Introduction. Major trauma during military conflicts involve heavily contaminated open fractures. Staphylococcus aureus (S. aureus) commonly causes infection within a protective biofilm. Lactoferrin (Lf), a natural milk glycoprotein, chelates iron and releases bacteria from biofilms, complimenting antibiotics. This research developed a periprosthetic biofilm infection model in rodents to test an Lf based lavage/sustained local release formulation embedded in Stimulin beads. Method. Surgery was performed on adult rats and received systemic Flucloxacillin (Flu). The craniomedial tibia was exposed, drilled, then inoculated with S. aureus biofilm. A metal pin was placed within the medullary cavity and treatments conducted. Lf in lavage solutions: The defect was subject to 2× 50 mL lavage with 4 treatment groups (saline only, Lf only, Bactisure with Lf, Bactisure with saline). Lf embedded in Stimulin beads: 4 bead types were introduced (Stimulin only, Lf only, Flu only, Lf with Flu). At day 7, rats are processed for bioluminescent and X-ray imaging, and tibial explants/pins collected for bacterial enumeration (CFU). Results. Rats without treatments established a mean infection of 2×106 CFU/tibia. 4 treatment groups with a day 0, one-off lavage demonstrated >95% reduction in bacterial load 7 days post-op, with a reduction in CFU from 1×106/tibia down to 1×104/tibia. There was no statistically significant difference between each group (p = 0.55 with one way ANOVA). The stimulin bead experiments are ongoing and complete results will be obtained in the end of July. Conclusions. This research demonstrated a clinically relevant animal model of implanted metalware that establishes infection. No additional benefit was observed with a one-off, adjuvant Lf lavage during the initial decontamination of the surgical wound, compared with saline alone, and in combination with the antiseptic Bactisure. This animal model provides the foundation for future antibiofilm therapies

Introduction. Management of open fractures is challenging and requires a multidisciplinary team approach. Gustilo Anderson Type IIIB fractures reportedly have a higher infection rate (up to 52%) and up to 16% amputation rate. This study aims to evaluate outcomes of using Adjuvant Local Antibiotic Hydroxyapatite Bio-Composite in management of Open Gustilo-Anderson IIIB fractures. Materials and Methods. We reviewed a prospective data of 80 patients who presented with Gustilo Anderson Type IIIB Open Fracture to a single ortho-plastic centre. Only patients who were managed with single-stage “Fix and Flap” along with intra-operative Adjuvant Local Antibiotic Bio-Composite were included. Results. Mean follow-up time was 22 months. The mean time from injury until definitive surgery was 7.73 days (1–30 days). Primary union achieved in 88.3% within 32 weeks on average. The delayed union reported in 7.8% of patients, for the bone healing stimulated by injecting the fracture site with Autologous Bone Marrow Aspirate Concentrate. Subsequent follow-up showed signs of successful fracture healing at 60 weeks post-injury. Three patients (3.9%) had non-union. Limb salvage rate was 96.25%, and only 1.25% deep infection rate. Conclusions. Our results highlight that low infection rates, high limb salvage rates and high union rates can be achieved in these complex injuries with a combined OrthoPlastic approach, MDT input, meticulous technique and the use of adjuvant local antibiotic bio-composite. Delay in definitive surgery, gentamicin resistance and smoking were not associated with any increased deep infection or non-union in our series. At 22 months of follow-up, deep infection rate was 1.25%, limbs salvage rate was 96.25%, fracture union rate was 96.1%, and reoperation rate 18.75%

Introduction. Sacro-coccygeal chordomas pose a difficult diagnostic and therapeutic problem due to late presentation, large size, soft-tisue extension, difficulties in obtaining adequate resection margins, higher local recurrence rate and uncertain effectiveness of adjuvant treatment. We present a series of 21 patients of sacral chordomas obtained from Scottish Bone Tumour Registry to analyse predictors of local control and survival. Patients and methods. The clinical and morphologic features, type of treatment and follow-up of 21 consecutive patients with sacral chordoma were retrospectively reviewed and analysed. Results. The average age at time of the biopsy was 59 years (range, 12 to 82 years): twelve patients were male and nine were female. Pain was the presenting symptom in all patients. Two had intralesional (both recurred), 9 marginal (4 recurred) and 3 wide resections (1 recurred). Fifteen of the twenty-one patients were treated with adjuvant radiation therapy. In seven patients, the chordoma was inoperable and all but one were treated with adjuvant radiotherapy. Local recurrence and metastases occurred in 7 (50%) and 5 (23.8%) patients. The 5-year and 10-year survival were 38% and 14.2%, respectively. Conclusion. Excision of the lesion combined with adjuvant radiation therapy provided satisfactory results. Local recurrence presents a major problem in the management of sacral chordomas (50%). Intralesional resection should be avoided as it is associated with 100% local recurrence in our series

Aim. The objective of this systematic review is to evaluate the current evidence for or against this up-and-coming treatment modality. Method. A comprehensive literature search in accordance with the Preferred Reporting Items for Systematic review and Meta-analysis (PRISMA) guidelines was conducted using PubMed, Embase, MEDLINE and Cochrane databases. Exclusion criteria included patients < 18 years of age, follow-up <11 months, and a score < 6 on the National Institute of Health quality assessment tool. Results. 15 articles, encompassing 631 PJIs in 626 patients, were included in the final analysis, all level IV case series. The quality of many studies was impeded by a retrospective design (14/15), a relative small study population (10 out of 15 studies had less than 50 patients), selection bias, and remarkable heterogeneity in terms of catheter type, antibiotic type, dose and duration of IA antibiotics and techniques of surgical revision. 347 were chronic infections, 66 acute infections and 218 unknown. The majority was treated with single-stage revision with adjuvant IA antibiotic infusion (499/631, 79.1%). The remaining PJIs were treated with stand-alone IA antibiotic infusion (77/631, 12.2%), DAIR with adjuvant IA antibiotic infusion (36/631, 5.7%) or two-stage revision with adjuvant IA antibiotic infusion (19/631, 3.0%). Mean duration of IA antibiotic infusion was 19 days (range 3–50), although most patients received a combination of both IA and systemic (IV or PO) antibiotics. An overall failure rate (defined as failures of infection eradication/total PJIs) of approximately 11% was found. The use of IA antibiotic infusion as a stand-alone treatment was associated with a higher failure rate. In total 117 complications occurred in 631 cases (18.5%). Of these, 71 were non-catheter-related (60.7%) and 46 were catheter-related (39.3%). The most common catheter-related complications were premature loss of the catheter (18/46), developing a fistula (5/46), and elevated blood urea nitrogen (BUN) and creatinine levels (12/46). Conclusions. Due to the lack of comparative studies the (added) benefit of IA antibiotic infusion in the treatment of PJI remains uncertain. From a theoretical point of view it seems likely that is should not be used as a stand-alone treatment. A prospective randomized controlled trial using a well-described infusion protocol is needed to see if the potential benefits justify the increased costs, labour and catheter-related complications of this treatment modality

Diffuse-type Tenosynovial Giant-Cell Tumour (d-TGCT) of large joints is a rare, locally aggressive, soft tissue tumour affecting predominantly the knee. Previously classified as Pigmented Villonodular Synovitis (PVNS), this monoarticular disease arises from the synovial lining and is more common in younger adults. Given the diffuse and aggressive nature of this tumour, local control is often difficult and recurrence rates are high. Current literature is comprised primarily of small, and a few larger but heterogeneous, observational studies. Both arthroscopic and open synovectomy techniques, or combinations thereof, have been described for the treatment of d-TGCT of the knee. There is, however, no consensus on the best approach to minimize recurrence of d-TGCT of the knee. Some limited evidence would suggest that a staged, open anterior and posterior synovectomy might be of benefit in reducing recurrence. To our knowledge, no case series has specifically looked at the recurrence rate of d-TGCT of the knee following a staged, open, posterior and anterior approach. We hypothesized that this approach may provide better recurrence rates as suggested by larger more heterogeneous series. A retrospective review of the local pathology database was performed to identify all cases of d-TGCT or PVNS of the knee treated surgically at our institution over the past 15 years. All cases were treated by a single fellowship-trained orthopaedic oncology surgeon, using a consistent, staged, open, posterior and anterior approach for synovectomy. All cases were confirmed by histopathology and followed-up with regular repeat MRI to monitor for recurrence. Medical records of these patients were reviewed to extract demographic information, as well as outcomes data, specifically recurrence rate and complications. Any adjuvant treatments or subsequent surgical interventions were noted. Twenty-three patients with a minimum follow-up of two years were identified. Mean age was 36.3 at the time of treatment. There were 10 females and 13 males. Mean follow-up was seven and a half years. Fourteen of 23 (60.9%) had no previous treatment. Five of 23 had a previous arthroscopic synovectomy, one of 23 had a previous combined anterior arthroscopic and posterior open synovectomy, and three of 23 had a previous open synovectomy. Mean time between stages was 87 days (2.9 months). Seven of 23 (30.4%) patients had a recurrence. Of these, three of seven (42.9%) were treated with Imatinib, and four of seven (57.1%) were treated with repeat surgery (three of four arthroscopic and one of four open). Recurrence rates of d-TGCT in the literature vary widely but tend to be high. In our retrospective study, a staged, open, anterior and posterior synovectomy provides recurrence rates that are lower than rates previously reported in the literature. These findings support prior data suggesting this approach may result in better rates of recurrence for this highly recurrent difficult to treat tumour

Giant cell tumors of bone (GCTs) are locally aggressive tumors with recurrence potential that represent up to 10% of primary tumors of the bone. GCTs pathogenesis is driven by neoplastic mononuclear stromal cells that overexpress receptor activator of nuclear factor kappa-B/ligand (RANKL). Treatment with specific anti-RANKL antibody (denosumab) was recently introduced, used either as a neo-adjuvant in resectable tumors or as a stand-alone treatment in unresectable tumors. While denosumab has been increasingly used, a percentage of patients do not improve after treatment. Here, we aim to determine molecular and histological patterns that would help predicting GCTs response to denosumab to improve personalized treatment. Nine pre-treatment biopsies of patients with spinal GCT were collected at 2 centres. In 4 patients denosumab was used as a neo-adjuvant, 3 as a stand-alone and 2 received denosumab as adjuvant treatment. Clinical data was extracted retrospectively. Total mRNA was extracted by using a formalin-fixed paraffin-embedded extraction kit and we determined the transcript profile of 730 immune-oncology related genes by using the Pan Cancer Immune Profiling panel (Nanostring). The gene expression was compared between patients with good and poor response to Denosumab treatment by using the nSolver Analysis Software (Nanostring). Immunohistochemistry was performed in the tissue slides to characterize cell populations and immune response in CGTs. Two out of 9 patients showed poor clinical response with tumor progression and metastasis. Our analysis using unsupervised hierarchical clustering determined differences in gene expression between poor responders and good responders before denosumab treatment. Poor responding lesions are characterized by increased expression of inflammatory cytokines as IL8, IL1, interferon a and g, among a myriad of cytokines and chemokines (CCL25, IL5, IL26, IL25, IL13, CCL20, IL24, IL22, etc.), while good responders are characterized by elevated expression of platelets (CD31 and PECAM), coagulation (CD74, F13A1), and complement classic pathway (C1QB, C1R, C1QBP, C1S, C2) markers, together with extracellular matrix proteins (COL3A1, FN1,. Interestingly the T-cell response is also different between groups. Poor responding lesions have increased Th1 and Th2 component, but good responders have an increased Th17 component. Interestingly, the checkpoint inhibitor of the immune response PD1 (PDCD1) is increased ~10 fold in poor responders. This preliminary study using a novel experimental approach revealed differences in the immune response in GCTs associated with clinical response to denosumab. The increased activity of checkpoint inhibitor PD1 in poor responders to denosumab treatment may have implications for therapy, raising the potential to investigate immunotherapy as is currently used in other neoplasms. Further validation using a larger independent cohort will be required but these results could potentially identify the patients who would most benefit from denosumab therapy

Diffuse-type Tenosynovial Giant-Cell Tumour (d-TGCT) of large joints is a rare, locally aggressive, soft tissue tumour affecting predominantly the knee. Previously classified as Pigmented Villonodular Synovitis (PVNS), this monoarticular disease arises from the synovial lining and is more common in younger adults. Given the diffuse and aggressive nature of this tumour, local control is often difficult and recurrence rates are high. Current literature is comprised primarily of small, and a few larger but heterogeneous, observational studies. Both arthroscopic and open synovectomy techniques, or combinations thereof, have been described for the treatment of d-TGCT of the knee. There is, however, no consensus on the best approach to minimize recurrence of d-TGCT of the knee. Some limited evidence would suggest that a staged, open anterior and posterior synovectomy might be of benefit in reducing recurrence. To our knowledge, no case series has specifically looked at the recurrence rate of d-TGCT of the knee following a staged, open, posterior and anterior approach. We hypothesized that this approach may provide better recurrence rates as suggested by larger more heterogeneous series. A retrospective review of the local pathology database was performed to identify all cases of d-TGCT or PVNS of the knee treated surgically at our institution over the past 15 years. All cases were treated by a single fellowship-trained orthopaedic oncology surgeon, using a consistent, staged, open, posterior and anterior approach for synovectomy. All cases were confirmed by histopathology and followed-up with regular repeat MRI to monitor for recurrence. Medical records of these patients were reviewed to extract demographic information, as well as outcomes data, specifically recurrence rate and complications. Any adjuvant treatments or subsequent surgical interventions were noted. Twenty-three patients with a minimum follow-up of two years were identified. Mean age was 36.3 at the time of treatment. There were 10 females and 13 males. Mean follow-up was seven and a half years. Fourteen of 23 (60.9%) had no previous treatment. Five of 23 had a previous arthroscopic synovectomy, one of 23 had a previous combined anterior arthroscopic and posterior open synovectomy, and three of 23 had a previous open synovectomy. Mean time between stages was 87 days (2.9 months). Seven of 23 (30.4%) patients had a recurrence. Of these, three of seven (42.9%) were treated with Imatinib, and four of seven (57.1%) were treated with repeat surgery (three of four arthroscopic and one of four open). Recurrence rates of d-TGCT in the literature vary widely but tend to be high. In our retrospective study, a staged, open, anterior and posterior synovectomy provides recurrence rates that are lower than rates previously reported in the literature. These findings support prior data suggesting this approach may result in better rates of recurrence for this highly recurrent difficult to treat tumour

Introduction. Fibula contributes to weight bearing and serves as a lateral buttress to the talus. Fibular shortening leads to ankle valgus, distal tibial epiphyseal wedging and ankle instability. Trauma, infection and skeletal dyplasias are the common causes of fibular shortening in children. Aim was to review this cohort who underwent fibular lengthening and ankle reconstruction. Materials and Methods. Retrospective review from a prospective database of clinical and radiographic data of all children who underwent fibular lengthening for correction of ankle valgus. Distraction osteogenesis with external fixator was performed for all cases. Results. Eight children with 10 fibulae (average age: 10 years) were followed up for an average of 75.6 months. In older children, corrective tibial osteotomy was performed in addition to fibular lengthening. TSF frame mounted with mini-rail fixator was used in seven children who required adjuvant tibial correction and mini-rail was used for bilateral fibular lengthening in one. Remodelling of the wedged distal tibial epiphysis was noted in 75%. Talar tilt and mLDTA improved in 66.7% and fibular station in 85.7% limbs. Seven year old girl required re-lengthening. Two children developed fibular non-union. Proximal fibular migration was observed in one child, in whom the tibial wire did not engage the fibula. Conclusions. Restoration of tibial mechanical axis and lateral talar buttress is necessary to correct ankle valgus. Stabilisation of fibula to the tibia is prudent during distraction. Younger children may require re-lengthening. Remodelling of the triangular tibial epiphysis can be achieved when done early

Tears of the rotator cuff tendons are a very common entity. Despite recent advances in arthroscopic rotator cuff repair, the re-tear rate remains high. Thus, new methods to improve healing rates following rotator cuff repair must be sought. The purpose of this prospective randomized double-blind controlled study is to compare the functional outcomes and healing rates of an adjuvant pre-operative bone microfracture technique prior to arthroscopic cuff repair. Patients undergoing arthroscopic rotator cuff repair were randomized to receive either a percutaneous bone microfracture of the supraspinatus footprint or a “soft tissue needling” technique, in which the pin was passed through the peripheral edges of the rotator cuff, five-seven days prior to index surgery, under ultrasound guidance. Follow-ups were completed at 3, 6, 12 and 24 months post-operatively. Healing status was determined by ultrasound at 6 and 24 months. The primary objective was to compare the WORC score at 24 months. Secondary objectives included the healing status via ultrasound, the Constant, and the ASES scores. A sample size calculation determined that 90 patients provided 80% power to detect a statistical difference between groups. Baseline demographic data did not differ between groups. No statistical differences were detected in the WORC outcome at any time points (p=0.47, baseline, p=0.60, 3 months, p=0.79, 6 months, p=0.50, 12 months, p=0.54, 24 months). Healing rates did not differ between groups (P=0.34) and no differences were observed in the ASES or Constant Scores at all time-points. Statistically significant improvements occurred in both groups from baseline to all time points in all clinical outcome scores (p < 0 .0001). No statistically significant differences in primary or secondary outcomes were identified between pre-operative bone microfracture and soft tissue needling techniques prior to arthroscopic rotator cuff repair. This study does not support pre-operative microfracture as a adjuvant technique prior to arthroscopic cuff repair

Aim. Here, we are aimed to evaluate bacteriophage (191219) to treat S. aureus implant-associated bone infections by means of testing against S. aureus during its planktonic, biofilm and intracellular growth phases and finally assessing antimicrobial effect on in vivo biofilm formed on metal K-wire in an alternative insect model Galleria mellonella. Method. The bacteriophages (191219) were provided from D&D Pharma GmbH. These bacteriophages were tested against S. aureus EDCC 5055 (MSSA) and S. aureus DSM 21979 (MRSA) strains. To assess the activity of bacteriophages against planktonic growth phase, bacteriophages, and S. aureus EDCC 5055(1×10. 7. CFU/ml) were co-cultured in LB media as multiplicity of infection (MOI) of 10, 1, 0.1, and 0.01 for 24 hours at 37. o. C and finally plated out on the LB agar plates to estimate the bacterial growth. The antimicrobial activity of bacteriophages on biofilms in vitro was measured by analysing the incubating the several fold dilutions of bacteriophages in LB media with biofilms formed on 96-well plate. The eradication of biofilm was analysed with crystal violet as well as CFU analysis methods. Later, the effect of bacteriophages on intracellular growth of S. aureus in side osteoblast was tested by treating the S. aureus infected osteoblasts at 2h, 4h and 24h time points of post treatment. In addition, we have analysed synergistic effect with gentamicin and rifampicin antibiotics to clear intracellular S. aureus. Finally, experiments are performed to prove the effect of bacteriophages to clear in vivo biofilm using alternative insect model G. mellonella as well as to detect the presence of bacteriophages inside the osteoblasts through transmission electron microscopy (TEM) analysis. Results. Our results demonstrate the in vitro efficacy of bacteriophages against planktonic S. aureus. Transmission electron microscopy (TEM) experiments revealed severe infection of bacteria by bacteriophages. Bacteriophages also eradicated in a dose-dependent manner in vitro S. aureus biofilm formation and were active against intracellular S. aureus in an osteoblastic cell line. TEM analysis visualized the effect of the bacteriophages on S. aureus inside the osteoblasts with the destruction of the intracellular bacteria and formation of new bacteriophages. For the Galleria infection model, single administration of phages failed to show improvement in survival rates, but exhibited some synergistic effects with gentamicin or rifampicin, which was not statistically significant. Conclusions. In summary, bacteriophages could be a potential adjuvant treatment strategy for patients with implant-associated biofilm infections. Further preclinical and clinical trials are required to establish adequate treatment protocols

We investigated the effect of adjuvant and neoadjuvant chemotherapy regimens on the tibial regenerate after removal of the external fixator in a rabbit model of distraction osteogenesis using New Zealand white rabbits. Forty rabbits were randomly distributed into two groups. In the neoadjuvant group, half of the rabbits received 1mg/kg cisplatinum & 2mg/kg adriamycin at eight weeks of age followed by 1mg/kg cisplatinum & 4mg/kg adriamycin at ten weeks of age. The remaining ten received an identical volume of normal saline using the same regimen. The adjuvant group differed only in the timing of the chemotherapy infusion. Half received the initial infusion ten days prior to the osteotomy, with the second infusion four days following the osteotomy. Again, the remaining ten rabbits received an identical volume of normal saline using the same regimen. This produced an identical interval between infusions and identical age at osteotomy in both groups. All rabbits underwent a tibial osteotomy at 12 weeks of age. Distraction started 24hours after osteotomy at a rate of 0.75mm a day for 10 days, followed by 18 days without correction to allow for consolidation of the regenerate. At week 16 there was no difference in Bone Mineral Density (BMD), Bone Mineral Content (BMC) or volumetric Bone Mineral Density (vBMD) in the adjuvant group. Neoadjuvant chemotherapy appears to have a significant detrimental effect on BMD, vBMD and BMC. Despite this there were no significant alterations in the mechanical properties of the regenerate. Histologically there was a trend for increased cortical thickness in the control groups compared to intervention however this did not prove statistically significant. In conclusion, adjuvant chemotherapy may be more beneficial for cases where distraction osteogenesis is being considered to replace segmental bone loss after tumour excision

Benign aggressive tumors are common and can be debilitating for patients especially if they are in peri-articular regions or cause pathological fracture as is common for giant cell tumor of bone (GCT). Although GCT rarely metastasize, the literature reports many series with high rates of local recurrence, and evidence about which risk factors influence recurrence is lacking. This study aims to evaluate the recurrence rate and identify local recurrence risk factors by reviewing patient data from a single high-volume orthopedic oncology center. A retrospective analysis of all patients treated for GCT at a tertiary orthopedic oncology center was conducted. In total 413 patients were treated for GCT between 1989 and 2017. Multiple patient and tumour characteristics were analysed to determine if they influenced local recurrence including: age, gender, anatomical site, Campanacci stage, soft tissue extension, presence of metastasis, pathologic fractures, and prior local recurrence. Additional variables that were analysed included type of treatment (en bloc resection or aggressive intralesional curettage) and use of local adjuvants. The main outcome parameters were local recurrence- free survival, metastasis-free survival and complications. Patients treated with Denosumab were excluded from analysis given its recently documented association with high rates of local recurrence. “There were 63/413 local recurrences (15.3%) at a mean follow-up of 30.5 months. The metastatic rate was 2.2% at a mean 50.6 months follow-up and did not vary based on type of treatment. Overall complication rate of 14.3% was not related to treatment modality. Local recurrence was higher (p=0.019) following curettage (55/310; 17.7%) compared to resection (8/103; 7.8%) however, joint salvage was possible in 87% of patients (270/310) in the curettage group. Use of adjuvant therapy including liquid nitrogen, peroxide, phenol, water versus none did not show any effect on local recurrence rates (p= 0.104). Pathological fracture did not affect local recurrence rates regardless of treatment modality (p= 0.260). Local recurrence at presentation was present in 16.3% (58/356) patients and did not show any significance for further local recurrence (p= 0.396). Gender was not associated with local recurrence (p=0.508) but younger patient age, below 20 years (p = 0.047) or below 30 years (p = 0.015) was associated with higher local recurrence rates. GCT in distal radius demonstrated the highest rate of local recurrence at 31.6% compared to other sites, although this was not significant (p=0.098). In addition, Campanacci stage and soft tissue extension were not risk factors for recurrence. The overall GCT local recurrence rate was 15.3%, but varied based on the type of resection: 17.7% following joint sparing curettage compared to 7.8% following resection. Local recurrence was also higher with younger patient age (30 years or less) and in distal radius lesions. In addition, neither Campanacci stage, soft tissue extension or presence of a pathologic fracture affected local recurrence. Most patients with GCT can undergo successful curettage and joint sparing, while only a minority require resection +/− prosthetic reconstruction. Even in the presence of soft tissue extension or a pathologic fracture, most joints can be salvaged with curettage

Osteosarcoma is the most common primary bone tumour worldwide. This disease presents a formidable challenge to the orthopaedic surgeon, with a mortality rate of 30 per cent, even after surgical clearance. Aberrant Wnt signalling has been implicated in the pathogenesis osteoblastic tumours. The objective of this study is 2 fold- to investigate if osteosarcoma does indeed demonstrate aberrant Wnt signaling, and if so, does osteosarcoma respond to a novel Wnt inhibitor(ETC159). This can potentially lead to the development of a new adjuvant treatment modality for osteosarcoma. A novel Wnt signaling pathway protein antibody (YJ5) was used in immunihistochemistry staining of clinical osteosarcoma samples. A Wnt high osteosarcoma cell line(SJSA-1) was then implanted subcutaneously in a mouse model. These mice were treated with a novel PORCN inhibitor, ETC 159 for a period of 4 weeks in a two-arm randomised control study. The results of treatment were evaulated by clinical outcome parameters as well as immunohstochemistry. 100 per cent of clinical osteosarcoma samples demonstrated increased WLS expression and Wnt protein expression. SJSA-1 showed no significant decrease in tumour volume after 30 days of drug treatment (3070 SD 625 mm3 vs 3480 SD 433 mm3 p= 0.605 and 2060 SD 209 vs 1677 SD 213 mm3 p=0.219 respectively). Significantly, SJSA-1 demonstrated increased tumour necrosis in the treatment arm(30–60 percent increase across all samples p < 0 .005) Treated tumours also demonstrated markedly less angiogenesis compared to the non treatment arm. Osteosarcoma demonstrates aberrant Wnt signaling in a large percentage of cases. The use of a novel PORCN inhibitor ETC 159 for the treatment of Osteosarcoma has a marked effect on tumour necrosis. Our results suggest that ETC159 may cause tumour necrosis by inhibiting angiogenesis within the tumour. Further evaluation and understanding of the mechanism of Wnt singaling in regulating tumour pathogenesis may hold the potential for developing a curative therapeutic drug for this deadly disease

Spinal metastases are seen in 10–30% of cancer patients. Twenty percent of these metastases occur in the lumbo-sacral spine. Lumbo-sacral spine has different mechanical properties and encloses the cauda equina. Few studies took interest in this spinal segment. The objective of this study is to evaluate prognostic factors of lumbo-sacral spinal metastasis treated in our center. We retrospectively reviewed 376 patients who were operated in our center from 2010 to 2018. Eighty-nine patients presented lumbo-sacral metastases and thus were included. Data collected included age, smoking, tumor histology, American spinal injury association (ASIA) score, modified Tokuhashi score, modified Bauer score, ambulation status and adjuvant treatment. The mean population age was 60.9 years old (35–85). The tumor histology was predominantly lung (19 patients, 21.3%), breast (13 patients, 14.6%), kidney (11 patients, 12.4%) and prostate (9 patients 10.1%). Twenty-two patients (24.7%) were unable to walk preoperatively. Seventy-nine patients (88.8%) underwent a posterior open approach with corpectomy in 65 patients (73%). Eighteen patients regained ambulation post-operatively (81.8%). The mean survival was 24.03 months (CI95% 17,38–30,67, Range 0–90) and the median of survival was 9 months (CI95% 4.38–13.62). Better preoperative ASIA score had a significant favorable effect (p=0.03) on survival. Patients who regained their ability to walk had better survival (25.1 months (CI95% 18.2–32) VS 0.5 months (CI95% 0–1.1). Postoperative radiotherapy had a benefic effect on survival (p=0.019): Survival Increased from 10.5 months (CI95% 2.4–18.7) to 27.6 months (CI95% 19.5–35.8). The modified Tokuhashi and the modified Bauer scores underestimated the survival of the patients with lumbosacral metastases. Lumbosacral spinal metastases has better survival than expected by Tokuhashi and Bauer score. Surgical procedure have an important impact on survival and the ability to walk

Dexmedetomidine, an alpha 2 agonist, has been approved for providing sedation in the intensive care unit. Along with sedative properties, it has analgesic activity through its highly selective action on alpha 2 receptors. Recent studies have examined the use of dexmedetomidine as an adjuvant to prolong the duration of peripheral nerve blocks. Studies showing effectiveness of dexmedetomidine for adductor canal block in knee surgery are small. Also, its effectiveness has not been compared to Epinephrine which is a strong alpha and beta receptor agonist. In a previous study, we showed that motor sparing knee blocks significantly increased the duration of analgesia compared with periarticular knee infiltration using local anesthetic mixture containing Epinephrine following total knee arthroplasty (TKA). In this study, we compared two local anesthetic mixtures: one containing Dexmedetomidine and the other Epinephrine for prolongation of motor sparing knee block in primary TKA patients. After local ethics board approval and gaining Notice of Compliance (NOC) from Health Canada for use of Dexmedetomidine perineurally, 70 patients between the ages 18 – 95 of ASA class I to III undergoing unilateral primary total knee arthroplasty were enrolled. Motor sparing knee block − 1) Adductor canal continuous catheter 2) Single shot Lateral Femoral Cutaneous Nerve block 3) Single shot posterior knee infiltration was performed in all patients using 60 ml mixture of 0.5% Ropivacaine, 10 mg Morphine, 30 mg Ketorolac. Patients randomized into the Dexmedetomidine group (D) received, in addition to the mixture, 1mcg/kg Dexmedetomidine and the Epinephrine (E) group received 200mcg in the mixture. The primary outcome was time to first rescue analgesia as a surrogate for duration of analgesia and secondary outcomes were NRS pain scores up to 24 hours and opioid consumption. The time to first rescue analgesia was not significantly different between Epinephrine and dexmedetomidine groups, Mean and SD 18.45 ± 12.98 hours vs 16.63 ± 11.80 hours with a mean difference of 1.82 hours (95% CI −4.54 to 8.18 hours) and p value of 0.57. Pain scores at 4, 6, 12, 18 and 24 hours were comparable between groups. Mean NRS pain scores Epinephrine vs Dexmedetomidine groups were 1.03 vs 0.80 at 4 hours, 1.48 vs 3.03 at 6 hours, 3.97 vs 4.93 at 12 hours, 5.31 vs 6.18 and 6.59 v 6.12 at 24 hours. Opioid consumption was also not statistically significant between both groups at 6, 12 18, 24 hours (p values 0.18, 0.88, 0.09, 0.64 respectively). Dexmedetomidine does not prolong the duration of knee motor sparing blocks when compared to Epinephrine for total knee arthroplasty. Pain scores and opioid consumption was also comparable in both groups. Further studies using higher dose of dexmedetomidine are warranted

Periprosthetic femoral shaft fractures are a significant complication of total hip arthroplasty. Plate osteosynthesis with or without onlay strut allograft has been the mainstay of treatment around well-fixed stems. Nonunions are a rare, challenging complication of this fixation method. The number of published treatment strategies for periprosthetic femoral nonunions are limited. In this series, we report the outcomes of a novel orthogonal plating surgical technique for addressing nonunions in the setting of Vancouver B1 and C-type periprosthetic fractures that previously failed open reduction internal fixation (ORIF). A retrospective chart review of all patients from 2010 to 2014 with Vancouver B1/C total hip arthroplasty periprosthetic femoral nonunions was performed. All patients were treated primarily with ORIF. Nonunion was defined as no radiographic signs of fracture healing nine months post-operatively, with or without hardware failure. Exclusion criteria included open fractures and periprosthetic infections. The technique utilised a mechanobiologic strategy of atraumatic exposure, resection of necrotic tissue, bone grafting with adjuvant recombinant growth factor and revision open reduction internal fixation. Initially, compression was achieved using an articulated tensioning device and application of an anterior plate. This was followed by locked lateral plating. Patients remained non-weight bearing for eight weeks. Six Vancouver B1/C periprosthetic femoral nonunions were treated. Five patients were female with an average age of 80.3 years (range 72–91). The fractures occurred at a mean of 5.8 years (range 1–10) from their initial arthroplasty procedure. No patients underwent further revision surgery; there were no wound dehiscence, hardware failures, infections, or surgical complications. All patients had a minimum of nine months follow up (mean 16.6, range 9–36). All fractures achieved osseous union, defined as solid bridging callus over at least two cortices and pain free, independent ambulation, at an average of 24.4 weeks (range 6.1–39.7 weeks). To our knowledge, this is the first case series describing 90–90 locked compression plating using modern implants for periprosthetic femoral nonunions. This is a rare but challenging complication of total hip arthroplasty and we present a novel solution with satisfactory preliminary outcomes. Orthogonal locked compression plating utilising an articulated tensioning device and autograft with adjuvant osteoinductive allograft should be considered in periprosthetic femur fractures around a well-fixed stem. Further biomechanical and clinical research is needed to improve our treatment strategies in this population

Aim. To study the antimicrobial effect of a gentamicin loaded bio-composite bone void filler in relation to a limited or extensive debridement of osteomyelitis lesions, respectively. Methods. Nine pigs were inoculated into the right proximal tibial bone with a high virulent gentamicin sensitive strain of Staphylococcus aureus (10. 4. CFU). Seven days after inoculation, Group A pigs (n=3) were exposed to a limited debridement of the bone lesion, whereas Group B pigs (n=3) were exposed to an extensive debridement. The bone defects of Groups A and B were filled with (2–5 ml) of an absorbable gentamicin (175 mg/10 mL) loaded bio-composite. The animals of Group A and B were euthanized 12 days after revision surgery. Group C animals did not undergo revision surgery and were euthanized seven (n=1) or nineteen (n=2) days post inoculation in order to follow the development of the untreated infection. None of the animals were treated with systemic antimicrobials. All bones were exposed to a post mortem CT scan and rigours pathological examinations. The surrounding bone tissue and the bio-composite were sampled for microbiology. Results. All animals developed a substantial purulent bone infection in the inoculated leg prior to revision surgery. In the cases of limited debridement, the bone lesions surrounding the bio-composite bone void filler had clearly expanded since revision surgery, and contained extensive amounts of pus, necrotic bone tissue and oedematous fibrotic tissue. In the cases of extensive debridement, the bio-composite bone void filler was surrounded by only a few mm of fibrosis and sclerotic bone tissue i.e. the bone lesions were not expanding. However, in one pig the bio-composite bone void filler was communicating with a small purulent osteolytic lesion without a sclerotic border indicating appearance after revision surgery. In all pigs, S. aureus bacteria were post mortem cultured from the adjacent bone tissue and the bio-composite surface. Conclusions. The gentamicin concentrations within the bio-composite could not eradicate the residual infection after debridement. However, extensive debridement and filling of the bone void with gentamicin loaded bio-composite contained the lesion formed by revision surgery, which are important complementing roles as adjuvant to systemic antimicrobial therapy and the immune system in eradication of the infection. The present study emphasizes that extensive debridement is fundamental for successful treatment of bone infections and that antimicrobial loaded bone void fillers or bone substitutes should not be used as an alternative to extensive debridement

Introduction. Polymicrobial infections are expected to complicate the treatment of bone and joint infections. Septic nonunions often occur after initial open fractures, which prophylactically receive broad-spectrum antibiotics. However, no data that describes frequencies of polymicrobial infections and pathogens evident in course of the treatment of septic nonunions is published. Therefore, this study aims at investigating the frequency and pathogen types in polymicrobial infections. Methods. Surgically treated Patients with long bone septic nonunion admitted between January 2010 and March 2018 were included in the study. Following parameters were examined: age, gender, American Society of Anesthesiologists (ASA) score, body mass index (BMI), and anatomical location of the infected nonunion. Microbiological culture data, polymerase-chain-reaction results of tissue samples, sonication, and joint fluid of the initial and follow-up revision surgeries were assessed. No exclusion criteria were determined. Results. The study encompassed 42 patients with a mean age of 53.9 ± 17.7 years (range, 23 – 93). Sixteen (38.1%) patients were female. In 46.3% of the patients open fractures led to septic nonunion. Twenty-six nonunions occurred at the tibia or fibula, 11 were localized at the femur, 2 at the humerus and 3 at the forearm. Only 2 patients were assessed as ASA type 1, while 26 were ASA type 2 and 12 patients ASA type 3. Mean number of performed surgeries was 6 ± 0.67 (range 2 – 21). In 6 patients (14.3%) polymicrobial infection were evident. A change of evidenced pathogens in course of the treatment occurred in 21 patients (50%). In 16 patients (38.1%) previously detected bacteria could be evidenced by microbial testing after further revision surgery. Staphylococcus aureus was most often evident (n=34, 30.6%), followed by Enterococcus species (n=25, 22.5%) and Staphylococcus epidermidis (n=18, 16.2%). Five Staphylococcus aureus were resistant to methicillin (MRSA). In patients without polymicrobial infection or further germ detection in course of the treatment 86.4% of the infections were due to Staphylococcus species. Patients with change of detected pathogens and polymicrobial infections suffered from more enterococci infections. Infections due to streptococci and gram-negative bacteria could only be evidenced in patients with polymicrobial infection and pathogen change in course of the treatment. Conclusion. The observed difference of microbiological patterns in septic nonunion may help to facilitate adjuvant local and systemic antibiotic treatment in septic nonunion patients. Reasons for the observed difference of microbiological patterns and its influence on patient outcome have still to be elucidated

Background. Although soft tissue sarcoma (STS) is a rare malignancy, myxofibrosarcoma is a common form diagnosed. Myxofibrosarcoma is complicated by a high local recurrence rate (18–54%) and significant morbidity following treatment, hence management can be challenging. Patients and Methods. Patients treated between 2003–2012 were identified via a database within the histopathology department and case notes were retrospectively assessed. All histology samples were reviewed by a senior histopathologist to ensure a correct diagnosis. Results. 29 patients (12 male, 17 female) with an average age of 61 years (range 19–89 years) underwent surgery at a single centre, with 24 patients receiving adjuvant and two receiving neo-adjuvant radiotherapy. 22 patients had lower limb and 7 had upper limb tumours. 3 were treated for secondary recurrence after having primary surgery elsewhere. 21 patients had Trojani Grade 2 or 3 tumours. All underwent limb-sparing surgery initially but six patients (20.7%) suffered local recurrence after an average follow-up of 28 months and all ultimately required above knee amputation. Four patients developed wound infection, with one requiring VAC therapy. One patient required a flap repair of the forearm. 5-year survival rate was 87.5%. Conclusions. Our results compare favourably against results published so far in the literature with a low local recurrence rate and mortality. Limb-sparing surgery aims to reduce morbidity and disability following treatment but more research is required in adjuvant treatments to further reduce the risk of local recurrence of tumour

Background. Myxofibrosarcomas are malignant soft tissue tumours that often present as painless slowly growing masses in the extremities of older males. Locally infiltrative growth means risks of local recurrence is high. Management emphasises negative surgical margins and adjuvant therapy. The aim of this retrospective case series was to review our experience of this tumour, and make recommendations about a minimum resection margin and how best to utilise the expertise of the multidisciplinary team. Methods. A computerised database identified patients with myxofibrosarcoma surgically treated in our centre between 1997 and 2011. Clinical records were reviewed. Margins were positive if tumour was at or within 1mm of the resection plane. Results. 43 patients (median age 68.6 years; 70% male) were identified. 42 underwent surgery: 26 (62%) by orthopaedics; 9 (21%) by plastics, and 7 (17%) jointly. The lower limb was the most common site (30/43, 70%). Mean tumour size was 5.9cm (range 1.5 to 20cm). 53% had grade III tumours. Of 39 tumours with available data, 21 were superficial fascially-based masses and 18 were deep. 23 (55%) had positive margins. Of these, 9 underwent re-excision, 5 of whom had adjuvant radiotherapy. 13 of the remaining 14 patients had adjuvant radiotherapy. Of the fascially-based tumours, there was microscopic spread beyond the macroscopic mass of between 3–25mm. 3 patients (7%) developed local recurrence at a mean of 25 months (14 to 30 months). 12 (29%) had metastases at a mean of 19 months (range 7 to 48 months). Conclusion. Myxofibrosarcoma poses a number of challenges for sarcoma teams; in particular, high positive margin rates, risks of further surgery and local failure. The infiltrative nature makes it suited to management by multidisciplinary teams. Microscopic tumour can present up to 2.5cm from the macroscopic mass for fascially-based tumours, and teams should plan appropriately