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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 117 - 117
23 Feb 2023
Zhou Y Shadbolt C Rele S Spelman T Dowsey M Choong P Schilling C
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Utility score is a preference-based measure of general health state – where 0 is equal to death, and 1 is equal to perfect health. To understand a patient's smallest perceptible change in utility score, the minimal clinically important difference (MCID) can be calculated. However, there are multiple methods to calculate MCID with no consensus about which method is most appropriate. The aim of this study is to calculate MCID values for the Veterans-RAND 12 (VR12) utility score using varying methods. Our hypothesis is that different methods will yield different MCID values.

A tertiary institutional registry (SMART) was used as the study cohort. Patients who underwent unilateral TKA for osteoarthritis from January 2012 to January 2020 were included. Utility score was calculated from VR12 responses using the standardised Brazier's method. Distribution and anchor methods were used for the MCID calculation. For distribution methods, 0.5 standard deviations of the baseline and change scores were used. For anchor methods, the physical and emotional anchor questions in the VR12 survey were used to benchmark utility score outcomes. Anchor methods included mean difference in change score, mean difference in 12 month score, and receiver operating characteristics (ROC) analysis with the Youden index.

Complete case analysis of 1735 out of 1809 eligible patients was performed. Significant variation in the MCID estimates for VR12 utility score were reported dependent on the calculation method used. The MCID estimate from 0.5 standard deviations of the change score was 0.083. The MCID estimate from the ROC analysis method using physical or emotional anchor question improvement was 0.115 (CI95 0.08-0.14; AUC 0.656).

Different MCID calculation methods yielded different MCID values. Our results suggest that MCID is not an umbrella concept but rather many distinct concepts. A general consensus is required to standardise how MCID is defined, calculated, and applied in clinical practice.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 118 - 118
23 Feb 2023
Zhou Y Dowsey M Spelman T Choong P Schilling C
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Approximately 20% of patients feel unsatisfied 12 months after primary total knee arthroplasty (TKA). Current predictive tools for TKA focus on the clinician as the intended user rather than the patient. The aim of this study is to develop a tool that can be used by patients without clinician assistance, to predict health-related quality of life (HRQoL) outcomes 12 months after total knee arthroplasty (TKA).

All patients with primary TKAs for osteoarthritis between 2012 and 2019 at a tertiary institutional registry were analysed. The predictive outcome was improvement in Veterans-RAND 12 utility score at 12 months after surgery. Potential predictors included patient demographics, co-morbidities, and patient reported outcome scores at baseline. Logistic regression and three machine learning algorithms were used. Models were evaluated using both discrimination and calibration metrics. Predictive outcomes were categorised into deciles from 1 being the least likely to improve to 10 being the most likely to improve.

3703 eligible patients were included in the analysis. The logistic regression model performed the best in out-of-sample evaluation for both discrimination (AUC = 0.712) and calibration (gradient = 1.176, intercept = -0.116, Brier score = 0.201) metrics. Machine learning algorithms were not superior to logistic regression in any performance metric. Patients in the lowest decile (1) had a 29% probability for improvement and patients in the highest decile (10) had an 86% probability for improvement.

Logistic regression outperformed machine learning algorithms in this study. The final model performed well enough with calibration metrics to accurately predict improvement after TKA using deciles. An ongoing randomised controlled trial (ACTRN12622000072718) is evaluating the effect of this tool on patient willingness for surgery. Full results of this trial are expected to be available by April 2023.

A free-to-use online version of the tool is available at smartchoice.org.au.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 86 - 86
23 Feb 2023
Rele S Shadbolt C Elsiwy Y Naufal E Gould D Bazargan A Lorenzo Y Choong P Dowsey M Stevens J
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Use of anticoagulants for thromboembolic prophylaxis is strongly supported by evidence. However, the use of these medications beyond the prophylactic period is poorly understood.

We identified anticoagulant naïve patients that underwent hip or knee replacement between 2012 and 2019 from an arthroplasty registry and probabilistically linked 3,018 surgeries with nationwide pharmaceutical claims data. Rates of anticoagulation use were examined during the early (<= 60 days post-discharge), mid-term (61–180 days post-discharge) and long-term (181–360 days post-discharge) periods. Multivariable logistic regression analysis was performed to identify patient- and surgery-related factors associated with long-term anticoagulant use.

Anticoagulants were supplied to 20% of arthroplasties within 60 days of discharge, 7% between 61–180 days, and 10% between 181–360 days. Older age, obesity, increased comorbidity burden, a longer length of stay, occurrence of a complication necessitating anticoagulation and dispensation of an anticoagulant within 60 days of discharge were all risk factors for long-term anticoagulant use.

Given the risks associated with unnecessary use of these medications, certain patients who are prescribed anticoagulants beyond prophylactic period may benefit from specialist medication review in the months following surgery.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 109 - 109
23 Feb 2023
Naufal E Shadbolt C Elsiwy Y Thuraisingam S Lorenzo Y Darby J Babazadeh S Choong P Dowsey M Stevens J
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This study aimed to evaluate the month-to-month prevalence of antibiotic dispensation in the 12 months before and after total knee arthroplasty (TKA) and total hip arthroplasty (THA) and to identify factors associated with antibiotic dispensation in the month immediately following the surgical procedure.

In total, 4,115 THAs and TKAs performed between April 2013 and June 2019 from a state-wide arthroplasty referral centre were analysed. A cross-sectional study used data from an institutional arthroplasty registry, which was linked probabilistically to administrative dispensing data from the Australian Pharmaceutical Benefits Scheme. Multivariable logistic regression was carried out to identify patient and surgical risk factors for oral antibiotic dispensation.

Oral antibiotics were dispensed in 18.3% of patients following primary TKA and 12.0% of patients following THA in the 30 days following discharge. During the year after discharge, 66.7% of TKA patients and 58.2% of THA patients were dispensed an antibiotic at some point. Patients with poor preoperative health status were more likely to have antibiotics dispensed in the month following THA or TKA. Older age, undergoing TKA rather than THA, obesity, inflammatory arthritis, and experiencing an in-hospital wound-related or other infectious complications were associated with increased antibiotic dispensation in the 30 days following discharge.

A high rate of antibiotic dispensation in the 30 days following THA and TKA has been observed. Although resource constraints may limit routine wound review for all patients by a surgeon, a select cohort may benefit from timely specialist review postoperatively. Several risk factors identified in this study may aid in identifying appropriate candidates for such changes to follow-up care.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_14 | Pages 7 - 7
1 Dec 2022
Bruschi A Donati DM Choong P Lucarelli E Wallace G
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The inability to replace human muscle in surgical practice is a significant challenge. An artificial muscle controlled by the nervous system is considered a potential solution for this. We defined it as neuromuscular prosthesis. Muscle loss and dysfunction related to musculoskeletal oncological impairments, neuromuscular diseases, trauma or spinal cord injuries can be treated through artificial muscle implantation. At present, the use of dielectric elastomer actuators working as capacitors appears a promising option. Acrylic or silicone elastomers with carbon nanotubes functioning as the electrode achieve mechanical performances similar to human muscle in vitro. However, mechanical, electrical, and biological issues have prevented clinical application to date. In this study, materials and mechatronic solutions are presented which can tackle current clinical problems associated with implanting an artificial muscle controlled by the nervous system. Progress depends on the improvement of the actuation properties of the elastomer, seamless or wireless integration between the nervous system and the artificial muscle, and on reducing the foreign body response. It is believed that by combining the mechanical, electrical, and biological solutions proposed here, an artificial neuromuscular prosthesis may be a reality in surgical practice in the near future.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_5 | Pages 113 - 113
1 Apr 2019
Gray H Guan S Young T Dowsey M Choong P Pandy M
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INTRODUCTION

The medial-stabilised (MS) knee implant, characterised by a spherical medial condyle on the femoral component and a medially congruent tibial bearing, was developed to improve knee kinematics and stability relative to performance obtained in posterior-stabilised (PS) and cruciate-retaining (CR) designs. We aimed to compare in vivo six-degree-of-freedom (6-DOF) kinematics during overground walking for these three knee designs.

METHODS

Seventy-five patients (42 males, 33 females, age 68.4±6.6 years) listed for total knee arthroplasty (TKA) surgery were recruited to this study, which was approved by the relevant Human Research Ethics committees. Each patient was randomly- assigned a PS, CR or MS knee (Medacta International AB, Switzerland) resulting in three groups of 23, 26 and 26 patients, respectively. Patients visited the Biomotion Laboratory at the University of Melbourne 6±1.1 months after surgery, where they walked overground at their self-selected speed. A custom Mobile Biplane X-ray (MoBiX) imaging system tracked and imaged the implanted knee at 200 Hz. The MoBiX system measures 6-DOF tibiofemoral kinematics of TKA knees during overground gait with maximum RMS errors of 0.65° and 0.33 mm for rotations and translations, respectively.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLI | Pages 80 - 80
1 Sep 2012
Peel T Buising K Choong P
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Prosthetic joint infection (PJI) remains a devastating complication of arthroplasty. There is significant heterogeneity in treatment approaches to these infections and information on their efficacy relies on single-centre studies. This is the first multi-centre study examining current treatment approaches to patients with PJI.

A retrospective cohort study was conducted over a 3-year period (January 2006 – December 2008) involving 10 hospitals in Victoria, Australia. Cases of prosthetic joint infections of hips and knees were identified using an established statewide nosocomial infection surveillance network. Individual medical records were accessed to describe the management and record the outcomes of these patients.

Interim analysis from seven hospitals revealed 121 patients with PJI. Staphylococcus aureus was isolated in half of the infections with equal representation of methicillin resistant and methicillin sensitive strains. Debridement and retention (DR) was the most common treatment modality (72%), followed by resection arthroplasty without reimplantation (10%), superficial debridement and antibiotics (9%), one-stage exchange (6%) and two-stage exchange arthroplasty (3%). The timing and number of surgical interventions was however highly variable. The majority of patients underwent arthrotomy with an average of 3 debridements of the infected joint (range 0–10, standard deviation 1.7). Two-thirds of the patients with staphylococcal infections received a rifampicin-containing regimen. The course of oral antibiotic therapy was prolonged with a median duration of 132 days (interquartile range 13–357) but ranged from no oral antibiotic therapy to 1032 days. Overall 72% of patients remained infection-free after a mean follow-up of 15 months, however there was marked variation in outcomes between hospitals with success ranging from 50%-95%.

This multi-centre study demonstrates that there is a wide spectrum of treatment approaches to PJI. In addition, DR is the favoured treatment modality, which differs to our European and Northern American counterparts. This study reports real-life management and outcomes from patients at several centres, including many that do not have dedicated research interest in PJI.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLI | Pages 35 - 35
1 Sep 2012
Di Bella C Gaston L Slavin J Hicks R Choong P
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Ewing sarcoma (ES) and Osteosarcoma (OS) are the 2 most common malignant primary bone tumors. A patient's response to neoadjuvant chemotherapy has important implications in subsequent patient management and prognosis, as a favourable response to chemotherapy allows orthopedic oncologists to be more aggressive in pursuing limb-sparing surgery. An accurate and non-invasive pre-operative marker of response would be ideal for planning surgical margins and as a prognostic tool.

ES and OS have differing biological characterisitcs and respond differently to chemotherapy. We reviewed 18F-FDG PET imaging characteristics of ES and OS patients at baseline and following treatment to determine whether this biological variation is reflected in their imaging phenotype. A retrospective review of ES and OS patients treated with neoadjuvant chemotherapy and surgery was done, correlating PET results with histologic response to chemotherapy.

Change in the maximum standardized Uptake Value (SUVmax) between baseline and post-treatment scanning was not significantly associated with histologic response for either ES or OS. Metabolic tumor volume (MTV) and the percentage of injected 18F-FDG dose (%ID) in the primary tumor were found to be different for ES and OS response subgroups. A 50% reduction in MTV (MTV2:1 < 0.5) was found to be significantly associated with histologic response in OS. Using the same criteria for ES incorrectly predicted good responders. Increasing the cut-offs for ES to a 90% reduction in MTV (MTV 2:1 < 0.1) resulted in association with histologic response.

Response to neoadjuvant chemotherapy as reflected by changes in PET characteristics should be interpreted differently for ES and OS.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIII | Pages 212 - 212
1 May 2012
Choong P
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Pelvic sarcomas are uncommon and pose considerable challenges to surgery. Tumour resections necessarily lead to destabilisation of the pelvic ring and this is believed to have a negative impact on lower limb function. Depending on the type of resection, there are a number of innovative reconstructions that can re-establish pelvic stability and optimise limb function.

Conservative approaches that ignore pelvic instability are also employed and these may be applied following type I, I+II, II+III, I+II+III resections. These reconstructions include ilio-femoral and ilio-ischial athrodeses. On occasions, no reconstruction may be employed.

Outcomes following minimal reconstructive efforts remain unclear. Reconstructing the pelvic ring may not be necessary in all cases to achieve satisfactory function


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIII | Pages 59 - 59
1 May 2012
Buckland A Dowsey M Stoney J Hardidge A Ng K Choong P
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The triple taper polished cemented stem (C-stem, DePuy) was developed to promote calcar loading, and reduce proximal femoral bone resorption and aseptic loosening. We aimed to evaluate the changes in peri-prosthetic bone mineral density using Dual Energy X-ray Absorbtiometry (DEXA) after total hip arthroplasty (THA) using the C-stem prosthesis.

One hundred and three patients were recruited voluntarily through and single institution for THA. The prosthesis used was the triple-taper polished cemented C-Stem (De Puy, Warsaw, Indiana, USA). DEXA scans were performed pre- operatively, then at day for, three months, nine months, 18 months and 24 months post-operativley. Scans were analysed with specialised software (Lunar DPX) to measure bone mineral density (BMD) in all seven Gruen zones at each time interval. Changes in calcar BMD were also correlated with patient age, sex, surgical approach, pre-operative BMD and post-operative mobility to identify risk factors for periprosthetic bone resorption.

One hundred and three patients underwent 103 primary THA over a five-year period (98 osteoarthritis; 5 AVN). No femoral components were loose at the two year review and none were revised. The most marked bone resorption occured in Gruen zones 1 and 7, and was best preserved in zone 5. BMD decreased rapidly in all zones in the first three months post-operatively, after which the rate of decline slowed substantially. BMD was better preserved medially (zones 6 and 5) than laterally (zones 2 and 3) at 24 months. There was delayed recovery of BMD in all zones except zones 4 and 5.

High pre-operative T-scores (>2.0) in the spine, ipsilateral and contralateral femoral neck were associated with the higher post-operative BMD and less bone resorption at all time intervals in Gruen zone 7. Pre-operative osteopenia and osteoporosis were associated with low BMD and accelerated post-operative bone resorption in zone 7.

Patients whose mobility rendered them housebound had lower post-operative BMD, and accelerated post-operative BMD loss in zone 7 when compared to non-housebound patients. Females had a lower post-operative BMD and greater loss of BMD in zone 7. Patient age and surgical approach did not effect post-operative BMD or rate of bone resorption in zone 7.

The triple-taper femoral stem design did not show an increase in periprosthetic bone density at the proximal femur at two years post-operative. Calcar bone resorption is accelerated by low pre-operative BMD, poor post-operative mobility, and in females. Age and surgical approach do not have significant effects on calcar bone remodelling.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIII | Pages 209 - 209
1 May 2012
Clark J Akiyama T Dass C Choong P
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Chondrosarcoma responds poorly to adjuvant therapy and therefore, new targeted therapy is required. Animal models have been utilised to test therapeutic candidates, however clinically relevant, orthotopic models are lacking. The aim of this study was to develop such a model.

In vitro: two human chondrosarcoma cell lines, JJ012 and FS090, were compared with respect to proliferation, colony formation, invasion, MMP-2 and MMP-9 secretion, osteoclastogenesis, endothelial tube stimulation, and expression of the angiogenic factor VEGF, and the anti-angiogenic factor RECK on western blotting. In vivo: 20,000 cells (JJ012 or FS090) were injected either into the intramedullary canal of the mouse tibia (n=5 for each cell line), or into the tibial periosteum (n=5 for each cell line). Animals were measured, and x-rayed weekly. Once euthanised, tibias and lungs were preserved, embedded and sectioned to determine the presence of tumour and lung metastases.

In vitro: compared with FS090, JJ012 demonstrated significantly higher proliferative capacity at both day two and day four (p=0.017, and p=0.01). JJ012 had a significantly greater ability to invade Matrigel with an average number of 812.5 invading cells, versus 140.8 FS090 cells (p=0.0005). JJ012 readily formed colonies in collagen I, while FS090 formed none. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium. In vivo: tumours formed in the intratibial and periosteal groups injected with JJ012, whilst no mice injected with FS090 cells developed discernable tumours on physical inspection, caliper measurement or histological section. Periosteal tumours grew to three times the non-injected limb size by seven weeks, whereas intratibial injected limbs required 10 weeks to achieve the same extent of tumour growth. All JJ012 periosteal tumours resulted in lung micrometastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases. Lung metastases stained positive with Von Kossa and alizarin red stains, indicating a tendency for calcification, which is similar to metastases in the human disease. Sectioned tumour tissue demonstrated features of grade II-III chondrosarcoma. Similarities with the human disease were also noted on the X-ray, including endosteal scalloping, and cortical thickening.

Both intratibial and periosteal JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIII | Pages 210 - 210
1 May 2012
Akiyama T Clark J Miki Y Choong P Shinoda Y Nakamura K Kawano H
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Introduction and aims

After internal hemipelvectomy for malignant pelvic tumors, pelvic reconstruction is necessary for eventual weight bearing and ambulation. Non-vascularised, fibular grafts (NVFG) offer fast, and stable reconstruction, post- modified Enneking's type I and I/IV resection. This study aimed to evaluate the success of graft union and patient function after NVFG reconstruction.

Methods

From 1996 to 2009, 10 NVFG pelvic reconstructions were performed after internal hemipelvectomy in four cases of chondrosarcoma, three of Ewing's sarcoma, and single cases of osteosarcoma, malignant peripheral nerve sheath tumour, and malignant fibrous histiocytoma. A key indication for internal hemipelvectomy was sciatic notch preservation confirmed by preoperative MRI. Operation time and complications were recorded. The mean follow-up was 31.1 months (range: 5 to 56), and lower limb function was assessed using the Musculoskeletal Tumour Society scoring system. Plain radiographs and/or computer tomography were used to determine the presence or absence of NVFG union.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 193 - 193
1 Mar 2010
Dowsey M Broadhead M Stoney J Choong P
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Australia is a society with a diverse mix of people, cultures and languages. Patients presenting at our institution in 2006 who underwent TKA originated from 39 countries and 14 different languages were represented. Little is reported on the outcomes for non-English speaking patients undergoing Orthopaedic surgery. We conducted a prospective study to determine if outcomes were comparable for English and non-English patients undergoing TKA. A prospective observational study of 278 consecutive, primary TKA was undertaken from January to December 2006. Pre-operative Body Mass Index (BMI), patient demographics, co-morbidities, operative data, complications, length of stay and discharge destination were recorded. Functional status was measured preoperatively and 12 months post TKA using the International Knee Society Score (IKS). An interpreter was used for non-English speaking patients for Surgeon assessment and consent, pre-admission assessment and during the in-patient stay. A total of 41 patients (15%) were non-English speaking and of these 38 were female. No patient was lost to follow-up and 94% of patients completed the IKS evaluation at 12 months. The median age, ASA scores and number of co-morbidities were comparable between English and non-English speaking patients presenting for TKA. Median BMI was higher in the non-English speaking group 33.2 kg/m2 compared to English speaking 30.9 kg/m2, (p=0.010). There were no differences in the length of stay, discharge destination or complication rates between the 2 groups. Median preoperative IKS scores were poorer in non-English speaking patients (61) compared to English speaking patients (72), (p=0.002). At 12 months the difference in IKS scores between the 2 groups was even greater. The median score for non-English speaking patients was (116), compared to (142) in English speaking patients. Of the total IKS evaluation, poorer ratings for pain was the predominant cause for the lower scores in non-English speaking patients compared to English speaking patients, p=0.016. Active flexion was also slightly poorer at 12 months in non-English speaking patients 102° compared to English speaking patients 110°, (p=0.075). As there were significant differences in BMI and gender between English speaking and non-English speaking patients, we analyzed English speaking patients separately for differences in outcomes according to BMI and gender. We found no difference in the IKS scores based on these variables.

Although non-English speaking patients undergoing TKA achieved comparable outcomes in the acute phase following surgery, this did not equate to achieving the same functional result at 12 months, compared to English speaking patients. Pain was the predominant cause for poorer results. Further exploration of patient expectations and pain management is required for non-English speaking patients.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 217 - 217
1 Mar 2010
Clark J Dass C Choong P
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Aims: RECK protein is involved in angiogenesis and matrix-metalloproteinase interaction. In common cancers RECK may exert tumour control, while in sarcomas, there is insufficient research to confirm this. Our study aims to investigate the role of RECK in osteo-sarcoma (OS) and chondrosarcoma (CS) angiogenesis, using clinical data and an in vitro angiogenesis assay.

Methods: Seven OS biopsy samples, 11 OS metastases and 24 samples of CS were stained for the RECK protein using immunohistochemistry. RECK expression in vessels supplying sarcoma tissue was semi-quantified using ImageProPlus software to determine staining density. RECK density in tumour vessels was compared with density in vessels of 18 normal tissues. The human endothelial cell line, HMEC-1, was cultured and then transfected with a plasmid containing the RECK gene. HMEC-1 cells over-expressing RECK were then distributed into wells containing 100% Matrigel. Formation of vessel-like structures was observed and photographed at 8 hours. Comparison was made with a non-transfected HMEC-1 group, and an empty vector transfected HMEC-1 group. Results: RECK is predominantly expressed in vessels supplying both sarcomas and less frequently in the tumour cells. RECK density in OS and CS primary tumour vessels was no different to normal vessels (p> 0.05). However there was a significantly higher RECK density in the vessels of OS metastasis tissue (0.76 ODU-optical density units), compared with primary OS vessels (0.57 ODU, p< 0.05), and normal vessels (0.56 ODU, p< 0.05).

The average number of tube formations in the RECK transfected HMEC-1 cells was 67.8, compared with 42 in the empty vector group (p=0.03) and 54.1 in the control group (p=0.03). The average maximal wall thickness of tube formations was 100.7um versus 77.4um in the empty vector group (p=0.04) and 83.0um in the control group (p=0.09).

Conclusions: RECK is upregulated in vessels supplying OS metastases compared to vessels in primary sarcoma and normal tissue, suggesting an active role in angiogenesis. Replication of these conditions in vitro using the HMEC-1 tube formation assay demonstrates the ability of RECK to increase vessel formation within a matrix while maintaining vessel wall thickness. In sarcoma RECK may have pro-angiogenic properties and could be an important part of the metastatic cascade.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 197 - 197
1 Mar 2010
Mandaleson A Dowsey M Choong P
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Infection after Total Knee arthroplasty is devastating. The primary aim of this study was to characterise deep prosthesis infection in patients presenting greater than 3 months from index surgery. A retrospective single centre case control study of 1641 primary knee arthroplasties conducted between 1998 and 2006. All infected patients were identified (n=35) and those occurring within 3 months of surgery (n = 12) were excluded. All remaining infections (n=23) were classified into “latent” and “haematogenous”. Latent infections (n=7) were classified as having symptoms persisting from the time of surgery. Haematogenous infections (n=16) were those with an uneventful recovery and then a sudden onset of symptoms immediately prior to diagnosis of deep prosthetic infection. Each haematogenous infection was matched with 2 controls. Statistical analysis was performed between controls and the 16 haematogenous infections to determine any differences.

The overall prosthetic infection rate was 2.13%. Early infections accounted for 0.73% of the total and “haematogenous” infections for 0.98% of the total. The median time to infection in the “haematogenous” group was 1.6 years (Range 103 to 1803 days) and the median follow up time was 3.3 years (Range 230–3410). 94% (n=15) of the “haematogenous” group described a sentinel event prior to infection compared with 66% (n=21) of patients in the control group who reported an event with no subsequent progression to infection (P=0.04). Common preceding events included traumatic haemarthrosis in 31%, distant infections (eg dental abscess, intrathecal pump site infection, infected permacath, sternal wound infection, UTI) in 31% and cellulitis in 19%. The most common infecting organism was staphylococcus aureus in 56.5% (2 MRSA, 11 MSSA). Significant risk factors included the presence of diabetes (P=0.042), obesity and diabetes (P=0.044) and the number of co-morbidities (P=0.07). Infections were managed with debridement and washout (n=9) or removal of the implant with or without revision (n=7).

A significant number of patients who develop haematogenous infection have a preceding sentinel event. Haematogenous infections are more likely to occur in patients with diabetes or those with multiple co-morbidities. This group should be counseled regarding the ongoing risk of deep prosthetic infection.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 217 - 217
1 Mar 2010
Clark J Dass C Choong P
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The human RECK protein is often downregulated in cancer, which is thought to contribute to tumour progression. The role of RECK is not yet characterised in bone sarcomas. This study aims to determine the effects of increased human RECK protein expression in osteo-sarcoma and chondrosarcoma using cell invasion assays and tumour size on MRI.

The human osteosarcoma and chondrosarcoma cell lines (SaOS-2 and OUMS27 respectively) were cultured then transfected with either a plasmid containing the RECK gene, an empty vector, or not at all (control). Cells were incubated at 37 degrees within invasion chambers containing 75% matrigel. Cells invading the matrigel were counted after 3 days. Fifteen chondrosar-coma samples were stained using immunohistochemistry for the human RECK protein. RECK expression was determined to be positive or negative. MRI scans corresponding to tumour samples were viewed and the maximal tumour diameter out of all planes was manually determined with computer imaging software.

The SaOS-2 invasion assay demonstrated increased cell invasion in the RECK transfected group with an average of 502.3 invading cells, compared with 129.0 for the empty vector group (p=0.004) and 100.6 for the control group (p=0.001).

The OUMS-27 invasion assay also demonstrated increased cell invasion in RECK transfected cells with an average of 86.3 invading cells compared with 22.8 in the empty vector group (p=0.067) and 67.8 in the control group (p=0.17).

For MRI data, there were two distinct groups with roughly equal distributions of tumour grades. Group 1 had maximal tumour diameters of less than 70 mm, compared to group 2, being greater than 70mm (p=0.0006). In group 1 only 1/8 demonstrated RECK expression, while in group 2, 5/7 were RECK positive (p=0.041 Fisher exact test).

RECK overexpression in osteosarcoma and chondro-sarcoma cell lines appears to increase invasive capacity, and stands in contrast to RECK data in carcinomas. Furthermore, RECK expression in patient chondrosar-coma samples is associated with larger tumours. RECK may therefore function differently in sarcoma.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 193 - 193
1 Mar 2010
Choong P Dowsey M
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The number of total knee arthroplasties (TKA) performed each year continues to rise and now outnumbers total hip arthroplasty (THA). Obesity is more predominant amongst TKA patients compared to THA. As such we conducted a review to determine if a relationship existed between obesity and acute prosthetic infection following primary TKA.

A review of 1214 consecutive primary TKA was performed from January 1998 to December 2005 with no exclusions. Pre-operative Body Mass Index (BMI), patient demographics, co-morbidities, and operative data were recorded. Patients were separated into obese (BMI => 30 kg/m2) and non-obese groups (BMI < 30 kg/m2) groups and compared for incidence of acute prosthetic infection in the first 12 months following surgery. The prevalence of obesity in patients who underwent primary (TKA) was 59% (n=715) and more females were obese (63%) than males (48%). The number of patients with multiple co-morbidities was similar for the 2 groups.

Median age was 70 yrs in obese patients and 74 yrs in non-obese patients, (p=< 0.001). Median operative time for obese patients was 105 minutes, compared to non-obese patients 100 minutes, (p=0.02).

The prosthetic infection rate was 1.5% (n=18). The rate was more than double in obese patients (2.0%) compared to non-obese patients, (0.8%), (p=0.16). Of the total, 206 patients had diabetes mellitus (DM) and the incidence of prosthetic infection in this group was 4.9%, compared to patients without DM, 0.8%, (p=< 0.001). However there were no cases of prosthetic infection in diabetic patients with a BMI < 30 kg/m2. Patients with combined DM and obesity had a significantly higher prosthetic infection rate 6.4%, compared to patients who only had one of these conditions or neither; DM only 0%, obesity only 0.7%, neither condition 0.9%, (p=< 0.001).

A post operative drain was used in 1109 patients. The prosthetic infection rate was 3 times higher in patients without a drain 3.8%, compared to patients with a drain, 1.3%. When analyzed together it was the obese group without a postoperative drain, who had the highest infection rate, 6%. This compared to: obese with a drain 1.7%, non-obese with a drain 0.7% and non-obese without a drain 1.8%, (p=0.027).

Obesity was a risk factor for the development of acute prosthetic infection in diabetic patients who underwent primary TKA at our institution. Using a post-operative drain reduced the risk of acute prosthetic infection in our obese patient group.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 253 - 253
1 May 2009
Yanagisawa M Choong P Lewallen D Sim FH
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We report a series of sixteen total hip arthroplasties utilizing a porous tantalum trabecular metal acetabular component in patients with tumors of the hip.

The study included eight men and eight women with an average age of 59.3 (range 22–80 years). Two patients had benign but locally recurrent disease destructive of bone (Langerhan’s Cell Histiocytosis and Rosi Dorfman Disease), while fourteen had malignant lesions. The latter included six myeloma, two lymphoma, and six metastatic carcinoma (three breast, one prostate, one lung, and one unknown site). Fifteen patients had prior radiation therapy. The technique used was determined by the extent of the lesion and the quality of remaining host bone.

In eight patients major deficiencies necessitated augmentation of the porous tantalum cup with an anti-protrusio device “over -the top” a cup-cage construct. Porous tantalum augments were utilised with the cup to fill defects in the acetabulum in seven patients. Postoperative complications were seen in four cases (DVT, DIC, pneumonia, and one death from c. difficile colitis).

Postoperatively, the majority of the patients had excellent pain relief and improved ambulatory status. No clinical failures have been observed at follow-up (mean 12.5 months, range twenty days-twenty-eight months). There have been no re-operations. Radiographically, no migration or evidence of implant loosening has been observed.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 252 - 252
1 May 2009
Choong P Dass C Ek E Sim F
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Pigment epithelium-derived factor (PEDF) is the most potent endogenous inhibitor of angiogenesis and decreased PEDF expression has been shown, in many tumours, to be associated with increased intratumoural microvascularity, enhanced tumour growth and metastases and poor patient prognosis. We evaluated the role of PEDF in osteosarcoma growth inhibition and examined it’s potential as a possible anti-cancer therapeutic agent.

We investigated the effects of overexpressed and recombinant PEDF (rPEDF) in several cell-based assays and in two orthotopic models of osteosarcoma (UMR 106-01 and SaOS-2).

In vitro, overexpression of PEDF significantly decreased cell proliferation, migration, invasion and increased adhesion to collagen-1. rPEDF resulted in a dose-dependent inhibition of cell proliferation, increased collagen adhesion, decreased invasion, and down-regulation of VEGF. The pro-differentiation ability of rPEDF was confirmed by upregulation of several osteoblastic markers after treatment of a pre-osteoblastic cell line (UMR 201). Furthermore, both cell lines displayed increased mineralised nodule formation after administration. In vivo, PEDF inhibited osteosarcoma growth and metastasis when overexpressed and in the recombinant form. In addition, anti-tumour activity was observed upon testing with shorter peptides of PEDF. Pharmacoevaluation of rPEDF demonstrated stability within media over several days, and no significant side effects in terms of wound healing.

From these results, PEDF demonstrates multi-modal anti-tumour activity via anti-proliferation, anti-angiogenesis, pro-differentiation and anti-metastasis. PEDF may be a promising therapeutic agent for the treatment of patients with osteosarcoma.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 321 - 322
1 Sep 2005
Yuen A Ek E Powell G Choong P
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Introduction and Aims: Improved survival has motivated aggressive surgery with musculoskeletal tumors. Pelvic resection is challenging because of the constraints of adjacent vital anatomy, and the considerable impact on limb and visceral function. The aims of this study was to assess the functional, oncologic and surgical outcomes following resections of the bony pelvis.

Method: Between 1996 and 2003, 49 patients underwent tumor resections of the pelvic ring. The mean age was 43 (range 15–72) years. There were 44 primary (36 bone, nine soft tissue) and five secondary tumors. Of the bone tumors, there were six osteosarcomas, five Ewings sarcomas, 12 chondrosarcomas and 13 others. Of the soft tissue tumors, nine were of neural origin. Tumor locations included the ilium, periacetabulum, pubic bones, sacrum or combinations of these. Neoadjuvant chemotherapy (seven patients) and pre-operative radiotherapy (eight patients) were also used. Function was assessed using the American Musculoskeletal Tumor Society Functional scoring system. No patient had metastases at presentation.

Results: Surgery – There were 40 limb sparing resections and nine hindquarter amputations. The surgical margins were intralesional (four), marginal (12), wide (28) and radical (five). Of the limb sparing surgery, prosthetic reconstructions were used in nine patients, biologic reconstructions in seven patients a combination of biologic and prosthetic reconstructions in three cases and no reconstructions in the others. The mean operating time was five (range 1.5–10) hours. The mean intra-operative blood loss was 10 (range 2–26) units. The average length of stay was 22 (range 2–110) days. Fifty percent of patients developed acute complications. Survival – There was one intra-operative death. There were nine local recurrences and 16 metastases. Death from disease occurred at a mean time of 13 (range 1–51) months. Mean follow-up was 28 (range 1–90) months. Functional assessment – Hind quarter amputation and periacetabular resections had the worse functional outcome. These accounted for almost 40% of all cases. Surprisingly, patients with periacetabular resections had the best score for emotional acceptance.

Conclusion: Pelvic resections are complex, demanding and accompanied by a high complication rate. Surgery significantly affects functional outcome. Disease control is similar to limb tumors and medium to long-term survival is possible. Emotional acceptance of surgery in survivors was surprisingly high. Major pelvic resection for malignancy appears justifiable.