CT angiography in Fontans with implanted stents

AbstractBackgroundCT angiography is used as a non-invasive method in the evaluation of patients with Fontan circulation. For good visualization of patients having undergone the Fontan operation the optimal scan timing and adequate intravenous route is important.PurposeThe aim of this study was to confirm that computer tomography is very a good tool for assessment of patients after Fontan procedure with implanted stents in pulmonary arteries or in fenestration.Material and methodsSix patients with Fontan circulation and implanted stent in left pulmonary artery or in fenestration underwent CT angiography. The CT angiography was successfully performed to all patients. For homogenous enhancement of Fontan pulmonary arteries and Fontan tract we decided to use 1-minute delay scan with right antecubital application of contrast agent. The optimal enhancement was evaluated at the right pulmonary artery (RPA), left pulmonary artery (LPA), and Fontan tract. Optimal enhancement was defined when evaluation of stent was possible.ResultsOptimal enhancement when the stent was possible to evaluate intraluminally was achieved in seven CT examinations. The Bland–Altman test demonstrated good agreement between readers.ConclusionsThis study demonstrates that CT angiography is a fast, accurate and reproducible method in the evaluation of patients with Fontan circulation, and implanted stent in pulmonary arteries or in fenestration

Comparison of Non-Gated vs. ECG-gated CT Angiography of Fontan Circulation in Patients with Implanted Stents in Pulmonary Branches

Background: Motion artifacts may degrade CT examination of Fontan pathway and hinder accurate diagnosis of in-stent restenosis. Purpose: We retrospectively compared ECG-gated multi-detector computed tomography (CT) with non-ECG-gated CT in order to demonstrate whether or not one of the methods should be preferred. Method: The study included 13 patients with surgically reconstructed Fontan pathway. A total of 16 CT examinations were performed between February 2010 and November 2015.The incidence of motion artifacts in Fontan pathway and pulmonary branches were analysed subjectively by two readers. The effective dose for each examination was calculated. Results: Just in one non-gated CT examination was evidence of motion artifact in distal part of left pulmonary artery. The mean normalized effective radiation dose was 2.33 mSv (±0.62) for the non-ECG-gated scans and 4.55 mSv (±0.85) for the ECG-gated scans (p ≤ 0.05). Conclusion: Non-gated CT angiography with single phase reconstruction significantly reduces radiation dose without loss of image quality compared with ECG-gated CT angiography

Characterization of mesenchymal stem cells of "no-options" patients with critical limb ischemia treated by autologous bone marrow mononuclear cells.

Application of autologous bone marrow mononuclear cells to "no option" patients with advanced critical limb ischemia (CLI) prevented major limb amputation in 73% patients during the 6-month follow-up. We examined which properties of bone marrow stromal cells also known as bone-marrow derived mesenchymal stem cells of responding and non-responding patients are important for amputation-free survival.Mesenchymal stem cells of 41 patients with CLI unsuitable for revascularisation were isolated from mononuclear bone marrow concentrate used for their treatment. Based on the clinical outcome of the treatment, we divided patients into two groups: responders and non-responders. Biological properties of responders' and non-responders' mesenchymal stem cells were characterized according to their ability to multiply, to differentiate in vitro, quantitative expression of cell surface markers, secretion of 27 cytokines, chemokines and growth factors, and to the relative expression of 15 mesenchymal stem cells important genes. Secretome comparison between responders (n=27) and non-responders (n=14) revealed significantly higher secretion values of IL-4, IL-6 and MIP-1b in the group of responders. The expression of cell markers CD44 and CD90 in mesenchymal stem cells from responders was significantly higher compared to non-responders (p<0.01). The expression of mesenchymal stem cells surface markers that was analyzed in 22 patients did not differ between diabetic (n=13) and non-diabetic (n=9) patient groups. Statistically significant higher expression of E-cadherin and PDX-1/IPF1 genes was found in non-responders, while expression of Snail was higher in responders.The quality of mesenchymal stem cells shown in the expression of cell surface markers, secreted factors and stem cell genes plays an important role in therapeutic outcome. Paracrine mechanisms are main drivers in the induction of reparatory processes in CLI patients. Differences in mesenchymal stem cells properties are discussed in relation to their involvement in the reparatory process

Improvement in asymmetric dimethylarginine and oxidative stress in patients with limb salvage after autologous mononuclear stem cell application for critical limb ischemia

Abstract Background Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, acts as an inhibitor of angiogenesis and is associated with an increased risk of cardiovascular mortality. Administration of stem cells may affect endogenous mechanisms that regulate ADMA production and metabolism. The aim of the present study was to analyze ADMA concentration and changes in oxidative stress in patients with advanced critical limb ischemia (CLI) after bone marrow-derived mononuclear cell (BM-MNC) therapy. Methods Fifty patients (age 64 ± 11 years, 44 males, 6 females) with advanced CLI (Rutherford category 5 or 6) not eligible for revascularization were treated by intramuscular (n = 25) or intra-arterial (n = 25) injection of 40 ml BM-MNC concentrate. Patients with limb salvage and improved wound healing after 6 months were considered responders to cell therapy. The concentrations of markers of oxidative stress and angiogenesis were analyzed before, and at 3 and 6 months after BM-MNC delivery. Results At 6-month follow-up, four patients died of reasons unrelated to stem cell therapy. Among the survivors, 80% (37/46) showed limb salvage and improved wound healing. At 6 months follow-up, ADMA concentration significantly decreased in patients with limb salvage (1.74 ± 0.66 to 0.90 ± 0.49 μmol/L, p < 0.001), in parallel with decreased tumor necrosis factor (TNF)-α (2.22 ± 0.16 to 1.94 ± 0.38 pg/ml, p < 0.001), and increased reduced glutathione (6.96 ± 3.1 to 8.67 ± 4.2 μmol/L, p = 0.02), superoxide dismutase activity (168 ± 50 to 218 ± 37 U/L, p = 0.002), and coenzyme Q10 concentration (468 ± 182 to 598 ± 283 μg/L, p = 0.02). The number of delivered BM-MNCs significantly correlated with the decrease in ADMA concentration at 3 months (p = 0.004, r = −0.48) and the decrease in TNF-α concentration at 6 months (p = 0.03, r = −0.44) after cell delivery. ADMA or TNF-α improvement did not correlate with the number of applied CD34+ cells, C-reactive protein concentration, leukocyte count, or the dose of atorvastatin. Conclusions The therapeutic benefit of BM-MNC therapy is associated with reduced ADMA levels and oxidative stress. Regulation of the ADMA-nitric oxide axis and improved antioxidant status may be involved in the beneficial effects of stem cell therapy. Trial registration The study was approved and retrospectively registered by ISRCTN registry, ISRCTN16096154 . Registered on 26 July 2016

Expression of cell surface markers characterizing MSCs.

<p>(A) Expression of MSCs markers on the surface of mesenchymal stem cells of group of responders versus non responders (** - statistic significance is ≤ 0.01; * - statistic significance is ≤ 0.02). (B) Expression of MSCs markers on the surface of mesenchymal stem cells of group of diabetic patients (n=13) versus non diabetic (n=9).</p

Secretion of factors from MSCs and gene expression.

<p>(<b>A</b>) Secretome comparison of several factors of responders (n=27) and non-responders (n=14) CLI patients; For detection of cytokines, chemokines and growth factors Bio-Plex Pro Human Cytokine 27-plex Assay from Bio-Rad was used. The concentration of each factor was calculated per mg of total proteins in 24 hour conditioned medium. The values of growth factors detected in control medium were deducted from values found in conditioned medium. (B) Relative expression of 15 genes typical for MSCs on the level of proteins. Cell extracts of MSCs in early passage of seven non-responders and eight responders were examined by Proteome Profiler Human Pluripotent Stem Cell Array.</p

Doubling time of continually cultivated MSCs from CLI patients in comparison to healthy young donor.

<p>(<b>A</b>) Ability of MSCs of CLI patient to differentiate to osteogenic, adipogenic and chondrogenic lineages; (<b>B</b>) Doubling time of MSCs of CLI patients in first passage. The value is an average of two independent estimations; (<b>C</b>) Doubling time of continually cultivated MSCs from four CLI patients in comparison to healthy young donor. Lines represent the trend.</p

Additional file 1: of Characteristics of responders to autologous bone marrow cell therapy for no-option critical limb ischemia

Presents the dataset supporting the conclusions of this article. (XLSX 26 kb