Baseline glycated albumin level and risk of type 2 diabetes mellitus in Healthy individuals: a retrospective longitudinal observation in Korea.

Glycated albumin (GA) reflects glycemic status for the past three weeks. GA level demonstrates a strong correlation with HbA1c level and is used as an adjunctive biomarker for diagnosis and monitoring of type 2 diabetes mellitus (T2DM). In this study, we validated the predictive performance of baseline GA for development of T2DM in healthy individuals in Korea. From August 2013 to September 2014, the medical records of 3,771 healthy Koreans were retrospectively reviewed. Each participant was categorized into tertiles based on initial GA level. During the follow-up period through May 2020, study participants were evaluated for T2DM using HbA1c, fasting glucose level, and a self-reported diagnosis history. Baseline GA level by tertile (T1 to T3) was 10.4 ± 0.8% (mean ± SD), 12.1 ± 0.3%, and 13.7 ± 0.9%, respectively. The median follow-up was 5.97 years, during which 4.9% (186 of 3,771) of the participants developed T2DM. After adjusting for confounding factors, the hazard ratio for the development of T2DM in the highest GA level group (T3) compared to the reference group (T1) was 2.46 (95% CI, 1.7 to 3.58, p < 0.001 for trend) with a Harrell's C index of 0.80 (95% CI, 0.76 to 0.83). Also, within highest group of baseline HbA1c and FG levels, higher GA levels were associated with an increased HRs for T2DM. In conclusion, Our study confirms that the risk of T2DM increases with baseline GA level. Additional follow-up of the cohort is warranted to investigate the correlations between GA and other clinical indicators including diabetic complications.

Evaluation of clinical usefulness of HPV-16 and HPV-18 genotyping for cervical cancer screening.

OBJECTIVE: High-risk human papillomavirus (HR-HPV) infection is a leading cause of cervical cancer, of which human papillomavirus (HPV)-16 and HPV-18 account for about 70% of cases. Since HPV infection is common, it is important to focus on the HPV genotypes that pose the highest risk for effective cervical cancer screening. In this study, we evaluated the clinical usefulness of HPV-16/HPV-18 genotyping for cervical cancer screening. METHODS: A total of 86,022 women aged 25 years or older was analyzed in this study. Sensitivity, specificity, positive predictive value, and negative predictive value of HPV genotyping and cytology were analyzed. In addition, we subdivided participants into two groups according to cytology results, negative for intraepithelial lesion of malignancy (NILM) and atypical squamous cells of undetermined significance (ASC-US), and analyzed absolute risk (AR) and relative risk (RR) of cervical intraepithelial neoplasia (CIN) 3 or worse according to HPV genotype. RESULTS: The AR of CIN 3 or worse was 77.0 times higher in HR-HPV-positive compared to HR-HPV-negative. Compared to 12 other HR-HPV-positive, the AR of CIN 3 or worse was 4.2 times higher in HPV-16 and/or HPV-18 positive. This finding was more evident in women with NILM than in women with ASC-US. The RR of CIN 3 or worse was 7.0 in women with NILM and 4.5 in women with ASC-US. CONCLUSION: Regardless of the cytology results, the risk of CIN 3 or worse was higher in HPV-16/HPV-18 than in other HR-HPV. HPV-16/HPV-18 genotyping is recommended to screen women with a high risk of cervical cancer.

Prevalence and molecular basis of null blood group phenotypes in the Korean population: Analysis using a public database.

BACKGROUND: Null phenotypes are characterized by complete absence of all antigens within a blood group system and caused by null variants (e.g., nonsense, frameshift, initiation codon, and canonical splice site variants) in the genes encoding the antigens. Knowing the prevalence and molecular basis of null phenotypes is essential to establish a rare donor program, and the aim of this study was to reveal the prevalence and molecular basis of null phenotypes using the Korean Reference Genome Database (KRGDB) containing whole-genome sequences of 1722 Korean individuals. STUDY DESIGN AND METHODS: Population allele frequencies of null alleles in 39 blood group systems except ABO, MNS, Rh, Lewis, and FORS were obtained from the KRGDB. The prevalence of null phenotypes was calculated using Hardy-Weinberg equation. RESULTS: The prevalence of null phenotypes were estimated to be less than 0.001% in all blood group systems except JR and SID. The prevalence of the Jr(a-) and Sd(a-) phenotypes were estimated to be 0.0453% and 0.2323%, respectively. The most frequent null allele of the JR system was ABCG2*01N.01, accounting for approximately 85% of null alleles. DISCUSSION: Our approach using a public database allowed us to investigate the prevalence and molecular basis of null phenotypes in the Korean population, which will serve as a guide for establishing a rare donor program in Korea. Considering the clinical significance, Jr(a-) is an important null phenotype that should be typed in the Korean population, and molecular assays targeting the most frequent allele ABCG2*01N.01 may be useful in detecting this phenotype.

Evaluation of molecular methods for plasma detection of EGFR mutations in non-small cell lung cancer.

AIM: Epidermal growth factor receptor (EGFR) mutations are detected in non-small cell lung cancer (NSCLC) and associated with responses to therapy with tyrosine kinase inhibitors (TKIs). We compared the analytical performances of two real-time PCRs and droplet digital PCR (ddPCR) to detect EGFR mutations using plasma. METHODS: Plasma EGFR tests were performed using 86 plasma samples from 75 prospectively enrolled NSCLC patients with early and advanced stages. Analytical performances of plasma-using two real-time PCR, Cobas EGFR mutation v2 and PANAMutyper, EGFR kit, and ddPCR were evaluated based on the tissue EGFR test results. The frequencies of EGFR mutations and acquired T790M mutation after TKI therapy were also assessed. RESULTS: The incidence of all EGFR mutations was 52.3% (23/44) in tissue and was up to 43.2% (19/44) in plasma. The Cobas detection rates of three EGFR mutations (exon 19 deletions, L858R, and T790M) in plasma were similar to those in tissue. The Cobas showed a higher detection rate (76.7%) than that by the PANAMutyper (60.5%). Sensitivity for T790M mutation was lower than the sensitivity for the exon 19 deletions or L858R in both tests. Mutant allele frequency measured by ddPCR was significantly correlated with the semi-quantitative values of the Cobas. CONCLUSIONS: Plasma EGFR tests showed similar detection rates for common EGFR mutations compared to the tissue EGFR tests. Cobas showed higher sensitivity in detection of EGFR mutations in body fluids than the PANAMutyper. Real-time PCR using plasma or body fluids could be a suitable first test for the detection of EGFR mutations.

Detection of SARS-CoV-2 in Fecal Samples From Patients With Asymptomatic and Mild COVID-19 in Korea.

BACKGROUND & AIMS: Although coronavirus disease 2019 (COVID-19) is characterized by fever and respiratory symptoms, some patients have no or mild symptoms. Severe acute respiratory syndrome-coronavirus (SARS-CoV-2) has been detected in feces of patients. We investigated gastrointestinal symptoms and shedding of virus into feces of patients with asymptomatic or mild COVID-19. METHODS: We collected data from 46 patients (median age, 26 y; 46% men) with asymptomatic or mild COVID-19 (without fever and pneumonia) and prolonged respiratory shedding of SARS-CoV-2, quarantined from April 4, 2020, through April 24, 2020, in Korea. Respiratory specimens included upper respiratory specimens (nasopharyngeal and oropharyngeal swabs) and lower respiratory specimens (sputum), and were collected twice per week. The median interval between COVID-19 diagnosis to the start of fecal sample collection was 37 days (range, 29-41 d); 213 stool specimens were collected from 46 patients. We used real-time reverse-transcription polymerase chain reaction to detect SARS-CoV-2 in the respiratory and fecal specimens. RESULTS: Gastrointestinal manifestations were observed in 16 of the 46 patients (35%); diarrhea was the most common (15%), followed by abdominal pain (11%), dyspepsia (11%), and nausea (2%). Virus RNA was detected in feces from 2 patients without gastrointestinal symptoms (4%). Mean cycle threshold values from the time of quarantine to the time of fecal collection tended to be lower in patients with virus detected in fecal samples than in patients without virus in fecal samples (29.91 vs 33.67 in the first week, 29.47 vs 35.71 in the fifth week, respectively). Shedding of virus into feces persisted until day 50 after diagnosis; fecal samples began to test negative before or at approximately the time that respiratory specimens also began to test negative. CONCLUSIONS: In an analysis of fecal and respiratory specimens from patients with COVID-19 in quarantine in Korea, we found that the gastrointestinal tract could be a route of transmission of SARS-CoV-2 even in patients with asymptomatic or mild disease, with no gastrointestinal symptoms. The viral load of the respiratory specimens appears be related to shedding of the virus into feces in this group of patients.

Evaluation of Cobas 8000 Analyzer Series Module e801 Analytical Performance.

BACKGROUND: Immunoassays are important tests that provide essential information for patient care. The e801, a module of the recently released Cobas 8000 series (Roche Diagnostics, Mannheim, Germany), is an automated immunoassay system based on streptavidin-biotin interactions. In this study, we evaluated the analytical performance of the e801. METHODS: We evaluated the precision, linearity, assay comparison, and reference range validation of 16 analytes (AFP, CA19-9, CA125, CEA, CYFRA, ferritin, NSE, PSA, Vitamin D, E2, fT4, TSH, FSH, insulin, NT-proBNP, and T) according to the guidelines of the Clinical Laboratory Standards Institute. RESULTS: In precision evaluations, the coefficients of variation were less than each allowable total error for all analytes. Linearity was observed for all analytes over the entire tested analytical range (r2≥0.99). Performance comparisons revealed that the two systems are comparable, with correlation coefficients (r)>0.975 for all analytes. The reference range validation was also within the allowable criteria. CONCLUSIONS: In this study, the Cobas 8000 e801 analyzer demonstrated acceptable performance with respect to precision, linearity, reference range validation, and correlation. Therefore, the e801 analyzer is expected to be useful for routine immunoassays in clinical laboratories, although education and awareness about biotin interference is necessary for successful implementation in clinical practice.

Evaluation of the Elecsys Syphilis electrochemiluminescence immunoassay as a first-line screening test in the reverse algorithms for syphilis serodiagnosis.

OBJECTIVES: With the development of the automated treponemal test, new syphilis serodiagnosis algorithms, reverse algorithm, and European Centre for Disease Prevention and Control (ECDC) algorithm have been recommended recently. We investigated the efficacy of an electrochemiluminescence immunoassay (ECLIA) as an initial screening test in the reverse and ECDC algorithms. METHODS: Samples from 4,771 subjects were included in this study. We performed rapid plasma reagin (RPR), ECLIA, and Treponema pallidum particle agglutination (TPPA) according to these three algorithms. The fluorescent treponemal antibody absorbed (FTA-ABS) test was additionally applied for discordant cases between the RPR and ECLIA results. The FTA-ABS results and the consensus of three algorithms were considered a gold standard. RESULTS: A total of 208 subjects were diagnosed with syphilis. The traditional algorithm had a sensitivity of 25.96%, specificity of 100%, and accuracy of 96.77%. Both the reverse and ECDC algorithms showed the same diagnostic performance, sensitivity of 95.19%, specificity of 99.96%, and accuracy of 99.75%. The agreements between the traditional algorithm and the other algorithms were 96.9% with a kappa value of 0.415. CONCLUSIONS: The diagnostic accuracy of the reverse and ECDC algorithms using the ECLIA as a first-line screening test was superior to that of the traditional algorithm.

The Relationship between Plasma Oxytocin Levels and Social Anxiety Symptoms.

OBJECTIVE: The pathophysiology of social anxiety disorder (SAD) is not yet well understood, but previous research has suggested that oxytocin is associated with social behavior and may play a role in human anxiety states and anxiety-related traits. The aim of this study was to investigate the possible relationship between social anxiety symptoms and plasma oxytocin levels. METHODS: Twenty-three male patients with SAD and 28 healthy male controls participated in this study. All participants were assessed using the Mini International Neuropsychiatric Interview (MINI) and the Liebowitz Social Anxiety Scale (LSAS). Multivariate regression analysis was performed to identify associations between plasma oxytocin levels and SAD. RESULTS: In multiple regression models, after controlling for age and years of education, we found that higher oxytocin levels were significantly associated with higher total LSAS scores (R2 =0.157, coefficient=0.145, 95% CI=-0.0005-0.291, p=0.051) and fear subscale scores (R2 =0.134, coefficient=0.083, 95% CI=0.007-0.159, p=0.034) in the SAD group. CONCLUSION: In this study, increased plasma oxytocin levels were associated with higher social anxiety symptoms among SAD patients, but not among controls. This might be because among SAD patients, higher oxytocin (OT) secretion is an insufficient compensatory attempt to reduce social anxiety symptoms.

Urine Cotinine level with smoking history predicts a risk of coronary artery calcification.

We investigated whether urine cotinine level, alone or combined with smoking status and cumulative smoking amount, could predict coronary calcium (CAC) score increase over time. The study population included 10,980 subjects. We analysed an association between CAC score increase over time and single or combined smoking-related factors. Urine cotinine level of ≥100 ng/mL, current or ex-smokers, and cumulative smoking amount of ≥1 pack-years (PY) showed significantly higher odds ratios (ORs) for CAC score increase over time. A combination of current smokers with >10 PY and urine cotinine level of ≥100 ng/mL showed the highest OR. Irrespective of smoking status and cumulative smoking amount, all combinations with urine cotinine of ≥100 ng/mL showed higher ORs than other combinations with urine cotinine level of <100 ng/mL. Urine cotinine levels can be useful to predict coronary artery calcification and encourage smokers to quit smoking.

Evaluation of the URiSCAN 2 ACR Strip to estimate the urine albumin/creatinine ratios.

BACKGROUND: The urine albumin/creatinine ratio (ACR) test is used to screen patients with chronic diseases, such as diabetes, hypertension and cardiovascular diseases that put them at an increased risk of developing kidney disease. Here, we evaluated the performance of the URiSCAN 2 ACR Strip (URiSCAN; YD diagnostics, Yongin, Korea), a semiquantitative point-of-care testing (POCT) assay, and we compared to an existing POCT assay and a quantitative assay. MATERIALS AND METHODS: A total of 1,020 random urine specimens were analyzed using the semiquantitative URiSCAN 2 ACR Strip and semiquantitative CLINITEK Microalbumin 2 Strip (CLINITEK; Siemens, New York, USA). We evaluated the precision of the URiSCAN 2 ACR Strip and compared the results of the ACR obtained from URiSCAN to those of CLINITEK with the quantitative results of a quantitative assay as a reference. RESULTS: The precision evaluation of the URiSCAN revealed a range between the cutoff (C50 )-20% and C50 +20% bounds, the C5 -C95 interval, with 85.8% confidence. URiSCAN and CLINITEK showed sensitivity and specificity of 87.7% and 72.2%, and 90.2% and 83.0%, respectively. The concordance rates of URiSCAN with CLINITEK and the quantitative assay were 75.6% and 79.1%, respectively. The concordance rate in the abnormal range (≥30 mg/g) between URiSCAN and the quantitative assay were higher than that between CLINITEK and the quantitative assay (78.8% vs 75.4%). CONCLUSIONS: URiSCAN showed good precision and comparable sensitivity with lower specificity than those of CLINITEK.

Comparison of AdvanSure HPV GenoBlot and Hybrid Capture 2 assays for detection of HPV infection.

BACKGROUND: We sought to compare the performance of the AdvanSure assay to the Hybrid Capture (HC) 2 for the detection of high-risk human papillomavirus (HR HPV). METHODS: A total of 855 cervical swab specimens were obtained. We submitted all specimens for HR HPV detection with HC2 and the AdvanSure assay. We subsequently analyzed discordant results and specimens that were positive on both assays using restriction fragment mass polymorphism (RFMP) genotyping analysis. RESULTS: HC2 yielded positive results in 12.0% of specimens, while the AdvanSure assay detected one of 13 HR HPV types in 11.5% of specimens. The overall agreement rate between the assays was 98.5% with a kappa coefficient of 0.928. Discordant results between these two assays were observed in 12 cases, seven were positive only on HC2 and five were positive only on AdvanSure. RFMP analysis of the 12 discordant cases revealed three false-positive results using HC2, and one false-positive and five false-negative results using AdvanSure. CONCLUSIONS: Considering the high agreement rate with HC2 and the ability to differentiate 35 HPV genotypes including HPV 16/18, the AdvanSure assay could be used as a laboratory testing method for HPV infection screening.

Binge eating is associated with trait anxiety in Korean adolescent girls: a cross sectional study.

BACKGROUND: Binge eating occurs more frequently in women than in men, and is known to be related to psychological factors such as stress, depression, and anxiety. This study examined the relationship between binge eating and depression, trait anxiety, and perceived stress in Korean adolescents. METHODS: Four hundred girls (aged 17-18 years) from two high schools located in Seoul completed self-report questionnaires. In total, 327 participants returned reliable responses, and were included in the final study. Binge eating was measured using the Bulimic Inventory Test Edinburgh. The questionnaire also included the Perceived Stress Scale (PSS), Trait Anxiety (TA) of State-Trait Anxiety Inventory, Anxiety Sensitivity Inventory (ASI), and Beck Depression Inventory (BDI). RESULTS: The binge-eating group had higher BMI than the control group. The binge-eating group showed higher scores than control on the PSS, BDI, ASI, and TA. The TA was most highly correlated with binge eating. From logistic regression analysis, TA was revealed to be the only factor that raised the risk of binge eating, whereas PSS, BDI, and ASI showed no statistical significance. CONCLUSION: Although binge eating was correlated with perceived stress, depression, and trait anxiety, when their influences were controlled, only binge eating appeared to be associated with trait anxiety.

Comparison of GeneFinder human papillomavirus (HPV) Liquid Beads Microarray PCR Kit and Hybrid Capture 2 Assay for Detection of HPV Infection.

BACKGROUND: Along with advances in methodological technologies, various assays for detecting high-risk human papillomavirus (HR HPV) have been introduced. The GeneFinder HPV liquid beads microarray PCR kit is one of the recently developed. Our aim was to compare the performance of GeneFinder to Hybrid Capture 2 for detection of HR HPV. METHODS: A total of 900 cervical swab specimens were obtained. All specimens were submitted for HR HPV detection with Hybrid Capture 2 (HC2) and GeneFinder and then additionally analyzed the discordant or both positive results using restriction fragment mass polymorphism (RFMP) genotyping analysis. RESULTS: Hybrid Capture 2 detected 12.8% cases and GeneFinder detected 15.8% cases with 13 HR HPV types. Also, GeneFinder detected 27.4% cases for 32 detectable HPV types. The overall agreement rate was 93.2% with 0.724 kappa coefficient. Discordant results between these two assays were observed in 56 cases. HC2 showed sensitivity of 83.5% and specificity of 95.9%, while GeneFinder showed sensitivity of 85.4% and specificity of 91.9%. For HPV 16 or HPV 18 detection, GeneFinder showed 95.0% or 66.7% of sensitivity and 99.2% or 100%, respectively. Overall coinfection rate was 15.4% (38/247) in GeneFinder analysis. CONCLUSIONS: Considering the high agreement rate with HC2, high sensitivity and the ability to differentiate 32 HPV genotypes including HPV 16/18, GeneFinder could be used as a laboratory testing method for the screening of HPV infections. The use of GeneFinder may also contribute to future research associated with the significance of various HPV types and multiple coinfections.

Poststroke glycemic variability increased recurrent cardiovascular events in diabetic patients.

BACKGROUND AND PURPOSE: The association between blood glucose fluctuation and poststroke cardiovascular outcome has been largely unknown. This study attempted to evaluate whether initial glycemic variability increases cardiovascular events and mortality in diabetic patients with acute ischemic stroke. METHODS: We recruited consecutive patients with acute ischemic stroke or transient ischemic attack from March 2005 to December 2014. A total of 674 patients with diabetes within 72 hours from stroke onset were included. The serum glucose levels were checked 4 times per day during the initial 3 hospital days. J-index, coefficients of variation and standard deviation were calculated for glycemic variability. Composite outcome (nonfatal stroke, nonfatal myocardial infarction, cardiovascular death) and all-cause mortality at 3 months were prospectively captured. Multivariable logistic regression analyses were done adjusting for covariates which can influence on cardiovascular outcomes. RESULTS: Cardiovascular composite outcomes at 3 months were identified in 71 (10.5%): 11 (6.5%), 15 (8.9%), 18 (10.7%) and 27 (16.0%) in each J-index quartiles (P = .035). The highest quartile of J-index had significantly higher cardiovascular death (4.2%, 3.6%, 6.5% and 11.8%; P = .008). In multivariable logistic regression, age (odds ratio [OR] 1.045; 95% confidence interval [CI] 1.006-1.084), P = .021), NIH stroke scale (OR 1.078; 95% CI 1.024-1.134, P = .004), and the highest J-index (OR 12.058; 95% 1.890-76.912, P = .008) were significantly associated with 3-month cardiovascular composite outcome. Increased cardiovascular outcomes in highest J-index quartile were similar in both euglycemic and hyperglycemic groups. CONCLUSION: The initial glycemic variability might increase cardiovascular events in acute ischemic stroke patients with diabetes.

Comparison of Abbott RealTime High-Risk HPV and Hybrid Capture 2 Assays for Detection of HPV Infection.

BACKGROUND: Various assays for detecting high-risk human papillomavirus (HR HPV) have been introduced recently, including the Abbott RealTime High-Risk HPV assay. We sought to compare the performance of Abbott PCR to Hybrid Capture 2 for the detection of HR HPV. METHODS: A total of 941 cervical swab specimens were obtained. We submitted all specimens for HR HPV detection with HC2 and Abbott PCR, and then additionally analyzed discordant and concordant positive results using restriction fragment mass polymorphism (RFMP) genotyping analysis. RESULTS: HC2 detected one of 13 HR HPV types in 12.3% (116/941) of cases, while Abbott PCR detected one of 14 detectable HR HPV types in 12.9% (121/941) of cases. The overall agreement rate was 97.3% with a kappa coefficient of 0.879. Discordant results between these two assays were observed in 25 cases. HC2 showed a sensitivity of 90.0% and specificity of 95.9%, while Abbott PCR showed a sensitivity of 98.0% and specificity of 96.8% when using RFMP results as the gold standard. For HPV 16/18 detection, Abbott PCR showed 95.8%/88.9% sensitivity and 99.2%/99.8% specificity, respectively. The overall coinfection rate between HPV 16, 18 and non-16/18 was 9.9% (12/121) in Abbott PCR analysis. CONCLUSIONS: Considering its high agreement rate with HC2, higher sensitivity/specificity compared to HC2, and ability to differentiate HPV 16/18 from other HPV types, Abbott PCR could be a reliable laboratory testing method for the screening of HPV infections.

Diagnostic performance and establishment of reference limits of HE4 in Korean healthy women.

OBJECTIVE: We aimed to establish distribution and reference limits of HE4 and risk of ovarian malignancy algorithm (ROMA) in healthy Korean women and investigated the factors influencing HE4 levels. We also investigated the diagnostic performances of HE4 and ROMA score, compared with CA125. METHODS: We collected specimens from 1809 healthy Korean women, 140 specimens from patients with ovarian cancers (OCs) and 123 specimens from patients with benign ovarian tumor. Serum HE4 and CA125 concentrations were measured using an electrochemiluminescence immunoassay. The receiver operator characteristic (ROC) curve analysis was done for ROMA, HE4, CA125 and combining of HE4 and CA125. RESULTS: HE4 level was influenced by age, not by menopausal status. The 97.5th percentile upper reference limit of HE4 of subjects <50years and ≥50year-old was 63.87pmol/L and 88.28pmol/L, respectively. The 97.5th percentile upper reference limits of ROMA score were 13.66 in premenopausal and 19.30 in postmenopausal women. The serum HE4 level was even lower in the patients with benign tumor compared to those in healthy controls. HE4 had significantly higher concentrations in OCs than benign ovarian tumor (P<0.001). ROMA and HE4 combined with CA125 or not performed better diagnostically than CA125 alone for distinguishing OCs, with AUCs of 0.844 for ROMA, 0.827 for combining of HE4 and CA125, 0.825 for HE4, and 0.795 for CA125. CONCLUSIONS: The reference limit of HE4 was different from those reported by other studies, suggesting racial or regional difference. HE4 and ROMA were better than CA125 for differentiation normal and benign ovarian tumor from OCs. (Word count: 253).