Intravenous Injection of Equine Mesenchymal Stem Cells in Dogs with Articular Pain and Lameness: A Feasibility Study.

Osteoarthritis is a frequently occurring joint disorder in veterinary practice. Current treatments are focused on pain and inflammation; however, these are not able to reverse the pathological condition. Mesenchymal stem cells (MSCs) could provide an interesting alternative because of their immunomodulatory properties. The objective of this study was to evaluate the potential of a single intravenous (IV) injection of xenogeneic equine peripheral blood-derived MSCs (epbMSCs) as treatment for articular pain and lameness. Patients with chronic articular pain were injected intravenously with epbMSCs. They were evaluated at three time points (baseline and two follow-ups) by a veterinarian based on an orthopedic joint assessment and an owner canine brief pain inventory scoring. Thirty-five dogs were included in the safety and efficacy evaluation of the study. Results showed that the epbMSC therapy was well tolerated, with no treatment-related adverse events and no increase in articular heat or pain. A significant improvement in lameness, range of motion, joint effusion, pain severity, and interference scores was found 6 weeks post-treatment compared with baseline. This study demonstrates that future research on IV administration of epbMSCs is warranted to further explore its possible beneficial effects in dogs with chronic articular pain and lameness. Clinical Trial gov ID: EC_2018_002.

Effect of dog-related parameters on the flexion test outcome: A large cohort retrospective study on physiological and orthopedic pathological-related factors.

Objectives: This retrospective study evaluates the dog-related factors of variation influencing the outcome of the flexion test (FT), when performed to localize pain to a joint area, on a large group of canine orthopedic patients. Materials and methods: The selection criteria for this retrospective study were dogs undergoing a FT in a referral orthopedic clinic between 2009 and 2020 with a complete medical record. The canine FT, described in a previously published protocol, was performed on dogs presented with an orthopedic problem. In summary, a dog's joint, identified as suspected of an orthopedic problem according to the clinical examination, was flexed for 1 min before walking 15 m on a hard and even surface. The FT was considered positive if the lameness increased after the application of the FT and negative when it remained unchanged. Statistical analysis was performed to determine which of the following criteria could influence the outcome of the flexion test: age, gender, neutered status, weight category, tested joint and initial lameness score. Results: Over 1,161 patients' files were collected and analyzed for this research. The FT showed 82.8% (95%IC: 80.5-84.9) of true positives and 17.2% of false negatives. None of the patient's intrinsic characteristics influenced the outcome of the test (age, gender, neutered status, and weight category). The orthopedic parameters, such as the initial lameness score and the tested joint, showed to have a statistically significant influence on the outcome of the test. Clinical relevance: The FT is an easy-to-perform technique presenting reliable results on most joints. This test presents an interest when performed in addition to a complete orthopedic examination to localize pain to a joint area. Only the orthopedic pathological-related parameters such as the lameness score and the tested joint seem to influence the outcome of the FT. The FT is not influenced by the physiological-related characteristic of the patient (age, weight category, sex, and neutered status).

Review: Mesenchymal Stem Cell Therapy in Canine Osteoarthritis Research: "Experientia Docet" (Experience Will Teach Us).

Osteoarthritis (OA) is currently an incurable and progressive condition in dogs causing chronic joint pain and possibly increasing disability. Due to the poor healing capacity of cartilage lesions that occur with OA, development of effective therapeutics is difficult. For this reason, current OA therapy is mostly limited to the management of pain and inflammation, but not directed ad disease modification. In the search for a safe and effective OA treatment, mesenchymal stem cells (MSCs) have been of great interest since these cells might be able to restore cartilage defects. The designs of OA studies on MSC usage, however, are not always consistent and complete, which limits a clear evaluation of MSC efficacy. The general study results show a tendency to improve lameness, joint pain and range of motion in dogs suffering from naturally-occurring OA. Assessment of the cartilage surface demonstrated the ability of MSCs to promote cartilage-like tissue formation in artificially created cartilage defects. Immunomodulatory capacities of MSCs also seem to play an important role in reducing pain and inflammation in dogs. It should be mentioned, however, that in the current studies in literature there are specific design limitations and further research is warranted to confirm these findings.

Intraobserver and interobserver agreement on the radiographical diagnosis of canine cranial cruciate ligament rupture.

Even though radiography is one of the most frequently used imaging techniques for orthopaedic disorders, it has been demonstrated that the interpretation can vary between assessors. As such, the purpose of this study was to examine the intraobserver and interobserver agreement and the influence of level of expertise on the interpretation of radiographs of the stifle in dogs with and without cranial cruciate ligament rupture (CCLR). Sixteen observers, divided in four groups according to their level of experience, evaluated 30 radiographs (15 cases with CCLR and 15 control stifles) twice. Each observer was asked to evaluate joint effusion, presence and location of degenerative joint disease, joint instability and whether CCLR was present or absent. Overall, intraobserver and interobserver agreement ranged from fair to almost perfect with a trend towards increased agreement for more experienced observers. Additionally, it was found that stifles that were classified with high agreement have either overt disease characteristics or no disease characteristics at all, in comparison to the ones that are classified with a low agreement. Overall, the agreement on radiographic interpretation of CCLR was high, which is important, as it is the basis of a correct diagnosis and treatment.

Arthroscopic, Computed Tomography, and Radiographic Findings in 25 Dogs With Lameness After Arthroscopic Treatment of Medial Coronoid Disease.

OBJECTIVE: To describe the radiographic, computed tomography (CT), and arthroscopic findings in the elbow of dogs admitted for elbow lameness after previous arthroscopic treatment of medial coronoid disease (MCD). STUDY DESIGN: Retrospective case series. ANIMALS: Client-owned dogs (n = 25) admitted for elbow lameness after arthroscopic treatment. METHODS: Clinical records (2005-2009), including radiographs, CT images, and arthroscopic findings, from the first and second presentation of dogs diagnosed with medial coronoid disease were searched and reviewed. RESULTS: Twenty-nine joints were included in this study. The mean age at first treatment was 2.2 years. Second presentation was at a mean of 2.7 years later and progressive osteoarthritis and cartilage damage was noticed in all joints. Arthroscopic findings included a calcified body in 11/29 joints (38%), multiple small calcified bodies in 1/29 joint (3%), loose scar tissue in 12/29 joints (42%), and immobile scar tissue in 2/29 joints (7%). Three of 29 joints (10%) did not have any calcified body or loose scar tissue found but had erosion of the medial compartment as the only pathology diagnosed in the coronoid region. Characteristics of flexor enthesopathy were identified in 9/29 joints (31%). CONCLUSION: Arthroscopic treatment of MCD, even with limited cartilage lesions, may not resolve lameness in some dogs. Calcified bodies or loose scar tissue near the medial coronoid process are a frequent followup finding in these joints.

Intra- and interobserver agreement on radiographic phenotype in the diagnosis of canine hip dysplasia.

OBJECTIVE: To investigate the repeatability and reproducibility of the presence of a circumferential femoral head osteophyte (CFHO), a curvilinear caudolateral osteophyte (CCO), osteosclerosis of the cranial acetabular edge (Scler CrAE), degenerative joint disease (DJD), and the diagnosis of suspected canine hip dysplasia (CHD) in different groups of experienced observers. STUDY DESIGN: Cross-sectional study. SAMPLE POPULATION: Standard hip extended radiographs (n = 50). METHODS: Nine experienced observers were divided into 3 groups: surgeons (DECVS), radiologists (DECVDI), and non-board certified observers (NBC) and 2 subgroups (academics and non-academics). Cohen's kappa (κ) was calculated for CFHO, CCO, Scler CrAE, DJD, and suspected CHD, and weighted κ was calculated for DJD score to determine inter- and intraobserver agreement. RESULTS: Intraobserver agreement on CFHO, CCO, Scler CrAE, DJD, and suspected CHD ranged from slight to almost perfect, but was not significantly different between NBC, DECVS, and DECVDI. Radiologists and non-board certified observers had a more uniform scoring than surgeons on the overall DJD score, as did academics versus non-academics. Interobserver agreement for NBC was more uniform than that of radiologists and surgeons on CCO and DJD. NBC and radiologists scored more uniformly than surgeons on CFHO, and radiologists scored more uniformly than NBC and surgeons on Scler CrAE. Academics scored more uniformly than non-academics, but only significantly for Scler CrAE. CONCLUSIONS: Recognition of specific radiographic markers is only fairly reliable within and between experienced observers. Therefore, care must be taken to apply these traits in official screening, surgical decision-making and scientific research.

TTA Rapid: Description of the Technique and Short Term Clinical Trial Results of the First 50 Cases.

OBJECTIVE: To (1) describe a modified technique for tibial tuberosity advancement (TTA) in dogs with cranial cruciate ligament (CCL) rupture and (2) report short term outcome and complications. STUDY DESIGN: Prospective clinical study. ANIMALS: Dogs with unilateral CCL rupture (n = 50). METHODS: TTA was performed with a novel implant to achieve advancement of the tibial crest. The technical protocol, specific implants and instrumentation, and the short term outcome are described. RESULTS: Various breeds (mean ± SD weight, 31.9 ± 13.3 kg) were included. Mean age at treatment was 64 ± 30.6 months. Minor complications occurred in 30% and major complications in 4% of the cases. Forty-eight (96%) dogs had a good to excellent outcome 3 months after surgery. CONCLUSION: The modified technique is a viable alternative to other osteotomy techniques.

Comparison of analgesic efficacy of epidural methadone or ropivacaine/methadone with or without pre-operative oral tepoxalin in dogs undergoing tuberositas tibiae advancement surgery.

OBJECTIVE: To investigate the clinical efficacy of four analgesia protocols in dogs undergoing tibial tuberosity advancement (TTA). STUDY DESIGN: Prospective, randomized, blinded study. ANIMALS: Thirty-two client owned dogs undergoing TTA-surgery. METHODS: Dogs (n = 8 per treatment) received an oral placebo (PM and PRM) or tepoxalin (10 mg kg(-1) ) tablet (TM and TRM) once daily for 1 week before surgery. Epidural methadone (0.1 mg kg(-1) ) (PM and TM) or the epidural combination methadone (0.1 mg kg(-1) )/ropivacaine 0.75% (1.65 mg kg(-1) ) (PRM and TRM) was administered after induction of anaesthesia. Intra-operative fentanyl requirements (2 µg kg(-1) IV) and end-tidal isoflurane concentration after 60 minutes of anaesthesia (Fe'ISO(60) ) were recorded. Post-operative analgesia was evaluated hourly from 1 to 8 and at 20 hours post-extubation with a visual analogue scale (VAS) and the University of Melbourne Pain Scale (UMPS). If VAS > 50 and/or UMPS > 10, rescue methadone (0.1 mg kg(-1) ) was administered IV. Analgesic duration (time from epidural until post-operative rescue analgesia) and time to standing were recorded. Normally distributed variables were analysed with an F-test (α = 0.05) or t-test for pairwise inter-treatment comparisons (Bonferonni adjusted α = 0.0083). Non-normally distributed data were analysed with the Kruskall-Wallis test (α = 0.05 or Bonferonni adjusted α = 0.005 for inter-treatment comparison of post-operative pain scores). RESULTS: More intra-operative analgesia interventions were required in PM [2 (0-11)] [median (range)] and TM [2 (1-2)] compared to PRM (0) and TRM (0). Fe'ISO(60) was significantly lower in (PRM + TRM) compared to (PM + TM). Analgesic duration was shorter in PM (459 ± 276 minutes) (mean ± SD) and TM (318 ± 152 minutes) compared to TRM (853 ± 288 minutes), but not to PRM (554 ± 234 minutes). Times to standing were longer in the ropivacaine treatments compared to TM. CONCLUSIONS AND CLINICAL RELEVANCE: Inclusion of epidural ropivacaine resulted in reduction of Fe'ISO(60) , avoidance of intra-operative fentanyl administration, a longer duration of post-operative analgesia (in TRM) and a delay in time to standing compared to TM.

Computed tomography findings in 32 joints affected with severe elbow incongruity and fragmented medial coronoid process.

OBJECTIVE: To describe the computed tomography (CT) findings in dogs with severe elbow incongruity combined with a fragmented medial coronoid process (FCP) and compare these with normal joints and congruent joints affected by FCP. STUDY DESIGN: Clinical study. ANIMALS: Client-owned dogs with elbow lameness (n = 40) and purpose bred dogs (n = 5; controls). METHODS: The CT features of 32 severely incongruent joints with concomitant FCP were compared with those of 32 congruent elbow joints affected with FCP and 10 normal joints. RESULTS: In severely incongruent elbow joints, a radioulnar step and widened joint spaces were visible on each CT plane. Additional features typically seen in severely incongruent elbows were a cyst at the radioulnar transition and fragmentation of the axial border of the medial coronoid incisure. None of these features appeared in normal or in congruent FCP joints. CONCLUSION: On CT, several features associated with severe elbow incongruity and concomitant FCP were detected, which were not found in normal joints or congruent joints affected by FCP.

Arthroscopic findings in 32 joints affected by severe elbow incongruity with concomitant fragmented medial coronoid process.

OBJECTIVE: To report arthroscopic findings in dogs with severe elbow incongruity combined with fragmented medial coronoid process (FCP) and compare these findings in normal joints and congruent joints affected by FCP. STUDY DESIGN: Clinical study. ANIMALS: Dogs with elbow lameness (n = 40) and purpose bred dogs (5; controls). MATERIALS AND METHODS: Arthroscopic features of 32 severely incongruent joints with concomitant FCP were compared with 32 congruent elbow joints affected with FCP and 10 normal joints. A radioulnar step of ≥ 3 mm on radiographs and computed tomography (CT) scans was the selection criterion for a severely incongruent joint. Intraarticular structures were visually assessed at various sites within the joint. Regions of interest were: the radioulnar transition, humeroradial and humeroulnar joint space, trochlear notch, primary and secondary lesions of the medial coronoid process, and radial head. RESULTS: Incongruent joints had a radioulnar step and changes at the cartilage in the center of the trochlear notch, an irregular radioulnar transition, and an abnormal surface of the radial head. Coronoid pathology was present in every pathologic joint. CONCLUSION: Arthroscopy allowed detection of several features that were signs or consequences of severe elbow incongruity or accompanying inflammation. After a prominent radioulnar step, cartilage changes involving the radial head and trochlear notch were most frequently seen.

Sensitivity and specificity of radiography for detection of elbow incongruity in clinical patients.

Elbow incongruity is an important factor regarding the treatment and prognosis of elbow dysplasia. Our purpose was to determine the sensitivity and specificity for radiographic detection of elbow incongruity in clinical patients, to establish inter- and intraobserver variation for different parameters, and to evaluate the possibility of radiographic grading of incongruity. Standard radiographic projections were acquired from 29 incongruent and nine congruent elbows of dogs of various ages and breeds. Computed tomography (CT) was used to diagnose and grade the incongruity. All radiographs were evaluated by four observers for detection and grading of elbow incongruity. Sensitivity, specificity, inter- and intraobserver variability were calculated. The mean sensitivity for detection of incongruity was very good (88.8%) with a mean specificity of 91.7%. Correct grading of incongruity was difficult. The radioulnar step and the widening of the humeroulnar and humeroradial joint space were seen most frequently. Intraobserver and interobserver variability were fair to excellent (Kappa = 0.372-0.809), depending on the investigated parameters. Radiography is valuable to screen for elbow incongruity. In over 91% of the patients, a clear distinction could be made between a congruent and an incongruent joint grading was not possible.