Abstract
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 <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 U 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 (P ≤ 0.0001). Nucleosomes and cfDNA concentrations were positively correlated (rs 0.475, P < 0.001). Concentrations of both cfDNA and nucleosomes were correlated with shock index (rs 0.367, P = 0.010, rs 0.358, P = 0.012 respectively), but only nucleosomes were correlated with ATT (rs 0.327, P = 0.022) and acute patient physiology and laboratory evaluation (APPLE) scores (rs 0.356, P = 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); P = 0.01]. Among illness severity scores, only APPLE was discriminant for survival (AUROC 0.912, P < 0.001). In summary, in moderately-severely injured dogs, high nucleosome concentrations are significantly associated with non-survival.
Highlights
Dogs are frequently presented to veterinary emergency rooms following trauma, and the injuries resulting from blunt force trauma and animal bites are associated with considerable morbidity and mortality [1]
The primary aim of the present study was to explore the association between plasma cell-free DNA (cfDNA) concentrations and survival to discharge in dogs following trauma
This is in contrast to the situation in people where cfDNA is prognostic after multiple trauma or after major surgery [37]
Summary
Dogs are frequently presented to veterinary emergency rooms following trauma, and the injuries resulting from blunt force trauma and animal bites are associated with considerable morbidity and mortality [1]. It is challenging for clinicians to predict the development of complications or assess the prognosis of traumatized dogs Systems such as the Animal Trauma Triage (ATT) score and the canine acute patient physiologic and laboratory evaluation (APPLE) score were developed to aid the initial evaluation of such patients [3, 4]. And repeated patient scoring can help guide therapeutic interventions and may aid assessment of prognosis [5,6,7]. While these methods aid prognostication of hospitalized patients, they provide limited biologic insight into the pathophysiologic effects of tissue injury and shock. Identification of an accurate, easy to measure bedside biomarker that correlates with injury severity and prognosis in injured dogs would be very valuable
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