Cobbaert, Christa M.

Abstract Background High-sensitivity cardiac troponin (hs-cTn) assays are recommended for the diagnosis of acute myocardial infarction. Here, we characterize the analytical performance of a next-generation hs-cTn assay, Elecsys® Troponin T hs Gen 6 (Roche Diagnostics International). Methods Surplus lithium-heparin plasma or serum samples from patients or healthy volunteers were run on Cobas® e 801, e 402, and Pro analyzers. Limits of blank (LoB), limits of detection (LoD), and limits of quantitation (LoQ) were determined according to CLSI EP17-A2, with target values of 1.0 and 1.5 ng/L for LoB/LoD and 3.0 ng/L (10% CV) and 1.5 ng/L (20% CV) for LoQ, respectively. Precision was measured, per CLSI EP17-A2, using 3 QC samples (approximately 4, 30, and 220 ng/L), 12 native samples, and 3 reagent lots. Linearity, per CLSI EP06-Ed2, was determined by diluting samples with cardiac troponin T (cTnT) concentration above the measuring range with a low/blank sample. Interference (per Glick) with endogenous and assay components at 5 cTnT concentrations was assessed. Results Measured values for LoB, LoD, and LoQ at 10% and 20% CV were 0.1 to 0.7 ng/L, 0.3 to 1.4 ng/L, 1.0 to 2.9 ng/L, and 0.4 to 1.2 ng/L, respectively. Repeatability CVs were 1.0 to 5.8% for mean cTnT concentrations of 2.6 to 9230 ng/L in lithium-heparin plasma. High precision was shown across lots, and linearity was observed across the measuring range (1.5 to 9500 ng/L, all Pearson's r = 1.00). No interferences were observed, specified up to ≤1000 mg/dL hemoglobin, ≤50 mg/dL [≤855 µmol/L] icterus/bilirubin, and ≤1200 ng/mL biotin. Conclusions The analytical performance characterization of the assay demonstrated high sensitivity, high precision at the low end and across the measuring range, and resistance to interference.

Abstract Background Measurement of cardiac troponin (cTn) using high-sensitivity assays is recommended for the diagnosis of myocardial infarction. We determined sex-specific and uniform 99th percentile upper reference limits (URLs) using the new Elecsys® Troponin T high-sensitivity Gen 6 assay in a global, healthy reference range cohort. Methods Lithium-heparin plasma and serum samples were prospectively collected from apparently healthy individuals aged ≥20 years across 34 global sites in the United States, Europe, China, and Japan. cTnT was measured using the Troponin T high-sensitivity Gen 6 assay on the Cobas® e 801 analyzer. Exclusion criteria were defined according to the 2022 IFCC guidance. Uniform and sex-specific 99th percentile URLs and nonparametric 95% CIs were determined in plasma and serum separately and combined. Results The final study population comprised 4147 participants (52.5% female) with a median (25th–75th percentiles) age of 48.0 (33.0–59.0) years; 45.8%, 47.9%, 5.2%, and 1.1% were White, Asian, Black, and other/unknown, respectively. For sample matrices combined (n = 8294), 81.0% and 99.2% of cTnT values were above the limit of detection in females and males, respectively. Sex-specific 99th percentile URLs (95% CI) were 18 (16–23) ng/L for females and 32 (28–35) ng/L for males; the uniform 99th percentile URL was 27 (24–31) ng/L. URLs were comparable in plasma and serum samples. Conclusions This study determined sex-specific and uniform 99th percentile URLs for the Troponin T high-sensitivity Gen 6 assay that were comparable irrespective of the matrix used in a large, global, healthy reference population.

Objectives: New methods are needed to detect pancreatic ductal adenocarcinoma (PDAC) earlier to improve outcomes. We previously reported that a panel of protein N-glycosylation traits (NGTs) discriminated PDAC from healthy controls with an area under the curve (AUC) of 0.81–0.88. However, it remained unclear whether this panel accurately differentiates PDAC from other benign pancreatic disorders. Our study aims to evaluate the performance of the NGT panel in combination with CA19-9 in a diverse cohort, including PDAC cases, healthy controls, and controls with benign pancreatic disorders. Methods: Protein N-glycosylation profiles were determined in plasma samples using an in-house developed mass spectrometry assay. CA19-9 levels were measured using a routine immunoassay test. Results of total plasma NGTs and CA19-9 were evaluated separately as well as in combination. Logistic regression was performed to calculate odds ratios (ORs), AUC, sensitivity, and specificity to determine the performance of NGTs and CA19-9 in distinguishing PDAC from controls. Results: In total, 221 individuals were included: 45 (20.4%) with PDAC, and 176 (79.6%) controls (53 healthy and 123 with benign pancreatic disease). The AUC for differentiating PDAC from the total control cohort based on the combination of the NGT panel and CA19-9 was 0.94 (95% CI, 0.90–0.97), with a sensitivity of 0.89 (95% CI, 0.78–0.98) and specificity of 0.86 (95% CI, 0.81–0.91). Comparison of PDAC cases with healthy controls only resulted in an AUC of 0.96 (95% CI, 0.93–0.99), with a sensitivity of 0.84 (95% CI, 0.73–0.93) and specificity of 0.98 (95% CI, 0.94–1.00). Conclusions: Both plasma NGTs and CA19-9 distinguish PDAC from a diverse control cohort. The accuracy further improves when these readouts are combined, showing promise for future early detection methods.