Histology is an established tool in diagnosing periprosthetic joint infections (PJIs). Different thresholds, using various infection definitions and histopathological criteria, have been described. This study determined the performance of different thresholds of polymorphonuclear neutrophils (≥ 5 PMN/HPF, ≥ 10 PMN/HPF, ≥ 23 PMN/10 HPF) , when using the European Bone and Joint Infection Society (EBJIS), Infectious Diseases Society of America (IDSA), and the International Consensus Meeting (ICM) 2018 criteria for PJI. A total of 119 patients undergoing revision total hip (rTHA) or knee arthroplasty (rTKA) were included. Permanent histology sections of periprosthetic tissue were evaluated under high power (400× magnification) and neutrophils were counted per HPF. The mean neutrophil count in ten HPFs was calculated (PMN/HPF). Based on receiver operating characteristic (ROC) curve analysis and the z-test, thresholds were compared.Aims
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Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model. The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA).Aims
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Within the UK, around 70,000 patients suffer neck of femur (NOF) fractures annually. Patients presenting with this injury are often frail, leading to increased morbidity and a 30-day mortality rate of 6.1%. COVID-19 infection has a broad spectrum of clinical presentations with the elderly, and those with pre-existing comorbidities are at a higher risk of severe respiratory compromise and death. Further increased risk has been observed in the postoperative period. The aim of this study was to assess the impact of COVID-19 infection on the complication and mortality rates of NOF fracture patients. All NOF fracture patients presenting between March 2020 and May 2020 were included. Patients were divided into two subgroup: those with or without clinical and/or laboratory diagnosis of COVID-19. Data were collected on patient demographics, pattern of injury, complications, length of stay, and mortality.Aims
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Platelet concentrates, like platelet-rich plasma (PRP) and platelet lysate (PL), are widely used in regenerative medicine, especially in bone regeneration. However, the lack of standard procedures and controls leads to high variability in the obtained results, limiting their regular clinical use. Here, we propose the use of platelet-derived extracellular vesicles (EVs) as an off-the-shelf alternative for PRP and PL for bone regeneration. In this article, we evaluate the effect of PL-derived EVs on the biocompatibility and differentiation of mesenchymal stromal cells (MSCs). EVs were obtained first by ultracentrifugation (UC) and then by size exclusion chromatography (SEC) from non-activated PL. EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and the expression of CD9 and CD63 markers by western blot. The effect of the obtained EVs on osteoinduction was evaluated in vitro on human umbilical cord MSCs by messenger RNA (mRNA) expression analysis of bone markers, alkaline phosphatase activity (ALP), and calcium (Ca2+) content.Aims
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Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI. In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI.Aims
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Current treatments of prosthetic joint infection (PJI) are minimally effective against The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load.Aims
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Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses.Aims
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Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation.Aims
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The primary aim was to assess the rate of postoperative COVID-19 following hip and knee arthroplasty performed in March 2020 in the UK. The secondary aims were to assess whether there were clinical factors associated with COVID-19 status, the mortality rate of patients with COVID-19, and the rate of potential COVID-19 in patients not presenting to healthcare services. A multicentre retrospective study was conducted of patients undergoing hip or knee arthroplasty during the first wave of the COVID-19 pandemic (1 March 2020 to 31 March 2020) with a minimum of 60 days follow-up. Patient demographics, American Society of Anesthesiologists grade, procedure type, primary or revision, length of stay (LOS), COVID-19 test status, and postoperative mortality were recorded. A subgroup of patients (n = 211) who had not presented to healthcare services after discharge were contacted and questioned as to whether they had symptoms of COVID-19.Aims
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Removal of infected components and culture-directed antibiotics are important for the successful treatment of chronic periprosthetic joint infection (PJI). However, as many as 27% of chronic PJI patients yield negative culture results. Although culture negativity has been thought of as a contraindication to one-stage revision, data supporting this assertion are limited. The aim of our study was to report on the clinical outcomes for one-stage and two-stage exchange arthroplasty performed in patients with chronic culture-negative PJI. A total of 105 consecutive patients who underwent revision arthroplasty for chronic culture-negative PJI were retrospectively evaluated. One-stage revision arthroplasty was performed in 30 patients, while 75 patients underwent two-stage exchange, with a minimum of one year's follow-up. Reinfection, re-revision for septic and aseptic reasons, amputation, readmission, mortality, and length of stay were compared between the two treatment strategies.Aims
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COVID-19 necessitated abrupt changes in trauma service delivery. We compare the demographics and outcomes of patients treated during lockdown to a matched period from 2019. Findings have important implications for service development. A split-site service was introduced, with a COVID-19 free site treating the majority of trauma patients. Polytrauma, spinal, and paediatric trauma patients, plus COVID-19 confirmed or suspicious cases, were managed at another site. Prospective data on all trauma patients undergoing surgery at either site between 16 March 2020 and 31 May 2020 was collated and compared with retrospective review of the same period in 2019. Patient demographics, injury, surgical details, length of stay (LOS), COVID-19 status, and outcome were compared.Aims
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The present study investigates the effectiveness of platelet-rich plasma (PRP) gel without adjunct to induce cartilage regeneration in large osteochondral defects in a rabbit model. A bilateral osteochondral defect was created in the femoral trochlear groove of 14 New Zealand white rabbits. The right knees were filled with PRP gel and the contralateral knees remained untreated and served as control sides. Some animals were killed at week 3 and others at week 12 postoperatively. The joints were harvested and assessed by Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) MRI scoring system, and examined using the International Cartilage Repair Society (ICRS) macroscopic and ICRS histological scoring systems. Additionally, the collagen type II content was evaluated by the immunohistochemical staining.Aims
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The diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been proposed, but there is no consensus on the place of many of these in the diagnostic pathway. Previous attempts to develop a definition of PJI have not been universally accepted and there remains no reference standard definition. This paper reports the outcome of a project developed by the European Bone and Joint Infection Society (EBJIS), and supported by the Musculoskeletal Infection Society (MSIS) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Implant-Associated Infections (ESGIAI). It comprised a comprehensive review of the literature, open discussion with Society members and conference delegates, and an expert panel assessment of the results to produce the final guidance.Aims
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In wound irrigation, 1 mM ethylenediaminetetraacetic acid (EDTA) is more efficacious than normal saline (NS) in removing bacteria from a contaminated wound. However, the optimal EDTA concentration remains unknown for different animal wound models. The cell toxicity of different concentrations of EDTA dissolved in NS (EDTA-NS) was assessed by Cell Counting Kit-8 (CCK-8). Various concentrations of EDTA-NS irrigation solution were compared in three female Sprague-Dawley rat models: 1) a skin defect; 2) a bone exposed; and 3) a wound with an intra-articular implant. All three models were contaminated with Aims
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Vertebrates have adapted to life on Earth and its constant gravitational field, which exerts load on the body and influences the structure and function of tissues. While the effects of microgravity on muscle and bone homeostasis are well described, with sarcopenia and osteoporosis observed in astronauts returning from space, the effects of shorter exposures to increased gravitational fields are less well characterized. We aimed to test how hypergravity affects early cartilage and skeletal development in a zebrafish model. We exposed zebrafish to 3 g and 6 g hypergravity from three to five days post-fertilization, when key events in jaw cartilage morphogenesis occur. Following this exposure, we performed immunostaining along with a range of histological stains and transmission electron microscopy (TEM) to examine cartilage morphology and structure, atomic force microscopy (AFM) and nanoindentation experiments to investigate the cartilage material properties, and finite element modelling to map the pattern of strain and stress in the skeletal rudiments.Aims
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Infection after surgery increases treatment costs and is associated with increased mortality. Hip fracture patients have historically had high rates of methicillin-resistant A total of 13,503 patients who presented with a hip fracture over 17 years formed the study population. Multivariable logistic regression was performed to determine risk factors for MRSA and SSI. Autoregressive integrated moving average (ARIMA) modelling adjusted for temporal trends in rates of MRSA. Kaplan-Meier estimators were generated to assess for changes in mortality.Aims
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The worldwide COVID-19 pandemic is directly impacting the field of orthopaedic surgery and traumatology with postponed operations, changed status of planned elective surgeries and acute emergencies in patients with unknown infection status. To this point, Germany's COVID-19 infection numbers and death rate have been lower than those of many other nations. This article summarizes the current regimen used in the field of orthopaedics in Germany during the COVID-19 pandemic. Internal university clinic guidelines, latest research results, expert consensus, and clinical experiences were combined in this article guideline.Aims
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The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented challenges to healthcare systems worldwide. Orthopaedic departments have adopted business continuity models and guidelines for essential and non-essential surgeries to preserve hospital resources as well as protect patients and staff. These guidelines broadly encompass reduction of ambulatory care with a move towards telemedicine, redeployment of orthopaedic surgeons/residents to the frontline battle against COVID-19, continuation of education and research through web-based means, and cancellation of non-essential elective procedures. However, if containment of COVID-19 community spread is achieved, resumption of elective orthopaedic procedures and transition plans to return to normalcy must be considered for orthopaedic departments. The COVID-19 pandemic also presents a moral dilemma to the orthopaedic surgeon considering elective procedures. What is the best treatment for our patients and how does the fear of COVID-19 influence the risk-benefit discussion during a pandemic? Surgeons must deliberate the fine balance between elective surgery for a patient’s wellbeing versus risks to the operating team and utilization of precious hospital resources. Attrition of healthcare workers or Orthopaedic surgeons from restarting elective procedures prematurely or in an unsafe manner may render us ill-equipped to handle the second wave of infections. This highlights the need to develop effective screening protocols or preoperative COVID-19 testing before elective procedures in high-risk, elderly individuals with comorbidities. Alternatively, high-risk individuals should be postponed until the risk of nosocomial COVID-19 infection is minimal. In addition, given the higher mortality and perioperative morbidity of patients with COVID-19 undergoing surgery, the decision to operate must be carefully deliberated. As we ramp-up elective services and get “back to business” as orthopaedic surgeons, we have to be constantly mindful to proceed in a cautious and calibrated fashion, delivering the best care, while maintaining utmost vigilance to prevent the resurgence of COVID-19 during this critical transition period. Cite this article:
Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines. We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay.Aims
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The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens from synovial fluid of prosthetic joint infection (PJI) patients. A group of 75 patients who underwent revision knee or hip arthroplasties were enrolled prospectively. Ten patients with primary arthroplasties were included as negative controls. Synovial fluid was collected for mNGS analysis. Optimal thresholds were determined to distinguish pathogens from background microbes. Synovial fluid, tissue, and sonicate fluid were obtained for culture.Aims
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