Reconstruction of the anterior cruciate ligament (ACL) allows to restore stability of the knee, in order to facilitate the return to activity (RTA). Although it is understood that the tendon autograft undergoes a ligamentous transformation postoperatively, knowledge about longitudinal microstructural differences in tissue integrity between types of tendon autografts (ie, hamstring vs. patella) remains limited. Diffusion tensor imaging (DTI) has emerged as an objective biomarker to characterize the ligamentization process of the tendon autograft following surgical reconstruction. One major limitation to its use is the need for a pre-injury baseline MRI to compare recovery of the graft, and inform RTA. Here, we explore the relationship for DTI biomarkers (fractional anisotropy, FA) between knees bilaterally, in healthy participants, with the hypothesis that agreement within a patient's knees may support the use of the contralateral knee as a reference to monitor recovery of the tendon autograft, and inform RTA. Fifteen participants with no previous history of knee injuries were enrolled in this study (age, 26.7 +/− 4.4 years; M/F, 7/8). All images were acquired on a 3T Prisma Siemens scanner using a secured flexible 18-channel coil wrapped around the knee. Both knees were scanned. A 3D anatomical Double Echo Steady State (DESS) sequence was acquired on which regions of interest (ROI) were placed consistent with the footprints of the ACL (femur, posteromedial corner on medial aspect of lateral condyle; tibia, anteromedial to intercondylar eminence). Diffusion images were acquired using fat saturation based on optimized parameters in-house. All diffusion images were pre-processed using the FMRIB FSL toolbox. The footprint ROIs of the ACL were then used to reconstruct the ligament in each patient with fiber-based probabilistic tractography (FBPT), providing a semi-automated approach for segmentation. Average FA was computed for each subject, in both knees, and then correlated against one another using a Pearson correlation to assess the degree of similarity between the ACLs. A total of 30 datasets were collected for this study (1/knee/participant; N=15). The group averaged FA (+/− standard deviation) for the FBPT segmented ACLs were found to equal 0.1683 +/− 0.0235 (dominant leg) and 0.1666 +/− 0.0225 (non-dominant leg). When comparing both knees within subjects, reliable agreement was found for the FBPT-derived ACL with a linear correlation coefficient (rho) equal to 0.87 (P < 0 .001). We sought to assess the degree of concordance in FA between the knees of healthy participants with hopes to provide a method for using the contralateral “healthy” knee in the comparison of autograft-dependent longitudinal changes in microstructural integrity, following ACL reconstruction. Our results suggest that good agreement in anisotropy can be achieved between the non-dominant and dominant knees using DTI and the FBPT segmentation method. Contralateral anisotropy of the ACL, assuming no previous injuries, may be used as a quantitative reference biomarker for monitoring the recovery of the tendon autograft following surgical reconstruction, and gather further insight as to potential differences between chosen autografts. Clinically, this may also serve as an index to supplement decision-making with respect to RTA, and reduce rates of re-injuries

The avascular nature of articular cartilage relies on diffusion pathways to obtain essential nutrients and molecules for cellular activity. Understanding these transport pathways is essential to maintaining and improving the health of articular cartilage and ultimately synovial joints. Several studies have shown that joint articulation is associated with fluid and solute uptake although it remains unclear what role sliding motion independently plays. This study investigates the role of sliding with a non-stationary contact area on the uptake of small molecular weight tracers into articular cartilage. Ten-millimeter diameter cartilage-bone plugs were obtained from porcine knee joints and sealed into purpose made diffusion chambers. The chambers were designed to eliminate diffusion from the radial edge and only allow diffusion through the articular surface. The bone side of the chamber was filled with PBS to maintain tissue hydration while the cartilage side was filled with 0.01mg/ml fluorescein sodium salt (FNa) prepared using PBS. Sliding loads with a non-stationary contact area were applied across the articular surface by a custom apparatus using a 4.5 mm diameter spherical indenter. A moving contact area was chosen to represent physiological joint motions. Reciprocal sliding was maintained at a rate of 5 mm/s for 2 and 4 hours. Control samples were subject to passive diffusion for 0, 4, and 88 hours. After diffusion tests, samples were snap frozen and 20 µm cross-sectional cuts were taken perpendicular to the sliding direction. Samples were imaged using a Zeiss AxioImager M2 epifluorescent microscope under 5× magnification with a filter for FNa. Intensity profiles were mapped from the articular surface to the subchondral bone. Unloaded control samples demonstrated minimal solute uptake at 4 hours penetrating less than 5% of the total cartilage depth. By 88 hours solute penetration had reached the subchondral bone although there was minimal accumulation within the cartilage matrix indicated by the relatively low intensity profile values. Samples that had been subjected to reciprocal sliding demonstrated accelerated penetration and solute accumulation compared to unloaded samples. After 1 hour of reciprocal sliding, the solute had reached 40% of the cartilage depth, this increased to approximately 80% at 4 hours, with much higher intensities compared to unloaded controls. Sliding motion plays an important role in the uptake of solutes into the cartilage matrix. Maintaining joint motion both post injury and in the arthritic process is a critical component of cartilage nutrition. Samples that had been subject to reciprocal sliding demonstrated accelerated solute penetration and accumulation in the cartilage matrix, exceeding steady state concentrations achieved by passive diffusion

Complex acetabular reconstruction for oncology and bone loss are challenging for surgeons due to their often hostile biological and mechanical environments. Titrating concentrations of silver ions on implants and alternative modes of delivery allow surgeons to exploit anti-infective properties without compromising bone on growth and thus providing a long-term stable fixation. We present a case series of 12 custom acetabular tri-flange and custom hemipelvis reconstructions (Ossis, Christchurch, New Zealand), with an ultrathin plasma coating of silver particles embedded between layers of siloxane (BioGate HyProtect™, Nuremberg, Germany). At the time of reporting no implant has been revised and no patient has required a hospital admission or debridement for a deep surgical site infection. Routine follow up x-rays were reviewed and found 2 cases with loosening, both at their respective anterior fixation. Radiographs of both cases show remodelling at the ilium indicative of stable fixation posteriorly. Both patients remain asymptomatic. 3 patients were readmitted for dislocations, 1 of whom had 5 dislocations within 3 weeks post-operatively and was immobilised in an abduction brace to address a lack of muscle tone and has not had a revision of their components. Utilising navigation with meticulous implant design and construction; augmented with an ultrathin plasma coating of silver particles embedded between layers of siloxane with controlled and long-term generation of silver ion diffusion has led to outstanding outcomes in this series of 12 custom acetabular and hemipelvis reconstructions. No patients were revised for infection and no patients show signs of failure of bone on growth and incorporation. Hip instability remains a problem in these challenging mechanical environments and we continue to reassess our approach to this multifaceted problem

Aim. Currently, gram-negative bacteria (GNB), including multidrug-resistant (MDR-GNB) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). To characterize the antimicrobial resistance patterns of Gram-negative bacteria (GNB) causing hip prosthetic joint infections in elderly patients treated at a Brazilian tertiary academic hospital. Method. This is a retrospective, cross-sectional study of patients over 60 years of age undergoing hip arthroplasty from 2018 to 2023 at a tertiary academic trauma, which were diagnosed with hip prosthetic joint infection. PJI diagnosed was based on EBJIS criteria, in which intraoperative tissue cultures identified the pathogens. Demographics, reason for arthroplasty, type of implant and susceptibility patterns using disk diffusion method were analysed. Results. Overall, among 17 elderly patients diagnosed with hip infected arthroplasty, 45 bacterial isolated were identified. Debridement, irrigation, antibiotic and implant retention (DAIR) procedures due to uncontrolled infection occurred in 47.0% (n=8/17), and five patients underwent more than two DAIR surgeries. Tissue cultures yielded eleven different bacterial species, with GNB accounted for 64.4% (n=29/45) of pathogens. Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa were identified in 34.5% (n=10/29), 17.25% (n=5/29), 13.8% (n=4/29), and 13.8% (n=4/29), respectively. In the resistance profile analysis, E. coli was most sensitive to antibiotics, whereas K. pneumoniae showed resistance rates higher than 70% for cephalosporins, carbapenems, and quinolones. All A. baumannii isolates were resistant to meropenem, and 80% of these isolates were resistant to amikacin. Conclusions. This study emphasizes the role of GNB in the microbiological profile of PJI among elderly patients at a tertiary hospital in a Brazilian centre. The present study portrays a worryingly higher rates of MDR-GNB, mainly to quinolones and cephalosporins resistance which have been the cornerstone of PJI antibiotic treatment. In addition, higher rates carbapenems and aminoglycosides resistance shows a threat to antibiotic treatment of PJI. More global studies need to be carried out to show a likely change in the microbial epidemiology of PJI

Aim. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is commonly associated with serious cases of community-onset skin and musculoskeletal infections (Co-SMSI). Molecular epidemiology analysis of CA-MRSA recovered from skin and soft tissues specimens is lacking in Latin America. This study aimed to identify phenotypic and genotypic features of MRSA isolates recovered from patients presenting Co-SMSI. Methods. Consecutive MRSA isolates recovered from Co-SMSI of patients admitted from March 2022 to January 2023 in a Brazilian teaching hospital were tested for antimicrobial resistance and characterized by their genotypic features. Identification was carried out by automated method and through MALDI-TOF MS. Antimicrobial susceptibility was tested by disk diffusion, broth microdilution and E-test strips for determination of the minimal inhibitory concentration (MIC) according to recommendations from the Brazilian Committee on Antimicrobial Susceptibility Testing (BrCAST) and European Committee on Antimicrobial Susceptibility Testing (EUCAST). Gene mecA characterization and Sccmec typing were performed by multiplex polymerase chain reaction (PCR) assay, and gene lukF detection by single PCR. Patients were prospectively followed up for two months, in order to determine their clinical characteristics and outcomes. Results. Overall, 48 Staphylococcus aureus isolates were obtained from 68 samples recovered from patients with Co-SMSI. Twenty two (42%) were phenotypically characterized as MRSA, although mecA gene was only identified in 20 of those samples. Sccmec was untypable in 12 isolates, Sccmec was type II in 4 isolates and 2 were classified as type IVa. LukF gene was identified in 5 isolates. Antimicrobial resistance profile showed that all isolates were susceptible to linezolid and vancomycin with MIC = 1 and MIC = 2 in 66,7% and 33.3%, respectively. Susceptibility to quinolones was worryingly low and none of the isolates were sensitive to usual doses of ciprofloxacin and levofloxacin, and showed increased rates of resistance to increased exposure to these drugs, as well. Isolates were both susceptible to gentamicin and tetracycline in 85% and resistance to also Sulfamethoxazole/Trimethoprim occurred in only 2 isolates. Mortality rate evaluated within 1 month of the initial evaluation was 10% among MRSA isolates. Conclusions. Our results showed that CA-MRSA isolates causing Co-SMSI demonstrated an alarming pattern of multidrug resistance, including to β-lactam and quinolones, which have been commonly prescribed as empirical therapy for patients with skin, soft tissue and musculoskeletal infections

Aim. Deadspace is the tissue and bony defect in a surgical wound after closure. This space is presumably poorly perfused favouring bacterial proliferation and biofilm formation. In arthroplasty surgery, an obligate deadspace surrounding the prosthesis is introduced and deadspace management, in combination with obtaining therapeutic prophylactic antibiotic concentrations, is important for limiting the risk of acquiring a periprosthetic joint infection (PJI). This study aimed to investigate cefuroxime distribution to an orthopaedic surgical deadspace in comparison with plasma and bone concentrations during two dosing intervals (8 h × 2). Method. In a setup imitating shoulder arthroplasty surgery, but without insertion of a prosthesis, microdialysis catheters were placed for cefuroxime sampling in a deadspace in the glenohumeral joint and in cancellous bone of the scapular neck in eighteen pigs. Blood samples were collected from a central venous catheter as a reference. Cefuroxime was administered according to weight (20 mg/kg). The primary endpoint was time above the cefuroxime minimal inhibitory concentration of the free fraction of cefuroxime for Staphylococcus aureus (fT > MIC (4 µg/mL)). Results. During the two dosing intervals, mean fT > MIC (4 µg/mL) was significantly longer in deadspace (605 min) compared with plasma (284 min) and bone (334 min). For deadspace, the mean time to reach 4 µg/mL was prolonged from the first dosing interval (8 min) to the second dosing interval (21 min), while the peak drug concentration was lower and half-life was longer in the second dosing interval. Conclusions. In conclusion, weight-adjusted cefuroxime fT > MIC (4 µg/mL) and elimination from the deadspace was longer in comparison to plasma and bone. Our results suggest a deadspace consolidation and a longer diffusions distance, resulting in a low cefuroxime turn-over. Based on theoretical targets, cefuroxime appears to be an appropriate prophylactic drug for the prevention of PJI. Acknowledgments. We would like to thank Department of Clinical Medicine, the surgical research laboratories, Aarhus University Hospital and Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark, for supporting this study. This research was funded by Novo Nordisk Foundation, grant number [NNF20OC0062032, 2020]

Aim. Bone and implant-associated infections caused by microorganisms that grow in biofilm are difficult to treat because of persistence and recurrence. Systemic administration of antibiotics is often inefficient because the poor vascularization of the site of infection. This issue has led to the development of biomaterials capable to locally deliver high doses of therapeutic agents to the injured bone with minimal systemic effects. In this context, calcium sulphate/hydroxyapatite (CS/HA) bone graft substitutes are widely used being safe, osteoconductive and resorbable biomaterials that can be easily enriched with consistent amounts of antibiotics. In this in vitro study, the capability of the eluted antibiotics to select the tested bacterial strains for antibiotic resistance was evaluated to confirm the safe use of the product. Method. S. aureus, S. epidermidis and P. aeruginosa isolated in our Institute from bone and joint infection with different resistance phenotypes were used. 6 × 2.5 mm CS/HA discs were generated by pouring the antibiotic loaded formulations in a mold and were used as a modified disk diffusion test. The resistance selection was evaluated by subculturing cells growing on the edge of the zone of inhibition (ZOI) for seven days. Minimum inhibitory concentrations (MICs) of gentamicin and vancomycin were determined by broth microdilution method before and after the selection of resistance assay. In addition, MICs were assessed after seven day passage on antibiotic free agar plates to evaluate if eventual decrease of antibiotic susceptibility was stable or only transient. Results. Commonly, no adaptation in presence of both CS/HA formulations was observed by analysing ZOI on agar medium. The kinetic of decrease of the ZOI was similar between the strains, with the exception of gentamicin resistant staphylococci in presence of gentamicin loaded CS/HA, which was faster with respect to the susceptible strains. Conclusions. The present study shows that elution of gentamicin and vancomycin from CS/HA bone graft substitutes did not induce a decrease in susceptibility to these antibiotics in an in vitro setting, suggesting the safe use of the product

Testing potential therapeutics in the regeneration of the disc requires the use of model systems. Although several animal models have been developed to test intervertebral disc (IVD) regeneration, application becomes costly when used as a screening method. The bovine IVD organ culture system offers an inexpensive alternative, however, in the current paradigm, the bony vertebrae is removed to allow for nutrient diffusion to disc cells. This provides limitations on the conditions and strategies one can employ in investigating IVD regeneration and mechanisms in degenerative disc disease (i.e. complex loading). Although one method has been attempted to extend the survival of bovine vertebrae containing IVDs (vIVD) cell viability declined after two weeks in culture. Our goal was to develop and validate a long-term organ culture model with vertebral bone, which could be used subsequently for studying biological repair of disc degeneration and biomechanics. Preparation of vIVDs: Bovine IVDs from the tails of 22–28-month-old steers were prepared for organ culture by parallel cuts through the adjacent vertebral bodies at 1cm from the endplates using an IsoMet®1000 Buehler precision sectioning saw. vIVDs were split into two groups: IVDs treated with PrimeGrowth Media kit (developed by Intervertech and licensed to Wisent Bioproducts) and IVDs with DMEM. The PrimeGrowth group was incubated for 1h in PrimeGrowth Isolation Medium (Cat# 319–511-EL) and the DMEM group for 1h in DMEM. After isolation, IVDs were washed in PrimeGrowth Neutralisation Medium (Cat# 319–512-CL) while the other IVDs were washed in DMEM. The discs isolated with PrimeGrowth and DMEM were cultured for up to 5 months in sterile vented 60 ml Leakbuster™ Specimen Containers in PrimeGrowth Culture Medium (Cat# 319–510-CL) and DMEM with no mechanical load applied. Live/Dead Assay: vIVDs cultured for 1 or 5 months were dissected and cell viability was assessed in different regions by confocal microscopy using Live/Dead® (Invitrogen) fluorescence assay. Glucose Diffusion: After one month of culture, vIVDs were incubated for 72h in diffusion medium containing PBS (1x), CaCl2 (1mM), MgCl2 (0.5mM), KCl2 (5mM), 0.1% BSA and 150µM 2-NDBG, a D-glucose fluorescent analogue. Discs were dissected and IVD tissues were incubated in guanidinium chloride extraction buffer. Extracts were measured for fluorescence. After 5 months in culture, vIVDs prepared with PrimeGrowth kit demonstrated approximately 95% cell viability in all regions of the disc. However, dramatic reductions (∼90%) in vIVD viability were measured in DMEM group after 1 month. vIVD viability was related to the amount of 2-NDBG incorporated into the disc tissue. We have developed a novel method for isolating IVDs with vertebral bone capable of long-term viability. This method may not only help in the discovery of novel therapeutics in disc regeneration, but could also advance our understanding on complex loading paradigms in disc degeneration

Aim. Many bone and joint infections, in spite of appropriated antibiotics therapy and surgery, lead to a therapeutic dead end. We are then faced with a chronic infection with or without continuous antibiotic treatment, with daily local care, and an exhorbitant economic and social cost. Pami the incriminated factors: the presence of foreign implant material, the poor diffusion of antibiotics at the infectious site, the presence of biofilm. The bacteriophages, biological drug, natural environmental viruses possess the properties to meet these difficulties: well diffusion to the infectious focus with possibilities of local use, destruction of the biofilm allowing a release of the bacteria and a synergistic effect with the antibiotics, antibiofilm effect for the restoration of osteoblastosis. Method and results. We report a cohort of phage - treated patients with or without antibiotics in bone and joint infections in a therapeutic dead end. Without disponibility of therapeutic phages available in the European Union, commercial cocktails of phages, antistaphylococcal or polyvalent, of Russian* or Georgian** origin were used. Ten patients have benefited since 2008 from phages, alone or in combination with an adapted antibiotic therapy. Patients were 40 to 89 years old and had chronic bone and joint infections except for one case with acute MRSA infection on femoral implant. Bacteria were Staphylococcus aureus 7 times, Pseudomonas aeruginosa 3 times, Klebsiella 2 times. In 4 cases implant was left in place (knee prosthesis, femoral screw plate) or introduced (1 screw in 1 case) during the procedure. In all cases except 1 patient, the phages were applied in per-operative. With a follow-up of up to 9 years for some patients, the initial bacteria were eradicated and in 2 cases replaced by another bacterium (Pseudomonas in place of S. aureus in one case and Enterococcus in place of P. aeruginosa for an elderly patient with a knee prosthesis without possible surgery. Conclusion. The combination of surgery, phages and antibiotics appear a very efficient option, to treat patients with bone and joint infections in therapeutic dead end. The quick availability of these treatments for these patients is a health emergency. *Microgen® Pharma. **Eliava Institute

Introduction. Radiation cross-linked UHMWPE is preferred in total hip replacements due to its wear resistance [1]. In total knees, where stresses are higher, there is concern of fatigue damage [2]. Antioxidant stabilization of radiation cross-linked UHMWPE by blending vitamin E into the polymer powder was recently introduced [3]. Vitamin E greatly hinders radiation cross-linking in UHMWPE [4]. In contrast peroxide cross-linking of UHMWPE is less sensitive to vitamin E concentration [5]. In addition, exposing UHMWPE to around 300°C, increases its toughness by inducing controlled chain scission and enhanced intergranular diffusion of chains, simultaneously [6]. We present a chemically cross-linked UHMWPE with high vitamin E content and improved toughness by high temperature melting. Methods and Materials. Medical grade GUR1050 UHMWPE was blended with vitamin E and with 2,5-Di(tert-butylperoxy)-2,5-dimethyl-3-hexyne or P130 (0.5% Vitamin-E and 0.9% P130). The mixed powder was consolidated into pucks. The pucks were melted for 5 hours in nitrogen at 300, 310 and 320°C. One set of pucks melted at 310°C was accelerated aged at 70°C at 5 atm. oxygen for 2 weeks. Tensile mechanical properties were determined using ASTM D638. Izod impact toughness was determined using ASTM D256 and F648. Wear rate was determined using a bidirectional pin-on-disc (POD) tester with cylindrical pins of UHMWPE against polished CoCr discs in undiluted, preserved bovine serum. Results. The vinyl index increased as a function of temperature (Fig 1a). Cross-link density steadily decreased and impact strength increased with increasing vinyl index (Fig 1b). The ultimate tensile strength (UTS) was not affected by HTM (Table 2). Impact strength was significantly improved for all treatment temperatures (P<0.05) and wear was significantly increased only for the sample melted at 320°C (Table 2). Discussion. High temperature melting (HTM) was shown to increase toughness of UHMWPEs presumably due to controlled chain scissioning and increased intergranular diffusion of chains [6]. For radiation cross-linked UHMWPE, it was shown that an increase in elongation-at-break and impact strength could be obtained without sacrificing wear resistance up to an elongation of about 500% [7]. This vitamin E-blended, peroxide cross-linked, high temperature melted UHMWPE has very high oxidation resistance due to its high antioxidant content, high wear resistance due to cross-linking and much improved toughness, representing an optimum joint replacement surface. For figures/tables, please contact authors directly.

This study was performed to investigate the concentration of silver ions release up to a time of 9 weeks as well as the antimicrobial activity of silver sulfate and Nano-silver mixed bone cement on Candida albicans, in expectation of a new way of therapy in manner of a time limited application – a silverions releasing bone cement spacer. Two different kinds of silver products were used and mixed with polymethylmetacrylate (PMMA, De Puy) bone cement:. Nano-silver with a particle size of 5–50 nm and active surface of 4 m2/ g. (Nanonet Styria, Austria). Silver sulfate in a finely powdered form (Fisher, GB). Concentrations of 0.1%, 0.5%, 1% and 5% of the Nano-silver and the silver-salt by weight were mixed with the dry powder portion of the cement. To test the silver-ions release from the silver-containing bone cement two models of elution, a static model and a dynamic model were created. To test the antifungal effectiveness of the various concentrations of Ag-PMMA the bone cement samples were tested by agar diffusion assay. With respect to minimal inhibition concentration (MIC) the sample containing 0.5 % silver sulfate showed required concentration at the dynamic elution model but none of the nano-silver samples did. In static elution model we measured the maximum concentration of 466.5 µg/l at the 0.5 % silver sulfate sample which is much below the toxic concentration. Agar diffusion assay showed no zone of inhibition from Nano-silver samples. In contrast, silver sulfate containing samples showed a zone of inhibition exactly growing, depending on the samples silver sulfate concentration. According to results, silver sulfate addition to PMMA might be another approach in treatment of candida associated periprosthetic joint infection

Ten RCTs published between 2000 and 2013 support treating distal radius buckle fractures and other low-risk distal radius fractures with a removable splint and with no orthopaedic follow-up. Application of this evidence has been shown to be variable and suboptimal resulting in unnecessary costs to a strained healthcare system. The Canadian evidence on this topic has been generated by subspecialist physicians working in paediatric hospitals. It is unclear what factors affect the dissemination of this information. We investigated the association of hospital type and physician type with the application of best-evidence treatment for low-risk distal radius fractures in children with the goal of improving our understanding of evidence diffusion in Ontario for this common injury. We performed a retrospective population-based cohort study using linked health care administrative data. We identified all children aged 2–14 treated in Ontario emergency departments from 2003–2015 with distal radius fractures with no reduction and no operation within a six week period. We excluded refractures and children with comorbidities. We evaluated the followup received – orthopaedic, general practitioner, or none. We examined the data for trends over time. Multivariable log binomial regression was used to quantify associations between hospital and physician type and best-evidence treatment. We adjusted for patient-related variables including age, sex, rural or urban location, and socioeconomic status. 70,801 fractures were analyzed. Best-evidence treatment was more likely to occur in a small (RR 1.86, 95%CI 1.72–2.01), paediatric (RR 1.16, 95%CI 1.07–1.26), or community (RR 1.13, 95%CI 1.06–1.20) hospital compared with treatment in a teaching hospital. Best-evidence treatment was more likely if initial management was by a paediatrician with additional emergency medicine training (RR 1.73, 95%CI 1.56–1.92) or paediatrician (RR 1.22, 95%CI 1.11–1.34). Paediatric and teaching hospitals have improved their use of best-evidence over time while other hospital types have stagnated or deteriorated. Paediatricians, paediatricians with additional emergency medicine training, and emergency medicine residency trained physicians have improved their use of best-evidence over time, while other physician types have stagnated or deteriorated. Overall, only 20% of patients received best-evidence treatment and 70% had orthopaedic follow-up. Significant over-utilization of resources for low-risk distal radius fractures continues decades after the first randomized trials showed it to be unnecessary. Physician type and hospital rurality are most strongly associated with best-evidence treatment. Physician types involved in generating, presenting, and publishing best-evidence for this fracture type are successfully implementing it, while others have failed to change their practices. Rural hospitals are excellent resource stewards by necessity, but are deteriorating over time. Our results strongly indicate the need for targeted implementation strategies to explicitly apply clinical evidence in clinical practice Canada-wide, with the goal of providing more cost-effective care for common children's fractures

Aim. Local concentration of antibiotic at the site of infection is a major parameter for its efficiency. However, bone diffusion is poor leading either to their non-use (ex: gentamicin) or the use of high concentration (ex: vancomycin). Local administration could optimize their local concentration combined with lower side effects. We report the clinical experience and pharmacological results of an antibiotic loaded porous alumina used to replace infected bone in 4 patients. Method. Two patients had a destroyed sternum following mediastinitis; one presented a femoral chronic osteomyelitis due to MRSA and one had an infected ankle arthroplasty. The ceramic was loaded with gentamicin in three cases and vancomycin for the ankle infection. Local dosages thanks to Redon's drain and blood samples were performed. Loading was done to protect the device while implanted in an infected area and was combined with conventional antibiotic therapy. Results. In comparison to pharmacological parameters: C. max. /MIC>8 for gentamicin or AUC/MIC>400 for vancomycin, local concentrations were dramatically higher than the one needed (table). Vancomycin concentration was still high after H48. Meanwhile, blood samples didn't find the presence of gentamicin during the 48 hours following implantation. After more than one year of follow-up for all the patients, there is no relapse of infection or signs of device infection, whereas all samples perform during implantations grew with bacteria, meaning that loaded antibiotic played a major role avoiding device colonization in combination with surgical debridement and cleaning. Conclusions. This mode of administration allows an optimization of the antibiotic delivery, maximizing local concentrations while reducing systemic toxicity. In addition, ceramic mechanical characteristics allow bone replacement (strength >3 times the one of the cancellous bone and osseointegration) and thus enables one-stage surgery instead of two-stage like for the patient with chronic osteomyelitis thanks to a good primary stability. For any figures or tables, please contact the authors directly

Aim. Intramedullary osteomyelitis remains a challenge in the treatment of bone infections, requires organized, sequential and effective management to prevent its spread and subsequent recurrence. Errors are often made in the comprehensive treatment of this type of infection classified as type 1 of Cierny-Mader, where you can perform an insufficient treatment or in some cases perform very extensive and unnecessary bone resections. A rigorous protocol is proposed, by stages to achieve the total eradication of the infection and a surgical tactic that avoids diffusion of the infection or recurrences. Method. In the prospective case series study, 16 patients with type 1 intramedullary infection of Cierny Mader, diagnosed by radiology, TAC or MRI were included. The microbiological protocol is carried out, with the germ typing and the corresponding antibiogram, at least 3 samples of deep tissues, the biofilm and segments of dead bone are taken. In the surgical tactic, intramedullary sequestrations are resected, the intramedullary canal is cleaned by stages, initially in the most inflammatory focus detected, the medullary canal is accessed through a planned and defined bone window, with round edges to avoid fractures and allowing access To the flexible reamer and cleaning guides, an additional window is made that avoids the blood dissemination of the infection, the septic embolisms or the contamination of the underlying soft tissues. It is defined if it requires stabilization of the bone with internal or external devices, therapies are applied locally to avoid recolonization, using Bioglass or absorbable substitutes with selective antibiotic. The treatment is associated with intravenous antibiotic therapy between 2 and 6 weeks according to the type of germ and if it is multiresistant. It guarantees skin coverage and protection of structures at risk such as nerves, tendons and exposed bone. Results. Successful treatment results are obtained, infection eradication in 100% of cases, the healing of osteomyelitis is achieved by applying an integral management of the intramedullary canal Osteomyelitis and a complete protocol is established. Conclusions. The tactic and surgical technique applied in the integral management of intramedullary bone infection is essential to obtain definitive results in the eradication of bone infection. Care must be taken that the debridement is complete of the intramedullary canal and additionally, segmental or exaggerated resection of viable bone must be avoided, which survives and heals after the integral management of the infection with effective antibiotic therapy

Background. Additive manufacturing (AM) has created many new avenues for material and manufacturing innovation. In orthopaedics, metal additive manufacturing is now widely used for production of joint replacements, spinal fusion devices, and cranial maxillofacial reconstruction. Plastic additive manufacturing on the other hand, has mostly been utilized for pre-surgical planning models and surgical cutting guides. The addition of pharmaceuticals to additively manufactured plastics is novel, particularly when done at the raw material level. The purpose of this study was to prove the concept of antibiotic elution from additively manufactured polymeric articles and demonstrate feasibility of application in orthopaedics. Methods. Using patented processes, three heat-stable antibiotics commonly used in orthopaedics were combined with six biocompatible polymers (2 bioresorbable) into filament and powder base materials for fused deposition modeling (FDM) and selective laser sintering (SLS) AM processes. Raw materials of 1%, 2%, and 5% antibiotic concentrations (by mass) were produced as well as a blend of all three antibiotics each at 1% concentration. Thin disks of 25 mm diameter were manufactured of each polymer with each antibiotic at all concentrations. Disks were applied to the center of circular petri dishes inoculated with a bacterium as per a standard zone of inhibition, or Kirby-Bauer disk diffusion tests. After 72 hours incubation, the zone of inhibited bacterial growth was measured. Periprosthetic joint infection (PJI) of the knee was selected as the proof-of-concept application in orthopaedics. A series of tibial inserts mimicking those of a common TKR system were manufactured via SLS using a bioresorbable base material (Figure 1). Three prototype inserts were tested on a knee wear simulator for 333,000 cycles following ISO 14242–1:2014 to approximate 2–4 months of in vivo use between surgeries of a 2-stage procedure for PJI. Gravimetric measurement and visual damage assessment was performed. Results. Bacterial growth was inhibited to a mean diameter of 32.3 mm (FDM) and 42.2 mm (SLS) for nearly all combinations of polymers and concentrations of antibiotics. Prototype tibial inserts experienced an average of 200 mg of wear during testing and demonstrated no evidence of cracking, delamination or significant deformation (Figure 2). Conclusion. Bench-level testing of these novel antibiotic-eluting polymers demonstrates feasibility for their application in orthopaedic medicine. In particular, treatment of stubborn PJI with potential for increased and sustained antibiotic elution, patient-specific cocktailing, and maintenance of knee joint structure and function compared to existing PJI products and practices. Subsequent testing for these novel polymers will determine static and dynamic (wear-induced) antibiotic elution rates. For any figures or tables, please contact the authors directly

Aim. Staphylococcus aureus (SA) chronic bone and joint infections (BJI) are characterized by a progressive destruction of bone tissue associated to SA persistence which results in a large number of relapses (10–20%). The main factors proposed for these failures are: i) a weak diffusion of antibiotics in bone tissue, ii) formation of biofilm, iii) the bacterial internalization by the cells responsible for bone mineralization, namely the osteoblasts (OB). Our in vitro and in vivo work aimed at providing new information on the impact of SA, more specifically of internalized SA, on bone homeostasis. Method. Effect of SA infection (8325–4/FnBP+; DU5883/FnBP-) on the viability, differentiation and mineralization of an OB cell line was measured in vitro by MTT and Phosphatase Alcaline (PAL) activity assays and quantification of calcium deposits using Alizarin red, respectively. A gentamicin protection assay (GPA) confirmed that the effects observed are due solely to the internalized SA. In vivo, X-ray microtomography (μCT) and 3D reconstruction was used to evaluate the impact of SA infection on bone formation and bone resorption in a mouse model of femur infection. Results. In vitro, the infection of pre-OB decreases their capacity of differentiation into mature OB displaying a PAL activity. This effect depends on both the multiplicity of infection and invasion capacities of the strains used (8325–4 (invasion competent) vs DU5883 (invasion incompetent)). The infection delays mineralization after 5 days (p <0.0001), likely due to a cytotoxic effect. Indeed, after bacterial clearance at J21, this delay is made up (no difference between infected and uninfected cells). These results are consistent with the preliminary in vivo observations (μCT) showing a significant decrease in the thickness of trabecular of infected femurs with 8325–4 compared to DU5883 and non-infected femurs (p< 0, 0041). Conclusions. These results suggest that the internalization of SA leads to an imbalance of bone remodeling, in particular by a cytotoxic effect on the pre-OB and a slowed-down formation of bone tissue by OB, leading to a significant bone loss. The ongoing study of the cellular and bacterial mechanisms involved in this internalization should allow a better management of chronic BJI

Aim. Aim of this study was to evaluate the ability of Sb-1 to enhance the antibiotic activity (tested in combination) degrading the biofilm matrix (impairing the freely diffusion of antimicrobials) and specifically targeting “persister” cells (biofilm sub-population tolerant to most antibiotics and responsible for the infection recalcitrance) of methicillin-resistant Staphylococcus aureus. Method. MRSA ATCC 43300 24h-old biofilm was treated for 18h with Sb-1 titers (from 10. 4. to 10. 6. pfu/ml). Biofilm matrix was evaluated by confocal laser scanning microscopy after staining with wheat germ agglutinin conjugate with Alexafluor488 (WGA488) to label exopolysaccharide matrix and Syto 85 to label bacterial cells. Persister status was induced using two different protocols: i) by exposing stationary phase S. aureus to 400 µg/ml carbonyl cyanide m-chlorophenylhydrazone (CCCP) in PBS for 3h at 37°C and ii) by treatment of 24h old biofilm with 512 µg/ml ciprofloxacin for further 24h at 37°C. Then, induced persister cells and non-induced controls (10. 6. CFU/ml) were treated with 10. 4. PFU/ml and 10. 7. PFU/ml Sb-1 for 3h, followed by CFU counting. Alternatively, bacteria were washed and incubated in fresh BHI medium for the resumption of normal growth and the bacterial growth assessed after further 24 hours. Results. Sb-1 showed a dose-dependent reduction of exopolysaccharide components of MRSA biofilm matrix at sub-inhibiting phage titers. With 10. 6. PFU/ml Sb-1, no fluorescent signal related to WGA488 was detected, although bacterial viability was not impaired. Higher Sb-1 titer (10. 7. PFU/ml) determined a strong reduction (ranging between 2.5 – 5 log CFU/ml) of persister cells. By contrast, in presence of 10. 4. PFU/ml Sb-1, no reduction was observed in persister cells. However, persister cells pre-treated with 10. 4. pfu/ml Sb-1 were completely killed when bacteria were inoculated after phage treatment in fresh medium, reverting to a normal-growing phenotype. Conclusions. Due to its ability to degrade the MRSA exopolysaccharide matrix at sub-inhibitory concentrations and kill persister cells, directly at higher titers or indirectly with lower titers, Sb-1 phage is a valid therapeutic option to be used alone or in combination with current antibiotics for the successful eradication of methicillin resistant S. aureus biofilm associated with prosthetic joint infections

Aim. The frequency of arthroplasty among older people is increasing. Taking care of Prosthetic Joint infection (PJI) in this specific population is a challenge. The purpose of this multicentric retrospective study was to evaluate the bacterial epidemiology of hip and knee PJI in octogenarians and nonagenarians over ten years. Method. Data were collected using two softwares* in each of the 4 Centers participating. Inclusion criteria:. -. age ≥ 80 years PJI (knee or hip). -. between January 2007 and December 2016. -. microbiological data available (strains isolated from osteo-articular samples). Bacterial identification: biochemical methods, followed by Malditof since 2009. For Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacteriaceae, resistance profiles to antibiotics frequently used in PJI were collected. Antimicrobial susceptibility testing: disk diffusion (recommendations: French Society of Microbiology yearly updated). Results. 413 patients were included: median age was 85 years and sex ratio was 0.6. 137 were knee PJI and 276 hip. 34% of the infections occurred < 1 month after implantation, and 49% > 6 months after implantation. Among all bacterial isolates (N=817), there was 55% of Gram positive cocci and 36% of Gram negative rods. 112 (27%) were polymicrobial infections. There was a majority of gram negative rods (41%) among isolates from polymicrobial infections. Concerning drug resistance, there was a stable proportion of ESBL among Enterobacteria (16%), whereas Methicillin resistance among S. aureus decreased from 43% in 2007 to 12% in 2016. Conclusions. An important proportion of PJI in older patients are polymicrobials, and a lot of them involve gram negative rods, almost as frequently as S. aureus. These infections are difficult to treat, and resistance of gram negative strains is one of the obstacles to overcome among these patients where surgery is not always possible. * Sirweb (I2A) and Glims (MIPS)

Background. Vancomycin and fosfomycin are antibiotic commonly used in Methicillin-resistant Staphylococcus aureus (MRSA) infection. This study compares the efficacy of articulating cement spacer implegnated with vancomycin and articulating cement spacer implegnated with fosfomycin to inhibit MRSA. Methods. Vancomycin implegnated articulating cement spacers and Fosfomycin implegnated articulating cement spacers were immersed in sterile phosphate buffered saline(PBS) and then incubated at 37 C. The samples were collected and change daily. Aliquots were tested for MRSA inhibition by disc diffusion method. The inhibition zones diameters were measured. Results. Vancomycin group showed an MRSA inhibition zone up to four weeks. However, Fosfomycin group showed inhibition zone in day 3 in some samples but after that no sample had the potential to inhibit MRSA. Conclusion. In this experiment. Vancomycin impregnated articulating cement spacers showed longer efficacy to inhibit MRSA when compared to Fosfomycin

Aim. Thermal stability is a key property determining the suitability of an antibiotic agent for local application. Long-term data describing thermal stability without interference from carrier materials are scarce. Method. In this study, a total of 38 common antibiotic agents have been maintained at 37 °C in saline solution, and degradation and antibacterial activity assessed over 6 weeks. The impact of an initial supplementary heat exposure mimicking exothermically-curing bone cement has also been tested. Antibiotic degradation was assessed by chromatography coupled to mass spectrometry or immunoassays, as appropriate. Antibacterial activity was determined by Kirby-Bauer disk diffusion assay. Results. The heat exposure mimicking curing bone cement had minimal effect on stability for most antibiotics, except for gentamicin, which experienced approximately 25% degradation as measured by immunoassay. Beta-lactam antibiotics were found to degrade quite rapidly at 37°C regardless of whether there was an initial heat exposure or not. However some of them maintained relevant concentrations and activity for 2–3 weeks, particularly aztreonam. Excellent long-term stability was observed for aminoglycosides, glycopeptides, tetracyclines and quinolones under both conditions. Conclusions. This study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics. For example, tobramycin would be more suitable for application with bone cement than gentamicin, as it was found to be resistant to heat exposure mimicking curing bone cement