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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 88 - 88
4 Apr 2023
Anjum S Kirby J Deehan D Tyson-Capper A
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The most common reason for revision surgery of total hip replacements is aseptic loosening of implants secondary to osteolysis, which is caused by immune-mediated reactions to implant debris. These debris can cause pseudotumour formation. As revision surgery is associated with higher mortality and infection, it is important to understand the pro-inflammatory process to improve implant survival. Toll-like receptor 4 (TLR4) has been shown to mediate immune responses to cobalt ions. Statin use in epidemiological studies has been associated with reduced risk of revision surgery. In-vitro studies have demonstrated the potential for statins to reduce orthopaedic debris-induced immune responses and there is evidence that statins can modulate TLR4 activity. This study investigates simvastatin's effect on orthopaedic biomaterial-mediated changes in protein expression of key inflammatory markers and soluble-ICAM-1 (sICAM-1), an angiogenic factor implicated in pseudotumour formation.

Human macrophage THP-1 cells were pre-incubated with 50µM simvastatin for 2-hours or a vehicle control (VC), before being exposed to 0.75mM cobalt chloride, 50μm3 per cell zirconium oxide or LPS as a positive control, in addition to a further 24-hour co-incubation with 50µM simvastatin or VC. Interleukin −8 (IL-8), sICAM-1, chemokine ligand 2 (CCL2), CCL3 and CCL4 protein secretion was measured by enzyme-linked immunosorbent assay (ELISA). GraphPad Prism 10 was used for statistical analysis including a one-way ANOVA.

Pre-treatment with simvastatin significantly reduced LPS and cobalt-mediated IL-8 secretion (n=3) and sICAM-1 protein secretion (n=2) in THP-1 cells. Pre-treatment with simvastatin significantly reduced LPS-mediated but not cobalt ion-mediated CCL2 (n=3) and CCL3 protein (n=3) secretion in THP-1 cells. Simvastatin significantly reduced zirconium oxide-mediated CCL4 secretion (n=3).

Simvastatin significantly reduced cobalt-ion mediated IL-8 and sICAM-1 protein secretion in THP-1 cells. This in-vitro finding demonstrates the potential for simvastatin to reduce recruitment of leukocytes which mediate the deleterious inflammatory processes driving implant failure.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 12 - 12
1 Nov 2021
Anjum S Jamieson S Deehan D Kirby J Tyson-Capper A
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Introduction and Objective

Total joint replacement is indicated for osteoarthritis where conservative treatment has failed, and in the UK the number of patients requiring hip and knee replacements is set to increase with an ageing population. Survival of total hip replacements is around 85% at 20 years with the most common reason for revision being aseptic loosening of the implant secondary to osteolysis, which is caused by immune-mediated reactions to implant debris. These debris can also cause pseudotumour formation. As revision surgery is associated with higher morbidity, mortality, infection rates, venous thromboembolism, resource demand and poorer subsequent function it is important to understand the mechanisms underlying the pro-inflammatory process to improve implant survival. Toll-like receptor 4 (TLR4), an innate immune receptor, has been demonstrated to mediate deleterious immune responses by the Tyson-Capper research group, including inflammatory cytokine interleukin-8 (IL-8) secretion. Statin use in epidemiological studies has been associated with reduced overall risk of revision surgery after hip replacement. In-vitro studies have demonstrated the potential for statins to reduce orthopaedic debris-induced immune responses which can lead to osteolysis and pseudotumour formation. As literature from cardiological investigations demonstrate that statins can reduce the expression and responsiveness of TLR4, this could be an exciting mechanism to exploit to reduce the host immune response to orthopaedic wear debris, thereby improving implant survival by reducing immune mediated osteolysis. This ongoing study investigates simvastatin's effect on cobalt ion-mediated changes in gene and protein expression of interleukin-8 and soluble-ICAM-1 (sICAM-1) which is an angiogenic factor implicated in pseudotumour formation.

Materials and Methods

TLR4-expressing human monocyte/macrophage THP-1 cells were pre-incubated with 50μM simvastatin for 2-hours or a vehicle control, before being exposed to exposed to 0.75mM cobalt chloride, in addition to a further 24-hour co-incubation with 50μM simvastatin or vehicle control. IL-8 protein and sICAM-1 secretion was measured by enzyme-linked immunosorbent assay (ELISA). Gene expression changes were quantified by TaqMan-based real time polymerase chain reaction.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 91 - 91
1 Mar 2021
Martin R Critchley R Anjum S
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Neck of femur fractures are a common presentation and certain patients can be managed with a total hip replacement. To receive a total hip replacement the pelvic X-rays should be templated as per AO guidelines and a common way this is performed is by including a calibration marker on the X-ray. The aim of this study is to assess and improve upon the use of the calibration marker.

Details of patients admitted with a neck of femur fracture from January 1st 2018 until December 31st 2018 were gathered and used to review each initial X-ray and determine if a calibration marker was included. 376 patients were admitted with a neck of femur fracture over the one year period. 36% of patients did not have a calibration marker on their initial pelvic X-ray and 11% did not have a chest X ray. 215 patients had an intracapsular fracture and 39 went on to have a total hip replacement. 12 patients were lacking a calibration marker on their original X ray and required a repeat X ray. After a poster was placed in the radiographer booth acting as a visual aid, the use of a calibration marker improved from 62% to 70%.

Calibration markers are useful tools which can aid the pre-operative planning for hip replacement surgeries shortening operative time, increase precision and reduce prosthetic loosening, lowers the risk of peri-prosthetic fractures, reduce leg length discrepancy and ensure the required implants are available. If a marker is not included on the initial X-rays, and a patient has a neck of femur fracture which requires a joint replacement, they may have to have additional X-rays performed as was the case for 12 patients in this study. This process leads to possible delays in surgery, additional radiation and increased healthcare costs.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_9 | Pages 10 - 10
1 May 2017
Mawdesley A Anjum S Lawrence H Deehan D Kirby J Tyson-Capper A
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Background

Increased revision rates and early failure of Metal-on-Metal (MoM) hip replacements are often due to adverse reaction to metal debris (ARMD). ARMD describes numerous symptoms in patients such as pain, osteolysis and soft tissue damage. Cobalt is a major component of MoM joints and can initiate an immune response via activation of the innate immune receptor Toll-like receptor 4 (TLR4). This leads to increased secretion of inflammatory cytokines e.g. interleukin-8 (IL-8). This study investigates whether TLR4-specific antagonists inhibit the inflammatory response to cobalt using IL-8 gene expression and protein secretion as a marker of TLR4 activation.

Methods

MonoMac 6 (MM6) cells, a human macrophage cell line, were treated with TLR4-specific antagonists followed by 0.75mM of cobalt chloride. Lipopolysaccharide (LPS), a known TLR4 agonist was used as a positive control. Enzyme-linked immunosorbent assay (ELISA) was used to assess IL-8 protein secretion and real time- polymerase chain reaction (RT-PCR) allowed quantification of IL-8 gene expression.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_9 | Pages 70 - 70
1 May 2017
Anjum S Mawdesley A Lawrence H Deehan D Kirby J Tyson-Capper A
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Background

Adverse reactions to metal debris are implicated in the failure of metal-on-metal hip arthroplasty. The peri-implant tissues are often infiltrated by leukocytes which may cause observed immunological effects, including soft tissue necrosis and osteolysis. Cobalt ions from orthopaedic implants aberrantly activate the innate immune receptor human toll-like receptor-4 (TLR4), leading to inflammatory cytokine release including interleukin-8 (IL-8). IL-8 has been shown to increase expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These factors are essential for leukocyte adhesion to endothelium, which is required for leukocyte migration into tissues. This study investigates cobalt's effect on gene and protein changes in IL-8, ICAM-1 and VCAM-1 to determine their potential role in immune cell infiltration of peri-implant tissues.

Methods

TLR4-expressing human dermal microvascular endothelial cells (HMEC-1) were treated with a range of clinically relevant cobalt ion concentrations. IL-8 protein secretion was measured by enzyme-linked immunosorbent assay (ELISA). Gene expression changes were quantified by TaqMan-based real time polymerase chain reaction.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_2 | Pages 36 - 36
1 Jan 2014
Singh A Anjum S Ramaskandhan J Siddique M
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Introduction:

The aim of this study was to assess patients reported fitness to return to work and to driving after ankle replacement.

Method:

Using Hospital Joint Registry, patients who underwent ankle replacement between 2006 and 2011 were invited to take part in the study. Questionnaires were sent to these patients. Participants were asked to report the nature and pattern of their work (full time or part time), time it took to return to work and subsequent nature of work. Participants were also asked about time to return to driving.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 298 - 299
1 Jul 2008
Anjum S Sherry P
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Abstract: resurfacing hip arthroplasty has shown promising early results in the treatment of hip arthrosis in younger patients as published from specialist centres in the United Kingdom. We are reporting early results and complications of Birmingham hip resurfacing arthroplasty (BHR) from a district general hospital.

This is a retrospective study of 216 hips in 186 patients during January 1999 to December 2004. The study included review of notes and X rays and a questionnaire based assessment of hip function and activities using Oxford Hip Score (OHS) and Duke’s activity score (DAS). This study has got national ethical committee approval.

The response rate for questionnaire was 76%. Average age was 53.3 years (range 20–72). Male: female ratio was 3:1. There were 152 unilateral and 32 bilateral cases. Majority of the cases had osteoarthritis in the hip. Average follow-up was 30.3 months (range 12–72). Average length of stay was 6 days (range 3–17). Average OHS and DAS were 15.8 and 51 respectively. 163 patients had OHS of less than 24. 113 patients had DAS of 58.2.

Radiological assessment showed six cases of hetero-topic calcification. Lysis was noted at prosthesis-neck junction in two cases but patients were asymptomatic.

The complications included superficial wound infection in 2, DVT in 6, neuroparaxia of sciatic and brachial plexus in one case each. There were six dislocations. There were nine revisions – seven following fracture neck of femur and two for aseptic loosening. The incidence of fracture neck of the femur was high in early part of the study suggesting technical improvement with experience.

Overall failure was 4.1%, slightly higher than other published literature. The OHS and DAS were comparable to other published results.

In conclusion the results of the BHR are encouraging and long-term prospective study is needed to find out the longevity of the implants and long-term results.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 433 - 434
1 Oct 2006
Anjum S Mevcha A Amir F O’Malley M Casserly H
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Trampoline was used by British & American fighter pilots as a training device during World War II. It became popular among Civilian as a recreational sports during 50s and 60s. Trampoline related injuries including quadriplegia and death have been reported from United States and Europe. We are reporting the incidence, type and distribution of trampoline-related injuries in children in a District General Hospital in United Kingdom.

Recently we treated three serious injuries – proximal tibial fracture associated with popliteal artery injury, subtrochanteric fracture of femur and cervical fracture-dislocation leading to quadriplegia, that lead to an audit study. This is a retrospective analysis of trampoline-related injuries in children seen in the Accident & Emergency Department over three months period. The casualty cards and admission records were reviewed.

The mechanism of injury was fall on or off the trampoline in 98.15%(53/54). All injuries occurred on back-garden or leisure-centre trampoline. 74% of injuries were sustained while unsupervised.

The incidence of soft tissue injuries were 59.25%(32/54) and fractures 40.75%(22/54). Soft tissue injuries commonly involved lower limb(16), upper limb(7) and head and neck(4). Fractures commonly involved upper limb(13), lower limb(8) and nasal bone(1). The fractures involved wrist and forearm in eight cases, ankle in five, elbow in four and one case each involving finger, hip, knee and toe. The treatment of trampoline-related injuries varied from reassurance, analgesia, tubigrip bandage to plaster cast. Fourteen(26%) patients were admitted into the wards and ten(18.5%) required surgical treatment.

The incidence of trampoline-related injuries in back-garden and leisure-centre when unsupervised was high. The supervision by an adult has not proved to be very effective in preventing the injuries as 26% of trampoline-related injuries occurred under supervision of an adult.

The morbidity related to leisure trampolining is high probably due to lack of training and non-compliance to the manufacturer instructions in the use of trampoline. We would recommend banning the routine use of back garden trampoline without proper training and supervision.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 20 - 20
1 Mar 2006
Anjum S Denolf F
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In moderate and severe Hallux Valgus metatarsus varus and incongruency of the joints are often important features. Basal osteotomy and distal soft tissue release can often achieve adequate correction of intermetatarsal angle (IMA) and joint alignment.. We retrospectively evaluated the results of Basal Osteotomy in 26 feet in 20 patients between January 1999 and December 2003. American Orthopaedics Foot & Ankle Society Score (AOFAS) was used for assessment. A subjective grading system was used to check patient’s satisfaction. The surgical technique consisted of crescentic basal osteotomy, lateral distal soft tissue release and medial capsular plication according to Roger Mann. Fourteen osteotomies were fixed with K wires that needed second operation to remove them. Barouk Screw was used to fix the osteotomy in 12 feet. Patients were mobilised in High heeled shoe postoperatively. Average age was 55.2 years and average follow-up was 25.8 months. The average preoperative Hallux Valgus Angle (HVA) and IMA were 37.38° and 17.27° respectively. At follow-up the HVA and IMA averaged 13.3° and 6.4° respectively. Sixteen feet had incongruent joint preoperatively that became congruent after surgery. In 25 feet sesamoid position improved after surgery. Average AOFAS score was 88.8. 94% patients were highly satisfied and graded their results as good to excellent. One patient had AOFAS score of < 50 due to her generalised poly-arthralgia and osteoporosis. K wire was broken across the TMT joint in one case and needed removal under GA. This lead to change of our practice as we started using Barouk screw to fix the osteotomy. Other complications consisted of decreased sensations over medial side of toe in three and mild metatarsalgia in one foot. Basal osteotomies with distal soft tissue release in the treatment of Hallux valgus give good correction of the deformity and high patient satisfaction. Barouk screw provides stable fixation.