Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
27574275 Mid-term outcome of total elbow replacement for rheumatoid arthritis. 2016 Aug PURPOSE: To review the outcome of total elbow replacement (TER) in 21 patients after a mean of 64 months. METHODS: Records of 12 women and 9 men aged 32 to 78 (mean, 59.1) years who underwent 22 TERs for rheumatoid arthritis by a single surgeon were reviewed. Functional outcome was assessed using the disability of the arm, shoulder and hand (DASH) questionnaire. The range of movement and Kaplan- Meier survival curve was determined. Adequacy of cementation was assessed on immediate postoperative radiographs. Aseptic loosening was assessed on radiographs using the Mayo clinic scoring system. RESULTS: After a mean follow-up of 64 (range, 10-145) months, the mean DASH score improved from 72.3 to 46.8, mean flexion improved from 96.9º to 128.1º, and mean extension lag from 37.3º to 24.0º. The 5-year survival rate with symptomatic aseptic loosening as the end point was 100%, and the revision rate for all reasons was 69%. Cement mantle was adequate in 17, marginal in 4 (most lacked cement around the prosthesis tip), and inadequate in one who was clinically asymptomatic. At the latest follow-up, 4 patients had a type-1 radiolucent line and one had a type-2 radiolucent line of both components; all remained clinically asymptomatic. Two patients developed transient radial nerve neuropraxia. One patient underwent revision for peri-operative fracture. One patient underwent a 2-stage revision for deep infection. One patient underwent revision for bilateral periprosthetic fracture. One patient underwent revision for symptomatic aseptic loosening. No patient had elbow dislocation. CONCLUSION: TER is a viable option for pain relief and functional improvement in patients with rheumatoid arthritis.
27107756 Withdrawal of biologic agents in rheumatoid arthritis: a systematic review and meta-analys 2016 Jul The aim of this study is to assess the efficacy of withdrawing biologics from patients with rheumatoid arthritis in sustained remission or low disease activity. This is a systematic review of clinical trials that randomized withdrawal or continuation of biologics. We searched MEDLINE, Embase, and other databases. Three authors independently selected and extracted the data from the studies. The GRADE approach was employed to assess the quality of the evidence. We calculated meta-analyses of random effects model and estimated the heterogeneity by I (2). The number needed to treat (NNT) was calculated for significant outcomes. We included six trials (N = 1927 patients), most were industry-sponsored. Compared to withdrawing, continuing biologics increased the probability of low disease activity (relative risk [RR] = 0.66, 95 % CI 0.51-0.84, I (2) = 91 %, NNT = 4, low quality), remission (0.57, 0.44-0.74, I (2) = 82 %, NNT = 3, low quality), and radiographic progression (RR = 0.91, 95 % CI 0.85-0.98, I (2) = 13 %, NNT = 12, moderate quality). No significant difference was detected in the incidence of serious adverse events, serious infection, malignancy, and scores of improvement of tender and swollen joints between these strategies (low quality). A worse profile of outcomes was experienced by those patients when compared to the ones that continued biologics, but almost half of patients maintained low disease activity after withdrawal. As the quality of evidence was low, the conclusions may change as new results become available. The potential harms and benefits of this decision must be discussed with patients.
26546893 Association between Peptidylarginine Deiminase Type 4 rs1748033 Polymorphism and Susceptib 2015 Jun There are controversial reports regarding the role of peptidylarginine deiminase type 4 (PADI4) gene polymorphisms and risk of Rheumatoid arthritis (RA). The aim of the present study was to investigate the impact of PADI4 rs1748033 polymorphism and susceptibility to RA in a sample of the Iranian population. This case-control study was done on 150 patients with RA and 150 healthy subjects.PADI4 rs1748033 genotyping was done using amplification refractory mutation system- polymerase chain reaction (ARMS-PCR) assay. The PADI4 rs1748033 variant increased the risk of RA in codominant (OR=1.67, 95%CI=1.03-2.71, p=0.048, CT vs CC; OR=2.73, 95%CI=1.25-5.97, p=0.013, TT vs CC) and dominant (OR=1.84, 95%CI=1.15-2.92, p=0.014, CT+TT vs CC) tested inheritance models. In addition, the PADI4 rs1748033 T allele increased the risk of RA (OR=1.63, 95%CI=1.16-2.29, p=0.006) in comparison with C allele. In conclusion, our finding indicated that PADI4 rs1748033 gene polymorphism increased the risk of RA in a sample of the Iranian population.
26976223 Gap Between Official Guidelines and Clinical Practice for the Treatment of Rheumatoid Arth 2016 May PURPOSE: Biological agents used for the treatment of rheumatoid arthritis (RA) are associated with serious adverse events. Guidelines provide standards for the prescribing and monitoring of these drugs. In São Paulo, health litigation for access to medicines has fueled the demand for biological therapy. The extent to which biological agents are being appropriately prescribed and patients are being appropriately monitored is uncertain. Our goal was to determine whether RA clinical guidelines are being translated into clinical practice for patients receiving treatment as a result of lawsuits against the government. METHODS: We identified patients through records of the State Secretary of Health of São Paulo from 2003 to 2011. We consulted guidelines from 5 countries and chose those recommendations endorsed by all of the guidelines reviewed as standards. Pharmacy records provided data regarding biologic use. The guidelines recommended the use of biological agents only when patients had been receiving treatment with at least 1 disease-modifying antirheumatic drug (DMARD) and recommended annual monitoring of laboratory blood tests. FINDINGS: Of the 238 patients identified in the database, 216 patients were interviewed, and 124 (57.4%) patients were still using biological agents at the time of the survey. Of the patients interviewed, 167 patients (77.3%) started biological treatment when using ≥2 DMARDs before, 22 patients (10.2%) were using 1 DMARD before, and 27 patients (12.5%) had never taken a DMARD. Of the 124 patients still taking biological drugs, 117 patients (94.3%) had visited a doctor at least once per year, but 28 patients (22.6%) did not undergo the recommended laboratory blood testing. Only 43 of the 124 patients (34.7%) still taking biological agents met the guideline criteria for both the use of previous agents and the appropriate monitoring. IMPLICATIONS: An important gap between clinical practice and the national guidelines exists among treatments prescribed for plaintiffs obtaining medicines for RA in São Paulo. The results suggest the need for intervention by health authorities.
27942777 Comparison of peripheral quantitative computed tomography forearm bone density versus DXA 2017 Apr Rheumatoid arthritis (RA) has been associated with osteoporosis. Quantitative computed tomography (QCT) is capable of assessing bone density and composition. We found lower bone density in RA compared to controls. Age and RA duration influenced bone density. QCT may be useful to assess bone metabolism in RA. INTRODUCTION: RA is associated with generalized and periarticular osteoporosis. In addition to DXA that determines areal bone mineral density (BMD), peripheral QCT also detects volumetric BMD. QCT differentiates between total, trabecular, and cortical BMD. Here, we compared DXA and QCT in RA patients and healthy controls. METHODS: BMD of 57 female RA patients and 32 age-matched healthy female controls were assessed by DXA. QCT of the forearm ultradistal region was also performed. Densitometry data were correlated with age, disease duration, disease activity, serum CRP, and anti-CCP levels. RESULTS: Total bone density (310.4 ± 79.7 versus 354.0 ± 54.1 mg/cm(3); p = 0.007) and attenuation (0.37 ± 0.05 versus 0.40 ± 0.03 1/cm; p = 0.001), trabecular density (157.6 ± 57.0 versus 193.8 ± 48.7 mg/cm(3); p = 0.005) and attenuation (0.28 ± 0.03 versus 0.32 ± 0.04 1/cm; p < 0.0001), and cortical density (434.3 ± 115.8 versus 492.5 ± 64.0 mg/cm(3); p = 0.006) and attenuation (0.44 ± 0.07 versus 0.47 ± 0.04 1/cm; p = 0.004) were significantly lower in RA. Both lumbar and femoral neck BMD, as well as T-scores, were significantly lower in RA versus controls (p < 0.001 in all cases). In RA, total and cortical QCT attenuation and density were associated with age, the presence of RA, and their combination. In contrast, trabecular density and attenuation were only affected by the presence of the disease but not by age. Also in RA, total trabecular and cortical density as determined by QCT significantly correlated with lumbar and/or femoral neck BMD as measured by DXA. Finally, anti-CCP seropositivity was associated with lower trabecular density and attenuation. CONCLUSIONS: Both DXA and QCT may be suitable to study bone metabolism in RA. Areal BMD determined by DXA may correlate with volumetric bone density measured by QCT. Moreover, trabecular osteoporosis may be associated by the underlying autoimmune-inflammatory disease, while cortical osteoporosis may rather be age-related.
26956118 SIRT1 inhibits differentiation of monocytes to macrophages: amelioration of synovial infla 2016 Aug Monocyte-to-macrophage differentiation plays a central role in the pathophysiology of rheumatoid arthritis (RA)-associated inflammation because it results in the secretions of various inflammatory mediators in inflamed synovium, and thus, this differentiation is viewed as a clinical target. We aimed to determine whether SIRT1 inhibits the differentiation of monocytes from RA patients into macrophages by suppressing PU.1 phosphorylation. Monocytes from synovial fluid of RA patients (RAMCs), THP-1 monocytes, and mouse bone marrow-derived monocytes (BMDCs) were studied. The phorbol 12-myristate 13-acetate (PMA)-stimulated RA monocyte adherence was significantly inhibited by resveratrol (a SIRT1 activator), and this inhibition by resveratrol was prevented by pretreating cells with sirtinol (a SIRT1 inhibitor). Furthermore, resveratrol pretreatment inhibited PMA-induced expressions of macrophage surface markers (CD11b, CD14, and CD36) and PMA-induced NF-κB transcriptional activation and, thus, suppressed the secretions of proinflammatory cytokines (TNF-α, IL-1β, and IL-6). In SIRT1 transgenic (Tg) mice, monocyte differentiation was inhibited and NF-κB transcriptional activity was suppressed and the expressions of TNF-α, IL-1β, and IL-6 were decreased at the protein and mRNA levels versus control C57BL/6 mice. Furthermore, SIRT1 activation by resveratrol suppressed PMA-induced phosphorylation and the nuclear translocation of PU.1 and, thus, inhibited monocyte differentiation. In conclusion, SIRT1 appears to inhibit monocyte to macrophage differentiation by suppressing PU.1 phosphorylation and inflammatory signaling, which suggests SIRT1 plays a critical role in the regulation of synovial inflammation in RA. KEY MESSAGE: SIRT1 overexpression inhibits monocyte to macrophage differentiation. SIRT1 suppresses PU.1 phosphorylation. Inactivation of PU.1 phosphorylation inhibits monocyte differentiation. SIRT1 regulates inflammation by inhibiting NF-κB during monocyte differentiation.
26317770 Serological and Progression Differences of Joint Destruction in the Wrist and the Feet in 2015 OBJECTIVE: To investigate clinical and radiological differences between joint destruction in the wrist and the feet in patients with RA. METHODS: A cross-sectional clinical study was conducted in an RA cohort at a single institution. Clinical data included age, sex and duration of disease. Laboratory data included sero-positivity for anti-cyclic citrullinated peptide (CCP) antibody and RF. Radiological measurements included Larsen grades and the modified Sharp/van der Heijde method (SHS) for the hands/wrists and the feet. Statistical analyses were performed using the Kruskal-Wallis H-test, a dummy variable linear regression model and multivariate logistic regression analysis with 95% confidence interval and odds ratios. RESULTS: A total of 405 patients were enrolled, and 314 patients were analysed in this study. The duration of disease in the foot-dominant group was significantly less than that in the wrist-dominant group. When patients were subdivided by duration of disease, the Larsen grade of the feet was significantly higher than that of the wrist in the first quadrant subgroup, but this was reversed with increasing duration of disease. Anti-CCP status was a significant predictive factor for joint destruction in the wrist but not in the feet, while RF status was not predictive in either the wrist or the feet. CONCLUSIONS: Joint destruction in the feet started earlier than in the wrist, but the latter progresses faster with increasing duration of disease. Anti-CCP status predicts joint destruction in the wrist better than in the feet.
26994322 Janus kinase inhibitors for rheumatoid arthritis. 2016 Jun Treatment of autoimmune diseases, such as rheumatoid arthritis (RA), has advanced substantially over the past decade with the development of biologics targeting inflammatory cytokines. Recent progress in treating RA has been achieved with janus kinase (JAK) inhibitors (Jakinibs), an orally available disease-modifying anti-rheumatic drug targeting the intracellular kinase JAK and with similar efficacy to biologics. The first Jakinib approved for RA was tofacitinib, which exerted superiority to methotrexate and non-inferiority to tumor necrosis factor (TNF) inhibitors. In recent years, the Jakinib baricitinib has demonstrated superiority to both methotrexate and a TNF inhibitor, adalimumab. Given these promising findings, Jakinibs are expected to represent the next generation compounds for treating RA, and a number of Jakinibs are currently in clinical trials. Jakinibs can differ substantially in their selectivity against JAKs; tofacitinib and baricitinib target multiple JAKs, whereas the most recently developed Jakinibs target only a single JAK. The influence of Jakinib selectivity on efficacy and side effects is of great interest, requiring further careful observation.
26608861 [IL-6 inhibitors prevent bone loss and cartilage degeneration in rheumatoid arthritis]. 2015 Dec Dysregulation of cytokines, including interleukin-6 (IL-6), is involved in joint destruction in rheumatoid arthritis (RA). The concentration of IL-6 is increased not only in the affected joints but also in the serum. Locally, IL-6 provides the formation of pannus through the synthesis of vascular endothelial growth factor (VEGF). In addition, IL-6 contributes to the production of matrix metalloproteinases which digest collagen and proteoglycan of cartilage. Furthermore, IL-6 induces the differentiation and activation of osteoclasts. IL-6 can be delivered systemically to a similar extent as hormones, may induce systemic osteoporosis. Tocilizumab (TCZ), a humanized anti-IL-6 receptor antibody, inhibiting IL-6 signaling, has provided beneficial outcomes, such as achievement of clinical remission, protective effects against bone and cartilage destruction. Because of the beneficial outcomes, new drugs inhibiting IL-6 signaling are developed, and the clinical trials are ongoing.
25371395 Modular analysis of peripheral blood gene expression in rheumatoid arthritis captures repr 2015 Feb OBJECTIVE: To establish whether the analysis of whole-blood gene expression is useful in predicting or monitoring response to anti-tumor necrosis factor (anti-TNF) therapy in patients with rheumatoid arthritis (RA). METHODS: Whole-blood RNA (using a PAXgene system to stabilize whole-blood RNA in the collection tube) was obtained at baseline and at 14 weeks from 3 independent cohorts, consisting of a combined total of 240 RA patients who were beginning therapy with anti-TNF. We used an approach to gene expression analysis that is based on modular patterns of gene expression, or modules. RESULTS: Good and moderate responders according to the European League Against Rheumatism criteria exhibited highly significant and consistent changes in multiple gene expression modules after 14 weeks of therapy, as demonstrated by hypergeometric analysis. Strikingly, nonresponders exhibited very little change in any modules, despite exposure to TNF blockade. These patterns of change were highly consistent across all 3 cohorts, indicating that immunologic changes after TNF treatment are specific to the combination of both drug exposure and responder status. In contrast, modular patterns of gene expression did not exhibit consistent differences between responders and nonresponders at baseline in the 3 study cohorts. CONCLUSION: These data provide evidence that using gene expression modules related to inflammatory disease may provide a valuable method for objective monitoring of the response of RA patients who are treated with TNF inhibitors.
25433918 Methotrexate revisited: considerations for subcutaneous administration in RA. 2015 Feb Rheumatoid arthritis (RA) is associated with significant disability, morbidity, early mortality, and substantial financial burden. Despite newer antirheumatics, methotrexate (MTX) remains the most widely used disease-modifying antirheumatic drug. Subcutaneous (SC) MTX provides consistent, reliable delivery, with improved absorption and enhanced polyglutamization leading to increased response rates and fewer gastrointestinal side effects than oral MTX. Optimizing MTX with use of the SC formulation can improve outcomes and may delay or negate the need for costly biologics.
26535595 Improvement Thresholds for Morning Stiffness Duration in Patients Receiving Delayed- Versu 2015 Jul BACKGROUND: Morning stiffness, a common patient reported symptom in rheumatoid arthritis, is associated with an increase in early morning inflammatory cytokines and significant disability. Little is known about categorical morning stiffness responses to glucocorticoid use in rheumatoid arthritis patients. Chronic pain threshold models have indicated previously that response rates of 15% to 30% indicate minimally important relief, 40% to 50% indicate substantial pain relief, and greater than 70% represents extensive pain relief. The objective of the present analysis was to assess differences in the percentages of patients achieving 25%(minimally important change), 50% (substantial change), and 75% (extensive change) reduction in the duration of patient-reported morning stiffness between patients receiving DR- and IR-prednisone in the Circadian Administration of Prednisone in Rheumatoid Arthritis (CAPRA-1) trial. MATERIALS AND METHODS: The CAPRA-1 trial was a 12-week, double-blind study followed by an additional 9-month open-label extension. Patients in the CAPRA-1 trial were randomized to IR-prednisone in the morning or DR-prednisone at bedtime in addition to stable disease modifying antirheumatic drug therapy. After the double-blind phase, patients randomized to IR-prednisone (N =110) were switched to DR-prednisone and followed at 3, 6, and 9 months in an open-label extension phase. Patients originally randomized to DR-prednisone (N = 97) continued that therapy in the open-label extension. Patient morning stiffness diary entries from 4 weeks before and 4 weeks after each scheduled visit were analyzed over 1 year for threshold response. The number of patients reaching threshold response (25%, 50%, and 75% improvement) and time to morning stiffness response were examined. RESULTS: The DR-prednisone arm had significantly more responders in all three morning stiffness threshold response categories at the end of the double-blind period compared with IR-prednisone (p ≤ 0.05). Patients who switched from IR- to DR-prednisone in the open-label extension had comparable responses in all categories within 3 months and significantly shorter time to response versus patients already receiving DR-prednisone. DISCUSSION: DR-prednisone produced significantly higher morning stiffness response rates compared with IR prednisone, as defined by 25%, 50%, and 75% improvement thresholds, at week 12. The time to reach these thresholds was quicker with DR-prednisone, and patients who switched to DR-prednisone from IR-prednisone achieved responses comparable to the continuous DR-prednisone group over 9 months of therapy. This analysis is the first to assess time-to-event and percentage threshold morning stiffness responses to differently timed glucocorticoid therapy and propose clinically meaningful response rates in RA patients.
25697137 Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis. 2015 May OBJECTIVE: Interleukin-35 (IL-35) is a heterodimeric member of the IL-12 family consisting of p35/IL-12a and EBI3/IL-27b subunits. Expressed in murine Treg cells, IL-35 controls inflammatory diseases in mouse models. However, human IL-35 is expressed in Teff cells rather than in Treg cells and is shown to be upregulated under inflammatory conditions. Our aim was to examine the involvement of IL-35 in the pathogenesis of rheumatoid arthritis (RA). METHODS: Immunohistochemical and immunofluorescence analysis was used to determine the expression and localization of IL-35 and its subunits (p35/EBI3) and IL-35 receptor (IL12Rβ2/gp130) in RA, osteoarthritis (OA) and psoriatic arthritis (PsA) synovial tissues. Expression of p35/EBI3 subunits and release of inflammatory cytokines upon stimulation with IL-35 were assessed in RA synovial fibroblasts (SFs) and peripheral blood mononuclear cells (PBMCs). RESULTS: Both IL-35 and its subunits were upregulated in RA in comparison with OA or PsA synovium. Using cell-specific markers, p35 and EBI3 were identified in macrophages, dendritic cells, SFs, and T as well as B cells in RA synovium. Both p35 and EBI3 were induced by TNFα in RASFs and PBMCs. IL-35 dose-dependently upregulated release of pro-inflammatory mediators IL-1β, IL-6 and MCP-1 in PBMCs. While gp130 receptor subunit was upregulated in RA synovium and was expressed in RASFs and PBMCs, there was no difference in IL12Rβ2 expression subunit among tissues and its presence in RASFs was lacking. CONCLUSION: Upregulation of IL-35 at sites of inflammation in RA and its pro-inflammatory potential suggests that IL-35 might play an important role in RA pathogenesis.
25577294 Association between VDR polymorphisms and rheumatoid arthritis disease: Systematic review 2015 Jun BACKGROUND: Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in rheumatoid arthritis (RA). However, published studies demonstrated differences concerning design and effect size. A meta-analysis is necessary to determine the magnitude of the association between VDR polymorphisms and RA risk. OBJECTIVE: The aim of the current study was to quantify the magnitude of the association between TaqI, BsmI, and FokI VDR polymorphisms with RA risk. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search and meta-analysis of the literature were conducted. Analyses were performed in the random effects model by using recessive, dominant, codominant, homozygous, and allele contrast models. RESULTS: A total of 1703 cases and 2635 controls in 12 case-control studies were included in the meta-analyses. Results indicated a significant association between TaqI polymorphism and RA disease in homozygous, codominant and allele contrast models (P=0.008, P=0.015, P=0.006 and P=0.002, respectively). Association between BsmI polymorphism and RA risk was marginal in the dominant, codominant and allele contrast models (P=0.057, P=0.071, and P=0.069, respectively). Te association between FokI polymorphism and RA risk was significant in the recessive, dominant and allele contrast models (P=0.045, P=0.027, and P=0.013, respectively). Subgroup analysis showed that publication year, ethnicity, age, latitude, and estimated 25(OH)D levels influenced significantly the association between VDR polymorphisms and RA risk. CONCLUSION: TaqI and FokI VDR polymorphisms contributed significantly to RA risk. Study characteristics influenced the association between VDR polymorphisms and RA disease.
24288014 Discontinuation of adalimumab after achieving remission in patients with established rheum 2015 Feb OBJECTIVES: To investigate the possibility of discontinuing adalimumab (ADA) for 1 year without flaring (DAS28-erythrocyte sedimentation rate (ESR) ≥3.2), and to identify factors enabling established patients with rheumatoid arthritis (RA) to remain ADA-free. METHODS: Of 197 RA patients treated with ADA+methotrexate (MTX), 75 patients who met the ADA-free criteria (steroid-free and sustained DAS28-ESR remission for 6 months with stable MTX doses) were studied for 1 year. RESULTS: The mean disease duration and DAS28-ESR score in 75 patients was 7.5 years and 5.1 at baseline, respectively. The proportion of patients who sustained DAS28-ESR <2.6 (48%) and DAS28-ESR <3.2 (62%) for 1 year were significantly lower in the ADA discontinuation group than in the ADA continuation group; however, in patients with deep remission (DAS28-ESR ≤1.98) identified by receiver operating characteristics analysis following logistic analysis, these rates increased to 68% and 79%, respectively, with no significant difference between both groups. Remarkably, ADA readministration to patients with flare was effective in returning DAS28-ESR to <3.2 within 6 months in 90% and 9 months in 100% patients; among the patients who sustained DAS28-ESR <3.2 during ADA discontinuation, 100% remained in structural remission and 94% in functional remission. CONCLUSIONS: The possibility of remaining ADA-free for 1 year was demonstrated in established patients with RA with outcomes that ADA can be discontinued without flaring in 79% patients with deep remission, with similar rates in the ADA continuation group, and showed no functional or structural damage in patients with DAS28-ESR <3.2. ADA readministration to patients with flare during ADA discontinuation was effective.
26386082 Clinicopathologic, Immunophenotypic, Cytogenetic, and Molecular Features of γδ T-Cell La 2015 Oct OBJECTIVES: T-cell large granular lymphocytic (T-LGL) leukemia is a rare disorder in which the neoplastic cells usually express the αβ T-cell receptor (TCR). To determine the significance of γδ TCR expression in this leukemia, we compared the clinicopathologic, immunophenotypic, and genetic features of patients with T-LGL leukemia expressing γδ TCR or αβ TCR. METHODS: We used the World Health Organization classification criteria to confirm the diagnosis. All patients were diagnosed and treated at our institution. RESULTS: We identified 14 patients with γδ T-LGL leukemia, 11 men and three women; six (43%) patients had a history of rheumatoid arthritis, 10 (71%) had neutropenia, four (29%) had thrombocytopenia, and three (21%) had anemia. Eight (67%) of 12 patients had a CD4-/CD8- phenotype, and four (33%) had a CD4-/CD8+ phenotype. The median overall survival was 62 months. Patients with γδ T-LGL leukemia were more likely to have rheumatoid arthritis (P = .04), lower absolute neutrophil count (P = .04), lower platelet count (P = .004), and a higher frequency of the CD4-/CD8- phenotype (P < .0001). However, there was no significant difference in overall survival between the two groups (P = .64). CONCLUSIONS: Although patients with γδ and αβ T-LGL leukemia show some different clinical or phenotypic features, overall survival is similar, suggesting that γδ TCR expression does not carry prognostic significance.
26003891 Reduced folate carrier 1 gene expression levels are correlated with methotrexate efficacy 2015 Jun Responsiveness to methotrexate (MTX), the "anchor drug" for treating rheumatoid arthritis (RA), varies among individual patients. In this study we investigated the effects of folate transporter gene expression levels on disease activity among 56 Japanese patients with RA who were undergoing MTX therapy. We also assessed gene expression levels for 15 healthy control subjects. The mRNA expression levels of reduced folate carrier 1 (RFC1) and proton-coupled folate transporter (PCFT) in PBMCs from these patients and controls were determined using real-time quantitative polymerase chain reaction (PCR). Compared with PCFT, there were large individual differences in RFC1 mRNA expression levels in both RA patients and healthy controls. RFC1 mRNA expression levels and RA disease activity scores were significantly negatively correlated, as disease activity scores were lower for patients with higher RFC1 mRNA expression levels. However, RFC1 mRNA levels were not correlated with MTX doses. Thus, the clinical efficacy of MTX for Japanese RA patients was associated with the expression level of a folate transporter gene. Increased RFC1 expression may increase MTX uptake by immune cells, such as lymphocytes, and as a result, RA disease activity would be reduced.
27096475 Evaluation of a rheumatology patient prioritization triage system. 2016 Oct PURPOSE: Patient triage systems have been used to prioritize referred patients to facilitate timely treatment of acutely ill patients, but there is limited data to support the effectiveness of these systems as implemented in the clinic setting. Therefore, the purpose of this study was to evaluate the accuracy of a specialty provider triage system. DATA SOURCES: A prospective study design was conducted (N = 103) to compare the pre- and postappointment provider-assigned, prioritization system acuity scores. The intraclass correlation coefficient (ICC), paired t-test, and the Bland-Altman plotting method were used to summarize and analyze the data. CONCLUSIONS: The ICC between the pre- and postappointment acuity scores was 0.50 (p < .001) with no significant difference between the average means (t = -1.17; p = .24). The Bland-Altman plot suggests scores were typically within the limits of agreement. Our findings suggest the specialty provider triage system was effective at accurately classifying rheumatologic patient acuity in this sample. IMPLICATIONS FOR PRACTICE: When resources are limited and delayed evaluations and treatments result in negative health outcomes, the use of triage systems is likely an effective strategy to reduce the impact of limited provider availability relative to patient census.
27769393 Simultaneous profiling of eicosanoid metabolome in plasma by UPLC-MS/MS method: Applicatio 2016 Dec 1 To evaluate the potential relationship between rheumatoid arthritis and arachidonic acid (AA) metabonomics via cyclooxygenase (COX) and lipoxygenase (LOX) pathways, a UPLC-MS/MS method has been developed and validated for simultaneous and quantitative profiling of eicosanoid metabolome in rat plasma. The analytes were extracted from plasma samples by protein precipitation procedure, and then separated on a Shim-pack XR-ODS column with mobile phase A (0.05% formic acid in water, pH=3.3 adjusted with dilute ammonium hydroxide) and mobile phase B [methanol: acetonitrile (20:80, v/v)]. The detection was performed on UPLC-MS/MS system with an electro spray ion source in the negative ion and multiple reaction-monitoring modes. The developed method was optimized to completely separate all twenty-three analytes and three internal standards in 12min. All standard calibration curves were linear and the calibration regression coefficients were ranged from 0.9903 to 0.9992 for all analytes. The recoveries of analytes were all more than 60%. By means of the method developed, the plasma samples from model rats and normal rats had been successfully determined. Results showed that AA and fifteen kinds of metabolites by LOX and COX pathways in model rat plasma were significant higher than those in normal ones(P<0.05), while 5-HpETE and LTD(4) in model rat plasma were significantly lower than those in normal ones(P<0.05). The methods demonstrated the changes of eicosanoid metabolome occurring in plasma from rat subjects with rheumatoid arthritis. It could be a powerful manner to diagnostic and/or prognostic values for rheumatoid arthritis.
25188646 Etanercept-induced sarcoidosis in rheumatoid arthritis: FDG PET findings. 2015 Jan We report the F-FDG PET/CT findings of an etanercept-induced sarcoidosis in a patient with rheumatoid arthritis. A 68-year-old woman with rheumatoid arthritis who had been treated with etanercept and methotrexate showed multiple lung nodules and hilar lymph node swellings on CT. She underwent FDG PET/CT for cancer screening. Intense FDG uptakes were found in the multiple lung nodules, bilateral hilar lymph nodes, a periurethral masslike lesion, and cranial meningeal nodules. A histopathological examination revealed epithelioid granuloma with multinucleated giant cells, which was compatible with sarcoidosis.