Chlorhexidine-alcohol versus iodine-alcohol for surgical site skin preparation in an elective arthroplasty (ACAISA) study: a cluster randomized controlled trial.

OBJECTIVES: Surgical site skin preparation is an effective method to prevent wound complications. The optimal agent has not been established, and guidelines contain conflicting recommendations. METHODS: The aim of alcoholic chlorhexidine or alcoholic iodine skin antisepsis (ACAISA) was to assess the efficacy of surgical site skin preparation with 0.5% chlorhexidine gluconate (w/v) in 70% ethanol (v/v) to 1% iodine (w/v) in 70% ethanol (v/v). This was a cluster randomized, controlled, single-centre, assessor-blinded, superiority trial in patients undergoing elective hip or knee arthroplasty. Each surgeon had a set operating day and the unit of randomization was the day of surgery. The primary outcome was superficial wound complication, defined as a composite endpoint of superficial incisional surgical site infection and/or clinically significant wound ooze in the 30 days following arthroplasty. The secondary outcome was any surgical site infection, including prosthetic joint infection. Outcome ascertainment was undertaken by an independent verification panel. The primary analysis was intention-to-treat, performed at the individual level. Taking into account the clustering effect, analysis of primary and secondary outcomes was undertaken at the level of the surgeon. RESULTS: A total of 780 participants were included; 390 participants were allocated chlorhexidine-alcohol and 390 participants were allocated iodine-alcohol. There was no difference in superficial wound complications: 19 (4.9%) versus 15 (3.8%) respectively (OR 1.28; 95%CI 0.62, 2.63; p 0.50). There was an increased odds of surgical site infection in the chlorhexidine-alcohol group compared to iodine-alcohol: 12 (3.1%) versus four (1.0%) respectively (OR 3.06; 95%CI 1.26, 7.46; p 0.014). The odds of prosthetic joint infection were also increased in the chlorhexidine-alcohol arm compared with iodine-alcohol: seven (1.8%) versus two (0.5%) respectively (OR 3.55; 95%CI 1.20, 10.44; p 0.022). CONCLUSIONS: No difference was observed in the primary outcome of superficial wound complications when chlorhexidine-alcohol and iodine-alcohol were compared. However, on a secondary analysis, iodine-alcohol had greater efficacy than chlorhexidine-alcohol for preventing surgical site infection. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614000177651.

Optimising the biocompatibility of 3D printed photopolymer constructs in vitro and in vivo.

3D printing is a rapid and accessible fabrication technology that engenders creative custom design solutions for cell scaffolds, perfusion systems and cell culture systems for tissue engineering. Critical to its success is the biocompatibility of the materials used, which should allow long-term tissue culture without affecting cell viability or inducing an inflammatory response for in vitro and in vivo applications. Polyjet 3D printers offer arguably the highest resolution with the fewest design constraints of any commercially available 3D printing systems. Although widely used for rapid-prototyping of medical devices and 3D anatomical modelling, polyjet printing has not been adopted by the tissue engineering field, largely due to the cytotoxicity of leachates from the printed parts. Biocompatibility in the context of cell culture is not commonly addressed for polyjet materials, as they tend to be optimised for their ability to fabricate complex structures. In order to study the potential issues surrounding the leaching of toxins, we prepared cell culture substrates using the commercially available MED610 photopolymer. The substrates were cleaned using either the manufacturer-specified 'biocompatible' washing procedures, or a novel protocol incorporating a sonication in isopropanol and water step. We then compared the effectiveness of these both in vitro and in vivo. Using primary mouse myoblast cultures, the manufacturer's protocol led to inconsistent and poorer cell viability when compared to the sonication protocol (p = 0.0002 at 48 h after indirect exposure). Subdermal implantation of MED610 into nude rats demonstrated a significant foreign body response with a greater number of giant cells (p = 0.0161) and foreign bodies (p = 0.0368) when compared to the sonication protocol, which was comparable to the control (sham) groups. These results present an improved, cytocompatible cleaning protocol of printable photopolymers to facilitate creative 3D-printed custom designs for cell culture systems for both in vitro and in vivo tissue engineering applications.

The impact of older age on patient outcomes following primary total knee arthroplasty.

AIMS: As the population ages, there is projected to be an increase in the level of demand for total knee arthroplasty (TKA) in octogenarians. We aimed to explore whether those aged ≥ 80 years achieved similar improvements in physical function to younger patients while also comparing the rates of length of stay (LOS), discharge to rehabilitation, postoperative complications, and mortality following TKA in older and younger patients. PATIENTS AND METHODS: Patients from one institution who underwent primary elective TKA between 1 January 2006 and 31 December 2014 were dichotomized into those ≥ 80 years old (n = 359) and those < 80 years old (n = 2479) for comparison. Multivariable regression was used to compare the physical status component of the 12-Item Short-Form Health Survey (SF-12), LOS, discharge to rehabilitation, complications, and mortality between the two groups. RESULTS: Both age groups demonstrated a clinically meaningful improvement in their self-reported physical health relative to their baseline with no clinically relevant difference noted between them. Being ≥ 80 years old was associated with a 0.58-day increase in LOS and older patients were more likely to be discharged to rehabilitation (odds ratio (OR) 3.06, p < 0.001). Medical complications and mortality were higher in elderly patients (OR 1.92 for complications, p < 0.001; hazard ratio 3.40 for death, p < 0.001). There was no statistically significant association between age group and experiencing a postoperative surgical or wound-related complication. CONCLUSION: Those aged over 80 years achieved a statistically significant lower median SF-12 physical score than the younger group, after adjusting for the preoperative score, but this difference of 4.46 was not considered to be clinically meaningful. However, clinicians should be aware that the elderly are at a higher risk of experiencing longer hospital stays, postoperative medical complications, and mortality. Cite this article: Bone Joint J 2018;100-B:1463-70.

Variations in pain and function before and after total knee arthroplasty: a comparison between Swedish and Australian cohorts.

OBJECTIVE: Preoperative pain and function is viewed as an important predictor of total knee arthroplasty (TKA) outcomes. We examined whether variations in pain and function outcomes existed at 12 months between two centres in Sweden and Australia, and whether this was explained by variations in patient presentation for TKA. METHODS: This was a retrospective analysis of prospectively collected data. Patients from one centre in Australia (St. Vincent's Hospital (SVH), N = 516) and in Sweden (Trelleborg (TBG), N = 899) who underwent primary TKA between 2012 and 2013. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was analysed pre- and 12 months' post TKA from which non-response to surgery was determined using the OMERACT-OARSI criteria. Multiple linear regression analysis was used to examine the relationship between change in pain and function and surgery centre, adjusting for preoperative patient characteristics and surgical technique. RESULTS: Despite worse preoperative outcomes in all subscales of the WOMAC for the SVH cohort, there were no clinically meaningful differences in 12-month WOMAC subscales nor change in WOMAC subscales between SVH and TBG. Almost identical proportions of patients were considered OMERACT-OARSI responders, 85.7% (SVH) and 85.9% (TBG), however for the SVH cohort 25 (4.9%) were moderate and 417 (80.8%) were high responders, compared to the TBG cohort of which 225 (25%) were moderate and 547 (60.9%) were high responders. CONCLUSION: Despite differences in preoperative presentation between 2 countries, improvements in pain and function and the proportion of individual who responded to TKA surgery at 1 year were similar. Factors related to poor response to TKA surgery require further elucidation.

Metastatic bone disease: A review of survival, prognostic factors and outcomes following surgical treatment of the appendicular skeleton.

Survival data and prognostic factors may help to provide insight when deciding on the appropriate orthopaedic treatment for patients presenting with metastatic bone disease. This review was conducted to look at the outcomes following orthopaedic surgery for metastatic lesions in the extremities. The literature was identified through the Medline and Embase database and further refined via a set of inclusion and exclusion criteria. Overall, patients presenting with metastatic bone disease from renal cell cancer or breast cancer had the longest survival rate. Important factors found to predict prognosis was the presence of visceral metastasis, multiple metastases, pathological fracture and the type of primary tumour involved. These prognostic factors may help to direct future inquiry into metastatic bone disease and help determine the type of surgery to use in a metastatic setting in order to avoid complications and unnecessary revisions as well as provide durability.

Diagnosing musculoskeletal tumours: How accurate is CT-guided core needle biopsy?

INTRODUCTION: Biopsy is a critical juncture in the diagnostic process for evaluating musculoskeletal tumours. The traditional diagnostic standard of open biopsy yields highly accurate diagnoses but associated with it is a significant rate of procedural complications. Imaging-guided needle biopsy is now being widely adopted as a competitive and minimally-invasive alternative with significantly lower complication rates. We assess its diagnostic outcomes at a tertiary referral centre in Melbourne, Australia. METHOD: Data pertaining to biopsy and surgical histology were retrieved from the musculoskeletal tumour database at St Vincent's Hospital, Fitzroy following approval from the Human Research Ethics Committee (HREC 091/13). Data analyses were performed in STATA 12 to assess diagnostic parameters and related outcomes. RESULTS: Bone tumours (n = 380) yielded accuracy of 80.8% with diagnostic error of 7.1% and undiagnostic rates of 12.1%. Soft-tissue tumours (n = 751) yielded accuracy of 83.2% with diagnostic error of 10.5% and undiagnostic rates of 6.3%. Biopsy of benign tumours (n = 648, accuracy = 85.3%, error = 5.9%, undiagnostic 8.8%) was more accurate than malignant tumours (n = 501, accuracy = 75.8%, error 14.0%, undiagnostic 7.4%). The overall procedural complication rate was 0.7%. DISCUSSION: CT-guided core needle biopsy is a safe, accurate, and highly effective procedure that obviates the need for open and surgical biopsy in a significant number of cases. When combined with fusion imaging, CT guidance is an accurate method of targeting specific regions of interest.

Latent Class Growth Analysis predicts long term pain and function trajectories in total knee arthroplasty: a study of 689 patients.

OBJECTIVE: To characterize groups of subjects according to their trajectory of knee pain and function over 1 to 5 years post total knee arthroplasty (TKA). METHODS: Patients from one centre who underwent primary TKA (N = 689) between 2006 and 2008. The Knee Society Score (KSS) was collected pre-operatively and annually post-operatively. Latent Class Growth Analysis (LCGA) was used to classify groups of subjects according to their trajectory of knee pain and function over 1-5 years post-surgery. RESULTS: LCGA identified a class of patients with persistent moderate knee pain (22.0%). Predictors (OR, 95% CI) of moderate pain trajectory class membership were pre-surgery SF12 mental component summary (MCS) per 10 points (0.65, 0.54-0.79) and physical component summary (PCS) per 10 points (0.50, 0.33-0.76), Charlson Comorbidity Index (CCI) one (1.70, 1.07-2.69) and ≥two (2.82, 1.59-4.81) and the absence of computer-navigation (2.26, 1.09-4.68). LCGA also identified a class of patients with poor function (23.0%). Predictors of low function trajectory class membership were, female sex (3.31, 1.95-5.63), advancing age per 10 years (2.27, 1.69-3.02), pre-surgery PCS per 10 points (0.50, 0.33-0.74), obesity (1.69, 1.05-2.72), morbid obesity (3.12, 1.55-6.27) and CCI ≥two (2.50, 1.41-4.42). CONCLUSIONS: Modifiable predictors of poor response to TKA included baseline co-morbidity, physical and mental well-being and obesity. This provides useful information for clinicians in terms of informing patients of the expected course of longer term outcomes of TKA and for developing prediction algorithms that identify patients in whom there is a high likelihood of poor surgical response.

Direct hospital cost determinants following hip and knee arthroplasty.

OBJECTIVE: Total joint arthroplasty (TJA) places a significant economic burden on health care resources. This cohort study examines the costs associated with arthroplasty in 827 patients undergoing hip and knee TJA from January 2011 to June 2012 at a single center in Melbourne, Australia. METHODS: Data included total inpatient, outpatient, and readmissions costs in the 30 days following TJA. Factors associated with cost were modeled using negative binomial regression and extrapolated to the Australian population. RESULTS: The base cost (i.e., the cost for a patient with no modifying factors) over the first 30 days following TJA was $13,060 Australian (AU) (interquartile range $12,126-14,067 AU). The median length of stay was 4 days (range 2-33 days) and 35 patients (4%) were readmitted in the first 30 days following index TJA, the majority of whom had a surgical site infection (SSI) (74%). The following factors were independently associated with increased costs: SSI, preoperative warfarin therapy, American Society of Anesthesiologists score of 3 or 4, hip TJA, increasing operation time, increasing postoperative blood transfusion requirements, other nosocomial infections, postoperative venous thromboembolism (VTE), pressure ulcers, postoperative confusion, and acute urinary retention. Based on data from the present study, the cost of TJA in Australia is estimated to exceed $1 billion AU per year. Preventable postoperative complications were major cost drivers: SSI and VTE added a further $97 million AU and $66 million AU, respectively, to arthroplasty costs in the first 30 days following surgery. CONCLUSION: This unique study has identified important factors influencing TJA costs and providing guidance for future research and resource allocation.

A phase Ib/II translational study of sunitinib with neoadjuvant radiotherapy in soft-tissue sarcoma.

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.

Alcoholic 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.

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.

Factors influencing the cost of prosthetic joint infection treatment.

BACKGROUND: Prosthetic joint infection (PJI) is associated with significant costs to the healthcare system. Current literature examines the cost of specific treatment modalities without assessing other cost drivers for PJI. AIMS: To examine the overall cost of the treatment of PJI and to identify factors associated with management costs. METHODS: The costs of treatment of prosthetic joint infections were examined in 139 patients across 10 hospitals over a 3-year period (January 2006 to December 2008). Cost calculations included hospitalization costs, surgical costs, hospital-in-the-home costs and antibiotic therapy costs. Negative binomial regression analysis was performed to model factors associated with total cost. FINDINGS: The median cost of treating prosthetic joint infection per patient was Australian $34,800 (interquartile range: 20,305, 56,929). The following factors were associated with increased treatment costs: septic revision arthroplasty (67% increase in treatment cost; P = 0.02), hypotension at presentation (70% increase; P = 0.03), polymicrobial infections (41% increase; P = 0.009), surgical treatment with one-stage exchange (100% increase; P = 0.002) or resection arthroplasty (48% increase; P = 0.001) were independently associated with increased treatment costs. Culture-negative prosthetic joint infections were associated with decreased costs (29% decrease in treatment cost; P = 0.047). Treatment failure was associated with 156% increase in treatment costs. CONCLUSIONS: This study identifies clinically important factors influencing treatment costs that may be of relevance to policy-makers, particularly in the setting of hospital reimbursement and guiding future research into cost-effective preventive strategies.

Cost analysis of debridement and retention for management of prosthetic joint infection.

Prosthetic joint infection remains one of the most devastating complications of arthroplasty. Debridement and retention of the prosthesis is an attractive management option in carefully selected patients. Despite this, there are no data investigating the cost of this management modality for prosthetic joint infections. The aim of this case-control study was to calculate the cost associated with debridement and retention for management of prosthetic joint infection compared with primary joint replacement surgery without prosthetic joint infection. From 1 January 2008 to 30 June 2010, there were 21 prosthetic joint infections matched to 42 control patients. Controls were matched to cases according to the arthroplasty site, age and sex. Cases had a greater number of unplanned readmissions (100% vs. 7.1%; p <0.001), more additional surgery (3.3 vs. 0.07; p <0.001) and longer total bed days (31.6 vs. 7.9 days; p <0.001). In addition they had more inpatient, outpatient and emergency department visits (p <0.001, respectively). For patients with prosthetic joint infection the total cost, including index operation and costs of management of the prosthetic joint infection, was 3.1 times the cost of primary arthoplasty; the mean cost for cases was Australian dollars (AUD) $69,414 (±29,869) compared with $22,085 (±8147) (p <0.001). The demand for arthroplasty continues to grow and with that, the number of prosthetic joint infections will also increase, placing significant burden on the health system. Our study adds significantly to the growing body of evidence highlighting the substantial costs associated with prosthetic joint infection.

Outcome of debridement and retention in prosthetic joint infections by methicillin-resistant staphylococci, with special reference to rifampin and fusidic acid combination therapy.

The management of prosthetic joint infections remains a clinical challenge, particularly infections due to methicillin-resistant staphylococci. Previously, this infection was considered a contraindication to debridement and retention strategies. This retrospective cohort study examined the treatment and outcomes of patients with arthroplasty infection by methicillin-resistant staphylococci managed by debridement and retention in conjunction with rifampin-fusidic acid combination therapy. Over an 11-year period, there were 43 patients with infection by methicillin-resistant staphylococci managed with debridement and retention. This consisted of close-interval repeated arthrotomies with pulsatile lavage. Rifampin was combined with fusidic acid for the majority of patients (88%). Patients were monitored for a median of 33.5 months (interquartile range, 20 to 54 months). Overall, 9 patients experienced treatment failure, with 12- and 24-month estimates of infection-free survival of 86% (95% confidence interval [CI], 71 to 93%) and 77% (95% CI, 60 to 87%), respectively. The following factors were associated with treatment failure: methicillin-resistant Staphylococcus aureus (MRSA) arthroplasty infection, a single surgical debridement or ≥4 debridements, and the receipt of less than 90 days of antibiotic therapy. Patients with infection by methicillin-resistant coagulase-negative staphylococci (MR-CNS) were less likely to fail treatment. The overall treatment success rate reported in this study is comparable to those of other treatment modalities for prosthetic joint infections by methicillin-resistant staphylococci. Therefore, the debridement and retention of the prosthesis and rifampin-based antibiotic therapy are a valid treatment option for carefully selected patients.

Early onset prosthetic hip and knee joint infection: treatment and outcomes in Victoria, Australia.

BACKGROUND: Prosthetic joint infection (PJI) remains a devastating complication of arthroplasty. There are no internationally endorsed consensus management guidelines and treatment approaches differ widely. AIM: The aim of this multicentre study was to examine treatment approaches and predictors of treatment failure in patients with early PJI managed in hospitals in Victoria, Australia. METHODS: This cohort study was conducted across 10 hospitals over a three-year period (January 2006 to December 2008) and involved 147 patients who presented with early PJI. FINDINGS: Most patients (76%) were managed with debridement and retention of the prosthesis. Patients were followed for a median 20 months (interquartile range: 7-36). Overall 43 patients experienced treatment failure with a 12-month infection-free survival estimate of 76% [95% confidence interval (CI): 68-83%]. The following factors were associated with treatment failure: septic revision arthroplasty (hazard ratio: 7.5; 95% CI: 2.4-23.1; P < 0.0001), hypotension at presentation (4.9; 1.5-15.7; P = 0.007), one-stage exchange (3.1; 1.0-9.2; P = 0.048), total duration of antibiotic therapy <90 days: specifically <30 days (18.5; 5.4-63.1; P < 0.001), 30-60 days (8.0; 2.6-23.9; P < 0.001) and 60-90 days (7.3; 2.2-24.4; P = 0.001), respectively. Effective empiric antibiotic therapy was associated with a decreased risk of treatment failure (0.20; 0.09-0.47; P < 0.001). CONCLUSIONS: The management approach in Australia differs from that used elsewhere in the world. We have identified a number of clinically relevant risk factors for treatment failure that may impact on treatment recommendations.

Associations between pre-operative radiographic changes and outcomes after total knee joint replacement for osteoarthritis.

OBJECTIVE: To assess the influence of pre-operative X-ray changes on the response to total knee joint replacement (TKR). METHODS: We included patients from one centre who underwent primary TKR (n = 478) for osteoarthritis in 2006 and 2007. The International Knee Society score (IKSS) and short form health survey were collected pre-operatively and at 1 and 2 years after surgery. Pre-operative radiographs were read to assess Kellgren and Lawrence (K-L) grading, individual radiographic features using the OARSI atlas, and subchondral bone attrition using the Ahlbach method. The main independent variable was a modified (K-L) grade. The outcome variables were the IKSS pain and function scores. Covariates included demographic features, co-morbidities, baseline pain and function, prosthesis type, and the use of patella resurfacing. Multivariable linear regression models were created to assess the relationships between pre-operative X-ray findings and pain and function outcomes. RESULTS: On average, pain and function improved greatly following surgery. However, pain relief was unsatisfactory in about 30%, and functional improvement suboptimal in about 50%. OR (95% CI) for ongoing moderate-severe pain at 12 months for modified K-L grades; <3: 5.39 (1.23-15.69), 3a: 2.62 (1.21-5.67), 3b: 1.81 (1.00-3.26), 4a: 2.06 (1.05-4.05) when compared to 4b. OR (95% CI) for poor function at 12 months were; 3a: 2.81 (1.23-6.39) and 4a: 2.45 (1.22-4.91), when compared to 4b. CONCLUSIONS: Patients with more severe radiographic knee damage at the time of surgery are most likely to have substantial gains in terms of both pain relief and improved function as a result of a TKR.

Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model.

BACKGROUND: Pigment epithelium-derived factor (PEDF) is an endogenous glycoprotein with a potential role as a therapeutic for osteosarcoma. Animal studies have demonstrated the biological effects of PEDF on osteosarcoma; however, these results are difficult to extrapolate for human use due to the chosen study design and drug delivery methods. METHODS: In this study we have attempted to replicate the human presentation and treatment of osteosarcoma using a murine orthotopic model of osteosarcoma. The effects of PEDF on osteosarcoma cell lines were evaluated in vitro prior to animal experimentation. Orthotopic tumours were induced by intra-tibial injection of SaOS-2 osteosarcoma cells. Treatment with PEDF was delayed until after the macroscopic appearance of primary tumours. Pigment epithelium-derived factor was administered systemically via an implanted intraperitoneal micro-osmotic pump. RESULTS: In vitro, PEDF inhibited proliferation, induced apoptosis and inhibited cell cycling of osteosarcoma cells. Pigment epithelium-derived factor promoted adhesion to Collagen I and inhibited invasion through Collagen I. In vivo, treatment with PEDF caused a reduction in both primary tumour volume and burden of pulmonary metastases. Systemic administration of PEDF did not cause toxic effects on normal tissues. CONCLUSION: Systemically delivered PEDF is effective in suppressing the size of primary and secondary tumours in an orthotopic murine model of osteosarcoma.

Joint line position correlates with function after primary total knee replacement: a randomised controlled trial comparing conventional and computer-assisted surgery.

The role of computer-assisted surgery in maintaining the level of the joint in primary knee joint replacement (TKR) has not been well defined. We undertook a blinded randomised controlled trial comparing joint-line maintenance, functional outcomes, and quality-of-life outcomes between patients undergoing computer-assisted and conventional TKR. A total of 115 patients were randomised (computer-assisted, n = 55; conventional, n = 60). Two years post-operatively no significant correlation was found between computer-assisted and conventional surgery in terms of maintaining the joint line. Those TKRs where the joint line was depressed post-operatively improved the least in terms of functional scores. No difference was detected in terms of quality-of-life outcomes. Change in joint line was found to be related to change in alignment. Change in alignment significantly affects change in joint line and functional scores.

Risk factors for prosthetic hip and knee infections according to arthroplasty site.

Prosthetic joint infection is a devastating complication of arthroplasty. Previous epidemiological studies have assessed factors associated with arthroplasty infections but have not assessed the impact of comorbidity on infection at different arthroplasty locations. We used a case-control design to investigate risk factors for prosthetic joint infection with reference to the anatomical site. During an eight-year period at a single hospital, 63 patients developed a prosthetic joint infection (36 hips, 27 knees). Cases of prosthetic hip or knee joint infection were matched 1:2 to controls. The results suggest that factors associated with arthroplasty infections differ with anatomical location. Following knee arthroplasty, wound discharge was associated with an increased risk of prosthetic joint infection whereas the presence of a drain tube reduced the risk. By contrast, increased body mass index, increased drain tube loss and superficial incisional surgical site infections (SSIs) were associated with prosthetic hip infection. When analysed as a combined cohort, systemic steroid use, increased SSI drain tube losses, wound discharge, and superficial incisional SSIs were predictors of infection.

Gram-negative prosthetic joint infection treated with debridement, prosthesis retention and antibiotic regimens including a fluoroquinolone.

Information is required about treatment outcomes of Gram-negative prosthetic joint infections treated with prosthesis retention and surgical debridement, especially where biofilm-active antibiotics such as fluoroquinolones are used. The outcome of 17 consecutive patients with an early Gram-negative prosthetic joint infection who had been treated with prosthesis retention and surgical debridement was analysed. Enterobacteriaceae were isolated in 16 patients and infections were mixed with other organisms in 13 (76%) patients. The median joint age was 17 days and the median duration of symptoms before debridement was 7 days. All patients initially received intravenous ß-lactam antibiotic therapy and 14 patients were then treated with oral ciprofloxacin. Treatment failure occurred in two patients over a median period of follow-up of 28 months. In only one patient was a relapsed Gram-negative infection responsible for the failure and this patient had not been treated with ciprofloxacin. The 2-year survival rate free of treatment failure was 94% (95% CI, 63-99%). Prosthesis retention with surgical debridement, in combination with antibiotic regimens including ciprofloxacin, was effective and should be considered for patients with early Gram-negative prosthetic joint infection.