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ID PMID Title PublicationDate abstract
29984996 High-Throughput Signal-On Photoelectrochemical Immunoassay of Lysozyme Based on Hole-Trapp 2018 Aug 24 A unique split-type photoelectrochemical (PEC) immunoassay has been constructed for detection of low-abundance biocompounds (lysozyme, Lyz, used in this case) via a new trigger strategy by disintegrating bioconjugates of dopamine-grafted silica nanospheres (DA@SiO(2)NSs) for signal amplification. The preferred electron donor assembly of DA@SiO(2)NSs is first used as a molecular printboard for positioning anti-Lyz secondary antibody (Ab(2)) through an amide reaction. With specific immunoreactions in a high-binding microplate, a sandwich immunoassay, the DA@SiO(2)NSs-based bioconjugate is achieved. By initiating the disintegration of the bioconjugates via acid etching, numerous electron donors of DA are released, thus efficiently triggering hole-trapping with amplified signals obtained. The smart integration of ZnIn(2)S(4)-based heterojunctions as photoactive material, a split-type detection mode, and a new trigger strategy by disintegrating the DA@SiO(2)NSs-based bioconjugate offer an attractive high-throughput signal-on PEC immunoassay for detection of Lyz. Such an unusual PEC sensor exhibits an outstanding linear response to the concentration in the range between 0.002 and 500 ng mL(-1), and the detection limit is as low as 0.6 ppt ( S/ N = 3). The as-fabricated assay is cost-effective and sensitive. It has been successfully used for measuring Lyz in real samples, which demonstrates great promise for practical applications.
29476078 Single-cell RNA-seq of rheumatoid arthritis synovial tissue using low-cost microfluidic in 2018 Feb 23 Droplet-based single-cell RNA-seq has emerged as a powerful technique for massively parallel cellular profiling. While this approach offers the exciting promise to deconvolute cellular heterogeneity in diseased tissues, the lack of cost-effective and user-friendly instrumentation has hindered widespread adoption of droplet microfluidic techniques. To address this, we developed a 3D-printed, low-cost droplet microfluidic control instrument and deploy it in a clinical environment to perform single-cell transcriptome profiling of disaggregated synovial tissue from five rheumatoid arthritis patients. We sequence 20,387 single cells revealing 13 transcriptomically distinct clusters. These encompass an unsupervised draft atlas of the autoimmune infiltrate that contribute to disease biology. Additionally, we identify previously uncharacterized fibroblast subpopulations and discern their spatial location within the synovium. We envision that this instrument will have broad utility in both research and clinical settings, enabling low-cost and routine application of microfluidic techniques.
29844438 Association of a rare variant of the TNFSF13B gene with susceptibility to Rheumatoid Arthr 2018 May 29 A rare variant (BAFF-var) of the tumor necrosis factor superfamily 13b (TNFSF13B) gene has been recently associated with multiple sclerosis (MS) and systemic lupus erythematosus (SLE). The aim of this study was to investigate the association between TNFSF13B BAFF-var and susceptibility to rheumatoid arthritis (RA) and replicate that association in SLE. 6,218 RA patients, 2,575 SLE patients and 4,403 healthy controls from three different countries were included in the study. TNFSF13B BAFF-var was genotyped using TaqMan allelic discrimination assay. PLINK software was used for statistical analyses. TNFSF13B BAFF-var was significantly associated with RA (p = 0.015, OR = 1.21, 95% CI = 1.03-1.41) in the Spanish cohort. A trend of association was observed in the Dutch (p = 0.115) and German (p = 0.228) RA cohorts. A meta-analysis of the three RA cohorts included in this study revealed a statistically significant association (p = 0.002, OR = 1.24, 95% CI = 1.10-1.38). In addition, TNFSF13B BAFF-var was significantly associated with SLE in the Spanish (p = 0.001, OR = 1.41, 95% CI = 1.14-1.74) and the German cohorts (p = 0.030, OR = 1.86, 95% CI = 1.05-3.28), with a statistically significant p-value obtained in the meta-analysis (p = 0.0002, OR = 1.46, 95% CI = 1.09-2.32). The results obtained confirm the known association of TNFSF13B BAFF-var with SLE and, for the first time, demonstrate that this variant contributes to susceptibility to RA.
30016691 Macroscopic investigation of failed Kudo type 5 total elbow arthroplasty. 2018 Aug BACKGROUND: On the basis of the intra-articular findings during Kudo type 5 elbow prosthesis revision surgery, we infer the mechanisms leading to implant failure. MATERIALS AND METHODS: We performed primary Kudo type 5 total elbow arthroplasty on 60 rheumatoid elbows in 45 patients between 1994 and 2003. Revision surgery was performed in 8 patients (9 elbows) because of implant failure. We radiographically assessed their status before this surgical procedure and then assessed the surgical intra-articular findings based on surgery records and photographs. RESULTS: In all cases, revision surgery was necessitated by failure of the ulnar component. There were 2 types of implant failure: fracture of the ulnar component neck (n = 3) and loosening of the ulnar component (n = 6). In the latter group, 2 elbows exhibited valgus deformity of the retrieved ulnar component. There were no cases of metallosis or wear of the articular surface. CONCLUSION: This study describes the types of implant failure in unlinked Kudo type 5 total elbow arthroplasties with all-polyethylene ulnar components based on the intra-articular findings. Failure of the all-polyethylene ulnar component could have been caused by ulnar neck distortion that occurred prior to polyethylene wear on the joint surface. In addition, valgus stress on the elbow joint may have contributed to these implant failures.
30160204 A cross sectional study of bone and cartilage biomarkers: correlation with structural dama 2018 Dec The aim of our study was to assess the relationship between bone and cartilage remodeling biomarkers and joint damage in Rheumatoid Arthritis (RA), and to detect whether they have the capacity to predict the progression of joint disease assessment by computed tomography (CT) erosion score. We analyzed 65 female patients with established RA in our Rheumatology Department. Serum levels of bone and cartilage markers were measured: osteocalcin (OC), N-propeptide of type I collagen (PINP), collagen type I and II, C-telopeptide (CTX I, CTX-II) and cartilage oligomeric matrix protein (COMP). Radiography of both wrist and MCP joints were available. Two expert-readers independently scored articular damage and progression using the High-resolution low dose CT scan in a blinded fashion. 65 female patients with established RA with a median age of 44 years were included. The median disease-duration was two years and the median (Disease activity score) DAS 28 score at 4.46 [2.65-7.36]. The percentage of patient with low disease activity was 13.8%, while 55.4 and 30.8% for those with moderate and high disease activity respectively. The resorption bone markers were high in active versus non-active RA. Wrist and MCP erosion scores were also associated with RA activity. Our study shows that biomarkers of bone and cartilage collagen breakdown were related to specific joint erosion in RA and could predict subsequent radiographic damage in RA. Further larger scale longitudinal studies maybe needed to confirm our data.
30185379 Efficacy and safety of biological agents in the older rheumatoid arthritis patients compar 2019 Apr OBJECTIVE: Biologic anti-rheumatic drugs are used with less frequency among older patients compared to young patients. This population is less represented in studies performed to evaluate the efficacy and safety of this drugs. We aimed to assess the efficacy and safety of biological agents between the older RA patients compared to young. METHODS: A comprehensive, systematic search was conducted in major indexing databases using key terms for RA and each biological agent. The review process was completed by 2 investigators. Both randomized controlled trials and observational studies of at least 6-month duration conducted in adult RA patients were included. Outcomes of interest were clinical efficacy and safety. Effect-estimates were pooled using random-effects modeling if 4 or more studies used the same scale and time-frame for measuring outcomes. RESULTS: 24 studies (16 focusing on anti-TNF agents) representing 63,705 patients (24% were older) were included. Older RA patients had worse baseline RA disease activity, longer disease duration at the time of enrollment in the trial (14.4 ± 3.6 vs. 10.9 ± 3.6 years; p < 0.001) and higher steroid use (73.2 vs. 64.7%, p < 0.001) than younger. 5 out of 6 studies assessing anti-TNF agents showed worse efficacy outcomes in older patients. The pooled OR of infection and ADRs with anti-TNF agents in older compared to young RA patients was OR 1.59 (95% CI: 1.45-1.76) and 1.40 (95% CI: 1.23-1.61) respectively. CONCLUSIONS: Older patients had worse safety and efficacy with biological agents but also had worse baseline disease activity. There was significant heterogeneity in reporting outcomes and very limited studies in biological agents other than anti-TNF drugs.
29737455 Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neopla 2018 Aug The process of finding new therapeutic indications for currently used drugs, defined as 'repurposing', is receiving growing attention. Chloroquine and hydroxychloroquine, with an original indication to prevent or cure malaria, have been successfully used to treat several infectious (HIV, Q fever, Whipple's disease, fungal infections), rheumatological (systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, Sjögren's syndrome), and other immunological diseases. Indeed, they have anti-inflammatory, immunomodulating, anti-infective, antithrombotic, and metabolic effects. Among the biological effects of chloroquine and hydroxychloroquine, it is important to highlight their antitumoral properties, likely due to their strong antiproliferative, antimutagenic, and inhibiting autophagy capacities. These effects make these drugs a possible option in the treatment of several tumors in association with radiotherapy and chemotherapy. Finally, the repurposing of chloroquine and hydroxychloroquine is currently being examined for neurological diseases such as neurosarcoidosis, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to corticosteroids, and primary progressive multiple sclerosis. Several ongoing clinical trials have been testing these drugs in non-neoplastic and neoplastic diseases. Moreover, the well-demonstrated good tolerability of chloroquine and hydroxychloroquine make them safe even during pregnancy. Gastrointestinal and cutaneous manifestations are considered not to be serious, while retinal, neuromuscular, and cardiac toxicities are classified as serious adverse events.
29673088 Is Perceived Growth Associated with Momentary Indicators of Health and Well-Being in Peopl 2018 Jul BACKGROUND: Perceived growth (PG) refers to perceptions of positive changes that unfold over time after experiencing trauma. Higher PG is often associated with positive long-term health, but the processes through which PG may influence health are unclear. The present study examines two potential pathways among individuals living with asthma or RA: (1) by promoting momentary indicators of health and well-being in everyday life, and (2) by buffering against stress. METHOD: In a micro-longitudinal design, 128 participants with asthma (n = 97) or rheumatoid arthritis (n = 31) reported perceived growth using the Post-Traumatic Growth (PTG) Inventory and subsequently completed ecological momentary assessments (EMAs) for one week. Participants were signaled five times a day to report on health-related indicators, including affect, disease interference, social interactions, and stress. RESULTS: Multilevel modeling revealed that higher PTG was associated with significantly less negative affect and greater positive affect in everyday life. There were no significant associations between PTG and momentary disease interference, pleasantness of social interactions, or stress, nor evidence that PTG buffered against effects of stress on health-related outcomes. CONCLUSIONS: This research highlights the utility of examining PG in everyday life. Results suggest that closer examination of momentary affect as a process by which PG may facilitate positive health outcomes is warranted.
30487323 [Secondary osteoporosis. Bone metabolic disorder in Rheumatoid arthritis.]. 2018 Rheumatoid arthritis(RA)is an immune-mediated disease marked by chronic synovial inflammation, which leads to cartilage and bone destruction as well as systemic bone loss. Osteoporosis or the systemic bone loss associated with RA increases the risk for fragility fractures, which can affect quality of life dramatically in RA patients. Inflammatory cytokines such as TNF and IL-6 in inflamed synovium induce the differentiation of osteoclasts, while suppresses the differentiation of osteoblasts, resulting in imbalance in bone metabolism. Although RA treatment targeting inflammatory cytokines can deter the progression of cartilage and bone destruction directly or indirectly, it can not stop systemic osteoporosis. Although it is important to avoid immobility by introducing an early remission, it is necessary to thoroughly manage the risks of individuals of RA patients and to effectively use osteoporosis drugs such as anti-RANKL antibodies that also have the effect of suppressing bone erosion in RA.
29228301 Targeted inhibition of Janus kinases abates interfon gamma-induced invasive behaviour of f 2018 Mar 1 OBJECTIVES: The aim was to explore the function of the T-cell cytokine IFNγ for mesenchymal tissue remodelling in RA and to determine whether IFNγ signalling controls the invasive potential of fibroblast-like synoviocytes (FLS). METHODS: To assess architectural responses, FLS were cultured in three-dimensional micromasses. FLS motility was analysed in migration and invasion assays. Signalling events relevant to cellular motility were defined by western blots. Baricitinib and small interfering RNA pools were used to suppress Janus kinase (JAK) functions. RESULTS: Histological analyses of micromasses revealed unique effects of IFNγ on FLS shape and tissue organization. This was consistent with accelerated migration upon IFNγ stimulation. Given that cell shape and cell motility are under the control of the focal adhesion kinase (FAK), we next analysed its activity. Indeed, IFNγ stimulation induced the phosphorylation of FAK-Y925, a phosphosite implicated in FAK-mediated cell migration. Small interfering RNA knockdown of JAK2, but not JAK1, substantially abrogated FAK activation by IFNγ. Correspondingly, IFNγ-induced FAK activation and invasion of FLS was abrogated by the JAK inhibitor, baricitinib. CONCLUSION: Our study contributes insight into the synovial response to IFNγ and reveals JAK2 as a potential therapeutic target for FLS-mediated joint destruction in arthritis, especially in RA.
29525846 Evaluation of work disability in Japanese patients with rheumatoid arthritis: from the TOM 2018 Jul To evaluate work disability and associated factors in patients with rheumatoid arthritis (RA) who participated in the TOMORROW study, a 10-year cohort study in Japan. Subjects in this cross-sectional analysis comprised 191 RA patients and 191 age- and sex-matched non-RA individuals. Work-related outcomes were measured using the Work Productivity and Activity Impairment questionnaire by employment status (full-time worker (FTW), employed ≥ 35 h/week; part-time worker (PTW), < 35 h/week; home worker (HW), non-employed). In addition, we assessed the EuroQol-5 Dimensions (EQ-5D) and Health Assessment Questionnaire (HAQ) to evaluate quality of life and activities of daily living. No significant differences were evident between groups in percentages of participants in each employment status (p = 0.11), percentages of absenteeism (FTW, p = 1.00; PTW, p = 0.29), presenteeism (FTW, p = 0.23; PTW, p = 0.54), overall work impairment (FTW, p = 0.23; PTW, p = 0.73), or percentage of activity impairment (AI) (FTW, p = 0.62; PTW, p = 0.60). In the HW group, percentage of AI was higher in RA patients than that in non-RA patients (p < 0.01). Among RA patients, HW showed lower EQ-5D and higher HAQ than FTW or PTW (p < 0.001 each). Higher disease activity was observed in HW than FTW (p < 0.01). In terms of the effect of biological disease-modifying anti-rheumatic drugs, no significant differences in work-related outcomes, health status, or daily activity were evident between users and non-users. No significant differences in employment status or work impairment were seen between RA and non-RA groups among paid workers. HW with RA showed more impaired daily activity and higher disease activity compared to working RA patients. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry: UMIN000003876 . Registered 1 Jun 2010.
29264637 Outcomes after rheumatoid arthritis patients complete their participation in a long-term o 2018 Apr To describe disease activity and disability during the first year of follow-up, from rheumatoid arthritis (RA) patients who discontinue tofacitinib after they end participation in a clinical trial. From 2008 to 2016, 36 patients were enrolled in the "Long term follow-up study with tofacitinib (and methotrexate) for RA treatment". At the end of the study, tofacitinib was discontinued and patients were proposed to enter an observational study; 35 agree and had scheduled evaluations at baseline, at 15 and 30 days of follow-up, at month 2 and 3, and thereafter every 3 months. Disease activity was evaluated as per DAS28-ESR and disability as per HAQ. During follow-up, treatment was treat-to-target oriented, only conventional DMARDs were indicated. Descriptive statistics and nonparametric test were used. The study was approved by IRB. Patients were primarily females (N = 34), had median (Q25-75) age of 52 years (45-58), and had received tofacitinib for a median of 7.9 years (6.3-8.3). The proportion of patients with remission and low disease activity decreased from day 30 of follow-up and recovered after 270 days, meanwhile patients with high disease activity increased from 0% at baseline to 6.3% at 1 year. At study entry, 20 patients had remission/low disease activity; during follow-up, 85% deteriorated after (median) 30 days; among them, 23.5% recovered their baseline status after a median of 172.5 days. The HAQ showed a similar behavior, but 66.7% recovered. A substantial proportion of RA patients deteriorated outcomes early after tofacitinib cessation; some patients recovered baseline status with traditional DMARDS.
30289926 Conceptual model for the health technology assessment of current and novel interventions i 2018 The objective of this study was to evaluate current approaches to economic modeling in rheumatoid arthritis (RA) and propose a new conceptual model for evaluation of the cost-effectiveness of RA interventions. We followed recommendations from the International Society of Pharmacoeconomics and Outcomes Research-Society of Medical Decision Making (ISPOR-SMDM) Modeling Good Research Practices Task Force-2. The process involved scoping the decision problem by a working group and drafting a preliminary cost-effectiveness model framework. A systematic literature review (SLR) of existing decision-analytic models was performed and analysis of an RA registry was conducted to inform the structure of the draft conceptual model. Finally, an expert panel was convened to seek input on the draft conceptual model. The proposed conceptual model consists of three separate modules: 1) patient characteristic module, 2) treatment module, and 3) outcome module. Consistent with the scope, the conceptual model proposed six changes to current economic models in RA. These changes proposed are to: 1) use composite measures of disease activity to evaluate treatment response as well as disease progression (at least two measures should be considered, one as the base case and one as a sensitivity analysis); 2) conduct utility mapping based on disease activity measures; 3) incorporate subgroups based on guideline-recommended prognostic factors; 4) integrate realistic treatment patterns based on clinical practice/registry datasets; 5) assimilate outcomes that are not joint related (extra-articular outcomes); and 6) assess mortality based on disease activity. We proposed a conceptual model that incorporates the current understanding of clinical and real-world evidence in RA, as well as of existing modeling assumptions. The proposed model framework was reviewed with experts and could serve as a foundation for developing future cost-effectiveness models in RA.
29409152 Is Rheumatoid Arthritis a Cardiovascular Risk-Equivalent to Diabetes Mellitus? 2018 Nov OBJECTIVE: The 2013 American College of Cardiology/American Heart Association cholesterol treatment guidelines recommend statins for patients with diabetes mellitus ages 40-75 years due to their elevated cardiovascular disease (CVD) risk. We compared the incidence of hospitalized acute myocardial infarction (MI), stroke, and coronary revascularization according to whether patients had diabetes mellitus, rheumatoid arthritis (RA), both, or neither. METHODS: Using 2006-2010 private and public health plan claims, we identified 4 mutually exclusive retrospective cohorts ages >40 years: patients with RA and diabetes mellitus, RA only, diabetes mellitus only, or neither condition. Patients with prevalent CVD were excluded. Outcomes included acute MI and stroke, identified from inpatient discharge diagnosis codes, and coronary revascularization from procedure codes. Across the 4 cohorts, we calculated incidence rates (IRs) of the outcomes, standardized to the 2010 US census age and sex distribution. RESULTS: We identified 920,772 eligible participants. The age- and sex-standardized IRs (per 1,000 person-years) for MI were highest among patients with RA and diabetes mellitus (IR 12.6 [95% confidence interval (95% CI) 10.7-14.7]), followed by patients with diabetes mellitus only (IR 10.7 [95% CI 10.3-11.0]), RA only (IR 5.7 [95% CI 5.2-6.3]), and with neither condition (IR 4.2 [95% CI 4.1-4.3]). CONCLUSION: Findings from the present study suggest that while CVD risk in RA is elevated, it is lower in magnitude compared to the CVD risk associated with diabetes mellitus. Therefore, considering RA a diabetes mellitus risk-equivalent with respect to hyperlipidemia management may not be appropriate.
29997080 Treatment of chronic inflammatory rheumatism by biotherapy in Gabon : eligibility and fol 2018 May 1 OBJECTIVE: to clarify the eligibility criteria for biotherapies in patients with chronic inflammatory rheumatism (CIR) in sub-Saharan Africa and to describe the characteristics of the first 8 patients treated with biotherapy in Gabon. MATERIALS AND METHODS: Patients who responded inadequately to treatments by cDMARDs (EULAR criteria) had a face-to-face interview to inform them about and obtain their consent to biotherapy for at least 3 months, with details of the cost and side effects of each available biotherapy and a certificate of "necessity of biotherapy". The inclusion and follow-up of patients took place in the outpatient rheumatology consultations at the University Hospital of Libreville (Gabon) between January 2010 and December 2016. RESULTS: Of the 30 patients who failed cDMARDs and required biologic treatment, 8 (26.6%) were able to start a biotherapy: 4 men and 4 women with rheumatoid arthritis (n = 4.50%), spondyloarthritis or psoriatic rheumatism (n = 2.25% each). The biotherapy was etanercept (n = 4, 50%), adalimumab, golimumab, infliximab and rituximab (n = 1, 12.5% each). The average duration of the biotherapy was 27.4 months (9-54). Biotherapy was stopped in 4 cases (50%), one each (12.5%) for multifocal tuberculosis, pregnancy, financial reasons, and remission. CONCLUSION: Our study shows that biotherapies, which are currently very expensive, can be prescribed in Africa provided that the usual recommendations are followed strictly. Here, access to biotherapies is only possible through private insurance and the rheumatologist must play the role of facilitator for needy and consenting patients.
29316341 Benefits and Sustainability of a Learning Collaborative for Implementation of Treat-to-Tar 2018 Oct OBJECTIVE: We conducted a 2-phase randomized controlled trial of a learning collaborative to facilitate implementation of treat-to-target (T2T) to manage rheumatoid arthritis (RA). We found substantial improvement in implementation of T2T in phase I. Here, we report on a second 9 months (phase II), where we examined the maintenance of response in phase I and predictors of greater improvement in T2T adherence. METHODS: We recruited patients from 11 rheumatology sites and randomized them to either receive the learning collaborative during phase I or to a wait-list control group that received the learning collaborative intervention during phase II. The outcome was change in T2T implementation score (0-100, where 100 = best) from pre- to postintervention. The T2T implementation score was defined as a percent of components documented in visit notes. Analyses examined the extent to which the phase-I intervention teams sustained improvement in T2T, as well as predictors of T2T improvement. RESULTS: The analysis included 636 RA patients. At baseline, the mean T2T implementation score was 11% in phase I intervention sites and 13% in phase II sites. After the intervention, T2T implementation score improved to 57% in the phase I intervention sites and to 58% in the phase II sites. Intervention sites from phase I sustained the improvement during the phase II (52%). Predictors of greater T2T improvement included having only rheumatologist providers at the site, academic affiliation of the site, having fewer providers per site, and the rheumatologist provider being a trainee. CONCLUSION: Improvement in T2T remained relatively stable over a postintervention period.
29043871 A review of sarilumab for the treatment of rheumatoid arthritis. 2018 Jan Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease predominantly affecting the peripheral diarthrodial joints. Sarilumab is a human monoclonal antibody against the IL-6 receptor-α. In Phase II and III clinical trials, sarilumab in the background of methotrexate showed superior clinical efficacy over placebo in RA patients with inadequate response to methotrexate or inadequate response or intolerance to TNF inhibitors. Sarilumab monotherapy also showed superior efficacy compared with adalimumab monotherapy in RA patients with inadequate response or intolerance to methotrexate. For safety, injection site reaction, neutropenia and elevation of liver enzymes and serum cholesterol were more commonly observed with sarilumab than with placebo. Overall, sarilumab is expected to serve as another useful antirheumatic drug against active RA.
29535013 Effect of individual distal femoral valgus resection in total knee arthroplasty for patien 2018 Apr BACKGROUND: Proper limb alignment and implant positioning are important for successful total knee arthroplasty (TKA). It remains unknown whether any differences exist in the restoration of limb alignment for valgus knees between fixed and individual femoral valgus correction angle (VCA) for distal femoral resection. METHODS: A total of 63 patients (66 knees) had fixed 4° VCA (fixed group), and 55 patients (59 knees) had individual VCA (individual group). We compared the VCA, mechanical femorotibial (MFT) angle, femoral component angle (α), and tibial component angle (β) between the two groups. RESULTS: There were statistically significant differences in postoperative MFT angle between the two groups (2.0° ± 1.2° versus 2.8° ± 1.6°, p < 0.002). A total of 51 (77.3%) patients in the individual group had postoperative alignment deviation within ±3° compared with that of 32 (54.2%) patients in the fixed group (p = 0.006). We found better postoperative alignment accuracies in the individual group for grade II knee valgus deformities (1.8° ± 1.2° versus 2.8° ± 1.5°, p = 0.00). There was a significant difference in α angle deviations between the two groups (1.7° ± 1.3° versus 2.5° ± 1.8°, p = 0.00). The number of patients with postoperative femoral coronal component alignment deviations within ±3° in the individual group was higher compared to that in the control group (87.8% versus 67.8%, p = 0.006). CONCLUSIONS: This radiological study showed that individual VCA for distal femoral resection could achieve better postoperative alignment accuracy and fewer outliers of limb and femoral component malalignment in the coronal plane.
29880835 Uncovering Cellular retinoic acid-binding protein 2 as a potential target for rheumatoid a 2018 Jun 7 Rheumatoid arthritis (RA) is a systemic autoimmune disease including synovitis and synovial hyperplasia that contribute to joint destruction. Pivotal pathogenic mechanisms in this process are the dysregulated proliferation and apoptosis of fibroblast-like synoviocytes (FLS). Unfortunately, the mechanisms of FLS dysregulation are not completely elucidated. Here, we explored a new hypothesis based in the potent anti-proliferative and pro-apoptotic activity of retinoids in some types of cancer. Specifically, we investigated the role of retinoids and of the retinoic acid binding proteins, CRABP2 and FABP5, on the proliferation and apoptosis of FLS from RA by adding all-trans retinoic acid (ATRA) or silencing CRABP2 and FABP5. We showed an unconventional behaviour of RA FLS, which were relatively insensitive to ATRA. In effect, ATRA increased the resistance to apoptosis despite the high CRABP2/FABP5 ratio of RA FLS; and CRABP2 suppression sensitized RA FLS to Fas-induced apoptosis. This latter effect was associated with changes in expression of kinases, ASK1 up-regulation and ERK down-regulation, and increased phosphorylation of JNK. In addition, the potentiation of FLS apoptosis by CRABP2 silencing persisted in the presence of pro-inflammatory mediators, TNF e IL1β. Therefore, the results point to CRABP2 as a potential target to decrease synovial hyperplasia in RA.
30210119 Fatal Chronic Active Epstein-Barr Virus Infection in a Rheumatoid Arthritis Patient Treate 2019 Feb 15 Chronic active Epstein-Barr virus (CAEBV) T-cell type infection, systemic form, is characterized by persistent infectious mononucleosis-like symptoms, high Epstein-Barr virus (EBV) DNA levels in the peripheral blood, organ damage, and a poor prognosis. The association between CAEBV and rheumatoid arthritis (RA) is unclear. We report a case of fatal CAEBV T-cell type infection in an RA patient undergoing treatment with cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin fusion protein (abatacept, ABT). CAEBV can rapidly worsen in RA patients receiving ABT. Thus, we should try to establish an early diagnosis in patients with CAEBV infection.