BackgroundAutologous chondrocyte implantation (ACI) can be used in the treatment of focal cartilage injuries to prevent the onset of osteoarthritis (OA). However, we are yet to understand fully why some individuals do not respond well to this intervention. Identification of a reliable and accurate biomarker panel that can predict which patients are likely to respond well to ACI is needed in order to assign the patient to the most appropriate therapy. This study aimed to compare the baseline and mid-treatment proteomic profiles of synovial fluids (SFs) obtained from responders and non-responders to ACI.MethodsSFs were derived from 14 ACI responders (mean Lysholm improvement of 33 (17–54)) and 13 non-responders (mean Lysholm decrease of 14 (4–46)) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Label-free proteome profiling of dynamically compressed SFs was used to identify predictive markers of ACI success or failure and to investigate the biological pathways involved in the clinical response to ACI.ResultsOnly 1 protein displayed a ≥2.0-fold differential abundance in the preclinical SF of ACI responders versus non-responders. However, there is a marked difference between these two groups with regard to their proteome shift in response to cartilage harvest, with 24 and 92 proteins showing ≥2.0-fold differential abundance between Stages I and II in responders and non-responders, respectively. Proteomic data has been uploaded to ProteomeXchange (identifier: PXD005220). We have validated two biologically relevant protein changes associated with this response, demonstrating that matrix metalloproteinase 1 was prominently elevated and S100 calcium binding protein A13 was reduced in response to cartilage harvest in non-responders.ConclusionsThe differential proteomic response to cartilage harvest noted in responders versus non-responders is completely novel. Our analyses suggest several pathways which appear to be altered in non-responders that are worthy of further investigation to elucidate the mechanisms of ACI failure. These protein changes highlight many putative biomarkers that may have potential for prediction of ACI treatment success.
Purpose The purpose of this study was to measure the improvement in quality of life (QoL) following isolated anatomical double-bundle medial patellofemoral ligament reconstruction. Methods This is a single-centre, prospective study of 56 consecutive patients (57 knees) who underwent isolated MPFL reconstruction between 2014 and 2017. Functional outcome and QoL were assessed with the Kujala score and the EQ-5D-3L questionnaire, respectively. Objective outcomes were obtained through clinical examination at the latest follow-up assessing redislocation rate, patella apprehension test, patellar tilt, pain and range of motion. ResultsThe median Kujala score increased from 60 (range 31-96) to 92 (range 34-100) at latest follow-up (p < 0.001). The median EQ-5D index also increased, from 0.69 (range 0.10-1) at baseline to 1 (range 0.16-1) at latest follow-up (p < 0.001), as well as the median EQ-5D VAS from 75 (range 20-95) to 92 (range 40-100) (p < 0.001). Four dimensions of the EQ-5D were signiicantly improved except for the anxiety/depression scores. Female patients reported lower scores at baseline and at latest follow-up, for all three outcomes (Kujala, EQ-5D index, EQ-5D VAS), however there was no evidence that gender negatively impacted on the beneit of surgery. The re-dislocation rate was 0%. Apprehension and patellar tilt test were negative in all patients and no lexion deicit was identiied at latest follow-up. Two patients had tenderness along the reconstruction requiring femoral screw removal in one of them. Conclusions Isolated anatomical double-bundle aperture MPFL reconstruction, ofered signiicantly improved short-term QoL along with excellent functional outcome. Female patients scored lower, but this did not afect the overall outcome. Including QoL tools in the assessment of ligament reconstruction operations, such as the MPFL, can provide more accurate understanding of the overall patient beneit. Level of evidence II.
4Background: Autologous chondrocyte implantation (ACI) is used worldwide in the 5 treatment of cartilage defects in the knee. Several demographic and injury specific risk 6 factors have been identified that can affect the success of ACI treatment. However, the 7 discovery of predictive biomarkers in this field has thus far been overlooked. 8Hypothesis/Purpose: The purpose of this study was to identify potential biomarkers in 9 synovial fluid (SF) and plasma that can be used in the pre-operative setting to help 10 optimise patient selection for cell-based cartilage repair strategies. 18Lysholm score, the independent variables were patient age and body mass index, 19defect location, defect area, having a bone-on-bone defect, type of defect patch type 20 (periosteum or collagen), requirement of an extra procedure and baseline biomarker 21 levels. 22Results Mean baseline Lysholm score was 47.4(+/-17.0), which improved to 64.6(+/- 27Lysholm score, age at ACI and the defect patch type used. 28Conclusions The absence of ADAMTS-4 activity in the synovial fluid of joints with 29 cartilage defects may be used in conjunction with known demographic risk factors in 30 the development of an ACI treatment algorithm to help inform the preclinical decision. 3What is known about the subject: There are no known predictive biomarkers for ACI. 32What this study adds to existing knowledge: This study has identified the first 33 biological predictor for ACI, which could be used in deciding the best treatment. 4 Introduction 35A recent white paper on how to move forward with cell-based advanced therapies has 36 highlighted the need for improved predictive preclinical efficacy testing within Europe 15 . 37Hence, the refinement and optimisation of cell therapy protocols for increased efficacy 85Gide®; Geistlich Ltd, Manchester, UK). A patient was described as a 'responder' or a 86'non-responder' based on the change in 1-year post-operative Lysholm score. 87Responders were patients who had improved by at least 10 points, which is 88 comparable to the published minimum clinically important difference for 100 point 89 functional knee scores reported in other studies 14,34,37 . 90Synovial fluid and plasma collection and storage 91To collect synovial fluid, patients' knee joints were injected with 20mls of saline 92followed by 20 cycles of extension and flexion prior to intra-articular aspiration. We 116COMP and HA were calculated to be 0.1ng/ml and 17.8ng/ml respectively. The inter- 117and intra-assay co-efficient of variance was 7.1% and 1.6% for COMP assays and 11819.1% and 4.5% for HA assays, respectively. 130substrate which is optimised to specifically detect ADAMTS-4 activity (down to 4ng/ml). 131For calculations of ADAMTS-4 activity linear standard curves were constructed by 135Statistical analysis 136The distributions of all continuous variables were investigated using quantile-quantile 137(QQ) plots. These showed that age, BMI and the Lysholm scores followed a normal 138 distribution, whereas defect area and the l...
Despite a potential for efficacy of exercise-based conditioning, this review highlights the scarcity of robust dose-response evidence to guide the formulation of total knee arthroplasty prehabilitation effectively.
The Mayo Conservative Hip femoral prosthesis has been designed to optimise proximal femoral loading as well as preserving proximal femoral bone stock. Between October 2003 and May 2006, 42 patients (49 hips) underwent total hip replacement (THR) using the Mayo Conservative Hip femoral component. The mean age at operation was 57.8 years (range 44 to 74) and the mean clinical follow up was 3.1 years (range 2.3 to 4.7 years). The aim of our study was to review the short term results of this unorthodox femoral component. We found that 18% degrees of stems were malaligned >or= 5 degrees and the prevalence of intra-operative femoral fracture was 4%. We feel this prosthesis is difficult to implant and has an unacceptable fracture rate.
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