bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining remission in rheumatoid arthritis: Results of an initial american college of rheumatology/european league against rheumatism consensus conference
Authors: van Tuyl Lilian H. D. , Vlad Steven C. , Felson David T. , Wells George , Boers Maarten 
Published: April 2009

AbstractObjectiveDue to advances in rheumatoid arthritis (RA) therapies over the last few years, an increasing proportion of patients are able to achieve a state of remission. However, the definition of remission is unclear. Currently, randomized controlled trials around the world use different remission definitions and consequently measure different aspects of a patient's disease state. The need for a uniform definition of remission is vital for research findings to be correctly interpreted.MethodsThe American College of Rheumatology (ACR) constituted a committee that included international clinical researchers, trialists, and clinical epidemiologists in order to redefine remission in RA. This group was asked to study current definitions of remission, explore the theoretical underpinning of the concept of remission, and develop a research agenda that would inform future work in the development of an ACR definition of remission.ResultsIn its first meeting, the committee preferred to develop a strict definition, implying no or very low disease activity. Such a definition would need to be validated against long‐term outcome, e.g., physical function and damage.ConclusionThe committee decided to consider both a definition for trials and a modified version for clinical practice. Since the first meeting, the ACR and the European League Against Rheumatism (EULAR) have decided to sponsor this initiative as an official ACR/EULAR collaboration.
Capillaroscopic skin ulcer risk index: A new prognostic tool for digital skin ulcer development in systemic sclerosis patients
Authors: Sebastiani M. , Manfredi A. , Colaci M. , D'amico R. , Malagoli V. , Giuggioli D. , Ferri C. 
Published: April 2009

AbstractObjectiveDigital ulcerations are one of the most frequent manifestations of microangiopathy in patients with systemic sclerosis (SSc; scleroderma). The early detection of SSc patients who are at high risk to develop digital ulcers could allow a preventive treatment of these complications with reduction of morbidity and social costs. The aim of our study was to develop a capillaroscopic skin ulcer risk index (CSURI) that can predict the onset of new digital ulcers by using nailfold videocapillaroscopy (NVC) in patients with SSc.MethodsWe performed NVC in 120 consecutive unselected patients with SSc (13 men, 107 women, mean ± SD age 56.1 ± 13.4 years, mean ± SD SSc duration 44.7 ± 60.7 months) to assess the total number of capillaries in the distal row (N), maximum loop diameter (D), number of megacapillaries (M), and the M:N ratio.ResultsWithin 3 months since NVC examination, 35 of 120 patients experienced digital ulcers. A significant association between ischemic lesions and the M:N ratio, N, and D was observed; the combination of these parameters allowed us to develop the CSURI, which is characterized by the formula D × M:N2. A receiver operating characteristic curve analysis showed an area under the curve of 0.926 for ulcer appearance, with specificity and sensitivity of 85.9% and 94.3%, respectively, at the cutoff value of 2.94. Interestingly, 33 of 35 patients with new skin ulcers had a CSURI >2.94, but only 2 of 35 had a CSURI ≤2.94.ConclusionThe proposed CSURI may represent a novel tool with the ability to predict the development of digital ulcers in patients with scleroderma.
Measuring shoulder function: A systematic review of four questionnaires
Authors: Roy Jean‐Sébastien , MacDermid Joy C. , Woodhouse Linda J. 
Published: April 2009

AbstractObjectiveTo conduct a systematic review of the quality and content of the psychometric evidence relating to 4 shoulder disability scales: the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, the Shoulder Pain and Disability Index (SPADI), the American Shoulder and Elbow Surgeons (ASES) score, and the Simple Shoulder Test (SST).MethodsWe conducted a structured search using 3 databases (Medline, CINAHL, EMBase). In total, 71 published primary studies were analyzed. A pair of raters conducted data extraction and critical appraisal using structured tools. A descriptive synthesis was performed.ResultsQuality ratings of 55% of the studies reviewed reached a level of ≥75%. Most studies suggest that all 4 questionnaires have excellent reliability (intraclass correlation coefficient ≥0.90). The 4 questionnaires are strongly correlated (r >0.70) with each other and with a number of similar indices, and the questionnaires were able to differentiate between different populations and disability levels. The minimal detectable change (MDC) is ∼9.4 for the ASES, 10.5 for the DASH, and 18 for the SPADI; the minimal clinically important difference (MCID) is ∼6.4 for the ASES and 10.2 for the DASH, and ranges between 8 and 13 for the SPADI. MDC and MCID have not been defined for the SST.ConclusionThe psychometric properties of the ASES, DASH, and SPADI have been shown to be acceptable for clinical use. Conversely, some properties of the SST still need be evaluated, particularly the absolute errors of measurement. Overall, validation studies have focused on less clinically relevant properties (construct validity or group reliability) than estimates of MDC and MCID.
Validation of a manual ability questionnaire in patients with systemic sclerosis
Authors: Vanthuyne Marie , Smith Vanessa , Arat Seher , Westhovens René , de Keyser Filip , Houssiau Frédéric A. , Thonnard Jean‐Louis , Vandervelde Laure 
Published: April 2009

AbstractObjectiveTo adapt and validate a manual ability questionnaire, the ABILHAND, developed through the Rasch methodology in patients with systemic sclerosis (SSc).MethodsThe original version of the ABILHAND, which includes 81 manual daily activities, was presented to 156 patients with SSc. They were asked to provide their perceived difficulty in performing each manual activity on a 3‐level scale: impossible, difficult, or easy. Items were selected from well‐established psychometric criteria. The patients were reassessed 1 month later to test the reproducibility. Concomitantly, they were clinically evaluated for their disease activity/severity, and their functional ability was tested with the Health Assessment Questionnaire (HAQ).ResultsThe 26 selected items defined a unidimensional and linear measure of manual ability and showed a continuous progression in their difficulty. The item difficulty hierarchy was invariant across 12 patient‐related factors and the manual ability score was reproducible over time. Finally, the manual ability was significantly poorer in SSc patients with more severe disease, and was negatively correlated with the HAQ score (ρ = −0.733).ConclusionThe SSc‐adapted ABILHAND questionnaire is a reliable, valid, reproducible, linear, and unidimensional measure to assess and followup on the manual ability of patients with SSc; therefore, it could become a useful additional tool in clinical trials to assess treatment efficacy.
Differences in the workforce experiences of women and men with arthritis disability: A population health perspective
Authors: Kaptein Simone A. , Gignac Monique A. M. , Badley Elizabeth M. 
Published: April 2009

AbstractObjectiveTo examine the employment status characteristics of people with arthritis disability, with a focus on gender differences and who remains in the workforce.MethodsAnalyses were based on cross‐sectional, self‐reported data of the Canadian Participation and Activity Limitation Survey, administered in 2001–2002 (n = 28,908). Labor force status was categorized into employed, unemployed, and not in the labor force. Prevalence estimates were derived from descriptive analyses, and logistic regression determined the factors associated with being out of the labor force. Chi‐square and sex‐stratified analyses examined gender differences.ResultsAn estimated 2.3% of the working‐age population (ages 25–64 years) reported arthritis disability, and >50% were out of the labor force. Being female, single, older, and having less education and more severe pain and disability were associated with being out of the labor force. Employed women with arthritis disability required more accommodations in the workplace and reported more activity limitations than men. Perceived discrimination was more likely to be reported by employed men, and men reported more changes to their work than women.ConclusionThis study underscores the importance of looking more closely at differences in the employment experiences of women and men. Specifically, the results suggest that arthritis may marginalize women and men in different ways. Women may be more likely to leave employment, whereas men may be more likely to remain working and report negative workplace experiences.
Predicting depression in rheumatoid arthritis: The signal importance of pain extent and fatigue, and comorbidity
Authors: Wolfe Frederick , Michaud Kaleb 
Published: April 2009

AbstractObjectiveTo determine the incidence of self‐reported depression (SRD) in rheumatoid arthritis and to identify and rank clinically useful predictors of depression.MethodsWe assessed 22,131 patients for SRD between 1999 and 2008. We collected demographic, clinical and treatment data, household income, employment and work disability status, comorbidity, scales for function, pain, global, and fatigue, the Regional Pain Scale (RPS), the Symptom Intensity (SI) scale (a linear combination of the RPS and the fatigue scales) and linear combinations of the Health Assessment Questionnaire, pain and global severity. We used logistic regression analyses with multivariable fractional polynomial predictors, and Random Forest analysis to determine the importance of the predictors.ResultsThe cross‐sectional prevalence of self‐reported depression was 15.2% (95% confidence interval [95% CI] 14.7–15.7%) and the incidence rate was 5.5 (95% CI 5.3–5.7) per 100 patient years of observation. The cumulative risk of SRD after 9 years was 38.3% (95% CI 36.6–40.1%). Almost all variables were significant predictors in logistic models. In Random Forest analyses, the SI scale, followed by comorbidity, best predicted self‐reported depression, and no other variable or combination of variables improved prediction compared with the SI scale.ConclusionPain extent and fatigue (SI scale) are the dominant predictors of SRD. These variables, also of central importance in the symptomatology of fibromyalgia, are powerful markers of distress. A strong case can be made for the inclusion of these assessments in routine rheumatology practice. In addition, actual knowledge of comorbidity provides important insights into the patient's global health and associated perceptions.
Rheumatoid arthritis joint progression in sustained remission is determined by disease activity levels preceding the period of radiographic assessment
Authors: Aletaha D. , Funovits J. , Breedveld F. C. , Sharp J. , Segurado O. , Smolen J. S. 
Published: April 2009

AbstractObjectiveJoint damage is related to disease activity in rheumatoid arthritis (RA), but the degree of its progression and the temporal associations between disease activity and joint damage are unclear. The aim of this study was to evaluate whether there is a latency in the effect of disease activity on radiographic progression in patients with RA.MethodsData were obtained from the PREMIER trial, a 2‐year randomized, controlled clinical trial of adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in early RA. Radiographic progression of joint damage was calculated using the modified total Sharp score in a subset of patients whose disease was in remission (Simplified Disease Activity Index ≤3.3) in the second year of the trial. The progression of damage in the second year was compared between groups of patients whose disease was already in remission for an additional period of 3, 6, or 9 months during the first year. Analysis of variance was used to test for a linear trend.ResultsAmong 794 patients with early RA, 119 (15%) achieved sustained remission during the second year, with no difference in radiographic progression across the 3 treatment groups. Radiographic progression in the second year was significantly different between patients with 3, 6, or 9 additional months of remission during year 1 (mean change in the modified Sharp score 1.19 in those with 3 additional months of remission versus 0.20 in those with 6 additional months of remission and −0.32 in those with 9 additional months of remission; P < 0.05). The results were supported by similar findings in a series of sensitivity analyses.ConclusionThese data indicate that the level of disease activity as well as the duration of remission affect subsequent progression of radiographic damage in RA. This latency between disease activity and its effects on radiographic progression should be considered when evaluating radiographic outcomes in trials of RA.
Regulation of pulmonary inflammation and fibrosis through expression of integrins αVβ3 and αVβ5 on pulmonary T lymphocytes
Authors: Luzina Irina G. , Todd Nevins W. , Nacu Natalia , Lockatell Virginia , Choi Jung , Hummers Laura K. , Atamas Sergei P. 
Published: April 2009

AbstractObjectivePulmonary diseases associated with fibrosis, including scleroderma lung disease, are characterized by the accumulation of T cells in the lungs. These cells are thought to facilitate lung fibrosis, but the exact mechanisms of their profibrotic action are not clear. Several αV‐containing integrins, including αVβ3 and αVβ5, have been shown to directly activate transforming growth factor β (TGFβ) and promote collagen accumulation. The aim of this study was to investigate whether pulmonary T cells express profibrotic integrins and regulate collagen accumulation.MethodsExpression of integrins was assessed by immunohistochemical analysis of lung tissue, by flow cytometry using bronchoalveolar lavage fluid from patients with systemic sclerosis (SSc), and in a CCL18 overexpression animal model of pulmonary T cell infiltration. Experiments in cell cultures were performed to determine whether integrin‐expressing T cells are profibrotic in cocultures with pulmonary fibroblasts and, if so, through what possible mechanism.ResultsLymphocytes and integrin‐positive cells were present in the lungs, and pulmonary T cells expressed integrins αVβ3 and αVβ5 in patients with SSc and in the animal model. Systemic administration of neutralizing anti–integrin αV antibody or a genetic deficiency of integrin β3 in the CCL18 overexpression model significantly attenuated CCL18‐driven pulmonary lymphocytic infiltration and collagen accumulation. Jurkat T cells overexpressing integrin αVβ3 or integrin αVβ5 in cocultures with primary pulmonary fibroblasts stimulated collagen accumulation and Smad2 nuclear translocation. Neutralizing anti‐TGFβ antibody attenuated the profibrotic effect of integrin‐expressing T cells.ConclusionPulmonary infiltrating T lymphocytes may express integrins αVβ3 and αVβ5 that are necessary for lymphocytic infiltration and T cell–associated TGFβ activation and collagen accumulation.
Regulation of autophagy in human and murine cartilage: Hypoxia‐inducible factor 2 suppresses chondrocyte autophagy
Authors: Bohensky Jolene , Terkhorn Shawn P. , Freeman Theresa A. , Adams Christopher S. , Garcia Joseph A. , Shapiro Irving M. , Srinivas Vickram 
Published: April 2009

AbstractObjectiveWe have previously demonstrated that the transcription factor hypoxia‐inducible factor 1 (HIF‐1) promotes the onset of autophagy in chondrocytes. The overall goal of this study was to test the hypothesis that another HIF family transcription factor, HIF‐2, modulates the induction of autophagy by chondrocytes.MethodsExpression of HIF‐1, HIF‐2, and light chain 3 (LC3) in human and murine articular cartilage was visualized by immunohistochemistry. Suppression of HIF‐2 was achieved using small interfering RNA technology. Assessments of autophagic flux and lysosomal activity, as well as ultrastructural analysis, were performed in chondrocytes in cell culture.ResultsHIF‐2 was expressed abundantly by cells in human and murine articular cartilage and in the cartilage of mineralizing vertebrae from neonatal mice. Protein levels were reduced in articular cartilage from older mice, in end‐plate cartilage from mice, and in chondrocytes from human osteoarthritic (OA) cartilage. HIF‐2 was robustly expressed in the prehypertrophic cells of mouse growth cartilage. When HIF‐2α was silenced, the generation of reactive oxygen species was found to be elevated, with a concomitant decrease in catalase and superoxide dismutase activity. Suppression of HIF‐2 was associated with decreased Akt‐1 and mammalian target of rapamycin activities, reduced Bcl‐xL expression, and a robust autophagic response, even under nutrient‐replete conditions. In these silenced chondrocytes, HIF‐1 expression was elevated. Decreased HIF‐2 expression was associated with autophagy in OA tissues and aging cartilage samples. The autophagic response of chondrocytes in HIF‐2α–knockout mouse growth plate showed an elevated autophagic response throughout the plate.ConclusionBased on these observations, we conclude that HIF‐2 is a potent regulator of autophagy in maturing chondrocytes. Our data suggest that this protein acts as a brake on the autophagy‐accelerator function of HIF‐1.
Indoleamine 2,3 dioxygenase–mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen‐induced arthritis
Authors: Criado Gabriel , Šimelyte Egle , Inglis Julia J. , Essex David , Williams Richard O. 
Published: April 2009

AbstractObjectiveIndoleamine 2,3 dioxygenase (IDO) is a catabolic enzyme that initiates the kynurenine pathway of tryptophan degradation and has immunomodulatory properties. The aim of this study was to investigate the regulation of collagen‐induced arthritis by tryptophan catabolism mediated by IDO.MethodsArthritis was induced by immunization with type II collagen. After induction of arthritis, the expression of IDO was analyzed by quantitative reverse transcription–polymerase chain reaction. The effect of IDO deficiency on collagen‐induced arthritis was assessed in vivo by administration of 1‐methyltryptophan and clinical and histologic evaluation of IDO‐deficient mice. The requirement for IDO activation was bypassed by administration of L‐kynurenine.ResultsIDO was induced in lymph node dendritic cells after collagen immunization. Systemic inhibition of tryptophan catabolism during active arthritis increased disease severity. Conversely, bypassing the requirement for tryptophan degradation by the administration of L‐kynurenine resulted in amelioration of arthritis. Furthermore, IDO‐deficient mice showed a higher incidence of arthritis and exacerbated disease severity compared with IDO‐competent mice. Such increased disease activity in IDO‐deficient mice correlated early with increased production of the proinflammatory cytokines interferon‐γ and interleukin‐17 by lymph node T cells and later with increased infiltration of Th1 and Th17 cells in the inflamed joints.ConclusionOur data indicate that the induction of IDO controls the accumulation of Th1 and Th17 pathogenic T cells at the site of inflammation during collagen‐induced arthritis. Therefore, manipulation of the kynurenine pathway of tryptophan degradation provides the potential for therapeutic intervention in rheumatoid arthritis.
Gene expression profiling in neutrophils from children with polyarticular juvenile idiopathic arthritis
Authors: Jarvis James N. , Jiang Kaiyu , Frank Mark Barton , Knowlton Nicholas , Aggarwal Amita , Wallace Carol A. , McKee Ryan , Chaser Brad , Tung Catherine , Smith Laura B. , McGhee Julie L. , Chen Yanmin , Osban Jeanette , O'Neil Kathleen M. , Centola Michael 
Published: April 2009

AbstractObjectiveWe have previously reported a defect in neutrophil activation in children with polyarticular juvenile idiopathic arthritis (JIA). The current study was undertaken to determine whether gene expression abnormalities persist in JIA in remission and to use systems biology analysis to elucidate pathologic pathways in polyarticular JIA.MethodsWe performed gene expression profiling on neutrophils from children with polyarticular JIA. Children were grouped according to disease status. We studied 14 children with active disease who were taking medication, 8 children with clinical remission of disease who were taking medication (CRM status), and 6 children with clinical remission of disease who were not taking medication (CR status). We also studied 13 healthy children whose age ranges overlapped those of the patients.ResultsNeutrophil abnormalities persisted in children with polyarticular JIA even after disease remission was achieved. Children with active disease and those with CRM status showed no differences in expression of specific genes, although they could be separated on cluster analysis. A comparison of children with CR status and healthy control children revealed networks of pro‐ and antiinflammatory genes that suggested that remission is a state of homeostasis and balance rather than a return to normal immune function. Furthermore, gene overexpression in patients with CR status supports the hypothesis that neutrophils play a role in regulating adaptive immunity in this disease.ConclusionNeutrophil gene profiling in polyarticular JIA suggests important roles for neutrophils in disease pathogenesis. These findings suggest the presence of complex interactions between innate and adaptive immunity, that are not easily modeled in conventional, linear, reductionist systems.
Oncostatin M–induced CCL2 transcription in osteoblastic cells is mediated by multiple levels of STAT‐1 and STAT‐3 signaling: An implication for the pathogenesis of arthritis
Authors: Kok Sang‐Heng , Hong Chi‐Yuan , Kuo Mark Yen‐Ping , Wang Chih‐Chiang , Hou Kuo‐Liang , Lin Yi‐Ting , Galson Deborah L. , Lin Sze‐Kwan 
Published: April 2009

AbstractObjectiveTo examine the roles of STATs 1 and 3 in CCL2 production in human osteoblastic cells and their influences on arthritis development.MethodsThe expression of CCL2 in primary human osteoblasts and U2OS human osteoblastic cells was examined by Northern blotting and enzyme‐linked immunosorbent assay. The roles of STAT‐1/3 and c‐Fos were assessed using short hairpin RNAs (shRNA) to silence their functions. Serine phosphorylation of STATs was assessed by Western blotting. Promoter activities of c‐Fos and CCL2 were assessed by chloramphenicol acetyltransferase and luciferase assays, respectively. Interactions of STAT‐1, STAT‐3, and c‐Fos with DNA were evaluated by electrophoretic mobility shift assay (EMSA) and immunoprecipitation. The effect of the JAK inhibitor AG‐490 on collagen‐induced arthritis (CIA) in rats was examined using immunohistochemistry.ResultsOncostatin M (OSM) stimulated CCL2 expression in primary human osteoblasts and U2OS cells. In U2OS cells, STAT‐1 and STAT‐3 were involved in OSM‐stimulated CCL2 expression, and both the phosphatidylinositol 3‐kinase/Akt and MEK/ERK pathways were implicated in the activation of these STATs. STAT‐1 and STAT‐3 modulated the expression of c‐Fos and directly transactivated the CCL2 promoter. Moreover, EMSA showed formation of a DNA–protein complex containing STAT‐1, STAT‐3, and interestingly, c‐Fos. Immunoprecipitation confirmed the binding between c‐Fos and STAT‐1/3. Reporter assay revealed synergistic attenuation of CCL2 promoter activity by shRNA targeting of STAT‐1, STAT‐3, and c‐Fos. AG‐490 suppressed OSM‐stimulated activation of STAT‐1/3 and synthesis of CCL2 in vitro and diminished the severity of CIA and the number of CCL2‐synthesizing osteoblasts in vivo.ConclusionThese findings show that multiple levels of STAT‐1/3 signaling modulate OSM‐stimulated CCL2 expression in human osteoblastic cells. Clinically, this pathway may be related to the pathogenesis of arthritis.