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Purpose The aim of this study is to evaluate the safety and efficacy of ex vivo activated and expanded natural killer (NK) cell therapy (SNK01) plus pembrolizumab in a randomized phase I/IIa clinical trial.Materials and Methods Overall, 18 patients with advanced non–small cell lung cancer (NSCLC) and a programmed death ligand 1 tumor proportion score of 1% or greater who had a history of failed frontline platinum-based therapy were randomized (2:1) to receive pembrolizumab every 3 weeks +/– 6 weekly infusions of SNK01 at either 2×109 or 4×109 cells per infusion (pembrolizumab monotherapy vs. SNK01 combination). The primary endpoint was safety, whereas the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), overall survival, and quality of life.Results Since no dose-limiting toxicity was observed, the maximum tolerated dose was determined as SNK01 4×109 cells/dose. The safety data did not show any new safety signals when SNK01 was combined with pembrolizumab. The ORR and the 1-year survival rate in the NK combination group were higher than those in patients who underwent pembrolizumab monotherapy (ORR, 41.7% vs. 0%; 1-year survival rate, 66.7% vs. 50.0%). Furthermore, the median PFS was higher in the SNK01 combination group (6.2 months vs. 1.6 months, p=0.001).Conclusion Based on the findings of this study, the NK cell combination therapy may consider as a safe treatment method for stage IV NSCLC patients who had a history of failed platinum-based therapy without an increase in adverse events.

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.

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.

Objective We designed a study to compare the efficacy of cryoprecipitate-reduced plasma (CRP) and fresh frozen plasma (FFP), at the level of individual sessions, for treating refractory thrombotic microangiopathy (TMA) with therapeutic plasma exchange (TPE). Materials and Methods Platelet counts (× 10³/μL) and lactate dehydrogenase (LD; IU/L) levels were measured before and after each session. We compared the mean-percentage and absolute changes in platelet count and LD after each TPE session. Results The data from 33 patients treated for TMA between 2009 and 2018 were collected for this study. Both absolute and percentage increases in the platelet count were statistically significant (P = .003 and P = .011, respectively) when CRP was used. However, when patients were divided into subgroups according to specific diagnosis, no significant differences were found among the groups, except in terms of the absolute platelet count increase in the thrombotic thrombocytopenic purpura group (P Conclusion The platelet count increase was higher when patients received CRP than when they received FFP. We found that CRP may be a rescue option for patients with refractory TMA.

Background Recent advances in desensitization techniques and immunosuppressive therapy have led to improved outcomes after ABO-incompatible (ABO-i) kidney transplantation (KT). However, questions remain unanswered, particularly regarding which type of ABO isoagglutinin-immunoglobulin M (IgM) or immunoglobulin M (IgG)-is significantly involved in antibody-mediated rejection (AMR). Study design and methods We retrospectively analyzed data from 120 patients who underwent ABO-i KT between 2012 and 2014. Preoperative plasma exchange was performed until the IgM isoagglutinin titer was 4 or less, regardless of the IgG titer. Clinical data were compared between patient groups with pre-KT IgG isoagglutinin titer 16 or greater (high IgG; titer range, 16-256; n = 39) and 8 or less (low IgG; titer range, -8; n = 81). Results The median follow-up periods were 59 (high IgG) and 55 (low IgG) months. Patient survival at 5 years (p = 0.314) was 100% (high IgG) and 97.4% (low IgG). Graft survival at 5 years (p = 0.480) was 100% (high IgG) and 98.7% (low IgG). AMR by anti-ABO antibody occurred in only one patient in the low-IgG group. Conclusion Patients with high pre-KT IgG isoagglutinin titers had equally successful outcomes as those with low IgG titers. ABO-i KT can be successfully performed by reducing the pre-KT IgM isoagglutinin titer to 4 or less, as determined by the immediate spin tube method.

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

Introduction Chimerism is defined as coexistence of different cell lines in an individual. 46,XX/46,XY chimerism is very rare and exhibits broad range of clinical phenotypes. Most cases are detected at infancy or younger age due to disorders of sex development, while phenotypically normal cases are incidentally discovered through abnormal blood grouping results or multiple genotypes in HLA. Objective Aim was to determine the genetic expression of numerous HLA alleles detected in phenotypically normal 46,XX/46,XY chimerism. Materials and methods A patient was admitted for lung transplantation due to end-stage pulmonary disease. Pre-transplantation work-up included blood group typing and HLA DNA typing analyses. Peripheral blood and hair follicle specimens were used to confirm unusual tri-allelic results by high-resolution PCR-SBT. Cytogenetic analyses of karyotyping, FISH and chromosomal microarray were done. Flowcytometry crossmatch analysis was conducted using lymphocytes and anti-HLA sera defined by Luminex panel reactive antibody test (One Lambda, Inc., Canoga Park, CA), to determine antigen expression of HLA alleles. Results 46,XX/46,XY chimerism was confirmed through series of cytogenetic analyses. HLA typing of the patient revealed three alleles from HLA-A, -B and -DRB1 loci. Antigen expression of all 3 HLA alleles was confirmed by flow cytometry crossmatch. Discussion A case of normal phenotype 46,XX/46,XY chimerism was detected for the first time in Korean patient admitted for lung transplantation. Cytogenetic results were confirmatory for chimerism and HLA typing using PCR-SBT method was able to detect the presence of 3 HLA alleles. Flowcytometry crossmatch was proven sensitive for detecting antigen expression of different cell lines of small proportions.

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

Affordable point-of-care (POC) CD4 + T lymphocyte counting techniques have been developed as alternatives to flow cytometry-based instruments caring for patients with human immunodeficiency virus (HIV)-1. However, POC CD4 enumeration technologies can be inaccurate. Here, we developed a microparticle-based visual detector of CD4 + T lymphocytes (ImmunoSpin) using microparticles conjugated with anti-CD4 antibodies, independent of microfluidic or fluorescence detection systems. Visual enumeration of CD4 + T cells under conventional light microscope was accurate compared to flow cytometry. Microparticle-tagged CD4 + T cells were well-recognized under a light microscope. ImmunoSpin showed very good precision (coefficients of variation of ImmunoSpin were ≤ 10%) and high correlation with clinical-grade flow cytometry for the enumeration of CD4 + T cells (y = 0.4232 + 0.9485 × for the %CD4 + T cell count, R2 = 0.99). At thresholds of 200 and 350 cells/µL, there was no misclassification of the ImmunoSpin system compared to the reference flow cytometry. ImmunoSpin showed clear differential classification of CD4 + T lymphocytes from granulocytes and monocytes. Because non-fluorescence microparticle-tags and cytospin slides are used in ImmunoSpin, they can be applied to an automatic digital image analyzer. Slide preparation allows long-term storage, no analysis time limitations, and image transfer in remote areas. Graphical abstract

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 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 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.

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.

Introduction ABO-incompatible transplantation has expanded the limited donor pool for kidney transplantation. Despite the successful desensitization protocols and immunosuppression, undesirable cases of hyperacute rejection occurs. Objective Flow cytometry was used to measure isoagglutinin titer and its IgG subclasses in assessment of the cause of hyperacute rejection in ABO-incompatible kidney transplantation. Materials and methods The recipient was admitted for kidney transplantation due to end-stage renal disease. Pre-transplantation work-up for ABO-incompatible kidney transplantation included blood group typing, HLA DNA typing and HLA antibody analyses. HLA crossmatch analysis was conducted using donor lymphocytes and anti-HLA antibody assay using Luminex panel reactive antibody test (One Lambda, Inc., Canoga Park, CA). Desensitization protocol was composed of therapeutic plasma exchange sessions and rituximab. Results Despite negative HLA crossmatch results, a case of hyperacute rejection occurred after living donor kidney transplantation. Rejection resulted in immediate removal of graft, and the patient later received a second kidney transplantation. Retrospective evaluation of isoagglutinin titer and its subclasses using flow cytometry identified the cause of rejection to increased IgG1 subclass. Desensitization protocol for ABO-incompatible kidney transplantation now implements further caution for blood group O recipients. Discussion Hyperacute rejection resulting from increased IgG1 isoagglutinin subclass has not been previously confirmed using flow cytometry. Unfortunate outcome of this rejection case provides insight to how we should approach and ensure successful ABO-incompatible kidney transplantation.

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.

Natural killer (NK) cells are key effectors in cancer immunosurveillance and can be used as a prognostic biomarker in diverse cancers. Nonetheless, the role of NK cells in pancreatic cancer (PC) remains elusive, given conflicting data on their association with disease prognosis. In this study, using conventional K562 target cells and complementary engineered target cells providing defined and synergistic stimulation for NK cell activation, a correlation between impaired NK cell cytotoxic degranulation and PC progression was determined. Peripheral blood mononuclear cells (PBMCs) from 31 patients with newly diagnosed PC, 24 patients with non-malignant tumors, and 37 healthy controls were analyzed by flow cytometry. The frequency, phenotype, and effector functions of the NK cells were evaluated, and correlations between NK cell functions and disease stage and prognosis were analyzed. The results demonstrated that effector functions, but not frequency, of NK cells was progressively decreased on a per-cell basis during PC progression. Impaired cytotoxic degranulation, but not IFN-γ production, was associated with clinical features indicating disease progression, such as high serum CA19-9 and high-grade tumors. Significantly, this impairment correlated with cancer recurrence and mortality in a prospective analysis. Furthermore, the impaired cytotoxic degranulation was unrelated to NKG2D downregulation but was associated with increased circulating and tumor-associated TGF-β1 expression. Thus, NK cell cytotoxic activity was associated with PC progression and may be a favorable biomarker with predictive and prognostic value in PC.

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.

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

Molecular diagnostics is a powerful technique for detecting pathogens with high sensitivity, but it has complicated sample preparation procedures that rely not only on a manual operation by experts but also on bulky equipment. Here, we report the use of an unpowered, microfluidic sample preparation device in on-site molecular diagnosis without the necessity of expertise and electrical devices. The device is assembled with two units, a plasma separation chip, and a nucleic acid extraction and purification chip. As a model pathogen, Escherichia coli (E. coli) O157:H7 was first separated from the blood sample using the unpowered plasma separation chip, and then the DNA was extracted and purified from the separated bacteria by using the finter-actuated nucleic acid extraction and purification chip. 103 to 108 CFU/mL of E. coli O157:H7 was infiltered from the blood sample with ∼1% of permeation efficiency. The extracted DNA was successfully purified and confirmed by gel electrophoresis after the polymerase chain reaction. This unpowered sample pretreatment method is precise and reliable, even at low concentrations of down to 103 CFU/mL of E. coli in the blood sample.

Exchange transfusion (ET) is an established, efficacious, and reliable practice for severe neonatal hyperbilirubinemia, hemolytic disease of the newborn, and neonatal sepsis. This study assessed the indications and clinical outcomes of ET performed in a tertiary hospital in Korea.We studied 64 ET sessions performed on 23 neonates between March 1999 and March 2018. ET was performed based on estimated double volume exchange transfusion using fresh red blood cells and fresh frozen plasma. Patients' clinical information, including demographic data and ET indication, and laboratory data were collected pre- and post-ET.The most common ET indication was hyperbilirubinemia with hemolytic anemia due to non-ABO maternal blood group discrepancies. In three preterm babies, ETs were performed for severe anemia, leukocytosis, and hyperkalemia cases. Before ET, the patients showed slightly high WBC counts, low hemoglobin levels, and low platelet counts. After ET, blood examination revealed normal WBC counts, increased hemoglobin levels, and decreased platelet counts (all P0.001). Bilirubin levels decreased immediately after ET (P0.001). Electrolyte and C-reactive protein levels showed no significant changes after ETs. Adverse events occurred in 11 (47.8 %) patients; the most common were hypoxemia and hypotension. One infant experienced cardiorespiratory arrest due to hypercalcemia and was successfully resuscitated. No one died within 24 h of ET. However, five infants showed hyperbilirubinemia aggravation.ET is an effective treatment modality for leukocytosis and hyperbilirubinemia with low mortality but involves common adverse events post-ET. This report provides an overview of current ET practices in Korea.

3037 Background: Despite the increased promise of checkpoint inhibitors in the treatment of lung cancer, the overall response rate is approximately 30% with up to 30% moderate to severe side effects. Natural killer (NK) cells have recently been implicated in antitumor response to immune checkpoint inhibitors. SNK01 is a novel non-genetically modified autologous natural killer cell therapy with enhanced cytotoxicity which has been found to have tumoricidal effects against several lung cancer cell lines. Methods: 18 patients with Stage IV NSCLC (PD-L1+, EGFR-, ALK-) who all failed prior frontline platinum-based therapy were randomized 2:1 to Pembrolizumab every three weeks +/- 6 weekly infusions of SNK01 at either 2 x 109 or 4 x 109 cells per infusion. Primary endpoint is safety and secondary endpoints are objective response rate (ORR), progression-free survival (PFS), overall survival (OS), time to progression (TPP), and quality of life (QoL). Results: 14 patients have been enrolled up to date and 9 have completed treatment. Median age is 69 (52-73). Two patients discontinued treatment prior to receiving their first dose of SNK01 due to Grade 3 toxicity to Pembrolizumab. Three patients have completed therapy with Pembrolizumab alone and all had progressive disease. Three patients have completed Pembrolizumab with 2 x 109 SNK01 and three patients have completed Pembrolizumab with 4 x 109 SNK01. Of patients receiving full combination therapy, there have been no adverse events or any reported toxicity while overall QoL has been improved. The week 9 overall response rate in the combination group is 66% using iRECIST (3/6 cPR, 1/6 PR). All remaining planned patients are currently being enrolled and a full update will be presented. Conclusions: These preliminary results demonstrate that combination therapy with Pembrolizumab and SNK01 is very safe and even appears to reduce checkpoint associated toxicity while increasing overall tumor response compared to Pembrolizumab monotherapy alone in Stage IV NSCLC patients who have failed prior platinum-based treatment.

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

Background Cardiac troponin I (TnI) is one of the most crucial biomarkers for the management of acute coronary syndrome. However, the TnI values can vary when using commercial TnI assays from different vendors. We assessed the feasibility of TnI harmonization using plasma and serum samples. Methods Leftover plasma and serum samples were collected from patients and stored for further analysis (n = 200). TnI measurements were performed using 3 different analyzers. The TnI values for plasma and serum were compared, and the mathematical recalibration was performed using the mean of 3 values from each analyzer as a reference value. The number of biased cases was counted before and after recalibration. Results The final analysis was performed in a total of 140 plasma and serum samples, and constant and/or proportional differences for each analyzer were observed. Mathematical recalibration of the TnI values resulted in improved correlation to the reference values. The number of TnI values that were remote from the reference values decreased after recalibration. The effects were more evident for serum samples. Conclusions In this study, we reassured the possibility of TnI harmonization among 3 different immunoassays using plasma and serum samples. It is important to note the differences between sample types during TnI harmonization.

The Jra antigen of the JR blood group system is a highly prevalent red blood cell antigen. Although anti-Jra-associated hemolytic disease of the fetus and newborn (HDFN) is generally considered mild-to-moderate, a rare fatal case was recently reported. We report the third example of HDFN-related anti-Jra with fatal outcomes. The clinical significance of anti-Jra antibody as a cause of HDFN should be reassessed.

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.

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.