Serotype-specific transduction of canine joint tissue explants and cultured monolayers by self-complementary adeno-associated viral vectors.

A formal screening of self-complementary adeno-associated virus (scAAV) vector serotypes in canine joint tissues has not been performed to date. Selecting appropriate serotypes is crucial for successful treatment due to their varying levels of tissue tropism. The objective of this study is to identify the most optimal scAAV vector serotype that maximizes transduction efficiencies in canine cell monolayer cultures (chondrocytes, synoviocytes, and mesenchymal stem cells) and tissue explant cultures (cartilage and synovium). Transduction efficiencies of scAAV serotypes 1, 2, 2.5, 3, 4, 5, 6, 8, and 9 were evaluated in each culture type in three different vector concentrations by encoding a green fluorescent protein. It was found that scAAV2 and 2.5 showed the overall highest transduction efficiency among serotypes with dose-response. Since possible immune response against conventional AAV2 was previously reported in dogs, the chimeric scAAV2.5 may be more suitable to use. Evaluation of the safety and efficacy of the scAAV2.5 vector with an appropriate therapeutic gene in vivo is indicated.

Prospective evaluation of complications associated with orthosis and prosthesis use in canine patients.

Introduction: The use of orthoses and prostheses is expanding in veterinary medicine. However, research evaluating the efficacy and complications of these devices in veterinary patients is limited. The primary objective of this study was to prospectively determine the complications and outcomes associated with custom orthosis and prosthesis use in the canine patient. Materials and Methods: This was a prospective, clinical trial that followed patients for 12 months following device fitting. Owner-perceived complications, clinical metrology instruments, and objective gait analysis were used as outcome measures at various time points. The patients were grouped into the following four major categories: Patients with a carpal orthosis, patients with a stifle orthosis, patients with a tarsal orthosis, and patients with a prosthetic device. Results: Forty-three patients were included in the study. Thirty-nine out of 43 patients (91%) experienced at least one complication, with 7/7 (100%) prosthesis patients experiencing at least one complication. At least one skin complication was reported for the following patient groups during the first 3 months of use: 8/14 (58%) stifle orthoses, 9/10 (90%) carpal orthoses, 6/10 (60%) tarsal orthoses, and 4/7 (58%) prostheses. Patient non-acceptance of the device was identified in 2/15 (14%) stifle orthoses, 1/10 (10%) tarsal orthoses, and 4/7 (55%) prostheses. One out of 15 (7%) stifle orthoses, 4/10 (40%) carpal orthoses, 4/10 (40%) tarsal orthoses, and 1/7 (15%) prostheses experienced mechanical device problems necessitating repair. The majority of patients with carpal and stifle orthoses showed improvement on objective gait analysis in percent body weight distribution of the affected limb between baseline and the most recent follow-up without the device donned: 83% (n = 6) of patients with carpal orthoses, 100% (n = 11) of patients with stifle orthoses. None of the patients with tarsal orthoses showed a similar improvement (0%; n = 4). Discussion and conclusion: Three major complications associated with canine orthosis and prosthesis use were identified in this study as follows: Skin complications (abrasions, loss of hair, and sores), mechanical device problems, and patient non-acceptance of the device. Owners should be notified of these potential complications prior to pursuing orthoses or prostheses as a potential treatment option. Although clinical improvement was noted in the majority of patients with stifle and carpal pathology, given the lack of a control group, it is unknown how much of this improvement can be attributed to the orthoses.

Appendicular skeletal muscle mass assessment in dogs: a scoping literature review.

BACKGROUND: Monitoring changes in appendicular skeletal muscle mass is frequently used as a surrogate marker for limb function. The primary objective of this study was to review scientific information related to the assessment of appendicular skeletal muscle mass in dogs. The secondary objective was to develop practical recommendations for serial evaluation of muscle mass. METHODS: A scoping review was conducted with a systematic search of PubMed, Web of Science, CAB abstract, and Cochrane from inception to June 2021. The following modalities were included in the search: limb circumference, diagnostic ultrasound, computed tomography, magnetic resonance imaging, and dual-energy x-ray absorptiometry. RESULTS: A total of 62 articles that measured appendicular skeletal muscle mass in dogs were identified. Limb circumference (55 articles) was the most commonly used modality. Its reliability was investigated in five studies. Several factors, including measuring tape type, body position, joint angles, and the presence of hair coat, were reported as variables that can affect measurements. Diagnostic ultrasound (five articles) was validated in three articles, but there is scarce information about observer reliability and variables affecting the measurement. Computed tomography (four articles) and magnetic resonance imaging (one article) have been used to validate other modalities at a single time point rather than as a clinical tool for serial muscle mass monitoring. Dual-energy x-ray absorptiometry (two articles) has been used to quantify specific skeletal muscle mass but was mainly used to evaluate body composition in dogs. CONCLUSION: Limb circumference and ultrasound are likely the main modalities that will continue to be used for serial muscle mass measurement in the clinical setting unless a new technology is developed. The reliability of limb circumference is questionable. Several key factors, including measuring tape type, body position, joint angles, and coat clipping, need to be controlled to improve the reliability of limb circumference measurements. Ultrasound may provide a reasonable alternative, but further studies are required to evaluate the reliability of this modality and identify factors that influence ultrasound measurements.

Evaluation of the Effect of Cannabidiol on Naturally Occurring Osteoarthritis-Associated Pain: A Pilot Study in Dogs.

The objective of this study was to provide preliminary data describing the safety and effect of cannabidiol (CBD) for symptom relief of canine osteoarthritis-associated pain in a clinical setting using objective outcome measures. Twenty-three client-owned dogs with naturally occurring osteoarthritis of appendicular joints completed this prospective, double-blinded, crossover, placebo-controlled study. Baseline data were acquired for 4 wk, followed by random allocation to either placebo or CBD treatment for 6 wk, followed by 6 wk with the opposite treatment. Outcome measures included objective gait analysis, activity counts (via accelerometry) and clinical metrology instruments. There were no differences noted between groups at any time point for any of the recorded outcome measures. Adverse events associated with CBD administration included elevation in liver enzymes (n = 14) and vomiting (n = 2).

Evaluation of acupuncture for the treatment of pain associated with naturally-occurring osteoarthritis in dogs: a prospective, randomized, placebo-controlled, blinded clinical trial.

BACKGROUND: Acupuncture has been used as a treatment for pain associated with osteoarthritis (OA) for thousands of years; however, there is a lack of definitive evidence for this indication in humans or animals. The aim of this study was to prospectively evaluate the efficacy of acupuncture on lameness and clinical function in dogs affected by naturally-occurring OA using objective outcome measures. A total of 32 client-owned dogs completed this prospective, randomized, placebo-controlled, blinded clinical trial, using a cross-over design. Participants were assigned to receive placebo or acupuncture treatment once weekly for 4 weeks in random order with a two-week wash-out period in between treatment phases. Outcome measures included ground reaction forces (GRF), subjective orthopedic scoring (SOS), activity counts (AC), and owner-completed clinical metrology instruments (CMI; Canine Brief Pain Inventory [CBPI] and Client Specific Outcome Measures [CSOM]). For statistical comparison, baseline GRF, SOS, and CMI data were compared to data obtained 1 week after each treatment phase. Similarly, total weekly AC of the final week of each treatment phase were compared to the baseline week. RESULTS: Evidence of differences between baseline versus acupuncture and placebo treatments was not identified for the following outcome measures: GRF, AC, or SOS. However, evidence of differences was identified for some of the CMI scores, including the CSOM questionnaire which showed evidence of improvement when comparing baseline versus acupuncture (p = 0.0002) as well as between placebo versus acupuncture treatments (p = 0.035) but not between baseline versus placebo treatments (p = 0.221). CONCLUSIONS: The applied acupuncture protocol did not show improvement in function when using objective outcome measures for OA in dogs; however, certain CMI measurements recorded some degree of treatment response.