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Osteoarthritis and Cartilage Jun 2024To investigate the effect of unilateral anterior cruciate ligament (ACL) injury on cartilage thickness and composition, specifically laminar transverse relaxation time...
OBJECTIVE
To investigate the effect of unilateral anterior cruciate ligament (ACL) injury on cartilage thickness and composition, specifically laminar transverse relaxation time (T2) by magnetic resonance imaging (MRI), in younger and older participants and to compare within-person side differences in these parameters between ACL-injured and healthy controls.
DESIGN
Quantitative double-echo steady-state (qDESS) 3 Tesla MRI-sequences were acquired in both knees of 85 participants in four groups: 20-30 years: healthy, HEA, n=24; ACL-injured, ACL, n=23; 40-60 years: healthy, HEA, n=24; ACL-injured, ACL, n=14 (ACL injury 2-10 years prior to study inclusion). Weight-bearing femorotibial cartilages were manually segmented; cartilage T2 and thickness were computed using custom software. Mean and side difference in subregional cartilage thickness, superficial and deep cartilage T2 were compared within and between groups using non-parametric statistics.
RESULTS
Cartilage thickness did not differ within or between groups. Only the side difference in medial femorotibial cartilage thickness was greater in ACL than in HEA. Deep zone T2 was longer in the ACL-injured than in the contralateral uninjured knees and than in healthy controls, especially in the lateral compartment. Most ACL-injured participants had side differences in femorotibial deep zone T2 above the threshold derived from controls.
CONCLUSION
In the ACL-injured knee, early compositional differences in femorotibial cartilage (T2) appear to occur in the deep zone and precede cartilage thickness loss. These results suggest that monitoring laminar T2 after ACL injury may be useful in the diagnosing and monitoring early articular cartilage changes.
PubMed: 38950877
DOI: 10.1016/j.joca.2024.06.014 -
Annals of Internal Medicine Jul 2024Rech J, Tascilar K, Hagen M, et al. Lancet. 2024;403:850-859. 38364841.
Rech J, Tascilar K, Hagen M, et al. Lancet. 2024;403:850-859. 38364841.
PubMed: 38950394
DOI: 10.7326/ANNALS-24-00740-JC -
The Journal of Clinical Investigation Apr 2024Ectopic lymphoid structures (ELSs) in the rheumatoid synovial joints sustain autoreactivity against locally expressed autoantigens. We recently identified recombinant...
Ectopic lymphoid structures (ELSs) in the rheumatoid synovial joints sustain autoreactivity against locally expressed autoantigens. We recently identified recombinant monoclonal antibodies (RA-rmAbs) derived from single, locally differentiated rheumatoid arthritis (RA) synovial B cells, which specifically recognize fibroblast-like synoviocytes (FLSs). Here, we aimed to identify the specificity of FLS-derived autoantigens fueling local autoimmunity and the functional role of anti-FLS antibodies in promoting chronic inflammation. A subset of anti-FLS RA-rmAbs reacting with a 60 kDa band from FLS extracts demonstrated specificity for HSP60 and partial cross-reactivity to other stromal autoantigens (i.e., calreticulin/vimentin) but not to citrullinated fibrinogen. Anti-FLS RA-rmAbs, but not anti-neutrophil extracellular traps rmAbs, exhibited pathogenic properties in a mouse model of collagen-induced arthritis. In patients, anti-HSP60 antibodies were preferentially detected in RA versus osteoarthritis (OA) synovial fluid. Synovial HSPD1 and CALR gene expression analyzed using bulk RNA-Seq and GeoMx-DSP closely correlated with the lympho-myeloid RA pathotype, and HSP60 protein expression was predominantly observed around ELS. Moreover, we observed a significant reduction in synovial HSP60 gene expression followed B cell depletion with rituximab that was strongly associated with the treatment response. Overall, we report that synovial stromal-derived autoantigens are targeted by pathogenic autoantibodies and are associated with specific RA pathotypes, with potential value for patient stratification and as predictors of the response to B cell-depleting therapies.
Topics: Arthritis, Rheumatoid; Animals; Humans; Mice; Autoantigens; Germinal Center; Chaperonin 60; Autoantibodies; Autoimmunity; Male; Synoviocytes; Arthritis, Experimental; Female; B-Lymphocytes; Tertiary Lymphoid Structures
PubMed: 38950333
DOI: 10.1172/JCI169754 -
Rheumatology (Oxford, England) Jul 2024
PubMed: 38950181
DOI: 10.1093/rheumatology/keae350 -
Drugs Jul 2024Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease which can induce progressive disability if not properly treated early. Over the last 20...
Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease which can induce progressive disability if not properly treated early. Over the last 20 years, the improvement of knowledge on the pathogenesis of the disease has made available several drugs targeting key elements of the pathogenetic process, which now represent the preferred treatment option after the failure of first-line therapy with conventional drugs such as methotrexate (MTX). To this category of targeted drugs belong anti-cytokine or cell-targeted biological agents and more recently also Janus kinase inhibitors (JAKis). In the absence to date of specific biomarkers to guide the therapeutic choice in the context of true precision medicine, the choice of the first targeted drug after MTX failure is guided by treatment cost (especially after the marketing of biosimilar products) and by the clinical characteristics of the patient (age, sex, comorbidities and compliance) and the disease (presence or absence of autoantibodies and systemic or extra-articular manifestations), which may influence the efficacy and safety profile of the available products. This viewpoint focuses on the decision-making process underlying the personalized approach to RA therapy and will analyse the evidence in the literature supporting the choice of individual products and in particular the differential choice between biological drugs and JAKis.
PubMed: 38949688
DOI: 10.1007/s40265-024-02059-8 -
Journal of Robotic Surgery Jun 2024Robotic assistance for total hip arthroplasty (THA) has been demonstrated to improve accuracy of acetabular cup placement relative to manual, unassisted technique. The... (Comparative Study)
Comparative Study
Robotic-assisted total hip arthroplasty utilizing a fluoroscopy-guided system produced similar cup accuracy and precision relative to a computerized tomography-based robotic platform.
Robotic assistance for total hip arthroplasty (THA) has been demonstrated to improve accuracy of acetabular cup placement relative to manual, unassisted technique. The purpose of this investigation was to compare the accuracy and precision between a fluoroscopy-based robotic total hip arthroplasty platform (FL-RTHA) and a computerized tomography-based (CT-RTHA) platform. The study included 98 consecutive FL-RTHA and 159 CT-RTHA procedures performed via direct anterior approach (DAA). All cases were performed for a pre-operative diagnosis of osteoarthritis, avascular necrosis, or rheumatoid arthritis. Primary outcome variables included cup implantation accuracy and precision (variance). Implantation accuracy was calculated as the absolute value of the difference between pre-operative target cup angles (inclination and anteversion) and the same post-operative angles. Percentage placement in the Lewinnek safe zone was also measured for both cohorts. The FL-RTHA and CT-RTHA cohorts demonstrated a 1.2° difference in absolute values for cup inclination accuracy (4.6° ± 3.6 vs. 3.4 ± 2.7; p = 0.005), and no difference in absolute values for cup anteversion accuracy (4.7° ± 4.1 vs. 4.6 ± 3.4; p = 0.991). Cohorts demonstrated similar precision for cup inclination and anteversion placement parameters, as well as equivalent Lewinnek safe zone placement. The use of a fluoroscopy-based robotic assistance platform for primary DAA THA resulted in similar accuracy and precision of acetabular cup placement when compared to a CT-based robotic assistance system.
Topics: Humans; Arthroplasty, Replacement, Hip; Robotic Surgical Procedures; Fluoroscopy; Tomography, X-Ray Computed; Female; Male; Middle Aged; Aged; Hip Prosthesis; Acetabulum; Surgery, Computer-Assisted
PubMed: 38949665
DOI: 10.1007/s11701-024-02033-2 -
Journal of Clinical Rheumatology :... Jul 2024The help-seeking process in rheumatoid arthritis (RA) patients is challenging, and its study is limited in Latin America. The study describes the real-life journey...
INTRODUCTION
The help-seeking process in rheumatoid arthritis (RA) patients is challenging, and its study is limited in Latin America. The study describes the real-life journey before patients' incorporation into an early arthritis clinic (EAC) and its impact on baseline and 1-year cumulative disease activity levels.
PATIENTS AND METHODS
The patient's journey was assessed through a questionnaire that captured the patient's path from the first disease-related symptom to the initial assessment in the EAC. A disease activity (28 joints evaluated)-erythrocyte sedimentation rate (DAS28-ESR) score >5.1 defined a high-disease activity level. The mean of individual consecutive DAS28-ESR scores summarized cumulative DAS28-ESR. Multiple logistic regression analysis identified factors associated with a DAS28-ESR score >5.1 at the first assessment. Linear regression analysis assessed the impact of general practitioner (GP)-first consultant and time on disease-modifying antirheumatic drugs (DMARDs) on baseline and cumulative DAS28-ESR scores.
RESULTS
Through January 2023, the EAC had 241 RA patients, among whom 209 (86.7%) completed the patients' journey questionnaire (PJQ) and 176 (84.2%) at least 1 year of follow-up. A GP was the first consultant in 76.6% of the patients, and only 12.4% were prescribed DMARDs. Patients had additional evaluations with either rheumatologists (38.6%) or other specialists (31.6%), and half of them were initiated DMARDs. GP-first consultant (adjusted odds ratio: 2.314, 95% confidence interval: 1.190-4.500, p = 0.013) and time on DMARDs (adjusted odds ratio: 0.738, 95% confidence interval: 0.585-0.929, p = 0.010) were associated with baseline DAS28-ESR score >5.1. The B coefficient magnitudes for GP-first consultant and time on DMARDs to predict cumulative DAS28 progressively decreased during the first year of follow-up.
CONCLUSIONS
Patients' journey before recent-onset RA diagnosis predicts first-year disease activity levels.
PubMed: 38949663
DOI: 10.1097/RHU.0000000000002098 -
Natural Product Research Jul 2024This study aimed to investigate the potential anti-inflammatory properties of aqueous extract of (AEMV) using various animal models. Several inflammatory models...
This study aimed to investigate the potential anti-inflammatory properties of aqueous extract of (AEMV) using various animal models. Several inflammatory models including xylene-induced ear edoema, carrageenan-induced paw edoema, and Freund's adjuvant-induced arthritis were employed to evaluate the anti-inflammatory effects of AEMV. LC-MS/MS of AEMV revealed that the major component was Marrubiin, a diterpenoid lactone. AEMV demonstrated significant anti-inflammatory effects in all animal models tested. It effectively reduced ear and paw edoema induced by xylene and carrageenan, respectively. Furthermore, AEMV attenuated arthritis symptoms and hyperalgesia in rats with Freund's adjuvant-induced arthritis. Biochemical analyzes revealed normalisation of inflammatory markers, including C-reactive protein (CRP) levels, in treated animals. The findings suggest that AEMV possesses promising anti-inflammatory properties, supporting its potential therapeutic application in inflammatory conditions such as arthritis. Further investigations are needed to clarify the underlying mechanisms and optimise dosing regimens for clinical use.
PubMed: 38949651
DOI: 10.1080/14786419.2024.2372656 -
Journal of Immunology (Baltimore, Md. :... Jul 2024The Krebs cycle enzyme aconitate decarboxylase 1 (ACOD1) mediates itaconate synthesis in monocytes and macrophages. Previously, we reported that administration of...
The Aconitate Decarboxylase 1/Itaconate Pathway Modulates Immune Dysregulation and Associates with Cardiovascular Disease Markers and Disease Activity in Systemic Lupus Erythematosus.
The Krebs cycle enzyme aconitate decarboxylase 1 (ACOD1) mediates itaconate synthesis in monocytes and macrophages. Previously, we reported that administration of 4-octyl itaconate to lupus-prone mice abrogated immune dysregulation and clinical features. In this study, we explore the role of the endogenous ACOD1/itaconate pathway in the development of TLR7-induced lupus (imiquimod [IMQ] model). We found that, in vitro, ACOD1 was induced in mouse bone marrow-derived macrophages and human monocyte-derived macrophages following TLR7 stimulation. This induction was partially dependent on type I IFN receptor signaling and on specific intracellular pathways. In the IMQ-induced mouse model of lupus, ACOD1 knockout (Acod1-/-) displayed disruptions of the splenic architecture, increased serum levels of anti-dsDNA and proinflammatory cytokines, and enhanced kidney immune complex deposition and proteinuria, when compared with the IMQ-treated wild-type mice. Consistent with these results, Acod1-/- bone marrow-derived macrophages treated in vitro with IMQ showed higher proinflammatory features. Furthermore, itaconate serum levels in systemic lupus erythematosus patients were decreased compared with healthy individuals, in association with disease activity and specific perturbed cardiometabolic parameters. These findings suggest that the ACOD1/itaconate pathway plays important immunomodulatory and vasculoprotective roles in systemic lupus erythematosus, supporting the potential therapeutic role of itaconate analogs in autoimmune diseases.
PubMed: 38949522
DOI: 10.4049/jimmunol.2400241 -
EFORT Open Reviews Jul 2024The aim of this study was to investigate the efficacy of calcitonin (CT) in animal models of experimental osteoarthritis (OA) and rheumatoid arthritis (RA), as new...
PURPOSE
The aim of this study was to investigate the efficacy of calcitonin (CT) in animal models of experimental osteoarthritis (OA) and rheumatoid arthritis (RA), as new stabilized CT formulations are currently being introduced.
METHODS
A comprehensive and systemic literature search was conducted in PubMed/MEDLINE and Embase databases to identify articles with original data on CT treatment of preclinical OA and RA. Methodological quality was assessed using the Systematic Review Centre for Laboratory Animal Experimentation's risk of bias tool for animal intervention studies. To provide summary estimates of efficacy, a meta-analysis was conducted for outcomes reported in four or more studies, using a random-effects model. Subgroup analyses were employed to correct for study specifics.
RESULTS
Twenty-six studies were ultimately evaluated and data from 16 studies could be analyzed in the meta-analysis, which included the following outcomes: bone mineral density, bone volume, levels of cross-linked C-telopeptide of type I collagen, histopathological arthritis score, and mechanical allodynia. For all considered outcome parameters, CT-treated groups were significantly superior to control groups (P = 0.002; P = 0.01; P < 0.00001; P < 0.00001; P = 0.04). For most outcomes, effect sizes were significantly greater in OA than in RA (P ≤ 0.025). High in-between study heterogeneity was detected.
CONCLUSION
There is preclinical evidence for an antioxidant, anti-inflammatory, antinociceptive, cartilage- and bone-protective effect of CT in RA and OA. Given these effects, CT presents a promising agent for the treatment of both diseases, although the potential seems to be greater in OA.
PubMed: 38949173
DOI: 10.1530/EOR-23-0133