Trial of Vancomycin and Cefazolin as Surgical Prophylaxis in Arthroplasty.

BACKGROUND: The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear. METHODS: In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery. RESULTS: A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical-site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3.5%) in the placebo group (relative risk, 1.28; 95% confidence interval [CI], 0.94 to 1.73; P = 0.11). Among patients undergoing knee arthroplasty, surgical-site infections occurred in 63 of 1109 patients (5.7%) in the vancomyin group and in 42 of 1124 patients (3.7%) in the placebo group (relative risk, 1.52; 95% CI, 1.04 to 2.23). Among patients undergoing hip arthroplasty, surgical-site infections occurred in 28 of 920 patients (3.0%) in the vancomyin group and in 29 of 930 patients (3.1%) in the placebo group (relative risk, 0.98; 95% CI, 0.59 to 1.63). Adverse events occurred in 35 of 2010 patients (1.7%) in the vancomycin group and in 35 of 2030 patients (1.7%) in the placebo group, including hypersensitivity reactions in 24 of 2010 patients (1.2%) and 11 of 2030 patients (0.5%), respectively (relative risk, 2.20; 95% CI, 1.08 to 4.49), and acute kidney injury in 42 of 2010 patients (2.1%) and 74 of 2030 patients (3.6%), respectively (relative risk, 0.57; 95% CI, 0.39 to 0.83). CONCLUSIONS: The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty among patients without known MRSA colonization. (Funded by the Australian National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12618000642280.).

Injectable ultrasound-powered bone-adhesive nanocomposite hydrogel for electrically accelerated irregular bone defect healing.

The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.

The deterioration of calcified cartilage integrity reflects the severity of osteoarthritis-A structural, molecular, and biochemical analysis.

The calcified cartilage zone (CCZ) is a thin interlayer between the hyaline articular cartilage and the subchondral bone and plays an important role in maintaining the joint homeostasis by providing biological and mechanical support from unmineralized cartilage to the underlying mineralized subchondral bone. The hallmark of CCZ characteristics in osteoarthritis (OA) is less well known. The aim of our study is to evaluate the structural, molecular, and biochemical composition of CCZ in tissues affected by primary knee OA and its relationship with disease severity. We collected osteochondral tissue samples stratified according to disease severity, from 16 knee OA patients who underwent knee replacement surgery. We also used meniscectomy-induced rat samples to confirm the pathophysiologic changes of human samples. We defined the characteristics of the calcified cartilage layer using a combination of morphological, biochemical, proteomic analyses on laser micro-dissected tissue. Our results demonstrated that the Calcium/Phosphate ratio is unchanged during the OA progression, but the calcium-binding protein and cadherin binding protein, as well as carbohydrate metabolism-related proteins, undergo significant changes. These changes were further accompanied by thinning of the CCZ, loss of collagen and proteoglycan content, the occurrence of the endochondral ossification, neovasculature, loss of the elastic module, loss of the collagen direction, and increase of the tortuosity indicating an altered structural and mechanical properties of the CCZ in OA. In conclusion, our results suggest that the calcified cartilage changes can reflect the disease progression.

Inflammatory macrophages interrupt osteocyte maturation and mineralization via regulating the Notch signaling pathway.

BACKGROUND: It is well-known that both macrophages and osteocytes are critical regulators of osteogenesis and osteoclastogenesis, yet there is limited understanding of the macrophage-osteocyte interaction, and how their crosstalk could affect bone homeostasis and mineralization. This research therefore aims to investigate the effects of macrophage polarization on osteocyte maturation and mineralization process. METHODS: A macrophage-derived conditioned medium based osteocyte culture was set up to investigate the impact of macrophages on osteocyte maturation and terminal mineralization. Surgically induced osteoarthritis (OA) rat model was used to further investigate the macrophage-osteocyte interaction in inflammatory bone remodeling, as well as the involvement of the Notch signaling pathway in the mineralization process. RESULTS: Our results identified that osteocytes were confined in an immature stage after the M1 macrophage stimulation, showing a more rounded morphology, higher expression of early osteocyte marker E11, and significantly lower expression of mature osteocyte marker DMP1. Immature osteocytes were also found in inflammatory bone remodeling areas, showing altered morphology and mineralized structures similar to those observed under the stimulation of M1 macrophages in vitro, suggesting that M1 macrophages negatively affect osteocyte maturation, leading to abnormal mineralization. The Notch signaling pathway was found to be down regulated in M1 macrophage-stimulated osteocytes as well as osteocytes in inflammatory bone. Overexpression of the Notch signaling pathway in osteocytes showed a significant circumvention on the negative effects from M1 macrophage. CONCLUSION: Taken together, our findings provide valuable insights into the mechanisms involved in abnormal bone mineralization under inflammatory conditions.

A technique for preparing undecalcified osteochondral fresh frozen sections for elemental mapping and understanding disease etiology.

The anatomy of the osteochondral junction is complex because several tissue components exist as a unit, including uncalcified cartilage (with superficial, middle, and deep layers), calcified cartilage, and subchondral bone. Furthermore, it is difficult to study because this region is made up of a variety of cell types and extracellular matrix compositions. Using X-ray fluorescence microscopy, we present a protocol for simultaneous elemental detection on fresh frozen samples. We transferred the osteochondral sample using a tape-assisted system and successfully tested it in synchrotron X-ray fluorescence. This protocol elucidates the distinct distribution of elements at the human knee's osteochondral junction, making it a useful tool for analyzing the co-distribution of various elements in both healthy and diseased states.

Prevalence and determinants of physical activity, sedentary behaviour and fatigue five years after total knee replacement.

OBJECTIVE: To determine the prevalence and predictors of physical activity, sedentary behaviour and fatigue five years after total knee replacement surgery. DESIGN: A longitudinal cohort study. SETTING: Community-dwelling adults who had previously undergone total knee replacement. METHODS: Five-year follow-up questionnaire data were obtained from participants previously enrolled in a randomised controlled trial examining rehabilitation after total knee replacement. Main study outcomes at one year did not differ between randomisation groups, hence data were pooled for the present longitudinal analysis. Before and one and five years after surgery, participants completed questionnaires (Active Australia Survey, WOMAC, SF12 v2, demographics and fatigue). RESULTS: 272/422 community-dwelling adults (45-74 years) completed the questionnaires at five years. Excessive sedentary behaviour was evident in 91% of the cohort, predicted by excessive sedentary behaviour and lack of energy at one year. Inadequate physical activity at five years was evident for 59% of the cohort, predicted by higher fatigue and comorbidity scores pre-surgery and inadequate physical activity at one year. Just under half (47%) of the cohort experienced clinically-important fatigue at five years, predicted by clinically-important fatigue before and one year after surgery, lack of sleep before surgery and physical activity one year after surgery. CONCLUSION: Documenting physical activity, sedentary behaviour and fatigue before and one year after knee replacement is important to identify those at risk of longer-term inadequate physical activity, excessive sedentary behaviour and clinically-important fatigue. Interventions to maintain activity and reduce sedentary behaviour are needed to reap the potential health benefits of total knee replacement surgery.

Targeting Early Healing Phase with Titania Nanotube Arrays on Tunable Diameters to Accelerate Bone Regeneration and Osseointegration.

Blood coagulation and inflammation are the earliest biological responses to implant surfaces. Implant nano-surfaces can significantly impact the osseointegration through the influence on the early phase of bone regeneration. However, the interplay between blood clot property and inflammatory reaction on nanosurfaces is rarely understood. Herein, titania nanotube arrays (TNAs) with different diameters are fabricated on titanium. In vitro evaluation with the whole blood indicates that TNA with a diameter of 15 nm (TNA 15) enables noteworthy platelet activation resulting in distinct clot features compared with that of pure Ti and TNA with a diameter of 120 nm (TNA 120). Further co-culture with macrophages on the clot or in the clot-conditioned medium shows that the clot on TNA 15 downregulates the inflammation and manipulates a favorable osteoimmunomodulatory environment for osteogenesis. In vivo studies further demonstrate that TNA 15 could downregulate the inflammation-related genes while upregulating growth metabolism-related genes in an early healing hematoma. Additionally, TNA 15 promotes de novo bone formation with improved extending of osteocyte dendrites, demonstrating the desired osseointegration. These findings indicate that surface nano-dimensions can significantly influence clot formation and appropriate clot features can manipulate a favorable osteoimmunomodulatory environment for bone regeneration and osseointegration.

Cutibacterium acnes in shoulder surgery: a scoping review of strategies for prevention, diagnosis, and treatment.

BACKGROUND: Cutibacterium acnes is a commensal, gram-positive, facultatively anaerobic bacillus that resides in the dermis. Historically thought to be a contaminant when identified on cultured specimens, recent advances in diagnostic technology have now implicated it as the most common organism responsible for postoperative shoulder infections. Despite a recognition of the role of this organism and a significant research interest in recent years, there is clear lack of consensus guideline on strategies to prevent, diagnose, and treat postoperative shoulder infection. METHOD: The electronic databases PubMed, MEDLINE, CINAHL, Scopus, and Web of Science were searched in March 2020. All experimental and nonexperimental studies that investigate C acnes in shoulder surgery were included. Inclusion was limited to articles published after 2000 and written in English; reviews, gray literature, or abstracts were excluded. A total of 70 studies were included in this review. This scoping review was performed in accordance with the Extended Preferred Reporting Items of Systematic Reviews and Meta-Analyses Statement for Scoping Reviews (PRISMA-ScR). RESULTS: Standard surgical prophylactic regimens such as intravenous antibiotics and topical chlorhexidine are ineffective at removing C acnes from the deep layer of the dermis, and there is a shift toward using topical benzoyl peroxide with significantly improved efficacy. An improved understanding of the bacteria has demonstrated that a prolonged culture time of up to 14 days is needed, especially in cases of established infection. Advances in diagnostics such as sonication and molecular-based testing are promising. Although usually thought to be susceptible to a broad range of antibiotics, resistance is emerging to clindamycin. An improved understanding of its ability to form a biofilm highlights the difficulty in treating an established infection. CONCLUSION: The role of C acnes causing postoperative infection following shoulder surgery is being increasingly recognized. Strategies for prevention, diagnosis, and treatment have been outlined from both an antimicrobial and surgical perspective. A number of these strategies are emerging and require further research to demonstrate efficacy before implementation into clinical guidelines.

Extraction of Common Task Features in EEG-fMRI Data Using Coupled Tensor-Tensor Decomposition.

The fusion of simultaneously recorded EEG and fMRI data is of great value to neuroscience research due to the complementary properties of the individual modalities. Traditionally, techniques such as PCA and ICA, which rely on strong non-physiological assumptions such as orthogonality and statistical independence, have been used for this purpose. Recently, tensor decomposition techniques such as parallel factor analysis have gained more popularity in neuroimaging applications as they are able to inherently contain the multidimensionality of neuroimaging data and achieve uniqueness in decomposition without making strong assumptions. Previously, the coupled matrix-tensor decomposition (CMTD) has been applied for the fusion of the EEG and fMRI. Only recently the coupled tensor-tensor decomposition (CTTD) has been proposed. Here for the first time, we propose the use of CTTD of a 4th order EEG tensor (space, time, frequency, and participant) and 3rd order fMRI tensor (space, time, participant), coupled partially in time and participant domains, for the extraction of the task related features in both modalities. We used both the sensor-level and source-level EEG for the coupling. The phase shifted paradigm signals were incorporated as the temporal initializers of the CTTD to extract the task related features. The validation of the approach is demonstrated on simultaneous EEG-fMRI recordings from six participants performing an N-Back memory task. The EEG and fMRI tensors were coupled in 9 components out of which seven components had a high correlation (more than 0.85) with the task. The result of the fusion recapitulates the well-known attention network as being positively, and the default mode network working negatively time-locked to the memory task.

On-Table and Short-Term Mortality: A Single-Institution Experience With Cementing All Hip Arthroplasties for Neck of Femur Fractures.

BACKGROUND: To review on-table, day 0, day 1, day 7, and day 30 mortality after hemiarthroplasty or total hip arthroplasty (THA) using cemented femoral stems for femoral neck fractures in order to evaluate risk factors for perioperative and short-term mortality. METHODS: The medical records of 751 consecutive cases with neck of femur fractures who underwent hemiarthroplasty (n = 602) or THA (n = 149) with cemented stems between January 2011 and December 2016 were retrospectively reviewed from a prospectively gathered database. The primary outcome measures were on-table, day 0, day 1, day 7, and day 30 mortality. Univariate and multivariate analyses were performed in order to identify various contributing patient and surgical variables. RESULTS: There were 2 on-table deaths (0.27%): one patient had a cardiorespiratory arrest at the time of inserting the femoral stem and the other had a cardiorespiratory arrest at the end of wound closure some 20 minutes after cementing. There were 3 further day 0 deaths meaning the day 0 mortality rate was 0.67% (5/751). All 5 patients were older than 80 years and had an American Society of Anesthesiologists grade 3 or more. The 1-day, 7-day, and 30-day mortality rates were 0.93% (7 patients), 2.7% (20 patients), and 6.8% (51 patients), respectively. There is significantly higher 30-day mortality risk associated with increasing American Society of Anesthesiologists grade (P < .001) when adjusted for age, gender, and type of surgery (hemiarthroplasty compared with THA). CONCLUSION: In our neck of femur fracture patients who were operated with cemented stems, 7-day and 30-day mortality rates were 2.7% and 6.8%, respectively. Cemented stems should be used with caution in elderly hip fracture patients with multiple comorbidities who are at high risk of perioperative mortality.

Mortality and Implant Survival With Simultaneous and Staged Bilateral Total Hip Arthroplasty: Experience From the Australian Orthopedic Association National Joint Replacement Registry.

BACKGROUND: Total hip arthroplasty (THA) is an effective procedure for relieving pain and restoring function in osteoarthritis. A significant proportion of patients have severe disease bilaterally. Consensus regarding safety and selection of patients for simultaneous bilateral THA or the optimal timing for staged THA has not been reached. The aim of this study is to compare rates, causes of revision, and 30-day mortality between simultaneous and staged bilateral THA using data from the Australian Orthopedic National Joint Replacement Registry. METHODS: Data for 12,359 bilateral THA procedures were collected from September, 1999 to December, 2017. Rates and causes of revision and 30-day mortality were obtained for simultaneous bilateral and staged procedures with intervals of 1 day-6 weeks, 6 weeks-3 months, and 3 months-6 months. Yearly cumulative percent revision or cumulative percent survival with 95% confidence intervals calculated by the Kaplan-Meier method, and adjusted hazard ratios were used for comparisons. RESULTS: Thirty-day mortality is lower in patients who have bilateral procedures within 6 months, regardless of timing, than those who have unilateral procedures (0.06% vs 0.18%). Staged bilateral THA had a significantly lower mortality than simultaneous bilateral THA (odds ratio 0.175, 95% confidence interval = 0.04-0.78, P = .022). When separate time intervals were compared, no significant differences were seen. Bilateral 6 week-3 months has a higher rate of revision from 1.5 years-2years compared with same day bilaterals (hazard ratio = 2.39, 95% confidence interval = 1.12, 5.09, P = .024). There were no other significant differences in the rate of revision between groups. The most common reasons for revision were fracture, loosening, and infection. Simultaneous bilateral procedures have a significantly higher rate of revision for fracture compared with staging 3-6 months (hazard ratio = 1.96 [1.27, 3.03], P = .002). CONCLUSION: This study demonstrates that bilateral THA has a low mortality rate regardless of time interval between procedures. Simultaneous and staged bilateral THA have similar rates of revision.

Fixation Method for Hip Arthroplasty Stem Following Hip Fracture: A Population-Level Cost-Effectiveness Analysis.

BACKGROUND: Hip arthroplasty is increasing in Australia. The number of procedures for fractured neck of femur was 7500 in 2017. Best practices for fixation method and procedure type require scrutiny. This paper is about the costs and health outcomes of cemented and uncemented hemiarthroplasty and total hip arthroplasty at a national level. METHODS: We created a Markov model for patients <75, aged 75-85, and over 85. Expected costs and health outcomes over 5 years from a decision to change from existing practice to a best practice policy in which all patients with fractured neck of femur received the same fixation method based on age and type of arthroplasty are estimated. The model was populated using prevalence and incidence data from the Australian Orthopedic Association National Joint Replacement Registry, costs from Metro North Hospital and Health Service in Queensland, and probabilities and utilities from the literature. We simulated the uncertainties in outcomes with probabilistic sensitivity analysis. RESULTS: We found that uncemented stem procedures were more costly and provided worse health outcomes compared to cemented stem fixation for hemiarthroplasty and total hip arthroplasty for all age groups. Moving from existing practice to cemented stem arthroplasty could save the Australian health system $2.0 million over 5 years with a gain of 203 quality-adjusted life years. CONCLUSION: We suggest that consideration be given to cemented fixation of the femoral stem for patients receiving both hemiarthroplasty and total hip arthroplasty for fractured neck of femur. Best practice guidelines focused on cost-effectiveness should recommend cemented stem fixation to both save costs and improve patient quality of life.

The Outcome of Total Knee Arthroplasty With and Without Patellar Resurfacing up to 17 Years: A Report From the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: Patellar resurfacing in total knee arthroplasty (TKA) remains a controversial issue after more than 4 decades of TKA. Despite a growing body of evidence from registry data, resurfacing is still based largely on a surgeon's preference and training. The purpose of this study is to provide long-term outcomes for patellar resurfaced compared to when the patella is not resurfaced. METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry (1999-2017) were used for this study. The analysis included 570,735 primary TKAs undertaken for osteoarthritis. Hazard ratios (HRs) and 17-year cumulative percent revision rates were used to compare revision rates between 4 subgroups: minimally stabilized (MS) patellar resurfacing, posterior stabilized (PS) patellar resurfacing, MS unresurfaced, and PS unresurfaced patella. Additional analyses of the patellar implant type and a comparison of inlay and onlay patellar resurfacing were also performed. RESULTS: For all primary TKA, procedures where the patella was not resurfaced have a higher rate of revision compared to procedures where the patella was resurfaced (HR, 1.31; confidence interval, 1.28-1.35; P < .001). Unresurfaced PS knees have the highest cumulative percent revision at 17 years (11.1%), followed by MS unresurfaced (8.8%), PS resurfaced (7.9%), and MS resurfaced (7.1%). Inlay patellar resurfacing has a higher rate of revision compared to onlay patellar resurfacing (HR, 1.27; confidence interval, 1.17-1.37; P < .001). CONCLUSION: Resurfacing the patella reduces the rate of revision for both MS and PS knees. MS knees with patellar resurfacing have the lowest rate of revision. Onlay patella designs are associated with a lower revision rate compared to inlay patella designs.

Application of Metabolomics to Osteoarthritis: from Basic Science to the Clinical Approach.

PURPOSE OF THE REVIEW: Osteoarthritis (OA) is a multifactorial and progressive disease affecting whole synovial joint. The extract pathogenic mechanisms and diagnostic biomarkers of OA remain unclear. In this article, we review the studies related to metabolomics of OA, discuss the biomarkers as a tool for early OA diagnosis. Furthermore, we examine the major studies on the application of metabolomics methodology in the complex context of OA and create a bridge from findings in basic science to their clinical utility. RECENT FINDINGS: Recently, the tissue metabolomics signature permits a view into transitional phases between the healthy and OA joint. Both nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry-based metabolomics approaches have been used to interrogate the metabolic alterations that may indicate the complex progression of OA. Specifically, studies on alterations pertaining to lipids, glucose, and amino acid metabolism have aided in the understanding of the complex pathogenesis of OA. The discovery of identified metabolites could be important for diagnosis and staging of OA, as well as for the assessment of efficacy of new drugs.

The Outcome of Cemented Acetabular Components in Total Hip Arthroplasty for Osteoarthritis Defines a Proficiency Threshold: Results of 22,956 Cases From the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: The declining popularity of cemented acetabular components is incongruous, given the published results of prostheses implanted using contemporary techniques. The outcome of arthroplasty has previously been demonstrated to correlate with surgeon experience and volume of practice. We aim to explore if surgeon volume alters outcomes of cemented acetabular components based on survivorship data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). METHODS: An observational study was undertaken using a cohort of 22,956 patients with a primary diagnosis of osteoarthritis in the period 2003-2016 in whom cemented acetabular components were implanted. The cohort was stratified by age (greater than or less than 65 years) and annualized surgical volume of ≤10, >10-≤25, and >25 cases. RESULTS: Stratified by age and volume, there was a protective benefit against revision conveyed at volume thresholds of 10 cases per annum and 25 cases per annum for patients ≥65 years of age and <65 years of age, respectively. CONCLUSION: Cemented total hip arthroplasty has excellent survivorship out to 15 years based on AOANJRR data. This survivorship is further improved if surgeons perform a higher volume of cases, with >25 cases conferring the greatest benefit. The AOANJRR data set is used to define best practice; surgeons who choose to utilize cemented acetabular fixation should be encouraged to perform this technique in adequate volumes to minimize revision risk and ensure the preservation of this important surgical skill set.

A decade of Australian and New Zealand orthopaedic publications: a bibliometric trend analysis from 2008 to 2018.

PURPOSE: We aimed to apply bibliometric tools to Australian and New Zealand orthopaedic publications produced between 2008 and 2018 to identify the most highly cited publications, author and institution collaboration networks and topic trends. Analysis of the literature can highlight areas of emerging interest and knowledge gaps, and direct future research. METHODS: A systematic search was conducted using Clarivate Analytics Web of Science. Citation analysis was carried out using Web of Science. Collaboration networks were constructed using chord diagrams. Trends in publication topics were analysed using simple linear regression to find the rate of change of publication volume on each topic. RESULTS: A total of 3097 publications contributed to by 8855 individual authors met inclusion criteria. Across the study period, there was a large increase in the annual volume of publications on the topic of ACL (Anterior Cruciate Ligament) surgery. We also found that collaboration between Australian and New Zealand authors was very low with only 1% (n = 31) of publications including authors from both countries and 0.4% (n = 12) including orthopaedic surgeons or trainees from both. CONCLUSIONS: Publications on ACL surgery have increased over the past decade, likely due to the presence of competing surgical approaches and the recently recognized risk of osteoarthritis following ACL reconstruction. The overall collaboration between Australian and New Zealand authors was very low which lends itself to opportunities for future research.

Mixed cell therapy of bone marrow-derived mesenchymal stem cells and articular cartilage chondrocytes ameliorates osteoarthritis development.

Of the many cell-based treatments that have been tested in an effort to regenerate osteoarthritic articular cartilage, none have ever produced cartilage that compare with native hyaline cartilage. Studies show that different cell types lead to inconsistent results and for cartilage regeneration to be considered successful, there must be an absence of fibrotic tissue. Here we report of a series of experiments in which bone marrow-derived stem cells (BMSCs) and articular cartilage chondrocytes (ACCs) were mixed in a 1:1 ratio and tested for their ability to enhance cartilage regeneration in three different conditions: (1) in an in vitro differentiation model; (2) in an ex vivo cartilage defect model implanted subcutaneously in mice; and (3) as an intra-articular injection in a meniscectomy-induced OA model in rats. The mixed cells were compared with monocultures of BMSCs and ACCs. In all three experimental models there was significantly enhanced cartilage regeneration and decreased fibrosis in the mixed BMSCs+ACCs group compared with the monocultures. Molecular analysis showed a reduction in vascularization and hypertrophy, coupled with higher chondrogenic gene expression resulting from the BMSCs+ACCs treatment. Together, our data suggest that mixed BMSCs+ACCs treatment is highly chondro-protective and is more effective in regenerating damaged cartilage in both the ex vivo cartilage defect and post-trauma OA disease models. The results from this approach could potentially be used for regeneration of cartilage in OA patients.

Protective effects of mitochondria-targeted antioxidants and statins on cholesterol-induced osteoarthritis.

The contribution of metabolic factors on the severity of osteoarthritis (OA) is not fully appreciated. This study aimed to define the effects of hypercholesterolemia on the progression of OA. Apolipoprotein E-deficient (ApoE-/-) mice and rats with diet-induced hypercholesterolemia (DIHC) rats were used to explore the effects of hypercholesterolemia on the progression of OA. Both models exhibited OA-like changes, characterized primarily by a loss of proteoglycans, collagen and aggrecan degradation, osteophyte formation, changes to subchondral bone architecture, and cartilage degradation. Surgical destabilization of the knees resulted in a dramatic increase of degradative OA symptoms in animals fed a high-cholesterol diet compared with controls. Clinically relevant doses of free cholesterol resulted in mitochondrial dysfunction, overproduction of reactive oxygen species (ROS), and increased expression of degenerative and hypertrophic markers in chondrocytes and breakdown of the cartilage matrix. We showed that the severity of diet-induced OA changes could be attenuated by treatment with both atorvastatin and a mitochondrial targeting antioxidant. The protective effects of the mitochondrial targeting antioxidant were associated with suppression of oxidative damage to chondrocytes and restoration of extracellular matrix homeostasis of the articular chondrocytes. In summary, our data show that hypercholesterolemia precipitates OA progression by mitochondrial dysfunction in chondrocytes, in part by increasing ROS production and apoptosis. By addressing the mitochondrial dysfunction using antioxidants, we were able attenuate the OA progression in our animal models. This approach may form the basis for novel treatment options for this OA risk group in humans.-Farnaghi, S., Prasadam, I., Cai, G., Friis, T., Du, Z., Crawford, R., Mao, X., Xiao, Y. Protective effects of mitochondria-targeted antioxidants and statins on cholesterol-induced osteoarthritis.

Prevalence and determinants of physical activity and sedentary behaviour before and up to 12 months after total knee replacement: a longitudinal cohort study.

OBJECTIVE: This study aims to evaluate the prevalence and determinants of inadequate physical activity and excessive sedentary behaviour before and after total knee replacement. DESIGN, SETTING AND SUBJECTS: Secondary analysis was performed on data from a cohort of 422 adults (45-74 years), drawn from 12 public or private hospitals, undergoing primary unilateral or bilateral total knee replacement surgery. MAIN MEASURES: Questionnaires were used to determine the presence of inadequate physical activity and excessive sedentary behaviour before and 6 and 12 months after total knee replacement surgery. Knee pain, activity limitations, comorbidities, muscle strength, psychological well-being, fatigue, sleep and body mass index were measured/assessed as possible determinants of physical activity or sedentary behaviour. RESULTS: Before surgery, 77% ( n = 326) of the cohort participated in inadequate physical activity according to World Health Organization guidelines, and 60% ( n = 253) engaged in excessive sedentary behaviour. Twelve months after surgery, 53% ( n = 185) of the cohort engaged in inadequate physical activity and 45% ( n = 157) in excessive sedentary behaviour. Inadequate physical activity before surgery ( P = 0.02), obesity ( P = 0.07) and comorbidity score >6 ( P = 0.04) predicted inadequate physical activity 12 months after surgery. Excessive sedentary behaviour and activity limitations before surgery predicted excessive sedentary behaviour 12 months after surgery. CONCLUSION: Although there were improvements after total knee replacement, 12 months after surgery about half the cohort did not meet World Health Organization recommendations for activity. Pre-surgery assessment of physical activity, activity limitations, sedentary behaviour and body mass index is essential to identify patients at risk for long-term inactivity.

Surgical Space Suits Increase Particle and Microbiological Emission Rates in a Simulated Surgical Environment.

BACKGROUND: The role of space suits in the prevention of orthopedic prosthetic joint infection remains unclear. Recent evidence suggests that space suits may in fact contribute to increased infection rates, with bioaerosol emissions from space suits identified as a potential cause. This study aimed to compare the particle and microbiological emission rates (PER and MER) of space suits and standard surgical clothing. METHODS: A comparison of emission rates between space suits and standard surgical clothing was performed in a simulated surgical environment during 5 separate experiments. Particle counts were analyzed with 2 separate particle counters capable of detecting particles between 0.1 and 20 µm. An Andersen impactor was used to sample bacteria, with culture counts performed at 24 and 48 hours. RESULTS: Four experiments consistently showed statistically significant increases in both PER and MER when space suits are used compared with standard surgical clothing. One experiment showed inconsistent results, with a trend toward increases in both PER and MER when space suits are used compared with standard surgical clothing. CONCLUSION: Space suits cause increased PER and MER compared with standard surgical clothing. This finding provides mechanistic evidence to support the increased prosthetic joint infection rates observed in clinical studies.