Opportunities for targeted therapies: trametinib as a therapeutic approach to canine oral squamous cell carcinomas.

Oral tumors are relatively common in dogs, and canine oral squamous cell carcinoma (COSCC) is the most prevalent oral malignancy of epithelial origin. COSCC is locally aggressive with up to 20% of patients showing regional or distant metastasis at the time of diagnosis. The treatment of choice most typically involves wide surgical excision. Although long-term remission is possible, treatments are associated with significant morbidity and can negatively impact functionality and quality of life. OSCCs have significant upregulation of the RAS-RAF-MEK-MAPK signaling axis, and we had previously hypothesized that small-molecule inhibitors that target RAS signaling might effectively inhibit tumor growth and progression. Here, we demonstrate that the MEK inhibitor trametinib, an FDA-approved drug for human cancers, significantly blocks the growth of several COSCC cell lines established from current patient tumor samples. We further show clinical evidence that the drug is able to cause significant tumor regression in some patients with spontaneously occurring COSCC. Given the limited treatment options available and the high rate of owner rejection of these offered options, these findings provide new hope that more acceptable treatment options may soon enter the veterinary clinic.

Clinical findings and outcome predictors for multinodular pulmonary fibrosis in horses: 46 cases (2009-2019).

BACKGROUND: Prognostic indicators for equine multinodular pulmonary fibrosis (EMPF), an interstitial fibrosing lung disease, are poorly described. HYPOTHESIS/OBJECTIVES: Describe diagnostic findings and outcome predictors for EMPF. ANIMALS: Forty-six adult horses with EMPF. METHODS: Retrospective multicenter case series from 2009 to 2019. Radiographic (n = 27) and ultrasonographic studies (n = 19) from EMPF horses and bronchoalveolar lavage fluid (BALF) cytology from 6 EMPF and 13 asthma cases were independently reviewed and blinded to diagnosis and outcome. Associations between predictor variables and survival were assessed by predictor screening followed by Fisher's exact and Wilcoxon rank sum tests. RESULTS: Primary clinical findings were weight loss (36/46, 78%), increased respiratory effort (33/46, 72%), tachypnea (32/46, 70%), and fever (18/46, 39%). Macrophage atypia was seen in more EMPF than asthmatic horse BALF (67% vs. 8%; P = .02). Equine herpesvirus 5 (EHV-5) was detected in 24 of 30 (80%) and hyperfibrinogenemia in 25 of 28 (89%) cases. Twenty-seven of 46 horses (59%) and 11 of 45 (24%) survived to discharge and to 3 months, respectively. Three-month survival was associated with lower median (range) respiratory rates (30 [24-36] vs. 41 [30-60] breaths per minute; P = .04), and higher BALF lymphocyte:neutrophil ratios (4.7 [1.4-22] vs. 0.47 [0.11-1.9]; P = .01) and blood lymphocyte counts (1.25 [0.93-2.55] vs. 0.90 [0.70-1.24] × 109/L; P = .03). Imaging findings, EHV-5 detection, and corticosteroid treatment were not associated with survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Fever is not a sensitive clinical sign of EMPF. Diagnostic testing should be pursued for horses with increased respiratory rate and effort and weight loss. The prognosis for EMPF horses is poor. Corticosteroid treatment does not improve 3-month survival.

Ultrasound is an accurate method compared to radiography for diagnosing the presence of acute hip luxation in cadaver dogs and can identify the direction of luxation with variable reliability.

Acute hip luxation is a common musculoskeletal injury in dogs, with radiographs being the preferred imaging modality for confirming the diagnosis. In large animal and human medicine, ultrasound is often utilized for this purpose. The objectives of this three-part study were to utilize a canine cadaver model to establish ultrasonographic features of hip luxation and evaluate the accuracy and reliability for diagnosing hip luxation with ultrasound. For the first prospective, exploratory study, a cadaver model was developed that allowed manual luxation and subsequent ultrasonography of the hip joint while in four directions of luxation. For the second prospective, anatomic study, a description of the ultrasonographic features for each direction of luxation was created. For the third prospective diagnostic accuracy, observer agreement study, 16 residency-trained and intern veterinarians without prior experience in this technique performed randomized, repeated ultrasound exams on cadaver hips assigned as normal or luxated (equally distributed between the 4 directions). A total of 1140 hip ultrasounds were performed with good accuracy (median, 90.8%; range, 61.4-100%), sensitivity (89.5%), and specificity (80.0%) for diagnosing the presence of hip luxation. Accuracy for identifying the correct quadrant of luxation was significantly lower (mean, 58.6%; range, 24.6-90.8%; P < 0.001). Intraobserver accuracy agreement varied widely from none to almost perfect agreement, and interobserver agreement ranged from slight to moderate agreement. The results of this study supported the use of ultrasound for diagnosing the presence of hip luxation but did not support replacing radiographs for diagnosing the direction of luxation.

Association of hydromyelia and acute compressive myelopathy caused by intervertebral disc extrusion in dogs.

BACKGROUND: Hydromyelia is a common magnetic resonance imaging (MRI) finding associated with compressive myelopathy caused by intervertebral disc extrusion (IVDE). OBJECTIVES: To describe the MRI features of hydromyelia and explore its relationship to clinical history, neurological severity, and the duration of cord compression. ANIMALS: Ninety-one client-owned dogs with a focal compressive myelopathy secondary to thoracolumbar IVDE. METHODS: A retrospective observational study was conducted in which MRIs were blindly evaluated to grade and localize hydromyelia and measure the degree of spinal cord compression. Duration and severity of clinical signs were recorded. Differences between hydromyelia grades in these variables were statistically assessed using a Wilcoxon and Kruskal Wallis test. Receiver operator curve analysis was used to determine the sensitivity and specificity for duration of clinical signs to predict the presence of hydromyelia. RESULTS: Hydromyelia was identified at sites of IVDE in 84 of 91 dogs. An absence of hydromyelia was associated a with statistically longer duration of clinical signs (mean 73.1, IQR 76 days) when compared to cases with mild (mean 17.7, IQR 7.25 days, P = .006) or severe (mean 17.9, IQR 10.25 days, P = .006) hydromyelia. Duration of clinical signs <14 days was 78.6% sensitive and 85.7% specific for predicting the presence of hydromyelia. CONCLUSIONS AND CLINICAL IMPORTANCE: The MRI finding of hydromyelia might be a predictor of lesion chronicity in focal IVDE, helping to guide planning of hemilaminectomy surgery.