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Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_4 | Pages 31 - 31
1 Apr 2022
Langton D Bhalekar R Joyce T Shyam N Nargol M Pabbruwe M Su E Nargol A
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Cobalt chrome alloy is commonly used in joint replacement surgery. However, it is recognised that some patients develop lymphocyte mediated delayed type hypersensitivity (DTH) responses to this material, which may result in extensive bone and soft tissue destruction.

Phase 1. United Kingdom: From an existing database, we identified extreme phenotype patient groups following metal on metal (MoM) hip resurfacing or THR: ALVAL with low wearing prostheses; ALVAL with high wear; no ALVAL with high wear; and asymptomatic patients with implants in situ for longer than ten years. Class I and II HLA genotype frequency distributions were compared between these patients’ groups, and in silico peptide binding studies were carried out using validated methodology.

Phase 2. United Kingdom: We expanded the study to include more patients, including those with intermediary phenotypes to test whether an algorithm could be developed incorporating “risk genotypes”, patient age, sex and metal exposure. This model was trained in phase 3.

Phase 3. United Kingdom, Australia, United States. Patients from other centres were invited to give DNA samples. The data set was split in two. 70% was used to develop machine learning models to predict failure secondary to DTH. The predictions were tested using the remaining blinded 30% of data, using time-dependent AUROCs, and integrated calibration index performance statistics.

A total of 606 DNA samples, from 397 males and 209 female patients, were typed. This included 176 from patients with failed prostheses, and 430 from asymptomatic patients at a mean of >10 years follow up. C-index and ROC(t) scores suggested a high degree of discrimination, whilst the IBS indicated good calibration and further backed up the indication of high discriminatory ability. At ten years, the weighted mean survival probability error was < 4%.

At present, there are no tests in widespread clinical use which use a patient's genetic profile to guide implant selection or inform post-operative management. The algorithm described herein may address this issue and we suggest that the application may not be restricted to the field of MoM hip arthroplasty.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_6 | Pages 25 - 25
1 May 2019
Langton D Sidaginamale R Wells S Wainwright B Holland J Deehan D Joyce T Jafri A Nargol A Natu S
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Introduction

We aimed to identify genes associated with the development of ALVAL at relatively low levels of wear.

Methods

At our unit all patients undergoing revision of a MoM hip prosthesis have periprosthetic tissue samples graded for ALVAL. Explants undergo volumetric wear testing of the bearing and taper surfaces. We identified patients with moderate/severe ALVAL who had been exposed to lower than the median wear rate of all recorded patients who had developed ALVAL (<3mm3/year). This was termed the “ALVAL” group. We then identified all patients whose tissues had shown no signs of ALVAL. The patients in the two groups were sent buccal DNA collection kits. DNA was examined using next generation sequencing. Alleleic frequencies in the two groups were compared using Fisher's test and compared to a background UK population group (n=8514). We then conducted binary logistic regression with patient age, sex, primary source of debris (taper/bearing) and HLA genotype as the predictors. With the hypothesis that a cobalt/albumin metalloprotein acts as the epitope, we used validated binding prediction software to determine the relative affinities of the binding grooves created by different DQA1/DQB1 genetic combinations for albumin derived peptides. Given the protection that male sex and younger age appears to confer against ALVAL, we hypothesized that testosterone peptides may compete for these binding sites.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_11 | Pages 7 - 7
1 Jun 2016
Sidaginamale R O'Hare J Natu S Joyce T Lord J Nargol A Langton D
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Background

Some reports have suggested that debris generated from the head neck taper junction is more destructive than equivalent doses from metal bearing surfaces.

Methods

Part 1. We examined the relationship between the source (taper/bearing) and volume of metal debris on Cr and Co concentrations in corresponding blood and hip synovial fluid samples and the observed agglomerated particle sizes in excised tissues using regression analysis of prospectively collected data at a single revision unit. Part 2. We investigated variables most strongly associated with macroscopic soft tissue injury as documented at revision surgery using ordinal logistic regression. Independent variables included source and volume of CoCr exposure, Cr and Co joint fluid concentrations, joint fluid grade, ALVAL (Aseptic Lymphocytic Vasculitis Associated Lesion) grade, presence of vascular hyalinisation, agglomerated particle size, implant type, patient sex and age.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_11 | Pages 4 - 4
1 Jun 2016
O'Hare J Langton D Nargol A Joyce T Brewster N Cooke N Jafri A Lord J Duffy P Holland J
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Introduction

Historical studies have reported incidences of taper corrosion in retrieved MoP hips of 20–50%. These studies relied on visual assessments, rather than using modern analytical techniques.

Patients/Materials and Methods

The Northern Retrieval Registry was initiated to routinely analyse all retrieved hips. The volumetric wear rates of retrieved Exeter head tapers were measured using a coordinate measuring machine using validated methods and compared to the available results obtained from an ongoing study of failed MoM prostheses. Power analysis suggested that we would need at least fifty Exeter head tapers to provide significant results. Non-parametric tests were used to assess differences. We have previously identified head diameter/offset/taper angle and taper surface roughness as variables associated with taper wear. The effect of bearing material combination remains unquantified. These design variables were entered into a multiple regression model following log normalisation of taper wear.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_12 | Pages 5 - 5
1 Nov 2015
Langton D Killen M Sidaginamale R Bowsher J Savisaar C Nargol A Joyce T Lord J
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Introduction

In this study, we aimed to investigate the effect of the topography of the female taper surface on taper wear.

Patients/Materials & Methods

We measured volumetric material loss at the female taper surface of the first consecutive 36mm MoM hips received at our centre. The MoM hips were from a single manufacturer and possessed matching: head size (36mm); taper geometry (5.65 degree 12 14 tapers); and metallurgy (cobalt chrome female taper mated with a titanium stem). Volume loss was measured with a coordinate measuring machine using validated methods. Surface roughness was measured using a Surftest SJ400. There were 111 head tapers available for analysis. The majority had been revised secondary to ARMD, and a minority for loosening. The mean duration of implantation was 56 months. Volumetric wear values were log normalised in order to construct a multiple regression model to investigate the interaction of head offset, the head taper angle and the Rp value of the female taper surface. Rp is a roughness parameter, which is a measure of the peaks above the plateau of a surface.