Bone Erosion Research Articles

Clinical outcomes and prognostic factors of parameningeal rhabdomyosarcoma in children and adolescents: results of two consecutive protocols.

Parameningeal rhabdomyosarcoma (PM-RMS) accounts for about 20% of all rhabdomyosarcoma (RMS) cases. At present, most research on PM-RMS has been conducted in Europe and the United States of America, and research in China has been very limited. This study sought to analyze the clinical outcomes and prognostic factors of PM-RMS in children and adolescents from two consecutive protocols at Beijing Children's Hospital (BCH). A total of 80 patients aged up to 18 years with previously untreated PM-RMS who had received treatment under two consecutive protocols [i.e., either the BCH-RMS-2006 protocol or the Chinese Children Cancer Group (CCCG)-RMS-2016 protocol] were included in the statistical analysis. The Kaplan-Meier method was used for the survival analysis, and Cox regression was used for the univariate and multivariate analyses. Of the 80 patients enrolled in the study, 69 (86.2%) had meningeal invasion (MI). Of these 69 MI patients, 18 (22.5%) had cranial nerve palsy (CNP), 64 (80.0%) had cranial base bone erosion (CBBE), 25 (31.3%) had intracranial extension (ICE), and 2 (2.5%) had positive cerebrospinal fluid (CSF) tumor cells. The median follow-up time was 20.5 months (range, 5-100 months). The 5-year overall survival (OS) and progression-free survival (PFS) rates for the entire cohort were 51.7% and 45.6%, respectively. The 5-year OS rates of the patients who received the BCH-RMS-2006 protocol (18/80, 22.5%) and the CCCG-RMS-2016 protocol (62/80, 77.5%) were 33.3% and 57.0%, respectively (P<0.05), while the PFS rates of these patients were 22.2% and 53.6%, respectively (P<0.05). In relation to the PM-RMS patients with MI, the 5-year OS rates were 21.4% and 52.7%, and the 5-year PFS rates were 14.3% and 51.1% for the patients who received the old and new regimens, respectively (P<0.05). The extent of surgical resection had no significant effect on survival. The multivariate analysis showed that the coexistence of CBBE and ICE, no radiotherapy, a poor response to induction chemotherapy, and the BCH-RMS-2006 protocol were risk factors affecting PFS and OS. Of the patients examined in this study, those with PM-RMS with CBBE accompanied by ICE had the worst prognosis. The patients with MI benefited from intensive chemotherapy combined with radiation therapy, but the effect of surgery was very limited.

A hierarchical cluster analysis for clinical profiling of tofacitinib treatment response in patients with rheumatoid arthritis.

Tofacitinib is the first oral JAK inhibitor approved for treating rheumatoid arthritis (RA). To enhance our understanding of tofacitinib drug response, we used hierarchical clustering to analyse the profiles of patient who responded to the treatment in a real-world setting. Patients who commenced on tofacitinib treatment were selected from 12 major rheumatology centres in Malaysia. The aim was to assess their response to tofacitinib defined as achieving DAS28-CRP/ESR ≤ 3.2 and DAS28 improvement > 1.2 at 12weeks. A hierarchical clustering analysis was performed using sociodemographic and clinical parameters at baseline. All 163 RA patients were divided into three clusters (Clusters 1, 2 and 3) based on specific clinical factors at baseline including bone erosion, antibody positivity, disease activity and anaemia status. Cluster 1 consisted of RA patients without bone erosion, antibody negative, low baseline disease activity measure and absence of anaemia. Cluster 2 comprised of patients without bone erosion, RF positivity, anti-CCP negativity, moderate to high baseline disease activity score and absence of anaemia. Cluster 3 patients had bone erosion, antibody positivity, high baseline disease activity and anaemia. The response rates to tofacitinib varied among the clusters: Cluster 1 had a 79% response rate, Cluster 2 had a 66% response rate, and Cluster 3 had a 36% response rate. The differences in response rates between the three clusters were found to be statistically significant. This cluster analysis study indicates that patients who are seronegative and have low disease activity, absence of bone erosion and no signs of anaemia may have a higher likelihood of benefiting from tofacitinib therapy. By identifying clinical profiles that respond to tofacitinib treatment, we can improve treatment stratification yielding significant benefits and better health outcomes for individuals with RA.

Invasive Fungal Sinusitis and Its Orbital Morbidity in Pediatric Population: A Strategic Treatment Algorithm and Outcomes.

Invasive fungal sinusitis, particularly mucormycosis, presents a significant clinical challenge, especially in pediatric populations. This retrospective epidemiologic study aimed to investigate the clinical characteristics, risk factors and outcomes associated with this rare but severe condition, with a focus on orbital morbidity. Clinical data of 12 pediatric patients diagnosed with invasive fungal sinusitis between 2021 and 2023 were retrospectively analyzed. Diagnosis involved microbiological and histopathologic examinations, alongside radiologic imaging. Treatment comprised surgical intervention and antifungal therapy, with a detailed evaluation of orbital involvement. Statistical analysis included descriptive statistics and logistic regression. Predominantly affecting males, the median age of the patients was 8 years. Common symptoms included orbital swelling and impaired vision. Imaging revealed characteristic features of invasive fungal sinusitis, including fat stranding and bone erosions. Orbital involvement was extensive, with poor visual outcomes observed in several cases. Surgical debridement and antifungal therapy, including transcutaneous retrobulbar Amphotericin B, were administered. Risk factors associated with poor orbital outcomes included duration of diabetes and glycated hemoglobin levels. Mortality rate stood at 22.2%. Early diagnosis, aggressive surgical intervention and combined antifungal therapy are essential for improving outcomes. Timely intervention showed stabilization of the orbital disease and better outcomes in pediatric patients. Further research with larger sample sizes is warranted to better understand and address this serious condition.

Angiectatic Polyp-An Unusual Nasal Mass in a Young Adult.

Angiectatic nasal polyps (ANP) are rare pseudo-neoplastic lesions that might raise intriguing pathophysiological issues and present a significant diagnostic challenge. They are also referred to as inflammatory granuloma telangiectaticum, vascular granuloma, pseudo-angioma, and angiomatous/angiectatic polyp. However, the name angiectatic polyp refers to the fact that the lesion is not a true tumour and is clinically distinguished by ectatic vasculature, haemorrhage, and persistent proliferation. The most confusing aspect of this polyp is its clinical appearance, which resembles a juvenile nasal angiofibroma. Despite its typical imaging characteristics, this lesion is difficult to differentiate radiologically. Hence, histopathology is paramount for establishing diagnosis. We report a rare case of a young adult who presented with complaints of nasal block and epistaxis. Examination revealed a vascular nasal mass and CT scan demonstrated the lesion to be epicentred in right nasal cavity extending to multiple sinuses with adjacent bone erosion. Patient underwent endoscopic excision of the mass with JNA as the predominant differential and only following histopathological examination, the final diagnosis was confirmed.

N6-methyladenosine methylation analysis of circRNAs in acquired middle ear cholesteatoma.

Middle ear cholesteatoma is a chronic middle ear disease characterized by severe hearing loss and adjacent bone erosion, resulting in numerous complications. This study sought to identify pathways involved in N6-methyladenosine (m6A) modification of circRNA in middle ear cholesteatoma. A m6A circRNA epitranscriptomic microarray analysis was performed in middle ear cholesteatoma tissues (n = 5) and normal post-auricular skin samples (n = 5). Bioinformatics analyses subsequently explored the biological functions (Gene Ontology, GO) and signaling pathways (Kyoto Encyclopedia of Genes and Genomes, KEGG) underlying middle ear cholesteatoma pathogenesis. Methylated RNA immunoprecipitation qPCR (MeRIP-qPCR) was performed to verify the presence of circRNAs with m6A modifications in middle ear cholesteatoma and normal skin samples. Microarray analysis identified 3,755 circRNAs as significantly differentially modified by m6A methylation in middle ear cholesteatoma compared with the normal post-auricular skin. Among these, 3,742 were hypermethylated (FC ≥ 2, FDR < 0.05) and 13 were hypomethylated (FC ≤ 1/2, FDR < 0.05). GO analysis terms with the highest enrichment score were localization, cytoplasm, and ATP-dependent activity for biological processes, cellular components, and molecular functions respectively. Of the eight hypermethylated circRNA pathways, RNA degradation pathway has the highest enrichment score. Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathway was hypomethylated. To validate the microarray analysis, we conducted MeRIP-qPCR to assess the methylation levels of five specific m6A-modified circRNAs: hsa_circRNA_061554, hsa_circRNA_001454, hsa_circRNA_031526, hsa_circRNA_100833, and hsa_circRNA_022382. The validation was highly consistent with the findings from the microarray analysis. Our study firstly presents m6A modification patterns of circRNAs in middle ear cholesteatoma. This finding suggests a direction for circRNA m6A modification research in the etiology of cholesteatoma and provides potential therapeutic targets for the treatment of middle ear cholesteatoma.

MDSCs are important osteoclast precursors primed by B cells in rheumatoid arthritis.

Osteoclast-mediated bone erosion and deformation represent significant pathological features in rheumatoid arthritis (RA). Myeloid-derived suppressor cells (MDSCs) and B cells have emerged as key contributors to the progression of RA. Nevertheless, their involvement, especially the interaction in RA osteoclastogenesis remains elusive. In this study, our results revealed a marked expansion of MDSCs in RA patients, and importantly, their abundance was positively correlated with radiographic damage evaluated by the Sharp/van der Heijde score. Notably, MDSCs derived from both RA patients and arthritic mice exhibited a heightened propensity to differentiate into osteoclasts compared with those from healthy individuals. Intriguingly, we observed that B cells from RA patients could augment the osteoclastogenic potential of MDSCs, which was also observed in arthritic mice. The impact of B cells on MDSC-mediated osteoclastogenesis was found to be most pronounced in switched memory B cells, followed by CD21low B cells and naïve B cells. MDSCs from B-cell-deficient mice exhibited diminished capacity to differentiate into osteoclasts, accompanied by distinct gene expression profiles associated with osteoclastogenesis. Taken together, our findings suggested that MDSCs were important osteoclast precursors primed by B cells in RA, serving as novel therapeutic targets for the persistent disease.

RGS1 Enhancer RNA Promotes Gene Transcription by Recruiting Transcription Factor FOXJ3 and Facilitates Osteoclastogenesis Through PLC-IP3R-dependent Ca2+ Response in Rheumatoid Arthritis.

Recent evidence has highlighted the functions of enhancers in modulating transcriptional machinery and affecting the development of human diseases including rheumatoid arthritis (RA). Enhancer RNAs (eRNAs) are RNA molecules transcribed from active enhancer regions. This study investigates the specific function of eRNA in gene transcription and osteoclastogenesis in RA. Regulator of G protein signaling 1 (RGS1)-associated eRNA was highly activated in osteoclasts according to bioinformatics prediction. RGS1 mRNA was increased in mice with collagen-induced arthritis as well as in M-CSF/soluble RANKL-stimulated macrophages (derived from monocytes). This was ascribed to increased RGS1 eRNA activity. Silencing of 5'-eRNA blocked the binding between forkhead box J3 (FOXJ3) and the RGS1 promoter, thus suppressing RGS1 transcription. RGS1 accelerated osteoclastogenesis through PLC-IP3R-dependent Ca2+ response. Knockdown of either FOXJ3 or RGS1 ameliorated arthritis severity, improved pathological changes, and reduced osteoclastogenesis and bone erosion in vivo and in vitro. However, the effects of FOXJ3 silencing were negated by RGS1 overexpression. In conclusion, this study demonstrates that the RGS1 eRNA-driven transcriptional activation of the FOXJ3/RGS1 axis accelerates osteoclastogenesis through PLC-IP3R dependent Ca2+ response in RA. The finding may offer novel insights into the role of eRNA in gene transcription and osteoclastogenesis in RA.

Clarifying the Diagnosis and Management of Acute Uncomplicated Pediatric Mastoiditis.

Acute pediatric mastoiditis is a bacterial infection of the mastoid bone most commonly associated with acute otitis media. Complicated mastoiditis is traditionally characterized by intracranial complications or subperiosteal abscess, but definitions are inconsistent in the literature. Surgical intervention is identified as the main treatment for complicated mastoiditis, but there is some evidence to support medical management of uncomplicated mastoiditis. This study sought to clarify the diagnostic criteria and management of uncomplicated acute mastoiditis. All cases of acute pediatric mastoiditis were identified from a single institution over a 16-year period and reviewed for demographic and clinical data. Two different definitions of uncomplicated mastoiditis were compared; the traditional one that excluded patients with intracranial complications or subperiosteal abscess (SPA) and the proposed definition that also excluded patients with any evidence of bony erosion including coalescence, not just SPA. Univariate and multivariate analysis was conducted. Eighty cases were identified. Using the traditional definition of uncomplicated mastoiditis, 46.3% of cases were uncomplicated, compared to 36.2% when using the proposed definition. Truly uncomplicated patients, categorized with the proposed definition, were treated more consistently: no patients underwent mastoidectomy and they were less likely to receive a long term course of antibiotics. On multivariate regression analysis, only categorization with the proposed definition of uncomplicated mastoiditis was independently associated with less long-term antibiotic therapy and non-surgical management. Uncomplicated acute mastoiditis should be defined using clinical criteria and exclude any cases with evidence of bony erosion, including coalescence or subperiosteal abscess. These truly uncomplicated patients often do not require mastoidectomy and can be prescribed a shorter course of antibiotics. Further research into treatment pathways is necessary to optimize the management of uncomplicated acute pediatric mastoiditis.

Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study

ObjectivesTo assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population.MethodsIn this multicentre...

Automated quantification of wrist bone marrow oedema, pre- and post-treatment, in early rheumatoid arthritis.

Bone inflammation (osteitis) in early RA (ERA) manifests as bone marrow oedema (BME) and precedes the development of bone erosion. In this prospective, single-centre study, we developed an automated post-processing pipeline for quantifying the severity of wrist BME on T2-weighted fat-suppressed MRI. A total of 80 ERA patients [mean age 54 years (s.d. 12), 62 females] were enrolled at baseline and 49 (40 females) after 1 year of treatment. For automated bone segmentation, a framework based on a convolutional neural network (nnU-Net) was trained and validated (5-fold cross-validation) for 15 wrist bone areas at baseline in 60 ERA patients. For BME quantification, BME was identified by Gaussian mixture model clustering and thresholding. BME proportion (%) and relative BME intensity within each bone area were compared with visual semi-quantitative assessment of the RA MRI score (RAMRIS). For automated wrist bone area segmentation, overall bone Sørensen-Dice similarity coefficient was 0.91 (s.d. 0.02) compared with ground truth manual segmentation. High correlation (Pearson correlation coefficient r = 0.928, P < 0.001) between visual RAMRIS BME and automated BME proportion assessment was found. The automated BME proportion decreased after treatment, correlating highly (r = 0.852, P < 0.001) with reduction in the RAMRIS BME score. The automated model developed had an excellent segmentation performance and reliable quantification of both the proportion and relative intensity of wrist BME in ERA patients, providing a more objective and efficient alternative to RAMRIS BME scoring.

The Minor Phytocannabinoid Delta-8-Tetrahydrocannabinol Attenuates Collagen-Induced Arthritic Inflammation and Pain-Depressed Behaviors.

Patients with arthritis report using cannabis for pain management, and the major cannabinoid delta-9-tetrahydrocannabinol (Δ9-THC) has anti-inflammatory properties, yet the effects of minor cannabinoids on arthritis are largely unknown. The goal of the present study was to determine the antiarthritic potential of the minor cannabinoid delta-8-tetrahydrocannabinol (Δ8-THC) using the collagen-induced arthritis (CIA) mouse model. Adult male DBA/1J mice were immunized and boosted 21 days later with an emulsion of collagen and complete Freund's adjuvant. Beginning on the day of the booster, mice were administered twice-daily injections of Δ8-THC (3 or 30 mg/kg), the steroid dexamethasone (2 mg/kg), or vehicle for two weeks. Dorsal-ventral paw thickness and qualitative measures of arthritis were recorded daily, and latency to fall from an inverted grid was measured on alternating days, to determine arthritis severity and functional impairment. On the final day of testing, spontaneous wire-climbing behavior and temperature preference in a thermal gradient ring were measured to assess CIA-depressed behavior. The Δ8-THC treatment (30 mg/kg) reduced paw swelling and qualitative signs of arthritis. Δ8-THC also blocked CIA-depressed climbing and CIA-induced preference for a heated floor without producing locomotor effects but did not affect latency to fall from a wire grid. In alignment with the morphologic and behavioral assessments in vivo, histology revealed that Δ8-THC reduced synovial inflammation, proteoglycan loss and cartilage and bone erosion in the foot joints in a dose-dependent manner. Together, these findings suggest that Δ8-THC not only blocked morphologic changes but also prevented functional loss caused by collagen-induced arthritis. SIGNIFICANCE STATEMENT: Despite increasing use of cannabis products, the potential effects of minor cannabinoids are largely unknown. Here, the minor cannabinoid delta-8-tetrahydrocannabinol blocked the development of experimentally induced arthritis by preventing both pathophysiological as well as functional effects of the disease model. These data support the development of novel cannabinoid treatments for inflammatory arthritis.

Juvenile Xanthogranuloma of the Head and Neck: Imaging Findings in 11 Cases.

Juvenile Xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis, occurring mainly in infancy. With an extracutaneous lesion, its diagnosis is difficult, because of a wide clinical spectrum. Here we demonstrate and characterize imaging features of 11 patients with JXG of the head and neck in various locations. We recorded clinical data and reviewed all imaging studies of 11 patients with JXG of the head and neck. Ultrasonography (US) alone was performed in 1 patient; MRI alone in 6 patients; US and MRI in 1 patient; and US, CT, and MRI in 3 patients. We evaluated the following characteristics in all studies: location and number of lesions, echogenicity and vascularization on US, density on CT, signal intensity on T 1 - and T 2 -weighted images, ADC and enhancement on MRI, and tumor boundaries and bone involvement. Lesions were well-defined in 9 cases, and bone erosion was present in 2. On US, lesions were hypoechoic or hyperechoic and with or without vascularization. On CT, lesions were hyper-dense, with no calcification. On MRI, lesions were mildly hyper-intense or iso-intense on T 1 -weighted images in 8 of 9 patients, hypo-intense on T2-weighted images in 7 of 10, low ADC in 7 of 9, and enhancement in 7 of 7. The diagnosis of extra cutaneous JXG may be proposed, with the following suggestive criteria: age < 1 year, well-defined lesion, mild hyper-intensity on T 1 -weighted images, hypo-intensity on T 2 -weighted images, low ADC, enhancement, and possible adjacent bone involvement.

SITE AND RATE OF OSSICULAR CHAIN EROSION IN PATIENTS UNDERWENT TYMPANOMASTOID SURGERY

Background: Chronic suppurative otitis media (CSOM) is a common problem affecting middle ear and it’s commonly presented with chronic ear discharge and decreased hearing. Hearing problem in CSOM is primarily caused perforated tympanic membrane and in some cases by the presence of erosion of the ossicular chain. The study aimed to show the rate and site of ossicular chain erosion in patients with chronic suppurative otitis media underwent tympanomastoid surgery. Patient and methods: a cross sectional study conducted on 87 patients performed tympanomastoid surgery for chronic middle ear infection where their ossicular status has been assessed intraoperatively. Results: our study shows that 40% of the operated ears has at least a single bone erosion and the Incus bone was the most affected ossicle while the Malleus was the least one 54% and 14% respectively. No statistically significant difference was seen between bone erosion and gender as well as the side of operation. Conclusion: ossicular erosion is a common problem affecting patient with chronic suppurative otitis media and the surgeons should be aware about this pathology and they should have the proper skill to correct such problem.

Clinical implications of persistent joint pain after gout flare

ObjectivesA subset of gout patients developed persistent joint pain after flares. Analysis of this clinical phenomenon may shed further light on the factors related to worsening gout and even provide clues to its pathogenesis. MethodsWe analyzed the clinical, laboratory, and ultrasound data of gout patients to explore the associations of these data with persistent joint pain after gout flares. ResultsA total of 1029 gout patients were included: 182 (17.7%) patients with persistent joint pain and 847 (82.3%) patients with nonpersistent joint pain. Patients with persistent joint pain had more total involved joints, more gout flares in the past year, and more joints with simultaneous gout flares (P<0.01). Among the ultrasound-detected lesions, patients with persistent joint pain had a higher incidence of tophus (36.4% vs. 21.1%) and bone erosion (18.6% vs. 8.6%) (P<0.05). Higher UA and lower TBil were found in patients with persistent joint pain (P<0.001). Hypertension (54.9% vs. 38.7%) and metabolic syndrome (58.8% vs. 46.4%) were both more frequent in patients with persistent joint pain (P<0.05). TBil was negatively correlated with the incidence of persistent joint pain (P<0.001, r=−0.190), UA values (P<0.001, r=−0.125), and metabolic syndrome scores (P<0.001, r=−0.192). A correlation curve was fitted using LOESS (locally weighted region). ConclusionPersistent joint pain after gout flares is a marker of increased disease burden in gout. The significance of the level of total bilirubin for the exacerbation of gout deserves further study.

Deep learning-based classification of erosion, synovitis and osteitis in hand MRI of patients with inflammatory arthritis

ObjectivesTo train, test and validate the performance of a convolutional neural network (CNN)-based approach for the automated assessment of bone erosions, osteitis and synovitis in hand MRI of patients with...

Posterior fossa primary intracranial extraosseous Ewing’s sarcoma: case report

BackgroundPrimary intracranial Ewing’s sarcoma (ES) is a type of primitive neuroectodermal tumour and is a rare malignant tumour in children and adolescents. The imaging features of ES overlap with other central nervous system embryonal tumours, making it difficult to pinpoint a specific diagnosis. We aim to explore the clinical, neuroimaging and differential diagnoses of this entity.Case presentationWe describe a 6-month-old infant who presented with complaints of enlarging the head size and poor feeding. Imaging revealed a contrast-enhancing large solid-cystic mass lesion with internal calcification, focal bone erosion and haemorrhage in the posterior fossa. Histopathological examinations, immunohistochemistry, and molecular analysis confirmed ES.ConclusionsThe confirmative diagnosis of primary intracranial ES requires histological examination, immunohistochemical analysis, and genetic detection, along with radiological findings. Surgical excision followed by combined radiotherapy and chemotherapy is the treatment of choice.

A rare cause of malignant otitis externa and skull base osteomyelitis.

An elderly male with type 2 diabetes presented with a 2-month history of otalgia and severe headaches. He was diagnosed with malignant otitis externa (MOE) and was commenced on empirical treatment with oral ciprofloxacin. Pseudomonas is the most common cause of MOE. A baseline CT scan was undertaken that demonstrated skull base osteomyelitis (SBO) due to findings of bone erosion at the mastoid tip and an infiltrating soft tissue mass eroding the clivus. Eight weeks later, he returned with worsening and bilateral symptoms of otitis externa, hearing loss, temporomandibular pain and dysfunction. Worsening and now bilateral malignant otitis externa were confirmed with an MRI scan that also demonstrated a small fluid collection in his left temporal region. The collection was aspirated and grew scedosporium apiospermum. He was diagnosed with fungal SBO and was commenced on treatment with the antifungal voriconazole, with significant improvement in symptoms and radiological findings. Fungal osteomyelitis is more likely in immunosuppressed patients, particularly those with type 2 diabetes. Fungal aetiology should be suspected in patients with progressive symptoms, despite treatment. A microbiology diagnosis of fungal SBO or MOE can be challenging to obtain and can lead to diagnostic delay. A sampling of the external auditory canal can aid in diagnosing MOE; however, scedosporium may also be isolated as a commensal organism. Aspirations from accessible fluid collections, infratemporal fossa needle sample and bone biopsy can provide material for diagnosis. Scedosporium is a rare cause of disease in humans, however, fungal infections are increasing in humans, due to an increase in susceptible populations. Scedosporium apiospermum is a rare cause of SBO and should be considered in patients not responding to standard treatment.

Machine learning-based identification and immune characterization of ferroptosis-related molecular clusters in osteoarthritis and validation.

Osteoarthritis (OA), a degenerative joint disease, involves synovial inflammation, subchondral bone erosion, and cartilage degeneration. Ferroptosis, a regulated non-apoptotic programmed cell death, is associated with various diseases. This study investigates ferroptosis-related molecular subtypes in OA to comprehend underlying mechanisms. The Gene Expression Omnibus datasets GSE206848, GSE55457, GSE55235, GSE77298 and GSE82107 were used utilized. Unsupervised clustering identified the ferroptosis-related gene (FRG) subtypes, and their immune characteristics were assessed. FRG signatures were derived using LASSO and SVM-RFE algorithms, forming models to evaluate OA's ferroptosis-related immune features. Three FRG clusters were found to be immunologically heterogeneous, with cluster 1 displaying robust immune response. Models identified nine key signature genes via algorithms, demonstrating strong diagnostic and prognostic performance. Finally, qRT-PCR and Western blot validated these genes, offering consistent results. In addition, some of these genes may have implications as new therapeutic targets and can be used to guide clinical applications.

Free Fatty Acid 4 Receptor Activation Attenuates Collagen-Induced Arthritis by Rebalancing Th1/Th17 and Treg Cells.

Dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) has been found to be beneficial in rodent rheumatoid arthritis models and human trials. However, the molecular targets of n-3 PUFAs and their beneficial effects on rheumatoid arthritis are under-researched. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor for n-3 PUFA. We aim to investigate whether FFA4 activation reduces collagen-induced rheumatoid arthritis (CIA) by using an FFA4 agonist, compound A (CpdA), in combination with DBA-1J Ffa4 gene wild-type (WT) and Ffa4 gene knock-out (KO) mice. CIA induced an increase in the arthritis score, foot edema, synovial hyperplasia, pannus formation, proteoglycan loss, cartilage damage, and bone erosion, whereas the administration of CpdA significantly suppressed those increases in Ffa4 WT mice but not Ffa4 gene KO mice. CIA increased mRNA expression levels of pro-inflammatory Th1/Th17 cytokines, whereas CpdA significantly suppressed those increases in Ffa4 WT mice but not Ffa4 gene KO mice. CIA induced an imbalance between Th1/Th17 and Treg cells, whereas CpdA rebalanced them in spleens from Ffa4 WT mice but not Ffa4 gene KO mice. In SW982 synovial cells, CpdA reduced the LPS-induced increase in pro-inflammatory cytokine levels. In summary, the present results suggest that the activation of FFA4 in immune and synovial cells could suppress the characteristics of rheumatoid arthritis and be an adjuvant therapy.

The clinical assessment of changes in bone density in rheumatoid arthritis patients': Role of DEXA scan and bone turnover biomarkers

In addition to generalised of bone loss and a higher fracture risk, rheumatoid arthritis (RA) causes periarticular bone erosions. Improvements in bone density/erosion and turnover may not go hand in hand with a positive clinical response to biological anti-inflammatory drugs assesed by disease activity score 28 (DAS28) in RA patients. This study aimed to understand how biologic anti-inflammatory drugs affect bone density, erosion, and turnover in RA patients. We examined bone mineral density (BMD) and bone turnover biomarkers. The study population consisted of 62 RA patients, 49 (79%) of whom were female and 13 (21%) of whom were male. The patients ranged in age from 40 to 79 years old. The patients' BMD was measured using a DEXA scan, and their plasma levels of bone turnover biomarkers CTX and osteocalcin were quantified utilizing an ELISA. BMD of the hip and lumbar spine in responder patients rose after therapy by 0.001g/cm2 (0.11 percent, p0.001 vs. before treatment) and 0.0396g/cm2 (3.96 percent, p0.001 vs. before treatment), respectively. Clinically non-responder patients' DAS28 revealed minor reductions in hip BMD values of −0.008g/cm2 (−0.78 percent, p0.001 vs. before therapy), as well as an improvement in lumbar spine BMD of 0.03g/cm2 (3.03 percent, p0.001 vs. before treatment). After 12 weeks of therapy, the CTX levels in responder patients dropped from 164 125 pg/ml to 131 129 pg/ml. Osteocalcin levels in non-responder patients increased substantially from 11.6 ng/ml to 14.9 ng/ml after 12 weeks of therapy compared to baseline (p = 0.01). Treatment with biologic anti-inflammatory medicines decreases widespread bone loss in RA patients' hip and lumbar spine. The beneficial effects of therapy on BMD were not associated with changes in disease activity of RA patients. Changes in plasma levels of bone turnover biomarkers such as sCTX and osteocalcin confirmed the treatment's beneficial effects.