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ID PMID Title PublicationDate abstract
24771112 Cost-effectiveness of treatment strategies using combination disease-modifying anti-rheuma 2014 Oct OBJECTIVE: The aim of this study was to estimate the cost-effectiveness of combination DMARDs with short-term glucocorticoids in early active RA using data from the 2-year Combination of Anti-Rheumatic Drugs in Early RA (CARDERA) trial. METHODS: CARDERA enrolled 467 patients with active RA of <24-months duration. All patients received MTX; half received step-down prednisolone and half ciclosporin in a placebo-controlled factorial design. Differences in mean costs and quality-adjusted life-years (QALYs) over 24-months follow-up were estimated using patient-level data from a UK health service perspective and 2011-12 costs. RESULTS: Two-year costs for each treatment strategy showed primary care costs were negligible across all groups. Drug costs were lowest with MTX/ciclosporin and triple therapy. Hospital costs were lowest with MTX/prednisolone and triple therapy. Triple therapy was least costly and most effective; it dominated all other strategies. At positive values for a QALY in the typical UK range (£20 000-30 000) the probability that triple therapy was the most cost-effective strategy was 0.9. Results were robust to methods used to impute missing data. CONCLUSION: Intensive treatment of early RA with triple therapy (two DMARDs and short-term glucocorticoids) is both clinically effective and cost effective.
25627307 [The influence of physical function on the risk of falls among adults with rheumatoid arth 2014 Sep OBJECTIVES: Identify fall prevalence in the last 12 months among patients with rheumatoid arthritis (RA) and verify the influence of disease activity and physical function in the risk of falls. METHODS: 43 patients with RA participated in this study. The following parameters were evaluated: clinical aspects; fall occurrence in the last 12 months; ESR (mm/h); pain on a visual analogue scale (VAS) ranging from 0 to 10cm; disease activity, measured by the Disease Activity Score 28/ESR (DAS-28/ESR); physical function, assessed by the Health Assessment Questionnaire (HAQ); and risk of falling, assessed by two tests, the 5-time sit down-to-stand up test (SST5) and the timed get up and go test (TUG). RESULTS: The fall prevalence in the last 12 months was 30.2% (13/43). The HAQ total score was the independent risk factor that had significant influence on SST5 performance, and the other variables did not succeeded to explain the SST5 variability. HAQ explained 42.9% of SST5 variability (P<0.001, adjusted R(2)=0.429). HAQ total score and ESR had a significant influence on TUG score performance. Together, these two variables explained 68.8% of the total variation in TUG score (adjusted R(2)=0.688). CONCLUSION: Patients with RA have high fall prevalence and the functional disability represents the main factor related to falls risk.
25363521 Body awareness in persons diagnosed with rheumatoid arthritis. 2014 Living with rheumatoid arthritis (RA) poses physiological and psychological demands on a person. RA is a autoimmune disease that can cause pain, disability, and suffering. The ability to notice bodily inner sensations and stimuli (body awareness, BA) is described in the literature in ways that could have either a positive or a negative impact on a person's health. The concept of BA is complex and a thorough understanding is needed about what BA means from the patient's perspective. This study was therefore conducted to acquire greater insight into this phenomenon. The study is grounded in a phenomenological life-world perspective. Eighteen narrative interviews were conducted in patients (age range 23-78 years) with RA. The interviews were analyzed using the Empirical Phenomenological Psychological method. General characteristics were found running through all 18 interviews, indicating that the disease resulted in a higher degree of negatively toned BA. BA was either a reactive process of searching or controlling after disease-related symptoms or a reactive process triggered by emotions. BA was an active process of taking an inventory of abilities. All participants had the ability to shift focus from BA to the outside world. Four typologies were identified: "A reactive process on symptoms," "A reactive process on emotional triggers," "An active process of taking an inventory of abilities," and "A shifting from BA to the outside world." In conclusion, because BA can be both positively and negatively toned, health care professionals must have a good understanding of when BA is positive and when it is negative in relation to the patient. RA had caused a higher degree of negatively toned BA. Thus, the ability to shift attention from BA to activity in the outside world could sometimes be beneficial for the patient's general health.
24564933 The separate impact of tight control schemes and disease activity on quality of life in pa 2014 May OBJECTIVES: To examine in patients with early rheumatoid arthritis (RA) whether quality of life (QoL), independently of disease activity, is affected by tight control treatment strategy schemes. METHODS: In the Computer Assisted Management in Early RA (CAMERA) trials, patients with early RA, disease duration <1 year, no prior use of DMARDs) had been randomised to a methotrexate (MTX)-based tight control strategy or usual care (CAMERA study) or to 10 mg/d prednisone or placebo both added from start to a MTX-based tight control strategy (CAMERA-II study). In either study, randomisation to the more intensive strategy resulted in lower disease activity. To assess QoL, the 'Influence of Rheumatic Diseases on General Health and Lifestyle' questionnaire (IRGL) was used. Baseline and 1- and/or 2-year measurements were analysed with regression analyses with the IRGL (sub)scales as outcome variables and treatment strategy and disease activity assessing 28 joints (DAS28) as independent variables, correcting for baseline values of each scale and possible confounders (gender, age, rheumatoid factor status). RESULTS: There was no clear association between either of the treatment strategies and QoL, but a decrease in DAS28 was associated with improvement in the majority of QoL (sub)scales. CONCLUSIONS: No independent effect of the specific tight control strategies schemes on QoL was found, while there was a clear disease activity related effect. Thus frequent outpatient visits or the inclusion of prednisone in a tight control strategy did not negatively influence QoL.
25627223 [Quality of life in adults and elderly patients with rheumatoid arthritis]. 2014 Jul OBJECTIVE: To analyze and compare quality of life (QoL) in adults and elderly patients with rheumatoid arthritis (RA). METHODS: This was a cross-sectional quantitative study. The tools include the Medical Outcomes Study Short Form-36 (SF-36), the Disease Activity Score 28 (DAS-28), the Assessment Health Questionnaire (HAQ), the Beck Depression Inventory (BDI) and the 6-Minute Walk Test (6MWT). Data analysis was done by descriptive statistics, Student's t test and linear regression test, with significance level of p <0.05. RESULTS: The sample consisted of 99 patients diagnosed with RA, divided into adults and elderly. Those considered adults were 18-59 years-old and those with 60 years or older where considered elderly. In SF-36, the groups showed the pain domain as the most compromised and the emotional aspects domain as the less compromised. Both showed moderate level of disease activity and mild disability. Applying the t test, it was found that there was no significant difference between groups with respect to QoL, functional ability, depression and disease activity. The difference was significant in the 6MWT, in which the elderly achieved an average of 330.8 m, and the adults, 412.2 m (p=0.000). In linear regression, a significant correlation (r=-0.31) between the 6MWT and increasing age was noted. CONCLUSION: QoL and functional capacity in RA were affected in adults and the elderly. How-ever, the results showed no significant difference between groups, with the exception of the 6MWT.
24720645 Transitional connective tissue diseases: description of four cases. 2014 The term overlap syndromes (OS) is used to define a group of disorders characterized by the presence, in the same patient, of clinical features typical for more than one definite connective tissue disease (CTD). OBJECTIVE: To show that patients may not only have an overlap of two or more CTDs but may also change their disease phenotype from that of a definite CTD to another. PATIENTS AND METHODS: Retrospective analysis of medical records of four patients with a disease duration of about thirty years and a transition from a well definite CTD into another. RESULTS: The first patient was diagnosed, at the beginning of the 1980s, as affected by diffuse cutaneous systemic sclerosis (dcSSc) and developed systemic lupus erythematosus (SLE) twenty-five years later. The second and the third patients were diagnosed with SLE at the beginning of their disease: the second patient developed, in the course of her disease, an overlap syndrome (OS) SSc/rheumatoid arthritis (RA) and the third SSc and finally microscopic polyangiitis (MPA). The fourth patient was diagnosed as primary Sjogren's syndrome (SS) then as rheumatoid arthritis (RA) and finally developed SLE. CONCLUSIONS: Patients may not only show an overlap of two or more CTDs but also a transition from a well definite CTD into another. We propose the term "transitional connective tissue diseases" (TCTDs) to define their disease. A higher number of patients may allow us to better identify this new subgroup of CTDs and probably, also, predictors of evolution.
24778468 Circulating miRNA-125b is a potential biomarker predicting response to rituximab in rheuma 2014 Although biologic therapies have changed the course of rheumatoid arthritis (RA), today's major challenge remains to identify biomarkers to target treatments to selected patient groups. Circulating micro(mi)RNAs represent a novel class of molecular biomarkers whose expression is altered in RA. Our study aimed at quantifying miR-125b in blood and serum samples from RA patients, comparing healthy controls and patients with other forms of rheumatic diseases and arthritis, and evaluating its predictive value as biomarker for response to rituximab. Detectable levels of miR-125b were measured in total blood and serum samples and were significantly elevated in RA patients compared to osteoarthritic and healthy donors. The increase was however also found in patients with other forms of chronic inflammatory arthritis. Importantly, high serum levels of miR-125b at disease flare were associated with good clinical response to treatment with rituximab three months later (P = 0.002). This predictive value was not limited to RA as it was also found in patients with B lymphomas. Our results identify circulating miR-125b as a novel miRNA over expressed in RA and suggest that serum level of miR-125b is potential predictive biomarker of response to rituximab treatment.
24637598 Role of SFB in autoimmune arthritis: an example of regulation of autoreactive T cell sensi 2014 Mar A key role for segmented filamentous bacteria (SFB) has recently been demonstrated in several mouse models of autoimmune diseases, including autoimmune arthritis and multiple sclerosis. The mechanism governing the activation of systemic autoreactive T cell responses by such commensals in the gut, however, remained elusive. In this addendum, we discuss recent results addressing the local regulation of autoreactive T cell sensitivity by these unique bacteria. We found that the presence of SFB in the gut microbiota was sufficient to promote a local inflammatory microenvironment altering the T cell-intrinsic desensitization process normally occurring in response to chronic self-antigen stimulation. In the absence of this key tolerance checkpoint, sustained chronic T cell proliferation, IFNγ production, and B cell activation eventually led to the development of enhanced pathologies in a Th1-driven T cell-transfer model of autoimmune arthritis.
25339644 SF Treg cells transcribing high levels of Bcl-2 and microRNA-21 demonstrate limited apopto 2015 May OBJECTIVE: The aim of this study was to investigate the turnover of Treg cells in the SF of RA patients. METHODS: Treg cells were enumerated in peripheral blood and SF of RA patients and analysed by flow cytometry for expression of the proliferation marker Ki-67 and binding of the apoptosis marker annexin V. Sorted Treg cells of RA patients were analysed for expression of anti-apoptotic regulators Bcl-2 and microRNA-21 (miR-21) by RT-PCR. RESULTS: Treg cells displaying a memory phenotype were abundant in the SF of RA patients. SF Treg cells more frequently expressed the proliferation marker Ki-67 than conventional T cells. Only few SF Treg cells were apoptotic, as indicated by limited annexin V staining of these cells. SF Treg cells displayed high transcription levels of Bcl-2 and miR-21 in comparison with SF conventional T cells and peripheral blood Treg cells. CONCLUSION: Treg cells with a memory phenotype accumulate in the SF of RA patients. These Treg cells have a high proliferative activity and demonstrate little apoptosis. The latter finding could be explained by high transcription of Bcl-2 and miR-21 in SF Treg cells.
23602936 Wnt signaling pathway in rheumatoid arthritis, with special emphasis on the different role 2013 Oct Rheumatoid arthritis (RA) is a chronic symmetrical autoimmune disease of unknown etiology that affects primarily the diarthrodial joints. Characteristic features of RA pathogenesis are synovial inflammation and proliferation accompanied by cartilage erosion and bone loss. Fibroblast-like synoviocytes (FLS) display an important role in the pathogenesis of RA. Several lines of evidence show that the Wnt signaling pathway significantly participates in the RA pathogenesis. The Wnt proteins are glycoproteins that bind to the Fz receptors on the cell surface, which leads to several important biological functions, such as cell differentiation, embryonic development, limb development and joint formation. Accumulated evidence has suggested that this signaling pathway plays a key role in the FLS activation, bone resorption and joint destruction during RA development. Greater knowledge of the role of the Wnt signaling pathway in RA could improve understanding of the RA pathogenesis and the differences in RA clinical presentation and prognosis. In this review, new advances of the Wnt signaling pathway in RA pathogenesis are discussed, with special emphasis on its different roles in synovial inflammation and bone remodeling. Further studies are needed to reveal the important role of the members of the Wnt signaling pathway in the RA pathogenesis and treatment.
24664868 Deficits in muscle mass, muscle density, and modified associations with fat in rheumatoid 2014 Nov OBJECTIVE: To quantify muscle outcomes, independent of fat mass, in rheumatoid arthritis (RA) patients compared to healthy controls. METHODS: Quantitative computed tomography scans measured calf muscle and fat cross-sectional area (CSA) and muscle density (an index of intramuscular adipose tissue), and isometric dynamometry was used to measure ankle muscle strength in 50 participants with RA ages 18-70 years and 500 healthy controls. Multivariable linear regression models assessed muscle deficits in RA after adjusting for group differences in adiposity and assessing for an altered muscle-fat association. Associations between RA disease characteristics and fat-adjusted muscle outcomes were also assessed. RESULTS: Compared to controls, RA subjects had significantly greater body mass index (BMI) and fat area, and lower muscle area, muscle density, and muscle strength (P < 0.001 for all). Strength deficits were eliminated with adjustment for the smaller muscle area. The magnitude of muscle deficits, relative to controls, was significantly greater (P < 0.03 for interaction) in participants with lower fat area and BMI. Among those in the lower tertiles of adiposity, RA subjects demonstrated more significant deficits compared to controls with similar adiposity. In contrast, among those in the highest tertile for adiposity, RA was not associated with muscle deficits. Among RA, greater Sharp/van der Heijde scores were associated with lower muscle CSA and muscle density. Greater disease activity and disability were associated with low muscle density. CONCLUSION: Deficits in muscle area and muscle density are present in RA patients compared to controls and are most pronounced in subjects with low fat mass. Greater joint destruction is associated with greater muscle deficits.
25377646 Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus e 2015 Jun Making a correct diagnosis is pivotal in the practice of clinical rheumatology. Occasionally, the consultation fails to provide desired clarity in making labeling an individual as having fibromyalgia (FM), systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). A chemokine and cytokine multiplex assay was developed and tested with the goal of improving and achieving an accurate differential diagnosis. 160 patients with FM, 98 with RA and 100 with SLE fulfilling accepted criteria were recruited and compared to 119 controls. Supernatant cytokine concentrations for IL-6, IL-8, MIP-1 alpha and MIP-1 beta were determined using the Luminex multiplex immunoassay bead array technology after mitogenic stimulation of cultured peripheral blood mononuclear cells. Each patient's profile was scored using a logistical regression model to achieve statistically determined weighting for each chemokine and cytokine. Among the 477 patients evaluated, the mean scores for FM (1.7 ± 1.2; 1.52-1.89), controls (-3.56 ± 5.7; -4.59 to -2.54), RA (-0.68 ± 2.26; -1.12 to -0.23) and SLE (-1.45 ± 3.34, -2.1 to -0.79). Ninety-three percent with FM scored positive compared to only 11% of healthy controls, 69% RA or 71% SLE patients had negative scores. The sensitivity, specificity, positive predictive and negative predictive value for having FM compared to controls was 93, 89, 92 and 91%, respectively (p < 2.2 × 10(-16)). Evaluating cytokine and chemokine profiles in stimulated cells reveals patterns that are uniquely present in patients with FM. This assay can be a useful tool in assisting clinicians in differentiating systemic inflammatory autoimmune processes from FM and its related syndromes and healthy individuals.
24469824 OX40L blockade is therapeutic in arthritis, despite promoting osteoclastogenesis. 2014 Feb 11 An immune response is essential for protection against infection, but, in many individuals, aberrant responses against self tissues cause autoimmune diseases such as rheumatoid arthritis (RA). How to diminish the autoimmune response while not augmenting infectious risk is a challenge. Modern targeted therapies such as anti-TNF or anti-CD20 antibodies ameliorate disease, but at the cost of some increase in infectious risk. Approaches that might specifically reduce autoimmunity and tissue damage without infectious risk would be important. Here we describe that TNF superfamily member OX40 ligand (OX40L; CD252), which is expressed predominantly on antigen-presenting cells, and its receptor OX40 (on activated T cells), are restricted to the inflamed joint in arthritis in mice with collagen-induced arthritis and humans with RA. Blockade of this pathway in arthritic mice reduced inflammation and restored tissue integrity predominantly by inhibiting inflammatory cytokine production by OX40L-expressing macrophages. Furthermore, we identify a previously unknown role for OX40L in steady-state bone homeostasis. This work shows that more targeted approaches may augment the "therapeutic window" and increase the benefit/risk in RA, and possibly other autoimmune diseases, and are thus worth testing in humans.
24215151 Therapeutic effect of farnesylthiosalicylic acid on adjuvant-induced arthritis through sup 2014 Mar Rheumatoid arthritis (RA) is an autoimmune disease characterized by pronounced inflammation and leucocyte infiltration in affected joints. Despite significant therapeutic advances, a new targeted approach is needed. Our objective in this work was to investigate the anti-inflammatory effects of the Ras inhibitor farnesylthiosalicylic acid (FTS) on adjuvant-induced arthritis (AIA) in rats, an experimental model for RA. Following AIA induction in Lewis rats by intradermal injection of heat-killed Mycobacterium tuberculosis, rats were treated with either FTS or dexamethasone and assessed daily for paw swelling. Joints were imaged by magnetic resonance imaging and computerized tomography and analysed histologically. The anti-inflammatory effect of FTS was assessed by serum assay of multiple cytokines. After adjuvant injection rats demonstrated paw swelling, leucocyte infiltration, cytokine secretion and activation of Ras-effector pathways. Upon FTS treatment these changes reverted almost to normal. Histopathological analysis revealed that the synovial hyperplasia and leucocyte infiltration observed in the arthritic rats were alleviated by FTS. Periarticular bony erosions were averted. Efficacy of FTS treatment was also demonstrated by inhibition of CD4(+) and CD8(+) T cell proliferation and of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-17 release. The Ras effectors PI3K, protein kinase B (AKT), p38, and extracellular-regulated kinase (ERK) were significantly attenuated and forkhead box protein 3 (FoxP3) transcription factor, a marker of regulatory T cells, was significantly increased. Thus, FTS possesses significant anti-inflammatory and anti-arthritic properties and accordingly shows promise as a potential therapeutic agent for RA. Its effects are apparently mediated, at least in part, by a decrease in proinflammatory cytokines.
23534379 Detection of oral bacterial DNA in synovial fluid. 2013 Jun OBJECTIVES: As periodontal bacteria might be involved in the aetiology of rheumatic diseases, we analysed synovial fluid obtained from patients with rheumatoid arthritis (RA) and controls for the presence of DNA of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Treponema denticola. METHODS: In all, 42 patients suffering from RA (mean age 53.8 ± 16.7 years, 40.4% females) and 114 controls with no rheumatic diseases (mean age 56.1 ± 15.2 years, 52.4% females) were included. DNA from synovial fluid was isolated by QiaAmp kit (Qiagen, Hilden, Germany). Polymerase chain reactions (PCRs) specific for the 16S rRNA genes of the above specified bacteria were developed. Subgingival bacterial colonization was analysed using micro-Ident(®) test (HAIN-Diagnostik, Nehren, Germany). RESULTS: In patients with RA DNA of P. gingivalis was detected in synovial fluid more often than in controls (15.7% versus 3.5%, p = 0.045). More patients than controls harboured DNA from P. gingivalis in both, oral plaque and synovial fluid (11.9% versus. 0.9%, p = 0.030). Among the patients group the number of missing teeth was correlated with the number of joints with movement restrictions caused by RA. CONCLUSIONS: DNA of periodontopathogens can be found in synovial fluid and oral bacteria may play a role in the pathogenesis of arthritis.
25180998 [Diagnosis and treatment of rheumatoid arthritis]. 2014 Sep Rheumatoid arthritis today is still not curable but satisfactory treatable. Treatment targets include clinical remission (or at least low disease activity), lack of radiological destructions and functional disability as well as acceptable life quality and unimpaired working ability. Diagnosing and adequately treating the disease as early as possible is essential for a favourable long-term outcome. Treatment to target with validation and if necessary modification at least every three months until target is achieved ensures good results. Predominantly treatment starts with a combination of methotrexate and glucocorticoids followed by a conventional DMARD combination and then addition of a biologic DMARD in case of failing target. Presence of adverse risk factors and/or high disease activity a cDMARD/bDMARD combination might be used already after starting treatment failure. Additional treatment options such as physiotherapy should be added. Altogether with current treatment possibilities burden of disease declined dramatically in recent years.
25146432 Heterogeneous expression pattern of interleukin 17A (IL-17A), IL-17F and their receptors i 2014 Aug 22 INTRODUCTION: Accumulating evidence suggests an important role for interleukin 17 (IL-17) in the pathogenesis of several inflammatory diseases, including rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Accordingly, clinical trials aimed at blocking IL-17 have been initiated, but clinical results between patients and across different diseases have been highly variable. The objective was to determine the variability in expression of IL-17A, IL-17F and their receptors IL-17RA and IL-17RC in the synovia of patients with arthritis. METHODS: Synovial biopsies were obtained from patients with RA (n = 11), PsA (n = 15) and inflammatory osteoarthritis (OA, n = 14). For comparison, synovia from noninflamed knee joints (n = 7) obtained from controls were included. Frozen sections were stained for IL-17A, IL-17F, IL-17RA and IL-17RC and evaluated by digital image analysis. We used confocal microscopy to determine which cells in the synovium express IL-17A and IL-17F, double-staining with CD4, CD8, CD15, CD68, CD163, CD31, von Willebrand factor, peripheral lymph node address in, lymphatic vessel endothelial hyaluronan receptor 1, mast cell tryptase and retinoic acid receptor-related orphan receptor γt (RORγt). RESULTS: IL-17A, IL-17F, IL-17RA and IL-17RC were abundantly expressed in synovial tissues of all patient groups. Whereas IL-17RA was present mostly in the synovial sublining, IL-17RC was abundantly expressed in the intimal lining layer. Digital image analysis showed a significant (P < 0.05) increase of only IL-17A in arthritis patients compared to noninflamed control tissues. The expression of IL-17A, IL-17F and their receptors was similar in the different patient groups, but highly variable between individual patients. CD4+ and CD8+ cells coexpressed IL-17A, and few cells coexpressed IL-17F. IL-17A and IL-17F were not expressed by CD15+ neutrophils. Mast cells were only occasionally positive for IL-17A or IL-17F. Interestingly, IL-17A and IL-17F staining was also observed in macrophages, as well as in blood vessels and lymphatics. This staining probably reflects receptor-bound cytokine staining. Many infiltrated cells were positive for the transcription factor RORγt. Colocalisation between RORγt and IL-17A and IL-17F indicates local IL-17 production. CONCLUSIONS: Increased expression of IL-17A is not restricted to synovial tissues of RA and PsA patients; it is also observed in inflammatory OA. The heterogeneous expression levels may explain nonresponse to anti-IL-17 therapy in subsets of patients.
24850878 Immune responses to stress in rheumatoid arthritis and psoriasis. 2014 Oct OBJECTIVE: Stress is one of the factors that may exacerbate the progression of chronic inflammatory diseases such as RA and psoriasis. We exploratively compared the effects of acute stress on levels of circulating cytokines involved in disease progression and/or the stress response in patients with RA, patients with psoriasis and healthy subjects. METHODS: Patients with RA, patients with psoriasis and healthy controls underwent a standardized psychosocial stress test (Trier Social Stress Test). Levels of circulating cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IFN-γ and TNF-α) were measured before and after the stress test. RESULTS: The baseline levels of all cytokines, except IL-8, were significantly higher in patients with RA. After correction for baseline levels, patients with RA showed higher stress-induced levels of IL-1β and IL-2 than patients with psoriasis and healthy controls. CONCLUSION: The results suggest that patients with RA have a different immune response to stress than patients with psoriasis or healthy controls. More needs to be learned about the complex interaction between stress, immune parameters and chronic inflammation.
23383679 Extended Neviaser portal approach to antegrade humeral nailing. 2013 Feb Certain arthropathies can distort the normal acromiohumeral relationship and make traditional anterolateral access to the proximal humerus for nailing difficult or impossible. This article presents a case of bilateral antegrade humeral nailing in which the Neviaser portal approach was used for humeral shaft fractures in a patient with distorted shoulder anatomy secondary to severe cuff tear arthropathy and rheumatoid arthritis. Based on a literature review, extending the traditional superomedial (Neviaser) portal to the shoulder to perform humeral nailing has never been described clinically. An 85-year-old woman with rheumatoid arthritis and bilateral cuff tear arthropathy presented after a mechanical fall from standing height with bilateral acute humeral shaft fractures. Preoperative fluoroscopy confirmed the inability to access the traditional starting point with an anterolateral approach due to a shield acromion resulting from cuff tear arthropathy and rheumatoid arthritis. Bilateral locked antegrade humeral nails were successfully placed through a 3-cm incision just off the medial border of the acromion and directly posterior to the acromioclavicular joint (the extended Neviaser portal approach). Postoperatively, the patient demonstrated early evidence of clinical and radiographic union. She was able to return to her preinjury function level, with an active range of motion comparable with her baseline. The Neviaser portal approach to antegrade humeral nailing is an effective solution to diaphyseal humeral fractures when access to the traditional anterolateral proximal humeral starting port is not possible due to distorted shoulder anatomy.
23968543 Inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) sig 2013 Dec Janus kinase (JAK) inhibitors have been developed as anti-inflammatory agents and have demonstrated clinical efficacy in rheumatoid arthritis (RA). We investigated if JAK-3-selective inhibition alone could disrupt cytokine signalling in rheumatoid synovial fibroblasts. In-vitro studies were performed using synovial fibroblasts isolated from patients with RA. Levels of activated JAK and signal transducer and activator of transcription (STAT) proteins were detected by immunoblot analysis. Target-gene expression levels were measured by reverse transcription-polymerase chain reaction (RT-PCR) or real-time PCR. The JAK inhibitors CP-690,550 and INCB028050 both suppressed activation of JAK-1/-2/-3 and downstream STAT-1/-3/-5, as well as the expression levels of target proinflammatory genes (MCP-I, SAA1/2) in oncostatin-M (OSM)-stimulated rheumatoid synovial fibroblasts. In contrast, the JAK-3-selective inhibitor, PF-956980, suppressed STAT-1/-5 activation but did not affect STAT-3 activation in OSM-stimulated rheumatoid synovial fibroblasts. In addition, PF-956980 significantly suppressed MCP-1 gene expression, but did not block SAA1/2 gene expression in OSM-stimulated rheumatoid synovial fibroblasts. These data suggest that JAK-3-selective inhibition alone is insufficient to control STAT-3-dependent signalling in rheumatoid synovial fibroblasts, and inhibition of JAKs, including JAK-1/-2, is needed to control the proinflammatory cascade in RA.