Search

Background: Osteoarthritis is a leading cause of pain and retirement in athletic horses. Hydro-expansive functionalized nanogels, acting as Drug Delivery Systems, constitute one of the current therapeutic prospects. These nanogels have the potential to combine mechanical benefits through polymers with the biological effect of prolonged release of bioactive molecules. The purpose of this double-blinded randomized tolerance study versus negative control was to evaluate the response of healthy joints to a single injection of the expected efficient dose (further referred to as the trial dose) and overdose of nanogels composed of chitosan and hyaluronic acid and featuring a type A endothelin receptor antagonist and a type B1 bradykinin receptor antagonist. The metacarpophalangeal joints of 8 healthy horses were randomly injected with 2.4 mL of functionalized nanogels and 2.4 mL of saline as control on the contralateral limb. Injections were repeated twice at one-week intervals, followed by injection of a triple dose of nanogel on week four. Clinical, ultrasonographic and synovial fluid cellular and biochemical follow-ups were performed up to three months following the first injection., Results: No change in general clinical parameters, lameness or sensitivity to passive flexion of the fetlocks was noted. Mild to moderate synovitis was noted on the day following injection in the treated group, with a significant difference (p < 0.05) compared to the control group. It spontaneously resolved on day 3 following the injections and did not increase with repeated injections. Similar effects were noted after injection of the triple dose but lasted for a week. Synovial fluid markers of inflammation also showed a transient significant increase in the treated group one week after each injection, but no differences were detected at the end of the study., Conclusions: Injections of the expected therapeutic dose of functionalized nanogel in healthy joints induced a mild transient inflammatory response in the joint. Three injections of the trial dose at one-week intervals and injection of thrice the trial dose induce a mildly greater inflammation without harmful effects on joints. Functionalized nanogels are well tolerated prospects for the treatment of osteoarthritis in horses. Their beneficial effects on arthritic joints have yet to be evaluated to determine their therapeutic potential., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the ComEth Anses/ENVA/UPEC (protocol code 21–037#30112 OA-ACTIVE). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

We aimed to evaluate the effect of the intravenous (IV) administration of blood cell secretome (BCS) compared to its intra-articular (IA) administration. In this cross-over study, ten dogs with bilateral hip osteoarthritis were initially assigned to an IA group (IAG). After a 180-day follow-up, the same 10 animals were assigned to an IV group (IVG). IAG received a single IA administration of 3 ml of BCS per hip joint, and IVG received a single 6 ml IV administration of BCS. Following each treatment, follow-up was conducted on days 0, 8, 15, 30, 60, 90, 120, 150, and 180. In each follow-up, copies of the Canine Brief Pain Inventory (divided into pain interference score - PIS and Pain Severity Score - PSS), Liverpool Osteoarthritis in Dogs (LOAD), and Canine Orthopedic Index (COI, divided into function, gait, stiffness, and quality of life) were obtained. Results were analyzed with the Mann-Whitney test, and Kaplan-Meier estimators were calculated and compared, p < 0.05. The animals had a mean age of 7.6 ± 2.9 years and bodyweight of 27.8 ± 3.6 kg. Seven hips were classified as moderate osteoarthritis, and three as severe. No differences were found between groups from days 0 to +60d, with both groups showing clinically significant improvements. Improvements in the IAG lasted up to +120d. Kaplan-Meier estimators showed that dogs in IAG took longer to record the considered events. IVG also showed positive clinically significant results with different instruments. IV administration of BCS can improve the overall condition of dogs with hip OA, but the IA administration produces longer-lasting results., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Few case reports describe equine coxofemoral joint osteoarthritis (CFJOA)., Objectives: To evaluate diagnostic findings and outcome of horses with CFJOA and to provide a score facilitating radiographic assessment., Study Design: Retrospective case series., Methods: History, clinical signs, ultrasonographic, radiographic and intra-articular anaesthesia findings, treatments, outcome, and necropsy results of horses with CFJOA presented between 2002 and 2023 were collated. Radiographic findings were categorised to develop a radiographic score which was applied by two masked examiners. Intra- and inter-observer reliability was determined using weighted Cohen's kappa (Cκ) and the correlation between radiographic and ultrasound findings via Spearman correlation coefficient., Results: The study included 24 horses (median age 14 years). Most of them (20/24) were chronically lame. Frequent clinical signs included unilateral gluteal muscle atrophy (18/21), lengthening of the stride of the affected limb (13/19) and locomotion on three tracks (13/20). Both imaging modalities enabled evaluation of periarticular osteophytes (correlation coefficient r = 0.64; p = 0.003). Additionally, radiography allowed detection of irregular joint spaces, subchondral bone opacity changes and femoral head flattening/tapering. Inter-observer (Cκ = 0.846) and intra-observer (Cκ = 0.853 and Cκ = 0.842) agreement was excellent. If treated, mostly intra-articular corticosteroids were administered (16/18). Nine horses were euthanised immediately or during follow-up examination. Post-mortem, the Ligamentum capitis ossis femoris was commonly found ruptured. All surviving horses remained lame., Main Limitations: Retrospective analysis of clinical records and subjective outcome assessment based on owner follow-up with potential recall bias. Due to overall disease severity, associations between different grades of clinical findings, radiographic abnormalities and outcome could not be evaluated., Conclusions: Typical clinical signs may indicate CFJOA. Standardised evaluation of ventrodorsal radiographs allows a comprehensive diagnosis. Postmortem findings suggest joint instability as a possible causative factor that may contribute to the poor prognosis and resistance to medical therapy of the disorder., (© 2024 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Equine practitioners frequently inject local anaesthetics (LA) intra-articularly in both diagnosis of lameness and for pain management intra- or post-operatively with synovial endoscopy. Recent reviews of the human and veterinary literature support the concept that chondrotoxicity of LA on joint tissues depends on the type of drug, dose administered, and duration of exposure. The purpose of this review is to summarise the current literature describing intra-articular local anaesthetic use, including both in vitro and in vivo studies, and to draw some comparisons to literature from other species where potential toxicity and duration of effect have been evaluated with the goal of advancing the field's understanding of intra-articular local anaesthetic use in horses, and indicating future directions for the field. The aggregate data available from all species, while generally sparse for horses, indicate that LA are rapidly cleared from the synovial fluid after injection, often within 30 min. In vitro data strongly suggest that lidocaine and bupivacaine are likely more chondrotoxic than other LA, although to what extent is still unknown, and cytotoxicity of LA may be mitigated through concurrent injection with HA, PRP, and drug combinations including nonsteroidal anti-inflammatories and opioids. The current body of in vitro research is not reflective of the in vivo environment, and further in vitro work, if performed, should focus on mimicking the native joint environment, utilising PK data and joint/injection volumes to replicate the native environment more accurately within the joint and the expected exposures to LA., (© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Objective: To provide a video tutorial on ultrasound-guided arthrocentesis and injection of the canine hip and shoulder joints., Animals: Dogs undergoing arthrocentesis or intra-articular injection for diagnostic or therapeutic purposes., Methods: The target joint is visualized in long axis with a 70% isopropyl alcohol medium and linear array probe with a frequency range of 2 to 14 MHz and footprint of 50 mm after clipping a window and preparing the region sterilely. The needle is inserted, bevel up, in long axis with the probe angled at the appropriate trajectory to enter the joint space. The needle is advanced until the tip is visualized entering the joint. Aspiration to obtain synovial fluid can further confirm needle placement or provide diagnostic sampling prior to injection. The aspirate syringe is exchanged for that containing the therapeutic agent, and injectate can then be visualized entering and/or expanding the joint upon injection., Results: Ultrasound-guided arthrocentesis will help identify deep appendicular joints (hip and shoulder), avoid surrounding vasculature, confirm needle placement, and target joint fluid pocketing. Needle guidance into a joint can reduce iatrogenic tissue damage from inappropriate needle placement and/or by minimizing attempts., Clinical Relevance: For arthrocentesis, ultrasound guidance can maximize joint fluid volume acquisition for diagnostic purposes (cytology, culture, and fluid analysis) while also avoiding blood contamination. For joint injections, ultrasound will help ensure real-time intra-articular delivery of the injectate (regardless of attaining synovial fluid feedback) to maximize the therapeutic effect. For either purpose, iatrogenic tissue damage and procedure time are minimized.

Objective: To determine the influence of arthroscopy and injection volume on post-procedure intra-articular (IA) injection extravasation., Study Design: Ex vivo prospective study., Sample Population: A total of 40 paired canine cadaver forelimbs., Methods: After radiographs and computed tomography (CT) scans with three-dimensional (3D) digital bone model reconstructions, elbows were randomly assigned to the arthroscopy or control group and randomly assigned to receive an IA injection of 2 or 4 mL of contrast. Elbow arthroscopy was performed on assigned specimens, followed by IA injections of contrast in all elbows, and imaging was repeated. 3D digital model volumes were compared. Images were interpreted and scored for extravasation by a radiologist unaware of treatment and volume assignments., Results: Based on CT images and regardless of treatment group, IA injections of 4 mL resulted in a mean extravasation score of 2.25 (SD 0.97) versus 1.55 (SD 1.05) (p = .02) for 2 mL IA injections. The change in 3D model volumes after IA injections was a mean of 13.2 cm 3 (SD 5.85) after 4 mL injections, compared to 6.97 cm 3 (SD 6.28) (p = .003) after 2 mL injections. On radiographic evaluation, but not CT, the mean extravasation scores were 2.45 (SD 1.15) for the arthroscopy group and 1.25 (SD 0.79) for the control group (p < .001)., Conclusion: A larger volume of IA injection resulted in higher CT extravasation scores and larger 3D volumes regardless of arthroscopic treatment., Clinical Significance: IA injections performed immediately after arthroscopy resulted in 50% or less extravasation, especially with a smaller IA injection volume., (© 2024 American College of Veterinary Surgeons.)

Objective: To determine with mechanical nociceptive threshold (MNT) testing whether distal limb skin sensation is affected by intra-articular anesthesia of the tarsometatarsal joint (TMTJ)., Animals and Procedure: This was a prospective cohort study. Ten client-owned horses that had intra-articular TMTJ anesthesia were included in the study. The MNT was measured at 6 sites on the distal limb at 3 time points: before anesthesia (T0) and at 10 min (T10) and 30 min (T30) post-injection. Linear mixed-model analyses were done, with the significance level set at P < 0.05., Results: There was an increase in MNT ( P = 0.001) across combined testing points between T0 and T30, indicating loss of skin sensation in the distal limb 30 min after TMTJ anesthesia. Regarding individual MNT sites, there were increases at the lateral proximal sesamoid bone ( P = 0.002) and dorsal coronary band ( P = 0.037) at T30 compared to T0., Conclusion: Intra-articular anesthesia of the TMTJ significantly increased the combined MNT of the skin of the distal limb at 30 min, indicating decreased skin sensation., Clinical Relevance: Diagnostic anesthesia of the distal hind limb should be performed before TMTJ block. However, if patient compliance prevents this, lameness evaluation 10 min after blocking may enhance the reliability of interpretation., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Lameness is a significant welfare concern in goats. Amphotericin B is used via intraarticular (IA) administration in models to study experimentally induced lameness in large animals. The main objective of this study was to estimate plasma pharmacokinetic (PK) parameters for amphotericin B in goats after a single IA administration. Liposomal amphotericin B was administered to ten Kiko-cross goats at a dose of 10 mg total (range: 0.34-0.51 mg/kg) via IA administration into the right hind lateral distal interphalangeal joint. Plasma samples were collected over 96 h. Amphotericin B concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was used to derive PK parameters. Following single IA administration, maximum plasma concentration was estimated at 54.6 ± 16.5 ng/mL, and time to maximum concentration ranged from 6 to 12 h. Elimination half-life was estimated at 30.9 ± 16.5 h, and mean residence time was 45.1 ± 10.4 h. The volume of distribution after IA administration was 13.3 ± 9.4 L/kg. The area under the curve was 1481 ± 761 h*ng/mL. The achieved maximum concentration was less than the observed concentrations for other species and routes of administration. Further research is needed into the pharmacodynamics of IA liposomal amphotericin B in goats to determine specific research strategies., (© 2024 John Wiley & Sons Ltd.)

Objective: To establish the pharmacokinetics of the cyclin-dependent kinase-9 inhibitor flavopiridol in equine middle carpal joints, using an extended-release poly lactic-co-glycolic acid (PLGA) microparticle formulation., Animals: 4 healthy horses without evidence of forelimb lameness., Methods: A 6-week longitudinal pharmacokinetic study was conducted in 2 phases (6 weeks each) in 4 healthy horses. The PLGA microparticles containing 122 μg flavopiridol in 3 mL saline were administered by intra-articular injection into 1 middle carpal joint, with empty PLGA microparticles injected into the contralateral joint as a control. Synovial fluid and plasma were collected at time points out to 6 weeks, and drug concentrations in synovial fluid and plasma were determined using validated protocols. Synovial fluid total protein and total nucleated cell count and differential, CBC, serum biochemistry, and lameness exams were performed at each of the time points., Results: Synovial fluid flavopiridol averaged 19 nM at week 1, gradually reduced to 1.4 nM by 4 weeks, and was generally below the detection limit at 5 and 6 weeks. There was no detectable flavopiridol in the plasma samples, and no adverse effects were observed at any time point., Clinical Relevance: Intra-articular injection of PLGA microparticle-encapsulated flavopiridol was well tolerated in horses, with detectable levels of flavopiridol in the synovial fluid out to 4 weeks with negligible systemic exposure. Flavopiridol is a cyclin-dependent kinase-9 inhibitor with potent anti-inflammatory and analgesic activity. The extended-release microparticle formulation promotes intra-articular retention of the drug and it may be an alternative to other intra-articular medications for treatment of equine joint disease.

Background: Pharmacokinetics of amikacin administered IV to neonatal foals are described, but little data are available regarding the plasma concentrations contributed by concurrent intra-articular (IA) administration., Hypothesis/objectives: Compare the pharmacokinetics of amikacin when the total dose is administered IV compared to being divided between IV and IA routes of administration in neonatal foals and predict the plasma concentrations from various combined IV and IA dosing regimens., Animals: Eight healthy neonatal foals., Methods: Foals received 3 amikacin treatment protocols: (1) IV-only (25 mg/kg q24h IV), (2) concurrent IV and IA (16.7 mg/kg q24h IV and 8.3 mg/kg q24h into 1 tarsocrural joint), and (3) IA-only (8.3 mg/kg q24h into 1 tarsocrural joint). Protocols were administered for 3 days beginning at 7, 14, and 21 days of age. Plasma concentrations ≥53 μg/mL at 30 minutes were considered therapeutic for isolates with intermediate susceptibility., Results: Foal age was a significant variable. The IV-only protocol met or exceeded the 30-minute plasma concentrations considered therapeutic (mean μg/mL [95% confidence interval, CI]) in 7- to 9-day-old (54.0 [52.2-56.9]), 14- to 16-day-old (58.1 [55.2-61.0]), and 21- to 23-day-old (66.6 [63.7-69.6]) foals. Concurrent IV and IA protocol did not reach the 30-minute concentration considered therapeutic in 7- to 9-day-old foals (46.5 [43.6-49.4]) but did in 14- to 16-day-old (62.9 [60.0-65.8]) and 21-to 23-day-old (62.6 [59.7-65.6]) foals., Conclusions and Clinical Importance: Concurrent IV and IA administration of amikacin produces 30-minute plasma concentrations considered therapeutic in foals 14 to 23 days old, but concentrations observed in younger foals might be below those considered therapeutic for isolates with intermediate susceptibility to amikacin., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: Polyacrylamide hydrogel (4% PAHG) is an inert viscoelastic supplement used to manage osteoarthritis in horses. Even with a prolonged clinical effect, horses may be administered multiple doses during their performance career. The effect of the serial 4% PAHG treatments is not known. The objectives of this study were to evaluate the clinical, histologic, and synovial fluid biomarker effects following serial administration of 4% PAHG in normal equine fetlock joints., Animals: 8 healthy horses., Methods: In a blinded, controlled in vivo study, horses received serial intra-articular injections of 4% PAHG (Noltrex Vet; Nucleus ProVets LLC) and contralateral 0.9% saline control on days 0, 45, 90, and 135. Treatment and control joints were randomly assigned. Synovial fluid was collected before administration of 4% PAHG or 0.9% saline on day 0 and at study completion for cellular and biomarker evaluation. Serial physical and lameness examinations were performed throughout the study. On day 240, gross examination and harvest of cartilage and synovial membrane for histology were completed., Results: There were no histologic changes in articular cartilage or synovial fluid biomarkers. The 4% PAHG was seen on the surface of the synovium in 5 of 8 treated joints 105 days after the last treatment. There are minimal effects following serial injections of 4% PAHG on normal joints in horses following administration at 0, 45, 90, and 135 days, with final evaluation on day 240., Clinical Relevance: Serial administration of intra-articular 4% PAHG in horses may provide long-term joint lubrication with no detrimental effects.

Background: Corticosteroids are a commonly used, inexpensive intra-articular treatment for osteoarthritis which may increase the risk for laminitis in horses due, in part, to hyperinsulinaemia. Humans with metabolic syndrome experience increases in insulin and glucose concentrations post-injection, but responses in horses are unknown., Objectives: To determine the effect of a single intra-articular (IA) dose of triamcinolone acetate (TA) on blood insulin and glucose concentrations., Study Design: Before-after study., Methods: Ten horses with normal insulin regulation as assessed by an oral sugar test received 18 mg of TA into one middle carpal joint. Insulin and glucose concentrations were evaluated at baseline and 4, 6, 8, 24, 48, and 72 h following IA corticosteroid injection. Differences from baseline were evaluated using a repeated measures ANOVA with Dunnett's multiple comparison testing or a Friedman test with Dunn's correction (significant at p < 0.05)., Results: Mean ± SD blood insulin concentration post IA TA injection was increased at 6 h (15.8 ± 3.1 μIU/mL, p = 0.01), 24 h (23 ± 5.8 μIU/mL, p ≤ 0.001), and 48 h (29 ± 13 μIU/mL, p ≤ 0.01) compared to baseline (10 ± 12.3 μIU/mL), with the peak at 48 h. Median ± 95% CI blood glucose concentration post IA TA injection was increased at 6 h (112.7 ± 20.3 mg/dL, p = 0.006), 8 h (112.9 ± 21.4 mg/dL, p = 0.004), 24 h (122.6 ± 14.6, p ≤ 0.0001), and 48 h (123.5 ± 15.4 mg/dL, p ≤ 0.0001) compared to baseline (89.2 ± 6.6 mg/dL), with the peak at 48 h., Main Limitations: Only horses with normal insulin regulation were evaluated., Conclusions: Blood insulin and glucose concentrations modestly increased for 48 h following IA TA., (© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Objective: To assess the efficacy of commercial intra-articular blood-derived allogeneic-induced mesenchymal stem cells (CIMSCs) to treat tarsometatarsal lameness in horses., Study Design: This was a retrospective cohort study., Animals: Records from 167 adult light breed horses with bilateral tarsometatarsal lameness., Methods: Horses with tarsometatarsal lameness were retrospectively selected from medical records. Diagnosis followed subjective graded lameness assessment before and after intra-articular analgesia, with graded radiographic tarsal examination. Horses were excluded if they were diagnosed or treated for any other concurrent lameness conditions during the study. Time to last follow-up and time of recurrence of lameness was recorded at veterinary re-assessment., Results: A total of 67 horses were recruited to the CIMSC-treated group and 100 to the corticosteroid (CS)-treated group. Median age was 9 years, with no difference in signalment, use or radiographic grade between groups. First re-examination was 38 days (95% CI: 38-49), with no difference between groups, CIMSC 42 (35-45), control 34 (25-42). Median follow-up was 438 days for CIMSC, 546 for controls. Symptoms of lameness recurred in 86/100 controls compared to 17/67 (25%) CIMSC. Median time to lameness recurring in CIMSC was 336 days (95% CI: 239-400), control 90 days (95% CI: 80-108), p < .0001. Cox proportional hazard ratio for treatment was 8.35, 95% CI: 4.67 to 14.92, p < .0001., Conclusions: Lameness was abolished in all treated horses. It recurred significantly less often, and later, in CIMSC-treated horses., Clinical Significance: Intra-articular CIMSC treatment results in prolonged soundness in horses with tarsometatarsal lameness., (© 2023 The Authors. Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Background: Intra-articular (IA) corticosteroids are regularly used in equine athletes for the control of joint inflammation., Objectives: The goal of this study was to use an acute synovitis inflammation model to determine the residual effects of IA betamethasone and triamcinolone acetonide on various inflammatory parameters and lameness., Study Design: Crossover randomised trial., Methods: Five mixed-breed, 2-year-old horses were randomly allocated to an IA treatment of the radiocarpal joint with 9 mg of either betamethasone or triamcinolone acetonide. Two weeks following treatment, horses were injected with 1 μg of lipopolysaccharide (LPS) diluted in 1 ml of saline. Following LPS injection, horses were crossed-over and both sets of injections were repeated after a washout period. Blood samples were collected at multiple time points for mRNA analysis, as well as serum amyloid A (SAA) and cortisol determination. At each time point, lameness was also subjectively scored. Additional injections with saline-only or LPS-only (twice) were conducted as negative and positive controls, respectively. Two-way repeated measures analysis of variance was used to analyse all data., Results: Corticosteroid-only treatments result in significant mRNA expression differences, as well as significant and prolonged cortisol suppression. Following LPS injection, there was a residual treatment effect with triamcinolone evidenced by a significant treatment effect on IL-6 and PTGS1 (cyclooxygenase-1), lameness, SAA and cortisol concentrations, while only IL-6 expression was affected by betamethasone., Main Limitations: The acute synovitis model used here results in significant inflammation and is not representative of the low-grade inflammation seen with typical joint disease and residual anti-inflammatory effects may be more profound in naturally occurring joint disease., Conclusions: Current regulatory guidelines may be insufficient if the concern is residual anti-inflammatory effects. Additionally, intra-articular corticosteroid administration is not without risk, as evidenced by a significant suppression of serum cortisol concentration and, as such, the benefits of their administration should be weighed against those risks., (© 2022 EVJ Ltd.)

The objective of this study was to describe the pharmacokinetics of intra-articular (IA) administered buprenorphine in horses with lipopolysaccharide (LPS)-induced synovitis. Radiocarpal synovitis was induced in six healthy adult horses with the IA injection of LPS (0.5 ng/joint) on two occasions in a randomized cross-over design. Treatments (IA buprenorphine (IAB) at 5 μg/kg plus intravenous saline; and intravenous buprenorphine (IVB) at 5 μg/kg plus IA saline) were administered 4 h following LPS injection. Concentrations of buprenorphine were assessed in plasma and synovial fluid (SF) at 0.5, 2, 6, 12, and 24 h after administration. Pharmacokinetic parameters after IVB and IAB in plasma and synovial fluid were calculated using a nonlinear mixed effects model. IAB was detectable in SF of all horses at 24 h [median concentration of 6.2 (3.46-22.6) ng/mL]. IAB resulted in a median plasma concentration of 0.59 (0.42-1.68) ng/mL at 0.5 h and was detectable in all subjects for up to 6 h and in two horses for up to 12 h. IVB resulted in SF concentrations detected up to 6 h in all horses [median concentration of 0.12 (0.07-0.82) ng/mL]. Results suggest that IA buprenorphine remains present in the inflamed joint for at least 24 h and systemic absorption occurs., (© 2023 John Wiley & Sons Ltd.)

The purpose of this study was to compare the extent of inflammation response in the middle carpal joints of healthy horses following intra-articular injection of 2% lidocaine, 0.5% bupivacaine, or 0.9% saline solution. The right middle carpal joint of 20 horses was injected with 5 mL of 0.5% bupivacaine (GB, n = 10) or 5 mL of 2% lidocaine (GL, n = 10). The left middle carpal joint of horses was used as a control (5 mL 0.9% saline). Serum and synovial fluid (SF) were aseptically collected before and at predetermined times after each injection. Serum and synovial fluid protein, albumin, transferrin, haptoglobin, ceruloplasmin, α1-antitripsin, and α1-acid glycoprotein concentrations were measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis and compared among treatments. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student-Newman-Keuls test (P < .05). Both lidocaine and bupivacaine induced serum and SF changes indicative of inflammation, but the magnitude of those changes was more pronounced for lidocaine. Administration of 0.9% saline also induced an inflammatory reaction, but the magnitude of these changes was less pronounced than those caused by GB and GL. The results suggested that bupivacaine is safer than lidocaine for intra-articular injection in horses. Saline solution should not be used as an adjunct to intra-articular injections in horses., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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&#95;2018&#95;002.

Background: The outcome and interpretation of intra-synovial diagnostic analgesia of the distal interphalangeal joint (DIPJ) and the navicular bursa (NB) remain in dispute, and no objective studies have been carried out to establish the percentage of improvement over time from these two analgesia techniques., Objectives: To investigate the qualitative and time-dependent outcome of DIPJ-A and NB-A in naturally occurring forelimb lameness., Study Design: Case series., Methods: Twenty-three clinical cases with forelimb lameness were evaluated objectively using a body mounted inertial sensor system (BMIS). Lameness was localised to the foot with a palmar digital nerve block and/or an abaxial sesamoidean nerve block on day 1, and analgesia of the DIPJ (DIPJ-A) and NB (NB-A) were performed on days 2 and 3. Improvement following perineural analgesia was measured after 10 min and intra-synovial blocks after 2-, 5- and 10-min. Horses with at least 70% improvement measured objectively after diagnostic analgesia were included in the study., Results: There was no significant association between improvement following perineural analgesia and the DIPJ-A and NB-A. The mean improvement in the lameness differed between DIPJ-A and NB-A at 2 min (p < 0.001) and at 5 min (p = 0.04), and it was no longer observed after 10 min (p = 0.06). A positive NB-A produced a high degree of improvement that remained stable, whereas the DIPJ-A improved over time., Main Limitations: Perineural and intra-synovial analgesia were performed without contrast medium to assess the diffusion of mepivacaine., Conclusions: Our results suggest that perineural analgesia is not reliable enough to differentiate pain originating from DIPJ and NB. Early evaluation of the DIPJ-A and NB-A can determine the origin of the pain. An improvement following NB-A was constant over time, but an improvement following DIPJ-A varied by up to 10 min., (© 2022 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

No current treatments available halt osteoarthritis progression in horses or humans. Intra-articular injection of mitochondria is a novel treatment that has the potential to improve cell metabolism and decrease inflammation, but safety of this treatment has yet to be established in the horse. Autologous blood-derived mitochondria isolated using a commercially available kit were injected into the left carpus joint of 3 horses which were monitored for 28 days. Horses received physical examinations, video recorded gait evaluations, joint diameter measurement, synovial fluid collection, and blood collection on day 0 (baseline prior to mitotherapy, day of mitochondria injection), 1, 3, 7, 14, and 28. Systemic inflammation was assessed via complete blood count, fibrinogen, and plasma serum amyloid A (SAA). Local inflammation was assessed via synovial fluid cytology and physical examination parameters. Physical exam parameters remained stable and no joint swelling was observed after mitotherapy. No change was noted in video recorded gait evaluations as determined by a blinded evaluator. Complete blood counts revealed no significant increase in white blood cells. SAA only increased mildly in 1 horse. Fibrinogen became slightly elevated above reference range in 2 horses at day 7, but later normalized. Mild increases in synovial fluid nucleated cell counts and total protein occurred on day 1 and 3, but resolved within 7 days without intervention. Autologous mitochondria injection into the equine intercarpal joint was well tolerated with no signs of inflammation. This safety information allows for future studies evaluating mitotherapy efficacy., Competing Interests: Financial disclosure Financial support was provided by the Center for Equine Health at UC Davis with funds provided by the State of California satellite wagering funds and contributions by private donors., (Published by Elsevier Inc.)

Objective: Evaluate effects of acellular equine liquid amnion allograft (ELAA) injected into healthy equine joints., Study Design: Randomized, blinded, controlled experiment., Animals: Eight healthy adult horses., Methods: One intercarpal joint (ICJ) of each horse was randomly assigned to be injected with 1.5 ml of ELAA (treatment) while the contralateral ICJ was injected with 1.5 ml of 0.9% NaCl (control). Subjective lameness evaluation, force plate analysis, and synovial fluid analysis, including interleukin-1 receptor antagonist (IL-1ra) analysis, were performed before (day 0) and at days 1, 3, 5, and 10. Synovial fluid analysis was also performed on days 20 and 30., Results: No difference in subjective lameness (P = .75) and no decrease in peak vertical force or vertical impulse were seen in any limb on any day. Total nucleated cell count (TNCC) was increased in treatment joints on days 1 (P = .0007; T: 6039 cells/μl, C: 240 cells/μl) and 3 (P < .0001; T: 1119 cells/μl, C: 240 cells/μl). Log-10 transformed values for IL-1ra were higher in treated joints on days 1 (P = .0005; T: 3553.7 pg/ml, C: 1890.1 pg/ml) and 3 (P = .01; T: 2283.2 pg/ml, C: 1250.7 pg/ml)., Conclusion: Injection of ELAA into the ICJ caused an increase in synovial fluid TNCC in comparison with saline control but no lameness was observed. There was increased IL-1ra on days 1 and 3 after ELAA injection., Clinical Significance: Intra-articular injection of ELAA into healthy equine joints results in no significant safety concerns. The observed increase in IL-1ra may provide beneficial effects in inflamed joints., (© 2022 American College of Veterinary Surgeons.)

Background: Intra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. Secondarily, pharmacodynamic effects, including effects on joint circumference, joint flexion, and lameness following intra-articular administration of isoflupredone acetate in the experimental model were described., Methods: Sixteen horses received a single intra-articular dose of 8 mg of isoflupredone acetate or saline 12 h post-administration of lipopolysaccharide. Blood and urine samples were collected up to 72 h and synovial fluid for 28 days post-administration, drug concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed. Joint circumference, maximum angle of pain free joint flexion and lameness were evaluated prior to and post-treatment., Results: The maximum isoflupredone plasma concentration was 2.45 ± 0.61 ng/mL at 2.5 ± 0.75 h and concentrations were less than the limit of quantitation by 72 h. Isoflupredone was below detectable concentrations in urine by 72 h post-administration in all horses and no longer detectable in synovial fluid by 96 h post-administration. Joint circumference was significantly decreased in the isoflupredone treatment group compared to the saline group at 24 and 48 h post drug administration. Pain free joint flexion was significantly different between the saline and isoflupredone treatment groups on day 4 post-treatment., Conclusions: Synovial fluid concentrations and maximum plasma concentrations of isoflupredone differed slightly between the current study and a previous one describing administration into a non-inflamed joint, however, the detection time of isoflupredone in blood was comparable. Effects of isoflupredone on joint circumference and degree of pain free joint flexion suggest a short duration of effect with respect to alleviation of lipopolysaccharide induced synovitis, however, results of this study support future studies of the anti-inflammatory effects of intra-articular isoflupredone acetate., (© 2022. The Author(s).)

Objective: The goal of this study was to determine plasma, urine, and synovial fluid concentrations and describe the effects on biomarkers of cartilage toxicity following intra-articular dexmedetomidine administration to horses., Animals: 12 research horses., Procedures: Horses received a single intra-articular administration of 1 μg/kg or 5 μg/kg dexmedetomidine or saline. Plasma, urine, and synovial fluid were collected prior to and up to 48 hours postadministration, and concentrations were determined. The effects on CS846 and C2C were determined in synovial fluid at 0, 12, and 24 hours postadministration using immunoassays., Results: Plasma concentrations of dexmedetomidine fell below the limit of quantification (LOQ) (0.005 ng/mL) by 2.5 and 8 hours postadministration of 1 and 5 μg/kg, respectively. Synovial fluid concentrations were above the LOQ (0.1 ng/mL) of the assay at 24 hours in both dose groups. Drug was not detected in urine samples at any time postdrug administration. CS846 concentrations were significantly decreased relative to baseline at 12 hours postadministration in the saline group and significantly increased in the 5-μg/kg-dose group at 24 hours. Concentrations of C2C were significantly decreased at 12 and 24 hours postadministration in the saline treatment group. There were no significant differences in CS846 or C2C concentrations between dose groups at any time., Clinical Relevance: Systemic concentrations of dexmedetomidine remained low, compared to synovial fluid concentrations. CS846, a marker of articular cartilage synthesis, increased in a dose-dependent fashion. Based on these findings, further dose titration and investigation of analgesic and adverse effects are warranted.

Recent clinical and experimental trials have demonstrated that intra-articular 2.5% Polyacrylamide hydrogel (PAAG) is highly effective (82.5% free of lameness horses at 2 year follow-up), lasting and safe for the treatment of equine osteoarthritis (OA). Over the last decade, intra-articular 2.5% PAAG has shown to be a potent and promising drug in the medication of OA in horses, as no other single medical treatment for OA has such prolonged efficacy. Most of these studies were presenting some limitations. Preliminary observations on the mechanisms of action of intra-articular 2.5% PAAG support a mechanical effect through integration into the synovial membrane, an increase in joint elasticity possibly reducing overall joint capsule stiffness, and provision of lasting viscosupplementation which contributes to protecting articular surfaces. In addition, no effects on pro-inflammatory cytokines have been observed. Studies also suggest that these positive effects occur in the absence of intra-articular neurotoxicity or fibrosis. The effect on the synovial membrane and joint capsule and the long-acting viscosupplementation represent new concepts in the management of equine OA. Horse; Osteoarthritis, Medication, 2.5% polyacrylamide hydrogel., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Osteoarthritis is a progressive degenerative disease affecting joints. It is associated with structural and functional changes that cause lameness and pain in dogs. Mesenchymal stem cells (MSCs) are considered an ideal therapeutic candidate for treating inflammatory musculoskeletal conditions due to their paracrine and immunomodulatory characteristics. They are delivered intravenously or as intra-articular injections for treating canine osteoarthritis. However, ex vivo studies have confirmed that the osteoarthritic synovial fluid is cytotoxic to cultured MSCs. Therefore, intra-articular transplantation of viable MSCs should be considered counterproductive since it minimizes cellular viability. Similarly, the intravenous administration of MSCs limits the therapeutic effects on the organ of interest since most of the administered cells get trapped in the lungs. Therefore, cell-free therapeutic strategies such as conditioned media and extracellular vesicles (EVs) can potentially become the future of MSC-based therapy in managing canine osteoarthritis. It overcomes the limitations of MSC-based therapy, such as tumor differentiation, immunogenicity, and pulmonary embolization, and has advantages like low immunogenicity and off-shelf availability. In addition, they eliminate problems such as low cell survival, transmission of infections, and unpredictable behavior of the transplanted MSCs, thereby acting as a safe alternative to cell-based therapeutics. However, very limited data is available on the efficacy and safety of cell-free therapy using MSCs for managing canine osteoarthritis. Therefore, large-scale, multicentric, randomized clinical controlled trials are required to establish the therapeutic efficacy and safety of MSC-based cell-free therapy in clinical cases of canine osteoarthritis.

Objective: To demonstrate the efficacy and safety of mesenchymal stem cells (MSCs) for xenogeneic use with intra-articular administration in dogs with osteoarthritis., Animals: 80 client-owned dogs with naturally occurring osteoarthritis in elbow or hip., Procedures: A multicentric, double-blinded, parallel, randomized and placebo-controlled clinical trial was performed. After intra-articular injection of equine umbilical cord MSCs, dogs were reexamined at weeks 4, 8, and 12 using a force platform (gait analysis), orthopedic assessment, and validated owner questionnaire. Eighteen months after treatment, a long-term follow-up was done., Results: Best results were obtained 8 weeks after treatment, where 63% of the patients showed an improvement in the gait analysis. Also 8 weeks after treatment, 77% of the dogs improved in the orthopedic examination; 65% of the owners considered that the treatment improved their pet's quality of life 8 weeks after treatment. The long-term follow-up revealed that 59% of the owners observed a duration of effect longer than 6 months after a single intra-articular injection of equine umbilical cord MSCs. No systemic or permanent adverse events were detected at any time point., Clinical Relevance: Results of this study demonstrated the safety and efficacy of intra-articular administration of xenogeneic MSCs for the treatment of canine osteoarthritis.

Objective: Mesenchymal stromal (stem) cells (MSCs) have been studied to treat many common orthopedic injuries in horses. However, there is limited information available on when and how to use this treatment effectively. The aim of this retrospective study is to report case features, treatment protocols, and clinical outcomes in horses treated with MSCs., Animals: 65 horses presenting with tendinous, ligamentous, and articular injuries, and treated with MSCs prepared by a single laboratory between 2016 and 2019. Outcome information was available for 26 horses., Procedures: Signalment, clinical signs, diagnostic methods, treatment protocol features (prior and concurrent therapies, cell origin, dose, application site and number), and effective outcomes were analyzed. The analysis was focused on comparing the effect of different MSC treatment protocols (eg, autologous vs allogeneic) on outcome rather than the effectiveness of MSC treatment., Results: MSC treatment resulted in 59.1% (clinical lameness) to 76.9% (imaging structure) improvement in horses with diverse ages, breeds, sex, and lesions. The use of other therapeutic methods before MSC application (eg, anti-inflammatories, shockwave, laser, icing, resting, bandage and stack wrap, intra-articular injections, and/or surgical debridement) was shown to be statistically more effective compared to MSCs used as the primary therapeutic procedure (P < .05). Autologous versus allogeneic treatment outcomes were not significantly different., Clinical Relevance: A prospective MSC treatment study with standardization and controls to evaluate the different features of MSC treatment protocols is needed. The various case presentations and treatment protocols evaluated can be used to inform practitioners who are currently using MSCs in clinical practice.

Background: Osteoarthritis represents a significant welfare problem for many dogs, with limited therapeutic options other than palliative pain control. To evaluate the effect of the intra-articular administration of blood cell secretome and triamcinolone, 15 dogs with bilateral hip osteoarthritis were randomly assigned to a blood cell secretome (BCSG, n = 5), triamcinolone (TG) or their combination group (BCS + TG, n = 5). BCSG received a single intra-articular administration of 3 ml of blood cell secretome, TG 0.5 ml of triamcinolone acetonide 40 mg/ml, and BCS + TG received the combined products. The volume to administrate was corrected to 3.5 ml with saline. On days 0, 8, 15, 30, 60, 90, 120, 150, and 180, a copy of the Canine Brief Pain Inventory (divided into pain interference score-PIS and Pain Severity Score-PSS), Liverpool Osteoarthritis in Dogs (LOAD), Hudson Visual Analogue Scale (HVAS), and Canine Orthopedic Index (COI, divided into function, gait, stiffness, and quality of life) was completed. Results were analyzed with the Kruskal-Wallis test and the Kaplan-Meier estimators were conducted and compared with the Log Rank test, p < 0.05., Results: Animals in the sample had a mean age of 9.0 ± 2.9 years and a bodyweight of 28.8 ± 4.1 kg. Hips were classified as moderate (8) and severe (7) osteoarthritis. No differences were found between groups at T0 regarding considered evaluations. Significant differences were observed between groups in pain scores from + 8d- + 150d, with BCS + TG exhibiting better results. The same was observed for HVAS and LOAD, from + 8d- + 120d. Improvements were also observed in several dimensions of the COI. Kaplan-Meier estimators showed that BCS + TG produced longer periods with better results, followed by BCSG and TG., Conclusion: The intra-articular administration of blood cell secretome improved the clinical signs and scores of several clinical metrology instruments in dogs with hip OA, particularly when combined with triamcinolone. Further studies are required., (© 2022. The Author(s).)

Intra-articular injections are routinely performed to alleviate pain and inflammation associated with osteoarthritis in horses. Intra-articular injections require accurate needle placement to optimize clinical outcomes and minimize complications. This study's objectives were to develop and validate a three-dimensional (3D) printed model of an equine cervical articular process joint to teach ultrasound-guided injections. Five identical models of an equine cervical articular process joint were 3D printed and embedded in 10% ballistic gelatin. Experts' and novices' ability to successfully insert a needle into the joint space of the model using ultrasound guidance was assessed and graded using an objective structured clinical examination (OSCE). Scores from experts and novices were compared to evaluate the construct validity of the model. Participants also answered a survey assessing the face and content validity of the model. Experts required less time (22.51 seconds) for correct needle placement into the model joint space than novices (35.96 seconds); however, this difference was not significant ( p = .53). Experts' median total OSCE score (14) was significantly higher ( p = .03) than novices' (12), supporting the model's construct validity. Participants agreed on the face and content validity of the model by grading all survey questions greater than 7 on a 10-point Likert-type scale. In summary, we successfully developed a 3D printed model of an equine cervical articular process joint, partially demonstrated the construct validity of the model, and proved the face and content validity of this new training tool.

Intra-articular injections are a nonsurgical treatment modality that can be used to manage osteoarthritis, naturally occurring or surgically induced acute synovitis, and intra-articular ligamentous or tendon injury. This option may be assistive for patients in which other conservative modalities are ineffective, or in conjunction with other forms of treatment. It may also be used as the primary treatment. Injectates labeled for use in companion animal joints include corticosteroids and viscosupplements. Additional injectates, that are not specifically approved for use in companion animals are but are reported in the literature, include orthobiologics and a radioisotope of Tin-117m., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Indications for injecting synovial joints may include diagnostic, therapeutic, or combination. Diagnostic injectates aim to reduce or eliminate the contribution of pain to lameness and may be assessed both subjectively or objectively by the clinician. Diagnostic joint injections are not specific for a disease and their limitations must be remembered when interpreting a response-including false-negative results. Patient selection and sterile technique throughout the procedure minimize adverse effects. Risks of intra-articular (IA) injections may include transient soreness, cartilage damage, and, rarely, septic arthritis. Ultrasound guidance with a trained clinician may provide further benefits including the reduction of periprocedural discomfort, reduction in iatrogenic cartilage damage during needle insertion, and improvement in synovial fluid feedback. The removal of some synovial fluid before administering an IA injection should be considered to confirm needle placement, provide diagnostic sampling, and help accommodate injectate volume., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Frequency of synovial sepsis in horses following intrasynovial injection has been reported, but not compared with respect to the environment in which the injection was performed., Objectives: To describe occurrence of synovial sepsis following intrasynovial injections performed in ambulatory vs hospital settings., Study Design: Retrospective cohort study., Methods: Records from the Colorado State University were evaluated (2014-2018) and horses receiving intrasynovial injections were identified. Patients presenting for septic synovial structures were excluded. Patient signalment, primary supervising service, medications injected, location (field/hospital), whether synovial sepsis resulted, and at what time sepsis was recognised were recorded. Logistic regression was used to estimate the contributions of covariates to the occurrence of synovial sepsis following injection., Results: During the study period, 3866 intrasynovial injections were performed in 1112 horses during 1623 sessions, with 643/1623 sessions performed in the field. The most frequently used medications were hyaluronate (846/1623, 52.1%), triamcinolone acetonide (780 /1623, 48.1%) and amikacin sulfate (684/1623, 42.1%). Four horses developed synovial sepsis (0.2% sessions, 0.1% synovial structures); 3/4 were injected in the field, 2/4 received antibiotics with the injection. The frequency of septic synovitis was 10.4 cases per 10 000 injections, or 1 in 967 injections. All horses recovered following synovial lavage and antibiotic therapy. Performing injections in the field (P = .2) or without antibiotics (P = .7) did not alter the risk of synovial sepsis., Main Limitations: Limitations include the retrospective nature of data collection and low rate of infection overall, which prohibited evaluation of individual medication regimes as factors associated with resultant infection., Conclusions: The frequency of synovial sepsis in this population of horses was not higher when injections were performed in the field or without concurrent antibiotic administration. These data may help to inform practitioners and clients regarding the relative potential risk of complications following intrasynovial medication in different environmental settings., (© 2021 EVJ Ltd.)

Background: Hemoderivatives such as autologous conditioned serum (ACS) and platelet-rich plasma (PRP) have been used as potential disease-modifying therapies in musculoskeletal disorders such as osteoarthritis (OA). These therapies are based on the delivery of multiple growth factors and anti-inflammatory cytokines that are known to participate in inflammatory processes. The variability of cytokine content due to the autologous nature of the product, the non-availability for immediate use and need for storage at low temperatures are limitations for its use in the field. An allogeneic freeze-dried conditioned serum (CS) and PRP would provide field clinicians with a more practical approach to use such products in daily practice. Based on in vitro preliminary data, this experimental study aimed to test the in vivo safety of allogeneic freeze-dried CS and PRP in healthy joints, using the horse as a model., Results: Eight horses were randomly assigned and treated with PRP or CS. Horses had three joints injected with ALLO-FD PRP or CS, and three contralateral joints injected with the AUTO version of the same product, by a blinded clinician. Horses were evaluated clinically, and had synovial fluid collected at different time points and evaluated for cell content, PGE 2 and protein. Both CS and PRP products triggered a self-limiting and mild inflammatory response in equine healthy joints. This was indicated by the transient increase in nucleated cell count, PGE 2 and total protein in synovial fluid. This mild inflammatory response did not result in significant lameness and was not different among the groups., Conclusions: The allogeneic freeze-dried PRP and CS showed to be overall safe and not dissimilar compared to their autologous frozen version in equine healthy joints. Further studies are necessary to evaluate the modulatory effects of these therapies in a clinical setting., (© 2022. The Author(s).)

Objective:  The aim of this study was to evaluate the functional, systemic, synovial and articular changes after intra-articular administration of a synthetic lubricin within healthy canine stifles., Study Design:  A prospective randomized blinded placebo-controlled study composed of 10 dogs equally divided into either a treatment group (intra-articular synthetic lubricin injection, n  = 5) or control group (saline, n  = 5). Clinical (orthopaedic examination, gait observation, gait analysis), biochemical (complete blood count and biochemistry profile) and local tissue outcomes (joint fluid analysis, joint capsule and articular cartilage histopathology) were evaluated over a time period of 3 months., Results:  No significant differences between the treatment group and control group were identified with regard to baseline patient parameters. No clinically significant orthopaedic examination abnormalities, gait abnormalities, biochemical alterations, joint fluid alterations or histopathological alterations were identified over the course of the study., Conclusion:  The synthetic lubricin studied herein is both biocompatible and safe for a single administration within the canine stifle joint. Further research is necessary to evaluate the clinical efficacy of the synthetic lubricin in canine osteoarthritic joints., Competing Interests: D.P. is listed as an inventor on various patents assigned to Cornell University that are associated with materials disclosed in this manuscript. There is no financial or other conflict of interest of any author related to a company or product used in the report. This study was never presented at any meetings., (Thieme. All rights reserved.)

Intra-articular administration of sustained-release anti-inflammatory drugs is indicated in horses suffering from joint inflammation, but no such drugs are labelled for veterinary use. To obtain initial data on synovial disposition and safety of a new sustained-release formulation of diclofenac (SYN321) in the joints of horses, an experimental interventional study of elimination and side effects of intra-articular administration of SYN321 was conducted. Nine clinically sound horses were included in the study, and SYN321 was administered by the intra-articular route. Dose ranges and sampling intervals were established in a pilot study with two horses, and then applied in a main study involving seven horses treated in the fetlock joint. Diclofenac was detected above lower limit of quantification (LOQ: 0.5 ng/ml) in synovial fluid throughout the study period (14 days), and below LOQ (0.1 ng/ml) in plasma after 4 days and in urine after 14 days. No obvious clinical side effects were detected. Clinical examination and objective lameness evaluation suggested that SYN321 has potential as a local joint NSAID treatment with sustained release in horses, but further studies on synovial fluid exposure, safety and clinical efficacy are warranted., (© 2021 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.)

Introduction: The sesamoid disease is a cause of lameness in dogs, and there is limited literature relating to diagnosis, treatment and outcome of treatment in dogs with the sesamoid disease. Our aim was to compare the efficacy of intra-articular metacarpophalangeal/metatarsophalangeal joint injection with methylprednisolone and bupivacaine (IMPB) or conservative management with nonsteroidal anti-inflammatories and rest (CMNR) for treatment of this disease., Materials and Methods: We conducted a retrospective survey of dogs treated for the sesamoid disease with IMPB or CMNR. The medical records of all dogs that received IMPB or were recommended CMNR for treatment of sesamoid pain were reviewed, and a client questionnaire was delivered to owners. Response to treatment, rapidity of response, length of resolution and recurrence of clinical signs associated with the sesamoid disease were assessed., Results: A total of 78 dogs were included in the study. One week after IMPB, 52/58 (89.7%) dogs demonstrated resolution of lameness compared with 1 week of CMNR, 0/18 (P < 0.001). There was limited statistical evidence in client satisfaction between treatment groups, IMPB 36/53 (67.9%) and CMNR 16/17 (94%) (P = 0.052). Dogs presenting with the sesamoid disease had comorbidities in 51/78 (65.4%) of cases. Elbow disease was the most common comorbidity 29/78 (37.2%)., Conclusion: Our results support the use of IMPB for short-term (1 week) resolution of lameness associated with sesamoid disease in dogs. Dogs treated with CMNR had slower improvement; however, there was no difference in lameness or client satisfaction between treatment groups at long-term follow-up (12 months)., (© 2021 Australian Veterinary Association.)

Botulinum toxin type A (BoNT-A) is a promising alternative for patients suffering from chronic joint pain. The aim of this study was to investigate whether a single injection of BoNT-A would produce adverse effects on clinical parameters and synovial parameters as well as lameness. One randomly selected radiocarpal joint was treated with 50 U of BoNT-A in eight horses, and the contralateral joint received saline solution. All horses received injections at day 0 and were re-evaluated twice daily for 7 days for heart rate (HR), respiratory rate (RR), rectal temperature (RT), mucous membrane color, capillary refill time, intestinal motility, appetite, water intake, defecation, urination, and attitude. At these same time points, joint pain and circumference were assessed. Objective lameness evaluations were performed once daily for 7 days and synovial fluid samples were collected at baseline, post-injection hour (PIH) 24 and PIH 168 and evaluated for synovial fluid parameters. HR and RT remained clinically unaltered, despite oscillations over time (P = .001). The remaining clinical parameters were unaltered by treatment or time (P > .05). Joint pain was not elicited by flexion and palpation in both limbs as well as carpal circumference was not altered (P = .88). Lameness was observed only on saline limbs. Cellular parameters evaluated in synovial fluid samples from both carpi had significantly increased from baseline to PIH 24, decreasing at PIH 168 (P < .05). It was concluded that the injection of 50 U BoNT-A is suggested to be a safe therapy for intra-articular use in horses and must be verified by further investigation., Competing Interests: Declaration of Competing Interest All authors declare no financial or personal relationships with people or organizations that could inappropriately influence or bias this study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The use of lipopolysaccharide to induce a localized source of inflammation (acute synovitis) and allow for monitoring of changes in systemic mRNA expression has been recently reported. Here, the goal was to maintain a significant systemic mRNA response while limiting the severity of lameness such that this model can be used to examine the effects of various anti-inflammatory treatment modalities on mRNA expression. Three mixed breeds, four-year-old geldings were utilized for this study. One milliliter of phosphate-buffered saline containing 1,000 ng or less of lipopolysaccharide from E. coli O111:B4 was aseptically injected into alternating radiocarpal joints following washout periods. Blood for complete blood cell count, serum amyloid A concentration, and mRNA analysis via RT-qPCR for 23 different genes were collected before each injection, as well as at multiple times post-injection. Lameness severity was also graded at each time point. Two-way, repeated measures analysis of variance was used for statistical analysis (P < .05). Results largely replicated those previously reported, with multiple genes exhibiting significant expression changes during the acute inflammatory period (including increases in CD14, TLR4, IL-1β, IL1RN, MMP1, and MMP9 expression) while some demonstrated dose-dependent changes; significant increases in complete blood cell count parameters and serum amyloid A concentrations were also noted. Attempts to temper the severity of lameness were not successful as nonweight bearing lameness was noted at doses of 10ng or higher, while a dose of 1ng elicited neither a detectable lameness nor a significant change in mRNA expression., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Antibiotics have been injected intra-articularly by equine veterinarians for decades, either prophylactically when other drugs are administered for osteoarthritis or therapeutically to treat septic arthritis. This route of administration has also more recently gained attention in human orthopaedic clinical practice, particularly as an alternative to systemic antibiotic administration to treat infections following prosthetic arthroplasty. While the rationale for injecting antibiotics intra-articularly has been largely focused on achieving high local drug concentrations, there has been relatively little focus on pharmacokinetic parameters of antibiotics administered by this route, or on the potential for local toxicity. The increasing incidence of antibiotic resistance in veterinary and human medicine prompts reconsideration of off-label antibiotic usage and evaluation of evidence-based dosing strategies. The purpose of this review was to summarise the current literature describing intra-articular antibiotic usage, including specific studies where pharmacokinetics, potential safety and toxicity have been evaluated. This review will advance practitioners' understanding of the use of intra-articularly administered antibiotics, including the overall pros and cons of the approach., (© 2021 EVJ Ltd.)

The purpose of this prospective double-blinded positive control study was to compare the efficacy of 2.5% polyacrylamide hydrogel (2.5% PAAG) in the management of middle carpal joint lameness in Thoroughbreds against treatments of triamcinolone acetonide (TA) or sodium hyaluronate (HA). A total of 31 flat-racing Thoroughbreds with lameness (grade 1-3/5) localized to the carpus by intra-articular analgesia were selected. Following a radiological assessment of the carpi confirming the absence of fragment/fracture, the horses were randomly assigned for intra-articular treatment with either 2 ml of 2.5% PAAG, 12 mg TA or 20 mg HA (followed by two further intravenous treatments of 40 mg, at weekly intervals in the HA group only), by a treating veterinarian. All horses were rested for 48 hours post-treatment and then re-entered an unaltered training regimen. Subsequent examinations at 2, 4, and 6 weeks were performed by a blinded examining veterinarian for all groups, while horses treated with 2.5% PAAG were monitored for 12 weeks for recurrence of lameness. Significantly more joints treated with 2.5% PAAG were lame free (83%) at 6 weeks compared to TA (27%; P = .007) and to HA (40%; P = .04). There was no significant difference between TA and HA groups at any time. All the joints treated within 2.5% PAAG that were lame free at 6 weeks (10/12) were still lame-free at 12 weeks. In conclusion, treatment with 2.5% PAAG led to statistically superior results compared to TA and HA in the management of selected middle carpal joint lameness in flat-racing Thoroughbreds, with therapeutic effects persisting up to 12 weeks., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Intra-articular triamcinolone acetonide is a widely used treatment for joint inflammation despite limited scientific evidence of its efficacy., Objectives: To investigate if intra-articular triamcinolone acetonide has sustained anti-inflammatory effects using an equine model of repeated joint inflammation., Study Design: Randomised controlled experimental study., Method: For three consecutive cycles 2 weeks apart, inflammation was induced in both middle carpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After the first LPS injection only, treatment with 12 mg triamcinolone acetonide (TA) followed in one randomly assigned joint, while the contralateral joint was treated with sterile saline (control). Clinical parameters (composite welfare scores, joint effusion, joint circumference) were recorded and synovial fluid samples were analysed for various biomarkers (total protein, WBCC; PGE 2 ; CCL2; TNFα; MMP; GAGs; C2C; CPII) at fixed timepoints (post injection hours 0, 8, 24, 72 and 168). The effects of time and treatment on clinical and synovial fluid parameters and the presence of time-treatment interactions were tested using a linear mixed model for repeated measures with horse as a random effect, and time and treatment as fixed effects., Results: The TA treated joints showed significantly higher peak synovial GAG concentrations (Difference in means 283.1875 µg/mL, 95% CI 179.8, 386.6, P < 0.000), and PGE 2 levels (Difference in means 77.8025 pg/mL, 95% CI 21.2, 134.4, P < 0.007) after the first inflammation induction. Significantly lower TP levels were seen with TA treatment after the second induction (Difference in means -7.5 g/L, 95% CI -14.8, -0.20, P < 0.04) . Significantly lower WBCC levels were noted with TA treatment after the first (Difference in means -23.7125 × 10 9  cells/L, 95% CI -46.7, -0.7, P < 0.04) and second (Difference in means -35.95 × 10 9  cells/L, 95% CI -59.0, -12.9, P < 0.002) inflammation inductions. Significantly lower general MMP activity was also seen with TA treatment after the second inflammation inductions (Difference in means -51.65 RFU/s, 95% CI -92.4, -10.9, P < 0.01)., Main Limitations: This experimental study cannot fully reflect natural joint disease., Conclusions: In this model, intra-articular TA seems to have some anti-inflammatory activity (demonstrated by reductions in TP, WBCC and general MMP activity) up to 2 weeks post treatment but not at 4 weeks. This anti-inflammatory effect appeared to outlast a shorter-lived, potentially detrimental effect illustrated by increased synovial GAG and PGE 2 levels after the first induction., (© 2020 EVJ Ltd.)

Background: Accuracy of intrasynovial injections can be challenging to assess in a clinical setting in horses. Contrast-enhanced ultrasonography (CEUS) using injectate agitated with air has been used to determine the success rates of synovial injections in human rheumatology., Objectives: To assess the diagnostic sensitivity and specificity of CEUS and to describe its clinical use., Study Designs: Cadaveric study followed by a prospective descriptive observational study., Methods: Part 1: CEUS was performed following injection of agitated methylene-blue solution targeting 13 different anatomical synovial structures from three equine cadavers. Contrast was seen as hyperechoic dots, patches or lines on ultrasonography. CEUS was classified as positive if contrast was considered to be intrasynovial and negative if contrast was considered to be extrasynovial. A second synoviocentesis was performed to determine if the injection was intrasynovial based on the presence or absence of methylene-blue. Estimates of sensitivity and specificity were calculated. Part 2: CEUS was performed following injection of agitated solutions targeting synovial structures as part of routine investigation and treatment of clinical cases., Results: Part 1: CEUS was correctly classified as positive or negative in all intrasynovial and extrasynovial injections respectively. The sensitivity estimate was 100% (CI 93%-100%) and the specificity estimates was 100% (CI 16%-100%). Part 2: The technique was used safely for 26 injections (14 horses; 19 different synovial structures) administered to localise or treat lameness. Traumatic intersynovial communications or synovial membrane defects were identified using CEUS in 3 horses., Main Limitations: The low number of extrasynovial injections in Part 1 resulted in an imprecise specificity estimate., Conclusions: In horses, CEUS performed following intended intrasynovial injection can be useful for identifying unsuccessful injections., (© 2020 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Dietary intervention may be a valuable strategy to optimize the intra-articular environment in young horses to prolong their performance career. To test the hypothesis that dietary supplementation of a Saccharomyces cerevisiae fermentation product would reduce markers of joint inflammation and increase markers of cartilage metabolism following a single inflammatory insult, Quarter Horse yearlings (mean ± SD; 9 ± 1.0 mo) were balanced by age, sex, body weight (BW), and farm of origin and randomly assigned to the following treatment groups: 1.25% BW/d (dry matter basis) custom-formulated concentrate only (CON; n = 9) or concentrate top-dressed with 21 g/d S. cerevisiae fermentation product (SCFP; n = 10) for 98 d. Horses had ad libitum access to Coastal bermudagrass hay. On day 84, one randomly selected radial carpal joint from each horse was injected with 0.5 ng lipopolysaccharide (LPS) solution. The remaining carpal joint was injected with sterile lactated Ringer's solution as a contralateral control. Synovial fluid obtained before supplementation (day 0) and on day 84 at preinjection hour 0 and 6, 12, 24, 168, and 336 h postinjection was analyzed for prostaglandin E2 (PGE2), carboxypropeptide of type II collagen (CPII), and collagenase cleavage neopeptide (C2C) by commercial assays. Rectal temperature, heart rate, respiration rate, carpal surface temperature, and carpal circumference were recorded prior to each sample collection and for 24 h postinjection. Data were analyzed using linear models with repeated measures. From day 0 to 84, synovial C2C declined (P ≤ 0.01) and the CPII:C2C ratio increased (P ≤ 0.01) in all horses with no effect of diet. In response to intra-articular LPS, synovial PGE2 increased by hour 6 (P ≤ 0.01) and returned to baseline by hour 336; CPII increased by hour 12, remained elevated through hour 168 (P ≤ 0.01), and returned to baseline by hour 336; and C2C increased by hour 6 (P ≤ 0.01) but did not return to baseline through hour 336 (P ≤ 0.01). Post-intra-articular injection, PGE2 levels were lower in SCFP than CON horses (P = 0.01) regardless of injection type. Synovial CPII and the CPII:C2C ratio demonstrated stability during the LPS challenge in SCFP compared with CON horses (P ≤ 0.01). Clinical parameters were not influenced by diet but increased in response to repeated arthrocentesis (P ≤ 0.01). Dietary SCFP may favorably modulate intra-articular inflammation following an acute stressor and influence cartilage turnover in young horses., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Objectives: To develop an ultrasound-guided cervical perineural injection technique for horses and to evaluate and compare the distribution of contrast agent among perineural, intra-articular and periarticular injections., Study Design: Prospective, experimental cadaveric study., Animals: A total of 14 equine cadaveric necks., Methods: Bilateral ultrasound-guided perineural injection technique for the caudal cervical spinal nerve roots (CSNRs 5-7) was developed. Paramagnetic or iodinated contrast was injected and the distribution of contrast was evaluated using magnetic resonance (MR) or computed tomography (CT) imaging, respectively. The presence of contrast in the CSNR region was determined by an observer unaware of the technique used for each injection performed. The ability of the perineural injection technique to distribute contrast agent to the CSNR region was compared with intra-articular and periarticular injection techniques., Results: Perineural injection delivered contrast agent to the CSNR region 100% of the time and was significantly different when compared with intra-articular injection (p = 0.008). There was no difference in ability to deliver contrast agent to the CSNR region between the perineural and periarticular injection techniques or between the intra-articular and periarticular injection techniques., Conclusion and Clinical Relevance: The ultrasound-guided perineural injection technique developed in this study accurately delivered contrast agent to the CSNR region in equine cadavers. This technique could potentially be used for the diagnosis and treatment of cervical pain in horses, particularly in cases where intra-articular cervical articular process joint injections have not been beneficial. Further studies are necessary to assess the effectiveness of the ultrasound-guided perineural injection technique in live horses., (Published by Elsevier Ltd.)

Background: Injection of the centrodistal (CD) joint in the horse is a commonly performed procedure for both diagnostic and therapeutic purposes. This procedure can be technically challenging, and while radiographic guidance has been previously used, ultrasound localised injection of the CD joint has not been described., Objectives: The purpose of this study was to explore the feasibility of using ultrasound localisation to increase the accuracy of CD joint injection., Study Design: Experimental method assessment., Methods: One operator performed the ultrasound and injection of 24 CD joints in 12 sedated horses. The joints were injected with iohexol (2 ml), sterile saline (1.5 ml) and amikacin (0.5 ml). Dorsoplantar and dorsomedial plantarolateral radiographic projections were obtained immediately after injection to evaluate the presence of contrast material in the CD joint., Results: The CD joint was successfully injected in 17/24 joints, representing a 70.8% accuracy., Main Limitations: The horses used in this study were from the University research herd, and not clinical cases. One investigator performed all the ultrasonography and CD joint injections., Conclusions: The use of ultrasound localisation could improve success of CD joint injection as well as improve the learning curve of less experienced practitioners learning this procedure., (© 2020 EVJ Ltd.)

Osteoarthritis is treated with COX or fosfolipase A2 inhibitors such as carprofen, a propionic acid NSAID. The enhancement of its action over the articular cartilage is mandatory to facilitate its therapeutic application. Drug uptake into the cartilage requires high synovial fluid concentrations, anticipating its rapid distribution towards bloodstream. Thus, intraarticular administration improves local targeting of the drug, lining with the site of action. A pharmacokinetic study in rabbits has been performed to evaluate carprofen nanoparticles after intraarticular administration. Pharmacokinetic analysis of plasma profiles through a modelling approach, has demonstrated the rapid distribution of drug outside of synovial chamber but mainly remaining in plasma. The data modelling has demonstrated the existence of two release-absorption processes when the nanoparticles are administered in the synovial space. Additionally, results are predictive of the PK profile of some other species such as cat, dogs or humans., (Copyright © 2021. Published by Elsevier Ltd.)

This prospective, comparative, randomized, horizontal, and double-blind clinical study investigated the clinical efficacy of leucocyte-poor platelet-rich plasma (PRP, n=8) or allogeneic adipose-derived stem cells (ADSC, n=8) in dogs with bilateral degenerative hip joint disease (DHJD). Sixteen dogs were treated with two intra-articular injections of PRP or ADSCs, within a 30-day interval. The Canine Brief Pain Inventory (CBPI), the Helsinki Chronic Pain Index (HCPI), and Visual Analogue Scales for pain (VAS-pain) and locomotion (VAS-loc) were assessed by the dog owners. Analysis-of-gait using a force plate, response to palpation (VAS-palp), and the descriptive numerical scale for pain (DNS) were measured by a veterinarian. The assessments were performed before (baseline), 30 and 60 days after the first treatment. Data were analyzed using the unpaired t test, paired Wilcoxon test, Fisher's exact test, and Mann-Whitney and Friedman tests (P<0.05). Compared with baseline HCPI, CBPI, VAS-pain, and VAS-palp scores reduced 41%, 52%, 51%, and 48% (P=0.0001-0.03) at 60 days in the ADSC group. In PRP-treated dogs, CBPI, VAS-loc, and DNS scores decreased by 43%, 43%, and 33% at 60 days, respectively (P=0.0003-0.011). Based on CBPI data, the rate of success at 60 days was 75% and 25% in the ADSC and PRP groups (P=0.13), respectively. Both therapies were apparently safe and effective to reduce chronic pain in dogs with bilateral DHJD during a 60-day period. However, a trend towards greater improvement was provided by the ADSC treatment.