Abstract. OBJECTIVES. Staphylococcus aureus is one of the most common pathogens in orthopaedic biomaterial-associated infections. The transition of planktonic S. aureus to its biofilm phenotype is critical in the pathogenesis of biomaterial-associated infections and the development of antimicrobial tolerance, which leads to ineffective eradication in clinical practice. This study sought to elucidate the effect of non-lethal dispersion on antimicrobial tolerance in S. aureus biofilms. METHODS. Using a methicillin-sensitive S. aureus reference strain, the effect of non-lethal dispersion on gentamicin tolerance, cellular activity, and the intracellular metabolome of biofilm-associated bacteria were examined. Gentamicin tolerance was estimated using the dissolvable bead biofilm assay. Cellular activity was estimated using the triphenyltetrazolium chloride assay. Metabolome analysis was performed using tandem high-performance liquid chromatography and mass spectrometry. RESULTS. Non-lethal dispersion of biofilm-associated S. aureus was associated with a four-fold reduction in gentamicin tolerance and a 25% increase in cellular respiration of both dispersed and adherent cells. Metabolome analysis found non-lethal dispersion reduced intracellular levels of L-ornithine and L-proline, with increased levels of cyclic nucleotides (p<0.05) in both liberated cells and the remaining biofilm-associated bacteria. These metabolomic changes have previously been shown to be associated with inactivation of the carbon catabolite repression mechanism, which is a key regulatory gatekeeper in the cellular resuscitation of dormant S. aureus cells. CONCLUSION. The metabolomic pipeline described in this study presents a valuable tool in the elucidation of molecular mechanistic pathways in biofilm pathogenesis. Kreb's cycle reactivation, through the carbon catabolite repression regulatory mechanism, has been shown to be associated with the reversal of biofilm-associated gentamicin tolerance. Understanding of the biosynthetic changes associated with the biofilm state will assist in the discovery of novel therapeutic targets in the management of biomaterial-related infections. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Background. After surgical correction of thoracic scoliosis, an improvement in the cardio-respiratory adaptation to exercise would be expected because of the correction of the rib cage associated with the spinal deformity. This work intended to evaluate the physiologic responses to incremental exercise in patients undergoing surgical correction of adolescent idiopathic scoliosis (AIS). The hypothesis of this study was that the exercise limitations described in patients with AIS could be related with the physical deconditioning instead of being linked to the severity of the vertebral deformity. Methods. Cross-sectional study of the exercise tolerance in a series of patients with AIS type Lenke 1A, before and 2 years after surgical correction. Twenty patients with AIS and 10 healthy adolescents aged between 12 and 17 years old were evaluated. The average magnitude of the curves was 60.3±12.9 Cobb. Cardio-respiratory function was assessed before surgery and at 2-year follow-up by maximal exercise tolerance test on treadmill following a Bruce standard protocol. Maximal oxygen uptake (VO2), VCO2, expiratory volume (VE), and VE/VO2 ratio were registered. Results. Before surgery, AIS patients showed lower values than healthy controls in all cardio-respiratory parameters. The most important restrictions were the VO2max in ml/kg/min. (30.3±5.4 vs 49.9±7.5), VE (43.2±10.3 vs 82.3±10.7) and VE/CO2 ratio (25.0±3.9 vs 29.6±4.2). Contrary to expectations, two years after surgery most of these parameters decreased but differences with preoperative data were no statistically significant. Besides the great correction of the deformity (coronal plane, 71.5%; axial rotation, 49.3%), the cardio-respiratory tolerance to the exercise was not modified by surgery. Conclusions. Patients with moderate-severe AIS showed a limited tolerance to maximal exercise that does not change 2 years after surgery. This findings suggests that the reduced cardio-pulmonary function during exercise is not strictly associated to the spinal deformity, since great corrections of the spinal curves does not improve functional ventilatory parameters. In addition, the results point out a severe exercise deconditioning in AIS patients. Level of evidence. Level IV

Fracture related infection remains a major challenge in musculoskeletal trauma surgery. Despite best practice, treatment strategies suffer from high failure rates due to antibiotic resistance and tolerance. Bacteriophages represent a promising alternative as they retain activity against such bacteria. However, optimal phage administration protocols remain unknown, although injectable hydrogels, loaded with phage and conventional antibiotics, may support conventional therapy. In this study we tested the activity of meropenem, and two newly isolated bacteriophages (ϕ9 and ϕ3) embedded within alginate-chitosan microbeads and a hydrogel. Antibiotic and phage stability and activity were monitored in vitro, over a period of 10 days. In vivo, the same material was tested in treatment of a 5-day old Pseudomonas aeruginosa infection of a tibial plate osteotomy in mice. Treatment involved debridement and 5 days of systemic antibiotic therapy plus: i- saline, ii-phages in saline, iii-phages and antibiotics loaded into a hydrogel (n=7 mice/group). To assess the efficacy of the treatments, the infection load was monitored during revision surgery with debridement of the infected tissue after 5,10 and 13 days (euthanasia) by CFU and PFU quantification. In vitro testing confirmed that the stability of meropenem and activity of ϕ9 and ϕ3, was not affected within the alginate beads or hydrogel over 10 days. The in vivo study showed that all mice receiving phages and antibiotics loaded into a hydrogel survived the infection with a reduction of the bacterial load in the soft tissue. Active phages could be recovered from the infected site at euthanasia (10. 4. PFU/g). The hydrogel loaded with bacteriophages and meropenem showed a positive result in locally reducing the infection load indicating a synergistic effect of the selected antimicrobials. Overall, our new strategy shows encouraging results for improving the treatment of antibiotic-resistant biofilm infections that are related to medical implants

Staphylococcus aureus is the main cause of osteomyelitis and forms biofilm and staphylococcal abscess communities (SACs) in humans. While S. aureus has several toxins with specificity for human targets and working with human host cells would be preferred, for SACs no in vitro models, two-dimensional (2D) or three-dimensional (3D), have been described in literature to date. Advanced 3D in vitro cell culture models enable the incorporation of human cells and resemble in vivo tissue more closely than conventional 2D cell culture. Therefore, the aim of this study was to develop an in vitro model of SACs by using a 3D system. The model should allow for studies into antibiotic tolerance and S. aureus - human host cells interactions. With a clinical isolate (S. aureus JAR) or a lab strain (S. aureus ATCC 49230-GFP), SACs were grown in a collagen gel (1.78 mg/ml, Gibco) supplemented with 200 µl human plasma at 37 °C. Transmission and scanning electron microscopy was used to obtain a detailed overview of SACs, whereas immunofluorescent stainings were done to determine whether the pseudocapsule around SACs consist of fibrin. Antibiotic tolerance of SACs was assessed with 100× the minimal inhibitory concentration (MIC) of gentamicin (Roth). Bacterial clearance of non-establised SACs and established SACs with or without pseudocapsule was determined by exposure to differentiated PLB neutrophil-like cells (differentiation with 1.25% DMSO and 5% FBS for 5 days; dPLB) or primary neutrophils isolated with lymphoprep from fresh heparin blood. Degradation of the pseudocapsule was done with 7.5 µl/ml plasmin (Sigma). Colony forming unit (CFU) counts were performed as quantification method. Statistical analysis was performed with the ANOVA multiple comparison test or, when data was not normally distributed, with a Mann-Whitney U test. We have developed a 3D in vitro model of SACs which after overnight growth were on average 200 micrometers in diameter, consisted of 8 log10 CFUs and were surrounded by an inner and outer fibrin pseudocapsule. The in vitro grown SACs tolerated 100× the MIC of gentamicin for 24h and did not significantly differ from control SACs (p=0.1000). dPLB neutrophil-like cells or primary neutrophils did not clear established in vitro SACs (p=0.1102 and p=0.8767, respectively). When the fibrin pseudocapsule was degraded by the enzyme plasmin, dPLB neutrophil-like cells or primary neutrophils caused for a significant decrease in total CFU compared the SACs that did had a pseudocapsule (p=0.0333 and p=0.0272, respectively). The in vitro SACs model offers a tool for host-pathogen interaction and drug efficacy assessments and is a valuable starting point for future research

Introduction and Objective. Knee osteoarthritis (KOA) is a frequent disease for which therapeutic possibilities are limited. In current recommendations, the first-line analgesic is acetaminophen. However, low efficacy of acetaminophen, frequently leads to the use of weak opioids (WO) despite their poor tolerance, especially in elderly patients. The primary objective was to compare the analgesic efficacy and safety of a new wearable transcutaneous electrical nerve stimulation (W-TENS) to weak opioids (WO) in the treatment of moderate to severe, nociceptive, chronic pain in knee osteoarthritis patients. Materials and Methods. ArthroTENS study is a phase 3, non-inferiority, multicentric, prospective, randomized, single-blinded for primary efficacy outcome, controlled, in 2-parallel groups, clinical study comparing W-TENS versus WO over a 3-month controlled period with an additional, optional, non-controlled, 3-month follow-up for patients in W-TENS group. The co-primary outcome was KOA pain intensity (PI) at month 3 and the number of adverse events (AEs) over 3 months. Results. The non-inferiority of W-TENS was demonstrated in both the PP and ITT populations. At M3, PI in PP population was 3.87 (2.12) compared to 4.66 (2.37) (delta: −0.79 (0.44); 95% CI (−1.65; 0.08)) in W-TENS and WO groups, respectively. Since the absolute value of the 95% CI of the between-treatments mean PI difference [−1.71, – 0.12] was above 0 in ITT set, the planned superiority analysis was performed, demonstrating that W-TENS was significantly superior to WO at M3 (P=0.0124). At M1 and M3, the W-TENS group reached the absolute minimal clinically important difference (MCID) for an analgesic (1.8 (2.1) and 2.1 (2.3), respectively), corresponding to a 20 mm reduction in PI (interquartile range: 15–30) on a 0–100 mm visual analogic scale – i.e. 2 points on a numerical rating scale – which equates to “much better”. Conversely, in the WO group, a 0.5 (1.8) and a 1.1 (2.1) reduction in PI were observed at M1 and M3, respectively, while a 1-point reduction in PI is required to be considered as a “slightly better” improvement. In WO group, AEs were the common systemic AEs reported with WO (nausea, constipation, drowsiness, dizziness, pruritus, vomiting, dry mouth). AEs in W-TENS group were local, such as local cutaneous reaction (erythema). Thirty-nine (70.9%) patients wished to extend W-TENS treatment for 3 additional months. Only one patient discontinued this additional period and results were maintained at M6. Conclusions. W-TENS was more effective and better tolerated than WO in the treatment of nociceptive KOA chronic pain and could represent an interesting non-pharmacological alternative to WO

Aims & Background. Congenital Talipes Equinovarus (CTEV) is the most common congenital musculoskeletal birth defect affecting 1 in 1000 births per annum. We have compared our surgical results to the British Society of Children's Orthopaedics (BSCOS) published guidelines. Methods. Between, 2006–16, patients who were referred for treatment of pathological CTEV were audited. Data from a combination of Clinical Portal, Orthotic Patient Administration System and Surgical Elogbook were assessed. In addition, the degree of deformity was classified by the Harrold & Walker method at the time of diagnosis (senior author). Most of this information was recorded prospectively and analysed retrospectively. Ponseti technique was the method of treatment. Results. 96 patients assessed (133 feet). There were 78 males and 18 females, 37 patients were affected bilaterally and 11 had associated syndromes. There were 23 Harrold & Walker (H&W) 1, 28 H&W 2 and 82 H&W 3 classification feet. Average time period in Ponseti boots and bars was 14.4 months (95% CI 12.9–15.9), average time in all types of bracing of was 17.1 months (95% CI 14.8–14.8). Number and rate of surgeries performed were as follows: 77 Tendoachilles release (63.1%), 19 Tibialis Anterior Transfer (5.6%), 15 Radical Release (12.3%), revision 25 Surgery (20.5%) & 5 Abductor Hallucis Release (4.1%). Conclusion. The audit confirms that the unit meets most of the current BSCOS guidelines. All surgical procedures apart from radical release surgery fall within accepted limits. This may be due, in part, to the syndromal cases. We do however demonstrate a significantly reduced average time period in bracing compared to that recommended by BSCOS. There are multiple reasons for this discrepancy including non-compliance and poor splint tolerance (child refusing to use). We feel this work demonstrates a reduced period in bracing can be achieved whilst maintaining standards of treatment

Objectives. We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model. Methods. We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice. Results. The mean error of 164 resections in 82 femurs in the AR group was 1.71 mm (0 to 6). The mean error of 82 resections in 41 femurs in the conventional resection group was 2.64 mm (0 to 11) (p < 0.05, one-way analysis of variance). The probabilities of a surgeon obtaining a 10 mm surgical margin with a 3 mm tolerance were 90.2% in AR-assisted resections, and 70.7% in conventional resections. Conclusion. We demonstrated that the accuracy of tumour resection was satisfactory with the help of the AR navigation system, with the tumour shown as a virtual template. In addition, this concept made the navigation system simple and available without additional cost or time. Cite this article: H. S. Cho, Y. K. Park, S. Gupta, C. Yoon, I. Han, H-S. Kim, H. Choi, J. Hong. Augmented reality in bone tumour resection: An experimental study. Bone Joint Res 2017;6:137–143

Introduction. Regular, repeated stretching increases joint range of movement (RoM), however the physiology underlying this is not well understood. The traditional view is that increased flexibility after stretching is due to an increase in muscle length or stiffness whereas recent research suggests that increased flexibility is due to modification of tolerance to stretching discomfort/pain. If the pain tolerance theory is correct the same degree of micro-damage to muscle fibres should be demonstrable at the end of RoM before and after a period of stretch training. We hypothesise that increased RoM following a 3 weeks hamstrings static stretching exercise programme may partly be due to adaptive changes in the muscle/tendon tissue. Materials and Methods. Knee angle and torque were recorded in healthy male subjects (n=18) during a maximum knee extension to sensation of pain. Muscle soreness (pain, creatine kinase activity, isometric active torque, RoM) was assessed before knee extension, and 24 and 48 hours after maximum stretch. An exercise group (n=10) was given a daily home hamstring stretching programme and reassessed after 3 weeks and compared to a control group (n=8). At reassessment each subject's hamstring muscles were stretched to the same maximum knee extension joint angle as determined on the first testing occasion. After 24 hours, a reassessment of maximum knee extension angle was made. Results. At the start of the study RoM was 71.3 ± 10.0 degrees and there was no significant difference between groups. After 3 weeks stretching RoM increased significantly (p=0.01) by 9 degrees; the control group showed no change. Stiffness did not differ for either group. Pain score and RoM were the most sensitive markers of muscle damage and were significantly changed 24 and 48 hours after the initial stretch to end of range, (p<0.005) and (p=0.004) respectively. Discussion. The results show that a 3 week stretching programme causes muscle adaptation resulting in an increase in the extensibility of the hamstring muscle/tendon unit but no change in stiffness. The lack of evidence of muscle damage suggests that participants in the stretching group are likely to have undergone a physical change/adaptation rather than simply an increase in pain threshold

Staphylococcus aureus is responsible for 60–70% infections of surgical implants and prostheses in Orthopaedic surgery, costing the NHS £120–200 million per annum. Its ability to develop tolerance to a diverse range of antimicrobial compounds, threatens to halt routine elective implant surgery. One strategy to overcome this problem is to look beyond traditional antimicrobial drug therapies and investigate other treatment modalities. Biophysical modalities, such as ultrasound, are poorly explores, but preliminary work has shown potential benefit, especially when combined with existing antibiotics. Using a methicillin-sensitive S. aureus reference strain and the dissolvable bead assay, bacterial biofilms were challenged by gentamicin +/− low-intensity ultrasound (1.5MHz, 30W/cm2, pulse duration 200µs/1KHz) for 20 minutes. The outcome measures were colony-forming units/mL (CFU/mL) and the minimum biofilm eradication concentration (MBEC) of gentamicin. The mean number of S. aureus within control biofilms was 1.04 × 109 CFU/mL. There was no clinically or statistically significant (p=0.531) reduction in viable S. aureus following ultrasound therapy alone. The MBEC of gentamicin for this S. aureus strain was 256 mg/L. The MBEC of gentamicin with the addition of ultrasound was 64mg/L. Low intensity pulsed ultrasound was associated with a four-fold reduction in the effective biofilm eradication concentration of gentamicin; bringing the MBEC of gentamicin to within clinically achievable concentrations

Staphylococcus aureus is responsible for 60–70% infections of surgical implants and prostheses in Orthopaedic surgery, costing the NHS £120–200 million per annum. Its ability to develop resistance or tolerance to a diverse range of antimicrobial compounds, threatens to halt routine elective implant surgery. One strategy to overcome this problem is to look beyond traditional antimicrobial drug therapies and investigate other treatment modalities. Biophysical modalities, such as ultrasound, are poorly explored, but preliminary work has shown potential benefit, especially when combined with existing antibiotics. Using a methicillin-sensitive S. aureus reference strain and the dissolvable bead assay, biofilms were challenged by a low-intensity ultrasound (1.5MHz, 30mW/cm. 2. , pulse duration 200µs/1KHz) for 20 minutes and gentamicin. The outcome measures were colony-forming units/mL (CFU/mL) and the minimum biofilm eradication concentration (MBEC) of gentamicin. The mean number of S. aureus within control biofilms was 1.04 × 10. 9. CFU/mL. There was no clinically or statistically significant (p=0.531) reduction in viable S. aureus following ultrasound therapy alone. The MBEC of gentamicin for this S. aureus strain was 256 mg/L. The MBEC of gentamicin with the addition of ultrasound was 64mg/L. Low intensity pulsed ultrasound was associated with a 4-fold reduction in the effective biofilm eradication concentration of gentamicin; bringing the MBEC of gentamicin to within clinically achievable concentrations

Blood transfusion, organ and bone marrow transplantation and allogeneic tissue grafting create the potential for significant immunological challenges through the introduction of non-genetically identical major (HLA) and minor histocompatibility antigens (“allo-antigens”) into the body. Strategies to avoid the complications of immune responses against allo-antigens (transfusion reactions, rejection and graft versus host disease) include HLA matching, immunosuppressive therapies and immune tolerance promoting protocols. In the case of allogeneic mesenchymal stem/stromal cells (allo-MSC), it was initially believed that their combined properties of low HLA expression and inherent immune modulatory functions would render them invisible to the host immune system and, therefore, capable of being permanently accepted without further interventions. For clinical indications such as bone and tendon repair, in which permanent engraftment of allo-MSC or MSC-derived tissue constructs is particularly desirable, this model of “immune privilege” seemed almost too good to be true – and indeed, a decade of experimental research in this area has now convincingly demonstrated that allo-MSC typically elicit cellular (T-cell) and humoral (B-cell/antibody) immune responses in immunocompetent hosts – raising concern about their safety and long-term efficacy in human conditions. However, questions related to the immunogenicity of allo-MSC have evolved beyond a simple yes/no scenario to involve interesting observations and concepts about the potency, diversity, duration, functional characteristics and even potential clinical benfits of immunological responses to allo-MSC. In this presentation, I will summarise and critically evaluate current understanding of allo-MSC immunogenicity under experimental and clinical trial conditions with an emphasis on the implications for orthopaedic therapeutics

Adipose derived mesenchymal stromal cells (ASC) are adult stem cells exhibiting functional properties that have open the way for cell-based clinical therapies. Primarily, their capacity of multilineage differentiation has been explored in a number of strategies for skeletal tissue regeneration. More recently, MSCs have been reported to exhibit immunosuppressive as well as healing capacities, to improve angiogenesis and prevent apoptosis or fibrosis through the secretion of paracrine mediators. Among the degenerative diseases associated with aging, osteoarthritis is the most common pathology and affects 16% of the female population over 65 years. Up to now, no therapeutic option exists to obtain a sustainable improvement of joint function beside knee arthroplasty. This prompted us to propose adipose derived stem cells as a possible cell therapy. We performed pre-clinical models of osteoarthritis and showed that a local injection of ASC showed a reduction of synovitis, reduction of osteophytes, joint stabilization, reducing the score of cartilage lesions. This work was completed by toxicology data showing the excellent tolerance of the local injection of ADSC and biodistribution showing the persistence of cells after 6 months in murine models. The aim of the ADIPOA trial is to demonstrate the efficacy of adipose derived stem cells therapy in knee osteoarthritis (OA) in a phase 2/3 controlled multicenter study controlled against standard of care. Safety and feasibility as well as dose response was previously assessed in the ADIPOA FP7 project. The bi-centric phase I clinical trial in Montpellier (France) and Würzburg (Germany) included 18 patients with moderate to severe knee OA, each patient received a single injection of autologous ADSC, in a open scale up dose trial, starting form 2 10 6 cells to 50 106 cells. The 107 dose appears to be well tolerated and showed preliminary response in terms of decreasing local inflammation. This first study confirmed the feasibility and safety of local injection of ADSC in knee OA and suggested the most effective dose (107 autologous ADSC). This work constituted a significant step forward treating this disease with ADSC to demonstrate safety of the procedure. we conduct a prospective multicenter randomized Phase 2/3 study with 86 patients with moderate to severe knee OA to demonstrate superiority of stem cell-based therapy compared to standard of care (SOC) in terms in reduction in clinical symptoms (WOMAC score) and structural benefit (assessed by T1rhoMRI that allow quantification of cartilage proteoglycan content). This project will offer EU a unique leadership in OA with strong positions in EU and US due to patents and quality of the methodology to demonstrate efficiency of ADSC. ADIPOA brings together a unique combination of expertises and leaders in clinical rheumatology, MRI specialists, Stem cell Institutes, national GMP grade adipose derived stem cell production platform (ECELLFRANCE) and SME specialized in cell therapy trials in the EU. The production of the cells will be granted to EFS through ECELLFRANCE national platform, which have the GMP facility and will work as a contracting manufacturing organization. The expertise, leadership and critical mass achieved by this Consortium should enable breakthroughs in ASC engineering directly amenable for clinical applications in OA

To date there has been no material for endoprosthetics providing excellent resistance to abrasion and corrosion combined with great tensile strength, fracture toughness, and bending strength, as well as adequate biocompatibility. Carbon-fiber-reinforced silicon carbide (C/SiC, C/C-SiC or C/SiSiC) is as a ceramic compound a potentially novel biomaterial offering higher ductility and durability than comparable oxide ceramics. Aim of this investigation was to test the suitability of C/SiC ceramics as a new material for bearing couples in endoprosthetics. One essential quality that any new material must possess is biocompatibility. For this project the in-vitro biocompatibility was investigated by using cuboid like scaffolds made of CMC. To determine whether the material is suited as a lubricant partner in endoprosthetics, we measured its abrasion coefficient and wear tolerance against various antibodies. The C/SiC samples tested were produced via the Liquid Silicon Infiltration (LSI) of pyrolized porous fiber preforms made by warm-flow pressing free-flowing granulates on a hydraulic downstroking press with a heated die of the type HPS-S, 1000 kN. After preparation of the composites, the tribological characteristics are determined. Flexural strength was determined at room temperature according to DIN685-3 with an universal testing machine Z100 and the Young”s -modulus was carried out via resonant frequency-damping analysis RFDA. The samples”surface as well as cell adhesion and cell morphology were assessed via ESEM. The human osteoblast-like cell line MG-63 and human ostoeblast were used for cel culture ecperiments (WST, Live/dead, Cytotoxicity, cell morphology). Based on the raw data the mean value and the standard deviation were calculated. The Mann-Whitney-U-Test was used to evaluate the differences between experiment and control samples. The flexural strength at room temperature is approx. 180 MPa, while the elongation at break is about 0.13%. The Young”s modulus is detected between 120 and 150 GPa. The density lies between 2.5 and 3.0 g/cm. 3. We noted a friction coefficient µ between 0.31. The cell lines exhibited no morphological alterations, and adhered well to the C/SiC samples. Vitality was not impaired by contact with the ceramic composite. Cell growth was observed evenly distributed over a 21-day period. In the future, investigators aiming to apply this composite in endoprosthetics will have to focus on its efficacy in conjunction with sudden, strong demands, and long-term performance in bodily fluids within joint simulators, etc. In conclusion: C/SiC can definitely be considered a new material with genuine potential for use in endoprosthetics

Background. Orthopedic trauma patients can have significant pain management requirements. Patient satisfaction has been associated with pain control and narcotic use in previous studies. Due to the multifactorial nature of pain, various injury patterns, and differences in pain tolerances the relationship between patient factors and narcotic requirements are poorly understood. The purpose of this study is to compare patient demographics for trauma patients requiring high doses of narcotics for pain control versus those with more minimal requirements. Methods. Our study sample included 300 consecutive trauma activations who presented to our emergency department during the 2015 calendar year. Opioids given to the patients during their hospital stay were converted to oral morphine equivalents using ratios available from the current literature. Patients were placed into two groups including those who were in the top 10% for average daily inpatient oral morphine equivalents and the other group was composed of the remaining patients. In addition to morphine equivalents, patient age, gender, injury severity score, length of stay, number of readmissions and urine toxicology results were also recorded. Injury severity score (ISS), morphine equivalents, and patient age were evaluated with the Shapiro-Wilk test of normality. Comparisons were performed with the Mann-Whitney U test. Between group comparisons for positive urine toxicology screen and gender were performed with Chi square and Fisher exact test. Pearson correlations were calculated between injury severity score, average daily oral morphine equivalents, and length of stay. P-value of 0.05 was used to represent significance. Statistical comparisons were made using SPSS version 23 (IBM, Aramonk, NY). Results. Median average daily morphine equivalents in the 10% of patients receiving the highest doses was 86.30 and 12.95 for the bottom 90%. The difference was statistically significant (p<0.001). The median ISS between the 2 groups was significant (p=0.018). There was no significant difference in age, readmission rate, and urine toxicology results. Patients in the top 10% were more likely to be male (p=0.003). Median length of stay for the top 10% group and bottom 90% group was 4 days and 2 days, respectively (p=0.005). No correlation between injury severity score and length of stay was found (p=0.475). A weak correlation of 0.115 was found between morphine equivalents and length of stay (p=0.047). Discussion. Our study shows male gender and ISS were correlated with higher oral morphine equivalents for the 10% of patients receiving the highest daily amounts when compared to the reaminder of the cohort. There was a significantly increased length of stay in the patients receiving higher narcotic doses. Whether this is due to ISS or increase in narcotics is unclear. However, positive correlation was not found between ISS and length of stay

The management of displaced forearm diaphyseal fractures in adults is predominantly operative. Anatomical reduction is necessary to infer optimal motion and strength. The authors have observed an intraoperative technique where passive pronosupination is examined to assess quality of reduction as a surrogate marker for active movement. We aimed to assess the value of this technique, but intentionally malreducing a simulated diaphyseal fracture of a radius in a cadaveric model, and measuring the effect on pronosupination. A single cadaveric arm was prepared and pronation/supination was examined according to American Academy of Orthopaedic Surgeons guidance. A Henry approach was then performed and a transverse osteotomy achieved in the radial diaphysis. A volar locking plate was used to hold the radius in progressive amounts of translation and rotation, with pronosupaintion measured with a goniometer. The radius could be grossly malreduced with no effect on pronation and supination until the extremes of deformity. The forearm showed more tolerance with rotational malreduction than translation. Passive pronation was more sensitive for malreduction than supination. The use of passive pronosupination to assess quality of reduction is misleading

Despite high success rates following total knee arthroplasty (TKA), knee kinematics are altered following TKA. Additionally, many patients report that their reconstructed knee does not feel ‘normal’ [1], potentially due to the absence of the anterior cruciate ligament (ACL), an important knee stabilizer and proprioceptive mechanism. ACL-retaining implants have been introduced with the aim of replicating native knee kinematics, however, there has yet to be a detailed comparison between knee kinematics in the native knee and one reconstructed with an ACL-retaining implant. Six fresh-frozen right legs (77±10 yr, 5 male) were mounted in a kinematic rig and subjected to squatting (40°-105°) motions. The vertical positon of the hip was manipulated with a linear actuator to induce knee flexion while the quadriceps were loaded with an actuator to maintain a vertical load of 90 N at the ankle [2]. Medial/lateral hamstring forces were applied with 50 N load springs. During testing, an infrared camera system recorded the trajectories of spherical markers rigidly attached to the femur and tibia. Two trials were performed per specimen. Following testing on the native knee, specimens were implanted with an ACL-retaining TKA (Vanguard XP, Zimmer Biomet) and all trials were repeated. Three inlay thicknesses were tested to simulate optimal balancing as well as over- (1 mm thicker) and understuffing (1 mm thinner) relative to the optimal thickness. Pre-operative computed tomography scans allowed identification of bony landmarks and marker orientation, which were used define anatomically relevant coordinate systems. The recorded marker trajectories were transformed to anatomical translations/rotations and resampled at increments of 1° of knee flexion. Translations of the medial and lateral femoral condyle centers were scaled to maximum anterior-posterior (AP) width of the medial and lateral tibial plateau, respectively. For all kinematics, statistical analysis between knee conditions was conducted using repeated measures ANOVA in increments of 10° knee flexion. Internal rotation of the tibia was significantly lower (p<0.05) for the three reconstructed conditions relative to the native knee at flexion angles of 60° and below. No significant differences in tibial rotation were observed between the balanced, overstuffed, or understuffed conditions. The varus orientation was not significantly influenced by implantation, regardless of inlay thickness, for all flexion angles. At 40° flexion, the AP position of the femoral medial condyle was significantly more anterior for the native knee relative to the balanced and understuffed conditions. This finding was not significant for the other flexion angles. No significant differences were found for the lateral condyle center AP position at any flexion angle. Preservation of the cruciate ligaments during total knee arthroplasty may allow better physiologic representation of knee kinematics. The implants tested in this study were able to replicate kinematics of the native knee, except for tibial rotation and AP position of the medial femoral condyle in early knee flexion. Interestingly, the impact of inlay thickness was generally small, suggesting some tolerance in the choice of inlay thickness

Background. Surgical resection of middle facet tarsal coalition is a well documented treatment option in symptomatic individuals that do not respond to conservative treatment. The ability to return to full recreational activity post resection may have implications on foot biomechanics and possibly degenerative changes in the subtalar and adjacent joints. Hypothesis. Open resection of middle facet tarsal coalitions should improve subtalar joint motion and biomechanical function and facilitate return to sports. Aim. The aim of this study was to assess the outcomes of open resection of middle facet tarsal coalitions (MFTCs) with particular emphasis on return to sports. Methods. Retrospective review of clinical and radiographic records of paediatric and adolescent patients who had open resection of middle facet tarsal coalitions. The ankle and hind foot were evaluated according to the American Orthopaedic Foot and Ankle Society Ankle-Hind foot Scale (AOFAS). We also quantified the return-to-activity time after tarsal coalition surgery. Results. We identified thirteen patients (Mean age; 13.7years Range; 7–21 years) with eighteen middle facet tarsal coalitions operated over a seven year period. Ten patients (12 feet) who underwent resection had an average return to recreational activity time of approximately twelve weeks and reported better exercise tolerance post resection. Conclusion. Surgical excision of middle facet tarsal coalitions has a favourable outcome with respect to return to sports

OBJECTIVES. Ischaemic preconditioning (IPC) is a phenomenon whereby tissues develop an increased tolerance to ischaemia and subsequent reperfusion if first subjected to sublethal periods of ischaemia. Despite extensive investigation of IPC, the molecular mechanism remains largely unknown. Our aim was to show genetic changes that occur in skeletal muscle cells in response to IPC. METHODS. Firstly, we established an in-vitro model of IPC using a human skeletal muscle cell line. Gene expression of both control and preconditioned cells at various time points was determined. The genes examined were HIF-1 alpha, EGR1, JUN, FOS, and DUSP1. HIF-1 alpha is a marker of hypoxia. EGR1, JUN, FOS and DUSP1 are early response genes and may play a role in the protective responses induced by IPC. Secondly, the expression of HSPB8 was examined in a cohort of preconditioned total knee arthroplasty patients. RESULTS. HIF-1 alpha was upregulated following 1 and 2 hours of simulated ischaemia (p = 0.076 and 0.841 respectively) verifying that hypoxic conditions were met using our model. Expression of EGR1, FOS and DUSP1 were upregulated and peaked after 1 hour of hypoxia (p = 0.001, <0.00, and 0.038 respectively). cFOS was upregulated at 2 and 3 hours of hypoxia. IPC prior to simulated hypoxia resulted in a greater level of upregulation of EGR1, JUN and FOS genes (p = <0.00, 0.047, and <0.00 respectively). HSPB8 was not significantly upregulated following IPC using the hypoxic model. It was, however, upregulated on an mRNA level in total knee arthroplasty patients (p = 0.15). CONCLUSION. This study has validated the use of our hypoxic model for studying IPC in-vitro. IPC results in a greater upregulation of protective genes in skeletal muscle cells exposed to hypoxia than in control cells. We have demonstrated hitherto unknown molecular mechanisms of IPC in cell culture and in patients undergoing TKA

Summary Statement. There were significant differences in the pain experience, behaviors, and perceptions on analgesics, between the Australia and Singapore cohorts, after hospital discharge following TKR. These findings may be influenced by the ethnicity and cultural differences between these two countries. Introduction. In recent years the hospital length of stay after total knee replacement (TKR) has shortened. Hence, patients have to self-manage their pain earlier after the surgery. The aim of this study was to examine if the pain experience, self-management behaviors and potential barriers to optimal analgesia after hospital discharge for TKR differed in different ethnicity groups. Patients & Methods. We administered a questionnaire to patients undergoing TKR in 10 Australian hospitals, and one large Singaporean hospital, two weeks following hospital discharge.1 We asked participants about their pain severity, use of analgesics, side-effects, perceptions of analgesics use, and satisfaction with pain relief at home. The two groups were compared using Chi-squared test with SPSS 20.0 with statistical significance set at p < 0.05. Results. 171 (98%) participants from the Australian centers and 105 (94%) from the Singaporean hospital completed the questionnaire. Compared with the Singaporean patients, significantly more participants in the Australian cohort reported that their worst pain period occurred during the first two weeks at home (52% vs. 20%, p < 0.0001), and that their average pain at home was ‘severe/extreme’ (23% vs. 6%, p < 0.0001). More participants in the Australian cohort consumed an opioid alone or in combination with non-opioid analgesics (69% vs. 33%, p < 0.0001). Although many in both cohorts experienced analgesic-related side-effects, the proportion was higher in the Australian cohort (84% vs. 41%, p < 0.0001). A very much larger proportion of participants in the Australian cohort sought further medical help for their pain (60% vs. 3%, p < 0.0001). A much small proportion of patients in the Australian cohort perceived that analgesics could not control pain (26% vs. 44%, p = 0.002); were concerned about addiction (26% vs. 42%, p = 0.005) or developing tolerance to analgesics (28% vs. 49%, p < 0.0001); or preferred enduring pain than analgesic-related side-effects (25% vs. 42%, p < 0.002). There was no significant difference in satisfaction with analgesia between the two cohorts (64% vs. 74%, p = 0.179). Discussion/Conclusion. Following hospital discharge for TKR, there were differences in the pain experience, opioid consumption, side-effects, and perceptions of analgesics, between the Australian and Singaporean cohorts. Ethnic or cultural differences might have influenced the differences found, as the Australian cohort mostly comprised of Caucasians while the Singaporean cohort comprised exclusively patients of Asian origin. Interestingly, despite more participants in the Australian cohort experiencing severe pain and higher incidence of analgesic-related side-effects, the proportion who were satisfied with analgesia during the first two weeks after hospital discharge were similar, suggesting that satisfaction is a complex concept influenced by the interplay of many factors. Future studies are required to examine the extent to which ethnicity and cultural factors determine the pain intensity, behaviours and perceptions reported by patients after TKR

ABSTRACT. The friction and lubrication behaviour of four Biomet ReCap components with a nominal diameter of 52 mm and diametral clearance ranging from 167-178 μm were investigated using a friction hip simulator. Friction testing was carried out using pure bovine serum and aqueous solutions of bovine serum (BS), with and without carboxymethyl cellulose (CMC), adjusted to a range of viscosities (0.001-0.236 Pas). The Stribeck analyses suggested mixed lubrication as the dominant mode with the lowest friction factor of 0.07 at a viscosity of 0.04 Pas. INTRODUCTION. The femoral resurfacing systems provide an alternative to hemi and total hip arthroplasty and offer several unique advantages including large resurfacing heads (>35–60 mm diameter) allowing increased range of motion (and stability) over the traditional 28 mm artificial hip joints, with excellent tolerances and surface finish leading to a reduction in wear, as well as preserving primary bone with the femoral canal remaining untouched. This work has investigated the friction and lubrication behaviour of four 52 mm metal-on-metal Biomet ReCap components with a clearance of 167-178 μm using serum-based lubricants. MATERIALS AND METHODS. Four as-cast, high carbon, cobalt-chrome resurfacing systems (supplied by Biomet UK Healthcare Ltd, Swindon) with a nominal diameter of 52 mm each and diametral clearance of 167-178 μm were used in this study. Frictional measurements of all the joints were carried out at University of Bradford, Medical Engineering Department, using a Prosim Hip Joint Friction Simulator (Simulation Solutions Ltd, Stockport, UK). For the friction factors, an average of three independent tests was taken and each test was run using; 100% bovine serum (BS) and then aqueous solutions of 25% v/v BS in distilled water with varying quantities of CMC to obtain viscosities of; 0.0015 Pas (pure BS), 0.0013 Pas (25% BS), 0.00612 Pas (25% BS, 1 g CMC), 0.01274 Pas (25% BS, 2 g CMC) and 0.236 Pas (25% BS, 5 g CMC) at a shear rate of 3000 s-1. All viscosities were measured using a RHEOPLUS/32 V3.40. RESULTS AND DISCUSSION. The Stribeck curves for all four ReCap components showed a very similar trend, i.e. the friction factors decreased from ∼0.11 to ∼0.07 as the Sommerfeld number increased (i.e. as viscosity increased from 0.0015 to 0.0127 Pas) indicating a mixed lubrication regime up to a viscosity of 0.0127 Pas; above which the friction factor increased to ∼ 0.13 at a viscosity of 0.236 Pas. These results clearly suggest that the Biomet ReCap components showed low friction (at the physiological viscosities ∼0.01 Pas) with mixed lubrication as the dominant mode