Analytical performance evaluation of the Norudia HbA1c assay.

BACKGROUND: Hemoglobin A1c (HbA1c) is arguably the most important biomarker used in the diagnosis and treatment monitoring of diabetes mellitus. We evaluated the analytical performance of the Norudia HbA1c assay (Sekisui Medical Co., LTD), which uses an enzymatic method incorporated into a fully automated, high-throughput system. METHODS: The precision, linearity, and carryover of the Norudia HbA1c assay were evaluated. Using 60 patient samples, comparative analysis of HbA1c measurements with two commonly used HbA1c assays, the D100 (Bio-Rad Laboratories, Inc) and HLC-723 G11 (Tosoh), was undergone. Thirteen commutable samples with known HbA1c concentrations measured using an IFCC reference measurement procedure were used to compare accuracy between methods. Interference of HbA1c measurement by Hb variants was evaluated using 16 known Hb variant samples. RESULTS: Repeatability (% CV) for low and high concentrations ranged from 1.12%-1.50% and 0.66%-0.75%, respectively, and within-laboratory precision for low and high concentrations ranged from 1.73%-2.89% and 0.98%-1.64%, respectively. For linearity, the coefficient of determination was 0.9987. No significant carryover was observed. When compared to the D100 and HLC-723 G11 assays, the Norudia HbA1c assay showed the best accuracy with the lowest mean bias (-1.72%). Furthermore, the Norudia was least affected by Hb variants and gave the most reliable HbA1c measurements. CONCLUSION: The Norudia HbA1c showed excellent analytical performance with good precision and linearity, and minimal carryover. When compared to other routine HbA1c methods, the Norudia HbA1c assay showed the highest accuracy and was least affected by Hb variants.

Quantification of Thiopurine Nucleotides in Erythrocytes and Clinical Application to Pediatric Acute Lymphoblastic Leukemia.

BACKGROUND: Concentrations of 6-thioguanine (6TG) nucleotides and 6-methylmercaptopurine (6MMP) nucleotides in RBCs were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay was validated for clinical use and was applied to blood samples from patients taking mercaptopurine (6MP). METHODS: RBCs were hemolyzed and deproteinized using perchloric acid, followed by heating for the hydrolysis of nucleotides, and the resultant base was measured using LC-MS/MS. Precision, recovery, linearity, matrix effect, and limit of quantification was validated for clinical application. Our results were compared with another institution's established LC-MS/MS assay. We measured the concentrations of 6TG and 6MMP in RBCs of pediatric patients with acute lymphoblastic leukemia (ALL), and the clinical impact of those metabolites was investigated. RESULTS: The imprecision coefficient of variations of 6TG and 6MMP were 5.7%-8.1%, and the bias was within 5%. Lower limits of quantification were set at 54 ng/mL for 6TG and 1036 ng/mL for 6MMP. Correlation coefficients for 6TG and 6MMP were 0.997 and 1.0 in a comparison study. For clinical proof-of-concept, 74 blood samples were collected from 37 pediatric ALL patients receiving maintenance therapy. Concentration of 6TG ranged from 16.1 to 880 pmol/8 × 10 RBCs and that of 6MMP from 55 to 20,937 pmol/8 × 10 RBCs. The 6MP metabolites were not correlated with WBC or absolute neutrophil count. On the other hand, the higher 6MMP level was associated with elevated alanine aminotransferase and aspartate aminotransferase. CONCLUSIONS: In this study, an assay for the quantification of 6TG and 6MMP in RBCs was established and applied to pediatric ALL patients. Interindividual variability in 6MP metabolite concentrations was considerable and associated with elevation of liver enzymes, which may be useful in the clinical monitoring of 6MP maintenance therapy in pediatric ALL patients.

CCL28 Cannot Replace IgE for Severity by Objective SCORAD Index in Atopic Dermatitis in Children.

BACKGROUND: Recently, CC chemokine ligand28 (CCL28) has been reported as a severity marker in atopic dermatitis. We studied the association between objectively observed lesions and the level of CCL28 in children patients. METHODS: A total of 105 children patients were grouped by the objective Scoring Atopic Dermatitis index (SCORAD). Total IgE, specific IgE, complete blood count, and serum level of CCL28 were evaluated. RESULTS: The mean age of the subjects was 5.3 (range, 0 - 12 years). The median SCORAD was 21.4 and consisted of mild 70%, moderate 25%, and severe 6% disease. There were no statistical differences among severity groups for CCL28 or for total IgE. Total IgE showed positive correlation with eosinophil count (r = 0.429, p < 0.01), and SCORAD (r = 0.210, p < 0.05). CONCLUSIONS: The disease severity of atopic dermatitis in children is not correlated to the level of CCL28, but rather related to that of total IgE.

A study on the relationship between purchases of meal kits and home meal replacements.

BACKGROUND/OBJECTIVES: Meal kits and home meal replacements (HMRs) are rapidly growing segments in the convenience food industry. Consequently, numerous studies have examined consumer perceptions of HMR and meal kits, respectively. HMR is an established segment, while meal kits are a recent category. Both segments offer convenience compared to home-cooked meals. However, meal kits offer a wider variety of recipes with fresh ingredients, requiring simple cooking steps to prepare the meal rather than merely heating the food. Despite the commonalities and differences, previous studies have only examined the purchasing behavior and influencing factors of either the meal kits or HMR. However, changes in the purchasing patterns of both segments may be correlated. This study investigates the relationship between consumer purchasing trends of meal kits and HMR and presents practical recommendations regarding the need of consumers for convenience foods. MATERIALS/METHODS: We conducted a panel regression analysis of consumer purchase data obtained from shopping receipts, spanning the 2019, 2020, and 2021 waves of the Korean Rural Development Administration. RESULTS: The results show that the purchases of meal kits and HMR increased during the period, suggesting a complementary relationship between the 2. We also found significant increases in purchases within 2 sub-categories of HMR, namely, ready-to-prepare and ready-to-cook, alongside meal kits. These findings were further supported by the results of the sub-regression analysis. CONCLUSION: The simultaneous growth of meal kits and HMR indicates that convenience foods continue to play a crucial role in meeting consumer needs in the food industry. In addition, considering the significant growth of the HMR sub-categories with fresh ingredients and cooking, we suggest that companies should aim to satisfy the desire of consumers for both convenience as well as freshness and culinary aspects.

Korean consumers' use and concerns about food delivery service.

BACKGROUND/OBJECTIVES: Despite the rapid growth of the online food delivery service market since the outbreak of coronavirus disease 2019, little research has focused on how consumers are using food delivery service and what they are concerned about when using food delivery service. Moreover, previous studies have not paid adequate attention to how these concerns are related to consumers' intention to use food delivery service. Therefore, our study examines behaviors and concerns regarding food delivery service and identifies the key factors in consumers' intention to use food delivery service. SUBJECTS/METHODS: Using data collected from 549 Korean consumers, we conducted descriptive analysis, exploratory factor analysis, and multiple regressions. RESULTS: We found that using food delivery service is not only for main meals at home or the office but also to meet a variety of dietary needs and occasions. The findings indicated that Korean consumers are most concerned about the sustainability of food delivery service, followed by health, hygiene, hedonic, and usability aspects of the service. Hygiene concerns and a hedonic aspect of the service were negatively associated with consumers' intention to use food delivery service among users, while health concerns decreased the intention of non-users. CONCLUSION: The findings have implications for practitioners and policy makers in food delivery service. To further propel market growth, they should help reduce health concerns of non-users, as well as hygiene and hedonic concerns of existing users.

Complete blood count and cell population data parameters from the Abbott Alinity hq analyzer are useful in differentiating myelodysplastic syndromes from other forms of cytopenia.

INTRODUCTION: Myelodysplastic syndromes (MDS) are characterized by morphologic dysplasia and cytopenia and have a propensity for acute leukemic transformation. However, dysplasia is diagnosed by morphology, thus having cell population data (CPD) that can differentiate cytopenic patients with MDS from other conditions may facilitate accurate diagnosis. We assessed the utility of complete blood count (CBC) parameters and CPD derived from an Abbott Alinity hq analyzer to discriminate MDS-related cytopenia. METHODS: The patient cohort (n = 345) included 64 samples from patients with MDS, 162 from patients with other cytopenia, and 119 from healthy controls. The hematological parameters and research use-only parameters of the Abbott Alinity hq analyzer were compared between the cytopenic groups. The effectiveness of the individual standard and research CBC parameters to differentiate MDS from other forms of cytopenia was assessed through a receiver operating characteristics (ROC) analysis. RESULTS: The percentage of MAC (Macrocytic RBCs) and hemoglobin distribution width (HDW) were higher in the MDS group than in the other cytopenia group and showed the greatest difference between both groups, with an area under the curve (AUC) of 0.766 (0.678-0.855) and 0.786 (0.702-0.870), respectively. The platelet distribution width was higher in the MDS group than in the other cytopenia group, with an AUC of 0.697 (0.623-0.770). WBC CPD extracted from histograms, especially Atyp-PMN-loc and Neu-ALL-M, showed high AUCs of 0.815 (0.750-0.879) and 0.778 (0.711-0.845), respectively. CONCLUSION: Our findings demonstrate the clinical utility of CPD and hematology parameters of the Abbott Alinity hq analyzer in the differential diagnosis of MDS.

Periodic Comparability Verification and Within-Laboratory Harmonization of Clinical Chemistry Laboratory Results at a Large Healthcare Center With Multiple Instruments.

BACKGROUND: Results from laboratories using multiple instruments should be standardized or harmonized and comparability-verified for consistent quality control. We developed a simple frequent comparability verification methodology applicable to large healthcare centers using multiple clinical chemistry instruments from different manufacturers. METHODS: Comparability of five clinical chemistry instruments (Beckman Coulter AU5800, Abbott Architect Ci16000, two Siemens Vista 1500, and Ortho Vitros 5600) was evaluated from 2015 to 2019 for 12 clinical chemistry measurements. Pooled residual patient samples were used for weekly verifications. Results from any instrument exceeding the allowable verification range versus the results from the comparative instrument (AU5800) were reported to clinicians after being multiplied by conversion factors that were determined via a linear regression equation obtained from simplified comparison. RESULTS: Over the five-year study period, 432 weekly inter-instrument comparability verification results were obtained. Approximately 58% of results were converted due to non-comparable verification. Expected average absolute percent bias and percentage of non-comparable results for non-converted and converted results after conversion action were much lower than those for data measured before conversion action. The inter-instrument CV for both non-converted and converted results after conversion action was much lower than that for measured data before conversion action for all analytes. CONCLUSIONS: We maintained within-laboratory comparability of clinical chemistry tests from multiple instruments for five years using frequent low-labor periodic comparability verification methods from pooled residual sera. This methodology is applicable to large testing facilities using multiple instruments.

What drives the use of wearable healthcare devices? A cross-country comparison between the US and Korea.

Objective: Given the rapid growth of the wearable healthcare device market, we examined the associations among health-related and technology-related characteristics of using wearable healthcare devices and demonstrated how the associations differ between the US and Korean users. Methods: Online self-administered surveys were conducted with 4098 participants (3035 in the US and 1063 in Korea) who were recruited through two online survey service providers based on quota sampling. The primary outcome was the use of wearable healthcare devices. Seven health-related, two technology-related, and five socio-demographic factors were included as explanatory variables. Binary logistic regression analyses and a Chow test were conducted. Results: The health-related characteristics that were significantly associated with using wearable healthcare devices included disease-related worries (ß = 0.11**), health information seeking (ß = 0.26***), physical activity (ß = 0.62***), and health-related expenditures ($50-$199, ß = 0.38***; $200 or more, ß = 0.56***). Hedonic (ß = 0.33***), social (ß = 0.31***), and cognitive innovativeness (ß = 0.14*) also exhibited positive relationships. Younger, higher earner, and individuals with a child were more likely to use wearable healthcare devices. However, for Korean users, several associations disappeared including health information seeking, hedonic and social innovativeness, age, and household income. Conclusions: Key drivers of using wearable healthcare devices include greater concern about a specific illness, active engagement in health-promoting behaviors, and hedonic and social motivation to adopt new technologies. However, more country-specific considerations are needed in future studies to identify the main benefits for target markets.

Korean clinical practice guidelines for the diagnosis of hereditary hemolytic anemia.

Although the prevalence of hereditary hemolytic anemia (HHA) is relatively low in Korea, it has been gradually increasing in recent decades due to increment in the proportions of hemoglobinopathies from immigrants of South East Asia, raising awareness of the disease among clinicians, and advances in diagnostic technology. As such, the red blood cell (RBC) Disorder Working Party (WP), previously called HHA WP, of the Korean Society of Hematology (KSH) developed the Korean Standard Operating Procedures (SOPs) for the diagnosis of HHA in 2007. These SOPs have been continuously revised and updated following advances in diagnostic technology [e.g., flow cytometric osmotic fragility test (FOFT) and eosin-5-maleimide (EMA) binding test], current methods for membrane protein or enzyme analysis [e.g., liquid chromatography-tandem mass spectrometry (LC-MS/MS), ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), high-performance liquid chromatography (HPLC)], and molecular genetic tests using next-generation sequencing (NGS). However, the diagnosis and treatment of HHA remain challenging as they require considerable experience and understanding of the disease. Therefore, in this new Korean Clinical Practice Guidelines for the Diagnosis of HHA, on behalf of the RBC Disorder WP of KSH, updated guidelines to approach patients suspected of HHA are summarized. NGS is proposed to perform prior to membrane protein or enzyme analysis by LC-MS/MS, UPLC-MS/MS or HPLC techniques due to the availability of gene testing in more laboratories in Korea. We hope that this guideline will be helpful for clinicians in making diagnostic decisions for patients with HHA in Korea.

COVID-19 and changes in Korean consumers' dietary attitudes and behaviors.

BACKGROUND/OBJECTIVES: The coronavirus disease 2019 (COVID-19) outbreak has dramatically changed nearly every aspect of our lives. Although Dietary lifestyle includes attitudes and behaviors to meet their most basic needs, but few studies have examined the pattern of changes in dietary lifestyle driven by COVID-19. This study explores changes in dietary attitudes and behaviors among Korean consumers after COVID-19. SUBJECTS/METHODS: An online survey was conducted with 549 Korean adults aged 20 and older to identify general demographics and changes in dietary attitudes and behaviors. Data were collected from Oct 12 to Oct 18, 2020. Frequency, percentage, and mean values were calculated and a K-means cluster analysis was performed to categorize consumers based on the 5S of dietary attitudes (i.e., savor-oriented, safety-oriented, sustainability-oriented, saving-oriented, and socializing-oriented). RESULTS: Findings indicate consumers considered safety, health, and freshness to be most important when choosing groceries and prepared meal such as home meal replacement and delivery food. Among the types of services, a large proportion of consumers increased their delivery and take-out services. Regarding retail channels, the increase in the use of online retailers was remarkable compared to offline retailers. Finally, consumers were classified into four segments based on changes in dietary attitudes: "most influenced," "seeking safety and sustainability," "abstaining from savor and socializing," and "least influenced." Each type of consumer exhibited statistically significant differences by sex, age, household composition, presence of disease, and perceived risk of COVID-19. CONCLUSIONS: This exploratory study provides initial insights for future research by identifying various aspects of dietary attitudes and behaviors among Korean consumers after COVID-19.

Multiplex LC-MS/MS for simultaneous determination of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D3, albumin, and vitamin D-binding protein with its isoforms: One-step estimation of bioavailable vitamin D and vitamin D metabolite ratio.

Bioavailable vitamin D and vitamin D metabolite ratio (VMR) have emerged as potential novel vitamin D markers. We developed a multiplex liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine all elements necessary for the calculation of bioavailable vitamin D and VMR, including 25-hydroxyvitamin D [25-(OH)D] and 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3], VDBP and its isoforms, and albumin. Following separate reactions of hexane extraction and trypsin digestion, serum samples were analyzed using LC-MS/MS to measure 25-(OH)D3, 25-(OH)D2, 24,25-(OH)2D3, VDBP and its isoforms, and albumin. Analytical performances were assessed. Korean (n = 229), Arab (n = 98), White (n = 99) and Black American (n = 99) samples were analyzed. Bioavailable vitamin D and VMR were calculated. All target molecules were clearly separated and accurately quantified by LC-MS/MS. Analytical performances, including imprecision, accuracy, ion suppression, limit of quantification, linearity, and comparison with existing methods were within acceptable levels. The allele frequencies of VDBP isoforms in various races resulted similar to previously known values. The levels of bioavailable vitamin D were highest in White Americans and lowest in Black Americans. We have successfully developed a multiplex LC-MS/MS-based assay method that can simultaneously perform the measurement of all parameters needed to calculate bioavailable vitamin D and VMR. Our devised method was robust and reliable in terms of analytical performances and could be applied to routine clinical samples in the future to more accurately assess vitamin D status.

Evaluation of analytical performance of Alinity i system on 31 measurands.

INTRODUCTION: Accurate, precise and reliable laboratory test results play a critical role in medical decision making. To satisfy the increasing needs in clinical laboratory tests, the analyzers have been advanced. In this study, authors aimed to evaluate the analytical performance of the Alinity i system (Abbott Laboratories, IL, USA) for diverse analytes measured by using immunoassay principle. MATERIALS AND METHODS: Analytical performance of recently launched Alinity i system has been evaluated for 31 assays in aspects of precision, linearity and analytical measurement range, correlation with the Architect i2000sr system (Abbott Laboratories), carry-over, and reference interval validation in accordance with CLSI guidelines. RESULTS: The within-laboratory CVs of the analytes tested in the study ranged between 1.00 and 7.84%, which met vendor claimed value in precision. In linearity test, most assays satisfied acceptable linearity criteria, best-fit first order regression or polynomial regression with nonlinearity smaller than ±10%, compared with linear regression. The recovery of each analyte distributed from 90.1 to 109.7%. The coefficient of determination (R2) for each test was larger than 0.95 except for folate when compared to the results obtained from existing routine analyzer and statistically or clinically equivalent. The carry-over rates were acceptable, and reference intervals were validated. CONCLUSION: Through this study, acceptable analytical performance of novel Alinity i system has been verified. It is expected to readily replace existing instrument and to be an option for laboratories considering introduction of automated immunoassay analyzer.

Cancer cell-induced neutrophil extracellular traps promote both hypercoagulability and cancer progression.

INTRODUCTION: Neutrophils can generate extracellular net-like structures by releasing their DNA-histone complexes and antimicrobial peptides, which is called neutrophil extracellular traps (NETs). Various stimuli can induce NET formation. In particular, neutrophils and NET formation are abundant in tumor tissue. This study investigated how cancer cells induce NET formation and whether this NET formation promotes plasma thrombin generation and cancer progression. METHODS: Induction of NET formation by a pancreatic cancer cell line (AsPC-1) was assessed by measuring the histone-DNA complex level. The endogenous thrombin potential (ETP) was measured by thrombin generation assay. In vitro migration, invasion, and tubule formation assays were performed. The circulating levels of NET markers and hypercoagulability markers were assessed in 62 patients with pancreatobiliary malignancy and 30 healthy controls. RESULTS: AsPC-1 significantly induced NET formation in a dose-dependent manner. Conditioned medium (CM) from AsPC-1 also induced NETs. Interestingly, NET-formation was abolished by heat-inactivated CM, but not by lipid-extracted CM, suggesting an important role of protein components. A reactive oxygen species inhibitor did not inhibit cancer cell-induced NET formation, but prostaglandin E1 (PGE1, cyclic adenosine monophosphate inducer) and antithrombin did. NETs significantly increased ETP of normal plasma. Of note, NETs promoted cancer cell migration and invasion as well as angiogenesis, which were inhibited by histone-binding agents (heparin, polysialic acid), a DNA-degrading enzyme, and Toll-like receptor neutralizing antibodies. In patients with pancreatobiliary malignancy, elevated NET markers correlated well with hypercoagulability makers. CONCLUSION: Our findings indicate that cancer cell-induced NET formation enhances both hypercoagulability and cancer progression and suggest that inhibitors of NET formation such as PGE1 and antithrombin can be potential therapeutics to reduce both hypercoagulability and cancer progression.

Targeted sequencing aids in identifying clonality in chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) typically shows monocytosis in the peripheral blood (PB), which must be differentiated from reactive monocytosis. To determine the clonality of CMML, we performed molecular and cytogenetic analysis in Korean patients. To investigate whether monocytes in the PB harbored clonal mutational changes, we performed single-cell sequencing after selecting monocytes, neutrophils, and lymphocytes by morphology-aided laser microdissection. Targeted sequencing was performed in 35 patients with CMML with 41 bone marrow samples. Single-cell analysis was performed in two cases. Most (94.3%) patients harbored at least one variant, in genes considered as potential therapeutic targets, while cytogenetic aberrations occurred in only 28.6% of cases. ASXL1 (54.3%), SRSF2 (37.1%), NRAS (31.4%), and TET2 (25.7%) were frequently mutated, with lower frequencies of TET2 mutation and higher frequencies of NRAS, DNMT3A (17.1%), and NPM1 (11.4%) mutations compared to in previous studies of Caucasians. Patients with SETBP1 mutation and those with more than two variants showed poorer survival than those without mutation (P < 0.001 and P = 0.007, respectively). Most (70.8%) variants were detected at diagnosis and follow-up with no significant differences in variant allele frequency, warranting sequencing during follow-up if diagnostic samples were unavailable. Single-cell analysis revealed clonal monocytes with mutations, and the same mutations were also identified in lymphocytes and neutrophils. Targeted sequencing aided in clonality detection in most patients with CMML and single-cell sequencing facilitated identification of clonal monocytes and the co-existence of mutations in non-myeloid cells, suggesting that certain mutations are acquired by pluripotent stem cells.