Clinimetric properties of WOMAC Index in Greek knee osteoarthritis patients: comparisons with both self-reported and physical performance measures.

This observational study aimed to examine the clinimetric properties of the Greek for Greece translation of the Western Ontario and McMaster Osteoarthritis Index (WOMAC(®)). One hundred and twenty-three patients with knee osteoarthritis (mean age 69.5 years) participated in the study. An extensive reliability study was carried out to assess WOMAC's internal consistency and repeatability (8-day interval). In addition, we examined the construct (convergent, nomological and known-groups) and criterion-related (concurrent and predictive) validity of the index against both self-report [SF-36 and combined visual analog/faces pain scale-revised (VAS/FPS-R)] and physical performance measures [timed up and go test (TUG)]. The internal consistency of the WOMAC subscales ranged from high (0.804) to excellent (0.956). Intra-class correlation coefficients for test-retest reliability were excellent, ranging from 0.91 to 0.95. Partial correlation analysis, adjusted for age and use of an assistive device, showed that WOMAC scores were significantly associated with all validation criteria, presenting fair to strong (-0.33 to -0.86) correlation coefficients. WOMAC-function was strongly associated with SF36-function (-0.86) and TUG (0.71), WOMAC-pain to VAS/FPS-R (0.71) and SF36-pain (-0.67). Of all WOMAC outcomes, stiffness subscale had the lowest, though still significant, correlations with all validation criteria. Multiple linear regression analyses indicated that WOMAC-function was a significant factor for TUG, WOMAC-pain for VAS/FPS-R and both for SF36-function and SF36-pain. The WOMAC LK3.1 Greek for Greece Index is a reliable and valid assessment tool for the evaluation of individuals with knee osteoarthritis, showing excellent reliability and significant validity properties.

Clinical results of linezolid in arthroplasty and trauma MRSA related infections.

AIM: To analyse the management of patients treated with linezolid for orthopaedic infections. METHODS: Twenty-two patients with orthopaedic related infections receiving a course of linezolid were reviewed retrospectively. Patients were classified into either post trauma, post arthroplasty and non trauma related infections. A diagnosis of infection was based on clinical findings, positive microbiological specimens, and positive signs of infection on radiological imaging and raised inflammatory markers. Pathogens isolated, inflammatory markers both at presentation and at final follow up, length of linezolid treatment, adverse drug reactions, concomitant anti-microbial therapy, length of hospital stay and any surgical interventions were recorded. RESULTS: Infections were classified as post arthroplasty (n = 10), post trauma surgery (n = 8) or non-trauma related infections (n = 4). Twenty patients (91%) underwent surgical intervention as part of their treatment. The number of required surgical procedures ranged from 1 to 6 (mean = 2.56). Mean total length of stay per admission was 28.5 d (range 1-160 d). Furthermore, the mean duration of treatment with linezolid of patients who had resolution of symptoms was 31 d (range 10-84 d). All patients within this group were discharged on oral linezolid. Pathogens isolated included methicillin resistant Staphylococcus aureus, coagulase negative staphylococci, coliforms, enterococcus, Staphylococcus epidermidis, streptococcus viridans, Escherichia coli, group B streptococcus and pseudomonas. An overall 77% of patients demonstrated resolution of infections at follow-up, with mean C-reactive protein reducing from 123 mg/L to 13.2 mg/L. CONCLUSION: This study demonstrates that the use of linezolid offers excellent efficacy in orthopaedic related infections when used alongside appropriate surgical management.

Anti-inflammatory role and immunomodulation of mesenchymal stem cells in systemic joint diseases: potential for treatment.

INTRODUCTION: Mesenchymal stem cells (MSCs) are multipotent stromal cells characterized by their ability to differentiate into adipocytes, chondrocytes, osteocytes and a number of other lineages. Investigation into their use has increased in recent years as characterization of their immunomodulatory properties has developed, and their role in the pathophysiology of joint disease has been suggested. AREAS COVERED: MSCs demonstrate immunosuppressive functionality by suppressing T- and B-cell responses following activation by cytokines such as IL-6 and IL-1α. They also can be induced to exert pro-inflammatory effects in the presence of acute inflammatory environment due to the actions of TNF-α and IFN-γ. In inflammatory joint diseases such as rheumatoid arthritis, MSCs in bone marrow migrate to joints by a TNF-α-dependent mechanism and may be in part responsible for the disease process. MSCs have also been demonstrated in increased numbers in periarticular tissues in osteoarthritis, which may reflect an attempt at joint regeneration. EXPERT OPINION: Clinical applications for MSCs have shown promise in a number of inflammatory and autoimmune disorders. Future work is likely to further reveal the immunosuppressive characteristics of MSCs, their role in the pathophysiology of joint diseases and provide the basis for new avenues for treatment.

Use of oral direct factor Xa inhibiting anticoagulants in elective hip and knee arthroplasty: a meta-analysis of efficacy and safety profiles compared with those of low-molecular-weight heparins.

Assessing the efficacy and safety profiles of new oral direct Factor Xa (FXa) inhibiting anticoagulants compared with low-molecular-weight heparins (LMWHs) in elective total hip and knee arthroplasty (THA and TKA). The literature review only searched for randomised-controlled trials (RCTs) published before September 2011. Five eligible THA RCTs with a total of 12,184 patients and 5 eligible TKA RCTs with a total of 13,169 patients were identified. Mantel- Haenszel random-effects model was used to create meta-analyses of pooled data for each surgical group. The primary efficacy outcome was the risk of venous thromboembolism (VTE) and all-cause mortality, and the primary safety outcome was the risk of major bleeding. The THA and TKA primary efficacy outcome meta-analyses calculated relative risks (RR) of 0.55 (95% confidence interval 0.32 to 0.94) and 0.68 (95% confidence interval 0.53 to 0.87), respectively in favor of the oral direct FXa inhibitors. The primary safety outcome meta-analyses for the THA and TKA surgical groups revealed an RR of 1.27 (95% confidence interval 0.56 to 2.86) and 0.94 (95% confidence interval 0.44 to 1.98), which shows no significant difference between oral FXa inhibitors and LMWHs. This review demonstrated that oral direct FXa inhibitors have a superior efficacy to LMWHs when used as thromboprophylaxis in both THA and TKA. The safety profile of these new oral anticoagulants was not significantly different to that of LMWHs.

Sclerostin monoclonal antibodies on bone metabolism and fracture healing.

INTRODUCTION: The biological enhancement of fracture healing may prevent complications such as non-union and revision surgery. Sclerostin is produced by osteocytes and binds to the LRP5/6 receptor. This inhibits the Wnt signalling pathway and thereby reduces bone formation. AREAS COVERED: Targeted deletion of the sclerostin gene has been found to enhance bone formation and fracture healing in rodent models. A number of in vivo studies have investigated the effect of sclerostin antibody on bone density with promising results. It also has an ability to promote fracture healing, screw fixation and metaphyseal bone healing in vivo. Early clinical studies have also demonstrated that it can increase bone mineral density, whilst being safe and well tolerated by patients. EXPERT OPINION: The data support the further investigation of this agent for the promotion of fracture healing. We aim to review the current literature and present an update on the use of this agent to promote bone formation and healing.

Preclinical and clinical data for the use of mesenchymal stem cells in articular cartilage tissue engineering.

INTRODUCTION: With an ageing population, the prevalence of osteoarthritis (OA) has increased. Mesenchymal Stem Cells (MSCs) have been proposed to be an attractive alternative candidate in the tissue engineering of articular cartilage primarily due to its abundant source, reduced cartilage donor site morbidity, and strong capacity for proliferation and potential to differentiate toward a chondrogenic phenotype. AREAS COVERED: A current overview of human, in vivo, and in vitro evidence on the use of MSCs in cartilage tissue engineering. EXPERT OPINION: We demonstrate robust evidence that MSCs have the potential to regenerate articular cartilage. We also identify the complexity of designing a suitable preclinical model and the challenges in considering its clinical application such as type of MSC, scaffold, culture construct and the method by which growth factors are delivered. Of great interest is further characterization of the factors that may prevent MSC-derived chondrocytes to undergo premature hypertrophy and to understand what enables the terminal developmental pathway for permanent hyaline cartilage regeneration. Despite this, there is an abundance of evidence suggesting that MSCs are a desirable cell source and will have significant impact in tissue engineering of cartilage in the future.

Stem cells combined with bone graft substitutes in skeletal tissue engineering.

INTRODUCTION: Bone grafting is used to repair large bone defects and autograft is recognised as producing the best clinical outcome, which is partly due to its cellular component. When autograft is unavailable, allograft and bone graft substitutes can be used; however, they rely on the host bed to provide cellular osteogenic activity. AREAS COVERED: Bone graft substitutes have the potential to benefit from the addition of stem cells aimed at enhancing the rate and quality of defect repair. Mesenchymal stem cells (MSCs) can be isolated from bone marrow or periosteum and culture expanded. Other sources of primary cells include muscle, adipose tissue, human umbilical cord and the pluripotent embryonic stem cells (ESCs). EXPERT OPINION: MSCs isolated from bone marrow have been the best characterised approach for osteogenic differentiation. Their use with synthetic scaffolds such as hydroxyapatite and tricalcium phosphate has produced promising clinical results. MSCs derived from adipose tissue, muscle or human umbilical cord cells combined with various scaffolds are an attractive option. Further in vivo and clinical investigation of their potential is required. Pluripotent ESCs have a theoretical advantage over MSCs; however, purification, cell-specific differentiation, effective delivery vehicles-scaffolds and teratogenesis control are still under in vitro and in vivo evaluation.

Pharmacological treatment of heterotopic ossification following hip surgery: an update.

Heterotopic ossification is a frequent complication following total hip arthroplasty and acetabular surgery. Formation of ectopic lamellar bone in tissues that exhibit no potential for ossification can lead to associated pain and decrease in function. Prophylaxis and treatment protocols aim to reduce the incidence, by both the use of nonsteroidal anti-inflammatory drug (NSAID) regimens and localized radiotherapy. New therapeutic modalities including bone morphogenetic proteins (BMP) inhibitors like Noggin, BMP type 1 receptor inhibition, nuclear retinoic acid receptor-gamma agonists (RAR-γ), and free radical scavengers are currently under investigation.