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ID PMID Title PublicationDate abstract
28741869 Increased baseline RUNX2, caspase 3 and p21 gene expressions in the peripheral blood of di 2017 Oct OBJECTIVE: To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment. METHODS: Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up. The gene expressions in the whole blood were measured using real-time reverse transcription polymerase chain reaction. The protein concentrations in peripheral blood mononuclear cells were quantified using enzyme-linked immunosorbent assay. Receiver operating characteristic curve analyses were used to suggest thresholds that were associated with the prediction of the response. RESULTS: Decreases in the disease activity at the end of the study were accompanied by significant increases in joint space narrowing score (JSN). Positive correlations between the expressions of the Unc-51-like kinase 1 (ULK1) and matrix metalloproteinase 9 (MMP-9) genes with the level of C-reactive protein and MMP-9 expression with Disease Activity Score of 28 joints (DAS28) and swollen joint count were noted at baseline. The baseline tumor necrosis factor (TNF)α gene expression was positively correlated with JSN at the end of the follow-up, whereas p21, caspase 3, and runt-related transcription factor (RUNX)2 were correlated with the ΔDAS28 values. CONCLUSIONS: Our results suggest that the expressions of MMP-9 and ULK1 might be associated with disease activity. Increased baseline gene expressions of RUNX2, p21 and caspase 3 in the peripheral blood might predict better responses to MTX therapy.
27793425 Impact of tofacitinib treatment on human B-cells in vitro and in vivo. 2017 Feb B-cells are pivotal to the pathogenesis of rheumatoid arthritis and tofacitinib, a JAK inhibitor, is effective and safe in its treatment. Tofacitinib interferes with signal transduction via cytokine receptors using the common γ-chain. Despite extensive data on T-lymphocytes, the impact of tofacitinib on B-lymphocytes is poorly understood. In this study we assessed the effect of tofacitinib on B-lymphocyte differentiation and function. Tofacitinib treatment strongly impaired in vitro plasmablast development, immunoglobulin secretion and induction of B-cell fate determining transcription factors, Blimp-1, Xbp-1, and IRF-4, in naïve B-cells. Interestingly, class switch and activation-induced cytidine deaminase (AICDA) induction was only slightly reduced in activated naïve B-cells. The effect of tofacitinib on plasmablast formation, immunoglobulin secretion and proliferation was less profound, when peripheral blood B-cells, including not only naïve but also memory B-cells, were stimulated. In line with these in vitro results, the relative distribution of B-cell populations remained stable in tofacitinib treated patients. Nevertheless, a temporary increase in absolute B-cell numbers was observed 6-8 weeks after start of treatment. In addition, B-cells isolated from tofacitinib treated patients responded rapidly to in vitro activation. We demonstrate that tofacitinib has a direct impact on human naïve B-lymphocytes, independently from its effect on T-lymphocytes, by impairing their development into plasmablasts and immunoglobulin secretion. The major effect of tofacitinib on naïve B-lymphocyte development points to the potential inability of tofacitinib-treated patients to respond to novel antigens, and suggests planning vaccination strategies prior to tofacitinib treatment.
28882464 Metacarpophalangeal joint of the thumb arthrodesis using intramedullary interlocking screw 2018 Sep The study objective was to assess the results of a thumb metacarpophalangeal joint (MCPJ) arthrodesis using intramedullary interlocking screws at 25°, XMCP ™ (Extremity Medical, Parsippany, NJ). Radiographs evaluated the angle of arthrodesis, time of fusion and fixation of the implant. Clinical and functional outcomes were assessed using the DASH questionnaire and the VAS scale. Any complications found during surgery or the follow-up period were noted. We studied 9 patients. The mean follow-up was 27.6 months. Patients showed clinical and radiological evidence of fusion in an average of 8 weeks, the angle of fusion was 25°. There were no complications and no implant had to be removed. The XMCP™ system provides a reliable method for MCPJ arthrodesis for several indications and can be used with other procedures in the complex hand.
28724365 Leflunomide is equally efficacious and safe compared to low dose rituximab in refractory r 2017 Jul 19 BACKGROUND: The standard dose of rituximab used in rheumatoid arthritis (RA) is 1000 mg but recent studies have shown that low dose (500 mg) is also effective. Efficacy of low dose rituximab in rheumatoid arthritis (RA) refractory to first-line non-biologic Disease Modifying Anti Rheumatic Drugs (DMARDs), compared to leflunomide is unknown. In a tertiary care referral setting, we conducted a randomized, double blind controlled clinical trial comparing the efficacy and safety of low-dose rituximab-methotrexate combination with leflunomide-methotrexate combination. METHODS: Patients on methotrexate (10-20 mg/week) with a Disease Activity Score (DAS) > 3.2 were randomly assigned to rituximab (500 mg on days 1 and 15) or leflunomide (10-20 mg/day). The primary end-point was ACR20 at 24 weeks. Sample of 40 had 70% power to detect a 30% difference. ACR50, ACR70, DAS, EULAR good response, CD3 + (T cell), CD19 + (B cell) and CD19 + CD27+ (memory B cell) counts, tetanus and pneumococcal antibody levels were secondary end points. RESULTS: Baseline characteristics were comparable in the two groups. At week 24, ACR20 was 85% vs 84% (p = 0.93), ACR50 was 60% vs. 64% (p = 0.79) and ACR70 was 35% vs 32% (P = 0.84), in rituximab and in leflunomide groups respectively. Serious adverse events were similar. With rituximab there was significant reduction in B cells (p < 0.001), memory B cells (p < 0.001) and pneumococcal antibody levels (P < 0.05) without significant changes in T cells (p = 0.835) and tetanus antibody levels (p = 0.424) at 24 weeks. With leflunomide, significant reduction in memory B cells (p < 0.01) and pneumococcal antibody levels (p < 0.01) occurred without significant changes in B cells (P > 0.05), T cells (P > 0.05) or tetanus antibody levels (P > 0.05). CONCLUSIONS: Leflunomide-methotrexate combination is as efficacious as low-dose rituximab-methotrexate combination at 24 weeks, in RA patient's refractory to initial DMARDs. The high responses seen in both groups have favorable cost implications for patients in developing countries. Changes in immune parameters with leflunomide are novel and need further characterization. TRIAL REGISTRATION: The trial was registered with the Sri Lanka Clinical Trials Registry (SLCTR), a publicly accessible primary registry linked to the registry network of the International Clinical Trials Registry Platform of the WHO (WHO-ICTRP) (registration number: SLCTR/2008/008 dated 16th May 2008).
29148403 Treatment patterns in rheumatoid arthritis after discontinuation of methotrexate: data fro 2018 Mar OBJECTIVES: In active rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX), guidelines support adding or switching to another conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) and/or a biologic DMARD (bDMARD). The purpose of this analysis was to describe treatment practices in routine care and to evaluate determinants of regimen selection after MTX discontinuation. METHODS: Biologic-naïve patients in the Ontario Best Practice Research Initiatives registry discontinuing MTX due to primary/secondary failure, adverse events, or patient/physician decision were included. RESULTS: Of 313 patients discontinuing MTX, 102 (32.6%) were on MTX monotherapy, 156 (49.8%) on double, and 55 (17.6%) on multiple csDMARDs. Patients on MTX monotherapy were older than patients on double or multiple csDMARDs (p=0.013), less likely to have joint erosions (p=0.009) and had lower patient global assessment (p=0.046) at MTX discontinuation. Post-MTX discontinuation, 169 (54.0%) transitioned to, or added new DMARD(s) (new csDMARD(s): 139 [44.4%]; bDMARD: 30 [9.6%]), and 144 (46.0%) opted for no new DMARD treatment. Patients on MTX monotherapy transitioning monotherapy, whereas patients on combination csDMARDs switched more to new csDMARDs and bDMARD combination therapy. Early RA (adjOR [95%CI]: 3.07 [1.40-6.72]) and treatment with multiple csDMARDs vs. MTX monotherapy (4.15 [1.35-12.8]) at MTX discontinuation were significant predictors of transitioning to or adding new csDMARD(s)/bDMARD treatment versus opting for no new DMARD treatment. CONCLUSIONS: Differences in subsequent treatment patterns exist between patients discontinuing MTX when used as monotherapy versus in combination with other csDMARDs where the former are more likely to use a subsequent monotherapy treatment.
28847766 Identification of a transitional fibroblast function in very early rheumatoid arthritis. 2017 Dec OBJECTIVES: Synovial fibroblasts actively regulate the inflammatory infiltrate by communicating with neighbouring endothelial cells (EC). Surprisingly, little is known about how the development of rheumatoid arthritis (RA) alters these immunomodulatory properties. We examined the effects of phase of RA and disease outcome (resolving vs persistence) on fibroblast crosstalk with EC and regulation of lymphocyte recruitment. METHODS: Fibroblasts were isolated from patients without synovitis, with resolving arthritis, very early RA (VeRA; symptom ≤12 weeks) and established RA undergoing joint replacement (JRep) surgery. Endothelial-fibroblast cocultures were formed on opposite sides of porous filters. Lymphocyte adhesion from flow, secretion of soluble mediators and interleukin 6 (IL-6) signalling were assessed. RESULTS: Fibroblasts from non-inflamed and resolving arthritis were immunosuppressive, inhibiting lymphocyte recruitment to cytokine-treated endothelium. This effect was lost very early in the development of RA, such that fibroblasts no longer suppressed recruitment. Changes in IL-6 and transforming growth factor beta 1 (TGF-β(1)) signalling appeared critical for the loss of the immunosuppressive phenotype. In the absence of exogenous cytokines, JRep, but not VeRA, fibroblasts activated endothelium to support lymphocyte. CONCLUSIONS: In RA, fibroblasts undergo two distinct changes in function: first a loss of immunosuppressive responses early in disease development, followed by the later acquisition of a stimulatory phenotype. Fibroblasts exhibit a transitional functional phenotype during the first 3 months of symptoms that contributes to the accumulation of persistent infiltrates. Finally, the role of IL-6 and TGF-β(1) changes from immunosuppressive in resolving arthritis to stimulatory very early in the development of RA. Early interventions targeting 'pathogenic' fibroblasts may be required in order to restore protective regulatory processes.
27550190 Subsidence of total ankle component associated with deterioration of an ankle scale in non 2017 May OBJECTIVES: Modern three-component total ankle arthroplasty (TAA) has favorable clinical results and survival rates. However, radiographic deterioration and worsening of clinical symptoms may occur in patients with rheumatoid arthritis (RA) or non-inflammatory arthritis (NA). The associations between outcomes and clinical and radiological factors are not clear. We compared midterm clinical and radiographic outcomes after TAA between patients with RA and those with NA. METHODS: Twenty-six TAAs were performed using a three-component prosthesis, the FINE Total Ankle System during the study period. Fourteen TAAs with 11 RA patients undergoing primary TAA were compared with twelve TAAs with 12 NA patients. Clinical and radiographic outcomes were evaluated before and after operation, and at the final follow-up. RESULTS: The Japanese Society for Surgery of the Foot (JSSF) scale improved significantly following TAA in both groups (p = 0.0039 and 0.0156, respectively). Tibial subsidence, talar subsidence and age were significantly associated with postoperative JSSF score only in the NA group (p = 0.0027, 0.0017 and p < 0.0001, respectively). Stepwise regression analysis showed that talar subsidence was an independent predictor of a worse JSSF score in the NA group (F = 10.3). CONCLUSIONS: The final clinical outcome was negatively influenced by talar subsidence in patients with NA, but not in those with RA.
29093249 [Clinical effect of tocilizumab on patients with severe active rheumatoid arthritis]. 2017 Oct 28 To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).
 Methods: Twelve patients with severe refractory RA were treated with tocilizumab. The clinical and laboratory indices and the side effects were recorded after treatment.
 Results: The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients, which were significantly improved after TCZ therapy (P<0.05), and no obvious adverse reactions were found.
 Conclusion: Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.
28125360 Monitoring total-body inflammation and damage in joints and entheses: the first follow-up 2017 Jul OBJECTIVE: To investigate changes in whole-body magnetic resonance imaging (WBMRI) inflammatory and structural lesions in most joints and entheses in patients with rheumatoid arthritis (RA) treated with adalimumab. METHODS: WBMRI was obtained at weeks 0, 6, 16, and 52 in a 52 week follow-up study of 37 RA patients starting treatment with adalimumab. Readability and reliability of WBMRI were investigated for 76 peripheral joints, 23 discovertebral units, the sacroiliac joints, and 33 entheses. Changes in WBMRI joint and entheses counts were investigated. RESULTS: The readability of peripheral and axial joints was 82-100%, being less for elbows and small joints of the feet. For entheses, 72-100% were readable, except for entheses at the anterior chest wall, elbow, knee, and plantar fascia. The intrareader agreement was high for bone marrow oedema (BMO), bone erosion (80-100%), and enthesitis (77-100%), and slightly lower for synovitis and soft tissue inflammation (50-100%). All synovitis, BMO, and soft tissue inflammation counts decreased numerically during treatment. The 26-joint synovitis WBMRI count decreased significantly during the first 16 weeks for patients with a good European League Against Rheumatism (EULAR) response (from median 6 to 4, p < 0.05), but not for patients with a moderate or no EULAR response. There were no overall changes in structural lesions. CONCLUSIONS: WBMRI allows simultaneous monitoring of most axial and peripheral joints and entheses in RA patients and can visualize a decrease in inflammatory counts during treatment. This first WBMRI follow-up study of patients with RA encourages further investigation of the usefulness of WBMRI in RA.
28202742 Invalidation in Patients with Rheumatic Diseases: Clinical and Psychological Framework. 2017 Apr OBJECTIVE: The term "invalidation" refers to the patients' perception that their medical condition is not recognized by the social environment. Invalidation can be a major issue in patients' lives, adding a significant burden to symptoms and limitations while increasing the risk of physical and psychological disability. In this study in patients with rheumatic diseases, we investigated the relationship between invalidation and sociodemographic, clinical, psychological, and personality characteristics. METHODS: This international cross-sectional study included 562 adults with rheumatoid arthritis (n = 124), spondyloarthritis (n = 85), systemic lupus erythematosus (n = 112), or fibromyalgia (FM; n = 241). Assessed were the family and health professionals subscales of the Illness Invalidation Inventory (3*I), happiness (Subjective Happiness Scale), personality (Ten-Item Personality Inventory), pain, and loneliness (numerical rating scales). Univariate and multivariate analyses were used to test different models. RESULTS: Invalidation occurred in all rheumatic diseases, but patients with FM reported the most invalidation. Including all correlated variables in the multivariate model, pain remained as a determinant of invalidation by health professionals, but not by family. Regarding psychological variables, loneliness remained as a determinant of invalidation by family, but not by health professionals. FM and low levels of happiness, agreeableness, and conscientiousness were associated with invalidation while taking account of other variables. CONCLUSION: Invalidation occurs in all rheumatic diseases and patients with FM experience the most invalidation. Psychological factors (happiness, agreeableness, and conscientiousness), loneliness, and pain intensity are associated with invalidation, irrespective of the rheumatic disease and may deserve dedicated interventions.
28421864 Selfie: Autoimmunity, boon or bane. 2017 The immune system provides protection to tissues damaged by infectious microrganisms or physical damage. In autoimmune diseases, the immune system recognizes and attacks its own tissues, i.e., self-destruction. Various agents such as genetic factors and environmental triggers are thought to play a major role in the development of autoimmune diseases. A common feature of all autoimmune diseases is the presence of autoantibodies and inflammation, including mononuclear phagocytes, autoreactive T lymphocytes, and autoantibody producing B cells (plasma cells). It has long been known that B cells produce autoantibodies and, thereby, contribute to the pathogenesis of many autoimmune diseases. Autoimmune diseases can be classified as organ-specific or non-organ specific depending on whether the autoimmune response is directed against a particular tissue or against widespread antigens as in chronic inflammatory autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Both SLE and RA are characterized by the presence of autoantibodies which play a major role in their etiopathogenesis. SLE is characterized by circulating antibodies and immune complex deposition that can trigger an inflammatory damage in organs. RA is a progressive inflammatory disease in which T cells, B cells, and pro-inflammatory cytokines play a key role in its pathophysiology.
27426444 NETosis: At the crossroads of rheumatoid arthritis, lupus, and vasculitis. 2017 May Suicidal NETosis differs from other mechanisms of cell death by the release of a lattice, composed of DNA associated with proteins citrullinated by protein-arginine deiminase 4, from neutrophils. These 'NETs' are composed of granule-derived proteins with microbicidal activity. A similar type of release occurs during vital NETosis, in which anuclear neutrophils maintain their chemotactic ability and imprison live bacteria, even after NET extrusion. Mitochondrial NETosis is limited to the expulsion of oxidised mitochondrial DNA and cytoplasmic enzymes. NETs include the targets of most autoantibodies found in rheumatoid arthritis, lupus, and vasculitis. The clinical and biological overlaps sometimes observed between bronchectiasis and RA, RA and SLE, or SLE and vasculitis, implicate NETosis as a major triggering event common to these disorders. NETosis increases the possibility of association between autoantigens and infectious antigens in mucosal biofilms, impairing the clearance of pathogens and possibly triggering autoimmune reactions. NETosis aggravates these three conditions and increases endothelial damage and the risk of thrombosis. However, the pathogenesis of RA, SLE, and vasculitis is not confined to autoantibodies against NET components, and other mechanisms have been suggested to explain the breakdown of tolerance to NET autoantigens, such as hypercitrullination. The question of whether continuous presentation of autoantigens mixed with antigens from dormant intracellular pathogens (released following suicidal, vital, or mitochondrial NETosis) is required to induce and sustain autoimmunity must be addressed. Inhibiting NETois may not be sufficient to improve autoimmune disorders whereas such latent infections remain uncontrolled.
28693000 A New Active Contours Approach for Finger Extensor Tendon Segmentation in Ultrasound Image 2018 Jul This work proposes a new approach for the segmentation of the extensor tendon in ultrasound images of the second metacarpophalangeal joint (MCPJ). The MCPJ is known to be frequently involved in early stages of rheumatic diseases like rheumatoid arthritis. The early detection and follow up of these diseases is important to start and adapt the treatments properly and, in that way, preventing irreversible damage of the joints. This work relies on an active contours framework, preceded by a phase symmetry preprocessing and with prior knowledge energies, to automatically identify the extensor tendon. Active contours methods are widely used in ultrasound images because of their robustness to speckle noise and ability to join unconnected smaller regions into a coherent shape. The tendon is formulated as a line so open ended active contours were used. Phase symmetry highlights the tendon, by setting a proper scale range and angle span. The distance between structures and the tendon slope were also included to enforce the model based on anatomical characteristics. And finally, the concavity measures were used because, given the anatomy of the finger, we know that the tendon line should have less than two concavities. To solve the active contours energy minimization a genetic algorithm approach was used. Several energy metric configurations were compared using the modified Hausdorff distance and results showed that this segmentation is not only possible, but exhibits errors smaller than 0.5 mm with a confidence of 95% with the phase symmetry preprocessing and energies based on the line neighborhood, area ratio, slope, and concavity measurements.
29151514 Dermatomyositis Complicated by Digital Ischemia and Lung Adenocarcinoma in a Patient with 2018 Mar 15 A 58-year-old Japanese woman was diagnosed with anti-signal recognition particle (SRP)-positive dermatomyositis associated with Sjögren's syndrome, rheumatoid arthritis and lung adenocarcinoma. She presented with cutaneous lesions, including ulceration of her right middle finger. Tissue specimens obtained from her right deltoid muscle were positive for CD4(+) T-cell infiltration and the sarcolemma showed the upregulation of major histocompatibility complex (MHC) class I antigens. The present case suggests that overlapping autoimmune diseases or complications of malignancy may result in an atypical clinical presentations and histological findings in patients with anti-SRP antibody-positive dermatomyositis.
28472221 Role of citrullination modification catalyzed by peptidylarginine deiminase 4 in gene tran 2017 Jul 1 Peptidylarginine deiminase 4 (PADI4), a new histone modification enzyme, which converts both arginine and monomethyl-arginine to citrulline, has gained massive attention in recent years as a potential regulator of gene transcription. Recent studies have shown that arginine residues R2, R8, R17, and R26 in the H3 tail and R3 in the H4 tail can be deiminated by PADI4. This kind of histone post-translational modification has the potential to antagonize histone methylation and coordinate with histone deacetylation to regulate gene transcription. PADI4 also deiminates non-histone proteins, such as p300, NPM1, ING4, RPS2, and DNMT3A. PADI4 has been shown to involve in cell apoptosis and differentiation. Moreover, PADI4 can interact with tumor suppressor p53 and regulate the transcriptional activity of p53. Dysregulation of PADI4 is implicated in a variety of diseases, including rheumatoid arthritis, tumor development, and multiple sclerosis. A wide variety of PADI4 inhibitors have been identified. Further understanding of PADI4 functions may lead to novel diagnostic and therapeutic approaches in these diseases. This review summarizes the recent progress in the study of the regulation mechanism of PADI4 on gene transcription and the major physiological functions of PADI4 in human diseases.
28833034 Rheumatoid arthritis fibroblast-like synoviocytes co-cultured with PBMC increased peripher 2017 Dec 'Circulating' T follicular helper cells (Tfh), characterized by their surface phenotypes CD4(+) chemokine receptor 5 (CXCR5)(+) inducible co-stimulatory molecule (ICOS)(+) , have been identified as the CD4(+) T cell subset specialized in supporting the activation, expansion and differentiation of B cells. Fibroblast-like synoviocytes (FLS) are critical in promoting inflammation and cartilage destruction in rheumatoid arthritis (RA), and the interaction between FLS and T cells is considered to facilitate FLS activation and T cell recruitment. However, it remains unknown whether RA-FLS co-cultured with activated peripheral blood mononuclear cells (PBMC) has immunoregulatory effects on peripheral Tfh. In the present study, we co-cultured RA-FLS with or without anti-CD3/CD28-stimulated PBMC. The results showed that RA-FLS co-cultured with stimulated PBMC could increase the numbers of CD4(+) CXCR5(+) ICOS(+) T cells of RA PBMC possibly via the production of interleukin (IL)-6, a critical cytokine involved in the differentiation of Tfh cells. We also observed increased reactive oxygen species (ROS) levels in the co-culture system of RA-FLS and PBMC. The percentage of CD4(+) CXCR5(+) ICOS(+) T cells was decreased when ROS production was inhibited by N-acetyl-L-cysteine (NAC), a specific inhibitor which can decrease ROS production. In addition, we showed that the higher levels of tumour necrosis factor (TNF)-α and IL-1β in the co-culture system and the blocking of TNF receptor 2 (TNF-R2) and IL-1β receptor (IL-1βR) both decreased the numbers of CD4(+) CXCR5(+) ICOS(+) T cells. Our study reveals a novel mechanistic insight into how the interaction of RA-FLS and PBMC participates in the RA pathogenesis, and also provides support for the biologicals application for RA.
28850029 Liver safety of non-tumour necrosis factor inhibitors in rheumatic patients with past hepa 2018 Jan OBJECTIVES: The risk of hepatitis B virus (HBV) reactivation with non-tumour necrosis factor inhibitor (non-TNFi) biologic agents in patients with rheumatic diseases and past HBV infection has not been definively elucidated. We assessed the comparative safety of non-TNFi and TNFi biologic agents in such patients in real-life clinical settings. METGODS: We carried out a retrospective cohort study from the Department of Rheumatology, University Hospital of Heraklion. Patients who received abatacept (ABA), tocilizumab (TCZ) or rituximab (RTX) during the period 2003-2016 and were HbsAg(-), anti-HBc(+), anti-HBs(±) at baseline, were monitored for HBV reactivation. Patients treated with TNFi agents during the same period were used as a control group. RESULTS: 101 cases of non-TNFi (39 ABA, 32 RTX and 30 TCZ) and 111 cases of TNFi treatment were identified. In non-TNFi, 76 cases (75.2%) were anti-HBc(+)/anti-HBs(+) and 25 (24.8%) were anti-HBc(+)/anti-HBs(-), as compared to 82 (73.9%) and 29 (26.1%) in TNFi-treated, respectively. After a median (IQR) observation of 24.0 (34.7) months, two cases (2.0%) of HBV reactivation were identified in the non-TNFi group; one with ABA, successfully treated with entecavir, and one fatal case with RTX and prior exposure to cyclophosphamide. No reactivation was observed in the TNFi group (p=0.226 vs. non-TNFi). Αnti-HBs titres were significantly reduced compared to baseline in the non-TNFi group [median (IQR) 203.9 (954.7) mIU/ml before treatment versus 144.9 (962.9) mIU/ml after treatment, p=0.03]. CONCLUSIONS: Two cases of HBV reactivation highlight the risk for this complication in patients with past HBV infection under biologic therapy.
28375195 Risk factors for late deep infection after total hip arthroplasty in patients with rheumat 2017 Apr OBJECTIVE: Postoperative infections, a serious complication of orthopedic surgery, occur 2-4 times more frequently in patients with rheumatoid arthritis (RA) without adjustment for medication. Some studies have demonstrated a similar risk of postoperative infection following orthopedic surgery regardless of whether patients underwent tumor necrosis factor-α (TNF-α) inhibitor therapy; however, other studies have reported a higher risk with TNF-α inhibitor use. However, few reports have focused on the correlation between TNF-α inhibitor use and postoperative late infection. Therefore, we investigated the correlation between TNF-α inhibitor therapy and serious postoperative late infection in patients with RA who underwent total hip arthroplasty (THA). METHODS: Ninety-nine patients with RA who were enrolled in our institution's and Konan Kakogawa Hospital's THA registry between January 2003 and December 2012 were eligible to participate. Data collected included clinical parameters and medications, including biological drugs, disease-modifying antirheumatic drugs, and glucocorticoids. Logistic regression analysis was performed to examine the association between clinical parameters, medications, and the development of postoperative late infection. RESULTS: One risk factor was identified in the multivariate analysis. TNF inhibitor therapy was found to be significantly associated with the development of late infection after THA (biological drugs: OR: 9.5, 95% CI: 1.0-88.8; TNF inhibitor: OR: 11.7, 95% CI: 1.2-109.7). CONCLUSION: Biological drug therapy, especially TNF inhibitors, may be associated with an increased rate of late deep infection after THA. When the use of TNF-α inhibitor therapy is considered, rheumatologists must be attentive to patients after THA.
29103482 Quantitative evaluation of knee cartilage and meniscus destruction in patients with rheuma 2017 Nov OBJECTIVE: To calculate T1ρ and T2 values of articular cartilage and menisci in knee joints of patients with RA, and compare the values between RA patients and healthy volunteers, to gain insight into the pathogenesis of cartilage and meniscus degradation in patients with RA. MATERIALS AND METHODS: Nine patients with RA and knee joints symptoms were enrolled in the study, twenty healthy volunteers without knee joint diseases were included as controls. Sagittal fat-saturated T1ρ and T2 mapping images were obtained on a 3T MR scanner (GE750, GE Healthcare, Waukesha, WI), using a dedicated 8-channel knee coil. In the T1rho mapping sequence, the amplitude of the spin-lock pulse was 500Hz, spin lock durations=10/20/30/50ms. In the T2 mapping sequence,TR/TE were 1794/6.5, 13.4, 27, 40.7ms. Both sequences were performed with the following parameters: flip angle (FA)=90°, matrix: 320×256, FOV: 16×16cm(2), slice thickness: 3mm, bandwidth: 62.5kHZ, and a total scan time of 5:11min. T1ρ- and T2-mapping images were used for the segmentation of the articular cartilage of the patella, femoral trochlea, medial and lateral femoral condyle, medial and lateral tibial plateau. These images were also used for the segmentation of the anterior and posterior horns of the medial and lateral menisci with livewire semi-automatic segmentation algorithm of MATLAB. A Mann-Whitney U test was performed to compare the T1ρ and T2 values of the above mentioned regions between the two groups. RESULTS: T1ρ (Z=-3.913 to -2.121, P=0.000-0.034) and T2 (Z=-3.866 to -2.216, P=0.000-0.026) values of knee cartilage in patients with RA were higher than that in healthy volunteers, except the cartilage of the patella (T1ρ: Z=-1.273, P=0.203,T2: Z=-0.236, P=0.814) and lateral tibial plateau (T1ρ:Z=-1.037, P=0.317). The T1ρ (Z=-1.462 to 0.572, P=0.095-0.908) and T2 (Z=-1.461 to 0.278, P=0.153-0.764) values of medial and lateral menisci showed no difference between the two groups. CONCLUSION: Patients with RA exhibit diffuse knee cartilage destruction in the medial and lateral tibiofemoral joints and in the femoral trochlea. However, we found no increase in T1ρ and T2 values in menisci, this finding warrants further investigation.
29303710 Vaccinations in adults with rheumatoid arthritis in an era of new disease-modifying anti-r 2018 Mar Patients with rheumatoid arthritis are at greater risk of infectious morbidity and mortality due to disease-related abnormalities and use of immunosuppressive medications. Vaccinations are recommended by international guidelines among infection control strategies, but vaccination rates are reported to be still suboptimal in both America and Europe. Furthermore, with the increasing number of immunomodulatory medications used in RA patients, safety and efficacy of vaccinations in RA patients on such therapies have been questioned. This paper reviews current data about the safety of the most relevant vaccinations for RA adult patients and on the extent to which RA treatment can affect vaccine efficacy. Although it is recognised that immunological and pathological reactions can occur following vaccination, especially in genetically susceptible hosts, early data in RA patients under treatment with bDMARDs or tsDMARDs indicate that vaccines might be safer in the setting of immunosuppression than previously thought. Reviewing safety and immunogenicity data about influenza, pneumococcal, HZ, HPV, and HBV vaccines, we here try to summarise updated, practical suggestions for rheumatologists. Improving the knowledge of the vaccination practice both in patients and physicians is of crucial importance. In RA patients, vaccination status should be assessed in the initial patients' work-up and vaccination strategies should be planned and then implemented ideally during stable disease, as recommended by international guidelines.