POS0372 LORECIVIVINT (SM04690), AN INTRA-ARTICULAR, SMALL-MOLECULE CLK2/DYRK1A INHIBITOR THAT MODULATES THE WNT PATHWAY, AS A POTENTIAL TREATMENT FOR MENISCAL INJURIES

Background:Meniscal injuries are the most common pathology of the knee and are associated with pain, stiffness, and localized swelling. Meniscal damage is a frequent finding on MRI images of knee osteoarthritis (OA).1 Efforts to repair meniscal damage have been largely unsuccessful and do not prevent the progression of degenerative changes that lead to knee OA.2 The Wnt signaling pathway has been shown to be regulated during meniscal development,3 suggesting that manipulation of this pathway may influence the regenerative capacity of the meniscus. Lorecivivint (LOR; SM04690) is an intra-articular (IA), small-molecule CLK2/DYRK1A inhibitor that modulates the Wnt pathway.4Objectives:LOR was evaluated in preclinical studies to determine its protective and anabolic effects in ex vivo explants and in a rat model of chemically induced inflammatory meniscal degeneration.Methods:Effects of LOR (30 nM) on matrix metalloproteinase (MMP) expression in cultured rat menisci treated with IL-1B were measured by qRT-PCR. In vivo, LOR activity was evaluated in a rat model of monosodium iodoacetate (MIA) injection-induced inflammatory meniscal degeneration. A single IA injection of MIA was immediately followed by a single IA injection of LOR (0.3 ug) or vehicle. Knees were harvested on Days 1, 4, and 11 and menisci were isolated. Anti-inflammatory effects were evaluated by qRT-PCR for TNFA and IL6 expression. Meniscal protection was evaluated by qRT-PCR for MMPs and aggrecanase. Anabolic effects were evaluated by qRT-PCR for collagens.Results:In ex vivo meniscal explants, LOR inhibited expression of MMP1, MMP3, and MMP13 compared with DMSO (P<0.01). In vivo, LOR significantly decreased expression of MMPs and aggrecanase (P<0.05) and reduced expression of inflammatory cytokines TNFA and IL6 compared with vehicle in the rat model of inflammatory meniscal degeneration at Day 4 after MIA injection. Additionally, LOR increased expression of collagen types I, II, and III at Day 11 after MIA injection (Figure 1).Conclusion:LOR exhibited protective effects in the meniscus ex vivo and in vivo by reducing catabolic enzyme expression compared with control. Anti-inflammatory effects of LOR were demonstrated by inhibition of inflammatory cytokine expression. Compared with vehicle, LOR increased collagen expression in vivo, indicating potential meniscal anabolic effects. These data support further investigation of LOR as a potential structure-modifying treatment for meniscal injuries.References:[1]Englund M, et al. Rheum Dis Clin North Am. 2009.[2]Collins JE, et al. Arthritis Care Res (Hoboken). 2019.[3]Pazin DE, et al. Dev Dyn. 2012.[4]Deshmukh V, et al. Osteoarthr Cartil. 2019.Disclosure of Interests:Tim Seo Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Vishal Deshmukh Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Yusuf Yazici Shareholder of: Samumed, LLC, Employee of: Samumed, LLC

880 Improving the Acute Knee Injury Pathway – A Regional Quality Improvement Project in the Oxford University Hospitals

Introduction There are many patients being referred from A&E to orthopaedic trauma clinics in OUH for suspected ligament or meniscal damage, without convincing evidence of injury. This has led to demand for providing point of care ultrasound and streamlining of the referral process. Method We conducted an audit of all A&E presentations at the OUH receiving a knee XR across 3 months and tracked their investigative and referral progress. Results: Conclusions Only 30% (57/182) patients referred to the Trauma clinic were deemed to have a serious ligament or meniscal injury. It is difficult to assess the extent of knee injury without specialist diagnostic equipment, which includes MRI or point of care ultrasound. This project has resulted in new trial protocols exploring the use of these technologies to improve this pathway.

Migration of a Meniscal Repair Implant Mimicking Meniscal Injury

Complications after arthroscopic meniscal suture repair have been reported. Migration of a meniscal repair implant mimicking meniscal injury is rare. A 28-year-old female had undergone Anterior Cruciate Ligament (ACL) reconstruction at another hospital 12 years ago . The remaining instability after ACL reconstruction resulted in medial meniscal damage, wear and narrowing in the posterior third. The H-fix that was used in the meniscal repair became detached, exposing the inside of the knee joint. Meniscal repair is a successful procedure in conjunction with ACL reconstruction. However, when knee instability after ACL reconstruction remains, the choice of meniscal repair implants may lead to potential complications even after long-term clinical follow-up.

Assessment of the Magnetic Resonance Imaging Features of Baker’s Cysts and Their Correlation with the Age of Patients

Objective. To determine the magnetic resonance imaging (MRI) morphological features of Baker’s cysts and to assess their correlation with the age of patients.Material and methods. The investigation was based on the assessment of MRI readings in 37 patients with Baker’s cysts; of them there were 29 (78.4%) women and 8 (21.6%) men. The mean age of the examinees was 60.3 years (25 to 82 years).Results. The mean dimensions of the cysts were measured. Their length, width, and height were 34 ± 2.1 mm, 5 ± 1.2 mm (range 4–31 mm), and 58 ± 2.9 mm, respectively. Their mean thickness was 0.7 mm. Intracystic chondral bodies were detected in 3 (7.5%) cases. These parameters were shown to be unrelated to age. It was found that all cysts were multi-chamber and an average of 6.8 chambers was detected. There was a weak, inversely proportional, statistically significant relationship between the age of the patients and the number of chambers in the cyst. The younger participants of the investigation exhibited no meniscal damage in an overwhelming case (57.1%); whereas complete and incomplete meniscal tears much more often occurred in older patients with Baker’s cysts (from 29 (78.4%) to 34 (91.9%) people, respectively).Conclusion. Degenerative bone and cartilage tissue changes in the joint increase with age, regardless of the cyst sizes.

AB0069 LORECIVIVINT (SM04690), AN INTRA-ARTICULAR, SMALL-MOLECULE CLK/DYRK1A INHIBITOR THAT MODULATES THE WNT PATHWAY, AS A POTENTIAL TREATMENT FOR MENISCAL INJURIES

Background:Meniscal injuries, associated with pain, stiffness, and localized swelling, are the most common pathology of the knee with a prevalence of 61 per 100,000.1Meniscal damage is a frequent finding on MRI images of knee osteoarthritis (OA)2; while a meniscal tear can lead to knee OA, knee OA can also lead to a spontaneous meniscal tear.3Efforts to repair meniscal damage have been largely unsuccessful and do not prevent the progression of degenerative changes that lead to knee OA.4The Wnt signaling pathway has been shown to be regulated during meniscal development,5,6suggesting that manipulation of this pathway may influence the regenerative capacity of the meniscus. Lorecivivint (LOR; SM04690) is an intra-articular (IA), small-molecule CLK/DYRK1A inhibitor that modulates the Wnt pathway.Objectives:LOR was evaluated in preclinical studies to determine its protective and anabolic effects in ex vivo explants and in a rat model of chemically induced inflammatory meniscus degeneration.Methods:Effects of LOR (30 nM) on expression of matrix metalloproteinases (MMPs) in cultured rat menisci treated with IL-1B were measured by qPCR. In vivo, LOR activity was evaluated in a rat model of monosodium iodoacetate (MIA) injection-induced inflammatory meniscus degeneration. A single IA injection of MIA was immediately followed by a single IA injection of LOR (0.3 ug) or vehicle. Knees were harvested on Days 1, 4, and 11 and menisci were isolated. Anti-inflammatory effects were evaluated by measuringTNFAandIL6expression by qPCR. Meniscus protection was evaluated by qPCR for MMPs and aggrecanase and anabolic effects by qPCR for collagens.Results:In ex vivo meniscal explants, LOR inhibited expression ofMMP1,MMP3, andMMP13compared to DMSO (P<0.01). In vivo, LOR significantly decreased expression of these MMPs and aggrecanase (P<0.05) compared to vehicle in the rat model of inflammatory meniscus degeneration at Day 4 after MIA injection. In addition, LOR reduced expression of inflammatory cytokinesTNFAandIL6at Day 4 compared to vehicle. Finally, LOR increased expression of collagen types I, II, and III at Day 11 after MIA injection.Conclusion:LOR exhibited protective effects in the meniscus ex vivo and in vivo by reducing the expression of catabolic enzymes compared to control. Anti-inflammatory effects of LOR were demonstrated by inhibition of inflammatory cytokine expression. Compared to vehicle, LOR increased expression of collagens in vivo, indicating potential meniscal anabolic effects. These data support further investigation of LOR as a potential disease-modifying therapy for meniscal injuries.References:[1]Logerstedt D and Snyder-Mackler L.J Orthop Sports Phys Ther. 2010[2]Englund M, et al.Rheum Dis Clin North Am. 2009[3]Englund M, et al.Radiol Clin North Am. 2009[4]von Lewinski, et al.Knee Surg Sports Traumatol Arthrosc. 2007[5]Pazin DE, et al.ORS 2012 Annual Meeting. Paper No. 0221[6]Pazin DE, et al.Dev Dyn. 2012Disclosure of Interests:Tim Seo Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Vishal Deshmukh Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Yusuf Yazici Shareholder of: Samumed, LLC, Grant/research support from: Bristol-Myers Squibb, Celgene, and Genentech, Consultant of: Celgene and Sanofi, Employee of: Samumed, LLC

The Use of Ultrasonography for Detection of Meniscal Damage in Dogs

<p><strong>PICO question</strong></p><p>In dogs, what is the sensitivity and specificity of using ultrasound as a diagnostic test to identify meniscal damage?</p><p><strong>Clinical bottom line</strong><strong><br /> </strong></p><p>Although there are limited studies assessing the accuracy of ultrasound for detecting meniscal damage, it appears to be a potentially useful diagnostic test with reported sensitivity varying from 82–95% and specificity from 82–93% when compared to arthroscopy or arthrotomy findings. Experience of the ultrasonographer is also likely to be an important factor to consider.</p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/pr-icon.jpg" alt="Peer Reviewed" />

Comparison of the Effect of Dog, Surgeon and Surgical Procedure Variables on Improvement in Eight-Week Static Weight-Bearing following Tibial Plateau Levelling Osteotomy

Objective The purpose of this article was to compare the effect of surgeon and tibial plateau levelling osteotomy (TPLO) procedure variations on the outcome of TPLO in naturally occurring cranial cruciate ligament disease. Materials and Methods Records from 142 dogs that had a TPLO procedure were reviewed for information regarding surgical procedure, status of meniscus at the time of surgery, surgeon identity, ACVS diplomate or resident, meniscal release, progression of healing at the progress evaluation based on radiographic interpretation and complications encountered. The primary outcome measure was static force on the affected limb at re-evaluation (42–84 days postoperatively) on a PetSafe Stance Analyzer. Results Re-evaluation tibial plateau angle (TPA) was negatively and significantly correlated with improvement (r = −0.2132, p = 0.013). Postoperative and re-evaluation TPA were all significantly correlated with one another. The amount of TPA change from initial to immediate postoperative values was significantly correlated with the preoperative TPA (r = 0.628, p < 0.001). Surgeon, surgical experience, arthrotomy, meniscal damage, meniscal intervention, complications, postoperative TPA and preoperative TPA had no significant effect on weight-bearing at recheck. Clinical Significance TPLO show improvement of 4.58% body weight on the affected limb at 6 to 12 weeks rechecks on a Stance Analyzer. Surgeon, surgical experience, arthrotomy, meniscal damage, meniscal intervention, complications, postoperative TPA and initial TPA have no effect on this measurement of surgical outcome.