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American Family Physician Dec 2021Septic arthritis must be considered and promptly diagnosed in any patient presenting with acute atraumatic joint pain, swelling, and fever. Risk factors for septic...
Septic arthritis must be considered and promptly diagnosed in any patient presenting with acute atraumatic joint pain, swelling, and fever. Risk factors for septic arthritis include age older than 80 years, diabetes mellitus, rheumatoid arthritis, recent joint surgery, hip or knee prosthesis, skin infection, and immunosuppressive medication use. A delay in diagnosis and treatment can result in permanent morbidity and mortality. Physical examination findings and serum markers, including erythrocyte sedimentation rate and C-reactive protein, are helpful in the diagnosis but are nonspecific. Synovial fluid studies are required to confirm the diagnosis. History and Gram stain aid in determining initial antibiotic selection. Staphylococcus aureus is the most common pathogen isolated in septic arthritis; however, other bacteria, viruses, fungi, and mycobacterium can cause the disease. After synovial fluid has been obtained, empiric antibiotic therapy should be initiated if there is clinical concern for septic arthritis. Oral antibiotics can be given in most cases because they are not inferior to intravenous therapy. Total duration of therapy ranges from two to six weeks; however, certain infections require longer courses. Consideration for microorganisms such as Neisseria gonorrhoeae, Borrelia burgdorferi, and fungal infections should be based on history findings and laboratory results.
Topics: Anti-Bacterial Agents; Arthralgia; Arthritis, Infectious; Blood Sedimentation; Borrelia burgdorferi; Fever; Humans; Neisseria gonorrhoeae; Staphylococcus aureus; Synovial Fluid
PubMed: 34913662
DOI: No ID Found -
Arteriosclerosis, Thrombosis, and... Jan 2021Extracellular vesicles (EVs) are a means of cell-to-cell communication and can facilitate the exchange of a broad array of molecules between adjacent or distant cells.... (Review)
Review
Extracellular vesicles (EVs) are a means of cell-to-cell communication and can facilitate the exchange of a broad array of molecules between adjacent or distant cells. Platelets are anucleate cells derived from megakaryocytes and are primarily known for their role in maintaining hemostasis and vascular integrity. Upon activation by a variety of agonists, platelets readily generate EVs, which were initially identified as procoagulant particles. However, as both platelets and their EVs are abundant in blood, the role of platelet EVs in hemostasis may be redundant. Moreover, findings have challenged the significance of platelet-derived EVs in coagulation. Looking beyond hemostasis, platelet EV cargo is incredibly diverse and can include lipids, proteins, nucleic acids, and organelles involved in numerous other biological processes. Furthermore, while platelets cannot cross tissue barriers, their EVs can enter lymph, bone marrow, and synovial fluid. This allows for the transfer of platelet-derived content to cellular recipients and organs inaccessible to platelets. This review highlights the importance of platelet-derived EVs in physiological and pathological conditions beyond hemostasis.
Topics: Animals; Blood Platelets; Bone Marrow; Cell Communication; Cell-Derived Microparticles; Hemostasis; Humans; Inflammation Mediators; Lymph; Platelet Activation; Synovial Fluid
PubMed: 33028092
DOI: 10.1161/ATVBAHA.120.314644 -
Autoimmunity Reviews Jul 2022While physiological levels of IL-7 are essential for T cell proliferation, survival and co-stimulation, its escalated concentration has been associated with autoimmune... (Review)
Review
While physiological levels of IL-7 are essential for T cell proliferation, survival and co-stimulation, its escalated concentration has been associated with autoimmune diseases such as Rheumatoid arthritis (RA). Expression of IL-7 and IL-7R in RA monocytes is linked to disease activity score and TNF transcription. TNF stimulation can modulate IL-7 secretion and IL-7R frequency in myeloid cells, however, only IL-7R transcription levels are downregulated in anti-TNF responsive patients. Elevated levels of IL-7 in RA synovial tissue and fluid are involved in attracting RA monocytes into the inflammatory joints and remodeling them into proinflammatory macrophages and mature osteoclasts. Further, IL-7 amplification of RA Th1 cell differentiation and IFNγ secretion, can directly prime myeloid IL-7R expression and thereby exacerbate IL-7-mediated joint inflammatory and erosive imprints. In parallel, IL-7 accentuates joint angiogenesis by expanding the production of proangiogenic factors from RA macrophages and endothelial cells. In preclinical models, blockade of IL-7 or IL-7R can effectively impair joint inflammation, osteoclast formation, and neovascularization primarily by impeding monocyte and endothelial cell infiltration as well as inhibition of pro-inflammatory macrophage and Th1/Th17 cell differentiation. In conclusion, disruption of IL-7/IL-7R signaling can uniquely intercept the crosstalk between RA myeloid and lymphoid cells in their ability to trigger neovascularization.
Topics: Arthritis, Rheumatoid; Autoimmunity; Endothelial Cells; Humans; Interleukin-7; Synovial Fluid; Tumor Necrosis Factor Inhibitors
PubMed: 35595051
DOI: 10.1016/j.autrev.2022.103120 -
International Orthopaedics Jan 2020Misconceptions and errors in the management of periprosthetic joint infection (PJI) can compromise the treatment success. The goal of this paper is to systematically... (Review)
Review
BACKGROUND
Misconceptions and errors in the management of periprosthetic joint infection (PJI) can compromise the treatment success. The goal of this paper is to systematically describe twenty common mistakes in the diagnosis and management of PJI, to help surgeons avoid these pitfalls.
MATERIALS AND METHODS
Common diagnostic and treatment errors are described, analyzed and interpreted.
RESULTS
Diagnostic errors include the use of serum inflammatory biomarkers (such as C-reactive protein) to rule out PJI, incomplete evaluation of joint aspirate, and suboptimal microbiological procedures (such as using swabs or collection of insufficient number of periprosthetic samples). Further errors are missing possible sources of distant infection in hematogenous PJI or overreliance on suboptimal diagnostic criteria which can hinder or delay the diagnosis of PJI or mislabel infections as aseptic failure. Insufficient surgical treatment or inadequate antibiotic treatment are further reasons for treatment failure and emergence of antimicrobial resistance. Finally, wrong surgical indication, both underdebridement and overdebridement or failure to individualize treatment can jeopardize surgical results.
CONCLUSION
Multidisciplinary teamwork with infectious disease specialists and microbiologists in collaboration with orthopedic surgeons have a synergistic effect on the management of PJI. An awareness of the possible pitfalls can improve diagnosis and treatment results.
Topics: Aged; Anti-Bacterial Agents; Biomarkers; Blood Sedimentation; C-Reactive Protein; Debridement; Diagnostic Errors; Female; Humans; Male; Medical Errors; Middle Aged; Prosthesis-Related Infections; Reoperation; Synovial Fluid; Therapeutic Irrigation; Treatment Outcome
PubMed: 31641803
DOI: 10.1007/s00264-019-04426-7 -
Frontiers in Immunology 2022To compare the proteomics of synovial fluid (SF)-derived exosomes in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), gout, and osteoarthritis (OA) patients.
OBJECTIVES
To compare the proteomics of synovial fluid (SF)-derived exosomes in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), gout, and osteoarthritis (OA) patients.
METHODS
Exosomes were separated from SF by the Exoquick kit combined ultracentrifugation method. Tandem mass tags (TMT)-labeled liquid chromatography mass spectrometry (LC-MS/MS) technology was used to analyze the proteomics of SF-derived exosomes. Volcano plot, hierarchical cluster, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted.
RESULTS
A total of 1,678 credible proteins were detected. Sixty-nine differentially expressed proteins were found in gout, compared with OA, axSpA, and RA simultaneously. Twenty-five proteins were found highly expressed in gout uniquely, lysozyme C and protein S100-A9 included, whose bioinformatic analysis was significantly involved in "neutrophil degranulation" and "prion diseases". Eighty-four differentially expressed proteins were found in axSpA, compared with OA, gout, and RA simultaneously. Thirty-nine proteins were found highly expressed in axSpA uniquely, RNA-binding protein 8A and protein transport protein Sec24C included, whose bioinformatic analysis was significantly involved in "acute-phase response" and "citrate cycle". One hundred and eighty-four differentially expressed proteins were found in RA, compared with OA, gout, and axSpA simultaneously. Twenty-eight proteins were found highly expressed in RA uniquely, pregnancy zone protein (PZP) and stromelysin-1 included, whose bioinformatic analysis was significantly involved in "serine-type endopeptidase inhibitor activity" and "complement and coagulation cascades". Enzyme-linked immunosorbent assay (ELISA) result showed that the exosome-derived PZP level of SF in RA was higher than that in OA ( < 0.05).
CONCLUSION
Our study for the first time described the protein profiles of SF-derived exosomes in RA, axSpA, gout, and OA patients. Some potential biomarkers and hypothetical molecular mechanisms were proposed, which may provide helpful diagnostic and therapeutic insights for inflammatory arthritis (IA).
Topics: Arthritis, Rheumatoid; Chromatography, Liquid; Exosomes; Gout; Humans; Osteoarthritis; Proteins; Proteomics; Synovial Fluid; Tandem Mass Spectrometry
PubMed: 35359923
DOI: 10.3389/fimmu.2022.800902 -
Science Advances Apr 2023Osteoarthritis (OA) was recently defined as an epidemic, and the lack of effective treatment is highly correlated to the limited knowledge regarding the underlying...
Osteoarthritis (OA) was recently defined as an epidemic, and the lack of effective treatment is highly correlated to the limited knowledge regarding the underlying pathophysiology. Failure to regenerate upon trauma is thought to be one of the underlying causes for degenerative diseases, including OA. To investigate why lesions within an OA environment fail to heal, a heterogeneous cell population was isolated from the synovial fluid (SF) of OA patients. The cells' ability to undergo processes required for functional tissue regeneration was evaluated in the presence or absence of autologous SF. The obtained mechanistic findings were then used for the development of an immunomodulatory cell treatment, aimed to restore the pro-regenerative environment. Intra-articular injection in a clinical compassionate use study showed that the treatment restored the articular cartilage and joint homeostasis of OA patients. These findings confirm the role of pro-regenerative immune cells and their targeted influence on progenitor cells for degenerative joint disease therapies.
Topics: Humans; Osteoarthritis, Knee; Synovial Fluid; Cartilage, Articular; Injections, Intra-Articular; Wound Healing
PubMed: 37083524
DOI: 10.1126/sciadv.ade4645 -
Acta Clinica Croatica Dec 2019Bone endures a lifelong course of construction and destruction, with bone marker (BM) molecules released during this cycle. The field of measuring BM levels in synovial... (Review)
Review
Bone endures a lifelong course of construction and destruction, with bone marker (BM) molecules released during this cycle. The field of measuring BM levels in synovial fluid and peripheral blood is a cardinal part of bone research within modern clinical medicine and has developed extensively in the last years. The purpose of our work was to convey an up-to-date overview on synovial fluid and serum BMs in the most common arthropathies.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Joint Diseases; Male; Middle Aged; Synovial Fluid
PubMed: 32595257
DOI: 10.20471/acc.2019.58.04.19 -
CMAJ : Canadian Medical Association... Feb 2021
Topics: Anti-Inflammatory Agents, Non-Steroidal; Comorbidity; Gout; Gout Suppressants; Humans; Microscopy; Prevalence; Risk Factors; Synovial Fluid; Uric Acid
PubMed: 33526544
DOI: 10.1503/cmaj.201392 -
Annals of the Rheumatic Diseases Apr 2023Syntenin-1, a novel endogenous ligand, was discovered to be enriched in rheumatoid arthritis (RA) specimens compared with osteoarthritis synovial fluid and normal...
OBJECTIVES
Syntenin-1, a novel endogenous ligand, was discovered to be enriched in rheumatoid arthritis (RA) specimens compared with osteoarthritis synovial fluid and normal synovial tissue (ST). However, the cellular origin, immunoregulation and molecular mechanism of syntenin-1 are undescribed in RA.
METHODS
RA patient myeloid and lymphoid cells, as well as preclinical models, were used to investigate the impact of syntenin-1/syndecan-1 on the inflammatory and metabolic landscape.
RESULTS
Syntenin-1 and syndecan-1 (SDC-1) co-localise on RA ST macrophages (MΦs) and endothelial cells. Intriguingly, blood syntenin-1 and ST SDC-1 transcriptome are linked to cyclic citrullinated peptide, erythrocyte sedimentation rate, ST thickness and bone erosion. Metabolic CD14CD86GLUT1MΦs reprogrammed by syntenin-1 exhibit a wide range of proinflammatory interferon transcription factors, monokines and glycolytic factors, along with reduced oxidative intermediates that are downregulated by blockade of SDC-1, glucose uptake and/or mTOR signalling. Inversely, IL-5R and PDZ1 inhibition are ineffective on RA MΦs-reprogrammed by syntenin-1. In syntenin-1-induced arthritis, F4/80iNOSRAPTORMΦs represent glycolytic RA MΦs, by amplifying the inflammatory and glycolytic networks. Those networks are abrogated in SDC-1 animals, while joint prorepair monokines are unaffected and the oxidative metabolites are moderately replenished. In RA cells and/or preclinical model, syntenin-1-induced arthritogenicity is dependent on mTOR-activated MΦ remodelling and its ability to cross-regulate Th1 cells via IL-12 and IL-18 induction. Moreover, RA and joint myeloid cells exposed to Syntenin-1 are primed to transform into osteoclasts via SDC-1 ligation and RANK, CTSK and NFATc1 transcriptional upregulation.
CONCLUSION
The syntenin-1/SDC-1 pathway plays a critical role in the inflammatory and metabolic landscape of RA through glycolytic MΦ and Th1 cell cross-regulation (graphical abstract).
Topics: Animals; Humans; Arthritis, Rheumatoid; Endothelial Cells; Macrophages; Monokines; Syndecan-1; Synovial Fluid; Synovial Membrane; Syntenins; Th1 Cells; TOR Serine-Threonine Kinases
PubMed: 36593091
DOI: 10.1136/ard-2022-223284 -
International Journal of Molecular... Aug 2021Endogenous DNA derived from the nuclei or mitochondria is released into the bloodstream following cell damage or death. Extracellular DNA, called cell-free DNA (cfDNA),... (Review)
Review
Endogenous DNA derived from the nuclei or mitochondria is released into the bloodstream following cell damage or death. Extracellular DNA, called cell-free DNA (cfDNA), is associated with various pathological conditions. Recently, multiple aspects of cfDNA have been assessed, including cfDNA levels, integrity, methylation, and mutations. Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis, and treatment of RA has highly varied outcomes. cfDNA in patients with RA is elevated in peripheral blood and synovial fluid and is associated with disease activity. Profiling of cfDNA in patients with RA may then be utilized in various aspects of clinical practice, such as the prediction of prognosis and treatment responses; monitoring disease state; and as a diagnostic marker. In this review, we discuss cfDNA in patients with RA, particularly the sources of cfDNA and the correlation of cfDNA with RA pathogenesis. We also highlight the potential of analyzing cfDNA profiles to guide individualized treatment approaches for RA.
Topics: Animals; Arthritis, Rheumatoid; Cell-Free Nucleic Acids; Humans; Prognosis; Synovial Fluid
PubMed: 34445645
DOI: 10.3390/ijms22168941