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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.

Platelet transfusion refractoriness (PTR), in which platelet counts do not increase after transfusion, occurs in many patients receiving platelet transfusions. PTR is a clinical condition that can harm patients. The causes of PTR can be divided into two types: immune and non-immune. Most cases of PTR are non-immune. Among immune causes, the most common is human leukocyte antigen (HLA) class I molecules. PTR caused by anti-HLA antibodies is usually managed by transfusing HLA-matched platelets. Therefore, it is important, especially for hemato-oncologists who frequently perform transfusion, to accurately diagnose whether the cause of platelet transfusion failure is alloimmune or non-immunological when determining the treatment direction for the patient. In this review, we discuss the definitions, causes, countermeasures, and prevention methods of PTR.

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 compared the clinical outcomes of recipients of ABO-incompatible (ABOi) kidney transplantation (KT) according to the blood group of the plasma transfused. Materials and Methods We retrospectively analyzed the data of 60 recipients of ABOi-KT with blood type O and A or B donors. Demographic and clinical characteristics were compared between 2 groups of recipients: 1 group received AB plasma regardless of the donor’s blood type (n = 30), and the other group received donor-type plasma (n = 30). Results There were no significant differences between the groups in terms of demographic characteristics. Transfusion of donor-type plasma was noninferior to transfusion of type AB plasma in terms of both rejection-free survival and rejection rate (P = .455, P = .335). Conclusion There was no significant prognostic difference between the 2 groups. In terms of blood supply and inventory management, we suggest that the blood group of the plasma should match the donor’s type.

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.

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.

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 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 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 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.