Bone Erosion Research Articles

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.

#2460 Haemodialysis-related periarticular calcifications as cause of recurrent severe inflammatory state

Abstract Background and Aims End stage chronic kidney disease (CKD) and haemodialysis (HD) are associated with disturbances in mineral and bone turnover ultimately leading to chronic kidney disease–mineral and bone disorder (CKD-MBD), which affects more than 90 % of patients with stage 5D CKD. The primary changes observed in CKD–MBD involve elevated phosphorus levels, decreased calcium levels, insufficient serum vitamin D, and heightened release of parathyroid hormone from the parathyroid glands, leading to secondary hyperparathyroidism. CKD-MBD leads to vascular calcification, increasing cardiovascular risk. There is also a correlation between abnormal bone remodeling activity in CKD-MBD and the likelihood of calcification in soft tissues. In rare instances, profound calcification occurs in periarticular tissues, resulting in severe inflammation and manifesting as systemic disease with articular involvement clinically. The objective of this case report is to demonstrate a recurrent inflammatory condition caused by severe periarticular calcification in a patient on HD. Case report We present a case of a middle-aged white male diagnosed with hypertension, hypercholesterolemia, chronic obstructive pulmonary disease, hepatitis C, and end-stage renal disease caused by hydronephrosis. He was undergoing HD since July 2020. From summer 2021 the patient experienced recurrent fever and arthralgias in the hips, elbows, and shoulders. Frequent acute hospitalizations were needed due to recurring fevers and severe inflammatory response with markedly elevated acute phase reactants (CRP was repeatedly >200 mg/l), raising suspicion of infection. Laboratory and imaging tests however showed no clear signs of infection, and antibiotic therapy was ineffective. An x-ray of the right AC-joint showed multiple periarticular calcifications dorsally from the AC-joint. Later, due to severe pain and swelling an MRI-scan of right elbow joint was conducted, revealing an osteomyelitis-suspect finding of the olecranon, and olecranon bursitis. No bacteria were detected in the punctate of olecranon bursa. X-ray scans of the elbows revealed bilateral soft tissue calcification dorsally from the proximal ulna. The x-ray scan of the right shoulder revealed calcific expansion in the AC-joint area, leading to total destruction of the lateral part of the clavicle. MRI and CT scans showed severe periarticular calcification around AC- and glenohumeral joints without inflammatory involvement of the synovium. Bony erosions were observed due to the pressure of calcified tissue on the bone. Whole-body CT-scan showed no sites of infection but there was a periarticular calcification observed around the hip joints. A PET-CT scan of the whole body, neck, and upper extremities revealed no signs of malignancy or infections, but there was an increased uptake of 18F-fluorodeoxyglucose detected in several periarticular sites, indicating a multi-site inflammatory process resulting from severe periarticular calcifications. A dual-energy CT-scan of upper extremities was performed, excluding the accumulation of monosodium urate crystals. The cycle of multiple hospitalizations and antibacterial therapies was broken with the diagnosis of CKD and HD-related inflammatory periarticular calcification. Initially, the inflammation was addressed with high-dose glucocorticoids. However, the dose was successfully tapered during the first month of treatment, and the patient continued to do well on a maintenance dose of 5 mg/day of prednisolone. Subsequently, hospitalizations, antibiotics, or surgical procedures were no longer required. Conclusion Severe CKD and HD cause disturbances in mineral and bone metabolism, that can lead to periarticular calcification. Like in our presented case, multi-site calcifications may mimic infection or autoimmune rheumatoid conditions making the way to correct diagnosis cumbersome and costly. Imaging techniques help us distinguish periarticular deposits from inflammatory and infectious arthritis. In our case low-dose prednisolone effectively reduced inflammation, obviating hospitalizations and minimizing healthcare burden.

Correlations of characteristics with tissue involvement in knee gouty arthritis: Magnetic resonance imaging analysis

ObjectiveThis study investigates the MRI features of knee gouty arthritis (KGA), examines its relationship with the extent of tissue involvement, and assesses whether risk factors can predict KGA. Materials and methodsPatients diagnosed with KGA underwent MRI examinations, and two independent observers retrospectively analyzed data from 44 patients (49 knees). These patients were divided into mild and severe groups based on tissue involvement observed during arthroscopy. MRI features were summarized, and the intraclass correlation coefficient evaluated interobserver reproducibility. Single-factor analysis compared clinical indicators and MRI features between groups, while Cramer's V coefficient assessed correlations. Multivariate logistic regression identified predictors of tissue involvement extent, and a ROC curve evaluated diagnostic performance. ResultsAmong 49 knees, 18 had mild and 31 had severe tissue involvement. Key MRI features included ligament sketch-like changes, meniscal urate deposition, irregularly serrated cartilage changes, low-signal signs within joint effusion, synovial proliferation, Hoffa's fat pad synovitis, gouty tophi, bone erosion, and bone marrow edema. The interobserver reliability of the MRI features was good. Significant differences (P < 0.05) were observed between the groups for anterior cruciate ligament (ACL) sketch-like changes, Hoffa's fat pad synovitis, and gouty tophi. ACL sketch-like changes (r = 0.309), Hoffa's fat pad synovitis (r = 0.309), and gouty tophi (r = 0.408) were positively correlated with the extent of tissue involvement (P < 0.05). ACL sketch-like changes (OR = 9.019, 95 % CI: 1.364–61.880), Hoffa's fat pad synovitis (OR = 6.472, 95 % CI: 1.041–40.229), and gouty tophi (OR = 5.972, 95 % CI: 1.218–29.276) were identified as independent predictors of tissue involvement extent (P < 0.05). The area under the ROC curve was 0.862, with a sensitivity of 67.70 %, specificity of 94.40 %, and accuracy of 79.14 %. ConclusionThis comprehensive analysis of MRI features identifies ligament sketch-like changes, meniscal urate deposition, and low-signal signs within joint effusion as characteristic MRI manifestations of KGA. Irregular cartilage changes are valuable for differential diagnosis in young and middle-aged patients. ACL sketch-like changes, Hoffa's fat pad synovitis, and gouty tophi correlate with tissue involvement severity and are critical in predicting and assessing the extent of tissue involvement in KGA.

Itaconate reduces proliferation and migration of fibroblast-like synoviocytes and ameliorates arthritis models

Fibroblast-like synoviocytes (FLS) play critical roles in rheumatoid arthritis (RA). Itaconate (ITA), an endogenous metabolite derived from the tricarboxylic acid (TCA) cycle, has attracted attention because of its anti-inflammatory, antiviral, and antimicrobial effects. This study evaluated the effect of ITA on FLS and its potential to treat RA. ITA significantly decreased FLS proliferation and migration in vitro, as well as mitochondrial oxidative phosphorylation and glycolysis measured by an extracellular flux analyzer. ITA accumulates metabolites including succinate and citrate in the TCA cycle. In rats with type II collagen-induced arthritis (CIA), intra-articular injection of ITA reduced arthritis and bone erosion. Irg1-deficient mice lacking the ability to produce ITA had more severe arthritis than control mice in the collagen antibody-induced arthritis. ITA ameliorated CIA by inhibiting FLS proliferation and migration. Thus, ITA may be a novel therapeutic agent for RA.

Osteosarcoma with widespread metastasis in a 1-year-old crossbred rabbit.

A 14-month-old female spayed, small crossbred rabbit presented for assessment of a small, hard subcutaneous nodule in the right axilla. Serum biochemistry showed markedly increased serum ALP activity. A whole-body CT revealed an aggressive, monostotic osteolytic, and productive lesion within the left alveolar process of the maxilla, with erosion of the alveolar bone and secondary premolar depression. Innumerable metastatic osseous masses were present throughout the body, including cerebral, pulmonary, hepatic, subcutaneous, and skeletal muscular metastases. Postmortem findings confirmed widespread, metastatic osteosarcoma, with the primary lesion within the left maxilla.

Large intracerebral hemorrhage secondary to functional endoscopic sinus surgery: risks in approaching anterior skull base

Rationale/objectiveThis is a rare case of a 54-years-old man affected by chronic erosive sinusitis who developed a large frontal intracerebral hemorrhage after functional endoscopic sinus surgery (FESS). The patient underwent urgent surgical hemorrhage evacuation and anterior skull-base bone defect repair. MethodsWe analyzed the possible causes of this complication following FEES, focusing on anterior skull base bone erosion by chronic sinusitis, anterior ethmoidal artery injury and/or aneurysm, and direct frontal lobe trauma. ResultsThe neurological outcome was good, and at three months follow-up, the patient showed only minor cognitive deficit and no cerebrospinal fluid leak. ConclusionDuring FESS, anatomical bone alteration of the anterior skull base such as in patients affected by chronic sinusitis, may increase the risk of severe complications such as intracerebral hemorrhage. A careful preoperative evaluation is mandatory.

Ethanol extract of Ziziphus nummularia ameliorates formaldehyde-induced arthritis in rats by regulating oxidative stress biomarkers and haematological profile.

Rheumatoid arthritis is an autoimmune inflammatory disorder that mainly affects bone and cartilage architecture. The continuous use of NSAIDs and DMARDs is associated with severe toxic effects. Therefore, the current study was designed to scrutinize herb-based therapy for the treatment of RA. To evaluate the anti-arthritic activity of ethanol extract of Ziziphus nummularia using formaldehyde-induced arthritic model in rats and elucidate the possible mechanism for anti-arthritic activity. Anti-arthritic activity of ETZN was studied at three oral doses, i.e., 200, 400, and 600mg/kg. Selected doses were studied using various clinical parameters viz. paw volume, inflammatory index, motility test, stair test, anti-nociceptive efficacy, walking track analysis, and motor activity) from day 1 to day 10. On the last day, the animals were killed for the evaluation of hematological parameters, oxidative stress biomarkers, and histological and radiographic studies of the hind paw. Treatment with ETZN 400mg/kg and 600mg/kg markedly elicited a significant reduction in paw volume, inflammatory index, and nociceptive action compared to diseased animals. Furthermore, the anti-inflammatory activity was confirmed by increased latency of pain threshold in thermal and mechanical algesia models. The anti-arthritic activity is mainly attributed to a reduction in oxidative stress biomarkers as well as restoration of haematological profile in treated animals when compared to diseased animals. Lastly, the anti-arthritic potential was confirmed by histological and radiological analysis which revealed a marked reduction in inflammatory cells and bone destruction as compared to diseased animals. The study revealed that ETZN exhibits significant anti-arthritic activity via modulation of oxidative stress biomarkers, restoration of hematological profile, and reduction in bone erosion.

TUBERCULOSIS OF THE WRIST

INTRODUCTIONTuberculosis (TB) is a public health challenge. However, musculoskeletal involvement represents 10–15% of all extrapulmonary cases. Upper extremity involvement is extremely rare. The slow progressive course of clinical symptoms and lack of radiological signs lead to difficulties in establishing early diagnosis. Hence, the patients who have tuberculosis of the wrist are usually misdiagnosed. We report 5 cases of tuberculosis of the wrist seen in our unit from the year 2012 to 2021.METHODSCases were retrospectively evaluated on demographics, nature of history, clinical presentation, culture finding, and histopathological findings from 2012 to 2021 at our unit.RESULTSA total of 5 cases were evaluated retrospectively. Three patients were more than 60 years old and two were less than 30 years old. Four of the patients presented with wrist swelling 2 of them had wrist pain and only 1 patient had discharge from the wound. The duration of the symptoms ranges from 2 months to 3 years. Only one of the patients had a history of pulmonary TB contact whereas the others didn't. All patients underwent surgery. All of the patients had positive cultures for Mycobacterium tuberculosis complex and histopathological examination showed necrotizing granulomatous inflammation from specimens taken intraoperatively, which confirmed the diagnosis of tuberculosis of the wrist.DISCUSSIONSOur cases show that the common presentation of tuberculosis of the wrist was comparable to other literature. Most of the patients presented with chronic wrist swelling with or without wrist pain. The diagnosis of the disease was delayed an average of 10 - 12 months from symptoms onset to diagnosis. S. Bayram et al reported a case where the diagnosis was made 45 months later. Due to its rarity, it often is misdiagnosed, resulting in delays in the proper treatment.CONCLUSIONThe diagnosis of the TB wrist remains difficult because of insidious and non-specific. presentation. However, early diagnosis is essential to avoid delays in treatment and complications. Hence, chronic wrist pain, and swelling with or without unexplained bone erosion around the wrist area must be highly suspected of being osteoarticular tuberculosis.

Celastrol nano-emulsions selectively regulate apoptosis of synovial macrophage for alleviating rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune inflammation. Excessive proliferation and inadequate apoptosis of synovial macrophages are the crucial events of RA. Therefore, delivering therapeutic molecules to synovial macrophages specifically to tackle apoptotic insufficiency probably can be an efficient way to reduce joint inflammation and bone erosion. Based on the characteristics of dextran sulphate (DS) specifically binding scavenger receptor A (SR-A) on macrophage and celastrol (CLT) inducing apoptosis, we designed synovial macrophage-targeted nano-emulsions encapsulated with CLT (SR-CLTNEs) and explored their anti-RA effect. After intravenous injection, fluorescence-labelled SR-CLTNEs successfully targeted inflammatory joints and synovial macrophages in a mouse model of RA, with the macrophage targeting efficiency of SR-CLTNEs, CLTNEs and free DID was 20.53%, 13.93% and 9.8%, respectively. In vivo and in vitro studies showed that SR-CLTNEs effectively promoted the apoptosis of macrophages, reshaped the balance between apoptosis and proliferation, and ultimately treated RA in a high efficiency and low toxicity manner. Overall, our work demonstrates the efficacy of using SR-CLTNEs as a novel nanotherapeutic approach for RA therapy and the great translational potential of SR-CLTNEs.

Potential Role of Dietary Phenolic Compounds in the Prevention and Treatment of Rheumatoid Arthritis: Current Reports.

Rheumatoid arthritis (RA) is a complex illness with both hereditary and environmental components. Globally, in 2019, 18 million people had RA. RA is characterized by persistent inflammation of the synovial membrane that lines the joints, cartilage loss, and bone erosion. Phenolic molecules are the most prevalent secondary metabolites in plants, with a diverse spectrum of biological actions that benefit functional meals and nutraceuticals. These compounds have received a lot of attention recently because they have antioxidant, anti-inflammatory, immunomodulatory, and anti-rheumatoid activity by modulating tumor necrosis factor, mitogen-activated protein kinase, nuclear factor kappa-light-chain-enhancer of activated B cells, and c-Jun N-terminal kinases, as well as other preventative properties. This article discusses dietary polyphenols, their pharmacological properties, and innovative delivery technologies for the treatment of RA, with a focus on their possible biological activities. Nonetheless, commercialization of polyphenols may be achievable only after confirming their safety profile and completing successful clinical trials.

Effective diagnosis of sacroiliitis in children: evaluating magnetic resonance imaging with the Canadian scoring system.

To reveal the differences by comparing the magnetic resonance imaging (MRI) findings of patients with clinically symptomatic sacroiliitis with those undergoing sacroiliac imaging for other reasons using the Canadian Spondyloarthritis Research Consortium-Sacroiliac Inflammatory Scoring System (SPARCC-SIS). In this retrospective single-center study, sacroiliac MRIs performed between 2017 and 2023 were evaluated from the database. The SPARCC-SIS scoring system is used to evaluate and grade the inflammation of the sacroiliac joints. Mild inflammation is indicated by a score below 24, moderate by a score of 24-48, and severe by a score above 49. Additionally, structural defects of the sacroiliac joint, such as erosion, sclerosis, and ankylosis, were observed. After MRI evaluation, clinically symptomatic (group 1) and non-symptomatic (group 2) patients were divided into two groups. The clinical and laboratory findings of the patients and MRI findings were compared. The patient's age, gender, clinical information from hospital records, acute phase reactants (APRs), and the presence of the Human Leukocyte Antigen (HLA-B27) gene (if applicable) were thoroughly recorded. One hundred thirty-six children who performed sacroiliac MRI for any indication were included in the study. The APRs positivity, presence of HLA-B27, and SPARCC scoring system were significantly higher in 24 patients with clinical sacroiliitis (group 1) than in 112 patients without sacroiliitis (group 2). In our study, the most common MRI findings in children were bone marrow edema, capsulitis, synovitis, and erosion, while chronic structural changes such as sclerosis and ankylosing were rare. In this study, the SPARCC scoring method, which shows the severity of sacroiliac joint inflammation, correlates with the clinical diagnosis of sacroiliitis. In cases with suspected sacroiliitis, except for extraordinary reasons, it can be evaluated with MRI without contrast material and can be graded to guide the clinician in treatment and approach.

Deletion of RANKL in regulatory T cells ameliorates bone erosion in arthritis

Abstract Rheumatoid arthritis (RA) is an autoimmune disease that leads to bone erosion mediated through osteoclasts.Osteoclast differentiation is promoted through engagement of RANK by its ligand (RANKL) expressed by multiple lineages. Whereas regulatory T cells (Tregs) typically suppress osteoclastogenesis, Tregs developing in a pro-inflammatory environment can express RANKL and promote osteoclast function (Levescot et al.2021).To test the importance of osteoclastogenic Tregs in vivo, we developed a mouse selectively lacking RANKL expression in Tregs (FoxP3YFP/creRANKLflox/flox, hereafter RANKLΔTreg). Arthritis was induced by administration of K/BxN serum containing arthritogenic IgG antibodies. Joint inflammation and synovial neutrophil infiltration in RANKLΔTreg mice were similar to WT animals. Compared with Tregs from lymph nodes, Tregs from inflamed joints exhibited increased expression of activation markers including CD25,Foxp3,CD44, and CTLA4, without a difference between RANKLΔTreg and WT animals; RANKLΔTreg mice exhibited a trend for higher Treg PD-1 expression. In WT mice, the percentage of Tregs expressing RANKL was elevated in synovial fluid compared to lymph nodes. Correspondingly, microCT showed a significant reduction in bone erosion in RANKLΔTreg compared to WT mice (p=0.003). These findings are consistent with a pathogenic role of RANKL-expressing Treg for RA bone erosion in arthritis; whether RANKL impacts other Treg functions remains to be established.

A watch, wait, and rescan approach for incidental benign-appearing notochordal lesions of the skull base.

The aim of this study was to describe the natural history of incidental benign-appearing notochordal lesions of the skull base with specific attention to features that can make differentiation from low-grade chordoma more difficult, namely contrast uptake and bone erosion. In this retrospective case series, the authors describe the clinical outcomes of 58 patients with incidental benign-appearing notochordal lesions of the clivus, including those with minor radiological features of bone erosion or contrast uptake. All lesions remained stable during a median follow-up of almost 3 years. Thirty-seven (64%) patients underwent contrast-enhanced MRI; lesions in 14 (38%) of these patients exhibited minimal contrast enhancement. Twenty-seven (47%) patients underwent CT; lesions in 6 (22%) of these patients exhibited minimal bone erosion. These data make the case for monitoring selected cases of benign-appearing notochordal lesions of the clivus in the first instance even when there is minor contrast uptake or minimal bone erosion.

Pediatric Unilateral Chronic Sinusitis: Clinical and Radiological Patterns Compared to Adults.

Upper respiratory tract infections and sinusitis are more prevalent in children than in adults. Unilateral sinusitis is not uncommon disease. Our aim was to analyze the disease characteristics in children with unilateral sinusitis and compare them with those of adults. This study included 124 patients with unilateral chronic sinusitis divided according to age into two groups: pediatric group ≤18 years (66 cases) and adult group >18 years (58 cases). The groups were compared in terms of demographic data, side, clinical manifestations and radiological findings. In pediatric patients, the most common inflammatory pathology was antrochoanal polyps, followed by allergic fungal sinusitis. On the other hand, chronic sinusitis without nasal polyps is the most common in adults, followed by antrochoanal polyps. The mean duration of clinical manifestations before diagnosis in pediatric patients was significantly shorter than that in adults (P=0.001). The most common symptoms in both pediatric and adult patients were anterior nasal discharge and nasal obstruction. Proptosis was significantly higher in pediatric group than in adult group (P=0.015). On computed tomography (CT), the most commonly affected sinus in both pediatric and adult patients was the maxillary sinus followed by the anterior ethmoid sinus. Bone expansion, erosion and involvement of adjacent structures were significantly higher in pediatric patients (P=0.028, 0.027 respectively). Pediatric patients have a high incidence of antrochoanal polyps and allergic fungal sinusitis as unilateral inflammatory lesions. These lesions require surgical management. Inflammatory paranasal sinus lesions in pediatric patients have a shorter duration of clinical manifestations and a higher incidence of bone erosion and involvement of adjacent structures; therefore, early diagnosis and management prevent complications.

A scapular statistical shape model can reliably predict premorbid glenoid morphology in conditions of severe glenoid bone loss

Knowledge of premorbid glenoid parameters at the time of shoulder arthroplasty, such as inclination, version, joint line position, height, and width, can assist with implant selection, implant positioning, metal augment sizing, and/or bone graft dimensions. The objective of this study was to validate a scapular statistical shape model (SSM) in predicting patient-specific glenoid morphology in scapulae with clinically relevant glenoid erosion patterns. Computed tomography scans of 30 healthy scapulae were obtained and used as the control group. Each scapula was then virtually eroded to create 7 erosion patterns (Walch A1, A2, B2, B3, D, Favard E2, and E3). This resulted in 210 uniquely eroded glenoid models, forming the eroded glenoid group. A scapular SSM, created from a different database of 85 healthy scapulae, was then applied to each eroded scapula to predict the premorbid glenoid morphology. The premorbid glenoid inclination, version, height, width, radius of best-fit sphere, and glenoid joint line position were automatically calculated for each of the 210 eroded glenoids. The mean values for all outcome variables were compared across all erosion types between the healthy, eroded, and SSM-predicted groups using a 2-way repeated measures analysis of variance. The SSM was able to predict the mean premorbid glenoid parameters of the eroded glenoids with a mean absolute difference of 3°±2° for inclination, 3°±2° for version, 2 ± 1 mm for glenoid height, 2 ± 1 mm for glenoid width, 5 ± 4 mm for radius of best-fit sphere, and 1 ± 1 mm for glenoid joint line. The mean SSM-predicted values for inclination, version, height, width, and radius were not significantly different than the control group (P>.05). An SSM has been developed that can reliably predict premorbid glenoid morphology and glenoid indices in patients with common glenoid erosion patterns. This technology can serve as a useful template to visually represent the premorbid healthy glenoid in patients with severe glenoid bony erosions. Knowledge of the premorbid glenoid preoperatively can assist with implant selection, positioning, and sizing.

Oxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the TLR4-MD2/NF-κB/MAPK signaling axis.

Rheumatoid arthritis (RA) is an idiopathic and chronic autoimmune disease for which there are currently no effective treatments. Oxypeucedanin hydrate (OXH) is a natural coumarin known for its potent anti-inflammatory properties. However, further investigations are needed to determine its therapeutic efficacy in treating RA. In this study, we evaluate the anti-inflammatory activity of OXH by treating LPS-induced RAW264.7 macrophages. Our results show that OXH treatment reverses the changes in iNOS, COX-2, IL-1β, IL-6, and TNF-α levels. Additionally, OXH reduces ROS production. Further analysis reveals that OXH suppresses the activation of the NF-κB/MAPK pathway. CETSA results show that OXH competes with LPS for binding to the TLR4/MD2 complex. MST experiments demonstrate the specific affinity of OXH for the TLR4/MD2 complex, with a Kd value of 33.7 μM. Molecular docking analysis suggests that OXH binds to the pocket of the TLR4/MD2 complex and interacts with specific amino acids, such as GLY-343, LYS-388, and PHE-345. Molecular dynamics simulations further confirm this conclusion. Finally, we investigate the potential of OXH in treating RA using a collagen-induced arthritis (CIA) model in rats. OXH effectively ameliorates the symptoms of CIA, including improving body weight, reducing swelling and redness, increasing talus volume, and decreasing bone erosion. OXH also decreases the mRNA levels of pro-inflammatory factors in synovial tissue. Transcriptome enrichment analysis and western blot analysis confirm that OXH suppresses the NF-κB/MAPK pathway, which is consistent with our in vitro findings.

Clinical and histopathological factors for recurrence and metastasis in lacrimal gland adenoid cystic carcinoma in Chinese patients.

To investigate the association of metabolism-related proteins and clinicopathological features with poor prognosis in lacrimal gland adenoid cystic carcinoma (LGACC). Clinicopathological data for 39 Chinese patients with LGACC enrolled were retrospectively analysed. Disease progression included death, recurrence, further nodal metastasis, and distant metastasis. Expression of ASCT2 and GLS1 were evaluated by immunohistochemistry. Kaplan-Meier survival curves and Cox proportional hazards regression models were used for risk factor analyses. At the end of follow-up, 14 patients (35.9%) developed local recurrence, 13 patients (33.3%) developed distant metastasis, 3 patients (7.7%) developed lymph node metastasis, and 9 patients (23.1%) died. Among the 13 patients who developed distant metastasis, lung metastasis was observed in 8 patients (61.5%), the brain in 8 patients (61.5%), and bone in 1 patient (7.7%). ASCT2 was expressed in 16 (57.14%) cases, while GLS1 had high expression in 19 (67.9%) cases. Advanced T category (≥T3), bone erosion, basaloid subtype, and ASCT2 (-) were associated with disease progression. Basaloid subtype was an independent risk factor for local recurrence (P = 0.028; HR, 12.12; 95% CI, 1.3-111.5). ASCT2(-) was an independent risk factor for distant metastasis (P = 0.016; HR, 14.46; 95% CI, 1.6-127.5) and was associated with basaloid subtype (P = 0.019). For LGACC, ≥T3 category, basaloid subtype, and bone erosion were high-risk predictors. ASCT2(-) was an independent risk factor for distant metastasis, which suggested that it could be a potential biomarker for LGACC.

Target Role of Monocytes as Key Cells of Innate Immunity in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory autoimmune condition characterized by synovitis, pannus formation (with adjacent bone erosion), and joint destruction. In the perpetuation of RA, fibroblast-like synoviocytes (FLSs), macrophages, B cells, and CD4+ T-cells-specifically Th1 and Th17 cells-play crucial roles. Additionally, dendritic cells, neutrophils, mast cells, and monocytes contribute to the disease progression. Monocytes, circulating cells primarily derived from the bone marrow, participate in RA pathogenesis. Notably, CCR2 interacts with CCL2, and CX3CR1 (expressed by monocytes) cooperates with CX3CL1 (produced by FLSs), facilitating the migration involved in RA. Canonical "classical" monocytes predominantly acquire the phenotype of an "intermediate" subset, which differentially expresses proinflammatory cytokines (IL-1β, IL-6, and TNF) and surface markers (CD14, CD16, HLA-DR, TLRs, and β1- and β2-integrins). However, classical monocytes have greater potential to differentiate into osteoclasts, which contribute to bone resorption in the inflammatory milieu; in RA, Th17 cells stimulate FLSs to produce RANKL, triggering osteoclastogenesis. This review aims to explore the monocyte heterogeneity, plasticity, antigenic expression, and their differentiation into macrophages and osteoclasts. Additionally, we investigate the monocyte migration into the synovium and the role of their cytokines in RA.

P023 A case of ANCA-associated vasculitis with possible IgG4-related disease

Abstract Background/Aims IgG4-related disease (IgG4-RD) and granulomatous polyangiitis (GPA) have apparent different pathology. There are infrequent reports of the two conditions occurring simultaneously. We add to the literature by describing a patient who appears to have both conditions. Methods A 65-year-old male presented with low back pain radiating to the perineum. His past history included T2DM, CABG and ablation for AF. Initial investigations showed a CRP of 102mg/ml and an eGFR of &amp;gt; 90ml/hr. A CT urogram revealed possible aortitis. A dedicated aortogram showed a cuff of added tissue around the infrarenal aorta and iliac arteries. A whole aortogram showed an increase in the abnormal tissue and detected a left upper lobe cavitating lesion. A PET-CT scan showed activity in the infrarenal aortic tissue, with focal uptake in the aortic arch and right superficial femoral artery. Several pleural based and parenchymal lesions showing moderate increased FDG activity were seen. A CT scan of the sinuses showed multifocal sinonasal mucosal thickening without bony erosions. C-ANCA was positive at 1/40, with raised PR3 of 32U/ml and IgG4 of 2.2g/L. Other immunoglobulin levels were normal and IGRA was negative. A biopsy of the lung lesion showed necrotising granulomatous inflammation and surrounding palisading histocytes, withno vasculitic element. Treatment with prednisolone 40mg daily and methotrexate 15mg weekly was started. A quick symptomatic improvement followed. CRP fell to 14mg/ml within two months. It was discussed in the national IgG4-RD MDT, and the consensus was that he had features of both GPA and IgG4-RD. A follow-up CT scan showed reduction in the volume of para-aortic tissue, with regression of some lesions in the chest, while others increased. However, he remains well with a normal CRP, stable renal function and normal urinalysis. His latest IgG4 level dropped to 0.67 g/L. Results The ANCA positivity and lung biopsy findings satisfy classification criteria of GPA. While aortic involvement is not commonly seen in GPA; it is typical of IgG4-RD; however, its diagnostic criteria require a confirmatory biopsy. This is challenging due to the risk of sampling around the aorta and ureters. Our case fulfils criteria for ‘possible’ IgG4-RD. In retrospect, an earlier PET CT scan may have spared the patient several CT scans. Conclusion The co-existence of IgG4-RD and ANCA-associated vasculitis may be more common than might be expected. Our case highlights the usefulness of early PET-CT scanning in rheumatic conditions. It is important to check ANCA in suspected IgG4-RD cases. It is possible that future AI programmes may help clinicians better judge the timing of investigations that may be more expensive, invasive or have increased radiation exposure in such complex cases. Finally, the usefulness of a national MDT for IgG4-RD is highlighted. Fortunately, treatment modalities are similar for both conditions. Disclosure H. Eltahir: None. M. Lloyd: None.

P120 Characteristics of difficult-to-treat rheumatoid arthritis: results from a systematic literature review

Abstract Background/Aims Estimates predict between 10-20% of RA patients meet difficult-to-treat Rheumatoid Arthritis (D2T-RA) classification, representing a clinically distinct cohort. There is a significant unmet need in the identification and management of these patients. Discerning significant characteristics across cohorts may identify predictors for D2T-RA, which may prompt earlier clinical recognition and patient-tailored, holistic management to improve clinical outcomes. This review aims to describe the clinical characteristics of patients with EULAR-defined D2T-RA to help identify and manage predictors, contributory factors, or consequences of difficult-to-treat disease. Methods A systematic literature search of PubMed, Embase and Web of Science databases for studies pertaining to characteristics of D2T-RA was undertaken from database inception to May 2023. Results were screened against strict inclusion/exclusion criteria. Risk-of-bias (RoB) assessments were performed using the Newcastle-Ottawa Scale (NOS) and a modified version for cross-sectional studies (mNOS). Significant (p &amp;lt; 0.05) baseline characteristics between D2T-RA and non-D2T patients were extracted for comparison following thematic analysis. Where there was conflict in the direction of the extracted characteristics; the number and quality of studies were used to resolve evidential disagreements. Results 1687 studies were identified, of which seven fulfilled the inclusion criteria. Included studies were observational, published between 2021 and 2023, with mean D2T and non-D2T sample sizes of 83 and 417 patients, respectively. Five of the seven cohorts were European, with two from Japan. Following RoB and dispute resolution, all seven identified studies were included for analysis. Key themes elucidated are shown in table 1. Of note, significant characteristics included female sex, autoantibody positivity, greater annual bone erosion progression, interstitial lung disease, mental health conditions, and non-adherence. Conclusion Greater awareness of clinical characteristics of D2T-RA patients will assist clinicians by promoting the assessment of traits associated with poor treatment response. This is the first review to systematically describe characteristics of D2T-RA patients across multiple cohorts. Several commonly recorded, modifiable characteristics were associated with D2T-RA. Evidential disagreements and heterogeneous study designs were analytical barriers, and clinical intervention studies are needed to determine if addressing these factors in the routine clinical setting improves clinical outcomes and prevention in D2T-RA. Disclosure S. Chambers: None. A.P. Croft: None. R. Singh: None.