Risk of cancer in first seven years after metal-on-metal hip replacement compared with other bearings and general population: linkage study between the National Joint Registry of England and Wales and hospital episode statistics.

addresses: Musculosketal Research Unit, School of Clinical Sciences, University of Bristol, Avon Orthopaedic Centre, Bristol BS10 5NB, UK. [email protected]: PMCID: PMC3318111types: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2012 by the BMJ Publishing Group Ltd. This articles was first published in: BMJ, 2012, Vol. 344, pp. e2383 -To determine whether use of metal-on-metal bearing surfaces is associated with an increased risk of a diagnosis of cancer in the early years after total hip replacement and specifically with an increase in malignant melanoma and haematological, prostate, and renal tract cancers

Re-Infection Outcomes following One- and Two-Stage Surgical Revision of Infected Hip Prosthesis:A Systematic Review and Meta-Analysis

The two-stage revision strategy has been claimed as being the "gold standard" for treating prosthetic joint infection. The one-stage revision strategy remains an attractive alternative option; however, its effectiveness in comparison to the two-stage strategy remains uncertain.To compare the effectiveness of one- and two-stage revision strategies in treating prosthetic hip infection, using re-infection as an outcome.Systematic review and meta-analysis.MEDLINE, EMBASE, Web of Science, Cochrane Library, manual search of bibliographies to March 2015, and email contact with investigators.Cohort studies (prospective or retrospective) conducted in generally unselected patients with prosthetic hip infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision. No clinical trials were identified.Data were extracted by two independent investigators and a consensus was reached with involvement of a third. Rates of re-infection from 38 one-stage studies (2,536 participants) and 60 two-stage studies (3,288 participants) were aggregated using random-effect models after arcsine transformation, and were grouped by study and population level characteristics.In one-stage studies, the rate (95% confidence intervals) of re-infection was 8.2% (6.0-10.8). The corresponding re-infection rate after two-stage revision was 7.9% (6.2-9.7). Re-infection rates remained generally similar when grouped by several study and population level characteristics. There was no strong evidence of publication bias among contributing studies.Evidence from aggregate published data suggest similar re-infection rates after one- or two-stage revision among unselected patients. More detailed analyses under a broader range of circumstances and exploration of other sources of heterogeneity will require collaborative pooling of individual participant data.PROSPERO 2015: CRD42015016559

Using home sensing technology to assess outcome and recovery after hip and knee replacement in the UK: the HEmiSPHERE study protocol

Over 160 000 people with severe hip or knee pain caused by osteoarthritis undergo total hip (THR) or knee replacement (TKR) surgery each year in the UK within the National Health Service (NHS), and this number is expected to increase. Innovative approaches to evaluating surgical outcomes will be needed to respond to the increasing burden of joint replacement surgery. The Sensor Platform for Healthcare in a Residential Environment, Interdisciplinary Research Collaboration (SPHERE-IRC) have developed a system of sensors that can monitor the health-related behaviours of people living at home. The system includes sensors for the home environment (measuring temperature, humidity, room occupancy, water and electricity usage), a wristband body-worn activity monitor and silhouette (body outline) sensors. The aim of HEmiSPHERE (Hip and knEe study of a Sensor Platform of HEalthcare in a Residential Environment) is to (1) determine the accuracy and feasibility of the sensory data as it compares with conventional assessment of health outcomes after surgery using patient self-reported questionnaires, and (2) to explore how the SPHERE system is useful for everyday clinical decision-making.A feasibility study recruiting and installing the SPHERE system in the homes of up to 30 NHS adult patients as they undergo a THR or TKR. Through a mixed-methods design, the SPHERE system will monitor and record continuous measurements of daily behaviour. Main outcomes will assess the relationships between environmental, behavioural and movement data and the parameters of interest from the standard clinical assessments measuring patient outcomes over time. Patient interviews and focus groups with consultant orthopaedic surgeons will provide in-depth understanding of the acceptability, feasibility and accuracy of the data.We aim to disseminate the findings through regional talks and seminars, international conferences and peer-reviewed journals and social media

Impaction bone grafting of the acetabulum at hip revision using a mix of bone chips and a biphasic porous ceramic bone graft substitute: Good outcome in 43 patients followed for a mean of 2 years

Background and purpose One of the greatest problems of revision hip arthroplasty is dealing with lost bone stock. Good results have been obtained with impaction grafting of allograft bone. However, there have been problems of infection, reproducibility, antigenicity, stability, availability of bone, and cost. Thus, alternatives to allograft have been sought. BoneSave is a biphasic porous ceramic specifically designed for use in impaction grafting. BoneSave is 80% tricalcium phosphate and 20% hydroxyapatite. Previous in vitro and in vivo studies have yielded good results using mixtures of allograft and BoneSave, when compared with allograft alone. This study is the first reported human clinical trial of BoneSave in impaction grafting

Zinc Finger Nuclease mediated knockout of ADP dependent Glucokinase in Cancer cell lines: Effects on cell survival and Mitochondrial Oxidative Metabolism

<div><p>Zinc finger nucleases (ZFN) are powerful tools for editing genes in cells. Here we use ZFNs to interrogate the biological function of <i>ADPGK</i>, which encodes an ADP-dependent glucokinase (ADPGK), in human tumour cell lines. The hypothesis we tested is that ADPGK utilises ADP to phosphorylate glucose under conditions where ATP becomes limiting, such as hypoxia. We characterised two ZFN knockout clones in each of two lines (H460 and HCT116). All four clones had frameshift mutations in all alleles at the target site in exon 1 of <i>ADPGK,</i> and were ADPGK-null by immunoblotting. <i>ADPGK</i> knockout had little or no effect on cell proliferation, but compromised the ability of H460 cells to survive siRNA silencing of hexokinase-2 under oxic conditions, with clonogenic survival falling from 21±3% for the parental line to 6.4±0.8% (p = 0.002) and 4.3±0.8% (p = 0.001) for the two knockouts. A similar increased sensitivity to clonogenic cell killing was observed under anoxia. No such changes were found when <i>ADPGK</i> was knocked out in HCT116 cells, for which the parental line was less sensitive than H460 to anoxia and to hexokinase-2 silencing. While knockout of <i>ADPGK</i> in HCT116 cells caused few changes in global gene expression, knockout of <i>ADPGK</i> in H460 cells caused notable up-regulation of mRNAs encoding cell adhesion proteins. Surprisingly, we could discern no consistent effect on glycolysis as measured by glucose consumption or lactate formation under anoxia, or extracellular acidification rate (Seahorse XF analyser) under oxic conditions in a variety of media. However, oxygen consumption rates were generally lower in the <i>ADPGK</i> knockouts, in some cases markedly so. Collectively, the results demonstrate that <i>ADPGK</i> can contribute to tumour cell survival under conditions of high glycolytic dependence, but the phenotype resulting from knockout of <i>ADPGK</i> is cell line dependent and appears to be unrelated to priming of glycolysis in these lines.</p></div

How long does a shoulder replacement last? A systematic review and meta-analysis of case series and national registry reports with more than 10 years of follow-up

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordBackground: Shoulder replacement is an increasingly common treatment for end-stage degenerative shoulder conditions. Some shoulder replacements are unsuccessful and additional operations might be required. It is important for patients and clinicians to know how long shoulder replacements last and how effectively they reduce pain and improve function. This study aims to determine the longevity and long-term efficacy of shoulder replacements. Methods: In this systematic review and meta-analysis, we searched MEDLINE and Embase from their inception to Sept 24, 2019, for case series and registry data reporting 10-year or longer survival of total shoulder replacements, humeral hemiarthroplasties, and reverse total shoulder replacements of a specific brand of implant. Survival, implant, and patient-reported outcome measures data were extracted. The primary outcome was implant survival. We reviewed and analysed national joint replacement registries separately. We weighted each series by SE and calculated a pooled survival estimate at years 10, 15, and 20. For patient-reported outcome measures we pooled the standardised mean difference at 10 years. This study is registered with PROSPERO, CRD42019140221. Findings: 927 non-duplicate articles were identified by our search, nine articles (reporting ten series) were eligible for analysis of survival and six articles were eligible for analysis of patient reported outcomes. The ten series reported all-cause survival of 529 total shoulder replacements and 364 humeral hemiarthroplasties; no series for reverse total shoulder replacement met the inclusion criteria. The estimated 10-year survival for total shoulder replacement was 94·6% (95% CI 93·6–97·6) and humeral hemiarthroplasties was 90·4% (87·0–94·0). A single registry contributed 7651 total shoulder replacements, 1395 humeral hemiarthroplasties, and 7953 reverse total shoulder replacements. The pooled registry 10-year survival was 92·0% (95% CI 91·0–93·0) for total shoulder replacement, 85·5% (83·3–87·7) for humeral hemiarthroplasties, and 94·4% (93·4–95·7) for patients with osteoarthritis who had reverse total shoulder replacement and 93·6% (91·1–95·8) for patients with rotator cuff arthropathy who had reverse total shoulder replacement. Pooled 10-year patient-reported outcome measures showed a substantial improvement from baseline scores, with a standardised mean difference of 2·13 (95% CI 1·93–2·34). Interpretation: Our data show that approximately 90% of shoulder replacements last for longer than 10 years and patient-reported benefits are sustained. Our findings will be of use to surgeons and patients in the informed consent process and to health-care providers for resource planning. Funding: The National Institute for Health Research, the National Joint Registry for England, Wales, Northern Ireland, and Isle of Man, and the Royal College of Surgeons of England.National Institute for Health Research (NIHR)National Joint Registry for England, Wales, Northern Ireland, and Isle of ManRoyal College of Surgeons of Englan

Death of a tumor: targeting CCN in pancreatic cancer

The matricellular protein CCN2 (connective tissue growth factor, CTGF) has been previously implicated in tumorigenesis. In pancreatic cancer cells, CCN2 expression occurs downstream of ras/MEK/ERK. Direct evidence that CCN2 mediates tumor progression in pancreatic cancer has been lacking. An exciting recent report by Bennewith et al. (Cancer Res 69:775–784, 2009) has used shRNA knockdown of CCN2 to illustrate that CCN2 contributes to growth of pancreatic tumor cells, both in vitro and in vivo. This report briefly summarizes these findings