Biomarker Guided Diagnosis of Septic Peritonitis in Dogs

Martiny, Pia; Goggs, Robert

doi:10.3389/fvets.2019.00208

Cited by 36 publications

(49 citation statements)

References 98 publications

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“…This is significantly lower than the concentration seen in the dogs with lymphoma reported in this study with median of 590 ng/mL. Comparisons between the concentrations of nucleosomes reported here and those in other reports of inflammation and control groups are difficult due to the fact that nucleosome concentrations have previously been reported only in arbitrary units(7)(8)(9)(20)(21)(22).…”

contrasting

confidence: 81%

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

Wilson-Robles

Miller

Jarvis

et al. 2020

Preprint

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AbstractIntroductionNucleosomes consist of small fragments of DNA wrapped around a histone octamer core. Diseases such as cancer or inflammation lead to cell death, which causes fragmentation and release of nucleosomes into the blood. The Nu.Q™ technology measures circulating nucleosome levels and exploits the different compositions of cancer derived nucleosomes in blood to detect and identify cancer even at early stages. The objectives of this study are to identify the optimal sample type for the Nu.Q™ H3.1 assay and to determine if it can accurately detect nucleosomes in the blood of healthy canines as well as those with cancer.Materials and MethodsBlood samples from healthy canine volunteers as well as dogs newly diagnosed with lymphoma were used. The blood was processed at a variety of times under a variety of conditions to determine the most reliable sample type and conditions, and to develop an appropriate processing strategy to ensure reliably accurate results.ResultsNucleosomes could be detected using a variety of sample collection and processing protocols. Nucleosome signals were highest in EDTA plasma and serum samples and most consistent in plasma. Samples should be processed within an hour of collection. Experiments showed that samples were able to withstand several freeze thaw cycles. Processing time and tcollection tube type did affect nucleosome detection levels. Finally, significantly elevated concentrations of nucleosomes were seen in a small cohort of dogs that had been newly diagnosed with lymphoma.ConclusionsWhen samples are collected and processed appropriately, the Nu.Q™ platform can reliably detect nucleosomes in the plasma of dogs. Further testing is underway to validate and optimize the Nu.Q™ platform for veterinary use.

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contrasting

confidence: 81%

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

Wilson-Robles

Miller

Jarvis

et al. 2020

Preprint

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“…This makes it a potentially useful biomarker of systemic inflammation (8,18,26). Recently, IL-6 has been highlighted as a novel diagnostic biomarker for neonatal and adult sepsis in people with a moderate diagnostic accuracy similar to procalcitonin (27)(28)(29)(30) and in dogs with septic peritonitis (12). Additionally, increased IL-6 concentrations correlate with the risk of death in sepsis in humans and dogs (8,31,32).…”

Section: Discussionmentioning

confidence: 99%

“…These latter two cytokines may be linked because Flt-3L can increase the number of dendritic cells in septic shock thereby increasing IL-12 concentrations (47). It is not clear why these cytokines differentiate sepsis severity in cats, and further investigation appears warranted, but MCP-1 has been documented to be increased (12), and to have prognostic value in dogs with sepsis (13).…”

Section: Discussionmentioning

confidence: 99%

“…Immunophenotyping data characterizing sepsis are scarce in veterinary medicine and are predominantly available for dogs (10)(11)(12)(13). Recognizing and characterizing sepsis in cats is more Abbreviations: A/G, albumin to globulin ratio; ALP, alkaline phosphatase; ALT, alanine transaminase; APPLE, acute patient physiologic and laboratory evaluation; AST, aspartate transaminase; BE, base excess; CCL-2, C-C motif chemokine ligand-2; Flt-3L, FMS-like tyrosine kinase-3 ligand; GGT, È-glutamyltransferase; GM-CSF, granulocyte macrophage-colony stimulating factor; Hb, hemoglobin concentration; HCT, hematocrit value; ICU, intensive care unit; IFN-γ, interferonγ; IL, interleukin; KC-like, keratinocyte chemoattractant-like; LLD, lower limit of detection; MCHC, mean cell hemoglobin concentration; MCP-1, monocyte chemoattractant protein-1; MCV, mean corpuscular volume; MFI, median fluorescence intensity; PDGF-BB, platelet-derived growth factor-BB; RANTES, Regulated upon Activation, Normal T-cell Expressed and Secreted; RDW, red cell distribution width; RI, reference interval; SAA, serum-amyloid A; SBP, systolic blood pressure; SCF stem cell factor; SDF-1, stromal cell-derived factor 1; SIRS, systemic inflammatory response syndrome; TNF-α, tumor-necrosis factor-α; WBC, white blood cell.…”

Section: Introductionmentioning

confidence: 99%

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Cytokine and Chemokine Profiling in Cats With Sepsis and Septic Shock

et al. 2020

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Background: Sepsis is a life-threatening condition associated with an exacerbated production of both pro-and anti-inflammatory cytokines that can promote a hyperactive response to infection or induce immunoparalysis. Data regarding the immune response to sepsis in cats are scarce. Establishing the profiles of cytokines and chemokines in feline sepsis to characterize the nature of the immune responses to sepsis might enable individualized treatments to be developed and targeted. Objective: To evaluate the cytokine and chemokine network in cats with sepsis and septic shock, and to investigate the associations of these analytes with disease severity and outcome. Methods: Blood samples prospectively collected at presentation of cats with sepsis and septic shock to two veterinary teaching hospitals were analyzed. Forty healthy cats were included as controls. A 19-plex feline cytokine/chemokine magnetic bead assay system was used to measure analytes in citrated plasma samples. Cytokine concentrations were compared between groups using the Kruskal-Wallis test with Dunn's post-hoc correction for multiple comparisons. Cytokine concentrations were compared between survivors and non-survivors with the Mann-Whitney U test. Odds ratios were calculated using logistic regression. A multivariable logistic regression model for prediction of septic shock was constructed. Results: The study enrolled 35 septic cats. Many cytokines were undetectable in both sick and healthy control cats and were excluded from subsequent analyses. Comparisons of cytokine concentrations among healthy controls, cats with sepsis (n = 12) and cats with septic shock (n = 23) revealed that sick cats (sepsis or septic shock) had significantly higher plasma concentrations of IL-6, IL-8, KC-like, and RANTES compared to healthy controls. The combination of MCP-1, Flt-3L, and IL-12 was predictive of septic shock. None of the cytokines analyzed was predictive of outcome in this study population. Conclusion: Plasma concentrations of IL-6, IL-8, KC-like, and RANTES are increased in cats with sepsis and may play important roles in pathogenesis. Multivariable modeling suggested that analysis of cytokines might aid differentiation of septic shock from sepsis. None of the cytokines analyzed was predictive of outcome. Measurement of these cytokines might enable future studies to better diagnose and characterize feline sepsis and septic shock.

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“…median of 590 ng/mL. Comparisons between the concentrations of nucleosomes reported here and those in other reports of inflammation and control groups are difficult due to the fact that nucleosome concentrations have previously been reported only in arbitrary units [7][8][9][20][21][22]. When evaluating nucleosome concentrations in plasma and serum at a variety of processing times plasma is more stable than serum.…”

Section: Plos Onementioning

confidence: 65%

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

et al. 2020

View full text Add to dashboard Cite

Introduction Nucleosomes consist of small fragments of DNA wrapped around a histone octamer core. Diseases such as cancer or inflammation lead to cell death, which causes fragmentation and release of nucleosomes into the blood. The Nu.Q™ technology measures circulating nucleosome levels and exploits the different compositions of cancer derived nucleosomes in blood to detect and identify cancer even at early stages. The objectives of this study are to identify the optimal sample type for the Nu.Q™ H3.1 assay and to determine if it can accurately detect nucleosomes in the blood of healthy canines as well as those with cancer. Materials and methods Blood samples from healthy canine volunteers as well as dogs newly diagnosed with lymphoma were used. The blood was processed at a variety of times under a variety of conditions to determine the most reliable sample type and conditions, and to develop an appropriate processing strategy to ensure reliably accurate results. Results Nucleosomes could be detected using a variety of sample collection and processing protocols. Nucleosome signals were highest in EDTA plasma and serum samples and most consistent in plasma. Samples should be processed within an hour of collection. Experiments showed that samples were able to withstand several freeze thaw cycles. Processing time and tcollection tube type did affect nucleosome detection levels. Finally, significantly elevated concentrations of nucleosomes were seen in a small cohort of dogs that had been newly diagnosed with lymphoma. Conclusions When samples are collected and processed appropriately, the Nu.Q™ platform can reliably detect nucleosomes in the plasma of dogs. Further testing is underway to validate and optimize the Nu.Q™ platform for veterinary use.

show abstract

Biomarker Guided Diagnosis of Septic Peritonitis in Dogs

Cited by 36 publications

References 98 publications

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

Cytokine and Chemokine Profiling in Cats With Sepsis and Septic Shock

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

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