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BMJ Case Reports Oct 2023A woman in her 50s presented with a 4-day history of left knee pain, erythema, swelling as well as malaise and rigours 1 month after undergoing a left knee meniscectomy....
A woman in her 50s presented with a 4-day history of left knee pain, erythema, swelling as well as malaise and rigours 1 month after undergoing a left knee meniscectomy. She was diagnosed with left native knee septic arthritis and underwent arthroscopic irrigation and debridement of the knee; cultures from synovial tissue grew spp are soil-dwelling and livestock-dwelling bacteria which occasionally cause disease in immunocompromised hosts. Infection in immunocompetent hosts is rare, and septic arthritis secondary to has not been reported previously.
Topics: Female; Humans; Debridement; Arthroscopy; Rhodococcus; Arthritis, Infectious
PubMed: 37802590
DOI: 10.1136/bcr-2023-256864 -
International Journal of Rheumatic... Nov 2023Costovertebral (CV), costotransverse (CTr), sternoclavicular (SC), and manubriosternal (MS) joints are impacted in spondyloarthritis (SpA) patients; however, clinical...
OBJECTIVES
Costovertebral (CV), costotransverse (CTr), sternoclavicular (SC), and manubriosternal (MS) joints are impacted in spondyloarthritis (SpA) patients; however, clinical aspects of these involvements require additional evaluation.
METHODS
A total of 281 SpA patients who had undergone chest computed tomography (CT) for any reason between 2010 and 2020 were included in the study. SpA patients were divided into three groups, ankylosing spondylitis (AS), non-radiographic axial SpA, and psoriatic arthritis. Thirty age- and sex-matched rheumatoid arthritis (RA) patients and 30 non-rheumatic disease individuals were selected for comparison. An experienced radiologist reviewed 24 CV, 20 CTr, 2 SC, and 1 MS joints from a thorax CT for each patient. All joints were classified as: normal (0); suspicious (1), mild (2), moderate (3), or severe (4).
RESULTS
Total CV and CTr joint scores differed between diseases (p < .001). Male AS patients had higher CV and CTr scores than female AS patients (male CV score: 52 [range 0-96] and CTr score: 22 [range 0-80]; female CV score: 20 [range 0-96] and CTr score: 12 [range 0-79]). Strong negative correlations were detected in AS patients between chest expansion and CV (r = -0.703 p = .007) and CTr (r = -0.763 p = .002) joint involvement; positive correlations between CV and CTr joints, and modified Stoke Ankylosing Spondylitis Spinal Score (p < .05); and no significant association for MS and SC joints.
CONCLUSIONS
CV and CTr joint involvement on thorax CT was more severe in AS and negatively affected chest expansion. The use of thorax CT scans performed for other indications in the examination of these joints may be advantageous for the early beginning of rehabilitation programs targeted at maintaining chest mobility.
Topics: Humans; Male; Female; Spondylitis, Ankylosing; Spondylarthritis; Spine; Arthritis, Psoriatic; Arthritis, Rheumatoid
PubMed: 37612889
DOI: 10.1111/1756-185X.14873 -
Ageing Research Reviews Mar 2024Arthritis has become the most common joint disease globally. Current attention has shifted towards preventing the disease and exploring pharmaceutical and surgical... (Review)
Review
Arthritis has become the most common joint disease globally. Current attention has shifted towards preventing the disease and exploring pharmaceutical and surgical treatments for early-stage arthritis. M2 macrophages are known for their anti-inflammatory properties and their ability to support cartilage repair, offering relief from arthritis. Whereas, it remains a great challenge to promote the beneficial secretion of M2 macrophages to prevent the progression of arthritis. Therefore, it is warranted to investigate new strategies that could use the functions of M2 macrophages and enhance its therapeutic effects. This review aims to explore the macrophage cell membrane-coated biomimetic nanovesicles for targeted treatment of arthritis such as osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA). Cell membrane-camouflaged biomimetic nanovesicle has attracted increasing attention, which successfully combine the advantages and properties of both cell membrane and delivered drug. We discuss the roles of macrophages in the pathophysiology and therapeutic targets of arthritis. Then, the common preparation strategies of macrophage membrane-coated nanovesicles are concluded. Moreover, we investigate the applications of macrophage cell membrane-camouflaged nanovesicles for arthritis, such as OA, RA, and GA. Taken together, macrophage cell membrane-camouflaged nanovesicles hold the tremendous prospect for biomedical applications in the targeted treatment of arthritis.
Topics: Humans; Biomimetics; Arthritis, Rheumatoid; Macrophages; Osteoarthritis
PubMed: 38387516
DOI: 10.1016/j.arr.2024.102241 -
Discovery of a First-in-Class GPR183 Antagonist for the Potential Treatment of Rheumatoid Arthritis.Journal of Medicinal Chemistry Dec 2023GPR183 is required for humoral immune responses, and its polymorphisms have been associated with inflammatory autoimmune diseases. Despite increasing attention to GPR183...
GPR183 is required for humoral immune responses, and its polymorphisms have been associated with inflammatory autoimmune diseases. Despite increasing attention to GPR183 as a potential therapeutic target for autoimmune diseases, relatively few antagonists have been reported, and none of them have progressed to the clinical stage. In this study, we discovered a highly potent GPR183 antagonist, compound , with good aqueous solubility, excellent selectivity, and pharmacokinetic properties. Meanwhile, compound showed exceptional efficacy for rheumatoid arthritis (RA) disease in a mouse collagen-induced arthritis (CIA) model, with an efficacious dose of 0.1 mg/kg. Functionally, compound significantly reduced the swelling of paws and joints, the gene expression of proinflammatory cytokines, MCP-1, MMPs, and VEGF, inflammatory cell infiltration, cartilage damage, pannus formation, and bone erosion in the joints of CIA mice in a dose-dependent manner. Hence, these findings suggest compound as a valuable molecule for further development.
Topics: Mice; Animals; Arthritis, Rheumatoid; Arthritis, Experimental; Disease Models, Animal; Cytokines
PubMed: 38047891
DOI: 10.1021/acs.jmedchem.3c01364 -
BMJ Open Dec 2023Exploring patients' perspectives for significant factors of relevance in living with a chronic disease is important to discover unmet needs and challenges. The primary...
Exploring disease-related and treatment-related issues and concerns experienced by adults with spondyloarthritis, inflammatory bowel disease and psoriasis to identify unmet needs: a qualitative clinical concept mapping study.
OBJECTIVES
Exploring patients' perspectives for significant factors of relevance in living with a chronic disease is important to discover unmet needs and challenges. The primary objective of this study was to explore disease-related and treatment-related issues and concerns experienced by adults with spondyloarthropathies (SpA) and associated diseases. As a secondary objective, we wanted to explore whether these factors were generic or disease dependent.
DESIGN
We used group concept mapping (GCM), a validated qualitative method, to identify disease-related and treatment-related issues and concerns. Participants generated statements in the GCM workshops and organised them into clusters to develop concepts. Furthermore, participants rated each statement for importance from 1: 'not important at all' to 5: 'of great importance'.
SETTING
Participants were recruited during routine care at the outpatient clinic at the hospitals in the period from May 2018 to July 2022.
PARTICIPANTS
Eligible participants were adults ≥18 years and diagnosed with axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), psoriasis (PsO) or inflammatory bowel disease -split into Crohn's disease (CD) and ulcerative colitis (UC).
RESULTS
52 patients participated in the 11 workshops divided into groups according to their diagnosis. They created a total of 1275 statements that generated 10 AxSpA concepts, 7 PsA concepts, 7 PsO concepts, 10 CD concepts and 11 UC concepts. The highest rated concepts within each disease group were: AxSpA, 'lack of understanding/to be heard and seen by healthcare professionals' (mean rating 4.0); PsA, 'medication (effects and side effects)' (mean rating 3.8); PsO, 'social and psychological problems, the shame' (mean rating 4.0); CD, 'positive attitudes' (mean rating 4.3) and UC; 'take responsibility and control over your life' (mean rating 4.0).
CONCLUSION
People with SpA and associated diseases largely agree on which concepts describe their disease-related and treatment-related issues and concerns with a few of them being more disease-specific.
Topics: Adult; Humans; Arthritis, Psoriatic; Spondylarthritis; Inflammatory Bowel Diseases; Psoriasis; Crohn Disease; Colitis, Ulcerative; Axial Spondyloarthritis
PubMed: 38081674
DOI: 10.1136/bmjopen-2023-071586 -
Frontiers in Immunology 2023Rheumatoid arthritis (RA) is a common autoimmune joint disease, the pathogenesis of which is still unclear. Cartilage damage is one of the main manifestations of the...
INTRODUCTION
Rheumatoid arthritis (RA) is a common autoimmune joint disease, the pathogenesis of which is still unclear. Cartilage damage is one of the main manifestations of the disease. Chondrocytes are the main functional component of articular cartilage, which is relevant to disease progression. Mechanical loading affects the structure and function of articular cartilage and chondrocytes, but the effect of weight bearing on chondrocytes in rheumatoid arthritis is still unclear.
METHODS
In this paper, single-cell RNA sequencing (scRNA-seq) was performed on collected cartilage from the weight-bearing region (Fb group) and non-weight-bearing region (Fnb group) of the femur, and the differences between the Fb and Fnb groups were analyzed by cell type annotation, pseudotime analysis, enrichment analysis, cell interactions, single-cell regulatory network inference and clustering (SCENIC) for each cell type.
RESULTS
A total of 87,542 cells were analyzed and divided into 9 clusters. Six chondrocyte subpopulations were finally identified by cellular annotation, and two new chondrocyte subtypes were annotated as immune-associated chondrocytes. The presence of each chondrocyte subpopulation and its distribution were verified using immunohistochemical staining (IHC). In this study, the atlas of femoral cartilage in knee rheumatoid arthritis and 2 new immune-related chondrocytes were validated using scRNA-seq and IHC, and chondrocytes in the weight-bearing and non-weight-bearing regions of the femur were compared. There might be a process of macrophage polarization transition in MCs in response to mechanical loading, as in macrophages.
CONCLUSION
Two new immune-associated chondrocytes were identified. MCs have contrasting functions in different regions, which might provide insight into the role of immune and mechanical loading on chondrocytes in the development of knee rheumatoid osteoarthritis.
Topics: Humans; Chondrocytes; Arthritis, Rheumatoid; Cartilage, Articular; Autoimmune Diseases; Osteoarthritis, Knee; Weight-Bearing; Sequence Analysis, RNA
PubMed: 37654485
DOI: 10.3389/fimmu.2023.1247355 -
Foot and Ankle Clinics Mar 2024With continuing advancements in total ankle arthroplasty (TAA), it is quickly becoming the procedure of choice for older patients with end-stage ankle arthritis.... (Review)
Review
With continuing advancements in total ankle arthroplasty (TAA), it is quickly becoming the procedure of choice for older patients with end-stage ankle arthritis. Multiple studies have been conducted on younger patients who have undergone TAA with promising results, but is it the procedure of choice? Considerations of TAA versus ankle arthrodesis, TAA implant longevity, outcomes of revision TAA, and whether patients should be offered an arthrodesis with plans for conversion to arthroplasty may help elucidate whether pursuing ankle arthroplasty in a younger, more active population is the correct approach for surgeons.
Topics: Humans; Ankle Joint; Ankle; Retrospective Studies; Arthroplasty, Replacement, Ankle; Arthritis; Arthrodesis; Treatment Outcome
PubMed: 38309803
DOI: 10.1016/j.fcl.2023.08.011 -
Italian Journal of Pediatrics Sep 2023Ataxia-telangiectasia (A-T) is a rare autosomal recessive DNA repair disorder, characterized by progressive cerebellar degeneration, telangiectasia, immunodeficiency,...
BACKGROUND
Ataxia-telangiectasia (A-T) is a rare autosomal recessive DNA repair disorder, characterized by progressive cerebellar degeneration, telangiectasia, immunodeficiency, recurrent sinopulmonary infections, radiation sensitivity, premature aging and predisposition to cancer. Although the association with autoimmune and chronic inflammatory conditions such as vitiligo, thrombocytopenia and arthritis has occasionally been reported, an onset with articular involvement at presentation is rare.
CASE PRESENTATION
We herein report the case of a 7-year-old Caucasian girl who was admitted to the Rheumatology Department with a history of febrile chough and polyarthritis which led initially to the suspicion of an autoinflammatory disease. She had overt polyarthritis with knees deformities and presented with severe pneumonia. A chest Computed Tomography (CT) scan showed bilateral bronchiectasis, parenchymal consolidation and interstitial lung disease; rheumatoid factor and type I interferon signature resulted negative, therefore excluding COatomer Protein subunit Alpha (COPA) syndrome. A diagnosis of sarcoidosis had been suspected based on histological evidence of granulomatous liver inflammation, but ruled out after detecting normal angiotensin converting enzyme and chitotriosidase blood levels. Based on her past medical history characterized by at least six episodes of pneumonia in the previous 4 years, immunological phenotyping was performed. This showed complete IgA and IgE deficiency with defective antigen-specific antibodies to Pneumococcal, Tetanus toxin and Hemophilus Influenzae B vaccines. Additionally, low numbers of B cells and recent thymic emigrants (RTE) were found (CD4Ra 1.4%), along with a low CD4+/CD8 + T cells ratio (< 1). Finally, based on gait disturbances (wobbly wide-based walking), serum alfa-fetoprotein was dosed, which resulted increased at 276 ng/ml (normal value < 7 ng/ml). A diagnosis of Ataxia-Telangiectasia was made, strengthened by the presence of bulbar telangiectasia, and then confirmed by Whole Exome Sequencing (WES).
CONCLUSIONS
Although rare, A-T should always be ruled out in case of pulmonary bronchiectasis and gait disturbances even in the absence of bulbar or skin telangiectasia. Autoimmune and granulomatous disorders must to be considered as differential diagnosis.
Topics: Female; Child; Humans; Ataxia Telangiectasia; Bronchiectasis; Arthritis; B-Lymphocytes; Lung Diseases
PubMed: 37667293
DOI: 10.1186/s13052-023-01509-5 -
The Lancet. Rheumatology Sep 2023Diseases affecting the soft tissues of the joint represent a considerable global health burden, causing pain and disability and increasing the likelihood of developing... (Review)
Review
Diseases affecting the soft tissues of the joint represent a considerable global health burden, causing pain and disability and increasing the likelihood of developing metabolic comorbidities. Current approaches to investigating the cellular basis of joint diseases, including osteoarthritis, rheumatoid arthritis, tendinopathy, and arthrofibrosis, involve well phenotyped human tissues, animal disease models, and in-vitro tissue culture models. Inherent challenges in preclinical drug discovery have driven the development of state-of-the-art, in-vitro human tissue models to rapidly advance therapeutic target discovery. The clinical potential of such models has been substantiated through successful recapitulation of the pathobiology of cancers, generating accurate predictions of patient responses to therapeutics and providing a basis for equivalent musculoskeletal models. In this Review, we discuss the requirement to develop physiologically relevant three-dimensional (3D) culture systems that could advance understanding of the cellular and molecular basis of diseases that affect the soft tissues of the joint. We discuss the practicalities and challenges associated with modelling the complex extracellular matrix of joint tissues-including cartilage, synovium, tendon, and ligament-highlighting the importance of considering the joint as a whole organ to encompass crosstalk across tissues and between diverse cell types. The design of bespoke in-vitro models for soft-tissue joint diseases has the potential to inform functional studies of the cellular and molecular mechanisms underlying disease onset, progression, and resolution. Use of these models could inform precision therapeutic targeting and advance the field towards personalised medicine for patients with common musculoskeletal diseases.
Topics: Animals; Humans; Musculoskeletal Diseases; Osteoarthritis; Arthritis, Rheumatoid; Cross Reactions; Disease Models, Animal
PubMed: 38251499
DOI: 10.1016/S2665-9913(23)00190-X -
Joint Bone Spine Jan 2024Axial psoriatic arthritis (axPsA) has considerable overlap with axial spondyloarthritis (axSpA) but has some unique features that sometimes preclude classification into...
Axial psoriatic arthritis (axPsA) has considerable overlap with axial spondyloarthritis (axSpA) but has some unique features that sometimes preclude classification into axSpA. It has some clinical and radiographic differences compared to axSpA. Imaging typically shows asymmetric syndesmophytes, mainly in the cervical spine, with less frequent sacroiliitis. It more commonly presents later in life and is associated with less severe inflammatory back pain than axSpA. The interleukin (IL) IL-23/IL-17 axis is central to the pathogenesis of both diseases. However, the response to therapies targeting these cytokines has been different. IL-23 inhibitors are ineffective in axSpA but may be effective in psoriatic arthritis (PsA). Recent post hoc analyses of clinical trial data with IL-23 inhibitors in PsA have raised the possibility of their efficacy in axPsA and need evaluation in future clinical trials. Moreover, there is a need for classification criteria for axPsA and better tools to assess therapeutic response.
Topics: Humans; Arthritis, Psoriatic; Spondylitis, Ankylosing; Sacroiliitis; Back Pain; Interleukin-23; Spondylarthritis
PubMed: 37495073
DOI: 10.1016/j.jbspin.2023.105625