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ID PMID Title PublicationDate abstract
31933536 Salivary interleukin 6, interleukin 8, interleukin 17A, and tumour necrosis factor α leve 2019 INTRODUCTION: Rheumatoid arthritis (RA) and periodontitis share risk factors and inflammatory pathways that could be related to cytokines, such as interleukin (IL)-6, IL-8, IL-17A, and tumour necrosis factor-α (TNF-α). The aim of this study was to compare periodontal status and salivary levels of selected cytokines between patients diagnosed with RA and periodontitis. RA patients were assessed for the potential influence of anti-rheumatic therapy. MATERIAL AND METHODS: One hundred and six patients were enrolled in a cross-sectional study. Medical assessment and periodontal examination were performed in 35 patients with chronic periodontitis, in 35 patients with RA and chronic periodontitis, and in 36 controls. Unstimulated whole saliva samples were analysed for IL-6, IL-8, IL-17A, and TNF-α. RESULTS: Significant differences in biomarkers and periodontal parameters were found among groups. Study groups exhibited higher mean pocket depth (PD), number of PD > 4 mm, and mean clinical attachment loss, when compared with controls. The RA group had lower bleeding on probing index and PD, but higher values of plaque indices than the periodontitis group. Concentration of evaluated cytokines were higher in the RA and periodontitis groups, compared with controls. The periodontitis group showed also higher levels of IL-6, IL-17A, and TNF-α in comparison to RA. RA patients were treated with disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticosteroids. CONCLUSIONS: Salivary levels of IL-6, IL-8, IL-17A, and TNF-α can be affected by periodontitis, RA, and presumably DMARDs. DMARD therapy appears to reduce destructive and inflammatory processes in periodontal tissues because lower values of PD, BOP, and salivary levels of IL-6, IL-17A, and TNF-α were found in RA.
31754941 Risk of Malignancies in Patients with Rheumatoid Arthritis Treated with Rituximab: Analyse 2020 Mar INTRODUCTION: Patients with rheumatoid arthritis (RA) are at an increased risk of developing malignancies, but it is unclear whether this increased risk is the result of disease pathobiology or immunosuppressant treatments for RA. This analysis evaluated the potential risk of malignancy in patients with RA treated with rituximab (MabThera(®)/Rituxan(®)) a CD20+ B-cell depleting agent manufactured by F. Hoffmann-La Roche Ltd. METHODS: Malignancy rates were obtained from the rituximab global company safety database for adverse event reporting and from the rituximab global clinical trial program for RA consisting of eight randomized clinical trials, two long-term open-label extensions, and one open-label prospective study. Global company safety database searches were performed using the standard Medical Dictionary for Regulatory Activities (MedDRA) queries "Malignant tumors wide" and "Skin malignant tumors wide" up to April 30, 2017. Age- and sex-specific comparator values from the general population were obtained from the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: For the 409,706 patients with RA in the rituximab global company safety database since first market approval in 2006, 1739 cumulative malignant events were reported, with an overall malignancy reporting rate of approximately 4.2 events per 1000 patients. No evidence of increased risk of malignancy, of any organ-specific type, was found following rituximab treatment. The rate of malignancies from rituximab-treated patients in RA clinical trials was 7.4 per 1000 patient-years. This is within the expected range, with no evidence for increased risk over time or with additional rituximab courses. CONCLUSIONS: Analyses of the global postmarketing safety database and long-term clinical trial data showed no evidence of an increased risk of malignancy of any type following rituximab treatment in patients with RA. FUNDING: F. Hoffmann-La Roche Ltd.
31664591 Effects of denosumab on bone mineral density and bone turnover markers in rheumatoid arthr 2019 Oct 29 BACKGROUND: To compare the efficacy of 12-month denosumab treatment on bone mineral density (BMD) and bone turnover markers (BTMs) between treatment-naïve osteoporosis patients with rheumatoid arthritis (RA) and those with previous bisphosphonate (BP) therapy. METHODS: A total of 36 RA patients with osteoporosis completed 12-month follow-up. Twenty-five patients were osteoporotic treatment-naïve (naïve group), and 11 patients were previously treated with BPs (switch group) (average 7.9 years). BMD and BTMs were measured before and 6 and 12 months after treatment. RESULTS: BTM levels were higher in the naïve group at baseline. However, the same level of suppression was achieved at 6 months in both groups. Spine BMD increased significantly in both groups. There was no significant difference in the mean percent changes of BMD of the spine (naïve group: 6.8 ± 0.8, switch group: 5.1 ± 1.5), femoral neck (2.9 ± 1.4, 2.9 ± 1.3), and total hip (1.7 ± 0.9, 1.4 ± 1.1) between these two groups at 12 months. CONCLUSIONS: The effects of denosumab on BMD and BTMs of the switch group after long-term BP treatment are comparable to those of the naïve group in RA patients. Thus, switching BPs to denosumab is one of the useful options to treat osteoporosis with RA.
31443559 Next-Generation Sequencing Profiles of the Methylome and Transcriptome in Peripheral Blood 2019 Aug 22 Using next-generation sequencing to decipher methylome and transcriptome and underlying molecular mechanisms contributing to rheumatoid arthritis (RA) for improving future therapies, we performed methyl-seq and RNA-seq on peripheral blood mononuclear cells (PBMCs) from RA subjects and normal donors. Principal component analysis and hierarchical clustering revealed distinct methylation signatures in RA with methylation aberrations noted across chromosomes. Methylation alterations varied with CpG features and genic characteristics. Typically, CpG islands and CpG shores were hypermethylated and displayed the greatest methylation variance. Promoters were hypermethylated and enhancers/gene bodies were hypomethylated, with methylation variance associated with expression variance. RA genetically associated genes preferentially displayed differential methylation and differential expression or interacted with differentially methylated and differentially expressed genes. These differentially methylated and differentially expressed genes were enriched with several signaling pathways and disease categories. 10 genes (CD86, RAB20, XAF1, FOLR3, LTBR, KCNH8, DOK7, PDGFA, PITPNM2, CELSR1) with concomitantly differential methylation in enhancers/promoters/gene bodies and differential expression in B cells were validated. This integrated analysis of methylome and transcriptome identified novel epigenetic signatures associated with RA and highlighted the interaction between genetics and epigenetics in RA. These findings help our understanding of the pathogenesis of RA and advance epigenetic studies in regards to the disease.
31872184 Comparison of Biologic Discontinuation in Patients With Elderly-Onset Versus Younger-Onset 2019 Dec OBJECTIVE: The objective of this study is to compare biologic drug discontinuation rates for older- versus younger-onset rheumatoid arthritis (YORA) because this is a key outcome measure that could impact prescribing practices. METHODS: We performed a retrospective medical record review of all patients who fulfilled the 1987 American College of Rheumatology (ACR) criteria for adult-onset rheumatoid arthritis (RA) in 1999-2013 among residents of a geographically defined area, with follow-up until death, migration, or July 1, 2017. Discontinuation rates were estimated using cumulative incidence adjusted for the competing risk of death. RESULTS: A total of 240 cases of elderly-onset rheumatoid arthritis (EORA) and 366 cases of YORA were identified (65% and 73% female, respectively; P = 0.025). Cumulative incidence of biologic initiation was lower among the EORA cohort compared with the YORA cohort (18% vs 33%, respectively, at 10 years after RA incidence; P < 0.001). Among those treated with a biologic, years from RA diagnosis to first biologic treatment was not significantly different between the two groups (P = 0.62). Drug survival of first biologic was 64% at 1 year (95% confidence interval [CI]: 45%-77%) and 53% at 2 years (95% CI: 33%-66%) for EORA, compared with 61% at 1 year (95% CI: 50%-69%) and 45% at 2 years (95% CI: 34%-53%) for YORA (P = 0.75). Concurrent glucocorticoid use at initiation of first biologic was statistically and significantly associated with a lower risk of discontinuation in EORA (hazard ratio 0.21; 95% CI: 0.08-0.53) but not in YORA (interaction P = 0.04). CONCLUSION: Drug survival rates of biologic medications did not differ significantly between patients with EORA and YORA.
31833011 A Comparative Study to Assess the Efficacy, Safety, and Immunogenicity of YLB113 and the E 2020 Mar INTRODUCTION: YLB113 is a biosimilar of the reference product (RP), etanercept, under development for treatment of patients with moderate-to-severe rheumatoid arthritis (RA) and other approved indications. A phase 3 study was conducted in Europe, Japan, and India to compare the efficacy, safety, and immunogenicity of YLB113 with the RP over a treatment period of 52 weeks. METHODS: Overall, 528 patients with moderate-to-severe RA receiving concomitant methotrexate were randomized to receive a once-weekly, subcutaneous dose of 50 mg YLB113 or the RP. The primary endpoint was ACR20 response rate at week 24, with similarity confirmed if the 95% confidence interval (CI) for YLB113 and the RP was within the range of - 15 to 15%. Safety and immunogenicity endpoints were assessed to week 52. RESULTS: Based on the European analysis, in the full analysis set, ACR20 response at week 24 was 83.3% and 88.5% for YLB113 and the RP, respectively. Responses were within the predefined clinical equivalence margin. The sensitivity analysis in the per protocol set revealed a similar proportion of subjects exhibiting ACR20 response at week 24 between groups, with a difference of - 5.1% (95% CI - 11.07 to 0.81). The incidence of treatment-emergent adverse events was comparable between groups, and the incidence of antidrug antibody development to week 24 favored YLB113 (0.8 vs. 8.3%). CONCLUSIONS: This study demonstrated biosimilarity of YLB113 to the RP regarding efficacy, safety, and immunogenicity in patients with moderate-to-severe RA. Based on the same mechanism of action, biosimilarity could be extrapolated to other therapeutic indications approved for etanercept. TRIAL REGISTRATION: EudraCT Number: 2015-002,809-12.
31737738 Risk of Recurrent Staphylococcus aureus Prosthetic Joint Infection in Rheumatoid Arthritis 2019 Nov BACKGROUND: Treatment of rheumatoid arthritis (RA) often involves immune-suppressive therapies. Concern for recurrent prosthetic joint infection (PJI) in RA patients might be high and could reduce use of joint implantation in these patients. We aimed to evaluate the risk of recurrence of PJI in RA patients compared with osteoarthritis (OA) patients by utilizing a large health care system. METHODS: We conducted a retrospective cohort study of all patients admitted for a Staphylococcus aureus PJI who underwent debridement, antibiotics, and implant retention (DAIR) or 2-stage exchange (2SE) between 2003 and 2010 at 86 Veterans Affairs Medical Centers. Both RA patients and the comparison group of osteoarthritis (OA) patients were identified using International Classification of Diseases, Ninth Revision, codes. All index PJI and recurrent positive cultures for S. aureus during 2 years of follow-up were validated by manual chart review. A Cox proportional hazards regression model was used to compare the time to recurrent PJI for RA vs OA. RESULTS: In our final cohort of 374 veterans who had either DAIR or 2SE surgery for their index S. aureus PJI, 11.2% had RA (n = 42). The majority of the cohort was male (97.3%), and 223 (59.6%) had a methicillin-susceptible S. aureus PJI. RA patients had a similar risk of failure compared with OA patients, after adjusting for covariates (hazard ratio, 0.81; 95% confidence interval, 0.48-1.37). CONCLUSIONS: Prior diagnosis of RA does not increase the risk of recurrent S. aureus PJI. Further studies are needed to evaluate the effect of different RA therapies on outcomes of episodes of PJI.
31721017 Spebrutinib (CC-292) Affects Markers of B Cell Activation, Chemotaxis, and Osteoclasts in 2020 Mar INTRODUCTION: Spebrutinib (CC-292) is an orally administered, covalent, small-molecule inhibitor of Bruton's tyrosine kinase (BTK), part of the B-cell and Fc receptor signaling pathways. This study evaluated spebrutinib pharmacology and mechanism of action over a 4-week treatment period in patients with active rheumatoid arthritis (RA). METHODS: Primary human B cells, T cells, natural killer cells, macrophages, dendritic cells, basophils, and osteoclasts were treated with spebrutinib in vitro. Clinical pharmacodynamics were studied in 47 patients with active RA on background methotrexate therapy randomized to oral spebrutinib 375 mg/day or placebo. RESULTS: In vitro, spebrutinib inhibited B-cell proliferation more potently than T-cell proliferation and reduced both lymphoid and myeloid cytokine production and degranulation, as well as osteoclastogenesis. Clinical efficacy trended higher in spebrutinib-treated RA patients, with 41.7% (10/24) achieving ≥ 20% improvement in ACR response criteria (ACR20) versus 21.7% (5/23) of placebo patients at week 4 (P = 0.25). Treatment-emergent adverse events were comparable between treatment groups. In spebrutinib-treated patients, median BTK occupancy in peripheral blood was 83%, and significant increases in total CD19(+) and mature-naive CD27(-)CD38(-)IgD(+) B cells and decreases in transitional CD27(-)CD38(+) B cells were observed. Spebrutinib significantly reduced serum chemokines chemokine ligand 13 (CXCL13), macrophage inflammatory protein-1β (MIP-1β), and the bone resorption biomarker carboxy-terminal collagen cross-linking telopeptide (CTX-I) (P < 0.05). Clinical response to spebrutinib was associated with lower increases in CD19(+) B cells and greater decreases in CXCL13 and MIP-1β from baseline to week 4. High CD19(+) B cells and low CTX-I at baseline were associated with better spebrutinib clinical response. CONCLUSIONS: Spebrutinib inhibited various leukocyte responses in vitro, including those of B cells and osteoclasts. In this small study in RA patients, spebrutinib was well tolerated, showed a downward trend for symptoms, significantly modulated B-cell populations, and reduced markers of chemotaxis and osteoclast activity. TRIAL REGISTRATION: NCT01975610.
31295961 Regulation of Th17 Cytokine-Induced Osteoclastogenesis via SKI306X in Rheumatoid Arthritis 2019 Jul 10 This study aimed to investigate the regulatory effect of SKI305X, a mixed extract of three herbs, in T helper (Th)17 cytokine-induced inflammation and joint destruction in rheumatoid arthritis (RA). Synovial fibroblasts were isolated from RA patients and cultured with Th17 cytokines including interleukin (IL)-17, IL-21, and IL-22 and SKI306X, and tumor necrosis factor (TNF)-, IL-1, and receptor activator of nuclear factor kappa-Î’ ligand (RANKL) expression and production were investigated using real-time PCR and ELISA of culture media. After peripheral blood (PB) cluster of differentiation (CD)14(+) monocytes were cultured in media supplemented with Th17 cytokines and SKI306X, tartrate-resistant acid phosphatase positive (TRAP(+)) multinucleated giant cells (mature osteoclasts) were enumerated and gene expression associated with osteoclast maturation was assessed via real-time PCR analysis. After PB monocytes were co-cultured with IL-17-stimulated RA synovial fibroblasts in the presence of SKI306, osteoclast differentiation was assessed. When RA synovial fibroblasts were cultured with IL-17, IL-21, and IL-22, TNF-, IL-1, and RANKL expression and production were increased; however, SKI306X reduced cytokine expression and production. When PB monocytes were cultured in media supplemented with Th17 cytokines, osteoclast differentiation was stimulated; however, SKI306X decreased osteoclast differentiation and osteoclast maker expression. When PB monocytes were co-cultured with IL-17-stimulated RA synovial fibroblasts, osteoclast differentiation was increased; however, SKI306X decreased osteoclast differentiation and osteoclast maker expression. SKI306X reduced Th17 cytokine-induced TNF-, IL-1, and RANKL expression and osteoclast differentiation, providing novel insights into adjuvant therapy for regulating inflammation and joint destruction in RA.
31856058 Pathogenesis, disease course, and prognosis of adult-onset Still's disease: an update and 2019 Dec 5 OBJECTIVE: Adult-onset Still's disease (AOSD) is a rare but clinically well-known polygenic systemic autoinflammatory disease. In this review, we aim to present frontiers in the pathogenesis, clinical features, diagnosis, biomarkers, disease course, prognosis, and treatment in AOSD. DATA SOURCES: We retrieved information from the PubMed database up to July 2019, using various search terms and relevant words, including AOSD and Still's disease. STUDY SELECTION: We included data from peer-reviewed journals. Both basic and clinical studies were selected. RESULTS: Pathogenesis of AOSD involves genetic background, infectious triggers, and immunopathogenesis, mainly the activation of macrophages and neutrophils followed by a cytokine storm. Diagnosis and prognosis evaluation of AOSD is still challenging; therefore, there is an urgent need to identify better biomarkers. Biologic agents, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α antagonists in the treatment of AOSD, have good prospect. CONCLUSION: This review highlights the advances in pathogenesis, potential biomarkers, disease course, and treatment in AOSD.
31396201 Preponderance of CTLA4 Variation Associated With Autosomal Dominant Immune Dysregulation i 2019 One of the primary targets of immune checkpoint inhibition is the negative immune regulatory molecule CTLA-4. Immune-related adverse events are commonly observed following CTLA-4 inhibition in melanoma treatment, and a spectrum of these conditions are also observed in individuals with germline haploinsufficiency of CTLA4. Here we describe a heterozygous de novo missense variant of CTLA4 in a young girl with childhood-onset autoimmune hepatitis and polyarthritis, the latter responding to treatment with CTLA-4-Ig fusion protein. This variant lay within the highly conserved MYPPPY motif of CTLA-4: a critical structural determinant of ligand binding, which is also bound by the anti-CTLA-4 monoclonal antibody ipilimumab. Within the spectrum of CTLA4 variants reported, missense variants in the MYPPPY motif were overrepresented when compared to variants within a control population, highlighting the physiological importance of this motif in both the genetic and pharmacological regulation of autoimmunity and anti-tumor immunity.
30062971 Neurological Involvement as the Initial Manifestation in Primary Sjögren's Syndrome - A C 2019 BACKGROUND: Sjögren's syndrome is an autoimmune disease characterised by exocrinopathy mainly involving the salivary and lacrimal glands. In addition, it is a multisystemic condition (i.e., affecting multiple organs and systems). Neurological involvement has been reported in ~20% of cases, with peripheral manifestations being the most frequent. METHODS: We analysed four cases in which neurological manifestations were the first symptoms of Sjögren's syndrome. RESULTS: In all four cases, neurological symptoms preceded sicca symptoms. In addition, immunosuppressive treatment with steroids and, in some cases, cyclophosphamide showed improvement. CONCLUSION: Neurological involvement in Sjögren's syndrome is common and often occurs as the first clinical manifestation. Since evidence is limited, more studies are required in order to determine appropriate diagnostic methods and treatments for each manifestation of Sjögren's syndrome.
31101786 [ORGAN-SPECIFIC AND ORGAN-NONESPECIFIC AUTOANTIBODIES AND DAMAGE OF ORGANS AND SYSTEMS AT 2019 Mar The aim of the study was to determine the presence of various organ-specific and organ - nonspecific autoantibodies and their association with Sjogren's syndrome - one of the most pervasive autoimmune disorders that affects entire body. The etiology of Sjogren's syndrome is not clearly understood. It may be due combination of factors: inherited, hormonal, infection from virus. 21 patients were examined, all women, mean age 53.5±0.9 years. Everyone was conducted clinical, laboratory and instrumental trial, definition of existence of antinuclear antibodies, a rhematoid factor, antibodies to antigens of a thyroid gland, smooth muscles, parietal cells of a stomach, antigens of sial glands and alpha- fodrin. In addition to SS- A and SS - B antibodies and a rheumatoid factor there are characteristic of Sjogren's syndrome, were revealed antibodies to the native and denatured DNA, antigens of a thyroid gland, stomach, smooth muscles, neutrophilic leukocytes, sial glands. It was found that in addition to a clinical manifestations Sjogren's syndrome is characterized by existence of a wide range of organ-specific and organ- nonspecific autoantibodies that is a consequence of polyclonal uncontrollable activation of the immune system. Existence of autoantibodies is associated with features of a course of a disease, existence of damage of organs and systems and requires individual treatment.
31269570 [The neurological manifestations in 52 patients with primary Sjögren's syndrome]. 2019 Jul 1 Objective: To summarize the neurological manifestations in patients with primary Sjögren's syndrome (pSS). Methods: A total of 68 patients were diagnosed as pSS in neurology department of Peking Union Medical College Hospital from March 2014 to February 2018, among whom sixteen cases were excluded due to modified final diagnoses of primary neurological diseases. Therefore 52 pSS patients with neurological involvement were enrolled and retrospectively analyzed. They were divided into two groups as extensive group in which both central and peripheral nervous system were involved, non-extensive group in which either central or peripheral nervous system was involved. Results: Neurological manifestations were presented as primary symptoms in 98.1%(51/52) patients, while 35 had neurological involvement as their only extraglandular manifestations. Thirteen cases were in extensive group. The other 39 in non-extensive group including 22 cases with only peripheral nervous system involved and 17 cases with only single central nervous system involved. Compared to non-extensive group, the proportion of woman patients [13/13 vs.71.8% (28/39), P=0.047], serum IgG level [17.73(11.11,22.41)g/L vs. 11.49(9.58,13.40)g/L, P=0.017] and positive rates of oligoclonal band (OB) in cerebral spinal fluid (CSF) [7/13 vs. 22.6%(7/31), P=0.042)] were significantly higher in extensive involvement group. Conclusions: Neurological manifestations in pSS patients could be extensive, both central and peripheral nervous system might be associated. Female patients, high serum IgG level and positive OB in CSF are risk factors of extensive neurological involvement, suggesting that the immune system may be generally over-stimulated.
31634170 Adult-Onset Still Disease Presenting With Dermatomyositis-Like Persistent Pruritic Lesions 2019 Nov Adult-onset Still disease (AOSD) is a rare autoinflammatory condition. The presence of an evanescent, salmon-pink, nonpruritic rash is one of the major diagnostic criteria for the disease. The rash occurs with fever and subsides with defervescence. The presence of dyskeratotic keratinocytes in the upper one-third layer of the epidermis is a distinctive histopathological feature of persistent pruritic lesions associated with AOSD. Here, we report 2 cases of AOSD characterized by persistent pruritic lesions resembling those observed in dermatomyositis. Identifying the clinical and histopathological manifestation of the cutaneous lesions is essential for the early diagnosis of AOSD and for differentiating this condition from those presenting with dyskeratotic cells in the epidermis.
30892751 Infections increase the risk of developing Sjögren's syndrome. 2019 Jun OBJECTIVE: Environmental factors have been suggested in the pathogenesis of rheumatic diseases. We here investigated whether infections increase the risk of developing primary Sjögren's syndrome (pSS). METHODS: Patients with pSS in Sweden (n = 945) and matched controls from the general population (n = 9048) were included, and data extracted from the National Patient Register to identify infections occurring before pSS diagnosis during a mean observational time of 16.0 years. Data were analysed using conditional logistic regression models. Sensitivity analyses were performed by varying exposure definition and adjusting for previous health care consumption. RESULTS: A history of infection associated with an increased risk of pSS (OR 1.9, 95% CI 1.6-2.3). Infections were more prominently associated with the development of SSA/SSB autoantibody-positive pSS (OR 2.7, 95% CI 2.0-3.5). When stratifying the analysis by organ system infected, respiratory infections increased the risk of developing pSS, both in patients with (OR 2.9, 95% CI 1.8-4.7) and without autoantibodies (OR 2.1, 95% CI 1.1-3.8), whilst skin and urogenital infections only significantly associated with the development of autoantibody-positive pSS (OR 3.2, 95% CI 1.8-5.5 and OR 2.7, 95% CI 1.7-4.2). Furthermore, a dose-response relationship was observed for infections and a risk to develop pSS with Ro/SSA and La/SSB antibodies. Gastrointestinal infections were not significantly associated with a risk of pSS. CONCLUSIONS: Infections increase the risk of developing pSS, most prominently SSA/SSB autoantibody-positive disease, suggesting that microbial triggers of immunity may partake in the pathogenetic process of pSS.
30580885 Pulmonary arterial hypertension in adult-onset Still's disease: A case series and systemat 2019 Aug OBJECTIVE: To investigate the prevalence, clinical characteristics and prognosis of pulmonary arterial hypertension (PAH) in adult onset Still's disease (AOSD). METHODS: We retrospectively reviewed all patients with AOSD diagnosed during a 33-year period in 2 referral tertiary care hospitals, selecting for analysis those who presented PAH confirmed as by right heart catheterization. A systematic review of the literature (PubMed 1990 to July 2018) was also performed, in order to determine the prognosis and the most appropriate treatment strategy for this complication. RESULTS: The overall prevalence of PAH in our AOSD population was 4.8% (2/41). Including our 2 cases, 20 well-documented patients have been reported. PAH may complicate AOSD at any time during its course, and usually occurs in patients who have persistent and severe disease, with a considerable frequency (35%) of previous or concomitant severe clinical complications. In all cases, the etiology of pulmonary hypertension was a group 1 PAH based on the 2015 ESC/ERS guidelines. Most patients in this series had advanced WHO functional classes III-IV at the time of PAH diagnosis, reflecting an important diagnostic delay. Thirty-three percent of patients had a poor outcome despite the therapy, with a mortality rate that reached 22%. The therapeutic strategy that achieved the best results was the use of glucocorticoids, immunosuppression and PAH-specific vasodilator therapy. CONCLUSION: HAP is an under-recognized complication of AOSD that should be kept in mind in the differential diagnosis of those patients who experience dyspnea on exertion or a decrease in exercise tolerance.
30508319 Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction i 2019 Apr Cannabinoid receptor 2 (CB2) has been implicated as an important clinical regulator of inflammation and malignant osteolysis. Here, we observed that CB2 expression was markedly higher in the collagen-induced arthritis (CIA) mice synovium and bone tissues than in the noninflamed synovium and bone tissues. The CB2 selective agonist (JWH133) but not antagonist (SR144528) suppressed CIA in mice without toxic effects, as demonstrated by the decreased synovial hyperplasia, inflammatory responses, cartilage damage, and periarticular and systemic bone destruction. JWH133 treatment decreased the infiltration of pro-inflammatory M1-like macrophages and repolarized macrophages from the M1 to M2 phenotype. Similarly, activation of CB2 increased the expression of anti-inflammatory cytokine interleukin (IL)-10 and reduced the expression of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), IL-1β, and IL-6. In addition, JWH133 treatment attenuated osteoclast formation and osteoclastic bone resorption, and reduced the expression of receptor activators of the nuclear factor-κB (NF-κB) ligand (RANKL), matrix metallopeptidase-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), and nuclear factor of activated T-cells 1 (NFAT-1) in CIA mice and osteoclast precursors, which were obviously blocked by pretreatment with SR144528. Mechanistically, JWH133 inhibited RANKL-induced NF-κB activation in the osteoclast precursors. We found that JWH133 ameliorates pathologic bone destruction in CIA mice via the inhibition of osteoclastogenesis and modulation of inflammatory responses, thereby highlighting its potential as a treatment for human rheumatoid arthritis. © 2018 American Society for Bone and Mineral Research.
31997900 Prevalence of complementary and alternative medicine use among rheumatoid arthritis patien 2019 Nov BACKGROUND AND AIM: The use of complementary and alternative medicine (CAM) is unexplored among Saudi rheumatoid arthritis (RA) patients. The aim of this study was to estimate the prevalence and types of CAM used among patients with RA and factors associated with their use. EXPERIMENTAL PROCEDURE: A cross-sectional study was conducted at rheumatology clinics in two tertiary hospitals located in Riyadh, Saudi Arabia. The data was collected between May 2017 and February 2018. Unpaired Student's t-tests, Chi-square tests, and Pearson correlation tests were used to compare users vs nonusers. RESULTS: A total of 438 patients (mean age = 49, SD ± 15 years; 89.7% females) were included in this study. Sixty seven percent of included patients had used CAM for their RA. The majority of CAM users were female (92.1%). The most frequently used CAM products were vitamin D (47%), calcium (37%), honey (15%), ginger (13%), turmeric (11%), black seeds (8%), and fenugreek (8%). One hundred ninety-six (45%) patients believe that CAM is safe, and 287 (96%) patients took it because they believed that CAM had "added benefits". Statistically significant differences were found for gender, RA duration, erythrocyte sedimentation rate (ESR) level, and seropositivity between CAM users and nonusers (P = 0.019, P = 0.011, P = 0.022, and P < 0.0001, respectively). A significant correlation was found between the Erythrocyte Sedimentation Rate (ESR) level, RA duration and CAM use (r = 0.110, P = 0.022 and r = 0.121, P = 0.012, respectively). These data indicated that patients who used CAM had higher ESR level and longer disease duration than patients didn't use CAM. CONCLUSION: There is a high prevalence of CAM use among RA patients. CAM use was perceived to add benefit and patients using it had higher ESR. Larger studies are needed to assess the use of CAM and its impact on RA and its management.
31487614 Therapeutic effects of gentiopicroside on adjuvant-induced arthritis by inhibiting inflamm 2019 Nov The purpose of this research was to evaluate the therapeutic effects of gentiopicroside (GPS) on adjuvant-induced arthritis (AA) rats. Rats were injected with complete Freund's adjuvant (CFA) for 0.1 mL in the right hind paw to induce AA. Thirty rats from three groups were treated with GPS (30, 60, 90 mg/kg) from day 15 to day 26. Arthritis was evaluated by arthritis index, paw volume, paw thickness, and X-ray. The effect of GPS on inflammation was assessed by measuring the levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6 and IL-17, as well as related mRNA. Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH) protein carbonyl (PCO) and malondialdehyde (MDA) were measured to assess the effect of GPS on oxidative stress. These results indicate that GPS increases the levels of GSH-Px, SOD and GSH, and reduces the levels of MDA and PCO. GPS can significantly down-regulate the levels of IL-1β, TNF-α, IL-6 and IL-17, as well as related mRNA. In addition, X-ray and histopathological results show that GPS has a therapeutic effect on joints in AA rats. In summary, the therapeutic effects of GPS on AA rats are associated with anti-inflammation and antioxidation.