Rapid developments in Regenerative Medicine and Tissue Engineering has witnessed an increasing drive toward clinical translation of breakthrough technologies. However, the progression of promising preclinical data to achieve successful clinical market authorisation remains a bottleneck. One hurdle for progress to the clinic is the transition from small animal research to advanced preclinical studies in large animals to test safety and efficacy of products. Notwithstanding this, to draw meaningful and reliable conclusions from animal experiments it is critical that the species and disease model of choice is relevant to answer the research question as well as the clinical problem. Selecting the most appropriate animal model requires in-depth knowledge of specific species and breeds to ascertain the adequacy of the model and outcome measures that closely mirror the clinical situation. Traditional reductionist approaches in animal experiments, which often do not sufficiently reflect the studied disease, are still the norm and can result in a disconnect in outcomes observed between animal studies and clinical trials. To address these concerns a reconsideration in approach will be required. This should include a stepwise approach using in vitro and ex vivo experiments as well as in silico modeling to minimize the need for in vivo studies for screening and early development studies, followed by large animal models which more closely resemble human disease. Naturally occurring, or spontaneous diseases in large animals remain a largely untapped resource, and given the similarities in pathophysiology to humans they not only allow for studying new treatment strategies but also disease etiology and prevention. Naturally occurring disease models, particularly for longer lived large animal species, allow for studying disorders at an age when the disease is most prevalent. As these diseases are usually also a concern in the chosen veterinary species they would be beneficiaries of newly developed therapies. Improved awareness of the progress
To evaluate the intra- and inter-observer measurement variability of an existing osteoarthritis (OA) stifle scoring system. Paired caudocranial and mediolateral canine stifle radiographs were selected randomly. A total of 15 assessment points were evaluated independently and graded twice (integer numeric scale: 1-4) at an interval of 2 weeks by three observers with different levels of experience. The grades for each of the 15 factors were summed to obtain the OA score for each patient. The 15 independent assessment points measured by the three observers showed high reproducibility and low intra-observer variability. Inter-observer variability was also low (mean: 1.09 ± 4.99, 95% CI [confidence interval]: -0.35 to 2.55). The most discordant ratings among the three observers involved sesamoid bones of gastrocnemius muscle (assessment point 11 of 15) and popliteal surface of femur (assessment point 10 of 15). A validated and feasible OA scoring method is prerequisite for reliable radiographic assessment of OA progression. The low overall inter- and intra-observer variabilities among the 15 independent measures of the OA scoring system presented herein support its feasibility for application in clinical practice as an objective tool for radiographic scoring of stifle OA.
Gait analysis has been extensively performed in dogs and horses; however, very little is known about feline biomechanics. It was, therefore, the aim of this study to determine the coefficient of variation (CV) among three ground reaction force (GRF) measurements taken for 15 client-owned European shorthaired cats without a training period and a short acclimatisation time. Gait was measured as each cat walked across a pressure-sensitive walkway, and measurements were made three times over a multi-week period (range: 2 to 17 weeks). The parameters evaluated were peak vertical force (PFz), vertical impulse (IFz), stance phase duration (SPD), step length (SL), paw contact area (PCA) and symmetry index (SI%) of the front and hind limbs. After averaging each of the values from the three measurements, the CV and 95% confidence interval (CI) were calculated for all parameters. PFz showed the lowest CV (~ 3%), while IFz showed the highest CV (~11%) when normalised to body mass. When the GRFs were normalised to total force, the CV of PFz dropped to ~2% and that of IFz dropped to ~3%. The CV of SL and PCA were lower (~6% respectively ~5%) compared to the CV for SPD (~10%). The SI% for both PFz and IFz were comparable to the values reported in the gait analysis literature for dogs. Results of the current study indicate that gait analysis of cats using pressure-sensitive walkways produces reliable data and is a promising approach for evaluation of lameness. The results also suggest that PFz may be a more reliable parameter than IFz and that normalisation to percent of total force may aid in interpretation of the evaluated data.
Summary Objective: The optimal surgical technique for treatment of cranial cruciate ligament rupture in canine has been scientifically discussed for decades. Despite the continuous debate, proximal tibial osteotomies such as tibial plateau leveling osteotomy (TPLO) and tibial tuberosity advancement (TTA) are increasingly common. The objective of this review was to systematically evaluate the literature reporting outcome and complications associated with TPLO and TTA. Materials and methods: A systematic search of literature databases identified articles published from August 2004 to February 2016 describing evaluations of short- or longterm outcomes as well as complications following TPLO or TTA. Results: Ninety-one studies were included in this review and assigned to one out of four evidence levels. Of those, 89 studies provided the lowest evidence level and only two were assigned to the third-best evidence level. A comparison of subjective gait analyses could not detect differences in the decrease of lameness between TPLO and TTA, while objective gait analysis supports the superiority of TPLO. Fewer patients treated with TPLO were diagnosed with postoperative joint instability and TPLO had a lower percent increase of osteoarthritis (OA) after surgery. Owner satisfaction was high for both techniques. For TPLO and TTA the average total, minor, major and catastrophic complication rates were 15.9 % and 20.8 %, 7.9 % and 11.6 %, 5.2 % and 13.2 % as well as 0.8 % and 5.6 %, respectively. Conclusion and clinical significance: The assessed literature supports the hypothesis that TPLO is associated with lower complication rates, an improved clinical-functional outcome and less increase of OA compared to TTA. The results are indicative for a long-term restoration of normal limb function after TPLO. However, the strength of available evidence and the comparability of each study’s results were poor and more comparative studies are needed to draw strong conclusions towards the superiority of the TPLO over the TTA.
Current research on gait analysis mostly involves horses and dogs. Feline kinetics and kinematics are being investigated and receiving more clinical interest at present. Ground reaction forces measured on pressure-sensitive mattresses have been established in healthy Domestic Shorthair cats (DSH). Currently, no further information exists on either breed-specific measured gait reaction forces or comparisons among breeds. Because Maine Coon (MC) cats appear to be over-represented with orthopaedic diseases of the hind limb (hip dysplasia, patellar luxation), we evaluated ground reaction force GRF measurements in MC cats and compared them with those of DSH cats. Pre-evaluation radiological and clinical exams determined that the cats were not lame. The parameters evaluated were peak vertical force (PFz), vertical impulse (IFz), time to PFz (TPFz), step length (SL), paw contact area (PCA), stance phase duration (SPD) and symmetry index (SI) for the fore- and hind limbs. In both breeds, PFz and IFz were greater in forelimbs than in hind limbs. The PFz and IFz in Newtons were higher in the MC cats compared to the DSH cats, but not after normalisation for total force (%TF) and body mass (%BM). Furthermore, due to their body conformation, MC cats have a longer SL, larger PCA, and higher body weight than DSH cats. No other parameters differed significantly, except that the TPFz displayed an earlier value in the MC hind limbs. Measured symmetry indices were similar to those reported in dogs and did not differ between breeds. This is the first study to report GRF values and temporospatial parameters in a healthy MC cat population. However, our results could not confirm differences between normalized PFz and IFz and temporospatial parameters between the breeds. The authors therefore conclude that genetic or other causes may be involved in orthopaedic hind limb pathogenesis seen in MC cats more often than in other breeds.
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