Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application. In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II.Aims
Methods
The aim of this audit was to assess and improve the completeness and accuracy of the National Joint Registry (NJR) dataset for arthroplasty of the elbow. It was performed in two phases. In Phase 1, the completeness was assessed by comparing the NJR elbow dataset with the NHS England Hospital Episode Statistics (HES) data between April 2012 and April 2020. In order to assess the accuracy of the data, the components of each arthroplasty recorded in the NJR were compared to the type of arthroplasty which was recorded. In Phase 2, a national collaborative audit was undertaken to evaluate the reasons for unmatched data, add missing arthroplasties, and evaluate the reasons for the recording of inaccurate arthroplasties and correct them.Aims
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Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism. A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry.Aims
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A review of the literature on elbow replacement found no consistency in the clinical outcome measures which are used to assess the effectiveness of interventions. The aim of this study was to define core outcome domains for elbow replacement. A real-time Delphi survey was conducted over four weeks using outcomes from a scoping review of 362 studies on elbow replacement published between January 1990 and February 2021. A total of 583 outcome descriptors were rationalized to 139 unique outcomes. The survey consisted of 139 outcomes divided into 18 domains. The readability and clarity of the survey was determined by an advisory group including a patient representative. Participants were able to view aggregated responses from other participants in real time and to revisit their responses as many times as they wished during the study period. Participants were able to propose additional items for inclusion. A Patient and Public Inclusion and Engagement (PPIE) panel considered the consensus findings.Aims
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This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously. Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes.Aims
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Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes – the main cellular components in BMAC – interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes. Cite this article:
This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.Aims
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Complete ruptures of the ulnar collateral ligament (UCL) of the thumb are a common injury, yet little is known about their current management in the UK. The objective of this study was to assess the way complete UCL ruptures are managed in the UK. We carried out a multicentre, survey-based cross-sectional study in 37 UK centres over a 16-month period from June 2022 to September 2023. The survey results were analyzed descriptively.Aims
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Two discrete legal factors enable the surgeon to treat an injured patient the fully informed, autonomous consent of the adult patient with capacity via civil law; and the medical exception to the criminal law. This article discusses current concepts in consent in trauma; and also considers the perhaps less well known medical exception to the Offences against the Person Act 1861, which exempts surgeons from criminal liability as long as they provide ‘proper medical treatment’. Cite this article:
Shoulder arthroplasty is effective in the management of end-stage glenohumeral joint arthritis. However, it is major surgery and patients must balance multiple factors when considering the procedure. An understanding of patients’ decision-making processes may facilitate greater support of those considering shoulder arthroplasty and inform the outcomes of future research. Participants were recruited from waiting lists of three consultant upper limb surgeons across two NHS hospitals. Semi-structured interviews were conducted with 12 participants who were awaiting elective shoulder arthroplasty. Transcribed interviews were analyzed using a grounded theory approach. Systematic coding was performed; initial codes were categorized and further developed into summary narratives through a process of discussion and refinement. Data collection and analyses continued until thematic saturation was reached.Aims
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Ankle fractures are common, mainly affecting adults aged 50 years and over. To aid recovery, some patients are referred to physiotherapy, but referral patterns vary, likely due to uncertainty about the effectiveness of this supervised rehabilitation approach. To inform clinical practice, this study will evaluate the effectiveness of supervised versus self-directed rehabilitation in improving ankle function for older adults with ankle fractures. This will be a multicentre, parallel-group, individually randomized controlled superiority trial. We aim to recruit 344 participants aged 50 years and older with an ankle fracture treated surgically or non-surgically from at least 20 NHS hospitals. Participants will be randomized 1:1 using a web-based service to supervised rehabilitation (four to six one-to-one physiotherapy sessions of tailored advice and prescribed home exercise over three months), or self-directed rehabilitation (provision of advice and exercise materials that participants will use to manage their recovery independently). The primary outcome is participant-reported ankle-related symptoms and function six months after randomization, measured by the Olerud and Molander Ankle Score. Secondary outcomes at two, four, and six months measure health-related quality of life, pain, physical function, self-efficacy, exercise adherence, complications, and resource use. Due to the nature of the interventions, participants and intervention providers will be unblinded to treatment allocation.Aims
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This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients. A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry.Aims
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Aims. The aim of this study was to produce clinical consensus recommendations about the non-surgical treatment of children with Perthes’ disease. The recommendations are intended to support clinical practice in a condition for which there is no robust evidence to guide optimal care. Methods. A two-round, modified Delphi study was conducted online. An advisory group of children’s orthopaedic specialists consisting of physiotherapists, surgeons, and clinical nurse specialists designed a survey. In the first round, participants also had the opportunity to suggest new statements. The survey included statements related to ‘Exercises’, ‘Physical activity’, ‘Education/information sharing’, ‘Input from other services’, and ‘Monitoring assessments’. The survey was shared with clinicians who regularly treat children with Perthes’ disease in the UK using clinically relevant specialist groups and social
The aim of this study was to explore clinicians’ experience of a paediatric randomized controlled trial (RCT) comparing surgical reduction with non-surgical casting for displaced distal radius fractures. Overall, 22 staff from 15 hospitals who participated in the RCT took part in an interview. Interviews were informed by phenomenology and analyzed using thematic analysis.Aims
Methods
Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells. HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential.Aims
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Aims. Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods. Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined
Ankle fracture is one of the most common musculoskeletal injuries sustained in the UK. Many patients experience pain and physical impairment, with the consequences of the fracture and its management lasting for several months or even years. The broad aim of ankle fracture treatment is to maintain the alignment of the joint while the fracture heals, and to reduce the risks of problems, such as stiffness. More severe injuries to the ankle are routinely treated surgically. However, even with advances in surgery, there remains a risk of complications; for patients experiencing these, the associated loss of function and quality of life (Qol) is considerable. Non-surgical treatment is an alternative to surgery and involves applying a cast carefully shaped to the patient’s ankle to correct and maintain alignment of the joint with the key benefit being a reduction in the frequency of common complications of surgery. The main potential risk of non-surgical treatment is a loss of alignment with a consequent reduction in ankle function. This study aims to determine whether ankle function, four months after treatment, in patients with unstable ankle fractures treated with close contact casting is not worse than in those treated with surgical intervention, which is the current standard of care. This trial is a pragmatic, multicentre, randomized non-inferiority clinical trial with an embedded pilot, and with 12 months clinical follow-up and parallel economic analysis. A surveillance study using routinely collected data will be performed annually to five years post-treatment. Adult patients, aged 60 years and younger, with unstable ankle fractures will be identified in daily trauma meetings and fracture clinics and approached for recruitment prior to their treatment. Treatments will be performed in trauma units across the UK by a wide range of surgeons. Details of the surgical treatment, including how the operation is done, implant choice, and the recovery programme afterwards, will be at the discretion of the treating surgeon. The non-surgical treatment will be close-contact casting performed under anaesthetic, a technique which has gained in popularity since the publication of the Ankle Injury Management (AIM) trial. In all, 890 participants (445 per group) will be randomly allocated to surgical or non-surgical treatment. Data regarding ankle function, QoL, complications, and healthcare-related costs will be collected at eight weeks, four and 12 months, and then annually for five years following treatment. The primary outcome measure is patient-reported ankle function at four months from treatment.Aims
Methods
To identify unanswered questions about the prevention, diagnosis, treatment, and rehabilitation and delivery of care of first-time soft-tissue knee injuries (ligament injuries, patella dislocations, meniscal injuries, and articular cartilage) in children (aged 12 years and older) and adults. The James Lind Alliance (JLA) methodology for Priority Setting Partnerships was followed. An initial survey invited patients and healthcare professionals from the UK to submit any uncertainties regarding soft-tissue knee injury prevention, diagnosis, treatment, and rehabilitation and delivery of care. Over 1,000 questions were received. From these, 74 questions (identifying common concerns) were formulated and checked against the best available evidence. An interim survey was then conducted and 27 questions were taken forward to the final workshop, held in January 2023, where they were discussed, ranked, and scored in multiple rounds of prioritization. This was conducted by healthcare professionals, patients, and carers.Aims
Methods
The February 2024 Research Roundup360 looks at: If you use a surgical helmet, you should seal your gown-glove interface; The use of iodophor-impregnated drapes in patients with iodine-related allergies: a case series and review of the literature; Location of the ovaries in children and efficacy of gonadal shielding in hip and pelvis radiography; Prehospital tranexamic acid administration does not improve outcomes in severe trauma patients; Silver-coated distal femur megaprosthesis in chronic infections with severe bone loss: a multicentre case series.
To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.Aims
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Aims. Social
To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections. EDTA-NS solutions were irrigated at different durations (1, 5, 10, and 30 minutes) and concentrations (1, 2, 5, 10, and 50 mM) to disrupt Aims
Methods
With up to 40% of patients having patellofemoral joint osteoarthritis (PFJ OA), the two arthroplasty options are to replace solely the patellofemoral joint via patellofemoral arthroplasty (PFA), or the entire knee via total knee arthroplasty (TKA). The aim of this study was to assess postoperative success of second-generation PFAs compared to TKAs for patients treated for PFJ OA using patient-reported outcome measures (PROMs) and domains deemed important by patients following a patient and public involvement meeting. MEDLINE, EMBASE via OVID, CINAHL, and EBSCO were searched from inception to January 2022. Any study addressing surgical treatment of primary patellofemoral joint OA using second generation PFA and TKA in patients aged above 18 years with follow-up data of 30 days were included. Studies relating to OA secondary to trauma were excluded. ROB-2 and ROBINS-I bias tools were used.Aims
Methods
Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses.Aims
Methods
Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants. pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs.Aims
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To identify factors influencing clinicians’ decisions to undertake a nonoperative hip fracture management approach among older people, and to determine whether there is global heterogeneity regarding these factors between clinicians from high-income countries (HIC) and low- and middle-income countries (LMIC). A SurveyMonkey questionnaire was electronically distributed to clinicians around the world through the Fragility Fracture Network (FFN)’s Perioperative Special Interest Group and clinicians’ personal networks between 24 May and 25 July 2021. Analyses were performed using Excel and STATA v16.0. Between-group differences were determined using independent-samples Aims
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Perthes’ disease is an idiopathic avascular necrosis of the developing femoral head, often causing deformity that impairs physical function. Current treatments aim to optimize the joint reaction force across the hip by enhancing congruency between the acetabulum and femoral head. Despite a century of research, there is no consensus regarding the optimal treatment. The aim of this study was to describe the experiences of children, their families, and clinicians when considering the treatment of Perthes’ disease. A qualitative study gathered information from children and their families affected by Perthes’ disease, along with treating clinicians. Interviews followed a coding framework, with the interview schedule informed by behavioural theory and patient and public involvement. Transcripts were analyzed using the framework method.Aims
Methods
Most patients with advanced malignancy suffer bone metastases, which pose a significant challenge to orthopaedic services and burden to the health economy. This study aimed to assess adherence to the British Orthopaedic Oncology Society (BOOS)/British Orthopaedic Association (BOA) guidelines on patients with metastatic bone disease (MBD) in the UK. A prospective, multicentre, national collaborative audit was designed and delivered by a trainee-led collaborative group. Data were collected over three months (1 April 2021 to 30 June 2021) for all patients presenting with MBD. A data collection tool allowed investigators at each hospital to compare practice against guidelines. Data were collated and analyzed centrally to quantify compliance from 84 hospitals in the UK for a total of 1,137 patients who were eligible for inclusion.Aims
Methods
The use of artificial intelligence (AI) is rapidly growing across many domains, of which the medical field is no exception. AI is an umbrella term defining the practical application of algorithms to generate useful output, without the need of human cognition. Owing to the expanding volume of patient information collected, known as ‘big data’, AI is showing promise as a useful tool in healthcare research and across all aspects of patient care pathways. Practical applications in orthopaedic surgery include: diagnostics, such as fracture recognition and tumour detection; predictive models of clinical and patient-reported outcome measures, such as calculating mortality rates and length of hospital stay; and real-time rehabilitation monitoring and surgical training. However, clinicians should remain cognizant of AI’s limitations, as the development of robust reporting and validation frameworks is of paramount importance to prevent avoidable errors and biases. The aim of this review article is to provide a comprehensive understanding of AI and its subfields, as well as to delineate its existing clinical applications in trauma and orthopaedic surgery. Furthermore, this narrative review expands upon the limitations of AI and future direction. Cite this article:
This is a multicentre, prospective assessment of a proportion of the overall orthopaedic trauma caseload of the UK. It investigates theatre capacity, cancellations, and time to surgery in a group of hospitals that is representative of the wider population. It identifies barriers to effective practice and will inform system improvements. Data capture was by collaborative approach. Patients undergoing procedures from 22 August 2022 and operated on before 31 October 2022 were included. Arm one captured weekly caseload and theatre capacity. Arm two concerned patient and injury demographics, and time to surgery for specific injury groups.Aims
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Aims. It has been established that mechanical stimulation benefits tendon-bone (T-B) healing, and macrophage phenotype can be regulated by mechanical cues; moreover, the interaction between macrophages and mesenchymal stem cells (MSCs) plays a fundamental role in tissue repair. This study aimed to investigate the role of macrophage-mediated MSC chondrogenesis in load-induced T-B healing in depth. Methods. C57BL/6 mice rotator cuff (RC) repair model was established to explore the effects of mechanical stimulation on macrophage polarization, transforming growth factor (TGF)-β1 generation, and MSC chondrogenesis within T-B enthesis by immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Macrophage depletion was performed by clodronate liposomes, and T-B healing quality was evaluated by histology and biomechanics. In vitro, bone marrow-derived macrophages (BMDMs) were stretched with CELLOAD-300 load system and macrophage polarization was identified by flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). MSC chondrogenic differentiation was measured by histochemical analysis and qRT-PCR. ELISA and qRT-PCR were performed to screen the candidate molecules that mediated the pro-chondrogenic function of mechanical stimulated BMDMs. Results. Mechanical stimulation promoted macrophage M2 polarization in vivo and in vitro. The conditioned
Gram-negative periprosthetic joint infection (PJI) has been poorly studied despite its rapidly increasing incidence. Treatment with one-stage revision using intra-articular (IA) infusion of antibiotics may offer a reasonable alternative with a distinct advantage of providing a means of delivering the drug in high concentrations. Carbapenems are regarded as the last line of defense against severe Gram-negative or polymicrobial infection. This study presents the results of one-stage revision using intra-articular carbapenem infusion for treating Gram-negative PJI, and analyzes the characteristics of bacteria distribution and drug sensitivity. We retrospectively reviewed 32 patients (22 hips and 11 knees) who underwent single-stage revision combined with IA carbapenem infusion between November 2013 and March 2020. The IA and intravenous (IV) carbapenem infusions were administered for a single Gram-negative infection, and IV vancomycin combined with IA carbapenems and vancomycin was applied for polymicrobial infection including Gram-negative bacteria. The bacterial community distribution, drug sensitivity, infection control rate, functional recovery, and complications were evaluated. Reinfection or death caused by PJI was regarded as a treatment failure.Aims
Methods
Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry.Aims
Methods
After a few passages of in vitro culture, primary human articular chondrocytes undergo senescence and loss of their phenotype. Most of the available chondrocyte cell lines have been obtained from cartilage tissues different from diarthrodial joints, and their utility for osteoarthritis (OA) research is reduced. Thus, the goal of this research was the development of immortalized chondrocyte cell lines proceeded from the articular cartilage of patients with and without OA. Using telomerase reverse transcriptase (hTERT) and SV40 large T antigen (SV40LT), we transduced primary OA articular chondrocytes. Proliferative capacity, degree of senescence, and chondrocyte surface antigen expression in transduced chondrocytes were evaluated. In addition, the capacity of transduced chondrocytes to synthesize a tissue similar to cartilage and to respond to interleukin (IL)-1β was assessed.Aims
Methods
Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of Aims
Methods
Aims. The effects of remnant preservation on the anterior cruciate ligament (ACL) and its relationship with the tendon graft remain unclear. We hypothesized that the co-culture of remnant cells and bone marrow stromal cells (BMSCs) decreases apoptosis and enhances the activity of the hamstring tendons and tenocytes, thus aiding ACL reconstruction. Methods. The ACL remnant, bone marrow, and hamstring tendons were surgically harvested from rabbits. The apoptosis rate, cell proliferation, and expression of types I and III collagen, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and tenogenic genes (scleraxis (SCX), tenascin C (TNC), and tenomodulin (TNMD)) of the hamstring tendons were compared between the co-culture medium (ACL remnant cells (ACLRCs) and BMSCs co-culture) and control medium (BMSCs-only culture). We also evaluated the apoptosis, cell proliferation, migration, and gene expression of hamstring tenocytes with exposure to co-culture and control
The December 2022 Foot & Ankle Roundup360 looks at: Evans calcaneal osteotomy and multiplanar correction in flat foot deformity; Inflammatory biomarkers in tibialis posterior tendon dysfunction; Takedown of ankle fusions and conversion to total ankle arthroplasty; Surgical incision closure with three different materials; Absorbable sutures are not inferior to nonabsorbable sutures for tendo Achilles repair; Zadek’s osteotomy is a reliable technique for treating Haglund’s syndrome; How to best assess patient limitations after acute Achilles tendon injury; Advances in the management of infected nonunion of the foot and ankle.
Multiligament knee injuries (MLKI) are devastating injuries that can result in significant morbidity and time away from sport. There remains considerable variation in strategies employed for investigation, indications for operative intervention, outcome reporting, and rehabilitation following these injuries. At present no study has yet provided a comprehensive overview evaluating the extent, range, and overall summary of the published literature pertaining to MLKI. Our aim is to perform a methodologically rigorous scoping review, mapping the literature evaluating the diagnosis and management of MLKI. This scoping review will address three aims: firstly, to map the current extent and nature of evidence for diagnosis and management of MLKI; secondly, to summarize and disseminate existing research findings to practitioners; and thirdly, to highlight gaps in current literature. A three-step search strategy as described by accepted methodology will be employed to identify peer-reviewed literature including reviews, technical notes, opinion pieces, and original research. An initial limited search will be performed to determine suitable search terms, followed by an expanded search of four electronic databases (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Web of Science). Two reviewers will independently screen identified studies for final inclusion.Aims
Methods
There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Aims
Methods
Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1PrαTACE’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation.Aims
Methods
The conventionally described mechanism of distal biceps tendon rupture (DBTR) is of a ‘considerable extension force suddenly applied to a resisting, actively flexed forearm’. This has been commonly paraphrased as an ‘eccentric contracture to a flexed elbow’. Both definitions have been frequently used in the literature with little objective analysis or citation. The aim of the present study was to use video footage of real time distal biceps ruptures to revisit and objectively define the mechanism of injury. An online search identified 61 videos reporting a DBTR. Videos were independently reviewed by three surgeons to assess forearm rotation, elbow flexion, shoulder position, and type of muscle contraction being exerted at the time of rupture. Prospective data on mechanism of injury and arm position was also collected concurrently for 22 consecutive patients diagnosed with an acute DBTR in order to corroborate the video analysis.Aims
Methods
Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67phox was involved in suramin-enhanced chondrocyte phenotype maintenance.Aims
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The extended wait that most patients are now experiencing for hip and knee arthroplasty has raised questions about whether reliance on waiting time as the primary driver for prioritization is ethical, and if other additional factors should be included in determining surgical priority. Our Prioritization of THose aWaiting hip and knee ArthroplastY (PATHWAY) project will explore which perioperative factors are important to consider when prioritizing those on the waiting list for hip and knee arthroplasty, and how these factors should be weighted. The final product will include a weighted benefit score that can be used to aid in surgical prioritization for those awaiting elective primary hip and knee arthroplasty. There will be two linked work packages focusing on opinion from key stakeholders (patients and surgeons). First, an online modified Delphi process to determine a consensus set of factors that should be involved in patient prioritization. This will be performed using standard Delphi methodology consisting of multiple rounds where following initial individual rating there is feedback, discussion, and further recommendations undertaken towards eventual consensus. The second stage will then consist of a Discrete Choice Experiment (DCE) to allow for priority setting of the factors derived from the Delphi through elicitation of weighted benefit scores. The DCE consists of several choice tasks designed to elicit stakeholder preference regarding included attributes (factors).Aims
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