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We investigated the utilization of apolipoprotein B (ApoB), an independent risk factor for cardiovascular disease, and developed and validated a translational equation for calculating low-density lipoprotein cholesterol (LDL-C) in the Korean population visiting local clinics and hospitals. Among a total of 469,520 data sets of the lipid profile panel (total cholesterol, triglycerides, and high-density lipoprotein cholesterols), 142,932 lipid test sets with data on LDL-C and/or ApoB were used for statistical analysis. Using linear regression analysis, we created ApoB percentile value-derived LDL-C equations in a creating set and validated them with previously reported equations (a total of 11 equations) in comparison to directly measured LDL-C using two independent validating sets. Among all lipid test sets, the simultaneously measured ApoB test only accounted for 2.0%, indicating its underutilization in Korea. The ApoB-derived equations, which were derived in this study and previous studies, showed an overall agreement of ≥94.3% for NCEP ATP III criteria. However, the accuracy of the equations varied among data sets of populations. Future studies are needed to validate translational equations for ApoB and LDL-C in different populations to clarify the clinical implications of these equations.

We aimed to investigate the number and prevalence of patients indicated for intravenous iron treatment in a large Korean population using criteria based on laboratory test results in an effort to extract indirect information on the need for intravenous iron treatment. Between 1 January 2019 and 31 December 2021, a total of 83,994 Korean patients (30,499 men and 53,495 women) with a median age of 46 years (interquartile range, 30–61) were evaluated using iron deficiency anemia–associated laboratory tests and serum creatinine tests of estimated glomerular filtration rates. The overall prevalence of anemia (Hb ≤ 11 g/dL) was 16.5%, and the proportion of patients with possible chronic kidney disease who had an estimated glomerular filtration rate < 60 mL/min/1.73 m2 was 11.4%. The number of patients indicated for reimbursable intravenous iron treatment was higher in women than in men, higher in older patients, and higher in 2021 than in 2019 (all p < 0.001). The prevalence of patients indicated for reimbursable intravenous iron treatment was up to 30.0% in those ≥ 80 years of age in 2019. The results of this study provide basic knowledge about the use of iron deficiency anemia-associated laboratory tests in planning nutritional support programs using an intravenous iron formulation in Korea.

The appropriate use of the thyroglobulin (Tg) test involves the concurrent measurement of Tg auto-antibodies (Tg Ab) due to the potential for false low or false high Tg due to Tg Ab interference.We retrospectively reviewed Tg and Tg Ab test results requested from local clinics and hospitals in Korea between July 1, 2020 and June 30, 2021.During the study period, 13,811 Tg tests were performed. Among them, 6,769 Tg tests were identified as being repeatedly measured from 2,988 Korean adults. Among the 6,769 performed Tg tests, 2,733 (40.4%) did not have concurrently performed Tg Ab tests. Among the 2,988 subjects, 1,089 (36.4%) had no concurrently measured Tg Ab test results. Among 4,036 Tg results with concurrently measured Tg Ab, 1,045 (25.9%) had positive Tg Ab results, which could interfere with Tg concentration measurements.The Tg Ab test appears to be underutilized in Korea.

Small dense low-density cholesterol (sdLDL) has been the focus of studies due to its potential as an independent risk factor for atherosclerotic cardiovascular diseases. We aimed to investigate the utilization of sdLDL testing by LDL particle size analysis and the prevalence of an sdLDL predominant phenotype in Korean adult patients by visiting local clinics and hospitals. Among 9222 Korean adults (4577 men and 4645 women) with a median age of 62.8 years (interquartile range, IQR 54.5 to 71.8 years) undergoing lipid profile testing using LDL particle size analysis, the prevalence of hypercholesterolemia (total cholesterol ≥ 240 mg/dL), hypo HDL cholesterolemia (

Glucose-5-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that affects red blood cells’ metabolism. This retrospective study aimed to investigate the prevalence and characteristics of G6PD testing in Korea. Data were collected from laboratory information systems between July 2021 and June 2022. A total of 5193 patients (1722 males and 3471 females) with a median age of 55.1 years (interquartile range, IQR 44.6 to 64.5) were tested for whole blood G6PD, with 1.6% of tests performed on patients of non-Korean ethnicity. The majority of tests were performed in hospitals (37.7%) or local clinics (34.5%). Interestingly, no female children were tested for whole blood G6PD during the study period. The prevalence of decreased G6PD activity (

In this paper we investigate serum lipoprotein(a), an independent risk factor for cardiovascular disease in the Korean pediatric population. Visiting local clinics and hospitals, 600 lipoprotein(a) tests were performed on 416 Korean children and adolescents (124 boys and 292 girls), with a median age of 11.1 years (interquartile range, IQR, 9.8–13.9). The median lipoprotein(a) level was 21.5 nmol/L (IQR, 8.2–51.7). Among the 416 patients, the 90th percentile value of the initial lipoprotein(a) measurement was 107.8 nmol/L. The proportion of patients with lipoprotein(a) ≥ 100 nmol/L was 11.3%. The lipoprotein(a) level and the proportion of patients with lipoprotein(a) ≥ 100 nmol/L were not significantly different among sex, or age group. Among the 416 patients, 122 (29.3%, 21 boys and 101 girls) underwent at least two follow-up lipoprotein(a) measurements. The median follow-up period was 6.7 months (IQR, 5.5–11.8). The median lipoprotein(a) level across the 122 patients was 25 nmol/L (IQR 10.0–72.0). Among those patients, seven (5.7%) experienced an increase in serum lipoprotein(a) to ≥100 nmol/L during follow-up measurements. Further studies are needed in the Korean pediatric population in order to clarify the clinical significance of this change long-term.

Limited data are available with reference intervals of serum anti-Müllerian hormone (AMH) level in Korean women.We retrospectively reviewed serum AMH test results performed with automated electrochemiluminescence immunoassay in Korean women who visited health promotion centers between January 2019 and December 2020. Serum AMH results by age group were compared with previously reported reference intervals.During the 2-year study period, a total of 1953 AMH test results from Korean women (age 20-49 years) undergoing general health checkups were obtained. Serum AMH level differed significantly by age group. Peak AMH level was observed at age 25-29 years and decreased to undetectable for subjects older than 44 years. The 2.5th, 5th, and 10th percentile values of the present study were comparable with previously assessed lower limits of reference intervals. The upper limit of the reference interval defined as the 97.5th percentile value in women younger than 35 years was higher than that of Western populations. The 90th percentile value of the present study population was similar to the 95th or 97.5th percentile value of reference intervals for Western populations of women younger than 35 years.Understanding patient populations and differences in reference intervals by age group and measurement method can help guide clinical decisions and clinical laboratory analysis.

BACKGROUND The association between NUDT15 polymorphisms and thiopurine-induced leucopenia is well known. AIM To investigate the association between NUDT15 polymorphisms and time-to-leucopenia in paediatric patients with inflammatory bowel disease (IBD) receiving azathioprine and to determine the relationship between NUDT15 polymorphisms and 6-thioguanine nucleotide (6-TGN) levels. METHODS This retrospective observational study included Korean paediatric patients with IBD who were treated with azathioprine and underwent NUDT15 and TPMT genotyping. Azathioprine doses were adjusted by regular thiopurine metabolite monitoring. Factors associated with time-to-leucopenia and the relationship between NUDT15 polymorphisms and 6-TGN levels were analysed. RESULTS Among the 167 patients included, leucopenia was observed in 16% (19/119), 44% (20/45) and 100% (3/3) of the NUDT15 normal, intermediate and poor metabolisers respectively (P

AIMS: This study explores the effects of various genetic polymorphisms in candidate genes on thiopurine metabolism and toxicity in adult patients with Crohn's disease in Korea. METHODS: A total of 131 adult patients with Crohn's disease receiving thiopurine treatment were included. The TPMT and NUDT15 genes and an additional 116 genetic polymorphisms (in 40 genes and 3 intergenic locations) were screened for genotyping. Among the polymorphisms screened, 91 genetic polymorphisms (in 34 genes and 3 intergenic locations) in addition to TPMT and NUDT15 genotypes were included for statistical analyses to investigate their effects on thiopurine metabolites and adverse outcomes (leukopenia, hepatotoxicity, gastrointestinal intolerance, skin rash and alopecia). RESULTS: The median duration of thiopurine treatment was 47.0 months (range 6.0–153.4 months). Patient sex, maintenance dose of thiopurine, and use of anti‐tumour necrosis factor agents were associated with thiopurine metabolite concentrations (P < .05). In the univariate analysis, the TPMT genotype was associated with 6‐thioguanine level (P < .05), although the significance of this did not remain in multivariate analysis. Genetic polymorphisms in the ATIC (rs3821353 and rs16853834), IMPDH2 (rs11706052) and ITPA (rs6139036) genes were associated with thiopurine metabolism (P < .05). Genetic polymorphisms in the ABCC5 (rs8180093) and NUDT15 genotypes were associated with leukopenia (P < .05). CONCLUSION: The results of this study may help clinicians to understand the effects of other various polymorphisms in addition to TPMT and NUDP15 in thiopurine metabolism for management of Crohn's disease patients.

Background Differences in the performance of suggested warfarin dosing algorithms among different ethnicities and genotypes have been reported; this necessitates the development of an algorithm with enhanced performance for specific population groups. Previous warfarin dosing algorithms underestimated warfarin doses in VKORC1 1173C carriers. We aimed to develop and validate a new warfarin dosing algorithm for Korean patients with VKORC1 1173C. Methods A total of 109 patients carrying VKORC1 1173CT (N=105) or 1173CC (N=4) were included in this study. Multiple regression analysis was performed to deduce a new dosing algorithm. Following literature searches for genotype-guided warfarin dosing algorithms, 21 algorithms were selected and evaluated using the correlation coefficient (ρ) of actual dose and estimated dose, mean error, and root mean square error. Results The developed algorithm is as follows: maintenance dose (mg/week)=exp [3.223-0.009×(age)+0.577×(body surface area [BSA])+0.178×(sex)-0.481×(CYP2C9 genotype)+0.227×(VKORC1 genotype)]. Integrated variables explained 44% of the variance in the maintenance dose. The predicted and actual doses showed moderate correlation (ρ=0.641) with the best performance with a mean error of -1.30 mg/week. The proportion of underestimated groups was 17%, which was lower than with the other algorithms. Conclusions This is the first study to develop and validate a warfarin dosing algorithm based on data from VKORC1 1173C carriers; it showed superior predictive performance compared with previously published algorithms.

Limited data are available with regard to biological variations of the Mac-2-binding protein glycosylation isomer (M2BPGi), a liver fibrosis biomarker.Long-term biological variation of M2BPGi was investigated using longitudinally measured M2BPGi test results from healthy Korean adult subjects. One-way analysis of variance (ANOVA) tests were used to calculate the reference change value (RCV) of M2BPGi based on biological variation estimates. Furthermore, asymmetric RCV was calculated according to a recent publication of the European Federation of Clinical Chemistry and Laboratory Medicine Working Group on Biological Variation and Task Group for the Biological Variation Database (EFLM TG-BVD).A total of 363 test results from 174 Korean subjects undergoing general health checkups were requested from 13 local clinics and hospitals during a 38-month period. The within-subjects biological variation (CVRCV based on biological estimates may be helpful for evaluating and interpreting serial M2BPGi measurements by physicians and in clinical laboratories.

The aim of this study was to evaluate the performance of chemiluminescence immunoassays for anti-GAD65 and anti-insulin antibodies following user verification guidelines.The analytical performance of anti-GAD65 and anti-insulin antibodies using a MAGLUMI 2000 analyzer was verified following user verification guidelines by the Clinical and Laboratory Standards Institute.Performance specifications including precision, linearity, carry-over, cutoffs for positive results, reference intervals, and comparability with pre-existing commercially available radioimmunoassays using patient specimens and certified reference material were verified (coefficients of variation for precision of anti-GAD65 and anti-insulin antibodies were 2.6% and 3.4%, respectively). Comparability assessed using clinical serum specimens showed overall agreement with radioimmunoassay of 87.2% (95% confidence interval 74.8% - 94.0%) for the anti-GAD65 antibody assay and 85.4% (95% confidence interval 71.6% - 93.1%) for the anti-insulin antibody assay.The results of this study verified the analytical performance of MAGLUMI anti-GAD65 and anti-insulin antibody assays for clinical use.

Limited data are available regarding intraindividual changes in the Mac-2 binding protein glycosylation isomer (M2BPGi), a liver fibrosis biomarker, performed for health checkups in Korean subjects.Through a laboratory information system, we retrospectively investigated longitudinally measured M2BPGi to assess intraindividual changes in M2BPGi test results.During a 38-month study period, 526 test results from 246 Korean subjects undergoing general health checkups were requested from 13 local clinics and hospitals. Among all 246 subjects, 190 (77.2%) exhibited negative M2BPGi (1.0 C.O.I.) during the initial measurement. Among all 246 subjects, 210 (85.4%) did not experience any changes in qualitative results during a follow-up. Among 42 subjects with initially 1+ positive results for M2BPGi, 17 (40.5%) changed to a negative M2BPGi result at least once during follow-up. No subjects with initially negative results or 1+ positive (1.0 ≤ C.O.I.3.0) results changed to 2+ positive (≥ 3.0 C.O.I.) results during the 38-month follow-up period.Some subjects exhibited qualitative changes in M2BPGi during follow-up health examinations. Future studies are needed to clarify the clinical implication of such changes.

Limited data are available on test utilization and intraindividual changes in rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) in Korean patients that visit local clinics and hospitals. We retrospectively reviewed longitudinally measured RF and anti-CCP data in Korean patients to investigate the utilization and changes in test results through a laboratory information system. During the 10-year study period, 256,259 specimens were tested for RF. Among them, 32,567 (12.7%) specimens from 31,110 Korean adults had simultaneously measured anti-CCP results. Among them, 1110 (3.6%) subjects had follow-up test results. Among 351 patients with initial positive RF results, 290 (82.6%) had no qualitative change in RF from positive to negative values during follow-up. About 3.8% (29/759) of patients with initial negative results experienced qualitative changes in RF that were positive on follow-up. Among 182 patients with an anti-CCP-positive result at initial measurement, 174 (95.6%) had no qualitative change in anti-CCP from positive to negative or equivocal results during follow-up. About 0.5% (5/928) of patients with initial negative values experienced qualitative changes in anti-CCP to positive values on follow-up. The agreement of qualitative results between RF and anti-CCP was 80.8% (95% confidence interval 78.4–83.1%) at initial measurement and 80.6% (95% confidence interval 79.0–82.1%) overall. The results of this study can help inform utilization of RF and anti-CCP testing for Korean patients visiting local clinics and hospitals.

Background Combined methylmalonic acidemia and homocystinuria is a rare inherited disorder of intracellular cobalamin metabolism caused by biallelic variants in one of the following genes: MMACHC (cblC), MMADHC (cblD), LMBRD1 (cblF), ABCD4 (cblJ), THAP11 (cblX‐like), and ZNF143 (cblX‐like), or a hemizygous variant in HCFC1 (cblX). Prenatal diagnosis of combined methylmalonic acidemia with homocystinuria is crucial for high‐risk couples since the disorder can be life‐threatening for offspring. We would like to describe two infant deaths both of which are likely attributable to cblC despite not having a genetic confirmation, and subsequent pregnancy and prenatal genetic testing. Methods Parental clinical exome sequencing and targeted Sanger sequencing of MMACHC gene in amniotic fluid was performed to check the carrier status of the fetus. Results Parental clinical exome sequencing revealed a heterozygous pathogenic variant [NM_015506.2:c.217C>T (p.Arg73*)] in the MMACHC gene of the mother and [NM_015506.2:c.609G>A (p.Trp203*)] in the MMACHC gene of the father. Targeted Sanger sequencing of MMACHC gene in amniotic fluid revealed that the fetus carried only one nonsense variant [NM_015506.2:c.609G>A (p.Trp203*)], which was inherited from the father. The mother delivered a healthy baby and the neonate did not show any symptoms or signs of combined methylmalonic acidemia and homocystinuria after birth. Conclusion We present a case of prenatal diagnosis with parental exome sequencing, which successfully diagnosed the carrier status of the fetus and parents in a combined methylmalonic acidemia and homocystinuria family., Figure shows the Sanger sequencing analysis of the family with methylmalonic acidemia and homocystinuria cobalamin C type. We did successfuly prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis.

BACKGROUND We aimed to investigate the associations between glycemic biomarkers (hemoglobin A1c [HbA1c], fructosamine, and glycated albumin [GA]) in Korean adults. METHODS We retrospectively reviewed data for HbA1c, fructosamine, and glycated albumin between August 28, 2017, and June 30, 2020, to investigate the association between HbA1c and fructosamine and between HbA1c and GA. RESULTS Overall, 961 fructosamine and 142 GA tests concurrently measured HbA1c. The equations were HbA1c (%) = 0.0175 x fructosamine (µmol/L) + 1.6255 and HbA1c (%) = 0.2029 x GA + 2.8102, respectively. The absolute difference between estimated and measured HbA1c ranged from -3.4% to 2.1% HbA1c with the fructosamine equation and -3.2% to 2.8% HbA1c with the GA equation. CONCLUSIONS Fructosamine and GA may be useful adjuncts to HbA1c in Korean patients.

Background Test utilization for the diagnosis of celiac disease may affect the prevalence and incidence of the disease in Korea. We aimed to investigate the test utilization of serological biomarkers for celiac disease in Korea. Methods We retrospectively investigated the test utilization of tissue transglutaminase IgA, gliadin IgA and IgG, and endomysial IgA antibody (Ab) assays between January 2011 and June 2020. Results During a nine‐year‐and‐six‐month study period, overall 307,322,606 clinical tests were requested from different clinical settings, such as local clinics, hospitals, university hospitals, and tertiary medical centers. Among them, only 58 tissue transglutaminase IgA, 22 gliadin IgA, 12 gliadin IgG, and 16 endomysial IgA Ab tests were performed on 79 Korean patients. Among them, one patient had positive transglutaminase IgA Ab result (1.3%). Conclusion Low prevalence and incidence of celiac disease in Korea may be due to an underutilization of diagnostic assays., Test utilization for the diagnosis of celiac disease may affect the prevalence and incidence of the disease in Korea. During a nine year and six month study period, overall 307,322,606 clinical tests were requested from different clinicalsettings, such as local clinics, hospitals, university hospitals, and tertiary medical centers. Among them, only 79 Korean patients were tested for celiac disease using tissue transglutaminase IgA, deaminatedgliadin IgA and IgG, and endomysial IgA antibody assays, revealing that these tests were extremely underutilized inKorea.

Purpose The current status of therapeutic drug monitoring (TDM) assay utilization by clinical laboratories in South Korea remains little known. We investigated the TDM status of five antibiotics known for nephrotoxicity (vancomycin, amikacin, gentamicin, tobramycin, and teicoplanin) for the improvement of TDM in South Korea among patients with infectious diseases using a cross-sectional nationwide survey. Patients and methods We developed an online questionnaire and collected responses using a user-friendly web-based platform. The survey included questions about laboratory characteristics, implementation and operation of drug assays, implementation and operation of TDM consulting services, patient needs, and barriers to providing better TDM service including expectations and concerns about other platform-based drug assays. Results Among a total of 235 clinical laboratories, 112 (47.7%) responded, and 62 of the responding laboratories (55.4%) possessed drug assay facilities. Only 41.2% to 58.1% of respondents were providing TDM consulting services for each antibiotic. Respondents indicated that there are unmet needs regarding drug assays and TDM consultation as well as barriers to TDM utilization including high operating costs, lack of knowledge about TDM, lack of user-friendly software, lack of medical and laboratory information systems that can access patient information critical for TDM dose calculation, and reimbursement issues. Conclusion This study, the first nationwide survey addressing these questions, showed that there are barriers against the utilization of TDM in South Korea. These barriers may be addressed by improving drug assays and TDM consulting services with the goals of new analytical method development, better interpretation of results, consultation services, and quality control.

AIMS: We aimed to investigate the impact of various genetic polymorphisms affecting thiopurine metabolism pathways and toxicity in paediatric acute lymphoblastic leukaemia patients for the first time in Korea. METHODS: From May 2006 to September 2016, 139 paediatric acute lymphoblastic leukaemia patients treated with combination chemotherapy including 6‐mercaptopurine were included in the study. One hundred and twenty‐three variants in 43 genes, including TMPT and NUDT15, were screened using targeted genotyping, such as a MassARRAY system, direct sequencing and polymerase chain reaction‐restriction fragment length polymorphism methods. Among the polymorphisms screened, 103 polymorphisms of 43 genes were included for further analyses. RESULTS: The genetic polymorphisms in the ABCC4, AHCY, ATIC, FAM8A6P, GART, GNG2, GSTA1, MTHFD1, MTHFR, NUDT15, PACSIN2, TYMS and XDH genes, and an intronic polymorphism between HIVEP2 and AIG1, and TPMT genotype were associated with thiopurine metabolism (P

Background Screening for congenital adrenal hyperplasia (CAH) using immunoassays for 17α-hydroxyprogesterone generates many false-positive results. We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous quantification of nine steroid hormones in dried blood spot (DBS) samples, and established reference intervals for these hormones. Methods We examined our method for linearity, precision, accuracy, extraction recovery, and matrix effects and determined the reference intervals of cortisol, 17α-hydroxyproges-terone, 11-deoxycortisol, 21-deoxycortisol, androstenedione, corticosterone, 11-deoxycorticosterone, testosterone, and progesterone in 1,146 DBS samples (from 272 preterm and 874 full-term neonates). Immunoassay and LC-MS/MS methods were compared for 17α-hydroxyprogesterone. Fourteen additional samples were tested to validate the clinical applicability of the LC-MS/MS method. Results The linearity range was 2.8–828.0 nmol/L for cortisol and 0.9–40.0 nmol/L for the other steroids (R2>0.99). Intra-day and inter-day precision CVs were 2.52–12.26% and 3.53–17.12%, respectively. Accuracy was 80.81–99.94%, and extraction recovery and matrix effects were 88.0–125.4% and 61.7–74.2%, respectively. There was a negative bias, with higher values measured by immunoassay compared with LC-MS/MS (r=0.8104, P

We retrospectively reviewed the estimated glomerular filtration rates (eGFR) calculated by three equations: (1) Modification of Diet in Renal Disease Study (MDRD), (2) Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) using serum creatinine in 2009 (CKD-EPI 2009), and (3) CKD-EPI suggested in 2021 (CKD-EPI 2021), in an adult Korean population visiting local clinics and hospitals for health check-ups between 2019 and 2021 to investigate the effect of changes in the prevalence of chronic kidney diseases using those equations. During the study period, serum creatinine tests were performed on 442,566 subjects (205,236 men and 237,330 women). The overall prevalence rates of decreased eGFR ( 30 mg/g creatinine), while those based on CKD-EPI 2021 were about half of those based on MDRD and CKD-EPI 2009. Future studies are needed to clarify the clinical impact of the changes in the calculations for eGFR.

BACKGROUND We aimed to investigate test utilization of the competition-based M22 thyroid-stimulating hormone receptor antibody (M22-TSH Rc Ab) and thyroid stimulating immunoglobulin (TSI) bioassay in Korea. METHODS We retrospectively reviewed data on M22-TSH Rc Ab assays and TSI assays from the laboratory information system between January 1, 2015, and June 30, 2020. RESULTS During the study period, 175,448 TSH-Rc Ab tests and including M22-TSH Ab assays and TSI assays were performed on 99,350 Korean adults (26,251 men and 73,099 women). Among 160,880 M22-TSH Rc Ab tests, 1,992 (1.2%) specimens from 1,771 Korean adults had undergone concurrent measurement with M22-TSH Rc Ab and TSI assays. The overall agreement between the M22-TSH-Rc Ab assay and TSI assay was 88.8% (95% confidence interval 87.3 - 90.1). CONCLUSIONS The results of this study provide basic information regarding test utilization of the M22-TSH-Rc Ab assay and TSI assay in Korean patients.

Background The aim of this study was to investigate the seroprevalence of cytomegalovirus (CMV) infection using the serologic status of CMV IgG and IgM antibodies in Korean women of childbearing age. Methods We retrospectively reviewed CMV IgG and IgM test results from Korean women aged 15–49 years who underwent testing between January 2009 and December 2019. Seroprevalence of CMV IgG and IgM by year and age was investigated. Results The study period was 11 years, and among 6837 samples tested, 95.8% were CMV IgG–positive. The seropositivity in women aged 15‐

Background When measuring thyroglobulin (Tg), simultaneous measurement of Tg autoantibodies (Ab) is recommended by clinical guidelines for follow-up of patients with differentiated thyroid cancers after thyroidectomy and radioactive iodine ablation. We aimed to investigate test utilization of Tg and Tg Ab assays in local clinics and hospitals in Korea. Methods We retrospectively reviewed data from the laboratory information system between November 6, 2017 and December 31, 2019. Results During the study period, 10,551 Tg tests were performed on 2,592 Korean adults from 97 local clinics and hospitals. Among them, 3,924 (37.2%) test results lacked concurrent Tg Ab assays, while 6,627 test results had concurrently measured Tg Ab, and 528 (8.0%) showed positive Tg Ab results, which could interfere with measurement of Tg concentration. Conclusions The results of this study provide basic information regarding test utilization of Tg Ab assays to improve test utilization for accurate Tg measurement in Korean patients.

We aimed to investigate serum folate level in Korean women of reproductive age and to evaluate the prevalence of folate deficiency by age using different cutoffs.We retrospectively reviewed data obtained with a serum folate assay traceable to World Health Organization international standard reference material 03/178.Between September 2017 and June 2019, data from a total of 8,380 Korean women aged 15 - 49 years were obtained. Mean (standard deviation) serum folate concentration for all women was 9.1 (6.7) ng/mL. Prevalence of folate deficiency using the cutoff of3 ng/mL was 6.2% and that for4 ng/mL was 14.9%. The prevalence of folate deficiency was higher in women of younger age (15 to25 years, even30% using the cutoff of 4 ng/mL) compared to other age groups.This study suggests that women aged 15 to25 years are at high risk of folate deficiency.

The gold standard for the laboratory diagnosis of central precocious puberty is based on the measurement of luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) stimulation. We sought to investigate the laboratory data for GnRH stimulation testing using samples collected from Korean children at different time points. Sampling times were at the basal time point (0) and 15, 30, 45, 60, 90, and 120 min after GnRH stimulation. Pubertal response was defined as occurring when the peak LH concentration was 5 IU/L or more and rose to at least 2 times the basal LH concentration after GnRH stimulation. During the study period, 19,990 test results from 1958 Korean children (1841 females aged 1.3&ndash, 8.9 years and 117 males aged 7.3&ndash, 9.9 years) were obtained. Among the 1958 children, 1232 (62.9%) showed pubertal responses. The receiver operating characteristic curve that demonstrated the greatest area under the curve (AUC) among all examined time points was 45 min after GnRH stimulation in males (AUC 0.982, 95% CI 0.938&ndash, 0.998) and 60 min in females (AUC 0.975, 95% CI 0.967&ndash, 0.981). The combination of 45 min and 60 min showed the greatest AUC (0.996, 95% confidence interval 0.991&ndash, 0.998), with a sensitivity level of 99.1% and a specificity of 100% for all children. The results of this study provide a possibility for a reduction in sampling time points (45 min and 60 min) to identify the presence of a pubertal response after GnRH stimulation in Korean children.

BACKGROUND Little is known about the reference interval of serum folate concentration if using recently re-standardized assays traceable to the World Health Organization (WHO) international standard reference 03/178 in a Korean population. This study aimed to investigate serum folate levels in Korean subjects without macrocytic anemia or increased homocysteine, for the assessment of folate deficiency. METHODS We retrospectively reviewed data from Korean adults whose hemoglobin, mean corpuscular volume, and serum total homocysteine values were within reference limits. RESULTS The median (interquartile range) serum folate level was 7.8 (5.4 - 12.6) ng/mL in men and 10.2 (6.9 - 15.6) ng/mL in women. The reference interval for serum folate (2.5th and 97.5th percentiles) ranged from 2.9 to 38.0 ng/ mL. From among 723 Korean adults, the lower limit of reference intervals of serum folate for folate deficiency, defined as the 2.5th percentile, was 2.9 ng/mL. The prevalence of folate deficiency was higher in men (6.5%) than in women (1.2%, p < 0.05) when a cutoff value of 3.0 ng/mL was applied. Using the cutoff value of 4 ng/mL for folate deficiency, which is in accordance with the instructions from the manufacturer of the new assay and the WHO 2012 guideline for homocysteine as a metabolic indicator before assay standardization, about 5% of subjects were reclassified as folate deficient. CONCLUSIONS Our study suggests that any change of reference limits using a re-standardized assay needs to be verified in clinical laboratories.

Background Large inter-individual variations in drug metabolism pose a challenge in determining 6-mercaptopurine (6MP) doses. As the last product of 6MP metabolism, DNA-thioguanine nucleotide (DNA-TGN) could reflect the efficacy of 6MP, especially in patients harboring variants in the 6MP metabolism pathway. The aim of this study was to investigate the clinical significance of DNA-TGN monitoring in Korean pediatric acute lymphoblastic leukemia (ALL) patients, focusing on the NUDT15 genotype. Methods The subjects of this study were patients who underwent ALL treatment with 6MP. Tests for the NUDT15 and TPMT genotypes were performed, and prospective DNA-TGN and erythrocyte TGN samples were collected after two weeks or more of 6MP treatment. DNA-TGN was quantified using the liquid chromatography-tandem mass spectrometry method. Results A total of 471 DNA-TGN measurements in 71 patients were analyzed, which ranged from 1.0 to 903.1 fmol thioguanine/μg DNA. The 6MP intensity demonstrated a significant relationship with DNA-TGN concentration (PNUDT15 variants were treated with a lower dose of 6MP (PNUDT15 (P = 0.261). These patients also presented higher variation in DNA-TGN levels (P = 0.002) and DNA-TGN/6MP intensity (P = 0.019) compared to patients carrying wild-type NUDT15. DNA-TGN concentration did not show a significant correlation with WBC count (P = 0.093). Conclusions Patients harboring NUDT15 variants demonstrated similar DNA-TGN concentrations even at low doses of 6MP and showed high variability in DNA-TGN. Particularly in patients with NUDT15 variants who need a reduced 6MP dose, DNA-TGN could be applied as a useful marker to monitor the therapeutic effect of 6MP.

BACKGROUND Limited data are available for test utilization and intraindividual changes in anti-thyroid peroxidase antibodies (anti-TPO Ab) in Korean patients. METHODS Using a laboratory information system, we retrospectively investigated longitudinally measured anti-TPO Ab along with thyroid function test (TFT) in Korean patients visiting local clinics. RESULTS During the two-year study period, 542 test results from 183 Korean patients were requested from 51 local clinics and hospitals. Among all 183 patients, 94 (51.4%) exhibited positive anti-TPO Ab (> 34 IU/mL) at initial measurement. Among them, 13.8% (13/94) changed to negative anti-TPO Ab at least once during follow-up. Among 89 patients with initial negative anti-TPO Ab result, five (5.6%) changed to positive anti-TPO Ab at least once during follow up. CONCLUSIONS Some patients exhibited qualitative changes in anti-TPO Ab. Future studies are needed to clarify the clinical implication of such changes.

We retrospectively reviewed serum 25-hydroxy vitamin D (25(OH)D) test results from an adult Korean population visiting local clinics and hospitals between July 2017 and December 2021 to gather recent information on the prevalence of vitamin D deficiency. The prevalence of vitamin D deficiency status was investigated according to criteria offered by various clinical guidelines. During the study period, 180,289 subjects (29,658 men and 150,631 women) were tested for 25(OH)D. The overall prevalence rates of vitamin D deficiency status based on 25(OH)D level were as follows: 0.4% for

Background Current guidelines pertaining to diagnosing macrocytic anemia in association with vitamin B12 and folate deficiency recommend that vitamin B12, folate, homocysteine, and methylmalonic acid assays should be assessed concurrently due to their close relationship in metabolism. We aimed to investigate the completion of these assays in local clinics and hospitals without in‐house clinical laboratories in Korea. Methods We retrospectively reviewed data from the laboratory information system between September 25, 2017, and June 30, 2019, to investigate usage rates of vitamin B12, folate, homocysteine, and methylmalonic acid assays in patients with macrocytic anemia. Results During the study period, 14 894 Korean adults among 109 524 (13.6%) total hemoglobin‐tested subjects underwent concurrent erythrocyte mean corpuscular volume (MCV) tests. Among these 14,894 adults, 265 (1.2%) from 94 local clinics or hospitals without in‐house clinical laboratories in Korea had macrocytic anemia. Furthermore, among these 265 adults, only one woman underwent serum vitamin B12 and folate assay and one man underwent serum homocysteine testing during the study period. No patients among the 265 individuals with macrocytic anemia received erythrocyte folate or methylmalonic acid testing (with either serum, plasma, random urine, or 24‐hour collected urine). Conclusions The results of this study provide basic information regarding utilization rates of assays in association with vitamin B12 and folate deficiency. Making more data available is expected to improve rates of testing in patients with macrocytic anemia in local clinics and hospitals without in‐house clinical laboratories in Korea.

Numerous studies have shown that vitamins reduce the risk of cancers, but the relationship between serum vitamin levels and breast cancer is still controversial. In this study, we evaluated serum levels of vitamins in Korean patients with benign breast disease or breast cancer and investigated their associations with clinical and laboratory parameters. Concentrations of vitamin A, D, and E, together with homocysteine and methylmalonic acid as biomarkers of vitamin B12 deficiency, were measured by high-performance liquid chromatography (HPLC) or liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the serum of 104 breast cancer patients, 62 benign breast disease patients, and 75 healthy Korean females. We further assessed possible associations between vitamin levels and breast cancer subtypes, the presence of lymph node metastasis, and tumor stages. Serum concentrations of vitamins A and E were significantly lower in breast cancer patients and in benign breast disease patients than in healthy controls. Severe vitamin D deficiency was more prevalent in breast cancer patients than in healthy controls. Vitamin D level was significantly lower in breast cancer patients with estrogen receptor-negative or triple-negative subtypes than in those with other subtypes. Further research with a larger study population is required to elucidate the role of vitamins in breast cancer.

Background We developed an assay to measure DNA-incorporated 6-thioguanine (DNA-TG) and validated its clinical applicability in Korean pediatric patients with acute lymphoblastic leukemia (ALL) in order to improve individualized thiopurine treatment and reduce the life-threatening cytotoxicity. Methods The DNA-TG assay was developed based on liquid chromatography-tandem mass spectrometry, with isotope-labeled TG-d3 and guanine-d3 as internal standards. This method was applied to 257 samples of pediatric ALL patients. The DNA-TG level was compared with erythrocyte TG nucleotide (RBC-TGN) level in relation to the TPMT and NUDT15 genotypes, which affect thiopurine metabolism, using Spearman’s rank test and repeated measure ANOVA. Results For DNA-TG quantification, a linearity range of 10.0-5,000.0 fmol TG/µg DNA; bias for accuracy of –10.4% –3.5%; coefficient of variation for intra- and inter-day precision of 3.4% and 5.8% at 80 fmol TG/µg DNA and of 4.9% and 5.3% at 800 fmol TG/µg DNA, respectively; and recovery of 85.7%–116.2% were achieved without matrix effects or carry-over. The median DNA-TG level in the 257 samples was 106.0 fmol TG/µg DNA (interquartile range, 75.8–150.9). There was a strong correlation between DNA-TG and RBC-TGN levels (ρ = 0.68, P < 0.0001). The DNA-TG/RBC-TGN ratio was significantly higher in NUDT15 intermediate metabolizers (*1/*2 and *1/*3) than in patients with wildtype alleles (P < 0.0001). Conclusions This simple and sensitive method for measuring DNA-TG level can improve therapeutic drug monitoring for thiopurine treatment.

BACKGROUND We retrospectively investigated soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratios and screen-positive rates according to cutoff values for preeclampsia risk assessment based on the number of fetuses. METHODS sFlt-1/PlGF ratios < 38.0 and < 53.0 were defined as low risk of preeclampsia (screen negative) for singleton and twin pregnancies, respectively. RESULTS During the study period, 442 test results from 403 pregnant women (374 with singleton and 29 twin pregnancies) from 32 local clinics and hospitals were analyzed. The overall rate of positive preeclampsia screening was 25.1% and this rate was higher when gestational age was ≥ 34 weeks than when it was < 34 weeks (58.7% vs. 18.6%, p < 0.05). Among 34 women with follow-up results, a change in interpretation category was observed during the follow-up period at ≥ 4.8 weeks for singleton and ≥ 1.6 weeks for twin pregnancies, respectively. CONCLUSIONS This study may help to understand the sFlt-1/PlGF ratio in pregnant Korean women.

IgG consists of four subclasses: IgG1, IgG2, IgG3, and IgG4. Changes in the serum concentration of each subclass reflect different clinical situations, and quantification of each subclass is important to assess patients' clinical states. Herein, we evaluated the analytical performance of the SPAPLUS turbidimetric analyzer (The Binding Site, Birmingham, UK) for IgG subclass. Precision, linearity, comparison with the BNII system (Siemens Healthineers, Erlangen, Germany), and reference interval were assessed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The repeatability and within-laboratory precision were within 5% for all IgG subclasses. The coefficient of determination (R

We developed and validated a quantification method for methotrexate (MTX) polyglutamates (MTX-PGs, MTX-PG1 to MTX-PG5) by liquid chromatography-tandem mass spectrometry using stable isotope-labeled internal standards and applied to 196 clinical samples collected from pediatric acute lymphoblastic leukemia patients treated with MTX. MTX-PGs levels and their proportions (%) in sum of all MTX-PGs (MTXSum) were evaluated in relation to TPMT, NUDT15, and MTHFR genotypes. For the developed method, linearity ranges 1-500 nmol/L, bias for accuracy 0.3-13.5 %, coefficient of variation for within- and between-run imprecision of 3.2-9.5% and 1.5-12.0%, respectively. Recoveries achieved were 74.2-105.8 %. There was no significant carryover. The median level of the MTXSum for 196 clinical samples was 129.4 nmol/L (interquartile range 28.1-241.2). MTX dose and MTX-PGs were associated (P < 0.05) and among five MTX-PGs, MTX-PG3 was the predominant form (median 41.7 %). The MTX-PG3 level was significantly higher in patients with TPMT *1/*3C than in patients with wild type and MTX-PG3% was significantly higher and MTX-PG5% was significantly lower in NUDT15 intermediate metabolizers than normal or indeterminate phenotypes (P < 0.05). This validated MTX-PGs quantification method can facilitate a better understanding of MTX metabolism and therapeutic drug monitoring for MTX treatment.

Purpose We aimed to identify the impact of NUDT15 variants on thiopurine intolerance and 6-thioguanine nucleotide (6-TGN) levels in Korean children with acute lymphoblastic leukemia (ALL). Materials and methods Genotyping of NUDT15 was tested in 258 patients with ALL registered at Samsung Medical Center. Patients were classified into normal-activity (wild-type), intermediate-activity (heterozygous variant), and low-activity groups (homozygous or compound heterozygous variant). Clinical and laboratory features during the first year of maintenance therapy were investigated. Results A total of 182 patients were included in the final analysis. There were five (2.7%), 46 (25.3%), and 131 (72.0%) patients in low-, intermediate-, and normal-activity groups, respectively. The lowest 6-mercaptopurine (6-MP) dose (mg/m2/day) was administered to the low-activity group (low-activity group 7.5 vs. intermediate-activity group 24.4 vs. normalactivity group 31.1, p l 0.01) from three months to a year after beginning maintenance therapy. The low-activity group experienced the longest duration of therapy interruption during the first year (low-activity group 169 days vs. intermediate-activity group 30 days vs. normal-activity group 16 days, p l 0.01). They also showed the lowest blood cell counts and had a longer duration of leukopenia (low-activity group 131 days vs. intermediate-activity group 92 days vs. normal-activity group 59 days, p l 0.01). 6-TGN level and its ratio to 6-MP dose were lowest in the low-activity group. Conclusion NUDT15 variants cause hematopoietic toxicity with low 6-TGN levels. NUDT15 genotyping should be conducted before administering thiopurine, and dose adjustments require caution regardless of 6-TGN levels.