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ID PMID Title PublicationDate abstract
19446344 TLR-3 enhances osteoclastogenesis through upregulation of RANKL expression from fibroblast 2009 May 14 This study was undertaken to determine the effect of toll-like receptor-3 (TLR3) on the regulation of osteoclastogenic activity in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). The expression of receptor activator of nuclear factor kappa B ligand (RANKL) mRNA and protein in RA-FLS after TLR3 activation was determined using RT-PCR, real-time PCR, western blot analysis, and immunohistochemistry. Human monocytes were cocultured with RA-FLS that had been prestimulated by the TLR3 ligand polyriboinosinic-polyribocytidylic acid and then stained for tartrate-resistant acid phosphatase (TRAP) activity. Other markers of osteoclasts were measured using RT-PCR and real-time PCR. The expression of TLR3 and RANKL was much higher in the RA synovium than in the osteoarthritis (OA) synovium. TLR3 activation induced RANKL expression in RA-FLS, but not in OA-FLS or in normal skin fibroblasts. TLR3 activation also induced the production of IL-1beta but had no effect on IL-17 or TNF-alpha production in RA-FLS. Inhibition of IL-1beta reversed the TLR3-induced upregulation of RANKL expression. Coculture of human monocytes with TLR3-activated RA-FLS or TLR3 ligand-stimulated human monocytes increased the expression of TRAP, RANK, cathepsin K, calcitonin receptor, and MMP-9, reflecting the differentiation of monocytes into osteoclasts. Our results suggest that TLR3 promotes osteoclastogenesis in the RA synovium both directly and indirectly. TLR3 stimulates human monocytes directly to promote osteoclast differentiation. TLR3 induces RANKL expression indirectly in RA-FLS, and the expression of RANKL promotes the differentiation of osteoclasts in the RA synovium. Targeting the TLR3 pathway may be a promising approach to preventing inflammatory bone destruction in RA.
20496420 Trex-1 deficiency in rheumatoid arthritis synovial fibroblasts. 2010 Sep OBJECTIVE: To explore whether the increased expression of long interspersed nuclear element 1 (LINE-1; L1) messenger RNA (mRNA) and protein in rheumatoid arthritis synovial fibroblasts (RASFs) is associated with decreased expression of Trex-1, an exonuclease involved in the metabolization of L1 DNA:RNA hybrids. METHODS: Chromatin immunoprecipitation was used to detect L1-related p40 protein (L1-ORF1p) binding sequences in RASFs. Luciferase activity was measured in the synovial fibroblasts following cotransfection of the episomal plasmid with pJM105 expressing L1-ORF1p and pGL3-TS3 carrying the target sequence for L1-ORF1p. This luciferase reporter assay was used to compare the activity between RASFs and osteoarthritis synovial fibroblasts (OASFs) and to assess correlations of luciferase activity with the expression of Trex-1 measured by flow cytometry. The expression of Trex-1 mRNA and protein was also compared using real-time polymerase chain reaction, immunohistochemistry, and Western blot analyses. The role of Trex-1 in the L1-ORF1p-mediated luciferase activity assay was studied using interfering RNAs (iRNA) and a Trex-1 expression vector. RESULTS: Increased luciferase activity occurred after cotransfection of synovial fibroblasts with pJM105 and pGL3-TS3. L1-ORF1p activity was increased in RASFs as compared with OASFs, and this was correlated inversely with the expression of Trex-1. Levels of Trex-1 mRNA and protein were lower in RASFs than in OASFs. After transfection of the L1 expression plasmid, Trex-1 mRNA levels increased in OASFs, but not in RASFs. The addition of iRNA against Trex-1, however, resulted in an enhancement of L1-ORF1p activity in OASFs to the levels measured in RASFs. Overexpression of Trex-1 inhibited 5-azacytidine-induced expression of p38δ MAPK, a gene carrying the TS3 sequence. CONCLUSION: The deficiency of Trex-1 in RASFs allows a longer half-life of gene products encoded by active endogenous L1 retrotransposons. This pathway may play a role in diseases in which the cells exhibit a "spontaneous" aggressive behavior.
20972592 Sarcoid-like granulomatosis in patients treated with anti-TNFα factors. A case report and 2011 Apr This report describes a 56-year-old woman who developed granulomatous lesions consistent with sarcoidosis during adalimumab therapy for rheumatoid arthritis. Cervical and axillary lymphadenopathy developed approximately 21 months after adalimumab administration. Non-caseating epithelioid cell granulomas consistent with sarcoidosis were detected both in an axillary lymph node specimen and in the bone marrow. Diseases showing similar histologic changes, especially tuberculosis, were excluded, and a diagnosis of sarcoidosis was made. Adalimumab was discontinued, and recovery was observed. The current case is, to our knowledge, the first to describe adalimumab-induced non-caseating granulomas in lymph nodes and bone marrow without pulmonary involvement in a patient treated for rheumatoid arthritis.
19287509 Genome-wide association study of determinants of anti-cyclic citrullinated peptide antibod 2009 May We carried out a genome-wide association study of genetic predictors of anti-cyclic citrullinated peptide antibody (anti-CCP) level in 531 self-reported non-Hispanic Caucasian Rheumatoid Arthritis (RA) patients enrolled in the Brigham Rheumatoid Arthritis Sequential Study (BRASS). For replication, we then analyzed 289 single nucleotide polymorphisms (SNPs) with P < 0.001 in BRASS in an independent population of 849 RA patients from the North American Rheumatoid Arthritis Consortium (NARAC). BRASS and NARAC samples were genotyped using the Affymetrix 100K and Illumina 550K platforms respectively. Association between SNPs and anti-CCP titer was tested using general linear models. The five most significant SNPs from BRASS all were within the major histocompatibility complex (MHC) region (P < or = 3.5 x 10(-6)). After controlling for the human leukocyte antigen shared epitope (HLA-SE), the top SNPs still yielded P values < 0.0002. In NARAC, a single SNP from the MHC region near BTNL2 and HLA-DRA, rs1980493 (r(2) = 0.85 with the top five SNPs from BRASS), was associated significantly with CCP titer (P = 6.1 x 10(-5)) even after adjustment for the HLA-SE (P = 0.0002). The top SNPs found in BRASS and NARAC had r(2) = 0.46 and 0.64, respectively, to HLA-DRB1 DR3 alleles. These results confirm that the most significant genome region affecting anti-CCP titers in RA is the MHC region. We identified a SNP in moderate linkage disequilibrium (LD) with HLA-DR3, which may influence anti-CCP titer independently of the HLA-SE.
19144569 Complement activation and inhibition: a delicate balance. 2009 Feb Complement is part of the innate immune defence and not only recognizes microbes but also unwanted host molecules to enhance phagocytosis and clearance. This process of opsonisation must be tightly regulated to prevent immunopathology. Endogenous ligands such as dying cells, extracellular matrix proteins, pentraxins, amyloid deposits, prions and DNA, all bind the complement activator C1q, but also interact with complement inhibitors C4b-binding protein and factor H. This contrasts to the interaction between C1q and immune complexes, in which case no inhibitors bind, resulting in full complement activation. Disturbances to the complement regulation on endogenous ligands can lead to diseases such as age-related macular degeneration, neurological and rheumatic disorders. A thorough understanding of these processes might be crucial to developing new therapeutic strategies.
19248135 Current risk factors for work disability associated with rheumatoid arthritis: recent data 2009 Mar 15 OBJECTIVE: To explore, using recent data, whether and how risk factors for rheumatoid arthritis (RA) work disability may differ from previous studies. METHODS: Subjects were 953 individuals with RA from a US cohort who provided data semiannually over 18 months (years 2002-2005). A nested case-control design was used with matching on time of baseline data collection. All subjects were employed at baseline; cases were consistently not employed at followup, whereas controls remained employed. Hierarchical conditional logistic regression assessed the roles of demographic, RA disease, general health, and work factors as predictors of work disability. Recursive partitioning and causal modeling procedures were also used. RESULTS: Sample characteristics were mean age 51 years, 82% female, and 92% white. Older age (odds ratio [OR] 1.2, 95% confidence interval [95% CI] 1.1-1.4) and lower income (OR 1.7, 95% CI 1.0-2.7) predicted work disability, whereas more hours worked (OR 0.9, 95% CI 0.8-0.9) and preference to work full time (OR 0.2, 95% CI 0.1-0.4) or part time (OR 0.4, 95% CI 0.2-0.6) versus not to work were protective in the regression analysis. In recursive partitioning analyses, RA disease factors predicted work disability among older subjects, and functional limitation was the fourth most important factor. Job physical demand was not a significant or important factor. CONCLUSION: In this contemporary data from a large RA cohort, older age, lower income, fewer working hours, and preference not to work were the risk factors for work disability. The impact of disease factors was limited to subjects ages >or=56 years. Job physical demand level had little impact.
21163672 Elevation of human tumor necrosis factor-like weak inducer of apoptosis in peripheral bloo 2011 Mar Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a recently identified proinflammatory cytokine of the TNF superfamily. Studies have indicated that TWEAK plays an important role in renal, vascular injury and immune disease. The aim of this study was to explore the expression of the TWEAK in peripheral blood mononuclear cells (PBMCs) and analyze the correlation between TWEAK and disease activity and renal damage of SLE. The expression of TWEAK in PBMCs was determined by RT-PCR and western blot. SLE disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 score. Next were analyzed the correlations of TWEAK mRNA and protein to serum IL-10, MCP-1 and some laboratory parameters of SLE disease activity. Subjects comprised 48 patients with SLE including 25 patients with renal damage and 23 without, 20 patients with rheumatoid arthrithis (RA) and 15 healthy controls. The results showed that TWEAK expressions in PBMCs from SLE patients were significantly higher than that in RA patients or healthy controls, especially higher in those patients with renal disease. Elevated production of TWEAK is correlated positively and significantly with SLEDAI, proteinuria, serum anti-dsDNA, IL-10 and MCP-1, but inversely associated with serum complements. Our results suggested that TWEAK in PBMCs is positively related to SLE disease activity and might be involved in the pathogenesis of SLE.
20929536 Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosi 2010 INTRODUCTION: Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to systematically analyse the phenotype, cytokine profile and frequency of interleukin-17 (IL-17) producing CD4-positive T cells in mononuclear cells isolated from peripheral blood, synovial fluid and synovial tissue of RA patients with established disease, and to correlate cell frequencies with disease activity. METHODS: Flow cytometry was used to analyse the phenotype and cytokine production of mononuclear cells isolated from peripheral blood (PBMC) (n = 44), synovial fluid (SFMC) (n = 14) and synovium (SVMC) (n = 10) of RA patients and PBMC of healthy controls (n = 13). RESULTS: The frequency of IL-17-producing CD4 T cells was elevated in RA SFMC compared with RA PBMC (P = 0.04). However, the frequency of this population in RA SVMC was comparable to that in paired RA PBMC. The percentage of IL-17-producing CD4 T cells coexpressing tumor necrosis factor alpha (TNFα) was significantly increased in SFMC (P = 0.0068). The frequency of IFNγ-producing CD4 T cells was also significantly higher in SFMC than paired PBMC (P = 0.042). The majority of IL-17-producing CD4 T cells coexpressed IFNγ. IL-17-producing CD4 T cells in RA PBMC and SFMC exhibited very little IL-22 or IL-23R coexpression. CONCLUSIONS: These findings demonstrate a modest enrichment of IL-17-producing CD4 T cells in RA SFMC compared to PBMC. Th17 cells in SFMC produce more TNFα than their PBMC counterparts, but are not a significant source of IL-22 and do not express IL-23R. However, the percentage of CD4 T cells which produce IL-17 in the rheumatoid joint is low, suggesting that other cells may be alternative sources of IL-17 within the joints of RA patients.
19516186 Factors associated with blood pressure changes in patients receiving diclofenac or etorico 2009 Apr OBJECTIVE: To evaluate the hypertensive effects of etoricoxib and diclofenac relative to baseline hypertension risk factors in arthritis patients. METHODS: Multivariate analysis of data from the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) study (n = 23 504). We evaluated risk factors for change in systolic blood pressure (BP) (SBP) and diastolic BP (DBP) at 4 months versus baseline; exceeding predefined limits of change (PLoC) in BP anytime during the study; and the effect of concomitant antihypertensive class on SBP and exceeding SBP PLoC. RESULTS: Increased SBP was most highly associated with history of hypertension (+3.04 mmHg; P < 0.0001), as were increased DBP (+1.28 mmHg; P < 0.0001), and exceeding DBP PLoC [odds ratio (OR) = 1.83; P < 0.0001]. Exceeding SBP PLoC (OR = 1.50; P < 0.0001) was most highly associated with age at least 65 years. Etoricoxib (vs. diclofenac) was also significantly associated with increased SBP (P < 0.0001), DPB (P < 0.0001 to P = 0.0015), and exceeding SBP PLoC (P < 0.0001 to P = 0.002). Compared with no antihypertensive medication, background calcium channel blockers (CCB) were associated with a small, nonsignificant decrease in SBP (-0.60 mmHg) and no increased odds of exceeding SBP PLoC [OR = 1.00 (95% CI 0.71, 1.42)]. All other antihypertensive classes were associated with either no change or numerically or statistically significantly increased SBP and increased odds of exceeding PLoC. CONCLUSION: History of hypertension and age at least 65 years were most strongly associated with increased BP. Treatment with etoricoxib vs. diclofenac was also a significant factor for increased BP. CCBs appear to maintain antihypertensive effects with concurrent NSAID therapy better than other examined antihypertensive drug classes.
20739637 Immunochemical and mass-spectrometry-based serum hepcidin assays for iron metabolism disor 2010 Oct BACKGROUND: Hepcidin is an iron-regulatory peptide hormone that consists of 3 isoforms: bioactive hepcidin-25, and inactive hepcidin-22 and hepcidin-20. Hepcidin is instrumental in the diagnosis and monitoring of iron metabolism disorders, but reliable methods for its quantification in serum are sparse, as is knowledge of their relative analytical strengths and clinical utility. METHODS: We developed a competitive (c)-ELISA and an immunocapture TOF mass-spectrometry (IC-TOF-MS) assay. Exploiting these 2 methods and our previously described weak cation exchange (WCX)-TOF-MS assay, we measured serum hepcidin concentrations in 186 patients with various disorders of iron metabolism and in 23 healthy controls. RESULTS: We found that (a) the relative differences in median hepcidin concentrations in various diseases to be similar, although the absolute concentrations measured with c-ELISA and WCX-TOF-MS differed; (b) hepcidin isoforms contributed to differences in hepcidin concentrations between methods, which were most prominent in patients with chronic kidney disease; and (c) hepcidin concentrations measured by both the c-ELISA and IC-TOF-MS correlated with ferritin concentrations <60 μg/L, and were suitable for distinguishing between iron deficiency anemia (IDA) and the combination of IDA and anemia of chronic disease. CONCLUSIONS: c-ELISA is the method of choice for the large-scale quantification of serum hepcidin concentrations, because of its low limit of detection, low cost, and high-throughput. Because of its specificity for bioactive hepcidin-25, WCX-TOF-MS can be regarded as a valuable special-purpose assay for disorders with variable concentrations of hepcidin isoforms, such as chronic kidney disease.
18975042 Survivorship of 2000 tapered titanium porous plasma-sprayed femoral components. 2009 Jan Tapered titanium porous plasma-sprayed components have performed well in primary THA. To confirm the literature at longer followup we retrospectively reviewed all 1639 patients who underwent 2000 THAs in which a specific porous femoral component was used. One hundred fourteen patients (134 hips) were lost to followup leaving a cohort of 1525 patients (1866 THAs). The component is a tapered titanium plasma spray-coated design that remained relatively unchanged since its first implantation except for circumferential proximal porous coating added in 1986 and an offset option added in 1999. Minimum followup was 24 months (average, 119 months; range, 24 to 275 months). To date there have been 39 femoral revisions for an implant survival of 98%. Using the Kaplan-Meier method, cumulative survival with any stem revision as the end point was 98.6% at 5 years, 98.4% at 10 years, 97.1% at 15 years, and 95.5% at 20 years. Using aseptic revision for failure of ingrowth as the endpoint, stem survival was 99.1%. Kaplan-Meier cumulative survival with aseptic revision for failure of ingrowth as the endpoint was 99.4% at 5 years, 99.3% at 10, 15 and 20 years. Harris hip pain and total scores improved. This titanium, porous plasma spray-coated femoral component continues to demonstrate high long-term survival with a low rate of component revision for any reason or aseptic failure of ingrowth. LEVEL OF EVIDENCE: Level IV, therapeutic study (case series). See the Guidelines for Authors for a complete description of levels of evidence.
21159824 Association of EMCN with susceptibility to rheumatoid arthritis in a Japanese population. 2011 Feb OBJECTIVE: Endomucin, an endothelial-specific sialomucin, is thought to facilitate "lymphocyte homing" to synovial tissues, resulting in the major histopathologies of rheumatoid arthritis (RA). We examined the association between RA susceptibility and the gene coding endomucin, EMCN. METHODS: Association studies were conducted with 2 DNA sample sets (initial set of 1504 patients, 752 controls; and validation set, 1113 patients, 940 controls) using 6 tag single-nucleotide polymorphisms (SNP) from the Japanese HapMap database. Immunohistochemistry for the expression of endomucin was conducted with synovial tissues from 4 patients with RA during total knee arthroplasty. Electromobility shift assays were performed for the functional study of identified polymorphisms. RESULTS: Within the initial sample set, the strongest evidence of an association with RA susceptibility was SNP rs3775369 (OR 1.20, p = 0.0075). While the subsequent replication study did not initially confirm the observed significant association (OR 1.13, p = 0.062), an in-depth stratified analysis revealed significant association in patients testing positive to anti-cyclic citrullinated peptide (anti-CCP) antibody in the replication data set (OR 1.15, p = 0.044). Investigating 2 sample sets, significant associations were detected in overall and stratified samples with anti-CCP antibody status (OR 1.17, p = 0.0015). Positive staining for endomucin was detected in all patients. The allele associated with RA susceptibility had a higher binding affinity for HEK298-derived nuclear factors compared to the nonsusceptible allelic variant of rs3775369. CONCLUSION: A significant association between EMCN and RA susceptibility was detected in our Japanese study population. The EMCN allele conferring RA susceptibility may also contribute to the pathogenesis of RA.
20230694 [Study on ratio imbalance of peripheral blood Th17/Treg cells in patients with rheumatoid 2010 Mar AIM: To observe the relationship between balance of peripheral blood Th17 cells and Foxp3(+) CD4(+) CD25(+) regulatory T (Treg) cells in patients with rheumatoid arthritis (RA), and to clarify the role the ratio imbalance of peripheral blood Th17/Treg cells playing in pathogenesis of RA. METHODS: The ratio of peripheral blood Th17 cells and Foxp3(+) CD4(+) CD25(+) Treg cells in RA patients and healthy subjects were determined by flow cytometry (FCM). RESULTS: Compared with healthy controls, the ratio of both CD3(+) CD4(+) T cells and Th17 cells in RA patients increased significantly (P<0.05), while the percentage of Foxp3(+) CD4(+) CD25(+) Treg cells was markedly lower (P<0.05). With the development of RA activity, the ratio of Th17 cells increased (P<0.05), and the ratio of Foxp3(+) CD4(+) CD25(+) Treg cells decreased (P>0.05). CONCLUSION: The disorder of peripheral blood T lymphocyte subsets in RA patients characterized by increased CD4(+) T cells. The imbalance between Th17 cells and Foxp3(+) CD4(+) CD25(+) Treg cells resulted from increased ratio of Th17 cells and decreased ratio of Foxp3(+) CD4(+) CD25(+) Treg cells may play a critical role in RA progression.
20482783 Remission in psoriatic arthritis: is it possible and how can it be predicted? 2010 INTRODUCTION: Since remission is now possible in psoriatic arthritis (PsA) we wished to examine remission rates in PsA patients following anti tumour necrosis factor alpha (TNFalpha) therapy and to examine possible predictors of response. METHODS: Analysis of a prospective patient cohort attending a biologic clinic, between November 2004 and March 2008, was performed prior to commencing therapy and at regular intervals. Baseline clinical characteristics including demographics, previous disease-modifying antirheumatic drug (DMARD) response, tender and swollen joint counts, early morning stiffness, pain visual analogue score, patient global assessment, C reactive protein (CRP) and health assessment questionnaire (HAQ) were collected. RESULTS: A total of 473 patients (152 PsA; 321 rheumatoid arthritis (RA)) were analyzed. At 12 months remission, defined according to the disease activity score using 28 joint count and CRP (DAS28-CRP), was achieved in 58% of PsA patients compared to 44% of RA patients, significant improvement in outcome measures were noted in both groups (P<0.05). Analysis of a subgroup of PsA and RA patients matched for DAS28-CRP at baseline also showed higher numbers of PsA patients achieving remission. Linear regression analysis identified the HAQ at baseline as the best predictor of remission in PsA patients (P<0.001). CONCLUSIONS: DAS28 remission is possible in PsA patients at one year following anti-TNF therapy, at higher rates than in RA patients and is predicted by baseline HAQ.
19887049 Elevated levels of serum IgA against Saccharomyces cerevisiae mannan in patients with rheu 2009 Oct This study was undertaken to investigate whether levels of anti-Saccharomyces cerevisiae mannan antibodies (ASCMA) in human sera, a marker for several autoimmune diseases, correlate with rheumatoid arthritis (RA). ASCMA-IgA, -IgG and -IgM levels were measured with enzyme linked immunosorbent assays (ELISA) in patients with RA (n = 30) and 152 healthy adult controls. ASCMA-IgA prevalence was significantly higher in RA patients (40%) than in healthy subjects (5.3%). A strong correlation between levels of ASCMA-IgA and CRP (r = 0.695; p < 0.01) and ESR (r = 0.708; p < 0.01) in RA patients was observed. No significant differences in ASCMA-IgG or IgM levels were noted between RA patients and healthy control subjects in the present study. This result differs from previous reports. It remains to be evaluated whether elevated ASCMA-levels are common to all rheumatic disorders.
21195737 Mucin from rheumatoid arthritis synovial fluid enhances interleukin-6 production by human 2011 Mar The carbohydrate chains represented by mucins (MUCs) are expressed by a variety of normal and malignant secretory epithelial cells and induce a variety of immunoreactions. To find new mucins related to the pathogenesis of rheumatoid arthritis (RA), we examined high-molecular-weight molecules inducing cytokines on human peripheral blood mononuclear cells (PBMCs) in synovial fluid from affected joints. We found a high-molecular-weight substance that induces interleukin 6 production on PBMCs in RA synovial fluid on gel filtration. MUC-1 was present in the resulting fractions, although they had been purified by CsCl density gradient centrifugation. We also found that MUC-1 was expressed on synovial cells and infiltrating inflammatory mononuclear cells on the sublining layer and lymphoid follicles in RA synovial tissues. CD68-positive superficial synovial cells colocalized with MUC-1 and CD68-positive macrophages were in contact with MUC-1-positive mononuclear cells. These findings imply that mucins, including MUC-1, may be related to immunoinflammatory reactions in the pathogenesis of RA.
20091035 Safety of biologic agents after rituximab therapy in patients with rheumatoid arthritis. 2011 Apr The safety of other biologic therapies in rheumatoid arthritis (RA) following B cell-depletion therapy with rituximab has not been established. This retrospective chart review of patients attending an outpatient rheumatology clinic aimed to assess the incidence of adverse events in patients receiving biologic agents to treat RA after an inadequate response or intolerance to rituximab. The charts of 22 patients (18 female; mean age 59 years) were reviewed. Duration of RA was >2 years. Before rituximab, patients had failed one (n = 10), two (n = 4) or three (n = 7) biologic therapies: 1 patient started on rituximab as a first-line biologic. Eighteen patients stopped rituximab due to an inadequate clinical response, while four patients stopped due to adverse events. The mean time to starting a new biologic after rituximab was 4 months, although five patients were started within 1 month of the last rituximab infusion. Abatacept (41%) was the most common biologic used after rituximab. The mean follow-up time from the last rituximab infusion was 14 months. Adverse events occurring after rituximab therapy, but before initiation of a new biologic, included disseminated herpes zoster and aseptic meningitis (both required hospitalization). Adverse events recorded after starting a new biologic post-rituximab included rash, carbuncle, upper respiratory tract infection, urinary tract infection, pneumonia, and eczema, but none was classified as serious. Most of these events occurred in patients receiving abatacept. In conclusion, in this retrospective analysis, no serious adverse events were recorded in patients who received biologic agents following rituximab therapy.
19254297 Edentulism and comorbid factors. 2009 Feb INTRODUCTION: Complete edentulism is the terminal outcome of a multifactorial process involving biological factors and patient-related factors. It continues to represent a tremendous global health care burden, and will for the foreseeable future. The purpose of this review is to determine what comorbid factors exist for the completely edentulous patient. METHODS: This literature review evaluated articles obtained via the National Library of Medicine's PubMed Website, using keywords of edentulism with various combinations of the terms comorbidity, incidence, health, nutrition, cancer, cardiovascular health, diabetes, osteoporosis, smoking, asthma, dementia, and rheumatoid arthritis. Abstracts were selected and screened, and selected full-text articles were reviewed. Articles were limited to those with adequate patient cohorts and a minimum of 2-year follow-up data. RESULTS: Edentulism was found to be a global issue, with estimates for an increasing demand for complete denture prostheses in the future. Completely edentulous patients were found to be at higher risk for poor nutrition, coronary artery plaque formation (odds ratio 2.32), to be smokers (odds ratio 2.42), to be asthmatic and edentulous in the maxillary arch (odds ratio 10.52), to being diabetic (odds ratio 1.82), to having rheumatoid arthritis (odds ratio 2.27), and to having certain cancers (odds ratios varying from 1.54 to 2.85, depending on the type of cancer). Chronic residual ridge resorption continues to be the primary intraoral complication of edentulation, and there appear to be few opportunities to reduce bone loss in the edentulous patient. CONCLUSIONS: While the completely edentulous patient seems to be at risk for multiple systemic disorders, whether development of these disorders is causal or casual has not been determined. To minimize the loss of residual alveolar ridges, exemplary complete denture therapy, along with the establishment of routine recall systems, should be the ultimate goal of treatment of this patient cohort.
20298138 Diagnostic performance of anti-citrullinated peptide antibodies for the diagnosis of rheum 2010 Jun BACKGROUND: The goal of our study was to evaluate the diagnostic performance of the anti-cyclic citrullinated peptide 2 (anti-CCP2) assay in patients with autoimmune and inflammatory disorders. METHODS: We tested the specificity and sensitivity of anti-CCP2 antibodies measured by ELISA in 787 patients with rheumatoid arthritis (RA), 1024 patients with other autoimmune/inflammatory rheumatic disease and 401 subjects without autoimmune rheumatic disease. The optimal cut-off value was defined as the value with the highest diagnostic accuracy (receiver operating characteristic curve analysis). Interval-specific likelihood ratios (LRs) were calculated for each range bounded by defined anti-CCP2 values. RESULTS: To distinguish between patients with RA and controls, the cut-off value with the highest diagnostic accuracy for anti-CCP2 was 2.8 U/mL. Comparing the optimal cut-off value for anti-CCP2 to that recommended by the manufacturer (5.0 U/mL), an increase in prevalence between the proportions of test-positive patients was found for RA, undifferentiated connective tissue disease and undifferentiated arthritis. Evaluating interval-specific LRs for the selected ranges bound by two anti-CCP2 values, in RA and diseased controls, the LRs were 0.40 for values <5.0 U/mL, 6.66 for 5.0-15.0 U/mL, 27.01 for 15.1-30.0 U/mL and 28.89 for >30.0 U/mL. CONCLUSIONS: The cut-off value of 2.8 U/mL for anti-CCP2 has the highest diagnostic accuracy. A value of anti-CCP2 >15 U/mL is associated with an increase in the likelihood of RA disease.
21125155 Anti-TNF therapy in renal amyloidosis in refractory rheumatoid arthritis: a new therapeuti 2010 Mar Amyloidosis is a heterogeneous group of diseases characterized by extracellular deposits of a material composed of aggregates of amyloid--a poorly coupled protein--far from the site of synthesis, causing target organ dysfunction and clinical disease. Systemic amyloidosis A (AA), secondary to infections and chronic inflammation, especially rheumatoid arthritis (RA), is the most common form of amyloid deposition. Treatment of AA consists in the control or resolution of the baseline condition. The objective of the present study was to report a case of secondary renal amyloidosis in a patient with long-term refractory RA who presented sustained clinical improvement after the use of anti-TNFα (etanercept).