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ID PMID Title PublicationDate abstract
29466233 Anti-streptavidin IgG antibody interference in anti-cyclic citrullinated peptide (CCP) IgG 2018 Jul 26 BACKGROUND: The detection of anti-cyclic citrullinated peptide (anti-CCP) IgG antibodies in blood is mainly used for the diagnosis of rheumatoid arthritis. Falsely elevated anti-CCP IgG antibodies due to anti-streptavidin IgG antibodies were suspected in our laboratory. METHODS: In this study, we evaluated, in a standardized approach, the prevalence of anti-streptavidin IgG antibodies in a primary care setting and the effect of anti-streptavidin IgG antibodies on anti-CCP IgG assays from three different important commercial manufacturers (Abbott, Roche Diagnostics, Thermo Fisher Scientific). Three different populations were consecutively and prospectively studied: serum samples from 1000 ambulatory patients, 286 serum samples from patients for which anti-CCP was requested and 89 serum samples from patients which had previously given a positive anti-CCP result on Architect® i2000. RESULTS: The frequency of confirmed anti-streptavidin IgG-positive samples detected in this study was 0.6% (8/1375). Anti-CCP IgG was determined on the eight samples with confirmed anti-streptavidin IgG antibodies: with the Cobas® method, seven positive anti-CCP results were observed and five positive anti-CCP results with the Architect® method. No positive anti-CCP IgG results were obtained with the EliA™ method. Rheumatoid factor was negative in these eight samples. CONCLUSIONS: Anti-streptavidin IgG antibodies rarely cause false-positive results in some anti-CCP assays. However, despite being an infrequent assay problem, it could possibly lead to diagnostic confusion or even an incorrect diagnosis of rheumatoid arthritis.
29991576 Associations between Cytokine Levels and CYP3A4 Phenotype in Patients with Rheumatoid Arth 2018 Oct Systemic inflammation has been linked to suppressed CYP3A4 activity. The aim of this study was to examine associations between levels of a broad selection of cytokines and CYP3A4 phenotype in patients with rheumatoid arthritis (RA). The study included 31 RA patients treated with tumor necrosis factor (TNF)-α inhibitors. CYP3A4 phenotype was measured as serum concentration of 4β-hydroxycholesterol (4βOHC) by ultra-performance liquid chromatography-tandem mass spectrometry in samples collected prior to and 3 months after initiation of treatment with TNF-α inhibitors. Serum levels of the following 21 cytokines were determined in the same samples using a bead-based multiplex immunoassay (Luminex technology): CCL2, CCL3, CXCL8, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon γ, interleukin (IL)-1β, IL-1 receptor antagonist (ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-13, IL-15, IL-17A, IL-18, IL-23, and TNF-α Correlations between levels of cytokines and 4βOHC were assessed by Spearman's rank correlation tests. Among the investigated cytokines, three were negatively correlated with CYP3A4 phenotype during treatment with TNF-α inhibitors: i.e., IL-1ra (r = -0.408, P = 0.023), IL-6 (r = -0.410, P = 0.022) and CXCL8 (r = -0.403, P = 0.025) (P ≥ 0.3 for all other cytokines). None of the analyzed cytokines were correlated with CYP3A4 phenotype prior to TNF-α inhibitor treatment (P > 0.1 for all cytokines). These findings suggest that immune responses associated with increased levels of IL-1ra, IL-6, and CXCL8 may suppress CYP3A4 metabolism. Further studies are required to evaluate these preliminary findings in different patient populations and also examine the possible molecular mechanisms behind our observations.
30001809 Identification of antibodies against extracellular matrix proteins in human osteoarthritis 2018 Sep 10 We investigated the presence of autoantibodies against the extracellular matrix proteins thrombospondin-4 (TSP-4), cartilage oligomeric matrix protein (COMP), C-type lectin domain family 3 member A (CLEC3A), collagen II, collagen VI, matrilin-3, and fibrillin-2 in the serum of osteoarthritis (OA) patients. We compared those results with the presence of such antibodies in rheumatoid arthritis (RA) patients and in healthy donors (HD). Our study examines whether antibodies against extracellular proteins can be used as potential biomarkers to support the clinical diagnosis of OA. 10 OA, 10 RA patients and 10 HD were enrolled in this explorative cross-sectional study. SDS-PAGE and immunoblot were used to investigate the presence of antibodies against extracellular matrix proteins. The serum of 5/10 OA patients but 0/10 HD exhibited TSP-4 IgG isotype antibodies (P = 0.033). The serum of 8/10 OA patients but only 1/10 HD exhibited IgG isotype antibodies against TSP-4 or COMP (P = 0.005). The serum of 9/10 OA patients but only 1/10 HD exhibited IgG isotype antibodies against TSP-4, COMP or CLEC3A (P = 0.005). We found strong evidence for the presence of IgG isotype autoantibodies against the cartilage extracellular matrix proteins TSP-4, COMP and CLEC3A in OA. The detection of IgG isotype autoantibodies against TSP-4, COMP and CLEC3A may support the clinical diagnosis of OA. OA with autoantibodies against cartilage extracellular matrix proteins defines a new OA subgroup suggesting that patients with high concentrations of autoantibodies may benefit from an immune suppressive therapy.
29508305 Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare 2018 Jun This report assesses the observed risk of PML in patients treated with the anti-CD20 monoclonal antibody rituximab in the regulatory authority-approved autoimmune indications rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). This was a cumulative analysis of confirmed PML cases in patients receiving rituximab for RA or GPA/MPA from both spontaneous reports and clinical trial sources, as captured in the manufacturer global company safety and clinical databases. Overall reporting rates were calculated and patient case details were summarized. As of 17 November 2015, there were nine confirmed PML cases among patients who had received rituximab for RA and two for GPA. Corresponding estimated reporting rates were 2.56 per 100,000 patients with RA (estimated exposure ≈ 351,396 patients) and < 1 per 10,000 patients with GPA/MPA (estimated exposure 40,000-50,000 patients). In all cases, patients had ≥ 1 potential risk factor for PML independent of rituximab treatment. In the RA population, the estimated reporting rate of PML generally remained stable and low since 2009 despite increasing rituximab exposure. There was no pattern of latency from time of rituximab initiation to PML development and no association of PML with the number of rituximab courses. Global post-marketing safety and clinical trial data demonstrated that the occurrence of PML is very rare among rituximab-treated patients with RA or GPA/MPA and has remained stable over time.
27644953 Association between shortened telomere length and rheumatoid arthritis : A meta-analysis. 2018 Mar OBJECTIVE: This study aimed to evaluate the relationship between telomere length and rheumatoid arthritis (RA). METHODS: We performed a meta-analysis of studies comparing the telomere length in RA patients and healthy controls, and conducted subgroup analysis based on ethnicity, age-matched status, study quality, sample type, assay method, subject number, and shared epitope (SE) status. RESULTS: Nine studies from seven articles, with 388 RA patients and 362 controls, were included. Meta-analysis showed that the telomere length was significantly shorter in all individuals of the RA group than in those of the control group (SMD = -0.833, 95 % CI = -1.332 to -0.334, p = 0.001). Stratification by ethnicity showed significantly shortened telomere lengths in both mixed and age-matched Caucasian populations with RA (SMD = -1.415, 95 % CI = -1.709 to -1.120, p < 1.0 × 10(-8); SMD = -0.658, 95 % CI = -1.187 to -0.0.128, p = 0.015). The telomere length was significantly shorter in the RA group than in the age-matched control group; however, this was not the case in the RA group that was not age-matched (SMD = -1.070, 95 % CI = -1.489 to -0.650, p = 5.7 × 10(-7); SMD = 0.155, 95 % CI = -0.119 to 0.429, p = 0.267). Stratification by SE status revealed a significantly shortened telomere length in the SE-positive group, but not in the SE-negative group (SMD = -1.033, 95 % CI = -1.398 to -0.768, p < 1.0 × 10(-8); SMD = -0.967, 95 % CI = -2.382 to 0.449, p = 0.181). In addition, the telomere length was significantly shorter in the SE-positive RA group than in the SE-negative RA group (SMD = -0.415, 95 % CI = -0.699 to -0.131, p = 0.004). CONCLUSIONS: Our meta-analysis demonstrated that the telomere length was significantly shorter in patients with RA, and was significantly more so in the SE-positive group than in the SE-negative group.
29519620 Therapeutic Perspectives for Interferons and Plasmacytoid Dendritic Cells in Rheumatoid Ar 2018 Apr Rheumatoid arthritis (RA) is a multifactorial immune disease exhibiting diverse clinical responses to specific therapeutic agents. Such heterogeneity reflects variable activation of signaling pathways. Consequently, RA physiopathology has been linked to many immune cells and factors, with controversial observations for interferons (IFNs). In this opinion article, we review the roles of these cytokines and the cells that produce them in light of recent data: clinical observations showing that expression of IFN-dependent genes does not reflect RA activity and RA mouse models in which the stimulation of IFN-dependent pathways provided disease protection. We suggest that epicutaneous stimulation of the IFN network is an attractive possibility to limit neutrophil infiltration or activation, thus providing therapeutic benefits to RA patients refractory to current therapies.
29301935 Inhibition of histone H3K27 demethylases selectively modulates inflammatory phenotypes of 2018 Feb 16 Natural killer (NK) cells are innate lymphocytes, important in immune surveillance and elimination of stressed, transformed, or virus-infected cells. They critically shape the inflammatory cytokine environment to orchestrate interactions of cells of the innate and adaptive immune systems. Some studies have reported that NK cell activation and cytokine secretion are controlled epigenetically but have yielded only limited insight into the mechanisms. Using chemical screening with small-molecule inhibitors of chromatin methylation and acetylation, further validated by knockdown approaches, we here identified Jumonji-type histone H3K27 demethylases as key regulators of cytokine production in human NK cell subsets. The prototypic JMJD3/UTX (Jumonji domain-containing protein 3) H3K27 demethylase inhibitor GSK-J4 increased global levels of the repressive H3K27me3 mark around transcription start sites of effector cytokine genes. Moreover, GSK-J4 reduced IFN-γ, TNFα, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-10 levels in cytokine-stimulated NK cells while sparing their cytotoxic killing activity against cancer cells. The anti-inflammatory effect of GSK-J4 in NK cell subsets, isolated from peripheral blood or tissue from individuals with rheumatoid arthritis (RA), coupled with an inhibitory effect on formation of bone-resorbing osteoclasts, suggested that histone demethylase inhibition has broad utility for modulating immune and inflammatory responses. Overall, our results indicate that H3K27me3 is a dynamic and important epigenetic modification during NK cell activation and that JMJD3/UTX-driven H3K27 demethylation is critical for NK cell function.
30511525 [Expression of c-FLIP in peripheral blood mononuclear cells of patients with rheumatoid ar 2018 Feb 25 OBJECTIVE: To investigate the expression of apoptosis related protein cellular Fas associated death domain like interleukin 1 converting enzyme inhibitory protein (c-FLIP) in peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis and its relation with extrinsic apoptotic pathway. METHODS: Sixty patients with rheumatoid arthritis were collected from Zhangzhou Affiliated Hospital of Fujian Medical University during January 2014 and June 2015, including 22 patients with low activities (DAS28<3.2), 20 patients with middle activities (3.2 ≤ DAS28 ≤ 5.1), and 18 patients with high activities (DAS28>5.1). And 25 healthy controls were also collected. The mRNA and protein expression levels of c-FLIP and the extrinsic apoptotic pathway related proteins Fas-associated protein with death domain (FADD), caspase-8 in PBMCs were detected by real-time RT-PCR and Western blot, respectively. Correlations between c-FLIP and FADD, caspase-8 in PBMCs were analyzed by pearson test. RESULTS: mRNA expression levels of c-FLIP, FADD and caspase-8 in PBMCs of patients with rheumatoid arthritis were all higher than those of healthy controls (all P<0.05). mRNA expression levels of FADD and caspase-8 in patients with middle activities were significantly higher than those in patients with low activities (all P<0.05), but the mRNA expression level of c-FLIP was not significantly higher than that in patients with low activities. mRNA expression level of c-FLIP in patients with high activities was higher than those in patients with middle or low activities (all P<0.05), while the mRNA expression level of caspase-8 was lower than those in patients with middle or low activities (all P<0.05). mRNA expression level of FADD in patients with high activities was higher than those in patients with low activities (P<0.05). Pearson analysis showed that there was a positive correlation between c-FLIP and FADD mRNA expression (r=0.323, P<0.05), and negative correlation between c-FLIP and caspase-8 mRNA expression (r=-1.104, P<0.05). The protein expression levels of c-FLIP and FADD in patients with middle activities were significantly higher than those in control group and patients with low or high activities (P<0.05 or 0.01). The protein expression levels of caspase-8 in patients with middle and high activities were significantly higher than those in control group and patients with low activities (P<0.05 or P<0.01), and the protein expression level of caspase-8 in patients with high activities was higher than that in patients with middle activities (P<0.05). CONCLUSIONS: c-FLIP may be involved in the extrinsic apoptotic pathway in rheumatoid arthritis, and can provide reference for the evaluation of disease activities.
31005814 Ethanolic extract of Kaempferia parviflora interrupts the mechanisms-associated rheumatoid 2019 Jun BACKGROUND: Kaempferia parviflora Wall. ex Baker (KP) has long been used in traditional medicine to treat various diseases because active compounds in rhizome extracts are important anti-inflammatory agents. PURPOSE: This study aims to investigate the effects of an ethanolic extract of KP on the molecular mechanisms associated with rheumatoid arthritis (RA), which was induced by a combination of proinflammatory cytokines (IL-1β or TNF-α with IL-17A) in a human synovial sarcoma cell line (SW982) culture model. METHODS: SW982 cells pretreated with cytokines were incubated with KP extract at 3-30 µg/ml, or three major compounds of KP (5,7-dimethoxyflavone, 5,7,4'-trimethoxyflavone, and 3,5,7,3',4'-pentamethoxyflavone) for up to 72 h. Dexamethasone was used as positive control. RA-associated genes and inflammatory products were measured in parallel with cell death genes. Apoptosis by flow cytometry and migration assay were also analyzed. Western blotting was used to examine the effects on intracellular signaling mechanisms. RESULTS: KP extract markedly reduced the expression of genes and levels of proinflammatory cytokines, inflammatory mediators, and matrix-degraded enzymes, but neither induced apoptosis nor altered the cell cycle. Its major constituents differently exerted suppressive effects on inflammatory genes. The KP extract downregulated the expression of genes associated with autophagosome and necroptosome formations. The extract also inhibited cell migration, reduced the mRNA expression of cadherin-11, and selectively reduced the phosphorylation of p38 MAPK, STAT1, and STAT3 signaling molecules, but did not interfere with the NF-κB pathway. CONCLUSION: These results suggest that the anti-arthritic potential of KP extract results from anti-inflammation and anti-migration via the suppression of the cytokines-induced p38/STAT1 and STAT3 pathways.
30620286 Attitudes about principle of autonomy in Hispanic patients from a dynamic early rheumatoid 2019 Jul OBJECTIVES: In 2004, we began assembling an incidental cohort of patients with recent-onset rheumatoid arthritis (RA). In February 2018, we performed a cross-sectional study with the objective to investigate patients' attitudes/knowledge regarding the autonomy principle. METHODS: Patients currently attending the cohort (n=146) were invited to participate. A 4-dimensional questionnaire was administered, and a rheumatologic evaluation performed in the 143 patients who agreed to participate. Dimension-4 (D-4) included 7 multiple-choice (strongly agree-strongly disagree) sentences, 3 of which were related to patients' rights/obligations about health-related decisions (group-1), and 4 additional sentences challenged physician's recommendations (group-2). The D-4 score was considered a surrogate of knowledge autonomy (KA). Additionally, the surveyor scored KA with a Likert scale (poor, borderline and superior), and a cut-off point for poor KA was set using Borderline methodology. Mann-Whitney U-tests and logistic regression analysis were used. The study received IRB approval. RESULTS: At the time the questionnaire was administered, mean (±SD) patient age was 46.9 (±13.6) years, and median (interquartile range) cohort follow-up time was 8.8 (4.3-11.9) years. Fifty-one patients (35.6%) had poor KA; increased age (OR: 0.97, 95% CI: 1.004-1.063, p=0.023) was associated with better KA. Patients more frequently agreed-strongly agreed with group-1 sentences than they did with group-2 sentences (86.7% vs. 58%, p≤0.001). The results were reproduced in the subpopulations with sufficient KA (98.9% vs. 88%, p=0.007) and poor KA for patients in whom the gap was extreme (64.9% vs. 3.9%, p≤0.001). CONCLUSIONS: Hispanic RA patients' sense of autonomy suggests paternalism in the physician-patient relationship.
30551432 Molecular modulators of celastrol as the keystones for its diverse pharmacological activit 2019 Jan In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development.
30289986 Functional and phenotypic heterogeneity of Th17 cells in health and disease. 2019 Jan BACKGROUND: Th17 cells have nonredundant roles in maintaining immunity, particularly at mucosal surfaces. These roles are achieved principally through the production of cytokines and the recruitment of other immune cells to maintain the integrity of mucosal barriers and prevent the dissemination of microorganisms. Th17 cells are heterogeneous and exhibit a considerable degree of plasticity. This allows these cells to respond to changing environmental challenges. However, Th17 cells also play pro-inflammatory roles in chronic autoimmune diseases. The trigger(s) that initiate these Th17 responses in chronic autoimmune diseases remain unclear. DESIGN: In this report, we provide an overview of studies involving animal models, patient data, genome wide association studies and clinical trials targeting IL-17 for treatment of patients to gain a better understanding of the pathogenic roles of Th17 cells play in a range of autoimmune diseases. RESULTS: The report sheds light on likely triggers that initiate or perpetuate Th17 responses that promote chronic inflammation and autoimmunity. The divergent effects of tumour necrosis factor alpha blockade on Th17 cells in patients, is explored. Furthermore, we highlight the role of Th17 cells in inducing autoreactive B cells, leading to autoantibody production. Pathogenic bacterial species can change Th17 cell phenotype and responses. These findings provide insights into how Th17 cells could be induced to promoting autoimmune disease pathogenesis. CONCLUSION: This article provides an overview of the distinct roles Th17 cells play in maintaining immunity at mucosal surfaces and in skin mucosa and how their functional flexibility could be linked with chronic inflammation in autoimmune rheumatic diseases.
29106053 Population Pharmacokinetics of Fosdagrocorat (PF-04171327), a Dissociated Glucocorticoid R 2018 Jan Dissociated agonists of the glucocorticoid receptor (DAGRs) show similar antiinflammatory effects but improved tolerability compared with standard glucocorticoid receptor (GR) agonists. The prodrug fosdagrocorat (PF-04171327), with active DAGR metabolite PF-00251802 (Metabolite-1), is postulated to show superior efficacy over placebo and prednisone in patients with moderate to severe rheumatoid arthritis (RA). We investigated the population pharmacokinetics of active Metabolite-1 and its active metabolite PF-04015475 (Metabolite-2) in patients with moderate to severe RA enrolled in a 12-week, phase II, randomized, double-blind study (NCT01393639). A simultaneous fit of a two-compartment model for Metabolite-1 and a one-compartment model for Metabolite-2 provided an adequate fit to the data. Significant covariates included weight, with an additional female effect on clearance of Metabolite-1 (∼26%) and Metabolite-2 (∼33%) compared with males. Age influenced clearance of Metabolite-1. In combination, age, weight, and sex predicted >twofold differences in area under the concentration-time curve of Metabolite-1 at the extremes.
30567550 A cross-sectional study on self-reported physical and mental health-related quality of lif 2018 Dec 19 BACKGROUND: Psychosocial models including illness perception might explain individual differences in health-related quality of life (HRQoL) and daily functioning in chronically ill patients. The aim of this study was to assess the association of illness perception among rheumatoid arthritis (RA) patients with physical and mental HRQoL, adjusted for demographic variables, clinical variables and social support. METHODS: A cross-sectional study conducted at a Viennese rheumatology outpatient clinic on 120 RA patients. Participants completed questionnaires on demographic and clinical characteristics, HRQoL (SF-36 Questionnaire), illness beliefs (Brief Illness Perception Questionnaire) and social support (Social Support Scale-8). Analyses were performed with multivariate linear regression. RESULTS: The mean physical was lower (38.38) than the mean mental SF-36 summary score (46.94). In univariate analysis, all domains of illness perception except belief in a chronic disease course were associated with physical and mental HRQoL. In multivariate analyses, illness perception accounted for 51% of variance in physical HRQoL. A stronger belief in the consequences of RA (consequences, β = - 0.33) and a stronger belief in repeated disease recurrence (timeline cyclical, β = - 0 .31) were significantly associated with physical HRQoL in the fully adjusted model. Illness perception accounted for 45% of variance in mental HRQoL. Emotional representation (β = - 0 .27) and fatigue (β = - 0 .36) were significantly associated with mental HRQoL in the fully adjusted model. CONCLUSION: This study highlights the importance of RA patients' beliefs about their illness and symptoms in relation to HRQoL. Identification of patients' perception of RA may be a way to positively influence disease outcomes such as quality of life as illness perception is amenable to intervention.
30289534 Randomized controlled trials and real-world data: differences and similarities to untangle 2018 Oct 1 Randomized controlled trials (RCTs) represent the gold-standard of medical evidence to assess the efficacy and safety of therapeutic interventions. However, the need to minimize bias and ensure the correct design to explore the study aims often affects the generalizability of results. As a consequence, the evidence derived from the most rigorous research strategy available is not always representative of the real-world settings for which this evidence is ultimately intended. Observational studies, in contrast, although affected by a number of potential confounders, can more effectively capture treatment characteristics and safety issues that had not been identified by previous RCTs, owing to the short duration of follow-up or highly selective inclusion criteria. The aim of this review is to provide a comparative summary of the main advantages and pitfalls of RCTs and real-world data, emphasizing the need for a constant integration of all available levels of evidence to provide the best care for patients.
28916968 HMGB proteins and arthritis. 2018 Jan The high-mobility group box (HMGB) family includes four members: HMGB1, 2, 3 and 4. HMGB proteins have two functions. In the nucleus, HMGB proteins bind to DNA in a DNA structure-dependent but nucleotide sequence-independent manner to function in chromatin remodeling. Extracellularly, HMGB proteins function as alarmins, which are endogenous molecules released upon tissue damage to activate the immune system. HMGB1 acts as a late mediator of inflammation and contributes to prolonged and sustained systemic inflammation in subjects with rheumatoid arthritis. By contrast, Hmgb2 (-/-) mice represent a relevant model of aging-related osteoarthritis (OA), which is associated with the suppression of HMGB2 expression in cartilage. Hmgb2 mutant mice not only develop early-onset OA but also exhibit a specific phenotype in the superficial zone (SZ) of articular cartilage. Given the similar expression and activation patterns of HMGB2 and β-catenin in articular cartilage, the loss of these pathways in the SZ of articular cartilage may lead to altered gene expression, cell death and OA-like pathogenesis. Moreover, HMGB2 regulates chondrocyte hypertrophy by mediating Runt-related transcription factor 2 expression and Wnt signaling. Therefore, one possible mechanism explaining the modulation of lymphoid enhancer binding factor 1 (LEF1)-dependent transactivation by HMGB2 is that a differential interaction between HMGB2 and nuclear factors affects the transcription of genes containing LEF1-responsive elements. The multiple functions of HMGB proteins reveal the complex roles of these proteins as innate and endogenous regulators of inflammation in joints and their cooperative roles in cartilage hypertrophy as well as in the maintenance of joint tissue homeostasis.
30043210 Clinical, Ultrasound, and Predictability Outcomes Following Certolizumab Pegol Treatment ( 2018 Aug INTRODUCTION: To assess the impact of certolizumab pegol (CZP) treatment on clinical, patient-reported, and musculoskeletal ultrasound outcomes and to determine the treatment response time point most predictive of long-term outcomes in Italian patients with rheumatoid arthritis (RA). METHODS: CZP-SPEED (NCT01443364) was a 52-week, open-label, prospective, interventional, multicenter study. Biologic-naïve patients with moderate-to-severe active RA, who had failed at least one DMARD treatment, received CZP (400 mg at weeks 0, 2, and 4, then 200 mg every 2 weeks) concomitantly with methotrexate. The primary objective was to identify the time point of clinical response {decrease in 28-joint Disease Activity Score [DAS28(ESR)] ≥ 1.2} most predictive of a clinical response at week 52. Additional clinical and patient-reported outcomes were measured. Power Doppler (PD) ultrasound was used to assess synovial effusion, synovial proliferation, PD signal, cartilage damage, and bone erosion according to international guidelines. RESULTS: A total of 132 patients were enrolled and received CZP; 91/132 (69%) completed to week 52. Predicted 52-week responses for early responders (week 2 onwards) were between 65% and 70%. Rapid improvements in joint cavity widening and PD signal were observed to week 8 and maintained to week 52. Cartilage damage and bone erosion were stable over 52 weeks. No new safety signals were identified. CONCLUSION: In Italian CZP-treated patients with moderate-to-severe RA, week 12 clinical responses may be predictive of long-term response at week 52. Rapid improvements in clinical, patient-reported, and musculoskeletal ultrasound outcomes were maintained to week 52. These data may aid rheumatologists to make earlier treatment decisions. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01443364. FUNDING: UCB Pharma.
28540605 Characteristics of rheumatoid arthritis patients undergoing reverse shoulder arthroplasty. 2018 Feb The risks and complication profile of reverse total shoulder arthroplasty (RSA) in rheumatoid arthritis (RA) patients has yet to be clearly defined as most studies have small cohorts. Using a large inpatient database, the purpose on our study was to determine the overall demographics, hospitalization characteristics, and early complication rates in rheumatoid patients and compared these to rotator-cuff arthropathy patients without RA undergoing RSA. Utilizing United States Nationwide Inpatient Sample from 2010 to 2013, we evaluated a total of 919 RA RSA and compared them to 8097 patients without RA undergoing RSA. The outcomes included demographic characteristics like age, race, sex, Deyo comorbidity score, perioperative complications, and mean length-of-stay. The RA cohort had 81% females versus 60% in the comparison cohort. This cohort was younger (p = 0.006) and had longer hospitalization time (p = 0.001), but the total inpatient costs were not significantly different (p = 0.15). In regards to Deyo index, rheumatoid patients had significantly higher scores (p < 0.001). The inpatient complication rates for infection (p = 0.9), nerve injury (p = 0.9), and instability (p = 0.19) were similar, but the RA cohort had more prosthetic-related (p = 0.001) and greater tuberosity-related (p = 0.008) complications. The mortality rates were also similar (p = 0.625). In RSA for RA patients, surgeons should be mindful of preoperative risk factors and demographic characteristics that may influence their outcomes. Caution should specifically be paid to the possibility of longer hospitalization time and increased incidence of certain complications, including intraoperative fracture, when compared to non-rheumatoid patients. Close collaboration between rheumatologists, surgeons, and primary care physicians is a must for optimizing and managing these patients.
29550468 Analysis of pulmonary sounds for the diagnosis of interstitial lung diseases secondary to 2018 May 1 The diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis is fundamental to improving their survival rate. In particular, the average survival time of patients affected by rheumatoid arthritis with pulmonary implications is approximately 3 years. The gold standard for confirming the diagnosis of this disease is computer tomography. However, it is very difficult to raise diagnosis suspicion because the symptoms of the disease are extremely common in elderly people. The detection of the so-called velcro crackle in lung sounds can effectively raise the suspicion of an interstitial disease and speed up diagnosis. However, this task largely relies on the experience of physicians and has not yet been standardized in clinical practice. The diagnosis of interstitial lung diseases based on thorax auscultation still represents an underexplored field in the study of rheumatoid arthritis. In this study, we investigate the problem of the automatic detection of velcro crackle in lung sounds. In practice, the patient is auscultated using a digital stethoscope and the lung sounds are saved to a file. The acquired digital data are then analysed using a suitably developed algorithm. In particular, the proposed solution relies on the empirical observation that the audio bandwidth associated with velcro crackle is larger than that associated with healthy breath sounds. Experimental results from a database of 70 patients affected by rheumatoid arthritis demonstrate that the developed tool can outperform specialized physicians in terms of diagnosing pulmonary disorders. The overall accuracy of the proposed solution is 90.0%, with negative and positive predictive values of 95.0% and 83.3%, respectively, whereas the reliability of physician diagnosis is in the range of 60-70%. The devised algorithm represents an enabling technology for a novel approach to the diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis.
29788308 PheProb: probabilistic phenotyping using diagnosis codes to improve power for genetic asso 2018 Oct 1 OBJECTIVE: Standard approaches for large scale phenotypic screens using electronic health record (EHR) data apply thresholds, such as ≥2 diagnosis codes, to define subjects as having a phenotype. However, the variation in the accuracy of diagnosis codes can impair the power of such screens. Our objective was to develop and evaluate an approach which converts diagnosis codes into a probability of a phenotype (PheProb). We hypothesized that this alternate approach for defining phenotypes would improve power for genetic association studies. METHODS: The PheProb approach employs unsupervised clustering to separate patients into 2 groups based on diagnosis codes. Subjects are assigned a probability of having the phenotype based on the number of diagnosis codes. This approach was developed using simulated EHR data and tested in a real world EHR cohort. In the latter, we tested the association between low density lipoprotein cholesterol (LDL-C) genetic risk alleles known for association with hyperlipidemia and hyperlipidemia codes (ICD-9 272.x). PheProb and thresholding approaches were compared. RESULTS: Among n = 1462 subjects in the real world EHR cohort, the threshold-based p-values for association between the genetic risk score (GRS) and hyperlipidemia were 0.126 (≥1 code), 0.123 (≥2 codes), and 0.142 (≥3 codes). The PheProb approach produced the expected significant association between the GRS and hyperlipidemia: p = .001. CONCLUSIONS: PheProb improves statistical power for association studies relative to standard thresholding approaches by leveraging information about the phenotype in the billing code counts. The PheProb approach has direct applications where efficient approaches are required, such as in Phenome-Wide Association Studies.