Serum amyloid A does not predict non-survival in hospitalised adult horses with acute colitis.

BACKGROUND: Predicting non-survival in horses with acute colitis improves early decision making. Therefore, this study aimed to determine the prognostic value of serum amyloid A (SAA) and other clinicopathological and clinical variables in adult horses with acute colitis. METHODS: Clinical variables, SAA and other blood biomarkers, including plasma L-lactate (lactate), were assessed in 176 horses with acute colitis. A multivariate model for the prediction of non-survival was constructed. Icelandic horses were analysed separately. RESULTS: Admission SAA was similar in survivors (median 548 mg/L; range 0-5453 mg/L) and non-survivors (396 mg/L; 0-5294) (p = 0.43). A model for non-survival included year of admission, lactate, heart rate, age and colic duration of more than 24 hours. Icelandic horses had a relative risk of 2.9 (95% confidence interval = 2.2-3.8) for acute colitis compared to other breeds. Lactate in Icelandic horses was higher than that in other breeds in both survivors (4.0 mmol/L, range 1.0-12.7 vs. 2.0, 0.7-12.5) and non-survivors (10.0, 1.5-26 vs. 5.4, 0.8-22) (p < 0.001). LIMITATIONS: The prognostic value of repeated measurements of SAA could not be assessed in this study, as 71% of the non-surviving horses died within a day of admission. CONCLUSION: Admission SAA did not predict non-survival. Breed needs consideration when lactate is evaluated as a predictor for non-survival in horses with colitis.

Short-term survival rates of 1397 horses referred for colic from 2010 to 2018.

BACKGROUND: Up-to-date and hospital-specific knowledge of prognoses for horses with various forms of colic is essential for helping to guide owners' decisions on costly treatments, and for assessing the continuous development of standards of care in the hospital. This study aimed to determine the short-term survival rates of horses admitted with colic to the University Hospital for Large Animals (UHLA), University of Copenhagen, Denmark, from 2010 to 2018, and to compare these to a previous local study as well as recent, comparable international studies. Short-term survival rates were calculated for horses grouped by treatment (surgical, medical) and diseases. Results were compared to the selected studies using Chi-square tests. RESULTS: A total of 1752 horses were admitted with colic during the period, of which 355 were excluded for reasons such as economic restrictions or immediate euthanasia. Short-term survival of the remaining 1397 cases was significantly higher (83.0% (95% CI 81.1-85.0%)) than a previous local study (76%) and a recent Dutch study (80%). Medical treatment was carried out in 77.1% of cases, and surgery in 22.9% of the cases. Short-term survival for medically (89.7%) and surgically (60.6%) treated horses was significantly higher in the present study compared to the previous study (87% and 42%, respectively), but was similar to that found in the Dutch study. Significantly fewer horses were euthanised during surgery than in the previous study (17.2 vs. 40%), and significantly more horses recovered from surgery (79.1 vs. 56%). Short-term survival rate of surgically treated horses (60.6%) did not differ from other European studies (55-62%). CONCLUSIONS: Short-term survival rates have increased since the previous study at UHLA, mainly due to a decrease in intraoperative euthanasia. Survival rates in this study are similar to those found in recent comparable colic studies.

A genetic investigation of equine recurrent uveitis in the Icelandic horse breed.

Equine recurrent uveitis (ERU) is an autoimmune disease defined by inflammation of the uveal tract of the eye. The cause of ERU is thought to be complex, involving both genetic and environmental factors. The purpose of this study was to investigate potential genetic risk factors for ERU in the Icelandic horse. Fifty-six Icelandic horses (11 affected with ERU and 45 controls) living in Denmark and the USA, eight years or older, were included in the study. A case-control GWAS was performed using the GGP Equine 80K array on the Illumina Infinium HD Beadchip using 40 horses. A mixed linear model analysis identified a single SNP on ECA 11 (BIEC2_141650; NC_009154.3:g.3817009A>G) that reached genome-wide significance (p = 1.79 × 10-7 ). This variant was within an intron of tissue inhibitor of metalloproteinase 2 (TIMP2), a gene previously implicated in ERU. Sanger sequencing identified a single coding variant in this gene; however it was a synonymous mutation (NC_009154.3:g.3858193C>T) and was not perfectly concordant with ERU phenotype (p = 0.68). Further investigation of TIMP2 is warranted. Additional horses and markers are needed to identify other potential loci worthy of further investigation as contributors to ERU risk in Icelandic horses.

A pilot study evaluating the Calibrated Automated Thrombogram assay and application of plasma-thromboelastography for detection of hemostatic aberrations in horses with gastrointestinal disease.

BACKGROUND: Critically ill horses, such as horses with gastrointestinal (GI) disease, often suffer from hemostatic aberrations. Global hemostatic tests examining the initiation of coagulation, clot strength and fibrinolysis, such as the Calibrated Automated Thrombogram (CAT) and plasma-thromboelastography (TEG) have not been evaluated in horses. This study aimed to evaluate CAT and apply plasma-TEG in horses. Test performance of CAT was evaluated on equine platelet poor plasma with intra- and inter-assay variability (CV) and a heparin dilution curve. To examine clinical performance of both tests, group comparisons were assessed comparing healthy horses, horses with mild and severe GI disease with both CAT and plasma-TEG. RESULTS: For CAT, intra- and inter-assay CVs were established for lag-time (1.7, 4.7%), endogenous thrombin potential (1.6, 4.6%), peak (2.6, 3.9%) and time to peak (ttPeak) (1.9, 3.4%). Increasing heparin concentrations led to the expected decrease in thrombin generation. In the group comparison analysis, CAT showed significant higher peak (p = 0.04) and ttPeak (p = 0.008) in the severe GI disease group compared to horses with mild GI disease and healthy horses, respectively. Plasma-TEG showed an increased angle (p = 0.032), maximum amplitude (p = 0.017) and shear elastic force (G) (p = 0.017) in the severe GI disease group compared to healthy horses. CONCLUSIONS: CAT performed well in horses. Both CAT and plasma-TEG identified hemostatic aberrations in horses with severe GI disease compared to healthy horses. Further studies including more horses, are needed to fully appreciate the use of CAT and plasma-TEG in this species.

Serum amyloid A and haptoglobin concentrations in serum and peritoneal fluid of healthy horses and horses with acute abdominal pain.

BACKGROUND: Peritoneal fluid (PF) analysis is a valuable diagnostic tool in equine medicine. Markers such as serum amyloid A (SAA) and haptoglobin (Hp) could facilitate the diagnosis of inflammatory abdominal conditions. OBJECTIVES: The objectives were to (1) establish reference intervals (RI) for SAA and Hp in serum and PF in healthy horses, (2) compare SAA and Hp concentrations between healthy horses and horses with colic, and (3) to assess the correlation between serum and PF concentrations. METHODS: Serum amyloid A and Hp concentrations were determined by automated assays in prospectively enrolled healthy reference horses and horses with colic. RIs were calculated, group concentrations were compared by Student's t-test, and Pearson's correlation for serum and PF concentrations were determined. RESULTS: In healthy horses (n = 62) the measurements for SAA were below the detection limit (0.5 mg/L) in 94% of serum samples and 98% of PF samples. Horses with colic (n = 61) had statistically significantly increased SAA concentrations in serum (P < .0001) and PF (P = .0013). While PF Hp concentrations were increased in horses with colic the serum concentrations of Hp were decreased (P < .0001). There was a strong correlation between paired serum and PF SAA concentrations (n = 94, R = .72, P < .0001), whereas the correlation between paired serum and PF Hp was weak (n = 94, R = .22, P = .0382). Finally, horses with colic tended to have serum SAA and PF Hp concentrations above the RIs. CONCLUSIONS: With the apparent difference between healthy horses and horses with colic and the presently established RIs, serum SAA and PF Hp concentrations represent potential valuable diagnostic markers for inflammatory abdominal conditions in that species.

Safety pharmacology, toxicology and pharmacokinetic assessment of human Gc globulin (vitamin D binding protein).

Gc globulin is an important protein of the plasma actin-scavenger system. As such, it has been shown to bind free actin and prevent hypercoagulation and shock in patients with massive actin release resulting from severe tissue injuries. Treatment of such patients with Gc globulin could therefore potentially be life-saving. This article presents pre-clinical toxicology experiments conducted on purified plasma-derived human Gc globulin. The Gc globulin formulation was shown to be stable for at least 4 years with full retention of actin-binding capacity. In vitro studies did not reveal activation of the kallikrein system or the complement system and cellular studies showed no toxic effects on a variety of human cell lines. In vivo studies showed no acute toxic effects in mice, rats or guinea pigs upon intravenous infusion. A 14-day local tolerance study in rabbits showed no adverse effects, and 14-day toxicity studies in rats and horses did not show any unwanted reactions. In a 14-day toxicology study in beagle dogs, formation of antibodies was seen and in the end of the study period, three out of four dogs showed clinical immunological reactions, which could be ascribed to the formation of antibodies. The half-life, T, for human Gc globulin was 12 hr in rats, 16 hr in horses and 30 hr in dogs. The safety profile of plasma-derived Gc globulin is concluded to be consistent to that required for use in man.