Application of the European Kidney Function Consortium Equation to Estimate Glomerular Filtration Rate: A Comparison Study of the CKiD and CKD-EPI Equations Using the Korea National Health and Nutrition Examination Survey (KNHANES 2008-2021).

Background and Objectives: The European Kidney Function Consortium (EKFC) equation has been newly proposed for estimating glomerular filtration rate (eGFR) across the spectrum of age. We compared the EKFC equation with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in a large-scale Korean population. Materials and Methods: Using the representative Korean health examination data, the Korea National Health and Nutrition Examination Survey (KNHANES 2008-2021), the records of 91,928 subjects (including 9917 children) were analyzed. We compared the EKFC equation with CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations and investigated their agreement across GFR categories. Results: In the total population, the CKD-EPI 2021 equation yielded the highest eGFR value, followed by the CKD-EPI 2009 and EKFC equations. In children, the distribution of eGFR differed significantly between the EKFC and CKiD equations (p < 0.001), with a wider range of eGFR values found with the CKiD equation. Each equation showed weak or moderate agreement on the frequency of the GFR category (κ = 0.54 between EKFC and CKD-EPI 2021; κ = 0.77 between EKFC and CKD-EPI 2009). The eGFR values found by the EKFC equation showed high or very high correlations with those by the CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations (r = 0.85, 0.97, and 0.97, respectively). As eGFR values increased, bigger differences were observed between equations. Conclusions: This large-scale study demonstrates that the EKFC equation would be applicable across the entire age spectrum in Asian populations. It also underscores that national kidney health would be highly affected by an eGFR equation being implemented. Additional investigation and more caution would be warranted for the transition of eGFR equations.

Performance Assessment of Sysmex DI-60: Is Digital Morphology Analyzer Reliable for White Blood Cell Differentials in Body Fluids?

BACKGROUND: Few studies have evaluated digital morphology (DM) analyzers on body fluids (BF). We evaluated the performance of a DM analyzer, Sysmex DI-60 (Sysmex, Kobe, Japan) for white blood cell (WBC) differentials in BF samples. METHODS: In five BF samples (two pleural fluids and three ascites) containing a single, dominant cell type (>80%, neutrophils, lymphocytes, macrophages, abnormal lymphocytes, and malignant cells in each sample), we evaluated the precision of the DI-60 and compared the WBC differentials and turnaround times (TAT) between DI-60 and manual counting. RESULTS: The precision of the DI-60 pre-classification and verification was excellent (%CV, 0.01-3.16%). After verification, the DI-60 showed high sensitivity, specificity, and efficiency (ranges: 90.8-98.1%, 96.8-97.9%, and 92.5-98.0%, respectively) for the dominant cell types in neutrophil- and lymphocyte-dominant samples. For all samples, the DI-60 and manual counting showed high correlations for major cell types (neutrophils, lymphocytes, macrophages, and others, r = 0.72 to 0.94) after verification. The agreement between the pre-classification and verification of the DI-60 was strong in the neutrophil-dominant sample (κ = 0.81). The DI-60 showed a significantly longer TAT (min: s) than manual counting for all samples (median TAT/slide: 6:28 vs. 1:53, p < 0.0001), with remarkable differences in abnormal lymphocyte- and malignant cell-dominant samples (21:05 vs. 2:06; 12:34 vs. 2:25). CONCLUSIONS: The DI-60 may provide reliable data in neutrophil- and lymphocyte-dominant BF samples. However, it may require longer times and higher workloads for WBC differentials especially in BF samples containing atypical cells. Further improvement would be needed before applying DM analyzers for routine clinical practice in BF analysis.

A Korean family with RHD*DNT only detectable after anti-D alloimmunization.

OBJECTIVES: Identification of DNT, a rare partial D, can be challenging, as it is difficult to distinguish from D+. This study aimed to identify DNT individuals by analyzing the DNT proband's family members, characterize DNT, and propose management strategies. METHODS: Family members of the first Korean DNT proband were recruited. RHD genotyping was conducted, and weak D tests were carried out using several anti-D reagents. RESULTS: Three DNT individuals were identified among 6 family members, including 1 with an anti-D alloantibody. As DNT red cells exhibited strong reactivity with all anti-D clones, DNT was serologically indistinguishable from D+. Moreover, unusual serologic findings in DNT individuals only became apparent after anti-D alloimmunization. CONCLUSIONS: We recommend DNT individuals as candidates for Rh immune globulin prophylaxis during the perinatal period and transfusions with D- blood components. An anticipatory RHD genotyping is suggested for partial D family members to prevent potential partial D individuals from becoming alloimmunized.

Detection of blasts using flags and cell population data rules on Beckman Coulter DxH 900 hematology analyzer in patients with hematologic diseases.

OBJECTIVES: White blood cell (WBC)-related flags are essential for detecting abnormal cells including blasts in automated hematology analyzers (AHAs). Cell population data (CPD) may characterize each WBC population, and customized CPD rules can be also useful for detecting blasts. We evaluated the performance of WBC-related flags, customized CPD rules, and their combination for detecting blasts on the Beckman Coulter DxH 900 AHA (DxH 900, Beckman Coulter, Miami, Florida, USA). METHODS: In a total of 239 samples from patients with hematologic diseases, complete blood count on DxH 900 and manual slide review (MSR) were conducted. The sensitivity, specificity, and efficiency of the five WBC-related flags, nine customized CPD rules, and their combination were evaluated for detecting blasts, in comparison with MSR. RESULTS: Blasts were detected by MSR in 40 out of 239 (16.7 %) samples. The combination of flags and CPD rules showed the highest sensitivity compared with each of flags and CPD rules for detecting blasts (97.5 vs. 72.5 % vs. 92.5 %). Compared with any flag, the combination of flags and CPD rules significantly reduced false-negative samples from 11 to one for detecting blasts (27.5 vs. 2.5 %, p=0.002). CONCLUSIONS: This is the first study that evaluated the performance of both flags and CPD rules on DxH 900. The customized CPD rules as well as the combination of flags and CPD rules outperformed WBC-related flags for detecting blasts on DxH 900. The customized CPD rules can play a complementary role for improving the capability of blast detection on DxH 900.

Utility of Presepsin and Interferon-λ3 for Predicting Disease Severity and Clinical Outcomes in COVID-19 Patients.

We explored the utility of novel biomarkers, presepsin and interferon-λ3 (IFN-λ3), for predicting disease severity and clinical outcomes in hospitalized Coronavirus (COVID-19) patients. In a total of 55 patients (non-critical, n = 16; critical, n = 39), presepsin and IFN-λ3 were compared with sequential organ failure assessment (SOFA) scores and age. Disease severity and clinical outcomes (in-hospital mortality, intensive care unit admission, ventilator use, and kidney replacement therapy) were analyzed using receiver operating characteristic (ROC) curves. In-hospital mortality was also analyzed using the Kaplan-Meier method with hazard ratios (HR). SOFA scores, age, presepsin, and IFN-λ3 predicted disease severity comparably (area under the curve [AUC], 0.67-0.73). SOFA score and IFN-λ3 predicted clinical outcomes comparably (AUC, 0.68-0.88 and 0.66-0.74, respectively). Presepsin predicted in-hospital mortality (AUC = 0.74). The combination of presepsin and IFN-λ3 showed a higher mortality risk than SOFA score or age (HR [95% confidence interval, CI], 6.7 [1.8-24.1]; 3.6 [1.1-12.1]; 2.8 [0.8-9.6], respectively) and mortality rate further increased when presepsin and IFN-λ3 were added to SOFA scores or age (8.5 [6.8-24.6], 4.2 [0.9-20.6], respectively). In the elderly (≥65 years), in-hospital mortality rate was significantly higher when both presepsin and IFN-λ3 levels increased than when either one or no biomarker level increased (88.9% vs. 14.3%, p < 0.001). Presepsin and IFN-λ3 predicted disease severity and clinical outcomes in hospitalized COVID-19 patients. Both biomarkers, whether alone or added to the clinical assessment, could be useful for managing COVID-19 patients, especially the elderly.

Performance of digital morphology analyzer Medica EasyCell assistant.

OBJECTIVES: The EasyCell assistant (Medica, Bedford, MA, USA) is one of the state-of-the-art digital morphology analyzers. We explored the performance of EasyCell assistant in comparison with manual microscopic review and Pentra DX Nexus (Horiba ABX Diagnostics, Montpellier, France). METHODS: In a total of 225 samples (100 normal and 125 abnormal samples), white blood cell (WBC) differentials and platelet (PLT) count estimation by EasyCell assistant were compared with the results by manual microscopic review and Pentra DX Nexus. The manual microscopic review was performed according to the Clinical and Laboratory Standards Institute guidelines (H20-A2). RESULTS: WBC differentials between pre-classification by EasyCell assistant and manual counting showed moderate correlations for neutrophils (r=0.58), lymphocytes (r=0.69), and eosinophils (r=0.51) in all samples. After user verification, they showed mostly high to very high correlations for neutrophils (r=0.74), lymphocytes (r=0.78), eosinophils (r=0.88), and other cells (r=0.91). PLT count by EasyCell assistant highly correlated with that by Pentra DX Nexus (r=0.82). CONCLUSIONS: The performance of EasyCell assistant for WBC differentials and PLT count seems to be acceptable even in abnormal samples with improvement after user verification. The EasyCell assistant, with its reliable performance on WBC differentials and PLT count, would help optimize the workflow of hematology laboratories with reduced workload of manual microscopic review.

Soluble ST2 as a Useful Biomarker for Predicting Clinical Outcomes in Hospitalized COVID-19 Patients.

Soluble suppression of tumorigenesis-2 (sST2) is an emerging biomarker for sepsis as well as for heart failure. We investigated the prognostic utility of sST2 for predicting clinical outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients. In a total of 52 hospitalized COVID-19 patients, sST2 levels were measured using the ichroma ST2 assay (Boditech Med Inc., Chuncheon-si, Gang-won-do, Republic of Korea). Clinical outcomes included intensive care unit (ICU) admission, ventilator use, extracorporeal membrane oxygenation (ECMO) use, and 30-day mortality. sST2 was analyzed according to clinical outcomes. sST2, sequential organ failure assessment (SOFA) score, critical disease, and 4C mortality score were compared using the receiver operating characteristic (ROC) curve and Kaplan−Meier methods for clinical outcomes. The sST2 level differed significantly according to ICU admission, ventilator use, ECMO use, and 30-day mortality (all p < 0.05). On ROC curve analysis, sST2 predicted ICU admission, ventilator use, ECMO use, and 30-day mortality comparable to SOFA score but significantly better than critical disease. sST2 predicted ICU admission, ventilator use, and ECMO use significantly better than the 4C mortality score. On Kaplan−Meier survival analysis, hazard ratios (95% confidence interval) were 8.4 (2.7−26.8) for sST2, 14.8 (3.0−71.7) for SOFA score, 1.8 (0.5−6.5) for critical disease, and 11.7 (3.4−40.1) for 4C mortality score. This study demonstrated that sST2 could be a useful biomarker to predict ICU admission, ventilator use, ECMO use, and 30-day mortality in hospitalized COVID-19 patients. sST2 may be implemented as a prognostic COVID-19 biomarker in clinical practice.

Clinical Impact of Recipient-Derived Isoagglutinin Levels in ABO-Incompatible Hematopoietic Stem Cell Transplantation.

ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). We hypothesized that recipient-derived isoagglutinin (RDI) levels could play a critical role in clinical outcomes. In this study, we compared clinical outcomes such as survival, GVHD, infection, relapse, transfusion, and engraftment, among ABO-compatible patients (ABOc), ABO-incompatible patients (ABOi) with low RDI, and ABOi patients with high RDI. The ABOi with high RDI group was defined as recipients with more than 1:16 RDI levels. We analyzed 103 recipients (ABOc, 53; ABOi with low RDI, 36; ABOi with high RDI, 14). The ABOi with high RDI group showed a decreased 1-year survival and increased acute GVHD grade IV and RBC transfusion (p = 0.017, 0.027, and 0.032, respectively). The ABOi with high RDI group was an independent risk factor for increased death, RBC transfusion, and poor platelet (PLT) engraftment (odds ratio (OR) = 3.20, p = 0.01; OR = 8.28, p = 0.02; OR = 0.18, p = 0.03, respectively). The ABOi with high RDI group showed significantly delayed PLT engraftment. In conclusion, this is the first study underscoring high RDI levels as a marker predicting unfavorable outcomes in ABOi HSCT.

Evaluation of Cellular Responses to ChAdOx1-nCoV-19 and BNT162b2 Vaccinations.

While numerous studies have evaluated humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, data on the cellular responses to these vaccines remain sparse. We evaluated T cell responses to ChAdOx1-nCoV-19 and BNT162b2 vaccinations using an interferon gamma (IFN-γ) release assay (IGRA). ChAdOx1-nCoV-19- and BNT162b2-vaccinated participants initially showed stronger T cell responses than unvaccinated controls. The T cell response decreased over time and increased substantially after the administration of a BNT162b2 booster dose. Changes in the T cell response were less significant than those in the anti-receptor-binding domain IgG antibody titer. The study results can serve as baseline data for T cell responses after SARS-CoV-2 vaccination and suggest that the IGRA can be useful in monitoring immunogenicity.

Performance of digital morphology analyzer CellaVision DC-1.

OBJECTIVES: CellaVision DC-1 (DC-1, Sysmex, Kobe, Japan) is a newly launched digital morphology analyzer that was developed mainly for small to medium-volume laboratories. We evaluated the precision, qualitative performance, comparison of cell counts between DC-1 and manual counting, and turnaround time (TAT) of DC-1. METHODS: Using five peripheral blood smear (PBS) slides spanning normal white blood cell (WBC) range, precision and qualitative performance of DC-1 were evaluated according to the Clinical and Laboratory Standards Institute (CLSI) EP15-A3, EP15-Ed3-IG1, and EP12-A2 guidelines. Cell counts of DC-1 and manual counting were compared according to the CLSI EP 09C-ED3 guidelines, and TAT of DC-1 was also compared with TAT of manual counting. RESULTS: DC-1 showed excellent precision (%CV, 0.0-3.5%), high specificity (98.9-100.0%), and high negative predictive value (98.4-100.0%) in 18 cell classes (12 WBC classes and six non-WBC classes). However, DC-1 showed 0% of positive predictive value in seven cell classes (metamyelocytes, myelocytes, promyelocytes, blasts, plasma cells, nucleated red blood cells, and unidentified). The largest absolute mean differences (%) of DC-1 vs. manual counting was 2.74. Total TAT (min:s) was comparable between DC-1 (8:55) and manual counting (8:55). CONCLUSIONS: This is the first study that comprehensively evaluated the performance of DC-1 including its TAT. DC-1 has a reliable performance that can be used in small to medium-volume laboratories for assisting PBS review. However, DC-1 may make unnecessary workload for cell verification in some cell classes.

Usefulness of KL-6 for Predicting Clinical Outcomes in Hospitalized COVID-19 Patients.

Background: Krebs von den Lungen 6 (KL-6) is a novel biomarker for interstitial lung disease, and it reflects acute lung injury. We explored the usefulness of KL-6 to predict clinical outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients. Methods: In a total of 48 hospitalized COVID-19 patients, KL-6 levels were measured using the HISCL KL-6 assay (Sysmex, Kobe, Japan) with the HISCL 5000 automated analyzer (Sysmex). Clinical outcomes (intensive care unit [ICU] admission, ventilator use, extracorporeal membrane oxygenation [ECMO] use, and 30-day mortality) were analyzed according to KL-6 percentiles. Age, initial KL-6 level, Charlson comorbidity index (CCI), and critical disease were compared using the receiver operating characteristic (ROC) curve and Kaplan-Meier methods for clinical outcomes. Results: KL-6 quartiles were associated with ICU admission, ventilator use, and ECMO use (all p < 0.05), except 30-day mortality (p = 0.187). On ROC curve analysis, initial KL-6 level predicted ICU admission, ventilator use, and ECMO use significantly better than age, CCI, and critical disease (all p < 0.05); age, initial KL-6 level, CCI, and critical disease predicted 30-day mortality comparably. On Kaplan−Meier survival analysis, hazard ratios (95% confidence interval) were 4.8 (1.2−19.3) for age, 4.7 (1.1−21.6) for initial KL-6 level, 3.9 (0.9−16.2) for CCI, and 2.1 (0.5−10.3) for critical disease. Conclusions: This study demonstrated that KL-6 could be a useful biomarker to predict clinical outcomes in hospitalized COVID-19 patients. KL-6 may contribute to identifying COVID-19 patients requiring critical care, including ICU admission and ventilator and/or ECMO use.

Distribution of Presepsin, Krebs von den Lungen 6, and Surfactant Protein A in Umbilical Cord Blood.

Presepsin is an early indicator of infection, and Krebs von den Lungen 6 (KL-6) and Surfactant Protein A (SP-A) are related to the pathogenesis of pulmonary infection and fibrosis. This study aimed to establish reference intervals (RIs) of presepsin, KL-6, and SP-A levels and to evaluate the possible influence of neonatal and maternal factors on presepsin, KL-6, and SP-A levels in umbilical cord blood (UCB). Among a total of 613 UCB samples, the outliers were removed. The RIs for presepsin, KL-6, and SP-A levels were defined using non-parametric percentile methods according to the Clinical and Laboratory Standards Institute guidelines (EP28-A3C). These levels were analyzed according to neonatal and maternal factors: neonatal sex, gestational age (GA), birth weight (BW), Apgar score, delivery mode, the presence of premature rupture of membranes (PROM), gestational diabetes mellitus (GDM), and pre-eclampsia. Presepsin, KL-6, and SP-A levels showed non-parametric distributions and left-skewed histograms. The RIs of presepsin, KL-6, and SP-A levels were 64.9-428.3 pg/mL, 43.0-172.0 U/mL, and 2.1-36.1 ng/mL, respectively. Presepsin, KL-6, and SP-A levels did not show significant differences according to sex, GA, BW, Apgar score, delivery mode, PROM, GDM, and pre-eclampsia. The median level and 97.5th centile RI of KL-6 showed a slight increase with increased GA. We established RIs for presepsin, KL-6, and SP-A levels in large-scaled UCB samples. Further investigation would be needed to determine the clinical significance.

Reference Interval for the Axis-Shield Clinical Chemistry Heparin-Binding Protein Assay.

The newly developed Axis-Shield clinical chemistry heparin-binding protein (HBP) assay (Axis-Shield Diagnostics Ltd., Dundee, Scotland) can be applied to fully automated platforms. We aimed to establish a reference interval (RI) of HBP using the Axis-Shield HBP assay, and to evaluate the analytical performance of this assay. An RI was established in 212 sodium citrated plasma samples using the non-parametric method (2.5th and 97.5th percentiles). Precision, linearity, and carry-over were evaluated according to the Clinical and Laboratory Standards Institute guidelines. The RI of HBP was between 5.3 ng/mL and 171.0 ng/mL, which could be applied regardless of gender and age. Percentage coefficients of variations (%CVs) of repeatability and within-laboratory precision were 4.9% and 6.3%, respectively, for low-concentration control and 1.6% and 3.0%, respectively, for high-concentration control. The linearity was excellent (coefficient of determination (R2) = 0.99), and the carry-over rate was negligible (0.05%). This is the first study to establish an RI of HBP using the newly developed and fully automated Axis-Shield HBP assay. The Axis-Shield HBP assay showed an acceptable level of analytical performance and could be used to measure HBP concentrations effectively in routine clinical practice. Further studies are awaited to evaluate the clinical utility of HBP using this automated assay.

European Kidney Function Consortium Equation vs. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Refit Equations for Estimating Glomerular Filtration Rate: Comparison with CKD-EPI Equations in the Korean Population.

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is the most commonly used equation for estimated glomerular filtration rate (eGFR). Recently, the European Kidney Function Consortium (EKFC) announced a full-age spectrum equation, and the CKD-EPI announced the CKD-EPI refit equations (CKD-EPI-R). We compared CKD-EPI, EKFC, and CKD-EPI-R equations in a large-scale Korean population and investigated their potential implications for CKD prevalence. In a total of 106,021 individuals who received annual check-ups from 2018 to 2020, we compared the eGFR equations according to the Clinical and Laboratory Standards Institute guidelines. Weighted kappa (κ) agreement was used to compare the potential implications for CKD prevalence across the equations. The median value of eGFR tended to increase in the order of EKFC, CKD-EPI, and CKD-EPI-R equations (92.4 mL/min/1.73 m2, 96.0 mL/min/1.73 m2, and 100.0 mL/min/1.73 m2, respectively). The EKFC and CKD-EPI-R equations showed a very high correlation of eGFR and good agreement for CKD prevalence with CKD-EPI equation (r = 0.98 and 1.00; κ = 0.80 and 0.82, respectively). Compared with the CKD-EPI equation, the EFKC equation overestimated CKD prevalence (3.5%), and the CKD-EPI-R equation underestimated it (1.5%). This is the first study comparing CKD-EPI, EKFC, and CKD-EPI-R equations simultaneously. The EKFC and CKD-EPI-R equations were statistically interchangeable with CKD-EPI equations in this large-scale Korean population. The transition of eGFR equations, however, would lead to sizable changes in the CKD prevalence. To improve kidney health, in-depth discussion considering various clinical aspects is imperative for the transition of eGFR equations.

Pharmacokinetics and Genetic Factors of Atorvastatin in Healthy Korean Subjects.

Background: Statins are the most popular agents for the primary and secondary prevention of cardiovascular disease; however, the pharmacokinetic parameters and associated genetic factors in the Korean population have not been fully elucidated. This study explored the pharmacokinetic properties of atorvastatin and the association between genetic variations and atorvastatin pharmacokinetics in healthy Korean subjects. Methods: Atorvastatin (80 mg) was administered to 35 healthy Korean volunteers. Plasma levels of atorvastatin and its metabolites were measured sequentially using liquid chromatography-tandem mass spectrometry from 0 to 24 h after atorvastatin administration. Customized next-generation sequencing analysis was performed covering all coding exons of 15 genes, as well as 46 single-nucleotide variants in 29 genes related to statin pharmacokinetics. Results: The mean area under the concentration-time (AUC) and Cmax (maximum peak concentration) were 269.0 ng/ml∙h and 84.3 ng/ml, respectively, which were approximately two times higher than those reported in Caucasians. Genetic analysis revealed that eight genetic variants in ABCB1, ABCG2, APOA5, CETP, and CYP7A1 contributed to the AUC of atorvastatin. The atorvastatin AUC0-24 h prediction model was developed based on age and eight genetic variants using multivariate linear regression (adjusted R 2 = 0.878, p < 0.0001). Conclusion: This study shows that the pharmacokinetic properties of atorvastatin in Koreans are different from those in Caucasians and that atorvastatin AUC0-24 h could be predicted based on age and eight genetic variants of ABCB1, ABCG2, APOA5, CETP, and CYP7A1.

Novel Usefulness of Krebs von den Lungen 6 (KL-6) with Hemoglobin and Lactate Dehydrogenase for Assessing Bone Marrow Fibrosis.

Bone marrow fibrosis (BMF) is manually assessed by reticulin and trichrome stain of bone marrow (BM) biopsy and graded on a semi-quantitative scale. Krebs von den Lungen 6 (KL-6) and Mac-2 binding protein glycosylation isomer (M2BPGi) are known to be associated with lung and liver fibrosis, respectively. We explored the usefulness of KL-6 and M2BPGi to assess BMF. A total of 250 patients who underwent BM biopsy with hematologic or non-hematologic diseases were included, and 42 patients with lung and liver diseases were excluded. The patients' data, including age, sex, diagnosis, white blood cell, hemoglobin (Hb), platelet, and lactate dehydrogenase (LDH) were collected. Measured KL-6 and M2BPGi levels were compared with reticulin grade (RG) (grade 0-3). KL-6 levels were significantly elevated with an increase in RG, but M2BPGi did not show a significant difference. Hb, LDH, or KL-6 were independent predictors for BMF (odds ratio: 1.96, 2.26, 2.91, respectively), but showed poor predictive ability (area under the curve [AUC] 0.62, 0.61, 0.60, respectively). The combination of Hb, LDH, and KL-6 showed a significantly improved predictive ability for BMF (AUC 0.73; integrated discrimination improvement 0.057; category-free net reclassification improvement 0.625). This is the first study to evaluate the usefulness of KL-6 for assessing BMF. The combination of Hb, LDH, and KL-6 would be an objective and relevant biomarker approach and be applied to risk stratification for BMF.

Digital Morphology Analyzer Sysmex DI-60 vs. Manual Counting for White Blood Cell Differentials in Leukopenic Samples: A Comparative Assessment of Risk and Turnaround Time.

BACKGROUND: Digital morphology (DM) analyzers are increasingly being used for white blood cell (WBC) differentials. We assessed the laboratory efficiency of the Sysmex DI-60 system (DI-60; Sysmex, Kobe, Japan) in comparison with manual counting in leukopenic samples. METHODS: In total, 40 peripheral blood smear samples were divided into normal, mild leukopenia, moderate leukopenia, and severe leukopenia groups based on WBC count. In each group, the risk and turnaround time (TAT) were compared between DI-60 and manual counting. Risk was determined by failure mode and effect analysis using the risk priority number (RPN) score, and TAT was recorded for the analytical phase. RESULTS: Overall, DI-60 showed a five-fold lower risk (70 vs. 350 RPN) and longer TAT than manual counting. In severe leukopenic samples, DI-60 showed a shorter TAT/slide and a remarkably lower cell count/slide than manual counting. In all samples, the TAT/cell for DI-60 was substantially longer than that for manual counting (DI-60 vs. manual: total, 1.8 vs. 1.0 sec; normal, 1.5 vs. 0.7 sec; mild leukopenia, 1.9 vs. 0.9 sec; moderate leukopenia, 1.8 vs. 1.0 sec; severe leukopenia, 28.8 vs. 19.0 sec). CONCLUSIONS: This is the first comparative assessment of risk and TAT between DI-60 and manual counting in leukopenic samples. DI-60 decreases the laboratory risk and improves patient safety, but requires more time to count fewer cells, especially in severe leukopenic samples. DM analyzers should be applied selectively depending on the WBC count to optimize laboratory efficiency.

Prognostic Utility of Procalcitonin, Presepsin, and the VACO Index for Predicting 30-day Mortality in Hospitalized COVID-19 Patients.

BACKGROUND: Biomarkers and clinical indices have been investigated for predicting mortality in patients with coronavirus disease (COVID-19). We explored the prognostic utility of procalcitonin (PCT), presepsin, and the Veterans Health Administration COVID-19 (VACO) index for predicting 30-day-mortality in COVID-19 patients. METHODS: In total, 54 hospitalized COVID-19 patients were enrolled. PCT and presepsin levels were measured using the Elecsys BRAHMS PCT assay (Roche Diagnostics GmbH, Mannheim, Germany) and HISCL Presepsin assay (Sysmex, Kobe, Japan), respectively. The VACO index was calculated based on age, sex, and comorbidities. PCT and presepsin levels and the VACO index were compared using ROC curve, Kaplan-Meier method, and reclassification analysis for the 30-day mortality. RESULTS: ROC curve analysis was used to measure PCT and presepsin levels and the VACO index to predict 30-day mortality; the optimal cut-off values were 0.138 ng/mL for PCT, 717 pg/mL for presepsin, and 12.1% for the VACO index. On Kaplan-Meier survival analysis, hazard ratios (95% confidence interval) were 15.9 (4.1-61.3) for PCT, 26.3 (6.4-108.0) for presepsin, and 6.0 (1.7-21.1) for the VACO index. On reclassification analysis, PCT and presepsin in addition to the VACO index significantly improved the prognostic value of the index. CONCLUSIONS: This study demonstrated the prognostic utility of measuring PCT and presepsin levels and the VACO index in COVID-19 patients. The biomarkers in addition to the clinical index were more useful than the index alone for predicting clinical outcomes in COVID-19 patients.