Untargeted metabolomic profiles reveal widespread metabolic perturbations and identify candidate biomarkers in aminoaciduric canine hypoaminoacidemic hepatopathy syndrome.

OBJECTIVE: To identify metabolites and metabolic pathways affected in dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) compared to healthy control (CON) dogs of similar ages and breeds. To improve our understanding of ACHES pathophysiology and identify novel candidate biomarkers associated with ACHES. ANIMALS: A prospective case-control study. Privately owned dogs with ACHES (n = 19) and healthy (CON) dogs (n = 9) were recruited between February 18, 2015, and April 18, 2018. METHODS: A prospective case-control study. Plasma and urine were collected from ACHES and CON dogs. The Cornell University Proteomics and Metabolomics Core Facility conducted an untargeted metabolomic analysis. RESULTS: After controlling for age, sex, and weight, 111 plasma and 207 urine metabolites significantly differed between ACHES and CON dogs. Data reduction and cluster analysis revealed robust segregation between ACHES and CON dogs. Enrichment analysis of significant compounds in plasma or urine identified altered metabolic pathways, including those related to AA metabolism, cellular energetics, and lipid metabolism. Biomarker analysis identified metabolites that best-distinguished ACHES from CON dogs, including pyruvic acid isomer and glycerol-3-phosphate in the plasma and an alanine isomer and choline in the urine. CLINICAL RELEVANCE: Our findings provide an in-depth analysis of metabolic perturbations associated with ACHES. Several affected metabolic pathways (eg, lipid metabolism) offer a new understanding of ACHES pathophysiology. Novel candidate biomarkers warrant further evaluation to determine their potential to aid in ACHES diagnosis, prognosis, and treatment monitoring.

Retrospective Evaluation of the Use and Complications of Small-Bore Wire-Guided Thoracostomy Tubes in Dogs and Cats: 156 Cases (2007-2019).

Background: Small-bore wire-guided thoracostomy tubes (SBWGTT) are commonly used in small animals for management of pleural space disease. We aimed to evaluate the indications, placement locations, types of complications, and complication rate of small-bore wire-guided thoracostomy tube placements in dogs and cats in a university setting. Methods: Electronic medical records of patients that underwent SBWGTT placement were reviewed. Signalment, disease, outcome, indication for thoracostomy tube, placement location, number of attempts, diagnostic imaging, number, and type (insertional, technical, and infectious) of complications were recorded. Logistic regression analysis was performed to determine risk factors for complications. Results: A hundred fifty-six cases were identified between 2007 and 2019. Traumatic pneumothorax (33%), pyothorax (25%), and spontaneous pneumothorax (16%) were the most common indications for placement of a SBWGTT. Complications developed in 50 cases (32%). Technical and insertional complications accounted for 21.7% and 14.1% of all cases. Infectious complications were rare with 3.1% of all cases. Pneumothorax (19%), soft tissue swelling at insertion site (14%), and kinking of the chest tube (13%) were most common. Accidental lung perforation was reported in 5/50 complications (7%). Multiple chest tube placement attempts were associated with complications (OR = 6.01 CI: 2.13 to 16.93 p = 0.0007). Conclusions: Complications of SBWGTT placement occurred in one third of cases. Serious complications such as accidental lung perforation was reported in two cases. Complications were associated with number of attempts.

Hypophosphatemia in Dogs With Presumptive Sepsis: A Retrospective Study (2008-2018).

Background: In humans with sepsis, hypophosphatemia is a marker of illness severity and a negative prognostic indicator. Hypophosphatemia has not been previously investigated in dogs with sepsis, however. This study aimed to estimate the prevalence of hypophosphatemia in dogs, the prevalence of presumptive sepsis in dogs with hypophosphatemia, the prevalence of hypophosphatemia in dogs with presumptive sepsis and the association between outcome and hypophosphatemia in dogs with presumptive sepsis. Methods: Electronic medical records of the Cornell University Hospital for Animals from 2008-2018 were queried to identify all dogs with hypophosphatemia and all dogs with presumptive sepsis. Hypophosphatemia was defined as a serum phosphate concentration <2.7 mg/dL. Sepsis was presumed where ≥2 of 4 systemic inflammatory response syndrome (SIRS) criteria were satisfied associated with a documented or highly suspected infection. Variables were assessed for normality using the D'Agostino-Pearson test. Continuous variables were compared between groups using the Mann-Whitney U test. Differences in frequency between categorical variables were analyzed using contingency tables, calculation of Fisher's exact test or Chi2 and estimation of odds ratios. Results: In the study period, 47,992 phosphate concentration measurements from 23,752 unique dogs were identified. After eliminating repeat analyses, the period prevalence of hypophosphatemia on a per dog basis over the 11-year study period was 10.6% (2,515/23,752). The prevalence of presumptive sepsis within dogs with hypophosphatemia was 10.7% (268/2,515). During the 11-year study period, 4,406 dogs with an infection were identified, of which 1,233 were diagnosed with presumptive sepsis and had a contemporaneous phosphate concentration. Hypophosphatemia was more prevalent in dogs with presumptive sepsis than in dogs without 21.7 vs. 10.2%; OR 2.44 [95% CI 2.12-2.81]; P < 0.0001. The mortality rate was greater in dogs with hypophosphatemia and presumptive sepsis than in dogs with hypophosphatemia without presumptive sepsis (15.3 vs. 3.1%; OR 5.70 [95% CI 3.76-8.52]; P < 0.0001), however hypophosphatemia was not associated with outcome in dogs with presumptive sepsis OR 0.87 [95% CI 0.60-1.26]; P = 0.518. Conclusions: In dogs with hypophosphatemia, a presumed diagnosis of sepsis was associated with increased mortality compared to other associated disease processes. In dogs with presumptive sepsis, hypophosphatemia was not associated with outcome.

The secretome from bovine mammosphere-derived cells (MDC) promotes angiogenesis, epithelial cell migration, and contains factors associated with defense and immunity.

Treatment of bovine mastitis with intramammary antibiotics is common, yet several concerns exist including failed efficacy for individual hosts or pathogens and the inability of approved drugs to revert mastitis-induced tissue damage to healthy tissue capable of returning to full milk production. These issues, in addition to aspects of public health such as accidental antibiotic residues in saleable milk and the potential for antimicrobial resistance, support the need to find alternative therapies for this costly disease. This study shows that the secretome, or collective factors, produced by mammosphere-derived cells (MDC) promotes angiogenesis, epithelial cell migration, and contains proteins associated with immunity and defense; all of which are necessary for healing damaged mammary gland tissue. Furthermore, we found that the MDC secretome remains effective after freezing and thawing, enhancing its therapeutic potential. Our results provide a foundation for further characterization of the individual secreted factors and the rationale for using the MDC secretome as a complementary treatment for bovine mastitis.