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• Analytical characteristics are reported for the novel Atellica IM TnIH assay. • The Atellica TnIH assay met criteria as a high-sensitivity cardiac troponin assay. • 1007 women & 1000 men established sex-specific 99th % upper reference limits. • HIGH-US is cohort of nearly of 2494 suspected acute myocardial infarction subjects. • 1.0 to 3.5 h post presentation Atellica's TnIH's negative predictive value was 99%. Cardiac troponin (cTn) is the keystone for diagnosis of acute myocardial infarction (AMI). We examined the analytical and diagnostic accuracy of the Atellica IM TnIH assay to determine high-sensitivity performance and appropriate diagnostic performance for clinical use. Sex-specific 99th percentile upper reference limits (URLs) were determined for a healthy cohort of 1007 women and 1000 men using non-parametric statistics. High-sensitivity performance was assessed by examining if imprecision was ≤10% at sex-specific URLs and if ≥50% of cTnI values for each sex exceeded the assay's limit of detection (LoD) with the AACC Universal Sample Bank. Precision, high-dose hook effect, endogenous/exogenous interferences were examined with CLSI guidance. Clinical characterization was with 2494 suspected AMI subjects presenting to emergency departments across the United States. AMI was adjudicated by expert cardiologists and emergency medicine physicians. There were no comorbidity exclusions. 99th percentile URLs were 34 ng/L, 53 ng/L and 45 ng/L for the female, male and overall populations, respectively. Total imprecision was <5% from 12 ng/L to 16,000 ng/L; ≥55% of cTnI values for each sex exceeded the LoD. No high-dose hook or endogenous/exogenous interferences were identified. After 2.5–3.5 h post presentation the sensitivity and specificity were >90%; negative and positive predictive value were ≥98% and >60%, respectively. Non-AMI subjects with comorbidities and values exceeding 99th percentile URLs had absolute and percent change at 2–4 h that were lower than AMI patients with comorbidities (p = 0.001). The Atellica IM TnIH assay is a high-sensitivity method and demonstrates clinical performance appropriate for AMI diagnosis. [ABSTRACT FROM AUTHOR]

We describe the diagnostics surrounding the deaths of five working dogs over six-months to provide an enhanced clinical and diagnostic understanding of canine Chagas disease. Cases were five dogs with antibodies to Trypanosoma cruzi. Medical records were reviewed for diagnostic history. Testing was performed from samples collected before or immediately after death, including measurement of cardiac troponin I, histology, PCR and serology for Leishmania spp. and T. cruzi. Four dogs had a 2 to 7-year history of T. cruzi antibodies, while one positive dog had an unknown duration of exposure. Age at death ranged from 2 to 11 years and four dogs were actively working. The cardiac troponin I was elevated in all four dogs for which it was measured, although postmortem reference ranges are not established. Histopathologic diagnoses included mild to severe, chronic, lymphoplasmacytic to histiocytic myocarditis with variable fibrosis. Notably, only one dog had T. cruzi amastigotes observed in the heart histologically. T. cruzi DNA was detected in three other hearts. Although all five dogs tested antibody-positive for T. cruzi using three independent tests, all were also indirect fluorescent antibody-positive for Leishmania spp., interpreted as cross-reaction. Chagas disease in dogs is a diagnostic challenge owing to cross-reactions and variable clinical, histologic and molecular presentations. The use and interpretation of multiple diagnostic strategies is useful in diagnosis. This study demonstrates techniques used to diagnose and characterize Chagas disease in an at-risk dog population., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Development of clinical biomarkers to guide therapy is an important unmet need in aneurysmal subarachnoid hemorrhage (SAH). A wide spectrum of plausible biomarkers has been reported for SAH, but none have been validated due to significant variabilities in study design, methodology, laboratory techniques, and outcome endpoints., Methods: A systematic review of SAH biomarkers was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The panel's recommendations focused on harmonization of (1) target cellular and molecular biomarkers for future investigation in SAH, (2) standardization of best-practice procedures in biospecimen and biomarker studies, and (3) experimental method reporting requirements to facilitate meta-analyses and future validation of putative biomarkers., Results: No cellular or molecular biomarker has been validated for inclusion as "core" recommendation. Fifty-four studies met inclusion criteria and generated 33 supplemental and emerging biomarker targets. Core recommendations include best-practice protocols for biospecimen collection and handling as well as standardized reporting guidelines to capture the heterogeneity and variabilities in experimental methodologies and biomarker analyses platforms., Conclusion: Significant variabilities in study design, methodology, laboratory techniques, and outcome endpoints exist in SAH biomarker studies and present significant barriers toward validation and translation of putative biomarkers to clinical use. Adaptation of common data elements, recommended biospecimen protocols, and reporting guidelines will reduce heterogeneity and facilitate future meta-analyses and development of validated clinical biomarkers in SAH.

Objectives To investigate mechanisms of in utero death in normally formed fetuses by measuring amniotic fluid (AF) biomarkers for hypoxia (erythropoietin [EPO]), myocardial damage (cardiac troponin I [cTnI]) and brain injury (glial fibrillary acidic protein [GFAP]), correlated with risk factors for fetal death and placental histopathology. Methods This retrospective, observational cohort study included intrauterine deaths with transabdominal amniocentesis prior to induction of labor. Women with a normal pregnancy and an indicated amniocentesis at term were randomly selected as controls. AF was assayed for EPO, cTnI and GFAP using commercial immunoassays. Placental histopathology was reviewed, and CD15-immunohistochemistry was used. Analyte concentrations >90th centile for controls were considered "raised". Raised AF EPO, AF cTnI and AF GFAP concentrations were considered evidence of hypoxia, myocardial and brain injury, respectively. Results There were 60 cases and 60 controls. Hypoxia was present in 88% (53/60), myocardial damage in 70% (42/60) and brain injury in 45% (27/60) of fetal deaths. Hypoxic fetuses had evidence of myocardial injury, brain injury or both in 77% (41/53), 49% (26/53) and 13% (7/53) of cases, respectively. Histopathological evidence for placental dysfunction was found in 74% (43/58) of these cases. Conclusion Hypoxia, secondary to placental dysfunction, was found to be the mechanism of death in the majority of fetal deaths among structurally normal fetuses. Ninety-one percent of hypoxic fetal deaths sustained brain, myocardial or both brain and myocardial injuries in utero. Hypoxic myocardial injury was an attributable mechanism of death in 70% of the cases. Non-hypoxic cases may be caused by cardiac arrhythmia secondary to a cardiac conduction defect.

Background: High-Sensitivity (hs) cardiac troponin (cTn) assays are categorized by two criteria: (i) cTn values above the limit of detection (LoD) for >50% of male and female healthy cohorts of ≥300 individuals; (ii) imprecision ≤10% total %CV for sex-specific 99th-percentile clinical decision values (CDVs). No documented hs-Tn assay has yet been FDA-cleared., Methods: The PATHFAST cTnI-II assay's LoD was 2.3 ng/L using CLSI EP-17. The AACC Universal Sample Bank of 847 healthy men (50.6%) and women (49.4%) was used to determine 99th-percentile CDVs with Nonparametric, Harrell-Davis and Robust modeling. Health/Medication questionnaires and Amino-terminal proBNP, Hemoglobin A 1c and estimated Glomerular Filtration Rate surrogates excluded underlying health conditions., Results: The cTnI-II test's total CV was 6.1% at 29 ng/L and 7.1% at 22 ng/L; the LoD was 2.3 ng/L. Of the full 847-member healthy cohort, 113 (13.3%) were excluded by abnormal surrogate biomarkers. The final 734-member healthy population had the following (% > LoD): overall, 487 (66.3%); women, 186 (52.8%); and men, 301 (78.8%). 99th-percentile CDVs by Nonparametric modeling were: 28 ng/L (90% CI: 20-30), overall final 732-member healthy population; 20 ng/L (90% CI: 13-30), 352 women; and 30 ng/L (90% CI: 21-37), 382 men. Differences between sex-specific CDVs were not significantly different (p > .05) with Nonparametric or Harrell-Davis modeling; however, Robust Modeling did show significance (<0.05), with lower CDVs at 11 ng/L (90% CI: 9-12) and 16 ng/L (90% CI: 15-18) for the female and male cohorts, respectively., Conclusions: cTnI-II is the only FDA-cleared assay that has demonstrated high-sensitivity cTn assay. Use of recommended modeling in >300 healthy subjects for determining sex-specific 99th-percentile CDVs did not show statistically significant differences except with the Robust modeling., (Copyright © 2018. Published by Elsevier Inc.)

Adulticide treatment of dogs with canine heartworm disease causes the death of the adult Dirofilaria immitis lodged in the vascular system of the host. During the death of the worms, pulmonary thromboembolisms (PTE), pulmonary inflammation, congestive heart failure, or renal disease are possible consequences. The aim of this study was to evaluate cardiopulmonary biomarkers and renal parameters during adulticide treatment of canine heartworm to compare the classic two-injection treatment protocol versus the American Heartworm Society (AHS) recommended protocol. Fourteen heartworm-infected dogs with high parasite burdens were divided in three groups and allocated to adulticide protocols as follows: Group A (n=5) was treated with the classic two-injection protocol; group B (n=5) was treated using the AHS recommended protocol, and group C (n=4) was treated as for group B but received diminishing anti-inflammatory doses of prednisone. To assess cardiorespiratory status, cardiac troponin I (cTnI), myoglobin, and D-dimer were measured. Renal function was evaluated by measuring urea, creatinine, and urine protein:creatinine (UP:C). Serum and urine samples were collected day 0 (day of diagnosis), 7 and 14 days after the first dose of adulticide, and 1 month after the last adulticide injection. Dogs that received classic treatment presented pathologic concentrations of D-dimer more frequently and showed higher average D-dimer levels, which may indicate the presence of more severe PTE. Group C showed the highest levels of D-dimer during treatment, which may be due to an exacerbation of PTE caused by the administration of prednisone. CTnI and myoglobin values remained above reference values in all groups during the study but reached the lowest values 1 month after the last injection. Levels of urea and creatinine were within normal ranges in all groups, and 28.5% of the dogs were proteinuric on day 0, progressing to better UP:C values at the end of the treatment, except in group A. The results of this study justify the treatment of canine heartworm disease using the AHS recommended adulticide guidelines and recommends re-evaluation of the role of glucocorticosteroids in the prevention and treatment of PTE., (Copyright © 2014 Elsevier B.V. All rights reserved.)