Search

Objectives Free light chain (FLC) is used for the diagnosis and prediction with regard to the progression risk of plasma cell disorders and Freelite reagent using the SPAplus analyzer (The Binding Site) has been one of the widely used option. However, N Latex FLC reagent with the Atellica CH 930 analyzer (Siemens Healthineers) has shown the advantages of automation and high throughput. We aimed to evaluated clinical implication by differential analytical performances of two assays. Methods A total of 322 serum samples were collected from 193 patients requested for FLC analysis including 131 multiple myeloma patients. The precision, linearity, dilution recovery of N Latex FLC assay was evaluated. We compared the two assays and analyzed the monomer-dimer pattern for discrepant results. Results The precision, linearity, and dilution recovery performance was appropriate for the routine use in clinical laboratories. Despite the good correlation within normal range, proportional bias up-to 170% was observed in samples with high concentrations especially for lambda. The higher value samples with N Latex FLC assay contained more monomer forms than controls. All opposite changes of FLC burden by the N Latex FLC assay proved to present concordant dynamic changes when assessed by serum protein electrophoresis. Conclusions Clinical laboratories should be aware of the inter-assay variability of FLC quantitative measurements using different platforms, especially for high concentrations of both kappa and lambda measurements, possibly due to monomer/dimer ratio diversity. Clinical interpretations for multiple myeloma disease status might not be dramatically affected only when the same assay is utilized during follow-up periods.

Background Total laboratory automation (TLA) is an innovation in laboratory technology; however, the high up-front costs restrict its widespread adoption. To examine whether the capital investment for TLA is worthwhile, we analyzed its clinical- and cost-effectiveness for the expected payback period. Methods Clinical chemistry tests and immunoassays performed in the clinical laboratory of a tertiary care hospital were divided into a post-TLA group, including 1,182,419 tests performed during December 2019, and a pre-TLA group, including 1,151,501 tests performed during December 2018. Laboratory information system data were used to measure clinical effectiveness, and depreciation data were used to calculate TLA costs. Results Laboratory performance improved after TLA adoption in all four key performance indicators: mean turn-around time (TAT), representing the timeliness of result reporting, decreased by 6.1%; the 99th percentile of TAT, representing the outlier rate, decreased by 13.3%; the TAT CV, representing predictability, decreased by 70.0%; and weighted tube touch moment (wTTM), representing staff safety, improved by 77.6%. Based on these effectiveness results, economic evaluation was performed using two approaches. First, the incremental cost-effectiveness ratio and wTTM were used as the most cost-effective performance indicators. Second, the expected payback period was calculated. Considering only staff cost reduction, it was anticipated that 4.75 yrs would be needed to payback the initial investment. Conclusions TLA can significantly enhance laboratory performance, has a relatively quick payback period, and can reduce total hospital expenses in the long term. Therefore, the capital investment for TLA adoption is considered to be worthwhile.

Apolipoprotein monitoring is useful for diagnosing cardiovascular diseases, as they are risk factors of arteriosclerosis and other neutral fat-related diseases. LC-MS/MS is advantageous for simultaneous apolipoprotein quantification, differentiation, and standardization including their isoforms. However, fast and straightforward sample preparation that retains quantification accuracy remains challenging in clinical MS.We developed a simultaneous assay for serum apolipoprotein A-I, apolipoprotein B100 family, and apolipoprotein C-III using a high-throughput LC-MS/MS platform coupled with a BRAVO system. The assay was simplified by using sodium deoxycholate and trypsin/lys-C without reduction and alkylation steps.Simple sample preparation reduced turnaround time by 1.5 h and neat goat serum was chosen as an optimal calibration matrix for accurate protein quantification. Assay precision, linearity, correlation, accuracy, LOD, LLOQ, and carryover were validated according to CLSI guidelines over 41 days using more than 100 human serum samples. Good correlation compared with TIA was observed by Deming regression for all analytes.A high-throughput LC-MS/MS and BRAVO assay for simultaneous apolipoprotein analysis was validated using a simple preparation method with a human serum calibrator in goat serum matrix. The assay is readily expandable to include other target serum proteins and/or their isoforms. This article is protected by copyright. All rights reserved.

Context.— The N-terminal prohormone of the brain natriuretic peptide (NT-proBNP) is a major diagnostic biomarker for heart failure. Objective.— To compare the analytical and clinical performance of 3 NT-proBNP immunoassays: the Atellica IM NT-proBNP assay (Siemens Healthcare Diagnostics), the Alere NT-proBNP assay (Abbott Laboratories), and the Elecsys proBNP II assay (Roche Diagnostics). Design.— For the Atellica IM NT-proBNP assay, analytical performance, including precision, linearity, and carryover, was fully evaluated. Method comparisons among the 3 assays were performed using the Passing-Bablok regression and κ agreement test. To evaluate the clinical performance of the assays, 160 patient samples were used from patients with (n = 81) or without (n = 79) heart failure. Results.— The analytical performance of the Atellica IM NT-proBNP assay was acceptable according to the manufacturer's claims. The Atellica IM NT-proBNP assay showed a positive bias compared with the Elecsys proBNP II assay. The Cohen κ values among the 3 assays were satisfactory (>0.80) and comparable. There were no significant differences in areas under the curve. However, for the diagnosis of heart failure, the Elecsys proBNP II showed a higher specificity and positive likelihood ratio than the other assays. Conclusions.— All 3 NT-proBNP assays showed acceptable concordance, and their clinical performance was comparable. However, the Elecsys proBNP II might be a more discriminating NT-proBNP assay to diagnose heart failure.

For organ transplantation patients, the therapeutic drug monitoring (TDM) of immunosuppressive drugs is essential to prevent the toxicity or rejection of the organ. Currently, TDM is done by immunoassays or liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods; however, these methods lack specificity or are expensive, require high levels of skill, and offer limited sample throughput. Although matrix-assisted (MA) laser desorption ionization (LDI) mass spectrometry (MS) can provide enhanced throughput and cost-effectiveness, its application in TDM is limited due to the limitations of the matrixes such as a lack of sensitivity and reproducibility. Here, we present an alternative quantification method for the TDM of the immunosuppressive drugs in the blood of organ transplant patients by utilizing laser desorption ionization mass spectrometry (LDI-MS) based on a tungsten disulfide nanosheet, which is well-known for its excellent physicochemical properties such as a strong UV absorbance and high electron mobility. By adopting a microliquid inkjet printing system, a high-throughput analysis of the blood samples with enhanced sensitivity and reproducibility was achieved. Furthermore, up to 80 cases of patient samples were analyzed and the results were compared with those of LC-MS/MS by using Passing-Bablok regression and Bland-Altman analysis to demonstrate that our LDI-MS platform is suitable to replace current TDM techniques. Our approach will facilitate the rapid and accurate analysis of blood samples from a large number of patients for immunosuppressive drug prescriptions.

Background Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is increasingly used for immunosuppressive drug tests. However, most LC-MS/MS tests are laboratory-developed and their agreement is unknown in different Korean laboratories. This interlaboratory comparison study evaluated test reproducibility and identified potential error sources. Methods Test samples containing three concentrations of tacrolimus, sirolimus, everolimus, cyclosporine, and mycophenolic acid were prepared by pooling surplus samples from patients undergoing routine therapeutic drug monitoring and tested in duplicate in the participating 10 clinical laboratories. Reconstitution and storage experiments were conducted for the commonly used commercial calibrator set. The robust estimators of reproducibility parameters were calculated. Spearman's rank correlation coefficient (rho, ρ) was used to evaluate the correlation between drugs. Multiple linear regression was used to determine whether the experimental conditions alter the calibration curves. Results The reproducibility coefficient of variation exceeded 10% only for sirolimus concentrations 1 and 2 (10.8% and 12.5%, respectively) and everolimus concentrations 1 and 2 (12.3% and 11.4%, respectively). The percent difference values showed weak correlations between sirolimus and everolimus (ρ=0.334, P =0.175). The everolimus calibration curve slope was significantly altered after reconstitution following prolonged 5°C storage (P =0.015 for 14 days; P =0.025 for 28 days); the expected differences at 6 ng/mL were 0.598% for 14 days and 0.384% for 28 days. Conclusions LC-MS/MS test reproducibility for immunosuppressive drugs seems to be good in the Korean clinical laboratories. Continuous efforts are required to achieve test standardization and harmonization, especially for sirolimus and everolimus.

Appropriate reference intervals of serum insulin-like growth factor I (IGF-I) is important for diagnosing and monitoring patients with growth hormone-related diseases. To establish reference intervals, adult individuals (n=1,334, 680 men and 654 women) were divided into six age groups (20–29, 30–39, 40–49, 50–59, 60–69, ≥70). Serum IGF-I was measured by chemiluminescence immunoassay (Liaison). Concordance of patient classification based on reference intervals, manufacturer’s intervals, and standard deviation score (SDS) was evaluated. New reference intervals had higher upper and lower limits than those specified by the manufacturer. The agreement between classification using new reference interval and the manufacturer’s reference interval, and that using new reference interval and SDS was 75.0% (weighted kappa, 0.17), 91.9% (weighted kappa, 0.51) in men and 91.0% (weighted kappa, 0.41), 92.5% (weighted kappa, 0.53) in women, respectively. Reference intervals should be established not only based on age and sex, but also on ethnicity and assay method.

In this paper, the displacement fields responsible for acoustic emission (AE), excited from a point source in a transversely isotropic cylinder, are derived by solving the Navier-Lamé (NL) equation. The point source as an internal defect is represented by a spatiotemporal concentrated force. The introduction of three potentials correlated with the point source to displacement field vector decouples the coupled NL equation in cylindrical coordinates. Under these conditions, we solve the radial, tangential, and axial displacement fields. Analytical simulations of AE were carried out at several point source locations. Our results demonstrate that analytical modeling is a powerful tool for characterizing AE features generated from an internal defect source.

Despite the superiority of non-HDL cholesterol (non-HDL-C) and apolipoprotein B (ApoB) as lipid markers for atherosclerotic cardiovascular disease (ASCVD), these are only suitable as secondary markers. We compared LDL cholesterol (LDL-C), non-HDL-C, and ApoB concentrations with respect to the occurrence of cardiovascular disease in adults enrolled in the Korean Genome and Epidemiology Study (KoGES).We used information on age; sex; medical history; family history of ASCVD; current lipid-lowering therapy; current smoking status; and creatinine, total cholesterol, HDL-C, LDL-C, triglyceride, and ApoB concentrations from 5,872 KoGES participants without ASCVD. New ASCVD development was monitored during the 8-year follow-up period. Adjusted hazard ratios (aHRs) for ASCVD of LDL-C, non-HDL-C, and ApoB concentrations were calculated based on the multivariate Cox regression analyses. The participants were also grouped as low and high according to the median values for each lipid marker, and calculated aHRs of each group combined by two lipid makers.ApoB showed the highest aHR per 1-SD for ASCVD (1.26; 95% confidence interval [CI], 1.11-1.43), followed by non-HDL-C (1.25; 95% CI, 1.11-1.41) and LDL-C (1.20; 95% CI, 1.06-1.37). The group with low LDL-C and high ApoB concentrations had a significantly higher aHR for ASCVD (1.61; 95% CI, 1.05-2.48) compared to the reference group values (low LDL-C and low ApoB concentrations). The aHR for the group with high LDL-C and low ApoB concentrations was not significant (1.30; 95% CI, 0.79-2.16).ApoB, non-HDL-C, and LDL-C are independent risk factors for ASCVD. Increases in the aHR per 1-SD for ASCVD were more strongly affected by ApoB, followed by non-HDL-C and LDL-C. Participants with low LDL-C and high ApoB concentrations showed increased ASCVD risk. For individuals with ASCVD risk factors, even those presenting normal LDL-C concentrations, measuring ApoB concentrations can provide useful information for better evaluation of ASCVD risk.

Accurate measurement of glycated hemoglobin (HbA1c) is crucial for a diabetes diagnosis and subsequent patient management. The detection method and presence of variant Hb can interfere with HbA1c measurements. We evaluated the HbA1c-measuring performance of the DxC 700 AU (Beckman Coulter, Brea, CA, USA) immunoassay-based device in comparison with another immunoassay device and the reference method.A total of 120 normal and 14 variant Hb samples were analyzed using the Cobas c 513 (Roche Diagnostics, Mannheim, Germany) and DxC 700 AU analyzers. Variant Hb samples were also analyzed using the reference method, along with 20 normal samples. The accuracy, precision, linearity, and carryover were determined.DxC 700 AU results strongly correlated with those of Cobas c 513 and exhibited accuracy in comparison with the reference method. The within-run, between-run, between-day, and total imprecision (%CV) values for the low- and high-concentration control materials were below 2%. The results of DxC 700 AU were linear over a wide HbA1c range (3.39%-18.30%). Although DxC 700 AU performed well in the presence of variant Hb, the HbA1c concentration was underestimated in the presence of fetal Hb. The possibility of interference from a high HbH proportion could not be ruled out.The overall analytical performance of DxC 700 AU was acceptable. The device is accurate, precise, and linear over a wide HbA1c concentration range. Although DxC 700 AU results highly correlated with those of Cobas c 513, caution should be exercised in cases of high HbF and HbH concentrations.

Quantitative analysis using laser desorption/ionization mass spectrometry (LDI-MS) has been limited because of the nonuniform distribution of analytes caused by the “coffee ring effect”. In this st...

Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor’s glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects., SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.

Recently, the parylene-matrix chip was developed for quantitative analysis of small molecules less than 1 kDa. In this study, MALDI-TOF MS based on the parylene-matrix chip was performed to clinically diagnose intrahepatic cholangiocarcinoma (IHCC) and colorectal cancer (CRC). The parylene-matrix chip was applied for the detection of small cancer biomarkers, including N-methyl-2-pyridone-5-carboxamide (2PY), glutamine, lysophosphatidylcholine (LPC) 16:0, and LPC 18:0. The feasibility of MALDI-TOF MS based on the parylene-matrix chip was confirmed via analysis of spot-to-spot and shot-to-shot reproducibility. Serum metabolite markers of IHCC, N-methyl-2-pyridone-5-carboxamide (2PY), and glutamine were quantified using MALDI-TOF MS based on the parylene-matrix chip. For clinical diagnosis of CRC, two water-insoluble (barely soluble) biomarkers, lysophosphatidylcholine (LPC) 16:0 and LPC 18:0, were quantified. Finally, glutamine and LPC 16:0 were simultaneously detected at a range of concentrations in sera from colon cancer patients using the parylene-matrix chip. Thus, this method yielded high-throughput detection of cancer biomarkers for the mixture samples of water-soluble analytes (2PY and glutamine) and water-insoluble analytes (LPC 16:0 and LPC 18:0).

Although tuberculosis (TB) is a severe health problem worldwide, the current diagnostic methods are far from optimal. Metabolomics is increasingly being used in the study of infectious diseases. We performed metabolome profiling to identify potential biomarkers in patients with active TB. Serum samples from 21 patients with active pulmonary TB, 20 subjects with latent TB infection (LTBI), and 28 healthy controls were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by multivariate and univariate analyses. Metabolic profiles indicated higher serum levels of glutamate, sulfoxy methionine, and aspartate and lower serum levels of glutamine, methionine, and asparagine in active TB patients than in LTBI subjects or healthy controls. The ratios between metabolically related partners (glutamate/glutamine, sulfoxy methionine/methionine, and aspartate/asparagine) were also elevated in the active TB group. There was no significant difference in the serum concentration of these metabolites according to the disease extent or risk of relapse in active TB patients. Novel serum biomarkers such as glutamate, sulfoxy methionine, aspartate, glutamine, methionine, and asparagine are potentially useful for adjunctive, rapid, and noninvasive pulmonary TB diagnosis.

Background Automated cellular analyzers are expected to improve the analytical performance in body fluid (BF) analysis. We evaluated the analytical performance of three automated cellular analyzers and established optimum reflex analysis guidelines. Methods A total of 542 BF samples (88 cerebrospinal fluid [CSF] samples and 454 non-CSF samples) were examined using manual counting and three automated cellular analyzers: UniCel DxH 800 (Beckman Coulter), XN-350 (Sysmex), and UF-5000 (Sysmex). Additionally, 2,779 BF analysis results were retrospectively reviewed. For malignant cell analysis, the receiver operating characteristic (ROC) curve was used, and the detection of high fluorescence-BF cells (HF-BFs) using the XN-350 analyzer was compared with cytology results. Results All three analyzers showed good agreement for total nucleated cell (TNC) and red blood cell (RBC) counts, except for the RBC count in CSF samples using the UniCel DxH 800. However, variable degrees of differences were observed during differential cell counting. For malignant cell analysis, the area under the curve was 0.63 for the XN-350 analyzer and 0.76 for manual counting. We established our own reflex analysis guidelines as follows: HF-BFs 83.4/100 WBCs or eosinophils >3.8% are the criteria for mandatory double check confirmation with 1,000× magnification examination. Conclusions The three automated analyzers showed good analytical performances. Application of reflex analysis guidelines is recommended for eosinophils and HF-BFs, and manual confirmation is warranted.

Pediatric cancer patients undergoing chemotherapy or radiation therapy generally require a central venous catheter (CVC). However, serum drawn from CVCs has several drawbacks for use in routine chemistry tests. Biochemical analytes were evaluated using heparin plasma instead of serum to maintain turnaround time and to prevent problems caused by micro-clot formation or delayed clotting time.Venous blood samples from 52 pediatric oncology patients with chemoports or Hickman catheters were collected in serum separating tubes (SSTs) and lithium heparin tubes (LHTs). A total of 29 parameters were analyzed on a Cobas c702 (Roche Diagnostics, Mannheim, Germany). Passing-Bablok regression and Bland-Altman difference plots were used for statistical analyses.When the mean value of each analyte measured from LHT was compared with those from SST, percentage bias was within the desirable bias limit in most of the analytes. However, albumin, potassium, and inorganic phosphorus showed a negative constant bias of -3.0%, -5.3%, and -1.6%, respectively, and total protein showed a positive constant bias of + 3.8%.The use of LHTs for sample collection from pediatric patients with CVCs could be helpful for routine chemistry analyses. The results of potassium and total protein should be interpreted with consideration of the difference between serum and plasma samples.

Intracellular accumulation of mutant proteins causes proteinopathies, which lack targeted therapies. Autosomal dominant hearing loss (DFNA67) is caused by frameshift mutations in OSBPL2. Here, we show that DFNA67 is a toxic proteinopathy. Mutant OSBPL2 accumulated intracellularly and bound to macroautophagy/autophagy proteins. Consequently, its accumulation led to defective endolysosomal homeostasis and impaired autophagy. Transgenic mice expressing mutant OSBPL2 exhibited hearing loss, but osbpl2 knockout mice or transgenic mice expressing wild-type OSBPL2 did not. Rapamycin decreased the accumulation of mutant OSBPL2 and partially rescued hearing loss in mice. Rapamycin also partially improved hearing loss and tinnitus in individuals with DFNA67. Our findings indicate that dysfunctional autophagy is caused by mutant proteins in DFNA67; hence, we recommend rapamycin for DFNA67 treatment. Abbreviations: ABR: auditory brainstem response; ACTB: actin beta; CTSD: cathepsin D; dB: decibel; DFNA67: deafness non-syndromic autosomal dominant 67; DPOAE: distortion product otoacoustic emission; fs: frameshift; GFP: green fluorescent protein; HsQ53R-TG: human p.Q53Rfs*100-transgenic: HEK 293: human embryonic kidney 293; HFD: high-fat diet; KO: knockout; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; NSHL: non-syndromic hearing loss; OHC: outer hair cells; OSBPL2: oxysterol binding protein-like 2; SEM: scanning electron microscopy; SGN: spiral ganglion neuron; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TG: transgenic; WES: whole-exome sequencing; YUHL: Yonsei University Hearing Loss; WT: wild-type.

Patients with diabetes are required to lance their fingers daily for self-monitoring their blood glucose level. Patients might be reluctant to use commercial lancets with thick outer diameters due to lancing pain; this results in the worsening of their health. A metallic microneedle is an ideal substitute to the commercial lancet system and offers a minimally invasive and patient friendly approach for capillary blood extraction. However, reports regarding the performance of sufficient long and high stiffness microneedles for innocuous and efficient capillary blood sampling for conducting clinical trials are rare. Here, we developed a novel micro-lancet (ML) that is 3 mm long and has a 130 µm outer diameter and a sharp beveled 15° tip. ML induced lesser tissue damage than the commercial ACCU-CHEK Softclix in a porcine skin test. Through a clinical study, we demonstrated that the pain scores using the commercial lancet and ML were 3.4 and 0.8 the numeric pain rating scale, respectively. The average blood volume drawn using the ML was 0.96 µL, which satisfies the minimum requirement (0.3 µL) for glucose detection. This novel ML may improve patient compliance to blood glucose monitoring procedures by reducing lancing-related pain.

A ketogenic diet (KD) is known to have beneficial health effects. Various types of KD interventions have been applied to manage metabolic syndrome based on modification of diet parameters such as duration of intervention, macronutrient components, and total calories. Nevertheless, the beneficial health impact of isocaloric KD is largely unknown, especially in healthy subjects. The present study investigated the acute effects of a 3-day isocaloric KD. In this non-randomized intervention study, we recruited 15 healthy volunteers aged 24-38 years (7 men and 8 women) and placed them on an isocaloric KD restricting intake of carbohydrates but not energy (75% fat, 20% protein, 5% carbohydrate) for 3 days. Biochemical profiles and laboratory measurements were performed. Peripheral blood monocular cells were cultured, and measured cell stimulated cytokines. After short-term isocaloric KD, subjects lost body weight and serum free fatty acid levels were increased. These results accompanied elevated serum β-hydroxybutyrate (BHB) concentration and fibroblast growth factor 21 (FGF21) levels and improved insulin sensitivity. Regarding the direct effect of BHB on inflammasome activation, interleukin-1β (IL-1β) and tumor necrosis factor-α secretion in response to adenosine triphosphate or palmitate stimulation in human macrophages decreased significantly after isocaloric KD. Inclinicaltrials.gov (NCT02964572).

Aims Obesity is the most common risk factor for type 2 diabetes. However, not all obese individuals develop diabetes. In the era of precision medicine, metabolomics may reveal the fundamental metabolic status of an individual. Our aim was to assess the association of metabolites with incident type 2 diabetes in obese individuals using Korean Genome and Epidemiology Cohort Study. Methods Using 12 years of metabolomic data from 2,580 individuals, we performed a metabolomic study to define metabolically healthy obesity in an obese population (n = 704) with incident type 2 diabetes. Cox proportional hazards regression model and survival analysis were performed adjusted for the traditional risk factors of type 2 diabetes. Results Our study revealed that spermine, acyl-alkyl phosphatidylcholines (C34:3, C36:3, C42:1), hydroxy sphingomyelin (C22:2, C14:1), and sphingomyelin (C16:0) were associated with incident type 2 diabetes in obese individuals after the adjustment for risk factors and correction of multiple comparisons by Bonferroni method. Five metabolites (except hydroxy sphingomyelin C14:1 and sphingomyelin C16:0) were also significantly associated with incident type 2 diabetes in lean individuals. Conclusions This study highlights the need for defining metabolically healthy obesity based on serum metabolites and elucidates potential biomarkers for type 2 diabetes in an obese population.

Background We established age‐group‐specific reference intervals for serum anti‐Müllerian hormone (AMH) levels in a Korean population and investigated the effectiveness of AMH assay for polycystic ovary syndrome (PCOS) diagnosis. Methods We analyzed serum levels of AMH, follicle‐stimulating hormone (FSH), and luteinizing hormone (LH) from 1540 Korean women. Subjects were divided into three groups: healthy, benign gynecologic diseases, and PCOS. Age‐group‐specific reference intervals and AMH diagnostic performance were estimated. Results The PCOS group had a median AMH level of 7.0 µg/L, which was higher than for the healthy (1.8 µg/L) and the benign gynecologic diseases (2.7 µg/L) groups. The upper 97.5% reference limits for age groups 12–20 years, 21–34 years, and 35–46 years were 13.2 µg/L, 15.8 µg/L, and 6.6 µg/L, respectively. The area under the curve (AUC) values to estimate AMH ability to discriminate PCOS from healthy women for each age group were 0.741, 0.785, and 0.789, respectively. AUCs for LH/FSH were 0.719, 0.672, and 0.590. Conclusions The better diagnostic ability of AMH over LH/FSH in women of late childbearing ages indicates that age and other clinical characteristics should be considered when interpreting these test results., Receiver operating characteristic curves of anti‐Müllerian hormone (AMH) and the luteinizing hormone to follicle‐stimulating hormone ratio (LH/FSH) were drawn according to age groups and control types. The better diagnostic ability of AMH over LH/FSH in women of late childbearing ages indicates that age and other clinical characteristics should be considered when interpreting these test results.

Background In Korea, the Korean Laboratory Accreditation Program (KLAP) has set minimum standards for verification of clinical test performance. This verification process is time-consuming and labor-intensive when performed manually. We developed a free, statistical software program for KLAP, using the R language (R Foundation for Statistical Computing, Vienna, Austria). Methods We used CLSI guidelines for the algorithm. We built graphic user interfaces, including data input, with Embarcadero Delphi EX4 (Embarcadero Technologies, Inc., Texas, USA). The R Base Package and MCR Package for Method Comparison Regression were used to implement statistical and graphical procedures. Results Our program LaboStats has six modules: parallel test, linearity, method comparison, precision, reference interval, and cutoff. Data can be entered into the field either manually or by copying and pasting from an MS Excel worksheet. Users can print out precise reports. Conclusions LaboStats can be useful for evaluating clinical test performance characteristics and preparing documents requested by KLAP.