Leeds Musculoskeletal Biomedical Research Unit

Leeds, United Kingdom

Leeds Musculoskeletal Biomedical Research Unit

Leeds, United Kingdom
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Baker J.F.,University of Pennsylvania | Tan Y.K.,Singapore General Hospital | Tan Y.K.,National University of Singapore | Conaghan P.G.,University of Leeds | Conaghan P.G.,Leeds Musculoskeletal Biomedical Research Unit
Best Practice and Research: Clinical Rheumatology | Year: 2015

Rheumatoid arthritis (RA) disease activity often remains difficult to define and to quantify. As a result, numerous techniques to estimate clinical activity have been developed and are in clinical use. Therefore, more objective biomarkers for early detection and accurate measurement and quantification of the disease burden are desired for clinical use and investigative studies. Several imaging and soluble biomarkers have been studied in the disease including conventional radiography, ultrasound, magnetic resonance imaging (MRI), and serum biomarker assays. While these tools are available to physicians in many settings, their role in routine clinical care remains unclear. The goals of this review are to outline the current state of the literature regarding each of these objective tools, assess their strengths and weaknesses, and clarify the knowledge gaps to be filled before these techniques may be more widely used. © 2015 Elsevier Ltd. All rights reserved.

Martel-Pelletier J.,University of Montréal | Barr A.J.,University of Leeds | Barr A.J.,Leeds Musculoskeletal Biomedical Research Unit | Cicuttini F.M.,Monash University | And 10 more authors.
Nature Reviews Disease Primers | Year: 2016

Osteoarthritis (OA) is the most common joint disorder, is associated with an increasing socioeconomic impact owing to the ageing population and mainly affects the diarthrodial joints. Primary OA results from a combination of risk factors, with increasing age and obesity being the most prominent. The concept of the pathophysiology is still evolving, from being viewed as cartilage-limited to a multifactorial disease that affects the whole joint. An intricate relationship between local and systemic factors modulates its clinical and structural presentations, leading to a common final pathway of joint destruction. Pharmacological treatments are mostly related to relief of symptoms and there is no disease-modifying OA drug (that is, treatment that will reduce symptoms in addition to slowing or stopping the disease progression) yet approved by the regulatory agencies. Identifying phenotypes of patients will enable the detection of the disease in its early stages as well as distinguish individuals who are at higher risk of progression, which in turn could be used to guide clinical decision making and allow more effective and specific therapeutic interventions to be designed. This Primer is an update on the progress made in the field of OA epidemiology, quality of life, pathophysiological mechanisms, diagnosis, screening, prevention and disease management. © 2016 Macmillan Publishers Limited. All rights reserved.

Mackie S.L.,Chapel Allerton Hospital | Mackie S.L.,Leeds Musculoskeletal Biomedical Research Unit | Pease C.T.,Leeds Teaching Hospitals NHS Trust | Fukuba E.,The University of Shimane | And 10 more authors.
Annals of the Rheumatic Diseases | Year: 2015

Objectives: To determine whether whole-body MRI defines clinically relevant subgroups within polymyalgia rheumatica (PMR) including glucocorticoid responsiveness. Methods: 22 patients with PMR and 16 with rheumatoid arthritis (RA), untreated and diagnosed by consultant rheumatologists, underwent whole-body, multiple-joint MRI, scored by two experts. Patients with PMR reported whether they felt 'back to normal' on glucocorticoid therapy and were followed for a median of 2 years. Results: All patients with PMR were deemed to respond to glucocorticoids clinically. A characteristic pattern of symmetrical, extracapsular inflammation, adjacent to greater trochanter, acetabulum, ischial tuberosity and/or symphysis pubis, was observed in 14/22 of the PMR cases. In PMR, this pattern was associated with complete glucocorticoid response (p=0.01), higher pretreatment Creactive protein (CRP) and serum interleukin-6 (IL-6), and better post-treatment fatigue and function. Only 1/14 in the extracapsular group could stop glucocorticoids within 1 year, compared with 4/7 of the others. A score derived from the five sites discriminating best between PMR and RA correlated with IL-6 (p<0.002). IL-6 levels ≥16.8 pg/mL had 86% sensitivity and 86% specificity for the extracapsular MRI pattern. Conclusions: A subset of patients with rheumatologist diagnosed PMR had a characteristic, extracapsular pattern of MRI inflammation, associated with elevated IL-6/CRP and with complete patient-reported glucocorticoid responsiveness.

Coates L.C.,University of Leeds | Coates L.C.,Leeds Musculoskeletal Biomedical Research Unit | Helliwell P.S.,Leeds Teaching Hospitals NHS Trust | Helliwell P.S.,University of Leeds
Annals of the Rheumatic Diseases | Year: 2016

Treating to target is becoming the standard of care in many medical specialities, including rheumatology. The Tight Control of Psoriatic Arthritis (TICOPA) trial has recently provided evidence of the benefit of treating to target in psoriatic arthritis (PsA), and the revised European League Against Rheumatism (EULAR) recommendations on the management of PsA suggest this approach. However, the question of the optimal measure to use and the practicalities of incorporating this into routine clinical practice remain problematic.

Ledsam J.R.,University of Leeds | Hodgson R.,Leeds Musculoskeletal Biomedical Research Unit | Moots R.J.,University of Liverpool | Sourbron S.P.,University of Leeds
Journal of Magnetic Resonance Imaging | Year: 2013

Purpose: To identify the optimal tracer-kinetic modeling strategy for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data acquired at low temporal resolution. Materials and Methods: DCE-MRI was performed on 13 patients with rheumatoid arthritis of the hand before and after anti-tumor necrosis factor alpha (TNFα) therapy, using a 3D sequence with a temporal resolution of 13 seconds, imaging for 4 minutes postcontrast injection. Concentration-time curves were extracted from regions of interest (ROIs) in enhancing synovium and fitted to the 3-parameter modified Tofts model (MT) and the 4-parameter two-compartment exchange model (2CXM). To assist the interpretation of the data, the same analysis was applied to simulated data with similar characteristics. Results: Both models fitted the data closely, and showed similar therapy effects. The MT plasma volume was significantly lower than with 2CXM, but the differences in permeability and interstitial volume were not significant. 2CXM was less precise than MT, with larger standard deviations relative to the mean in most parameters. The additional perfusion parameter determined with 2CXM did not provide a statistically significant trend due to low precision. Conclusion: The standard MT model is the optimal modeling strategy at low temporal resolution. Advanced models improve the accuracy and generate an additional parameter, but these benefits are offset by low precision. © 2013 Wiley Periodicals, Inc.

Tan Y.K.,University of Leeds | Tan Y.K.,Singapore General Hospital | Conaghan P.G.,University of Leeds | Conaghan P.G.,Leeds Musculoskeletal Biomedical Research Unit
International Journal of Rheumatic Diseases | Year: 2012

Magnetic resonance imaging (MRI) has added a new dimension to the study of osteoarthritis, a long-known degenerative joint disease with limited therapeutic options. It has advanced our understanding of joint pathophysiology and identifying that osteoarthritis as a simple 'wear and tear' process of the articular cartilage has indeed become a thing of the past. Recent work has focused on the study and validation of MRI scoring/quantification systems, as well as the identification of MRI predictors of symptoms/disease progression. The latter may serve to identify patients at greater risk for osteoarthritis disease progression to be enrolled in clinical trials. Like all imaging tools, MRI use has its associated problems. Structural changes seen in patients with osteoarthritis are often seen in asymptomatic subjects and this makes an MRI definition of osteoarthritis less straightforward. The ability to pick up multiple structural abnormalities simultaneously and high sensitivity in delineating structural changes can makes interpretation of true pathology more complicated. Although there has been much progress in the field of MRI in osteoarthritis, there remain many clinical/technical issues that need to be addressed. Until more data are obtained from clinical trials, the question of whether MRI is useful in therapeutics intervention in osteoarthritis remains unanswered. © 2011 The Authors. International Journal of Rheumatic Diseases © 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.

Dunbar J.A.T.,Leeds General Infirmary | Sandoe J.A.T.,Leeds General Infirmary | Rao A.S.,Leeds General Infirmary | Crimmins D.W.,Leeds General Infirmary | And 3 more authors.
Clinical Radiology | Year: 2010

Aim: To describe the magnetic resonance imaging (MRI) appearances in patients with a clinical history suggestive of vertebral osteomyelitis and discitis who underwent MRI very early in their clinical course. Materials and methods: A retrospective review of the database of spinal infections from a spinal microbiological liaison team was performed over a 2 year period to identify cases with clinical features suggestive of spinal infection and an MRI that did not show features typical of vertebral osteomyelitis and discitis. All patients had positive microbiology and a follow up MRI showing typical features of spinal infection. Results: In four cases the features typical of spinal infection were not evident at the initial MRI. In three cases there was very subtle endplate oedema associated with disc degeneration, which was interpreted as Modic type I degenerative endplate change. Intravenous antibiotic therapy was continued prior to repeat MRI examinations. The mean time to the repeat examination was 17 days with a range of 8-22 days. The second examinations clearly demonstrated vertebral osteomyelitis and discitis. Conclusion: Although MRI is the imaging method of choice for vertebral osteomyelitis and discitis in the early stages, it may show subtle, non-specific endplate subchondral changes; a repeat examination may be required to show the typical features. © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Rankine J.J.,Leeds General Infirmary | Rankine J.J.,Leeds Musculoskeletal Biomedical Research Unit | Dickson R.A.,Orthopaedic Surgery
Spine | Year: 2010

Study Design. Retrospective review of the CT scans performed in a group of patients examined for a possible spondylolysis. Objective. To investigate whether there is an association between unilateral spondylolysis and facet joint tropism. Summary of Backgrounf Data. Spondylolysis is a fatigue fracture of the pars interarticularis of great importance in sports injury. The demonstration of a unilateral spondylolysis is important because there is a potential for full healing if the athletic activity is modified, whereas bilateral spondylolysis frequently leads to established nonunion. Coronally orientated facet joints are known to predispose to spondylolysis by increasing the point loading of the pars interarticularis. The importance of this finding has not been investigated in unilateral spondylolysis. Methods. A review of patients with low back pain and a possible diagnosis of spondylolysis who were investigated with multislice CT was performed. The coronal orientation of the facet joints at L4/5 and L5/S1 was measured and comparison was done between those with and without a spondylolysis. Results. The coronal angle of 140 facet joints in 35 patients was recorded. Of 35 patients, 23 had a spondylolysis which was unilateral in 12 patients. The facet joint angle was significantly more coronally orientated in the presence of a spondylolysis when compared with an intact pars (means, 53° and 43°, respectively; P < 0.01). In the presence of a unilateral spondylolysis, the facet joint was significantly more coronally orientated on the side of the spondylolysis (means, 52° and 45°, respectively; P < 0.01). Conclusion. This study is the first investigation of facet joint anatomy in unilateral spondylolysis. Asymmetric facet joints do increase the force through one side of the spine, with a unilateral spondylolysis occurring on the side of the more coronally orientated facet joint. © 2010, Lippincott Williams & Wilkins.

Mankia K.,Chapel Allerton Hospital | Mankia K.,Leeds Musculoskeletal Biomedical Research Unit | Emery P.,Chapel Allerton Hospital | Emery P.,Leeds Musculoskeletal Biomedical Research Unit
Current Opinion in Rheumatology | Year: 2016

Purpose of review Progress in our understanding of the preclinical events in rheumatoid arthritis (RA) has provided important insights into disease pathogenesis. Studying prospective cohorts of individuals at risk for RA development offers the opportunity to accurately characterize the sequence of events in preclinical disease as well as quantify the risk of different preclinical phenotypes. These data may provide the basis for preventive strategies in RA. Recent findings RA-related systemic autoimmunity and inflammation occur long before clinical arthritis. There is growing evidence that initiating events may occur at mucosal surfaces including the periodontium, lung and gut and may be influenced by the local microbiome. For potential preventive strategies to be feasible, it is important that individuals at high risk for RA development can be readily identified from the general population. To this end, studying multiple biomarkers in prospective cohorts of at-risk individuals enables risk prediction in different at-risk phenotypes. RA prevention using immunomodulation is currently being investigated in individuals at high risk of RA development. Summary The prospective study of at-risk individuals can provide invaluable aetiological insights as well as facilitating accurate risk prediction data. In this way, high-risk individuals may be identified for preventive interventions. © 2016 Wolters Kluwer Health, Inc. All rights reserved.

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