403. Salivary mucins induce a Toll-like receptor 4-mediated pro-inflammatory response in human submandibular salivary cells: are mucins involved in Sjögren's syndrome?
作者: María-José Barrera.;Sergio Aguilera.;Enno Veerman.;Andrew F G Quest.;David Díaz-Jiménez.;Ulises Urzúa.;Juan Cortés.;Sergio González.;Isabel Castro.;Claudio Molina.;Verónica Bahamondes.;Cecilia Leyton.;Marcela A Hermoso.;María-Julieta González.
来源: Rheumatology (Oxford). 2015年54卷8期1518-27页
A hallmark characteristic of SS patients is the ectopic presence of the mucins MUC5B and MUC7 in the extracellular matrix of salivary glands that have lost apical-basolateral acinar-cell polarity. This study aims to determine whether exogenous salivary mucins induce gene expression of pro-inflammatory cytokines, as well as to evaluate whether the Toll-like receptor-4 (TLR4) pathway is involved in this response.
404. The impact of rheumatoid arthritis on work capacity in Chinese patients: a cross-sectional study.
作者: Xiaoying Zhang.;Rong Mu.;Xiuru Wang.;Chuanhui Xu.;Tianjiao Duan.;Yuan An.;Shuling Han.;Xiaofeng Li.;Lizhi Wang.;Caihong Wang.;Yongfu Wang.;Rong Yang.;Guochun Wang.;Xin Lu.;Ping Zhu.;Lina Chen.;Jinting Liu.;Hongtao Jin.;Xiangyuan Liu.;Lin Sun.;Ping Wei.;Junxiang Wang.;Haiying Chen.;Liufu Cui.;Rong Shu.;Bailu Liu.;Zhuoli Zhang.;Guangtao Li.;Zhenbin Li.;Jing Yang.;Junfang Li.;Bin Jia.;Fengxiao Zhang.;Jiemei Tao.;Jinying Lin.;Meiqiu Wei.;Xiaomin Liu.;Dan Ke.;Shaoxian Hu.;Cong Ye.;Xiuyan Yang.;Hao Li.;Cibo Huang.;Ming Gao.;Pei Lai.;Xingfu Li.;Lijun Song.;Yi Wang.;Xiaoyuan Wang.;Yin Su.;Zhanguo Li.
来源: Rheumatology (Oxford). 2015年54卷8期1478-87页
To evaluate the impact of RA on work capacity and identify factors related to work capacity impairment in patients with RA.
405. Severe flare as a predictor of poor outcome in ankylosing spondylitis: a cohort study using questionnaire and routine data linkage.
作者: Roxanne Cooksey.;Sinead Brophy.;Michael Dennis.;Helen Davies.;Mark Atkinson.;Elizabeth Irvine.;Stefan Siebert.
来源: Rheumatology (Oxford). 2015年54卷9期1563-72页
To explore severe flare and constant disease pattern (no periods of remission) in AS as predictors of poor outcomes [impaired function, unemployment/early retirement, work impairment, anti-TNF, surgery, frequent general practitioner (GP) visits, depression and anxiety].
406. The clinical spectrum of autoimmune congenital heart block.
作者: Pilar Brito-Zerón.;Peter M Izmirly.;Manuel Ramos-Casals.;Jill P Buyon.;Munther A Khamashta.
来源: Nat Rev Rheumatol. 2015年11卷5期301-12页
Autoimmune congenital heart block (CHB) is an immune-mediated acquired disease that is associated with the placental transference of maternal antibodies specific for Ro and La autoantigens. The disease develops in a fetal heart without anatomical abnormalities that could otherwise explain the block, and which is usually diagnosed in utero, but also at birth or within the neonatal period. Autoantibody-mediated damage of fetal conduction tissues causes inflammation and fibrosis and leads to blockage of signal conduction at the atrioventricular (AV) node. Irreversible complete AV block is the principal cardiac manifestation of CHB, although some babies might develop other severe cardiac complications, such as endocardial fibroelastosis or valvular insufficiency, even in the absence of cardiac block. In this Review, we discuss the epidemiology, classification and management of women whose pregnancies are affected by autoimmune CHB, with a particular focus on the autoantibodies associated with autoimmune CHB and how we should test for these antibodies and diagnose this disease. Without confirmed effective preventive or therapeutic strategies and further research on the aetiopathogenic mechanisms, autoimmune CHB will remain a severe life-threatening disorder.
407. Active-comparator design and new-user design in observational studies.
Over the past decade, an increasing number of observational studies have examined the effectiveness or safety of treatments for rheumatoid arthritis. Unlike randomized controlled trials (RCTs), however, observational studies of drug effects have methodological limitations such as confounding by indication. Active-comparator designs and new-user designs can help mitigate such biases in observational studies and improve the validity of their findings by making them more closely approximate RCTs. In an active-comparator study, the drug of interest is compared with another agent commonly used for the same indication, rather than with no treatment (a 'non-user' group). This principle helps to ensure that treatment groups have similar treatment indications, attenuating both measured and unmeasured differences in patient characteristics. The new-user study includes a cohort of patients from the time of treatment initiation, enabling assessment of patients' pretreatment characteristics and capture of all events occurring during follow-up. These two principles should be considered when designing or reviewing observational studies of drug effects.
408. Cellular imaging in rheumatic diseases.
作者: Robert A Benson.;Iain B McInnes.;James M Brewer.;Paul Garside.
来源: Nat Rev Rheumatol. 2015年11卷6期357-67页
Developments in cellular imaging now enable the real-time visualization of the choreographed sequence of events that underlie the development of immune responses in vivo. The previously unappreciated dynamics and anatomical context of cellular interactions, revealed in these studies, can have profound consequences for the 'decision' by the immune system to induce immunological priming versus immunological tolerance. Importantly, dysregulation of this balance can result in autoimmune diseases such as rheumatoid arthritis (RA). By further developing our understanding of how, where and when cells interact during immune responses, we can further dissect these events to assess how cell interactions might be aberrant in autoimmunity. A better knowledge of the mechanisms involved in cellular interactions by means of cellular imaging can help the development and targeting of therapies to particular disease stages and tissues in patients with RA in efforts to restore immune homeostasis.
409. Clocking in: chronobiology in rheumatoid arthritis.
作者: Frank Buttgereit.;Josef S Smolen.;Andrew N Coogan.;Christian Cajochen.
来源: Nat Rev Rheumatol. 2015年11卷6期349-56页
Circadian rhythms are of crucial importance for cellular and physiological functions of the brain and body. Chronobiology has a prominent role in rheumatoid arthritis (RA), with major symptoms such as joint pain and stiffness being most pronounced in the morning, possibly mediated by circadian rhythms of cytokine and hormone levels. Chronobiological principles imply that tailoring the timing of treatments to the circadian rhythm of individual patients (chronotherapy) could optimize results. Trials of NSAID or methotrexate chronotherapy for patients with RA suggest such an approach can improve outcomes and reduce adverse effects. The most compelling evidence for RA chronotherapy, however, is that coordinating the timing of glucocorticoid therapy to coincide with the nocturnal increase in blood IL-6 levels results in reduced morning stiffness and pain compared with the same glucocorticoid dose taken in the morning. Aside from optimizing relief of the core symptoms of RA, chronotherapy might also relieve important comorbid conditions such as depression and sleep disturbances. Surprisingly, chronobiology is not mentioned in official guidelines for conducting RA drug registration trials. Given the imperative to achieve the best value with approved drugs and health budgets, the time is ripe to translate the 'circadian concept' in rheumatology from bench to bedside.
411. Does disease activity at the start of biologic therapy influence health care costs in patients with RA?
作者: Kari Johansson.;Jonas K Eriksson.;Ronald van Vollenhoven.;Heather Miller.;Johan Askling.;Martin Neovius.; .
来源: Rheumatology (Oxford). 2015年54卷8期1472-7页
To investigate whether disease activity at baseline influences health care costs in patients with RA initiating biologic treatment.
413. Changes in forced vital capacity over time in systemic sclerosis: application of group-based trajectory modelling.
作者: Ada Man.;Todd Davidyock.;Laura T Ferguson.;Michael Ieong.;Yuqing Zhang.;Robert W Simms.
来源: Rheumatology (Oxford). 2015年54卷8期1464-71页
An accelerated rate of decline in forced vital capacity (FVC) affects >50% of patients with SSc but data on the variability and determinants of this change are scarce. We sought to identify trajectories of FVC and their associated variables in SSc patients over a 12-year period.
414. Autoimmunity: lungs and citrullination.
Anti-citrullinated protein antibodies are a distinctive feature of a subset of patients with rheumatoid arthritis (RA). A new report investigates how lung inflammation in patients with chronic obstructive pulmonary disease affects protein citrullination, providing an additional piece of information on the potential link between airway inflammation and RA.
415. Gene therapy approaches to regenerating the musculoskeletal system.
Injuries to the musculoskeletal system are common, debilitating and expensive. In many cases, healing is imperfect, which leads to chronic impairment. Gene transfer might improve repair and regeneration at sites of injury by enabling the local, sustained and potentially regulated expression of therapeutic gene products; such products include morphogens, growth factors and anti-inflammatory agents. Proteins produced endogenously as a result of gene transfer are nascent molecules that have undergone post-translational modification. In addition, gene transfer offers particular advantages for the delivery of products with an intracellular site of action, such as transcription factors and noncoding RNAs, and proteins that need to be inserted into a cell compartment, such as a membrane. Transgenes can be delivered by viral or nonviral vectors via in vivo or ex vivo protocols using progenitor or differentiated cells. The first gene transfer clinical trials for osteoarthritis and cartilage repair have already been completed. Various bone-healing protocols are at an advanced stage of development, including studies with large animals that could lead to human trials. Other applications in the repair and regeneration of skeletal muscle, intervertebral disc, meniscus, ligament and tendon are in preclinical development. In addition to scientific, medical and safety considerations, clinical translation is constrained by social, financial and logistical issues.
416. The current state of scaffolds for musculoskeletal regenerative applications.
Musculoskeletal disease and injury are highly prevalent conditions that lead to many surgical procedures. Autologous tissue transfer, allograft transplantation and nontissue prosthetics are currently used for the surgical treatment of critical-sized defects. However, the field of tissue engineering is actively investigating tissue-replacement solutions, many of which involve 3D scaffolds. Scaffolds must provide a balance of shape, biomechanical function and biocompatibility in order to achieve tissue replacement success. Different tissues can have different requirements for success, which has led to the development of various materials with unique characteristics. Articular cartilage scaffolds have the most robust clinical experience, with many scaffolds, mostly constructed of natural materials, showing promise, but levels of success vary. Tendon scaffolds also have proven clinical applications, with human-dermis-derived scaffolds showing the most potential. Synthetic and naturally derived meniscus scaffolds have been investigated in few clinical studies, but the results are encouraging. Bone scaffolds are limited to amorphous pastes and putties, owing to difficulties achieving adequate vascularization and biomechanical optimization. The complex physiological function and vascular demands of skeletal muscle have limited the widespread clinical use of scaffolds for engineering this tissue. Continued progress in preclinical study, not only of scaffolds, but also of other facets of tissue engineering, should enable the successful translation of musculoskeletal tissue engineering solutions to the clinic.
417. Cytokines in systemic juvenile idiopathic arthritis and haemophagocytic lymphohistiocytosis: tipping the balance between interleukin-18 and interferon-γ.
作者: Karen Put.;Anneleen Avau.;Ellen Brisse.;Tania Mitera.;Stéphanie Put.;Paul Proost.;Brigitte Bader-Meunier.;René Westhovens.;Benoit J Van den Eynde.;Ciriana Orabona.;Francesca Fallarino.;Lien De Somer.;Thomas Tousseyn.;Pierre Quartier.;Carine Wouters.;Patrick Matthys.
来源: Rheumatology (Oxford). 2015年54卷8期1507-17页
To study the role of IFN-γ in the pathogenesis of systemic JIA (sJIA) and haemophagocytic lymphohistiocytosis (HLH) by searching for an IFN-γ profile, and to assess its relationship with other cytokines.
418. Drug survival of anti-tumour necrosis factor α therapy in spondyloarthropathies: results from the Spanish emAR II Study.
作者: José Luis Rosales-Alexander.;Jerónimo Balsalobre Aznar.;Sabina Pérez-Vicente.;César Magro-Checa.
来源: Rheumatology (Oxford). 2015年54卷8期1459-63页
To assess drug survival and the reasons for switching anti-TNF-α therapy in SpA patients in a Spanish nationwide study.
419. Performance of the new ACR/EULAR classification criteria for systemic sclerosis in clinical practice.
作者: Suzana Jordan.;Britta Maurer.;Martin Toniolo.;Beat Michel.;Oliver Distler.
来源: Rheumatology (Oxford). 2015年54卷8期1454-8页
The preliminary classification criteria for SSc lack sensitivity for mild/early SSc patients, therefore, the new ACR/EULAR classification criteria for SSc were developed. The objective of this study was to evaluate the performance of the new classification criteria for SSc in clinical practice in a cohort of mild/early patients.
420. Successes, challenges and developments in Australian rheumatology.
Australia is a geographically vast but sparsely populated country with many unique factors affecting the practice of rheumatology. With a population comprising minority Indigenous peoples, a historically European-origin majority population, and recent large-scale migration from Asia, the effect of ethnic diversity on the phenotype of rheumatic diseases such as systemic lupus erythematosus (SLE) is a constant of Australian rheumatology practice. Australia has a strong system of universal healthcare and subsidized access to medications, and clinical and research rheumatology are well developed, but inequitable access to specialist care in urban and regional centres, and the complex disconnected structure of the Australian healthcare system, can hinder the management of chronic diseases.
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