Analytical validation of the Mindray CL1200i analyzer high sensitivity cardiac troponin I assay: MERITnI study.

OBJECTIVES: This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of detection (LoD), precision, linearity, analytical specificity and sex-specific 99th percentile upper reference limits. METHODS: LoB, LoD, precision, linearity and analytical specificity were studied according to Clinical and Laboratory Standards Institute. We used one reagent lot and one CL1200i analyzer. Skeletal troponin I and T, cardiac troponin T, troponin C, actin, tropomyosin, myosin light chain, myoglobin and creatine kinase (CK-MB) were studied for cross-reactivity. Interference with biotin was examined. Lithium heparin samples (one freeze thaw cycle) from healthy males and females were measured to determine the 99th percentiles by using the non-parametric method. Analyses were performed before and after excluding subjects with clinical conditions and/or increased surrogate biomarkers. RESULTS: The Mindray hs-cTnI assay met criteria to be considered as a hs-cTn assay. LoB and LoD was <0.1 ng/L and 0.1 ng/L, respectively. Repeatability had a coefficient of variation 1.2-3.8 %, and within-laboratory imprecision 1.7-5.0 %. The measuring interval ranged from 1.1 to 28,180 ng/L. The analytical specificity was clinically acceptable for the interferents studied. After exclusions, the 99th percentile URLs obtained were 10 ng/L overall, 5 ng/L for females and 12 ng/L for males. CONCLUSIONS: Analytical observations of the Mindray hs-cTnI assay demonstrated excellent LoB, LoD, precision, linearity and analytical specificity, that were in alignment with the manufacturer's claims and regulatory guidelines for hs-cTnI. The assay is suitable for clinical investigation for patient-oriented studies.

Rapid Rule-Out of Myocardial Infarction Using a Single High-Sensitivity Cardiac Troponin I Measurement Strategy at Presentation to the Emergency Department: The SAFETY Study.

BACKGROUND: Our study addressed the diagnostic performance of the Atellica® IM High-Sensitivity Troponin I (hs-cTnI) assay for the rapid rule-out of myocardial infarction (MI) using a single hs-cTnI measurement at presentation in patients presenting to a US emergency department (ED). METHODS: This was a prospective, observational, cohort study of consecutive ED patients with suspected acute coronary syndrome, using 12-lead electrocardiogram and serial hs-cTnI measurements ordered on clinical indication (SAFETY, NCT04280926). ST-segment elevation MI patients were excluded. The optimal threshold required a sensitivity ≥99% and a negative predictive value (NPV) ≥99.5% for MI during index hospitalization as primary outcome. Type 1 MI (T1MI), myocardial injury, and 30-day adverse events were considered secondary outcomes. Event adjudications were established using the hs-cTnI assay used in clinical care. RESULTS: In 1171 patients, MI occurred in 97 patients (8.3%), 78.3% of which were type 2 MI. The optimal rule out hs-cTnI threshold was <10 ng/L, which identified 519 (44.3%) patients as low risk at presentation, with sensitivity of 99.0% (95% CI, 94.4-100) and NPV of 99.8% (95% CI, 98.9-100). For T1MI, sensitivity was 100% (95% CI, 83.9-100) and NPV 100% (95% CI, 99.3-100). Regarding myocardial injury, the sensitivity and NPV were 99.5% (95% CI, 97.9-100) and 99.8% (95% CI, 98.9-100), respectively. For 30-day adverse events, sensitivity was 96.8% (95% CI, 94.3-98.4) and NPV 97.9% (95% CI, 96.2-98.9). CONCLUSIONS: A single hs-cTnI measurement strategy enabled the rapid identification of patients at low risk of MI and 30-day adverse events, allowing potential discharge early after ED presentation. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT04280926.

Growth differentiation factor 15 and malnutrition in older adults.

OBJECTIVES: Growth differentiation factor 15 (GDF-15) levels increase due to systemic inflammation and chronic disease burden. Since these biological processes are pathogenic factors of malnutrition, we examined the prospective association between GDF-15 serum levels and subsequent malnutrition in older adults. METHODS: We used data from 723 women and 735 men aged ≥65 years [mean age (SD): 71.3 (4.18) years] participating in the Seniors-ENRICA-2 cohort, who were followed-up for 2.2 years. Malnutrition was assessed with the Mini Nutritional Assessment-Short form (MNA-SF), where a 12-14 score indicates normal nutritional status, an 8-11 score indicates at risk of malnutrition, and a 0-7 score malnutrition. Associations of GDF-15 and malnutrition were analyzed, separately in women and men, using linear and logistic regression and adjusted for the main potential confounders. RESULTS: The mean (SD) MNA-SF score at baseline was 13.2 (1.34) for women and 13.5 (1.13) for men. Incident malnutrition (combined endpoint "at risk of malnutrition or malnutrition") over 2.2 years was identified in 55 (9.7%) of women and 38 (5.4%) of men. In women, GDF-15 was linearly associated with a decrease in the MNA-SF score; mean differences (95% confidence interval) in the MNA-SF score were -0.07 (-0.13; -0.01) points per 25% increase in GDF-15, and -0.49 (-0.83; -0.16) for the highest versus lowest quartile of GDF-15. Also in women, GDF-15 was linearly associated with a higher malnutrition incidence, with odds ratio (95% confidence interval) of 1.24 (1.06; 1.46) per 25% increment in GDF-15 and of 3.05 (1.21; 7.65) for the highest versus lowest quartile of GDF-15. Results were similar after excluding subjects with cardiovascular disease and diabetes. No association of GDF-15 with changes in MNA score or malnutrition incidence was found in men. CONCLUSION: Higher serum GDF-15 concentrations are associated with worsening nutritional status in older women. Further studies should elucidate the reasons for the sex differences in this association and explore the therapeutic potential of modifying GDF-15 to prevent malnutrition.

Use of point-of-care glucometers during an oral glucose tolerance test in children for prediabetes and diabetes diagnosis: a comparison study.

Objectives: Despite clinical guidelines do not recommend the use of point-of-care testing (POCT) glucometers for diagnostic purposes yet, the analytical performance is continuously improving. Thus, we evaluate the technical accuracy and clinical concordance of POCT glucometers during an oral glucose tolerance test (OGTT) in children for prediabetes and diabetes diagnosis in a comparison study. Methods: Pediatric patients with an OGTT indication who attended the Diabetes Unit between December 2020 and September 2021 were recruited for this prospective observational study. During the functional test, glycaemia was immediately measured in venous blood using two glucometers (unconnected and connected) and sent to the central laboratory. Results: The study included 98 patients. There was a high correlation between the glucometers and the central laboratory (Pearson correlation coefficient=0.912 and 0.950, for unconnected and connected glucometer, respectively). The median OGTT turnaround time (TAT) was significantly decreased (connected glucometer: 2.02 h [interquartile range, 2.00-2.07], central laboratory: 11.63 h [6.09-25.80]), with similar overall cost. The diagnostic concordance between connected glucometer and the central laboratory was 71.1 % (95 % confidence interval (CI) 61.5-79.2). The clinical decision would have been the same in the 92.8 % of the cases, but treatment would have not been indicated in 4 patients (4.1 %). Conclusions: POCT glucometers have demonstrated a high correlation and an acceptable diagnostic concordance with the central laboratory during an OGTT, as well the connected device offers a significant decrease in TAT, without increasing costs. However, as severe clinical impact could happen, POCT glucometers may not be used for diagnosis yet.

Device-measured movement behaviors and cardiac biomarkers in older adults without major cardiovascular disease: the Seniors-ENRICA-2 study.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are biomarkers of myocardial infarction and heart failure, respectively, and indicate cardiovascular risk. Since low physical activity (PA) and sedentary behavior (SB) are also associated with higher cardiovascular risk, and this association could be a consequence of higher levels of cardiac biomarkers, we examined the association of device-measured movement behaviors with hs-cTnT and NT-proBNP in older men and women without major cardiovascular disease (CVD). METHODS: We used data from 1939 older adults from the Seniors-ENRICA-2 study. Accelerometers were used to assess time spent in sleep, SB, light PA (LPA), and moderate-to-vigorous PA (MVPA). Linear regression models were fitted separately in eight strata defined by sex, by median total PA time, and by the presence of subclinical cardiac damage according to cardiac biomarkers levels. RESULTS: In the less active men with subclinical cardiac damage, spending 30 min/day more of MVPA was associated with a mean percentage difference (MPD) (95% confidence interval) in hs-cTnT of - 13.1 (- 18.3, - 7.5); MPDs in NT-proBNP per 30 min/day increment were 5.8 (2.7, 8.9) for SB, - 19.3 (- 25.4, - 12.7) for LPA and - 23.1 (- 30.7, - 14.6) for MVPA. In women with subclinical cardiac damage who were less physically active, 30 min/day more of SB, LPA and MVPA were associated with MPDs in hs-cTnT of 2.1 (0.7, 3.6), - 5.1 (- 8.3, - 1.7) and - 17.5 (- 22.9, - 11.7), respectively, whereas in those more active, LPA and MVPA were associated with MPDs of 4.1 (1.2, 7.2) and - 5.4 (- 8.7, - 2.0), respectively. No associations were found with NT-proBNP in women. CONCLUSIONS: The relationship between movement behaviors and cardiac biomarkers in older adults without major CVD depends on sex, subclinical cardiac damage and PA level. More PA and less SB were generally related to lower cardiac biomarkers levels among less active individuals with subclinical cardiac damage, with greater benefits for hs-cTnT in women than men and no benefits for NT-proBNP in women.