Comparative Analysis of Seven Equations for Estimated Glomerular Filtration Rate and Their Impact on Chronic Kidney Disease Categorization in Korean Patients at Local Clinics and Hospitals.

(1) Background: Accurate estimation of the glomerular filtration rate (eGFR) is essential for the early detection of chronic kidney disease (CKD), targeted interventions, and ongoing monitoring. Although various equations for calculating eGFR exist, comparative studies on eGFR levels and the impact of these equations on CKD prevalence are limited in the Korean population. (2) Methods: We compared eGFR levels calculated using seven equations and investigated the prevalence of CKD through a retrospective analysis of the data from Korean adult patients who visited local clinics and hospitals and underwent simultaneous serum creatinine (Cr) and cystatin C (Cys-C) measurements. The equations analyzed were: 2006 MDRD, 2009 CKD-EPI Cr, 2012 CKD-EPI Cys-C, 2012 CKD-EPI Cr & Cys-C, 2021 CKD-EPI Cr, 2021 CKD-EPI Cr & Cys-C, and 2021 EKFC. (3) Results: This study included 6688 Korean patients (3736 men and 2952 women; median age: 61.4; IQR: 47.2-73.4). Among the equations, the median eGFR levels were the highest when using the 2021 CKD-EPI Cr & Cys-C equation (85.1 mL/min/1.73 m2) and the lowest when using the 2006 MDRD equation (73.4 mL/min/1.73 m2). The highest prevalence of decreased eGFR < 60 mL/min/1.73 m2 (equivalent to or worse than G3a CKD) was noted with the 2012 CKD-EPI Cys-C equation (32.4%), while the lowest was with the 2021 CKD-EPI Cr equation (22.9%), resulting in a maximum prevalence difference of 9.5%. (4) Conclusions: The prevalence of CKD varies based on the eGFR equation used and the patient's age. Equations that include Cys-C may identify a larger number of patients with decreased kidney function.

Gender differences in hepatitis A seropositivity rates according to the Republic of Korea's vaccination policy.

BACKGROUND: This study aimed to investigate differences in the anti-hepatitis A virus (HAV) antibody seropositivity rate by age and gender. METHODS: We collected information on anti-HAV immunoglobulin G and immunoglobulin M status from samples submitted for HAV antibody testing in 2012-2022. A total of 1,333,615 cases were included in the analysis. RESULTS: By age, the seropositivity rate was represented by a U-shaped curve, such that the rate was low for the group aged 20 to 39 years and higher in those who were younger or older. Over time, the curve shifted rightward, and the seropositivity rate declined gradually in the group aged 35 to 39 years and older. A gender-based difference in antibody seropositivity rate was especially noticeable in the group aged 20 to 29 years. This difference between genders widened in the participants' early 20s-when men in the Republic of Korea enlist in the military-and the divergence continued subsequently for older individuals. CONCLUSION: These results indicate a higher risk of severe infection among older individuals and a gender-based difference in seroprevalence. Therefore, it is necessary to implement policies to promote vaccination in adults.

Effect of Adding Apolipoprotein B Testing on the Prevalence of Dyslipidemia and Risk of Cardiovascular Disease in the Korean Adult Population.

Traditional lipid parameters-including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and non-HDL-C (calculated as TC minus HDL-C)-have long been used as indicators of cardiovascular disease (CVD) risk. The laboratory records of 9604 Korean adults who underwent traditional lipid panel tests (TC, TG, and HDL), as well as ApoB testing, were analyzed to evaluate the prevalence of dyslipidemia and high CVD risk (utilizing the NCEP ATP III criteria for traditional lipid panels and various ApoB test cutoffs recommended by international guidelines (145 mg/dL, 130 mg/dL, and 100 mg/dL)). The overall prevalence of dyslipidemia, as determined by traditional lipid panel criteria, was 27.4%. Utilizing the ApoB cutoffs of 145 mg/dL, 130 mg/dL, and 100 mg/dL resulted in prevalence figures of 5.3%, 11.0%, and 36.3%, respectively. The concordance in dyslipidemia classification between traditional lipid tests and ApoB at cutoffs of 145 mg/dL, 130 mg/dL, and 100 mg/dL was 78.4%, 81.3%, and 74.7%, respectively. Up to 17.5% of participants, based on an ApoB cutoff of ≥100 mg/dL, exhibited isolated high ApoB in the absence of traditional lipid test anomalies. Incorporating ApoB testing could enhance the identification of Koreans at high CVD risk.

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.

Exploring Utilization and Establishing Reference Intervals for the Apolipoprotein B Test in the Korean Population.

We investigated the reference intervals for Apolipoprotein B (ApoB), a valuable biomarker for cardiovascular diseases, in Korean adults who had undergone health check-ups and showed normal lipid levels under traditional lipid tests, including total cholesterol, triglyceride, and high-density lipoprotein cholesterol, along with ApoB. We compared the findings with different cutoffs for ApoB from international clinical guidelines. Among a total of 264,105 traditional lipid test sets, only 464 (0.2%) included ApoB tests, indicating underutilization of this test in health check-up clinics in Korea. From these 464 samples, 334 ApoB results (164 men and 170 women) with normal traditional lipid test results were used to establish reference intervals. Using the parametric method (mean ± 2 SD), the reference intervals ranged from 46 to 134 mg/dL for men and 49 to 129 mg/dL for women. Employing the non-parametric method (central 95th percentile value), the reference intervals ranged from 50 to 131 mg/dL for men and 51 to 127 mg/dL for women. The prevalence of high ApoB did not significantly differ by sex when considering the established reference intervals for each sex and the cutoffs recommended by international clinical guidelines. This study enhances knowledge on ApoB reference intervals in the Korean population, and it will in aid test result interpretation for clinicians and laboratories.

Investigation of the Prevalence of Diminished Ovarian Reserve in Korean Women of Reproductive Age.

Diminished ovarian reserve can be assessed biochemically using serum anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) tests. This study aimed to evaluate the prevalence of diminished ovarian reserve in a large population of reproductive-aged women by age and geographic region in Korea using different cutoffs of serum AMH and FSH levels. In 2022, 13,351 women underwent both AMH and FSH tests. The prevalence of diminished ovarian reserve increased markedly with age. Although cutoffs for AMH and FSH levels are different in USA and Korean guidelines, the overall prevalence of diminished ovarian reserve was comparable. The maximum prevalence was 3.8%, 6.0%, 11.0%, 28.6%, 69.3%, and 95.0% in women aged 20-24, 25-29, 30-34, 35-39, 40-44, and 45-49 years, respectively. The overall prevalence and age-adjusted prevalence of diminished ovarian reserve were 37.2% and 38.4%, respectively. Women who had only increased serum FSH without decreased AMH represented 1.1% (by Korean guidelines) and 2.5% (by USA guidelines) of all women. Serum AMH and FSH tests were underutilized on Jeju Island. The results of this study provide basic knowledge about diminished ovarian reserve for use in infertility support programs and the field of maternal aging.

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 [...].

The Utilization of Serum Folate and Homocysteine Tests and the Prevalence of Folate Deficiency in Reproductive-Age Korean Women during the COVID-19 Pandemic.

We investigated the prevalence of folate deficiency and associated factors in a large population of Korean women of reproductive age during the COVID-19 pandemic. We utilized different cut-offs and evaluated age, year of testing, geographical region, and the utilization of serum homocysteine levels. Out of the 27,758 women evaluated, the overall prevalence of folate deficiency was 12.5% (<4 ng/mL, metabolic indicator) and 5.4% (<3 ng/mL, hematologic indicator). Homocysteine testing was observed in 8.4% of women, with 2.7% having elevated homocysteine levels (>15.4 µmol/L). According to our multiple logistic regression analysis, younger women, particularly those aged 20 to 24 years, tested in 2020, and from Jeolla province, Gyeongsang province, and Jeju Island, were identified as being more prone to folate deficiency. Receiver operating characteristic curve analysis demonstrated that a cut-off of >8.4 µmol/L provided the most accurate definition of folate deficiency with serum folate levels <4 ng/mL, while a cut-off of >8.8 µmol/L best defined folate deficiency with serum folate levels <3 ng/mL, with both cut-offs being lower than 15.4 µmol/L. Our study emphasizes the prevalence of folate deficiency, associated factors, and the role of homocysteine in planning nutritional support programs in Korea.

Development and Validation of Multiple Equations for Low-Density Lipoprotein and Apolipoprotein B in Korean Patients Visiting Local Clinics and Hospitals.

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.

Utilization of Glucose-6-Phosphate Dehydrogenase Test and the Prevalence of Enzyme Deficiency in Korea.

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 (<7.9 U/g Hb) was 0.4% (19/5111 Koreans and 2/82 non-Koreans), and only seven male patients with G6PD deficiency (<30% of the male median) were identified, with ages ranging from 4.8 months to 50.2 years. No female patients with G6PD deficiency were found. Further research is necessary to determine the clinical significance of G6PD test results and monitor their use.

Different interpretations of inconclusive results of SARS-CoV-2 real-time RT PCR.

We investigated whether inconclusive results could be interpreted differently depending on the situation. First, data from retesting of the initial samples from subjects without a confirmed COVID-19 history were analyzed. And by analyzing the results of consecutive tests with new specimens after receiving inconclusive results between arrivals and locals for 2 periods. As a result, 179 of 219 cases (81.7%) showed still inconclusive or weakly positive results. If contamination is well controlled in a general laboratory, the effectiveness of retesting with the same sample is limited. The rate of the subsequently positive patient was significantly higher in locals than in arrivals and periods with a higher positive rate. The inconclusive results could be interpreted differently depending on the epidemiologic background and the positive rate at that time.

Prevalence of Iron Deficiency Anemia Indicated for Intravenous Iron Treatment in the Korean Population.

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.

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.

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.

Clinical Usefulness of Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry Method for Low Serum Testosterone Measurement.

Background: Mass spectrometry methods exhibit higher accuracy and lower variability than immunoassays at low testosterone concentrations. We developed and validated an ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for quantifying serum total testosterone. Methods: We used an ExionLC UPLC (Sciex, Framingham, MA, USA) system and a Sciex Triple Quad 6500+ (Sciex) MS/MS system in electrospray ionization and positive ion modes with multiple reaction monitoring transitions to evaluate precision, accuracy, linearity, lower limit of quantitation (LLOQ), carryover, ion suppression, stability, and reference intervals. For method comparison, we measured serum testosterone concentrations using this method in 40 subjects whose testosterone concentrations ranged from 0.14 to 55.48 nmol/L as determined using the Architect i2000 immunoassay (Abbott Diagnostics, Abbott Park, IL, USA) and in an additional 160 sera with testosterone concentrations <1.67 nmol/L. Results: The intra- and inter-run precision CVs were <2.81%, and the accuracy bias values were <3.85%, which were all acceptable. The verified linear interval was 0.03-180.84 nmol/L; the LLOQ was 0.03 nmol/L. No significant carryover and ion suppression were observed. The testosterone in serum was stable at 4°C, at -20°C, and after three freeze-thaw cycles. The reference intervals were successfully verified. The correlation was good at testosterone concentrations of 0.14-55.48 nmol/L; however, the Architect assay showed positive percent bias at concentrations <1.67 nmol/L. Conclusions: The UPLC-MS/MS assay shows acceptable performance, with a lower LLOQ than the immunoassay. This method will enable the quantitation of low testosterone concentrations.

Detection of paradoxical carbon dioxide gas embolism with opening of patent foramen ovale by perioperative transesophageal echocardiography during laparoscopic hepatectomy - A case report.

BACKGROUND: Due to its various advantages, laparoscopic surgery is preferred over laparotomy in patients who require hepatic resection. Carbon dioxide embolism -which occurs approximately ten times more often in laparoscopic hepatectomy than in general laparoscopic surgery-presents with insignificant symptoms and may be overlooked. CASE: A 70-year-old male with hepatic cell carcinoma underwent laparoscopic hepatectomy. Though his vital signs were stable during the initiation of surgery, they became unstable during the procedure. The surgeon detected portal vein rupture, and transesophageal echocardiography was subsequently performed. A large amount of gas in the heart chamber and paradoxical embolism through a patent foramen ovale due to a right-to-left shunt were observed. We treated the symptoms, and the surgery was completed without any further issues. CONCLUSIONS: Active use of transesophageal echocardiography to identify and monitor heart functions during a suspected carbon dioxide embolism can significantly reduce morbidity and mortality associated with that embolism.

Intra-Individual Changes in Total Procollagen-Type 1 N-terminal Propeptide in a Korean Adult Population.

We aimed to investigate intra-individual changes in total procollagen-type 1 N-terminal pro-peptide (P1NP), a biochemical marker of bone turnover, to understand patient populations and test utilization in a Korean adult population while considering different definitions of least significant changes by sex, age, and medical institution type. Overall, 31,501 P1NP tests were performed on 24,644 Korean adults (3389 men and 21,255 women) with a median age of 68.9 years (interquartile range, IQR, 61.2-77.2) for osteoporosis evaluation. Among these, 1331 (5.4%) patients (127 men and 1204 women) underwent ≥3 follow-up P1NP measurements. The median follow-up period was 12.5 months (IQR, 11.7-15.9). Among 1331 patients, 64.4% experienced a decrease in P1NP and 35.6% experienced an increase in P1NP during follow-up. Among these, the proportion of patients who experienced serum P1NP changes ≥14.4% from baseline was 92.3%, and the proportion of patients who achieved ≤40 ng/mL (a median level of premenopausal Korean women) during follow-up was 31.8%. The overall proportion of patients that experienced a serum P1NP change exceeding the least significant change during follow-up was not significantly different by the type of medical institution.

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.