Relationship between Machine-Learning Image Classification of T2-Weighted Intramedullary Hypointensity on 3 Tesla Magnetic Resonance Imaging and Clinical Outcome in Dogs with Severe Spinal Cord Injury.

Early prognostic information in cases of severe spinal cord injury can aid treatment planning and stratification for clinical trials. Analysis of intraparenchymal signal change on magnetic resonance imaging has been suggested to inform outcome prediction in traumatic spinal cord injury. We hypothesized that intraparenchymal T2-weighted hypointensity would be associated with a lower potential for functional recovery and a higher risk of progressive neurological deterioration in dogs with acute, severe, naturally occurring spinal cord injury. Our objectives were to: 1) demonstrate capacity for machine-learning criteria to identify clinically relevant regions of hypointensity and 2) compare clinical outcomes for cases with and without such regions. A total of 95 dogs with complete spinal cord injury were evaluated. An image classification system, based on Speeded-Up Robust Features (SURF), was trained to recognize individual axial T2-weighted slices that contained hypointensity. The presence of such slices in a given transverse series was correlated with a lower chance of functional recovery (odds ratio [OR], 0.08; confidence interval [CI], 0.02-0.38; p < 10-3) and with a higher risk of neurological deterioration (OR, 0.14; 95% CI, 0.05-0.42; p < 10-3). Identification of intraparenchymal T2-weighted hypointensity in severe, naturally occurring spinal cord injury may be assisted by an image classification tool and is correlated with functional recovery.

Surgical decompression, with or without adjunctive therapy, for palliative treatment of primary vertebral osteosarcoma in dogs.

Vertebral osteosarcoma (OSA) is the most common primary vertebral tumor in dogs, however studies examining the survival time after surgical decompression of these tumors are limited. There is also limited information regarding the benefit of adjunctive treatments such as radiation therapy or chemotherapy in these patients. The goal of this study was to determine survival time of dogs with primary vertebral OSA after palliative decompressive surgery alone and combined with radiation therapy and/or chemotherapy. Records from 22 client-owned dogs diagnosed with primary vertebral OSA and treated with decompressive surgery were collected retrospectively from eight referral institutions. Survival time was assessed for dogs treated with surgery alone as well as dogs who received adjunctive radiation therapy and/or chemotherapy. Median survival time in the 12 dogs treated with surgery alone was 42 days (range: 3-1333 days). The three dogs treated with surgery and chemotherapy had a median survival time of 82 days (range: 56-305 days). Only one dog was treated with surgery and radiation therapy; this dog survived 101 days. Six dogs were treated with surgery, radiation therapy and chemotherapy; these dogs had a median survival time of 261 days (range: 223-653 days). Cause of death in all cases that survived the initial postoperative period was euthanasia secondary to confirmed or suspected tumor regrowth. The results of this study suggest that definitive radiation therapy, possibly combined with concurrent chemotherapy, significantly improves survival in dogs treated with palliative decompressive surgery for vertebral OSA and should be the treatment of choice in selected cases.

Population pharmacokinetics of extended-release levetiracetam in epileptic dogs when administered alone, with phenobarbital or zonisamide.

BACKGROUND: Extended-release levetiracetam (LEV-XR) has gained acceptance as an antiepileptic drug in dogs. No studies have evaluated its disposition in dogs with epilepsy. HYPOTHESIS/OBJECTIVES: To evaluate the pharmacokinetics of LEV-XR in epileptic dogs when administered alone or with phenobarbital or zonisamide. ANIMALS: Eighteen client-owned dogs on steady-state maintenance treatment with LEV-XR (Group L, n = 6), LEV-XR and phenobarbital (Group LP, n = 6), or LEV-XR and zonisamide (Group LZ, n = 6). METHODS: Pharmacokinetic study. Blood samples were collected at 0, 2, 4, 8, and 12 hours after LEV-XR was administered with food. Plasma LEV concentrations were determined by high-pressure liquid chromatography. A population pharmacokinetic approach and nonlinear mixed effects modeling were used to analyze the data. RESULTS: Treatment group accounted for most of the interindividual variation. The LP group had lower CMAX (13.38 µg/mL) compared to the L group (33.01 µg/mL) and LZ group (34.13 µg/mL), lower AUC (134.86 versus 352.95 and 452.76 hours·µg/mL, respectively), and higher CL/F (0.17 versus 0.08 and 0.07 L/kg/hr, respectively). The half-life that defined the terminal slope of the plasma concentration versus time curve (~5 hours) was similar to values previously reported for healthy dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Considerable variation exists in the pharmacokinetics of LEV-XR in dogs with epilepsy being treated with a common dose regimen. Concurrent administration of phenobarbital contributed significantly to the variation. Other factors evaluated, including co-administration of zonisamide, were not shown to contribute to the variability. Drug monitoring may be beneficial to determine the most appropriate dose of LEV-XR in individual dogs.

Detraining differentially preserved beneficial effects of exercise on hypertension: effects on blood pressure, cardiac function, brain inflammatory cytokines and oxidative stress.

AIMS: This study sought to investigate the effects of physical detraining on blood pressure (BP) and cardiac morphology and function in hypertension, and on pro- and anti-inflammatory cytokines (PICs and AIC) and oxidative stress within the brain of hypertensive rats. METHODS AND RESULTS: Hypertension was induced in male Sprague-Dawley rats by delivering AngiotensinII for 42 days using implanted osmotic minipumps. Rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise (ExT) for 42 days, whereas, detrained groups underwent 28 days of exercise followed by 14 days of detraining. BP and cardiac function were evaluated by radio-telemetry and echocardiography, respectively. At the end, the paraventricular nucleus (PVN) was analyzed by Real-time RT-PCR and Western blot. ExT in AngII-infused rats caused delayed progression of hypertension, reduced cardiac hypertrophy, and improved diastolic function. These results were associated with significantly reduced PICs, increased AIC (interleukin (IL)-10), and attenuated oxidative stress in the PVN. Detraining did not abolish the exercise-induced attenuation in MAP in hypertensive rats; however, detraining failed to completely preserve exercise-mediated improvement in cardiac hypertrophy and function. Additionally, detraining did not reverse exercise-induced improvement in PICs in the PVN of hypertensive rats; however, the improvements in IL-10 were abolished. CONCLUSION: These results indicate that although 2 weeks of detraining is not long enough to completely abolish the beneficial effects of regular exercise, continuing cessation of exercise may lead to detrimental effects.