Effect of plasma transfusion on serum amyloid A concentration in healthy neonatal foals and foals with failure of transfer of passive immunity.

BACKGROUND: Anecdotal evidence suggests plasma transfusions increase serum amyloid A (SAA) concentrations in healthy neonatal foals making this marker of inflammation inappropriate for therapeutic decision making in such animals. HYPOTHESIS/OBJECTIVES: Administration of hyperimmune fresh frozen plasma (FFP) increases SAA concentration in healthy foals and in foals with failure of transfer of passive immunity (FTPI). ANIMALS: Eighty-six healthy foals. METHODS: Prospective cohort study. Foals <24 hours of age receiving plasma transfusion for treatment of FTPI (serum immunoglobulin G [IgG] concentrations <8 g/L; n = 17) or as a preventative measure for Rhodococcus equi infection (IgG >8 g/L; n = 33) were enrolled. A healthy nontransfused group of foals (IgG >8 g/L; n = 21) also was included. Serum amyloid A concentration was determined before (t0h) and after (t24h) administration of FFP. Changes in blood SAA concentration were assessed using linear regression models. RESULTS: No statistical differences were found in SAA concentration at t0h or t24h among the 3 groups (P > .05, for all comparisons). The variation in SAA concentration before (t0h) and after (t24h) plasma transfusion showed that administration of FFP was not associated with the changes in SAA concentration (P > .05). An association between SAA concentration at t0h and at 24 hours (P < .05) was identified, where foals with higher SAA concentration at t0h also had higher SAA concentration at t24h. CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of FFP to newborn foals was not associated with changes in SAA concentration.

Field Safety Experience With an Autologous Cancer Vaccine in 41 Horses: A Retrospective Study (2019-2021).

Autologous cancer vaccines (ACV) are an emerging option for adjuvant cancer treatment in veterinary medicine. With this form of active immunotherapy, the patient's tumor cells are processed ex vivo and returned to the patient with the goal of stimulating an immune response to unique, patient-specific antigens. The case accession database at Torigen was queried to identify horses that underwent biopsy or surgical resection of their primary tumor and received at least one subcutaneous dose of an adjuvanted whole-cell autologous cancer vaccine. The records were then reviewed for any reported adverse events (AE). Forty-one horses met the inclusion criteria and received 252 doses of Torigen's ACV (ACV-T). There were seven AEs reported in four horses, which were associated with 1.6% of the administered doses of the ACV-T. Of the reported AE, all were characterized as mild. The ACV-T appears to be well tolerated by horses, and may be useful as a treatment option for owners who are concerned about AEs that can occur with other types of adjuvant cancer therapy. Additional studies are warranted to evaluate the efficacy of this ACV in horses with solid tumors.

A nonsense variant in Rap Guanine Nucleotide Exchange Factor 5 (RAPGEF5) is associated with equine familial isolated hypoparathyroidism in Thoroughbred foals.

Idiopathic hypocalcemia in Thoroughbred (TB) foals causes tetany and seizures and is invariably fatal. Based upon the similarity of this disease with human familial hypoparathyroidism and occurrence only in the TB breed, we conducted a genetic investigation on two affected TB foals. Familial hypoparathyroidism was identified, and pedigree analysis suggested an autosomal recessive (AR) mode of inheritance. We performed whole-genome sequencing of the two foals, their unaffected dams and four unaffected, unrelated TB horses. Both homozygosity mapping and an association analysis were used to prioritize potential genetic variants. Of the 2,808 variants that significantly associated with the phenotype using an AR mode of inheritance (P<0.02) and located within a region of homozygosity, 1,507 (54%) were located in a 9.7 Mb region on chr4 (44.9-54.6 Mb). Within this region, a nonsense variant (RAPGEF5 c.2624C>A,p.Ser875*) was significantly associated with the hypoparathyroid phenotype (Pallelic = 0.008). Affected foals were homozygous for the variant, with two additional affected foals subsequently confirmed in 2019. Necropsies of all affected foals failed to identify any histologically normal parathyroid glands. Because the nonsense mutation in RAPGEF5 was near the C-terminal end of the protein, the impact on protein function was unclear. Therefore, we tested the variant in our Xenopus overexpression model and demonstrated RAPGEF5 loss-of-function. This RAPGEF5 variant represents the first genetic variant for hypoparathyroidism identified in any domestic animal species.

Rapid clinical progression of B-cell chronic lymphocytic leukemia in a horse.

CASE DESCRIPTION: A 17-year-old Friesian gelding was examined at a referral hospital because of a 1-month history of mild exercise intolerance and marked lymphocytosis. CLINICAL FINDINGS: Physical examination revealed no peripheral lymphadenopathy or other abnormalities. Results of an abdominal palpation examination per rectum and thoracic and abdominal ultrasonographic examinations were unremarkable. B-cell chronic lymphocytic leukemia (CLL) was diagnosed on the basis of severe lymphocytosis and positive expression of the B-cell marker CD20 by lymphocytes in the bone marrow and peripheral blood. TREATMENT AND OUTCOME: Treatment with prednisolone (2 mg/kg [0.9 mg/lb], PO, every other day) and chlorambucil (20 mg/m2, PO, every 3 weeks for 2 doses, then every 2 weeks) was initially associated with improvement in clinical signs and a decrease in the lymphocyte count. However, 3 weeks after administration of the first dose of chlorambucil, the lymphocyte count began to increase. One week later, the horse developed episodes of recurrent fever and the lymphocyte count continued to increase. Despite continued administration of the prednisolone-chlorambucil protocol, the horse's clinical condition deteriorated rapidly, and it was euthanized 6 weeks after initial examination at the referral hospital because of a poor prognosis. A necropsy was not performed. CLINICAL RELEVANCE: B-cell CLL has been infrequently described in horses. This report was the first to describe the use of chemotherapy, albeit unsuccessful, for the treatment of B-cell CLL in a horse. This information should be useful for guiding expectations for prognosis and management of other horses affected with the disease.

Comparison of surgical and medical treatment of 49 postpartum mares with presumptive or confirmed uterine tears.

OBJECTIVE: To determine outcome after medical or surgical treatment of postpartum mares with confirmed or presumptive uterine tears. STUDY DESIGN: Case series. METHODS: Postpartum mares were included if foaling had occurred within 7 days and uterine tear was confirmed surgically or, in medically treated mares, by palpation or presumed based on peritonitis. Information (age, breed; physical examination, laboratory and abdominocentesis findings; treatment, survival rates, length of hospital stay, treatments costs, and breeding performance after discharge) was obtained from the medical records (1990-2007). The influence of variables was compared between medical and surgical treatment, and between survivors and nonsurvivors. RESULTS: For 49 mares, survival was 75%, with no significant difference between medical (11/15; 73%) or surgical (26/34; 76%) treatment. Admission variables, treatment cost, duration of hospital stay, and likelihood of foaling after discharge were not significantly different between treatment groups. Nonsurvivors were significantly more likely to have gastric reflux, higher heart rate, anion gap, lower total CO(2), and leukocyte count, compared with survivors. Tears were significantly (P=.018) more likely to occur in the right uterine horn than in other parts of the uterus. CONCLUSIONS: Uterine tears occur more commonly in the uterine horns, more so the right horn, and survival is similar with surgical or medical treatment of uterine tears in postpartum mares. CLINICAL RELEVANCE: Medical treatment may be a reasonable alternative to surgical treatment for uterine tears, although the severity of tear that can resolve with medical treatment is unknown, and medical therapy can be as expensive as surgical treatment.