Aims. This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms. Methods. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes. Results. Signal transducer and activator of transcription 3 (STAT3) was notably expressed in both conditions. Single-cell analysis pinpointed specific cells with high STAT3 expression, and microRNA (miRNA)-125a-5p emerged as a potential regulator. Experiments confirmed the crucial role of STAT3 in osteoclast differentiation and muscle proliferation. Conclusion. STAT3 has emerged as a key gene in both POMP and sarcopenia. This insight positions STAT3 as a potential common therapeutic target, possibly improving management strategies for these age-related diseases. Cite this article: Bone Joint Res 2024;13(8):411–426

Aim. Unexpected negative-cultures (UNC) are a common diagnostic problem in periprosthetic joint infection (PJI) of the hip and knee when using culture-based methods. A novel molecular approach (MC)1 based on the identification of the vast majority of bacterial species in a single assay using species-specific bacterial interspacing region length polymorphisms and phylum-specific 16S rDNA sequence polymorphisms has demonstrated clinical utility in PJI diagnostics (1). In addition, MC provides an estimate of the leukocyte concentration in the specimen analysed. The aim of this retrospective, blinded study was to evaluate the performance of MC in identifying the microbiological content and determining the leukocyte count in synovial fluid (SF) collected from hip and knee revision arthroplasty cases with UNC. It was also assessed whether antibiotic treatment would have been changed if the result from MC had been known. Method. A total of 89 SF samples from 70 patients (43 female; 27 male) who underwent revision arthroplasty (14 hip; 75 knee) were included. Using European and Bone Joint Infection Society (EBJIS) criteria, 82 cases were classified as infected (77 UNC and 5 septic culture-positive controls), five as non-infected (aseptic culture-negative controls), and two as likely infected, but infected by clinical observation. MC was performed and evaluated together with SF parameters. Antibiotic treatment, clinical outcome, patient demographics and surgical details were analysed. Results. Overall, 29.1% (23/79) of UNC had a positive yield by MC, of which 2/23 (8.7%) had two microorganisms detected simultaneously. Of the 25 microorganisms identified by MC, 12/25 (48%) were clinically relevant after re-evaluation of the patients’ microbiological history. The microorganisms detected were 5/25 (20%) Streptococcus pneumoniae/mitis, 4/25 (16%) Staphylococcus epidermidis, 3/25 (12%) Cutibacterium acnes, 3/25 (12%) Streptococcus agalactiae, 2/25 (8%) Streptococcus bovis, 2/25 (8%) Staphylococcus aureus, and 2/25 (8%) Haemophilus parainfluenzae. The prevalence of Enterococcus faecalis, Bacteroides fragillis, Staphylococcus lugdunensis, Corynebacterium striatum among all MC results was 1/25 (4%) each species. In total, 13/23 (56%) cases were associated with patients receiving antibiotic therapy at the time of SF collection. The yield for leukocyte counts provided the molecular technique was consistently much higher in the UNC and clearly septic groups than in the clearly aseptic group. Overall, 20/61 (32.8%) patients with UNC could have been managed differently and more accurately after MC assessment. Conclusions. MC shows clinical value in the diagnosis and management of PJI with UNC. The included leukocyte count shows promising results. Acknowledgments. This work was partially funded by Inbiome

Aim. Bone and joint infections (BJIs) are serious infections requiring early optimized antimicrobial therapy. BJIs can be polymicrobial or caused by fastidious bacteria, and the patient may have received antibiotics prior to sampling, which may decrease the sensitivity of culture-based diagnosis. Furthermore, culture-based diagnosis can take up to 14 days. Molecular approaches can be useful to overcome these concerns. The BioFire® system performs syndromic multiplex PCR in 1 hour, with only a few minutes of sample preparation. The BioFire® Joint Infection (JI) panel (BF-JI), recently FDA-cleared, detects both Gram-positive (n=15) and Gram-negative bacteria (n=14), Candida, and eight antibiotic resistance genes directly from synovial fluids. The aim of this study was to evaluate its performance in acute JIs in real-life conditions. Method. BF-JI was performed on synovial fluid from patients with clinical suspicion of acute JI, either septic arthritis or periprosthetic JI, in 6 French centers. The results of BF-JI were compared with the results of culture of synovial fluid and other concomitantly collected osteoarticular samples obtained in routine testing in the clinical microbiology laboratory. Results. From July 2021 to May 2022, 319 patients (including 10 children < 5y and 136 periprosthetic infections) had been included in the study. The BF-JI test was invalid for one patient (not retested). Among the 318 remaining patients, overall concordance with comparative microbiology methods was 88% (280/318): 131 samples were negative with both BF-JI and culture, and 149 samples were positive with the same microorganisms using complementary techniques. In 33 cases (10.4%), BF-JI was negative while culture was positive: 18 microorganisms were not targeted by BF-JI (including Staphylococcus epidermidis, n=10, and Cutibacterium acnes, n=2); 15 microorganisms targeted by BF-JI were obtained in culture but not by the molecular test (false-negative 4.7%). In 20 cases, BF-JI was positive while culture was not: 12 patients had received antibiotics before sampling, and 7 cases involved fragile and fastidious bacteria (Kingella kingae, n=5; Neisseria gonorrhoeae, n=2). In 6 cases, both BF-JI and culture were positive, but no yielding the same bacteria (polymicrobial specimens). Conclusions. In acute JIs, the BF-JI panel shows a good concordance with culture for the microorganisms targeted by the panel. Therefore, this molecular tool may have a place in microbiological diagnosis of acute JIs in order to confirm JI faster than culture. Moreover, it allows easy detection of difficult-to-culture bacteria. Acknowledgements. study was supported by bioMérieux, who provided all reagents

R Appleyard, Murray Maxwell Biomechanics Lab, Royal North Shore Hospital, Sydney. The fundamental mechanisms that underlie tendon breakdown are ill understood. There is an emerging hypothesis that altered mechanical strain modulates the metabolism and/or phenotype of tenocytes, disrupting the balance of matrix synthesis and degradation, and that rupture then occurs through an abnormal tendon matrix. The critically regulated genes have not yet been determined. We have developed sheep model in sheep where both stress-deprived and over-stressed areas can be examined in the one tendon, to evaluate the pathological and molecular changes over time. We have also used ‘wild type’ and genetically modified mice to determine the role of specific enzymes and proteoglycans in tendon degeneration. Stress-deprived and over-stressed regions showed classical changes of increased cellularity and vascularity, rounded tenocytes and interfascicular matrix infiltration. These structural changes resolved for up to one year after injury. Resolution was more rapid in over-stressed regions. Irrespective of the initiating stress, proteoglycan staining and chondroid metaplasia increased in tendon with time. There were distinct molecular and temporal differences between regions, which are reviewed here. While tendon degeneration has traditionally been regarded as a single field of change, our studies show that at a molecular level, the injured tendon may be regarded as a number of distinct regions—overloaded and underloaded, adjacent to bone or adjacent to muscle. Each region manifests distinct molecular changes, driven by relevant gene expression. While collagen metabolism in pathological tendon has received much attention, accumulation of proteoglycan is also consistently induced by altered mechanical loading. We suggest that ADAMTS enzymes, which cleave aggrecan, versican and small proteoglycans, may play a significant role in tendon homeostasis and pathology. Regulating proteoglycan turnover may represent a novel target for treating tendon degeneration. We have initiated studies using mesenchymal stem cells (MSC), not to directly augment healing but to modify the molecular pathology in tendon resulting from altered loading. Preliminary data indicates that injection of MSC into an acute tendon defect significantly abrogates the increase in expression of aggrecan and collagen degrading metalloproteinases in the adjacent over-stressed tendon. This may decrease the resultant degeneration. The effects of MSC in treating tendon degeneration are reviewed here, as are the possible benefits of radiofrequency microtenotomy

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

Introduction. Aseptic loosening is a major cause of revision of total joint arthroplasty (TJA). Although crosslinked Ultra-high molecular weight polyethylene (UHMWPE) have improved wear resistance, residual radicals remaining in the material have a possibility to increase bio-reactivity of particles [2]. In this study, we attempt to evaluate the effects of irradiation and residual radicals on bio-reactivity of the material with a new method called the inverse culture method [1]. Material and methods. UHMWPE particles (10µm diameter in average, Mitsui chemicals Co., LTD) along with irradiated particles (RAD, 300kGy electron irradiation) and particles annealed after the irradiation (RAD+ANN, 100°C 72 hours) are co-incubated with mouse macrophage cell line RAW264 using the inverse culture method. The amount of TNF-α was measured with ELISA. Results and discussion. The amount of TNF-α released by macrophages reacting with virgin UHMWPE, RAD and RAD+ANN is shown in Figure 1. The horizontal axis represents the total surface area of the particles. The coefficient of determination and inclination of the approximate curve are calculated to analyze the result. The coefficient of determination suggested that cytokines released from macrophage is dose-dependent to the surface area of polyethylene particles, which was consistent with the result of our former study[1]. We use the inclination of the approximation curve in Figure 1 as an index to evaluate the bio-reactivity. The values of the index of virgin, RAD and RAD+ANN were 21×10. -4. gLm. -2. , 100×10. -4. gLm. -2. and 59×10. -4. gLm. -2. The inclination of the approximation line of RAD is significantly larger than that of virgin (test for the difference of regression line angle). These suggest that the irradiation to UHMWPE particles increases their bio-reactivity possibly due to radicals. The increased reactivity cannot be eliminated by annealing (100°C 72 hours) completely. Conclusion. Although electron irradiation increases the bio-reactivity of UHMWPE particles, annealing after the irradiation can decrease it, but cannot restore to original reactivity. For any figures or tables, please contact authors directly

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. 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?, EGR1, JUN, FOS, and DUSP1. HIF-1? 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 HSP22 was examined in a cohort of preconditioned total knee arthroplasty patients. Results. HIF-1? was upregulated following 1 and 2 hours of simulated ischaemia (p = 0.076 and 0.841 respectively) verifying that hypoxic conditions were met. 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). HSP22 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

Aim

We prospectively evaluated four different microbiological tools for diagnostics of prosthetic joint infections (PJI), and assessed their impact on the categorization of infection according to EBJIS guidelines. We compared culture, in-house real-time mPCR for S. aureus, S. lugdunensis, S. hominis, S. epidermidis, S. capitis, S. haemolyticus, C. acnes (mPCR), broad-spectrum PCR (Molzym) with 16S rRNA V3-V4 amplicon Sanger sequencing (16S PCR), and 16S rRNA V3-V4 amplicon next-generation sequencing (16S NGS) on MiSeq (Ilumina).

INTRODUCTION. Ultra-High Molecular Weight Polyethylene (UHMWPE) wear debris is thought to be a main factor in the development of osteolysis (1). However, the method for the evaluation of the biological response to UHMWPE particles has not yet been standardized. In this study, four different types of UHMWPE particles were generated using a mechanized pulverizing method and the biological responses of macrophages to the particles were investigated using an inverted cell culturing process (2). MATERIALS & METHODS. Virgin samples were manufactured via Direct Compression Molding (DCM) technique from UHMWPE GUR1050 resin powder (Ticona, USA). For vitamin E (VE)-blended sample, the resin was mixed with VE at 0.3 wt% and the mixture was then molded using DCM. The crosslinked virgin samples were made by gamma ray irradiation to UHMWPE GUR1020 resin sheet (Meditech, USA) with doses of 95kGy ±10% and annealed. The VE-blended crosslinked samples were made by electron beam irradiation to VE-blended samples with doses of 300kGy and annealed. The material conditions were summarized in Figure 1. To pulverize the samples, the Multi-Beads Shocker (Yasui Kikai, Japan) was used. After pulverization, samples were dispersed in an ethanol solution and sequentially filtered through polycarbonate filters. Over 100 sections of the filter were selected randomly and images of the particles were analyzed using scanning electron microscope (SEM). To analyze the macrophage biological response, an inverted cell culturing process was used (2). The mouse macrophage-like cells were seeded at densities of 4×105cells per well in a 96-well culture plate and incubated for 1h. UHMWPE particles suspended in the culture medium were then added to each well in the appropriate amount. After that, fresh medium was added to fill the wells, and a sealing film was used to cover the culture plate. The culture plate was then inverted to cause the UHMWPE particles interact with the adhered macrophages. The inverted culture plate was incubated for 8h. The amount of TNF-α was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS & DISCUSSION. Geometric measurements showed no significant difference in the UHMWPE particles (Figure 2). The amount of TNF-α released stimulated by the crosslinked virgin particles showed significantly higher relative to the other UHMWPE particles (Figure 3). During crosslinking irradiation, the carbon free radicals are generated in the main chain (3). In the presence of oxygen, these radicals can react to form peroxy radicals and when the peroxy free radicals react with hydrogen they form hydroperoxides, which can further degrade into other oxidation products (4). It has been reported that VE hinders this cascading in UHMWPE (5). Therefore, it is possible that oxidation of the crosslinked virgin UHMWPE was involved in the cytokine response observed in this study. However resin material, molding technique and the irradiation method were different between crosslinked virgin and VE-blended crosslinked samples. Further consideration will be needed to examine the relationship between residual radicals, hydroperoxides and biological response

Introduction. Ultra-high molecular weight polyethylene (UHMWPE) tape, which comprised threads of UHMWPE fibers with the thickness less than 0.5 mm, was developed as a flexible fixation device. We describe new techniques using UHMWPE tape for the reattachment of the osteotomised fragment and the repair of intraoperative calcar fractures in total hip arthroplasty (THA). Patients & Methods. We reviewed the medical records and radiographs of the studied subjects after approval of this study by the institutional review board committee. Experiment 1: Between October 2011 and May 2012, 60 consecutive primary THAs were performed with the mini-trochanteric approach, which involved reattaching the osteotomised fragment using UHMWPE tape (Nesplon; Alfresa Pharma, Osaka, Japan). [Fig.1] By splitting the anterior one-fourth of the gluteus medius, the minitrochanteric osteotomy, a half-ellipsoid body about 15 mm long, 10 mm wide, and 5 mm deep, is performed using a curved chisel. After implanting of the prosthesis, the osteotomised fragment is reattached by using two 3-mm wide Nesplon tapes. Using 2.4 mm Kirshner wire, two sets of drill holes are created below the trochanteric bed of the femur. Nesplon tapes are passed through each drill hole and penetrated over the trochanteric fragment. Nesplon tape is tied using a double-loop sliding knot in conjunction with a special tightening gun tensioner up to 20 kgf. [Fig.2] The radiographic results were retrospectively analyzed to determine the incidence of nonunion and complications related to trochanteric site. Hip functional results were rated according to the Japanese Orthopedic Association (JOA) hip score. Experiment 2: Between July 2011 and May 2012, 5-mm wide Nesplon tapes were used for restoration of intraoperative femoral fractures in 4 primary THAs. For the repair of intraoperative proximal femoral fractures, 5-mm wide Nesplon tape is tightened with cerclage wiring technique using the gun tensioner up to 30 kgf. [Fig.3] The postoperative radiographic changes were analyzed. Results. Experiment 1: Nonunions occurred in no (0%) patient. Bone union with minimally displaced was present in three (5.0%) patients. The mean JOA scores improved 47.1 to 84.6 at 1 year postoperatively. Experiment 2: There were no migrations of the femoral prosthesis in the postoperative period. Discussion. These techniques using UHMWPE tapes are simple and more advantageous to prevent the complications resulting from metal wires. UHMWPE tape, which has flat configuration with high flexibility, can provide a greater contact area avoiding the risk of bone cutout. Using a special tightening gun can easy reattachment with precise tension even in the setting of poor bone quality

Aim. Thromboprophylaxis in total hip replacement (THR) and total knee replacement (TKR) remains controversial, conspicuous by absence of consensus. Because of protracted and variable mobilisation, there is an extended risk of Venous Thromboembolism (VTE). We hypothesised that a combination of low molecular weight heparin and miniwarfarin would minimise the initial and extended risk. Therefore we evolved a protocol of enoxaparin sodium 40 mgs for 5 days starting preoperatively and miniwarfarin 1-2mg for 6 weeks following surgery. We undertook a retrospective study of total hip and knee replacements in a District General Hospital between January 2000 and December 2005 to determine the effectiveness of the protocol. Methods. We analysed the incidence of symptomatic VTE in 1307 patients, of who 681 underwent THR and 626 TKR. We evaluated the incidence of symptomatic DVT and PE between 0-6 weeks, 6 weeks-3months and 3-6 months following surgery. Results. Total incidence of VTE in the study group as a whole including both total hip and knee arthroplasty in 6 months following surgery was 29/1307 (2.22%), after THR 12/681 (1.76%) and after TKR 17/626 (2.72%). VTE at 6 weeks following TKR was 12/626 (1.92%) and THR 4/681(0.59%); between 6 weeks-3 months following TKR 1/626 (0.16%) and THR 6/681 (0.88%); between 3- 6 months 4/626 (0.64%) following TKR and 2/681 (0.29%) after THR. DVT following TKR was 12/626 (1.92%) at 6 months and following THR 7/681 (1.03%). PE at 6 months after TKR was 5/626 (0.80%) and THR 5/681(0.73%) with no attributable mortality. Conclusions. The incidence of VTE using our thromboprophylaxis protocol - low molecular weight heparin (LMWH) and very low dose warfarin - in THR and TKR not only compares favourably with other modes of thrombo-prophylaxis in literature, but also is cheap and cost effective

Since artificial joints are expected to operate for more than decades in human body, animal and clinical studies are not suitable for evaluation of their durability. Instead, in-vitro mechanical tests have been employed, but they cannot fully reproduce complex in-vivo mechanical and biochemical environment. For instance, lipids in synovial fluid have been known to be absorbed in ultra-high molecular weight polyethylene (UHMWPE) components of artificial joints in vivo, and recently it was found that absorbed lipids have potential to degrade UHMWPE. In order to assure clinical relevance of the in-vitro mechanical tests, understanding of the effect of the in-vivo environment on mechanical properties is indispensable. However, well-developed mechanical tests cannot be applied to retrieved components, because they require large specimens. In this study, we attempted to develop methods to evaluate mechanical properties of retrieved UHMWPE components. We prepared five kinds of UHMWPE. Those are molded UHMWPE made from GUR 1020 resin without any further treatment, remelted highly crosslinked UHMWPE, annealed highly crosslinked UHMWPE, squalene absorbed UHMWPE which was prepared by immersing in squalene at 80°C for 7 days (SQ) and squalene absorbed and artificially aged UHMWPE which was prepared by artificially aging SQ at 80°C for 21 days in air (SQA). SQ and SQA were employed in this study to mimic lipid absorption and lipid induced degradation. These materials were tested by two well-established mechanical tests, namely, tensile tests and compression tests, and two proposed mechanical tests that can be applied to retrieved components, namely, tensile punch tests and micro indentation tests. It was possible to clearly identify the difference between materials by any of test methods used in this study. Stiffness obtained from tensile punch tests and elastic modulus obtained from micro indentation tests were shown to be highly correlated with elastic modulus obtained from compression tests except for SQA, which was inhomogeneous due to degradation at the surfaces. The results showed that the elastic modulus of the local surface could be evaluated by micro indentation tests, while the average of that of the entire specimen could be evaluated by compression tests. ield load, fracture load and maximum load obtained from tensile punch tests showed little correlation with yield stress, fracture stress and maximum stress obtained from tensile tests, respectively. These differences were considered to be attributed to the differences in a stress condition between these two test methods. It is multi-axial tension in tensile punch tests, while it is uniaxial in tensile tests. Although some of the parameters obtained by tensile punch tests showed no or limited correlation with those obtained by tensile tests, it was possible to clearly identify the difference between materials by these proposed test methods. In particular, micro indentation tests could evaluate the mechanical properties very locally. These proposed test methods have the potential to provide useful information on mechanical properties of retrieved UHMWPE components

Background. dl-α-Tocopherol (vitamin E) blended ultra-high molecular weight Polyethylene (UHMWPE) was originally developed as a bearing material for use in knee prostheses . (1). The reduced biological response observed for vitamin E (VE) blended UHMWPE wear particles in in vitro experimentation . (2). has also demonstrated the materials potential for use in other orthopedic applications, especially total hip arthroplasty (THR). However, due to the excellent results achieved by highly crosslinked UHMWPE in hip simulator testing . (3). , the use of VE blended UHMWPE in THR would similarly require crosslinking. It was previously reported that VE radicals are formed during radiation crosslinking of VE blended UHMWPE . (4). , and it is hypothesized that these VE radicals may negatively impact the materials biological activity. In this study, ascorbic acid 6-palmitate (lipophilic vitamin C) was applied to electron-beam-irradiated VE blended UHMWPE in an attempt to oxidatively reduce the VE radicals. Electron Spin Resonance (ESR) was used to measure the number of VE radicals within the material and evaluate the regenerating effect of ascorbic acid 6-palmitate. Materials & Methods. UHMWPE resin powder (GUR 1050, Ticona, USA) was mixed with dl-a-Tocopherol (vitamin E) at 0.3 wt% and molded under direct compression at 25 MPa and 220°C. Virgin samples were produced by the same process, but without the addition of vitamin E (VE). Cylindrical pins (length: 40 mm, diameter: 3.5 mm) were then machined from these samples, packaged in a vacuum, and irradiated by electron-beam at 300 kGy. Samples were subsequently doped with either ascorbic acid 6-palmitate (Sigma, Japan) or ethanol (Ethanol 99.5%, Kishida, Japan) and subjected to a hydrostatic pressure of 100 MPa for 7, 14, and 21 days at room temperature. Radical measurements were made using ESR at 9.44 GHz and room temperature. All ESR spectra were recorded at 0.1 mW microwave power and 0.1 mT modulation amplitude. Results & Discussion. The observed characteristic ESR peak for VE radicals was shown to decrease with time in the electron-beam-irradiated VE blended UHMWPE samples that were doped with ascorbic acid 6-palmitate (Figure 1 & 2). This particular spectrum was confirmed as that for VE radicals through g-value and line width analysis (Figure 3). These results showed that the number of VE radicals in electron-beam-irradiated VE blended UHMWPE was reduced by doping with ascorbic acid 6-palmitate at 100 MPa. The reduced VE radical may transform into a quinine, or react with other VE radicals to form dimmers/trimers. Due to the fact that VE radicals in UHMWPE have been shown to be stable at room temperature, it is thought that the observed reduction in number of VE radicals is a result of the direct action ascorbic acid 6-palmitate

Background. The National Institute for Health and Clinical Effectiveness recommends both low molecular weight heparin (LMWH) and Rivaroxaban for venous thromboembolic (VTE) prophylaxis following lower limb arthroplasty. Despite evidence in the literature that suggests Rivaroxaban reduces VTE events, there are emerging concerns from the orthopaedic community regarding an increase in wound complications following its use. Methods. Through the orthopaedic clinical directors forum, Trusts replacing LMWH with Rivaroxaban for lower limb arthroplasty thromboprophylaxis during 2009 were identified. Prospectively collected Hospital episode statistics (HES) data was then analysed for these units so as to determine rates of 90-day symptomatic deep venous thrombosis (DVT), pulmonary embolism (PE), major bleed (cerebrovascular accident or gastrointestinal haemorrhage), all-cause mortality, and 30-day wound infection and readmission rates before and after the change to Rivaroxaban. 2752 patients prescribed Rivaroxaban following TKR or THR were compared to 10358 patients prescribed LMWH. Data was analysed using odds ratios (OR). Results. There were significantly more wound infections in the Rivaroxaban group (3.85% vs. 2.81%, OR=0.72; 95% CI 0.58–0.90). There were no significant differences between the two groups for PE (OR=1.52; 0.77–2.97), major bleed (OR=0.73; 0.48–1.12), all-cause mortality (OR=0.93; 0.46–1.87) and re-admission rate (OR=1.21; 0.88–1.67). There were significantly fewer symptomatic DVTs in the Rivaroxaban group (0.91% vs. 0.36%, OR=2.51; 1.30–4.82). Discussion. This study is the first to describe the real impact of the use of Rivaroxaban in the NHS. When compared with LMWH in lower limb arthroplasty patients, there were fewer DVTs in the Rivaroxaban group. However, wound infection rates were significantly higher following Rivaroxaban use whilst providing no reduction in symptomatic PE or all-cause mortality

Since its introduction in total hip replacements in the 1960's, Ultra High Molecular Weight Polyethylene (UHMWPE) has played a major role as a bearing component material for joint arthroplasty. Concerns were raised when issues of wear resistance became apparent, and therefore Highly Crosslinked Polyethylenes were introduced. Such materials undergo a thermal treatment to quench the free radicals and reduce progressive oxidation. However, said thermal treatment weakens the material mechanical properties and hence the use of antioxidants has been proposed and implemented in clinical use, mainly Vitamin-E. This can be added to the material before or after irradiation. If it is done before, part of the anti-oxydant is consumed during irradiation and so will not be available for its main purpose, and part reacts before irradiation with the free radicals thus reducing the crosslinking effect. If it is added after irradiation, high temperatures are required in order to diffuse it in the bulk material, and anyway the surface will be mainly rich in antioxidant. However, Vitamin-E tends to neutralize the free radicals on the oxidized lipid chain present in our body fluids and so in direct contact with the prosthetic components: such mechanism reduces the Vitamin-E quantity available for anti-oxidation purposes in the long run. A UHMWPE doped with Hindered Amine Light Stabilizer (HALS) has been developed and tested for applications in large joint replacements where highest resistance to wear and tough mechanical properties are simultaneously required, such as tibial inserts for knee joints or acetabular inserts for large diameter heads. Mechanical and biocompatibility tests were run in accordance with ASTM F 2565-06 and ISO 10993-1 with successful results and good reproducibility. In particular, electro spin resonance exhibited a very high level of free radicals in the three samples, which confirms the properties of this new material. Free radicals are the result of the activation of the HALS molecules during irradiation, creating nitroxide radicals that will destroy the residual alkyl radicals responsible for the oxidation before and after implantation. Biocompatibility tests proved absence of cytotoxicity, sensitization, irritation, genotoxicity or pyrogenic reactions. The possible future applications for this new material in the arthroplasty field will be discussed along with the expected advances and advantages

Alpha Lipoic Acid (L.A.) is an effective natural antioxidant discovered in the human body in 1951 from L.J. Reed and I.C. Gunslaus from liver.

It is inside broccoli, spinach and red meats, especially liver and spleen.

Actually it is largely used as antioxidant in antiaging products according to the low toxicity level of the product.

The present study take into consideration the possibility to reduce oxidation of medical irradiated UHMWPE GUR 1050, mixing together polyethylene powder and Alpha Lipoic Acid powder.

The study is composed of two parts.

Part 1 Thermostability of alpha lipoic acid during polyethylene fusion Part 2 detection of oxygen level in artificially aged irradiated polyethylene

Solid pieces were made with Gur 1050 powder (Ticona Inc., Bayport, Tex, USA) and mixed with Alpha Lipoic Acid (Talamonti, Italy, Stock 1050919074) 0,1%-­‐0,3%-­‐0,5%-­‐1%-­‐2% and gamma ray irradiated with 30 kGy (Isomedix, Northborough, MA).

An owen (80° Celsius) was used to produce an aging effect for 35 days in the doped and control samples (Conventional not doped polyethylene). This process simulate an aging effect of 10 years into the human body.

Part 1 : THERMAL STABILITY : a Fourier Transfer Infra Red (FTIR) test was made in pieces molded in a cell at 150° and 200°Celsius and pressure of 200 MPa comparing to the UHMWPE powder mixed with alpha lipoic acid. The presence of Alpha Lipoic Acid in the polyethylene was found at any depth in the manufacts.

Part 2 : OXIDATION OF THE SURFACE : After 5 weeks at 80° Celsius in a owen (ASTM standard F-­‐2003-­‐02)A FOURIER TRANSFER INFRA RED TEST (FTIR) was made in the superficial layer and deeper on the undersurface of doped 0,1% and conventional UHMWPE.

The antioxidation limit is defined as the ratio of the area under 1740cm/−­‐1 carbonyl and 1370 cm/−­‐1 Methylene absorbance peaks.

In conventional UHMWPE oxidation is detected on the surface and decreases in the deeper layers down to zero under 1500 Micron.

In the doped UHMWPE, FTIR demonstrate a very low oxidation limit on the surface and at any depth, comparing to conventional UHMWPE.

The examples show that Lipoic Acid is effective as antioxidant in irradiated UHMWPE and it is stable with respect to thermal treatment.

For any figures or tables, please contact authors directly.

Introduction. Osteolysis caused by wear of the ultrahigh molecular weight polyethylene (UHMWPE) often leads to failure. Cross-linking improves wear, but also produces residual free radicals that decrease oxidative stability. In vitro studies have shown that the anti-oxidative properties of vitamin E UHMWPE stabilize free radicals while retaining the physical and chemical properties of UHMWPE. The porous surface of the Regenerex™ shell was developed for improved bone in-growth fixation. The increased porosity of the Regenerex™ shell promotes early bony in-growth with the goal of greater long-term stability. The purpose of this study was to evaluate vitamin E infused polyethylene (VEPE) wear and stability of acetabular and femoral components using RSA. Methods. 58 patients (64 observed hips), all with osteoarthritis, gave informed consent to participate in a 5 year RSA study. Each patient received a VEPE liner, a Regenerex™ acetabular shell, and an uncemented stem with either a 32mm or 36 mm cobalt chrome femoral head. Tantalum beads were inserted into the VEPE, the pelvic and the femoral bone to measure head penetration into the polyethylene, and shell and stem stability over time, using RSA. RSA radiographs were scheduled immediately postoperatively (up to 6 weeks) and 6 months, 1, 2, 3, and 5 years after surgery. The Wilcoxon signed-ranks nonparametric test was used to determine if changes in penetration or migration were significant over time at p≤0.05. Results. 58 hips have been followed for 6 months, 55 at 1 year, 52 at 2 years, 47 at 3 years and 18 at 5 years. The 36mm cohort data is not reported at this time due to insufficient follow-up. The median± standard error (SE) superior head penetration into the polyethylene was 0.05±0.01mm at 2 years, 0.05±0.01mm at 3 years, and 0.05±0.02 mm at 5 years. The acetabular components had a median± SE cup translation in the proximal direction of 0.09±0.03mm at 2 years, 0.04±0.04mm at 3 years, and 0.06±0.06mm at 5 years. The median± SE cup rotation was −0.09±0.16 degrees at 2 years, −0.02±0.15 degrees at 3 years, and 0.30±0.20 degrees at 5 years. There was a statistically significant difference in cup rotation between the 6 month and 1 year intervals (p=0.007), but no significant differences in translation or head penetration. The median± SE stem distal migration was 0.08±0.07mm at 2 years, 0.05±0.23mm at 3 years, and 0.02±0.17mm at 5 years, with a significant difference between the 6 month and 3 year intervals (p=0.029). Discussion. The VEPE liners show low head penetration at 5 years. The early head penetration, probably due to creep, is substantially lower relative to that reported for non-vitamin E stabilized UHMWPE measured by similar techniques. At 5 years, all acetabular components were stable, with the early significant difference in rotation at 1 year likely due to early settling of the cup. This study documents the longest-term evaluation of in vivo wear performance of vitamin E stabilized UHMWPE. The stability of the Regenerex™ shell and femoral stem shows promise for long-term survivorship

Statement of Purpose:. The wear rate of Ultra High Molecular Weight Polyethylene (UHMWPE) in joint replacements has been correlated to both contact area and contact stress in the literature, [1], [2]. In both publications and our experiment, UHMWPE articulated with a polished surface of cobalt-chromium alloy was evaluated using a Pin-On-Disk (POD) apparatus (AMTI) implementing bi-directional movement. In publication [1], volumetric wear was independent of normal load and dependent upon increasing contact area. The results demonstrated that increasing contact stress decreased wear rates twofold. In publication [2], at maximum cross-shear, wear was proportional to nominal contact area and wear factors normalized to area are more appropriate than load based wear factors. In both studies, the contact surface areas of the POD pins were reduced by decreasing the diameters of the POD Pins. In our experiment, the contact area was dependent on textured POD Pin 390 (T390) which had low wear [3]. T390 reduced the normal POD contact area from 71 mm. 2. to 8.26 mm. 2. Hydroxylapatite (HA) particles were introduced to the serum to simulate third body wear debris. We hypothesized that the normal POD Pins would have greater wear rates than the textured POD Pins. A measurement of 0.14 mg HA particles per 250 mL of serum was used for each test 0.33 million cycles. Methods:. The GUR 1020 resin XLK POD Pins were gamma irradiated to 50 kGy in a vacuum package and then remelted. Three (3) T390 POD pins and nine (9) untextured XLK POD Pins were used. Three untextured XLK POD Pins were tested against three T390 POD pins. The other six (6) untextured XLK POD Pins were used as soak controls. Each pin articulated against a polished, high carbon wrought CoCr metal alloy counterface (ASTM F1537; diameter = 38.1 mm; thickness = 12.7 mm). Wear rate tests were for 1.98 million cycles. In order to perform the t-test analysis, the wear rates for each pin were given by the slope of the linear regression line through the individual data points (cycle count, cumulative wear), excluding the (0, 0) point. Results:. The probability for the means between the T390 POD pins and the untextured XLK POD Pins was *p = 0.009. T390 wear rates were statistically significant as compared to the untextured XLK POD Pin wear rates. The T390 POD Pin is illustrated in Figure 1. Figures 2 and 3 summarize the wear rates between T390 POD Pins and the untextured POD Pins with and without HA particles. Conclusions:. The wear rates between T390 and untextured POD pins did not take into account that the POD pins were not cleaned using a solution to remove potentially embedded HA particles. The follow-on experiment will use a special cleaning method to remove all HA particles after each test cycle

Aim

Cutibacterium acnes, a skin commensal, is responsible for 5–10% of prosthetic joint infections (PJI). All current microbiological definitions of PJI require two or more identical commensal isolates to be recovered from the same procedure to diagnose PJI and rule out contamination. Unlike coagulase negative staphylococci, C.acnes shows a highly stereotypical susceptibility profile making impossible to phenotypically assess the clonal relationship of isolates. In order to determine the clonal relationship of multiple C.acnes isolates recovered from arthroplasty revisions, we analyzed by multi-locus sequence typing (MLST) C.acnes isolates grown from orthopedic device-related infections (ODRI) in a reference center for bone and joint infection.

Introduction

About 2% of primary total joint replacement arthroplasty (TJA) procedures become infected. Periprosthetic joint infection (PJI) is currently one of the main reasons requiring costly TJA revisions, posing a burden on patients, physicians and insurance companies.¹ Currently used drug-eluting polymers such as bone cements offer limited drug release profiles, sometimes unable to completely clear out bacterial microorganisms within the joint space. For this study we determined the safety and efficacy of an antibiotic-eluting UHMWPE articular surface that delivered local antibiotics at optimal concentrations to treat PJI in a rabbit model.