Risk factors for osteoarthritis include raised BMI and female gender. Whether these two factors influenced synovial gene expression was investigated using a triangulation and modelling strategy which generated 12 datasets of gene expression in synovial tissue from three knee pathologies with matching BMI groups, obese and overweight, and gender distributions. Intra-operative synovial biopsies were immersed in RNAlater at 4oC before storage at -80oC. Total RNA was extracted using RNAeasy with gDNA removal. Following RT- PCR and quality assessment, cDNA was applied to Affymetrix Clariom D microarray gene chips. Bioinformatics analyses were performed. Linear models were prepared in limma with gender and BMI factors incorporated sequentially for each pathology comparison, generating 12 models of probes differentially expressed at FDR p<0.05 and Bayes number, B>0. Data analysis of differently expressed genes utilized Ingenuity Pathway Analysis and Cytoscape with Cluego and Cytohubba plug-ins.Abstract
Introduction
Methodology
It is increasingly evident that synovium may play a larger role in the aetiology of osteoarthritis. We compared gene expression in whole tissue synovial biopsies from end-stage knee osteoarthritis and knee trauma patients with that of their paired explant cultures to determine how accurately cultured cells represent holistic synovial function. Synovial tissue biopsies were taken from 16 arthroplasty patients and 8 tibial plateau fracture patients with no osteoarthritis. Pairs of whole tissue fragments were either immediately immersed in RNAlater Stabilisation Solution at 4o C before transfer to -80o C storage until RNA extraction; or weighed, minced and cultured at 500mg tissues/5ml media in a humidified incubator at 37oC, 5% CO2. After sub-culturing total RNA was extracted using RNAeasy Plus Mini Kit with gDNA removal. Following RT-PCR and quality assessment, cDNA was applied to Affymetrix Clariom D microarray gene chips. Bioinformatics analyses were performed.Abstract
Introduction
Methodology
Articular cartilage degradation is a defining feature of osteoarthritis. Synovium is a reactive tissue with synovial villae, neoangiogenesis and intimal hyperplasia common to many joint pathologies. The consequences of cartilage debris in osteoarthritis impacting the synovial intima is not well understood. We analysed the immunohistology of synovium from 16 patients with osteoarthritis and 17 patients undergoing knee surgery for non-arthritic pathologies. This data was integrated with imaging and functional scores to correlate synovitis in osteoarthritis. Formalin-fixed paraffin embedded synovial biopsy sections were cut in serial sequence and processed for routine staining (H&E or CD3, CD68, CD20, Vimentin, vWF and PCNA IHC) using standardised Dako monoclonal mouse anti-human antibodies. Digital images scanned at x20 were evaluated for fragments of cartilage and aggregates of inflammatory cells. Clinical data (gender, BMI, KL grade, WOMAC & SF-12 scores) was aligned with histopathological data.Abstract
Introduction
Methodology
Synovitis impacts osteoarthritis symptomatology and progression. The transcription factors controlling synovial gene expression have not been described. This study analyses gene expression in synovium samples from 16 patients with osteoarthritis with 9 undergoing arthroscopic and 8 knee trauma surgery for non-arthritic pathologies. Intra-operative synovial biopsies were immersed in RNAlater at 4oC before storage at -80oC. Total RNA was extracted using RNAeasy. After purification, RT-PCR and quality assessment, cDNA was applied to Affymetrix Clariom D microarray gene chips. Bioinformatics analyses were performed. Linear models were prepared in limma with gender and BMI factors incorporated sequentially for each pathology comparison, generating 12 models of probes differentially expressed at FDR p<0.05 and Bayes number, B>0. Data analysis of differently expressed genes utilized Ingenuity Pathway Analysis and Cytoscape with Cluego and Cytohubba plug-ins.Abstract
Introduction
Methodology
We set out to demonstrate the 10-year survivorship of the PFC sigma TKA in a young patient group. Demographic and clinical outcome data were collected prospectively at 6 months, 18 months, 3 years, 5 years and 8-10 years post surgery. The data were analysed using Kaplan Meier survival statistics with end point being regarded as death or revision for any reason. 203 patients were found to be ≤55 years at the time of surgery. Four patients required revision and four patients died. Another four patients moved away from the region and were excluded from the study. A total of 224 knees in 199 patients (101 male and 98 females.) 168 patients had a diagnosis of Osteoarthritis and 28 with inflammatory arthritis. Average age 50.6 years range 28-55 years (median 51). Ten-year survivorship in terms of revision 98.2% at ten years 95% confidence interval. Our results demonstrate that the PFC Sigma knee has an excellent survival rate in young patients over the first 10 years. TKR should not be withheld from patients on the basis of age.
The aim of this study was to compare the long-term outcome from total knee replacement (TKR) in young versus old patients in terms of pain and functional outcome. We used our arthroplasty database which recorded prospectively pain and American Knee Society scores at regular intervals over ten years after TKR. The procedures used a modern, cemented resurfacing type cruciate retaining prosthesis. A cohort of young patients (≤55 years) were identified. A control group of patients > 56 was identified, matching for ASA, body mass index and underlying condition. Change over time was analysed using a factorial repeated measures ANOVA test, which allowed for investigation of difference between groups. 40 Knees in 26 patients were identified. 2 patients died prior to follow up, 2 were revised within the study period. (1 for infection at 2 years and one for change of poly at 7 years) and a further 4 were lost to follow up. 7 knees could not be matched and were excluded. This left a study group of 24 young and 24 older knees. Pain scores (p=0.025) and American Knee Society “Knee” (p<0.001) and “Function” (p<0.001) scores changed significantly over time. There were however no statistical differences over the 10 year period in pain (p=0.436) and knee performance (0.618) but overall function was higher throughout the period in the younger group (=0.004). Knee replacement in younger patients produces similar outcomes in terms of pain and function compared with older patients and TKR should not be withheld purely on account of age.
