Knee osteoarthritis (KOA) is a debilitating degenerative joint disorder characterized by chronic low-grade inflammation and metabolic dysregulation. The gut microbiota has emerged as an important regulator of systemic inflammatory responses. Building upon our previous clinical findings that Bifidobacterium longum subsp. infantis B8762 (B8762) improved clinical symptoms and inflammatory markers in patients with KOA, the present study investigated the associated alterations in the gut microbiome and fecal metabolome. Fecal samples were collected from probiotic (n = 20) and placebo (n = 20) groups at baseline (0 M) and after a 1-month intervention (1 M). Integrated metagenomic and untargeted metabolomic analyses were performed to characterize changes in gut microbial composition, functional potential, and metabolic profiles. Metagenomic reads mapped to the B8762 reference genome showed a greater increase in B8762-associated mapping rates in the probiotic group than in the placebo group, supporting an association between B8762 supplementation and longitudinal changes in the gut microbiome. Longitudinal analysis further demonstrated greater increases in microbial alpha diversity in the probiotic group. Species-level analyses suggested selective alterations in gut microbial composition, with nominally higher relative abundances of Bifidobacterium pseudocatenulatum and Anaerostipes caccae and lower relative abundances of Holdemania filiformis and Lachnospira SGB5077 (nominal P < 0.05). HUMAnN3-based functional profiling identified enrichment of microbial pathways related to carbon utilization and amino acid biosynthesis, including the bifidobacterial shunt and branched-chain amino acid biosynthesis pathways. Untargeted metabolomics identified nominal between-group differences in metabolites primarily related to lipid metabolism, including lower relative abundances of aldosterone and 7α-hydroxy-4-cholesten-3-one in the probiotic group (nominal P < 0.05). Correlation analysis further revealed associations between differential taxa and selected metabolites, suggesting potential links between gut microbial alterations and steroid-related metabolic pathways. Overall, B8762 supplementation was associated with longitudinal changes in B8762-associated genomic signals, gut microbial diversity and composition, microbial functional potential, and fecal metabolic profiles. These findings provide exploratory multi-omics evidence supporting an association between B8762 supplementation and gut microbial-metabolic remodeling in KOA and generate hypotheses for future mechanistic studies of the gut-joint axis.

Coccidioidomycosis is an endemic mycosis in some regions of the Americas including the southwestern United States with recognized potential for extra-pulmonary dissemination. Nevertheless, its neuroradiologic spectrum in children, particularly with respect to longitudinal evolution and head and neck involvement, remains incompletely characterized. We retrospectively reviewed n=16 pediatric patients with definitive or probable infection evaluated at a single quaternary care center in an endemic region, analyzing clinical/laboratory data and serial neuroimaging findings. Most children were previously healthy. Neuroimaging abnormalities represented the initial manifestation in more than one-third of cases and were frequently multifocal and temporally dynamic, including both clinically silent and delayed lesions. Craniospinal meningitis and related complications such as hydrocephalus, stroke, intracranial vasculopathy and chronic arachnoiditis were the most common and severe findings of central nervous system involvement. Parenchymal granulomas were more common than previously described, while cerebrovenous thrombosis and diffuse white matter signal abnormalities could also occur. Head and neck involvement was identified in 56% of patients, most commonly craniofacial osteomyelitis, but also temporomandibular joint septic arthritis, necrotic cervical lymphadenopathy/lymphadenitis, cutaneous lesions, and chorioretinitis, suggesting these features may be more prevalent in children than previously recognized. These findings expand the known imaging spectrum of pediatric coccidioidomycosis and underscore the importance of neuroradiologist familiarity with these patterns to facilitate early disease recognition within the appropriate clinical and epidemiologic context followed by timely initiation of antifungal therapy. A low threshold for neuroimaging, coupled with comprehensive, multi-compartment evaluation over time, is essential for accurate delineation of disease extent and for monitoring therapeutic response.

Juvenile idiopathic arthritis (JIA) is one of the most prevalent chronic childhood inflammatory diseases. Patients with JIA often present with morning stiffness, swelling, pain, muscle weakness, and muscle atrophy around the affected joints and activity limitations. Fear of exercises results in functional limitations. High-dose corticosteroids provide good effects in the short term but have no long-term effect. Physical therapy focused on pain reduction and improvement of musculoskeletal function is an essential part of the management of JIA. Mobilization with movement (MWM) is considered a system of manual therapy techniques to return pain-free range of motion. In the present case report, authors reported the effect of MWM techniques on pain and range of elbow extension in one case of Juvenile idiopathic arthritis. Result demonstrated that these techniques can be beneficial to improve pain and range of elbow extension in JIA.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Fibroblast-like synoviocytes (FLS) play a central role in RA pathogenesis by promoting inflammatory signaling and extracellular matrix (ECM) degradation. Although isoliquiritigenin (ISL) exhibits anti-inflammatory and antioxidant activities, its direct molecular target in RA remains unclear. Therefore, this study aimed to identify the molecular target of ISL and elucidate its underlying mechanism. To address this, integrated bioinformatics analysis, target validation (CETSA, DARTS, and molecular docking), together with mechanistic studies in H2O2-treated synovial cells and CIA rats, were performed. Bioinformatics analysis identified NADPH oxidase 4 (NOX4) as one of the overlapping candidate targets of ISL for further investigation. Target engagement of NOX4 by ISL was supported by CETSA, DARTS, and molecular docking analyses. ISL suppressed NOX4-mediated reactive oxygen species (ROS) production, thereby inhibiting inflammasome activation, pro-inflammatory cytokine production, apoptosis, and ECM degradation.ISL improved cell survival and reduced apoptosis in H2O2-treated synovial c ells while preserving ECM integrity. These protective effects were further confirmed in CIA rats, where ISL alleviated arthritis severity, oxidative stress, and cartilage destruction. Collectively, these findings identify NOX4 as a critical upstream regulator linking oxidative stress to inflammasome activation and support pharmacological targeting of the NOX4-ROS-inflammasome axis by ISL as a promising therapeutic approach for RA.

Chronic joint pain, most caused by osteoarthritis, is one of the leading causes of disability worldwide. When conservative management fails, interventional therapies are introduced, with corticosteroid injections being one of the most utilized. However, its clinical utility is limited by its short-term efficacy and by potential structural adverse effects. Platelet-rich plasma has emerged as a compelling alternative, providing both anti-inflammatory and regenerative properties. This review will evaluate platelet-rich plasma as an autologous alternative to corticosteroid injections for the treatment of chronic joint pain due to osteoarthritis.

Background Knee osteoarthritis (OA) is a common, chronic condition associated with significant pain and functional limitations. Patients who receive inadequate relief from conservative care and are not indicated for or are unwilling to undergo arthroplasty procedures have previously faced a significant treatment gap. To address this, we examined the implantable shock absorber (ISA) in a cohort of patients over 65 years old, at follow-up through five years. Methods Patients from two clinical studies (Atlas and Calypso) aged 65 and over during the five-year observation period were evaluated in this secondary analysis. Primary outcomes included pain and functional ability (measured via the Western Ontario and McMaster Universities Arthritis Index (WOMAC)). Secondary outcomes included return-to-activities and adverse events. Outcomes were collected at baseline and at routine follow-up assessments for five years post ISA treatment. Follow-up measurements are compared with baseline at each interval.  Results A total of 18 participants (12 females) were eligible for inclusion in the analysis (mean age at final follow-up: 68.0 years, mean body mass index (BMI): 28.1). Five years after treatment with ISA, pain scores had improved by 70% over baseline (mean of 17.1 (SD 19.3) vs. mean of 55.0 (SD 11.9); p<0.01), and function scores had improved by 64% (mean of 19.5 (SD 22.2) vs. mean of 53.4 (SD 17.0); p<0.01). Additionally, 13/14 (93%) of participants achieved a clinically meaningful improvement in pain, with an 11/14 (79%) incidence of functional improvement after five years. Patients reported limitations in the performance of desired physical activities at baseline; at five-year follow-up, 14/18 (77.8%) of participants were able to perform one activity with no or minimal limitations (p<0.0001 vs. baseline). One device malfunction was reported at 105 days post procedure. Three participants were elected for conversion to total knee arthroplasty (TKA) in the study period. Conclusions Our study demonstrates that the ISA is a viable intervention for a selected population of patients with knee OA aged 65 and older. In this particular population, ISA was associated with significant long-term and sustained improvements in pain and function without compromising joint integrity, thus preserving options for future arthroplasty. For patients suffering in the treatment gap between the limited effectiveness of non-surgical approaches and the finality of arthroplasty, treatment with ISA offers a viable and effective proven option.

Chikungunya virus (CHIKV) infection causes acute febrile illness and severe joint inflammation, with some patients progressing to chronic arthritis. Early isotype-switched neutralizing antibody (nAb) responses have been associated with protection from chronic arthritis, but the cellular and molecular features of these early responses remain poorly defined.

Psoriatic arthritis is a chronic inflammatory disease that can affect the axial skeleton as well as the joints and enthesis. Following the failure of conventional synthetic disease-modifying antirheumatic drugs (DMARDs), numerous biological DMARDs (b-DMARDs) or targeted synthetic DMARDs are now available, although current guidelines do not recommend a specific mode of action in the absence of comorbidities or contraindications. The aim of the study is to identify markers associated with the achievement of Minimal Disease Activity (MDA) at week 16 in patients treated with tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i) or interleukin-23 inhibitors (IL-23i).

Background Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, joint destruction, and systemic complications. Despite therapeutic advances, disease activity remains variable, and modifiable factors influencing severity are under investigation. Vitamin D, beyond its role in bone metabolism, exerts immunomodulatory effects and may influence RA pathogenesis. However, evidence regarding its association with disease activity remains inconsistent. This study aimed to evaluate the clinical and biochemical correlates of serum 25-hydroxyvitamin D (25(OH)D) levels in RA patients within an Indian cohort. Methodology A cross‑sectional study was conducted among 50 newly diagnosed, treatment‑naïve patients with RA, aged over 18 years, at a tertiary care center in India. Demographic details, tender and swollen joint counts, visual analog scale (VAS) scores, erythrocyte sedimentation rate (ESR), C‑reactive protein (CRP), and Disease Activity Score 28 (DAS‑28) were recorded, while serum 25(OH)D concentrations were measured and categorized as normal, insufficient, or deficient. Statistical analyses were performed using SPSS version 20, with descriptive statistics expressed as mean ± SD and interquartile ranges (IQRs). Group differences in serum 25(OH)D were assessed using one‑way analysis of variance, followed by Tukey's post hoc test. To determine the structural independent effects of circulating vitamin D levels on baseline RA severity, a multiple linear regression analysis was performed on the cohort. Receiver operating characteristic (ROC) curve analysis was conducted to determine sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for ESR and DAS‑28 in predicting disease activity, with statistical significance set at p-values ≤0.05. Results Of the 50 patients tested, rheumatoid factor (RF) was positive in 46 (92.00%), while the remaining four patients were negative for RF but positive for anti‑cyclic citrullinated peptide (anti‑CCP) antibodies. The mean age was 40.32 ± 3.46 years (IQR = 35-46). The median tender joint count was 2.0 (IQR = 1-3), and the swollen joint count was 4.00 (IQR = 2.00-5.00). The mean DAS‑28 score was 4.11 ± 1.50 (IQR = 3.20-5.10), indicating predominantly moderate disease activity. Pain intensity assessed by VAS averaged 4.58 ± 1.88 (IQR = 3-6). ESR averaged 30.92 ± 18.89 mm/hour (IQR = 20-42), while CRP was 5.18 ± 4.65 mg/dL (IQR = 2.10-7.80). Serum 25(OH)D levels were relatively low, with a mean of 26.84 ± 3.96 ng/mL (IQR = 18.00-32.00), highlighting the prevalence of vitamin D deficiency in this population. The multiple linear regression model significantly predicted continuous DAS‑28 scores (F (3, 46) = 21.34, p < 0.001), explaining 58.2% of the variance (R² = 0.582). Serum 25(OH)D emerged as a highly significant and independent inverse determinant of baseline disease severity (B = -0.091, SE = 0.011, β = -0.741, p < 0.001). The area under the curve was 0.87 for ESR and 0.82 for serum 25(OH)D, underscoring good overall accuracy in predicting disease severity. Conclusions Vitamin D deficiency is a robust independent determinant of disease activity in Indian RA patients, underscoring the importance of monitoring vitamin D status alongside composite disease activity scores.