AUTHOR=Letendre Jo-Annie , Goggs Robert 

TITLE=Concentrations of Plasma Nucleosomes but Not Cell-Free DNA Are Prognostic in Dogs Following Trauma

JOURNAL=Frontiers in Veterinary Science

VOLUME=5

YEAR=2018

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2018.00180

DOI=10.3389/fvets.2018.00180

ISSN=2297-1769

ABSTRACT=<p>Trauma is common in dogs and causes significant morbidity and mortality, but it remains a challenge to assess prognosis in these patients. This study aimed to investigate the use of plasma cell-free DNA (cfDNA) and nucleosome concentrations as prognostic biomarkers in canine trauma. Using a prospective, observational case-control study design, 49 dogs with trauma were consecutively enrolled from 07/2015 to 10/2017 and followed to hospital discharge. Dogs with animal trauma triage (ATT) scores ≥3 at presentation were eligible for enrollment. Dogs &lt;3 kg or with pre-existing coagulopathies were excluded. Thirty-three healthy control dogs were also enrolled. Illness and injury severity scores were calculated using at-presentation data. Plasma cfDNA was measured in triplicate using a benchtop fluorimeter. Plasma nucleosome concentrations were determined in duplicate by ELISA. Mann-Whitney <italic>U</italic> tests were used to compare biomarker concentrations between groups and between survivors and non-survivors. Associations between biomarkers were evaluated using Spearman's correlation coefficients. Alpha was set at 0.05. Concentrations of cfDNA and nucleosomes were significantly higher in injured dogs compared to healthy controls (<italic>P</italic> ≤ 0.0001). Nucleosomes and cfDNA concentrations were positively correlated (<italic>r</italic><sub>s</sub> 0.475, <italic>P</italic> &lt; 0.001). Concentrations of both cfDNA and nucleosomes were correlated with shock index (<italic>r</italic><sub>s</sub> 0.367, <italic>P</italic> = 0.010, <italic>r</italic><sub>s</sub> 0.358, <italic>P</italic> = 0.012 respectively), but only nucleosomes were correlated with ATT (<italic>r</italic><sub>s</sub> 0.327, <italic>P</italic> = 0.022) and acute patient physiology and laboratory evaluation (APPLE) scores (<italic>r</italic><sub>s</sub> 0.356, <italic>P</italic> = 0.012). Median nucleosome concentrations were significantly higher in non-survivors than in survivors [8.2 AU (3.1–26.4) vs. 1.6 AU (0.5–5.2); <italic>P</italic> = 0.01]. Among illness severity scores, only APPLE was discriminant for survival (AUROC 0.912, <italic>P</italic> &lt; 0.001). In summary, in moderately-severely injured dogs, high nucleosome concentrations are significantly associated with non-survival.</p>