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.

Differential regulation of HIF-mediated pathways increases mitochondrial metabolism and ATP production in hypoxic osteoclasts

Abstract: Inappropriate osteoclast activity instigates pathological bone loss in rheumatoid arthritis. We have investigated how osteoclasts generate sufficient ATP for the energy-intensive process of bone resorption in the hypoxic microenvironment associated with this rheumatic condition. We show that in human osteoclasts differentiated from CD14+ monocytes, hypoxia (24 h, 2% O2): (a) increases ATP production and mitochondrial electron transport chain activity (Alamar blue, O2 consumption); (b) increases glycolytic flux (glucose consumption, lactate production); and (c) increases glutamine consumption. We demonstrate that glucose, rather than glutamine, is necessary for the hypoxic increase in ATP production and also for cell survival in hypoxia. Using siRNA targeting specific isoforms of the hypoxia-inducible transcription factor HIF (HIF-1α, HIF-2α), we show that employment of selected components of the HIF-1α-mediated metabolic switch to anaerobic respiration enables osteoclasts to rapidly increase ATP production in hypoxia, while at the same time compromising long-term survival. We propose this atypical HIF-driven metabolic pathway to be an adaptive mechanism to permit rapid bone resorption in the short term while ensuring curtailment of the process in the absence of re-oxygenation. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Polyethylene wear of mobile-bearing unicompartmental knee replacement at 20 years

Abstract: The Oxford unicompartmental knee replacement (UKR) was designed to minimise wear utilising a fully-congruent, mobile, polyethylene bearing. Wear of polyethylene is a significant cause of revision surgery in UKR in the first decade, and the incidence increases in the second decade. Our study used model-based radiostereometric analysis to measure the combined wear of the upper and lower bearing surfaces in 13 medial-compartment Oxford UKRs at a mean of 20.9 years (17.2 to 25.9) post-operatively. The mean linear penetration of the polyethylene bearing was 1.04 mm (0.307 to 2.15), with a mean annual wear rate of 0.045 mm/year (0.016 to 0.099). The annual wear rate of the phase-2 bearings (mean 0.022 mm/year) was significantly less (p = 0.01) than that of phase-1 bearings (mean 0.07 mm/year). The linear wear rate of the Oxford UKR remains very low into the third decade. We believe that phase-2 bearings had lower wear rates than phase-1 implants because of the improved bearing design and surgical technique which decreased the incidence of impingement. We conclude that the design of the Oxford UKR gives low rates of wear in the long term.

The do's, don't and don't knows of supporting transition to more independent practice.

Abstract: Transitions are traditionally viewed as challenging for clinicians. Throughout medical career pathways, clinicians need to successfully navigate successive transitions as they become progressively more independent practitioners. In these guidelines, we aim to synthesize the evidence from the literature to provide guidance for supporting clinicians in their development of independence, and highlight areas for further research. Drawing upon D3 method guidance, four key themes universal to medical career transitions and progressive independence were identified by all authors through discussion and consensus from our own experience and expertise: workplace learning, independence and responsibility, mentoring and coaching, and patient perspectives. A scoping review of the literature was conducted using Medline database searches in addition to the authors’ personal archives and reference snowballing searches. 387 articles were identified and screened. 210 were excluded as not relevant to medical transitions (50 at title screen; 160 at abstract screen). 177 full-text articles were assessed for eligibility; a further 107 were rejected (97 did not include career transitions in their study design; 10 were review articles; the primary references of these were screened for inclusion). 70 articles were included of which 60 provided extractable data for the final qualitative synthesis. Across the four key themes, seven do’s, two don’ts and seven don’t knows were identified, and the strength of evidence was graded for each of these recommendations. The two strongest messages arising from current literature are first, transitions should not be viewed as one moment in time: career trajectories are a continuum with valuable opportunities for personal and professional development throughout. Second, learning needs to be embedded in practice and learners provided with authentic and meaningful learning opportunities. In this paper, we propose evidence-based guidelines aimed at facilitating such transitions through the fostering of progressive independence.

Persistent foetal alignment of the hip.

Abstract: 1. The condition of persistent foetal alignment is discussed both as an entity and in its relationship to the development of a normal hip, and also to the varying degrees of congenital dislocation of the hip. A possible connection with osteoarthritis is also mentioned. 2. The secondary deformities to which it may give rise are discussed, and the way in which both primary and secondary deformities may be corrected is described. 3. The importance of estimating rotation with the hip in full extension is emphasised. 4. The results in eight patients so treated are mentioned.