Arthroscopic partial meniscectomy versus placebo surgery for a degenerative meniscus tear : a 2-year follow-up of the randomised controlled trial

Objective To assess if arthroscopic partial meniscectomy (APM) is superior to placebo surgery in the treatment of patients with degenerative tear of the medial meniscus. Methods In this multicentre, randomised, participant-blinded and outcome assessor-blinded, placebo-surgery controlled trial, 146 adults, aged 35-65 years, with knee symptoms consistent with degenerative medial meniscus tear and no knee osteoarthritis were randomised to APM or placebo surgery. The primary outcome was the between-group difference in the change from baseline in the Western Ontario Meniscal Evaluation Tool (WOMET) and Lysholm knee scores and knee pain after exercise at 24 months after surgery. Secondary outcomes included the frequency of unblinding of the treatment-group allocation, participants' satisfaction, impression of change, return to normal activities, the incidence of serious adverse events and the presence of meniscal symptoms in clinical examination. Two subgroup analyses, assessing the outcome on those with mechanical symptoms and those with unstable meniscus tears, were also carried out. Results In the intention-to-treat analysis, there were no significant between-group differences in the mean changes from baseline to 24 months in WOMET score: 27.3 in the APM group as compared with 31.6 in the placebo-surgery group (between-group difference, -4.3; 95% CI, -11.3 to 2.6); Lysholm knee score: 23.1 and 26.3, respectively (-3.2; -8.9 to 2.4) or knee pain after exercise, 3.5 and 3.9, respectively (-0.4; -1.3 to 0.5). There were no statistically significant differences between the two groups in any of the secondary outcomes or within the analysed subgroups. Conclusions In this 2-year follow-up of patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear, the outcomes after APM were no better than those after placebo surgery. No evidence could be found to support the prevailing ideas that patients with presence of mechanical symptoms or certain meniscus tear characteristics or those who have failed initial conservative treatment are more likely to benefit from APM.Peer reviewe

The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis.

Osteoarthritis (OA) is a degenerative disease that affects various tissues surrounding joints such as articular cartilage, subchondral bone, synovial membrane, and ligaments. No therapy is currently available to completely prevent the initiation or progression of the disease partly due to poor understanding of the mechanisms of the disease pathology. Cartilage is the main tissue afflicted by OA, and chondrocytes, the sole cellular component in the tissue, actively participate in the degeneration process. Multiple factors affect the development and progression of OA including inflammation that is sustained during the progression of the disease and alteration in biomechanical conditions due to wear and tear or trauma in cartilage. During the progression of OA, extracellular matrix (ECM) of cartilage is actively remodeled by chondrocytes under inflammatory conditions. This alteration of ECM, in turn, changes the biomechanical environment of chondrocytes, which further drives the progression of the disease in the presence of inflammation. The changes in ECM composition and structure also prevent participation of mesenchymal stem cells in the repair process by inhibiting their chondrogenic differentiation. This review focuses on how inflammation-induced ECM remodeling disturbs cellular activities to prevent self-regeneration of cartilage in the pathology of OA

Risk factors for first hospitalization due to meniscal lesions - a population-based cohort study with 30 years of follow-up

Background: Meniscal lesions are among the most common injuries of the knee, yet limited epidemiologic data is available on their risk factors. We investigated the association of lifestyle factors and physical strenuousness of work on knee injuries with a focus on meniscal lesions. Methods: We examined a nationally representative sample of persons aged 30 to 59 years, who participated in a comprehensive health examination (the Mini-Finland Health Survey). Subjects without any injury or osteoarthritis in the knee joint at baseline (n = 4713) were subsequently followed via the National Hospital Discharge Register up to 30 years. Results: During the follow-up, 338 knee injuries were identified of which 224 were meniscal lesions. Obesity and regular leisure time physical exercise were associated with an increased risk of first hospitalization due to meniscal lesions (hazard ratio (HR) 1.62 and 95% confidence interval (CI) 1.06-2.48 and 1.53, 95% CI 1.05-2.23, respectively). The types of sports predicting the highest risk of meniscal lesions were ballgames, gymnastics and jogging. Physical strenuousness of work did not predict meniscal lesion. The hazard of other knee injury was increased among those reporting irregular or regular physical exercise at baseline (HR 1.64, 95% CI 1.03-2.64 and 1.88 CI 1.05-2.36, respectively). Smoking or alcohol intake were not associated with knee injuries. Conclusions: Better safety measures in high-risk sports and weight control would likely improve the prevention of meniscal lesions in populations.Peer reviewe

Chronic tendon pathology: molecular basis and therapeutic implications

Tendons are frequently affected by chronic pain or rupture. Many causative factors have been implicated in the pathology, which until relatively recently was under-researched and poorly understood. There is now a greater knowledge of the molecular basis of tendon disease. Most tendon pathology (tendinopathy) is associated with degeneration, which is thought to be an active, cell-mediated process involving increased turnover and remodelling of the tendon extracellular matrix. Degradation of the tendon matrix is mediated by a variety of metalloproteinase enzymes, including matrix metalloproteinases and ‘aggrecanases’. Neuropeptides and other factors released by stimulated cells or nerve endings in or around the tendon might influence matrix turnover, and could provide novel targets for therapeutic intervention

The biomechanical basis for glenoid labral tears

Froth flotation is the most widely used and versatile method for separating and concentrating minerals. Recent industrial experimental work has shown a positive metallurgical response can be achieved from a bank of flotation cells bv distributil1!.! the same volume of gas differently. This studv developed a froth based model of a rougher flotation bank to determine. by simulation. an air profile that will produce a high !.!rade concentrate from the first cell of the bank and a hi!.!h cumulative recovery. FrothSim is a phvsics based model of the froth zone in a flotation cell. This simulator has previously been used to model the !.!radc and recovery of multiple minerals from a sinulc tank. However. FrothSil1l requires experimental measurements of the overflowing bubble sizc and the fraction of the inlet air which overflows the \Veir of the cell as unburst bubbles. the air recavcn'. to make predictions. In this work FrothSil1l was used. for the first time. to develop a base case model of a bank of roLH!her flotation cells based on industrial experimental data. A close a!.!reement was obtained betwcen the modelled results and the experimental results for both floatable and cntrained minerals. A rigorous and robust procedure for the development of sin!.!le cell and full bank models was produced. An empirical model to predict the superficial velocity of the gas lost throu!.!h the froth surface has been developed. This model can be used to predict the air recovery from a flotation cell at different air rates. In conjunction. overflowin!.! bubble sizes were inferred from expcrimental data usin!.! a theoretical model. These were found not to vary significantly with air rate. These two models were combined with the FrothSil1l base case model to predict flotation performance at different gas distribution profiles. A new profile was found to vield the desired performance. The improved perfomlance can be attributed to an increase in froth recovery at all points in the hank. An industrial sampling campai!.!n was carried out to verifv the predicted operatin!.! performance for three eas distribution profiles. The experimental !.!rade rccoven' curves. for both floatable and primarilY entrained minerals. showed the same trends as the predicted results. The new gas distribution profile eave a hi!.!h grade concentrate from cell 1 and the hi!.!hest cumulatiye recoven'. This froth modelling approach. in which empirical models are combined with a physics based froth model can therefore be used to successfully manage gas distribution to a bank of cells.Imperial Users onl

Novel Approaches in Meniscal Repair Utilizing Mesenchymal Stem Cells, New Generation Bioscaffolds and Biological Adhesives as Cell Delivery Vehicles

Mesenchymal stem cells (MSCs) have been widely applied in the repair of the knee-joint menisci which have a limited ability to undergo spontaneous repair. The menisci stabilise the knee-joint and are weight-bearing structures subjected to considerable tensional and compressive forces during flexion-extension and torsional loading of the knee. Traumatic loading of the knee-joint menisci can generate a number of lesions in the inner avascular meniscal regions. These have a limited capability of intrinsic repair and predispose the underlying articular cartilages to premature osteoarthritis. A number of strategies have therefore been developed for meniscal repair employing MSCs, bioscaffolds, hydrogels, biological glue cell delivery systems and agents which promote cell proliferation/matrix synthesis. Meniscal implants have also been developed in combination with the above procedures. It is important that meniscal defects be repaired not only to maintain knee-joint stability but also to prevent further degenerative changes in other knee joint tissues. Degenerative menisci contribute degradative proteinases and inflammatory mediators to the total synovial degradative proteinase pool. Partial or total surgical removal of the menisci is not a solution since this leads to premature osteoarthritis. Meniscal integrity needs to be maintained or repair strategies implemented in a timely manner to maintain knee joint function

Contaminants in commercial preparations of ‘purified’ small leucine-rich proteoglycans may distort mechanistic studies

The authors are grateful to Genodisc (EC’s 7th Framework Programme (FP7, 2007-2013) under grant agreement no. HEALTH-F2-2008-201626) and the Orthopaedic Institute Ltd for funding.This paper reports the perplexing results that came about because of seriously impure commercially available reagents. Commercial reagents and chemicals are routinely ordered by scientists and are expected to have been rigorously assessed for their purity. Unfortunately, we found this assumption to be risky. Extensive work was carried out within our laboratory using commercially-sourced preparations of the small leucine-rich proteoglycans, decorin and biglycan, to investigate their influence on nerve cell growth. Unusual results compelled us to analyse the composition and purity of both preparations of these proteoglycans using both mass spectrometry and Western blotting, with and without various enzymatic deglycosylations. Commercial ‘decorin’ and ‘biglycan’ were found to contain a mixture of proteoglycans including not only both decorin and biglycan but also fibromodulin and aggrecan. The unexpected effects of ‘decorin’ and ‘biglycan’ on nerve cell growth could be explained by these impurities. Decorin and biglycan contain either chondroitin or dermatan sulphate glycosaminoglycan chains whilst fibromodulin only contains keratan sulphate and the large (>2,500 kDa), highly glycosylated aggrecan, contains both keratan and chondroitin sulphate. The different structure, molecular weights and composition of these impurities significantly affected our work and any conclusions that could be made. These findings beg the question as to whether scientists need to verify the purity of each commercially obtained reagent used in their experiments. The implications of these findings are vast, since the effects of these impurities may already have led to inaccurate conclusions and reports in the literature with concomitant loss of researchers’ funds and time.Publisher PDFPeer reviewe

Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilages compared with age-matched macroscopically normal and control tissues

Introduction: The small leucine-rich proteoglycans (SLRPs) modulate tissue organization, cellular proliferation, matrix adhesion, growth factor and cytokine responses, and sterically protect the surface of collagen type I and II fibrils from proteolysis. Catabolism of SLRPs has important consequences for the integrity of articular cartilage and meniscus by interfering with their tissue homeostatic functions. Methods: SLRPs were dissociatively extracted from articular cartilage from total knee and hip replacements, menisci from total knee replacements, macroscopically normal and fibrillated knee articular cartilage from mature age-matched donors, and normal young articular cartilage. The tissue extracts were digested with chondroitinase ABC and keratanase-I before identification of SLRP core protein species by Western blotting using antibodies to the carboxyl-termini of the SLRPs. Results: Multiple core-protein species were detected for all of the SLRPs (except fibromodulin) in the degenerate osteoarthritic articular cartilage and menisci. Fibromodulin had markedly less fragments detected with the carboxyl-terminal antibody compared with other SLRPs. There were fewer SLRP catabolites in osteoarthritic hip than in knee articular cartilage. Fragmentation of all SLRPs in normal age-matched, nonfibrillated knee articular cartilage was less than in fibrillated articular cartilage from the same knee joint or total knee replacement articular cartilage specimens of similar age. There was little fragmentation of SLRPs in normal control knee articular cartilage. Only decorin exhibited a consistent increase in fragmentation in menisci in association with osteoarthritis. There were no fragments of decorin, biglycan, lumican, or keratocan that were unique to any tissue. A single fibromodulin fragment was detected in osteoarthritic articular cartilage but not meniscus. All SLRPs showed a modest age-related increase in fragmentation in knee articular and meniscal cartilage but not in other tissues. Conclusion: Enhanced fragmentation of SLRPs is evident in degenerate articular cartilage and meniscus. Specific decorin and fibromodulin core protein fragments in degenerate meniscus and/or human articular cartilage may be of value as biomarkers of disease. Once the enzymes responsible for their generation have been identified, further research may identify them as therapeutic targets

Treating navicular disease

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