Objectives: To assess the role of musculoskeletal ultrasound (MSUS) in selecting patients with rheumatoid arthritis (RA) in sustained clinical remission, suitable for tapering of biologic therapy (BT), and monitoring for a subclinical relapse. Methods: In this prospective study, seventy-eight patients with RA in sustained Disease Activity for twenty-eight joints (DAS28) clinical remission underwent ultrasound (US) examination of twenty-two joints (bilaterally wrists and metacarpophalangeal and proximal interphalangeal joints). US assessment was performed on gray scale ultrasound (GSUS) and power Doppler US (PDUS) to select patients in imaging remission, defined as a total PD score of synovitis = 0. Group 1 consisted of patients in clinical and imaging remission, in which tapering of BT was done through spacing of the Tumour Necrosis Factor Alpha (TNF-$\alpha$) blocker. Group 2 consisted of patients only in clinical remission (PDUS > 0), who continued standard therapy. Clinical and US assessment was done at months 6 and 12, and the rate of a clinical (defined as DAS28 ≥ 2.6) and an US relapse (PDUS score ≥ 1) was recorded. Results: Thirty-eight patients were in clinical and US remission (group 1) and forty patients only in clinical remission (group 2). At month 6, 26% of patients in group 1 and 10% in group 2 experienced a clinical and an US relapse, whereas 20% and 15% of them, respectively, only an US relapse. At month 12, 26% of patients in group 1 and 20% of patients in group 2 experienced a clinical and an US relapse, whereas 35% and 22% of them, respectively, only an US relapse. Conclusions: Real-world data show that MSUS is a useful tool to identify RA patients in sustained clinical remission appropriate for BT tapering. US monitoring could predict a clinical relapse and the need to re-escalate treatment in patients with subclinical US relapse during BT tapering.

Background: Distinguishing between osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PsA) remains challenging despite different underlying mechanisms. Synovial fluid reflects metabolic changes within affected joints, yet comprehensive metabolomic comparisons across these conditions are limited. We aimed to identify disease-specific metabolic signatures in synovial fluid that could improve differential diagnosis and reveal therapeutic targets. Methods: We collected synovial fluid from 39 patients (20 OA, 5 RA, and 14 PsA) during routine knee arthrocentesis between January 2023 and February 2024. Following metabolite extraction, we performed untargeted metabolomic profiling using quadrupole time-of-flight liquid chromatography–mass spectrometry (Q-TOF LC/MS). Data underwent multivariate statistical analysis, including principal component analysis (PCA) and partial least squares–discriminant analysis (PLS-DA), to identify discriminatory metabolites. Results: While unsupervised analysis showed overlap between groups, supervised PLS-DA achieved clear metabolic separation. RA samples showed elevated itaconic acid, indicating inflammatory macrophage activation, and increased O-acetylserine, suggesting altered one-carbon metabolism. Hypoxanthine was decreased, which reflected severe metabolic stress. PsA exhibited the unique elevation of 4,4-dimethylcholestane and 2-oxoarginine. These metabolites have previously been unreported in this disease. OA demonstrated increased hippuric acid and indoleacetic acid, which are both gut microbiota products, supporting the gut–joint axis hypothesis. Conclusions: Each arthritis type displayed distinct metabolic fingerprints in synovial fluid. Candidate discriminatory metabolites, including gut-derived metabolites in OA and specific lipid alterations in PsA, open new diagnostic and therapeutic avenues. Given the limited RA sample size (n = 5), RA-related results should be viewed as exploratory and requiring validation in larger independent cohorts. These metabolites may, after rigorous validation in larger and independent cohorts, contribute to multi-metabolite biomarker panels for earlier diagnosis and to the rational design of targeted therapeutics addressing disease-specific metabolic disruptions.

Introduction/Objectives: Osteoarthritis (OA) is a chronic systemic disease that affects the entire array of joint structures. It is one of the most common chronic, socially significant diseases, associated with a decline in the quality of life of patients and constantly increasing the cost of treatment. Clinical trial outcomes are largely inconclusive, and OA remains one of the few musculoskeletal diseases without an established disease-modifying therapy. One potential explanation is the use of ineffective tools for OA classification, patient stratification, and the assessment of disease progression. There is growing interest in musculoskeletal ultrasonography (MSK US), as it enables the dynamic visualization of the examined structures and gives information about both inflammatory and structural changes that have occurred. Determining the leading ultrasound phenotype, which depends on the most damaged tissue at a given time (bone, cartilage, synovial membrane, joint capsule, ligaments, tendons, menisci, etc.), can rationalize therapy use by selecting patients more suitable for specific treatments. This article aims to evaluate and summarize the potential of MSK US in the process of determining the clinical phenotype of OA and to emphasize the importance of this imaging modality in evaluating further therapeutic strategies. Method: A single-center prospective study conducted in the period of September 2023–June 2024 enrolled 259 consecutive patients with proven OA. The statistical program Minitab version 22.2.1 (2025) was used to analyze the data. The predominant and secondary phenotypes were tabulated for each OA localization and were presented numerically and as relative proportions (%). The rate of the most frequently occurring phenotypes was compared against that of the less frequent ones through paired z-tests. The initially acceptable type I error was set at 5%; it was further adjusted for the number of comparisons (Bonferroni). Results: The most frequent and predominant US phenotype for patients with knee OA was intra-articular effusion (n = 47, 37.90%). It was significantly higher compared to the rest of the US phenotypes: synovial proliferation (n = 22, 17.70%; p < 0.001), cartilage destruction (n = 26, 21%; p = 0.001), altered subchondral bone (n = 8, 6.50%; p < 0.001), extra-articular soft tissue changes (n = 12, 9.70%; p < 0.001), crystal deposits (n = 6, 4.8%; p < 0.001), and post-traumatic (n = 3, 2.40%; p < 0.001). The most common US phenotype for hip OA was altered subchondral bone (n = 32, 47.1%), with significant differences from intra-articular effusion (n = 12, 17.60%; p = 0.001), synovial proliferation (n = 5, 7.40; p = 0.001), cartilage destruction (n = 12, 17.60%; p = 0.001), extra-articular soft tissue changes (n = 3, 4.40%; p = 0.001), crystal deposits (n = 3, 4.40%; p = 0.001), and post-traumatic (n = 0). Altered subchondral bone was also the leading US phenotype for hand OA (n = 31, 55.40%), with significant differences compared to intra-articular effusion (n = 1, 1.80%; p < 0.001), synovial proliferation (n = 7, 12.50%; p < 0.001), cartilage destruction (n = 11, 19.60%; p < 0.001), extra-articular soft tissue changes (n = 2, 3.60%; p < 0.001), crystal deposits (n = 3, 5.40%; p < 0.001), and post-traumatic (n = 1, 1.80%, p < 0.001). For shoulder OA, extra-articular soft tissue changes were the most frequent (n = 8, 46.20%), followed by post-traumatic (n = 4, 30.70%), as the rate of both phenotypes was significantly higher compared to that of intra-articular effusion (n = 0), synovial proliferation (n = 0), cartilage destruction (n = 1, 7.70%; p = 0.003), and crystal deposits (n = 0). Conclusions: The therapeutic approach for OA is a dynamic and intricate process, for which the type of affected joint and the underlying pathogenetic mechanism at a specific stage of the disease’s evolution is essential. MSK US is one of the options for the clinical phenotyping of OA. Some of the suggested ultrasound subtypes may serve as the rationale for selecting a particular treatment.

Objectives: The present study aimed to examine the role of two-dimensional shear wave elastography (SWE) in the assessment of the vascular wall of the carotid arteries and atherosclerotic plaques in patients with rheumatoid arthritis with moderate and low disease activity versus healthy controls. Methods: An observational case–control study was carried out at the University Medical Hospital “Kaspela” in Plovdiv, Bulgaria, from June 2023 to August 2024. This study included 24 patients with rheumatoid arthritis (RA) and 25 healthy controls. We employed two-dimensional SWE (2D-SWE) to examine the vessels around the plaques. The potential links with the degree of stenosis, plaque type, and cardiovascular risk were analyzed. Results: In the RA group, the 2D-SWE values showed significant positive correlations with the severity of the atherosclerotic plaques (rs = 0.461; 95% CI: 0.049 to 0.739; p = 0.023) and the degree of stenosis (rs = 0.920; 95% CI: 0.793 to 0.970; p < 0.001). Based on 2D-SWE, a ROC curve analysis distinguished higher severity plaques from lower severity plaques with an AUC = 0.818, 95% CI: 0.683 to 0.913. The optimal cut-off value of 2D-SWE > 32.40 kPa was associated with a sensitivity of 96%, a specificity of 56%, a positive predictive value (PPV) of 66.70%, and a negative predictive value (NPV) of 92.90%. Conclusion: Elastography can be an effective technique for assessing and stratifying atherosclerotic plaques in patients with RA, as well as for aiding in the early detection and subsequent prevention of future complications.