Comparative Evaluation of Commercial Test Kits Cleared for Use in Modified Two-Tiered Testing Algorithms for Serodiagnosis of Lyme Disease.

BACKGROUND: Modified 2-tiered testing (MTTT) for Lyme disease utilizes automatable, high throughput immunoassays (AHTIs) in both tiers without involving western immunoblots, offering performance and practical advantages over standard 2-tiered testing (STTT; first-tier AHTI followed by immunoglobulin M (IgM) and immunoglobulin G (IgG) western immunoblots). For MTTT, Centers for Disease Control and Prevention recommends using AHTI test kits that have been cleared by Food and Drug Administration (FDA) specifically for this intended use. We evaluated performance of FDA-cleared MTTT commercial test kits from 3 manufacturers by comparing with STTT results. METHODS: We performed MTTT (total antibody AHTI with reflex to separate IgM and IgG AHTIs) using test kits from Diasorin, Gold Standard Diagnostics (GSD), and Zeus Scientific on 382 excess serum samples submitted to the clinical laboratory for routine Lyme disease serologic testing in July 2018, measuring agreement between MTTT and STTT using the κ statistic. RESULTS: Overall agreement with STTT was 0.87 (95% confidence interval [CI], .77-.97) using Diasorin assays (almost perfect agreement), 0.80 (95% CI, .68-.93) using GSD assays (substantial agreement) and 0.79 (95% CI, .68-.90) using Zeus assays (substantial agreement). For detection of IgM reactivity, agreement between MTTT and STTT was 0.70 (.51-.90; substantial), 0.63 (95% CI, .44-.82; substantial) and 0.56 (95% CI, .38-.73; moderate), respectively. For detection of IgG reactivity, MTTT/STTT agreement was 0.73 (95% CI,.58-.88), 0.78 (95% CI, .62-.94), and 0.75 (95% CI, .60-.90), respectively (substantial agreement in all cases). CONCLUSIONS: MTTT results obtained using commercial test kits from 3 different manufacturers had substantial to almost perfect agreement with STTT results overall and moderate to substantial agreement for IgM and IgG detection independently. Commercial MTTT tests can be used broadly for the diagnosis of Lyme disease.

ST2 Predicts Mortality and Length of Stay in a Critically Ill Noncardiac Intensive Care Unit Population.

OBJECTIVES: The biomarker suppression of tumorigenicity 2 (ST2) is a well-established clinical biomarker of cardiac strain and is frequently elevated in a variety of cardiac conditions. Here, we sought to evaluate the prognostic value of ST2 in critically ill medical intensive care unit (MICU) patients without primary cardiac illness. METHODS: We measured ST2 and high-sensitivity troponin T (hsTnT) on plasma specimens collected on 441 patients following admission to a noncardiac MICU and evaluated the prognostic power of ST2 both alone and in multivariate models. RESULTS: Of these critically ill patients, 96% exhibited ST2 concentrations above the reference interval. ST2 concentrations were highly predictive of intensive care unit and hospital length of stay, as well as in-hospital mortality, with high concentrations predicting a poor prognosis. Rates of in-hospital mortality were more than four times higher in patients with ST2 concentrations in the highest compared with the lowest quartile. In multivariate analysis, ST2 remained an important predictor of death after adjustment for age, hsTnT, and common diagnoses. CONCLUSIONS: ST2 is increased and predictive of prognosis in critically ill patients without primary cardiac disease, suggesting that critically ill patients may often have unrecognized cardiac injury. Clinical decision support algorithms incorporating ST2 and hsTnT results may be useful in patient risk stratification.

Measurement of high-sensitivity troponin T in noncardiac medical intensive care unit patients. Correlation to mortality and length of stay.

OBJECTIVES: To assess the frequency, magnitude, and prognostic significance of elevations in cardiac troponin T in noncardiac critically ill patients, including elevations at levels below the limit of detection of traditional assays. METHODS: Using a high-sensitivity assay, we measured troponin T (high-sensitivity troponin T [hsTnT]) in 451 unique patients within 12 hours of their admission to a noncardiac medical intensive care unit. Outcomes of patients, grouped by hsTnT level, were compared. RESULTS: Overall, 98% of the study patients had detectable levels of hsTnT (>3 ng/L), and 33% had levels above the diagnostic cutoff of a traditional fourth-generation cardiac troponin T assay. Patient groups with higher hsTnT levels had markedly higher rates of in-hospital mortality (P < .001) and longer stays in the hospital and intensive care unit (P < .01). CONCLUSIONS: In noncardiac critically ill patients, cardiac troponin T elevations are common but often at levels undetectable by traditional assays. hsTnT elevations predict a more complex clinical course and an increased risk of death.

Reference interval evaluation of high-sensitivity troponin T and N-terminal B-type natriuretic peptide in Vietnam and the US: The North South East West Trial.

BACKGROUND: Reference intervals of high-sensitivity troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been determined from Western populations. No data are available regarding expected values in Asian populations. METHODS: A total of 1157 age- and sex-matched healthy individuals (mean age, 41.2 years; 48.0% male) were prospectively enrolled from the US (n = 565) and Vietnam (n = 592). Blood samples were analyzed for hs-cTnT and NT-proBNP. Median values were determined for each country and compared in unadjusted analyses and in analyses adjusted for age, sex, body mass index, study site, race, and vital signs. RESULTS: Median hs-cTnT concentrations were slightly higher for individuals from the US than for those from Vietnam, but both were below the limit of detection (3.7 vs 3.0 ng/L, respectively; P = 0.03). More US participants had an hs-cTnT concentration above the limit of detection (57.2% vs 47.3%; P = 0.001), but the 99th percentile concentration was slightly higher for Asians (US 15.1 vs Vietnam 19.0 ng/L). Concentrations for >98% of both populations were below the standard hs-cTnT 99th percentile of 14.0 ng/L (P = 0.54). Median NT-proBNP concentrations were slightly higher for US participants compared with Vietnamese participants (28 vs 16 ng/L, respectively; P < 0.001). Following adjustment, differences in concentrations of NT-proBNP between healthy US and Vietnamese populations remained significant, whereas for hs-cTnT the differences were no longer significant. Inclusion of hs-cTnT values down to the limit of blank did not change the result. CONCLUSIONS: The differences in hs-cTnT and NT-proBNP between healthy individuals from the US and Vietnam are small. Previously derived reference intervals for both analytes may be applied in Asian populations.

Cardiac blood biomarkers in patients receiving thoracic (chemo)radiation.

Cardiotoxicity is a known consequence of thoracic irradiation and there are multiple overlapping risk factors for cardiac disease and thoracic malignancies. In this study, we quantified the impact of thoracic (chemo)radiation on cardiac troponin T (TnT), creatine kinase-myocardial band (CK-MB) and aminoterminal pro-brain natriuretic peptide (NT-proBNP). Thirty patients receiving radiation therapy to the thorax with or without concurrent chemotherapy were evaluated. Serum was collected at baseline, 2 weeks into treatment and at the completion of radiation therapy. TnT, CK-MB and NT-proBNP were quantified using commercially available immunoassays. Cardiac dosimetric parameters and clinical risk factors were examined. In 29 of 30 patients, serum TnT remained undetectable (<0.01ng/mL) throughout (chemo)radiation. In the one patient with detectable serum TnT, levels did not change significantly with treatment. Similarly, thoracic (chemo)radiation did not cause statistically significant elevations in serum CK-MB and NT-proBNP. Thus, contemporary thoracic (chemo)radiation does not commonly result in elevations of serum TnT, CK-MB or NT-proBNP. Elevations in these markers during treatment merit further evaluation.