Alternative antibody for the detection of CA125 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access OV Monitor assay on the UniCel Dxl 800 Immunoassay System

BACKGROUND: Cancer antigen CA125 is known as a valuable marker for the management of ovarian cancer. METHODS: The analytical and clinical performance of the Access OV Monitor Immunoassay System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA125 on the Elecsys System (Roche Diagnostics). RESULTS: Total imprecision (% CV) of the OV Monitor ranged between 3.1% and 8.8%, and inter-laboratory reproducibility between 4.7% and 5.0%. Linearity upon dilution showed a mean recovery of 100% (SD + 8.1%). Endogenous interferents had no influence on OV Monitor levels (mean recoveries: hemoglobin 107%, bilirubin 103%, triglycerides 103%). There was no high-dose hook effect up to 27,193 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access OV Monitor and Elecsys CA125 (R = 0.982, slope = 0.921, intercept = +1.951). OV Monitor serum levels were low in healthy individuals (n = 267, median = 9.7 kU/L, 95th percentile = 30.8 kU/L), higher in individuals with various benign diseases (n = 549, medians = 10.9-16.4 kU/L, 95th percentiles = 44.2-355 kU/L) and even higher in individuals suffering from various cancers (n = 995, medians = 12.4-445 kU/L; 95th percentiles = 53.4-4664 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the OV Monitor was found for ovarian cancer [area under the curve (AUC) 0.898]. Results for the reference CA125 assay were comparable (AUC 0.899). CONCLUSIONS: The Access OV Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with Elecsys CA125. The best diagnostic accuracy for the OV Monitor was found in ovarian cancer. Our results also suggest a clinical value of the OV Monitor in other cancers.     

High clinical performance and quantitative assessment of antibody kinetics using a dual recognition assay for the detection of SARS-CoV-2 IgM and IgG antibodies

ObjectivesSeveral serological SARS-CoV-2 immunoassays have been developed recently but require external validation before widespread use. This study aims at assessing the analytical and clinical performance of the iFlash® anti-SARS-CoV-2 chemiluminescence assay for the detection of both IgM and IgG antibodies. The kinetics of the antibody response was also evaluated.Design & MethodsThe precision, carry-over, linearity, limit of blank, detection and quantification were assessed. Sensitivity analysis was performed by using 178 sera collected from 154 RT-PCR confirmed COVID-19 patients. The specificity analysis was performed from 75 selected non-SARS-CoV-2 sera with a potential cross-reaction to the SARS-CoV-2 immunoassay.ResultsThis iFlash® SARS-CoV-2 assay showed excellent analytical performance. After 2 weeks since symptom onset, the sensitivities for IgM and IgG were 62.2% (95% CI: 52.3–71.2%) and 92.9%% (95% CI: 85.7–96.7%), respectively by using the cut-off provided by the manufacturer. After cut-off optimization (i.e. >2.81 for IgM and >4.86 for IgG), the sensitivity for IgM and IgG were 81.6 (95% CI: 72.7–88.1%) and 95.9% (95% CI: 89.4–98.7%), respectively. Optimized cut-off for IgG improved the sensitivity to reach 100% (95%CI: 87.6–100) from 28 days since symptom onset.ConclusionsThis study shows that the iFlash® SARS-CoV-2 assay from YHLO biotechnology, has satisfactory analytical performance. Nevertheless, the sensitivity of the IgM is limited for a proper clinical use compared to IgG. The determination of anti-SARS-CoV-2 IgG antibodies from 28 days since symptom onset was associated with high sensitivity, especially using optimized cut-offs (i.e. 100%).     

Suspected myocardial infarction in the emergency department: An evaluation of clinical thresholds for the Beckman Coulter Access hsTnI high-sensitivity cardiac troponin I assay

Objective

The primary objective was to determine rapid rule-out (RRO) criteria for the outcome of myocardial infarction (MI) using the Beckman Coulter Access high-sensitivity cardiac troponin I (hs-cTnI) assay. Secondary objectives were to explore cut-points for rapid rule-in (RRI) and amount of change at 3-h (3-h delta) indicative of MI.

Methods

A retrospective study included ED patients with suspected MI between June and September 2019. hs-cTnI levels were performed at baseline and after 3 h. The performance benchmark for RRO criteria was a negative predictive value (NPV) for MI with a lower 95% confidence limit >99%, and for RRI and 3-h delta cut-points was a positive predictive value (PPV) for MI >70%. Delta calculation required rising hs-cTnI levels, with at least one above the 99th percentile of the upper reference limit. Analyses utilised receiver operating characteristic (ROC) curves and contingency tables.

Results

Baseline hs-cTnI levels from 935 patients were available for RRO analyses. Of tested criteria, baseline hs-cTnI <6 ng/L (females) or <11 ng/L (males) plus symptom onset >2 h met the performance benchmark (NPV: 100% [95% confidence interval 99–100]). hs-cTnI levels were available for RRI and 3-h delta analyses from 935 and 52 patients, respectively. A 3-h delta cut-point >35 ng/L met the performance benchmark (PPV: 81% [95% confidence interval 58–95]) but no RRI cut-point did so.

Conclusions

For the Beckman Coulter Access hs-cTnI assay, RRO criteria of baseline hs-cTnI <6 ng/L (females) or <11 ng/L (males) plus symptom onset >2 h met our performance benchmark. A 3-h delta cut-point >35 ng/L met the performance benchmark, but poor precision means further adequately powered research is required.