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The Iowa Orthopaedic Journal 2024Septic arthritis is an orthopedic emergency. Diagnosis is difficult in patients with concomitant crystalline arthropathy (gout or pseudogout). The symptomatology of...
BACKGROUND
Septic arthritis is an orthopedic emergency. Diagnosis is difficult in patients with concomitant crystalline arthropathy (gout or pseudogout). The symptomatology of crystal arthritis mimics septic arthritis, clouding clinical diagnosis. Arthrocentesis and synovial fluid analysis are the standard diagnostic tests for both pathologies. Crystals on microscopy are diagnostic of crystal arthritis, however their presence does not rule out septic arthritis. Septic arthritis is diagnosed by positive microbiology culture. Though septic arthritis is associated with elevated synovial total nucleated count (TNC), TNC elevations can also occur with gout. The literature suggests that a TNC count of > 50,000 cells in a crystal-positive joint should raise suspicion for concurrent septic arthritis, however data is limited. Further diagnostic indicators are needed to help clinicians promptly identify crystal positive septic arthritis as the treatments and prognoses are different.
METHODS
Patients were retrospectively identified who had arthrocentesis of a native joint positive for monosodium urate (MSU) and/or (CPPD) crystals. Laboratory data was collected including synovial fluid cultures, total nucleated cell count (TNC), percent polymorphic neutrophils (%PMN), and crystal analysis; and serum CRP, ESR, and white blood cell count (WBC). Statistical analysis performed using Spearman correlation, Univariate-Fischer's exact and Wilcoxon tests, and multivariate analysis.
RESULTS
442 joints identified with positive CPPD and/or MSU crystals, 31% female, 69% male. Of 442 aspirates, 58 had positive cultures. Patients were more likely to have positive cultures if synovial TNC > 50,000 (odds ratio 7.7), CRP > 10 mg/dL (OR 3.2), PMN > 90% (OR 2.17), and if the patient was female (OR 1.9), all were statistically significant with p < 0.05. There were 55 patients who underwent irrigation and debridement based on clinical suspicion or a positive gram stain, 37 of these ultimately had a positive culture (67%), the remaining 18 had negative cultures.
CONCLUSION
Results are consistent with the literature, a TNC > 50,000 warrants a high suspicion for concurrent septic arthritis and should prompt providers to critically evaluate other patient laboratory data. Results further suggests that a patient with positive crystals, synovial TNC > 50,000 cells, PMN > 90%, and serum CRP > 10mg/dL is at high risk for having a concurrent septic arthritis and may warrant urgent irrigation and debridement and antibiotic therapy. This data serves as a supporting to develop an infection risk calculator for crystal positive septic arthritis. .
Topics: Humans; Arthritis, Infectious; Female; Male; Retrospective Studies; Synovial Fluid; Aged; Middle Aged; Crystal Arthropathies; Arthrocentesis; Uric Acid; Adult; Aged, 80 and over
PubMed: 38919362
DOI: No ID Found -
BMC Immunology Jun 2024Rheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for...
BACKGROUND
Rheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for RA is of necessity to improve the prevention and management of RA.
OBJECTIVES
This study focused on miR-146b-3p evaluating its clinical significance and revealing the underlying regulatory mechanisms.
MATERIALS AND METHODS
A total of 107 RA patients were enrolled, and both serum and synovial tissues were collected. Another 78 osteoarthritis patients (OA, providing synovial tissues), and 72 healthy individuals (providing serum samples) were enrolled as the control group. The expression of miR-146b-3p was analyzed by PCR and analyzed with ROC and Pearson correlation analyses evaluating its significance in diagnosis and development prediction of RA patients. In vitro, MH7A cells were treated with TNF-α. The regulation of cell proliferation, motility, and inflammation by miR-146b-3p was assessed by CCK8, Transwell, and ELISA assays.
RESULTS
Significant upregulation of miR-146b-3p was observed in serum and synovial tissues of RA patients, which distinguished RA patients and were positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) of RA patients. TNF-α promoted the proliferation and motility of MH7A cells and induced significant inflammation in cells. Silencing miR-146b-3p alleviated the effect of TNF-α and negatively regulated the expression of HMGCR. The knockdown of HMGCR reversed the protective effect of miR-146b-3p silencing on TNF-α-stimulated MH7A cells.
CONCLUSIONS
Increased miR-146b-3p served as a biomarker for the diagnosis and severity of RA. Silencing miR-146b-3p could suppress TNF-α-induced excessive proliferation, motility, and inflammation via regulating HMGCR in MH7A cells.
Topics: Arthritis, Rheumatoid; Humans; MicroRNAs; Cell Proliferation; Cell Movement; Tumor Necrosis Factor-alpha; Male; Middle Aged; Female; Cell Line; Up-Regulation; Biomarkers; Inflammation; Synovial Membrane; Adult; Aged
PubMed: 38902605
DOI: 10.1186/s12865-024-00629-9 -
The New Zealand Medical Journal Jun 2024To quantify and characterise patients with coexistent septic arthritis (SA) and crystal arthritis (CA) (SACA) in an emergency department (ED) setting. (Observational Study)
Observational Study
AIM
To quantify and characterise patients with coexistent septic arthritis (SA) and crystal arthritis (CA) (SACA) in an emergency department (ED) setting.
METHODS
A single-centre, retrospective, 10-year observational study was conducted at a major referral centre. Patients with a positive joint aspirate for CA or SA carried out in ED, were included. The Newman criteria were utilised to define SA.
RESULTS
Of the 567 patients included in the final analysis, 427 had CA and 140 had a final diagnosis of SA. Twenty-three point six percent of patients diagnosed with SA had concomitant CA, while 7.2% of patients diagnosed with CA had concomitant SA. The greatest predisposing factors for SACA were previous history of gout, rheumatoid arthritis, being immunocompromised or having joint metalware. Synovial fluid (SF) white cell count (WCC) showed excellent predictive capability for joint infection with the area under the receiver operating characteristic curves (AUROCs) of 0.81 and 0.87 for SA and SACA respectively. The receiver operating characteristic curves (ROCs) reported a SF WCC cutoff of 32,000/mm3 allowed for 100% sensitivity and approximately 50% specificity.
CONCLUSIONS
SACA remains a small but important sub-group of patients at risk of misdiagnosis of CA alone. SF WCC of 32,000/mm3 may be a better cutoff than the traditionally accepted 50,000/mm3, possibly warranting inpatient admission for investigation and management of presumed SA.
Topics: Humans; Arthritis, Infectious; Retrospective Studies; Male; Female; New Zealand; Aged; Middle Aged; Crystal Arthropathies; Synovial Fluid; Emergency Service, Hospital; Aged, 80 and over; Risk Factors; Adult; Leukocyte Count; Gout
PubMed: 38901050
DOI: 10.26635/6965.6510 -
Biomacromolecules Jun 2024Rheumatoid arthritis (RA) is a complicated chronic disorder of the immune system, featured with severe inflammatory joints, synovium hyperplasia, articular cartilage,...
Rheumatoid arthritis (RA) is a complicated chronic disorder of the immune system, featured with severe inflammatory joints, synovium hyperplasia, articular cartilage, and bone damage. In the RA microenvironment, RA-involved cells, overproduced nitric oxide (NO), and pro-inflammatory cytokines are highly interplayed and mutually reinforced, which form a vicious circle and play crucial roles in the formation and progression of RA. To comprehensively break the vicious circle and obtain the maximum benefits, we have developed neutrophil membrane-camouflaged NO scavenging nanoparticles based on an NO-responsive hyaluronic acid derivative for delivery of MTX. These multifunctional nanoparticles (NNO-NPs/MTX), by inheriting the membrane functions of the source cells, possess prolonged circulation and specific localization at the inflamed sites when administrated in the body. Remarkably, NNO-NPs/MTX can neutralize the pro-inflammatory cytokines via the outer membrane receptors, scavenge NO, and be responsively disassociated to release MTX for RA-involved cell regulation and HA for lubrication in the RA sites. In a collagen-induced arthritis mouse model, NNO-NPs/MTX exhibits a significant anti-inflammation effect and effectively alleviates the characteristic RA symptoms such as synovial hyperplasia and cartilage destruction, realizing the synergistic and boosted therapeutic outcome against intractable RA. Thus, NNO-NPs/MTX provides a promising and potent platform to integrately treat RA.
PubMed: 38899740
DOI: 10.1021/acs.biomac.4c00556 -
ACS Pharmacology & Translational Science Jun 2024Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease, that causes joint damage, deformities, and decreased functionality. In addition, RA can also... (Review)
Review
Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease, that causes joint damage, deformities, and decreased functionality. In addition, RA can also impact organs like the skin, lungs, eyes, and blood vessels. This autoimmune condition arises when the immune system erroneously targets the joint synovial membrane, resulting in synovitis, pannus formation, and cartilage damage. RA treatment is often holistic, integrating medication, physical therapy, and lifestyle modifications. Its main objective is to achieve remission or low disease activity by utilizing a "treat-to-target" approach that optimizes drug usage and dose adjustments based on clinical response and disease activity markers. The primary RA treatment uses disease-modifying antirheumatic drugs (DMARDs) that help to interrupt the inflammatory process. When there is an inadequate response, a combination of biologicals and DMARDs is recommended. Biological therapies target inflammatory pathways and have shown promising results in managing RA symptoms. Close monitoring for adverse effects and disease progression is critical to ensure optimal treatment outcomes. A deeper understanding of the pathways and mechanisms will allow new treatment strategies that minimize adverse effects and maintain quality of life. This review discusses the potential targets that can be used for designing and implementing precision medicine in RA treatment, spotlighting the latest breakthroughs in biologics, JAK inhibitors, IL-6 receptor antagonists, TNF blockers, and disease-modifying noncoding RNAs.
PubMed: 38898941
DOI: 10.1021/acsptsci.4c00067 -
Frontiers in Immunology 2024Osteoarthritis (OA) is the most common form of arthritis, characterized by osteophyte formation, cartilage degradation, and structural and cellular alterations of the... (Review)
Review
Osteoarthritis (OA) is the most common form of arthritis, characterized by osteophyte formation, cartilage degradation, and structural and cellular alterations of the synovial membrane. Activated fibroblast-like synoviocytes (FLS) of the synovial membrane have been identified as key drivers, secreting humoral mediators that maintain inflammatory processes, proteases that cause cartilage and bone destruction, and factors that drive fibrotic processes. In normal tissue repair, fibrotic processes are terminated after the damage has been repaired. In fibrosis, tissue remodeling and wound healing are exaggerated and prolonged. Various stressors, including aging, joint instability, and inflammation, lead to structural damage of the joint and micro lesions within the synovial tissue. One result is the reduced production of synovial fluid (lubricants), which reduces the lubricity of the cartilage areas, leading to cartilage damage. In the synovial tissue, a wound-healing cascade is initiated by activating macrophages, Th2 cells, and FLS. The latter can be divided into two major populations. The destructive thymocyte differentiation antigen (THY)1 phenotype is restricted to the synovial lining layer. In contrast, the THY1 phenotype of the sublining layer is classified as an invasive one with immune effector function driving synovitis. The exact mechanisms involved in the transition of fibroblasts into a myofibroblast-like phenotype that drives fibrosis remain unclear. The review provides an overview of the phenotypes and spatial distribution of FLS in the synovial membrane of OA, describes the mechanisms of fibroblast into myofibroblast activation, and the metabolic alterations of myofibroblast-like cells.
Topics: Humans; Osteoarthritis; Fibroblasts; Animals; Phenotype; Fibrosis; Synoviocytes; Synovial Membrane
PubMed: 38895122
DOI: 10.3389/fimmu.2024.1385006 -
Cells May 2024Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterised by the formation of a hyperplastic pannus, as well as cartilage and bone damage. The... (Review)
Review
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterised by the formation of a hyperplastic pannus, as well as cartilage and bone damage. The pathogenesis of RA is complex and involves broad interactions between various cells present in the inflamed synovium, including fibroblast-like synoviocytes (FLSs), macrophages, and T cells, among others. Under inflammatory conditions, these cells are activated, further enhancing inflammatory responses and angiogenesis and promoting bone and cartilage degradation. Novel treatment methods for RA are greatly needed, and mesenchymal stromal cells (MSCs) have been suggested as a promising new regenerative and immunomodulatory treatment. In this paper, we present the interactions between MSCs and RA-FLSs, and macrophages and T cells, and summarise studies examining the use of MSCs in preclinical and clinical RA studies.
Topics: Humans; Arthritis, Rheumatoid; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; Animals; Macrophages; T-Lymphocytes; Synovial Membrane; Synoviocytes
PubMed: 38891047
DOI: 10.3390/cells13110915 -
Advanced Science (Weinheim,... Jun 2024Effectively neutralizing inflammatory cytokines is crucial for managing a variety of inflammatory disorders. Current techniques that target only a subset of cytokines...
Effectively neutralizing inflammatory cytokines is crucial for managing a variety of inflammatory disorders. Current techniques that target only a subset of cytokines often fall short due to the intricate nature of redundant and compensatory cytokine networks. A promising solution to this challenge is using cell membrane-coated nanoparticles (CNPs). These nanoparticles replicate the complex interactions between cells and cytokines observed in disease pathology, providing a potential avenue for multiplex cytokine scavenging. While the development of CNPs using experimental animal models has shown great promise, their effectiveness in scavenging multiple cytokines in human diseases has yet to be demonstrated. To bridge this gap, this study selected macrophage membrane-coated CNPs (MФ-CNPs) and assessed their ability to scavenge inflammatory cytokines in serum samples from patients with COVID-19, sepsis, acute pancreatitis, or type-1 diabetes, along with synovial fluid samples from patients with rheumatoid arthritis. The results show that MФ-CNPs effectively scavenge critical inflammatory cytokines, including interleukin (IL)-6, IL-8, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, in a dose-dependent manner. Overall, this study demonstrates MФ-CNPs as a multiplex cytokine scavenging formulation with promising applications in clinical settings to treat a range of inflammatory disorders.
PubMed: 38884169
DOI: 10.1002/advs.202401423 -
Experimental Biology and Medicine... 2024Rheumatoid fibroblast-like synoviocytes (RFLS) have an important role in the inflammatory pathogenesis of rheumatoid arthritis (RA). Toll-like receptor 3 (TLR3) is...
Rheumatoid fibroblast-like synoviocytes (RFLS) have an important role in the inflammatory pathogenesis of rheumatoid arthritis (RA). Toll-like receptor 3 (TLR3) is upregulated in RFLS; its activation leads to the production of interferon-β (IFN-β), a type I IFN. IFN-stimulated gene 56 (ISG56) is induced by IFN and is involved in innate immune responses; however, its role in RA remains unknown. Therefore, the purpose of this study was to investigate the role of TLR3-induced ISG56 in human RFLS. RFLS were treated with polyinosinic-polycytidylic acid (poly I:C), which served as a TLR3 ligand. ISG56, melanoma differentiation-associated gene 5 (MDA5), and C-X-C motif chemokine ligand 10 (CXCL10) expression were measured using quantitative reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. Using immunohistochemistry, we found that ISG56 was expressed in synovial tissues of patients with RA and osteoarthritis. Under poly I:C treatment, ISG56 was upregulated in RFLS. In addition, we found that the type I IFN-neutralizing antibody mixture suppressed ISG56 expression. ISG56 knockdown decreased CXCL10 expression and MDA5 knockdown decreased ISG56 expression. In addition, we found that ISG56 was strongly expressed in the synovial cells of patients with RA. TLR3 signaling induced ISG56 expression in RFLS and type I IFN was involved in ISG56 expression. ISG56 was also found to be associated with CXCL10 expression, suggesting that ISG56 may be involved in TLR3/type I IFN/CXCL10 axis, and play a role in RA synovial inflammation.
Topics: Humans; Toll-Like Receptor 3; Arthritis, Rheumatoid; Poly I-C; Signal Transduction; Synoviocytes; Chemokine CXCL10; Interferon-Induced Helicase, IFIH1; Cells, Cultured; Synovial Membrane; Adaptor Proteins, Vesicular Transport; RNA-Binding Proteins; Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins
PubMed: 38881847
DOI: 10.3389/ebm.2024.10122 -
Journal of Orthopaedic Surgery and... Jun 2024This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC)...
BACKGROUND
This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC) and synovial tissues of animal hip osteoarthritis (OA) models.
METHODS
Animals were assigned to the control (no treatment), sham (25 µL of sterile saline), and OA (25 µL of sterile saline and 2 mg of monoiodoacetate) groups. Microcomputed tomography scan, histopathological assessment and pain threshold measurement were performed after induction. The mRNA expression of the DNA methylation machinery genes and global DNA methylation in the PBMC and hip synovial tissue were evaluated.
RESULTS
The OA group presented with hip joint OA histopathologically and radiologically and decreased pain threshold. The mRNA expression of DNA methyltransferase (Dnmt 3a), ten-eleven translocation (Tet) 1 and Tet 3 in the synovial tissue of the OA group was significantly upregulated. Global DNA methylation in the synovial tissue of the OA group was significantly higher than that of the control and sham groups.
CONCLUSIONS
The intra-articular administration of monoiodoacetate induced hip joint OA and decreased pain threshold. The DNA methylation machinery in the synovial tissues of hip OA was altered.
Topics: DNA Methylation; Animals; Osteoarthritis, Hip; Disease Models, Animal; Male; Rats; Iodoacetic Acid; Synovial Membrane; Leukocytes, Mononuclear; Rats, Sprague-Dawley; DNA Methyltransferase 3A; Pain Threshold
PubMed: 38880910
DOI: 10.1186/s13018-024-04847-0