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ID PMID Title PublicationDate abstract
28484154 [Spontaneous regression of methotrexate-related diffuse large B-cell lymphoma following bl 2017 A 71-year-old woman who had been treated with methotrexate (MTX) and prednisolone for rheumatoid arthritis since 2010 presented with hematuria. Cystitis was diagnosed. Chest and abdominal CT images revealed a bladder tumor, with lung and bilateral adrenal metastases. Transurethral resection of the bladder tumor (TUR-BT) confirmed these findings in September 2014. Histological findings of the bladder included large atypical lymphoid cells indicating diffuse large B-cell lymphoma. After TUR-BT, CT imaging showed that the tumor had shrunk. Still, MTX was continued. She was diagnosed with MTX-related lymphoproliferative disorders in November 2014 and MTX was discontinued. Fluorodeoxyglucose-positron emission tomography on March 2015 showed a complete response.
28265680 Indirubin inhibits the migration, invasion, and activation of fibroblast-like synoviocytes 2017 May OBJECTIVES: To evaluate the inhibition of indirubin in FLSs migration, invasion, activation, and proliferation in RA FLSs. METHODS: The levels of IL-6 and IL-8 in cultural supernatants were measured by ELISA. RA FLS migration and invasion in vitro were measured by the Boyden chamber method and the scratch assay. Signal transduction protein expression was measured by western blot. FLS proliferation was detected by Edu incorporation. F-actin was measured by immunofluorescence staining. RESULTS: We found that indirubin reduced migration, invasion, inflammation, and proliferation in RA FLSs. In addition, we demonstrated that indirubin inhibited lamellipodium formation during cell migration. To gain insight into molecular mechanisms, we evaluated the effect of indirubin on PAK1 and MAPK activation. Our results indicated that indirubin inhibited the activity of PAK1 and MAPK. CONCLUSIONS: Our observations suggest that indirubin may be protective against joint destruction in RA by regulating synoviocyte migration, invasion, activation, and proliferation.
29051108 A Bayesian model that jointly considers comparative effectiveness research and patients' p 2018 Jan OBJECTIVES: The objective of the study was to estimate the preferred treatment for early rheumatoid arthritis using a novel Bayesian approach that jointly considers patients' preferences and comparative effectiveness research. STUDY DESIGN AND SETTING: We estimated the preferred treatment using patients' preferences measured in a discrete-choice experiment to apply weights to benefit and harm outcomes from a network meta-analysis and other considerations (dosing, rare adverse events). Using Bayesian analyses, we considered the variability in patients' preferences and the imprecision in both patients' preferences and the treatment effects; all key considerations in the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: We estimated that most patients in our population would prefer triple therapy as initial treatment (78%) or after an inadequate response to methotrexate (62%). The probability of choosing triple therapy as initial treatment was further from 50% (the point of indifference) for more patients, making our prediction more confident, and suggesting a stronger recommendation could be made. After an inadequate response to methotrexate, the choice was more split, suggesting a decision aid may be helpful. CONCLUSION: Using a novel approach, we estimated that many patients with early rheumatoid arthritis may prefer triple therapy to other treatment options, in contrast to existing guidelines. This offers an approach that may help inform Grading of Recommendations Assessment, Development, and Evaluation treatment recommendations.
28843845 Synthesis, pH dependent, plasma and enzymatic stability of bergenin prodrugs for potential 2017 Oct 15 Bergenin is a unique C-glycoside natural product possessing anti-inflammatory and anti-arthritic activity. It is hydrophilic molecule and stable under acidic conditions however is unstable at neutral-basic pH conditions. The rate of degradation is directly proportional to the increase in pH which might be one of the reasons for its low oral bioavailability. Thus, herein our objective was to improve its stability using prodrug strategy. Various ester and ether prodrugs were synthesized and studied for lipophilicity, chemical stability and enzymatic hydrolysis in plasma/esterase. The stability of synthesized prodrugs was evaluated in buffers at different pH, in biorelevant media such as SGF, SIF, rat plasma and in esterase enzyme. All prodrugs displayed significantly improved lipophilicity compared with bergenin, which was in accordance with the criteria of drug-like compounds. Acetyl ester 4a(2) appeared to be the most promising prodrug as it remained stable at gastric/intestinal pH and was completely transformed to the parent compound bergenin in plasma as desired for an ideal prodrug. The data presented herein, will help in designing stable prodrugs of unstable molecules with desired physicochemical properties in structurally similar chemotypes.
28554192 Triple Therapy Versus Biologic Therapy for Active Rheumatoid Arthritis: A Cost-Effectivene 2017 Jul 4 BACKGROUND: The RACAT (Rheumatoid Arthritis Comparison of Active Therapies) trial found triple therapy to be noninferior to etanercept-methotrexate in patients with active rheumatoid arthritis (RA). OBJECTIVE: To determine the cost-effectiveness of etanercept-methotrexate versus triple therapy as a first-line strategy. DESIGN: A within-trial analysis based on the 353 participants in the RACAT trial and a lifetime analysis that extrapolated costs and outcomes by using a decision analytic cohort model. DATA SOURCES: The RACAT trial and sources from the literature. TARGET POPULATION: Patients with active RA despite at least 12 weeks of methotrexate therapy. TIME HORIZON: 24 weeks and lifetime. PERSPECTIVE: Societal and Medicare. INTERVENTION: Etanercept-methotrexate first versus triple therapy first. OUTCOME MEASURES: Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: The within-trial analysis found that etanercept-methotrexate as first-line therapy provided marginally more QALYs but accumulated substantially higher drug costs. Differences in other costs between strategies were negligible. The ICERs for first-line etanercept-methotrexate and triple therapy were $2.7 million per QALY and $0.98 million per QALY over 24 and 48 weeks, respectively. The lifetime analysis suggested that first-line etanercept-methotrexate would result in 0.15 additional lifetime QALY, but this gain would cost an incremental $77 290, leading to an ICER of $521 520 per QALY per patient. RESULTS OF SENSITIVITY ANALYSIS: Considering a long-term perspective, an initial strategy of etanercept-methotrexate and biologics with similar cost and efficacy is unlikely to be cost-effective compared with using triple therapy first, even under optimistic assumptions. LIMITATION: Data on the long-term benefit of triple therapy are uncertain. CONCLUSION: Initiating biologic therapy without trying triple therapy first increases costs while providing minimal incremental benefit. PRIMARY FUNDING SOURCE: The Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, Canadian Institutes for Health Research, and an interagency agreement with the National Institutes of Health-American Recovery and Reinvestment Act.
28962581 Large country differences in work outcomes in patients with RA - an analysis in the multin 2017 Sep 29 BACKGROUND: We aimed to explore whether country of residence or specific country characteristics are associated with work outcomes in rheumatoid arthritis (RA). METHODS: Data from the 17 countries participating in the Comorbidities in RA (COMORA) study were used. Work outcomes were measured by the Work Productivity and Activity Impairment Questionnaire, addressing employment (yes/no), absenteeism (percentage of time; 3 categories) and presenteeism (percentage of at-work productivity restrictions; 4 categories). Contribution of country of residence, gross domestic product (GDP), Human Development Index (HDI), unemployment rate, social protection expenditures (SPE) or world region to work outcomes was investigated in adjusted (ordered) logistic regressions. RESULTS: The patients (n = 2395) were younger than 60 years; mean age 48 (SD 9.2) years, 1972 (84%) female and 1065 (45%) employed. Large country differences were found. Taking the country with the best work outcome as reference, Moroccan patients had the lowest odds of being employed (OR 0.2 (95% CI 0.1; 0.3) vs. Germany) and highest odds of absenteeism (OR 13.2 (3.6; 48.3) vs. Japan). Patients in Taiwan had the highest odds of presenteeism (OR 13.0 (5.5; 30.9) vs. Venezuela). All country indices except SPE were associated with work outcomes. For example, patients in low-GDP countries had lower odds of employment (OR 0.6 (0.5; 0.8)), higher odds of absenteeism (OR 2.8 (2.0; 4.1)), but lower odds of presenteeism (OR 0.5 (0.4; 0.7)) compared to higher-GDP countries. CONCLUSION: Substantial differences in work outcomes among patients with RA were observed between countries. Lower economic wealth and human development of countries were associated with worse employment and higher absenteeism, but lower presenteeism.
28509333 Altered glycan accessibility on native immunoglobulin G complexes in early rheumatoid arth 2017 Sep The goal of this study was to investigate the glycosylation profile of native immunoglobulin (Ig)G present in serum immune complexes in patients with rheumatoid arthritis (RA). To accomplish this, lectin binding assays, detecting the accessibility of glycans present on IgG-containing immune complexes by biotinylated lectins, were employed. Lectins capturing fucosyl residues (AAL), fucosylated tri-mannose N-glycan core sites (LCA), terminal sialic acid residues (SNA) and O-glycosidically linked galactose/N-acetylgalactosamine (GalNac-L) were used. Patients with recent-onset RA at baseline and after 3-year follow-up were investigated. We found that native IgG was complexed significantly more often with IgM, C1q, C3c and C-reactive protein (CRP) in RA patients, suggesting alterations of the native structure of IgG. The total accessibility of fucose residues on captured immune complexes to the respective lectin was significantly higher in patients with RA. Moreover, fucose accessibility on IgG-containing immune complexes correlated positively with the levels of antibodies to cyclic citrullinated peptides (anti-CCP). We also observed a significantly higher accessibility to sialic acid residues and galactose/GalNAc glyco-epitopes in native complexed IgG of patients with RA at baseline. While sialic acid accessibility increased during treatment, the accessibility of galactose/GalNAc decreased. Hence, successful treatment of RA was associated with an increase in the SNA/GalNAc-L ratio. Interestingly, the SNA/GalNAc-L ratio in particular rises after glucocorticoid treatment. In summary, this study shows the exposure of glycans in native complexed IgG of patients with early RA, revealing particular glycosylation patterns and its changes following pharmaceutical treatment.
29141677 Factors associated with oral glucocorticoid use in patients with rheumatoid arthritis: a d 2017 Nov 15 BACKGROUND: Glucocorticoids (GCs) are used in ~ 60% of patients with rheumatoid arthritis (RA). Although disease-modifying, they also have significant adverse effects. Understanding factors associated with GC use may help minimise exposure. The aims of the present study were to describe oral GC use in RA; determine any change in use over time; and determine factors associated with oral GC use, commencement or cessation. METHODS: Adult patients with RA were identified in the Australian Rheumatology Association Database (ARAD), a national Australian registry that collects long-term outcome data from patients with inflammatory arthritis. Patients were categorised by their ARAD date of entry (DOE), with population-averaged logistic regression and transition state analysis used to determine any change in GC use over time. Fixed-effects panel regression was used to examine whether GC current use was associated with pain/arthritis activity/Health Assessment Questionnaire (HAQ) scores or medication use. Transition state analysis was used to assess whether these factors influenced the commencement or cessation of GCs. RESULTS: A total of 3699 patients with RA completed a baseline ARAD questionnaire (73% female, mean age 57 years). The probability of GC use decreased over time according to ARAD DOE: September 2001 to March 2005, 55% (95% CI 52-58%); March 2005 to September 2008, 47% (45-49%); September 2008 to March 2012, 42% (39-45%); and March 2012 to October 2015, 39% (34-43%) (p < 0.001). Conventional synthetic disease-modifying anti-rheumatic drugs (OR 10.13; 95% CI 8.22-12.47), non-steroidal anti-inflammatory drugs (1.18; 1.02-1.37) and opioids (2.14; 1.84-2.48) were associated with GC current use, as were lower pain scores (0.94; 0.90-0.98), higher arthritis activity scores (1.09; 1.05-1.14) and poorer HAQ scores (1.52; 1.30-1.79). Use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) was not associated with GC current use (0.98; 0.83-1.15) or GC cessation (HR 0.87; 95% CI 0.75-1.01), but it was associated with GC commencement (0.54; 0.47-0.62). CONCLUSIONS: The probability of oral GC use decreased over time, with reduced commencement and increased cessation of GCs. The modest effect of bDMARDs on GC cessation was not statistically significant.
28323130 Monocyte activation drives preservation of membrane thiols by promoting release of oxidise 2017 Jul The redox state of cellular exofacial molecules is reflected by the amount of available thiols. Furthermore, surface thiols can be considered as indicators of immune cell activation. One group of thiol containing proteins, peroxiredoxins, in particular, have been associated with inflammation. In this study, we assessed surface thiols of the U937 and Thp1 monocyte cell lines and primary monocytes in vitro upon inflammatory stimulation by irreversibly labelling the cells with a fluorescent derivative of maleimide. We also investigated exofacial thiols on circulating blood mononuclear cells in patients with rheumatoid arthritis and healthy controls. When analysing extracellular vesicles, we combined thiol labelling with the use of antibodies to specific CD markers to exclude extracellular vesicle mimicking signals from thiol containing protein aggregates. Furthermore, differential detergent lysis was applied to confirm the vesicular nature of the detected extracellular events in blood plasma. We found an increase in exofacial thiols on monocytes upon in vitro stimulation by LPS or TNF, both in primary monocytes and monocytic cell lines (p<0.0005). At the same time, newly released extracellular vesicles showed a decrease in their exofacial thiols compared with those from unstimulated cells (p<0.05). We also found a significant elevation of surface thiols on circulating monocytes in rheumatoid arthritis patients (p<0.05) and newly released extracellular vesicles of isolated CD14(+) cells from rheumatoid arthritis patients had decreased thiol levels compared with healthy subjects (p<0.01). Exofacial peroxiredoxin 1 was demonstrated on the surface of primary and cultured monocytes, and the number of peroxiredoxin 1 positive extracellular vesicles was increased in rheumatoid arthritis blood plasma (p<0.05). Furthermore, an overoxidised form of peroxiredoxin was detected in extracellular vesicle-enriched preparations from blood plasma. Our data show that cell surface thiols play a protective role and reflect oxidative stress resistance state in activated immune cells. Furthermore, they support a role of extracellular vesicles in the redox regulation of human monocytes, possibly representing an antioxidant mechanism.
28978351 The caspase-8/RIPK3 signaling axis in antigen presenting cells controls the inflammatory a 2017 Oct 4 BACKGROUND: Caspase-8 is a well-established initiator of apoptosis and suppressor of necroptosis, but maintains functions beyond cell death that involve suppression of receptor-interacting serine-threonine kinases (RIPKs). A genome-wide association study meta-analysis revealed an SNP associated with risk of rheumatoid arthritis (RA) development within the locus containing the gene encoding for caspase-8. Innate immune cells, like macrophages and dendritic cells, are gaining momentum as facilitators of autoimmune disease pathogenesis, and, in particular, RA. Therefore, we examined the involvement of caspase-8 within these antigen-presenting cell populations in the pathogenesis of an arthritis model that resembles the RA effector phase. METHODS: Cre (LysM) Casp8 (flox/flox) and Cre (CD11c) Casp8 (flox/flox) mice were bred via a cross between Casp8 (flox/flox) and Cre (LysM) or Cre (CD11c) mice. RIPK3 (-/-) Cre (LysM) Casp8 (flox/flox) and RIPK3 (-/-) Cre (CD11c) Casp8 (flox/flox) mice were generated to assess RIPK3 contribution. Mice were subjected to K/BxN serum-transfer-induced arthritis. Luminex-based assays were used to measure cytokines/chemokines. Histological analyses were utilized to examine joint damage. Mixed bone marrow chimeras were generated to assess synovial cell survival. Flow cytometric analysis was employed to characterize cellular distribution. For arthritis, differences between the groups were assessed using two-way analysis of variance (ANOVA) for repeated measurements. All other data were compared by the Mann-Whitney test. RESULTS: We show that intact caspase-8 signaling maintains opposing roles in lysozyme-M- and CD11c-expressing cells in the joint; namely, caspase-8 is crucial in CD11c-expressing cells to delay arthritis induction, while caspase-8 in lysozyme M-expressing cells hinders arthritis resolution. Caspase-8 is also implicated in the maintenance of synovial tissue-resident macrophages that can limit arthritis. Global loss of RIPK3 in both caspase-8 deletion constructs causes the response to arthritis to revert back to control levels via a mechanism potentially independent of cell death. Mixed bone marrow chimeric mice demonstrate that caspase-8 deficiency does not confer preferential expansion of synovial macrophage and dendritic cell populations, nor do caspase-8-deficient synovial populations succumb to RIPK3-mediated necroptotic death. CONCLUSIONS: These data demonstrate that caspase-8 functions in synovial antigen-presenting cells to regulate the response to inflammatory stimuli by controlling RIPK3 action, and this delicate balance maintains homeostasis within the joint.
28341837 Enhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhib 2017 Mar 24 Cysteine-rich 61 (Cyr61 or CCN1), a secreted protein from the CCN family, is an important proinflammatory cytokine. Migration and infiltration of mononuclear cells to inflammatory sites play a critical role in the pathogenesis of rheumatoid arthritis (RA). Monocyte chemoattractant protein-1 (MCP-1/CCL2) is the key chemokine that regulates migration and infiltration of monocytes. Here, we examined the role of CCN1 in monocyte migration, and CCL2 expression in osteoblasts. We found higher levels of CCN1 and CCL2 in synovial fluid from RA patients compared with levels from non-RA controls. We also found that the CCN1-induced increase in CCL2 expression is mediated by the MAPK signaling pathway and that miR-518a-5p expression was negatively regulated by CCN1 via the MAPK cascade. In contrast, inhibition of CCN1 expression with lentiviral vectors expressing short hairpin RNA ameliorated articular swelling, cartilage erosion, and infiltration of monocytes in the ankle joints of mice with collagen-induced arthritis. Our study describes how CCN1 promotes monocyte migration by upregulating CCL2 expression in osteoblasts in RA disease. CCN1 could serve as a potential target for RA treatment.
28850026 Interleukin-35 inhibits angiogenesis through STAT1 signalling in rheumatoid synoviocytes. 2018 Mar OBJECTIVES: We studied the anti-angiogenic effect of interleukin-35 (IL-35) by investigating its effects on signal transmission through the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway in fibroblast-like synoviocytes (FLS). METHODS: Using the collagen-induced arthritis (CIA) model of rheumatoid arthritis (RA), we derived and cultured FLS, stimulated FLS with IL-35 at different concentrations and examined the expression levels of mRNA and protein of both vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), endostatin, TNF-α, and IL-6 using reverse transcription polymerase chain reaction (RT-PCR) and immunoblotting. We used Western blotting to study the effects of IL-35 on the function of the JAK-STAT pathway in FLS. RESULTS: IL-35 treatment inhibited the expression of VEGF, FGF-2, TNF-α and IL-6, and increased the expression of endostatin in FLS. Western blotting showed that IL-35 treatment of CIA-derived FLS resulted in signalling through STAT1, but not through STAT3 or STAT5. CONCLUSIONS: IL-35 signalling through STAT1 and inhibition of the expression of mediators of angiogenesis and inflammation in FLS provide a likely mechanism for anti-angiogenic effects seen in experimental models of RA. Our data suggest that IL-35 and its signalling pathway represent a therapeutic target for the treatment of RA and other angiogenesis-related diseases.
27733582 Synovial IL-21/TNF-producing CD4(+) T cells induce joint destruction in rheumatoid arthrit 2017 Mar Bone and cartilage destruction is one of the key manifestations of rheumatoid arthritis (RA). Although the role of T helper (Th)17 cells in these processes is clear, the role of IL-21-producing cells T cells has been neglected. We sought to investigate the role of IL-21 in RA by focusing on the functional characteristics of the main producers of this cytokine, synovial CD4(+)IL-21(+) T cells. We show that the frequency of both synovial fluid (SF) CD4(+)IL-21(+) or CD4(+)IL-21(+)TNF(+) T cells in patients with RA was significantly higher compared with patients with psoriatic arthritis (PsA). The frequency of peripheral blood (PB) IL-21(+)CD4(+) T cells in patients with RA positively correlated with disease activity score 28 (DAS28), serum anticyclic citrullinated peptide (anti-CCP) antibodies and IgM-rheumatoid factor (IgM-RF). IL-21 levels in RA SF were associated with matrix metalloproteinase (MMP)-1 and MMP-3. Related to this, IL-21 induced significantly the secretion of MMP-1 and MMP-3 in RA synovial biopsies. Sorted SF CD4(+)IL-21(+) T cells significantly induced the release of MMP-1 and MMP-3 by fibroblast-like synoviocytes (FLS) compared with medium or CD4(+)IL-21(-) T cells in a coculture system. Neutralization of both IL-21 and TNF resulted in significantly less production of MMP by FLS. The results of this study indicate a new role for synovial CD4(+)IL-21(+)TNF(+) T cells in promoting synovial inflammation/joint destruction in patients with RA. Importantly, IL-21 blockade in combination with anti-TNF might be an effective therapy in patients with RA by inhibiting MMP-induced inflammation/joint destruction.
28349184 The Reliability of a Semi-automated Algorithm for Detection of Cortical Interruptions in F 2017 Aug We developed a semi-automated algorithm for the detection of cortical interruptions in finger joints using high-resolution peripheral quantitative computed tomography (HR-pQCT). Here, we tested its reliability compared to microCT (µCT) as gold standard. Nineteen joints of 10 female anatomic index fingers were imaged by HR-pQCT and µCT (82 and 18 µm isotropic voxel sizes, respectively). The algorithm was applied for detection of cortical interruptions of different minimum diameters (range >0.16 to >0.50 mm). Reliability was tested at the joint level with intra-class correlation coefficient (ICC) for the number of interruptions and interruption surface, and at the level of a single interruption for matching between HR-pQCT and µCT with a fixed interruption diameter (>0.10 mm) on µCT. The positive predictive value (PPV(0.10mm)) and sensitivity(0.10mm) were evaluated. The mean number of interruptions per joint depended on the diameter cut-off and ranged from 3.4 to 53.5 on HR-pQCT and from 1.8 to 45.1 on µCT for interruptions >0.50 to >0.16 mm, respectively. Reliability at the joint level was almost perfect (ICC ≥0.81) for both the number and surface of interruptions >0.16 and >0.33 mm. As expected, the PPV(0.10mm) increased with increasing interruption diameter from 84.9 to 100%, for interruptions >0.16 and >0.50 mm, respectively. However, the sensitivity(0.10mm) decreased with increasing interruption diameter from 62.4 to 4.7%. This semi-automated algorithm for HR-pQCT in finger joints performed best for the detection of cortical interruptions with a minimum diameter of >0.16 or >0.33 mm, showing almost perfect reliability at the joint level and interruptions matched with those on µCT.
27215233 Association of PTPN22 rs2476601 Polymorphism with Rheumatoid Arthritis and Celiac Disease 2017 Jan BACKGROUND: Single-nucleotide polymorphism (SNP) rs2476601 within protein tyrosine phosphatase non-receptor type 22 gene (PTPN22) has been shown to be a risk factor for different autoimmune diseases. This study explored the association of 1858 C/T SNP with rheumatoid arthritis (RA) and celiac disease (CD) in a region covering south-west of Iran. METHODS: Totally, 52 patients with CD, 120 patients with RA, and 120 healthy subjects were selected. The samples were genotyped for the rs2476601 in PTPN22 gene using the tetra-amplification refractory mutation system polymerase chain reaction. RESULTS: The frequency of +1858T risk allele was significantly increased in both RA (P=0.021, OR=2.56, 95%CI=1.19-5.47) and CD (P=0.002, OR=3.87, 95%CI=1.68-8.95) patients, as compared to the control group. However, no association was found between the +1858C/T PTPN22 gene SNP and the anti-cyclic citrullinated peptide and rheumatoid factor positivity in RA patients. CONCLUSIONS: PTPN22 gene could play a crucial role in people's susceptibility to certain autoimmune diseases.
28124758 Treatments and in-hospital mortality in acute myocardial infarction patients with rheumato 2017 May No previous study has examined the differences in treatments and outcomes after acute myocardial infarction (AMI) between patients with and without rheumatoid arthritis (RA) in a setting where coronary reperfusion therapy was readily available. This study aimed to examine whether coexisting RA affected likelihood of receiving coronary reperfusion therapy and in-hospital mortality among AMI patients in a Japanese nationwide setting where coronary reperfusion therapy was readily available. Using the Diagnosis Procedure Combination database, we retrospectively identified patients admitted with AMI between 2010 and 2014 and created a matched-pair cohort of patients with and without RA based on age, sex, hospital, and admission year at a maximum ratio of 1:5. We performed multivariable logistic regression analyses for associations of RA with likelihood of coronary reperfusion therapy and 30-day in-hospital mortality. There were no significant differences between the RA group (n = 938) and non-RA group (n = 3839) in the proportions of patients receiving coronary reperfusion therapy (on the day of admission 75.8% vs. 77.2%, P = 0.364; during hospitalization 87.1% vs. 87.3%, P = 0.913) and 30-day in-hospital mortality (5.9% vs. 5.9%, P = 1.000). Multivariable logistic regression analyses showed that RA was not significantly associated with either likelihood of receiving coronary reperfusion therapy during hospitalization (odds ratio 1.02; 95% confidence interval 0.82-1.27; P = 0.837) or 30-day in-hospital mortality (odds ratio 1.16; 95% confidence interval 0.81-1.65; P = 0.419). Coexisting RA did not affect likelihood of receiving coronary reperfusion therapy or in-hospital mortality among AMI patients in a setting where reperfusion therapy was readily available.
27696731 Incidence and Management of Cardiovascular Risk Factors in Psoriatic Arthritis and Rheumat 2017 Jan OBJECTIVE: To examine the prevalence and incidence of cardiovascular (CV) risk factors, including hypertension, hyperlipidemia, diabetes mellitus (DM), and obesity among patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) compared to the general population, and to examine the treatment of incident CV risk factors in PsA and RA compared to controls. METHODS: A cohort study was conducted within The Health Improvement Network, a medical record database in the UK, using data from 1994 to 2014. Patients ages 18-89 years with PsA or RA were matched to controls on practice and start date. The prevalence and incidence of CV risk factors identified by diagnostic codes were calculated. Cox proportional hazards models were used to examine the relative incidence of these CV risk factors. Finally, pharmacologic therapies for incident CV risk factors were examined. RESULTS: Study subjects included patients with PsA (n = 12,548), RA (n = 53,215), and controls (n = 389,269). The prevalence of all CV risk factors was significantly elevated in PsA. Only the prevalence of DM and obesity was increased in RA. Incidence of hypertension, hyperlipidemia, and DM was elevated in PsA and RA. Receipt of therapy within 1 year following incident diagnosis of CV risk factors was not substantially different between the groups; approximately 85%, 65%, and 45% of patients received prescriptions for hypertension, hyperlipidemia, and DM, respectively. CONCLUSION: Patients with PsA have an increased prevalence of CV risk factors, and both patients with PsA and patients with RA have increased incidence of a new diagnosis of CV risk factors. Pharmacologic treatment of CV risk factors in patients with PsA and RA was similar to controls in the UK.
28495692 Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and famili 2017 May Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12; p=9.45×10(-4)). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or PARN mutation than in controls (p=2.87×10(-2)).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.
28460514 [The 456th case: polyarthritis, dry cough, dyspnea on exertion]. 2017 May 1 A 53-year-old woman presented with arthralgia and dyspepsia on exertion.Symmetrical joint swelling and pain of bilateral hands with pigmentation sedimentation in the articular surfaces, dry cough and short of breath were the main clinical manifestations.Elevated levels of erythrocyte sedimentation rate(89 mm/1 h), C-reactive protein (64.45 mg/L), IgG(31.22 g/L) and IgA (5.44 g/L). Rheumatoid factor was positive and anti-cyclic citrullinated peptide antibody was negative.Chest high-resolution computed tomography scan found that diffusely distributed lung nodules, round cysts with varying sizes and patchy ground glass opacities.A significant plasma cell infiltration and amyloid deposition were seen in lung tissue.The patient was finally diagnosed as rheumatoid arthritis, interstitial lung disease and pulmonary nodules.Combination therapy of prednisone 7.5 mg qodpo, thalidomide 50 mg qdpo, tocilizumab 560 mg iv once per month for 1 month.Chest computed tomography showed stable lung nodules, however, pulmonary interstitial lesions gradually aggravated.
28793978 Patellofemoral arthroplasty conversion to total knee arthroplasty: Retrieval analysis and 2017 Oct BACKGROUND: Patellofemoral arthroplasty (PFA) can be a successful, bone-sparing treatment for isolated patellofemoral arthritis. However, progression of tibio-femoral arthritis or incorrect indications may predispose patients to early conversion to total knee arthroplasty (TKA). The purpose of this study was to review the clinical cases and perform retrieval analysis of PFA conversions to TKA at our institution. METHODS: Twenty one patellofemoral arthroplasties in 18 patients that were converted to TKA were identified through our implant retrieval registry. Sixteen implants were available for review by biomechanical engineers, who recorded surface markings, wear patterns, and integrity of fixation. Patient charts were reviewed and time to conversion, tourniquet time, conversion implant, additional surgeries, infections, and Kellgren & Lawrence grade of the tibio-femoral joint on pre-operative radiographs were recorded. RESULTS: PFAs converted to TKAs at our institution were implanted for an average of 2.7years. The most common reason for conversion was pain, but most patients had significant tibio-femoral arthritis, as indicated by an average Kellgren & Lawrence grade of 2.6. The average tourniquet time for these conversions was 67min. These patients underwent an average of one additional surgery per PFA converted, and the infection rate of these conversions was approximately 14%. CONCLUSION: Success of PFA depends upon correct patient selection rather than implant failure or wear. Conversion of PFA to TKA is technically similar to primary TKA, with similar post-operative pain relief and range of motion. However, infection rates and complications requiring further surgery are more consistent with results seen in revision TKA. LEVEL OF EVIDENCE: IV.