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.

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.

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.

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.

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.

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.

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).

Performance Evaluation of Three URiSCAN Devices for Routine Urinalysis.

BACKGROUND: This study compares the diagnostic performance (in routine urinalysis) of three URiSCAN devices and three Roche analyzers to manual microscopy and quantitative assays. METHODS: We analyzed eight dipstick tests using three URiSCAN devices. The results were compared to those of the tests performed using three Roche analyzers. The results of leukocyte and erythrocyte screens were compared to those obtained using manual microscopy. Protein, glucose, pH, and specific gravity (SG) assays performed on the URiSCAN devices were compared with the results of corresponding quantitative assays. RESULTS: The rates of agreement within one grade difference were found to be more than 94.3%. When compared with manual microscopy, the Optima provided better diagnostic performance for the detection of leukocytes compared with the Urisys 1100. Compared to the Urisys 2400, the Super plus provided better diagnostic performance with regard to both leukocytes and erythrocytes. There was good correlation between the three URiSCAN devices and each quantitative assay, except for SG detection. CONCLUSION: There were well correlated results between those of the three URiSCAN devices and those obtained using the corresponding Roche analyzers, quantitative assays, and manual microscopy. URiSCAN series devices are therefore suitable for routine urinalysis in clinical laboratories.

Analysis of 25-Hydroxyvitamin D Status According to Age, Gender, and Seasonal Variation.

BACKGROUND: The effects of age, gender, and seasonal variation on human levels of 25-hydroxyvitamin D (25(OH)D) are not well understood. In this study, we aimed to investigate 25(OH)D status according to these factors in a Korean population. METHODS: A total of 303,943 serum 25(OH)D levels were measured using an electrochemiluminescence immunoassay between October 2011 and May 2014. Potential participants were ineligible for the study if they had significant renal, hepatic, or thyroid dysfunction, as well as any major ongoing disease that could influence serum 25(OH)D levels. RESULTS: A total of 95,137 subjects (49,662 men and 45,475 women) were included in this study. The mean 25(OH)D levels were higher in men (42.4 nmol/l) than in women (32.9 nmol/l, P < 0.001). Among the men and women, 73.0% and 88.9%, respectively, had 25(OH)D levels <50 nmol/l, whereas only 3.8% of men and 1.4% of women had levels >75 nmol/l. The highest mean 25(OH)D value was noted in individuals aged ≥70 for both genders. The proportion of those with 25(OH)D levels <50 nmol/l appeared to be higher among younger subjects (P < 0.001). Lastly, there were significant differences between 25(OH)D levels in individuals during summer to fall and winter to spring in both genders, indicating seasonal periodicity (P < 0.001). CONCLUSIONS: Serum 25(OH)D status varied according to gender, age, and season. Therefore, analyses of vitamin D status require individualized gender, age, and seasonally adjusted thresholds. Clinicians should consider these factors when determining optimal serum 25(OH)D levels in clinical practice.

Comparison of clinical performances among Roche Cobas HPV, RFMP HPV PapilloTyper and Hybrid Capture 2 assays for detection of high-risk types of human papillomavirus.

The cervical cancer screening guidelines suggest that early detection of HPV16 and HPV18 is helpful for identifying women with cervical intraepithelial neoplasia (CIN) grade two or higher. We comparatively evaluated three HPV DNA assays, Roche Cobas HPV, RFMP HPV PapilloTyper, and Hybrid Capture 2 (HC2). A total of 861 cervical swab samples from women over 30 years of age were classified into two groups, that is, high grade squamous intraepithelial lesion (HSIL) and non-HSIL, according to cervical cytology results and analyzed by three assays. The results of direct sequencing or Linear array HPV genotyping test were considered true when the three assays presented discrepancies. The concordance rates between Roche Cobas HPV versus RFMP HPV PapilloTyper, RFMP HPV PapilloTyper versus HC2, and Roche Cobas versus HC2 were 94.5%, 94.3%, and 95.9%, respectively. For detection of HPV16 and HPV18, Roche Cobas HPV showed the concordance rates of 98.3% (κ = 0.73) and 99.4% (κ = 0.40) with the confirmation tests, respectively; and RFMP HPV PapilloTyper showed the concordance rates of 99.5% (κ = 0.92) and 100.0% (κ = 1.00), respectively. In conclusion, Roche Cobas HPV, RFMP HPV PapilloTyper, and HC2 showed high agreement rates. Roche Cobas HPV and RFMP HPV PapilloTyper are particularly useful, since both provide HPV specific genotypes, HPV16 and HPV18.

Comparison of chronic kidney disease prevalence examined by the chronic kidney disease epidemiology collaboration equation with that by the modification of diet in renal disease equation in Korean adult population.

BACKGROUND: The new estimated glomerular filtration (eGFR) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, was recently introduced. We compared the prevalence of CKD examined by the CKD-EPI equation with that by the Modification of Diet in Renal Disease (MDRD) equation. METHODS: We analyzed the data from a total of 14,605 Korean adults (age ≥20 years), who were enrolled in the Korean National Health and Nutrition Examination Survey in 2007, 2009, and 2010. CKD stages 1 and 2 were defined as eGFR ≥60 mL/min/1.73 m(2) with proteinuria measured by dipstick. CKD stages 3-5 were defined as eGFR <60 mL/min/1.73 m(2) . RESULTS: The eGFRs calculated by the CKD-EPI equation were higher than those calculated by the MDRD equation (P < 0.001), especially in women and young people. The prevalence of CKD stages 3-5 calculated by the MDRD equation was 6.8%, 3.0%, and 3.0% in 2007, 2009, and 2010, respectively. The prevalence of CKD stages 3-5 calculated by CKD-EPI equation was 7.7%, 2.7%, and 2.6% in 2007, 2009, and 2010, respectively. When defining the CKD using the CKD-EPI equation, 55 (32.7%) of 350 cases were reclassified into more advanced stages and 295 cases (67.3%) were reclassified into less-advanced stages. CONCLUSION: The CKD-EPI equation caused an overall low prevalence of CKD compared to the MDRD. Therefore, CKD-EPI equation might be helpful to prevent an overestimation of CKD.

Intracranial arterial calcification can predict early vascular events after acute ischemic stroke.

BACKGROUND: Intracranial arterial calcification (IAC) is an evidence of advanced atherosclerosis. This study was aimed to investigate whether IAC predicts early vascular events (EVEs) during acute period of ischemic stroke. METHODS: We prospectively enrolled consecutive patients with acute ischemic stroke and transient ischemic attack within 48 hours from January 2005 to October 2012. Three IAC categories were defined according to the total IAC score as follows: no IAC (0 point), mild IAC (1-2 points), and severe IAC (≥3 points). EVEs included early progression/recurrence of stroke, coronary events, and vascular deaths within 2 weeks from stroke onset. We used multivariable Cox regression analyses to determine the effect of IAC on EVE. RESULTS: In the trend analysis of 1017 total patients, there were significant trends of increased IAC toward higher total EVEs (10.5% versus 13.8% versus 21.2%, P < .001). Severe IAC was related to increased rate of early progression/recurrence (hazard ratio [HR] 2.00; 95% confidence interval [CI] 1.07-3.71, P = .029) and coronary events (HR 3.51; 95% CI 1.00-12.31, P = .050) but did not show an association for mortality (HR .54; 95% CI .19-1.53, P = .224). Increased IAC was also related to a poor functional outcome after 3 months (odds ratio 2.23; 95% CI 1.38-3.59). CONCLUSIONS: IAC was significantly associated with increased early progression/recurrence of stroke and coronary events during acute period of ischemic stroke. IAC on the initial brain computed tomography would be used as a predictor for recurrent vascular events after acute ischemic stroke before further angiographic evaluation.

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.

Low glomerular filtration rate increases hemorrhagic transformation in acute ischemic stroke.

BACKGROUND: Decreased glomerular filtration rate (GFR) can increase the risk of bleeding tendency and hemorrhagic stroke. However, the relationship between the levels of GFR and hemorrhagic transformation (HT) after acute ischemic stroke is largely unknown. The aim of this study was to assess whether GFR level is associated with HT in acute ischemic stroke. METHODS: We reviewed 770 consecutive patients with acute ischemic stroke within 7 days from September 2007 to February 2012 in a prospective stroke registry database. We calculated the patient's GFR using the Cockcroft-Gault equation, and divided them into 3 groups: ≥60, 30-59 and <30 ml/min/1.73 m(2). HTs were identified by follow-up computed tomography (CT) or magnetic resonance imaging, and were defined as (1) any degree of high density within the area of low attenuation of vascular territory on noncontrast brain CT, or (2) low-signal intensity area in gradient echo within high-signal intensity meaning acute infarct on diffusion-weighted imaging. Multivariable logistic regression analyses were used to estimate the risk of GFR for HT. Stratification analyses were done according to the presence of HT high risk factors: atrial fibrillation (AF), thrombolysis and large size infarction. Additional logistic regression model for symptomatic HTs was established with the same variables. RESULTS: HTs were noted in 131 patients (17.0%) and symptomatic HTs in 63 patients (8.2%). In univariate analysis, HTs were more frequent in patients with AF (51.9 vs. 16.7%, p < 0.001) and large-size infarction (42.0 vs. 5.3%, p < 0.001). The risk of HT was associated with decreased GFR among 3 subgroups classified according to the value of estimated GFR: 49/394 (12.4%) in the GFR ≥60 group, 66/312 (21.2%) in the 30≤ GFR <59 group and 16/64 (25.0%) in the GFR <30 group (p = 0.002). We found a significant association between the GFR <30 group and HTs in acute ischemic stroke (OR 2.90; 95% CI 1.26-6.68, p = 0.012) after adjusting for other risk factors. Moreover, the incidence of HTs was higher in the subgroups without thrombolysis (OR 3.49; 95% CI 1.44-8.46) and without AF (OR 3.44; 95% CI 1.10-10.76). Decreased GFR also had a tendency of increasing symptomatic HTs (OR 2.39; 95% CI 0.72-7.94, p = 0.154). CONCLUSIONS: Low levels of GFR are associated with a high risk of HT after acute ischemic stroke. Further studies are needed to elucidate whether HT in the patients with renal insufficiency are related to a worse outcome after acute ischemic stroke.

The Asian project for collaborative derivation of reference intervals: (2) results of non-standardized analytes and transference of reference intervals to the participating laboratories on the basis of cross-comparison of test results.

BACKGROUND: The 2009 Asian multicenter study for derivation of reference intervals (RIs) featured: 1) centralized measurements to exclude reagent-dependent variations; 2) inclusion of non-standardized analytes (hormones, tumor makers, etc.) in the target; and 3) cross-check of test results between the central and local laboratories. Transferability of centrally derived RIs for non-standardized analytes based on the cross-check was examined. METHODS: Forty non-standardized analytes were centrally measured in sera from 3541 reference individuals recruited by 63 laboratories. Forty-four laboratories collaborated in the cross-check study by locally measuring aliquots of sera from 9 to 73 volunteers (average 22.2). Linear relationships were obtained by the major-axis regression. Error in converting RIs using the regression line was expressed by the coefficient of variation of slope b [CV(b)]. CV(b) <10% was set as the cut-off value allowing the conversion. The significance of factors for partitioning RIs was determined similarly as in the first report. RESULTS: Significant sex-, age-, and region-related changes in test results were observed in 17, 15, and 11 of the 40 analytes, respectively. In the cross-comparison study, test results were not harmonized in the majority of immunologically measured analytes, but their average CV(b)s were <10% except for total protein, cystatin C, CA19-9, free thyroxine, and triiodothyronine. After conversion, 74% of centrally derived RIs were transferred to each local laboratory. CONCLUSIONS: Our results point to the feasibility of: 1) harmonizing test results across different laboratories; and 2) sharing centrally derived RIs of non-standardized analytes by means of comparative measurement of a set of commutable specimens.

Measurement of serum total vitamin D (25-OH) using automated immunoassay in comparison [corrected] with liquid chromatography tandem-mass spectrometry.

BACKGROUND: The associations of vitamin D deficiency with many nonskeletal diseases are still being discovered. We evaluated the use of an automated immunoassay to measure serum total vitamin D (25-OH) and assessed vitamin D status in a Korean adult population. METHODS: We compared the Elecsys Vitamin D (25-OH) Total Assay (Roche Diagnostics) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) using 300 serum samples. Total imprecision was calculated using three levels of quality control materials and serum samples. We also investigated the vitamin D status using data for 70,762 cases who had a routine health check-up in our hospitals. RESULTS: The regression equation: Elecsys = 0.882 × LC-MS/MS + 6.814 (r = 0.926). Total imprecision was within 10% for all quality control materials and serum samples. The prevalence of vitamin D deficiency using cut-off values of <50 nmol/l (<20 ng/ml) were 70.3% in males and 86.4% in females, respectively. The prevalence of vitamin D deficiency was higher in younger subjects than in older subjects (P for linear-by-linear association was <0.001). Serum vitamin D levels were highest in September and lowest in February. CONCLUSION: The Elecsys Vitamin D (25-OH) Total Assay was comparable to LC-MS/MS and appropriate for routine clinical use. Vitamin D deficiency is common in Korean adults.

Conventional blood tests in predicting influenza A (H1N1) rapidly.

PURPOSE: Although real-time reverse transcriptase-polymerase chain reactions (rRT-PCR) are gold standard for the diagnosis of influenza A (H1N1), the results can be delayed up to several days, which is problematic during a pandemic. Because of this limitation of rRT-PCR, clinicians have often had to set a treatment plan that was solely based on clinical suspicion. We investigated the hematological and biochemical factors that are associated with rRT-PCR results, in order to help clinicians deal with acute febrile patients during influenza pandemics. METHODS: We conducted a retrospective, cross-sectional study of 465 emergency department patients who underwent both rRT-PCR and blood tests at the same time. Hematological and biochemical findings were compared between the rRT-PCR-positive group and rRT-PCR-negative group. RESULTS: Levels of leukocytes, hemoglobin, platelets, blood urea nitrogen (BUN), total bilirubin, lactate dehydrogenase, serum glucose, C-reactive protein (CRP), and procalcitonin were significantly different between the two groups in the univariate analyses. In the multivariate analyses, leukocyte counts ≤ 10.8 (× 10(9))/L [odd ratio (OR) = 8.2, sensitivity = 93.7%, NPV = 85.3%], BUN levels ≤ 7.1 µmol/L (OR = 3.0, sensitivity = 93.7%, NPV = 85.3%), and CRP levels ≤ 60 mg/L (OR = 2.4, sensitivity = 93.7%, NPV = 85.3%) were independently associated with positive rRT-PCR results. CONCLUSIONS: Leukocyte counts, BUN levels and CRP levels were important predictors of rRT-PCR-positive results for 2009 influenza A (H1N1) in adults.

Differences of the association of anti-Müllerian hormone with clinical or biochemical characteristics between women with and without polycystic ovary syndrome.

The aim of the present study was to compare the associations of anti-Müllerian hormone (AMH) with clinical or biochemical characteristics between women with and without polycystic ovary syndrome (PCOS). We also explored the optimal cutoff point of AMH to diagnose PCOS. A cross-sectional study was performed in 87 women diagnosed with PCOS and 53 healthy control subjects. Body mass index (BMI), indices of insulin resistance, metabolic syndrome-related variables, reproductive hormones and serum AMH were measured in all subjects. We conducted receiver operating characteristic (ROC) curve analysis to determine the cutoff of AMH for diagnosis of PCOS. Serum AMH levels were significantly (p <0.001) higher in women with PCOS after adjustment for age and BMI. AMH levels were not significantly related with obesity, indices of insulin resistance, and metabolic syndrome-related variables in both PCOS and control groups. In the control group, AMH levels showed positive correlations with total testosterone (p <0.001), free testosterone (p=0.024), and adiponectin (p=0.002), and showed negative correlations with age (p=0.010) and estradiol (E2) (p=0.012). However, only total (p=0.044) and free testosterone (p=0.012) levels showed significant positive correlations with serum AMH level in PCOS group. ROC curve analysis showed a cutoff point for AMH of 7.82 ng/mL (sensitivity 75.9%, specificity 86.8%) for diagnosis of PCOS. Differences of the association of AMH with clinical or biochemical characteristics between women with PCOS and control groups were observed. This might contribute to the pathogenesis of PCOS, although further investigation is necessary to elucidate the detailed mechanism.