A 50-step walking test for analysis of recovery after decompressive surgery for thoracolumbar disc herniation in dogs.

BACKGROUND: Despite its importance, there is no agreed definition of recovery of ambulation in dogs with spinal cord injury. OBJECTIVES: To validate a new walking test in dogs recovering from thoracolumbar spinal cord injury. ANIMALS: Two hundred twenty-four dogs weighing <20 kg: 120 normally ambulatory dogs, plus 104 dogs undergoing decompressive surgery for acute thoracolumbar intervertebral disc herniation. METHODS: Prospective cohort studies. The distance each freely-ambulatory dog walked during 50 step cycles was regressed on ulna length. For each postsurgical dog, we recorded when the calculated 50-step distance was completed without falling, or their inability to complete this distance by 4 months or more after surgery. Bayesian analysis compared outcomes for presurgical neurologic categories; association of recovery with several preoperative variables was explored using logistic and time-to-event regression. RESULTS: For control dogs, 50-step distance (m) = 1.384 × ulnar length (cm) + 2.773. In postsurgical dogs, the 50-step test provided decisive evidence that deep pain-negative dogs were less likely to recover ambulation than dogs with intact pain perception (12/29 recovered vs 71/75; Bayes factor [BF] = 5.9 × 106 ) and, if they did recover, it took much longer (median 91 days vs median 14 days; BF = 1.5 × 103 ). Exploratory analysis suggested that presurgical neurologic status (subhazard ratio [SHR] = 0.022; P < .001) and duration of presurgical anesthesia (SHR = 0.740; P = .04) were associated with rapidity of recovery. CONCLUSIONS AND CLINICAL IMPORTANCE: This straightforward 50-step walking test provides robust data on ambulatory recovery well-suited to large scale pragmatic trials on treatment of thoracolumbar spinal cord injury in dogs.

Intratumoral collagen signatures predict clinical outcomes in feline mammary carcinoma.

Breast cancer is the most common cause of cancer-related deaths in women worldwide. Identification of reliable prognostic indicators and therapeutic targets is critical for improving patient outcome. Cancer in companion animals often strongly resembles human cancers and a comparative approach to identify prognostic markers can improve clinical care across species. Feline mammary tumors (FMT) serve as models for extremely aggressive triple negative breast cancer (TNBC) in humans, with high rates of local and distant recurrence after resection. Despite the aggressive clinical behavior of most FMT, current prognostic indicators are insufficient for accurately predicting outcome, similar to human patients. Given significant heterogeneity of mammary tumors, there has been a recent focus on identification of universal tumor-permissive stromal features that can predict biologic behavior and provide therapeutic targets to improve outcome. As in human and canine patients, collagen signatures appear to play a key role in directing mammary tumor behavior in feline patients. We find that patients bearing FMTs with denser collagen, as well as longer, thicker and straighter fibers and less identifiable tumor-stromal boundaries had poorer outcomes, independent of the clinical variables grade and surgical margins. Most importantly, including the collagen parameters increased the predictive power of the clinical model. Thus, our data suggest that similarities with respect to the stromal microenvironment between species may allow this model to predict outcome and develop novel therapeutic targets within the tumor stroma that would benefit both veterinary and human patients with aggressive mammary tumors.

Case Report: Mineralized Pulmonary Artery Thrombi in Two Dogs Treated for Meningoencephalitis of Unknown Origin.

Meningoencephalitis of unknown origin (MUO) is a relatively common and very serious canine neurologic condition, which is typically associated with a poor long term prognosis despite treatment. This case series chronicles two dogs diagnosed with MUO who were treated with long term corticosteroids and cytosine arabinoside and lived well-beyond the typical survival time for this condition. Both eventually succumbed to respiratory signs associated with mineralized thrombi in their pulmonary arteries. Adverse effects from the two drugs used for treatment are reviewed in order to propose a possible mechanism to explain how long term use of these medications could result in such a phenomenon.

Identification of prognostic collagen signatures and potential therapeutic stromal targets in canine mammary gland carcinoma.

Increasing evidence indicates that the tumor microenvironment plays a critical role in regulating the biologic behavior of breast cancer. In veterinary oncology, there is a need for improved prognostic markers to accurately identify dogs at risk for local and distant (metastatic) recurrence of mammary gland carcinoma and therefore would benefit from adjuvant therapy. Collagen density and fiber organization have been shown to regulate tumor progression in both mouse and human mammary tumors, with certain collagen signatures predicting poor outcomes in women with breast cancer. We hypothesized that collagen signatures in canine mammary tumor biopsies can serve as prognostic biomarkers and potential targets for treatment. We used second harmonic generation imaging to evaluate fibrillar collagen density, the presence of a tumor-stromal boundary, tumor associated collagen signatures (TACS) and individual collagen fiber characteristics (width, length and straightness) in grade I/II and grade III canine mammary tumors. Collagen density, as well as fiber width, length and straightness, were inversely correlated with patient overall survival time. Notably, grade III cases were less likely to have a tumor-stromal boundary and the lack of a boundary predicted poor outcome. Importantly, a lack of a defined tumor-stromal boundary and an increased collagen fiber width were associated with decreased survival even when tumor grade, patient stage, ovariohysterectomy status at the time of mammary tumor excision, and histologic evidence of lymphovascular invasion were considered in a multivariable model, indicating that these parameters could augment current methods to identify patients at high risk for local or metastatic progression/recurrence. Furthermore, these data, which identify for the first time, prognostic collagen biomarkers in naturally occurring mammary gland neoplasia in the dog, support the use of the dog as a translational model for tumor-stromal interactions in breast cancer.