Introduction. Various anti-infective agents can be added to the surface of orthopaedic implants to actively kill bacteria and prevent infection. Silver (Ag) is a commonly used agent in various anti-infective applications. Silver disrupts bacterial membranes and binds to bacterial DNA and to the sulfhydryl groups of metabolic enzymes in the bacterial electron transport chain, thus inactivating bacterial replication and key metabolic processes. Recently we are implanting Silver coated megaprosthesis for the treatment of post-traumatic septic non unions/bone defects and for infected hip or knee prosthesis revision. We treat these complications utilizing a two steps procedure: 1° step: devices removal, resection, debridment and antibiotic spacer implantation; 2° step: spacer removal and megaprosthesis implantation. This technique produce a reactive pseudosynovial membrane, well known in traumatology (Masquelet technique), following the Chamber Induction Technique principles. This chamber creates the perfect environment in which implant the prosthesis with safety. We are nowadays investigating if this membrane could optimize the Silver antimicrobical effects reducing the Silver ions dispersion and reducing toxicity on the human body. Objectives. The aim of this study is to perform a review of the literature about Silver coated implants in Orthopaedics and Trauma and to analyze our cases treated with this implants in order to measure their efficacy and the ion dispersion in urine and blood. Methods. We performed a literature review using the universally validated search engines in the biomedical field: PubMed / Medline, Google Scholar, Scopus, EMBASE. The keywords used were: “Silver”, “Silver coating”, “Silver surface”, “were crossed with “Prosthesis”, “Megaprosthesis”, “Infection”, “Sepsis”, “Revision”. We also analized all our patients treated with Silver coated implants measuring Silver dose in blood and urine before implantation, 1 day after implantation and then after 15 days, 3,6,12,24,36 months. Results. The search led to 468 items, of these were considered only article in English with full text available. We found 1 in vitro study, 1 animal study and 2 human studies. The animal study showed a reduction in periprosthetic infection from 47% to 7%, 1 human study in Oncology application of megaprosthesis showed a reduction of septic complications from 17,6% to 5,9%. Te other human study demonstrated that Silver surface implants don't have toxicity cause the blood level of silver Ions were only 56,4 parts per billion. The analysis of our casuistry is giving good results with low level of Silver in the blood and urine, lower concentrations are observed in patients treated with the 2 steps-CIT technique. Conclusions. The use of silver-coated prosthesis can reduce the infection rate in the medium-long term with no toxicity for the patients. Further studies with longer term follow-up periods and larger numbers of patients are warranted in order to confirm these encouraging results most of all in the patients treated with the 2 steps procedure in order to better understand the role of the membrane and of the Chamber Induction Technique in Silver ions dispersions

Introduction. The FitBone lengthening nail (Orthofix UK) is an intramedullary device licensed for the lengthening of long bones in adults in the UK. It contains a motor powered by electricity transmitted via an induction coil placed underneath the skin. It was developed in Germany two decades ago but uptake in the UK has only started more recently. The aim of this study was to review the first cohort of FitBone lengthening nails in a unit with significant experience of other lengthening nails (including PRECICE and Stryde). Materials & Methods. Demographic, clinical and radiological data was prospectively collected on all FitBone cases starting in February 2022. Accuracy of lengthening rate, patient satisfaction and implant issues were all considered. Complications and learning points were recorded and discussed by the multidisciplinary team involved in the patients care. Results. Eleven lengthening nails were inserted between February and November 2022 (6 right femurs, 5 left femurs). The average patient age was 31 (16–57) with 4 females and 7 males. The average lengthening achieved was 44mm (13– 70) over an average of 59 days (35 to 104). Significant technical issues were encountered in this cohort of patients including slow opening up at osteotomy site (3 requiring speeding up of programme), early consolidation (one requiring re-do osteotomy) and backing out of locking screws (3 out of 11 nails). There were also patient use concerns with difficulty using the motor and the inability to reverse the lengthening without an additional component to the motor. Conclusions. We present the first UK cohort of patients with femoral lengthening using the FitBone implant and device. We highlight the technical and patient issues encountered during this learning curve and propose solutions to avoid these pitfalls

Aim. Periprosthetic joint infection (PJI) is a severe complication after total joint arthroplasty. To prevent PJI, strict infection prevention measures are followed in combination with surgical antibiotic prophylaxis (SAP). To date, scientific reports concerning the optimal duration of SAP in revision arthroplasty are scarce. The aim of this multicenter open-label, randomized controlled trial in the Netherlands, is to investigate the superiority of 5 days (extended) versus a single dose of cefazolin to prevent PJI within the first year after revision arthroplasty of the hip and knee. Method. Included patients with an assumed aseptic hip or knee revision procedure received a single dose of 2 or 3 gram cefazolin preoperatively. Patients were randomly assigned in a 1:1 ratio to receive extended prophylaxis of cefazolin during 5 days postoperatively versus no prophylaxis after wound closure. Patients were excluded if evidence of PJI at revision. The primary endpoint was the incidence of PJI within one year after revision arthroplasty. PJI was defined according to the 2018 Philadelphia consensus criteria. With a sample size of 746 patients, an alpha of 5% and a power of 80%, superiority of the extended regimen would be shown if the lower boundary of the 95% confidence interval (CI) of the absolute between-group difference of the percentage of PJI is below −4%. Results. In total 751 patients were included for analysis: 379 in the single dose cefazolin group and 372 in the extended group. Within one year, PJI occurred in 2.6% (10/379) in the single dose group and 2.4% (9/372) in the extended group (risk difference, −0.2 percentage points; 95% CI, −2.5 to 2.0%), thus superiority was not shown. Adverse drug events were seen in 20 cases with extended and 7 cases with a single dose prophylaxis. Conclusions. Extended prophylaxis is not significantly superior to a single dose of cefazolin to prevent PJI within the first year after revision arthroplasty of the hip or knee. This is the first randomized controlled trail in which the duration of SAP in the selected group of patients undergoing revision arthroplasty was studied. Extending SAP after closure of the wound could increase the selection or induction of antimicrobial resistance, has an increased risk for adverse drug events, and is therefore not in line with the primary goal of antimicrobial stewardship, comprising optimizing clinical outcomes and ensuring cost-effective therapy while minimizing unintended consequences of antimicrobial use

Aim. To make an inoculum for induction of Implant-Associated Osteomyelitis (IAO) in pigs based on bacterial aggregates resembling those found on the human skin, i.e. aggregates of 5–15 µm with low metabolic activity. The aggregates were evaluated and compared to a standard planktonic bacterial inoculum. Method. The porcine Staphylococcus aureus strain S54F9 was cultured in Tryptone Soya Broth for seven days. Subsequently, the culture was filtered through cell strainers with pore sizes of 15 µm and 5 µm, respectively. The fraction of 5–15 µm aggregates in the top of the 5 µm filter was collected as the aggregate-inoculum. The separation of aggregates into different size fractions was evaluated by light microscopy. The metabolism of the aggregate-inoculum and a standard overnight planktonic inoculum was evaluated with isothermal microcalorimetry. In total, six female minipigs were allocated into three groups (n=2), receiving different inoculums. Group A: overnight planktonic inoculum; 10. 4. CFU S. aureus (S54F9), Group B: seven days old 5–15 µm aggregate-inoculum; 10. 4. CFU S. aureus (S54F9), Group C: saline. All inoculums were placed in a pre-drilled implant cavity in the right tibia of the pig and a sterile stainless-steel implant was inserted. The pigs were euthanized seven days after surgery. Postmortem macroscopic pathology, microbiology, computed tomography and histopathology were performed. Results. The separation of aggregates into different size fractions was done successfully by the filtering method. Isothermal microcalorimetry showed, a delayed Time-to-peak metabolic activity of the aggregate-inoculum compared to the planktonic inoculum. S. aureus was isolated from subcutis, bone and implants from all animals in groups A and B. Both group A animals showed osteomyelitis at gross inspection with suppuration and sequestration, while groups B and C animals had no macroscopic lesions. From CT scans, both group A animals also showed positive signs of osteomyelitis, i.e., osteolysis, while only one animal in group B did, and none in group C. Histopathological examination of the bones showed more extensive inflammation in group A animals compared to those in group B, which showed more osteoid formation. Conclusions. Formation and separation of low metabolism bacterial aggregates into different size fractions was possible. The aggregates can be used as inoculum in the porcine IAO model, with microbiological re-isolation from both implants and tissue. Furthermore, the aggregates caused a less aggressive IAO, than the planktonic counterparts. Using aggregated bacteria as inoculum appears to be more relevant to the clinical situation of infecting bacteria

Aim. Melioidosis is a significant public health problem in endemic regions such as India. Lack of awareness, predominant empiric antibiotic use reducing culture yields, morphotypic variability of cultures and frequent misidentification by automated blood culture systems, pose myriad challenges in diagnosis and treatment. Through this series, we present our experience of Hematogenous Osteomyelitis with Burkholderia pseudomallei. Method. This was a single centre, retrospective, observational study performed at a tertiary case hospital in Mumbai, India from June 2011 to June 2021. Results. The study comprised of 7 cases (6:1, M: F). Mean age was 53.7 years (5 to 75). All had an underlying co- morbidity or were immunosuppressed. 3 patients were misidentified by automated systems prior to presentation (e coli, burkholderia cepacieae, acinetobacter). Most common site of infection was femur (n= 3), followed by tibia and foot and ankle (n= 2, each). One had disseminated meliodosis involving the spleen, lymph nodes, pulmonary) in addition to involvement of bilateral feet and ankles. B. pseudomallei was identified in all following surgical debridement at our institute. Each patient underwent mean 2 procedures. 3 needed local rotation flap surgeries for wound cover. All were treated with ceftazidime along with trimethoprim- sulfamethoxazole (TMP- SMX) during the 6 week induction phase. TMP- SMX was continued for a further 6 months in the consolidation phase. All patients had infection remission at a mean 19.3 months follow up. There were no mortalities in our series. Conclusions. Clinically Burkholderia infections mimic other pyogenic infections, Gram-negative sepsis, tuberculosis and has been referred to as the “remarkable imitator” and the “mimicker of maladies”. Diabetes and alcoholism are risk factors. The need for diagnosing this entity is due to the fact that the septicemic form has a mortality rate that exceeds 90%. Melioidosis is frequently misidentified. A high clinical suspicion, communication with microbiologist, knowledge about the biochemical, cultural and phenotypic susceptibility patterns may help in optimising diagnosis. Adequate debridement coupled with targeted prolonged antibiotics help achieve good outcomes

Aims. The COVID-19 pandemic has had a significant impact on the provision of orthopaedic care across the UK. During the pandemic orthopaedic specialist registrars were redeployed to “frontline” specialties occupying non-surgical roles. The impact of the COVID-19 pandemic on orthopaedic training in the UK is unknown. This paper sought to examine the role of orthopaedic trainees during the COVID-19 and the impact of COVID-19 pandemic on postgraduate orthopaedic education. Methods. A 42-point questionnaire was designed, validated, and disseminated via e-mail and an instant-messaging platform. Results. A total of 101 orthopaedic trainees, representing the four nations (Wales, England, Scotland, and Northern Ireland), completed the questionnaire. Overall, 23.1% (23/101) of trainees were redeployed to non-surgical roles. Of these, 73% (17/23) were redeployed to intensive treatment units (ITUs), 13% (3/23) to A/E, and 13%(3/23%) to general medicine. Of the trainees redeployed to ITU 100%, (17/17) received formal induction. Non-deployed or returning trainees had a significant reduction in sessions. In total, 42.9% (42/101) % of trainees were not timetabled into fracture clinic, 53% (53/101) of trainees had one allocated theatre list per week, and 63.8%(64/101) of trainees did not feel they obtained enough experience in the attached subspecialty and preferred repeating this. Overall, 93% (93/101) of respondents attended at least one weekly online webinar, with 79% (79/101) of trainees rating these as useful or very useful, while 95% (95/101) trainees attended online deanery teaching which was rated as more useful than online webinars (p = 0.005). Conclusion. Orthopaedic specialist trainees occupied an important role during the COVID-19 pandemic. COVID-19 has had a significant impact on orthopaedic training. It is imperative this is properly understood to ensure orthopaedic specialist trainees achieve competencies set out in the training curriculum. Cite this article: Bone Joint Open 2020;1-11:676–682

Aim. Leading etiology of Bone and Join infections (BJI), Staphylococcus aureus (SA) is responsible for difficult-to-treat infections mainly because of three persistence factors: (i) biofilm formation, (ii) persistence within bone cells and (iii) switch to the small colony variant (SCV) phenotype. The impact of rifampin on these mechanisms gave it a prominent place in orthopedic device-associated BJI. However, resistance emergence, intolerance and drug interactions cause significant concerns. In this context, other rifamycins – namely rifapentine and rifabutin – have poorly been evaluated, particularly toward their ability to eradicate biofilm-embedded and intracellular reservoirs of SA. Method. This study aimed at comparing the intracellular activities of and SCV induction by rifampin, rifabutin and rifapentine in an in vitro model of osteoblast infection. Four concentrations were tested (0.1xMIC, MIC, 10xMIC, 100xMIC) against three SA strains (6850 and two clinical isolates involved in recurrent BJI). Results. Each rifamycin had a similar intracellular activity, decreasing by 50% the intracellular inoculum from a concentration equal to MIC. Rifabutin was more efficient at low concentrations, with a reduction of 19.9% at 0.1MIC. At all concentrations, a 1.5-fold increase in cellular viability was observed for all molecules. A dose-dependent induction of intracellular SCVs was observed, which was significantly lower for rifabutin than rifampicin at 10MIC (p<0.0001). Conclusions. Each rifamycin was efficient to eradicate intraosteoblastic SA reservoir, one bacterial phenotype in recurrent's BJI. Rifabutin was more efficient at low concentration, suggesting an important intracellular accumulation. This can be explained by its oil/water coefficient of partition 100 time superior than other rifamycins. Using rifabutin at lower concentration, limiting adverses effect and the emergence of SCVs, could be an interesting therapeutic alternative in BJI's treatment. The comparison of rifamycin ability to eradicate biofilm-embedded SA, another chronicity and relapse factor, is an ongoing work

London's Air Ambulance (LAA) was first set-up in 1989 as a direct result of a Royal College of Surgeons of England Report highlighting poor trauma care provision. Since its inception, the service's mission is to be an innovative and effective provider of advanced pre-hospital care. The service provides a senior Doctor and senior Paramedic to the scene of any incident within the M25 by helicopter, during the day, and by fast-response car at night. The vast majority of doctors are usually Emergency Medicine Physicians or Anaesthetists. During a 6-month tenure, doctors will usually have completed a number of procedures, which include rapid sequence induction of anaesthesia, pre-hospital blood transfusion, and, procedural sedation. In terms of innovations, the organisation was the first in the UK to provide a 24/7 service. It was also the first to start pre-hospital Rapid Sequence Induction of Anaesthesia for the severely injured; Resuscitative Thoracotomy for the victims of penetrating trauma; and pre-hospital Blood Transfusion for shocked polytrauma patients. The service also has a very thorough induction programme, for new Doctors and Paramedics, and a highly structured Clinical Governance process. The post offers a unique and privileged opportunity to treat the most severely injured at the roadside

Bone is a connective tissue that undergoes constant remodeling. Any disturbances during this process may result in undesired pathological conditions. A single nucleotide substitution (596T-A) in exon eight which leads to a M199K mutation in human RANKL was found to cause osteoclast-poor autosomal recessive osteopetrosis (ARO). Patients with ARO cannot be cured by hematopoietic stem cell transplantation and, without proper treatments, will die in their early age. To date, how this mutation alters RANKL function has not been characterized. We thus hypothesized that hRANKL M199 residue is a structural determinant for normal RANKL-RANK interaction and osteoclast differentiation. By sharing our findings, we aim to achieve an improved clinical outcome in treating bone-related diseases such as osteoporosis, ARO and osteoarthritis. Site-directed mutagenesis was employed to create three rat RANKL mutants, replacing the methionine 200 (human M199 equivalent residue) with either lysine (M200K), alanine (M200A) or glutamic acid (M200E). Recombinant proteins were subsequently purified through affinity chromatography and visualized by Coomassie blue staining and western blot. MTS was carried out before osteoclastogenesis assay in vitro to measure the cellular toxicity. Bone resorption pit assay, immuno-fluorescent staining, luciferase reporter assay, RT-PCR, western blot and calcium oscillation detection were also conducted to explore the biological effect of rRANKL mutants. Computational modeling, thermal Shift Assay, western blot and protein binding affinity experiments were later carried out for structural analyses. rRANKL mutants M200K/A/E showed a drastically reduced ability to induce osteoclast formation and did not demonstrate features of competitive inhibition against wild-type rRANKL. These mutants are all incapable of supporting osteoclastic polarization and bone resorption or activating RANKL-induced osteoclast marker gene transcription. Consistently, they were unable to induce calcium flux, and also showed a diminished induction of IκBa degradation and activation of NF-kB and NFATc1 transcriptional activity. Furthermore, the transcriptional activation of the antioxidant response element (ARE) crucial in modulating oxidative stress and providing cytoprotection was also unresponsive to stimulation with rM200s. Structural analyses showed that rM200 is located in a hydrophobic pocket critical for protein folding. Thermal shift and western blot assays suggested that rM200 mutants formed unstructured proteins, with disturbed trimerisation and the loss of affinity to its intrinsic receptors RANK and OPG. Taken together, we first demonstrates the underlying cause of M199-meidated ARO in a cellular and molecular level by establishing a phenotype in BMMs similar to observed in human samples. Further investigation hints the structural significance of a hydrophobic pocket within the TNF-like region. Combined with pharmaceutical studies on small-molecule drugs, this finding may represent a therapeutic target motif for future development of anti-resorptive treatments

Objectives. Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA). Methods. OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O. Results. Salubrinal suppressed the progression of OA by downregulating p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation level of eIF2α, it did not suppress the progression of OA. Conclusions. Administration of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can be considered as a potential therapeutic agent for alleviating symptoms of OA. Cite this article: Bone Joint Res 2015;4:84–92

Bone regeneration includes a well-orchestrated series of biological events of bone induction and conduction. Among them, the Wnt/β-catenin signaling pathway is critical for bone regeneration. Being involved in several developmental processes, Wnt/β-catenin signaling must be safely targeted. There are currently only few specific therapeutic agents which are FDA-approved and already entered clinical trials. A published work has shown that Tideglusib, a selective and irreversible small molecule non-ATP-competitive glycogen synthase kinase 3-β(GSK-3β) inhibitor currently in trial for Alzheimer's patients, can promote tooth growth and repair cavities. [1]Despite some differences, they are some similarities between bone and tooth formation and we hypothesise that this new drug could represent a new avenue to stimulate bone healing. In this work, we locally delivered Tideglusib (GSK3β inhibitor) in the repair of femoral cortical window defects and investigated bone regeneration. A biodegradable FDA-approved collagen sponge was soaked in GSK-3βinhibitor solution or vehicle only (DMSO) and was implanted in 1 × 2 mm unicortical defects created in femora of 35 adult wild-type male mice. Bone defect repair on control and experimental (GSK-3βinhibitor) groups was assessed after 1 week (n=22), 2 weeks (n=24) and 4 weeks (n=24) with microCT and histological analysis foralkaline phosphatase (ALP, osteoblast activity), tartrate resistant acid phosphatase (TRAP, osteoclasts), and immunohistochemistry to confirm the activation of the Wnt/β-catenin pathway. Our results showed that Tideglusib significantly enhanced cortical bone bridging (20.6 ±2.3) when compared with the control (12.7 ±1.9, p=0.001). Activity of GSK-3β was effectively downregulated at day 7 and 14 resulting in a higher accumulation of active β-catenin at day 14 in experimental group (2.5±0.3) compared to the control (1.1±0.2, p=0.03). Furthermore, the onset of ALP activity appears earlier in the experimental group (day 14, 1.79±0.28), a level of activity never reached at any end-point by the control defects. At 4 weeks treatment, we observed a significant drop in ALP in the experimental group (0.47±0.05) compared to the control (1.01±0.19, p=0.02) and a decrease in osteoclast (experimental=1.32±0.36, control=2.23±0.67, p=0.04). Local downregulation of GSK-3β by tideglusib during bone defect repair resulted in significant increase in amount of new bone formation. The early upregulation of osteoblast activity is one explanation of bone healing augmentation. This is likely the effect of upregulation of β-catenin following pharmaceutical inhibition of GSK-3β since β-catenin activation is known to positively regulate osteoblasts, once committed to the osteoblast lineage. As a GSK-3β inhibitor, Tideglusib demonstrates a different mechanism of action compared with other GSK-3β antagonists as treatment was started immediately upon injury and did not interfere with precursor cells recruitment and commitment. This indicates that tideglusib could be used at the fracture site during the initial intraoperative internal fixation without the need for further surgery. This safe and FDA-approved drug could be used in prevention of non-union in patients presenting with high risk for fracture-healing complications

Age-related fragility fractures are highly correlated with the loss of bone integrity and deteriorated morphology of the osteocytes. Previous studies have reported low-magnitude high-frequency vibration(LMHFV) promotes osteoporotic diaphyseal fracture healing to a greater extent than in age-matched normal fracture healing, yet how osteoporotic fractured bone responds to the mechanical signal has not been explored. As osteocytes are prominent for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance fracture healing in ovariectomized metaphyseal fracture through morphological changes and mineralisation in the osteocyte Lacuno-canalicular Network(LCN). As most osteoporotic fractures occur primarily at the metaphysis, an osteoporotic metaphyseal fracture model was established. A total of 72 six-month old female Sprague-Dawley rats (n=72) were obtained(animal ethical approval ref: 16–037-MIS). Half of the rats underwent bilateral ovariectomy(OVX) and kept for 3 months for osteoporosis induction. Metaphyseal fracture on left distal femur was created by osteotomy and fixed by a plate. Rats were then randomized to (1) OVX+LMHFV(20 mins/day and 5 days/week, 35Hz, 0.3g), (2) OVX control, (3) SHAM+LMHFV, (4) SHAM control. Assessments of morphological structural changes, functional markers of the LCN(Scanning Electron Microscopy, FITC-Imaris, immunohistochemistry), mineralization status(EDX, dynamic histomorphometry) and healing outcomes(X-ray, microCT, mechanical testing) were performed at week 1, 2 and 6 post-fracture. One‐way ANOVA with post-hoc test was performed. Statistical significance was set at p < 0.05. Our results showed LMHFV could significantly enhance the morphology of the LCN. There was a 65.3% increase in dendritic branch points(p=0.03) and 93% increase in canalicular length(p=0.019) in the OVX-LMHFV group at week 2 post-fracture. Besides, a similar trend was also observed in the SHAM+LMHFV group, with a 43.4% increase in branch points and 53% increase in canaliculi length at week 2. A significant increase of E11 and DMP1 was observed in the LMHFV groups, indicating the reconstruction of the LCN. The decreasing sclerostin and increasing FGF23 at week 1 represented the active bone formation phase while the gradual increase at week 6 signified the remodelling phase. Furthermore, Ca/P ratio, mineral apposition rate and bone formation rate were all significantly enhanced in the OVX+LMHFV group. The overall bone mineral density in BV was significantly raised in the OVX+LMHFV group at week 2(p=0.043) and SHAM+LMHFV at week 6(p=0.04). Quantitative analysis of microCT showed BV/TV was significantly increased at week 2 in OVX+LMHFV group(p=0.008) and week 6(p=0.001) in both vibration groups. In addition, biomechanical testing revealed that the OVX+LMHFV group had a significantly higher ultimate load(p=0.03) and stiffness(p=0.02) at week 2. To our best knowledge, this is the first report to illustrate LMHFV could enhance osteocytes' morphology, mineralisation status and healing outcome in a new osteoporotic metaphyseal fracture animal model. Our cumulative data supports that the mechanosensitivity of bone would not impair due to osteoporosis. The revitalized osteocyte LCN and upregulated osteocytic protein markers implied a better connectivity and transduction of signals between osteocytes, which may foster the osteoporotic fracture healing process through an enhanced mineralisation process. This could stimulate further mechanistic investigations with potential translation of LMHFV to our fragility fracture patients

Aim. There is an ongoing controversy whether the observed benefit of infection risk reduction by ALBC outweighs the risk of possible antimicrobial resistance development. Methods. The scientific & clinical literature in PubMed, Medline and Embase has been systematically reviewed with the keywords “antibiotic resistance”, “antibiotic loaded bone cement”, “local antibiotics”, “bacterial colonization” and “joint infection”. In total 28 relevant publications were found with the majority of them reporting laboratory results. Only 7 papers focused on clinical septic situations & patient data. Results. Although rare as consequence of the initially high drug concentrations in situ, experimental and clinical studies demonstrated survival of resistant bacteria on ALBC with subsequent bacterial re-colonisation of the biomaterial. This was most notable for coagulase-negative staphylococci (CoNS). Bacterial survival in presence of ALBC represents a selection process of already pre-existing high-level resistant mutants and not antibiotic resistance induction. The use of antibiotic combinations with gentamicin in bone cement is associated with a markedly lower risk of survival of resistant bacteria. This is particularly important in patients at high infection risks and in septic revision cases. There is no clinical evidence for a widespread increase of clinically important gentamicin resistancies in the orthopaedic ward because of routine use of ALBC. On an individual basis, the benefit of a lower infection probability with combined systemic & local antibiotic application should outweigh the risk of selecting pre-existing resistant bacteria. Each prevented infection case means that a complex and extended antibiotic therapy with risk of antibiotic resistance development over time has been avoided for a patient. In those cases where pre-existing resistant bacteria have survived the prophylactic exposure to antibiotics in bone cement, they remain in vast majority still susceptible to the clinically important antibiotics used for treatment of prosthetic joint infections. Conclusions. The benefit of a lower infection probability with ALBC should outweigh the risk of selecting resistant bacteria against the particular antibiotic used in bone cement. A trend towards broad resistance development which may complicate treatment of infection cases was not found

Introduction. Highly cross-linked ultrahigh molecular weight polyethylene (UHMWPE) is the most common bearing surface used in total joint arthroplasty due to its excellent wear resistance. While radiation cross-linking is currently used, cross-linking using a cross-linking agent such as a peroxide can also be effective with improved oxidative stability, which can be achived by an antioxidant such as vitamin E. The peroxide cross-linking behavior of UHMWPE in the presence of vitamin E was unknown. We investigated the cross-linking behavior and the clinically relevant mechanical and wear properties of peroxide cross-linked, vitamin E-blended UHMWPE. Materials and Methods. Medical grade UHMWPE (GUR1050) was blended with vitamin E and the peroxide (2,5-Dimethyl-2,5-di(t-butylperoxy)hexyne-3 or P130) before compression molding. Various vitamin E (0.1, 0.2, 0.3, 0.5, 0.6, 0.8 and 1.0 wt%) and peroxide concentrations (0.5, 1 and 1.5 wt%) were studied. The cross-link density was calculated as previously described (Oral 2010). The wear rate was determined using a custom-designed pin-on-disc wear tester against CoCr polished discs at 2 Hz and a rectangular path of 5 × 10 mm in undiluted bovine serum (Bragdon 2001). Tensile mechanical properties were determined using Type V dogbones according to ASTM D638. Oxidative stability was determined using oxidation induction testing (Braithwaite 2010). Double-notching and IZOD impact testing was performed according to ASTM D256. Samples prepared with vitamin E concentrations of 0.3 wt% and above and P130 concentrations of 0.5 and 1 wt% were also terminally gamma sterilized. Controls were 150-kGy irradiated vitamin E blends of UHMWPE. Results and Discussion. The cross-link density of peroxide cross-linked UHMWPEs were higher than the irradiated controls at a given vitamin E concentration (For example 250, 301 and 355 mol/dm3 for 0.5, 1 and 1.5 wt% peroxide cross-linked UHMWPE compared to 217 mol/dm3 for 150 kGy irradiated UHMWPE; Figure 1). The cross-link density dependence of wear was similar to radiation cross-linked UHMWPE, resulting in clinically relevant wear rates of 0.5 to 1.5 mg/MC. While the cross-link density of radiation cross-linked UHMWPE became saturated at vitamin E concentrations above 0.3 wt% (Oral 2008), this was not observed in peroxide cross-linked UHMWPE (Figure 2), suggesting more efficient cross-linking in the presence of the antioxidant. The impact strength was 30% higher for the peroxide cross-linked UHMWPEs at the comparable wear rate compared to irradiated controls (72 vs. 56 kJ/m2). The oxidation induction time of all peroxide cross-linked UHMWPEs (up to 57 min) was higher than that of the 0.1 wt% vitamin E-blended, 150-kGy irradiated UHMWPE (6 min). Gamma sterilization of peroxide cross-linked vitamin E blends decreased wear (0.5 wt% peroxide in Figure 3). Thus, peroxide concentration for cross-linking can be reduced if terminal sterilization is used. The mechanical properties and the oxidative stability of the material were not significantly affected by gamma sterilization. Significance. Peroxide cross-linking enabled good wear resistance for high vitamin E concentration blends of UHMWPE (>0.3 wt%), previously not possible by irradiation. Peroxide cross-linking of vitamin E-blended UHMWPE can provide a one-step, cost-effective method to manufacture wear resistant total joint implants with improved oxidative stability

We reviewed 100 consecutive primary sarcoma patients identified from coding records from January 2009 to April 2011. A computerised system was used to access theatre records, and operative details were checked against patient notes to ensure accuracy. Data on demographics, pathology, surgical and oncological management was collected. Of the 100 patients reviewed, 52 were male and 48 female with an average age of 64.9 years (range 23–102 years). Of the 100 operations performed, 13 had primary reconstruction with a myocutanoeus flap, of which 9 varieties were used. Twenty-five patients had reconstruction with a split or full thickness skin graft and 9 patients had a limb amputation. Length of inpatient stay ranged from 0 to 63 days and was greatest for our amputee's. Mean operative time did not increase significantly with rise in case complexity. 31 of our patients received post-operative radiotherapy, one patient had induction radiotherapy whilst another had induction chemotherapy. 5 out of the 100 patients underwent re-excision due to incomplete margins being obtained at primary wide local excisions. We had one patient with a failed free latissimus dorsi flap, in which secondary reconstruction with pedicled gastrocnemius and skin grafting was successful. One patient had a scalp flap following a re-excision of a positive margin of an angiosarcoma. Using a combined oncological orthopaedic and reconstructive plastic surgery approach, in our centre 38% of patients require some form of soft tissue reconstruction following tumour resection, with 13% of all patients requiring microvascular flap reconstruction. We have a 9% amputation rate, which is comparable with other published series. Reconstruction following soft tissue sarcoma is complex and highly demanding, the challenges being best met by a combined orthoplastic surgical team

Aims

Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers.

INTRODUCTION. Recently the evolution of prosthesis technology allows the surgeon to replace entire limbs. These special prostheses or megaprostheses were born for the treatment of severe oncological bone loss. Recently, however, the indications and applications of these devices are expanding to other orthopaedic and trauma situations. Since some years we are implanting megaprostheses in non-oncological conditions such as septic post-traumatic failures represented by complex non-unions and critical size bone defects. The purpose of this study is to retrospectively evaluate the clinical outcome of this treatment and register all the complications and infection recurrence. MATERIAL AND METHOD. Between January 2008 and January 2016 we have treated 55 patients with septic post-traumatic bone defects In 48/55 cases we perform a 2 steps procedure: 1° step: resection, debridment, devices removal and antibiotic spacer implantation; 2° step: spacer removal and megaprosthesis implantation. In 7/55 patients in whom all the femur was infected, we performed a one step procedure by the complete removal of the femur and a megaprosthesis (Total Femur) implantation. RESULTS. We obtained good results from a clinical, laboratory and radiological point of view with restoration of the function of the affected limb. Only in 5/55 cases the infection recurred. All the Total Femur megaprosthesis implanted in a one step procedure healed without recurrence of infection. CONCLUSION. Megaprosthesis in severe septic bone loss can be considered, in extreme cases appropriately selected, as an available solution for the orthopedic surgeon. The two steps procedure gives the best results with safety and lower infection recurrence creating a membrane (Chamber Induction Technique) that can protect the prosthesis in a safe environment. We can perform a one step procedure only when all the infected segment is entirely removed. This type of complex surgery must be performed in specialized centers where knowledge and technologies are present

Background. Despite promising results have shown by osteogenic cell-based demineralized bone matrix composites, they need to be optimized for grafts that act as structural frameworks in load-bearing defects. The purpose of this experiment is to determine the effect of bone marrow mesenchymal stem cells seeding on partially demineralized laser-perforated structural allografts that have been implanted in critical femoral defects. Materials and Methods. Thirty-two wistar rats were divided into four groups according to the type of structural bone allograft; the first: partially demineralized only (Donly), the second: partially demineralized stem cell seeded (DST), the third: partially demineralized laser-perforated (DLP), and the fourth: partially demineralized laser-perforated and stem cell seeded (DLPST). Trans-cortical holes were achieved in four rows of three holes approximated cylindrical holes 0.5 mm in diameter, with centres 2.5 mm apart. P3 MSCs were used for graft seeding. Histologic and histomorphometric analysis were performed at 12 weeks. Results. DLP grafts had the highest woven bone formation, where most parts of laser pores were completely healed by woven bone. DST and DLPST grafts surfaces had extra vessel-ingrowth-like porosities. Furthermore, in the DLPST grafts, a distinct bone formation at the interfaces was noted. Conclusion. This study indicated that surface changes induced by laser perforation, accelerated angiogenesis induction by MSCs, which resulted in endochondral bone formation at the interface. Despite non-optimal results, stem cells showed a tendency to improve osteochondrogenesis, and the process might have improved, if they could have been supplemented with the proper stipulations

Blood conservation is an essential aspect of total hip arthroplasty (THA). As recently as 10 years ago, it was standard practice across North America for patients to undergo pre-operative autologous blood donation (PAD) prior to an elective TJA. Though the cost of PAD is about the same as allogenic blood transfusion, it has fallen out of favor due to mixed results. Instead, most surgeons have implemented a practice of obtaining pre-operative hemoglobin levels. If anemia is diagnosed, the patient should be worked up for the underlying cause. In cases of pre-operative anemia where a specific deficiency cannot be elucidated, consideration can be given to the use of erythropoietin (EPO). The routine use of tranexamic acid (TXA) has become the standard of care at most institutions since it is safe, inexpensive, easy to administer, and very effective at minimizing peri-operative blood transfusion. Intravenous TXA can be administered effectively in a variety of different ways and a number of different protocols are described. The popularised Mayo Clinic protocol is to administer TXA once prior to incision (1g IV in 50mL of normal saline) and once during wound closure. Acute normovolemic hemodilution is a technique utilised just before or after the induction of anesthesia in which whole blood is removed while keeping the patient normovolemic with acellular fluids (i.e. crystalloids or colloids). This technique is rarely used. Hypotensive anesthesia is a technique utilised to keep mean arterial pressures (MAP) at a level around 50mm Hg. It appears to be most effective with the use of epidural anesthesia. Certain patients may not be good candidates for hypotensive anesthesia (high cardiac risk factors), but it can be an effective corollary to other intra-operative measures. Historically, many surgeons practiced reflexive transfusion protocols rather than treating patients on an individual basis. Current practice has adopted a more pragmatic approach to transfusion. Specifically, patients are assessed for signs of anemia and are often allowed to drift well below 8g/dL as long as they remain asymptomatic and have a suitable cardiac risk

Introduction. Throughout the world the number of large joint arthroprosthetic implants continues to increase and consequently the number of septic complications with prosthesis mobilizations, periprostehtic bone loss or non-unions. The implant of large resection prosthesis (megaprosthesis) in selected patients could be a good solution both in hip and knee infected prosthesis with bone defects. The two stage techniques with a first operation to debride, prosthesis components removal and antibiotic spacer implantation followed by a subsequent final prosthetic implant offer great results even in highly complex patients. Objectives. The purpose of this study is to evaluate retrospectively the outcome after the implantation of megaprosthesis of the lower limbs in prosthetic infected revision. Methods. We have retrospectively evaluated all the patients we have treated with implantation of megaprosthesis in septic prosthesis revision. Between January 2008 and January 2014 we have treated 25 patients: 18 cases of hip revision and 7 cases of knee revision. All patients were treated with a two steps procedure. Results. We obtained good results from a clinical, laboratory and radiological point of view with restoration of the function of the affected limb in 22/25 cases. In 3/25 cases the infection recurred and an additional surgery was necessary. Conclusions. Megaprosthesis in large septic revision can be considered, in extreme cases appropriately selected, an available solution for the orthopedic surgeon able to restore function to the patient. The two steps procedure gives the best results with safety and lower infection recurrence creating a membrane (Chamber Induction Technique) that can protect the prosthesis in a safe environment. This type of complex surgery must be performed in specialized centers where knowledge and technologies are present