Pasteurella Infections in South Korea and Systematic Review and Meta-analysis of Pasteurella Bacteremia.

Pasteurella spp. can cause fatal zoonotic infections in humans. We performed a multicenter study to investigate the prevalence and clinical features of Pasteurella infections in South Korea during 2018‒2022. We also conducted a collaborative systematic review and meta-analysis of the global burden of Pasteurella bacteremia. The study included 283 cases found an increasing trend in Pasteurella infections. Blood cultures were positive in 8/35 (22.9%) cases sampled, for overall bacteremia-associated rate of 2.8% (8/283). Aging was a significant risk factor for bacteremia (odds ratio 1.05 [95% CI 1.01-1.10]), according to multivariate analyses. For the meta-analysis, we included a total of 2,012 cases from 10 studies. The pooled prevalence of bacteremia was 12.4% (95% CI 7.3%-18.6%) and of mortality 8.4% (95% CI 2.7%-16.5%). Our findings reflect the need for greater understanding of the increase in Pasteurella infections and the global burden of Pasteurella bacteremia to determine appropriate case management.

Guidelines for Antibacterial Treatment of Carbapenem-Resistant Enterobacterales Infections.

This guideline aims to promote the prudent use of antibacterial agents for managing carbapenem-resistant Enterobacterales (CRE) infections in clinical practice in Korea. The general section encompasses recommendations for the management of common CRE infections and diagnostics, whereas each specific section is structured with key questions that are focused on antibacterial agents and disease-specific approaches. This guideline covers both currently available and upcoming antibacterial agents in Korea.

Prevalence and risk factors of urinary incontinence in pregnant Korean women.

OBJECTIVE: This study aimed to evaluate the prevalence of urinary incontinence (UI) and its associated risk factors among pregnant Korean women, as UI significantly impacts their quality of life. METHODS: A cross-sectional study involving singleton pregnant women was conducted between April and December 2023. Data were collected using a questionnaire assessing demographic information and UI symptoms. The International Consultation on Incontinence Questionnaire-UI short form was used to diagnose UI. RESULTS: A total of 824 pregnant women from three centers participated, with an overall prenatal UI prevalence of 40.2% (331/824). Stress UI was most common (77.1%), followed by mixed UI (16.9%), and urgency UI (6.0%). Risk factors for UI included prior delivery mode, specifically vaginal delivery (adjusted odds ratio [aOR], 5.61; 95% confidence interval [CI], 1.40-22.50; P=0.015) and combined vaginal and cesarean delivery (aOR, 23.14; 95% CI, 1.77-302.74; P=0.017). Additionally, second trimester (aOR, 1.99; 95% CI, 1.19-3.32; P=0.009) and third trimester (aOR, 4.44; 95% CI, 2.65-7.40; P<0.001) were associated with increased UI risk. Conversely, drinking alcohol before pregnancy was a protective factor (aOR, 0.72; 95% CI, 0.53-0.99; P=0.046). CONCLUSION: Approximately 40% of Korean pregnant women experience prenatal UI. Prior delivery mode and advanced gastrointestinal age are significant risk factors. Further research with postpartum and long-term follow-ups is needed.

Standardization of an antimicrobial resistance surveillance network through data management.

Introduction: The rapid spread of COVID-19 worldwide within 2 months demonstrated the vulnerability of the world's population to infectious diseases. In 2015, the Global Antimicrobial Resistance and Use Surveillance System (GLASS) was launched to combat antimicrobial resistance (AMR). However, there has been no comprehensive assessment of the decade-long global battle against AMR based on GLASS data. Methods: South Korea established Kor-GLASS (Korean-GLASS) to proactively monitor data quality and enable international collaborations. A unique feature of Kor-GLASS is the quality control center (QCC), which uses network hubs and ensures standardized, high-quality data through interlaboratory proficiency testing (IPT) and external quality assessment (EQA). In addition, the QCC multifaceted endeavors for integrated data quality management. Results: Since 2020, high-quality AMR data have indicated fluctuating antibiotic resistance rates in South Korea. This trend does not align with the decrease in antibiotic usage seen in humans but coincides with non-human antibiotic sales, indicating a need for greater monitoring of non-human antibiotic resistance. Comprehensive and robust management taking account of the intricate interplay among humans, animals, and the environment is essential. Kor-GLASS has been expanded into a "One Health" multiagency collaborative initiative. Discussion: Although a standardized solution is not suitable for all countries, it must align with the local context and international standards. A centralized top-down management structure such as that of the QCC is essential to ensure continuous data quality coordination. Sustained efforts and surveillance systems are crucial for monitoring and managing AMR and safeguarding human health.

Fitness costs of Tn1546-type transposons harboring the vanA operon by plasmid type and structural diversity in Enterococcus faecium.

BACKGROUND: This study analyzed the genetic traits and fitness costs of vancomycin-resistant Enterococcus faecium (VREfm) blood isolates carrying Tn1546-type transposons harboring the vanA operon. METHODS: All E. faecium blood isolates were collected from eight general hospitals in South Korea during one-year study period. Antimicrobial susceptibility testing and vanA and vanB PCR were performed. Growth rates of E. faecium isolates were determined. The vanA-positive isolates were subjected to whole genome sequencing and conjugation experiments. RESULTS: Among 308 E. faecium isolates, 132 (42.9%) were positive for vanA. All Tn1546-type transposons harboring the vanA operon located on the plasmids, but on the chromosome in seven isolates. The plasmids harboring the vanA operon were grouped into four types; two types of circular, nonconjugative plasmids (Type A, n = 50; Type B, n = 46), and two types of putative linear, conjugative plasmids (Type C, n = 16; Type D, n = 5). Growth rates of vanA-positive E. faecium isolates were significantly lower than those of vanA-negative isolates (P < 0.001), and reduction in growth rate under vancomycin pressure was significantly larger in isolates harboring putative linear plasmids than in those harboring circular plasmids (P = 0.020). CONCLUSIONS: The possession of vanA operon was costly to bacterial hosts in antimicrobial-free environment, which provide evidence for the importance of reducing vancomycin pressure for prevention of VREfm dissemination. Fitness burden to bacterial hosts was varied by type and size of the vanA operon-harboring plasmid.

The immunohistochemical expression of c-MET and RON in lung adenocarcinoma with clinicopathologic correlation.

BACKGROUND: Mesenchymal epidermal transition (MET) and receptor originating from nantes (RON) are transmembrane tyrosine kinase receptors. Both are members of a proto-oncogene family and thus play a role in the pathogenesis of various cancers and acquired resistance to kinase inhibitors in lung cancer. AIMS: The aim of this study was to investigate the immunohistochemical expression of c-MET and RON in lung adenocarcinoma and its clinicopathologic correlation. SETTINGS AND DESIGN: Retrospective study. MATERIALS AND METHODS: The immunohistochemical c-MET and RON expression in specimens obtained from lung adenocarcinoma (n = 175) and associated clinicopathologic parameters were evaluated. STATISTICAL ANALYSIS USED: The correlation between c-MET and RON expression was analyzed by Chi-square test. A Cox proportional hazards model and Kaplan-Meier curve analysis were used to evaluate the risk factors and prognosis. RESULTS: High expression of the c-MET protein showed a strong correlation with that of RON (P = 0.013, kappa = 0.183). Five-year survival and recurrence-free 5-year survival were not associated with high expression of c-MET or RON. High c-MET expression was significantly associated with age older than 60 years (P = 0.000), tumor differentiation (P = 0.009), lymphovascular invasion (P = 0.016), and pleural invasion (P = 0.005). High RON expression was associated with a solid growth pattern (P = 0.001) and pleural invasion (P = 0.002). CONCLUSIONS: The results point to the potential of immunohistochemical expression of c-MET and RON as useful prognostic markers of unfavorable histopathologic features in lung adenocarcinoma.

Development of a multiplex droplet digital PCR method for detection and monitoring of Mycobacterium tuberculosis and drug-resistant tuberculosis.

BACKGROUND: The prevalence of multidrug-resistant tuberculosis (MDR-TB) among Korean tuberculosis patients is about 4.1%, which is higher than the OECD average of 2.6%. Inadequate drug use and poor patient compliance increase MDR-TB prevalence through selective pressure. Therefore, prompt detection of drug resistance in tuberculosis patients at the time of diagnosis and quantitative monitoring of these resistant strains during treatment are crucial. METHODS: A multiplex droplet digital PCR (ddPCR) assay was developed and assessed using DNA material of nine Mycobacterium tuberculosis strains with known mutation status that were purchased from the Korean National Tuberculosis Association. We collected a total of 18 MDR-TB residual samples referred for PCR analysis. Total DNA was extracted from the samples and subjected to the quadruplex ddPCR assay. Their results were compared to those of known resistance phenotypes. RESULTS: The analytical sensitivity and specificity of the multiplex ddPCR assay for detecting INH, RIF, EMB, FQ, and SM resistance-causing mutations ranged from 71.43 to 100% and 94.12-100%, respectively. Follow-up sample results showed that the quadruplex ddPCR assay was sensitive enough to detect IS6110 and other mutations even after onset of treatment. CONCLUSIONS: We developed a sensitive and accurate multiplex ddPCR assay that can detect the presence of tuberculosis quantitatively and resistance-conveying mutations concurrently. This tool could aid clinicians in the diagnosis and treatment monitoring of tuberculosis.

Microwave-Mediated, Catalyst-Free Synthesis of 1,2,4-Triazolo[1,5-a]pyridines from Enaminonitriles.

A catalyst-free, additive-free, and eco-friendly method for synthesizing 1,2,4-triazolo[1,5-a]pyridines under microwave conditions has been established. This tandem reaction involves the use of enaminonitriles and benzohydrazides, a transamidation mechanism followed by nucleophilic addition with nitrile, and subsequent condensation to yield the target compound in a short reaction time. The methodology demonstrates a broad substrate scope and good functional group tolerance, resulting in the formation of products in good-to-excellent yields. Furthermore, the scale-up reaction and late-stage functionalization of triazolo pyridine further demonstrate its synthetic utility. A plausible reaction pathway, based on our findings, has been proposed.

STAT3 Decoy Oligodeoxynucleotides Suppress Liver Inflammation and Fibrosis in Liver Cancer Cells and a DDC-Induced Liver Injury Mouse Model.

Liver damage caused by various factors results in fibrosis and inflammation, leading to cirrhosis and cancer. Fibrosis results in the accumulation of extracellular matrix components. The role of STAT proteins in mediating liver inflammation and fibrosis has been well documented; however, approved therapies targeting STAT3 inhibition against liver disease are lacking. This study investigated the anti-fibrotic and anti-inflammatory effects of STAT3 decoy oligodeoxynucleotides (ODN) in hepatocytes and liver fibrosis mouse models. STAT3 decoy ODN were delivered into cells using liposomes and hydrodynamic tail vein injection into 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed mice in which liver injury was induced. STAT3 target gene expression changes were verified using qPCR and Western blotting. Liver tissue fibrosis and bile duct proliferation were assessed in animal experiments using staining techniques, and macrophage and inflammatory cytokine distribution was verified using immunohistochemistry. STAT3 decoy ODN reduced fibrosis and inflammatory factors in liver cancer cell lines and DDC-induced liver injury mouse model. These results suggest that STAT3 decoy ODN may effectively treat liver fibrosis and must be clinically investigated.

Identification of acute myocardial infarction and stroke events using the National Health Insurance Service database in Korea.

OBJECTIVES: The escalating burden of cardiovascular disease (CVD) is a critical public health issue worldwide. CVD, especially acute myocardial infarction (AMI) and stroke, is the leading contributor to morbidity and mortality in Korea. We aimed to develop algorithms for identifying AMI and stroke events from the National Health Insurance Service (NHIS) database and validate these algorithms through medical record review. METHODS: We first established a concept and definition of "hospitalization episode," taking into account the unique features of health claims-based NHIS database. We then developed first and recurrent event identification algorithms, separately for AMI and stroke, to determine whether each hospitalization episode represents a true incident case of AMI or stroke. Finally, we assessed our algorithms' accuracy by calculating their positive predictive values (PPVs) based on medical records of algorithm- identified events. RESULTS: We developed identification algorithms for both AMI and stroke. To validate them, we conducted retrospective review of medical records for 3,140 algorithm-identified events (1,399 AMI and 1,741 stroke events) across 24 hospitals throughout Korea. The overall PPVs for the first and recurrent AMI events were around 92% and 78%, respectively, while those for the first and recurrent stroke events were around 88% and 81%, respectively. CONCLUSIONS: We successfully developed algorithms for identifying AMI and stroke events. The algorithms demonstrated high accuracy, with PPVs of approximately 90% for first events and 80% for recurrent events. These findings indicate that our algorithms hold promise as an instrumental tool for the consistent and reliable production of national CVD statistics in Korea.

Prenatal to peripubertal exposure to Di(2-ethylhexyl) phthalate induced endometrial atrophy and fibrosis in female mice.

Di(2-ethylhexy) phthalate (DEHP) is a widely used plasticizer that is ubiquitously found in the environment. Using a mouse model, we investigated the impact of early life DEHP exposure ranging from the prenatal to peripubertal developmental period of the female reproductive system. Pregnant female mice were allocated to three groups as follows: control, 100 mg/kg/day, and 500 mg/kg/day DEHP treatment. DEHP exposure was introduced through feeding during pregnancy (3 weeks) and lactation (3 weeks). After weaning, the offspring were also exposed to DEHP through feeding for another 2 weeks. Observations were conducted on female offspring at 10 and 24 weeks. The number of live offspring per dam was significantly lower in the high-DEHP-exposed group (500 mg/kg/day) compared to the control group (7.67 ± 1.24 vs. 14.17 ± 0.31; p < 0.05) despite no difference in pregnancy rates across the groups. Low-DEHP exposure (100 mg/kg/day) resulted to a decreased body weight (36.07 ± 3.78 vs. 50.11 ± 2.11 g; p < 0.05) and decreased left uterine length (10.60 ± 1.34 vs. 14.77 ± 0.82 mm; p < 0.05) in 24-week- old female mice. As early as 10 weeks, endometrial atrophy and fibrosis were observed, and endometrial cystic hyperplasia was noted in female mice at 24 weeks. Our study is the first to demonstrate that female mice exposed to DEHP in the early life developed endometrial fibrosis in the female offspring. Further studies on the consequences of these observations in fecundity and other reproductive functions are warranted.

Nursing diagnoses as factors associated with delirium among intensive care unit patients with sepsis: A retrospective correlational study.

AIMS: To examine whether nursing diagnoses were associated with delirium in patients with sepsis. BACKGROUND: Nursing diagnosis is a nurse's clinical judgement about clients' current or potential health conditions. Delirium is regarded as an important nurse-sensitive outcome. Nonetheless, nursing diagnoses associated with delirium have not yet been identified. DESIGN: Retrospective correlational study. METHODS: This study was carried out from December 2021 to January 2023. We analysed electronic health records of patients with sepsis admitted to the intensive care units (ICUs) of a tertiary hospital in Seoul, South Korea. Delirium was defined based on the Intensive Care Delirium Screening Checklist score. Nursing diagnoses established within 24 h of admission to the ICU were included and were based on the North American Nursing Diagnosis Association diagnostic classification. The data were analysed using logistic regression. Demographics, comorbidities, procedures and physiological measures were adjusted. Regression model was evaluated via receiver operating characteristic curve, Nagelkerke R2, accuracy and F1 score. RESULTS: The prevalence of delirium in patients with sepsis was 51.8%. Ineffective breathing patterns, decreased cardiac output and impaired skin integrity were significant nursing diagnoses related to delirium. Age ≥ 65 years, Acute Physiology and Chronic Health Evaluation II score, mechanical ventilation, continuous renal replacement therapy, physical restraint and comatose state were also associated with delirium in patients with sepsis. The area under the receiver operating characteristic curve was 0.806. CONCLUSION: Ineffective breathing patterns, decreased cardiac output and impaired skin integrity could manifest as prodromal symptoms of delirium among patients with sepsis. IMPACT: The prodromal symptoms of delirium revealed through nursing diagnoses can be efficiently used to identify high-risk groups for delirium. The use of nursing diagnosis system should be recommended in clinical practice caring for sepsis patients. REPORTING METHODS: STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

Improving Depression Severity Prediction from Passive Sensing: Symptom-Profiling Approach.

Depression is a significant mental health issue that profoundly impacts people's lives. Diagnosing depression often involves interviews with mental health professionals and surveys, which can become cumbersome when administered continuously. Digital phenotyping offers an innovative approach for detecting and monitoring depression without requiring active user involvement. This study contributes to the detection of depression severity and depressive symptoms using mobile devices. Our proposed approach aims to distinguish between different patterns of depression and improve prediction accuracy. We conducted an experiment involving 381 participants over a period of at least three months, during which we collected comprehensive passive sensor data and Patient Health Questionnaire (PHQ-9) self-reports. To enhance the accuracy of predicting depression severity levels (classified as none/mild, moderate, or severe), we introduce a novel approach called symptom profiling. The symptom profile vector represents nine depressive symptoms and indicates both the probability of each symptom being present and its significance for an individual. We evaluated the effectiveness of the symptom-profiling method by comparing the F1 score achieved using sensor data features as inputs to machine learning models with the F1 score obtained using the symptom profile vectors as inputs. Our findings demonstrate that symptom profiling improves the F1 score by up to 0.09, with an average improvement of 0.05, resulting in a depression severity prediction with an F1 score as high as 0.86.

Non-invasive chronic kidney disease risk stratification tool derived from retina-based deep learning and clinical factors.

Despite the importance of preventing chronic kidney disease (CKD), predicting high-risk patients who require active intervention is challenging, especially in people with preserved kidney function. In this study, a predictive risk score for CKD (Reti-CKD score) was derived from a deep learning algorithm using retinal photographs. The performance of the Reti-CKD score was verified using two longitudinal cohorts of the UK Biobank and Korean Diabetic Cohort. Validation was done in people with preserved kidney function, excluding individuals with eGFR <90 mL/min/1.73 m2 or proteinuria at baseline. In the UK Biobank, 720/30,477 (2.4%) participants had CKD events during the 10.8-year follow-up period. In the Korean Diabetic Cohort, 206/5014 (4.1%) had CKD events during the 6.1-year follow-up period. When the validation cohorts were divided into quartiles of Reti-CKD score, the hazard ratios for CKD development were 3.68 (95% Confidence Interval [CI], 2.88-4.41) in the UK Biobank and 9.36 (5.26-16.67) in the Korean Diabetic Cohort in the highest quartile compared to the lowest. The Reti-CKD score, compared to eGFR based methods, showed a superior concordance index for predicting CKD incidence, with a delta of 0.020 (95% CI, 0.011-0.029) in the UK Biobank and 0.024 (95% CI, 0.002-0.046) in the Korean Diabetic Cohort. In people with preserved kidney function, the Reti-CKD score effectively stratifies future CKD risk with greater performance than conventional eGFR-based methods.

Determination of HIF-1α degradation pathways via modulation of the propionyl mark.

The hypoxia-inducible factor-1α (HIF-1α) is a key regulator of hypoxic stress under physiological and pathological conditions. HIF-1α protein stability is tightly regulated by the ubiquitin-proteasome system (UPS) and autophagy in normoxia, hypoxia, and the tumor environment to mediate the hypoxic response. However, the mechanisms of how the UPS and autophagy interplay for HIF-1α proteostasis remain unclear. Here, we found a HIF-1α species propionylated at lysine (K) 709 by p300/CREB binding protein (CBP). HIF-1α stability and the choice of degradation pathway were affected by HIF-1α propionylation. K709-propionylation prevented HIF-1α from degradation through the UPS, while activated chaperon-mediated autophagy (CMA) induced the degradation of propionylated and nonpropionylated HIF-1α. CMA contributed to HIF-1α degradation in both normoxia and hypoxia. Furthermore, the pan-cancer analysis showed that CMA had a significant positive correlation with the hypoxic signatures, whereas SIRT1, responsible for K709-depropionylation correlated negatively with them. Altogether, our results revealed a novel mechanism of HIF-1α distribution into two different degradation pathways. [BMB Reports 2023; 56(4): 252-257].

Risk factors and microbiological features of recurrent Escherichia coli bloodstream infections.

Understanding the risk factors and microbiological features in recurrent Escherichia coli BSI is helpful for clinicians. Data of patients with E. coil BSI from 2017 to 2018 were collected. Antimicrobial resistance rates of E. coli were determined. We also identified the ST131 and ESBL genotype to evaluate the molecular epidemiology of E. coli. Whole genome sequencing was conducted on the available ESBL-producing E. coli samples. Of 808 patients with E. coli BSI, 57 (6.31%) experienced recurrence; 29 developed at 4-30 days after initial BSI (early onset recurrence) and 28 at 31-270 days after initial BSI (late onset recurrence). One hundred forty-nine patients with single episode, whose samples were available for determining the molecular epidemiology, were selected for comparison. Vascular catheterization (adjusted odds ratio [aOR], 4.588; 95% confidence interval [CI], 1.049-20.068), ESBL phenotype (aOR, 2.037; 95% CI, 1.037-3.999) and SOFA score ≥9 (aOR, 3.210; 95% CI, 1.359-7.581) were independent risk factors for recurrence. The proportion of ST131 and ESBL genotype was highest in early onset recurrent BSI (41.4% and 41.4%, respectively), from which E. coil had the highest resistance rates to most antimicrobial agents. Whole genome sequencing on 27 of ESBL-producing E. coli (11 from single episode, 11 from early onset recurrence, and 5 from late onset recurrence) demonstrated that various virulence factors, resistant genes, and plasmid types existed in isolates from all types of BSI. Risk factors contributing to the recurrence and microbiological features of E. coli causing recurrent BSI may be helpful for management planning in the clinical setting.

Performance Comparison Between Fourier-Transform Infrared Spectroscopy-based IR Biotyper and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for Strain Diversity.

Background: Development of an accessible method to routinely evaluate the clonality of strains is needed in microbiology laboratories. We compared the discriminatory power of the Fourier-transform infrared (FTIR) spectroscopy-based IR Biotyper (Bruker Daltonics GmbH, Bremen, Germany) to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), using whole-genome sequencing (WGS) as the reference method. Methods: Eighty-three extended-spectrum ß-lactamase-producing Escherichia coli isolates were tested using WGS, MALDI-TOF MS, and IR Biotyper. Simpson's diversity index (SDI), a statistical analysis for testing the homogeneity of a dendrogram, and the adjusted Rand index (aRI) were used to compare the discriminatory ability between typing tests. Results: The SDI (95% confidence interval) was 0.969 (0.952-0.985) for WGS, 0.865 (0.807-0.924) for MALDI-TOF MS, and 0.974 (0.965-0.983) for IR Biotyper. Compared with WGS, IR Biotyper showed compatible diversity, whereas MALDI-TOF MS did not. The concordance and aRI improved from 66.3% to 84.3% and from 0.173 to 0.538, respectively, for IR Biotyper versus MALDI-TOF MS with WGS as the reference method. IR Biotyper showed substantially improved performance in strain typing compared with MALDI-TOF MS. Conclusions: IR Biotyper is useful for diversity analysis with improved discriminatory power over MALDI-TOF MS in comparison with WGS as a reference method. IR Biotyper is an accessible method to evaluate the clonality of strains and could be applied in epidemiological analysis during an outbreak of a health care facility, as well as for research on the transmission of resistant bacteria in community settings.