Tissue mitral annular displacement — a novel technique for rapid quantitative assessment of global left ventricular systolic function based on speckle-tracking algorithm

Wstęp. Tkankowe przemieszczenie pierścienia mitralnego (TMAD) jest nową techniką szybkiej oceny funkcji skurczowej mięśnia lewej komory opartą na śledzeniu markerów akustycznych. Pozwala ona na ocenę przemieszczenia pierścienia mitralnego w stosunku do koniuszka w typowych projekcjach koniuszkowych (cztero- i dwujamowej).Celem pracy było porównanie parametrów otrzymanych przy użyciu TMAD z analizą trójwymiarowego (3D) pomiaru frakcji wyrzutowej lewej komory (LVEF) jako metody referencyjnej.Materiał i metody. Badaniem objęto 49 pacjentów (w tym 33 mężczyzn, średni wiek 65 ± 10 lat) hospitalizowanychz powodu bólów stenokardialnych, których poddano przezklatkowemu badaniu echokardiograficznemu z oceną LVEF 3D podczas analizy off-line na podstawie zbiorów uzyskanych z badania. Poza tym dokonano pomiarów przemieszczenia skurczowego pierścienia mitralnego przy użyciu algorytmu TMAD u wszystkich pacjentów.Wyniki. Ze względu niewystarczającą dla funkcji śledzenia markerów akustycznych jakość obrazu z badania wykluczono 5 pacjentów. Analiza TMAD w jednej z projekcji koniuszkowych zajęła przeciętnie 10 ± 4 s. Średnia wartość LVEF wyniosła 46,0% ± 12,3%. W grupie badanych pacjentów otrzymano istotną statystycznie korelację między LVEF a przemieszczeniem środka pierścienia mitralnego w kierunku koniuszka w projekcji koniuszkowej czterojamowej (r = 0,57; p &lt; 0,0001) oraz procentowym przemieszczeniem pierścienia w kierunku koniuszka (r = 0,63; p &lt; 0,0001). Porównywalne wyniki otrzymano dla przemieszczenia środka pierścienia mitralnego w kierunku koniuszka w projekcji koniuszkowej dwujamowej (r = 0,6; p &lt; 0,0001) oraz jego wartości procentowej (r = 0,65; p &lt; 0,0001).Wnioski. Pomiar skurczowego przemieszczenia pierścienia mitralnego przy użyciu algorytmu TMAD koreluje z referencyjnym pomiarem LVEF 3D, ale technika ta wymaga zbioru danych bardzo dobrej jakości.Introduction. Tissue mitral annular displacement (TMAD) is a new technique for rapid quantitative assessment of global left ventricular function based on tracking of acoustic markers. It allows for the assessment of mitral annulus displacement relative to the apex, based on standard apical views. Objective was to assess the feasibility and accuracy of measurements obtained with TMAD technique for the analysis of global left ventricular function using three-dimensional (3D) left ventricular ejection fraction (LVEF) measurements as a reference technique. Material and methods. The study included 49 patients (33 men, mean age 65 ± 10 years) admitted with stenocardia, who underwent two-dimensional and 3D transthoracic echocardiography with off-line measurement of LVEF using 3D datasets. Furthermore, measurements of mitral annulus displacement relative to apex with a TMAD algorithm were performed in all patients. Results. Due to the suboptimal quality of the data, insufficient for tracking the acoustic markers by the TMAD algorithm, 5 patients were excluded. TMAD analysis of one apical view took 10 ± 4 s. Mean LVEF was 46.0% ± 12.3%. Among this group of patients there was a statistically significant correlation between LVEF and the midpoint mitral annulus displacement towards the apex in the apical four-chamber view (r = 0.57, p < 0.0001) and the percentage of the midpoint mitral annulus displacement (r = 0.63, p < 0.0001). A similar correlation was observed between midpoint mitral annulus displacement in the apical two-chamber view (r = 0.6, p < 0.0001) and the percentage of the midpoint mitral annulus displacement (r = 0.65, p < 0.0001). Conclusion. Measurement of midpoint mitral annulus displacement by TMAD technique is very rapid and provides satisfactory correlation with 3D LVEF measurements. This technique, however, requires echocardiographic recording of good quality

Evaluation of monocyte-derived dendritic cells, T regulatory and Th17 cells in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors

Immunotherapy with dendritic cells (DC) may constitute a new and advantageous option for patients with chronic myeloid leukemia (CML) who respond to therapy with tyrosine kinase inhibitors (TKI), but do not reach complete cytogenetic or molecular remission. In this study, we evaluated the immunophenotype of DC generated from monocytes (Mo-DC) of patients with CML and the influence of TKI therapy on the results of CML-DC generation. We also measured the percentages of T regulatory cells (Tregs) as well as Th17 cells in 19 untreated patients suffering from CML, and in 28 CML patients treated with TKI. We found that DC can be reliably generated from the peripheral blood CD14+ cells of untreated CML patients. But we observed a persistent expression of CD14 monocyte marker on DC from CML patients, together with lower percentages of Mo-DC with expression of CD1a (p = 0.002), CD80 (p = 0.0005), CD83 (p = 0.0004), and CD209 (p = 0.02) compared to healthy donors. There was an adverse correlation between WBC count and the percentage of Mo-DC with co-expression of CD80 and CD86 (R = &#8211;0.63; p = 0.03). In patients treated with TKI, we observed higher efficacy of DC generation in seven-day cultures, compared to untreated patients. Expression of CD209 on DC was higher in patients treated with TKI (0.02). The duration of TKI therapy correlated adversely with MFI for CD1a (R = &#8211;0.49; p = 0.006) and positively with MFI for CD83 (R = 0.63; p = 0.01). Percentages of CD4+CD25highFoxP3+ cells (p = 0.0002) and Th17 cells (p = 0.02) were significantly higher in untreated CML patients compared to healthy controls. There was a significant correlation between the percentage of Treg cells and the percentage of peripheral blood basophiles (R = 0.821; p = 0.02). There were no changes in Tregs or Th17 cell percentages in CML patients after six months of TKI therapy. However, the expression of intracellular IL-17 in Th17 cells correlated negatively with the time of TKI therapy in the whole group of treated patients (R = &#8211;0.516; p = 0.04). We noted a correlation between IL-6 serum level and peripheral blood WBC count (R = 0.492; p = 0.04). There was also an inverse correlation between the serum level of IL-6 and the duration of TKI therapy (R = &#8211;0.66; p = 0.03). Taken together, our data shows that mature DC can be generated from CML patients treated with TKI, and that the yield of Mo-DC is higher in patients treated with TKI than in patients with active disease. This should encourage further trials with DC immunotherapy in patients with cytogenetic response after TKI therapy. We also found increased frequencies of T regulatory and Th17 cells in CML patients, which might suggest their potential role in immunity against this disease. Further studies are needed to determine if manipulation of these cell populations might improve the results of DC immunotherapy. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 153&#8211;160

Dendritic cells based immunotherapy of patient with chondrosarcoma--case report.

We present a case report of patient with intracranial chondrosarcoma and attempt to use vaccination of dendritic cells as the salvage therapy. To our knowledge, this is the first case report of DCs vaccination in the head and neck chondrosarcoma. Immunotherapy with allogeneic DCs stimulated with tumor cell lysates in this case was demonstrated to be feasible, safe and well tolerated. Unfortunately we did not observe any clinical or immune response during vaccination. CD4+ and CD8+ regulatory cells could be responsible for ineffectiveness of immunotherapy

Fusion of morphological data obtained by coronary computed tomography angiography with quantitative echocardiographic data on regional myocardial function

Background: Three-dimensional (3D) fusion of morphological data obtained by coronary computed tomography angiography (CCTA) with functional data from resting and stress echocardiography could potentially provide additional information compared to examination results analyzed separately and increase the diagnostic and prognostic value of non-invasive imaging in patients with suspected coronary artery disease (CAD). Using vendor-independent software developed in our institution, we aimed to assess the feasibility and reproducibility of 3D fusion of morphological CCTA data with echocardiographic data regarding regional myocardial function. Methods: Thirty patients with suspected CAD underwent CCTA and resting transthoracic echocardiography. From CCTA we obtained 3D reconstructions of coronary arteries and left ventricle (LV). Offline speckle-tracking analysis of the echocardiographic images provided parametric maps depicting myocardial longitudinal strain in 17 segments of the LV. Using our software, 3 independent investigators fused echocardiographic maps with CCTA reconstruc­tions in all patients. Based on the obtained fused models, each segment of the LV was assigned to one of the major coronary artery branches. Results: Mean time necessary for data fusion was 65 ± 7 s. Complete agreement between independent investigators in assignment of LV segments to coronary branches was obtained in 94% of the segments. The average coefficient of agreement (kappa) between the investigators was 0.950 and the intra-class correlation coefficient was 0.9329 (95% CI 0.9227–0.9420). Conclusions: Three-dimensional fusion of morphological CCTA data with quantitative echocardiographic data on regional myocardial function is feasible and allows highly repro­ducible assignment of myocardial segments to coronary artery branches

CD3+/CD16+CD56+ cell numbers in peripheral blood are correlated with higher tumor burden in patients with diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma is the commonest histological type of malignant lymphoma, andremains incurable in many cases. Developing more efficient immunotherapy strategies will require betterunderstanding of the disorders of immune responses in cancer patients. NKT (natural killer-like T) cells wereoriginally described as a unique population of T cells with the co-expression of NK cell markers. Apart fromtheir role in protecting against microbial pathogens and controlling autoimmune diseases, NKT cells havebeen recently revealed as one of the key players in the immune responses against tumors. The objective of thisstudy was to evaluate the frequency of CD3+/CD16+CD56+ cells in the peripheral blood of 28 diffuse largeB-cell lymphoma (DLBCL) patients in correlation with clinical and laboratory parameters. Median percentagesof CD3+/CD16+CD56+ were significantly lower in patients with DLBCL compared to healthy donors(7.37% vs. 9.01%, p = 0.01; 4.60% vs. 5.81%, p = 0.03), although there were no differences in absolute counts.The frequency and the absolute numbers of CD3+/CD16+CD56+ cells were lower in advanced clinical stagesthan in earlier ones. The median percentage of CD3+/CD16+CD56+ cells in patients in Ann Arbor stages 1–2 was5.55% vs. 3.15% in stages 3–4 (p = 0.02), with median absolute counts respectively 0.26 G/L vs. 0.41 G/L (p == 0.02). The percentage and absolute numbers of CD3+/CD16+CD56+ cells were significantly higher in DL-BCL patients without B-symptoms compared to the patients with B-symptoms, (5.51% vs. 2.46%, p = 0.04;0.21 G/L vs. 0.44 G/L, p = 0.04). The percentage of CD3+/CD16+CD56+ cells correlated adversely with serumlactate dehydrogenase (R= –445; p < 0.05) which might influence NKT count. These figures suggest a relationshipbetween higher tumor burden and more aggressive disease and decreased NKT numbers. But it remains tobe explained whether low NKT cell counts in the peripheral blood of patients with DLBCL are the result of theirsuppression by the tumor cells, or their migration to affected lymph nodes or organs

Ocena funkcji prawego przedsionka za pomocą echokardiografii metodą śledzenia markerów akustycznych

Introduction. Speckle tracking echocardiography (STE) is a well-established tool to assess cardiac function parameters, however, the value of this tool in the assessment of right atrial (RA) function is still largely unknown. The aim of the study is to investigate the feasibility of RA function assessment by STE and the relationship between right ventricular (RV) deformation and the function of the RA. Material and methods. 94 patients with various cardiovascular pathologies have been included in the study group. All patients underwent transthoracic echocardiography with subsequent off-line analysis using speckle tracking technique and measurement of numerous RA deformation parameters, including peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS), as well as established indices of RV function, such as tricuspid annular peak systolic excursion (TAPSE) and global longitudinal strain (GLS). Results. RA function assessment by STE was feasible in all patients. A statistically significant correlation was observed between RA strain (PACS and PALS) and RV parameters. RV-GLS showed weak correlation with PALS (r = –0.38; p = 0.0015) and PACS (r = –0.30; p = 0.013). Similarly, TAPSE correlated with PALS and PACS (r = 0.34; p = 0.02) and (r = 0.23; p = 0.04) respectively. Conclusion. RA function assessment by STE is feasible. The RA deformation parameters weakly correlate with RV function indices, indicating that other factors significantly influence RA function. Therefore, the RA function cannot be regarded as a direct barometer of the RV function.Wstęp. Echokardiografia metodą śledzenia markerów akustycznych (STE) jest uznanym narzędziem oceny parametrów czynności serca, jednak wartość tego narzędzia w ocenie czynności prawego przedsionka (RA) jest nadal w dużej mierze nieznana. Celem pracy jest zbadanie możliwości oceny funkcji RA za pomocą STE oraz związku między deformacją prawej komory (RV) a funkcją RA. Materiał i metody. Do badanej grupy włączono 94 osoby z różnymi patologiami sercowo-naczyniowymi. U wszystkich pacjentów wykonano echokardiografię przezklatkową z późniejszą analizą off-line z wykorzystaniem techniki śledzenia markerów akustycznych i pomiarem licznych parametrów deformacji RA, w tym szczytowe odkształcenie podłużne przedsionków (PALS) i szczytowe napięcie skurczowe przedsionków (PACS), a także ustalonych wskaźników funkcji RV, takich jak: wychylenie skurczowe pierścienia trójdzielnego (TAPSE) i globalne odkształcenie podłużne (GLS). Wyniki. Ocena funkcji RA za pomocą echokardiografii śladowej plamki była możliwa u wszystkich pacjentów. Zaobserwowano statystycznie istotną korelację między odkształceniem prawej komory (PACS i PALS) a parametrami RV. RV-GLS wykazało słabą korelację z PALS (r = –0,38; p = 0,0015) i PACS (r = –0,30; p = 0,013). Podobnie TAPSE korelowało z PALS i PACS (r = 0,34; p = 0,02) i (r = 0,23; p = 0,04). Wnioski. Ocena funkcji RA za pomocą echokardiografii metodą śledzenia markerów akustycznych jest możliwa. Parametry deformacji RA słabo korelują ze wskaźnikami funkcji RV, co wskazuje, że inne czynniki mają istotny wpływ na funkcję RA. Dlatego funkcja RA nie może być traktowana jako bezpośredni barometr funkcji RV

Quality control of B-lines analysis in stress Echo 2020

Background The effectiveness trial “Stress echo (SE) 2020” evaluates novel applications of SE in and beyond coronary artery disease. The core protocol also includes 4-site simplified scan of B-lines by lung ultrasound, useful to assess pulmonary congestion. Purpose To provide web-based upstream quality control and harmonization of B-lines reading criteria. Methods 60 readers (all previously accredited for regional wall motion, 53 B-lines naive) from 52 centers of 16 countries of SE 2020 network read a set of 20 lung ultrasound video-clips selected by the Pisa lab serving as reference standard, after taking an obligatory web-based learning 2-h module ( http://se2020.altervista.org ). Each test clip was scored for B-lines from 0 (black lung, A-lines, no B-lines) to 10 (white lung, coalescing B-lines). The diagnostic gold standard was the concordant assessment of two experienced readers of the Pisa lab. The answer of the reader was considered correct if concordant with reference standard reading ±1 (for instance, reference standard reading of 5 B-lines; correct answer 4, 5, or 6). The a priori determined pass threshold was 18/20 (≥ 90%) with R value (intra-class correlation coefficient) between reference standard and recruiting center) > 0.90. Inter-observer agreement was assessed with intra-class correlation coefficient statistics. Results All 60 readers were successfully accredited: 26 (43%) on first, 24 (40%) on second, and 10 (17%) on third attempt. The average diagnostic accuracy of the 60 accredited readers was 95%, with R value of 0.95 compared to reference standard reading. The 53 B-lines naive scored similarly to the 7 B-lines expert on first attempt (90 versus 95%, p = NS). Compared to the step-1 of quality control for regional wall motion abnormalities, the mean reading time per attempt was shorter (17 ± 3 vs 29 ± 12 min, p < .01), the first attempt success rate was higher (43 vs 28%, p < 0.01), and the drop-out of readers smaller (0 vs 28%, p < .01). Conclusions Web-based learning is highly effective for teaching and harmonizing B-lines reading. Echocardiographers without previous experience with B-lines learn quickly.info:eu-repo/semantics/publishedVersio

Selection and validation of endogenous controls for microRNA expression studies in endometrioid endometrial cancer tissues

AbstractObjectivesmicroRNAs comprise a family of small, non-coding RNAs, which regulate gene expression at the posttranscriptional level. Multiple studies implicated important roles of microRNAs in various malignancies including endometrioid endometrial carcinoma (EEC). qPCR is widely used in the studies investigating microRNA expression. Relative quantification of microRNA expression requires proper normalization methods and endogenous controls are widely used for this purpose. The aim of this study was experimental identification of stable endogenous controls for normalization of microRNA qPCR expression studies in EEC.MethodsExpression of twelve candidate endogenous controls (miR-16, miR-26b, miR-92a, RNU44, RNU48, U75, U54, U6, U49, RNU6B, RNU38B, U18A) was investigated in tissue samples obtained from 45 patients (30 EEC, 15 normal endometrium) using qPCR. Stability of candidate endogenous controls was evaluated using NormFinder, geNorm, BestKeeper and equivalency test. The results were then validated using larger group of samples.ResultsRNU48, U75 and RNU44 were identified as stably and equivalently expressed between malignant and normal tissues. Both NormFinder and geNorm indicated that those three snRNAs were optimal for qPCR data normalization in EEC tissues.ConclusionsIn conclusion, we suggest that average expression of those snoRNAs could be used as a reliable endogenous control in microRNA qPCR studies in endometrioid endometrial cancer. In addition to identifying suitable endogenous controls in EEC, our study presents an appropriate strategy for validation of candidate reference genes for any microRNA qPCR study

Continuous hands-free monitoring of echocardiographic exercise test using probe fixation device

Background: Stress echocardiography has been widely used in clinical practice for decades and has recently gained even more importance in diagnostic approaches to ischemic heart disease. However, it still has numerous limitations. Despite advantages of physical exercise as most physiologic stressor, it is impossible to continuously monitor the cardiac function during treadmill test and difficult to maintain an optimal acoustic window during cycle ergometer exercise tests. The aim herein, is to assess the feasibility of probe fixation for use during exercise echocardiography. Methods: Forty-eight subjects (47 men, mean age 42 ± 17 years, 25 healthy volunteers, 23 patients with suspected coronary artery disease) were included in this study. All subjects underwent exercise stress test on treadmill (32 cases) or cycle ergometer (16 cases). Both sector and matrix probes were used (in 17 and 31 tests, respectively). The semi-quantitative quality of acquired apical views were assessed at each stage using a four-point grading system. Results: The mean time required for probe fixation was 9 ± 2 min. At baseline, 10 patients had at least one apical window of quality precluding reliable analysis. Twenty-five patients required probe repositioning during exercise (more often on a treadmill). During peak exercise quality of images in all views declined, but for diagnostic purposes it remained sufficient in 29 patients. Thus, 76% of performed tests (60% study population) had sufficient image quality. Conclusions: Probe fixation offers the possibility of continuous acquisition of echocardiographic images during physical exercise. The device is suitable almost exclusively for male patients and in some patients requires repositioning