Utility of cell-free DNA concentrations and illness severity scores to predict survival in critically ill neonatal foals.
Abstract: Plasma cell-free DNA (cfDNA) levels have been associated with disease and survival status in septic humans and dogs. To date, studies investigating cfDNA levels in association with critical illness in foals are lacking. We hypothesized that cfDNA would be detectable in the plasma of foals, that septic and sick-nonseptic foals would have significantly higher cfDNA levels compared to healthy foals, and that increased cfDNA levels would be associated with non-survival. Animals used include 80 foals of 10 days of age or less admitted to a tertiary referral center between January and July, 2020 were stratified into three categories: healthy (n = 34), sick non-septic (n = 11) and septic (n = 35) based on specific criteria. This was a prospective clinical study. Blood was collected from critically ill foals at admission or born in hospital for cfDNA quantification and blood culture. Previously published sepsis score (SS) and neonatal SIRS score (NSIRS) were also calculated. SS, NSIRS, blood culture status and cfDNA concentrations were evaluated to predict survival. Continuous variables between groups were compared using Kruskal-Wallis ANOVA with Dunn's post hoc test. Comparisons between two groups were assessed using the Mann-Whitney U-test or Spearman rank for correlations. The performance of cfDNA, sepsis score and NSIRS score to predict survival was assessed by receiver operator characteristic (ROC) curve analysis including area under the curve, sensitivity and specificity using cutoffs. Plasma cfDNA was detectable in all foals. No significant differences in cfDNA concentration were detected between healthy foals and septic foals (P = 0.65) or healthy foals and sick non-septic foals (P = 0.88). There was no significant association between cfDNA and culture status, SS, NSIRS or foal survival. SS (AUC 0.85) and NSIRS (AUC 0.83) were superior to cfDNA (AUC 0.64) in predicting survival. Although cfDNA was detectable in foal plasma, it offers negligible utility to diagnose sepsis or predict survival in critical illness in neonates.
Publication Date: 2021-04-26 PubMed ID: 33901192PubMed Central: PMC8075268DOI: 10.1371/journal.pone.0242635Google Scholar: Lookup
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Summary
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This research investigates plasma cell-free DNA (cfDNA) levels in critically ill neonatal foals and its link with sepsis and survival rate. However, it concludes that although cfDNA is detectable in the blood of foals, it does not significantly aid in diagnosing sepsis or predicting survival rates in critically ill newborn horses.
Overview of the Study
- The study aims to assess the usefulness of plasma cell-free DNA (cfDNA) levels as potential markers of disease and survival in critically ill neonatal foals. The research team hypothesized that cfDNA levels would be higher in septic and sick-nonseptic foals compared to healthy ones, and that raised cfDNA levels would correlate with non-survival.
- For the experiment, 80 foals aged 10 days or younger and admitted to a tertiary referral center between January and July 2020 were used. The young horses were divided into three categories: healthy, sick non-septic, and septic, based on certain criteria.
- This was a prospective clinical study where blood samples collected from the foals were analyzed for cfDNA concentration and blood culture. The statistical tools used for comparison included Kruskal-Wallis ANOVA with Dunn’s post hoc test, Mann-Whitney U-test, and Spearman rank.
Primary Outcomes
- It was found that plasma cfDNA was present in all the foals. However, the levels did not significantly differ between healthy foals and septic foals or sick non-septic foals, contradicting the initial hypothesis.
- There was no significant link between cfDNA levels and culture status, sepsis score (SS), and neonatal Systemic Inflammatory Response Syndrome score (NSIRS).
- The analysis further indicated that SS and NSIRS were more accurate than cfDNA in predicting survival, as seen from the receiver operator characteristic (ROC) curve analysis. The ROC score for SS and NSIRS was found to be 0.85 and 0.83 respectively, while it was only 0.64 for cfDNA.
Conclusion
- The study concludes that although cfDNA can be detected in foal plasma, its utility in diagnosing sepsis or predicting survival in critical illnesses in neonates is negligible. This underlines the discrepancy between the study’s initial hypothesis and the results obtained.
Cite This Article
APA
Colmer SF, Luethy D, Abraham M, Stefanovski D, Hurcombe SD.
(2021).
Utility of cell-free DNA concentrations and illness severity scores to predict survival in critically ill neonatal foals.
PLoS One, 16(4), e0242635.
https://doi.org/10.1371/journal.pone.0242635 Publication
Researcher Affiliations
- Department of Clinical Sciences, The University of Pennsylvania School of Veterinary Medicine, New Bolton Center, Philadelphia, Pennsylvania, United States of America.
- Department of Clinical Sciences, The University of Pennsylvania School of Veterinary Medicine, New Bolton Center, Philadelphia, Pennsylvania, United States of America.
- Department of Clinical Sciences, The University of Pennsylvania School of Veterinary Medicine, New Bolton Center, Philadelphia, Pennsylvania, United States of America.
- Department of Clinical Sciences, The University of Pennsylvania School of Veterinary Medicine, New Bolton Center, Philadelphia, Pennsylvania, United States of America.
- Department of Clinical Sciences, The University of Pennsylvania School of Veterinary Medicine, New Bolton Center, Philadelphia, Pennsylvania, United States of America.
MeSH Terms
- Animals
- Animals, Newborn / genetics
- Cell-Free Nucleic Acids / genetics
- Critical Illness / mortality
- Horse Diseases / genetics
- Horse Diseases / mortality
- Horses / genetics
- Prospective Studies
- ROC Curve
- Sensitivity and Specificity
- Sepsis / genetics
- Sepsis / mortality
- Sepsis / veterinary
- Severity of Illness Index
- Statistics, Nonparametric
- Systemic Inflammatory Response Syndrome / genetics
- Systemic Inflammatory Response Syndrome / mortality
- Systemic Inflammatory Response Syndrome / veterinary
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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Citations
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