Genotypic and phenotypic characteristics of Korean children with childhood-onset Leber's hereditary optic neuropathy.

PURPOSE: We sought to identify the phenotypic and genotypic characteristics of Korean children with genetically confirmed Leber's hereditary optic neuropathy (LHON). METHODS: The medical records of 64 genetically confirmed LHON patients were reviewed. Seventeen patients aged 13 years or younger with optic atrophy with positive mitochondrial DNA (mtDNA) mutations were considered to demonstrate childhood-onset LHON. The non-childhood-onset group included 47 patients with genetically confirmed LHON who experienced disease onset later than 13 years of age. The type of mtDNA mutation, visual acuity (VA), color vision, fundus photography, retinal nerve fiber layer (RNFL) thickness, and visual field were investigated. RESULTS: Sequence analysis of the mitochondrial genome revealed five different kinds of LHON-associated mtDNA mutations among our childhood-onset patients, including m.11778G>A (58.8%), m.3496G>T (11.8%), m.3497C>T (5.9%), m.11696G>A (5.9%), and m.14502T>C (5.9%). The mean final best-corrected VA in the childhood-onset group was better than that in the non-childhood-onset group with the value of logMAR 0.29 (0.09-0.75) vs. 0.55 (0.27-1.29) (expressed as median (interquartile range); p = 0.05). Spontaneous visual recovery was observed in 35.3% of the childhood-onset group but in only 12.8% of the non-childhood-onset group (p = 0.04). Eight patients (47.1%) showed interocular asymmetry of the disease, with two presenting true unilateral involvement of the optic nerve and the other six patients demonstrating unilateral subclinical manifestations with bilateral optic atrophy. CONCLUSION: Involvement of secondary mitochondrial mutations was confirmed in patients with childhood-onset LHON. Characteristic clinical features of childhood-onset LHON included a higher proportion of subacute or insidious onset of symptoms, better VA, higher spontaneous recovery, and asymmetrical ocular involvement.

Evaluation of posaconazole plasma concentrations achieved with the delayed-release tablets in Korean high-risk patients with haematologic malignancy.

BACKGROUND: Posaconazole (PCZ) is a triazole approved for prophylaxis of invasive fungal infections. OBJECTIVES: Herein, the impact of clinical variables on PCZ plasma concentrations (PPCs) attained with PCZ delayed-release tablet (DRT) was investigated and compared with a historical cohort treated with PCZ oral suspension (OS). PATIENTS/METHODS: Steady-state PCZ PPCs in 513 patients with haematologic malignancy treated with PCZ-DRT were assessed and impact of variables were analysed. Also, a comparison with matched historical cohort treated with PCZ-OS was made. RESULTS: The median PPC in the PCZ-DRT group was 1,308.9 ng/mL (range: 29.8-10 455.9). Use of proton pump inhibitor (1181 vs 1344 ng/mL, P = .0337) in the AML/myelodysplastic syndrome remission induction group, diarrhoea (867 vs 1543 ng/mL, P = .0325) and gastrointestinal graft-versus-host disease (870 vs 1713 ng/mL, P = .0178) in the HSCT group were associated with lower PPCs. There was lack of evidence that hepatotoxicity was related with PCZ-DRT. Higher prevalence of UGT1A4*3 allele (33.0%) was noted compared to allele frequency in Koreans in those with PPCs < 500 mg/mL. The median PPC in the PCZ-DRT group was significantly higher than that in the PCZ-OS group (1308.9 vs 713.0 ng/mL, P < .0001). Significantly less patients had PPCs < 700 ng/mL in the PCZ-DRT group compared to the PCZ-OS group (18.7% vs 48.0%, P < .0001). CONCLUSIONS: Our study demonstrates that PCZ-DRT has enhanced absorption and bioavailability than PCZ-OS in real-world clinical settings. In addition, specific factors associated with lower PPCs should prompt consideration of therapeutic drug monitoring in patients treated with PCZ-DRT.

Measurement of Teicoplanin Concentration With Liquid Chromatography-Tandem Mass Spectrometry Method Demonstrates the Usefulness of Therapeutic Drug Monitoring in Hematologic Patient Populations.

BACKGROUND: Teicoplanin is a glycopeptide antibiotic that has become increasingly popular with the spread of methicillin-resistant Staphylococcus aureus. The aim of the study was to develop and validate an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for teicoplanin, and analyze trough teicoplanin concentrations achieved in patients with hematological diseases. METHODS: The UHPLC-MS/MS method for teicoplanin was developed, validated, and applied in a retrospective analysis of trough plasma teicoplanin concentrations from 305 patients receiving standard dose, and 17 patients receiving therapeutic drug monitoring (TDM)-guided individualized dose. RESULTS: The linear range was 3.9-52.9 mg/L. The imprecision was less than 12%, the limits of detection and quantification were less than 0.13 and 0.72 mg/L, respectively. The sample carry-over and ion suppression were insignificant. In the standard dose group, the median teicoplanin concentrations were 7.5 mg/L (days 3-5) and 8.9 mg/L (on days 6-8); and the proportion of trough levels achieving ≥10 mg/L was 20% (days 3-5) and 38% (days 6-8), respectively. In the TDM-guided individualized dose group, median teicoplanin concentration was higher (16.9 mg/L), and the proportion of trough levels ≥10 mg/L was also higher (77%) when compared with the standard dose group. CONCLUSIONS: Based on these results, the present UHPLC-MS/MS method can be considered suitable for routine TDM of teicoplanin. Also, based on the insufficient trough teicoplanin concentrations achieved with standard dose regimen, and the higher trough teicoplanin concentrations achieved with TDM-guided individualized dose regimen, this study highlights the importance of TDM of teicoplanin, especially in high-risk patient groups.

Identification of large genomic rearrangement of BRCA1/2 in high risk patients in Korea.

BACKGROUND: While the majority of germline inactivating mutations in BRCA1/2 are small-scale mutations, large genomic rearrangements (LGRs) are also detected in a variable proportion of patients. However, routine genetic methods are incapable of detecting LGRs, and comprehensive genetic testing algorithm is necessary. METHODS: We performed multiplex ligation-dependent probe amplification assay for small-scale mutation negative patients at high-risk for LGR, based on previously published LGR risk criteria. The inclusion criteria for the high-risk subgroup were personal history of 1) early-onset breast cancer (diagnosed at ≤36 years); 2) two breast primaries; 3) breast cancer diagnosed at any age, with ≥1 close blood relatives (includes first-, second-, or third-degree) with breast and/or epithelial ovarian cancer; 4) both breast and epithelial ovarian cancer diagnosed at any age; and 5) epithelial ovarian cancer with ≥1 close blood relatives with breast and/or epithelial ovarian cancer. RESULTS: Two LGRs were identified. One was a heterozygous deletion of exon 19 and the other was a heterozygous duplication of exon 4-6. The prevalence of LGRs was 7% among Sanger-negative, high-risk patients, and accounted for 13% of all BRCA1 mutations and 2% of all patients. Moreover, LGRs reported in Korean patients, including our 2 newly identified cases, were found exclusively in families with at least one high-risk feature. CONCLUSIONS: Our result suggests that selective LGR screening for Sanger-negative, high-risk patients is necessary for Korean patients.

Mirror Syndrome Associated with 18p Deletion Syndrome.

BACKGROUND: Mirror syndrome is defined as the development of maternal edema in association with fetal hydrops. This rare disease is called mirror syndrome due to the presence of maternal edema that "mirrors" the fetal and placental condition. CASE: We report the first case of mirror syndrome associated with 18p deletion. CONCLUSION: Cytogenetic analysis should be considered in mirror syndrome to identify the underlying cause.

Analytical Performance Evaluation of Infopia Element™ Auto-coding Blood Glucose Monitoring System for Self-Monitoring of Blood Glucose.

BACKGROUND: Element™ Auto-coding Blood Glucose Monitoring System (BGMS; Infopia Co., Ltd., Anyang-si, Korea) was developed for self-monitoring of blood glucose (SMBG). METHODS: Precision, linearity, and interference were tested. Eighty-four capillary blood samples measured by Element™ BGMS were compared with central laboratory method (CLM) results in venous serum. Accuracy was evaluated using ISO 15197:2013 criteria. RESULTS: Coefficients of variation (CVs; mean) were 2.4% (44.2 mg/dl), 3.7% (100.6 mg/dl), and 2.1% (259.8 mg/dl). Linearity was shown at concentrations 39.25-456.25 mg/l (y = 0.989 + 0.984x, SE = 17.63). Up to 15 mg/dl of galactose, ascorbic acid, and acetaminophen, interference > 10.4% was not observed. Element™ BGMS glucose was higher than CLM levels by 3.2 mg/dl (at 200 mg/dl) to 8.2 mg/dl (at 100 mg/dl). The minimum specification for bias (3.3%) was met at 140 and 200 mg/l glucose. In the Clarke and consensus error grids, 100% of specimens were within zone A and B. For Element™ BGMS values, 92.9% (78/84) to 94.0% (79/84) were within a 15 mg/dl (< 100 mg/dl) or 15% (> 100 mg/dl) of the average CLM value. CONCLUSION: Element™ BGMS was considered an appropriate SMBG for home use; however, the positive bias at low-to-mid glucose levels requires further improvement.

Founder haplotype analysis of Fanconi anemia in the Korean population finds common ancestral haplotypes for a FANCG variant.

A common ancestral haplotype is strongly suggested in the Korean and Japanese patients with Fanconi anemia (FA), because common mutations have been frequently found: c.2546delC and c.3720_3724delAAACA of FANCA; c.307+1G>C, c.1066C>T, and c.1589_1591delATA of FANCG. Our aim in this study was to investigate the origin of these common mutations of FANCA and FANCG. We genotyped 13 FA patients consisting of five FA-A patients and eight FA-G patients from the Korean FA population. Microsatellite markers used for haplotype analysis included four CA repeat markers which are closely linked with FANCA and eight CA repeat markers which are contiguous with FANCG. As a result, Korean FA-A patients carrying c.2546delC or c.3720_3724delAAACA did not share the same haplotypes. However, three unique haplotypes carrying c.307+1G>C, c.1066C > T, or c.1589_1591delATA, that consisted of eight polymorphic loci covering a flanking region were strongly associated with Korean FA-G, consistent with founder haplotypes reported previously in the Japanese FA-G population. Our finding confirmed the common ancestral haplotypes on the origins of the East Asian FA-G patients, which will improve our understanding of the molecular population genetics of FA-G. To the best of our knowledge, this is the first report on the association between disease-linked mutations and common ancestral haplotypes in the Korean FA population.

Molecular analysis of the CHST6 gene in Korean patients with macular corneal dystrophy: Identification of three novel mutations.

PURPOSE: To identify the underlying genetic defect in Korean patients with macular corneal dystrophy (MCD). METHODS: Genomic DNA was isolated from peripheral blood leukocytes of seven patients from six unrelated families with MCD (three men and four women). Polymerase chain reaction was performed for coding regions of the carbohydrate sulfotransferase (CHST6), gene followed by bidirectional sequencing. Targeted mutational analysis (exons 4, 11-12, 14) of the transforming growth factor, beta-induced (TGFBI) gene was performed for all patients. RESULTS: All seven patients were found to have compound heterozygous mutations in the CHST6 gene. In addition to six previously reported mutations, c.95C>A (p.Ser32*), c.521A>G (p.Lys174Arg), c.557C>G (p.Pro186Arg), c.613C>T (p.Arg205Trp), c.820G>A (p.Glu274Lys), and c.1072T>C (p.Tyr358His), three novel mutations were identified in this study, including two missense mutations, c.353C>T (p.Ser118Phe) and c.922C>T (p.His308Tyr), and one frameshift mutation, c.786delC (p.L264Cfs*117). Among the three novel mutations, only the c.353C>T mutation had been reported in the Exon Aggregation Consortium database at an extremely low frequency of 0.00005072. In addition, these three novel mutations were absent from controls in 1,000 genomes, dbSNP, and the TIARA genome database, which is a Korean personal genome database. The most frequent mutation was c.613C>T (p.Arg205Trp), revealed in four unrelated Korean families, which has not previously been reported in other populations. No mutations were detected in the TGFBI gene. DISCUSSION: This is the first report on genetic analysis of Korean MCD patients. Three novel and six previously reported disease-causing CHST6 mutations were identified, which expands the mutational spectrum of MCD.

Autistic and Rett-like features associated with 2q33.3-q34 interstitial deletion.

We describe the fourth reported case of a de novo 2q33.3-q34 interstitial deletion and review the literature in attempt to identify relevant candidate genes. A 15-month-old female patient presented for evaluation with poor eye contact and developmental delay. She had microcephaly and mild dysmorphic features, such as downslanting palpebral fissures, high forehead, small mouth, high palate, and general hypotonia. At 30 months of age, she was referred to the genetic clinic for an evaluation of persistent developmental delay, autistic traits, and Rett-like features, including bruxism and repetitive movement of the left hand. Chromosome analysis revealed 46,XX at the 550 band level. No abnormalities were found on analysis of MECP2 gene for Rett syndrome and a DNA methylation test for Prader-Willi syndrome. An array comparative genomic hybridization analysis revealed a de novo 2q33.3-q34 heterozygous deletion (206,048,173-211,980,867). The deletion was estimated to be 5.9 Mb in size and contained 34 known genes. Candidate genes were identified as NRP2, ADAM23, KLF7, CREB1, MAP2, UNC80, and LANCL1 for the 2q33.3-q34 interstitial deletion.

Evaluation of the INNOVANCE PFA P2Y assay and its association with CYP2C19 genotypes.

The purpose of this study was to evaluate associations between INNOVANCE PFA P2Y (PFA P2Y) test results and CYP2C19 genotypes and provide baseline data for PFA P2Y testing to establish a therapeutic monitoring strategy for clopidogrel. A total of 75 new patients with acute coronary syndrome with planned percutaneous coronary intervention were enrolled between June 2012 and September 2012. All patients received clopidogrel at an initial loading dose of 600 mg followed by a 75-mg daily maintenance dose. Blood samples were obtained on the third morning after clopidogrel loading. PFA P2Y, VerifyNow P2Y12 and VASP assays were used to determine platelet inhibition due to clopidogrel, and the Verigene CYP2C19 test was used for CYP2C19 genotyping. The genotype frequency of 75 patients was as follows: CYP2C19 *1/*1 (wild type), 28 (37.3%); *1/*2, 31 (41.3%); *1/*3, 4 (5.3%); *2/*2, 5 (6.7%); *2/*3, 5 (6.7%); *1/*17, 1 (1.3%); and *2/*17, 1 (1.3%). Classified according to CYP2C19 genotypes, there were 29 (38.7%) extensive metabolizers (EM) or ultra rapid metabolizers (UM), 35 (46.7%) intermediate metabolizers (IM), and 10 (13.3%) poor metabolizers (PM). Median (interquartile range) PFA P2Y closure times (seconds) were 119 (101-260), 300 (130-300) and 300 (300-300) in the PM, IM and EM or UM groups, respectively (p < 0.05). Median (interquartile range) VerifyNow PRUs were 294 (213-297), 215 (165-320) and 189 (118-279); and the VASP platelet reactivity index (%) was 52.7 (33.3-91.9), 59.9 (41.4-72.8) and 38.9 (26.8-62.2) in the PM, IM and EM or UM groups, respectively (p > 0.05). Compared with non-carriers, carriers of reduced function CYP2C19 alleles tended to have higher platelet reactivity after clopidogrel treatment. The cut-off for PM versus other groups (IM and EM or UM) was ≤ 141 seconds (AUC 0.704, sensitivity 70%, specificity 76.6%) on the ROC curve. A statistically significant correlation between PFA P2Y (seconds) and VerifyNow (PRU) was found (ρ = -0.47, p < 0.0001). In conclusion, the PFA P2Y test showed a statistically significant association with CYP2C19 metabolizer phenotypes based on CYP2C19 genotyping and effectively determined the risk groups resistant to clopidogrel therapy, including PM.

LEGO plot for simultaneous application of multiple quality requirements during trueness verification of quantitative laboratory tests.

BACKGROUND: We developed a two-dimensional plot for viewing trueness that takes into account potential shift and variable quality requirements to verify trueness using certified reference material (CRM). METHODS: Glucose, total cholesterol (TC), and creatinine levels were determined by two kinds of assay in two levels of a CRM. Available quality requirements were collected, codified, and sorted in an ascending order in the plot's header row. Centering on the mean of measured values from CRM, the "mean ± US CLIA '88 allowable total error" was located in the header of the leftmost and rightmost columns. Twenty points were created in intervening columns as potential shifts. Uncertainties were calculated according to regression between certified values and uncertainties of CRM, and positioned in the corresponding columns. Cells were assigned different colors where column and row intersected based on comparison of the 95% confidence interval of the percentage bias with each quality requirement. RESULTS: A glucose assay failed to meet the highest quality criteria, for which shift of +0.13-0.14 mmol/l was required. A TC assay met the quality requirement and a shift of ±0.03 mmol/l was tolerable. A creatinine assay also met the quality requirement but any shift was not tolerable. CONCLUSION: The plot provides a systematic view of the trueness of quantitative laboratory tests.

The analytical performance evaluation of Freelite™ Human Kappa Free and Human Lambda Free on the SPAPLUS™ immunoturbidimetric analyzer.

BACKGROUND: SPAPLUS™ is a turbidimetric immunoassay analyzer for detection of excess free light chain (FLC) antigens in serum. Here, we evaluated the analytical performance of Freelite™ Human Kappa Free and Lambda Free on a SPAPLUS™ instrument. METHODS: We evaluated the precision, linearity, sample carryover, and drift of the SPAPLUS™ instrument and compared it with Hitachi 7600 and BN™ II instruments. We evaluated the detection of antigen excess for 12 specimens from patients with monoclonal gammopathy. RESULTS: The coefficients of variations of κFLC and λFLC were below 5.0%. Linearity was shown in the range of 9.68-152.25 mg/l for κFLC and 4.96-171.09 mg/l for λFLC, and no drift was observed. The κFLC sample carryover was statistically significant, but much smaller than the optimum allowable bias. Agreement rates with the two comparative methods were 87.1, 87.1, and 97.1% or higher for κFLC, λFLC, and the κ/λ ratio, respectively. Antigen excess signals were observed for all 12 antigen excess specimens. CONCLUSIONS: The Freelite™ on the SPAPLUS™ exhibited appropriate precision, linearity, and relative comparability to the reagents on the other instruments. It was good at detecting specimens that had previously demonstrated the hook effect due to antigen excess.

Novel COL9A3 mutation in a family diagnosed with multiple epiphyseal dysplasia: a case report.

BACKGROUND: Multiple epiphyseal dysplasia is a common skeletal dysplasia characterized by mild short stature, early-onset osteoarthritis mainly involving the hip and knee joints, and abnormally small and/or irregular epiphyses. Multiple epiphyseal dysplasia is clinically and genetically heterogeneous and six genes are associated with the phenotype of multiple epiphyseal dysplasia. CASE PRESENTATION: A 12-year-old Korean boy presented with intermittent knee pain. His height was 144.6 cm (20th percentile) and family history was notable for early-onset osteoarthritis in his father. The proband's x-rays revealed epiphyseal changes characteristic of multiple epiphyseal dysplasia associated with a collagen IX defect, with manifestations primarily restricted to the knees. Mutational analysis identified a novel c.104G>A substitution in exon 2 of COL9A3, resulting in p.Gly35Asp in the proband and his father. In silico analyses predicted the p.Gly35Asp amino acid change to be detelerious, and molecular dynamics simulation demonstrated a major structural change in the heterotrimeric collagen IX. CONCLUSION: So far, three COL9A3 mutations, have been reported. These three mutations are located at the splice donor or acceptor site of COL9A3 and cause skipping of exon 3, resulting in the deletion of 12 aminoacids in the COL3 domain of COL9A3. In contrast, the novel missense mutation identified in this two-generation family with multiple epiphyseal dysplasia is a missense mutation affecting the Gly residue of the Pro-Pro-Gly repeat sequence in the COL3 domain of collage IX, with accompanying major structural change of the collagen peptide.

Limited Contribution of Creatine Kinase-Myocardial Band Alongside High-Sensitivity Cardiac Troponin in Diagnosing Acute Myocardial Infarction in an Emergency Department.

Cardiac biomarkers, especially high-sensitivity cardiac troponin C or I (hs-cTnC or hs-cTnI, respectively), are vital for diagnosing acute myocardial infarction (AMI). Despite the specificity of hs-cTn as a biomarker, the creatine kinase-myocardial band (CK-MB) is commonly used alongside hs-cTn in emergency departments (EDs). We analyzed 23,771 simultaneous hs-cTn (hs-cTnT or hs-cTnI) and CK-MB requests for 17,185 patients in tertiary hospital ED in 2022. The objective of this study was to assess their practical value in diagnosing AMI in real-world settings. Among all 17,185 patients tested, 98.0% underwent hs-cTnT and CK-MB tests, and substantially fewer underwent hs-cTnI testing. We observed concordance between the initial hs-cTn and CK-MB results in 71.3% of patients. Of 131 AMI cases, 57 were positive for both biomarkers, 63 for hs-cTn only, and none for CK-MB alone. CK-MB positivity was often found in the absence of AMI. Discrepancies between the hs-cTnT and hs-cTnI results occurred in 30.0% of patients. Indiscriminate CK-MB testing for diagnosing AMI in EDs should be reconsidered. Efficient use of CK-MB is important for reducing costs and ensuring optimal patient care.

Comparative analysis of the quantitative point-of-care CareSTART™ total bilirubin with central laboratory total bilirubin assays in neonatal blood samples.

This study aimed to assess and compare the accuracy of point-of-care CareSTART™ S1 Total Bilirubin test with a central laboratory total bilirubin assay using neonatal samples. This study was conducted using 152 paired measurements obtained from 122 neonates admitted to the neonatal intensive care unit. Total serum bilirubin (TSB) levels assayed with the central laboratory assay, laboratory bilirubinomter, trancutaneous bliribubin (TcB) instrument and CareSTART were compared using Bland-Altman analysis. The mean difference between the CareSTART and TSB values was -1.43 mg/dL and the 95% limit of agreement (LoA) was -4.25 to 1.39 mg/dL. CareSTART tended to underestimate total bilirubin concentrations compared with TcB, however, the LoA was narrower due to the smaller SD of mean difference for CareSTART. The CareSTART Total Bilirubin test provides an accurate alternative to TcB for total serum bilirubin measurement. Given its low-cost, ease-of-use, and portability, the use of CareSTART is expected to provide point-of-care measurements, especially in low-resource settings.

A comprehensive Exdia TRF-LFIA for simultaneous quantification of GFAP and NT-proBNP in distinguishing ischemic and hemorrhagic stroke.

The goal of this study is to create a highly sensitive time-resolved fluorescence lateral flow immunoassay (TRF-LFIA) capable of concurrently measuring glial fibrillary acidic protein (GFAP) and the N-terminal fragment of B-type natriuretic peptide precursor (NT-proBNP). This assay is designed as a diagnostic tool and aims to provide an algorithm for stroke management, specifically for distinguishing between Ischemic stroke (IS) and Hemorrhagic stroke (HS). However, LFIA to quantify simultaneous serum NT-proBNP and GFAP are not yet available. We have developed and validated a novel TRF-LFIA for the simultaneous quantitative detection of NT-proBNP and GFAP. The sensitivity and reproducibility of the immunoassay were significantly improved by employing specific monoclonal antibodies linked to europium nanoparticles (EuNPs) that specifically target NT-proBNP and GFAP. The detection area on the nitrocellulose membrane featured sandwich-style complexes containing two test lines for NT-proBNP and GFAP, and one Control line. The fluorescence intensity of these test lines and control line was measured using an in-house developed Exdia TRF-Plus analyzer. As proof-of-concept, we enrolled patients suspected of having a stroke who were admitted within a specific time frame (6 h). A small amount of clinical specimen (serum) was used. To optimize the LFIA, an EuNPs conjugated antibodies were investigated to improve the detection sensitivity and decrease the background signal as well shorten the detection time. The Exdia TRF-LFIA cartridge offers a wide linear dynamic detection range, rapid detection, high sensitivity, and specificity. The limit of detection was determined to be 98 pg/mL for NT-proBNP and 68 pg/mL for GFAP, with minimal cross-reactivity. There were 200 clinical human serum samples that were used to evaluate this platform with high correlation. By combining the results of NT-proBNP and GFAP, we formulated an algorithm for the clinical assessment of Ischemic Stroke (IS) and Hemorrhagic Stroke (HS). According to our proposed algorithm, the combination of GFAP and NT-proBNP emerged as the most effective biomarker combination for distinguishing between IS and HS. Exdia TRF-LFIA shows great potential as a supplemental method for in vitro diagnostics in the laboratory or in other point-of-care testing (POCT) applications. Its development substantially decreases the diagnosis time for IS and HS. The proposed algorithm not only minimizes treatment delays but also lowers medical costs for patients.

Evaluation of enzymatic BM Test HbA1c on the JCA-BM6010/C and comparison with Bio-Rad Variant II Turbo, Tosoh HLC 723 G8, and AutoLab immunoturbidimetry assay.

BACKGROUND: A novel enzymatic HbA1c assay was introduced for use in an automated chemistry analyzer. With this unique method, HbA1c and plasma glucose can be measured from the same EDTA tube. We evaluated the analytical performance of this enzymatic HbA1c assay in a JCA-BM6010/C analyzer and compared the HbA1c values with the results from other widely used methodological instruments. METHODS: The imprecision, linearity, carry-over and concordance rate of the enzymatic HbA1c test (BM Test HbA1c) using the JCA-BM6010/C analyzer were evaluated. Three hundred and seventy-seven specimens with HbA1c concentrations from 16 to 133 mmol/mol were used for a comparison study with two high performance liquid chromatography methods: Variant II Turbo and Tosoh HLC 723 G8 and the AutoLab Hemoglobin A1c immunoturbidimetry reagent using a Hitachi 7600-110. Forty specimens were used for the glucose method comparison. RESULTS: The HbA1c coefficients of variation of the within-run imprecision for low and high levels were 0.6% and 0.4%, respectively. The linearity of the BM Test HbA1c using the JCA-BM6010/C analyzer was excellent in the range between 31 mmol/mol and 143 mmol/mol. The carry-over rate was 0.2%. The relationships between the BM test and the other three methods were 0.916×Tosoh G8+3.644, r=0.986; 0.887×Bio-Rad Variant II+1.896, r=0.972; and 0.941×AutoLab+4.532, r=0.977. The concordance rates using a cut-off of 48 mmol/mol were 91.5% with Tosoh G8, 82.8% with Bio-Rad Variant II, and 91.0% with AutoLab. The simultaneously assayed plasma glucose with HbA1c was 1.002×Routine plasma glucose+0.625, r=1.000 CONCLUSIONS: The enzymatic BM Test HbA1c in the JCA-BM6010/C analyzer showed excellent precision and linearity, and a minimal carry-over rate. The simultaneously assayed plasma glucose analysis showed good performance.

Plasma Glial Fibrillary Acidic Protein and N-Terminal Pro B-Type Natriuretic Peptide: Potential Biomarkers to Differentiate Ischemic and Hemorrhagic Stroke.

Acute stroke management is critically time-sensitive and challenging. Blood-based biomarkers that can differentiate acute ischemic stroke (IS) from hemorrhagic stroke (HS) can greatly facilitate triage and early management. Admission blood samples obtained within 6 h of stroke symptom onset were analyzed in a derivation/validation design. GFAP, N-FL, NT-proBNP, copeptin, neutrophils (%), NLR, and platelet counts were assessed in the derivation cohort. The informative markers and the derived cutoff values were evaluated in the validation cohort. GFAP > 703 pg/mL showed a PPV of 76.9% and NPV of 95.8% for differentiating HS from IS. Multiple logistic regression analysis showed that GFAP and NT-proBNP were independent variables associated with IS and HS differentiation. Furthermore, applying a combined cutoff (GFAP > 703 pg/mL and NT-proBNP ≤ 125 pg/mL) for HS detection increased the PPV in both the derivation and validation cohorts (93.3% and 100%, respectively). GFAP and NT-proBNP levels were validated as informative blood biomarkers in the differentiation of IS and HS and using a combination of GFAP and NT-proBNP is suggested as a feasible strategy to differentiate stroke subtypes in the hyperacute phase of stroke.