An increased number of neutrophils (NEUs) has long been associated with infections in the knee joints; their contribution to knee osteoarthritis (KOA)
Specific and rapid detection methods for spinal tuberculosis, with sufficient sensitivity in HIV-1 co-infected individuals, are needed, to ensure early initiation of appropriate treatment to prevent physical disability and neurological fallout. In addition, understanding the systemic and local
In approximately 20 years, surgical treatment of femoro-acetabular impingement (FAI) has been widely accepted, and its indications refined. However, the current approach of the disease prevents a good understanding of its
The
Shoulder injury related to vaccine administration (SIRVA) is a prolonged episode of shoulder dysfunction that commences within 24 to 48 hours of a vaccination. Symptoms include a combination of shoulder pain, stiffness, and weakness. There has been a recent rapid increase in reported cases of SIRVA within the literature, particularly in adults, and is likely related to the mass vaccination programmes associated with COVID-19 and influenza. The
Intervertebral disc (IVD) degeneration is one of the major contributors to low back pain, the leading cause of disability worldwide. This multifactorial pathological process involves the degradation of the extracellular matrix, inflammation, and cell loss due to apoptosis and senescence. While the deterioration of the extracellular matrix and cell loss lead to structural collapse of the IVD, increased levels of inflammation result in innervation and the development of pain. Amongst the known regulators of inflammation, toll-like receptors (TLRs) and more specifically TLR-2 have been shown to be specifically relevant in IVD degeneration. As strong post-transcriptional regulators, microRNAs (miRNAs) and their dysregulation has been connected to multiple pathologies, including degenerative diseases such as osteoarthritis and IVD degeneration. However, the role of miRNAs in TLR signalling in the IVD is still poorly understood and was hence investigated in this study. Human Nucleus pulposus (hNP) and Annulus fibrosus (hAF) cells (n=5) were treated with the TLR-2/6 specific agonist PAM2CSK4 (100 ng/mL for 6 hours) in order to activate the TLR2 signalling pathway. After the activation both miRNA and mRNA were isolated, followed by next-generation sequencing and qPCR analysis of proinflammatory cytokines respectively. Furthermore, cell supernatants were used to analyze the secretion of proinflammatory cytokines with enzyme-linked immunosorbent assay. TLR-2 knockdown (siRNA) cells were used as a control. Statistical analysis was conducted by performing Kolmogorov-Smirnov test and a two-tailed Student's t-test using GraphPad Prism version 9.0.2 for Windows (GraphPad Software, La Jolla California USA).Introduction and Objective
Materials and Methods
Aims. This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in
Total joint arthroplasty is the most significant advance in the treatment of end-stage arthritic disease of major joints. Despite the clinical success of this surgical procedure, however, some total joint prostheses fail, and although a failed prosthesis can be replaced, the results of revision arthroplasty are not as good as the first time. Studying the failed prosthesis and the associated bone and soft tissues provides insight into the causes of failure. Most prosthetic failures are the result of structural limitations of the implant components. Although material failure may be sudden, a much more common cause is gradual aseptic loosening of the prostheses. Aseptic loosening is caused by both mechanical (gradual loss of material by wear) and biological (osteoclastic resorption of adjacent bone) factors. Wear particles induce a foreign body reaction characterized by a pseudomembrane composed of granulomatous tissues including macrophages, fibroblasts, giant cells, and osteoclasts in addition to debris particles. The extent of this response is driven by the number, size, composition, surface area, and types of particles present. Although there are differences in the relative local toxicity of each of these particles, the end result is the same. These mechanical and biological factors are unavoidable, and the success of a total joint prosthesis depends on the rate with which they occur. Polyethylene wear particles (1–200 ?) are the primary cause of loosening. They are strongly birefringent under polarized light microscopy. Smaller particles are phagocytized by histiocytes, whereas larger particles are surrounded by foreign body giant cells. Fragmentation of PMMA may also cause particulate debris. The presence of these particles (30–100 ?) may be deduced by empty spaces into the soft tissues, often bordered by foreign body giant cells, since PMMA is dissolved by xylene during routine histological techniques. Metal oxides form on the surface of chrome-cobalt or titanium alloys due to an electrolytic process, and stresses on the surface of the metal shear the oxides into the surrounding tissues, causing a black pigmentation of the tissues. Histologically, the black deposits of oxidized metals are seen extracellularly as well as in the cytoplasm of histiocytes. In addition to oxidation, metal undergoes corrosion and, as a result, metal ions enter the soft tissues and the bloodstream. A ceramic-on-ceramic coupling generates a significantly lower amount of debris as compared to the conventional metal-on polyethylene solution. When present, ceramic debris cause a mild histiocytic reaction without giant cells and virtually no osteoclastic bone resorption. There are various secretory proteins at the interfacial membrane that can affect bone turnover, including the cytokines IL-1, IL-6, Il-10, and TNF-a. Other factors involved with bone resorption include the enzymes responsible for catabolism of the organic component of bone, such as MMPs. Prostaglandins, in particular PGE2, are also known to be important intercellular messengers in the osteolytic cascade. More recently, several mediators known to be involved in stimulation or inhibition of osteoclast differentiation and maturation, such as RANKL and osteoprotegerin, have been suggested as key factors in the development and progression of osteolysis. Infection around a prosthesis also causes loosening in approximately 1–5% of cases. Total joint prostheses become infected by two mechanisms, wound contamination at the time of surgery by Staph. aureus or Staph.epidermidis, and late hematogenous spread of organisms (Staphylo- and Streptococci, E. Coli, Pseudomonas, and anaerobes). The following factors facilitate bacterial growth. First, reaming and sawing, as well as PMMA polymerization, cause necrosis of necrotize bone adjacent to the implant, and such nonvascularized area permits bacteria to grow, safe from circulating host defenses. Second, a highly hydrated matrix of extracellular polymeric substances (biofilm) is formed that defends bacteria from antibiotics and phagocytosis. Third, some metals, such as nickel or cobalt, may depress macrophage function. The distinguishing histologic features of an infected prosthesis is an acute inflammatory reaction: a finding of >
5 PMN or of >
50 lymphocytes/hp field are presumptive for infection. Because some low-grade infections fail to stimulate an acute inflammatory reaction, they go undiagnosed until postoperative period when microbacterial culture results are available. To date, no single routinely used clinical or laboratory test has been shown to achieve ideal sensitivity and specificity for the diagnosis of prosthetic joint infection, and in most cases the diagnosis depends on a combination of clinical features, radiographic findings, and laboratory results. Intra-operative tissue cultures may be falsely negative because of prior antimicrobial exposure, a low number of organisms, inappropriate culture media, or atypical organisms. Conversely, cultures may be falsely positive because of contamination in the operating room, during transport, or in the laboratory. If the implant is removed, the entire prosthesis can be cultured. Moreover, because prosthetic joint infection is a biofilm-mediated infection, techniques that sample bacteria in biofilm, such as sonication or enzymatic treatment, may improve the diagnosis of prosthetic joint infection. More recently, molecular techniques are being used to detect nucleic acid in samples from infected patients even when conventional techniques are negative because of unusual microbial growth requirements or failure to grow after antimicrobial exposure or due to unfavourable environmental conditions. A disadvantage of such approach is its extreme sensitivity, leading to the possibility of false positive results. The clinical presentation of prosthetic joint infection may be indistinguishable from that of aseptic implant failure. In many cases, culture of granulomatous tissue around failed prostheses, preoperatively diagnosed as aseptically loosened, reveals the presence of bacteria that may per se significantly contribute to the recruitment, maturation and activation of osteoclasts and that superimpose to the foreign body reaction to wear debris. The presence of a smouldering infection in case of “aseptic” failure observed in revision arthroplasties. A systematic investigation on all retrieved implants is mandatory to define the precise role of each potential factor contributing to the pathogenesis of failure, in order to further improve the quality of care of patients having total joint arthroplasty.
The paramount importance of synovial fluid in lubrication and protection of articular joints has long been recognized. Synovial fluid, a dialysate of plasma, forms an interface with both the synovium and cartilage and plays a crucial role in joint lubrication and bearing functions. In an osteoarthritic joint, damage to the articular cartilage causes modifications in the rheological properties of synovial fluid and, reducing the viscoelasticity and increasing the friction between articular surfaces. Viscosupplementation is a treatment for osteoarthritis that uses hyaluronic acid as a (visco)supplement to the diseased joint. The aim of this treatment is to restore the rheological properties of synovial fluid. Osteoarthritis is the most common disease affecting the joints in human population and among the most important causes of pain, disability and economic loss. Therefore, innovative methods are needed to more effectively treat osteoarthritis, directly addressing the disease process. Among various locomotor mechanisms that could serve to illustrate the integrated nature of functional morphology, perhaps none is more complex than the equine locomotor system. Confronting the need for evaluating the current methods to control joint disease, the horse provides an excellent animal model. As it suffers similar clinical manifestations to those seen in human, it may provide tentative biomedical extrapolations.
Eleven patients with arthrogryposis multiplex congenita neurologica have been reviewed. Distinct patterns of deformity and muscle activity were identified which have been correlated with specific levels of segmental neurological motor deficit without sensory loss. The clinical picture was consistent with localised lesions of the anterior horn cell cell columns. This finding agreed with the recorded pathological lesions. Orthopaedic treatment should take account of the paralytic nature of the deformities.
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Avascular necrosis is poorly understood. The etiological factors have not been fully delineated. This disease process had a huge cost impact on the health system due to surgical treatment. Patients with avascular necrosis seen at a single institution underwent DNA extraction and analysis, coagulation-related analysis and buccal smears with DNA analysis. In this patient group 60% tested positive for at least one thrombophilic or hypofibrinolysis factor. We make recommendations depending on the defect in the cascade, allowing for potential non-surgical management of osteonecrosis in patients undergoing therapy with known antagonistic medications (i.e. corticosteroids). The etiology and pathogenesis of nontraumatic AVN need to be better elucidated. Our study identifies the potential association of thrombophilic and hypofibrinolytic factors and osteonecrosis of the hip, particularly genetic markers as identified through DNA markers The significance of this study:
Osteonecrosis is a devastating musculoskeletal condition; Tends to occur in young people; Treatments are suboptimal mostly palliative and not curative; currently unable to identify persons at risk for AVN; cannot reverse the process once AVN has developed. 60% of patients had at least one tested thrombophilic or hypofibrinolysis factor positive. Most patients never had a thrombotic event. Genetic screening, multiple hematological paramteres were tested on patients with avascular necrosis.
hypercoagulability plays a role in the development of AVN of the hip, mainly at the microvascular level; an impairment at the level of the fibrinolytic system through high PAI-1 levels is a potential mechanism responsible for the development of AVN; a genetic predisposition is implicated, at least in part, in the development of AVN of the hip. most patietns had a multifactorial problem and genetic screening and blood testing will lead to recommended therapy (medical) for those patients at risk.
Vascular inflammation and activation of myofibroblasts are significant contributors to the progression of fibrosis, which can severely impair tissue function. In various tissues, including tendons, Transforming growth factor beta 1 (TGF-β1) has been identified as a critical driver of adhesion and scar formation. Nevertheless, the mechanisms that underlie fibrotic peritendinous adhesions are still not well comprehended, and human microphysiological systems to help identify effective therapies remain scarce. To address this issue, we developed a novel human Tendon-on-a-Chip (hToC), comprised of an endothelialized vascular compartment harboring circulating monocytes and separated by a 5 μm/100 nm dual-scale ultrathin porous membrane from a type I/III collagen hydrogel with primary tendon fibroblasts and tissue-resident macrophages, all under defined serum-free conditions. The hToC models the crosstalk of the various cells in the system leading to the induction of inflammatory and fibrotic pathways including the activation of mTOR signaling. Consistent with phenotypes observed in vivo in mouse models and clinical human samples, we observed myofibroblast differentiation and senescence, tissue contraction, excessive extracellular matrix deposition, and monocytes’ transmigration and macrophages’ secretion of inflammatory cytokines, which were dependent on the presence of the endothelial barrier. This model offers novel insights on the role of vasculature in the
Tendinopathy can commonly occur around the foot and ankle resulting in isolated rupture, debilitating pain and degenerative foot deformity. The
Aims. Children with spinal dysraphism can develop various musculoskeletal deformities, necessitating a range of orthopaedic interventions, causing significant morbidity, and making considerable demands on resources. This systematic review aimed to identify what outcome measures have been reported in the literature for children with spinal dysraphism who undergo orthopaedic interventions involving the lower limbs. Methods. A PROSPERO-registered systematic literature review was performed following PRISMA guidelines. All relevant studies published until January 2023 were identified. Individual outcomes and outcome measurement tools were extracted verbatim. The measurement tools were assessed for reliability and validity, and all outcomes were grouped according to the Outcome Measures Recommended for use in Randomized Clinical Trials (OMERACT) filters. Results. From 91 eligible studies, 27 individual outcomes were identified, including those related to clinical assessment (n = 12), mobility (n = 4), adverse events (n = 6), investigations (n = 4), and miscellaneous (n = 1). Ten outcome measurement tools were identified, of which Hoffer’s Functional Ambulation Scale was the most commonly used. Several studies used unvalidated measurement tools originally developed for other conditions, and 26 studies developed new measurement tools. On the OMERACT filter, most outcomes reported
Aims. Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA. Methods. We used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs. Results. During OA, there were 626, 97, 1,060, and 2,330 differentially expressed genes in articular cartilage, meniscus, synovium, and subchondral bone, respectively. Gene Ontology enrichment revealed that these genes were enriched in extracellular matrix and structure organization, ossification, neutrophil degranulation, and activation at different degrees. Through ligand-receptor pairing and proteome of OA synovial fluid, we predicted ligand-receptor interactions and constructed a crosstalk atlas of the whole joint. Several interactions were reproduced by transwell experiment in chondrocytes and synovial cells, including TNC-NT5E, TNC-SDC4, FN1-ITGA5, and FN1-NT5E. After lipopolysaccharide (LPS) or interleukin (IL)-1β stimulation, the ligand expression of chondrocytes and synovial cells was upregulated, and corresponding receptors of co-culture cells were also upregulated. Conclusion. Each tissue displayed a different expression pattern in transcriptome, demonstrating their specific roles in OA. We highlighted tissue molecular crosstalk through ligand-receptor pairs in OA
Imaging can provide valuable information about the function of tissues and organs. The capacity for detecting and measuring imaging biomarkers of biological activities, allows for a better understanding of the
The pathophysiological basis of alterations in trabecular bone of patients with osteonecrosis of the femoral head (ONFH) remains unclear. ONFH has classically been considered a vascular disease with secondary changes in the subchondral bone. However, there is increasing evidence suggesting that ONFH could be a bone disease, since alterations in the functionality of bone tissue distant from the necrotic lesion have been observed. We comparatively studied the transcriptomic profile of trabecular bone obtained from the intertrochanteric region of patients with ONFH without an obvious aetiological factor, and patients with osteoarthritis (OA) undergoing total hip replacement in our Institution. To explore the biological processes that could be affected by ONFH, we compared the transcriptomic profile of trabecular bone from the intertrochanteric region and the femoral head of patients affected by this condition. Differential gene expression was studied using an Affymetrix microarray platform. Transcriptome analysis showed a differential signature in trabecular bone from the intertrochanteric region between patients with ONFH and those with OA. The gene ontology analyses of the genes overexpressed in bone tissue of patients with ONFH revealed a range of enriched biological processes related to cell adhesion and migration and angiogenesis. In contrast, most downregulated transcripts were involved in cell division. Trabecular bone in the intertrochanteric region and in the femoral head also exhibited a differential expression profile. Among the genes differentially expressed, we highlighted those related with cytokine production and immune response. This study identified a set of differently expressed genes in trabecular bone of patients with idiopathic ONFH, which might underlie the
The aim of this study was to examine the incidence of obesity in patients undergoing primary total shoulder replacement (TSR) (stemmed and reverse) for osteoarthritis (OA) in Australia compared to the incidence of obesity in the general population. A 2017–18 cohort of 2,621 patients from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) who underwent TSR, were compared with matched controls from the Australian Bureau of Statistics (ABS) National Health Survey from the same period. The two groups were analysed according to BMI category, sex and age. According to the 2017–18 National Health Survey, 35.6% of Australian adults are overweight and 31.3% are obese. Of the primary TSR cases performed, 34.2% were overweight and 28.6% were obese. The relative risk of requiring TSR for OA increased with increasing BMI category. Class-3 obese females, aged 55–64, were 8.9 times more likely to require TSR compared to normal weight counterparts. Males in the same age and BMI category were 2.5 times more likely. Class-3 obese patients underwent TSR 4 years (female) and 7 years (male) sooner than their normal weight counterparts. Our findings suggest that the obese population is at risk for early and more frequent TSR for OA. Previous studies demonstrate that obese patients undergoing TSR also exhibit increased risks of longer operative times, higher superficial infection rates, higher periprosthetic fracture rates, significantly reduced post-operative forward flexion range and greater revision rates. Obesity significantly increases the risk of requiring TSR. To our knowledge this is the first study to publish data pertaining to age and BMI stratification of TSR Societal efforts are vital to diminish the prevalence and burden of obesity related TSR. There may well be reversible
Osteoporosis can cause significant disability and cost to health services globally. We aim to compare risk fractures for both osteoporosis and fractures at the L1-L4 vertebrae (LV) and the neck of femurs (NOFs) in patients referred for DEXA scan in the North-West of England. Data was obtained from 31546 patients referred for DEXA scan in the North-West of England between 2004 and 2011. Demographic data was retrospectively analysed using STATA, utilising chi-squared and t-tests. Logistical models were used to report odds ratios for risk factors included in the FRAX tool looking for differences between osteoporosis and fracture risk at the LV and NOFs. In a study involving 2530 cases of LV fractures and 1363 of NOF fractures, age was significantly linked to fractures and osteoporosis at both sites, with a higher risk of osteoporosis at NOFs compared to LV. Height provided protection against fractures and osteoporosis at both sites, with a more pronounced protective effect against osteoporosis at NOFs. Weight was more protective for NOF fractures, while smoking increased osteoporosis risk with no site-specific difference. Steroids were unexpectedly protective for fractures at both sites, with no significant difference, while alcohol consumption was protective against osteoporosis at both sites and associated with increased LV fracture risk. Rheumatoid arthritis increased osteoporosis risk in NOFs and implied a higher fracture risk, though not statistically significant compared to LV. Results summarised in Table 1. Our study reveals that established osteoporosis and fracture risk factors impact distinct bony sites differently. Age and rheumatoid arthritis increase osteoporosis risk more at NOFs than LV, while height and steroids provide greater protection at NOFs. Height significantly protects LV fractures, with alcohol predicting them. Further research is needed to explore risk factors’ impact on additional bony sites and understand the observed differences’
Aims. The increase in prescription opioid misuse and dependence is now a public health crisis in the UK. It is recognized as a whole-person problem that involves both the medical and the psychosocial needs of patients. Analyzing aspects of
In the past decades, a huge amount of effort has been devoted to translate evidence based on standard preclinical models of bone tumours to effective tools for clinical applications. Although cancer is a genetic disease, hence the emphasis on -omics approaches, the complexity of cancer tissue, a mix of competing clones of transformed elements that react differently to microenvironmental stimuli, may hardly be reproduced by standard approaches. Cost, biological differences and ethical concerns are increasingly recognized as weaknessess of animal models. To overcome these limitations and provide reliable, reproducible, and affordable tools for predicting the effectiveness of treatments, environmental-controlled 3D cultures and co-cultures (spheroids, organoids) coupled with microfluidics and advanced imaging have recently being considered as effective instrument to increase knowledge on the
Osteogenesis Imperfecta (OI) is a heritable bone disorder characterized by bone fragility and often caused by mutations in the Type I collagen-encoding genes COL1A1 and COL1A2. The
Breast cancer is the most frequent malignancy in women with an estimation of 2.1 million new diagnoses in 2018. Even though primary tumours are usually efficiently removed by surgery, 20–40% of patients will develop metastases in distant organs. Bone is one of the most frequent site of metastases from advanced breast cancer, accounting from 55 to 58% of all metastases. Currently, none of the therapeutic strategies used to manage breast cancer bone metastasis are really curative. Tailoring a suitable model to study and evaluate the disease
Recently, the use of metal-on-metal articulations
in total hip arthroplasty (THA) has led to an increase in adverse
events owing to local soft-tissue reactions from metal ions and
wear debris. While the majority of these implants perform well,
it has been increasingly recognised that a small proportion of patients
may develop complications secondary to systemic cobalt toxicity
when these implants fail. However, distinguishing true toxicity
from benign elevations in cobalt ion levels can be challenging. . The purpose of this two part series is to review the use of cobalt
alloys in THA and to highlight the following related topics of interest:
mechanisms of cobalt ion release and their measurement, definitions
of pathological cobalt ion levels, and the
OA
Evaluating musculoskeletal conditions of the lower limb and understanding the
Introduction. Missile injuries are very serious injuries particularly in the cervical region. They are classified into high and low missile injuries when it involves the cervical spine. In modern guerrilla warfare, one must be aware of ballistic pathology with bullets as well as from explosives. In particular, improvised explosive devices commonly known as IED's play a new and important
A previously fit and well 58 year old male suffered from a bilateral psoas haematoma (PH) following 52 days of veno-venous extracorporeal membranous oxygenation (VV-ECMO) for severe Coronavirus disease (COVID-19), refractory to all non-invasive and medical therapies. He developed multiple complications, including inability to walk or weight-bear, due to lumbar plexopathy triggered by bilateral PH compression, compounded by COVID-19-related mononeuritis multiplex. The patient was referred to our institution with a known diagnosis of bilateral PH and after spinal multidisciplinary team (MDT) input, was deemed not for surgical or interventional radiology treatments. The patient received extensive neurorehabilitation, coordinated by multiple MDTs. Although PH has been correlated to COVID-19, to the best of our knowledge this is the first reported case of such a complex presentation resulting in a dramatic bilateral PH. Health records from 3 large UK teaching hospitals were collected regarding treatment and follow up appointments, following patient's written informed consent. Patient's comorbidities, duration in hospital units, MDT inputs, health assessments, mobilisation progress and neurologic assessments, were all recorded. Data was collected retrospectively then prospectively due to lengthy in-patient stay. The literature review was conducted via PubMed and open access sources, selecting all the relevant studies and the ECMO guidelines. Patient received treatment from 3 different units in 3 hospitals over 212 days including 103 days in neurorehabilitation. Involvement of physiotherapy, dietitians, speech and language teams, neurologist, neurophysiotherapists, occupational therapists was required. The patient progressed from a bed-bound coma and inability to walk, to standing with lower limb backslab at discharge. Additionally, he was referred for elective exploratory surgery of the psoas region for scar debridement and potential nerve graft repair of the lumbosacral plexus. The surgery outcome is cautiously optimistic, with some improvement in nerve conduction studies, however is currently unknown regarding recovery progress and return to premorbid functional baseline. The novelty of this presentation yields significant learning points regarding early recognition of PH, requirements for vast MDT input and specialist use of VV-ECMO in severe COVID-19 patients. It also highlights the broad
Aims. Patient engagement in adaptive health behaviours and interactions with their healthcare ecosystem can be measured using self-reported instruments, such as the Patient Activation Measure (PAM-13) and the Effective Consumer Scale (ECS-17). Few studies have investigated the influence of patient engagement on limitations (patient-reported outcome measures (PROMs)) and patient-reported experience measures (PREMs). First, we assessed whether patient engagement (PAM-13, ECS-17) within two to four weeks of an upper limb fracture was associated with limitations (the Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH), and Patient-Reported Outcome Measurement Information System Upper Extremity Physical Function computer adaptive test (PROMIS UE PF) scores) measured six to nine months after fracture, accounting for demographic, clinical, and psychosocial factors. Secondly, we assessed the association between patient engagement and experience (numerical rating scale for satisfaction with care (NRS-C) and satisfaction with services (NRS-S) six to nine months after fracture. Methods. A total of 744 adults with an isolated fracture of the proximal humerus, elbow, or distal radius completed PROMs. Due to multicollinearity of patient engagement and psychosocial variables, we generated a single variable combining measures of engagement and psychosocial factors using factor analysis. We then performed multivariable analysis with p < 0.10 on bivariate analysis. Results. Patient engagement and psychosocial factors combined to form a single factor (factor 1) accounting for 20% (QuickDASH, semi-partial R. 2. = 0.20) and 14% (PROMIS UE PF, semi-partial R. 2. = 0.14) of the variation in limitations six to nine months after fracture. Factor 1 also accounted for 17% (NRS-C, semi-partial R. 2. = 0.17) of variation in satisfaction with care, and 21% (NRS-S, semi-partial R. 2. = 0.21) of variation in satisfaction with services. Demographic factors (age, sex, work status) and measures of greater
While knee osteoarthritis (OA) is now recognized as a complex disease affecting the whole joint, not just the cartilages, there remains a paucity of data regarding the interactions between knee components. One relationship of particular interest is between the spatial variations in cartilage thickness (CTh) and subchondral bone mineral density (BMD). Indeed, bone and cartilage are two mechanosensitive tissues that interact as a functional unit and there is evidence of a biomechanical coupling between both tissues. Particularly, a recent in vivo study has shown a positive relationship in non-OA knees with thicker cartilage where bone is denser, and an alteration of this relationship in OA knees. These observations support the concept of an osteochondral unit and warrant additional research to assess the influence of bone depth. Therefore, this study aimed to characterize the relationship between spatial variations in CTh and BMD measured at various depths below the bone surface. CT-arthrography of 20 non-OA tibias and 20 severe medial-compartment OA tibias were segmented to build 3D mesh models of the bones and cartilages. Each individual tibia model was registered to a reference tibia, allowing to calculate BMD maps at 1, 3, 5 and 10mm below the bone-cartilage interface in the medial compartment. Pearson correlations between CTh maps and the four BMD maps were then calculated for each knee. Lastly, differences in correlation coefficients between successive bone layers were assessed using Wilcoxon signed-rank tests. In both OA and non-OA tibias, the correlation coefficients were higher with the BMD measured in the 1mm layer, and followed a pattern of statistically significant decrease with bone layers of increasing depth (p < 0.021). In non-OA tibias, the median relationship was positive with a strong effect size in the 1, 3 and 5mm layers, while in OA tibias the median relationship was positive only in the 1mm layer and with a medium effect size. In the OA tibias, the median relationship was negative with a weak effect size in the 3 and 5mm layers, and it was negative with a medium effect size in the 10mm layer. In conclusion, the results of the present study support the value of considering bone and cartilage as a unit, and more generally support OA
Spinal cord injury (SCI) is a devastating disorder for which the identification of exacerbating factors is urgently needed. Although age, blood pressure and infection are each considered to be prognostic factors in patients with SCI, exacerbating factors that are amenable to treatment remain to be elucidated. Microglial cells, the resident immune cell in the CNS, form the first line of defense after being stimulated by exposure to invading pathogens or tissue injury. Immediately after SCI, activated microglia enhance and propagate the subsequent inflammatory response by expressing cytokines, such as TNF-α, IL-6 and IL-1β. Recently, we demonstrated that the activation of microglia is associated with the neuropathological outcomes of SCI. Although the precise mechanisms of microglial activation remain elusive, several basic research studies have reported that hyperglycemia is involved in the activation of resident monocytic cells, including microglia. Because microglial activation is associated with secondary injury after SCI, we hypothesized that hyperglycemia may also influence the
Periprosthetic joint infection (PJI) is a potentially devastating complication of joint replacement surgery. Osteocytes comprise 90–95% of all cells in hard bone tissue, are long-lived and are becoming increasingly recognised as a critical cell type in the regulation of bone and systemic physiology. The purpose of this study was to examine role of these cells in PJI
Tendon disease causes widespread morbidity ranging from mild pain to catastrophic end-stage rupture. The
Objectives. Diabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the
Aim. Cutibacterium acnes (CA) is one of the crucial actors in spine instrumentation or shoulder prosthesis. Its population is subdivided into 6 major phylotypes: IA1, IA2, IB, IC, II and III. Recent methods for discriminating subpopulations within CA phylotypes highlight the predominance of SLST types H1 to 6 or K1 to 20 in bone and joint infection (BJI). The impact of their ability to produce a biofilm during the development of the infection (with resistance / tolerance to antibiotics used for treatment) remains little studied. Method. The purpose of this study was to determine whether the ability to establish a biofilm varied according to the different subtypes of clinical strains of CA previously characterized and involved in BJI (hip, knee and shoulder prosthesis). The BioFilm ring test (BioFilm Control®) method with index determination, called BFI (BioFilm Index) inversely proportional to the level of biofilm production was used (BFI = 0.00 indicates a high production of biofilm versus BFI = 20.00 indicates zero production). The BFI was determined after 3 h (T3) and 6 h (T6) incubation. The strains used came from patients, 5 belonging to the IA1 phylotype (SLST A1 and D1 types) and 4 to different phylotypes (IA2, IB, II and III). Results. The results show that the kinetics of establishment of an early CA biofilm turns out to be phylotype dependent. The most productive strains are those belonging to phylotype II (BFI T3 = 5.73, BFI T6 = 0.00) and to type SLST D1 belonging to phylotype IA1 (BFI T3 = 4.07, BFI T6 = 0.00). The other strains did not demonstrate saturated BFI, even after 6 h of incubation. Conclusions. The exact role of CA, as well as its ability to produce a biofilm in the
Human in vitro models of the neuromuscular junction (NMJ) are currently moving from embryonic stem cells to induced Pluripotent Stem Cells (iPSCs). With this, a robust model could be optimised for physiology and
Appropriate in vivo models can be used to understand atrophic non-union
Complex
Dynamic loading is necessary for the preservation of native cartilage, but mechanical disuse is one major risk factor for osteoarthritis (OA). As post-transcriptional regulators, microRNAs (miRs) represent promising molecules to quickly adjust the cellular transcriptome in a stimulus-dependent manner. Several miR clusters were related to skeletal development, joint homeostasis and OA
Synovitis has been shown to play a role in
Ligaments and tendons are vital musculoskeletal soft tissues, which are commonly injured due to overuse and trauma. Their distinct functions are well known however their unique structure and biochemical composition and how they change with disease is poorly described. The most commonly injured ligament in the dog and man is the cranial cruciate (CCL) and anterior cruciate ligament (ACL) respectively. Therefore, the structure, function and
Objectives. To evaluate the contribution of leptin, an adipose-derived hormone, to the
Objectives. Legg–Calvé–Perthes’ disease (LCP) is an idiopathic osteonecrosis of the femoral head that is most common in children between four and eight years old. The factors that lead to the onset of LCP are still unclear; however, it is believed that interruption of the blood supply to the developing epiphysis is an important factor in the development of the condition. Methods. Finite element analysis modelling of the blood supply to the juvenile epiphysis was investigated to understand under which circumstances the blood vessels supplying the femoral epiphysis could become obstructed. The identification of these conditions is likely to be important in understanding the biomechanics of LCP. Results. The results support the hypothesis that vascular obstruction to the epiphysis may arise when there is delayed ossification and when articular cartilage has reduced stiffness under compression. Conclusion. The findings support the theory of vascular occlusion as being important in the
Introduction. Degenerative disc disease results from mechanical alteration of the intervertebral disc. Biochemical modifications of the nucleus matrix are also incriminated. Furthermore, genetic predispositions as well as vascular factors have been advocated in the process of disc degeneration. A relationship between sciatica and Propionibacterium acnes has been described. However, it remains unclear if the hypothesis of a subclinical spondylodiscitis might play a role in the
In this study, we describe a morphological classification
for greater tuberosity fractures of the proximal humerus. We divided
these fractures into three types: avulsion, split and depression.
We retrospectively reviewed all shoulder radiographs showing isolated
greater tuberosity fractures in a Level I trauma centre between
July 2007 and July 2012. We identified 199 cases where records and
radiographs were reviewed and included 79 men and 120 women with
a mean age of 58 years (23 to 96). The morphological classification
was applied to the first 139 cases by three reviewers on two occasions
using the Kappa statistic and compared with the AO and Neer classifications.
The inter- and intra-observer reliability of the morphological classification
was 0.73 to 0.77 and 0.69 to 0.86, respectively. This was superior
to the Neer (0.31 to 0.35/0.54 to 0.63) and AO (0.30 to 0.32/0.59
to 0.65) classifications. The distribution of avulsion, split and
depression type fractures was 39%, 41%, and 20%, respectively. This
classification of greater tuberosity fractures is more reliable
than the Neer or AO classifications. These distinct fracture morphologies
are likely to have implications in terms of
CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration. We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry.Aims
Methods