Francesco Ciciarello

Effect of therapeutic inhibition of TNF on circulating endothelial progenitor cells in patients with rheumatoid arthritis.

Endothelial dysfunction has been detected in RA patients and seems to be reversed by control of inflammation. Low circulating endothelial progenitor cells (EPCs) have been described in many conditions associated with increased cardiovascular risk, including RA. The aim of this study was to investigate the effect of inhibition of TNF on EPCs in RA patients. Seventeen patients with moderate-severe RA and 12 sex and age-matched controls were evaluated. Endothelial biomarkers were tested at baseline and after 3 months. EPCs were identified from peripheral blood mononuclear cells by cytofluorimetry using anti-CD34 and anti-vascular endothelial growth factor-receptor 2. Asymmetric dimethylarginine (ADMA) was tested by ELISA and flow-mediated dilatation (FMD) by ultrasonography. Circulating EPCs were significantly lower in RA patients than in controls (P = 0.001). After 3 months EPCs increased significantly (P = 0.0006) while ADMA levels significantly decreased (P = 0.001). An inverse correlation between mean increase in EPCs number and mean decrease of DAS28 after treatment was observed (r = −0.56, P = 0.04). EPCs inversely correlated with ADMA (r = −0.41, P = 0.022). No improvement of FMD was detected. Short-term treatment with anti-TNF was able to increase circulating EPCs concurrently with a proportional decrease of disease activity suggesting that therapeutic intervention aimed at suppressing the inflammatory process might positively affect the endothelial function.

Serum Levels of Asymmetric Dimethylarginine and Apelin as Potential Markers of Vascular Endothelial Dysfunction in Early Rheumatoid Arthritis

Objectives. Impaired endothelial function represents the early stage of atherosclerosis, which is typically associated with systemic inflammatory diseases like rheumatoid arthritis (RA). As modulators of endothelial nitric oxide synthase expression, asymmetric-dimethylarginine (ADMA) and apelin might be measured in the blood of RA patients to detect early atherosclerotic changes. We conducted a prospective, case-control study to investigate serum ADMA and apelin profiles of patients with early-stage RA (ERA) before and after disease-modifying antirheumatic drug (DMARD) therapy. Methods. We enrolled 20 consecutively diagnosed, treatment-naïve patients with ERA and 20 matched healthy controls. Serum ADMA and apelin levels and the 28-joint disease activity scores (DAS28) were assessed before and after 12 months of DMARDs treatment. All patients underwent ultrasonographic assessment for intima-media tickness (IMT) evaluation. Results. In the ERA group, ADMA serum levels were significantly higher than controls at baseline (P = 0.007) and significantly decreased after treatment (P = 0.012 versus controls). Baseline serum apelin levels were significantly decreased in this group (P = 0.0001 versus controls), but they were not significantly altered by treatment. IMT did not show significant changes. Conclusions. ERA is associated with alterations of serum ADMA and apelin levels, which might be used as biomarkers to detect early endothelial dysfunction in these patients.

Correlation between coronary artery disease severity, left ventricular mass index and carotid intima media thickness, assessed by radio-frequency

BackgroundIntima-media thickness of the common carotid artery (CCA-IMT) is a validated marker of systemic atherosclerosis process. The aim of this study was to evaluate the association between coronary artery disease (CAD), left ventricular hypertrophy (LVH) and CCA-IMT, assessed by Radio Frequency-Quality Intima Media Thickness (RFQIMT) method, the next generation of IMT real-time measurement, based on the direct analysis of the radiofrequency signal and endowed with high accuracy and reproducibility in early detection of arterial wall thickness.Methods115 patients (76 men, mean age: 65.1 ± 12 years) referred to our department and shown significant (≥ 70% luminal obstruction) stenosis at least in one major epicardial coronary artery were studied. Coronary angiograms were divided for severity and extent of the disease: 79 patients (69%) had one, 24 patients (21%) two, 12 patients (10%) three major epicardial coronary arteries with ≥ 70% stenosis. All patients underwent echocardiography and carotid ultrasound examination, assessed by RF.ResultsDividing RFQIMT data in tertiles, dyslipidaemia (31 patients with IMT ≥ 1.20 mm vs 16 with IMT = 0.91-1.19 vs 25 with IMT ≤ 0.9, p = 0.004), LVMI (153.5 ± 20.6 g/m2 in IMT ≥ 1.20 mm vs 131.2 ± 8.4 g/m2 in IMT = 0.91-1.19 mm vs 114.3 ± 11.1 g/m2 in IMT ≤ 0.9 mm, P < 0.001) and number of high stenosed coronary arteries (IMT ≥ 1.20 mm population more often showed three vessel diseases than IMT ≤ 0.90 mm one, P < 0.001) seemed to be significantly related to CCA-IMT increases. Furthermore, LVMI is positively related to IMT (r = 0.91; P < 0.001). In a multivariate regression model (R2 = 0.88), RFQIMT remained significantly associated with the dyslipidemia (regression coefficient ± standard error [SE]: 0.057 ± 0.023; p = 0.017), LVMI (regression coefficient ± SE: 0.01 ± 0.001; P < 0.0001) and number of damaged coronaries (regression coefficient ± SE: 0.0174 ± 0.028; P < 0.0001).ConclusionsRFQIMT is a sophisticated method for carotid ultrasound evaluation. Its evaluation in patients with at least one important major epicardial coronary vessel stenosis would help the accuracy in the general assessment of the number of coronary lesions in these patients.

Doppler ultrasound venous mapping of the lower limbs.

Background The study aim was to test the accuracy (intra and interobserver variability), sensitivity, and specificity of a simplified noninvasive ultrasound methodology for mapping superficial and deep veins of the lower limbs. Methods 62 consecutive patients, aged 62 ± 11 years, were enrolled. All underwent US-examinations, performed by two different investigators, of both legs, four anatomical parts, and 17 veins, to assess the interobserver variability of evaluation of superficial and deep veins of the lower limbs. Results Overall the agreement between the second versus the first operator was very high in detecting reflux (sensitivity 97.9, specificity 99.7, accuracy 99.5; P = 0.80 at McNemar test). The higher CEAP classification stages were significantly associated with reflux (odds ratio: 1.778, 95% confidence interval: 1.552–2.038; P < 0.001) as well as with thrombosis (odds ratio: 2.765, 95% confidence interval: 1.741–4.389; P < 0.001). Thus, our findings show a strict association between the symptoms of venous disorders and ultrasound evaluation results for thrombosis or reflux. Conclusion This study demonstrated that our venous mapping protocol is a reliable method showing a very low interobserver variability, which makes it accurate and reproducible for the assessment of the morphofunctional status of the lower limb veins.

PVF velocity pattern in patients with heart failure: transesophageal echocardiographic assessment.

In order to assess the role of the pulmonary venous flow (PVF) velocity pattern in the evaluation of patients with congestive heart failure (CHF), we studied 41 CHF patients by means of transthoracic echocardiography (TTE) and multiplane transesophageal echocardiography (TEE). The etiology of CHF was idiopathic or ischemic dilated cardiomyopathy in 19 patients and hypertensive heart disease in 22. Sixteen subjects without cardiovascular disease were selected as normal controls. PVF peak systolic and peak early diastolic (D) velocities were recorded by TEE and TTE and the systolic fraction (SF) was measured (i.e., the systolic velocity-time integral-VTI-expressed as a fraction of the sum of systolic and early diastolic (VTI). TEE tracings were obtained in all patients and had more laminar-appearing spectral signals, thus were used for analysis. By TEE the mitral flow velocity patterns were also evaluated: peak early diastolic velocity (E), peak velocity at atrial contraction, E velocity normalized for VTI (E/VTI), deceleration time (DT), and left ventricular isovolumic relaxation time (LVIRT). The left ventricular ejection fraction (LVEF) was calculated by two-dimensional echocardiographic images using the modified Simpson method. The SF was lower in CHF patients as compared with normal controls (p < 0.0001). The E/VTI ratio was higher, and DT and LVIRT were shorter (p < 0.0001) in CHF patients. A significant correlation was observed between SF and LVEF in CHF patients (r = 0.76, p < 0.001). Two different PVF velocity patterns (type A:SF << 50%, D > 50 cm/s; type B:SF approximately 50%, D > 50 cm/s) were recognized in patients with a low LVEF (type A) and a nearly normal or normal LVEF (type B). Patients with LVEF < 40% showed mean SF values significantly lower than patients with LVEF > 40% (33.26 +/- 10.84 vs. 51.00 +/- 4.00%, p < 0.0001). Mean DT and LVIRT values were not significantly different in patients with LVEF < 40% and > 40%. Thus in CHF patients TEE PVF velocity patterns help in distinguishing patients with systolic dysfunction (low LVEF and SF) from patients with predominant diastolic impairment (normal or nearly normal LVEF, high D velocities).

A three-dimensional electronic report of a venous echo color Doppler of the lower limbs: MEVeC®.

Background The reports of ultrasound evaluation of lower limb veins are difficult to understand by general practitioners (GPs) and physicians who are not specialized. We developed software for a three-dimensional (3D) electronic report of venous hemodynamic mapping (MEVeC®) in order to represent lower limb venous vasculature in a 3D way. The aim of the study is to compare the novel 3D report with the standard report. Methods Thirty subjects (medical students and GPs) evaluated a standard report and a novel 3D report of the lower limb veins of a prespecified patient. The cases were randomly and blindly taken from an archive of 100 cases. GPs and students answered a questionnaire made up of 13 questions that were structured in order to investigate the readability and comprehension of the two reports. A score ranging from 0 to 10 (0= not understandable; 10= full comprehension) was attributed to each report for each question according to the readability of the venous scheme proposed. Results The scores from each question of the questionnaire were compared. The 3D report (MEVeC®) obtained higher scores than those from the evaluation of the standard report (P<0.0001). Each question revealed the superiority of the 3D report (MEVeC®) as compared with the standard report of the ultrasound evaluation of lower limbs. When dividing the scores according to percentiles, the 3D report (MEVeC®) still continued to show more readability than the standard report in a statistically significant way (P<0.0001). Conclusion The new 3D report (MEVeC®) concerning ultrasound evaluation of lower limb veins is more reproducible than the standard report when evaluated by medical physicians not specialized in the evaluation of the vein tree of lower limbs.

Chronic cerebrospinal venous insufficiency as a cause of inner ear diseases

Abstract Conclusion: The present study confirms a correlation between chronic cerebrospinal venous insufficiency (CCSVI) diagnosis and Ménière’s disease (MD). CCSVI could be considered a new ultrasound vascular pattern of the cerebrospinal venous system in patients affected by definite MD. Conversely, the present results showed that CCSVI cannot be considered a pathogenic mechanism for idiopathic sudden sensorineural hearing loss (ISSNHL). Objectives: The aim of this study is to investigate the correlation between CCSVI and MD and to evaluate if CCSVI can be considered a risk factor also for ISSNHL. Moreover, this study seeks to establish if, even with a different timing of onset and natural history, MD and ISSNHL may share a common pathogenic mechanism. Method: One hundred and eighty-two patients affected by definite MD, 60 patients affected by ISSNHL, and 100 healthy control patients were enrolled in this study. All subjects underwent an echo-color Doppler (ECD) of the cerebrospinal venous flow. Results: One hundred and fifty-two patients affected by definite MD (83,5%) and 13 patients affected by ISSNHL (21.6%) were positive for CCSVI at the ECD examination of the cerebrospinal venous flow. The healthy control group consisted of 100 subjects and only 21 (21%) showed positivity for CCSVI.

Chronic muscular Pain treatment with Muscular Acoustic Modulator Device in elderly

Background Muscles Contractures are an important part of multi-factorial etiology of chronic pain. MAM® is an acoustic waves device modulated in power and frequency (0-50 Hz, 0-5 Bar) for treatment of muscular contractures. If the treatment of the chronic muscular contractures with MAM® can improve quality life in elderly.