Efficacy and cost-effectiveness of Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis: protocol for a randomised placebo-controlled trial (the SCUlpTOR trial).

INTRODUCTION: Knee osteoarthritis (KOA) is a highly prevalent disabling joint disease. Intra-articular stem cell therapy is increasingly being used for treating KOA with little high-quality evidence to support its use. The aim of this study is to investigate the efficacy, safety and cost-effectiveness of allogeneic mesenchymal stem cells (Cymerus MSCs) for treating symptomatic tibiofemoral KOA and improving knee structure over 24 months. METHODS AND ANALYSIS: The Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis study is a phase III, multi-centre, parallel, superiority, randomised, double-blind, placebo-controlled trial, which will be conducted in Sydney and Hobart, Australia. 440 participants (220 per arm) aged over 40 years with painful KOA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) with medial minimum joint space width between 1 and 4 mm in the study knee will be recruited from the community and randomly allocated to receive either intra-articular MSCs or saline at baseline, week 3 and week 52. The coprimary outcomes will be the proportion of participants achieving patient-acceptable symptom state for knee pain at 24 months and quantitative central medial femorotibial compartment cartilage thickness change from baseline to 24 months. Main secondary outcomes include change in knee pain, Patient Global Assessment, physical function, quality of life and other structural changes. Additional data for cost-effectiveness analysis will also be recorded. Adverse events will be monitored throughout the study. The primary analysis will be conducted using modified intention-to-treat. ETHICS AND DISSEMINATION: This protocol has been approved by The University of Sydney (USYD) Human Research Ethics Committee (HREC) #: 2020/119 and The University of Tasmania (UTAS) HREC #: H0021868. All participants will be required to provide informed consent. Dissemination will occur through conferences, social media, and scientific publications. TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trials Registry (ACTRN12620000870954); U1111-1234-4897.

Efficacy of intra-articular injections of platelet-rich plasma as a symptom- and disease-modifying treatment for knee osteoarthritis - the RESTORE trial protocol.

BACKGROUND: Knee osteoarthritis (OA) causes substantial pain, physical dysfunction and impaired quality of life. There is no cure for knee OA, and for some people, the disease may involve progressive symptomatic and structural deterioration over time. Platelet-rich plasma (PRP) is a therapeutic agent that aims to address underlying biological processes responsible for OA pathogenesis. As such, it has the potential to improve both symptoms and joint structure. The aim of this clinical trial is to determine whether a series of injections of PRP into the knee joint will lead to a significantly greater reduction in knee pain, and less loss of medial tibial cartilage volume over 12 months when compared to a series of placebo saline injections in people with knee OA. METHODS: This will be a two-group, superiority, randomised, participant-, interventionist- and assessor-blinded, placebo-controlled trial. Two hundred and eighty-eight participants aged over 50 years with painful knee OA and mild to moderate structural change on x-ray (Kellgren and Lawrence grade 2 and 3) will be randomly allocated to receive either three PRP injections or three normal saline injections into the knee joint at weekly intervals. The primary outcomes will be 12-month change in average overall knee pain severity (numeric rating scale) and medial tibial cartilage volume (magnetic resonance imaging (MRI)). Secondary outcomes include additional measures of knee pain and other symptoms, function in daily living and sport and recreation, quality of life, participant-perceived global ratings of change, and other MRI structural outcomes including meniscal and cartilage morphology, synovitis, effusion, bone marrow lesions and cartilage defects. A range of additional measures will be recorded, and a separate health economic evaluation will be performed. DISCUSSION: The findings from this study will help determine whether PRP improves both clinical and structural knee OA outcomes over 12 months when compared to a series of placebo saline injections. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry reference: ACTRN12617000853347 . Prospectively registered 9th of June 2017.

Validation of an MRI Protocol for Routine Quantitative Assessment of Tunnel Position in Anterior Cruciate Ligament Reconstruction.

BACKGROUND: No standardized methodology and objective criteria currently exist to accurately and objectively assess tunnel placement and consequent graft orientation in anterior cruciate ligament (ACL) reconstruction (ACLR) through a single imaging modality. Advances in magnetic resonance imaging (MRI) technology have enabled the use of volumetric high spatial and contrast resolution proton density-weighted sequencing, which allows precise delineation of graft orientation, tunnel position, and quantitative assessment of tunnel position relationship to adjacent reproducible anatomic landmarks. PURPOSE: To establish an MRI protocol that would provide an accurate alternative to 3-dimensional computed tomography (3D-CT) for standardized assessment of bone tunnel placement in ACLR, as a component of assessing ACLR outcomes and to assist in presurgical planning for revision ACLR. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Twenty-four participants diagnosed with a failed ACLR underwent MRI and 3D-CT per the imaging protocols of the Sydney Orthopaedic Research Institute, in which the acquired data were converted to 3D models. The bone tunnels of the previous ACLR were then intraoperatively digitized at the tunnel aperture and along the length of the tunnel (barrel) and used as the reference standard to evaluate the accuracy of high-resolution MRI and 3D-CT. Differences in geometry between the image-based model and the reference point cloud were calculated through point-to-point comparison. RESULTS: At the tunnel apertures, no significant differences were detected between the MRI and 3D-CT models versus the reference models for the femur ( P = .9472) and tibia ( P = .5779). Mean ± SD tunnel barrel deviations between MRI and 3D-CT were 0.48 ± 0.28 mm (femur) and 0.46 ± 0.27 mm (tibia). No significant differences were detected between the MRI and 3D-CT models versus the reference models for the femoral ( P = .5730) and tibial ( P = .3002) tunnel barrels. CONCLUSION: This study demonstrated that, in addition to being the optimum modality for assessment of soft tissue injury of the knee, a high-resolution 3D turbo spin echo proton density sequence can provide an accurate assessment of tunnel placement, without the use of ionizing radiation. Therefore, this protocol provides the foundation for an objective standardized platform to quantitatively evaluate the location of ACL bone tunnels and graft orientation for routine postoperative assessment, presurgical planning, and evaluation of clinical outcomes.

Reliability of MRI assessment of supraspinatus tendinopathy.

OBJECTIVE: To determine the interobserver and intraobserver reliability of the interpretation of MRIs for supraspinatus tendinosis. METHODS: In the interobserver trial, the MRIs of 52 athletes' shoulders were observed by 3 observers on one occasion within a 2-month period. All 52 images were read by the most experienced musculoskeletal radiologist on 3 different occasions on separate days without access to the previous readings for the intraobserver trial. Supraspinatus tendinosis was graded using a modified 4-point scale from grades 0 to grade 3. RESULTS: The grading of MRI-determined supraspinatus tendinosis was reliable, having an intraclass correlation (ICC) of 0.85 when assessed by the single well-trained observer. Interobserver reliability was only fair to good (ICC = 0.55). CONCLUSIONS: Supraspinatus tendinosis can be accurately identified on MRI with little variation by a single well-trained observer. Interobserver reliability was only fair to good. Our data indicated that the reliability of the assessment was much greater in more experienced radiologists than in those with less experience.