Surgery (St Vincent's) - Research Publications
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ItemNo Preview AvailableHeterogeneity of Osteosarcoma Cell Lines Led to Variable Responses in Reprogramming(IVYSPRING INT PUBL, 2014)Four osteosarcoma cell lines, Saos-2, MG-63, G-292 and U-2 OS, were reprogrammed to pluripotent state using Yamanaka factors retroviral transduction method. Embryonic stem cell (ESC)-like clusters started to appear between 15 to 20 days post transduction. Morphology of the colonies resembled that of ESC colonies with defined border and tightly-packed cells. The reprogrammed sarcomas expressed alkaline phosphatase and pluripotency markers, OCT4, SSEA4, TRA-1-60 and TRA-1-81, as in ESC up to Passage 15. All reprogrammed sarcomas could form embryoid body-like spheres when cultured in suspension in a low attachment dish for up to 10 days. Further testing on the directed differentiation capacity of the reprogrammed sarcomas showed all four reprogrammed sarcoma lines could differentiate into adipocytes while reprogrammed Saos-2-REP, MG-63-REP and G-292-REP could differentiate into osteocytes. Among the 4 osteosarcoma cell lines, U-2 OS reported the highest transduction efficiency but recorded the lowest reprogramming stability under long term culture. Thus, there may be intrinsic differences governing the variable responses of osteosarcoma cell lines towards reprogramming and long term culture effect of the reprogrammed cells. This is a first report to associate intrinsic factors in different osteosarcoma cell lines with variable reprogramming responses and effects on the reprogrammed cells after prolonged culture.
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ItemChondrogenesis of Infrapatellar Fat Pad Derived Adipose Stem Cells in 3D Printed Chitosan Scaffold(PUBLIC LIBRARY SCIENCE, 2014-06-11)Infrapatellar fat pad adipose stem cells (IPFP-ASCs) have been shown to harbor chondrogenic potential. When combined with 3D polymeric structures, the stem cells provide a source of stem cells to engineer 3D tissues for cartilage repair. In this study, we have shown human IPFP-ASCs seeded onto 3D printed chitosan scaffolds can undergo chondrogenesis using TGFβ3 and BMP6. By week 4, a pearlescent, cartilage-like matrix had formed that penetrated the top layers of the chitosan scaffold forming a 'cap' on the scaffold. Chondrocytic morphology showed typical cells encased in extracellular matrix which stained positively with toluidine blue. Immunohistochemistry demonstrated positive staining for collagen type II and cartilage proteoglycans, as well as collagen type I. Real time PCR analysis showed up-regulation of collagen type II, aggrecan and SOX9 genes when IPFP-ASCs were stimulated by TGFβ3 and BMP6. Thus, IPFP-ASCs can successfully undergo chondrogenesis using TGFβ3 and BMP6 and the cartilage-like tissue that forms on the surface of 3D-printed chitosan scaffold may prove useful as an osteochondral graft.
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ItemA phase Ib/II translational study of sunitinib with neoadjuvant radiotherapy in soft-tissue sarcoma(NATURE PUBLISHING GROUP, 2014-12-09)BACKGROUND: Preoperative radiotherapy (RT) is commonly used to treat localised soft-tissue sarcomas (STS). Hypoxia is an important determinant of radioresistance. Whether antiangiogenic therapy can 'normalise' tumour vasculature, thereby improving oxygenation, remains unknown. METHODS: Two cohorts were prospectively enrolled. Cohort A evaluated the implications of hypoxia in STS, using the hypoxic tracer (18)F-azomycin arabinoside (FAZA-PET). In cohort B, sunitinib was added to preoperative RT in a dose-finding phase 1b/2 design. RESULTS: In cohort A, 13 out of 23 tumours were hypoxic (FAZA-PET), correlating with metabolic activity (r(2)=0.85; P<0.001). Two-year progression-free (PFS) and overall (OS) survival were 61% (95% CI: 0.44-0.84) and 87% (95% CI: 0.74-1.00), respectively. Hypoxia was associated with radioresistance (P=0.012), higher local recurrence (Hazard ratio (HR): 10.2; P=0.02), PFS (HR: 8.4; P=0.02), and OS (HR: 41.4; P<0.04). In Cohort B, seven patients received sunitinib at dose level (DL): 0 (50 mg per day for 2 weeks before RT; 25 mg per day during RT) and two patients received DL: -1 (37.5 mg per day for entire period). Dose-limiting toxicities were observed in 4 out of 7 patients at DL 0 and 2 out of 2 patients at DL -1, resulting in premature study closure. Although there was no difference in PFS or OS, patients receiving sunitinib had higher local failure (HR: 8.1; P=0.004). CONCLUSION: In STS, hypoxia is associated with adverse outcomes. The combination of sunitinib with preoperative RT resulted in unacceptable toxicities, and higher local relapse rates.
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ItemBioactive Coatings for Orthopaedic Implants-Recent Trends in Development of Implant Coatings(MDPI AG, 2014-07)Joint replacement is a major orthopaedic procedure used to treat joint osteoarthritis. Aseptic loosening and infection are the two most significant causes of prosthetic implant failure. The ideal implant should be able to promote osteointegration, deter bacterial adhesion and minimize prosthetic infection. Recent developments in material science and cell biology have seen the development of new orthopaedic implant coatings to address these issues. Coatings consisting of bioceramics, extracellular matrix proteins, biological peptides or growth factors impart bioactivity and biocompatibility to the metallic surface of conventional orthopaedic prosthesis that promote bone ingrowth and differentiation of stem cells into osteoblasts leading to enhanced osteointegration of the implant. Furthermore, coatings such as silver, nitric oxide, antibiotics, antiseptics and antimicrobial peptides with anti-microbial properties have also been developed, which show promise in reducing bacterial adhesion and prosthetic infections. This review summarizes some of the recent developments in coatings for orthopaedic implants.
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ItemThe immediate post-operative radiograph is an unreliable measure of coronal plane alignment in total knee replacement(FRONTIERS MEDIA SA, 2014)BACKGROUND: Restoration of a neutral mechanical axis is a primary goal of total knee replacement (TKR). A mechanical axis within 3° of neutral has been correlated with improved implant longevity, function, and patient satisfaction. We hypothesize that the immediate post-operative radiograph is an unreliable method of measuring alignment following TKR surgery. METHODS: Seventy-five consecutive patients had supine X-rays performed on day two post-operatively followed by standing long-leg radiographs (LLRs) 6 weeks post-operatively. Correlation was sought between the mechanical axis measured on the LLR and surrogate markers of alignment on the post-operative X-ray including component alignment and an estimation of anatomical alignment using the available length of femoral and tibial shafts. Inter- and intra-observer reliabilities were assessed. RESULTS: The mean mechanical axis on the LLR was 180.5 (SD 3.0, range 175.1-187.1). Mean offset between anatomical axis and mechanical axis was 6.4°. The mean anatomical axis measured on the short-leg X-ray was 174.9 (SD 2.4, range 169.5-181.3). Mechanical axis on the LLR was compared to the anatomical axis measured on the short-leg radiograph (SLR) + 6° with an interclass correlation coefficient of 0.588 (p < 0.001). The level of disagreement between the short- and long-leg X-rays was assessed using the Bland-Altman method and demonstrated clinically important discrepancies of 5 or more degrees in 9% of cases. Inter- and intra-observer agreements were high on all measures (p < 0.001). CONCLUSION: The long-leg weight bearing X-ray is an essential tool to accurately assess coronal plane alignment post TKR. While the immediate post-operative X-ray taken supine provides useful information to the surgeon on any immediate complications, our results indicate that it cannot be relied upon to determine correct restoration of the mechanical axis.
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ItemThe effect of mindfulness training prior to total joint arthroplasty on post-operative pain and physical function: study protocol for a randomised controlled trial(BioMed Central, 2014-06-05)BACKGROUND: Osteoarthritis is a leading cause of disability in developed nations. In Australia it afflicts 16.5% of the adult population. Total joint arthroplasty is considered the treatment of choice for end stage osteoarthritis. The number of total joint arthroplasties undertaken in Australia has doubled over the last decade (more than 80,000 procedures in 2011). The incidence of pre-operative psychological distress in this group of patients is reported between 30% and 60% and pre-operative psychological distress is associated with poorer pain and functional outcomes after surgery. This study will use a mindfulness-based psychological intervention to enhance outcomes in people undergoing total joint arthroplasty and, in addition, will test hypotheses about coping with chronic illness in an aged population. This study is the first of its kind and will provide a greater understanding of the role of a mental health enhancement program on the physical recovery of total joint arthroplasty patients. METHODS/DESIGN: One hundred and fifty people with end-stage arthritis on the waiting list for total hip or knee arthroplasty will be recruited and randomly allocated to one of two groups using computer-generated block randomisation. A randomised controlled trial adhering to CONSORT guidelines will evaluate the efficacy of a mindfulness training program (weekly group-based classes in mindfulness practice, 2 ½ hours, for 8 weeks plus a 7-hour Saturday session in Week 6) prior to total joint arthroplasty, compared to a "standard care" group who will undergo routine total joint arthroplasty. Primary outcomes will be evaluated by a blinded examiner at baseline, 3 and 12 months post-surgery, using a validated self-reported pain and physical function scale. Secondary outcomes will include i) a range of validated measures of psychological wellbeing and ii) health economic analysis. All analyses will be conducted on an intention to treat basis using linear regression models. Health economic modelling will be applied to estimate the potential cost-effectiveness of mindfulness training and total joint arthroplasty.
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ItemNo Preview AvailableSelecting those to refer for joint replacement: Who will likely benefit and who will not?(ELSEVIER SCI LTD, 2014-02)Osteoarthritis (OA) is one of the 10 most disabling diseases in developed countries and worldwide estimates are that 10% of men and 18% of women aged over 60 years have symptomatic OA, including moderate and severe forms. Total joint replacement (TJR) is considered the most effective treatment for end-stage OA in those who have exhausted available conservative interventions. The demand for TJR is continually rising due to the ageing population; in the United States, more than 1 million TJRs were performed in 2010 and the number of procedures is projected to exceed 4 million in the US by 2030. It has been estimated that of all hip and knee replacements performed, approximately one quarter of the patients may be considered inappropriate candidates. Predicting who will benefit from TJR and who will not would seem critical in terms of containing the current and projected expenditure as well as improving satisfaction in TJR recipients. Few formal predictive tools are available to aid referring clinicians to determine those likely to be good or poor responders to surgery and current available tools tend to focus on disease severity alone with little consideration of risk factors that may predict a poor outcome or impede an effective response to surgery. This review examines the tools available to assist with assessing appropriateness for TJR; investigates the modifiable risk factors associated with poor outcome; and identifies areas for future research in selecting those appropriate for joint replacement.
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ItemOutcomes following large joint arthroplasty: does socio-economic status matter?(BIOMED CENTRAL LTD, 2014-05-06)BACKGROUND: We sought to determine whether socio-economic status (SES) is an independent predictor of outcome following total knee (TKR) and hip (THR) replacement in Australians. METHODS: In this prospective cohort study, we included patients undergoing TKR and THR in a public hospital in whom baseline and 12-month follow-up data were available. SES was determined using the Australian Bureau of Statistics 'Index of Relative Advantage and Disadvantage'. Other independent variables included patients' demographics, comorbidities and procedure-related variables. Outcome measures were the International Knee Society Score and Harris Hip Score pain and function subscales, and the Short Form Health Survey (SF-12) physical and mental component scores. RESULTS: Among 1,016 patients undergoing TKR and 835 patients undergoing THR, in multiple regression analysis, SES score was not independently associated with pain and functional outcomes. Female sex, older age, being a non-English speaker, higher body mass index and presence of comorbidities were associated with greater post-operative pain and poorer functional outcomes following arthroplasty. Better baseline function, physical and mental health, and lower baseline level of pain were associated with better outcomes at 12 months. In univariate analysis, for TKR, the improvement in SF-12 mental health score post arthroplasty was greater in patients of lower SES (3.8 ± 12.9 versus 1.5 ± 12.2, p=0.008), with a statistically significant inverse association between SES score and post-operative SF-12 mental health score in linear regression analysis (coefficient-0.28, 95% CI: -0.52 to -0.04, p=0.02). CONCLUSIONS: When adjustments are made for other covariates, SES is not an independent predictor of pain and functional outcome following large joint arthroplasty in Australian patients. However, relative to baseline, patients in lower socioeconomic groups are likely to have greater mental health benefits with TKR than more privileged patients. Large joint arthroplasty should be made accessible to patients of all SES.
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ItemAlcoholic Chlorhexidine or Alcoholic Iodine Skin Antisepsis (ACAISA): protocol for cluster randomised controlled trial of surgical skin preparation for the prevention of superficial wound complications in prosthetic hip and knee replacement surgery(BMJ PUBLISHING GROUP, 2014)INTRODUCTION: Wound complications following arthroplasty are associated with significant impact on the patient and healthcare system. Skin cleansing prior to surgical incision is a simple and effective method to prevent wound complications however, the question of which agent is superior for surgical skin antisepsis is unresolved. METHODS AND ANALYSIS: This cluster randomised controlled trial aims to compare the incidence of superficial wound complications in patients undergoing elective prosthetic hip or knee replacement surgery receiving surgical skin antisepsis with either: 0.5% chlorhexidine gluconate (CHG) in 70% alcohol or 10% povidone in 70% alcohol. The trial will be conducted at an Australian tertiary, university affiliated hospital over a 3-year period involving 750 participants. Participants will be drawn from the surgical waiting list. Consent for this study will be 'opt-out' consent. On a given day, all eligible participants will have skin preparation either with 0.5% chlorhexidine in 70% alcohol or 10% povidone iodine in 70% alcohol. The primary outcome is superficial wound complications (comprised of superficial incisional surgical site infections (SSI) and/or prolonged wound ooze) in the first 30 days following prosthetic joint replacement surgery. Secondary outcomes will include the incidence of wound complications according to the joint replaced, assessment of the causative agents of SSI and cost-effectiveness analysis. The primary analysis is an intention-to-treat analysis including all participants who undergo randomisation and will be performed at the individual level taking into account the clustering effect. ETHICS AND DISSEMINATION: The study design and protocol was reviewed and approved by the St Vincent's Hospital Human Research Ethics Committee (HREC-A 016/14 10/3/2014). Study findings will be disseminated in the printed media, and learned forums. A written lay summary will be available to study participants on request. TRIAL REGISTRATION NUMBER: The trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614000177651.
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ItemThe Grand Challenge Managing End-Staged Joint Osteoarthritis(FRONTIERS MEDIA SA, 2014)