Aims. Patients receiving cemented hemiarthroplasties after hip fracture have a significant risk of deep surgical site infection (SSI). Standard UK practice to minimize the risk of SSI includes the use of antibiotic-loaded bone cement with no consensus regarding type, dose, or antibiotic content of the cement. This is the protocol for a randomized clinical trial to investigate the clinical and cost-effectiveness of high dose dual antibiotic-loaded cement in comparison to low dose single antibiotic-loaded cement in patients 60 years and over receiving a cemented hemiarthroplasty for an intracapsular hip fracture. Methods. The WHiTE 8 Copal Or Palacos Antibiotic Loaded bone cement trial (WHiTE 8 COPAL) is a multicentre, multi-surgeon, parallel, two-arm, randomized clinical trial. The pragmatic study will be embedded in the World Hip Trauma Evaluation (WHiTE) (ISRCTN 63982700). Participants, including those that lack capacity, will be allocated on a 1:1 basis stratified by recruitment centre to either a low dose single antibiotic-loaded bone cement or a high dose dual antibiotic-loaded bone cement. The primary analysis will compare the differences in deep SSI rate as defined by the Centers for Disease Control and Prevention within 90 days of surgery via medical record review and patient self-reported questionnaires. Secondary outcomes include UK Core Outcome Set for hip fractures, complications, rate of antibiotic prescription, resistance patterns of deep SSI, and resource use (more specifically, cost-effectiveness) up to four months post-randomization. A minimum of 4,920 patients will be recruited to obtain 90% power to detect an absolute difference of 1.5% in the rate of deep SSI at 90 days for the expected 3% deep SSI rate in the control group. Conclusion. The results of this trial will provide evidence regarding clinical and cost-effectiveness between low dose single and high dose dual antibiotic-loaded bone cement, which will inform policy and practice guidelines such as the National Institute for Health and Care Excellence guidance on management of hip fractures. Cite this article: Bone Jt Open 2021;2(2):72–78

Background. We switched our antibiotic prophylaxis for elective hip and knee surgery from cefuroxime to flucloxacillin with single dose gentamicin in order to reduce the incidence of C. Diff diarrhoea. More patients subsequently appeared to develop acute kidney injury (AKI). Methods. During a twelve month period we examined the incidence of AKI sequentially in 198 patients undergoing elective hip or knee surgery: cefuroxime (n = 48); high dose flucloxacillin (median 8g) (n = 52); low dose flucloxacillin (median 4g) (n = 46); and cefuroxime again (n = 52). Results. There were no statistically significant differences between the four groups by chi-square tests for age, gender, nature of operation (hip or knee surgery), American Society of Anaesthesia (ASA) grade, mode of anaesthesia (spinal ± general anaesthetic v GA), baseline serum creatinine, pre-operative co-morbidity (hypertension, diabetes), pre-operative medication (NSAIDs, ACEI/ARBs or betablockers) and post-operative hypotension. Patients receiving high dose flucloxacillin required more vasopressors during surgery (p = 0.02 by Kruskal-Wallis test). The proportion of patients in each antibiotic group with any form of AKI by RIFLE criteria was: first cefuroxime group (8%), high dose flucloxacillin (52%), low dose flucloxacillin (22%), second cefuroxime (14%) (p < 0.0001). Odds ratios (OR) for AKI derived from a multivariate logistic regression model and arbitrarily assigning an OR of 1 to first cefuroxime group, were: high dose flucloxacillin 14.5 (95% CI, 4.2–49.7); low dose flucloxacillin 3.0(0.8–10.8); cefuroxime again 2.0(0.5–7.7). Three patients required temporary haemodialysis. Biopsies in two of these showed acute tubulo-interstitial nephritis. All three patients belonged to the high dose flucloxacillin group. None of the patients developed C Diff diarrhoea. Summary. We have shown a strong association between high dose flucloxacillin with single dose gentamicin prophylaxis and subsequent development of AKI which was not confounded by any of the co-variates we measured

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’

Aims. Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella. Methods. For the haematogenous infection, G. mellonella larvae were implanted with a Kirschner wire (K-wire), infected with S. aureus, and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with S. aureus suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses. Results. In the haematogenous infection, a single combined dose of phages and gentamicin, and repetitive injections with gentamicin or in combination with phages, resulted in significantly improved survival rates. In the early-stage biofilm infection, only repetitive combined administration of phages and gentamicin led to a significantly increased survival. Additionally, a significant reduction in number of bacteria was observed in the larvae after receiving repetitive doses of phages and/or gentamicin in both infection models. Conclusion. Based on our results, a single dose of the combination of phages and gentamicin is sufficient to prevent a haematogenous S. aureus implant-related infection, whereas gentamicin needs to be administered daily for the same effect. To treat early-stage S. aureus implant-related infection, repetitive doses of the combination of phages and gentamicin are required. Cite this article: Bone Joint Res 2024;13(8):383–391

Antibiotic prophylaxis aims to reduce wound and prosthetic infection, with minimal adverse effects. The 3 dose Cefuroxime regime is widely used, despite the risk of infective diarrhoea. We describe the results of single dose intraoperative Gentamicin and Amoxicillin compared to this standard regime. We retrospectively reviewed 220 patients following hip hemiarthroplasty, creating 2 demographically matched cohorts; Group 1: 3 doses of Cefuroxime (n=113) and Group 2: single dose Gentamicin and Amoxicillin (n=107). End points were evidence of infection, length of stay and Clostridium difficile (CD) rates. results showed a significant reduction in group 2 for average length of stay (17 Vs. 13 days p=0.0432) and CD rates (7/113 Vs 0/107 p=0.0158). Considering antibiotic therapies administered; significant reductions in group 2 for the number of patients that required post-operative antibiotics (99/113 Vs 73/107 p=0.0005), the median antibiotic DDDs (Defined Daily Doses) in 1st 2 post-operative days (0.25 Vs 0 p=0.0000) and those that received Ciprofloxacin or Cefuroxime post-operatively (82/113 Vs 24/107 p=0.0000). No significant difference was found for median antibiotic DDDs, median antibiotic DDDs from 2nd post-operative day, patients that received Flucloxacillin post-operatively. Measured microbiological outcomes showed a significant reduction in the number of patients with confirmed growth requiring treatment with antibiotics in group 2 (21/23 Vs 12/22 p=0.0053). No difference was found between number patients with operation site swabbed and those with confirmed microbial growth. We demonstrate single dose Gentamicin and Amoxicillin significantly reduces length of stay, CD rates and the number of patients requiring post-operative antibiotics for wound infection, inferring a reduction in the rate of wound infection. We would recommend this as an effective alternative to the 3 dose Cefuroxime regime

Introduction. The vast majority of orthopaedic surgeons use C-arm fluoroscopy in the operating theatre when building a circular external fixator. In the absence of previous research in this area, we hypothesised that the surgeon who builds a circular external fixator is exposed to a greater amount of radiation purely as a result of the presence of the metallic fixator in the x-ray beam. The aim of our study therefore was to investigate how the presence of a circular external fixator affects the radiation dose to the surgeon and the surgical assistant. Materials & Methods. A simulated environment was created using a radiolucent operating table, an acrylic lower limb phantom (below knee segment), various configurations of metalic circular external fixation, and a standard size C-arm image intensifier. The variables investigated were 1. the amount of metal in the beam 2. the orientation of the beam (PA vertical vs lateral) 3. the horizonal distance of the person from the beam (surgeon vs assistant) and 4. the vertical distance of the various body parts from the beam (e.g. thyroid, groin). In terms of radiation dose, we recorded two things : 1. the dose produced by the image intensifier 2. the dose rate at standardised positions in the operating theatre. The latter was done using a solid-state survey sensor. These positions represented both where the surgeon and surgical assistant typically stand plus the heights of their various body regions relative to the operating table. Results. The effect of the presence of the circular external fixator : all frame constructs tested resulted in a statistically significant greater radiation dose both produced by the image intensifier and received by the surgical team. The effect of the beam orientation : the PA (vertical) orientation resulted in a statistically significant greater radiation dose for the surgeon than did the lateral orientation, but made no difference for the assistant. The effect of horizontal distance from the beam : unsurprisingly, the surgeon (who was closer to the beam) received a statistically significant greater radiation dose than the assistant. The effect of vertical distance from the beam : for the surgeon, the dose received was highest at the level of the phantom leg / frame, whilst for the assistant there was no statistically significant difference for any level. Conclusions. To our knowledge, this is the first study investigating the radiation dose rate to the orthopaedic surgeon when building a circular external fixator. We found that the surgeon does indeed receive a ‘double whammy’ because the image intensifier puts out a greater amount of radiation plus the metalic frame scatters more of the x-ray beam. Whilst the amounts are relatively small, we think that it's important to quantify doses that orthopaedic surgeons receive to ensure optimal radiation practices

As patients live longer following treatment for soft tissue sarcomas, complications from treatment will continue to emerge. Predicting which patients are at risk allows for improved preoperative planning, treatment, and surveillance. The data presented here suggests that females greater than fifty-five years of age treated with high dose, postoperative radiotherapy in combination with limb salvage surgery for soft tissue sarcomas are at an increased risk of post irradiation fractures. Unlike previous reports, a significantly higher rate of fracture occurred in patients who received higher doses (60 or 66Gy) of radiation versus lower doses (50 Gy). This retrospective study was performed to determine if the timing and dosage of radiotherapy are related to the risk of post radiation pathologic fracture following combined therapy for lower extremity soft tissue sarcomas. Three hundred sixty-four patients with sarcomas treated with external beam radiation therapy and limb salvage surgery were evaluated. High dose radiation was defined as 60 Gy or 66 Gy; low dose as 50Gy. Radiation timing schedules were preoperative, postoperative, or preoperative with a postoperative boost. Univariate and multivariate analysis was used to determine which factors were associated with fracture risk. Twenty- seven pathologic fractures occurred in twenty-three patients. Twenty- four fractures occurred in twenty patients who were treated with high dose radiation. Sixteen of these patients had postoperative radiation (fourteen patients received 66Gy, two received 60Gy), and four had pre-operative radiation with a postoperative boost (total dose = 66Gy). Three fractures occurred in three patients who received low dose preoperative radiation (50Gy). Both high dose radiation (versus low dose) (p=.001) and preoperative radiation (versus postoperative) (p =0.002) were associated with a risk of fracture. Findings in this study were consistent with previous reports in that females over fifty-five years of age who undergo removal of a thigh sarcoma combined with radiation therapy are at a higher risk of a pathologic fracture, and differs in that there was a significantly higher rate of fracture in patients who received higher doses (60 or 66Gy) of radiation versus lower doses (50 Gy), and when radiation therapy was given postoperatively versus preoperatively

Objectives. We have increased the dose of tranexamic acid (TXA) in our enhanced total joint recovery protocol at our institution from 15 mg/kg to 30 mg/kg (maximum 2.5 g) as a single, intravenous (IV) dose. We report the clinical effect of this dosage change. Methods. We retrospectively compared two cohorts of consecutive patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) surgery in our unit between 2008 and 2013. One group received IV TXA 15 mg/kg, maximum 1.2 g, and the other 30 mg/kg, maximum 2.5 g as a single pre-operative dose. The primary outcome for this study was the requirement for blood transfusion within 30 days of surgery. Secondary measures included length of hospital stay, critical care requirements, re-admission rate, medical complications and mortality rates. Results. A total of 1914 THA and 2537 TKA procedures were evaluated. In THA, the higher dose of TXA was associated with a significant reduction in transfusion (p = 0.02, risk ratio (RR) 0.74, 95% confidence interval (CI) 0.58 to 0.96) and rate of re-admission (p < 0.001, RR 0.50, 95% CI 0.35 to 0.71). There were reductions in the requirement for critical care (p = 0.06, RR 0.55, 95% CI 0.31 to 1.00), and in the length of stay from 4.7 to 4.3 days (p = 0.02). In TKA, transfusion requirements (p = 0.049, RR 0.64, 95% CI 0.41 to 0.99), re-admission rate (p = 0.001, RR 0.56, 95% CI 0.39 to 0.80) and critical care requirements (p < 0.003, RR 0.34, 95% CI 0.16 to 0.72) were reduced with the higher dose. Mean length of stay reduced from 4.6 days to 3.6 days (p < 0.01). There was no difference in the incidence of deep vein thrombosis, pulmonary embolism, gastrointestinal bleed, myocardial infarction, stroke or death in THA and TKA between cohorts. Conclusion. We suggest that a single pre-operative dose of TXA, 30 mg/kg, maximum 2.5g, results in a lower transfusion requirement compared with a lower dose in patients undergoing elective primary hip and knee arthroplasty. However, these findings should be interpreted in the context of the retrospective non-randomised study design. Cite this article: R. J. M. Morrison, B. Tsang, W. Fishley, I. Harper, J. C. Joseph, M. R. Reed. Dose optimisation of intravenous tranexamic acid for elective hip and knee arthroplasty: The effectiveness of a single pre-operative dose. Bone Joint Res 2017;6:499–505. DOI: 10.1302/2046-3758.68.BJR-2017-0005.R1

Background. Bone Morphogenetic Protein (BMP) has been used in clinical practice to stimulate fracture healing and spinal arthrodesis. Difficulty in localising and maintaining BMP at the target site has resulted in the use of large doses of BMP, and has been associated with significant adverse effects. We have previously shown clay hydrogels can bind growth factors for localised efficacy. We hypothesised that localisation of BMP within clay gels would reduce the dose required to mediate bone formation. Methods. 2×10-4mg and 1×10-5 mg BMP were mixed in Laponite and applied to collagen sponge. 3 sponges containing high dose, and 3 containing low dose BMP were implanted subcutaneously in a mouse. This process was repeated in 8 mice, for controls, alginate hydrogel was used in a further 8 mice, and 1 mouse received 6 blank collagen scaffolds. Micro Computed Tomography was used to assess bone formation fortnightly; at 8 weeks the mice were culled and underwent histological analysis. Results. Mean Bone Volume formed within collagen per μg BMP was significantly greater with Laponite and low dose BMP compared to Alginate and Laponite with high dose BMP (p<0.0001). No bone formation was observed with Alginate and low dose BMP. Conclusions. We have demonstrated that Laponite is able to reduce, by several orders, the effective dose of BMP required to mediate ectopic bone formation compared to current gold standard methods of BMP delivery. Clinical translation of this finding offers, potentially, great significance to orthopaedic surgery. Level of Evidence. In vivo study. Approval. Our study received ethical approval complied with Home Office licensing. Acknowledgments. Funded by grants from EU(FP7) Biodesign, Rosetrees Trust, BBSRC and EPSRC

Introduction. Immunomodulation represents a novel strategy to improve bone healing in combination with low doses of bone morphogenetic growth factors like BMP-2. This study aims to investigate the effect and timing of monoclonal anti-IL-1ß antibody administration with 1μg BMP-2 on bone healing over 14 weeks in a rat femur segmental defect model. Method. 2 mm femoral defects were created in 22-27 weeks-old female Fischer F344 rats, internally fixed with a plate (animal license: GR/19/2022) using established protocols for analgesia and anesthesia. Animals (n=4/group) received either a collagen sponge, a collagen sponge+1μg BMP-2 (InductOs, Medtronic) or a collagen sponge+1μg BMP-2 with a monoclonal anti-IL-1ß antibody (BioXCell, 10 mg/ml), administered intravenously under anesthesia every third day until day 15, from day 0 or 3. In vivo micro-CT was performed after surgery and at 2, 3, 4, 6, 8, 10 and 14-weeks post-OP. Mechanical properties of the operated femurs were assessed by 4-point bending (Instron5866) and compared to contralateral femurs (one-way ANOVA, GraphPad Prism8). Histopathological analysis was performed semi-quantitatively on Giemsa-Eosin-stained sections (Olympus BX63) using a six-grade severity grading scale. Result. Operated femurs with BMP-2 reached an average stiffness of 91±37% of contralateral femurs, femurs in IL-1ß groups 105±11% (day 0) and 111±12% (day 3). Administration of anti-IL-1ß+1μg BMP-2 led to faster cortical bridging (3/4 femurs bridged by week 4 for day 0, 4/4 for day 3) than 1μg BMP-2 alone (0/4 by week 4). Micro-CT results confirmed histopathological evaluation, as collagen sponge alone led to non-union, complete bicortical bridging was observed for 3/4 femurs in the BMP-2 group and for 4/4 femurs in the IL-1β groups after 14 weeks. Conclusion. Anti-IL-1ß had a beneficial effect on late fracture healing with faster cortical bridging and new bone formation than 1μg BMP-2 alone. Acknowledgments. AO foundation. We thank Andrea Furter, Alisa Hangartner and Thomas Krüger for technical support

Background. Recent literature points out the potential interest of standing and sitting X-rays for the evaluation of THA patients. The accuracy of the anterior pelvic plane measures is questionable due to the variations in the quality of lateral standing and sitting X-rays. The EOS® (EOS imaging, Paris, France) is an innovative slot-scanning radiograph system allowing the acquisition of radiograph images while the patient is in weightbearing position with less irradiation than standard imagers. This study reports the “functionnal” positions of a 150 THA cohort, including the lateral orientation of the cups. Methods. The following parameters were measured: sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI) and anterior pelvic plane (APP) sagittal inclination (ASI), frontal inclination (AFI) and planar anteversion (ANT). Irradiation doses were calculated in standing and sitting acquisitions. Variations of sagittal orientation of the cup were measured on lateral standing and sitting images. Descriptive and multivariate analysis were performed for the different parameters studied. Results. The mean doses for full body were 0,80 mGy ± 0,13 for standing position and 0,94 mGy ± 0,25 for sitting position. The mean value for PI was 55,8° ± 11,4. The mean values standing position were 39,01° ± 9,9 for SS, 17,23° ± 10,2 for PT, and 0,74° ± 8,4 for APP. The mean values were 46,36° ± 9,8 for AFI, 39,49° ± 15,1 for ASI and 22,09° ± 11,1 for ANT. In sitting position, the mean values were 20,87° ± 10,2 for SS, 35,37° ± 13,1 for PT and 21,13° ± 11,2 for APP. The mean values were 56,41° ± 12,3 for AFI, 51,71° ± 14,7 for ASI and 33,45° ± 12,9 for ANT. Conclusions and Clinical Relevance. Unexpected variations of the anterior pelvic plane can be observed as well as the influence of pelvic incidence on pelvic orientation. The EOS® imaging system provides new informations regarding the pelvis functionnal anatomy in THA patients with potential applications for the study of unstable cases and wear phenomenons

This study aims to investigate that a single dose of tranexamic acid (TXA) will reduce blood loss and transfusion rates in elderly patients, undergoing intertrochanteric (IT) or femoral neck fractures surgery. Consecutive elderly patients receiving hip fracture surgery for stable or unstable IT fracture, treated with short intramedullary nail (IMN) insertion as well as cemented hemiarthroplasty for acute femoral neck (subcapital) hip fracture, were screened for inclusion in this single-centre randomized trial. Patients were randomly allocated to a study group by sealed envelope. One TXA dose of 15 mg/kg i.v. diluted in 100 ml N/S or one placebo dose i.v. in 100 ml N/S were administered 5 mins before the skin cut. Haemoglobin (Hb) concentration was measured at admission time and prior to surgery. Post-operatively it was measured on a daily basis until day 4, giving a total of four Hb measurements (days 1 to 4). The transfusion trigger point was determined in accordance with the French guidelines for erythrocyte blood transfusion. The transfusion trigger was 10 g/dl for patients at risk, while in all other cases, it was 9 g/dl. Information regarding the transfusions number was assessed directly by the hospital blood bank database. Blood loss was calculated by the Hb dilution method. Nadler's formula was used to calculate patients' blood volume. For calculation of total blood loss (TBL) expressed to total Hb loss and total Volume loss, the number of transfusions (55 grams of Hb per transfusion), the Hb concentration on preoperatively (Hgbi) and the Hb concentration on the last measure (Hgbe) were used. (Hb balance method). The primary efficacy outcome was the number of transfusions of allogeneic RBC from surgery up to day 4. The secondary ones were the total blood loss from surgery to day 4 as it was calculated by Hb-balance method. After randomization, 35 patients with femoral neck fracture and 30 patients with IT fracture received TXA prior to surgery. Respectively, 30 patients with femoral neck fracture and 55 with IT fracture didn't receive TXA. The groups did not differ significantly in their basic demographics (age, gender, BMI, injury mechanism, ASA score, co-morbidities). Results showed that patients undergoing hemiarthroplasty after receiving TXA, were transfused with less allogeneic RBC and had less total blood loss than patients that didn't receive TXA, but without statistical significance. While patients treated with IMN in the TXA group received a significantly lower number of RBC units than the control group (1.28 ± 1.049 vs 2.075 ± 1.685), (P = 0.0396), had a significantly lower loss of Hb (98.59 ± 55.24 vs 161.6 ± 141.7), (P = 0.0195) and a lower total blood volume loss (951.3 ± 598.9 ml vs 1513 ± 1247 ml), (P = 0.023). This trial confirmed TXA administration efficacy in reducing blood loss and transfusion rate in elderly patients undergoing hip fracture surgery. A TXA single dose may be a safer option, taking into account these patients' physiological status and co-morbidities

Aim: To assess the infection rate following Lower Limb Arthroplasty using single dose gentamicin antibiotic prophylaxis compared to a traditional three doses of cephalosporin. Material and Methods: All patients undergoing Total Hip and Knee joint replacements over 6 months (October 2007 to March 2008) at 3 participating hospitals were prospectively followed up to assess perioperative infection rates. Joint replacements were defined as having infection by the UK Health Protection Agency Surgical Site Surveillance criteria. All patients received single dose antibiotic prophylaxis using intravenous Gentamicin 4.5mg/kg body weight adjusted for body mass index. This group of patients were compared with previous data collected over a 6 month period (Jan to Mar 2007 and Oct to Dec 2005) from the same hospitals for infection rates in Lower Limb Arthroplasty using 3 doses of Cefuroxime 750mg as antibiotic prophylaxis. Results: 408 patients underwent Total Hip Replacements (THR) and 458 patients underwent Total Knee Replacements (TKR) during the study period. This was compared with 414 patients who underwent THR and 421 patients who underwent TKR during a 6 month period over 2 years. Surgical site infection was detected in 9 THRs (2.2%) and 2 TKRs (0.44%) in the study group as compared to infection in 13 THRs (3.1%) and 12 TKRs (2.9%) in the control group. Using the Fisher Exact test the infection rates in THRs were not significantly different between the 2 groups (p value – 0.52) but the infection rates were significantly reduced in the study group for TKRs (p value – 0.005). There were no complications with the use of Gentamicin as antibiotic prophylaxis. Cefuroxime is known to promote Clostridium difficile infection and was removed from the hospital pharmacy to help meet a UK government targets to reduce the incidence. The rate of Clostridium difficile infection was reduced within the hospital with the use of single dose antibiotic prophylaxis although other measures to reduce its incidence were also introduced. Conclusions: This study shows that the use of single dose antibiotic prophylaxis using Gentamicin is effective for elective Lower Limb Arthroplasty. This is recommended for routine use in all elective joint replacements as it is safe, effective and easy to administer

Aim: To assess the infection rate following Primary Lower Limb Arthroplasty using single dose gentamicin antibiotic prophylaxis compared to a traditional three doses of cephalosporin. Material And Methods: All patients undergoing primary Total Hip and Knee joint replacements over 6 months (October 2007 to March 2008) at 3 participating hospitals were prospectively followed up to assess perioperative infection rates. Joint replacements were defined as having infection by the UK Health Protection Agency Surgical Site Surveillance (SSI) criteria. All patients received single dose antibiotic prophylaxis using intravenous Gentamicin 4.5mg/kg body weight adjusted for body mass index. This group of patients were compared with previous data collected over a 6 month period (Jan to Mar 2007 and Oct to Dec 2005) from the same hospitals for infection rates in Lower Limb Arthroplasty using 3 doses of Cefuroxime 750mg as antibiotic prophylaxis. Return to theatre data was collected independently after introduction of gentamicin to compare with previous data. Results: 408 patients underwent Total Hip Replacements (THR) and 458 patients underwent Total Knee Replacements (TKR) during the study period. This was compared with 414 patients who underwent THR and 421 patients who underwent TKR during a 6 month period over 2 years. Surgical site infection was detected in 9 THRs (2.2%) and 2 TKRs (0.44%) in the study group as compared to infection in 13 THRs (3.1%) and 12 TKRs (2.9%) in the control group. Using the Fisher Exact test the infection rates in THRs were not significantly different between the 2 groups (p value – 0.52) but the infection rates were significantly reduced in the study group for TKRs (p value – 0.005). There were no complications with the use of Gentamicin as antibiotic prophylaxis. The return to theatre was 2.42% (28/1157) after introduction of Gentamicin as compared with 1.85% (37/2005) [p value – 0.172] before this. This was a cause for concern, although not a significant difference. Cefuroxime is known to promote Clostridium difficile infection and was removed from the hospital pharmacy to help meet a UK government targets to reduce the incidence. The rate of Clostridium difficile infection was reduced within the hospital with the use of single dose antibiotic prophylaxis although other measures to reduce its incidence were also introduced. Conclusions: This study shows that the use of single dose antibiotic prophylaxis using Gentamicin is effective in preventing SSI as defined in the HPA definition. It is safe to use and reduces rate of Clostridium difficile associated diarrhoea. However, be wary of increased rate of return to theatre following use of gentamicin. Further period of evaluation and study is needed before it is recommended for routine use in present or modified form

Purpose: To assess the infection rate following Lower Limb Arthroplasty using single dose gentamicin antibiotic prophylaxis compared to a traditional three doses of cephalosporin. Method: All patients undergoing Total Hip and Knee replacements over six months (October 2007 to March 2008) at three participating hospitals were prospectively followed to assess perioperative infection rates using Surgical Site Surveillance(SSI) criteria. All patients received single dose antibiotic prophylaxis using intravenous Gentamicin 4.5mg/kg. This was compared with previous data collected over a 6 month period (Jan to Mar 2007 and Oct to Dec 2005) from the same hospitals using 3 doses of Cefuroxime 750mg. Return to theatre data was collected independently after introduction of gentamicin to compare with previous data. The change in creatinine level postoperatively was also measured in a selected group of patients. Results: Four hundred and eight patients underwent Total Hip Replacements (THR) and 458 patients Total Knee Replacements (TKR) during the study period. This was compared with 414 and 421 patients who underwent THRs and TKRs respectively during a previous six month period. SSI was detected in 9 THRs(2.2%) and 2 TKRs(0.44%) in the study group as compared to 13 THRs(3.1%) and 12 TKRs(2.9%) in the control group. The infection rates in THRs were not significantly different between the 2 groups(p value−0.52) but were significantly reduced in the study group for TKRs(p value−0.005). The rate of Clostridium difficile infection was reduced within the hospital with the use of gentamicin, although other measures to reduce its incidence were also introduced. The return to theatre was 1.64%(23/1402) after introduction of Gentamicin as compared with 1.05%(21/2005) [p value−0.092] before this. This was a cause for concern although not significant. The day1 postoperative creatinine level increased by more than 30 units in 6% of patients on Gentamicin. Conclusion: This study shows that the use of single dose prophylaxis using Gentamicin is effective for Lower Limb Arthroplasty. However, be wary of increased rate of return to theatre and the rise in creatinine level following use of gentamicin. Further period of evaluation and study is needed before it is recommended for routine use in present or modified form

Study design. Retrospective study. Objectives. To optimise the radiation doses and image quality for the cone-beam O-arm surgical imaging system in spinal surgery. Summary of Background. Neurovascular compromise has been reported following screw misplacement during thoracic pedicle screw insertion. The use of O-arm with or without navigation system during spinal surgery has been shown to lower the rate of screw misplacement. The main drawback of such imaging surgical systems is the high radiation exposure. Methods. Chest phantom and cadaveric pig spine were examined on the O-arm with different scan settings: two were recommended by the O-arm manufacturer (120 kV/320 mAs, and 120 kV/128 mAs), and three low-dose settings (80 kV/80 mAs, 80 kV/40 mAs, and 60 kV/40 mAs). The radiation doses were estimated by Monte Carlo calculations. Objective evaluation of image quality included interobserver agreement in the measurement of pedicular width in chest phantom and assessment of screw placement in cadaveric pig spine. Results. The effective dose/cm for 120 kV/320 mAs-scan was 13, 26, and 69 times higher than those delivered with 80 kV/80 mAs, 80 kV/40 mAs, and 60 kV/40 mAs-scans, respectively. Images with 60 kV/40 mAs were unreliable. Images with 80 kV/80 mAs were considered reliable with good interobserver agreement when measuring the pedicular width (random error 0.38 mm and intraclass correlation coefficient 0.979) and almost perfect agreement when evaluating the screw placement (κ-value 0.86). Conclusions. The radiation doses of the O-arm system can be reduced 5–13 times without negative impact on image quality with regard to information required for spinal surgery

Purpose: Multiple studies have demonstrated the efficacy of Tranexamic Acid (TA) in reducing blood loss and red blood cell transfusion in patients undergoing primary total hip (THA) or knee (TKA) arthroplasty. However, the dosing schedules of either an initial bolus followed by a 6–12 hour infusion or multiple intravenous bolus doses are not ‘user-friendly’ for regular application. The purpose of this study was to assess the efficacy and acceptance of a single dose protocol for the use of TA in primary THA or TKA. Method: We selected a single dosing schedule of 20mg/kg TA given either prior to skin incision for THA or approximately ten minutes prior to tourniquet release for TKA. The hospital pharmacy supplied the TA rounded off to the nearest 5kg/100mg in a 100ml mini-bag. In March 2008, we introduced the routine use of TA to all patients undergoing primary THA or TKA at our institution. Mini-bags were pre-ordered at the time of the preoperative clinic visit and delivered to the pre-surgical preparation area on day of surgery. One month after implementation of this protocol we compared blood loss, transfusion rates, and hemoglobin at discharge between the patients operated on from April 1 to June 30, 2007 (when this protocol was not in place) to those from April 1 to June 30, 2008. No other routine patient care practices were altered during this time period. Results: We found a significant reduction in the decrease in hemoglobin from 2007 compared to 2008 for both THA and TKA (46g/L to 39g/L, and 45g/L to 36g/L, respectively), which led to both a reduction in transfusion rates (13.5% to 3.6%, and 13.1% to 2.0%, respectively) and higher hemoglobin levels at discharge. All patients received the TA as ordered. Conclusion: Dosing and timing of TA is critical to maximize its antifibrinolytic effect. Our weight increment dose protocol led to minimal dose variability, facilitated pharmacy drug preparation, and minimized wastage. This simple ‘user-friendly’ protocol was found to reduce the decrease in hemoglobin and transfusion rates, demonstrating similar efficacy to other more complex dosing schedules. This protocol was well received and accepted by surgeons, anesthesiologists, pharmacy, and nursing staff

Purpose. Developmental exposure to estrogens has been shown to affect a number of organ systems, including long and short bones. Epigenetic effects of DES exposure have been shown to affect the third generation of progeny. Furthermore, recent studies have shown that environmental exposure to estrogen-like compounds is much higher than originally anticipated. This study aims to discover the effect of in utero exposure to a well-known estrogen agonist, diethylstilbestrol (DES), on lumbar bone, intervertebral disc (IVD), and articular cartilage. Femoral bone was studied to determine the specificity of the effect. Method. C57bl/6n pregnant mice were dosed orally with vehicle (peanut oil) or 0.1, 1.0 and 10 g/kg/day of DES on gestational days 11–14. Male and female pups were allowed to mature without further treatment until 3 months of age, at which point they were divided into swim and sedentary groups. After sacrifice, bone mineral density (BMD), bone mineral content (BMC), bone area (BA), and trabecular bone area (TBA) of the lumbar vertebrae and femur were measured using a PIXImus Bone Densitometer System (GE Medical Systems). Glycosaminoglycan (GAG) content (proteoglycan) was measured by the DMMB assay. Histological analysis of proteoglycan was performed with Safranin O staining. Intervertebral disc height was measured using NDP software (Leeds, UK). Statistical analysis was performed using analysis of variance (ANOVA) followed by Fisher's Protected Least Significant Difference (PLSD). A p-value of < 0.05 was considered statistically significant. Results. At all the doses studied, DES had no significant effect on lumbar and femoral BMD in both males and females. The lumbar BMC, however, was significantly increased in female swims at both the highest and lowest dose of DES, while the femoral BMC was only increased at the highest. The males, on the other hand, showed a decreased BMC at the highest dose of DES for both lumbar and femoral bone. Female swim group had an increased BA at the highest dose of DES while the male swims showed a decreased BA for femoral bone. The TBA showed a similar pattern. GAG analysis of lumbar IVDs showed a decrease at the lowest doses but a significant increase at the highest doses for both swim and sedentary groups. Histology showed morphological changes of the IVD and articular cartilage for all doses of DES. Conclusion. The effect of in utero DES exposure is more important on lumbar than on femoral bone. The effect was mainly observed at high dose of DES, except for BA that is also affected by low dose DES in lumbar bones. Results suggest that environmental estrogen contaminants might impact developmental lumbar bone growth and mineralization in mice. Further studies measuring the impact of environmental estrogen mimics, such as bisphenol A, are then warranted

Summary Statement. An autologous thrombin activated 3-fold PRP, mixed with a biphasic calcium phosphate at a 1mL:1cc ratio, is beneficial for early bone healing in older age sheep. Introduction. The management of bone defects continues to present challenges. Upon activation, platelets secrete an array of growth factors that contribute to bone regeneration. Therefore, combining platelet rich plasma (PRP) with bone graft substitutes has the potential to reduce or replace the reliance on autograft. The simple, autologous nature of PRP has encouraged its use. However, this enthusiasm has failed to consistently translate to clinical expediency. Lack of standardisation and improper use may contribute to the conflicting outcomes reported within both pre-clinical and clinical investigations. This study investigates the potential of PRP for bone augmentation in an older age sheep model. Specifically, PRP dose is controlled to provide clearer indications for its clinical use. Methods. Eighty 11mm diameter defects of 20mm in depth were created in the cancellous bone within the epiphyseal region of the medial proximal tibia and distal femur of twenty five-year-old sheep. The defects were treated with three doses of an autologous thrombin activated PRP combined with a biphasic calcium phosphate (BCP). Activated platelet poor plasma (PPP) and the BCP alone provided reference groups, while the autograft and empty defects served as controls. All animals were sacrificed at four weeks post-operatively for radiographic assessment, micro-computed tomography quantification, histological assessment, histomorphometric quantification of new bone area and bone ingrowth, and weekly fluorochrome bone label quantification. TGF-β1 concentrations were quantified using enzyme-linked immunosorbent assays. Results. The PRP had a 2.9-fold (0.4) increase in platelet concentration, a 0.57-fold (0.09) decrease in leukocytes, and a 0.65-fold (0.11) decrease in fibrinogen. After activation, the PRP had an 8.9-fold (1.5) increase in TGF-β1 serum concentration above baseline. Eleven (11) mm diameter cancellous bone defects in the hind legs of five-year-old sheep do not spontaneously heal within four weeks. PRP dose had a significant effect on the radiographic grade. The highest dose of PRP treatment had a significantly greater micro-CT BV/TV over the BCP alone (PRP: 30.6±1.8%; BCP: 24.5±0.1%). All doses of PRP treatment were significantly greater than the BCP alone for both the histomorphometric new bone area (PRP: 14.5±1.3%; BCP: 9.7±1.5%) and bone ingrowth depth (PRP: 2288±210µm; BCP:1151±268µm). From week two onwards, PRP had a significant effect on the weekly bone ingrowth over BCP, however, autograft had the greatest amount of fluorescently labelled bone within the first three weeks. PRP has a significant effect on the shape and density of osteoblasts within the central region of the defect compared to the BCP alone, however, was not significantly different to autograft. TGF-β1 appeared a better predictor of healing outcomes than platelet concentration, however both had relatively weak correlations (r<.324). Conclusion. PRP induces new bone formation with a dose dependant response at four weeks when used with a biphasic calcium phosphate in older age sheep

With the dramatic improvement of conservative surgery in patients with bone sarcoma, infection becomes 1 of the most devastating complication, leading frequently to amputation. The aim of this monocentric study is to precise the influence of spacer loaded with high doses of vancomycin on late Results: PATIENTS From 1984 to 2007, we operated more than 600 patients (p)with bone sarcoma. Age of p. was 4,5 to 82 years (mean 25 y). Histology was osteosarcoma (304), Ewing (142), chondrosarcomas (148), fibrosarcomas or MFH (23), giant cell tumours in others. In 484 cases, p received chemotherapy, and radiotherapy in 50 cases. The mean follow-up from tumour removal is 15 years. 57 p suffered of deep infection of the material used to reconstruct the skeletal defect. We have seen also 3 p for recurrence of deep infection initially treated elsewhere. Altogether, we treated 60 patients for deep infections. Methods: 26 p had debridment and cleaning of the pros-thesis and long adapted antibiotherapy as first treatment. When ineffective (23/26), a removal of the prosthesis was performed with immediate replacing the new prosthesis in 19 cases. When infection recurred (16/19) and in all other patients the treatment included a two stages protocol with interposition of a spacer with antibiotic loaded cement during 4 to12 weeks. Until 2004, the spacer was made with gentamycin containing palacos mixed with conventional doses of antibiotics adapted to the germ. From 2004/6 we used high doses of vancomycin (4 g per batch of 40 g) with an average total dose of 11g of vancomycin per spacer. The new prosthesis was placed in a later time, when infection, cutaneous and muscular problems were solved. Results: At the last control, 15 were amputated, following a mean of 6 ineffective procedures. 45 p. benefited from conservation surgery but a new prosthesis could be inserted only in 43, following a mean of 3.2 surgical procedures, Analysis shows the bad prognostic value of initial radiotherapy, of distal locations, and of insufficient muscular coverage and the better efficacy of high dose antibiotics in spacer. Up to date, none of the high dose antibiotic loaded spacers was followed by amputation. Conclusion: Infection of massive prostheses is the most serious orthopaedic complication of limb salvage. Treatment must be preventive, avoiding any radiotherapy. Good prognostic factors are early removal of the prosthesis, effective antibiotherapy, improvement of the muscular coverage, and use of spacers with high dose vancomycin