The prognosis for canine and feline pyothorax is variable but can be good with appropriate treatment. A review of the current veterinary literature revealed an overall reported survival rate of 83% in dogs and 62% in cats. As the clinical presentation of pyothorax in small animals is often delayed and nonspecific, rapid diagnosis and treatment are required to ensure successful outcome.
Objective -To investigate the use of plasma cell-free DNA (cfDNA) and nucleosome concentrations as prognostic biomarkers in canine sepsis. Design -Prospective, observational cohort study conducted from June 2015 to February 2016. Setting -University teaching hospital. Animals -Forty-five dogs with sepsis, 10 dogs with nonseptic systemic inflammatory response syndrome (nSIRS), and 15 healthy controls were consecutively enrolled and followed to hospital discharge. Patients were eligible for enrollment if they met ࣙ2 SIRS criteria and had a documented or highly suspected bacterial infection. Dogs <3 kg or with a known coagulopathy were excluded. Interventions -None.Measurements and Main Results -Acute Patient Physiology and Laboratory Evaluation scores (APPLE) were calculated and outcomes recorded. Plasma cfDNA was measured using a benchtop fluorimeter. Plasma nucleosome concentrations were determined by ELISA. Plasma nucleosome and cfDNA concentrations in dogs with sepsis or nSIRS were compared to those of healthy controls and cfDNA concentrations in septic dogs with and without bacteremia were compared. Associations between cfDNA concentrations and nucleosomes, leukocyte count, neutrophil count, and APPLE scores were evaluated. For septic dogs, cfDNA concentrations relative to neutrophil count and nucleosome concentrations in survivors and nonsurvivors were compared. Alpha was set at 0.05. cfDNA concentrations were significantly higher in dogs with sepsis or nSIRS compared to healthy controls (P < 0.0001 and P = 0.0034, respectively). Nucleosome concentrations were significantly higher in dogs with sepsis compared to healthy controls (P = 0.007). There was limited association between cfDNA and nucleosome concentrations (r s = 0.266), and no association between cfDNA concentration and leukocyte count, neutrophil count, and APPLE full scores. Concentrations of cfDNA were positively correlated with APPLE fast score (r s = 0.335, P = 0.025); however, cfDNA concentrations were significantly higher in dogs with bacteremia (P = 0.0299). In dogs with sepsis, cfDNA concentrations relative to neutrophil count were significantly higher in nonsurvivors than in survivors (P = 0.008). Conclusions -In dogs with sepsis, high cfDNA concentrations relative to neutrophil count are associated with nonsurvival. Point-of-care cfDNA measurement may aid identification of bacteremia. (J Vet Emerg Crit Care 2018; 28(6): 503-511)
cfDNA can be readily identified in canine plasma using 2 fluorescence assays. DNA extraction offers no advantage over direct measurement. Compared to healthy controls, dogs with sepsis or moderate-severe trauma have significantly increased plasma cfDNA concentrations.
Objective: To quantify plasma cytokine concentrations in dogs with sepsis and noninfectious systemic inflammation and to evaluate the association between plasma cytokines and outcome in dogs with sepsis.Design: Prospective, observational cohort study. Setting: University teaching hospital.Animals: Forty-five dogs with sepsis, 10 dogs with noninfectious systemic inflammation (nSIRS), and 15 healthy controls were consecutively enrolled from June 2015 to February 2016 and followed to hospital discharge. Dogs with sepsis satisfied ≥2 SIRS criteria and had a documented or highly suspected bacterial infection. Dogs with nSIRS satisfied ≥2 SIRS criteria but had no evidence of infection. Dogs <3 kg and those with documented coagulopathy were excluded.Interventions: Measurement of inflammatory cytokines and high-mobility group box-1 (HMGB-1) was performed on each group. Measurements and Main Results:High-mobility group box-1 concentrations were analyzed by ELISA. Plasma concentrations of 13 cytokines were measured in singlet using multiplex magnetic bead assays. Kruskal-Wallis with Dunn's multiple comparison tests were used to compare biomarker concentrations between groups. Mann-Whitney U-tests were used to compare biomarker concentrations between survivors and nonsurvivors. Associations between biomarkers were evaluated using Spearman's correlation coefficients. Independent outcome predictors were identified using multivariable logistic regression. Alpha was set at 0.05. Concentrations of interleukin (IL)-6, C-X-C motif chemokine (CXCL)-8, keratinocyte-derived chemokine (KC)-like, C-C motif chemokine ligand 2 (CCL2), and HMGB-1 were significantly greater in dogs with sepsis versus healthy controls (all P ≤ 0.034). In dogs with sepsis, only CCL2 was independently associated with survival (odds ratio [OR] 0.996, 95% CI 0.993-0.999, P = 0.004). A cut-off of 385 pg/mL for CCL2 was 80% sensitive and 91.4% specific for nonsurvival (area under the ROC curve [AUROC] 0.866). Conclusions:Dogs with sepsis have significantly increased concentrations of HMGB-1 and inflammatory cytokines, including IL-6, CXCL8, and KC-like. Increased CCL2 concentration is a negative prognostic indicator in dogs with sepsis. These findings should be confirmed using duplicate analyses in larger, distinct populations of dogs with sepsis before applying them to clinical patients. K E Y W O R D Scanine, CCL2, HMGB-1, outcome, SIRS
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