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Objective. Fibromyalgia (FM) is a disorder characterized by chronic diffuse pain and enhanced pain response to stimuli and is caused by central sensitization. Tinnitus also is related to central sensitization. So we investigated the impact of tinnitus on FM. Methods. We included 22 FM patients with tinnitus and 25 FM patients without tinnitus. We assessed a range of symptoms using the Widespread Pain Index; Symptom Severity Score scale; Visual Analogue Scale of pain; and the Korean versions of the Fibromyalgia Impact Questionnaire (FIQ), the Insomnia Severity Index, and the Short-form Health Survey (SF-36). Information about the severity of tinnitus in FM patients was evaluated using the Korean version of the Tinnitus Handicap Questionnaire (THQ-K). Results. There were significant differences between the group that had mild tinnitus (THQ＜38) and the group that had moderate-to-severe tinnitus (THQ≥38) for FIQ score (p=0.025) and for the physical functioning (p=0.003), social functioning (p=0.035), and mental health (p=0.017) components of the SF-36. Also, after dividing patients into 2 groups according to insomnia severity, significant differences were observed in FIQ score (p=0.002) and in body pain (p=0.001), general health (p=0.008), vitality (p=0.003), social functioning (p=0.003), role limitation due to emotional condition (p=0.001), and mental health (p＜0.001) components of the SF-36. Conclusion. The FM patients with severe tinnitus had more functional impairments and lower quality of life than those with mild tinnitus. Severe insomnia also was accompanied by worse health status and lower quality of life. (J Rheum Dis 2021;28:31-37)

Behçet’s disease (BD) is a rare, chronic, auto-inflammatory disorder of unknown origin. Mucocutaneous lesions and pan-uveitis constitute the hallmark of BD. Additionally, vessels of all sizes and types are affected. In this article, we report a 53-year-old female patient diagnosed with neurovascular BD with diplopia, ipsilateral headache and ophthalmoplegia associated with cavernous sinus thrombosis, leading to Tolosa-Hunt-like syndrome. To our knowledge, this is the first report of a patient with complicated cavernous sinus thrombosis in BD.

Vigeo is a mixture of fermented extracts of Eleutherococcus senticosus Maxim (ESM), Achyranthes japonica (Miq.) Nakai (AJN), and Atractylodes japonica Koidzumi (AJK) manufactured using the traditional Korean nuruk fermentation method. Although the bioactive effects of ESM, AJN, and AJK have already been reported, the pharmacological effects of Vigeo have not been proven. Therefore, in this study, we investigated whether Vigeo had inhivitory effects on lipopolysaccharide (LPS)-induced inflammatory bone loss in vivo and receptor activator of nuclear factor-B ligand (RANKL)-induced osteoclastogenesis and the related mechanism in vitro. Vigeo administration conferred effective protection against bone loss induced by excessive inflammatory response and activity of osteoclasts in LPS-induced inflammatory osteoporosis mouse model. In addition, Vigeo significantly suppressed the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by RANKL and inhibited F-actin formation and bone resorbing activity without any cytotoxicity. Moreover, Vigeo significantly inhibited RANKL-induced phosphorylation of p38, ERK, JNK, IκB, and AKT and degradation of IkB. Additionally, Vigeo strongly inhibited the mRNA and protein expression of c-FOS and NFATc1 and subsequently attenuated the expression of osteoclast specific marker genes induced by RANKL. We demonstrated for the first time the anti-osteoporosis effect of Vigeo, suggesting that it could be a potential therapeutic candidate for the treatment of osteoclast-mediated inflammatory bone diseases.

Background:Semaphorin has been found as a neuronal guidance molecule, but has recently been called “immune semaphorin”, as their critical role in immune cell activation, differentiation and migration has been revealed. In particular, class 4 semaphorin has been shown to contribute to lymphocyte activation and immune homeostasis.Objectives:This study was aimed to investigate the expression of neuropilin-1 (NRP-1), the receptor of class 4 semaphorin, in the murine mouse model of systemic lupus erythematosus (SLE) and the patients with SLE and the correlation between the expression of NRP-1 and disease activity of SLE.Methods:The expression of NRP-1 was measured in T cells in spleen and renal tissue in control mouse and TLR-7 agonist-induced lupus mouse by flow cytometry, PCR, and immunofluorescence (IF). CD4+ T cells from human peripheral blood were isolated to investigate the expression of NRP-1 in healthy control and the patients with SLE (n=40).Results:The frequency of NRP-1 positivity in CD4+ T cells in spleen was significantly higher in lupus mouse group (median [interquartile range]: 15.34 [14.84] %) compared to vehicle mouse group (4.0 [2.77]%). The quantitative analysis of fluorescense intensity in kidney stained for NRP-1 revealed the increased level in lupus group compared to vehicle group. The CD4+ T cells from peripheral blood mononuclear cells in the patients with lupus also showed significantly higher frequency of NRP-1 positive CD4+ T cells than those from healthy controls. Comparing the correlation of the expression of NRP-1 and disease activity with SLEDAI, C3, C4, and anti-DNA antibodies, the significant correlation between NRP-1 and disease activity markers were confirmed.Conclusion:Our results demonstrate that higher expression of NRP-1 in CD4+ T cells and its significant correlation with disease activity of SLE. These results indicate that pathologic contribution of NRP-1 in the pathogenesis of SLE and potential of targeting NRP-1 for the treatment of SLE.References:[1]Nishide M, Kumanogoh A. The role of semaphorins in immune responses and autoimmune rheumatic diseases. Nat Rev Rheumatol. 2018 Jan;14(1):19-31.Disclosure of Interests:None declared

Background: Anthrax toxin receptor 1 (ANTXR1) has been known to have relationship with extracellular transmembrane protein deeply associated with the process of bone formation and exert important role in angiogenesis. However, there have been no reports to prove the effects of ANTXR1 on bone metabolism mediated by two types of bone cells, osteoclasts and osteoblasts. The aim of this study is to reveal the role of ANTXR1 in the differentiation and function of osteoclasts and osteoblasts. Objectives: The aim of this study is to reveal the role of ANTXR1 in the differentiation and function of osteoclasts and osteoblasts. Methods: To determine the effect of ANTXR1 on osteoclastogenesis or osteoblast differentiation, we examined TRAP staining, F-actin staining and Pit assay, or ALP and Alizarin Red-mineralization staining, respectively. The mechanism of ANTXR1 by transfection of retrovirus or siRNA analyzed using real-time PCR and western blot analysis. Also, the effect of ANTXR1 on osteoclast-mediated angiogenesis of endothelial cells assessed by in vitro vascular tubule formation assay of human umbilical vein endothelial cells (HUVECs). Results: Through performing gain- and loss-of-function studies, we found that ANTXR1 positively regulated receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation and bone resorption with no effects on osteoblast differentiation. During ANTXR1-mediated regulation of osteoclastogenesis, phosphorylation of early signal transducers, c-jun N-terminal kinase (JNK), Akt, and inhibitor of kappa B (IκB) was affected, which in turn alteration of mRNA and protein levels of c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). In addition, genetic manipulation of ANTXR1 in bone marrow macrophages (BMMs) modulated the capillary-like tube formation by HUVECs via two kinds of angiogenic factors, matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor-A (VEGF-A). These results explained the important role of ANTXR1 in osteoclast differentiation and functional activity, as well as, osteoclast-mediated angiogenesis of endothelial cells. Conclusion: Taken together, it was proposed that ANTXR1 might be a promising candidate for gene therapy related with bone metabolic diseases and further, have potential to be served as an important biomarker in the research fields of bone metastasis associated with vascularization. Disclosure of Interests: None declared

Background: A third of knee osteoarthritis presents with bilateral symptomatic arthritis. In these patients, treatment options include either a staged Unilateral Total knee arthroplasty (UTKA) procedure, or a simultaneous Bilateral TKA (BTKA) procedure. Even though literature regarding outcomes in BTKA procedure has not consistently been favorable, it remains popular in select patients due to use of a single anesthetic, shorter overall surgical time, lower cost and lower overall use of narcotics. African Americans (AAs) have lower utilization and worse outcomes in UTKA literature. It is unclear whether these racial variations extend to BTKA. Objectives: We sought to examine BTKA vs UTKA utilization rates and outcomes comparing AA and White patients. Methods: National Inpatient Sample (NIS) - Healthcare Cost and Utilization Project (HCUP) database (2007-2016) was used. We identified all patients ≥ 50 years who underwent elective primary TKA using ICD-9-CM code 81.54 for UTKA and BTKA from January 1, 2012 to September 30, 2015, and ICD-10-CM codes 0SRC0x and 0SRD0x thereafter. Patients with inflammatory arthritis, pathologic fractures, metastatic disease and avascular necrosis were excluded. Major in-hospital complications included post-operative myocardial infarction, prosthetic device complication, surgical wound infection, and venous thromboembolism. Differences in temporal trends in utilization and major in-hospital complications of BTKA vs UTKA were compared between AAs and Whites. Multivariable logistic regression models were used to assess differences in both these trends between AAs and Whites after adjusting for individual (age, sex, Elixhauser comorbidity index, and morbid obesity), hospital level (hospital volume, bed size, region and teaching status) and community level (median household income) variables. Discharge weights were used to enable nationwide estimates. Multiple imputation was performed for missing race variable (11.9%). Results: From 2007 to 2016, an estimated 276,194 BTKA (unweighted observations 56,675) and 5,528,429 UTKA (unweighted observations 1,131,329) were identified (Table 1). Females had a higher proportion of TKAs performed (62.1% UTKA vs 55.9% BTKA). Patients had fewer comorbidities (measured by the Elixhauser Index) when undergoing BTKA compared to UTKA. The proportion of BTKA amongst all TKAs declined from 5.53% in 2007-08 to 4.03% in 2015-16. AAs continued to have significantly lower proportion of BTKA utilization compared to Whites (4.68% in AAs vs 6.08% in Whites in 2007-08, whereas 3.28% in AAs vs 4.19% in Whites in 2015-16, adjusted p Conclusion: In this nationwide sample of patients from 2007 to 2016, we found that AAs have lower utilization rate of BKTA compared to Whites, however the in-hospital complication rates were significantly higher in Whites. References: N/A Disclosure of Interests: Bella Mehta: None declared, Kaylee Ho: None declared, Jennifer Bido: None declared, Michael Parks Consultant of: Zimmer Biomet, Linda Russell: None declared, Susan Goodman Shareholder of: Reginosine- Investment, Grant/research support from: Novartis, Horizon, Consultant of: Novartis, Celgene, UCB, Said Ibrahim: None declared

Background:Betulinic acid (BA), a natural plant-derived pentacyclic triterpenoid compound, is known to possess numerous pharmacological and biochemical properties including anti-inflammatory, anti-cancer, and anti-adipogenic activity.Objectives:we investigated that BA could suppress RANKL-induced osteoclastogenesis and bone resorption.Results:BA significantly suppressed osteoclastogenesis by decreasing the phosphorylation of Akt and IkB, as well as PLCγ2-Ca2+signaling, in pathways involved in early osteoclastogenesis as well as through the subsequent suppression of c-Fos and NFATc1. The inhibition of these pathways by BA was once more confirmed by retrovirus infection of constitutively active (CA)-Akt and CA-Ikkβ retrovirus and measurement of Ca2+influx. BA also significantly inhibited the expression of osteoclastogenesis-specific marker genes. Moreover, we found that BA administration restored the bone loss induced through acute lipopolysaccharide injection in mice by a micro-CT and histological analysis.Conclusion:Our findings suggest that BA is a potential therapeutic candidate for bone diseases involving osteoclasts.Disclosure of Interests:None declared