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The number of ABO-incompatible solid organ transplantations (ABOi SOTs) has markedly increased worldwide since the early 2000s. We investigated the choice of ABO group for blood component transfusion in ABOi SOT. We conducted a survey by e-mailing a questionnaire to blood bank specialists at 77 major hospitals in Korea, among whom 34 responded to the survey. In major ABOi SOT, for red blood cells (RBCs), the recipient's type (70.6%) was the most common choice, followed by group O (29.4%); for platelets, group AB (50.0%) was the most common choice, followed by the donor type (38.2%); for plasma, group AB (55.9%) was the most common choice, followed by the donor type (32.4%). In bidirectional ABOi SOT, for RBCs, the recipient's type (55.9%) was the most common choice, followed by group O (44.1%); for platelets and plasma, group AB was the most common choice (94.1% and 97.1%, respectively). The policies for transfusion in ABOi SOT were diverse. We suggest a guideline on the choice of ABO group for transfusion in ABOi SOT to secure patient health and enable an efficient use of blood components.

Rapid, simple, and inexpensive diagnostic point-of-care tests (POCTs) are essential for controlling infectious diseases in resource-limited settings. In this study, we developed a new detection system based on nanoparticle–DNA aggregation (STat aggregation of tagged DNA, STAT-DNA) to yield a visual change that can be easily detected by the naked eye. This simplified optical detection system was applied to detect hepatitis C virus (HCV). Reverse transcription-polymerase chain reaction (RT-PCR) was performed using primers labeled with biotin and digoxigenin. Streptavidin-coated magnetic particles (1 μm) and anti-digoxigenin antibody-coated polystyrene particles (250–350 nm) were added to form aggregates. The limit of detection (LoD) and analytical specificity were analyzed. The STAT-DNA results were compared with those of the standard real-time PCR assay using serum samples from 54 patients with hepatitis C. We achieved visualization of amplified DNA with the naked eye by adding nanoparticles to the PCR mixture without employing centrifugal force, probe addition, incubation, or dilution. The LoD of STAT-DNA was at least 101 IU/mL. STAT-DNA did not show cross-reactivity with eight viral pathogens. The detection using STAT-DNA was consistent with that using standard real-time PCR.

Background and objectives: The ABO antibody (Ab) titration tests are used in monitoring in ABO-incompatible (ABOi) solid organ transplantation (SOT). However, currently developed ABO Ab tests show Ab binding reactions. This study attempted to measure ABO Ab level using complement-dependent cytotoxicity (CDC). Materials and methods: We studied 93 blood group O serum samples from patients who underwent ABOi SOT from January 2019 to May 2021. Patients’ sera were incubated with A1 or B cells and added to a human complement solution. Supernatants were collected after centrifugation, and free hemoglobin (Hb) was measured by spectrophotometry. We converted plasma Hb value to hemolysis (%), which were compared with ABO Ab titer. Results: We found a mild correlation between hemolysis and ABO Ab titers. In simple regression analysis, the correlation coefficients were within 0.3660–0.4968 (p < 0.0001) before transplantation. In multiple linear regression analysis, anti-A hemolysis (%) was higher in immunoglobulin M (IgM) (β = 12.9) than in immunoglobulin G (IgG) (β = −3.4) (R2 = 0.5216). Anti-B hemolysis was higher in IgM (β = 8.7) than in IgG (β = 0.0) (R2 = 0.5114). There was a large variation in hemolysis within the same Ab titer. Conclusions: CDC can be used in a new trial for ABO Ab measurement. Furthermore, IgM rather than IgG seems to play a significant role in vivo activity, consistent with previous knowledge. Thus, this study may help in the development of the ABO Ab titration supplement test for post-transplant treatment policy establishment and pre-transplant desensitization.

Background Reference intervals defined for adults or children of other ethnicities cannot be applied in the evaluation of Korean pediatric patients. Pediatric reference intervals are difficult to establish because children are in their growing stage and their physiology changes continuously. We aimed to establish reference intervals for routine laboratory tests for Korean pediatric patients through retrospective multicenter data analysis. Methods Preoperative laboratory test results from 1,031 pediatric patients aged 0 month-18 years who underwent minor surgeries in four university hospitals were collected. Age- and sex-specific reference intervals for routine laboratory tests were defined based on the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines. Results The pediatric reference intervals determined in this study were different from existing adult reference intervals and pediatric reference intervals for other ethnicities. Most tests required age-specific partitioning, and some of those required sex-specific partitioning for at least one age-partitioned subgroup. Erythrocyte sedimentation rate, monocyte percentage, basophil percentage, activated partial thromboplastin time, glucose, cholesterol, albumin, bilirubin, chloride, and C-reactive protein did not show any difference between age- or sex-partitioned subgroups. Conclusions We determined Korean pediatric reference intervals for hematology, coagulation, and chemistry tests by indirect sampling based on medical record data from multiple institutions. These reference intervals would be valuable for clinical evaluations in the Korean pediatric population.

Objectives Rh(D)-incompatible (Rh-i) solid organ transplantations are not considered for organ matching, but no consensus guidelines exist regarding the need for anti-D immunoglobulin (RhIG) prophylaxis. Methods We reviewed 35 Rh(D)-negative patients who had received Rh-i solid organ transplantation. We divided the patients into a RhIG-administered group and a nonadministered group. All patients also underwent an antibody screening test to assess Rh alloimmunization. Graft function was monitored with serum creatinine or bilirubin and kidney or liver biopsy whenever a rejection was suspected. Overall survival was also assessed. Results The median (range) age of transplant recipients was 48.5 (4-69) years, and 73.5% of patients were male. Median (range) follow-up time after transplantation was 60 (2-246) months. In the RhIG nonadministered group (n = 16), anti-D was not detected in any of the patients. More rejection episodes occurred in the RhIG-administered group among those undergoing kidney transplant (P = .0278). Conclusions The low rate of Rh(D) alloimmunization is associated with the immunosuppressive state of the patients. RhIG prophylaxis seems to have no clinical benefit in Rh-i solid organ transplantation.

To ensure safe red blood cell (RBC) transfusion practice, it is important to comply with storage and transport requirements of RBC units. We conducted a comprehensive survey on the practice of RBC transport and storage to explore the awareness of and compliance with the 30-minute rule, the current status of RBC unit transport, and possible utility of temperature indicators (TIs) to reduce RBC wastage.From June to August of 2019, 64 blood bank physicians (14 questions) in 64 secondary- and tertiary-care hospitals and 673 nurses (13 questions) in 42 tertiary-care hospitals replied to a questionnaire survey. The results of the survey were analyzed with descriptive statistics.Among the physicians surveyed, 97.0% (N=62) of hospitals had transfusion guidelines in place. The RBC wastage in 2018 ranged from less than five units to more than 200 units. Among the nurses surveyed, 99.4% (N=669) were aware of and complied with the 30-minute rule; 13.5% (N=91) of the nurses had experience of RBC wastage due to violation of the 30-minute rule. Both physicians (67%, N=43) and nurses (83.1%, N=559) responded that TIs would help reduce RBC wastage.This is the first survey on the practices related to RBC transport and storage in Korea. This study provides fundamental data on current practice for the blood cold chain, insights into RBC wastage, and highlights the utility of TIs.

BACKGROUND AND OBJECTIVES Temperature indicators (TIs) are used to monitor the surface temperature of red blood cell (RBC) units. We compared the utility of a newly developed time-temperature indicator (TTI) prototype, Freshzone TTI (FZTTI) (Freshzone, Seoul, South Korea) and two US Food and Drug Administration-approved TIs, Safe-T-Vue 10 (STV10; Temptime Corporation, Morris Plains, NJ) and Blood Temp 10 (BT10; Timestrip UK Ltd, Cambridge, UK). MATERIALS AND METHODS FZTTI, STV10 and BT10 were attached to 91 RBC units after issue (including eight units that were stored in refrigerators in the ward before transfusion). The time for colour change (CC) was monitored based on the 30-min rule. The CC of FZTTI indicated the total time elapsed since the temperature of RBC units exceeded 10°C, and the CC of STV10 and BT10 indicated that the temperature of RBC units exceeded 10°C. RESULTS In 83 units, the median time for CC differed significantly between FZTTI and the TIs (51.4 min in FZTTI vs. 13.9 min in STV10 and 10.5 min in BT10, both at p

Bisphenol A (BPA) is an endocrine-disrupting chemical thought to mimic the action of oestrogens. There have been reports suggesting an association between BPA exposure and infertility in hu...

Background Krebs von den Lungen 6 (KL-6) is a sensitive marker for diagnosing, monitoring, and predicting the prognoses of interstitial lung diseases (ILDs). This study aimed to evaluate the performance of the Nanopia KL-6 assay (Sekisui Medical, Tokyo, Japan) and to test the relationship between KL-6 concentrations and clinical results. Methods In total, 230 patients diagnosed as having ILDs were enrolled. All underwent high-resolution computed tomography (HRCT) followed by the pulmonary function test (PFT). We also enrolled 116 disease controls and 200 healthy controls. Evaluation of the Nanopia KL-6 assay involved determination of precision, linearity, and limit of quantification (LOQ). Results from the Nanopia KL-6 assay were compared with those from ELISA and correlated with the HRCT and PFT results. Results The within-laboratory precisions were

Background The Automated Fluorescent Immunoassay System (AFIAS) rotavirus assay (Boditech Med Inc., Chuncheon, Korea) is a new rapid antigen test for rotavirus detection. We evaluated the performance of this assay for detecting rotaviruses and their specific genotypes in clinical stool samples. Methods AFIAS rotavirus assay was performed in 103 rotavirus-positive and 103 rotavirus-negative stool samples (confirmed by both PCR and ELISA), and its results were compared with those of PCR, ELISA, and immunochromatographic assay (ICA). We evaluated diagnostic sensitivity/specificity, the detectability of rotavirus subtypes, lower limit of detection (LLOD), reproducibility, cross-reactivity, and interference of AFIAS rotavirus assay. Results Based on PCR and ELISA results, diagnostic sensitivity and specificity of the AFIAS rotavirus assay were both 99.0%. LLOD results showed that the AFIAS assay had sensitivity similar to or greater than ICA and ELISA. High reproducibility was confirmed, and no cross-reactivity or interference was detected. This assay could detect genotypes G1P[8], G2P[4], G3P[8], G4P[6], G4P[8], G8P[4], G8P[8], G9P[4], and G9P[8]. Conclusions The AFIAS rotavirus assay showed high reproducibility, sensitivity, and specificity as well as excellent agreement with ELISA, PCR, and ICA. It detected the most common as well as unusual genotypes of rotavirus prevalent in Korea. It could be a useful on-site assay for rapid, convenient, and cost-effective detection of rotavirus infection.

Background Criteria for selection of FFP blood type has not been clearly established and use of group AB plasma is preferred by numerous transplantation protocols. Aims This study assesses the safety and efficacy of alternative group A or B plasma in ABO incompatible solid organ transplantation. Materials & methods Alternative use of group A or B plasma (incompatible plasma) was inevitable during the shortage of group AB plasma. Experience from select number of patients during the period of extreme group AB plasma shortage is described. Results The result of alternative use of group A or B plasma was within expectation, showing effective reduction of isoagglutinin titers for pre-operative desensitization and efficacy for treatment of post-operative patients. No immediate hemolytic transfusion reaction was reported. Discussion While validation in a larger cohort of patients is necessary, our limited experience have shown satisfactory clinical outcomes without adverse events. Conclusions Use of incompatible group A or B plasma is a viable option when group AB plasma is limited.

Background The urinary albumin/creatinine ratio (ACR) is an important indicator of albuminuria. We aimed to estimate ACR uncertainty and its impact on test results and proposed imprecision quality goals based on the estimated uncertainty. Methods The combined ACR uncertainty was calculated using the individual uncertainties of urinary albumin and creatinine. ACR confidence intervals (CIs) were estimated based on the expanded uncertainty. When the CI contained the ACR category boundary (30 or 300 mg/g), the cases were considered ambiguous. Quality goals for ACR were suggested using the number of ambiguous cases among actual patient results. Results The number of ambiguous cases resulting from the combined ACR uncertainty was higher than expected based on biological variation (BV) quality goals. When the ACR met BV quality specifications, we estimated that 4.8-15.5% of the results may have been misclassified. To minimize the number of ambiguous results, the minimum, desirable, and optimum quality goals were set at 34.0%, 18.0%, and 4.5%, respectively. Conclusions We expressed ACR uncertainty using the uncertainties of urinary albumin and creatinine and assessed the impact of this combined uncertainty on the test results. Subsequently, we proposed imprecision quality goals for ACR based on ambiguous results.

Objectives We reanalyzed the data from proficiency testing (PT) to assess the effect of the geometric mean in the statistical analysis of immunohematologic data. Methods Using the five most recent anti–blood group antibody titer participant summary results, the geometric mean (GM) ±2 × geometric standard deviation (GSD) was used as the comparative consensus criterion to mode ±2 titers. Results Using the PT evaluation criterion of mode ±2 titers, the mean percentages of participants with acceptable results were 97.5% and 97.8% for anti-A and anti-D, respectively. When applying GM ±2 GSD, the mean percentages of acceptable results were 96.1% (anti-A) and 96.1% (anti-D). The percentages of responses included in each consensus criterion were lower using GM ±2 GSD, with a few exceptions. Conclusions Geometric means are more robust and precise in visualizing the central tendency. This method can improve the statistical robustness of PT evaluations.

Background The manual microscopic examination (MME) of urine sediment is labor-intensive, time-consuming, and imprecise. Therefore, automated urinalysis systems based on flow cytometry or digital imaging techniques could replace MME. The purpose of this study was to evaluate the rate of MME using two automated urine sediment analyzers, alone and in combination. Methods This study was conducted using the freshly collected urine specimens of 1055 in-patients and 1119 out-patients. All samples were analyzed using UF-1000i (Sysmex Corporation) and Cobas 6500 instrument (Roche Diagnostics International). The rate of MME was evaluated using two analyzers, both individually and in combination. Results Using the UF-1000i alone, 34.2% and 16.8%, respectively, of in- and out-patient samples were analyzed by MME, compared to 15.6% and 3.7%, respectively, using the Cobas 6500. In combined assay using the UF-1000i followed by the Cobas 6500, 27.9% and 11.3% in-patient samples required on-screen review and MME, respectively. And the respective rates were 10.3% and 2.7% of out-patient. Samples using the Cobas 6500 followed by the UF-1000i, 42.3% and 11.3% in-patient needed on-screen review and MME, respectively. And the respective rates were 18.9% and 2.7% of out-patient samples. Conclusions Use of the Cobas 6500 compared to the UF-1000i resulted in decreases in the rate of MME from 34.2% to 15.6% for in-patient samples, and from 16.8% to 3.7% for out-patient samples. Use of the Cobas 6500 reduced the rate of MME, and compared to use of only the Cobas 6500, the combined use resulted in a reduction in the rate of on-screen review.

Urine erythrocyte (Ery) and leukocyte (Leu) dipstick tests are essential for detecting microhematuria and urinary tract infection. Currently, there is no suggestion for establishing the cut-off limits in an ordinal scale test. This study aimed to establish the cut-off limits for urine Ery and Leu dipstick tests via probit regression. From 1 January 2016 to 30 June 2016, laboratory data were collected from patients at one teaching hospital whose specimen had analytical results from both a urine dipstick test and an automated urine particle analyzer. Probit regression was used to estimate the probability of positive urine dipstick results as a function of log-transformed urine Ery and Leu concentrations. Based on the analysis of 22,122 specimens, the estimated concentration that yields 50% positive results (C50) of the Ery weak+, 1+, 2+, 3+, and 4 + dipstick results were 14.6, 40.4, 51.6, 136.3 and 219.0 × 106/L, respectively. The estimated C50 of the Leu 1+, 2+ and 3 + dipstick results were 22.7, 67.9 and 283.9 × 106/L, respectively. The estimated values were different from arbitrary concentrations provided for each dipstick category by the manufacturer. If a quantitative comparison method/procedure is available, the cut-off limits of an ordinal scale test can be established using probit regression. Each laboratory should investigate the transferability of the arbitrary concentrations provided by the manufacturer, and if necessary, determine its own cut-off limits of urine Ery and Leu dipstick tests.

Background Diarrhea has been the second leading cause of death among children under the age of five, and the rapid and accurate pathogen diagnosis in patients with diarrhea is crucial for reducing morbidity and mortality. A newly developed one-step multiplex real-time PCR assay, the Allplex GI-Virus Assay, was evaluated for its ability to detect six diarrhea-causing viruses (rotavirus, norovirus genogroup I (GI) and genogroup II (GII), enteric adenovirus, astrovirus, and sapovirus) in stool samples. Methods The performance of the Allplex assay was compared with those of another multiplex PCR assay (Seeplex Diarrhea-V Ace Detection) and genotyping by sequencing, using 446 stool samples from patients with acute gastroenteritis. Results The overall agreement rates between the results of the Allplex and Seeplex assays were 98.7% for rotavirus, 99.1% for norovirus GI, 93.3% for norovirus GII, 98.0% for adenovirus, and 99.6% for astrovirus. The overall agreement rates between the Allplex assay and genotyping were 99.1% for rotavirus, 99.1% for norovirus GI, 98.7% for norovirus GII, 89.7% for adenovirus, 98.2% for astrovirus, and 99.8% for sapovirus. In addition, eight rotavirus genotypes, three norovirus GI genotypes, four norovirus GII genotypes, eight adenovirus genotypes, two astrovirus genotypes, and two sapovirus genotypes were detected. Conclusions The Allplex assay showed high agreement with Seeplex and genotyping results, and was able to additionally detect sapoviruses. The Allplex assay could be useful in identifying viral gastrointestinal infections in patients with acute gastroenteritis symptoms.

Objectives To assess the utility of reference change values (RCVs) as delta check limits. Methods A total of 1,650,518 paired results for 23 general chemistry test results from June 1, 2014, to October 31, 2016, were analyzed. The RCVs for each analyte were calculated from the analytical imprecision and within-subject biological variation. The percent differences between two consecutive results in one patient were categorized into one of four groups: outpatients, inpatients, emergency care, and general health care. For each, 2.5th and 97.5th percentile values were computed and compared with their RCVs. The distributions were assessed for normality using the Kolmogorov-Smirnov test. Results Most of the estimated limits were larger than the corresponding RCVs and, furthermore, with notable differences across the groups. Patients in the emergency care group usually demonstrated larger delta percent values than those in the other groups. None of the distributions of the percent differences passed tests of normality when subjected to Kolmogorov-Smirnov analysis. Conclusions Comparison of estimated RCVs and real-world patient data revealed the pitfalls of applying RCVs in clinical laboratories. Laboratory managers should be aware of the limitations of RCVs and exercise caution when using them.

Background:Reliable quantitative measurements of HE4 and CA125 levels are required to calculate the risk of ovarian malignancy algorithm (ROMA) value. We suggest a new reporting strategy for interpreting ROMA values based on analytical measurement range (AMR) and qualified-intervals of the HE4 and CA125 results.Methods:HE4 and CA125 assays from Abbott and Roche were used. The AMRs and the qualified-intervals were as follows: Architect HE4 assay, 20–1500 and 17.2–2637.8 pmol/L; Architect CA125 II assay, 1–1000 and 3.9–14,163.0 U/mL; Elecsys HE4 assay, 15–1500 and 28.8–3847 pmol/L; Elecsys CA125 II assay, 0.6–5000 and 6.5–5000 U/mL. These values were used to simulate the ROMA values.Results:Reporting algorithm for the ROMA value could be classified into three categories. (1) If quantitative HE4 and CA125 levels are reliable, the numerical ROMA value can be reported. (2) If HE4 value is Conclusions:New reporting strategy will provide more informative reporting of ROMA values in clinical practice.

Background Since the 99th percentile reference limit for cardiac troponin (Tn) can vary depending on the reference population, Sandoval et al. published systematic selection criteria. In this study, these systematic criteria were applied for the first time to obtain the 99th percentile reference limits for 6 Tn tests. Methods The reference population was selected in accordance with the systematic criteria, and reference limits were set with respect to the six types of Tn assays. The coefficient of variation (CV) at the reference limit was determined using 3–4 concentrations of frozen serum. Results In total, 641 South Koreans (303 males, 338 females) were selected as the reference population. The 99th percentile reference limit of Tn in the six assays ranged from 13.4 to 34.2 pg/ml. The measurable fractions among the reference population ranged from 1.3% to 80.5%. The CVs at the reference limit ranged from 5.3% to 43.0%, and three were Conclusions In this study, a reference population was selected for the first time in accordance with the systematic criteria of Sandoval et al., and the reference limit for South Koreans was established. The values obtained in this study are different from those proposed by manufacturers, which confirms the importance of having a reference population. Four out of six assays did not fulfill the criteria for high-sensitivity tests.

Background Drug resistance in Mycobacterium tuberculosis (MTB) is a major health issue worldwide. Recently, next-generation sequencing (NGS) technology has begun to be used to detect resistance genes of MTB. We aimed to assess the clinical usefulness of Ion S5 NGS TB research panel for detecting MTB resistance in Korean tuberculosis patients. Methods Mycobacterium tuberculosis with various drug resistance profiles including susceptible strains (N = 36) were isolated from clinical specimens. Nucleic acids were extracted from inactivated culture medium and underwent amplicon-based NGS to detect resistance variants in eight genes (gyrA, rpoB, pncA, katG, eis, rpsL, embB, and inhA). Data from previous studies using the same panel were merged to yield pooled sensitivity and specificity values for detecting drug resistance compared to phenotype-based methods. Results The sequencing reactions were successful for all samples. A total of 24 variants were considered to be related to resistance, and 6 of them were novel. Agreement between the phenotypic and genotypic results was excellent for isoniazid, rifampicin, and ethambutol, and was poor for streptomycin, amikacin, and kanamycin. The negative predictive values were greater than 97% for all drug classes, while the positive predictive values varied (44% to 100%). There was a possibility that common mutations could not be detected owing to the low coverage. Conclusions We successfully applied NGS for genetic analysis of drug resistances in MTB, as well as for susceptible strains. We obtained lists of polymorphisms and possible polymorphisms, which could be used as a guide for future tests applying NGS in mycobacteriology laboratories. When analyzing the results of NGS, coverage analysis of each samples for each gene and benign polymorphisms not related to drug resistance should be considered.

Para-Bombay phenotypes are rare blood groups that have inherent defects in producing H antigens associated with FUT1 and/or FUT2. We report the first case of para-Bombay blood type in a Southeast Asian patient admitted at a tertiary hospital in Korea. A 23-year-old Indonesian man presented to the hospital with fever and was diagnosed with a disseminated nontuberculous mycobacterium infection and anemia. During blood group typing for blood transfusion, cell typing showed no agglutination with both anti-A and anti-B reagents. Serum typing showed strong reactivity against B cells and trace agglutination pattern with A1 cells. His red blood cells failed to react with anti-H reagents. Direct sequencing of FUT1 and FUT2 revealed a missense variation, c.328G>A (p.Ala110Thr, rs56342683, FUT1*01W.02), and a synonymous variant, c.390C>T (p.Asn130=, rs281377, Se357), respectively. This highlights the need for both forward and reverse grouping., Graphical Abstract

The aim of this study was to report the experience of large-scale performance evaluation of 238 Accu-Chek Inform II point-of-care (POC) glucose meters in a single medical setting.The repeatability of 238 POC devices, the within-site imprecision of 12 devices, and the linearity of 49 devices were evaluated using glucose control solutions. The glucose results of 24 POC devices and central laboratory were compared using patient samples.Mean concentration of control solutions was 2.39 mmol/L for Level 1 and 16.52 mmol/L for Level 2. The pooled repeatability coefficient of variation (CV) of the 238 devices was 2.0% for Level 1 and 1.6% for Level 2. The pooled within-site imprecision CV and reproducibility CV of the 12 devices were 2.7% and 2.7% for Level 1, and 1.9%, and 1.9% for Level 2, respectively. The test results of all 49 devices were linear within analytical measurement range from 1.55-31.02 mmol/L. The correlation coefficient for individual POC devices ranged from 0.9967-0.9985. The total correlation coefficient for the 24 devices was 0.998.The Accu-Chek Inform II POC blood glucose meters performed well in terms of precision, linearity, and correlation evaluations. Consensus guidelines for the large-scale performance evaluations of POC devices are required.

Background: Anti-hepatitis C virus antibody (anti-HCV) assays are recommended for screening HCV-infected persons. The VIDAS Anti-HCV Assay (bioMerieux, France), based on the enzyme-linked fluorescence test principle, was recently introduced in Korea. We evaluated the clinical performance of the VIDAS assay. Methods: One hundred HCV-positive and 1,002 HCV-negative blood samples confirmed by Architect anti-HCV (Abbott Laboratories, USA) and COBAS TaqMan HCV real-time PCR (Roche Diagnostics, USA) or the Procleix Ultrio Plus Assay (Gen-Probe Incorporated, USA) were obtained from the Human Serum Bank (HSB) and tested by VIDAS. In case of discrepant results, we conducted a recombinant immunoblot assay (RIBA). Results: The agreement rates for known HCV-positive and HCV-negative samples between the VIDAS assay and the HSB testing were 100% (95% confidence interval [CI]: 96.4-100%) and 99.5% (95% CI: 98.8-99.8%), respectively. One of the five discrepant samples was positive for Core 2+ and NS3-2 2+ reactivity, two samples were negative, and the other two were indeterminate regarding NS4 2+ reactivity in RIBA. We observed a significant but weak positive correlation between the titers of VIDAS and Architect assays (r=0.315, P

Background Serum pepsinogen (PG) I and the PG I/PG II ratio have been used for atrophic gastritis (AG) diagnosis for decades. Low levels of PG I and/or PG I/PG II are closely related to AG and predict the risk of gastric cancer. We evaluated the performance of the chemiluminescent immunoassay-based Architect Pepsinogen I/II assay. Methods The evaluation consisted of determination of the precision, linearity, limit of blank (LoB), limit of detection (LoD) and method comparison with Eiken and Biohit assays. Results The total CVs were below 5% for both PG I and PG II. Acceptable linearity was observed for PG I and PG II in their respective reportable ranges. The PG I LoB was 0.317 ng/mL and the PG II LoB was 0.418 ng/mL, and LoDs were 0.412 ng/mL and 0.497 ng/mL, respectively. Correlation analysis indicated that results of the Architect assay were comparable to those of the Eiken and Biohit assays, but the three methods lead to different estimations of the cancer risk. Conclusion The overall analytical performance of Architect Pepsinogen I/II assay is acceptable for the detection of patients with suspected AG. The categorization results of gastric cancer risk showed some difference among test methods suggesting the need for harmonization among the methods from vendors.

Therapeutic drug monitoring of tacrolimus and cyclosporine is crucial to the success of organ transplantation. We evaluated the analytical performances and accuracy of two commercially available tacrolimus and cyclosporine assays (Roche ISD and Siemens) in comparison with liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 342 leftover whole blood samples requested for tacrolimus or cyclosporine assays were stored at -20 °C until analysis. Repeatability and between-run imprecision were evaluated using quality control materials provided by the manufacturer. Ring trial samples were used for the assessment of recovery. The results of the Roche ISD assay were compared with those of Siemens tacrolimus and cyclosporine assays and LC-MS/MS. Repeatability and between-run imprecision were 2.1-5.3% and 2.6-7.5%, respectively. Recovery of Roche ISD was 85.7 - 90.6% for cyclosporine and 96.2-98.5% for tacrolimus. The two immunoassays showed slight positive biases relative to LC-MS/MS for cyclosporine. For tacrolimus, Roche ISD produced virtually identical results to those of LC-MS/MS, whereas Siemens showed proportional differences, especially in patients receiving kidney transplantation. The analytical performances of Roche ISD were generally acceptable, especially regarding accuracy. Clinical laboratory staff should be aware of the strengths and weaknesses of commercial immunoassays in order to ensure accurate results.

Human adenoviruses (HAdVs) cause a wide range of diseases, including respiratory infections and gastroenteritis, and have more than 65 genotypes. To investigate the current genotypes of circulating HAdV strains, we performed molecular genotyping of HAdVs in the stool from patients with acute gastroenteritis and tried to determine their associations with clinical symptoms. From June 2014 to May 2016, 3,901 fecal samples were tested for an AdV antigen, and 254 samples (6.5%) yielded positive results. Genotyping using PCR and sequencing of the capsid hexon gene was performed for 236 AdV antigen-positive fecal specimens. HAdV-41, of species F, was the most prevalent genotype (60.6%), followed by HAdV-2 of species C (13.8%). Other genotypes, including HAdV-3, HAdV-1, HAdV-5, HAdV-6, HAdV-31, HAdV-40, HAdV-12, and HAdV-55, were also detected. Overall, 119 patients (50.4%) showed concomitant respiratory symptoms, and 32 patients (13.6%) were diagnosed with intussusception. HAdV-1 and HAdV-31 were significantly associated with intussusception (P<0.05). Our results demonstrate the recent changes in trends of circulating AdV genotypes associated with gastroenteritis in Korea, which should be of value for improving the diagnosis and developing new detection, treatment, and prevention strategies for broad application in clinical laboratories.

Background The accurate and rapid identification of the causative viruses is important for the timely diagnosis and management of respiratory infections. Multiplex molecular diagnostic techniques have been widely adopted to detect respiratory viruses. We compared the results of a newly upgraded, multiplex, molecular bead-based respiratory viral panel (RVP) assay with the results of Anyplex II RV16 detection kit and AdvanSure RV real-time RT-PCR assay. Methods We tested 254 respiratory specimens and cultured viral strains using the Luminex xTAG RVP Fast v2 assay (Luminex Molecular Diagnostics, Canada) and Anyplex II RV16 detection kit and compared the results. Specimens showing discordant results between the two assays were tested with a AdvanSure RV real-time RT-PCR assay. Results Of the 254 respiratory specimens, there was total agreement in the results between the xTAG RVP Fast v2 assay and the other real-time PCR assay in 94.1-100% of the specimens. The agreement levels were relatively low (94.1-97.6%) for specimens of adenovirus, coronavirus NL63, and parainfluenza type 3. In comparison to the other assay, the xTAG RVP Fast v2 assay detected a higher number of parainfluenza type 3 (4 cases) and metapneumovirus (9 cases). Conclusions The xTAG RVP Fast v2 assay showed comparable capabilities compared with the other assays; it will be useful for identifying respiratory viral infections in patients with respiratory symptoms. Clinicians should be aware of the characteristics of the assays they use, since different assays show different detectability for each virus.

Background: Quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. We evaluated the impact of various Hb variants on five routine HbA1c assays by comparing with the IFCC reference measurement procedure (RMP). Methods: Whole blood samples showing warning flags or no results on routine HPLC HbA1c assays were confirmed for Hb variants and were submitted to HbA1c quantification using Sebia Capillarys 2 Flex Piercing, Roche Tina-quant HbA1c Gen. 2, Bio-Rad Variant II Turbo 2.0, ADAMS HA-8180, Tosoh G8 standard mode, and IFCC RMP using LC-MS. Results: Among 114 samples, the most common variants were Hb G-Coushatta (n=47), Queens (n=41), Ube-4 (n=11), Chad (n=4), Yamagata (n=4), G-His-Tsou (n=2), G-Taipei (n=1), Fort de France (n=1), Hoshida (n=1), and two novel variants (Hb α-globin, HBA 52 Gly>Cys and Hb β-globin, HBB 146 His>Asn). In terms of control samples, all the result of HbA1c were “acceptable”, within the criteria of ±7% compared to IFCC RMP target values. However, percentage of “unacceptable” results of samples with Hb variants were 16% for Capillarys 2, 7% for Tina-quant, 51% for Variant II Turbo 2.0, 95% for G8 standard mode, and 89% for HA-8180. The Capillarys 2 and HA-8180 assay did not provide the results in 5 and 40 samples with Hb variants, respectively. Conclusions: HbA1c results from five routine assays in patients with relatively common Hb variants in Korea showed various degrees of bias compared to those of IFCC RMP. Therefore, laboratories should be aware of the limitation of their methods with respect to interference from Hb variants found commonly in their local population and suggest an alternative HbA1c quantification method.

AIM To investigate the clinical implications of infliximab trough levels (IFX-TLs) and antibodies to infliximab (ATI) levels in Crohn’s disease (CD) patients in Asian countries. METHODS IFX-TL and ATI level were measured using prospectively collected samples obtained with informed consent from CD patients being treated at Asan Medical Center, South Korea. We analyzed the correlations between IFX-TLs/ATI levels and the clinical activity of CD (quiescent vs active disease) based on the CD activity index, C-reactive protein level, and physician’s judgment of patients’ clinical status at enrollment. The impact of concomitant immunomodulators was also investigated. RESULTS This study enrolled 138 patients with CD (84 with quiescent and 54 with active disease). In patients with quiescent and active diseases, the median IFX-TLs were 1.423 μg/mL and 0.163 μg/mL, respectively (P < 0.001) and the median ATI levels were 8.064 AU/mL and 11.209 AU/mL, respectively (P < 0.001). In the ATI-negative and -positive groups, the median IFX-TLs were 1.415 μg/mL and 0.141 μg/mL, respectively (P < 0.001). In patients with and without concomitant immunomodulator use, there were no differences in IFX-TLs (0.632 μg/mL and 1.150 μg/mL, respectively; P = 0.274) or ATI levels (8.655 AU/mL and 9.017 AU/mL, respectively; P = 0.083). CONCLUSION IFX-TL/ATI levels were well correlated with the clinical activity in South Korean CD patients. Our findings support the usefulness of IFX-TLs/ATI levels in treating CD patients receiving IFX in clinical practice.

The results of urine sediment analysis have been reported semiquantitatively. However, as recent guidelines recommend quantitative reporting of urine sediment, and with the development of automated urine sediment analyzers, there is an increasing need for quantitative analysis of urine sediment. Here, we developed a protocol for urine sediment analysis and quantified the results.Based on questionnaires, various reports, guidelines, and experimental results, we developed a protocol for urine sediment analysis. The results of this new protocol were compared with those obtained with a standardized chamber and an automated sediment analyzer. Reference intervals were also estimated using new protocol.We developed a protocol with centrifugation at 400 g for 5 min, with the average concentration factor of 30. The correlation between quantitative results of urine sediment analysis, the standardized chamber, and the automated sediment analyzer were generally good. The conversion factor derived from the new protocol showed a better fit with the results of manual count than the default conversion factor in the automated sediment analyzer.We developed a protocol for manual urine sediment analysis to quantitatively report the results. This protocol may provide a mean for standardization of urine sediment analysis.

Alpha 1-antitrypsin (AAT) deficiency is a genetic disorder that primarily affects the lungs and liver. While AAT deficiency is one of the most common genetic disorders in the Caucasian population, it is extremely rare in Asians. Here, we report the case of a 36-year-old Korean woman with AAT deficiency who visited the emergency department of our hospital for the treatment of progressive dyspnea that had begun 10 years ago. She had never smoked. Chest computed tomography revealed panlobular emphysema in both lungs, which suggested AAT deficiency. The serum AAT level was 33 mg/dL (reference interval: 90-200 mg/dL). Four exons of the SERPINA1 gene, which is responsible for AAT deficiency, and their flanking regions were analyzed by PCR-direct sequencing. The patient was found to have 1 missense mutation (c.230C>T, p.Ser77Phe; S(iiyama)) and 1 frameshift mutation (c.1158dupC, p.Glu387ArgfsX14; QO(clayton)). This is the first Korean case of AAT deficiency confirmed by genetic analysis and the second case of a compound heterozygote of S(iiyama) and QO(clayton), the first case of which was reported from Japan.

Background Point-of-care (POC) tests are used increasingly due to fast results and simple test procedures, which enables rapid diagnosis and therapeutic monitoring. We evaluated the performance of the Piccolo xpress Chemistry Analyzer (Abaxis, USA) a POC chemistry analyzer. Methods Fourteen analytes, Na(+), K(+), Cl(-), Ca(2+), total carbon dioxide, AST, ALT, total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, albumin, total protein, and glucose; were measured simultaneously with a 100 microL of whole blood sample using a Comprehensive Metabolic Reagent disk. Within-run and total precision and linearity were evaluated according to CLSI EP15-A and EP6-A guidelines, respectively. Comparison with a central laboratory chemistry analyzer was performed using 144 patient samples. Results The coefficients of variations of within-run and total precision were all within 5% for three levels except for total carbon dioxide, ALT, alkaline phosphatase, total bilirubin, and creatinine in low level, and creatinine in middle level. The results of 14 analytes were linear within a commonly encountered range in clinical samples (r(2)> or =0.98). More than 10% of samples in Na(+), AST, ALT, glucose, BUN did not satisfy CLIA analytical quality requirement. Conclusions The Piccolo xpress Chemistry Analyzer can analyze multiple analytes with a minimal amount of whole blood in a short time. It showed an acceptable performance for precision, linearity and comparison with central laboratory analyzer. It can be useful as a screening tests modality in mobile clinics, ambulances, and field clinics for military use, and for pediatric patients from whom enough sample volume is difficult to obtain.

Background Quality control (QC) procedures using stable control materials are important for preventing systematic errors (SEs). While the current QC methods assess QC results semi-quantitatively, we designed a novel quantitative QC procedure (QQCP). Methods QC results were expressed as Z-scores to analyze results quantitatively. The decision values were accumulated up to 30, with three decision values per run, and were compared to rejection criteria at each run. The probability for false rejection (Pfr) and error detection (Ped) for the QQCP and Westgard multirule methods were estimated using simulated QC data with SEs ranging from 0 to 3 standard deviations (SDs). Results The Pfr of the QQCP was 3.4% at the 10th run. When 2 QC materials with the same SEs (0.5 SD and 1.0 SD) were used, the Peds were 36.1% and 95.7% at run 10, respectively. When the SE of each material was greater than 1.5 SDs, the Ped reached 100% at run 10. The QQCP could detect more than 99% of errors in the 6th, 4th, 3rd, and 2nd runs for 2 QC results with 1.5, 2.0, 2.5, and 3.0 SD SEs, respectively. Conclusion The QQCP exhibited a Ped value up to 3.3-fold higher than the Westgard method. Implementation of the QQCP would satisfy the high quality goals derived from biological variations.

Haptoglobin, the product of the Hp gene, is a glycoprotein involved in the scavenging of free hemoglobin. Haptoglobin levels increase or decrease in response to various acquired conditions, and they are also influenced by genetic predisposition. There were 2 major alleles, Hp (1) and Hp (2), and 1 minor allele, Hp (del) . Many researchers have attempted to study the haptoglobin types and their association with disease; however, no definitive conclusions have been reached yet. It is reported that patients who are genetically deficient in haptoglobin are at risk of anaphylaxis against blood components containing haptoglobin. Haptoglobin genotypes also affect the reference intervals of haptoglobin levels. Many studies have attempted to establish simple and accurate typing methods. In this paper, we have broadly reviewed several methods for haptoglobin typing-phenotyping, Southern blotting, conventional PCR, real-time PCR, and loop-mediated isothermal amplification. We discuss their characteristics, clinical applications, and limitations. The phenotyping methods are time consuming and labor intensive and not designed to detect patients harboring Hp (del) . The rapid and robust haptoglobin genotyping may help in preventing fatal anaphylactic reactions and in establishing the relationships between the haptoglobin phenotypes and diseases.

Background : In unrelated hematopoietic stem cell transplantation, the accuracy of HLA registry typing (RT) of donors is important for timely search and coordination of HLA-matched donors. We analyzed discrepancies between HLA RT and confirmatory typing (CT) results of stem cell donors in Korean and foreign registries. Methods : We analyzed the HLA typing results of 834 donors for whom CT was performed at Seoul National University Hospital between April 1997 and March 2010. For CT, DNA typing was used in majority of the cases and HLA-A and HLA-B serological typing was used in some early cases. The discrepancies between the typing results were analyzed at the serological/generic level. Results : The overall discrepancy rate (RT error rate) was 3.2%, and the rate was similar in the Korean and foreign registries. The discrepancy rates in the Korean and foreign registries were more than 10% in the 1997-2001 searches, but decreased to less than 3% in the 2002-2010 searches. Analysis of 19 cases of RT errors in the Korean registry revealed 3 cases of sample switchover errors and 16 cases of typing errors in one of the HLA-A, HLA-B, or HLA-DR loci. The RT error rate in Japan Marrow Donor Program was lower than those in other foreign registries. Conclusions : The error rate of HLA RT results of unrelated stem cell donors in the Korean registry was similar to those in the foreign registries, and has decreased in the recent searches following the change in the typing method from serological to DNA typing.

Background Three different types of galactosemia have been described, and the most common form occurs due to a deficiency in the galactose-1-phosphate uridyltransferase (GALT) enzyme activity. Methods To investigate the molecular defects of the GALT gene, PCR-direct sequencing was performed with genomic DNA from 18 Korean patients with reduced GALT activity. Results Of the 18 patients tested, 13 (72.2%) had previously reported variants: Duarte variant (12 patients), p.R201H (1 patient), and g.A1962G. In addition, we identified six novel sequence variations by PCR-direct sequencing: five sequence variations in coding regions (p.H31R, p.L116I, p.Q169H, p.H186P and p.R333R), and one in an intron (g.2621A>G). Of 100 normal individuals tested, 4 were heterozygous for the Duarte variant, which indicates a Duarte allele frequency of 2%. Biochemical characteristics of the novel genetic alterations were determined: enzyme activity for exonic alterations and splicing for intron. Conclusion The genetic constitution of the GALT gene is responsible for galactosemia in the Korean population.