bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and Functional Properties of Deep Abdominal Subcutaneous Adipose Tissue Explain Its Association With Insulin Resistance and Cardiovascular Risk in Men
Authors: Marinou Kyriakoula , Hodson Leanne , Vasan Senthil K. , Fielding Barbara A. , Banerjee Rajarshi , Brismar Kerstin , Koutsilieris Michael , Clark Anne , Neville Matt J. , Karpe Fredrik 
Published: November 2013

OBJECTIVE
Fat distribution is an important variable explaining metabolic heterogeneity of obesity. Abdominal subcutaneous adipose tissue (SAT) is divided by the Scarpa’s fascia into a deep subcutaneous adipose tissue (dSAT) and a superficial subcutaneous adipose tissue (sSAT) layer. This study sought to characterize functional differences between the two SAT layers to explore their relative contribution to metabolic traits and cardiovascular risk (CVR) profile.

RESEARCH DESIGN AND METHODS
We recruited 371 Caucasians consecutively from a local random, population-based screening project in Oxford and 25 Asian Indians from the local community. The depth of the SAT layers was determined by ultrasound (US), and adipose tissue (AT) biopsies were performed under US guidance in a subgroup of 43 Caucasians. Visceral adipose tissue (VAT) mass was quantified by dual-energy X-ray absorptiometry scan.

RESULTS
Male adiposity in both ethnic groups was characterized by a disproportionate expansion of dSAT, which was strongly correlated with VAT mass. dSAT depth was a strong predictor of global insulin resistance (IR; homeostatic model assessment of IR), liver-specific IR (insulin-like growth factor binding protein-1), and Framingham risk score independently of other measures of adiposity in men. Moreover, dSAT had higher expression of proinflammatory, lipogenic, and lipolytic genes and contained higher proportions of saturated fatty acids. There was increased proportion of small adipocytes in dSAT.

CONCLUSIONS
SAT is heterogeneous; dSAT expands disproportionally more than sSAT with increasing obesity in Caucasian males (confirmed also in Asian Indians). Its expansion is related to increased CVR independent of other adiposity measures, and it has biological properties suggestive of higher metabolic activity contributing to global IR.
Clinical and Genetic Determinants of Progression of Type 2 Diabetes: A DIRECT Study
Authors: Zhou Kaixin , Donnelly Louise A. , Morris Andrew D. , Franks Paul W. , Jennison Chris , Palmer Colin N.A. , Pearson Ewan R. 
Published: November 2013

OBJECTIVE
To identify the clinical and genetic factors that explain why the rate of diabetes progression is highly variable between idividuals following diagnosis of type 2 diabetes.

RESEARCH DESIGN AND METHODS
We studied 5,250 patients with type 2 diabetes using comprehensive electronic medical records in Tayside, Scotland, from 1992 onward. We investigated the association of clinical, biochemical, and genetic factors with the risk of progression of type 2 diabetes from diagnosis to the requirement of insulin treatment (defined as insulin treatment or HbA1c ≥8.5% [69 mmol/mol] treated with two or more noninsulin therapies).

RESULTS
Risk of progression was associated with both low and high BMI. In an analysis stratified by BMI and HbA1c at diagnosis, faster progression was independently associated with younger age at diagnosis, higher log triacylglyceride (TG) concentrations (hazard ratio [HR] 1.28 per mmol/L [95% CI 1.15–1.42]) and lower HDL concentrations (HR 0.70 per mmol/L [95% CI 0.55–0.87]). A high Genetic Risk Score derived from 61 diabetes risk variants was associated with a younger age at diagnosis and a younger age when starting insulin but was not associated with the progression rate from diabetes to the requirement of insulin treatment.

CONCLUSIONS
Increased TG and low HDL levels are independently associated with increased rate of progression of diabetes. The genetic factors that predispose to diabetes are different from those that cause rapid progression of diabetes, suggesting a difference in biological process that needs further investigation.
Disease Control and Safety of Belimumab Plus Standard Therapy Over 7 Years in Patients with Systemic Lupus Erythematosus
Authors: Ginzler Ellen M. , Wallace Daniel J. , Merrill Joan T. , Furie Richard A. , Stohl William , Chatham W. Winn , Weinstein Arthur , McKay James D. , McCune W. Joseph , Zhong Z. John , Freimuth William W. , Petri Michelle A. ,   The LBSL02/99 Study Group
Published: November 2013

Objective.To evaluate the efficacy/safety of belimumab plus standard therapy in patients (n = 449) with active systemic lupus erythematosus (SLE) treated up to 7 years (n = 177 currently ongoing).Methods.Patients (n = 345) who completed a double-blind, placebo-controlled, 52-week study of belimumab 1, 4, or 10 mg/kg and 24-week extension of belimumab (placebo switched to 10 mg/kg; belimumab same dose or switched to 10 mg/kg) could receive belimumab 10 mg/kg in an open-label continuation study (n = 296). Disease activity was analyzed in patients with active SLE at baseline of the initial study. Biomarker and SLE medication changes were evaluated, and adverse events (AE) were monitored throughout the study.Results.Total belimumab exposure over 7 years (double-blind and open-label periods): 1746 patient-years. SLE Responder Index (SRI) response rates at Week 52 in autoantibody-positive patients: placebo, 29%; belimumab, 46% (p < 0.05). In the continuation study, 57% of auto-antibody-positive patients had an SRI response by Year 2 and 65% by Year 7; severe flares occurred in 19% with placebo and 17% with belimumab during the first year, with the annual rate declining to 2%–9% during years 2–7. Anti-dsDNA autoantibodies in patients positive for them at baseline had a progressive decline of 40%–60% from baseline over 2–7 years with belimumab. Corticosteroid use decreased over time with ≥ 50–55% reduction in median dose during years 5–7. Serious and overall annual AE rates, including infections, were generally stable or decreased during 7-year treatment.Conclusion.Disease control and safety profile were maintained in patients with active SLE taking belimumab plus standard therapy for up to 7 years. [ClinicalTrials.gov numbers: NCT00071487 and NCT00583362]
Higher Frequency of Peripheral Blood Interleukin 21 Positive Follicular Helper T Cells in Patients with Ankylosing Spondylitis
Authors: Xiao Fei , Zhang Hai-Yu , Liu Yi-Jun , Zhao Ding , Shan Yu-Xing , Jiang Yan-Fang 
Published: November 2013

Objective.The role of follicular Th (TFH) cells remains unclear in the pathogenesis of ankylosing spondylitis (AS). Our study examined the frequency of different subsets of circulating CXCR5+CD4+ T cells in patients with AS before and after receiving therapy.Methods.Percentages of peripheral blood inducible costimulator (ICOS)+, programmed death 1 (PD-1)+, and interleukin 21 (IL-21)+ CXCR5+CD4+ T cells in 26 patients with AS and 12 healthy controls (HC) were examined by flow cytometry, and the disease activity of individual patients was measured by Bath AS Disease Activity Index (BASDAI). The concentrations of serum IL-21, IgG, IgA, IgM, and C-reactive protein (CRP) were examined and the values of erythrocyte sedimentation rate (ESR) were measured. The potential association among these measures was analyzed.Results.In comparison with that in HC, significantly increased percentages of CXCR5+CD4+, CXCR5+CD4+PD-1+, and CXCR5+CD4+IL-21+, but not CXCR5+CD4+ICOS+ and PD-1+ICOS+CXCR5+CD4+ T cells, and elevated concentrations of serum IL-21 were detected in patients with AS (p = 0.001, p = 0.012, p < 0.001, p = 0.233, p = 0.216, p < 0.001, respectively). Treatment with meloxicam, thalidomide, and etanercept for 1 month significantly reduced percentages of IL-21+CXCR5+CD4+ T cells and concentrations of serum IL-21 (p < 0.001, p < 0.001, respectively), accompanied by significantly minimized disease activity in drug responders, but not in the drug nonresponders. Further, percentages of IL-21+CXCR5+CD4+ T cells were positively correlated with BASDAI in patients (r = 0.6, p = 0.0012) and in the drug-responders 1 month after treatment (r = 0.68, p = 0.005), while the percentages of PD-1+CXCR5+CD4+ T cells were negatively correlated with BASDAI (r = −0.58, p = 0.0018).Conclusion.These data suggest that IL-21+CXCR5+CD4+ T cells may be associated with development of AS and that the frequency of IL-21+CXCR5+CD4+ T cells may be a biomarker for evaluation of disease activity and drug responses in patients with AS, particularly in drug-responding patients.
Risk Markers of Juvenile Idiopathic Arthritis-associated Uveitis in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry
Authors: Angeles-Han Sheila T. , Pelajo Christina F. , Vogler Larry B. , Rouster-Stevens Kelly , Kennedy Christine , Ponder Lori , McCracken Courtney , Lopez-Benitez Jorge , Drews-Botsch Carolyn , Prahalad Sampath ,   The CARRA Registry Investigators
Published: November 2013

Objective.To characterize the epidemiology and clinical course of children with juvenile idiopathic arthritis-associated uveitis (JIA-U) in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and explore differences between African American (AA) and non-Hispanic white (NHW) children.Methods.There were 4983 children with JIA enrolled in the CARRA Registry. Of those, 3967 NHW and AA children were included in this study. Demographic and disease-related data were collected from diagnosis to enrollment. Children with JIA were compared to those with JIA-U. Children with JIA-U were also compared by race.Results.There were 459/3967 children (11.6%) with JIA-U in our cohort with a mean age (SD) of 11.4 years (± 4.5) at enrollment. Compared to children with JIA, they were younger at arthritis onset, more likely to be female, had < 5 joints involved, had oligoarticular JIA, and were antinuclear antibody (ANA)-positive, rheumatoid factor (RF)-negative, and anticitrullinated protein antibody-negative. Predictors of uveitis development included female sex, early age of arthritis onset, and oligoarticular JIA. Polyarticular RF-positive JIA subtype was protective. Nearly 3% of children with JIA-U were AA. However, of the 220 AA children with JIA, 6% had uveitis; in contrast, 12% of the 3721 NHW children with JIA had uveitis.Conclusion.In the CARRA registry, the prevalence of JIA-U in AA and NHW children is 11.6%. We confirmed known uveitis risk markers (ANA positivity, younger age at arthritis onset, and oligoarticular JIA). We describe a decreased likelihood of uveitis in AA children and recommend further exploration of race as a risk factor in a larger population of AA children.
Effectiveness and Safety of Tocilizumab: Postmarketing Surveillance of 7901 Patients with Rheumatoid Arthritis in Japan
Authors: Koike Takao , Harigai Masayoshi , Inokuma Shigeko , Ishiguro Naoki , Ryu Junnosuke , Takeuchi Tsutomu , Takei Syuji , Tanaka Yoshiya , Sano Yoko , Yaguramaki Hitomi , Yamanaka Hisashi 
Published: November 2013

Objective.An all-patient postmarketing surveillance program was conducted to evaluate the safety and effectiveness of tocilizumab (TCZ) for rheumatoid arthritis (RA) in the real-world clinical setting in Japan.Methods.Patients received 8 mg/kg TCZ every 4 weeks and were observed for 28 weeks. Data were collected on patient characteristics, and drug safety and effectiveness.Results.A total of 7901 patients were enrolled. Percentages of total and serious adverse events (AE) were 43.9% and 9.6%, respectively. The most common serious AE were infections (3.8%). Logistic regression analysis identified the following risk factors for the development of serious infection: age ≥ 65 years, disease duration ≥ 10 years, previous or concurrent respiratory disease, and concomitant corticosteroid dose > 5 mg/day (prednisolone equivalent). The incidence rate of serious infections in patients with ≥ 3 risk factors was 11.2%, compared with 1.2% for patients without risk factors. The Week 28 rates of 28-joint Disease Activity Score–erythrocyte sedimentation rate remission, Boolean remission, and European League Against Rheumatism (EULAR) Good Response were 47.6%, 15.1%, and 59.4%, respectively. Contributing factors for effectiveness were body weight ≥ 40 kg, less advanced RA, no previous biologics, no concomitant corticosteroids or nonsteroidal antiinflammatory drugs, and low disease activity at baseline. From the benefit-risk balance analysis, patients with a high probability of remission and a low probability of developing serious infection were most likely to have less advanced RA and to have not received biologics previously.Conclusion.These data confirm the safety and effectiveness of TCZ in patients with RA in the real-world clinical setting in Japan and identify factors that contribute to the successful use of TCZ for RA.
Chronic Widespread Pain in Patients with Rheumatoid Arthritis and the Relation Between Pain and Disease Activity Measures over the First 5 Years
Authors: Andersson Maria L.E. , Svensson Björn , Bergman Stefan 
Published: November 2013

Objective.To study the prevalence of chronic widespread pain (ChWP), chronic regional pain (ChRP), and fibromyalgia in patients with early rheumatoid arthritis (RA) followed for 5 years after inclusion, and to study the effect of pain on measures of disease activity and function.Methods.A questionnaire was sent to 1910 patients participating in the Better Anti-Rheumatic Pharmacotherapy study. The responders (73%) were divided into 3 groups according to the reported pain duration and distribution — patients having no chronic pain (NChP), ChWP, and ChRP. Outcome measures were the 28-joint Disease Activity Score (DAS28), the Health Assessment Questionnaire (HAQ), and C-reactive protein (CRP).Results.Thirty-four percent of respondents reported ChWP, 46% ChRP, and 20% NChP. Patients reporting ChWP were more often women and had more pain and tender joints at inclusion. From 6 months to 5 years of followup, mean DAS28, visual analog scale (VAS) pain, VAS global health, and HAQ were significantly higher in the ChWP group than in the other groups. However, all groups showed a similar pattern in swollen joint count, erythrocyte sedimentation rate (ESR), and CRP. From 12 months the ChWP group was treated with prednisolone to a greater extent than the ChRP group, and it had a rate of treatment with disease-modifying antirheumatic drugs similar to that of the ChRP group.Conclusion.ChWP is a common feature in RA, more associated with high values for variables related to pain such as the DAS28 and HAQ than to indicators of ongoing inflammation such as swollen joint count, ESR, and CRP. Patients with ChWP should be identified so that adequate treatment also of the noninflammatory pain may be instituted.
Clinical Investigation of Nontuberculous Mycobacterial Lung Disease in Japanese Patients with Rheumatoid Arthritis Receiving Biologic Therapy
Authors: Yamakawa Hideaki , Takayanagi Noboru , Ishiguro Takashi , Kanauchi Tetsu , Hoshi Toshiko , Sugita Yutaka 
Published: November 2013

Objective.To review patients with rheumatoid arthritis (RA) receiving biologic therapy following a diagnosis of nontuberculous mycobacterial (NTM) lung disease and to evaluate disease deterioration according to clinical and radiological features and anti-NTM therapy.Methods.We retrospectively analyzed medical records of 11 human immunodeficiency virus-negative patients with RA (median age, 64 years) receiving biologic therapy following diagnosis of NTM lung disease.Results.NTM species includedMycobacterium aviumcomplex in 9 patients (81.8%) andM. gordonaein 2 (18.2%). Underlying respiratory disease was present in 6 patients (54.5%), and most (81.8%) had radiographic features of nodular/bronchiectatic disease. Extent of NTM disease was 1–2 pulmonary lobes in 6 patients (54.5%), 3–4 lobes in 5 patients (45.5%), and 5–6 lobes in none. The results of radiological evaluations were unchanged or improved in 7 patients (63.6%) and worsened in 4 (36.4%). Radiological outcome was worse in patients with poor RA control despite their receiving biologic therapies for RA. Two of 3 patients receiving anti-NTM therapy as initial management for NTM improved, and 1 worsened. Three of 4 patients with worsened radiological outcome had high erythrocyte sedimentation rate (> 50 mm/h).Conclusion.Radiological deterioration was not observed in the majority of patients with RA receiving biologic therapy with NTM lung disease, and radiological outcome of pulmonary NTM was favorable in some patients undergoing anti-NTM therapy. Further studies focusing on disease deterioration according to biologic therapy received during NTM followup are warranted to determine appropriate treatment of RA patients with NTM lung disease.
Treatment of Refractory Takayasu Arteritis with Tocilizumab: 7 Italian Patients from a Single Referral Center
Authors: Tombetti Enrico , Franchini Stefano , Papa Maurizio , Sabbadini Maria Grazia , Baldissera Elena 
Published: November 2013

Objective.The aim of our study was to evaluate the safety and the efficacy of tocilizumab (TCZ) for refractory Takayasu arteritis (TA).Methods.We retrospectively assessed the outcome of blocking interleukin (IL)-6 with TCZ in 7 consecutive patients with refractory TA using a combination of clinical and imaging assessment.Results.During a median followup visit at 14 months, 4 patients taking TCZ [including 2 nonresponders to tumor necrosis factor (TNF) inhibitors] achieved clinical response, suggesting a nonredundant role for IL-6 in TA. Inflammatory markers normalized in all patients treated with TCZ. However, vascular progression occurred in 4 patients, suggesting the involvement of other inflammatory pathways and confirming the limitations of erythrocyte sedimentation rate and C-reactive protein for disease activity assessment while taking TCZ. Three patients experienced adverse events and 2 suspended TCZ.Conclusion.TCZ may be effective in a subset of patients with refractory TA, even in cases of unresponsiveness to TNF inhibitors. Inflammatory markers are not valid markers of TA activity on TCZ. Further studies are needed to confirm these preliminary observations.
Correlation of Radiographic Progression with the Cumulative Activity of Synovitis Estimated by Power Doppler Ultrasound in Rheumatoid Arthritis: Difference Between Patients Treated with Methotrexate and Those Treated with Biological Agents
Authors: Ikeda Kei , Nakagomi Daiki , Sanayama Yoshie , Yamagata Mieko , Okubo Ayako , Iwamoto Taro , Kawashima Hirotoshi , Takahashi Kentaro , Nakajima Hiroshi 
Published: November 2013

Objective.Our prospective study aimed to demonstrate that the cumulative synovial power Doppler (PD) ultrasound scores correlate with radiographic progression better than conventional measures in patients with rheumatoid arthritis (RA). We also investigated the difference between antirheumatic agents.Methods.Sixty-nine patients with RA who had recently received either methotrexate (MTX; n = 23), tumor necrosis factor (TNF) antagonists (n = 28), or tocilizumab (TCZ; n = 18) were enrolled. Patients underwent clinical, laboratory, and ultrasonographic assessment at baseline, 12 weeks, and 24 weeks. Radiographic damage was evaluated using van der Heijde modified total Sharp score (TSS) at baseline and 24 weeks.Results.Fifty-seven patients continued the same treatment regimen for 24 weeks and completed the study, and 21 patients (36.8%) showed radiographic progression during the study period. In all patients, ΔTSS significantly correlated both with cumulative 28-joint Disease Activity Score–C-reactive protein (DAS28-CRP; ρ = 0.342, p = 0.009) and cumulative total PD scores (ρ = 0.357, p = 0.006). In MTX-treated patients, cumulative total PD scores significantly correlated with ΔTSS (ρ = 0.679, p = 0.004), whereas cumulative DAS28-CRP did not (ρ = 0.487, p = 0.056). However, cumulative total PD scores did not correlate with ΔTSS in TNF antagonist–treated or TCZ-treated patients.Conclusion.Our data confirm the evidence that synovial PD activity more accurately reflects active synovial inflammation (which actually causes joint destruction) than do conventional measures in patients treated with MTX. Our data also indicate that TNF antagonists can inhibit short-term radiographic progression in the presence of active synovitis.
COMP-C3b Complexes in Rheumatoid Arthritis with Severe Extraarticular Manifestations
Authors: Happonen Kaisa E. , Saxne Tore , Jacobsson Lennart , Sturfelt Gunnar , Rönnelid Johan , Mollnes Tom Eirik , Heinegård Dick , Turesson Carl , Blom Anna M. 
Published: November 2013

Objective.To investigate biomarker patterns in rheumatoid arthritis (RA) with extraarticular manifestations.Methods.Cartilage oligomeric matrix protein (COMP), COMP-C3b, and soluble terminal complement complexes (sTCC) were measured by ELISA.Results.COMP-C3b levels were higher in patients with RA than in healthy controls and lower in extraarticular RA (ExRA) than in RA controls. In patients with ExRA, sTCC levels were higher than in RA controls, and correlated inversely with serum COMP-C3b levels in the ExRA group.Conclusion.Patients with ExRA had lower levels of COMP-C3b. This may be a consequence of complement consumption or a lower potential for COMP from these patients to activate complement.
Ultrasound and Magnetic Resonance Imaging in the Evaluation of Psoriatic Dactylitis: Status and Perspectives
Authors: Bakewell Catherine J. , Olivieri Ignazio , Aydin Sibel Z. , Dejaco Christian , Ikeda Kei , Gutierrez Marwin , Terslev Lene , Thiele Ralf , D’Agostino Maria Antionetta , Kaeley Gurjit S. 
Published: November 2013

Objective.Dactylitis, a characteristic feature of the spondyloarthropathies, occurs in up to 48% of patients with psoriatic arthritis (PsA). No clear consensus on the underlying components and pathogenesis of dactylitis exists in the literature. We undertook a systematic review of ultrasound (US) and magnetic resonance imaging (MRI) literature to better define imaging elements that contribute to the dactylitic digit seen in PsA. Our objectives were to determine first the level of homogeneity of each imaging modality’s definition of the components of dactylitis, and second, to evaluate the metric properties of each imaging modality according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) filter.Methods.Searches were performed in PUBMED and EMBASE for articles pertaining to MRI, US, and dactylitis. Data regarding the reported features of dactylitis were collected and categorized, and the metrological qualities of the studies were assessed.Results.The most commonly described features of dactylitis were flexor tendon tenosynovitis and joint synovitis (90%). Extratendinous soft tissue thickening and extensor tendonitis were described nearly equally as being present and absent. Discrepancy exists as to whether entheses proper contribute to the etiology of dactylitis. An increasing number of studies categorize abnormalities in several tissue compartments including the soft tissue, tendon sheaths, and joints, as well as ligaments.Conclusion.The understanding of which tissues contribute to dactylitic inflammation has evolved. However, there is a lack of literature regarding the natural history of these abnormalities. This systematic review provides guidance in defining elementary lesions that may discriminate dactylitic digits from normal digits, leading to development of a composite measure of activity and severity of dactylitis.