Nuffield Orthopaedic Centre

About: Nuffield Orthopaedic Centre is a healthcare organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Population & Arthroplasty. The organization has 2082 authors who have published 2920 publications receiving 145718 citations.

Cytokines in tendon disease: A Systematic Review.

Abstract: Objectives Emerging evidence indicates that tendon disease is an active process with inflammation that is critical to disease onset and progression. However, the key cytokines responsible for driving and sustaining inflammation have not been identified. Methods We performed a systematic review of the literature using MEDLINE (U.S. National Library of Medicine, Bethesda, Maryland) in March 2017. Studies reporting the expression of interleukins (ILs), tumour necrosis factor alpha (TNF-α) and interferon gamma in diseased human tendon tissues, and animal models of tendon injury or exercise in comparison with healthy control tissues were included. Results IL-1β, IL-6, IL-10, and TNF-α are the cytokines that have been most frequently investigated. In clinical samples of tendinopathy and tendon tears, the expression of TNF-α tended not to change but IL-6 increased in tears. Healthy human tendons showed increased IL-6 expression after exercise; however, IL-10 remained unchanged. Animal tendon injury models showed...

In vivo kinematics of the ACL-deficient limb during running and cutting

Abstract: Anterior cruciate ligament-deficient (ACLD) knee kinematics during high-demand activities are poorly understood. We have devised a new method, using gait analysis, to more accurately assess 3-D in vivo kinematics of the knee. This has enabled us to report on how knee kinematics are altered after ACL rupture, during running and cutting. Fifteen unilaterally ACLD subjects were assessed using a 12-camera 100 Hz VICON motion analysis system. Simultaneous electromyographical (EMG) recordings were used to assess the role of the sensorimotor system in knee joint stability. All subjects were able to perform demanding cutting activities without experiencing symptoms of instability. We found that running produces fundamentally different kinematic patterns to those seen during walking. Tibiofemoral translation in the anteroposterior plane is controlled to within normal limits. Conversely, coronal translation and rotation are poorly controlled. We found that the injured leg was maintained in greater extension during the stance phase of all running activities studied and that the quadriceps muscle was active for longer during this period. We believe that low-demand activities, such as walking, do not reproduce kinematics relevant to ACLD instability and that future investigations into functional instability in the ACLD knee should focus on coronal and rotational displacements.

Serum osteoprotegerin (OPG) levels are associated with disease progression and response to androgen ablation in patients with prostate cancer.

Abstract: BACKGROUND Osteoprotegerin (OPG) is a tumour and/or bone derived factor that may protect tumour cells from apoptosis. In this study, we have measured serum OPG levels in untreated prostate cancer patients with advanced prostate cancer compared to patients with organ confined disease and in treated patients receiving androgen ablation. METHODS Serum OPG levels were measured by ELISA in samples collected from 104 patients with either newly diagnosed (n = 59) or advanced prostate cancer treated by androgen ablation (n = 45) and compared with levels in serum from patients with benign prostatic hyperplasia (BPH) (n = 10) and young healthy men (n = 10). RESULTS Untreated patients with locally advanced disease had significantly higher OPG levels than those with organ confined disease. Patients with advanced disease responding to androgen ablation (serum PSA 10 ng/ml). OPG levels in the latter were not significantly different from levels in patients with early signs of biochemical progression (PSA >1 but <10 ng/ml). CONCLUSIONS OPG is a potential new marker, which is elevated in the serum of patients with advanced prostate cancer and may be an indicator of early disease progression. © 2004 Wiley-Liss, Inc.

Coding algorithms for defining Charlson and Elixhauser co-morbidities in Read-coded databases

Abstract: Comorbidity measures, such as the Charlson Comorbidity Index (CCI) and Elixhauser Method (EM), are frequently used for risk-adjustment by healthcare researchers. This study sought to create CCI and EM lists of Read codes, which are standard terminology used in some large primary care databases. It also aimed to describe and compare the predictive properties of the CCI and EM amongst patients with hip fracture (and matched controls) in a large primary care administrative dataset. Two researchers independently screened 111,929 individual Read codes to populate the 17 CCI and 31 EM comorbidity categories. Patients with hip fractures were identified (together with age- and sex-matched controls) from UK primary care practices participating in the Clinical Practice Research Datalink (CPRD). The predictive properties of both comorbidity measures were explored in hip fracture and control populations using logistic regression models fitted with 30- and 365-day mortality as the dependent variables together with tests of equality for Receiver Operating Characteristic (ROC) curves. There were 5832 CCI and 7156 EM comorbidity codes. The EM improved the ability of a logistic regression model (using age and sex as covariables) to predict 30-day mortality (AUROC 0.744 versus 0.686). The EM alone also outperformed the CCI (0.696 versus 0.601). Capturing comorbidities over a prolonged period only modestly improved the predictive value of either index: EM 1-year look-back 0.645 versus 5-year 0.676 versus complete record 0.695 and CCI 0.574 versus 0.591 versus 0.605. The comorbidity code lists may be used by future researchers to calculate CCI and EM using records from Read coded databases. The EM is preferable to the CCI but only marginal gains should be expected from incorporating comorbidities over a period longer than 1 year.

Canonical and non-canonical pathways of osteoclast formation.

Abstract: Physiological and pathological bone resorption is mediated by osteoclasts, multinucleated cells which are formed by the fusion of monocyte / macrophage precursors. The canonical pathway of osteoclast formation requires the presence of the receptor activator for NFkappaB ligand (RANKL) and macrophage colony stimulating factor (M-CSF). Non-canonical pathways of osteoclast formation have been described in which cytokines / growth factors can substitute for RANKL or M-CSF to induce osteoclast formation. Substitutes for RANKL include LIGHT, TNFalpha and interleukins 6, 11 and 8. M-CSF substitutes include vascular endothelial growth factor (VEGF), placental growth factor (PlGF), FLt-3 ligand and hepatocyte growth factor (HGF). These growth factors can also influence canonical (RANKL / M-CSF-induced) osteoclast formation. Both canonical and non-canonical pathways of osteoclast formation play a role in the formation of osteolytic lesions where there is increased osteoclast formation and activity, such as in giant cell tumour of bone.