Evaluation of a Diazo-Based Point-Of-Care Bilirubin Assay careSTART S1 Total Bilirubin Strip.

BACKGROUND: Neonatal jaundice (NNJ) affects a significant proportion of newborns globally, with an increased burden in low-resource settings. Effective health risk management of NNJ is hindered, particularly in resource-constrained environments, where early detection and treatment are challenging. The careSTART S1 Total Bilirubin Strip, a point-of-care testing (POCT) device based on a diazo-method, offers a potential solution by enabling onsite bilirubin measurement, thus, addressing the gap in early NNJ detection and management. METHODS: The current study evaluated the analytical performance of the careSTART S1 Total Bilirubin Strip for precision, linearity, method comparison, and lot-to-lot consistency following CLSI guidelines. For method comparison, 105 residual EDTA whole blood samples were analyzed with the careSTART S1 Total Bilirubin Strip and compared with reference measurements from the Roche Cobas c702 analyzer. Additionally, statistical analyses, including Passing-Bablok regression and Bland-Altman plots, were performed. RESULTS: The careSTART S1 Total Bilirubin Strip showed allowable (<10%) within-laboratory imprecision of 2.5%-3.6% across all levels and demonstrated linearity over the range of 4.16-439.3 µmol/L. Method comparison revealed a constant negative bias with a mean bias -4.19 µmol/L. However, the 95% confidence interval (-7.10 to -1.28 µmol/L) of the bias is covered by the prespecified allowable bias of 8.3%, at medical decision point. Lot-to-lot variation ranged from 0.14%-6.49%, and was within the acceptable critical difference of 8.3%. CONCLUSION: The careSTART S1 Total Bilirubin Strip provided accurate and reliable bilirubin measurements that could contribute to neonatal care in settings lacking central laboratory facilities.

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.

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.

Identification of a frit-related sample carryover in newborn screening by tandem mass spectrometry.

The need for high-throughput analysis of multiple analytes for inborn errors of metabolism in newborn screening (NBS) has led to the introduction of tandem mass spectrometry (MS/MS) into the NBS laboratory. In a flow-injection analysis (FIA), the predominant MS/MS method utilized for NBS, samples are introduced directly into the mass spectrometer without chromatographic separation. When a high-throughput FIA-based MS/MS method is implemented on newer generations of mass spectrometers with increased sensitivity, the risk of carryover and contamination increases. In the present study, we report the carryover of ornithine identified during the implementation of the NeoBase™ 2 (PerkinElmer) non-derivatized kits on the Xevo-TQD platform (Waters Corporation) and describe the source of the carryover, which was traced to the stainless-steel frit-type inline filter. Furthermore, a possible compound-dependent interaction with the stainless-steel frit is suggested based on the structure of ornithine and its effect on separation techniques. Investigation and mitigation of carryover can be a time and resource consuming process, and to this end, our report on identification of a stainless-steel frit as the source of delayed elution and carryover of ornithine should be recognized as a rare, albeit possible source of carryover in FIA-MS/MS methods adopted for NST.

Laboratory characteristics of IgG4-related disease: A retrospective study from a single tertiary medical center.

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition with unique histopathological features that can affect most organs, making diagnosis challenging. This study characterized detailed laboratory characteristics of IgG4-RD. Baseline clinical and laboratory features of 33 patients with IgG4-RD were reviewed, including serum IgG4 concentrations, serum free light chains (sFLCs), IgGĸ- and IgGλ-heavy/light chains (HLCs), capillary serum protein electrophoresis (SPE), and immunofixation electrophoresis (IFE) of IgG4 subclass. The cohort of 33 patients showed male predominance (94%), with 8 (24%) exhibiting multiple organ involvement. Most patients (88%) had an elevated IgG4 concentration, and 67% had elevated erythrocyte sedimentation rate and IgE levels. Median IgG4 concentration at baseline was significantly higher in patients with >2 organs involved than those with ≤2. Furthermore, erythrocyte sedimentation rate was significantly correlated with serum IgG4 concentrations at baseline. SPE results demonstrated polyclonal gammopathy in most patients. Half of the patients had an increased κ/λ sFLC ratio, 42% had an increased IgGκ/IgGλ HLC ratio. Most patients exhibited hypergammaglobulinemia in the anodal end of the ɤ region on SPE. This study describes detailed laboratory features of IgG4-RD. Although none of these tests are considered diagnostically sufficient by itself, the provided laboratory characteristics can increase awareness of this disorder and help distinguish it from other IgG4-RD mimics.

Body fluid matrix effect evaluation on the Hitachi Labospect 008 system.

BACKGROUND: Non-standard body fluids (NSBFs) can provide essential clinical information otherwise unobtainable with conventional biological specimens. However, as most commercial chemistry reagents are only validated for serum, plasma, and urine by manufacturers, individual laboratories have to validate testing with NSBF to comply with regulatory standards. However, the heightened level of oversight and uncertainty of validation requirements to comply with regulatory standards pose a significant challenge for NSBF testing in clinical laboratories. METHODS: 28 combinations of high-volume chemistry tests requested on NSBF with established clinical utility were selected from retrospective data analysis. Specimens were analyzed with both closed and open channel chemistry reagents on a LABOSPECT 008AS platform (Hitachi High-Tech Co., Tokyo, Japan). Recovery studies were performed using a high concentration serum sample and 5 clinical NSBF samples at varying concentrations for each analyte. Acceptable performance limits were defined as 100 ± 10% of expected recovery. RESULTS: The average percent recovery ranged from 94.5% to 106.6% depending on the analyte/NSBF combination evaluated, and for each of the 28 combinations, the average percent recovery was within the predefined acceptable limits of ± 10%. CONCLUSIONS: The recovery results from this study on the LABOSPECT 008AS platform demonstrates that any systematic matrix interference of high-volume chemistry testing on NSBF samples is well within the defined limits of acceptability. This work also demonstrates recovery studies performed by an individual laboratory are practial and it is feasible to demonstrate compliance with regulatory requirements for accuracy of chemistry testing on NSBF samples.

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.

Heavy/light chain assay as a biomarker for diagnosis and follow-up of multiple myeloma.

BACKGROUND: The heavy-light chain (HLC) assay enables the accurate measurement of each isotype-specific heavy and light chain (i.e., IgGĸ, IgGλ, IgAĸ, and IgAλ) and the derivation of an HLC-pair ratio. However, to date, only limited data have validated the usefulness of serial HLC measurements in the routine follow-up of intact immunoglobulin multiple myeloma (MM) patients. METHODS: A total of 36 diagnostic and 671 post-treatment sera from 115 IgG and 61 IgA MM patients were assessed with capillary zone electrophoresis, immunosubtraction electrophoresis, total immunoglobulin measurement, free light chain, and HLC assay. The correlations between M-protein levels and the HLC and FLC assay-derived parameters were examined and the clinical significance of the biomarkers was evaluated according to patients' status. RESULTS: Involved HLC (iHLC) was the best biomarker correlating with M-protein concentration in both IgG and IgA MM, and could provide a surrogate marker substituting M-protein levels to follow the course of the disease, especially in ß-migrating IgA M-proteins. The distribution of iHLC values as well as HLC-pair ratios (rHLC) yielded significantly different results among the various response categories in both IgG and IgA MM. In addition, we detected 2 cases in which an abnormal rHLC in a stringent complete remission (sCR) sample was a marker of early non-symptomatic relapse. CONCLUSION: In this study of a cohort of 176 patients in a routine clinical setting, we have provided evidence of the clinical utility of real world HLC assays for the identification of M-proteins and to monitor M-proteins with an emphasis on IgA monoclonal gammopathies.