Search Results (770)

Background/Objectives: Axial spondyloarthritis (axSpA) was long considered a male disease, yet women often report higher disease activity; whether this reflects sex differences or comorbidity is unclear. In an under-studied Saudi cohort, we examined sex differences in disease activity and function and associations with fibromyalgia and body mass index (BMI). Methods: A retrospective cross-sectional analysis of de-identified baseline data included 160 adults who met the Assessment of SpondyloArthritis International Society (ASAS) criteria at a single center. Between-sex comparisons used Benjamini–Hochberg correction; sequential multivariable regression evaluated attenuation of the sex–disease activity association after covariate adjustment. Results: Of 160 patients, 56 (35%) were women. Women more often had non-radiographic disease, higher BMI, fibromyalgia, and elevated erythrocyte sedimentation rate (ESR) (all q < 0.05), and scored higher on the symptom-based Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; median 5.65 [IQR 4.67–6.60] vs. 5.15 [4.30–5.72]; p = 0.007, q = 0.044). The Bath Ankylosing Spondylitis Functional Index (BASFI) was borderline (q = 0.052), and C-reactive protein (CRP)-anchored Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) did not differ significantly (median 3.70 [IQR 3.00–3.90] vs. 3.50 [3.00–3.80]; p = 0.099, q = 0.148). The female BASDAI difference was attenuated after adjustment for concomitant fibromyalgia. Higher ESR was partly attenuated after adjustment for BMI, whereas CRP did not differ by sex. In the analysis restricted to participants without fibromyalgia, between-sex estimates for BASDAI, BASFI, and ASDAS-CRP were smaller and imprecise. Conclusions: The attenuation of the female-sex association with BASDAI after adjustment for concomitant fibromyalgia should be interpreted as statistical attenuation only. Because fibromyalgia and BASDAI share symptom domains, particularly pain and fatigue, this attenuation may partly reflect overlapping symptom content and possible classification circularity rather than an explanatory or causal relationship. Full article

Background: Pharmacological blockade of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has emerged as an attractive pharmacological strategy for a broad range of inflammatory and metabolic disorders. However, translating preclinical efficacy into clinical success remains a major bottleneck. We previously reported the discovery of a novel, potent NLRP3 inhibitor, KBD3536, but its in vivo efficacy across different pathological conditions remains uncharacterized. Here, we systematically evaluated the in vivo efficacy of KBD3536 across diverse preclinical models of NLRP3-related pathologies. Methods: KBD3536 was evaluated in established rodent models of monosodium urate (MSU)-induced acute inflammation (mouse air pouch and rat gouty arthritis models), radiation-induced dermatitis (RID), and high-fat diet (HFD)-induced obesity. Results: In the MSU models, KBD3536 markedly suppressed local interleukin-1β and interleukin-6 secretion in air pouch exudates and dose-dependently alleviated acute arthritis symptoms, including joint swelling and joint pain. In the RID model, KBD3536 significantly attenuated radiation-induced skin injury and ameliorated radiation-induced systemic weight loss. Under HFD challenge, early intervention with KBD3536 mitigated HFD-induced adiposity, early hepatic steatosis and its associated inflammatory responses, and preserved physical performance. Mechanistically, KBD3536 partially restored AMP-activated protein kinase α1 (AMPKα1) mRNA expression in adipose tissue and restored hepatic Cyp3a11 transcriptional activity. Conclusions: NLRP3 inhibitor KBD3536 exhibited broad-spectrum anti-inflammatory efficacy across multiple preclinical models, supporting its potential as a promising candidate for diverse NLRP3-related disorders. Full article

Background/Objectives: Shoulder pain or instability have different causes and therefore different treatment approaches. The most common are surgical approaches, ranging from more conservative to more radical, such as arthroplasty. In the presence of irreparable rupture or tears of the supraspinatus and subscapularis muscles, particularly in younger patients without arthritis or osteoarthrosis, it becomes a surgical challenge to avoid early arthroplasty. Despite the development and proposal of various surgical techniques to restore stability and function, and eliminate pain of the glenohumeral joint, there remains a lack of consensus on the most effective approach in the absence of arthritis. This work aims to systematically review the available evidence on surgical procedures for treating shoulder joint instability and pain due to irreparable subscapularis and supraspinatus tendon tears, excluding cases with coexisting arthritis or arthrosis. Methods: This systematic review was conducted following PRISMA 2020 guidelines. Search was performed across the major databases PubMed, Scopus, and Web of Science, up to 2025. Inclusion criteria comprised clinical studies (randomised controlled trials, cohort studies, case series), reviews and systematic reviews reporting on surgical interventions for shoulder instability and pain caused by irreparable tears of the subscapularis and supraspinatus in patients without degenerative joint disease. As shoulder surgery techniques have been continually evolving since the early procedures, no lower limit was set for the time interval. The related literature that was not identified in the mentioned databases was added manually through parallel searches of associated themes and suggestions from the websites of those databases. To be eligible, papers had to describe shoulder instability surgery, surgical techniques, indications, and patients’ recovery outcomes. The key tasks, such as title and abstract screening, were performed by V. M., L. R., and M. A. N. to ensure thoroughness and reduce bias. Results: From an initial search result of 98 works, a total of 66 titles and abstracts were analysed, resulting in a final selection of 24 studies that fulfilled the mentioned criteria and were therefore included in this review. The oldest paper mentioning a shoulder surgery in this context was published in 2003. The most frequently described procedures included total joint replacement, tendon transfers, Superior Capsule Reconstruction, partial rotator cuff repair and others. Across studies, improvements were noted in shoulder stability, range of motion, and functional scores. However, heterogeneity in surgical techniques and outcome measures limited direct comparison. Conclusions: The conducted systematic review reveals an important gap and highlights the need to evolve beyond traditional shoulder surgery techniques and, if possible, to provide a single solution for the different origins of shoulder instability. Several surgical options demonstrate promising outcomes in managing shoulder instability and pain due to irreparable subscapularis and supraspinatus tears in patients without glenohumeral arthritis. However, those procedures are associated with anatomical changes in the shoulder joint, compromising the joint’s full function and prolonging recovery time. Nevertheless, this conclusion is based on a small sample size of the current literature and a lack of high-level evidence. Further comparative and long-term studies are needed to establish optimal treatment strategies. Full article

The introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) has significantly enhanced the prognosis for patients with rheumatoid arthritis (RA). Nevertheless, improving quality of life remains a major clinical challenge requiring the implementation of multidirectional therapeutic measures. Pain reduction plays a particularly important role in this context, representing one of the primary treatment goals for many patients. Scientific evidence indicates that effective pain management is a crucial predictive factor for the improvement of mental and physical health in patients with RA. The aim of this literature review was to summarise the mechanisms of action of Janus kinase inhibitors (JAKi), with particular emphasis on their modulation of pain generation and transmission. Furthermore, the study aimed to compare the results of clinical studies and assess the actual effectiveness of these drugs in reducing pain in clinical practice. JAKi exhibit peripheral analgesic effects by directly reducing the production of pro-nociceptive cytokines and modulating macrophage polarisation. Moreover, they influence central pain processing mechanisms by modulating the IL-6/JAK/STAT3 pathway and by reducing microglial and astrocyte proliferation in the dorsal horn of the spinal cord. The results of randomised clinical trials confirm that JAKi provide rapid, clinically significant pain reduction. Some studies also point to the persistence of this effect over a longer period, and to their greater efficacy compared with conventional disease-modifying antirheumatic drugs (cDMARDs) and bDMARDs. The efficacy of this group of drugs has also been noted in patients with an inadequate response to prior therapy with biological drugs. A key focus of future research remains determining the optimal timing for introducing JAKi in the treatment of RA and identifying predictive factors to enable the selection of patients most likely to benefit from this class of drugs. Full article

Background: Nationwide epidemiologic data on comorbidity burden in early rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are limited. We compared coded diagnoses for concurrent disorders in incident RA and PsA based on administrative healthcare data (AHC). Methods: This retrospective cohort study used AHCs from the National Health Fund between 2009 and 2021. Using composite proxy definitions for RA and PsA diagnosis (combination of ICD-10 codes and prescription data), we identified all new cases of RA and PsA between 2019 and 2021. We utilized a ten-year lookback window for the accrual of concurrent disorder claims. Age-, sex-, serostatus- and calendar year-adjusted models were considered. Crude, relative and adjusted prevalence estimates were calculated using generalized linear models. Results: Using NHF data, we identified 36,285 and 1603 patients with incident RA/PsA, respectively. We estimated the burden of 31 multisystem comorbidities. Most disorders (N = 23, 74.2%) were more frequently coded among RA patients, while only liver diseases were significantly more prevalent in PsA. Chronic back pain (+21.2 pp) and osteoarthritis (+18.3 pp) were tied to the greatest absolute differences, likely mirroring medical contact patterns throughout the differential diagnostic process. Hospitalization due to heart failure and stroke, but not myocardial infarction, was more common in RA vs. PsA. Conclusions: Newly diagnosed patients with RA and PsA show distinct patterns of healthcare utilization for multiple organ disorders. Early RA may be tied to higher comorbidity rates not fully explained by age and sex, as compared to PsA; further studies are necessary to clarify these observations. Full article

Background/Objectives: Intra-articular injections are used for temporomandibular disorders (TMDs) resistant to conservative treatment. However, many reviews assess injectable agents combined with arthrocentesis or other co-interventions, limiting interpretation of their standalone effects. This overview aimed to summarize meta-analytic evidence on standalone intra-articular injections for temporomandibular joint disorders. Methods: MEDLINE, BASE, and Europe PMC were searched on 29 March 2026. Systematic reviews with quantitative meta-analyses evaluating standalone intra-articular TMJ injections were included. Data regarding injectable substances, clinical indications, and outcome domains were extracted and synthesized descriptively. Results: Three systematic reviews with meta-analyses were included. The evidence addressed platelet-rich plasma, corticosteroids, sodium hyaluronate, and physiological saline. Reported indications included degenerative joint disease, osteoarthritis, internal derangement, and arthritis. All included agents were reported to be associated with pain reduction. Conclusions: Meta-analytic evidence on standalone intra-articular injections for TMDs remains limited and heterogeneous. Available data suggest potential benefits, mainly for pain reduction, but do not establish clear superiority of any agent. The potential therapeutic activity of physiological saline should be considered when designing future injection trials. Full article

Background/Objectives: The aim of this study is to analyze outcomes in patients who underwent genicular artery embolization (GAE) with respect to pain, symptoms, physical activity, quality of life, and knee joint range of motion and muscle strength of the knee joint. The study will provide evidence of the treatment’s effectiveness using both subjective and objective measurements. In addition, the study will examine the impact of the severity of radiological changes in the knee joint and the number of embolized vessels on the extent of improvement in outcomes following the procedure. Methods: Patients eligible for GAE who exhibited symptoms of chronic exudative knee arthritis, confirmed by USG and MRI with contrast, did not have laboratory markers of inflammation, nor did they respond effectively to standard non-surgical treatments. The analysis included 34 patients. Subjective parameters were assessed using the VAS and KOOS scales. Knee range of motion and muscle strength were assessed using an electronic dynamometer and goniometer. Measurements were performed according to the same schedule before GAE, and at 1, 3 and 6 months after the procedure. The results were subjected to statistical analysis. Results: In the analysis up to 6 months, a significant time effect was demonstrated for the VAS and all KOOS subscales. The improvement was visible after 1 month and continued after 3 and 6 months. No significant changes over time were demonstrated for objective parameters. Exploratory analysis demonstrated a relationship between increased knee extensor strength and pain reduction up to 3 months and increased range of motion up to 6 months after the GAE. There was no significant association between radiological changes and the number of embolized vessels with improved outcomes after GAE. Conclusions: GAE appears to be a promising minimally invasive treatment option for patients with chronic knee synovitis. Clinically meaningful improvements were observed in patient-reported outcomes. Full article

Background/Objectives: Patellofemoral joint (PFJ) replacement is a bone-preserving option for isolated patellofemoral osteoarthritis; however, reported survivorship and failure patterns remain variable. This study evaluated implant survivorship, functional outcomes, reoperations, and failure mechanisms following PFJ replacement using standard second-generation implant systems, with or without patellar resurfacing. Methods: We retrospectively reviewed a consecutive cohort of 39 patients (48 knees) who underwent PFJ replacement for isolated patellofemoral osteoarthritis between 2011 and 2021. Median age at surgery was 59 years, and median body mass index (BMI) was 31 kg/m². Median follow-up for clinical and revision surveillance was 9 years (IQR 8–10). Functional outcomes were assessed using the Oxford Knee Score (OKS) and SF-12 Physical and Mental Component Scores (PCS and MCS). Implant survivorship was analyzed using Kaplan–Meier methodology, with conversion to total knee arthroplasty (TKA) as the endpoint. Statistical analyses were primarily descriptive and exploratory because only five TKA revisions occurred. Results: Median OKS improved from 19 (IQR 16–24) preoperatively to 36 (IQR 24–42) at the latest follow-up, with a median paired improvement of 17 points. SF-12 PCS improved from 25 to 47, and SF-12 MCS from 36 to 55. Eight knees (16.7%) underwent non-revision reoperation, and five knees (10.4%) underwent conversion to TKA. All TKA revisions were performed for the progression of tibiofemoral osteoarthritis. Kaplan–Meier survivorship free from TKA revision was 89.6% at 9 years (95% CI 76.8–95.5). No clear difference in TKA-free survivorship was detected between resurfaced and non-resurfaced knees. Conclusions: PFJ replacement demonstrated substantial functional improvement and mid- to long-term survivorship comparable to published registry ranges in a selected cohort with isolated patellofemoral osteoarthritis. TKA revision was uncommon and was attributable to the progression of tibiofemoral osteoarthritis. Because of the retrospective design, small cohort size, bilateral cases, and limited number of revision events, subgroup and risk-factor analyses should be interpreted as exploratory. Full article

Psoriasis and psoriatic arthritis (PsA) are systemic immune-mediated diseases, but the features that distinguish cutaneous-dominant psoriasis from musculoskeletal involvement remain unclear. We analyzed four core public cross-sectional datasets spanning whole-blood methylation, PBMC single-cell RNA sequencing summarized at the subject level, skin RNA sequencing, and purified CD4⁺ T-cell methylation, and used two additional public skin cohorts for external contextual checks to define a disease inflammatory response axis (DIR) and a contrast-resolved systemic state coordinate (CRS) representing systemic immune state variation associated with PsA. In whole-blood methylation, DIR primarily separated healthy controls from psoriasis, whereas CRS separated psoriasis from PsA with minimal correlation to DIR. In untreated-only PBMC single-cell reanalysis, CRS separated PsA from PsO; the source-defined PSX subgroup (joint pain without CASPAR-classified PsA) showed heterogeneous subject-level positioning, with above-band enrichment concentrated at the cell-type level. Cell-type-resolved analyses localized CRS-related shifts to T-cell, monocyte, B-cell, and regulatory compartments and identified multicompartment pathway state remodeling along the CRS continuum. In contrast, skin RNA sequencing mainly captured lesional inflammatory burden and showed only limited additional PsA-related separation within the same tissue state. These findings support a model in which PsA is distinguished from psoriasis by an additional systemic immune state axis rather than by skin inflammatory burden alone. Full article

When assessing hip pain in athletes, it is important to focus on the extra-articular soft tissues that may clinically mimic joint pathology. One such extra-articular structure is the synovial bursa. Bursitis can clinically be misdiagnosed as joint-, tendon- or muscle-related pain. These pathological processes are a result of inflammation that is often secondary to acute trauma, overuse injuries, arthritis, or infection. Traumatic and overuse hip bursitis occur frequently in amateur and professional athletes and clinical presentation is often nonspecific. After clinical assessment, imaging plays an important role in diagnosis and in work-up of these lesions. Ultrasonography (US) is being increasingly used in the assessment of the hip because of the wide availability of US machines, the lower cost, and the unique real-time imaging capability which allows both static and dynamic evaluation as well as guidance of interventional procedures such as fluid aspiration and steroid injection. In order to obtain a correct diagnosis, an efficient US examination requires a thorough understanding of hip anatomy. In this setting, a structured approach based on identification of important US landmarks and compartmentalization of hip anatomy can significantly simplify the task. Sports physicians must be aware about the diagnostic and therapeutic possibilities offered by US in order to expedite rapid referral to a musculoskeletal specialist who can perform a point-of-care US examination of the hip by using a structured diagnostic approach. The purpose of this narrative review is to illustrate both the normal and pathological features of anterior and lateral hip compartments bursae using schematic diagrams and corresponding US images. We will concentrate on sport-related bursitis, of which we will discuss the etiology, clinic and principles of care management. Our aim is to promote the acquisition of these concepts in sports medicine in order to improve patient outcomes. Full article

Systemic inflammation plays a pivotal role in the progression of rheumatoid arthritis (RA) and its associated comorbidities, ranging from cardiovascular (CV) disease to neurodegenerative conditions such as Alzheimer’s disease (AD). This narrative review examines the molecular cross-talk linking these pathologies, with a specific focus on the distinction between pentameric C-reactive protein (pCRP) and its proinflammatory monomeric form (mCRP). We discuss evidence suggesting that mCRP is not merely a passive marker but also an active driver of endothelial dysfunction, atherosclerosis, and synovial inflammation. This review further explores the connections among inflammatory biomarkers, blood vessel integrity, and neurodegeneration, detailing how persistent cytokine elevation (IL-6, TNF-α) and vascular injury contribute to cerebral small vessel disease (cSVD) and cognitive decline, with neurofilament light chain (NfL) serving as a key biomarker of neuroaxonal injury. Additionally, we address the neurobiology of pain in RA, highlighting the mechanisms of central sensitization (CS) and neuroimmune signalling that sustain pain-independent joint swelling. This evidence indicates that understanding the dynamic connection between CRP isoforms and neuronal markers should offer new insights for risk stratification and suggests that targeting mCRP may provide a novel therapeutic avenue to mitigate both articular and extra-articular manifestations of RA. Full article

This review aims to provide a comprehensive and integrative evaluation of the therapeutic potential of curcumin in arthritis, focusing on its molecular mechanisms, preclinical evidence, and clinical applications. A systematic literature search was conducted across major databases, and a total of 165 studies were included in this review. Curcumin exerts multi-target effects on key pathogenic pathways involved in arthritis. At the molecular level, it inhibits inflammatory signaling pathways, particularly NF-κB, and reduces the production of pro-inflammatory mediators, including TNF-α, IL-1β, IL-6, COX-2, and PGE2. In parallel, curcumin modulates oxidative stress by enhancing antioxidant defenses, including superoxide dismutase (SOD) and glutathione (GSH), while reducing lipid peroxidation. It also regulates cell death pathways, including apoptosis, autophagy, and emerging mechanisms such as pyroptosis and ferroptosis, and preserves cartilage integrity by inhibiting matrix metalloproteinases and ADAMTS while promoting extracellular matrix components. Preclinical studies consistently demonstrate anti-inflammatory, antioxidant, and chondroprotective effects across in vitro and animal models. Clinical evidence, particularly in osteoarthritis, indicates improvements in pain and functional outcomes, with some studies suggesting efficacy comparable to nonsteroidal anti-inflammatory drugs. However, this evidence remains limited and should be interpreted with caution. However, variability in formulations and limited bioavailability remain key challenges influencing clinical outcomes. Overall, curcumin represents a promising multi-target therapeutic agent for arthritis. Further large-scale, well-designed randomized controlled trials using standardized and bioavailable formulations are required to confirm its efficacy and optimize its clinical application. Full article

Gelsemium elegans is a traditionally utilized medicinal plant in China, renowned for its well-documented therapeutic properties and substantial economic potential. The primary bioactive components in this plant are indole alkaloids. It is used clinically to treat conditions including rheumatoid arthritis, neuropathic pain, and some cancers. Additionally, the whole plant can be processed into livestock feed. Climate change is anticipated to substantially impact the future suitable habitat of this species. Utilizing the Biomod2 ensemble model and 18 environmental variables (bio01, bio03, bio04, bio05, bio06, bio09, bio11, bio17, hf, elev, aspect, slope, gm_lc, gm_ve, ph_water, usda, d1_swr, annual_mean_uv-b) this study projected the geographical distribution of G. elegans under current and future climate scenarios; the periods of the 2050s, 2070s, and 2090s were analyzed using SSP1-2.6, SSP2-4.5, and SSP5-8.5. Current ecological niche modeling predicts that G. elegans is predominantly distributed in southern China, with its climatically and edaphically most suitable habitats concentrated in Guangxi, Guangdong, Fujian, and Hainan provinces. Across the three future time periods under various scenarios, the overall extent of suitable habitat is projected to increase, with a northward expansion of the suitable distribution range. Key environmental factors shaping the distribution of G. elegans include Isothermality (bio03), Max Temperature of Warmest Month (bio05), Min Temperature of Coldest Month (bio06), Precipitation of Driest Quarter (bio17), and Annual Average UV Radiation. The study aims to develop a scientifically grounded theoretical framework to support the conservation-oriented management and climate-resilient utilization of G. elegans resources under ongoing climate change. Full article

Rheumatoid arthritis (RA) is a chronic inflammatory disorder associated with a substantially increased risk of cardiovascular (CV) disease, driven by both persistent systemic inflammation and a high burden of traditional cardiometabolic risk factors. In recent years, glucagon-like peptide-1 receptor agonists (GLP-1RAs), licensed for type 2 diabetes mellitus and obesity, have attracted attention for their broader metabolic and cardiovascular benefits, raising the question of their potential role in RA. This scoping review summarizes current evidence on the impact of GLP-1RAs on RA disease activity, CV comorbidities, and the underlying immuno-metabolic mechanisms. Experimental studies suggest that GLP-1RAs could modulate key inflammatory pathways in synovial cells, reducing pro-inflammatory cytokine production, oxidative stress, and tissue-degrading enzymes, while improving mitochondrial function. Although clinical data remains limited, observational studies report improvements in disease activity, inflammatory markers, and pain in patients with RA treated with GLP-1RAs in addition to immunosuppressive treatment. Extensive evidence from randomized trials in metabolic populations demonstrates that GLP-1RAs improve glycemic control, induce significant weight loss, and reduce modestly but consistently blood pressure and atherogenic lipids, ultimately lowering major CV events and mortality. Although this evidence cannot be directly translated to RA populations, early real-world data specific to the disease suggest similar favorable trends, including reductions in cardiometabolic risk factors and thromboembolic events. Taken together, these findings suggest that GLP-1RAs may offer dual benefits in RA by addressing both metabolic dysfunction and inflammation. However, the current evidence base is heterogeneous and largely non-randomized, underscoring the need for dedicated trials. Full article

Juvenile idiopathic arthritis (JIA) is the most common systemic chronic inflammatory connective tissue disease in children, characterized by joint inflammation lasting at least six months. Temporomandibular joint (TMJ) involvement can occur in conjunction with other joints and may often be asymptomatic in its early stages. Objective: This study aims to evaluate the relationship between clinical symptoms of the stomatognathic system and radiologically confirmed cone beam computed tomography (CBCT)-detected structural TMJ changes in children with JIA. The research hypothesis posits that specific clinical symptoms are more prevalent in patients with CBCT-confirmed structural TMJ changes. Methods: A cohort of children diagnosed with JIA was examined. Clinical symptoms, including facial asymmetry, limited mandibular movement, and joint and masticatory muscle pain upon palpation, were assessed. CBCT imaging was performed to assess osseous TMJ structural changes. Results: The frequency of orofacial clinical symptoms was assessed and compared between patients with and without radiological evidence of TMJ involvement. Children with CBCT-confirmed TMJ changes demonstrated significantly higher rates of facial asymmetry, reduced maximum mouth opening, mandibular deviation during opening, and limitations in lateral or protrusive movements compared with those without TMJ involvement. Pain-related symptoms (TMJ pain, muscle tenderness, and pain during movement) and joint sounds occurred at similar frequencies in both groups. Conclusions: Facial asymmetry, mandibular deviation during opening and reduced mandibular mobility are the clinical signs most strongly associated with structural TMJ involvement in JIA and should prompt targeted imaging. Pain-related symptoms show limited diagnostic value, highlighting the need for focused clinical assessment and future studies integrating CBCT and MRI to refine early screening protocols. Full article