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Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_10 | Pages 1 - 1
1 Jul 2014
Hester T Bond D Phillips S
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Gold standard for the management of non-union is open surgical debridement, stabilisation, and autologous bone grafting. LIPUS is becoming more popular, yet the evidence is still inconclusive. LIPUS involves the use of ultrasound at the fracture site with little risk to the patient.

The purpose of this study was to assess effectiveness and cost benefit of LIPUS in the management of non-unions post sustaining an open fracture.

We retrospectively reviewed 29 patients with open fractures with established non-union undergoing LIPUS since 2010 (4 females, mean age 48) range 3–27 months, mean 9 months, either post injury or last intervention. All were tertiary referrals, sustaining injuries to the following areas; Tibial 21, Femur 6, Humerus 2, Radius 1. Definitive fixation being; 9 TSF's, 11 IMN's, 9 plates. (undergoing a mean 2.4 procedures). Aside from sustaining an open fracture, 7 had risk factors for non-unions 5 smokers, 2 NSAID's. Failure of treatment was based on undertaking bone grafting.

In 28 patients (1 lost to follow up) union was achieved in 71% (mean 157 days). All were screened for infection, 4 had organisms on enrichment culture. 8 (5 Gustillo Anderson Grade 3A/B) injuries did not show evidence of callus formation, LIPUS was discontinued and grafting performed. Open fractures were graded as; 7 Grade 1, 4 Grade 2, 8 Grade 3A, 10 Grade 3B being received. Of these; 20 underwent primary closure, 6 free flaps and 3 SSG. The cost of LIPUS is approx £2500, compared bone grafting using autologous iliac crest graft with no medical comorbidities of £3715.

This case series further supports union rates after LIPUS. Cost and morbidity benefit of utilising LIPUS over opting for bone grafting initially is £1215 per patient. Whilst autologous bone grafting is currently the gold standard, it is not without morbidity. We achieved union rates of 71% despite a number of patients having recognised risk factors, showing that LIPUS is a useful resource in the management of non-union.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 83 - 83
1 Feb 2012
Hart A Hester T Goodship A Powell J Pele L Fersht N Skinner J
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It is thought that metal ions from metal on metal bearing hip replacements cause DNA damage and immune dysfunction in the form of T cell mediated hypersensitivity. To explore the hypothesis that there is a relationship between metal ion levels and DNA damage and immune dysfunction in matched patient groups of hip resurfacings and standard hip replacements reflected in the levels of lymphocyte subtypes (CD3+ T cells, CD4+ T helper cells, CD8 +T cytotoxic/suppressor cells, CD16 +Natural Killer and CD19+ B cells) in peripheral blood samples, we analysed peripheral blood samples from 68 patients: 34 in the hip resurfacing group and 34 in the standard hip arthroplasty group. Samples were analysed for counts of each sub-group of lymphocyte and cytokine production. Whole blood cobalt and chromium ion levels were measured using inductively-coupled mass spectrometry. All hip components were well fixed.

Cobalt and chromium levels were significantly elevated in the resurfacing group compared to the hybrid group (p<0.001). There was a statistically significant decrease in the resurfacing group's level of CD8+ cells (T cytotoxic/suppressor) (p=0.010). No other subgroup of lymphocytes was significantly affected. Gamma interferon levels post antigen challenge were severely depressed in the hip resurfacing group.

A threshold level of blood cobalt and chromium ions for depression of CD8+ T cells was observed. Hip resurfacing patients have levels above this threshold whilst standard hip replacements fall below it. The patients all had normal levels of CD16 +Natural Killer and CD19+ B cells suggesting that this is not a bone marrow toxic effect. Cytokine analysis confirmed that some aspects of T cell function in hip resurfacing patients are severely depressed.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 132 - 133
1 Mar 2009
Hart A Tarrassoli P Patel C Buddhdev P Hester T Muirhead-Allwood S Skinner J
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Introduction: We have previously shown an association between whole blood metal particles from unilateral metal on metal (MOM) hip resurfacing and reduced CD8+ T cells (JBJS Br April 2006). There are no reported clinical effects of these findings. Certain patients maybe at high risk of developing clinical effects; one such group is patients with bilateral hip resurfacings. There are no published studies of bilateral hip resurfacings. Our aim was to investigate the association between whole blood metal ions and reduced CD8+ T cells in a follow up cohort of bilateral MOM hip resurfacings.

Method : Peripheral blood samples were analysed from patients with bilateral MOM hip resurfacings (n=25), unilateral hip resurfacings (n=34) and metal on polyethylene (MOP) hip arthroplasty (n=34). Samples were analysed for: lymphocyte subsets (FACS analysis); whole blood cobalt and chromium ion levels (using inductively-coupled mass spectrometry). Xrays revealed all hip components were well fixed.

Results : When compared to patients with standard MOP hip replacements there was a 30% reduction in both the bilateral and unilateral resurfacing groups’ level of CD8+ cells (T cytotoxic) (p=0.010). All other lymphocyte subgroups were not significantly different. There was evidence of a threshold effect of raised metal ions and reduced CD8+ T cells but no evidence of a dose-response relationship.

Conclusions : Bilateral MOM hip resurfacing is associated with a reduced CD8+ T cell count when compared to MOP hip arthroplasty. This association is not significantly different from the levels seen after unilateral MOM hip resurfacing.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 133 - 133
1 Mar 2009
Hart A Pele L Fersht N Hester T Skinner J Powell J
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Introduction and aim: We have previously shown suppressed levels of CD8+ T lymphocytes in patients with metal-on-metal (MOM) hip resurfacing compared to patients with metal on polyethylene hip replacements. Functional assessment of T lymphocytes may help to determine the importance of this CD8+ reduction following hip resurfacing.

Method: We isolated peripheral blood mononuclear cells (PBMC) from patients with unilateral MOM hip resurfacing (n=7) and healthy controls without hip replacement (n=8). Patients with hip resurfacing had excellent Harris Hip scores (mean 90) and well fixed components on radiographs. Whole blood and serum levels of Cobalt (Co) and Chromium (Cr) ions were measured with Inductively-Coupled Mass Spectrometry. T cell function was assessed by

cell proliferation assays (3H-thymidine incorporation) and

cytokines secretion (ELISA) following exposure to antigen challenge using Tetanus Toxoid and polyclonal mitogen phytohaemoagglutinin (PHA).

Results: Co and Cr ion levels were significantly elevated in the MOM hip resurfacing group compared to the control group (p< 0.001). Proliferation rates of T cells were comparable between the two groups over one week, but interferon-gamma (IFN-γ) production in the MOM hip resurfacing group was significantly decreased (p < 0.05), when compared to the control group.

Conclusion: IFN-γ is normally produced by CD8+ (T cytotoxic cells) and CD4+ (T helper 1 cells) in response to viral infection and high levels of IFN-γ is associated with autoimmune disease. Raised levels of metal ions from hip resurfacing reduces the production of IFN-γ following stimulation with PHA. This finding has been patented for potential therapeutic use through MRC technology.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 313 - 313
1 Jul 2008
Hart A Hester T Goodship A Powell J Pele L Fersht N Skinner J
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Introduction: There have been 70,000 hip resurfacings implanted, predictions are for it to become 12% of the US hip replacement market by 2010 (Goldmann Sachs report Oct 2005). There is concern that the cobalt and chromium ions released from metal on polyethylene hip replacements cause immune dysfunction in the form of T cell mediated hypersensitivity (indicated by increased numbers and stimulation of T cells). If metal ions cause significant effects on white blood cells we might reasonably expect to detect this by simply measuring numbers of white blood cells.

Aim : To examine the possibility that raised metal ions may cause an abnormal number of white blood cells, termed a blood dyscrasia.

Method : Peripheral blood samples were analysed from 68 patients: 34 in the hip resurfacing group and 34 in the standard hip arthroplasty group. Samples were analysed for counts of each sub-group of lymphocyte. Functional assessment was also performed using a activation panel of white cell CD markers. Whole blood cobalt and chromium ion levels were measured using inductively-coupled mass spectrometry. All hip components were well fixed.

Results : Cobalt and chromium levels were significantly elevated in the resurfacing group compared to the hybrid group (p< 0.001). There was a statistically significant decrease in the resurfacing groups’ level of CD8+ cells (T cytotoxic/suppressor) (p=0.010). There was a characteristic pattern of immune modulation seen on the activation panel.

Conclusions : We found an immune modulation in patients with metal on metal hip resurfacing. This was not a hypersensitivity reaction. This change in T cell function may be detrimental or beneficial to patients.