A comparison of risk factors for metastasis at diagnosis in humans and dogs with osteosarcoma.

BACKGROUND: Canine osteosarcoma (OS) is a relevant spontaneous model for human OS. Identifying similarities in clinical characteristics associated with metastasis at diagnosis in both species may substantiate research aimed at using canine OS as a model for identifying mechanisms driving distant spread in the human disease. METHODS: This retrospective study included dog OS cases from three academic veterinary hospitals and human OS cases from the Surveillance, Epidemiology, and End Results program. Associations between clinical factors and metastasis at diagnosis were estimated using logistic regression models. RESULTS: In humans, those with trunk tumors had higher odds of metastasis at diagnosis compared to those with lower limb tumors (OR = 2.38, 95% CI: 1.51, 3.69). A similar observation was seen in dogs with trunk tumors compared to dogs with forelimb tumors (OR = 3.28, 95% CI 1.36, 7.50). Other associations were observed in humans but not in dogs. Humans aged 20-29 years had lower odds of metastasis at diagnosis compared to those aged 10-14 years (OR = 0.67, 95% CI: 0.47, 0.96); every 1-cm increase in tumor size was associated with a 6% increase in the odds of metastasis at diagnosis (95% CI: 1.04, 1.08); compared to those with a white, non-Hispanic race, higher odds were observed among those with a black, non-Hispanic race (OR: 1.51, 95% CI: 1.04, 2.16), and those with a Hispanic origin (OR 1.35, 95% CI: 1.00, 1.81). CONCLUSION: A common mechanism may be driving trunk tumors to progress to detectable metastasis prior to diagnosis in both species.

Evaluation of the Environmental Bias on Accelerometer-Measured Total Daily Activity Counts and Owner Survey Responses in Dogs with Osteoarthritis.

Objective To determine if environmental variables affect the average daily activity counts (AC) of dogs with osteoarthritis (OA) and/or owners' perception of their dog's clinical signs or quality of life. Methods The AC and Canine Brief Pain Inventory (CBPI) owner questionnaires of 62 dogs with OA were compared with daily environmental variables including the following: average temperature (°C), high temperature (°C), low temperature (°C), relative humidity (%), total precipitation (mm), average barometric pressure (hPa) and total daylight hours. Results Daily AC significantly correlated with average temperature and total daylight hours, but average temperature and total daylight hours accounted for less than 1% of variation in AC. No other significant relationships were found between daily AC and daily high temperature, low temperature, relative humidity, total precipitation or average barometric pressure. No statistical relationship was found between daily AC and the CBPI, nor between environmental variables and the CBPI. Canine Brief Pain Inventory scores for pain severity and pain interference decreased significantly over the test period. Clinical Significance The relationship between daily AC and average temperature and total daylight hours was significant, but unlikely to be clinically significant. Thus, environmental variables do not appear to have a clinically relevant bias on AC or owner CBPI questionnaires. The decrease over time in CBPI pain severity and pain interference values suggests owners completing the CBPI in this study were influenced by a caregiver placebo effect.

Efficacy of an oral nutraceutical for the treatment of canine osteoarthritis. A double-blind, randomized, placebo-controlled prospective clinical trial.

OBJECTIVES: To assess the safety and efficacy of an orally administered nutraceutical (Glu/CS+; + for additional ingredient) for the treatment of clinical osteoarthritis (OA) in dogs. METHODS: In this double-blind, randomized, placebo-controlled clinical trial, client-owned dogs with clinical signs of OA in one or more joints were assigned to a Glu/CS+ (n = 30) or placebo (n = 30) group. Dogs were administered Glu/CS+ or placebo orally and wore an activity monitor (AM) continuously throughout a 97 day study period. Prior to the initiation of the treatment, seven days of baseline activity was collected. On days -7, 30, 60 and 90 of the study, owners completed a patient assessment form (Canine Brief Pain Inventory). Data between groups were compared. RESULTS: No serious adverse events were reported. No difference was found between groups when evaluating daily activity counts during the seven-day pre-treatment period and the 90-day treatment period. Owner assessment (pain interference and pain severity scores) improved over the 90-day treatment period for both groups, however no difference was found between treatment groups. CONCLUSIONS: Treatment with oral Glu/CS+ for a 90 day treatment period when compared to placebo treatment did not result in a significant increase in activity counts in dogs with clinical OA. However, owner assessment scores similarly improved throughout the study period for dogs in both groups, suggesting a caregiver placebo effect in this outcome measure.

Long-term outcome of an intra-articular allograft technique for treatment of spontaneous cranial cruciate ligament rupture in the dog.

OBJECTIVE: To determine the 12-month outcome in dogs with spontaneous cranial cruciate ligament (CCL) rupture after repair with an intra-articular decellularized allograft. STUDY DESIGN: Prospective pilot case series. ANIMALS: Ten client-owned dogs with unilateral CCL rupture. METHODS: An intra-articular, decellularized, deep digital flexor tendon allograft was secured in the stifle with a femoral cross pin and tibial spiked washers and screws. An interference screw was placed in the tibial tunnel. Dogs were evaluated with an owner questionnaire, radiographs, and force platform gait analysis before and 2, 6, and 12 months after surgery. RESULTS: Owners reported improvement in level of pain and mobility throughout the study, especially over the first 6 months. Peak vertical force and vertical impulse improved across all time points. Ground reaction force asymmetry index for peak vertical force and vertical impulse at 12 months showed 3 dogs within a normal index (<6%), 4 dogs as nonvisibly lame (6-20%), and 3 dogs as visibly lame (≥20%). For most dogs, osteoarthritis scoring did not change over the 12-month period and some femoral-tibial translation was detected on standing horizontal beam radiographs. CONCLUSION: Intra-articular repair using a decellularized allograft can provide functional clinical outcomes in dogs with CCL disease. A better understanding of long-term engraftment after this procedure is needed.

Biochemical, histologic, and biomechanical characterization of native and decellularized flexor tendon specimens harvested from the pelvic limbs of orthopedically normal dogs.

OBJECTIVE: To evaluate the biochemical and biomechanical properties of native and decellularized superficial digital flexor tendons (SDFTs) and deep digital flexor tendons (DDFTs) harvested from the pelvic limbs of orthopedically normal dogs. SAMPLE: 22 commercially supplied tendon specimens (10 SDFT and 12 DDFT) harvested from the pelvic limbs of 13 canine cadavers. PROCEDURES: DNA, glycosaminoglycan, collagen, and protein content were measured to biochemically compare native and decellularized SDFT and DDFT specimens. Mechanical testing was performed on 4 groups consisting of native tendons (5 SDFTs and 6 DDFTs) and decellularized tendons (5 SDFTs and 6 DDFTs). All tendons were preconditioned, and tension was applied to failure at 0.5 mm/s. Failure mode was video recorded for each tendon. Load-deformation and stress-strain curves were generated; calculations were performed to determine the Young modulus and stiffness. Biochemical and biomechanical data were statistically compared by use of the Wilcoxon rank sum test. RESULTS: Decellularized SDFT and DDFT specimens had significantly less DNA content than did native tendons. No significant differences were identified between native and decellularized specimens with respect to glycosaminoglycan, collagen, or protein content. Biomechanical comparison yielded no significant intra- or intergroup differences. All DDFT constructs failed at the tendon-clamp interface, whereas nearly half (4/10) of the SDFT constructs failed at midsubstance. CONCLUSIONS AND CLINICAL RELEVANCE: Decellularized commercial canine SDFT and DDFT specimens had similar biomechanical properties, compared with each other and with native tendons. The decellularization process significantly decreased DNA content while minimizing loss of extracellular matrix components. Decellularized canine flexor tendons may provide suitable, biocompatible graft scaffolds for bioengineering applications such as tendon or ligament repair.