Total hip arthroplasties are known to corrode predominantly at the taper junctions between Cobalt Chromium Molybedenum (CoCrMo) and Titanium (Ti) alloy components. We aimed to understand the modes underlying clinically significant tissue reactions to metals from corroded implants by determining: (1) what type of metal is present in the tissues, (2) which cells contain the metal species and (3) how this compares with results from metal-on-metal (MOM) hip resurfacings (HRs). This study involved periprosthetic tissue from patients that had undergone revision surgery due to adverse reactions to metal debris (ARMD) from dual-taper prostheses consisting of Ti-based alloy stems paired with CoCrMo necks. We used Synchrotron micro X-ray Fluorescence Spectroscopy (µXRF) and micro X-ray Absorption Near Edge Spectroscopy (µXANES) for detection of Co, Cr and Ti, and determination of their oxidation state. Synchrotron radiation has shown that the chromium in tissues is Cr. 2. O. 3. when derived from corroded CoCrMo/Ti junctions beside the CrPO. 4. species found when hip implants release CoCrMo nanoparticles from their bearing surfaces (MoM HRs). Presence of Cr. 2. O. 3. was associated with titanium oxide TiO. 2. This may be the outcome of the chemical interaction between the two species. Histological examination showed corrosion products present within viable macrophages and in the extracellular connective tissue, Figure 1. Understanding corrosion at taper junctions and the pathogenesis of the biological response is of significant clinical importance. This is the first study to co-register histology and metal distribution maps and to explore the potential synergy effect of CoCrMo with Ti alloy. This study provides guidance for toxicological studies on wear/corrosion particles, how they stimulate the host response and the cellular mechanisms involved in the pathogenesis of ARMD. For any figures or tables, please contact the authors directly by clicking on ‘Info & Metrics’ above to access author contact details

Aims

To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMD_SV) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ).

Circulating cobalt and chromium from metal-on-metal implants cause rare but fatal autopsy-diagnosed cardiotoxicity. Concern exists that milder cardiotoxicity may be common and under-recognized. Unacceptably high failure rates of metal-on-metal hip implants have prompted regulatory authorities to issue worldwide safety alerts. Despite this, approximately 1 million patients continue to live with metal-on-metal implants, putting them at risk of systemic toxicity. Although blood cobalt and chromium levels are easily measured and track local toxicity, no non-invasive tests for organ deposition exist. We recently demonstrated the utilisation of a T2* protocol (cardiovascular MRI) to detect cobalt and chromium deposition within the liver of a patient with elevated blood cobalt levels (confirmed by liver biopsy tissue analysis and X-ray fluorescence spectroscopy). We sought to detect and constrain the correlation between blood metal ions and a comprehensive panel of established markers of early cardiotoxicity. In addition we applied T2* protocols with the aim of detecting cardiac metal deposition. 90 patients were recruited through RNOH clinics into this prospective single centre blinded study. Patients were divided into 3 age and gender-matched groups according to type of implant and blood metal ion levels as follows: [Group A] Non-metal bearing hip implants; [Group B] Metal-on-metal implants, low blood metal ion levels (<7ppb); and [Group C] Metal-on-metal implants, high blood levels (>7ppb). All underwent detailed cardiovascular phenotyping using cardiac MRI (with T2*, T1 and ECV mapping, in addition to LV size and ejection fraction), advanced echocardiography (LV size and ejection fraction), and cardiac blood biomarker (Troponin and BNP) sampling in the same sitting at the Heart Hospital London. Primary outcomes were pre-specified. See study flow diagram – figure 1. (The study was registered with . clinicaltrials.gov. : NCT02331264). Blood cobalt levels were significantly different between groups (0.17ppb (range 0·10–0·47, SD 0·08) vs. 2·47 (0·72–6·9, SD 1·81) vs. 30·0 (7·54–118.0, SD 29·1) respectively for groups A, B and C). No significant between-group differences were found for LV size, ejection fraction (CMR or echocardiography), LA size, T1, T2*, ECV, BNP or troponin, with all results within normal ranges. There was no relationship between blood cobalt levels and either left ventricular ejection fraction or T2* (r=-0·022 and r=-0·108 respectively). Although small, the study was sufficiently powered to detect, as a minimum, a difference in ejection fraction of 4.8% (Cohen's d effect size 0·8). Using best available technologies, exposure of patients with metal-on-metal hip implants to high (but not extreme) blood cobalt and chromium levels has no detectable effect on the heart. We believe these findings will offer reassurance to one million patients worldwide living with a metal-on-metal hip implant and will support clinicians caring for such patients. For any figures or tables, please contact the authors directly by clicking on ‘Info & Metrics’ above to access author contact details

Aims

Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH.

Aims

Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism.

Objectives

T-cells are considered to play an important role in the inflammatory response causing arthroplasty failure. The study objectives were to investigate the composition and distribution of CD4+ T-cell phenotypes in the peripheral blood (PB) and synovial fluid (SF) of patients undergoing revision surgery for failed metal-on-metal (MoM) and metal-on-polyethylene (MoP) hip arthroplasties, and in patients awaiting total hip arthroplasty.