Evaluation of Group Genetic Counseling Sessions via a Metaverse-based Application

Background@#Group genetic counseling has been implemented to meet growing demand.A metaverse platform, in which a society is built and activities are carried out in the virtual world, has not yet been implemented in group genetic counseling. We investigated whether a metaverse platform could be an alternative service-delivery model for group genetic counseling. @*Methods@#Participants (N=131) were divided into three groups: patient (N=45), family (N= 43), and interested (N = 43) groups. Participants entered the metaverse through a link sent to their mobile phones and attended a 20-min group genetic counseling session reviewing hereditary breast cancer, followed by a 10-min question-and-answer period. @*Results@#The overall median score of post-educational knowledge (9.0, range 8.0–10.0) significantly increased compared to that of pre-educational knowledge (6.0, range 3.0– 8.0) (P 0.05). Most participants (95%) responded that their understanding of hereditary breast cancer had increased after the group genetic counseling session and that their satisfaction was high. The main advantage noted with metaverse was no limit of space and location while attending the session (97%), and the main disadvantage was a possibility of missing content due to an unstable internet connection (67%). @*Conclusions@#The metaverse platform would be acceptable as an alternative group genetic counseling service. More studies are needed to investigate how, for whom, and in what circumstances metaverse can be effectively utilized.

Evaluation of Vancomycin Area Under the Concentration–Time Curve Predictive Performance Using Bayesian Modeling Software With and Without Peak Concentration: An Academic Hospital Experience for Adult Patients Without Renal Impairment

Background@#The revised U.S. consensus guidelines on vancomycin therapeutic drug monitoring (TDM) recommend obtaining trough and peak samples to estimate the area under the concentration–time curve (AUC) using the Bayesian approach; however, the benefit of such two-point measurements has not been demonstrated in a clinical setting. We evaluated Bayesian predictive performance with and without peak concentration data using clinical TDM data. @*Methods@#We retrospectively analyzed 54 adult patients without renal impairment who had two serial peak and trough concentration measurements in a ≤1-week interval. The concentration and AUC values were estimated and predicted using Bayesian software (MwPharm++; Mediware, Prague, Czech Republic). The median prediction error (MDPE) for bias and median absolute prediction error (MDAPE) for imprecision were calculated based on the estimated AUC and measured trough concentration. @*Results@#AUC predictions using the trough concentration had an MDPE of –1.6% and an MDAPE of 12.4%, whereas those using both peak and trough concentrations had an MDPE of –6.2% and an MDAPE of 16.9%. Trough concentration predictions using the trough concentration had an MDPE of –8.7% and an MDAPE of 18.0%, whereas those using peak and trough concentrations had an MDPE of –13.2% and an MDAPE of 21.0%. @*Conclusions@#The usefulness of the peak concentration for predicting the AUC on the next occasion by Bayesian modeling was not demonstrated; therefore, the practical value of peak sampling for AUC-guided dosing can be questioned. As this study was conducted in a specific setting and generalization is limited, results should be interpreted cautiously.

Accuracy of the New Creatinine-based Equations for Estimating Glomerular Filtration Rate in Koreans

Background@#New creatinine-based estimated glomerular filtration rate (eGFR) equations, including the 2021 Chronic Kidney Disease Epidemiology Collaboration (2021 CKD-EPI) and European Kidney Function Consortium (EKFC) equations, have been introduced recently. We assessed the performance of the 2021 CKD-EPI and EKFC equations in the Korean population. @*Methods@#We analyzed 1,654 Korean patients aged ≥18 years who underwent chromium-51-ethylenediamine tetraacetic acid GFR measurements (mGFR). Bias (eGFR–mGFR), root mean square error (RMSE), and proportion of eGFR within 30% of mGFR (P30) of the 2009 CKD-EPI, 2021 CKD-EPI, and EFKC equations were compared. The concordance rate between eGFR and mGFR categories was evaluated. Both eGFR and mGFR categories were classified into six groups: ≥90, 89–60, 59–45, 44–30, 29–15, and <15 mL/min/1.73 m2. @*Results@#The median bias (mL/min/1.73 m2) was 1.8 for the 2009 CKD-EPI equation, 4.8 for the 2021 CKD-EPI equation, and –0.3 for the EKFC equation. The P30 and RMSE were 78.2% and 17.0 for the 2009 CKD-EPI equation, 75.6% and 17.4 for the 2021 CKD-EPI equation, and 80.0% and 16.7 for the EKFC equation, respectively. The overall GFR category concordance rate between eGFR and mGFR was 63.4% for the 2009 CKD-EPI equation, 60.5% for the 2021 CKD-EPI equation, and 61.0% for the EKFC equation. @*Conclusions@#Among the three eGFR equations, the EKFC equation had the smallest bias and highest P30 in Koreans. The 2009 CKD-EPI equation had a lower bias than the 2021 CKD-EPI equation.

A New Strategy for Evaluating the Quality of Laboratory Results for Big Data Research: Using External Quality Assessment Survey Data (2010–2020)

Background@#To ensure valid results of big data research in the medical field, the input laboratory results need to be of high quality. We aimed to establish a strategy for evaluating the quality of laboratory results suitable for big data research. @*Methods@#We used Korean Association of External Quality Assessment Service (KEQAS) data to retrospectively review multicenter data. Seven measurands were analyzed using commutable materials: HbA1c, creatinine (Cr), total cholesterol (TC), triglyceride (TG), alpha-fetoprotein (AFP), prostate-specific antigen (PSA), and cardiac troponin I (cTnI). These were classified into three groups based on their standardization or harmonization status. HbA1c, Cr, TC, TG, and AFP were analyzed with respect to peer group values. PSA and cTnI were analyzed in separate peer groups according to the calibrator type and manufacturer, respectively. The acceptance rate and absolute percentage bias at the medical decision level were calculated based on biological variation criteria. @*Results@#The acceptance rate (22.5%–100%) varied greatly among the test items, and the mean percentage biases were 0.6%–5.6%, 1.0%–9.6%, and 1.6%–11.3% for all items that satisfied optimum, desirable, and minimum criteria, respectively. @*Conclusions@#The acceptance rate of participants and their external quality assessment (EQA) results exhibited statistically significant differences according to the quality grade for each criterion. Even when they passed the EQA standards, the test results did not guarantee the quality requirements for big data. We suggest that the KEQAS classification can serve as a guide for building big data.

Recent Trends in Creatinine Assays in Korea: LongTerm Accuracy-Based Proficiency Testing Survey Data by the Korean Association of External Quality Assessment Service (2011–2019)

Background@#Accurate serum creatinine (Cr) concentration measurement is essential for evaluating kidney function. In 2011, the Korean Association of External Quality Assessment Service (KEQAS) launched an accuracy-based Cr proficiency testing (ABCr PT) survey. We analyzed long-term data of the KEQAS ABCr PT survey collected between 2011 and 2019 to assess recent trends in Cr assays in Korea. @*Methods@#The ABCr PT survey including three commutable fresh-frozen serum samples was performed twice a year. The target Cr concentration was assigned using isotope-dilution mass spectrometry. We analyzed data obtained from the participating laboratories, calculated the yearly bias, and evaluated bias trends for the major reagents and instruments. Outliers were excluded from all analysis. @*Results@#The mean percentage bias based on the total data of all participating laboratories was 10.8% in the 2011-A survey and 0.2% in 2019-B survey. Bias for the major reagents and instruments differed depending on the manufacturer. Enzymatic assays generally showed desirable bias ranging from –3.9% to 3.2% at all Cr concentrations and lower interlaboratory variability than non-enzymatic assays (enzymatic vs. non-enzymatic, 3.3%– 7.2% vs. 6.3%–9.1%). @*Conclusions@#Although the mean percentage bias of Cr assays tends to decrease over time, it is necessary to continuously strive to improve Cr assay accuracy, especially at low concentrations.

Association of Vitamin D Deficiency with Diabetic Nephropathy

Background@#Low 25-hydroxyvitamin D (25OHD) levels are associated with the incidence of type 2 diabetes mellitus (T2DM). However, the association between 25OHD and metabolic health status or diabetic complications is inconclusive. We evaluated this relationship between vitamin D status and metabolic parameters and complications of T2DM. @*Methods@#This study included 1,392 patients with T2DM who visited Eulji and Ewha Diabetes Center between January 2011 and August 2016. Anthropometric parameters and laboratory tests including glycated hemoglobin (HbA1c), lipid profile, liver and kidney function, and urinary albumin-to-creatinine ratio (UACR) were evaluated. Diabetic macro- and microvascular complications were determined through a medical record review. Serum 25OHD concentrations were measured by chemiluminescent immunoassay. @*Results@#The mean 25OHD level was 16.8±9.6 ng/mL. Vitamin D deficiency (<20 ng/mL) and severe deficiency (<10 ng/mL) were observed in 990 (71.1%) and 351 (25.2%) participants, respectively. 25OHD level was positively correlated with age and highdensity lipoprotein cholesterol (HDL-C) level and negatively correlated with HbA1c, triglyceride level, and UACR. HDL-C and UACR were significantly associated with 25OHD after adjusting for other variables. Vitamin D deficiency was independently related to nephropathy after adjusting for confounding variables. @*Conclusion@#Vitamin D deficiency was common among Korean T2DM patients; it was independently associated with microalbuminuria and HDL level, and positively related to diabetic nephropathy.

Application of Six Sigma Metrics to Improve Quality Control for Point-of-care Glucose Testing / 이화의대지

Objectives@#Six sigma is a quality management system for the assessment of precisionand accuracy. We aim to apply the six sigma rule to quality control (QC) of point-of-care(POC) glucose meters in a tertiary hospital. @*Methods@#Thirty POC glucose meters installed at Ewha Womans University MokdongHospital were monitored between January 2013 and March 2014. The QC data fromthe POC glucose meters at low and high levels were collected. The monthly mean, standarddeviation, bias, coefficient of variation, and mean sigma metrics were calculated.The correlation between accuracy and precision was assessed based on the percentagebias and coefficient of variation. Comprehensive instructions on the QC and maintenanceof the devices were provided in the departments with poor sigma scores. Afollow-up assessment was performed after the intervention. @*Results@#The mean sigma values for the low and high controls were 3.29 and 3.71, respectively.At the low and high controls, 36.6% and 10% of the glucose meters showeda sigma value <3. The causes of low sigma values included the use of expired controlmaterials, prolonged air exposure of the sample strip, lack of user training, and errors indevice maintenance. On follow-up monitoring for 3 months following QC intervention,23.3% (low control) and 6.6% (high control) of the glucose meters scored a sigma value<3, indicating improved QC. @*Conclusion@#Sigma metrics-based QC can successfully improve accuracy and precisionof POC glucose meters in an objective and quantitative manner and can be usedfor follow up after QC intervention.

Estimated Glomerular Filtration Rates Show Minor but Significant Differences Between the Single and Subgroup Creatinine-Based Chronic Kidney Disease Epidemiology Collaboration Equations

The creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation can be calculated according to race, sex, and creatinine concentration (subgroup equation) or in the form expressed by one equation (single equation). Minor differences in the constants used in the CKD-EPI equations (subgroup vs single equations) could result in a significant difference in the estimated glomerular filtration rate (eGFR). We evaluated the impact of this difference in 79,709 Korean patients. The eGFR was calculated as an integer using the single and subgroup CKD-EPI equations. The differences in eGFR and GFR categories between the equations were analyzed. eGFR was higher in the subgroup equation than the single equation by 1 mL/min/1.73 m² for 12,476 (27.4%) Korean females. The GFR category based on the subgroup equation was reclassified using the single equation for 352 (0.77%) females. Based on the results, the constant of the single equation was optimized. There was no difference in eGFR values between equations using a multiplier of 1.0213 instead of 1.018 for the “white or other” females constant in the single CKD-EPI equation. Clinicians should carefully apply the CKD-EPI equation because eGFR values may differ by 1 mL/min/1.73 m² depending on the manner of calculation. To minimize these differences, the constants of the single equation should be revised.

A Clue to Discovering Unstable Hemoglobin Variants via Abnormal WBC Differential Scattergrams Using the Sysmex Automated Hematology Analyzer

Incidentally, hemoglobin (Hb) variants can be detected using HbA1c tests in clinical laboratories. We found 38 patients with Hb variants after reviewing a total of 29,398 HbA1c test results from January 2017 to December 2017. While reviewing the complete blood count results of the patients (N=36) using the Sysmex XN-9000 analyzer (Sysmex, Japan), 35 patients were flagged as unremarkable with respect to differential white blood cell (WBC) counts. However, 1 patient with a normal WBC count did not obtain a differential WBC count while being flagged for an abnormal WBC scattergram in the white blood cell differential (WDF) channel. The WBC histogram showed an abnormally low fluorescent signal in the WDF channel; however, the differential WBC count was normal upon microscopic examination. After testing the patient's buffy coat suspended in normal saline and removing red blood cells (RBCs), the WBC scattergram and differential WBC count returned to normal. This finding suggests that the presence of a patient's RBCs may affect WBC scattergrams and Hb variants may interfere with the fluorescent dye in the differential WBC count. Therefore, when an abnormal WBC scattergram with an abnormally low fluorescent signal is encountered on the Sysmex XN-9000 analyzer, the presence of an Hb variant can be suspected.

Accuracy-Based Proficiency Testing of Creatinine Measurement: 7 Years' Experience in Korea

BACKGROUND: Standardization of creatinine assay is consistently performed and much effort has been put into improving the accuracy of the results. We aimed to analyze the results of accuracy-based proficiency testing of creatinine assays performed by the Korea Association of External Quality Assessment Service from 2011 to 2017 to assess the current state of creatinine assays in Korea. METHODS: From 2011 to 2017, the accuracy-based proficiency testing of creatinine was performed twice a year. We analyzed the results obtained from the participating laboratories and calculated the year-wise bias. The acceptable limit of bias was as follows: ±11.4% for creatinine concentration >1.0 mg/dL, and 0.114 mg/dL for creatinine concentration ≤1.0 mg/dL. The trend of bias with the major instruments and reagent manufacturers were analyzed. RESULTS: The number of participating laboratories was 54 in 2011, which gradually increased to 146–178 after 2015. For each of the three samples used in the survey, the percentage of laboratories whose biases in the results were within the acceptable limits was 33.3% for the first time in 2011, which gradually increased to 74.7%–85.0% after 2014. The mean biases in all the results of the participating laboratories were 11.1% in 2011 (1st trial) and 2.4% in 2017 (2nd trial). The biases in the results with the major instruments and reagents differed according to the manufacturers. CONCLUSIONS: The mean bias in the results obtained from the participating laboratories in the accuracy-based proficiency testing of creatinine surveys showed a decreasing trend.

Effects of Pre-analytical Variables on Cell-free DNA Extraction for Liquid Biopsy

BACKGROUND: Extraction of cell-free DNA (cfDNA) is a key step for determining the quality of cfDNA-related molecular diagnostics. We evaluated the effect of sample containers and sample storage conditions on cfDNA extraction. METHODS: The cfDNA extraction using the MagMAX Cell-Free DNA Isolation Kit from five healthy controls and five lung cancer patients was evaluated according to the type of sample container and storage conditions: K2-EDTA container, <1, 6, 24, and 48 hr storage at 4℃ after immediate plasma separation; and Cell-Free DNA BCT container, <1, 3, 7, and 14 days stored at room temperature. Mutation analysis of EGFR exons 18–21 was performed. To assess the effect of a delay in centrifugation, EDTA whole blood samples from five healthy individuals were stored at 4℃ for 6, 12, and 24 hr before plasma separation. RESULTS: There was no significant difference in the amount and nucleic acid size of cfDNA in both controls and patients with cancer when EDTA plasma was stored at 4℃ up to 48 hr. The amount and size of cfDNA in the BCT container were not different up to 7 days; however, the 14-day sample showed an increase in cfDNA concentration due to genomic DNA contamination. EGFR mutations were detected on EDTA containers up to 48 hr and with BCT containers up to 14 days. When EDTA whole blood was stored at 4℃ and plasma separation was delayed, the cfDNA concentration increased from 24 hr. CONCLUSIONS: The cfDNA extraction was affected by the sample containers and storage conditions.

Performance Evaluation of the Point-of-Care Cardiac Troponin T Assay

BACKGROUND: The point-of-care (POC) troponin T assay has been used in various clinical settings. Recently, a POC troponin T assay with an extended measurable range (40 ng/L-2,000 ng/L) was introduced. We aimed to evaluate the analytical performance of the Roche Cardiac POC Troponin T assay (POC TnT, Roche Diagnostics, Switzerland) using the cobas h 232 POC system. METHODS: The repeatability and within-laboratory imprecision of the POC TnT assay were evaluated using the Roche Cardiac POC Troponin T level 2 control. Repeatability was also assessed using patient samples. Linearity of the POC TnT assay was evaluated using patient samples containing five different concentrations of troponin T. Performance of the Elecsys Troponin T high sensitivity assay (hs-TnT) was compared with that of the POC TnT assay using 40 patient samples. RESULTS: The repeatability (%CV), and within-laboratory imprecision (%CV) using the level 2 control solution (mean troponin T, 441.6 ng/L) were 8.5% and 8.6%, respectively. The repeatability of patient samples containing 88.7 ng/L and 454.6 ng/L TnT was 7.5% and 7.2%, respectively. The POC TnT assay was confirmed to produce linear data between 54.0 ng/L and 1,347.7 ng/L. Relative to the hs-TnT assay, the Passing-Bablok linear regression equation (correlation coefficient) was y=0.8933x+6.24 (r=0.988). At a troponin T concentration of 40 ng/L, the estimated bias of the POC TnT assay was 1.972 ng/L (4.93%). CONCLUSIONS: Our data suggest that the Roche Cardiac POC Troponin T assay is reliable in cases where POC troponin T testing is required.

Evaluation of the 1B Equation to Estimate Glomerular Filtration Rate in Pediatric Patients with Cancer

The 1B equation is recommended for calculating the glomerular filtration rate (GFR) in children. Since few reports have evaluated the performance of the 1B equation, we investigated the performance of estimated GFR (eGFR) equations with the blood urea nitrogen (BUN) variable for pediatric cancer patients. In total, 203 children with cancer who underwent measured GFR (mGFR) assessment were enrolled. The median (range) mGFR and eGFR calculated using the updated Schwartz equation were 118 (43–241) and 135 (34–257) mL/min/1.73 m², respectively. The bias, precision (root mean square error [RMSE]), and accuracy (P30, mGFR±30%) of three eGFR equations including updated Schwartz, 1B, and full age spectrum (FAS) were compared. The median bias (mL/min/1.73 m²) was: updated Schwartz, 8.5; 1B, −9.0; and FAS, 4.2. The biases for all three eGFR equations were significantly different from zero. The P30 was: updated Schwartz, 63.5%; 1B, 66.0%; and FAS, 66.0%. The RMSE was the lowest for the 1B equation (40.4), followed by FAS (42.3), and updated Schwartz (45.5). The median eGFR/mGFR ratio for the eGFR equations decreased with age and reduced kidney functions (i.e., increased creatinine and BUN concentrations). The bias may be further reduced by using the average from two equations, such as the updated Schwartz and 1B, or FAS equation, rather than using the updated Schwartz or 1B equation alone. The use of the 1B equation may underestimate the GFR. Using creatinine and BUN variables in the eGFR equation may yield a more accurate estimate of the GFR in pediatric cancer patients.

Intactness of Medical Nonsterile Gloves on Use of Alcohol Disinfectants

No abstract available.

Plasma Neutrophil Gelatinase-Associated Lipocalin as a Marker of Tubular Damage in Diabetic Nephropathy

BACKGROUND: An increase in neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular injury. Diabetic nephropathy causes typical changes in the kidney, characterized by glomerulosclerosis and eventual tubular damage. We validated the usefulness of plasma NGAL (pNGAL) as a biomarker of tubular damage in patients with diabetic nephropathy. METHODS: We included 376 patients with diabetes mellitus (260 patients with chronic renal insufficiency who had not received hemodialysis and 116 hemodialyzed due to diabetic nephropathy) and 24 healthy controls. Patients with chronic renal insufficiency were divided into three groups according to urinary albumin excretion (UAE) levels. pNGAL levels were measured using the Triage NGAL test (Alere, San Diego, CA, USA) and were compared between groups. We also examined whether pNGAL level was related to the degree of albuminuria and cystatin C-based glomerular filtration rate (GFR). RESULTS: Mean pNGAL levels of the healthy controls, chronic renal insufficiency patients with diabetes mellitus, and hemodialyzed patients were 61.9±5.3 ng/mL, 93.4±71.8 ng/mL, and 1,536.9±554.9 ng/mL, respectively. pNGAL level increased significantly in patients with severe albuminuria (P < 0.001) and had a moderate correlation with the degree of albuminuria (r=0.467; P < 0.001) and GFR (r=0.519; P < 0.001). Multivariate regression analysis showed that the pNGAL level was associated with tubular damage independent of patient age, sex, and GFR. CONCLUSIONS: pNGAL level independently reflects the degree of tubular damage in patients with diabetic nephropathy. Measurement of pNGAL, combined with UAE, would enable simultaneous, highly reliable assessments of tubular damage for such patients.

Prognostic Implications of Elevated Cardiac Troponin T in Patients with Acute Ischemic Stroke

BACKGROUND: Elevated cardiac troponin T (cTnT) levels have been reported in patients with acute ischemic stroke, however, the prognostic relevance is not well established. We evaluated the association between cTnT elevation and prognosis in patients with acute ischemic stroke. METHODS: The 182 consecutive patients enrolled had new-onset acute ischemic stroke. Their clinical and laboratory findings were collected retrospectively. Stroke severity and prognosis were determined using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) scores, as well as 30-day all-cause mortality. The patients were divided into two groups according to their cTnT levels: ≤14 and >14 ng/L. Cox proportional hazards regression analysis was performed to determine the associations between clinical or laboratory variables and 30-day all-cause mortality. The Kaplan-Meier method was used to compare the overall survival rate in patients with elevated and normal cTnT levels. RESULTS: The cTnT level was elevated in 14.8% of the patients. Age, NIHSS and mRS scores, creatinine kinase-MB, and 30-day all-cause mortality were significantly higher in patients with elevated cTnT levels than in those with normal cTnT levels. The hazard ratio of the elevated vs. normal cTnT group for 30-day all-cause mortality was 8.06 (95% confidence interval: 1.13-57.25, P=0.037). A Kaplan-Meier survival analysis revealed a significantly higher survival rate in patients with normal cTnT levels compared to those with elevated cTnT levels (P<0.0001). CONCLUSIONS: An elevated cTnT level is significantly associated with poor short-term outcomes in patients with acute ischemic stroke.

Accuracy Assessment of Five Equations Used for Estimating the Glomerular Filtration Rate in Korean Adults

BACKGROUND: We aimed to assess the performance of the five creatinine-based equations commonly used for estimates of the glomerular filtration rate (eGFR), namely, the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr), Asian CKD-EPI, revised Lund–Malmö (revised LM), full age spectrum (FAS), and Korean FAS equations, in the Korean population. METHODS: A total of 1,312 patients, aged 20 yr and above who underwent ⁵¹Cr-EDTA GFR measurements (mGFR), were enrolled. The bias (eGFR–mGFR) and precision (root mean square error [RMSE]) were calculated. The accuracy (P30) of four eGFR equations was compared to that of the CKD-EPIcr equation. P30 was defined as the percentage of patients whose eGFR was within±30% of the mGFR. RESULTS: The mean bias (mL·min⁻¹·1.73 m⁻²) of the five eGFR equation was as follows: CKD-EPIcr, -0.6; Asian CKD-EPI, 2.7; revised LM, -6.5; FAS, -2.5; and Korean FAS, -0.2. The bias of the Asian CKD-EPI, revised LM, and FAS equations showed a significant difference from zero (P<0.001). The RMSE values were as follows: CKD-EPIcr, 15.6; Asian CKD-EPI, 15.6; revised LM, 17.9; FAS, 16.3; and Korean FAS, 15.8. There were no significant differences in the P30 except for the Asian CKD-EPI equation: CKD-EPIcr, 76.6%; Asian CKD-EPI, 74.7%; revised LM, 75.8%; FAS, 76.0%; and Korean FAS, 75.8%. CONCLUSIONS: The CKD-EPIcr and Korean FAS equations showed equivalent analytical and clinical performances in the Korean adult population.

Prognostic relevance of the Ki-67 proliferation index in patients with mantle cell lymphoma

BACKGROUND: A high Ki-67 proliferation index (PI) in neoplastic cells is associated with poor survival in mantle cell lymphoma (MCL). We aimed to determine the cut-off values for the Ki-67 PI as a prognostic factor in MCL according to bone marrow findings. METHODS: Immunohistochemical (IHC) staining for Ki-67 was performed on formalin-fixed paraffin-embedded biopsy tissues from 56 patients with MCL. Patients were grouped based on their Ki-67 PI values. Survival analyses were carried out and the cut-off value for the Ki-67 PI was determined. RESULTS: Of the 56 patients, 39 (69.6%) showed bone marrow involvement of MCL; 21 of these patients had leukemic manifestations at the time of diagnosis. The results of the Ki-67 IHC staining were as follows: ≤10% in 22 patients, 11-20% in 14 patients, 21-30% in 3 patients, 31-40% in 4 patients, 41-50% in 4 patients, and >50% in 9 patients. A cut-off value of 20% revealed significantly different survival rates with mean survival times of 69.8 months (Ki-67 PI≤20%) and 47.9 months (Ki-67 PI>20%), irrespective of bone marrow findings (P=0.034). Clinical outcomes did not differ, regardless of bone marrow findings. However, in cases with bone marrow involvement, the Ki-67 cut-off value of 30% for overall survival was required to yield statistical significance (P=0.033). CONCLUSION: The 20% cut-off value for the Ki-67 PI was clinically meaningful, regardless of bone marrow involvement of MCL. For patients with bone marrow involvement, the statistically significant cut-off value increased to 30%.

Annual Report on the External Quality Assessment Scheme for Therapeutic Drug Monitoring and Testing for Drugs of Abuse in Korea (2014) / 임상검사와정도관리

As the Therapeutic Drug Monitoring Subcommittee (TDMS) of the Korean Association of Quality Assurance for Clinical Laboratories (KAQACL), we organised two trials as an external quality assessment of therapeutic drug monitoring (TDM) and testing for drugs of abuse (DOA) in 2014. In each trial, low and high level control materials for TDM testing, and positive and negative control materials for DOA testing, were requested from institutions. The number of participating laboratories was 107 for the first trial and 106 for the second. The average number of drug items provided was 5.7 per institution. The most commonly tested substances were, in descending order, valproic acid, digoxin, tacrolimus, phenytoin, and vancomycin. The mean inter-laboratory coefficients of variation for low- and high-level TDM control materials were 8.5% and 7.2%, respectively. The most widely used TDM analysers were the Architect i System (Abbott Diagnostics, USA), followed by the Cobas Integra (Roche Diagnostics, Switzerland) and the Cobas c501 analyser (Roche Diagnostics). The number of participating laboratories for DOA testing was 23% higher that than in 2013. In 96.9% of cases, our analysis confirmed the suitability of the tests at participating DOA laboratories in both trials. In the external quality assessment of TDM by the TDMS of KAQACL in 2014, the overall performance of TDM testing was found to be similar to that observed in the previous years, and inter-laboratory precision was higher than that in 2013. Continuous quality improvement of TDM testing by participation in a proficiency-testing program is necessary.

Performance Evaluation of the Elecsys Neuron-Specific Enolase Assay

BACKGROUND: Neuron-specific enolase (NSE) is an enzyme specifically found in neurons and neuroendocrine tissue. It is a common marker for small cell lung cancer diagnosis and is also useful as a predictor of brain damage. This study evaluates the performance of Elecsys NSE (Roche Diagnostics, Switzerland), an electrochemiluminescent immunoassay. METHODS: The precision, linearity, limit of detection, and reference interval of the Elecsys NSE, as well as the correlation between Elecsys NSE and ELSA-NSE (Cis-Bio International, France) were evaluated in accordance with the Clinical Laboratory Standards Institute (CLSI) guidelines. PreciControl Tumor Marker (Roche Diagnostics), patient sera, and sera from healthy individuals were used for the analysis. RESULTS: The measured coefficient of variation for the assay was below 3%, and it demonstrated linearity from 0.20 to 234.5 ng/mL. The detection limit was 0.032 ng/mL and the reference interval ranged from 0.05 to 16.3 ng/mL. Compared with the ELSA-NSE assay, the correlation coefficient was 0.9128. CONCLUSIONS: The Elecsys assay showed suitable precision, linearity, limit of detection and reference range for clinical laboratory use; however, the correlation coefficient of Elecsys NSE as compared to ELSA-NSE was below 0.975. This result may be associated with the use of different monoclonal antibodies in the two different NSE assays. Elecsys NSE demonstrated a high sensitivity without the use of radioactive reagents; therefore, Elecsys NSE will be quite useful for NSE analysis in the clinical laboratory setting.