To be able to assess the biomechanical and functional effects of ankle injury and disease it is necessary to characterise healthy ankle kinematics. Due to the anatomical complexity of the ankle, it is difficult to accurately measure the Tibiotalar and Subtalar joint angles using traditional marker-based motion capture techniques. Biplane Video X-ray (BVX) is an imaging technique that allows direct measurement of individual bones using high-speed, dynamic X-rays. The objective is to develop an in-vivo protocol for the hindfoot looking at the tibiotalar and subtalar joint during different activities of living. A bespoke raised walkway was manufactured to position the foot and ankle inside the field of view of the BVX system. Three healthy volunteers performed three gait and step-down trials while capturing Biplane Video X-Ray (125Hz, 1.25ms, 80kVp and 160 mA) and underwent MR imaging (Magnetom 3T Prisma, Siemens) which were manually segmented into 3D bone models (Simpleware Scan IP, Synopsis). Bone position and orientation for the Talus, Calcaneus and Tibia were calculated by manual matching of 3D Bone models to X-Rays (DSX Suite, C-Motion, Inc.). Kinematics were calculated using MATLAB (MathWorks, Inc. USA). Pilot results showed that for the subtalar joint there was greater range of motion (ROM) for Inversion and Dorsiflexion angles during stance phase of gait and reduced ROM for Internal Rotation compared with step down. For the tibiotalar joint, Gait had greater inversion and internal rotation ROM and reduced dorsiflexion ROM when compared with step down. The developed protocol successfully calculated the in-vivo kinematics of the tibiotalar and subtalar joints for different dynamic activities of daily living. These pilot results show the different kinematic profiles between two different activities of daily living. Future work will investigate translation kinematics of the two joints to fully characterise healthy kinematics

Aims. Dislocation of the hip remains a major complication after periacetabular tumour resection and endoprosthetic reconstruction. The position of the acetabular component is an important modifiable factor for surgeons in determining the risk of postoperative dislocation. We investigated the significance of horizontal, vertical, and sagittal displacement of the hip centre of rotation (COR) on postoperative dislocation using a CT-based 3D model, as well as other potential risk factors for dislocation. Methods. A total of 122 patients who underwent reconstruction following resection of periacetabular tumour between January 2011 and January 2020 were studied. The risk factors for dislocation were investigated with univariate and multivariate logistic regression analysis on patient-specific, resection-specific, and reconstruction-specific variables. Results. The dislocation rate was 13.9% (n = 17). The hip COR was found to be significantly shifted anteriorly and inferiorly in most patients in the dislocation group compared with the non-dislocation group. Three independent risk factors were found to be related to dislocation: resection of gluteus medius (odds ratio (OR) 3.68 (95% confidence interval (CI) 1.24 to 19.70); p = 0.039), vertical shift of COR > 18 mm (OR 24.8 (95% CI 6.23 to 128.00); p = 0.001), and sagittal shift of COR > 20 mm (OR 6.22 (95% CI 1.33 to 32.2); p = 0.026). Conclusion. Among the 17 patients who dislocated, 70.3% (n = 12) were anterior dislocations. Three independent risk factors were identified, suggesting the importance of proper restoration of the COR and the role of the gluteus medius in maintaining hip joint stability. Cite this article: Bone Joint J 2022;104-B(10):1180–1188

Abstract

Abstract. Objectives. Impingement of total hip replacements (THRs) can cause rim damage of polyethylene liners, and lead to dislocation and/or mechanical failure of liner locking mechanisms[1]. A geometric model of a THR in situ was previously developed to predict impingement for different component orientations and joint motions of activities[2]. However, the consequence of any predicted impingement is unknown. This study aimed to develop an in-vitromethod to investigate the effects of different impingement scenarios. Method. A ProSim electro-mechanical single-station hip simulator (Simulation Solutions) was used, and the 32mm diameter metal-on-polyethylene THRs (DePuy Synthes) were assessed. The THR was mounted in an inverted orientation, and the input (motion and loading) applied simulated a patient stooping over to pick an object from the floor[3]. The impingement severity was varied by continuing motion past the point of impingement by 2.5° or 5°, and compressive load applied in the medial-lateral direction was varied from 100N to 200N. Each test condition was applied for 40,000 cycles (n=3). Rim penetration was assessed using a CMM and component separation was measured during the tests. Results. Varying the impingement severity from 2.5° to 5° increased rim penetration two-fold (by >0.05mm) and increased medial-lateral component separation three-fold (by >0.3mm) (both p<0.001). Increasing the medial-lateral load had less effect on the rim penetration and component separation, with exception of rim penetration with the higher impingement severity condition. Conclusion. The impingement severity influenced the medial-lateral component separation, suggesting that increasing the impingement severity could increase the risk of dislocation. The impingement severity, which could be predicted from geometric modelling, was also found to significantly affect rim penetration, meaning this method could be used alongside geometric modelling to predict impingement severity in a range of scenarios. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Introduction

Diabetic foot disease is a major public health problem with an annual NHS expenditure in excess of £1 billion. Infection increases risk of major amputation fivefold. Due to the polymicrobial nature of diabetic foot infections, it is often difficult to isolate the correct organism with conventional culture techniques, to deliver appropriate narrow spectrum antibiotics. Rapid DNA-based technology using multi-channel arrays presents a quicker alternative and has previously been used effectively in intensive care and respiratory medicine.

Aims. In recent conflicts, most injuries to the limbs are due to blasts resulting in a large number of lower limb amputations. These lead to heterotopic ossification (HO), phantom limb pain (PLP), and functional deficit. The mechanism of blast loading produces a combined fracture and amputation. Therefore, to study these conditions, in vivo models that replicate this combined effect are required. The aim of this study is to develop a preclinical model of blast-induced lower limb amputation. Methods. Cadaveric Sprague-Dawley rats’ left hindlimbs were exposed to blast waves of 7 to 13 bar burst pressures and 7.76 ms to 12.68 ms positive duration using a shock tube. Radiographs and dissection were used to identify the injuries. Results. Higher burst pressures of 13 and 12 bar caused multiple fractures at the hip, and the right and left limbs. Lowering the pressure to 10 bar eliminated hip fractures; however, the remaining fractures were not isolated to the left limb. Further reducing the pressure to 9 bar resulted in the desired isolated fracture of the left tibia with a dramatic reduction in the fractures to other sites. Conclusion. In this paper, a rodent blast injury model has been developed in the hindlimb of cadaveric rats that combines the blast and fracture in one insult, necessitating amputation. Experimental setup with 9 bar burst pressure and 9.13 ms positive duration created a fracture at the tibia with total reduction in non-targeted fractures, rendering 9 bar burst pressure suitable for translation to a survivable model to investigate blast injury-associated diseases. Cite this article: Bone Joint Res 2021;10(3):166–173

We have developed a novel technique to analyse bone, using imaging mass cytometry (IMC) without the constraints of using immunofluorescent histochemistry. IMC can measure the expression of over 40 proteins simultaneously, without autofluorescence. We analysed mitochondrial respiratory chain (RC) protein deficiencies in human bone which are thought to contribute to osteoporosis with increasing age.

Osteoporosis is characterised by reduced bone mineral density (BMD) and fragility fractures. Humans accumulate mitochondrial mutations and RC deficiency with age and this has been linked to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of 30 onwards, coincidently the age BMD begins to decline. Mitochondria contain their own genome which accumulates somatic variants at around 10 times the rate of nuclear DNA. Once these mutations exceed a threshold, RC deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model expresses a proof-reading deficient version of PolgA, a mtDNA polymerase. These mice accumulate mutations 3-5 times higher than wild-type mice showing enhanced levels of age-related osteoporosis and RC deficiency in osteoblasts.

Bone samples were analysed from young and old patients, developing a protocol and analysis framework for IMC in bone tissue sections to analyse osteoblasts in-situ for RC deficiency.

Samples from the femoral neck of 10 older healthy volunteers aged 40 – 85 were compared with samples from young patients aged 1-19. We have identified RC complex I defect in osteoblasts from 6 of the older volunteers, complex II defects in 2 of the older volunteers, complex IV defect in just 1 older volunteer, and complex V defect in 4 of the older volunteers.

These observations are consistent with the PolgD257A/D257A mouse-model and suggest that RC deficiency, due to age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis.

Aims. Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods. For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results. Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion. Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143–151

Introduction. Total hip arthroplasty (THA) is an effective surgery for the treatment of advanced osteoarthritis but increasing numbers of these procedures are having a significant impact on healthcare budgets. One route to mitigate the increasing costs is outpatient THA, discharging patients on the same day as their surgery. The purpose of this study was to determine the cost of outpatient THA compared to standard overnight stay in hospital. Methods. This was a prospective-randomized controlled trial for patients undergoing primary THA through a direct anterior approach. Participants were randomized to be discharged on the same day as surgery, as outpatients, or on day one post-surgery, as inpatients, using a Zelen consent model. Adverse events were assessed, and participants completed self-reported cost questionnaires at two-, six- and 12-weeks post-surgery, and the WOMAC preoperatively and at 12-weeks post-surgery. We performed a cost analysis from health care payer (HCP) and societal perspectives. Results. 106 patients were enrolled in this study, with 50 randomized to outpatient and 56 randomized to inpatient THA. Seven patients from the outpatient group and five patients from the inpatient group crossed-over. Adverse event rate was similar between the groups with seven events in four participants in the inpatient group and three events in two participants in the outpatient group. WOMAC scores were not significantly different between the groups (p=0.12). From both a HCP and societal perspective, inpatient THA was more costly than outpatient THA. The cost difference was $3,353.15 for HCP (p<0.0001) and $3,703.30 for societal (p=0.003) in favour of outpatient THA. Conclusion. Our results suggest that outpatient THA is a cost-saving procedure when compared to inpatient THA from both HCP and societal perspectives. We will continue recruitment to investigate whether these results hold true in a larger sample as well as assess for cost-effectiveness, patient safety and satisfaction. Acknowledgements. This study was supported by the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario (AMOSO). We also received funding from the PSI Foundation. For any tables or figures, please contact the authors directly

Aims. Surgery is often indicated in patients with metastatic bone disease (MBD) to improve pain and maximize function. Few studies are available which report on clinically meaningful outcomes such as quality of life, function, and pain relief after surgery for MBD. This is the published protocol for the Bone Metastasis Audit — Patient Reported Outcomes (BoMA-PRO) multicentre MBD study. The primary objective is to ascertain patient-reported quality of life at three to 24 months post-surgery for MBD. Methods. This will be a prospective, longitudinal study across six UK orthopaedic centres powered to identify the influence of ten patient variables on quality of life at three months after surgery for MBD. Adult patients managed for bone metastases will be screened by their treating consultant and posted out participant materials. If they opt in to participate, they will receive questionnaire packs at regular intervals from three to 24 months post-surgery and their electronic records will be screened until death or five years from recruitment. The primary outcome is quality of life as measured by the European Organisation for Research and the Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ) C30 questionnaire. The protocol has been approved by the Newcastle & North Tyneside 2 Research Ethics Committee (REC ref 19/NE/0303) and the study is funded by the Royal College of Physicians and Surgeons of Glasgow (RCPSG) and the Association for Cancer Surgery (BASO-ACS). Discussion. This will be the first powered study internationally to investigate patient-reported outcomes after orthopaedic treatment for bone metastases. We will assess quality of life, function, and pain relief at three to 24 months post-surgery and identify which patient variables are significantly associated with a good outcome after MBD treatment. Cite this article: Bone Jt Open 2021;2(2):79–85

Aims. To investigate metallosis in patients with magnetically controlled growing rods (MCGRs) and characterize the metal particle profile of the tissues surrounding the rod. Methods. This was a prospective observational study of patients with early onset scoliosis (EOS) treated with MCGRs and undergoing rod exchange who were consecutively recruited between February 2019 and January 2020. Ten patients were recruited (mean age 12 years (SD 1.3); 2 M:8 F). The configurations of the MCGR were studied to reveal the distraction mechanisms, with crucial rod parts being the distractable piston rod and the magnetically driven rotor inside the barrel of the MCGR. Metal-on-metal contact in the form of ring-like wear marks on the piston was found on the distracted portion of the piston immediately outside the barrel opening (BO) through which the piston rod distracts. Biopsies of paraspinal muscles and control tissue samples were taken over and away from the wear marks, respectively. Spectral analyses of the rod alloy and biopsies were performed to reveal the metal constituents and concentrations. Histological analyses of the biopsies were performed with haematoxylin and eosin staining. Results. Titanium (Ti), vanadium (V), and neodymium (Nd) concentrations in the biopsies taken near the wear marks were found to be significantly higher than those in the control tissue samples. Significantly increased Nd concentrations were also found in the tissues near the barrel of the MCGR. Chronic inflammation was revealed by the histological studies with fibrosis and macrophage infiltration. Black particles were present within the macrophages in the fibrotic tissues. Conclusion. Ti and V were generated mainly at the BO due to metal-on-metal contact, whereas the Nd from the rotor of the MCGR is likely released from the BO during distraction sessions. Phagocytotic immune cells with black particles inside raise concern regarding the long-term implications of metallosis. Cite this article: Bone Joint J 2020;102-B(10):1375–1383

In the course of uneventful secondary bone healing, a fracture gap is progressively overgrown by callus which subsequently calcifies and remodels into new bone. It is widely accepted that callus formation is promoted by mechanical stimulation of the tissue in the fracture gap. However, the optimal levels of the interfragmentary motion's amplitude, frequency and timing remain unknown. The aim of this study was to develop an active fixation system capable of installing a well-controlled mechanical environment in the fracture gap with continuous monitoring of the bone healing progression. The experimental model was adapted from Tufekci et al. 2018 and required creation of a critical size defect and an osteotomy in a sheep tibia. They were separated by a mobile bone fragment. The distal and proximal parts of the tibia were fixed with an external fixator, whereas the mobile fragment was connected to the proximal part with an active fixator equipped with a linear actuator to move it axially for mechanical stimulation of the tissue in the fracture gap. This configuration installed well-controlled mechanical conditions in the osteotomy, dependent only on the motion of the active fixator and shielded from the influence of the sheep's functional weightbearing. A load sensor was integrated to measure the force acting in the fracture gap during mechanical stimulation. The motion of the bone fragment was controlled by means of a custom-made controller allowing to program stimulation protocols of various profiles, amplitudes and frequencies of loading events. Following in vitro testing, the system was tested in two Swiss White Alpine Sheep. It was configured to simulate immediate weightbearing for one of the animals and delayed weightbearing for the other. The applied loading protocol consisted of 1000 loading events evenly distributed over 12 hours resulting in in a single loading event every 44 seconds. Bench testing confirmed the ability of the system to operate effectively with frequencies up to 1Hz over a range of stimulation amplitudes from 0.1 to 1.5 mm. Continuous measurements of in vivo callus stiffness revealed progressive fracture consolidation in the course of each experiment. A delayed onset of fracture healing was observed in the sheep with simulated delayed weightbearing. The conducted preclinical experiments demonstrated its robustness and reliability. The system can be applied for further preclinical research and comprehensive in-depth investigation of fracture healing

Purpose. Great expense is accumulated in investigation and management, often with poor outcome, of a patient with a painful TKR. We aim to produce guidelines for their investigation and careful, successful management. Method. We studied 42 cases of patients with a painful TKR. Costs were calculated of appointments, serological and radiological investigations for these patients and an average cost of investigating a patient was obtained. We also calculated costs of various forms of management, both surgical and non-surgical and correlated these with patient outcomes. Results. 41 patients with an average investigation time of 20 months had on average 4 Orthopaedic appointments for the investigation of a painful TKR. On average, 8 blood tests were performed along with 8 radiographs. The average cost of investigating a patient with a painful TKR was £2337. 22 patients underwent operative intervention compared to 19 having solely pharmaceutical intervention. There was a significant difference between the amounts spent in each group with £5051 spent per patient in the operative group compared to £190 per patient on the non-operative group. There was a higher percentage of patient improvement in the non-operative group. Conclusion: Costs for investigation of a patient with a painful TKR were high because of exceedingly high numbers of repeated investigations. There is no guidance currently on how to manage painful TKR which is becoming an increasing clinical problem because of the increasing number of TKR's being performed per year. A lot of money is wasted on over investigating patients and performing operations that do not improve symptoms or prognosis. Careful thought needs to be given to careful investigation and management of patients in order to achieve optimal patient improvement. We have proposed a protocol for the investigation and management that allows prompt diagnosis and intervention and helps improve symptoms while keeping costs down

Aims. There is increasing evidence that flexible flatfoot (FF) can lead to symptoms and impairment in health-related quality of life. As such we undertook an observational study investigating the aetiology of this condition, to help inform management. The hypothesis was that as well as increased body mass index (BMI) and increased flexibility of the lower limb, an absent anterior subtalar articulation would be associated with a flatter foot posture. . Patients and Methods. A total of 84 children aged between eight and 15 years old were prospectively recruited. The BMI for each child was calculated, flexibility was assessed using the lower limb assessment scale (LLAS) and foot posture was quantified using the arch height index (AHI). Each child underwent a sagittal T1-weighted MRI scan of at least one foot. . Results. An absent anterior subtalar articulation (p < 0.001) and increased LLAS (p = 0.001) predicted a low AHI. BMI was not a significant predictive factor (p = 0.566). . Conclusion. This is the first study to demonstrate the importance of the morphology of the subtalar joint on the underlying foot posture in vivo. . Take home message: Flexibility of the lower limb and absence of the anterior facet of the subtalar joint are associated with flexible FF and may influence management of this common condition. Cite this article: Bone Joint J 2016;98-B:564–8

Aims. Carpal malalignment after a distal radial fracture occurs due to loss of volar tilt. Several studies have shown that this has an adverse influence on function. We aimed to investigate the magnitude of dorsal tilt that leads to carpal malalignment, whether reduction of dorsal tilt will correct carpal malalignment, and which measure of carpal malalignment is the most useful. Methods. Radiographs of patients with a distal radial fracture were prospectively collected and reviewed. Measurements of carpal malalignment were recorded on the initial radiograph, the radiograph following reduction of the fracture, and after a further interval. Linear regression modelling was used to assess the relationship between dorsal tilt and carpal malalignment. Receiver operating characteristic (ROC) analysis was used to identify which values of dorsal tilt led to carpal malalignment. Results. A total of 250 consecutive patients with 252 distal radial fractures were identified. All measures of carpal alignment were significantly associated with dorsal tilt at each timepoint. This relationship persisted after adjustment for age, sex, and the position of the wrist. Capitate shift consistently had the strongest relationship with dorsal tilt and was the only parameter that was not influenced by age or the position of the wrist. ROC curve analysis identified that abnormal capitate shift was seen with > 9° of dorsal tilt. Conclusion. Carpal malalignment is related to dorsal tilt following a distal radial fracture. Reducing the fracture and improving dorsal tilt will reduce carpal malalignment. Capitate shift is easy to assess visually, unrelated to age and sex, and appears to be the most useful measure of carpal malalignment. The aim during reduction of a distal radial fracture should be to realign the capitate with the axis of the radius and prevent carpal malalignment. Cite this article: Bone Joint J 2020;102-B(1):137–143

Objectives. The medially spherical GMK Sphere (Medacta International AG, Castel San Pietro, Switzerland) total knee arthroplasty (TKA) was previously shown to accommodate lateral rollback while pivoting around a stable medial compartment, aiming to replicate native knee kinematics in which some coronal laxity, especially laterally, is also present. We assess coronal plane kinematics of the GMK Sphere and explore the occurrence and pattern of articular separation during static and dynamic activities. Methods. Using pulsed fluoroscopy and image matching, the coronal kinematics and articular surface separation of 16 well-functioning TKAs were studied during weight-bearing and non-weight-bearing, static, and dynamic activities. The closest distances between the modelled articular surfaces were examined with respect to knee position, and proportions of joint poses exhibiting separation were computed. Results. Overall, 1717 joint poses were analyzed. At a 1.0 mm detection threshold, 37 instances of surface separation were observed in the lateral compartment and four medially (p < 0.001). Separation was activity-dependent, both laterally and medially (p < 0.001), occurring more commonly during static deep flexion in the lateral compartment, and during static rotation in the medial compartment. Lateral separation occurred more frequently than medial during kneeling (7/14 lateral vs 1/14 medial; p = 0.031) and stepping (20/1022 lateral vs 0/1022 medial; p < 0.001). Separation varied significantly between individuals during dynamic activities. Conclusion. No consistent association between closest distances of the articular surfaces and knee position was found during any activity. Lift-off was infrequent and depended on the activity performed and the individual knee. Lateral separation was consistent with the design rationale. Medial lift-off was rare and mostly in non-weight-bearing activities. Cite this article: S. Key, G. Scott, J. G. Stammers, M. A. R. Freeman†, V. Pinskerova, R. E. Field, J. Skinner, S. A. Banks. Does lateral lift-off occur in static and dynamic activity in a medially spherical total knee arthroplasty? A pulsed-fluoroscopic investigation. Bone Joint Res 2019;8:207–215. DOI: 10.1302/2046-3758.85.BJR-2018-0237.R1

Introduction. Current strategies to treat back pain address the symptoms but not the underlying cause. Here we are investigating a novel hydrogel material (NPgel) which can promote MSC differentiation to Nucleus pulposus cells. Current in vitro studies have only explored conditions that mimic the native disc microenvironment. Here, we aim to determine the stem cells regenerative capacity under conditions that mimic the degenerate environment seen during disc degeneration. Methods. hMSCs were encapsulated in NPgel and cultured for 4 weeks under hypoxia (5%) with ± calcium (2.5mM and 5.0mM CaCl. 2. ), IL-1β and TNFα either individually or in combination to mimic the degenerate microenvironment. Cell viability was assessed by Alamar blue assay. Histological and immunohistochemical analysis investigated altered matrix and matrix degrading enzyme expression. Results. Viability of hMSCs was maintained under all culture conditions. Matrix deposition of glycosaminoglycans were observed under all conditions, MMP13 expression was upregulated by calcium but not by pro-inflammatory cytokines IL-1β and TNFα. Conclusions. We are developing an in vitro modelling system which can be used to test novel therapies within a degenerate microenvironment. Interestingly, our preliminary findings suggest calcium is a major contributor to regulating MMP13 in this model system. Investigating the degenerate niche will identify targets for inhibition to provide the correct niche to promote regeneration of the IVD. No conflict of interest. Funding: BMRC, MERI Sheffield Hallam University, for joint funding the Daphne Jackson Trust fellowship

It is well documented that implant loosening rate in sickle cell disease patients is higher than that seen in patients with hip arthroplasty from other indications. The Hypoxic inducible factor(HIF) - is activated in the microcellular hypoxic environment and this through a cascade of other enzymatic reactions promotes the activity of other factors and further help enhance angiogenesis and osteogenesis. The aim of this study was to investigate and propose a potential model for investigating osseointegration in a hypoxic microcellular environment using osteoblasts(MG63). Human MG63 osteoblastic cells were cultured under normoxia and hypoxic conditions (20%; and 1% oxygen saturation) for 72 hours under two different condition- with and without cobalt chloride. The samples cultured under normoxic condtions without cobalt chloride acted as control. Using qualitative polymerase chain reaction-(qPCR) - HIF expression was assessed under the above conditions in relation to the control. The results showed there was significant expression of the HIF 1 alpha protein under hypoxic condition with cobalt chloride in comparison with the control samples- all at 72hours incubation. Mann-Whitney U test was used to deduce level of significance of fold change.(p=0.002; <0.05). This was deemed as being a significant difference in the level of expression of HIF compared to the control. The results show that the hypoxic inducible factor can be expressed using the above tested. experimental invitro-model with significant results which can be a foundation for further research into improving hip implant prosthesis design to help enhance osseo-integration in sickle cell disease patient with AVN

The ankle radiograph is a commonly requested investigation as the ankle joint is commonly injured. Each radiograph exposes 0.01 mSv of radiation to the patient that is equivalent to 1.5 days of natural background radiation [1]. The aim of the clinical audit was to use the Ottawa Ankle Rule to attempt to reduce the number of ankle radiographs taken in patients with acute ankle injuries and hence reduce the dose of ionising radiation the patient receives. A retrospective audit was undertaken. 123 ankle radiograph requests and radiographs taken between May and July 2018 were evaluated. Each ankle radiograph request including patient history and clinical examination was graded against the Ottawa Ankle Rule. The rule states that 1 point(s) indicates radiograph series; (1) malleolar and/or midfoot pain; (1) tenderness over the posterior 6cm or tip of the lateral or medial malleolus (ankle); (1) tenderness over the navicular or the base of the fifth metatarsal (foot); (1) unable to take four steps both immediately and in the emergency department [2]. Patients who score 0 do not need radiograph series. Each radiograph was reviewed if a fracture was present or not. The clinical audit identified 14 true positives where the Ottawa Ankle Rule scored 1 and the patient had an ankle fracture, and 2 false negatives (sensitivity 88%). There were 81 false positives, and 23 true negatives (specificity 22%). Therefore, a total of 23/123 ankle radiographs were unnecessary which is equivalent to 34.5 days of background radiation. The negative predictive value of the Ottawa Ankle Rule in this audit was 92%. The low rate of Ottawa rule utilisation may unnecessarily cause patient harm that should be addressed. An educational intervention with physicians combined with integration of the Ottawa rule scoring in ankle radiograph requests is planned with re-audit in 6 months