Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis: an observational study.

INTRODUCTION: Neovascularization contributes to the development of sustained synovial inflammation in the early stages of Rheumatoid Arthritis. Ultrasound (US) provides an indirect method of assessing synovial blood flow and has been shown to correlate with clinical disease activity in patients with Rheumatoid Arthritis. This study examines the relationship of US determined synovitis with synovial vascularity, angiogenic/lymphangiogenic factors and cellular mediators of inflammation in a cohort of patients with early Rheumatoid Arthritis (RA) patients prior to therapeutic intervention with disease modifying therapy or corticosteroids. METHODS: An ultrasound guided synovial biopsy of the supra-patella pouch was performed in 12 patients with early RA prior to treatment. Clinical, US and biochemical assessments were undertaken prior to the procedure. Ultrasound images and histological samples were obtained from the supra-patella pouch. Histological samples were stained for Factor VIII and a-SMA (a-smooth muscle actin). Using digital imaging analysis a vascular area score was recorded. QT-PCR (quantitative-PCR) of samples provided quantification of angiogenic and lymphangiogenic gene expression and immunohistochemistry stained tissue was scored for macrophage, T cell and B cell infiltration using an existing semi-quantitative score. RESULTS: Power Doppler showed a good correlation with histological vascular area (Spearman r--0.73) and angiogenic factors such as vascular endothelial growth factor-A (VEGF-A), Angiopoietin 2 and Tie-2. In addition, lymphangiogenic factors such as VEGF-C and VEGF-R3 correlated well with US assessment of synovitis. A significant correlation was also found between power Doppler and synovial thickness, pro-inflammatory cytokines and sub-lining macrophage infiltrate. Within the supra-patella pouch there was no significant difference in US findings, gene expression or inflammatory cell infiltrate between any regions of synovium biopsied. CONCLUSION: Ultrasound assessment of synovial tissue faithfully reflects synovial vascularity. Both grey scale and power Doppler synovitis in early RA patients correlate with a pro-angiogenic and lymphangiogenic gene expression profile. In early RA both grey scale and power Doppler synovitis are associated with a pro-inflammatory cellular and cytokine profile providing considerable validity in its use as an objective assessment of synovial inflammation in clinical practice

Intramachine and intermachine variability in transesophageal color doppler images of pulsatile jets: in vitro studies

Background: Color Doppler flow mapping is widely used as a marker of severity of valvular regurgitation, and the transesophageal approach has provided high-quality images in patients with poor acoustic windows. However, different instruments produce significantly variable images. Techniques that use jet spatial information to determine the severity of the lesion may need to be derived specifically for the instrument used. Given a lack of standardization of the many commonly used instruments, the goal of this study was to quantify variability between instruments by imaging well-defined jet flow fields created in vitro. Methods and Results: Pulsatile jets were created in vitro using a blood analogue fluid through physiological orifice diameters and imaged from a distal window using six commonly used color Doppler instruments. Transesophageal transducers (5.0 MHz) were used with all instruments studied. Peak jet areas were planimetered and averaged with systematic variations in Nyquist limit, color filter, and sector angle (which produced variations in frame rate). Changes in instrument settings produced significant variation in jet size for all instruments studied. Comparisons within instruments and among instruments were difficult because of preset and ambiguous setting levels. When comparisons were possible between similar settings, variability was dramatic (eg, 57% variability between instruments with very similar Nyquist limits). Conclusions: A lack of standardized color Doppler instrument settings prohibits translation of jet area techniques from one instrument to another. This should be taken into consideration when using different machines for clinical study

Preliminary definitions for the sonographic features of synovitis in children

Objectives Musculoskeletal ultrasonography (US) has the potential to be an important tool in the assessment of disease activity in childhood arthritides. To assess pathology, clear definitions for synovitis need to be developed first. The aim of this study was to develop and validate these definitions through an international consensus process. Methods The decision on which US techniques to use, the components to be included in the definitions as well as the final wording were developed by 31 ultrasound experts in a consensus process. A Likert scale of 1-5 with 1 indicating complete disagreement and 5 complete agreement was used. A minimum of 80% of the experts scoring 4 or 5 was required for final approval. The definitions were then validated on 120 standardized US images of the wrist, MCP and tibiotalar joints displaying various degrees of synovitis at various ages. Results B-Mode and Doppler should be used for assessing synovitis in children. A US definition of the various components (i.e. synovial hypertrophy, effusion and Doppler signal within the synovium) was developed. The definition was validated on still images with a median of 89% (range 80-100) of participants scoring it as 4 or 5 on a Likert scale. Conclusions US definitions of synovitis and its elementary components covering the entire pediatric age range were successfully developed through a Delphi process and validated in a web-based still images exercise. These results provide the basis for the standardized US assessment of synovitis in clinical practice and research

One year in review: ultrasound in arthritis

Musculoskeletal ultrasound (MSUS) has become a relevant part of rheumatology practice and research because it substantially allows us to optimize management of rheumatic and musculoskeletal diseases. This non-invasive imaging modality is a valuable point-of-care tool to accurately evaluate intra-articular and periarticular structures involved in a wide range of rheumatic diseases in adults and children. In addition, MSUS is an invaluable bedside aid for guiding accurate and safe musculoskeletal aspirations, injections and biopsies. This review provides an overview of the literature of the last year on the role of MSUS in arthritis

S-Nitrosoglutathione reduces asymptomatic embolization after carotid angioplasty

Background: The major complication of carotid angioplasty is embolic stroke, which may occur after balloon inflation and deflation or in the early postintervention period. Platelet adhesion and aggregation to the angioplasty site with subsequent embolization seems to plays a major role in early postangioplasty embolization and stroke. During this period, asymptomatic embolic signals can be detected in patients by transcranial Doppler ultrasound despite aspirin and heparin treatment. S-Nitrosoglutathione (GSNO) is a nitric oxide donor that appears to have relative platelet specificity. We evaluated its effectiveness in reducing embolization after carotid angioplasty. Methods and results: Sixteen patients undergoing carotid angioplasty and stenting for symptomatic 70% internal carotid artery stenosis were randomized in a double-blind manner to GSNO or placebo given after surgery for 90 minutes. All patients were pretreated with aspirin and given heparin for 24 hours after the procedure. Transcranial Doppler recordings were made from the ipsilateral middle cerebral artery for 1 hour before treatment and at 0 to 3, 6, and 24 hours after treatment. GSNO resulted in a rapid reduction in the frequency of embolic signals of 95% at 0 to 3 hours and 100% at 6 hours (P=0.007 and P=0.01 versus placebo, respectively). In the placebo group, 2 patients experienced ipsilateral stroke after the angioplasty. No cerebrovascular events occurred in the GSNO group. Conclusions: S-Nitrosoglutathione was highly effective in rapidly reducing the frequency of embolic signals after endovascular treatment for symptomatic high-grade carotid stenosis

EFSUMB Recommendations and Guidelines for Gastrointestinal Ultrasound - Part 1: Examination Techniques and Normal Findings (Long version).

Abstract ▼ In October 2014 the European Federation of Societies for Ultrasound in Medicine and Biology formed a Gastrointestinal Ultrasound (GIUS) task force group to promote the use of GIUS in a clinical setting. One of the main objectives of the task force group was to develop clinical recommendations and guidelines for the use of GIUS under the auspices of EFSUMB. The first part, gives an overview of the examination techniques for GIUS recommended by experts in the field. It also presents the current evidence for the interpretation of normal sonoanatomical and physiological features as examined with different ultrasound modalities

Early diagnosis of cardiovascular diseases in workers: role of standard and advanced echocardiography

Cardiovascular disease (CVD) still remains the main cause of morbidity and mortality and consequently early diagnosis is of paramount importance. Working conditions can be regarded as an additional risk factor for CVD. Since different aspects of the job may affect vascular health differently, it is important to consider occupation from multiple perspectives to better assess occupational impacts on health. Standard echocardiography has several targets in the cardiac population, as the assessment of myocardial performance, valvular and/or congenital heart disease, and hemodynamics. Three-dimensional echocardiography gained attention recently as a viable clinical tool in assessing left ventricular (LV) and right ventricular (RV), volume, and shape. Two-dimensional (2DSTE) and, more recently, three-dimensional speckle tracking echocardiography (3DSTE) have also emerged as methods for detection of global and regional myocardial dysfunction in various cardiovascular diseases, and applied to the diagnosis of subtle LV and RV dysfunction. Although these novel echocardiographic imaging modalities have advanced our understanding of LV and RV mechanics, overlapping patterns often show challenges that limit their clinical utility. This review will describe the current state of standard and advanced echocardiography in early detection (secondary prevention) of CVD and address future directions for this potentially important diagnostic strategy