The experience and reflections of GC labs as an independent clinical laboratory to the COVID-19 pandemic in South Korea.

BACKGROUND: Amid the COVID-19 pandemic, extensive testing was undertaken by independent clinical laboratories (ICLs), yet limited research exists on this matter. Drawing from Green Cross Laboratories (GC Labs)' pandemic response experience, this study seeks to offer insights for preparation for the next pandemic. METHODS: This retrospective study analyzed the outcomes of SARS-CoV-2 real-time reverse transcription polymerase chain reaction (SARS-CoV-2 rRT PCR) tests administered by GC Labs for COVID-19 diagnosis, upon request by different organizations, between February 2020 and April 2022. The distribution of institutions that requested the tests, the type of tests, and the positive rate were analyzed. We investigated resource allocation details. RESULTS: ICLs were responsible for conducting 85.6% of all tests carried out under South Korea's COVID-19 testing policy during the pandemic. The availability of free testing regardless of symptoms led to a significant increase in the use of pooled tests, which accounted for more than 80% of all tests conducted after August 2021. The gender and age distribution of COVID-19 cases nationwide and GC Labs' positive cases were similar. When we analyzed the positive rate by requesting organizations during the COVID-19 pandemic, despite an overall nationwide positivity rate of 35%, high-risk facilities exhibited a positivity rate of less than 5% by maintaining preemptive testing. The most notable increase in resources during the pandemic was seen in human resource input. CONCLUSIONS: South Korea's ICLs were able to conduct large volumes of testing during the COVID-19 pandemic because of their logistics and computer systems, scalable testing space, and trained testing personnel. They also had the flexibility to bring in additional resources to expand testing capacity because they are specialized testing organizations. Hence, ICLs could execute the pooled test that the government had introduced for extensive general population screening. The preemptive periodic testing of high-risk populations kept the positive rate much lower than in the general population. This study's findings will aid in refining mass testing-based policies for the next pandemic.

Understanding the Utilization of the Krebs von den Lungen 6 Test in a Clinical Laboratory.

BACKGROUND: We aimed to investigate Krebs von den Lungen 6 (KL-6) assay results in a clinical laboratory to better understand patient population and test utilization. METHODS: We investigated serum KL-6 test results in Korean adults by the type of medical institution visited between October 2019 and December 2021. RESULTS: Overall, 7,677 KL-6 tests were performed in 5,527 Korean adults (3,627 men and 1,900 women) with a median age of 68.3 years (interquartile range 59.6 - 75.8). The median KL-6 level in 507 patients who visited health promotion centers was lower than the other 5,020 patients who visited other types of medical institutions (196 U/mL vs. 588.0 U/mL, respectively, p < 0.05). Increased KL-6 levels (≥ 500 U/mL) were observed in 0.8% of patients who visited health promotion centers and in 57.1% of patients who visited other types of medical institutions. CONCLUSIONS: This study will help to understand patient populations and test utilization for KL-6 in clinical laboratories in Korea.

Understanding Utilization and Seroprevalence of Syphilis Tests in Local Clinics and Hospitals in Korea.

BACKGROUND: Diagnosis of syphilis, a sexually transmitted infection, can be based on clinical information and various combinations of results of both non-treponemal and treponemal assays. Because understanding a patient population is helpful for test utilization in the clinical laboratory, we aimed to investigate the results of syphilis serology tests requested from local clinics in Korea. METHODS: We retrospectively evaluated the syphilis serology test results of serum Rapid Plasma Reagin (RPR), Treponema pallidum latex agglutination (TPLA), RPR titer, and fluorescent treponemal antibody absorption (FTA-ABS) IgG, and IgM tests performed in Korean adults in the laboratory information system of Green Cross Laboratories. We investigated the patterns of syphilis serology test results and possible interpretation according to combinations of syphilis serology based on a traditional testing algorithm. RESULTS: During the one-year study period, 33,746 RPR tests were performed in Korean adults (7,622 men and 26,124 women) with a median age of 35.1 years (interquartile range 30.8 - 43.4 years). Among these RPR tests, 317 (0.9%) showed RPR+ results and were performed simultaneous with TPLA tests. Among these 317 patients, 187 (59.0%) had RPR+/TPLA+ results. Among 130 patients with RPR+/TPLA- results, FTA-ABS IgG and IgM were only tested in 15 (11.5%): 14 were IgG-/IgM-, and one who underwent only the IgM test showed a negative result (probably a biological false positive of RPR). Among 187 RPR+/TPLA+ patients, 60 (2.1%) had RPR titer ≥ 1:8, and 10 were FTA-ABS IgM+ (including weak reactive results probably due to current infection or rare biological false-positive). Among 121 patients with RPR+/TPLA+/RPR titer ≤ 1:4, 30 were tested for FTA-ABS IgG and/or IgM: the two FTA-ABS IgM+ (including weak reactive) patients had an RPR titer of 1:4. CONCLUSIONS: This study will help to understand patient populations and test utilization for syphilis serology test interpretation in clinical laboratories in Korea. Further studies are needed to investigate the clinical impact of test utilization of syphilis serology in Korea.

Blockchain-Based Federated Learning System: A Survey on Design Choices.

The vanilla federated learning is made for a trusted environment, while in contrast, its actual use cases require collaborations in an untrusted setting. For this reason, using blockchain as a trusted platform to run federated learning algorithms has gained traction lately and has become a significant research interest. This paper performs a literature survey on state-of-the-art blockchain-based federated learning systems and analyzes several design patterns researchers often take to solve existing issues through blockchain. We find about 31 design item variations throughout the whole system. Each design is further analyzed to find pros and cons, considering fundamental metrics such as robustness, efficiency, privacy, and fairness. The result shows a linear relationship between fairness and robustness in which, if we focus on improving fairness, it will indirectly become more robust. Furthermore, improving all those metrics altogether is not viable because of the efficiency trade-off. Finally, we classify the surveyed papers to spot which designs are popular among researchers and determine which areas require immediate improvements. Our investigation shows that future blockchain-based federated learning systems require more effort regarding model compression, asynchronous aggregation, system efficiency evaluation, and the application for cross-device settings.

Correction: Witanto et al. Distributed Data Integrity Verification Scheme in Multi-Cloud Environment. Sensors 2023, 23, 1623.

The authors make the following corrections to the published paper [...].

Distributed Data Integrity Verification Scheme in Multi-Cloud Environment.

Most existing data integrity auditing protocols in cloud storage rely on proof of probabilistic data possession. Consequently, the sampling rate of data integrity verification is low to prevent expensive costs to the auditor. However, in the case of a multi-cloud environment, the amount of stored data will be huge. As a result, a higher sampling rate is needed. It will also have an increased cost for the auditor as a consequence. Therefore, this paper proposes a blockchain-based distributed data integrity verification protocol in multi-cloud environments that enables data verification using multi-verifiers. The proposed scheme aims to increase the sampling rate of data verification without increasing the costs significantly. The performance analysis shows that this protocol achieved a lower time consumption required for verification tasks using multi-verifiers than a single verifier. Furthermore, utilizing multi-verifiers also decreases each verifier's computation and communication costs.

Seroprevalence of Anti-Thyroglobulin Antibodies in Korea.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The Tg Ab test appears to be underutilized in Korea.

Intraindividual Changes in Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Performed in Korean Subjects.

BACKGROUND: 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. METHODS: Through a laboratory information system, we retrospectively investigated longitudinally measured M2BPGi to assess intraindividual changes in M2BPGi test results. 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. CONCLUSIONS: Some subjects exhibited qualitative changes in M2BPGi during follow-up health examinations. Future studies are needed to clarify the clinical implication of such changes.

Method Performance Verification of Anti-GAD65 and Anti-Insulin antibody Assays.

BACKGROUND: The aim of this study was to evaluate the performance of chemiluminescence immunoassays for anti-GAD65 and anti-insulin antibodies following user verification guidelines. METHODS: 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. RESULTS: 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. CONCLUSIONS: The results of this study verified the analytical performance of MAGLUMI anti-GAD65 and anti-insulin antibody assays for clinical use.

Reference intervals of anti-Müllerian hormone in Korean women.

BACKGROUND: Limited data are available with reference intervals of serum anti-Müllerian hormone (AMH) level in Korean women. METHODS: 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. RESULTS: 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. CONCLUSION: Understanding patient populations and differences in reference intervals by age group and measurement method can help guide clinical decisions and clinical laboratory analysis.

Biological variation and reference change values of serum Mac-2-binding protein glycosylation isomer (M2BPGi).

BACKGROUND: Limited data are available with regard to biological variations of the Mac-2-binding protein glycosylation isomer (M2BPGi), a liver fibrosis biomarker. METHODS: 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). RESULTS: 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 (CVI ), between-subject biological variation (CVG ), analytical variation (CVA ), RCV, and individuality index (II) values for serum M2BPGi were 23.3%, 30.0%, 4.3%, 65.6%, and 0.78, respectively. Asymmetric RCV calculated using formulae by a recent EFLM TG-BVD publication ranged from -41.9 to 72.0%. Desirable analytical performance specifications for M2BPGi derived from biological variation were as follows: imprecision 11.6%, bias 9.6%, and total allowable error 28.7%. CONCLUSIONS: RCV based on biological estimates may be helpful for evaluating and interpreting serial M2BPGi measurements by physicians and in clinical laboratories.

Utilization of Anti-Thyroid Peroxidase Antibody in Local Clinics and Hospitals and Intraindividual Changes in Korean Patients.

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.

Test Utilization for Thyroglobulin and Anti-Thyroglobulin Antibody Assays in Korea.

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.

Prevalence of Folate Deficiency in Korean Women of Reproductive Age Using a Serum Folate Assay Traceable to the WHO International Standard.

BACKGROUND: 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. METHODS: We retrospectively reviewed data obtained with a serum folate assay traceable to World Health Organization international standard reference material 03/178. RESULTS: 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 of < 3 ng/mL was 6.2% and that for < 4 ng/mL was 14.9%. The prevalence of folate deficiency was higher in women of younger age (15 to < 25 years, even > 30% using the cutoff of 4 ng/mL) compared to other age groups. CONCLUSIONS: This study suggests that women aged 15 to < 25 years are at high risk of folate deficiency.

Association Among Glycemic Biomarkers in Korean Adults: Hemoglobin A1c, Fructosamine, and Glycated Albumin.

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.

Test Utilization for Thyroid Stimulating Hormone Receptor Antibody and Thyroid Stimulating Immunoglobulin Assays in Korea.

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.

Thyroid Function Tests in the First Trimester of Pregnancy According to Maternal Age in Asia.

BACKGROUND: The American Thyroid Association suggested selective performance of the thyroid function test (TFT) in pregnant women with risk factors such as age over 30 years. We evaluated the limited indication of TFT based on age by analyzing our institution's retrospective data about TFT in pregnant women. METHODS: We retrospectively analyzed the results of thyroid stimulating hormone (TSH) and free thyroxine (FT4) with the antithyroid autoantibody test using the Cobas 8000 e801 module (Roche Diagnostics, Mannheim, Germany) performed during the first trimester of pregnancy. Data were analyzed and compared between subjects younger or older than 30 years. RESULTS: The mean values of TSH and FT4 did not show any significant differences according to age. Also, the two groups had similar prevalence of overt/subclinical hypothyroidism. It was analyzed that over 20% of overt hypothyroidism could be missed by applying age-based screening. CONCLUSIONS: Selective screening according to age (> 30 years) can miss a considerable number of pregnant women with hypothyroidism. Considering the value of appropriate screening and treatment in pregnant women with hypothyroidism, universal screening is necessary rather than selective screening considering the age of pregnant women.

Reference Interval for Korean Serum Folate Assay Traceable to the WHO International Standard.

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.

Validation of multiple equations for estimating low-density lipoprotein cholesterol levels in Korean adults.

BACKGROUND: Limited data are available for validation of low-density lipoprotein cholesterol (LDL) calculation (LDLcal) in the adult Korean population. The aim of this study was to develop and validate a new equation for LDLcal and to compare it with previous such equations in a Korean population. METHODS: A new equation for LDLcal was developed (LDLChoi). LDLChoi and 11 other previously published equations were applied and compared with directly measured LDL concentration (LDLdirect) in a development cohort (population 1), an independent validation cohort in the same laboratory (population 2), and the Korea National Health and Nutrition Examination Survey 2017 cohort (population 3). RESULTS: Among the 12 equations, the newly-developed equation (LDLChoi = total cholesterol - 0.87 x high-density lipoprotein cholesterol - 0.13 x triglycerides) had the highest intraclass correlation coefficient (ICC) and the lowest mean systemic difference and median absolute percentage error in populations 1 and 2 but not in population 3. Subgroup analysis showed good agreement between LDLChoi and LDLdirect (ICC > 0.75) in population 2, whose LDLdirect < 70 mg/dL. For samples with high triglycerides (> 400 mg/dL), equation accuracy varied. Categorization concordance according to the National Cholesterol Education Program Adult Treatment Panel III criteria with the other 11 equations were less than 80%; that of LDLChoi was 87.6 and 87.4% in populations 1 and 2, respectively. CONCLUSIONS: Accuracy of 12 equations for LDLcal varied by cohort and subgroup based on LDLdirect and triglycerides. A laboratory-specific equation for LDLcal and/or LDLdirect may be needed for accurate evaluation of LDL status.

Underutilization of diagnostic assays for celiac disease in Korea.

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.