During the last 3 months of life, 74.6% of hospiceand 79.0% of non-hospice users received at least one broad-spectrum antibiotic (P＜0.001).The proportion of patients receiving broad-spectrum antibiotics was generally lower amonghospice users across all time intervals (P＜0.001), and the number of days of therapy wasalso lower, with the largest differences observed during the final week and last 3 days of life.Subgroup analyses showed the highest antibiotic exposure among patients with hematologic and pancreatobiliary cancers, particularly in the non-hospice group. Conclusion Hospice involvement was associated with lower use and reduced exposure to broad-spectrum antibiotics among patients with cancer near the end of life. These findings support the alignment of end-of-life treatment decisions with the comfort-oriented goals of hospice care.

Punica granatum L. has been widely used in traditional medicine and is known to contain bioactiveellagitannins with potential antidiabetic properties. The primary objective of this study was to develop and validate a reliable HPLC-DAD method for the quantitative analysis of major compounds isolated from stems and pericarpium of P. granatum, namely pedunculagin (1), flavogallonic acid (2), casuarinin (3), isocorilagin (4), methyl brevifolincarboxylate (5), eschweilenol C (6), ellagic acid-4-O-β-D-xylopyranoside (7), ellagic acid (8), and quercitrin (9), and to futher evaluate their α-glucosidase inhibitory activity. The analytical method demonstrated linearity with correlation coefficients (R²) exceeding 0.9991. The limits of detection (LOD) and limits of quantification (LOQ) ranged from 2.75 to 7.44 μg/mL and 8.33 to 22.54 μg/mL, respectively. Intra-day and inter-day precision showed relative standard deviation (RSD) values below 2.85% and 2.72%, while recovery values ranged from 96.87% to 107.72%, confirming the accuracy and reliability of the method.Quantitative results revealed that ellagitannins were the predominant constituents in both stems and pericarpium of P. granatum. Biological evaluation demonstrated that several isolated compounds exhibited strong αglucosidase inhibitory activity, with compounds 1–3 showing significantly stronger activity than the reference inhibitor acarbose. Enzyme kinetic studies and molecular docking analyses were conducted to clarify their inhibition mechanisms, revealing mixed, uncompetitive and competitive inhibition modes associated with binding to catalytic or allosteric sites of the enzyme. This study integrates quantitative analysis with mechanistic enzyme inhibition evaluation, providing a practical analytical tool for quality control of P. granatum and scientific evidence supporting its potential application in antidiabetic therapy.

Purpose: This study compared healthy lifestyle (HLS) practices and awareness regarding the use of chatbots (A-uC) for health management between childhood and adolescent cancer survivors (CACSs) and their parents, with the aim of assessing the feasibility of tailored artificial intelligence (AI) chatbot-based interventions for holistic survivorship care. Methods: A descriptive comparative design was employed involving 80 CACSs and 80 parents (N=160) recruited through the Korean Pediatric Cancer Foundation. HLS practices were assessed using a validated seven-domain instrument encompassing physical activity, nutrition, interpersonal relations, stress management, positive life perspective, health responsibility, and spiritual health. A-uC was evaluated using an extended technology acceptance model-based tool. Responses to the open-ended question addressing unmet HLS practices were analyzed using latent Dirichlet allocation topic modeling. Results: No significant differences were observed between CACSs and parents in overall HLS (CACSs: 3.16±0.80; parents: 3.18±0.36, p=.74). While perceptions across most A-uC domains did not differ significantly, parents demonstrated a significantly higher “intention to use” chatbots for health management than CACSs (p=.03). The mean A-uC scores exceeded 4 (out of 5) in both groups, reflecting positive perceptions of chatbot-based HLS support. Topic modeling identified “exercise,” “healthy diet,” and “regular lifestyle” as common unmet areas. Conclusion CACSs and their parents share largely concordant views on HLS and A-uC, with a strong interest in chatbot interventions. These findings underscore the potential of tailored AI chatbot programs to address unmet lifestyle needs and promote holistic survivorship care.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Enterococcus faecium, particularly in its multidrug-resistant forms, causes invasive nosocomial infections. Given the limited data comparing the effectiveness of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the CLSI clinical breakpoints (CBPs) for quinupristin–dalfopristin (QD) resistance and the need to evaluate their practical application, we retrospectively investigated the susceptibility patterns of 287 E.faecium bloodstream isolates from Korean hospitals to QD using the updated EUCAST and CLSI CBPs and two antimicrobial susceptibility testing methods: disk diffusion (DD) and Sensititre broth microdilution (Sensititre). QD resistance rates were 5.9% (CLSI) and 18.8% (EUCAST) for DD and 22.6% (CLSI) and 28.2% (EUCAST) for Sensititre. The most prevalent QD resistance gene types among QD-resistant isolates were ermB+msrC+ or ermB– msrC+. Categorical agreement between DD and Sensititre ranged from 77.7% to 90.7%, depending on the testing method and CBPs applied. The EUCAST zone diameter CBPs more effectively help identify QD-resistant E. faecium isolates using the DD method than the CLSI zone diameter CBPs. In comparison, the CLSI minimum inhibitory concentration (MIC) CBPs provide more reliable results for resistance classification in the Sensititre method than EUCAST MIC CBPs. These findings would help improve clinical decision-making for treating multidrug-resistant E. faecium infections.

Background: Haemophilus influenzae is the causative pathogen for various infectious diseases, such as respiratory infections, otitis media, sinusitis, and meningitis. This study aimed to investigate the prevalence and molecular characteristics of β-lactam resistance in non-typeable H. influenzae isolates in South Korea. Methods: In total, 115 non-duplicated H. influenzae isolates were included in this study.Bacterial identification and serotyping were performed using matrix assisted laser desorption ionization-time of flight mass spectrometry and polymerase chain reaction (PCR) of bexA, respectively. Antimicrobial susceptibility was tested using the broth microdilution method.The production of β-lactamase was determined using nitrocefin disks. The presence of blaTEM and blaROB was confirmed using PCR. ftsI was analyzed to identify amino acid mutations in penicillin-binding protein (PBP) 3. Results: Resistance rates to ampicillin, amoxicillin–clavulanate, and cefuroxime were 67.8%, 13.9%, and 32.2%, respectively. None of the isolates were resistant to cefotaxime or ceftriaxone. Among 78 ampicillin-resistant isolates, 71 were β-lactamase-producing ampicillinresistant (BLPAR), and 7 were β-lactamase-non-producing ampicillin-resistant. All BLPAR isolates carried blaTEM, and none carried blaROB. Among 16 amoxicillin–clavulanate-resistant isolates, 15 β-lactamase producers harbored blaTEM. Four to 7 PBP3 mutations per isolate were detected in all 16 non-β-lactamase-producing ampicillin-resistant or cephalosporinresistant isolates. Conclusion Beta-lactam resistance in non-typeable H. influenzae isolates is highly prevalent in South Korea, primarily because of blaTEM and various PBP3 mutations. Therefore, continuous monitoring of antimicrobial resistance rates and mechanisms in non-typeable H.influenzae is necessary.