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PMR is an inflammatory rheumatic disease of elderly people characterized by pain and stiffness in the neck, shoulder and pelvic girdles. No specific diagnostic confirmatory tests exist and clinical symptoms, as well as increased acute phase reactants, are unspecific. The diagnostic value of imaging including ultrasound, MRI and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) with/without CT for PMR is increasingly studied. These techniques, particularly FDG-PET/CT, may help to detect underlying GCA in PMR patients with an incomplete response to glucocorticoids and/or recurrent relapses. Recent imaging studies provide novel insights into the anatomical basis of inflammation in PMR, particularly at hip and spine, which may help to distinguish this disease from other mimicking conditions. In this review, we discuss novel insights into the pathoanatomy of PMR, compare the diagnostic values of different imaging techniques and summarize current data on the role of imaging for monitoring and outcome prediction. [ABSTRACT FROM AUTHOR]

GCA and PMR are conditions of older persons that frequently overlap. The traditional concept of GCA has focused on cranial symptoms such as headache and visual disturbance, but extra-cranial manifestations such as constitutional symptoms, polymyalgia and limb claudication have also long been recognized. These symptoms may coincide with cranial GCA, occur as an independent clinical subset [large-vessel (LV) GCA] or overlap with PMR. Imaging studies have demonstrated that up to one-third of patients with PMR have subclinical LV inflammation at disease outset. The implication of this finding for PMR management is unclear. Pathophysiological studies have emphasized the pivotal role of dendritic cells (DCs) and T cells in the pathogenesis of GCA, and the activation of certain pattern recognition receptors on DCs may determine the clinical subset of GCA. In patients with only PMR clinically, it is conceivable that transmural arterial inflammation has either not yet started or is prevented by unexplored regulatory pathways. This concept is supported by vasculitis of peri-adventitial small-vessels and activated DCs in the adventitia of temporal arteries, in the absence of media-infiltrating T cells. This review examines the clinical and pathophysiological spectrum of GCA and its subsets with PMR, the role of newer imaging techniques for GCA diagnosis and the management of these diseases. [ABSTRACT FROM AUTHOR]

The aim of the study is to assess the clinical implementation of musculoskeletal ultrasound (MSUS) in rheumatology in Austria. A survey was conducted among Austrian rheumatologists and physicians of other specialties with a focus on rheumatology. The questionnaire was designed by the members of the Austrian Radiology-Rheumatology Initiative for Musculoskeletal UltraSound including the following items: demographics, access to MSUS and MSUS training, application of MSUS to support diagnosis, monitoring and treatment decisions, and obstacles for the routine performance of MSUS. Eighty-eight (21.9 %) out of the 402 surveyed physicians responded. No access to MSUS and/or inadequate training in the technique was more commonly reported by senior (>50 years; 64.3 and 67.7 %, respectively) than by younger physicians (16.7 %, p = 0.01 and 18.5 %, p < 0.001, respectively). The lowest availability of sonography was found among senior rheumatologists (25.0 %, p = 0.001 compared to the total group). MSUS is routinely used for diagnosis and/or monitoring purposes by 12.5 % of physicians and 20.5 % perform sonography in clinically unclear cases. A limited number of physicians apply the method to support treatment decisions and/or to evaluate treatment success. The most important obstacles for routine application of MSUS in rheumatology are limited access to ultrasound machines, lack of training/education in the technique, and time constraints in daily routine. Low access to high-end ultrasound devices, lack of training, and time constraints may explain the low appreciation of MSUS among Austrian physicians evaluating patients with rheumatic diseases. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibodies (aPLs) frequently occur in autoimmune and cardiovascular diseases and correlate with a worse clinical outcome. In the present study, we evaluated the association between antiphospholipid antibodies (aPLs), markers of inflammation, disease progression and the presence of an intra-aneurysmal thrombus in abdominal aortic aneurysm (AAA) patients. APLs ELISAs were performed in frozen serum samples of 96 consecutive AAA patients and 48 healthy controls yielding positive test results in 13 patients (13.5%) and 3 controls (6.3%; n.s.). Nine of the 13 aPL-positive AAA patients underwent a second antibody testing >12 weeks apart revealing a positive result in 6 cases. APL-positive patients had increased levels of inflammatory markers compared to aPL-negative patients. Disease progression was defined as an increase of the AAA diameter >0.5 cm/year measured by sonography. Follow-up was performed in 69 patients identifying 41 (59.4%) patients with progressive disease. Performing multipredictor logistic regression analysis adjusting for classical AAA risk factors as confounders, the presence of aPLs at baseline revealed an odds ratio of 9.4 (95% CI 1.0–86.8, p = 0.049) to predict AAA progression. Fifty-five patients underwent a computed tomography in addition to ultrasound assessment indicating intra-aneurysmal thrombus formation in 82.3%. Median thrombus volume was 46.7 cm3 (1.9–377.5). AAA diameter correlated with the size of the intra-aneurysmal thrombus (corrcoeff = 0.721, p<0.001), however neither the presence nor the size of the intra-aneurysmal thrombus were related to the presence of aPLs. In conclusion, the presence of aPLs is associated with elevated levels of inflammatory markers and is an independent predictor of progressive disease in AAA patients. [ABSTRACT FROM AUTHOR]

Background: Pro-inflammatory, cytotoxic CD4+CD28- T-cells with known defects in apoptosis have been investigated as markers of premature immuno-senescence in various immune-mediated diseases. In this study we evaluated the influence of polyclonal antilymphocyte globulins (ATG-Fresenius, ATG-F) on CD4+CD28- T-cells in vivo and in vitro. Principal Findings: Surface and intracellular three colour fluorescence activated cell sorting analyses of peripheral blood mononuclear cells from 16 consecutive transplant recipients and short-term cell lines were performed. In vivo, peripheral levels of CD3+CD4+CD28- T-cells decreased from 3.7±7.1% before to 0±0% six hours after ATG-F application (P = 0.043) in 5 ATG-F treated but not in 11 control patients (2.9±2.9% vs. 3.9±3.0%). In vitro, ATG-F induced apoptosis even in CD4+CD28- T-cells, which was 4.3-times higher than in CD4+CD28+ T-cells. ATG-F evoked apoptosis was partially reversed by the broadspectrum caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) and prednisolon-21- hydrogensuccinate. ATG-F triggered CD25 expression and production of pro-inflammatory cytokines, and induced downregulation of the type 1 chemokine receptors CXCR-3, CCR-5, CX3CR-1 and the central memory adhesion molecule CD62L predominately in CD4+CD28- T-cells. Conclusion: In summary, in vivo depletion of peripheral CD3+CD4+CD28- T-cells by ATG-F in transplant recipients was paralleled in vitro by ATG-F induced apoptosis. CD25 expression and chemokine receptor down-regulation in CD4+CD28- Tcells only partly explain the underlying mechanism. [ABSTRACT FROM AUTHOR]

Modern ultrasonography enables clinicians to sensitively assess the progression of inflammatory joint and tendon disease, and to investigate vasculitides, connective tissue diseases and nerve lesions. Despite the advantages of musculoskeletal ultrasonography for diagnostic, prognostic and monitoring purposes, fewer than 10% of European rheumatologists use this technique in routine clinical practice. The reliability and limitations of rheumatic ultrasonography remain a concern, although good interobserver and intraobserver agreement in results from ultrasonography have been demonstrated among experienced sonographers. International recommendations for assessments and ultrasonography training courses are available, and will improve the standardization of the use of these techniques. In clinical practice, ultrasonography can complement the diagnostic evaluation of patients with rheumatic disease and might have value in confirming and extending clinical findings. Musculoskeletal ultrasonography can also be a valuable follow-up tool to monitor disease activity and support treatment decisions for specific patients. Furthermore, ultrasonography-guided articular injections provide better precision and a higher success rate for synovial fluid aspiration than clinically-guided injections. In the future, three-dimensional ultrasonography techniques, the fusion of ultrasonography and other imaging methods, and real time sonoelastography will be interesting new fields of investigation. [ABSTRACT FROM AUTHOR]

Objective of this study is to retrospectively compare the third generation anti-cyclic citrullinated peptide (anti-CCP3) test with the second generation (anti-CCP2) assay as markers of disease activity and predictors of clinical response in rheumatoid arthritis (RA) patients treated with TNF-α blocking agents. This study was performed in 42 RA patients treated either with infliximab ( n = 11), etanercept ( n = 7) or adalimumab ( n = 24). Serum anti-CCP3 and anti-CCP2 levels were tested before and 6 months after starting a TNF-α blocking treatment using commercially available ELISA kits. Anti-CCP3 and anti-CCP2 antibody levels did not significantly change after 6 months of TNF-α blocking treatment. Furthermore, neither anti-CCP3 nor anti-CCP2 was useful to predict anti-TNF-α treatment response using receiving operating characteristic curve and logistic regression analyses. Both anti-CCP3 and anti-CCP2 are not differentially influenced by TNF-α blocking agents in RA patients and failed to predict anti-TNF-α treatment response. [ABSTRACT FROM AUTHOR]

The objective of the present study was to assess the prevalences of naive, memory, memory/effector, regulatory and activated T-cells in peripheral blood (PB) and synovial fluid (SF) of patients with spondyloarthritis (SpA), rheumatoid arthritis (RA), polymyalgia rheumatica/giant cell arteritis (PMR/GCA) and healthy controls (HC). Twenty-two patients with SpA, 15 patients with RA, 38 patients with PMR/GCA and 17 HC were prospectively enrolled. The expression of differentiation and activation markers (CD3, CD4, CD8, CD25, CD28, CD45RA, CD45RO) characterizing T-cell subsets were analyzed by flow cytometry. The frequency of CD3+CD4+CD28− memory/effector T-cells was increased in PB of patients with SpA (median 1.1%, range 0.1–69.6), RA (2.5%, 0–42.9) and PMR/GCA (2.7%, 0–49.5) when compared with HC (0.7%, 0–38.0) and tended to be higher in SF of SpA patients (4.5%, 0.2–7.2, P = 0.084). CD28+CD45RA+CD4+ (9.6%, 4.1–10.3) and CD28+CD45RA+CD8+ naive T-cells (15.0%, 12.9–26.2) were reduced and CD28+CD45RO+CD4+ (93.5%, 51.0–99.0), CD28+CD45RO+CD8+ memory (81.2%, 38.9–83.5), CD8+CD25+ activated T-cells (10.9%, 2.7–13.8) and CD4+CD25hi TREGs (10.2%, 7.0–13.3) were increased in SF compared to PB ( P < 0.05 each). These findings demonstrate altered T-cell subsets in patients with immune-mediated disease, particularly at sites of inflammation. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Macrophages and pro-inflammatory CD3+CD4+CD28− T lymphocytes are involved in atherosclerotic plaque destabilization. Whether neopterin, a macrophage-specific activation-marker, and circulating CD3+CD4+CD28− cells are also related to the severity and extent of coronary artery disease (CAD) in stable patients is still unclear. Methods: Coronary angiograms of 30 patients with stable angina pectoris were graded using the Gensini severity and an extent score. Patients were grouped according to the median of each score. Lymphocyte subsets were determined by FACS analysis and neopterin by radioimmunoassay. Peripheral endothelial function of the brachial artery (FMD) shown to correlate with cardiovascular risk factors was evaluated using high-resolution ultrasound. Results: More extensive CAD was associated with increased neopterin levels (8.3±3.3 vs. 5.5±1.2 nmol/L, p <0.001) and increased CD3+CD4+CD28− cells (3.1±1.6 vs. 2.0±1.2%, p <0.05). A high Gensini severity score was associated with increased neopterin levels (7.8±2.7 vs. 6.3±1.7 nmol/L, p <0.05), but not with CD3+CD4+CD28− cells. Neopterin correlated with both the extent (r =0.59, p <0.001) and the Gensini score (r =0.57, p <0.003). FMD was not correlated with both scores. Conclusions: Neopterin and CD3+CD4+CD28− lymphocytes are associated with CAD extent in stable patients, thereby emphasizing the inherent role of inflammation in atherogenesis itself beyond plaque destabilization. Neopterin''s correlation with CAD severity might be additionally useful in identifying patients eligible for revascularization procedures. [Copyright &y& Elsevier]

Dose adjustments of NSAIDs according to body weight may be reasonable for an optimal efficacy/tolerance profile in the therapy of musculoskeletal disorders, but are unusual in adults. In this post hoc analysis of a prospective, one-arm clinical study of a short-term treatment with acemetacin, a total of 406 patients with pain because of various musculoskeletal diseases with or without joint inflammation was evaluated for the influence of body mass index (BMI) on the reduction of pain at rest, pain at movement and for mobility restriction between visits one and three (primary outcome parameters). No association was found between BMI and the efficacy of acemetacin regarding the primary outcome parameters and no influence of BMI on the occurrence of adverse events was observed. Dose adjustment of acemetacin according to BMI thus appears not necessary in a short-term treatment of musculoskeletal disorders, but prospective controlled trials are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Animal models for abdominal aortic aneurysms (AAAs), immunogenetical and pathophysiological studies support the importance of immune-mediated processes in the pathogenesis of AAA disease. Neutrophils, natural killer (NK) cells, monocytes/macrophages, and proinflammatory cytokines are involved in the complex and dynamic tissue remodeling of the AAA vessel wall. Our group showed an increased prevalence of circulating interferon-γ (IFN-γ) producing CD28− T cells especially in smaller AAAs, thus supporting the concept of a T cell-mediated pathophysiology of AAAs, especially during the early development of AAAs. Further research should now assess the possible benefit of anti-inflammatory therapeutic approaches in AAA patients, especially with small AAAs. [ABSTRACT FROM AUTHOR]

Abstract: There is increasing evidence for an active and ‘dominant’ tolerance mediated by regulatory T-cells. Out of these CD4+ ‘naturally occurring’ regulatory T-cells (TREGs) are currently the main research focus in this field. TREGs exert their suppressive function in vitro in a contact-dependent manner and preferentially express high levels of CD25 and the forkhead and winged-helix family transcription factor forkhead box P3 (FOXP3). Age-related increment of the prevalences of CD4+CD25hi TREGs were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. During aging thymic TREG output may decrease with significant loss of thymic capacity to generate new T-cells, and TREG homeostasis has been shown to be sustained by alternative pathways like peripheral generation of TREGs. An imbalance of TREG homeostasis would then predispose to immune dysfunction in aged individuals explaining their higher risk of immune-mediated diseases, cancer or infections. [Copyright &y& Elsevier]

The breakdown of mechanisms assuring the recognition of self and non-self is a hallmark feature of autoimmune diseases. In the past 10 years, there has been a steadily increasing interest in a subpopulation of regulatory T cells, which exert their suppressive function in vitro in a contact-dependent manner and preferentially express high levels of CD25 and forkhead and winged-helix family transcription factor forkhead box P3 (FOXP3) (TREGs). Recent findings of changed prevalences and functional efficiencies indicate that these TREGs play a unique role in autoimmune diseases. Clinical findings in patients with mutated FOXP3 genes and a specific polymorphism in the promotor region of FOXP3 also support the role of FOXP3 as a ‘master control gene’ in the development and functioning of TREGs. Both altered generation of TREGs and insufficient suppression of inflammation in autoimmune diseases are considered to be crucial for the initiation and perpetuation of disease. TREG-related somatic cell therapy is considered as an intriguing new intervention to approach autoimmune diseases. [ABSTRACT FROM AUTHOR]

Objectives While >50% of medical students and residents are women, their proportion drastically diminishes within higher ranks and leadership roles; this is known as the 'leaky pipeline'. We aimed to evaluate the leaky pipeline among rheumatologists across Europe and to assess determinants inducing rheumatologists to leave hospitals. Methods Experts in the field of economics developed a questionnaire with scientific focus on the leaky pipeline among rheumatologists, which was distributed electronically by national scientific societies of EULAR countries and by individual contacts. We performed common factor analysis, univariate t -tests and multivariate regression analyses to appraise our dataset. Results A total of 311 hospital-based rheumatologists from 23/45 EULAR countries (52.7% females, 47.3% males) answered the questionnaire. The presence of the leaky pipeline was evident for the entire sample. Of 64% female rheumatologists only 34.2% of departments' directors were female, with noteworthy regional differences. Female doctors reported higher intentions to leave their hospital (β = 0.28, P  < 0.05) and lower commitment towards their current organization (β = –0.34, P  < 0.05) when compared with males. Women reported lower levels of job satisfaction (β = –0.26, P  < 0.10), promotion justice (β = –0.55, P  < 0.01) and career perspectives (β = –0.26, P  < 0.10, one-tailed) than men, explaining their lower organizational commitment. Conclusion Female rheumatologists perceive worse job opportunities and satisfaction than males. Many reasons for the leaky pipeline are beyond the control of organizations. Based on our results, organizations should be encouraged to reconsider and adjust their performance management practices to enable an equitable work environment. [ABSTRACT FROM AUTHOR]

Objective To evaluate tender joints (TJ) and swollen joints (SJ) for the assessment of ultrasound (US) defined inflammation in PsA. Methods Eighty-three PsA patients underwent clinical and US examinations at two scheduled study visits 12 months apart. Tenderness and swelling were assessed at 68 and 66 joints, respectively, and US examinations were conducted at all 68 joints. At patient level, associations with clinical composites and US scores were performed using correlations and by analysing patients with predominantly tender (pTender) or swollen joints (pSwollen). At joint level, a Power Doppler (PD) value ≥ 1 was defined as active synovitis. A generalized linear mixed model was created to assess the predictive value of TJ and SJ for active synovitis after 12 months. Results SJC showed better correlations with GS/PD scores (r  = 0.37/0.47) than with TJC (PD: r  = 0.33), while TJC correlated better with patient reported outcomes (PROMs) like patient global assessment (TJC: r  = 0.57; SJC r  = 0.39). Patients with pTender showed poorer results for PROMs and disease activity scores than patients with pSwollen, but not for laboratory or US markers of inflammation. Swollen joints showed active synovitis in 35% of cases, while only 16% of tender joints were active according to US. Swelling at baseline better predicted active synovitis at the same joint after 12 months [odds ratio (OR) 6.33, P  <0.001] as compared with tenderness (OR 3.58, P  <0.001). Conclusions SJ are more closely linked with US signs of inflammation as compared with TJ in PsA. Joint swelling is a better predictor for signs of US inflammation than tenderness after one year of follow-up. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) play a dominant role in the regulation of immune responses. Quantitative and/or qualitative abnormalities of Tregs were observed in patients with autoimmune diseases and therapeutic interventions focusing Tregs are an attractive new target with the potential to cure these disorders. Biological agents approved for treatment of inflammatory rheumatic diseases transiently influence Treg prevalences and function and experimental therapies including novel biological agents, gene therapy, activation and ex vivo expansion of purified Tregs as well as substances influencing tolerogenic dendritic cells will be developed for selective Treg therapy. Although many of these interventions are effective in vitro, in animal models as well as in early clinical trials, significant concerns exist regarding the stability of Treg modifications as well as the long-term safety of Treg-based therapies. [ABSTRACT FROM AUTHOR]

Objectives The aim of this prospective study was to examine whether ultrasound or clinical abnormalities at enthesal sites predict radiographic progression at entheses in psoriatic arthritis (PsA). Methods Consecutive PsA patients were included and subjected to clinical and ultrasound assessments at 14 entheses at baseline, 6 and 12 months. Radiographs were performed at 0 and 12 months. By US, we investigated structural (erosions, osteophytes) and inflammatory changes [grey scale (0–32) and power Doppler (0–14, range global ultrasound score 0–140)], and radiographs were evaluated for enthesophytes and erosions (score range 0–56). Multivariate regression models were conducted to identify the possible association of clinical and ultrasound findings with radiographic progression. Results We examined 83 patients at baseline, of whom 43 (51.8%) had complete clinical, ultrasound and X-ray data. Twenty-four of 43 patients (55.8%) developed radiographic progression of entheses. These patients were younger (49.6 vs 59.3, P  =0.005), had shorter disease duration (9.7 vs 17.9 years, P =0.015) and lower clinical disease activity at 6-months [disease activity in psoriatic arthritis (DAPSA) 6.7 vs 17.0, P =0.018] as compared with patients without progression. Non-progressors had higher ultrasound enthesophyte scores at baseline than progressors (20 vs 15, P <0.05). The multivariate regression analysis revealed that 48.6% of the variance of the X-ray score at 12-months follow-up (RegcoeffB = 0.827, P =0.000) could be explained by the baseline US enthesophyte score. Conclusion Our data indicate that radiographic progression at entheses is linked with age, disease duration and ultrasound verified enthesophytes at baseline. No other ultrasound parameter predicted radiographic progression at entheses. [ABSTRACT FROM AUTHOR]

The article presents the guideline of the British Society for Rheumatology on diagnosis and treatment of giant cell arteritis (GCA). Topics discussed include objectives of the guideline, important stakeholder representation in the guideline, and methods used to formulate the recommendations. Also mentioned are the general principles of the guideline, specific recommendations for diagnostic tests in suspected GCA, and potential organizational barriers to implementation.

The article presents a summary of the guideline on diagnosis and treatment of giant cell arteritis (GCA) by the British Society for Rheumatology. Topics discussed include how suspected GCA should be treated, evaluations that should be performed when starting treatment, and education that patients with GCA should be offered.

Objective To evaluate low disease activity (LDA) cut-offs in psoriatic arthritis (PsA) using ultrasound. Methods Eighty-three PsA patients underwent clinical and ultrasound examinations at two visits. LDA was assessed using the Disease Activity index for Psoriatic Arthritis (DAPSA ⩽ 14), the Psoriatic ArthritiS Disease Activity Score (PASDAS ⩽ 3.2), the Composite Psoriatic Disease Activity Index ⩽ 4, the DAS28-CRP ⩽ 2.8 and the minimal disease activity criteria. Ultrasound was performed at 68 joints and 14 entheses. Minimal ultrasound disease activity (MUDA-j/e) was defined as a Power Doppler score ⩽ 1, respectively at joints, paratendinous tissue, tendons and entheses. A global ultrasound score was calculated by summing Grey Scale and Power Doppler information (GUIS-j/e). Results LDA was present in 33.7–65.0% at baseline and in 44.3–80.6% at follow-up, depending on the criteria used. MUDA-j/e was observed in 16.9% at baseline and in 30% at follow-up. GUIS-j/e was significantly higher in patients with moderate/high disease activity vs LDA according to DAPSA and PASDAS at baseline and DAPSA, PASDAS, Composite Psoriatic Disease Activity Index and minimal disease activity at follow-up. Patients in moderate/high disease activity had MUDA-j/e in 8.1–21.4% at baseline and in 8.3–20.0% at follow-up, depending on the applied clinical composite. MUDA-j/e patients with moderate/high disease activity had higher levels of pain and pain-related items than those with LDA. Conclusion The LDA cut-offs of DAPSA, PASDAS, Composite Psoriatic Disease Activity Index, minimal disease activity, but not DAS28-CRP are capable of distinguishing between high and low ultrasound activity. Pain and pain-related items are the main reason why PsA patients without signs of ultrasound inflammation are classified with higher disease activity. [ABSTRACT FROM AUTHOR]

Objectives To develop and test the reliability of a new semiquantitative scoring system for the assessment of cartilage changes by ultrasound in a web-based exercise as well as a patient exercise of patients with RA. Methods A taskforce of the Outcome Measures in Rheumatology Ultrasound Working Group performed a systematic literature review on the US assessment of cartilage in RA, followed by a Delphi survey on cartilage changes and a new semiquantitative US scoring system, and finally a web-based exercise as well as a patient exercise. For the web-based exercise, taskforce members scored a dataset of anonymized static images of MCP joints in RA patients and healthy controls, which also contained duplicate images. Subsequently, 12 taskforce members used the same US to score cartilage in MCP and proximal interphalangeal joints of six patients with RA in in a patient reliability exercise. Percentage agreement and prevalence of lesions were calculated, as intrareader reliability was assessed by weighted kappa and interreader reliability by Light's kappa. Results The three-grade semiquantitative scoring system demonstrated excellent intrareader reliability (kappa: 0.87 and 0.83) in the web-based exercise and the patient exercise, respectively. Interreader reliability was good in the web-based exercise (kappa: 0.64) and moderate (kappa: 0.48) in the patient exercise. Conclusion Our study demonstrates that ultrasound is a reliable tool for evaluating cartilage changes in the MCP joints of patients with RA and supports further development of a new reliable semiquantitative ultrasound scoring system for evaluating cartilage involvement in RA. [ABSTRACT FROM AUTHOR]

Abstract: We read with great interest the comments of Avanzas et al. on our recent article. In acute coronary syndromes, inflammatory markers such as neopterin – a macrophage-specific activation marker – reflect plaque instability, i.e. disease activity. In stable coronary artery disease (CAD) patients, inflammatory markers such as C-reactive protein (CRP) not only predict the incidence of future events, but are also associated with disease prevalence and severity. In our study population including male, non-diabetic patients with stable CAD, neopterin serum concentrations also correlated with angiographically evaluated CAD. In contrast to our study, Avanzas et al. did not find such an association in 297 stable CAD patients, but neopterin serum levels were predictive for the incidence of a combined clinical endpoint. Different patient populations, e.g. the inclusion of diabetic patients and women, the higher event rate as well as the correction for age in the multivariate analyses in the latter study might explain the divergent results. In light of these observations, the association of neopterin or of other inflammatory markers with CAD activity, severity and/or extent should probably not be separated from each other and might be interpreted in the context of the broad spectrum of clinically stable CAD. [ABSTRACT FROM AUTHOR]

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the value of real-time sonoelastography (RTS) of salivary glands for the diagnosis and assessment of glandular damage in primary Sjögren's syndrome (pSS). After institutional review board approval, 45 pSS patients, 24 sicca patients and 11 healthy controls were investigated prospectively. Questionnaires were completed and Saxon and Schirmer tests and routine blood tests carried out in all patients. All patients underwent B-mode ultrasonography and RTS of parotid and submandibular glands. Abnormal findings were graded from 0 to 48 and from 0 to 16, respectively. Sialoscintigraphy was done according to a routine protocol; scoring ranged from 0 to 12. Statistical analysis comprised receiver operating characteristic curve and multivariate regression analysis. Patients with pSS had higher B-mode (median score = 25 [range: 2-44] vs. 9 [1-20], p < 0.001) and RTS (6.5 [2-13] versus 4 [1-9], p < 0.001) scores than controls with sicca syndrome, yielding areas under the curve of 0.83 and 0.85 (p < 0.05 each), respectively for pSS diagnosis. In cases with an inconclusive B-mode ultrasonography result, RTS (cutoff score: ≥ 6) led to a sensitive (66.7%) and specific (85.7%) classification of patients and sicca controls. In multivariate regression analysis, RTS (regression coefficient = -0.48, p = 0.005), but not B-mode ultrasonography, reflected impaired salivary gland function according to the Saxon test, whereas none of the subjective measures of dryness or discomfort were related to ultrasonography results. B-mode and RTS results were both associated with sialoscintigraphy scores (regression coefficient = 0.66, p < 0.001, and regression coefficient = 0.55, p = 0.001, respectively). Reproducibility of B-mode ultrasonography and RTS was good, with intra-class correlation coefficients of 0.93 (95% confidence interval: 0.57-0.98) and 0.93 (95% confidence interval: 0.79-0.98), respectively. In summary, RTS might be a useful adjunct to B-mode ultrasonography for diagnosis and assessment of salivary gland impairment in primary Sjögren's syndrome. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the value of real-time sonoelastography (RTS) of salivary glands for the diagnosis and assessment of glandular damage in primary Sjögren’s syndrome (pSS). After institutional review board approval, 45 pSS patients, 24 sicca patients and 11 healthy controls were investigated prospectively. Questionnaires were completed and Saxon and Schirmer tests and routine blood tests carried out in all patients. All patients underwent B-mode ultrasonography and RTS of parotid and submandibular glands. Abnormal findings were graded from 0 to 48 and from 0 to 16, respectively. Sialoscintigraphy was done according to a routine protocol; scoring ranged from 0 to 12. Statistical analysis comprised receiver operating characteristic curve and multivariate regression analysis. Patients with pSS had higher B-mode (median score = 25 [range: 2–44] vs. 9 [1–20], p < 0.001) and RTS (6.5 [2–13] versus 4 [1–9], p < 0.001) scores than controls with sicca syndrome, yielding areas under the curve of 0.83 and 0.85 ( p < 0.05 each), respectively for pSS diagnosis. In cases with an inconclusive B-mode ultrasonography result, RTS (cutoff score: ≥6) led to a sensitive (66.7%) and specific (85.7%) classification of patients and sicca controls. In multivariate regression analysis, RTS (regression coefficient = –0.48, p = 0.005), but not B-mode ultrasonography, reflected impaired salivary gland function according to the Saxon test, whereas none of the subjective measures of dryness or discomfort were related to ultrasonography results. B-mode and RTS results were both associated with sialoscintigraphy scores (regression coefficient = 0.66, p < 0.001, and regression coefficient = 0.55, p = 0.001, respectively). Reproducibility of B-mode ultrasonography and RTS was good, with intra-class correlation coefficients of 0.93 (95% confidence interval: 0.57–0.98) and 0.93 (95% confidence interval: 0.79–0.98), respectively. In summary, RTS might be a useful adjunct to B-mode ultrasonography for diagnosis and assessment of salivary gland impairment in primary Sjögren’s syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Juvenile idiopathic arthritis is a heterogeneous T cell-mediated autoimmune disease with symptoms of premature aging of the immune system (immunosenescence). The present work is an investigation of immunosenescence parameters, such as quantity of naive and CD28- T cells, T cell receptor excision circles, relative telomere length and alterations of peripheral T cell replication, and was performed via comparison of a case of acute exacerbation of juvenile idiopathic arthritis against six patients with juvenile idiopathic arthritis with disease remission and six age-matched healthy donors over a follow-up course of 12 months.Case Presentation: Phenotypical T cell characterization and intracellular interferon γ, tumor necrosis factor α, and interleukin 2 production were studied in peripheral blood mononuclear cells from seven patients with juvenile idiopathic arthritis and six healthy control donors, with findings determined by flow cytometry. T cell receptor excision circles and relative telomere length quantification were performed on deoxyribonucleic acid isolated from naive (CD4+CD28+CD45RA+) T cells and investigated via reverse transcription polymerase chain reaction. Ki67 expression was studied by immunohistochemistry on naive T cells. The non-parametric Mann-Whitney U test and Wilcoxon test for two independent groups of variables were used to compare healthy donors with patients with juvenile idiopathic arthritis. During follow-up, patients with juvenile idiopathic arthritis showed lower total counts of naive and CD28-expressing T cells compared to healthy donors. Acute exacerbation led to low naive and CD28+ T cell populations and elevated proportions of Ki67-expressing CD4+ naive T cells. In conditions of exacerbation, T cell receptor excision circle numbers were in the lower range in patients with juvenile idiopathic arthritis and increased after follow-up. Healthy donors showed significantly higher relative telomere lengths compared to patients with juvenile idiopathic arthritis.Conclusions: This investigation illustrates that the changes in T cell homeostasis in patients with juvenile idiopathic arthritis may be the result of several mechanisms, such as diminished thymus function and peripheral exertions to maintain the peripheral T cell pool. The results also demonstrate that hallmarks of immunosenescence such as decreased naive T cell levels and lower T cell receptor excision circle numbers can only be interpreted together with replication markers such as relative telomere length or Ki67 expression. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop European League Against Rheumatism/American College of Rheumatology classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new-onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of rheumatoid factor and/or anti-citrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness >45 minutes, elevated C-reactive protein and/or erythrocyte sedimentation rate, and new hip pain. These criteria are not meant for diagnostic purposes. [ABSTRACT FROM AUTHOR]

Abstract: Immunologic memory is a critical feature of the adaptive immune system to fight recurrent infections. However, the mechanisms that shape the composition and function of the human memory T-cell pool remain incompletely understood. We here demonstrate that post-thymic human T-cell differentiation was associated with the downregulation, but not loss, of the inhibitory molecule CD5. The sensitivity of human CD8+ and CD4+ memory T cells to interleukin (IL)–15 was inversely associated with the level of CD5 expression. CD5 expression was downregulated by IL-15–mediated signaling in vitro and CD5lo memory T cells accumulated in the bone marrow. Persistent antigenic stimulation, as in the case of cytomegalovirus infection and rheumatoid arthritis (RA), was also associated with an increased number of CD5lo memory T cells. In conclusion, CD5 may be a useful marker to identify memory T-cell subsets with distinct responsiveness to the homeostatic cytokine IL-15. [Copyright &y& Elsevier]