Showing papers by "Nuffield Orthopaedic Centre published in 2008"
TL;DR: The Medical Research Council's evaluation framework (2000) brought welcome clarity to the task and now the council has updated its guidance.
Abstract: Evaluating complex interventions is complicated. The Medical Research Council9s evaluation framework (2000) brought welcome clarity to the task. Now the council has updated its guidance
8,896 citations
TL;DR: Each bisphosphonates has a unique profile that may help to explain potential clinical differences among them, in terms of their speed and duration of action, and effects on fracture reduction.
Abstract: Summary
Bisphosphonates (BPs) are well established as the leading drugs for the treatment of osteoporosis. There is new knowledge about how they work. The differences that exist among individual BPs in terms of mineral binding and biochemical actions may explain differences in their clinical behavior and effectiveness.
1,280 citations
TL;DR: The most common symptom was discomfort in the region of the hip and other symptoms included spontaneous dislocation, nerve palsy, a noticeable mass or a rash as mentioned in this paper, and the common histological features were extensive necrosis and lymphocytic infiltration.
Abstract: We report 17 patients (20 hips) in whom metal-on-metal resurfacing had been performed and who presented with various symptoms and a soft-tissue mass which we termed a pseudotumour. Each patient underwent plain radiography and in some, CT, MRI and ultrasonography were also performed. In addition, histological examination of available samples was undertaken. All the patients were women and their presentation was variable. The most common symptom was discomfort in the region of the hip. Other symptoms included spontaneous dislocation, nerve palsy, a noticeable mass or a rash. The common histological features were extensive necrosis and lymphocytic infiltration. To date, 13 of the 20 hips have required revision to a conventional hip replacement. Two are awaiting revision. We estimate that approximately 1% of patients who have a metal-on-metal resurfacing develop a pseudotumour within five years. The cause is unknown and is probably multifactorial. There may be a toxic reaction to an excess of particulate metal wear debris or a hypersensitivity reaction to a normal amount of metal debris. We are concerned that with time the incidence of these pseudotumours may increase. Further investigation is required to define their cause.
914 citations
TL;DR: Steeply-inclined acetabular components, with abduction angles greater than 55 degrees, combined with a small size of component are likely to give rise to higher serum levels of cobalt and chromium ions, probably due to a greater risk of edge-loading.
Abstract: We examined the relationships between the serum levels of chromium and cobalt ions and the inclination angle of the acetabular component and the level of activity in 214 patients implanted with a metal-on-metal resurfacing hip replacement. Each patient had a single resurfacing and no other metal in their body. All serum measurements were performed at a minimum of one year after operation. The inclination of the acetabular component was considered to be steep if the abduction angle was greater than 55°.
There were significantly higher levels of metal ions in patients with steeply-inclined components (p = 0.002 for chromium, p = 0.003 for cobalt), but no correlation was found between the level of activity and the concentration of metal ions. A highly significant (p < 0.001) correlation with the arc of cover was found. Arcs of cover of less than 10 mm were correlated with a greater risk of high concentrations of serum metal ions. The arc of coverage was also related to the design of the component and to size as well as to the abduction angle of the acetabular component. Steeply-inclined acetabular components, with abduction angles greater than 55°, combined with a small size of component are likely to give rise to higher serum levels of cobalt and chromium ions. This is probably due to a greater risk of edge-loading.
536 citations
TL;DR: Because osteoarthritis involves all of the tissues of the synovial joint, the emphasis on the loss of cartilage, in particular, is misguided, it is argued that OA is best defined as failed repair of damage that has been caused by excessive mechanical stress on joint tissues.
Abstract: In this article, the authors posit that, because osteoarthritis (OA) involves all of the tissues of the synovial joint, the emphasis on the loss of cartilage, in particular, is misguided. In contrast, the authors view OA as a process that is attempting to contain a mechanical problem in the joint. They argue that OA is best defined as failed repair of damage that has been caused by excessive mechanical stress on joint tissues. Because the body's innate mechanisms for repairing the damaged tissues cannot be effective in the face of the overwhelming mechanical abnormality, they cannot solve the problem of OA.
372 citations
TL;DR: The majority of persistent symptoms were mild, with pain being the most common complaint, and those with the most severe symptoms at condition onset had the worst long-term prognosis, P < .001.
363 citations
TL;DR: There is a potential for much higher concentrations of metal wear products in the joint fluid in the vicinity of the bearing surfaces of poorly functioning metal-on-metal implants, and there is concern about the relatively high levels of metallic ions released into the body as a consequence.
Abstract: Metal-on-metal bearings for hip replacement are gaining popularity as an alternative to the most widely used bearing couple of metal on polyethylene1. The recent resurgence of hip resurfacing with the so-called third and fourth generations of hip resurfacing arthroplasty devices has played a substantial role in the wider use of metal-on-metal bearings2-4. Concerns about the wear of polyethylene and the role of polyethylene wear debris in the process of aseptic loosening have also increased the use of hard-on-hard bearing couples.
However, wear still takes place with metal-on-metal bearings, and there is concern about the relatively high levels of metallic ions released into the body as a consequence. Cobalt-chromium alloy is the metal used for metal-on-metal implants and, while these elements are required for normal biological function, high concentrations of cobalt and chromium are toxic and are known to interfere with a number of biological processes5,6. The metal ion levels typically seen in patients with well-functioning metal-on-metal implants are not thought to be close to toxic levels7 and in many instances are not much higher than those in patients with metal-on-polyethylene implants8. However, there is a potential for much higher concentrations of metal wear products in the joint fluid in the vicinity of the bearing surfaces of poorly functioning metal-on-metal implants. It is these very high levels that are thought to be responsible for adverse reactions such as osteolysis9 and the formation of soft-tissue masses10,11 and that give rise to metallosis (defined as gray discoloration of the hip joint)12. It is not clear whether the levels of metal ions measured in blood serum are indicative of the metal ion concentrations in the joint fluid. Perhaps more importantly, the serum concentrations that are …
329 citations
TL;DR: The panel formulated a consensus scheme for the diagnosis of diabetic foot osteomyelitis (DFO) for research purposes, and undertook a systematic review of the evidence relating to treatment.
Abstract: The International Working Group on the Diabetic Foot appointed an expert panel to provide evidence-based guidance on the management of osteomyelitis in the diabetic foot. Initially, the panel formulated a consensus scheme for the diagnosis of diabetic foot osteomyelitis (DFO) for research purposes, and undertook a systematic review of the evidence relating to treatment. The consensus diagnostic scheme was based on expert opinion; the systematic review was based on a search for reports of the effectiveness of treatment for DFO published prior to December 2006. The panel reached consensus on a proposed scheme that assesses the probability of DFO, based on clinical findings and the results of imaging and laboratory investigations. The literature review identified 1168 papers, 19 of which fulfilled criteria for detailed data extraction. No significant differences in outcome were associated with any particular treatment strategy. There was no evidence that surgical debridement of the infected bone is routinely necessary. Culture and sensitivity of isolates from bone biopsy may assist in selecting properly targeted antibiotic regimens, but empirical regimens should include agents active against staphylococci, administered either intravenously or orally (with a highly bioavailable agent). There are no data to support the superiority of any particular route of delivery of systemic antibiotics or to inform the optimal duration of antibiotic therapy. No available evidence supports the use of any adjunctive therapies, such as hyperbaric oxygen, granulocyte-colony stimulating factor or larvae. We have proposed a scheme for diagnosing DFO for research purposes. Data to inform treatment choices in DFO are limited, and further research is urgently needed.
270 citations
TL;DR: In theatre the simulator-trained group performed significantly better than the untrained group using the Orthopaedic Competence Assessment Project score and assessment by the global rating scale, demonstrating the transfer of psychomotor skills from simulator training to arthroscopy in the operating theatre.
Abstract: The aim of this study was to investigate the effect of laboratory-based simulator training on the ability of surgical trainees to perform diagnostic arthroscopy of the knee. A total of 20 junior orthopaedic trainees were randomised to receive either a fixed protocol of arthroscopic simulator training on a bench-top knee simulator or no additional training. Motion analysis was used to assess performance objectively. Each trainee then received traditional instruction and demonstrations of diagnostic arthroscopy of the knee in theatre before performing the procedure under the supervision of a blinded consultant trainer. Their performance was assessed using a procedure-based assessment from the Orthopaedic Competence Assessment Project and a five-point global rating assessment scale. In theatre the simulator-trained group performed significantly better than the untrained group using the Orthopaedic Competence Assessment Project score (p = 0.0007) and assessment by the global rating scale (p = 0.0011), demonstrating the transfer of psychomotor skills from simulator training to arthroscopy in the operating theatre. This has implications for the planning of future training curricula.
259 citations
TL;DR: The five-year clinical outcome and seven-year survival of an independent series of Birmingham Hip Resurfacing arthroplasties support the use of resurfacing and address the early failures, particularly those related to fracture and metal debris.
Abstract: Few independent studies have reported the outcome of resurfacing arthroplasty of the hip. The aim of this study was to report the five-year clinical outcome and seven-year survival of an independent series. A total of 610 Birmingham Hip Resurfacing arthroplasties were performed in 532 patients with a mean age of 51.8 years (16.5 to 81.6). They were followed for between two and eight years; 107 patients (120 hips) had been followed up for more than five years. Two patients were lost to follow-up. At a minimum of five years' follow-up, 79 of 85 hips (93%) had an excellent or good outcome according to the Harris hip score. The mean Oxford hip score was 16.1 points (sd 7.7) and the mean University of California Los Angeles activity score was 6.6 points (sd 1.9). There were no patients with definite radiological evidence of loosening or of narrowing of the femoral neck exceeding 10% of its width. There were 23 revisions (3.8%), giving an overall survival of 95% (95% confidence interval 85.3 to 99.2) at seven years. Fractured neck of femur in 12 hips was the most common indication for revision, followed by aseptic loosening in four. In three hips (three patients) (0.5%), failure was possibly related to metal debris. Considering that these patients are young and active these results are good, and support the use of resurfacing. Further study is needed to address the early failures, particularly those related to fracture and metal debris.
216 citations
TL;DR: This is the largest reported series of infections following posterior spinal instrumented fusions, of which the author is aware, and successful eradication of infection cannot be reliably achieved with antibiotics and wound debridement alone.
Abstract: A 10-year retrospective audit. (1) The incidence of infection; (2) causative organisms; (3) whether eradication of infection is achievable with spinal implant retention; (4) patient outcome. The reported incidence of infection following posterior spinal instrumentation is between 2.6 and 3.8%. Management of infection is controversial, with some advocating serial wound debridement while others report that infection cannot be eradicated with retention of implants. There are no published data demonstrating that propionibacteria are associated with early postoperative infection. The management of infected cases at our institution includes eventual removal of their implants. Our population was identified by studying the case notes of all patients who had undergone removal of spinal implants and cross-referencing this population with positive microbiology or histology reports. The incidence of infection was 3.7%. Propionibacteria were isolated in 45% of cases. The diagnosis of infection was unexpected in 25% of patients, following removal of implants for prominence of implants or back pain. Sixty per cent of patients with acute postoperative deep wound infection had continuing active infection on subsequent removal of implants, despite long-term antibiotics and wound debridement. Fourty-six per cent of patients had a stable, pain-free spine at the end of their treatment. This is the largest reported series of infections following posterior spinal instrumented fusions of which we are aware. Propionibacteria are a common cause of infection and successful eradication of infection cannot be reliably achieved with antibiotics and wound debridement alone.
TL;DR: The first series of extra-axial skeletal chordomas are described, bringing the total number of such cases reported in the literature to 11, and the first report of 2 soft tissue chordomas as defined by brachyury expression is presented.
Abstract: Axial chordoma represents approximately 1% of malignant bone tumors. This tumor expresses cytokeratins, specifically cytokeratin 19, and commonly S100. More recently brachyury, a transcription factor important in mesodermal differentiation, including notochord development, has been detected by immunohistochemistry in axial chordomas and hemangioblastomas but not chondrosarcomas or other neoplasms. In this report, we describe 10 cases (6 men, 4 women: age 18 to 68 y; mean 44.6) of extra-axial tumors, 8 in bone and 2 in soft tissue, with morphologic and immunohistochemical features identical to those of axial chordoma. Imaging excluded metastases from axial chordoma. Three tumors occurred in the tibia, the others in the rib, metatarsal, ulna, femur, pubis: 2 intracortical, 6 intramedullary. Both soft tissue brachyury-positive tumors, one involving the thumb the other the wrist, were sited in the juxta-articular region. Seven of the tumors were widely excised and these patients are disease-free but of the 3 tumors that recurred, 1 was curetted, 1 was marginally excised, and 1 had a pathologic fracture on presentation. Metastases have not occurred in any of the patients. We also confirm the expression of brachyury in hemangioblastomas, and for the first time demonstrates its expression in spermatogonia and testicular germ cell tumors by immunohistochemistry. Brachyury was not detected in a wide range of tumors including carcinomas, lymphomas, and sarcomas. In conclusion, we describe the first series of extra-axial skeletal chordomas bringing the total number of such cases reported in the literature to 11, and present the first report of 2 soft tissue chordomas as defined by brachyury expression.
TL;DR: Obese and morbidly obese patients have as much to gain from total hip replacement as non-obese patients.
Abstract: A prospective, multi-centre study was carried out on 1421 total hip replacements between January 1999 and July 2007 to examine if obesity has an effect on clinical outcomes. The patients were categorised into three groups: non-obese (body mass index (BMI) 40 kg/m(2)). The primary outcome measure was the change in Oxford hip score at five years. Secondary outcome measures included dislocation and revision rates, increased haemorrhage, deep infection, deep-vein thrombosis and pulmonary embolism, mean operating time and length of hospital stay. Radiological analysis assessing heterotopic ossification, femoral osteolysis and femoral stem positioning was performed. Data were incomplete for 362 hips (25.5%) There was no difference in the change in the Oxford hip score, complication rates or radiological changes at five years between the groups. The morbidly obese group was significantly younger and required a significantly longer operating time. Obese and morbidly obese patients have as much to gain from total hip replacement as non-obese patients.
TL;DR: A questionnaire to assess patient-reported outcome after surgery of the elbow from interviews with patients is developed, which comprises three unidimensional domains, 'elbow function', 'pain' and 'social-psychological'; with each domain comprising four items with good measurement properties.
Abstract: We developed a questionnaire to assess patient-reported outcome after surgery of the elbow from interviews with patients. Initially, 17 possible items with five response options were included. A prospective study of 104 patients (107 elbow operations) was carried out to analyse the underlying factor structure, dimensionality, internal and test-retest reliability, construct validity and responsiveness of the questionnaire items. This was compared with the Mayo Elbow performance score clinical scale, the Disabilities of the Arm, Shoulder and Hand questionnaire, and the Short-Form (SF-36) General Health Survey. In total, five questions were considered inappropriate, which resulted in the final 12-item questionnaire, which has been referred to as the Oxford elbow score. This comprises three unidimensional domains, 'elbow function', 'pain' and 'social-psychological'; with each domain comprising four items with good measurement properties. This new 12-item Oxford elbow score is a valid measure of the outcome of surgery of the elbow.
TL;DR: A meta-analysis combining data from the UK and the Netherlands with the three published studies of Europe and Asia provides strong evidence of a positive association of the GDF5 SNP with knee OA for Europeans as well as for Asians.
Abstract: We have performed a meta-analysis combining data for over 11,000 individuals. It provides compelling evidence for a positive association between a functional SNP in the 5' UTR of GDF5 (+104T/C; rs143383) and osteoarthritis (OA) in European and Asian populations. This SNP has recently been reported to be associated with OA in Japanese and Han Chinese populations. Attempts to replicate this association in European samples have been inconclusive as no association was found in the case-control cohorts from the UK, Spain and Greece when studied individually. However, the pooled data of UK and Spain found an association of the T-allele with an odds ratio (OR) 1.10. Whilst the European studies had adequate power to replicate the original findings from the Japanese cohort (OR = 1.79), these results suggest that the role of the GDF5 polymorphism may not be as strong in Europeans. To clarify whether the European studies were hampered by insufficient power we combined new data from the UK and the Netherlands with the three published studies of Europe and Asia. The results provide strong evidence of a positive association of the GDF5 SNP with knee OA for Europeans as well as for Asians. The combined association for both ethnic groups is highly significant for the allele frequency model (P = 0.0004, OR = 1.21) and the dominant model (P <0.0001, OR = 1.48). These findings represent the first highly significant evidence for a risk factor for the development of OA which affects two highly diverse ethnic groups.
TL;DR: There was no significant difference in the rate of return to sport according to the type of operation, and the largest decline was in high-impact sports including badminton, tennis and dancing.
Abstract: Our aim was to determine the pre-operative sporting profiles of patients undergoing primary joint replacement and to establish if they were able to return to sport after surgery. A postal survey was completed by 2085 patients between one and three years after operation. They had undergone one of five operations, namely total hip replacement, hip resurfacing, total knee replacement, unicompartmental knee replacement or patellar resurfacing. In the three years before operation 726 (34.8%) patients were participating in sport, the most common being swimming, walking and golf. A total of 446 (61.4%) had returned to their sporting activities by one to three years after operation and 192 (26.4%) were unable to do so because of their joint replacement, with the most common reason being pain. The largest decline was in high-impact sports including badminton, tennis and dancing. After controlling for the influence of age and gender, there was no significant difference in the rate of return to sport according to the type of operation.
Journal Article•
TL;DR: The findings highlight the need to improve early diagnosis and initiation of targeted therapy, thereby reducing treatment-related toxicity and comorbidities in patients with systemic vasculitis.
Abstract: There has been a considerable improvement in the survival of patients with systemic vasculitis since the introduction of immunosuppressive therapy and improved diagnostic tools to allow earlier diagnosis. We review the published literature on current risk of mortality in patients with small vessel antineutrophil cytoplasm antibody- (ANCA) associated vasculitis including Wegener's granulomatosis (survival rate of approximately 75% at 5 years), microscopic polyangiitis (survival rate of 45% to 75% at 5 years), Churg-Strauss syndrome (survival rate of 68% to 100% at 5 years), and Henoch-Schonlein purpura (survival rate of 75% in adult-onset, greater in childhood onset); medium vessel vasculitis including polyarteritis nodosa (survival rate of 75% to 80% at 5 years), Kawasaki disease (survival rate of greater than 99% at 5 years); large vessel vasculitis including giant cell arteritis (survival rate equivalent to the age-matched population), and Takayasu arteritis (survival of 70% to 93% at 5 years). Mortality rates are falling as a result of more effective intervention but remain elevated substantially in severe disease. Early deaths are usually attributable to active vasculitis with multiorgan failure or infection, or both. The incidence of late deaths may be increased by long-term effects of therapy and development of comorbidities. These findings highlight the need to improve early diagnosis and initiation of targeted therapy, thereby reducing treatment-related toxicity and comorbidities.
TL;DR: It is concluded that penetration in the first six months is creep-dominated, but after one year virtually all penetration is due to wear and highly cross-linked polyethylene will probably perform better in the long term.
Abstract: The creep and wear behaviour of highly cross-linked polyethylene and standard polyethylene liners were examined in a prospective, double-blind randomised, controlled trial using radiostereometric analysis. We randomised 54 patients to receive hip replacements with either highly cross-linked polyethylene or standard liners and determined the three-dimensional penetration of the liners over three years. After three years the mean total penetration was 0.35 mm (SD 0.14) for the highly cross-linked polyethylene group and 0.45 mm (SD 0.19) for the standard group. The difference was statistically significant (p = 0.0184). From the pattern of penetration it was possible to discriminate creep from wear. Most (95%) of the creep occurred within six months of implantation and nearly all within the first year. There was no difference in the mean degree of creep between the two types of polyethylene (highly cross-linked polyethylene 0.26 mm, SD 0.17; standard 0.27 mm, SD 0.2; p = 0.83). There was, however, a significant difference (p = 0.012) in the mean wear rate (highly cross-linked polyethylene 0.03 mm/yr, SD 0.06; standard 0.07 mm/yr, SD 0.05). Creep and wear occurred in significantly different directions (p = 0.01); creep was predominantly proximal whereas wear was anterior, proximal and medial. We conclude that penetration in the first six months is creep-dominated, but after one year virtually all penetration is due to wear. Highly cross-linked polyethylene has a 60% lower rate of wear than standard polyethylene and therefore will probably perform better in the long term.
TL;DR: The aim of this work was to develop a low-cost automated system to measure the three-dimensional shape of the back in patients with scoliosis that reduces the dependence on serial radiography and reduces radiation exposure when monitoring spinal deformity.
Abstract: The aim of this work was to develop a low-cost automated system to measure the three-dimensional shape of the back in patients with scoliosis. The resulting system uses structured light to illuminate a patient’s back from an angle while a digital photograph is taken. The height of the surface is calculated using Fourier transform profilometry with an accuracy of ±1 mm. The surface is related to body axes using bony landmarks on the back that have been palpated and marked with small coloured stickers prior to photographing. Clinical parameters are calculated automatically and presented to the user on a monitor and as a printed report. All data are stored in a database. The database can be interrogated and successive measurements plotted for monitoring the deformity changes. The system developed uses inexpensive hardware and open source software. Accurate surface topography can help the clinician to measure spinal deformity at baseline and monitor changes over time. It can help the patients and their families to assess deformity. Above all it reduces the dependence on serial radiography and reduces radiation exposure when monitoring spinal deformity.
TL;DR: The findings indicate that comprehensive disease assessment in vasculitis requires documentation of disease activity, chronic irreversible damage and impairment of function.
Abstract: The systemic vasculitides are multisystem disorders with considerable mortality and morbidity and frequent relapses. In the absence of reliable serological markers, accurate clinical tools are required to assess disease activity and damage for treatment decisions, and for the performance of clinical trials. This article reviews and summarises the development and use of disease assessment tools for determining activity and damage in systemic vasculitis and reports ongoing initiatives for further development of disease assessment tools. A literature search was conducted using PubMed and reference lists for vasculitis, assessment, clinical trials, outcome and prognosis. The findings indicate that comprehensive disease assessment in vasculitis requires documentation of disease activity, chronic irreversible damage and impairment of function.
01 Jan 2008
TL;DR: The recent development of the genome-wide association study approach has revolutionized genetic studies of such diseases as mentioned in this paper, with two major breakthroughs in the identification of genes contributing roughly one third of the population attributable risk of the disease, and pointing directly to a potential therapy.
Abstract: Ankylosing spondylitis (AS), the prototypic seronegative arthropathy, is known to be highly heritable, with >90% of the risk of developing the disease determined genetically. As with most common heritable diseases, progress in identifying the genes involved using family-based or candidate gene approaches has been slow. The recent development of the genome-wide association study approach has revolutionized genetic studies of such diseases. Early studies in ankylosing spondylitis have produced two major breakthroughs in the identification of genes contributing roughly one third of the population attributable risk of the disease, and pointing directly to a potential therapy. These exciting findings highlight the potential of future more comprehensive genetic studies of determinants of disease risk and clinical manifestations, and are the biggest advance in our understanding of the causation of the disease since the discovery of the association with HLA-B27.
TL;DR: There is a wide diversity in studies investigating the effects of stretching on spasticity, and the available evidence on its clinical benefit is overall inconclusive, recognizing the need for consensus on a paradigm for stretching and for good-quality studies.
TL;DR: In vitro evaluation of a collagen scaffold fabricated using an indirect 3D printing technique demonstrated that the resultant collagen based scaffolds have the ability to support hMSC cell attachment and proliferation; cells can migrate and survive deep within the structure of the scaffold.
Abstract: This article reports the mechanical properties and in vitro evaluation of a collagen scaffold fabricated using an indirect 3D printing technique. Collagen scaffolds, featuring predefined internal channels and capillary networks, were manufactured using phase change printing. It was observed that the collagen scaffolds featured internal channels and a hierarchical structure that varied over length scales of 10-400 microm. In vitro evaluation using hMSCs demonstrated that the resultant collagen based scaffolds have the ability to support hMSC cell attachment and proliferation; cells can migrate and survive deep within the structure of the scaffold. The cell numbers increased 2.4 times over 28 days in culture for the lysine treated scaffolds. The cells were spread along the collagen fibers to form a 3D structure and extracellular matrix was detected on the surface of the scaffolds after 4 weeks in culture. The crosslinking treatment enhanced the biostability and dynamic properties of the collagen scaffolds significantly.
TL;DR: Recent advances in the understanding of the pathology, imaging and progression of early osteoarthritis are reviewed, with a focus on patients with a clear predisposing factor.
Abstract: Treatment strategies for osteoarthritis most commonly involve the removal or replacement of damaged joint tissue. Relatively few treatments attempt to arrest, slow down or reverse the disease process. Such options include peri-articular osteotomy around the hip or knee, and treatment of femoro-acetabular impingement, where early intervention may potentially alter the natural history of the disease. A relatively small proportion of patients with osteoarthritis have a clear predisposing factor that is both suitable for modification and who present early enough for intervention to be deemed worthwhile. This paper reviews recent advances in our understanding of the pathology, imaging and progression of early osteoarthritis.
TL;DR: Evidence from sound clinical studies is urgently needed to guide consensus and to underpin clinical practice, and it is only in this way that patients suffering with these frequently neglected complications of diabetes can be offered the best hope for a favourable outcome, at the least cost.
Abstract: Management of diabetic foot ulcers presents a major clinical challenge. The response to treatment is often poor and the outcome disappointing, while the costs are high for both healthcare providers and the patient. In such circumstances, it is essential that management should be based on firm evidence and follow consensus. In the case of the diabetic foot, however, clinical practice can vary widely. It is for these reasons that the International Working Group on the Diabetic Foot has published guidelines for adoption worldwide. The Group has now also completed a series of non-systematic and systematic reviews on the subjects of soft tissue infection, osteomyelitis, offloading and other interventions designed to promote ulcer healing. The current article collates the results of this work in order to demonstrate the extent and quality of the evidence which is available in these areas. In general, the available scientific evidence is thin, leaving many issues unresolved. Although the complex nature of diabetic foot disease presents particular difficulties in the design of robust clinical trials, and the absence of published evidence to support the use of an intervention does not always mean that the intervention is ineffective, there is a clear need for more research in the area. Evidence from sound clinical studies is urgently needed to guide consensus and to underpin clinical practice. It is only in this way that patients suffering with these frequently neglected complications of diabetes can be offered the best hope for a favourable outcome, at the least cost.
TL;DR: The model produced by the current study provides a tool for simulating mechanical test conditions on a human tibia and has considerable value in reducing the costs of physical testing by pre-selecting the most appropriate test conditions or most favorable prosthetic designs for final mechanical testing.
Abstract: Finite element (FE) models of long bones are widely used to analyze implant designs. Experimental validation has been used to examine the accuracy of FE models of cadaveric femurs; however, although convergence tests have been carried out, no FE models of an intact and implanted human cadaveric tibia have been validated using a range of experimental loading conditions. The aim of the current study was to create FE models of a human cadaveric tibia, both intact and implanted with a unicompartmental knee replacement, and to validate the models against results obtained from a comprehensive set of experiments. Seventeen strain rosettes were attached to a human cadaveric tibia. Surface strains and displacements were measured under 17 loading conditions, which consisted of axial, torsional, and bending loads. The tibia was tested both before and after implantation of the knee replacement. FE models were created based on computed tomography (CT) scans of the cadaveric tibia. The models consisted of ten-node tetrahedral elements and used 600 material properties derived from the CT scans. The experiments were simulated on the models and the results compared to experimental results. Experimental strain measurements were highly repeatable and the measured stiffnesses compared well to published results. For the intact tibia under axial loading, the regression line through a plot of strains predicted by the FE model versus experimentally measured strains had a slope of 1.15, an intercept of 5.5 microstrain, and an R(2) value of 0.98. For the implanted tibia, the comparable regression line had a slope of 1.25, an intercept of 12.3 microstrain, and an R(2) value of 0.97. The root mean square errors were 6.0% and 8.8% for the intact and implanted models under axial loads, respectively. The model produced by the current study provides a tool for simulating mechanical test conditions on a human tibia. This has considerable value in reducing the costs of physical testing by pre-selecting the most appropriate test conditions or most favorable prosthetic designs for final mechanical testing. It can also be used to gain insight into the results of physical testing, by allowing the prediction of those variables difficult or impossible to measure directly.
TL;DR: It is proposed that early diagnosis (with ultrasound confirmation) and management of this condition would offer a better prognosis and allow less interventional surgery.
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TL;DR: Results indicate that the lymphatic circulation is unlikely to play a role in bone fluid transport in normal bone and that lymphatic vessels are absent from most primary and secondary tumors confined to bone, suggesting that lymphangiogenesis is not involved in the disease progression of most primary bone tumors and that carcinomatous metastasis to bone does not occur via lymphatics.
TL;DR: It is suggested that local hypoxia could indirectly influence osteoclastogenesis via autocrine and paracrine secretion of VEGF under the control of HIF.
Abstract: Hypoxia is an important regulator of bone biology and stimulates osteoclast differentiation from monocytic precursors. Hypoxia-inducible factor (HIF) is a key pro-tumourigenic transcription factor mediating pathways of hypoxia-inducible gene expression. We have described expression of HIF-1α and HIF-2α in the multi-nucleated, osteoclast-like giant cells and the mononuclear stromal component of giant cell tumour of bone (GCTB), a locally osteolytic primary bone tumour. HIF induction was observed in culture in the osteoblastic MG-63 cell line, primary GCTB stromal cells, and monocyte-derived osteoclasts following stimulation with hypoxia (0.1% O2) or the osteoclastogenic cytokines hepatocyte growth factor (HGF) and macrophage colony-stimulating factor (M-CSF). This was accompanied by increased expression of the downstream target genes Bcl-2/adenovirus E1B 19 kD-interacting protein 3 (BNIP3), Glut-1, and vascular endothelial growth factor (VEGF). As VEGF can substitute for M-CSF to support osteoclastogenesis in the presence of receptor activator for nuclear factor κB ligand (RANKL), we assessed the effect of MG-63 hypoxic conditioned media on osteoclast differentiation. In the presence of RANKL, hypoxic conditioned media induced the formation of active osteoclasts, as assessed from the numbers of TRAP-positive multi-nucleated cells and the area of lacunar bone resorption, which was inhibited by co-incubation with a neutralizing anti-VEGF antibody. Targeted siRNA ablated HIF-1α and/or HIF-2α expression in MG-63 cells and reduced hypoxic secretion of VEGF. Hypoxic conditioned media from cells treated with siRNA for (HIF-1α + HIF-2α) produced a significant decrease in osteoclast number (p < 0.005) and activity (p < 0.05) in comparison with the scrambled siRNA control. These results suggest that local hypoxia could indirectly influence osteoclastogenesis via autocrine and paracrine secretion of VEGF under the control of HIF. This is potentially an important mechanism of pathogenesis for GCTB and other osteolytic lesions. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
TL;DR: The aim of this article was to review the current status of ultrasound imaging of patients with rheumatological disorders of the hands and feet and find out if there is increasing evidence that ultrasound detects synovitis that is silent to clinical examination.
Abstract: The aim of this article was to review the current status of ultrasound imaging of patients with rheumatological disorders of the hands and feet. Ultrasound machines with high-resolution surface probes are readily available in most radiology departments and can be used to address important clinical questions posed by the rheumatologist and sports and rehabilitation physician. There is increasing evidence that ultrasound detects synovitis that is silent to clinical examination. Detection and classification of synovitis and the early detection of bone erosions are important in clinical decision making. Ultrasound has many advantages over other imaging techniques with which it is compared, particularly magnetic resonance. The ability to carry out a rapid assessment of many widely spaced joints, coupled with clinical correlation, the ability to move and stress musculoskeletal structures and the use of ultrasound to guide therapy accurately are principal amongst these. The use of colour flow Doppler studies provides a measure of neovascularisation within the synovial lining of joints and tendons, and within tendons themselves, that is not available with other imaging techniques. Disadvantages compared to MRI include small field of view, poor image presentation, and difficulty in demonstrating cartilage and deep joints in their entirety. Contrast-enhanced magnetic resonance provides a better measure of capillary permeability and extracellular fluid than does ultrasound. The ability to image simultaneously multiple small joints in the hands and feet and their enhancement characteristics cannot be matched with ultrasound, though future developments in 3-D ultrasound may narrow this gap. Magnetic resonance provides a more uniform and reproducible image for long-term follow-up studies.