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
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
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
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.
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.
Neuropathic changes in the foot are common with
a prevalence of approximately 1%. The diagnosis of neuropathic arthropathy
is often delayed in diabetic patients with harmful consequences
including amputation. The appropriate diagnosis and treatment can
avoid an extensive programme of treatment with significant morbidity
for the patient, high costs and delayed surgery. The pathogenesis
of a Charcot foot involves repetitive micro-trauma in a foot with impaired
sensation and neurovascular changes caused by pathological innervation
of the blood vessels. In most cases, changes are due to a combination
of both pathophysiological factors. The Charcot foot is triggered
by a combination of mechanical, vascular and biological factors
which can lead to late diagnosis and incorrect treatment and eventually
to destruction of the foot. This review aims to raise awareness of the diagnosis of the Charcot
foot (diabetic neuropathic osteoarthropathy and the differential
diagnosis, erysipelas, peripheral arterial occlusive disease) and
describe the ways in which the diagnosis may be made. The clinical
diagnostic pathways based on different classifications are presented. Cite this article:
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
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
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
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
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