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.

Real-time analysis of nanopore-based metagenomic sequencing from infected orthopaedic devices

Abstract: Prosthetic joint infections are clinically difficult to diagnose and treat. Previously, we demonstrated metagenomic sequencing on an Illumina MiSeq replicates the findings of current gold standard microbiological diagnostic techniques. Nanopore sequencing offers advantages in speed of detection over MiSeq. Here, we report a real-time analytical pathway for Nanopore sequence data, designed for detecting bacterial composition of prosthetic joint infections but potentially useful for any microbial sequencing, and compare detection by direct-from-clinical-sample metagenomic nanopore sequencing with Illumina sequencing and standard microbiological diagnostic techniques. DNA was extracted from the sonication fluids of seven explanted orthopaedic devices, and additionally from two culture negative controls, and was sequenced on the Oxford Nanopore Technologies MinION platform. A specific analysis pipeline was assembled to overcome the challenges of identifying the true infecting pathogen, given high levels of host contamination and unavoidable background lab and kit contamination. The majority of DNA classified (> 90%) was host contamination and discarded. Using negative control filtering thresholds, the species identified corresponded with both routine microbiological diagnosis and MiSeq results. By analysing sequences in real time, causes of infection were robustly detected within minutes from initiation of sequencing. We demonstrate a novel, scalable pipeline for real-time analysis of MinION sequence data and use of this pipeline to show initial proof of concept that metagenomic MinION sequencing can provide rapid, accurate diagnosis for prosthetic joint infections. The high proportion of human DNA in prosthetic joint infection extracts prevents full genome analysis from complete coverage, and methods to reduce this could increase genome depth and allow antimicrobial resistance profiling. The nine samples sequenced in this pilot study have shown a proof of concept for sequencing and analysis that will enable us to investigate further sequencing to improve specificity and sensitivity.

Investigation into the formation and mechanical properties of a bioactive material based on collagen and calcium phosphate

Abstract: A biomaterial composite was formed by the room-temperature precipitation of calcium phosphate (in the form of brushite) on to collagen. It was found that the addition of 1 mM O-phosphoserine (Ser P) causes the morphology of the brushite crystals to change from large plates to small needles. An increase in the surface coverage and weight fraction of brushite incorporated into the collagen was observed. The mechanical properties of this composite were tested in the wet state. The ultimate tensile strength (UTS) was 45 MPa compared with 34 MPa for the wet collagen. Osteoblastic differentiation was promoted on the surface of the material and new bone formed.

Failure of Surgery for Scaphoid Non-Union is Associated with Smoking

Abstract: Scaphoid fractures predominantly affect young men, in whom the UK smoking prevalence approaches 40%. We examined the association between smoking and failure of non-vascularized bone grafting and screw fixation for scaphoid non-union and delayed union in a retrospective cohort study. Adequate follow-up was obtained in 64 of 87 patients treated (74%). Union was defined as the presence of trabecular continuity on at least two films from a four-view radiographic series. Union was achieved in 47 of 64 cases. Seventeen were smokers. Thirteen of the 17 patients with non-union were smokers (relative risk 3.7; 95% CI: 1.3-10.1, p=0.005). Proximal pole fractures, long injury-grafting interval and non-compliance were not more frequent in smokers than non-smokers. Smoking is strongly associated with failure of union after screw fixation and non-vascularized bone grafting of the scaphoid. Smokers should be advised to avoid smoking pre-operatively and during the healing period.

Effect of vitamin A on bone resorption: evidence for direct stimulation of isolated chicken osteoclasts by retinol and retinoic acid

Abstract: The effects of retinol (vitamin A) and retinoic acid on primary cultures of isolated chicken osteoclasts have been studied. The experiments were performed to establish the direct actions of these two agents on the organization of cytoskeletal structures, on the acid phosphatase contents, and on the bone resorption activities of these cells. The results showed that by treating the cultures with retinol or retinoic acid, from 10(-8) to 10(-5) M, there were dose-related responses of the osteoclasts. Adhesion to the substratum was stimulated by increasing the number of cells exhibiting the specialized dot-like adhesion structures, or podosomes, which represent the active part of the sealing zone. The treatments also induced rearrangement of the microtubular patterns with reversible depolymerization of microtubules. Acid phosphatase activity was significantly higher both in vitamin A-treated osteoclasts and in their media. When [3H]proline-labeled bone particles were added to the retinoid-treated osteoclasts, the release of [3H]proline was increased significantly compared to controls. These results suggest that the two vitamin A metabolites cause several modifications of the metabolic status of isolated osteoclasts that result in augmented rates of bone resorption.

Recommendations of the ESSR Arthritis Subcommittee for the Use of Magnetic Resonance Imaging in Musculoskeletal Rheumatic Diseases.

Abstract: This article presents the recommendations of the European Society of Musculoskeletal Radiology Arthritis Subcommittee regarding the standards of the use of MRI in the diagnosis of musculoskeletal rheumatic diseases. The recommendations discuss (1) the role of MRI in current classification criteria of musculoskeletal rheumatic diseases (including early diagnosis of inflammation, disease follow-up, and identification of disease complications); (2) the impact of MRI on the diagnosis of axial and peripheral spondyloarthritis, rheumatoid arthritis, and juvenile spondyloarthritis; (3) MRI protocols for the axial and peripheral joints; (4) MRI interpretation and reporting for axial and peripheral joints; and finally, (5) methods for assessing MR images including quantitative, semiquantitative, and dynamic contrast-enhanced MRI studies.