Comparison of antinuclear antibody profiles obtained using line immunoassay and fluorescence enzyme immunoassay.

OBJECTIVE: LIA-ANA-Profile-17S is a multiplex line immunoassay that simultaneously detects 17 antinuclear antibodies (ANAs) against extractable nuclear antigens (ENAs). We evaluated the utility of LIA-ANA-Profile-17S as a supplement to ANA indirect immunofluorescence (IIF) and EliA ENA (a fluorescence enzyme immunoassay) for diagnosis of ANA-associated rheumatic diseases. METHODS: Sera were collected from 245 patients referred for an ANA IIF test. LIA-ANA-Profile-17S results were compared with those of EliA ENA. The kappa coefficients, agreement rates, and diagnostic performance of these tests were assessed for systemic lupus erythematosus (SLE) and Sjögren's syndrome (SjS). RESULTS: We observed almost perfect interassay agreement for antibodies against Ro52/Ro60, CENP-B, and Scl-70 (kappa = 0.91, 0.97, and 1.00, respectively); strong agreement for anti-SS-B/La antibody (kappa = 0.81); and relatively low agreement for other antibodies, including those against dsDNA, Sm, RNP, and Jo-1. For SLE diagnosis, LIA-ANA-Profile-17S showed lower sensitivity and similar specificity compared with EliA ENA. The sensitivity and specificity of these two assays were similar for SjS diagnosis. CONCLUSIONS: The specificity of LIA-ANA-Profile-17S was enhanced when combined with ANA IIF and was comparable with that of EliA ENA. LIA-ANA-Profile-17S showed relatively good agreement with EliA ENA. In combination with ANA IIF, these assays showed enhanced diagnostic performance.

Comparison of two ß-D-glucan assays for detecting invasive fungal diseases in immunocompromised patients.

(1-3)-ß-D-glucan (BDG) is a major biomarker of invasive fungal diseases (IFDs), which are life-threatening for immunodeficient patients. We compared the clinical performance of two BDG-detection assays. The precision, linearity, reference interval, and limit of quantitation of the Wako BDG assay were analyzed and the performance was compared with that of the Goldstream BDG assay using 272 clinical serum samples. The repeatability, within-laboratory imprecision, and limit of quantitation of the Wako BDG assay were 3.8%, 5.9%, and 7.35 pg/mL, respectively (linearity, 23.8-557 pg/mL; R2 = 0.998). The correlation coefficient, slope, and y-intercept for the Wako BDG assay versus Goldstream BDG assay were 0.29, 3.82, and 0.04, respectively. The sensitivity and specificity were 43.8% and 94.9% for the Wako BDG assay and 39.6% and 83.5% for the Goldstream BDG assay, respectively. In clinical settings, the Wako BDG assay is suitable for diagnosing patients with IFDs.

Performance evaluation of the Roche cobas 6800 system for quantifying cytomegalovirus DNA in plasma and urine samples.

INTRODUCTION: Cytomegalovirus (CMV) nucleic acid amplification testing is important for CMV infection diagnosis and management. CMV DNA is found in plasma and various other fluids, including urine. If CMV can be reliably detected in urine, it may be considered a non-invasive alternative to blood tests. The cobas 6800 system (Roche Diagnostics, Mannheim, Germany) is a Food and Drug Administration-approved testing platform for measuring CMV DNA in plasma. OBJECTIVE: To evaluate the analytical performance of the cobas 6800 system and compare the clinical feasibility of CMV detection in plasma and urine samples. STUDY DESIGN: Imprecision, linearity, limit of quantitation (LOQ), and cross-reactivity of the cobas 6800 system were assessed, and reference interval verification was performed. Plasma CMV DNA quantification was compared to CMV DNA values in urine samples obtained from 129 pediatric patients (<18 years of age) from March 2020 to May 2020 at a tertiary hospital. RESULTS: The assay precision was within the acceptable range. Linearity was observed within the tested concentration range (2.36-6.33 log IU/mL) with a coefficient of determination of 0.9972. The LOQ was 34.5 IU/mL. The assay did not show cross-reactivity with 15 other viruses. Plasma and urine detection results were stratified into three categories: negative,

Broadband acoustic signal variability induced by internal solitary waves and semidiurnal internal tides in the northeastern East China Sea.

The relation between high-frequency broadband acoustic signal variability and two types of internal waves (short-period internal solitary waves; ISWs, and semidiurnal internal tides; ITs) is investigated using data collected during the shallow-water acoustic variability experiment 2015 in the northeastern East China Sea. In this flat (∼100 m depth) region, an underwater sound channel with sound speed profile (SSP) variability observed during the experiment significantly affects the acoustic variability induced by the ISW, and the arrival structure of the channel impulse response (CIR) modeled by ray tracing. To model the range-dependent SSP due to ISW, the location and characteristics of the mode-1 ISW of wavelength (0.5-1 km) are estimated and verified based on the two-layer Korteweq-de Vries theory and by analyzing the observed temperature fluctuations. It is found from comparison between the measured and modeled CIRs that the ISW scatters the arrival structures of refracted rays. Meanwhile, semidiurnal ITs change the channel size modeled as range-independent considering the wavelengths (15-40 km) longer than the model range (3 km). Higher centroid of acoustic arrival time is found with lower isotherm depressions owing to the multimode ITs, indicative of acoustic energy focusing at the lower channel region.

Stability of lyophilized pooled sera as quality control materials for tumor marker assays in external quality assessment.

BACKGROUND: External quality assessment (EQA) requires stable quality control (QC) materials. We evaluated the stability of QC materials made of lyophilized and liquid pooled sera for the tumor markers α-fetoprotein, carcinoembryonic antigen, carbohydrate antigen 125, and carbohydrate antigen 19-9. METHODS: Specimens of the 4 tumor markers were collected from the sera of patients and stored at -20°C. After sera collection and pooling, liquid or lyophilized samples were stored at -20°C, 5°C, or room temperature. Tumor markers were quantified on days 0, 1, 4, 7, 14, 30, and 90 of storage. Internal QC results were analyzed, and the effects of heat inactivation and sucrose addition were assessed. RESULTS: Heat inactivation lowered tumor marker levels in lyophilized pooled sera, whereas sucrose addition had no effect. The coefficients of variation of the internal QC results were stable, whereas those of lyophilized samples were higher than those of liquid samples. Tumor marker levels were significantly lower in lyophilized samples (p<0.05) and did not significantly differ according to storage temperature. A declining trend over time was observed for all tumor markers. CONCLUSIONS: Lyophilized QC materials are insufficiently stable for use in EQA among clinical laboratories.

Evaluation of the UniCel™ DxI 800 immunoassay analyzer in measuring five tumor markers.

PURPOSE: Tumor marker concentrations in a given specimen measured by different analyzers vary according to assay methods, epitopes for antibodies used, and reagent specificities. Although great effort in quality assessment has been instituted, discrepancies among results from different analyzers are still present. We evaluated the assay performance of the UniCel™ DxI 800 automated analyzer in measuring the alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA 15-3 and CA 19-9 tumor markers. MATERIALS AND METHODS: The linearity and precision performance of the five tumor marker assays were evaluated, and concentrations of the respective markers as measured by DxI were compared to those measured by other conventional analyzers (ADVIA Centaur™ and Vitros™ ECi) using 200 specimens collected from 100 healthy persons and 100 patients with respective cancers. RESULTS: The linear fits for all five tumor markers were statistically acceptable (F=4648 for AFP, F=15846 for CEA, F=6445 for CA 125, F=2285 for CA 15-3, F=7459 for CA 19-9; p<0.0001 for all). The imprecision of each tumor marker assay was less than 5% coefficient of variation, except for low and high concentrations of AFP. The results from UniCel™ DxI 800 were highly correlated with those from other analyzers. CONCLUSION: Our results demonstrate that UniCel™ DxI 800 has good linearity and precision performance for the tumor markers assayed in this study. However, there were discrepancies between assaying methods. Efforts to standardize tumor marker assays should be undertaken, and the redetermination of cut-off levels is necessary when developing methods of analyzing tumor markers.

ADIPOQ Gene Variants Associated with Susceptibility to Obesity and Low Serum Adiponectin Levels in Healthy Koreans.

OBJECTIVES: This study aimed to measure the association between the adiponectin, C1Q and collagen domain-containing (ADIPOQ) gene variants and obesity in Koreans. METHODS: Three single nucleotide polymorphisms located in the ADIPOQ gene were genotyped in a population-based cross-sectional study of 986 healthy Koreans. Three different case-control groups (i.e. G1, G2, and G3) were defined according to body mass index (BMI) and serum adiponectin levels. Allelic and genotypic associations of this gene with obesity were measured using multivariate logistic regression analyses in each group. RESULTS: The G allele of -11377C>G, a polymorphism located in the promoter region of the ADIPOQ gene (odds ratio (OR), 1.48; 95% confidence interval, 1.13-1.94) and most haplotypes including this allele significantly increased the risk for obesity. However, the OR decreased from 3.98 (G1 group) to 2.90 (G2 group) and 2.30 (G3 group) when a less strict definition of obesity was used. Most haplotypes, including this allele, significantly increased the risk of obesity. The statistical evidence from the GG genotype of -11377C>G (OR, 3.98) and the GT/GT diplotype composed of -11377G>C and +45T>G (OR, 5.20) confirmed the contribution of the G allele toward a predisposition for obesity. CONCLUSION: These results suggest the contribution of the ADIPOQ gene toward susceptibility to obesity in healthy Koreans. The high-risk genotypes and haplotypes identified here may provide more information for identifying individuals who are at risk of obesity.

A new automated multiple allergen simultaneous test-chemiluminescent assay (MAST-CLA) using an AP720S analyzer.

BACKGROUND: In the diagnosis of atopic diseases, allergen detection is a crucial step. Multiple allergen simultaneous test-chemiluminescent assay (MAST-CLA) is a simple and noninvasive method for in vitro screening of allergen-specific IgE antibodies. METHODS: The Korean Inhalant Panel test on 20 patients and Food Panel test on 19 patients were performed using the conventional manual MAST-CLA kit and the new automated MAST-CLA method (automated AP720S system for the Optigen Assay; Hitachi Chemical Diagnostics, Inc., USA) simultaneously. The results were evaluated for positive reactivity and concordance. RESULTS: The results of inhalant panel gave a relatively higher class level result than the food panel. The 8 patients out of 20 (40%) of the inhalation panel, and 9 patients out of 18 (47.4%) of the food panel showed 100% concordance between the 2 systems. Eighteen patients (90%) of the Inhalation Panel and sixteen patients (84.2%) of the Food Panel showed more than 91% concordance. CONCLUSIONS: These results suggest that the MAST-CLA assay using the new, automated AP720S analyzer performs well, showing a high concordance rate with conventional MAST-CLA. Compared to manual MAST-CLA, the automated AP720S system has a shorter assay time and uses a smaller serum volume (500 microl) along with other conveniences.

The association between adiponectin and diabetes in the Korean population.

As indicators of obesity, waist circumference (WC), body mass index (BMI), and adiponectin are well-known risk factors for diabetes mellitus. The objectives of this study were to measure the independent association between these obesity indicators and diabetes and to examine the combined effect of these indicators on diabetes in a Korean population. The WC, BMI, and serum adiponectin were measured in 4459 healthy Koreans and were classified into tertile groups for men and women. The independent and combined associations of the obesity indicators with diabetes were measured using logistic regression analyses. Diabetes was defined as fasting serum glucose greater than 126 mg/dL or taking medication. Levels of adiponectin were inversely associated with BMI and WC and directly associated with age and high-density lipoprotein (HDL) cholesterol (P < .001). After adjusting for age, BMI, WC, and other lifestyle factors, low levels of adiponectin were associated with an increased prevalence of diabetes. Further adjustment for HDL cholesterol and triglyceride attenuated this association in women but not men. The combined effects of WC and adiponectin on diabetes progressively increased; however, the interaction of these 2 variables was not statistically significant. The combined effect of BMI and adiponectin on diabetes showed similar results. These results suggest that adiponectin was associated with diabetes. The association was independent of BMI and WC and was partly modified by HDL and triglyceride. There were no effect modifications of adiponectin with WC and BMI on diabetes.

A membrane-bound form of IL-4 enhances proliferation and antigen presentation of CD40-activated human B cells.

CD40-activated B (CD40-B) cells might be an attractive source of autologous antigen-presenting cells (APCs) for immunotherapy due to the ability to obtain them from peripheral blood and expand them in vitro. However, soluble IL-4 (sIL-4) in B-cell culture may not represent the "immunological synapse" between B and CD4+ T cells. In this study, the K562 cell line, which expresses CD40L and membrane-bound IL-4 (mbIL-4), could induce higher B-cell proliferation and antigen-presenting surface molecules, including adhesion, costimulatory and HLA molecules, compared with sIL-4. The differentiation to plasmablasts was decreased in CD40-B cells treated with mbIL-4 (CD40-B/mbIL-4) based on flow cytometry analysis. Furthermore, CD40-B/mbIL-4 cells were as potent as mature dendritic cells in the allogeneic lymphocyte reaction and the ability to generate cytotoxic T lymphocytes specific for cytomegalovirus pp65 antigen in vitro. Our results suggest that mbIL-4 could be used to generate CD40-B cells as potent APCs for cellular vaccines and adoptive immunotherapy.

MSX1 polymorphism associated with risk of oral cleft in Korea: evidence from case-parent trio and case-control studies.

Orofacial clefts, including cleft lip with or without palate (CL/P) and cleft palate (CP), are one of the most common congenital malformations in Asian populations, where the rate of incidence is higher than in European or other racial groups. A number of candidate genes have been identified for orofacial clefts, although no single candidate has been consistently identified in all studies. We performed case-parent trio and case- control studies on 6 single nucleotide polymorphisms (SNPs) in the MSX1 gene using a sample of 52 CL/P and CP probands from Korea. In the case-control study, the allele frequencies of 6 MSX1 SNPs were compared between 52 oral cleft cases and 96 unmatched controls. For the case-parent trio study, single-marker and haplotype-based tests of transmission disequilibrium using allelic and genotypic tests revealed significant evidence of linkage in the presence of disequilibrium for 1170 G/A of exon 2. With the GG genotype as a reference group among GG, GA, and AA genotypes at 1170G/A, the disease risk decreased with the presence of the A allele (AA genotype: OR=0.26, 95% CI=0.10-0.99). These results are consistent with evidence from other studies in the US and Chile and confirm the importance of the MSX1 genotype in determining the risk of CL/P and CP in Koreans.

Smoking and atherosclerotic cardiovascular disease in women with lower levels of serum cholesterol.

This cohort study of Koreans examines the relationship between smoking on atherosclerotic cardiovascular disease (ASCVD) and whether serum levels of total cholesterol modify the impact of smoking on ASCVD. A 10-year prospective cohort study was carried out on 234,399 Korean women, ranging 40-69 years of age who received health insurance from the National Health Insurance Corporation and had a medical evaluation in 1993. The main outcome measures were hospital admissions and deaths from ischemic heart disease (IHD), cerebrovascular disease (CVD), and total ASCVD. At baseline, 13,696 (5.8%) were current smokers and 105,755 (45.1%) had a total cholesterol <200mg/dl. Between 1994 and 2003, 4534 IHD (176/100,000 person year), 7961 CVD (310/100,000 person year), and 2418 other ASCVD events (94/100,000 person year) occurred. In multivariate Cox proportional hazard models controlling for age, hypertension, hypercholesterolemia, diabetes and alcohol drinking, current smoking increased the risk of IHD [hazard ratio (HR)=1.7 (95% CI: 1.5-1.9)], CVD [HR=1.6 (95% CI: 1.5-1.6)], and total ASCVD events [HR=1.6 (95% CI: 1.5-1.7)]. Throughout the range of serum cholesterol levels, current smoking significantly increased the risk of myocardial infarction and CVD, but not angina pectoris. There was no evidence of an interaction between smoking and serum cholesterol (p for interaction=0.469, 0.612, and 0.905 for IHD, CVD, and total ASCVD, respectively). This study demonstrated that smoking was a major independent risk factor for IHD, CVD and ASCVD in Korean women. A low cholesterol level confers no protective benefit against smoking-related ASCVD.

Body-mass index and mortality in Korean men and women.

BACKGROUND: Obesity is associated with diverse health risks, but the role of body weight as a risk factor for death remains controversial. METHODS: We examined the association between body weight and the risk of death in a 12-year prospective cohort study of 1,213,829 Koreans between the ages of 30 and 95 years. We examined 82,372 deaths from any cause and 48,731 deaths from specific diseases (including 29,123 from cancer, 16,426 from atherosclerotic cardiovascular disease, and 3362 from respiratory disease) in relation to the body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters). RESULTS: In both sexes, the average baseline BMI was 23.2, and the rate of death from any cause had a J-shaped association with the BMI, regardless of cigarette-smoking history. The risk of death from any cause was lowest among patients with a BMI of 23.0 to 24.9. In all groups, the risk of death from respiratory causes was higher among subjects with a lower BMI, and the risk of death from atherosclerotic cardiovascular disease or cancer was higher among subjects with a higher BMI. The relative risk of death associated with BMI declined with increasing age. CONCLUSIONS: Underweight, overweight, and obese men and women had higher rates of death than men and women of normal weight. The association of BMI with death varied according to the cause of death and was modified by age, sex, and smoking history.

Cigarette smoking, elevated fasting serum glucose, and risk of pancreatic cancer in Korean men.

Pancreatic cancer is one of the most fatal human cancers and continues to be a major unsolved health problem. The goal of this study was to estimate the independent effects and interactions between cigarette smoking and diabetes on the risk of pancreatic cancer in Korean male population. Cigarette smoking and the risk of incidence and death from pancreatic cancer were examined in a 10-year prospective cohort study of 446,407 Korean men aged 40 to 65 years who received health insurance from the National Health Insurance Corporation and who had a medical evaluation in 1992. Relative risks (RR) and 95% confidence intervals (CI) were calculated using a Cox proportional hazards model after adjusting for age, body mass index, exercise and alcohol use. Current smoking was associated with an increased risk of incidence (RR = 1.7, 95% CI = 1.6-1.9) and mortality (RR = 1.6, 95% CI = 1.4-1.7) from pancreatic cancer. The RR for pancreatic cancer increased with both duration and amount of smoking. Diabetes was also associated with an increased risk of both incidence (RR = 1.8, 95% CI = 1.5-2.2) and mortality (RR = 1.7, 95% CI = 1.4-2.1) from pancreatic cancer. There was no interaction between smoking and fasting serum glucose in terms of pancreatic cancer risk. Thus, our prospective study has demonstrated that cigarette smoking and elevated fasting serum glucose are independently associated with an increased risk of pancreatic cancer in a large cohort of Korean males.

A nursing home telehealth system: keeping residents connected.

Live video and detailed images of nursing home residents can be transmitted in real time via the Internet. This telehealth system allows residents and long-term care health professionals to connect with experts not available on-site. Electronic stethoscope, otoscope, dermascope, dentalscope, and electrocardiogram are available for use via the Internet. Impediments to implementing telehealth systems in long-term care include costs and the lack of reimbursement for telehealth services. Reimbursement for telemedicine in nursing homes is limited by originating site, current procedural terminology codes, and facility location.