Periprosthetic joint infection (PJI) is a potentially devastating complication of joint replacement surgery. Osteocytes comprise 90–95% of all cells in hard bone tissue, are long-lived and are becoming increasingly recognised as a critical cell type in the regulation of bone and systemic physiology. The purpose of this study was to examine role of these cells in PJI pathophysiology and aetiology, with the rationale that their involvement could contribute to the difficulty in detecting and clearing PJI. This study examined the ability of human osteocytes to become infected by Staphylococcus aureus and the responses of both the host cell and pathogen in this scenario.

Several S. aureus (MRSA) strains were tested for their ability to infect human primary osteocyte-like cells in vitro and human bone samples ex vivo. Bone biopsies were retrieved from patients undergoing revision total hip arthroplasty for either aseptic loosening associated with osteolysis, or for PJI. Retrieved bacterial colony number from cell lysates and colony morphology were determined. Gene expression was measured by microarray/bioinformatics analysis and/or real-time RT-PCR.

Exposure to planktonic S. aureus (approx. 100 CFU/cell) resulted in intracellular infection of human osteocyte-like cells. We found no evidence of increased rates of osteocyte cell death in bacteria exposed cultures. Microarray analysis of osteocyte gene expression 24h following exposure revealed more than 1,500 differentially expressed genes (fold-change more than 2, false discovery rate p < 0.01). The gene expression patterns were consistent with a strong innate immune response and altered functionality of the osteocytes. Consistent patterns of host gene expression were observed between experimentally infected osteocyte-like cultures and human bone, and in PJI patient bone samples. Internalised bacteria switched to the quasi-dormant small colony variant (SCV) form over a period of 5d, and the ensuing infection appeared to reach a stable state. S. aureus infection of viable osteocytes was also identified in bone taken from PJI patients.

We have demonstrated [1] that human osteocytes can become infected by S. aureus and respond robustly by producing immune mediators. The bony location of the infected osteocyte may render them refractory to clearance by immune cells, and osteocytes may therefore be an immune-privileged cell type. The phenotypic switch of S. aureus to SCV, a form less sensitive to most antibiotics and one associated with intracellular survival, suggests that infection of osteocytes may contribute to a chronic disease state. The osteocyte may therefore serve as a reservoir of bacteria for reinfection, perhaps explaining the high prevalence of infections that only become apparent after long periods of time or recur following surgical/medical treatment. Our findings also provide a biological rationale for the recognised need for aggressive bone debridement in the surgical management of PJI.

Introduction

To evaluate the clinical success and hip pain and function of patients with infected hip replacement treated by two-stage exchange using a temporary implant with high dose vancomycin added to the antibiotic cement at the first stage revision.

Introduction

There has been almost universal adoption of highly cross-linked polyethylene as the polyethylene of choice in metal-on-polyethylene articulations in total hip replacement (THR). Although wear of conventional polyethylene has been shown to be related to periprosthetic osteolysis, the relationship between wear of highly cross-linked polyethylene and osteolysis remains uncertain. Our aim was to determine the incidence and volume of periacetabular osteolysis at a minimum of seven years following primary THR with metal on highly cross-linked polyethylene articulations.

Patients with pelvic and acetabular fractures have a high risk of developing thromboembolic complications. Despite routine screening, the risk of PE remains high and may develop in patients with negative DVT screening. The search for a means to identify the patient ‘at risk’ has been elusive.

537 consecutive patients, referred to Royal Adelaide Hospital over a 20 year period for treatment of pelvic and acetabular fractures, were evaluated prospectively for pulmonary embolus (PE). 352 patients referred directly to the author were treated with variable dose heparin as prophylaxis to venous thromboembolic (VTE) disease. 184 patients primarily admitted under the general surgeons or to ITU, prior to referral to the author, were treated with fixed dose heparin or Enoxaparin. All patients were followed prospectively to determine the rate of pulmonary embolus. The heparin dosage requirements of those who developed pulmonary emboli were compared to those who did not. Patients were also identified for whom a clinical diagnosis of deep venous thrombosis (DVT) was made during the study and their heparin dosage requirements were determined.

7 of 352 patients treated with variable dose heparin developed PE (1.98%). 13 of 184 patients treated with fixed dose heparin, Enoxaparin, or combinations, developed PE (7.06%). An incidental finding of DVT was made in 36 patients. Of these, 10 patients (2.8%) were treated with variable dose heparin and 26 patients (14.1%) with fixed dose heparin or Enoxaparin.

The average Injury Severity Score was higher in patients treated with variable dose heparin than those treated with fixed dose regimes. Patients treated with variable dose heparin who developed PE showed a progressively increasing heparin requirement. The majority of patients who did not develop PE (72%) showed a progressively decreasing heparin requirement (suggesting reversal of a prothrombotic state). 21% showed an initial increasing heparin requirement followed by a decreasing requirement (suggesting a prothrombotic state that was reversed, e.g. a DVT successfully treated by the increasing heparin dose provided by a variable dose regime). 4% manifested a static heparin requirement (suggesting maintenance of a prothrombotic state). 8 patients treated with variable dose heparin developed DVT. 6/8 patients manifested a phase of progressively increasing heparin requirement, followed by a decreased requirement, and 2/8 patients manifested a sustained level of heparin requirement.

Patients with pelvic and acetabular fractures treated with variable dose heparin showed a rate of PE (1.98%). This is remarkably low compared with published rates of PE in such patients, and particularly compared with those patients treated only with chemoprophylaxis. The rate of PE was 3.5x higher and the rate of DVT was 5x higher in patients treated with fixed dose heparin or Enoxaparin. Patients who developed PE or DVT manifested an increasing heparin requirement. An increasing dosage of heparin may protect the ‘at risk’ patient from venous thromboembolism. Fixed dose unfractionated heparin/LMWH may be insufficient to treat the ‘at risk’ patient. An increasing heparin requirement may identify the patient ‘at risk’.

Patient controlled analgesia (PCA) is commonly used after TKR. Prolonged use of PCA may however have a negative impact on patients delaying their rehabilitation and therefore discharge. We aimed to evaluate the effect of the duration of PCA on the hospital length of stay (LOS) in patients who undergo TKR. We reviewed the casenotes of all patients who underwent a primary TKR in two South Australian teaching hospitals between 2006 and 2007. After excluding patients whose LOS was determined by placement issues and patients who developed intra-hospital post-operative complications, a number of 345 patients were included in this study. Data collected included: age, gender, ASA grade, regional blocks used, duration of postoperative PCA (< 24 hours, 24-48 hours, > 48 hours) and hospital LOS. Using SAS Version 9.2 statistical analysis software the data was analysed using univariate and multivariate Poisson regression models. Risk ratios, confidence intervals and P values were calculated.

Univariate regression models showed that there was a significant difference in length of stay between the three PCA groups (p < 0.0001). Post hoc tests revealed that the length of stay was longer in the 24 to 48 hours and > 48 hours groups compared to the < 24 hours group (p < 0.0001). There was also a significant difference in hospital LOS between males and females (p = 0.0049) with females expected to stay on average 9.7% longer (risk ratio = 1.097, 95% CI 1.028, 1.169). Patients in the ASA categories (1 and 2) recorded shorter lengths of stay than patients in the ASA categories (3 and 4) (p < 0.0001). Also patients treated at one hospital had longer LOS than the patients treated at the other hospital (risk ratio = 1.122, p = 0.0001). There was no evidence for a relationship between the patients' ages, and use or type of regional block used and the hospital LOS. Results from the multivariate regression models showed that each of the four variables found to influence LOS significantly, did so independent of the other variables. Therefore, duration of PCA, gender, ASA and hospital were all independent predictors of hospital LOS after primary TKR.

Longer administration of PCA, higher ASA grades and female gender are associated with longer hospital LOS after TKR. Reducing postoperative PCA, as well as improving ASA grading, could reduce LOS in these patients. A multimodal pain management strategy that shortens PCA use could reduce hospital LOS and costs after TKR.

The purpose of this paper is to review the early results of Prostalac system under licence from Therapeutic Goods Administration for Professor Howie in the management of two stage exchange hip arthroplasty for infection (restricted to Royal Adelaide Hospital) and the addition of vancomycin and teicoplanin powder to tobramycin cement without additional tobramycin.

Thirteen patients were treated for an infected THR with the Prostalac system. Preoperative and intra-operative cultures were taken to identify the infective organisms. Vancomycin 3 gm was added to the Prostalac cement mantle per 40 gm packet of antibiotic bone cement containing tobramycin 1 gm. Teicoplanin 2.4 gm was used in one case where the patient had a known vancomycin allergy. Postoperatively patients underwent six weeks of IV antibiotics followed by four to six weeks of oral.

A short term successful clinical outcome was determined by implantation of a total hip prosthesis at the time of second stage operation and no reoperations resulting from recurrent infection and off antibiotics for â□¥ 6 months with normal clinical and CRP lab values.

Thirteen patients received the Prostalac system. No patient was lost to follow-up. Nine have progressed to second stage revision, eight of which had femoral impaction grafting. Two deaths occurred not attributed to the Prostalac system. Three superficial wound infections and two required washout and debridement. One Prostalac stem subsidence. There has been no recurrence of deep joint infection. Retention of the second stage prosthesis has been 100% at 17 months.

The PROSTALAC system with the addition of vancomycin or teicoplanin to the tobramycin antibiotic cement has encouraging short-term results for treatment of deep joint infection. Complication rate has been well within the range reported in literature. Successful early outcomes are encouraging with all patients in the Prostalac study having retained their permanent hip prosthesis following second stage surgery.

This study aimed to compare the early clinical results and stem subsidence between three consecutive series of revision hip replacement cases with femoral impaction bone grafting to evaluate the effects of developments in technique. In the original series 1 (n=23), bone graft was irradiated at 25kG. I n series 2 (n=12) non-irradiated double washed graft and long stems were used as required.

In series 3 (n=21) modular tamps were used. Sensitive radiographic analysis techniques, EBRA and RSA, were used to measure stem subsidence. Major stem re-revision was required in five hips in series one, one hip in series two and no hips in series three. Two periprosthetic fractures occurred in series one. There was a statistically significant reduction in stem subsidence at the cement-bone interface at 12 months between series one and series two and three (p<0.05). In series three there was negligible stem subsidence at the cement-bone interface.

Technique developments in femoral impaction grafting, including the use of modular tamps designed to simply the procedure, yields excellent early clinical and radiographic results. Using RSA, we have shown that the fixation of the stems in bone is comparable to that achieved in primary hip replacement.