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ID PMID Title PublicationDate abstract
29356462 A randomized multicenter clinical trial of (99) Tc-methylene diphosphonate in treatment of 2018 Jan AIM: To investigate the efficacy and safety of technetium-99 conjugated with methylene diphosphonate ((99) Tc-MDP, Yunke Pharmaceutical industry) in the treatment of rheumatoid arthritis (RA). METHODS: A total of 120 patients with active RA were randomly divided into three groups: Group A (receiving oral meloxicam tablets); Group B (receiving intravenous drip of (99) TC-MDP); Group C (receiving combination treatment of intravenous drip of (99) Tc-MDP and oral meloxicam tablets). The main clinical and laboratory parameters were evaluated at baseline and after 14 days of therapy. RESULTS: After 14 days of treatment, American College of Rheumatology 20 response was 15.62%, 34.04% and 48.78% in the three groups, respectively. The incidence of adverse events in three groups were 3.13%, 8.51% and 9.76% respectly, and has no significant difference. In addition, biochemical markers of bone metabolism including bone alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP) and dickkopf-1 (DKK-1), all improved in the three groups, although more significant in Group B than Group A, and more significant in the combination group than monotherapy groups. CONCLUSION: (99) Tc-MDP has good efficacy and safety in the treatment of active RA patients; the benefit was more remarkable when (99) Tc-MDP was combined with NSAIDs. (99) Tc-MDP may also have potential to improve bone metabolism.
29915585 Signal Transducer and Activator of Transcription 3 Hyperactivation Associates With Follicu 2018 Follicular helper T (Tfh) cells are the specialized CD4(+) T cell subset that supports B cells to produce high-affinity antibodies and generate humoral memory. Not only is the function of Tfh cells instrumental to mount protect antibodies but also to support autoantibody production and promote systemic inflammation in autoimmune diseases. However, it remains unclear how the activation of Tfh cells is driven in autoimmune diseases. Here, we report that in patients with rheumatoid arthritis (RA), excessive generation of CXCR5(+)PD-1(+) memory Tfh cells was observed and the frequency of memory Tfh cells correlated with disease activity score calculator for RA (DAS28). The differentiation of Tfh cells is dependent on signal transducer and activator of transcription 3 (STAT3), the key transcription factor downstream of cytokine signal pathways. A drastic increase of phosphorylated STAT3 (pSTAT3) in CD4(+) T cells were detected in RA patients who also produced larger amounts of STAT3-stimulating cytokines, including IL-6, IL-21, IL-10, and leptin than those of healthy controls. Importantly, the phosphorylation status of STAT3 in CD4(+) T cells positively correlated with the plasma concentration of IL-6 and the frequency of memory Tfh cells. This study reveals an IL-6-pSTAT3-Tfh immunoregulatory axis in the pathogenesis of RA and reinforces its candidature as biomarkers and targets for diagnosis and therapy.
28880691 Changes in serum interleukin-6 levels as possible predictor of efficacy of tocilizumab tre 2018 Jul OBJECTIVES: We aimed to evaluate the association between the change in serum IL-6 during the clinical course of tocilizumab (TCZ) therapy and rheumatoid arthritis (RA) disease activity or occurrence of adverse events. METHODS: General laboratory data including serum IL-6 levels and physical findings were obtained every 4 weeks, and, in addition, at the time when any adverse events occurred. RESULTS: The proportion achieving Clinical Disease Activity Index (CDAI) remission at 52 weeks was significantly lower in 20 patients with serum IL-6 ≥ 30 pg/ml at 12 weeks than 24 patients with serum IL-6 < 30 pg/ml. In 17 patients with serum IL-6 ≥ 30 pg/ml at 24 weeks, the proportion achieving CDAI remission was also significantly lower than 27 patients with serum IL-6 < 30 pg/ml then. In these 17 patients, Disease Activity Score (DAS) 28-ESR and CDAI at 52 weeks were significantly higher than those with serum IL-6 < 30 pg/ml. Age- and sex-adjusted logistic regression analysis showed logIL-6 at 12 weeks to be a predictive factor for DAS28-ESR remission at 52 weeks. CONCLUSION: Serum IL-6 levels from 12 to 24 weeks after TCZ initiation better reflect the efficacy of TCZ at 52 weeks.
30506403 A TRAF6 genetic variant is associated with low bone mineral density in rheumatoid arthriti 2019 Apr OBJECTIVES: This study was aimed to investigate the association of the single nucleotide polymorphism of tumor necrosis factor receptor associated factor 6 (TRAF6), rs540386, with low bone mineral density (BMD) among patients with rheumatoid arthritis (RA). METHODS: TRAF6 rs540386 genotyping was performed by mutagenically separated PCR in a cohort of 188 (23 men, 165 women, median age, 56.2 years) adult RA patients and 224 age and gender-matched controls. BMD was measured using dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy advance scans, GE Healthcare, USA). RESULTS: Among the RA patients, 64 (55 women, 9 men) had low BMD comprising of 57 patients with osteoporosis and 7 with osteopenia. Whereas TRAF6 rs540386 was not associated with RA susceptibility, it was however found to be a risk factor for reduced lumbar spine Z-score in the recessive model (OR = 3.34, 95% CI = (1.01-11.00), p = 0.038). This association was confirmed further in the multivariate logistic regression analysis taking into account several potential confounding factors (OR = 3.34 (1.01-11.00), p = 0.048). In addition, mean total femur Z-score was found to be reduced in TT patients when compared to CC + CT patients (- 1.30 ± 1.32 versus - 0.60 ± 1.05, p = 0.034). No association between TRAF6 rs540386 and local bone damage was observed. CONCLUSIONS: This study for the first time ever demonstrated an association between a genetic variant of TRAF6 and low BMD among patients with RA. Further investigations are needed to elucidate the exact role of this variant.
30062938 Mid-term results of alumina ceramic unlinked total elbow arthroplasty with cement fixation 2018 Aug AIMS: The aim of this study was to report the mid-term clinical outcome of cemented unlinked J-alumina ceramic elbow (JACE) arthroplasties when used in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: We retrospectively reviewed 87 elbows, in 75 patients with RA, which was replaced using a cemented JACE total elbow arthroplasty (TEA) between August 2003 and December 2012, with a follow-up of 96%. There were 72 women and three men, with a mean age of 62 years (35 to 79). The mean follow-up was nine years (2 to 14). The clinical condition of each elbow before and after surgery was assessed using the Mayo Elbow Performance Index (MEPI, 0 to 100 points). Radiographic loosening was defined as a progressive radiolucent line of >1 mm that was completely circumferential around the prosthesis. RESULTS: The mean MEPI scores significantly improved from 40 (10 to 75) points preoperatively to 95 (30 to 100) points at final follow-up (p < 0.0001). Complications were noted in ten elbows (ten patients; 11%). Two had an intraoperative humeral fracture which was treated by fixation and united. One had a postoperative fracture of the olecranon which united with conservative treatment and one had a radial neuropathy which resolved. Further surgery was required for one with a dislocation, three with an ulnar neuropathy and one with a postoperative humeral fracture. Revision with removal of the components was performed in one elbow due to deep infection. There was no radiographic evidence of loosening around the components. With any revision surgery or revision with implant removal as the endpoint, the rates of survival up to 14 years were 93% (95% confidence interval (CI), 83.9 to 96.6) and 99% (95% CI 91.9 to 99.8), respectively, as determined by Kaplan-Meier analysis. CONCLUSION: With the appropriate indications, the mid-term clinical performance of the cemented JACE TEA is reliable and comparable to other established TEAs in the management of the elbow in patients with RA. Cite this article: Bone Joint J 2018;100-B:1066-73.
29957465 1,25(OH)(2)D(3) promotes chondrocyte apoptosis and restores physical function in rheumatoi 2018 Oct We explored the modulatory effect of 1,25(OH)(2)D(3) on chondrocytes and physical function in rats with RA and its mechanism underlying the regulation of NF-κB signal pathway. RA patients and healthy volunteers were selected. Sprague-Dawley (SD) rats were used to establish RA models. The paw volume of rats was estimated. Chondrocytes were isolated from RA rats. The protein levels in both cartilage tissues and chondrocytes were determined using western blotting. Apoptosis was evaluated using TUNEL assay. Serum levels of IL-1β, IL-6, IL-10 and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). Serum levels of 1,25(OH)(2)D(3) were lower in RA patients than in healthy volunteers. Rats in the RA + VD(3) group were lighter than those in normal and PBS groups, with an increased paw volume, severer joint swelling, higher expression levels of p-IκBα, p-p65, IL-1β, IL-6, and IL-17, and lower expression level of IL-10, while those in RA and RA + VD(3) + NF-κB group differed more significantly. In addition, by comparing RA rats and RA + NF-κB rats, we found that TNF-α stimulation exacerbated RA, increased expression levels of p-IκBα, p-p65, IL-1β, IL-6, and IL-17, and decreased the expression level of IL-10. Compared with RA chondrocytes, chondrocytes from RA + VD(3) rats exhibited lower expression levels of p-IκBα and p-p65, and had more apoptotic cells, while those from RA + NF-κB rats showed an opposite trend. Taken together, 1,25(OH)(2)D(3) accelerates chondrocyte apoptosis and improve physical function in rats with RA by the inhibition of NF-κB signal pathway.
29149821 Statins Therapy for Connective Tissue Diseases: New Therapeutic Opportunities. 2018 Feb 13 BACKGROUND AND OBJECTIVE: Statins, 3-hydroxyl-3-methyl-glutharyl Coenzyme A reductase inhibitors showed their therapeutic potential in the treatment of atherosclerosis-related diseases. Recently, the properties of statins, separate from their lipid lowering activity have attracted much attention. These properties that cover a wide area of physiopathological activities including cell maturation, immune response regulation, tissue fibrosis, endothelial activity and are called pleiotropic activity. Many in vitro studies demonstrated significant, statins-dependent regulation of immune system reactivity, reduction of pro-inflammatory and pro-fibrotic cytokines as well as suppression of endothelial activity and damage. METHODS: The present study reviewed the potential utility of statins as a concomitant regimen in the treatment of various connective tissue diseases. To address this we performed a methodical search though Pubmed database searching for term statins and pleiotropic effects and connective tissue disease or rheumatology. RESULTS: One hundred and thirty one prominent research and review papers were identified and analyzed. Majority of research papers focused on laboratory models of statins activity, only a few of them analyzed data from human studies. CONCLUSION: Statins may have a therapeutic potential as a concomitant treatment for connective tissue diseases, that has been elegantly proven in many animal and laboratory studies. They deep interfere with immunological mechanism of autoantigen presentation, expressions of adhesion molecules. These phenomena may be recognized as the most important mode of action. Less is known about the potential of statins in clinical practice. Many small trials examined therapeutic potentials in various autoimmune diseases with contradictory results, disabling making the final conclusions. The future human studies should answer what patients population may benefit with concomitant statins' treatment.
29224946 Revision Arthroplasty of the Wrist in Patients With Rheumatoid Arthritis, Mean Follow-Up 6 2018 May PURPOSE: Management of failed total wrist arthroplasty (TWA) can be challenging; surgical treatment options include salvage arthrodesis, revision arthroplasty, and resection arthroplasty. There are few studies regarding salvage arthrodesis, and revision arthroplasty has been infrequently investigated. The aim of the study was to report the outcome after revision arthroplasty of the wrist. METHODS: A retrospective cohort of 16 revision TWAs was evaluated between 2003 and 2016. Data were collected before surgery and 1 and 5 years after surgery. The indication for revision arthroplasty was failed TWA. The primary end point was implant survival. Secondary outcome measures included visual analog scale (VAS) pain scores, range of motion, handgrip strength, and functional scoring with the Canadian Occupational Performance Measure (COPM), Patient-Rated Wrist Evaluation (PRWE), and Disabilities of the Arm, Shoulder, and Hand (DASH). RESULTS: Mean follow-up was 6.6 years. Synthetic bone graft was used in 9 cases, allograft corticocancellous bone graft in 1 case, and cement in 6 cases. Of the 16 revision TWAs, 4 were re-revised, 1 because of infection, and 3 cases underwent total wrist arthrodesis. In the non-re-revised cases, range of motion and grip strength was preserved compared with preoperative results. The VAS pain score in activity improved, but not significantly, at 1 (median, 1; range, 0-4.5) and 5 years after surgery (median, 0) compared with before surgery (median, 5). The COPM performance and satisfaction as well as PRWE scores improved significantly at 1 year (median COPM performance, 4.8; COPM satisfaction, 5.6; and PRWE, 24) and improved, but not significantly, at the 5-year follow (median COPM performance, 4.8; COPM satisfaction, 5.0; and PRWE, 37) in the non-re-revised cases. CONCLUSIONS: Revision arthroplasty of the wrist is a valid motion-preserving option to wrist arthrodesis in the management of failed TWA. However, the outcome is uncertain and as many as 25% require additional surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
30340316 Poor Dietary Quality Is Associated with Increased Inflammation in Swedish Patients with Rh 2018 Oct 18 The aim was to study whether dietary quality was associated with disease activity and inflammation among patients with rheumatoid arthritis (RA). This cross-sectional analysis included 66 Swedish participants, who each completed a food frequency questionnaire (FFQ) at screening. Food intake was scored by a dietary quality index created by the Swedish National Food Agency. Disease activity was measured as Disease Activity Score 28 (DAS28), based on erythrocyte sedimentation rate (ESR), a patient administered visual analogue scale of perceived global health and the number of tender and swollen joints out of 28 examined. Inflammation was measured as ESR and C-reactive protein (hs-CRP). Associations between dietary quality, disease activity and inflammation were evaluated using multivariable linear regression analysis. High dietary quality (high intake of fish, shellfish, whole grain, fruit and vegetables and low intake of sausages and sweets) was not related to DAS28 (B = -0.02, p = 0.787). However, dietary quality was significantly negatively associated with hs-CRP (B = -0.6, p = 0.044) and ESR (B = -2.4, p = 0.002) after adjusting for body mass index, age, education, smoking and gender. Both hs-CRP and ESR decreased with increasing dietary quality. In conclusion, among patients with RA, high dietary quality was associated with reduced inflammation but not with disease activity.
30327147 White blood cell mitochondrial DNA copy number is decreased in rheumatoid arthritis and li 2019 Jan Low mitochondrial DNA copy number (mtDNA CN) has been associated with e.g. cancer, cardiovascular and autoimmune diseases. We aimed to study a potential association between mtDNA CN and rheumatoid arthritis (RA). The relative quantity of mitochondrial DNA compared to nuclear DNA was measured in peripheral white blood cells from 149 RA affected twin pairs and 1321 non-affected twin pairs. Multiple regression analysis including RA discordant twin pairs was performed in order to separate specific effects of RA and familial RA predisposition using non-RA affected twin pairs as reference group. In addition, we performed a twin pair level analysis including only RA discordant twin pairs evaluating the effect of cell type, auto antibodies and RA genetic risk factors. Both the RA twins and their non-affected co-twins had significantly lower mtDNA CN than non-affected twins (-28.7 and -23.1 mtDNA CN, respectively). Adjusting for cell count attenuated these differences (-23.1 mtDNA CN and -20.1 mtDNA CN respectively). Within RA discordant twin pairs PTPN22(T) positive RA twins had a significantly lower amount than their co-twins (-16.3 mtDNA CN). PTPN22(T) had no effect among twins from non-affected twin pairs. MtDNA CN is significantly lower in persons with established RA and in predisposed non-affected RA co-twins suggesting that mitochondrial variation may be involved in the RA disease pathways. Our results also suggest that the RA associated genetic risk factor, PTPN22(T), further decreases the mtDNA CN, but only in carriers with established RA.
30619268 Th22 Cells Promote Osteoclast Differentiation via Production of IL-22 in Rheumatoid Arthri 2018 T helper (Th) cells can differentiate into functionally distinct subsets and play a pivotal role in inflammatory and autoimmune diseases such as rheumatoid arthritis (RA). Th22 cells have been identified as a new subset secreting interleukin (IL)-22. Although elevated levels of IL-22 in the synovial fluids of RA patients were reported, its pathological roles remain unclear. Here, we demonstrated that IL-22 was characteristically produced from CD3(+)CD4(+)CC-chemokine receptor (CCR)4(+)CCR6(+)CCR10(+) cells and their ability of the production of IL-22 markedly exceeded that of other Th subsets and the subset, thereby, designated Th22 cells. Th22 cells were efficiently induced by the stimulation with tumor necrosis factor-α, IL-6, and IL-1β. Th22 cells were markedly infiltrated in synovial tissue in patients with active RA, but not in patients with osteoarthritis (OA). CCL17, CCL20, and CCL28, which are chemokine ligands of CCR4, CCR6, and CCR10, respectively, were abundantly expressed in RA synovial tissue compared to OA. By in vitro Trans-well migration assay, Th22 cells efficiently migrated toward CCL28. Co-culture of Th22 cells, which were sorted from peripheral blood, with monocytes in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor (NF)-κB ligand induced osteoclasts formation more efficiently than that of either Th1 cells or Th17 cells. Furthermore, IL-22 markedly augmented osteoclast differentiation by promoting nuclear factor of activated T cells c1 expression in CD14(+) monocytes. Contrarily, the addition of IFN-γ to the culture significantly decreased osteoclasts number, whereas IL-17 had marginal effects. IL-22 neutralizing antibody inhibited osteoclast formation in the co-culture of Th22 cells with CD14(+) monocytes. Collectively, the results indicated that Th22 cells, which co-express chemokine receptors CCR4, CCR6, and CCR10, possess strong potency of tissue migration and accumulate into inflamed synovial tissues where the ligands such as CCL28 are highly expressed. Thus, Th22 cells have the capacity to promote osteoclast differentiation through production of IL-22 and thus play a pivotal role in bone destruction in patients with RA.
30426234 Persistent eosinophilia in rheumatoid arthritis: a prospective observational study. 2019 Feb Eosinophilia is an uncommon manifestation in Rheumatoid arthritis (RA), and there is a paucity of data regarding the relationship of eosinophilia with disease-related factors. We prospectively evaluated the clinical and disease-specific characteristics of RA patients with eosinophilia. Consecutive patients with RA with an absolute eosinophil count ≥ 500/mm(3) without an apparent cause for eosinophilia, were investigated for parasitic infestation. Patients with a definite parasitic infestation received targeted therapy, and the rest were treated with albendazole empirically. The RA disease-specific characteristics of the patients with persistent eosinophilia were compared with the patients without eosinophilia. Of the 160 patients with eosinophilia, 30 patients (19%) had allergic diseases, six patients had bronchiectasis, and one patient had hypereosinophilia of undetermined significance. Intestinal helminthiasis was found in 34 patients (21%). Eosinophilia was unexplained in 89 patients (56%) and it resolved after empirical albendazole therapy in about two-thirds (58 patients). Thirty-one patients had persistent eosinophilia. Nonsteroidal anti-inflammatory drug and disease-modifying antirheumatic drug modification did not show any effect on eosinophilia. The disease-related characteristics were similar between patients with persistent eosinophilia and those without eosinophilia. Eosinophilia is due to secondary causes in the majority of RA patients, and the most common cause in our setting is an intestinal helminthic infection. Persistent eosinophilia in our cohort of RA did not indicate a more severe disease phenotype.
30032973 On the origin of rheumatoid factors: Insights from analyses of variable region sequences. 2019 Feb OBJECTIVES: Rheumatoid factors (RFs) are thought to play an important role in rheumatoid arthritis (RA), but are also found in healthy donors (HDs). Previous studies examined variable region sequences of these autoantibodies at a time when knowledge of the human germline repertoire was incomplete. Here we collected and analyzed RF sequence data from the literature to elucidate how RFs develop and whether their characteristics differ between RA patients and HDs. METHODS: A database was built containing nucleotide sequences of RF heavy and light chain variable domains and characteristics including affinity, isotype and specificity, all collected from published papers. Gene usage and mutation frequencies were analyzed using IMGT/HiV-QUEST. Selection strength was assessed with the BASELINe tool. RESULTS: Sequences were retrieved for 183 RF clones (87 RA; 67 HDs; 29 other). No biased gene usage was observed for RA and HDs. However, there does appear to be skewed gene usage in RFs from patients with mixed cryoglobulinemia. Mutation frequency varies considerably between RFs, and isotype-switched clones have significantly more mutations. Monospecific RFs carry more mutations than polyspecific RFs; no difference was found for RA- versus HD-derived RFs. Overall, reported affinity is low (median 1 µM), with a non-significant trend toward higher affinity of RA-derived RFs. Mutation frequency and affinity did not appear to be correlated. BASELINe analysis suggests an overall lack of positive selection and less negative selection strength in RA-derived RFs. CONCLUSIONS: RFs derived from RA patients have similar properties as those derived from HDs. The RF response can be characterized as a moderately matured autoantibody response, with variable levels of somatic hypermutation, but low affinity.
29187287 Relationship between leptin concentrations and disease activity in patients with rheumatoi 2018 May 11 BACKGROUND AND OBJECTIVE: Multiple studies have found a direct relationship between leptin concentrations and disease activity in rheumatoid arthritis. PATIENTS AND METHODS: We studied 77 patients with the diagnosis of rheumatoid arthritis; the leptin determination was through an enzyme immunoassay. Disease activity was assessed by the DAS-28 CRP. A multivariate logistic regression model was used to determine the association between significant variables and leptin concentrations. RESULTS: 40.3% of the patients were in remission, 41.6% were mildly active, 11.7% were moderately active and 6.5% were severely active. The results show an independent association between higher concentrations of leptin and disease activity (OR 1.7; 95% CI 1.4-3.2; p .03), the number of swollen joints (OR 4.6; 95% CI 1.7-8.3; p .000), the number of painful joints (OR 3.4; 95% CI 1.6-4.6; p .000), and the presence of metabolic syndrome (OR 1.3; 95% IC 1.2-1,9; p .045). CONCLUSION: The data suggest that serum leptin is elevated in patients with active RA.
29575803 Sustained Response Following Discontinuation of Methotrexate in Patients With Rheumatoid A 2018 Aug OBJECTIVE: To evaluate whether tocilizumab (TCZ) monotherapy is noninferior to treatment with TCZ plus methotrexate (MTX) for maintaining clinical responses in patients with rheumatoid arthritis (RA) in whom low disease activity is achieved with TCZ plus MTX. METHODS: Patients with RA who experienced an inadequate response to MTX received MTX plus TCZ 162 mg subcutaneously. At 24 weeks, patients who achieved a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) of ≤3.2 were randomized to receive TCZ monotherapy or to continue treatment with TCZ plus MTX until week 52. The primary outcome measure was the comparison of the mean change in the DAS28-ESR from week 24 to week 40 between the TCZ monotherapy and TCZ plus MTX arms (noninferiority margin of 0.6). Secondary outcome measures included worsening of the DAS28-ESR by ≥1.2, achievement of a DAS28-ESR of <2.6 and ≤3.2, and safety and immunogenicity. RESULTS: Among the 718 patients enrolled, 296 were randomized at week 24 to receive TCZ monotherapy (n = 147) or TCZ plus MTX (n = 147). The mean changes in the DAS28-ESR from week 24 to week 40 were 0.46 and 0.14 in the TCZ monotherapy arm and the TCZ plus MTX arm, respectively (weighted difference between the groups, 0.318 [95% confidence interval 0.045, 0.592]); discontinuing MTX in TCZ responders was noninferior to continuing MTX. Safety events were broadly similar between the randomized treatment groups; the most common serious adverse event was infection, which occurred in 2.1% of patients in the TCZ monotherapy group and 2.2% of patients receiving TCZ plus MTX. CONCLUSION: Patients with RA receiving TCZ plus MTX who achieve low disease activity can discontinue MTX without significant worsening of disease activity during the 16 weeks following MTX discontinuation.
30158166 High power Doppler ultrasound score is associated with the risk of triangular fibrocartila 2019 Feb In the distal radioulnar joint, the triangular fibrocartilage complex (TFCC) is an important stabilizer and are frequently found in patients with rheumatoid arthritis (RA) with wrist pain. This study was designed to predict TFCC tears using high-resolution ultrasound in severe RA. We retrospectively reviewed patients with severe RA. MRI and ultrasound were performed at baseline and after 1 year of follow-up. TFCC tears were recorded. The predictive factors for TFCC tears were analyzed by logistic regression. During the 1-year follow-up period, 54 patients were enrolled (42 females and 12 males), of whom 21 (38.9%) developed TFCC tears. The body mass index was 22.81±2.59 kg/m(2) in the TFCC tear group compared with 23.61±2.76 kg/m(2) in the non-tear group (p=0.136). The mean age was 55.14±9.54 years in the TFCC tear group compared with 56.45±14.04 years in the non-tear group (p=0.596). The tear group had a higher Disease Activity Score in 28 joints (DAS28) (6.36±0.47 vs 5.58±0.65, p=0.011) and higher power Doppler (PD) ultrasound score at the dorsal radiocarpal joint (1.90±1.30 vs 1.33±0.99, p=0.011) than the non-tear group. We found that high DAS28 (OR 2.96, 95% CI 1.95 to 4.50; p=0.001) and higher baseline PD score (OR 1.51, 95% CI 1.07 to 2.14; p=0.019) were significantly associated with a higher risk of TFCC tears by logistic regression. So we conclude a higher wrist PD score in severe RA predicted future TFCC tears. Therefore, we suggest to use PD score in such patients to monitor the risk of future TFCC tears.
29688897 Frequency and Predictors of Communication About High Blood Pressure in Rheumatoid Arthriti 2018 Jun BACKGROUND/OBJECTIVE: Given heightened cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) and that higher blood pressure (BP) represents greater CVD risk, we hypothesized that higher BP would predict more BP-related communication in rheumatology visits. We examined predictors of documented BP communication during RA clinic visits. METHODS: This was a retrospective cohort study of RA patients identified in electronic health record records with uncontrolled hypertension (HTN) receiving both primary and rheumatology care. Trained abstractors reviewed RA visit notes for "BP communication" using a standardized tool to elicit documentation about BP or HTN beyond recording vital signs. We used multivariate logistic regression to examine the impact of BP category (American Heart Association: ideal normotension, pre-HTN, and stages I and II HTN) on odds ratios (95% confidence intervals) of BP communication. RESULTS: Among 1267 RA patients, 40% experienced BP elevations meeting the definition of uncontrolled HTN. Of 2677 eligible RA visits, 22% contained any documented BP communication. After adjustment, models predicted only 31% of visits with markedly high BPs 160/100 mm Hg or greater would contain BP communication. Compared with stage I, stage II elevation did not significantly increase communication (odds ratio, 2.0 [95% confidence interval, 1.4-2.8] vs. 1.5 [1.2-2.2]), although both groups' odds exceeded pre-HTN and normotension. Less than 10% of eligible visits resulted in documented action steps recommending follow-up of high BP. CONCLUSIONS: Regardless of BP magnitude, most RA clinic visits lacked documented communication about BP despite compounded CVD risk. Future work should study how rheumatology clinics can facilitate follow-up of high BPs to address HTN as the most common and reversible CVD risk factor.
29458275 Structural damage and inflammation on radiographs or magnetic resonance imaging are associ 2018 Nov OBJECTIVES: To study the relationship between structural damage and inflammatory features on magnetic resonance imaging (MRI) or radiography and other risk factors [anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) seropositivity, hand dominance, disease duration] and the presence or number of cortical interruptions in finger joints on high-resolution peripheral quantitative computed tomography (HR-pQCT). METHOD: Finger joints of 38 healthy subjects and 39 patients with rheumatoid arthritis (RA) were examined through radiographs, MRI, and HR-pQCT. Radiographs were scored according to the Sharp/van der Heijde (SvH) method; MRI for the presence of cortical interruptions, bone marrow oedema (BMO), and synovitis; and HR-pQCT images for cortical interruptions. Descriptive statistics were calculated and associations examined using generalized estimating equations. RESULTS: Cortical interruptions were found in healthy subjects and patients with RA on HR-pQCT (mean ± sd 0.33 ± 0.63 vs 0.38 ± 0.64 per joint quadrant, respectively, p < 0.01). Structural damage on MRI (cortical interruptions) or radiographs (SvH ≥ 1) was associated with the presence of cortical interruptions on HR-pQCT [odds ratio (OR) 12.4, 95% confidence interval (CI) 7.5-21.4, p < 0.01 and OR 4.8, 95% CI 1.9-11.7, respectively, p < 0.01]. The presence of BMO or synovitis was associated with more cortical interruptions on HR-pQCT (β 0.47, 95% CI 0.4-0.6, p < 0.01 and β 1.9, 95% CI 0.6-3.1, p < 0.01). In patients with RA, ACPA, and/or RF seropositivity, hand dominance and disease duration were not associated with more cortical interruptions on HR-pQCT. CONCLUSION: Structural damage and inflammatory features on MRI and radiographs are associated with cortical interruptions on HR-pQCT. No association between other risk factors and cortical interruptions was demonstrated.
29554943 Methotrexate inhibits effects of platelet-derived growth factor and interleukin-1β on rhe 2018 Mar 20 BACKGROUND: A key feature of joints in rheumatoid arthritis (RA) is the formation of hyperplastic destructive pannus tissue, which is orchestrated by activated fibroblast-like synoviocytes (FLS). We have demonstrated that the RA risk gene and tumor suppressor Limb bud and heart development (LBH) regulates cell cycle progression in FLS. Methotrexate (MTX) is the first-line treatment for RA, but its mechanisms of action remain incompletely understood. Here, we studied the effects of MTX on mitogen-induced FLS proliferation and expression of cell cycle regulators in vitro. METHODS: Primary FLS from patients with RA or osteoarthritis were stimulated with the mitogen platelet-derived growth factor (PDGF) and the cytokine interleukin-1β (IL-1β) in the presence or absence of MTX. Cells were then subjected to qPCR for gene expression and cell cycle analysis by flow cytometry. RESULTS: Stimulation with PDGF and IL-1β increased the percentage of FLS in the G2/M phase and shifted the cell morphology to a dendritic shape. These effects were inhibited by MTX. Furthermore, PDGF + IL-1β reduced LBH mRNA expression. However, MTX treatment yielded significantly higher transcript levels of LBH, and of CDKN1A (p21) and TP53 (p53), compared to untreated samples upon mitogen stimulation. The expression of DNA methyltransferase-1 (DNMT1) was also higher in the presence of MTX and there was strong correlation between DNMT1 and LBH expression. CONCLUSIONS: Therapeutic concentrations of MTX abolish the effects of PDGF and IL-1β on tumor suppressor expression and inhibit mitogen-promoted FLS proliferation. These data demonstrate novel and important effects of MTX on pathogenic effector cells in the joint, which might involve epigenetic mechanisms.
29256110 Serum substance P: an indicator of disease activity and subclinical inflammation in rheuma 2018 Apr The aim of the is study is to examine the role of serum substance P (SP) levels as a simple biomarker for rheumatoid arthritis (RA) disease activity, its correlation with other markers of disease activity, and with selected clinical parameters. The study comprised 90 RA patients and 24 healthy controls. RA activity was assessed by means of the disease activity 28-C-reactive protein (DAS28-CRP) index and ultrasound power Doppler (USPD) by the German ultrasound score based on seven joints. SP serum values were obtained by means of an ELISA commercial kit. Statistics were achieved by the Student's t test and Spearman correlation analysis with Bonferroni correction. As a group, RA patients had significantly increased levels of SP compared with healthy controls (p < 0.0001). SP levels correlated with DAS28-CRP (r = 0.5050, p < 0.0001), number of tender joints (NTJ, r = 0.4668, p < 0.0001), number of swollen joints (NSJ, r = 0.4439, p < 0.0001), visual analogue scale (VAS, r = 0.5131, p < 0.0001). However, SP did not correlate with CRP levels (r = 0.0468, p = 0.6613), nor with the USPD (r = 0.1740, p = 0.1009). Elevated serum SP is a common feature of RA patients, which also appears to correlate with clinical measurements of disease activity and with subjective clinical data (NTJ and VAS). Thus, although SP is higher in RA patients with high disease activity, it also detects subtle RA disease activity even in patients in apparent remission, which suggests its usefulness for therapeutic decisions.