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Sepsis is a life-threatening disorder with high incidence and mortality rate. However, the early detection of sepsis is challenging due to lack of specific marker and various etiology. This study aimed to identify robust risk factors for sepsis via cluster analysis. The integrative task of the automatic platform (i.e., electronic medical record) and the expert domain was performed to compile clinical and medical information for 2,490 sepsis patients and 16,916 health check-up participants. The subjects were categorized into 3 and 4 groups based on seven clinical and laboratory markers (Age, WBC, NLR, Hb, PLT, DNI, and MPXI) by K-means clustering. Logistic regression model was performed for all subjects including healthy control and sepsis patients, and cluster-specific cases, separately, to identify sepsis-related features. White blood cell (WBC), well-known parameter for sepsis, exhibited the insignificant association with the sepsis status in old age clusters (K3C3 and K4C3). Besides, NLR and DNI were the robust predictors in all subjects as well as three or four cluster-specific subjects including K3C3 or K4C3. We implemented the cluster-analysis for real-world hospital data to identify the robust predictors for sepsis, which could contribute to screen likely overlooked and potential sepsis patients (e.g., sepsis patients without WBC count elevation).

Moderately elevated albuminuria (30–300 mg/g) is a marker of renal dysfunction and a risk factor of cardiovascular disease. Additionally, several recent studies have reported a relationship between moderately elevated albuminuria and triglyceride (TG) levels. Therefore, we aimed to evaluate the relationship between the urine albumin-to-creatinine ratio (UACR) and total cholesterol (TC), TG, and high-density lipoprotein C (HDL-C) levels. We analyzed data from 19,340 patients from the 2011–2014 and 2019–2020 from the Korea National Health and Nutrition Examination Surveys. Multivariate linear regression analysis showed that the UACR was positively associated with TC and TG levels and negatively associated with HDL-C levels in both Korean women and men. These results were reanalyzed according to the degree of proteinuria (normal, moderately elevated albuminuria, and severely elevated albuminuria (≥ 300 mg/g)). We found a positive relationship between UACR and TC and TG levels, but a negative association with HDL-C levels, except for TC (moderately elevated albuminuria) and HDL-C (moderately elevated albuminuria) in Korean men and TC (severely elevated albuminuria), TG (severely elevated albuminuria), and HDL-C (normal range albuminuria) in Korean women. The correlation between albuminuria and lipid profiles became more evident as albuminuria shift from normal to the severely elevated albuminuria. Thus our multivariate linear regression analysis showed that lipid profiles (TG, TC, and HDL-C levels) were associated with the UACR.

The association between microalbuminuria and cardiovascular disease (CVD) is accumulating in various patient populations. However, when stratified by sex, the relationship between microalbuminuria and CVD remains unclear. We obtained data from the 2011-2014 and 2019-2020 Korea National Health and Nutrition Examination Survey (KNHANES). Microalbuminuria was measured based on spot urine albumin-creatinine ratio (UACR). The Framingham risk score (FRS) model was implemented to evaluate the CVD risk. Linear and logistic regression models were used to identify the associations of microalbuminuria status with cardiometabolic predictors and CVD status determined by the FRS score. Among 19,340 representative Korean participants, the (UACR) in Korean women and men with history of CVD was higher than in those without history of CVD. Among patients without history of CVD, multivariate regression analysis showed that a high UACR was related to older age, lower high-density lipoprotein cholesterol level, higher total cholesterol level, higher systolic blood pressure, higher prevalence of current smoking, higher prevalence of diabetes, and higher anti-hypertensive medication use in both women and men. The UACR showed a positive linear correlation with the Framingham risk score in both women and men. The presence of microalbuminuria was significantly associated with the cardiometabolic risk factors and the increased risk of CVD evaluated by FRS model in both women and men in a nationally representative sample of Korea.

Endometriosis is a complex disease with diverse etiologies, including hormonal, immunological, and environmental factors; however, its exact pathogenesis remains unknown. While surgical approaches are the diagnostic and therapeutic gold standard, identifying endometriosis-associated genes is a crucial first step. Five endometriosis-related gene expression studies were selected from the available datasets. Approximately, 14,167 genes common to these 5 datasets were analyzed for differential expression. Meta-analyses utilized fold-change values and standard errors obtained from each analysis, with the binomial and continuous datasets contributing to endometriosis presence and endometriosis severity meta-analysis, respectively. Approximately 160 genes showed significant results in both meta-analyses. For Bayesian analysis, endometriosis-related single nucleotide polymorphisms (SNPs), the human transcription factor catalog, uterine SNP-related gene expression, disease–gene databases, and interactome databases were utilized. Twenty-four genes, present in at least three or more databases, were identified. Network analysis based on Pearson’s correlation coefficients revealed the HLA-DQB1 gene with both a high score in the Bayesian analysis and a central position in the network. Although ZNF24 had a lower score, it occupied a central position in the network, followed by other ZNF family members. Bayesian analysis identified genes with high confidence that could support discovering key diagnostic biomarkers and therapeutic targets for endometriosis.

We investigated the clinical outcomes and molecular mechanisms of fluconazole-resistant (FR) Candida glabrata bloodstream infections. Among 1,158 isolates collected during multicenter studies in South Korea during 2008–2018, 5.7% were FR. For 64 patients with FR bloodstream infection isolates, the 30-day mortality rate was 60.9% and the 90-day mortality rate 78.2%; these rates were significantly higher than in patients with fluconazole-susceptible dose-dependent isolates (30-day mortality rate 36.4%, 90-day mortality rate 43.8%; p<0.05). For patients with FR isolates, appropriate antifungal therapy was the only independent protective factor associated with 30-day (hazard ratio 0.304) and 90-day (hazard ratio 0.310) mortality. Sequencing of pleiotropic drug-resistance transcription factor revealed that 1–2 additional Pdr1p amino acid substitutions (except genotype-specific Pdr1p amino acid substitutions) occurred in 98.5% of FR isolates but in only 0.9% of fluconazole-susceptible dose-dependent isolates. These results highlight the high mortality rate of patients infected with FR C. glabrata BSI isolates harboring Pdr1p mutations.

Background Due to limited therapeutic options, the spread of extended-spectrum beta-lactamases (ESBLs) have become a major public health concern. We conducted a prospective, randomized, open-label comparison of the therapeutic efficacy of piperacillin-tazobactam (PTZ), cefepime, and ertapenem in febrile nosocomial urinary tract infection with ESBL-producing Escherichia coli (ESBL-EC). Methods This study was conducted at three university hospitals between January 2013 and August 2015. Hospitalized adult patients presenting with fever were screened for healthcare-associated urinary tract infection (HA-UTI). When ESBL-EC was solely detected and susceptible to a randomized antibiotic in vitro, the case was included in the final analysis. Participants were treated for 10–14 days with PTZ, cefepime, or ertapenem. Results A total of 66 participants were evenly assigned to the PTZ and ertapenem treatment groups. After the recruitment of six participants, assignment to the cefepime treatment group was stopped because of an unexpectedly high treatment failure rate. The baseline characteristics of these participants did not differ from participants in other treatment groups. The clinical and microbiological response to PTZ treatment was estimated to be 94% and was similar to the response to ertapenem treatment. The efficacy of cefepime was 33.3%. In the cefepime group, age, Charlson comorbidity index, genotype, and minimal inhibitory concentration (MIC) did not significantly affect the success of treatment. Similarly, genotype seemed to be irrelevant with respect to clinical outcome in the PTZ group. Expired cases tended to involve septic shock with a high Charlson comorbidity index and high MIC. Conclusion Results from this study suggest that PTZ is effective in the treatment of urinary tract infection caused by ESBL-EC when the in vitro test indicates susceptibility. In addition, cefepime should not be used as an alternative treatment for urinary tract infection caused by ESBL-EC. Trial registration The trial was registered with the Clinical Research Information Service of Korea Centers for Disease Control and Prevention. (KCT0001895)

Serum creatinine level (SCr) typically decreases during pregnancy due to physiologic glomerular hyperfiltration. Therefore, the clinical practice of estimated glomerular filtration rate (eGFR) based on SCr concentrations might be inapplicable to pregnant women with kidney disease since it does not take into account of the pregnancy-related biological changes. We integrated the Wonju Severance Christian Hospital (WSCH)-based findings and prior knowledge from big data to reveal the relationship between the abnormal but hidden SCr level and adverse pregnancy outcomes. We analyzed 4004 pregnant women who visited in WSCH. Adverse pregnancy outcomes included preterm birth, preeclampsia, fetal growth retardation, and intrauterine fetal demise. We categorized the pregnant women into four groups based on the gestational age (GA)-unadjusted raw distribution (Q1–4 raw ), and then GA-specific (Q1–4 adj ) SCr distribution. Linear regression analysis revealed that Q1-4 adj groups had better predictive outcomes than the Q1–4 raw groups. In logistic regression model, the Q1–4 adj groups exhibited a robust non-linear U-shaped relationship with the risk of adverse pregnancy outcomes, compared to the Q1–4 raw groups. The integrative analysis on SCr with respect to GA-specific distribution could be used to screen out pregnant women with a normal SCr coupled with a decreased renal function.

Increased body fluids during pregnancy complicates the application of estimated glomerular filtration rate (eGFR) formulas that are based on body surface area. Furthermore, gestational renal dysfunction cannot be identified if the serum creatinine (SCr) concentration is within the non-pregnant reference interval (RI) despite inadequate pregnancy-related renal hyperfiltration. 1484 SCr measurements from 957 healthy pregnant women were collected. The average SCr value of gestational week (GW) 0–3 was the representative SCr value of non-pregnant status. While the distribution of SCr measurements varied across GWs, it was transformed into a normal distribution using the bootstrap resampling method. A polynomial linear regression method was applied to achieve a continuous and smooth transformation of values. The normally distributed SCr values of each GW were compared to the non-pregnant status, leading to the calculation of SCr hyperfiltration. The final equation, (2 − SCr (μmol/L) / 55.25) × 103.1 × 55.25/(56.7 − 0.223 × GW − 0.113 × GW 2 + 0.00545 × GW 3 − 0.0000653 × GW 4 ), and reference intervals for both SCr and eGFR for each GW were obtained. These RIs and novel equations can be effectively used to monitor renal dysfunction in pregnant women.

Background This study analyzed the genetic traits and fitness costs of vancomycin-resistant Enterococcus faecium (VREfm) blood isolates carrying Tn 1546 -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 Tn 1546 -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.

Introduction/ObjectivesAnti-cyclic citrullinated peptide antibody (anti-CCP) is one of the most important serologic markers for diagnosing rheumatoid arthritis (RA). This study aimed to compare the analytical and clinical performances of the second- and third-generation anti-CCP assays.MethodsFour automated anti-CCP assays were evaluated: Chorus anti-CCP (Diesse Diagnostica), Elecsys anti-CCP (Roche Diagnostics), Atellica® IM anti-CCP IgG (Siemens Healthineers), and Quanta Flash® CCP3 (Inova Diagnostics Inc.). Analytical performance included the precision, linearity, correlation, and concordance rate. For evaluating the clinical performance, 240 patient samples (120 positive and 120 negative samples, determined by the Chorus anti-CCP assay) were used, including those with a diagnosis of RA (n = 132) and non-RA (n = 108). Using receiver operating characteristic (ROC) curve analysis, the sensitivity and specificity were evaluated.ResultsAll four assays that were evaluated showed good precision and linearity, and their correlation and concordance rates were in acceptable ranges. The area under the curve (AUC) values ranged from 0.888 to 0.914, showing a good diagnostic performance. The sensitivity and specificity of all assays were similar (88.0–97.2%).ConclusionsAll four anti-CCP assays showed good analytical and diagnostic performances for diagnosing RA. After adjusting the cutoff values, these assays are expected to show enhanced sensitivity and specificity.Key Points• Previous studies have described the diagnostic performance of a few immunologic markers in RA diagnosis, but nothing has been proven to be sufficiently good in clinical practice.• All four automated anti-CCP assays showed good analytical and diagnostic performances for diagnosing RA in clinical practice.• After adjusting the cutoff values, these assays are expected to show enhanced sensitivity and specificity.• The present study provides reassuring evidence that any of the studied commercially available anti-CCP tests for detecting rheumatoid arthritis provide similar diagnostic information to institutions that adopt these specific testing systems.