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101.
Daria Gognieva Yulia Mitina Timur Gamilov Roman Pryamonosov Yuriy Vasilevskii Sergey Simakov Fuyou Liang Sergey Ternovoy Natalya Serova Ekaterina Tebenkova Valentin Sinitsyn Ekaterina Pershina Sergey Abugov Gaik Mardanian Narek Zakarian Vardan Kirakosian Vladimir Betelin Dmitry Shchekochikhin Abram Syrkin Philippe Kopylov 《Global Heart》2021,16(1)
Background:Until recently, Russia did not utilize noninvasive fractional flow reserve (FFR) assessment. We developed an automated algorithm for noninvasive assessment of FFR based on a one-dimensional (1D) mathematical modeling.Objective:The research aims to evaluate the diagnostic accuracy of this algorithm.Methods:The study enrolled 80 patients: 16 of them underwent 64-slice computed tomography – included retrospectively, 64 – prospectively, with a 640-slice CT scan. Specialists processed CT images and evaluated noninvasive FFR. Ischemia was confirmed if FFR < 0.80 and disproved if FFR ≥ 0.80. The prospective group of patients was hospitalized for invasive FFR assessment as a reference standard. If ischemic, patients underwent stent implantation. In the retrospective group, patients already had invasive FFR values.Statistical analysis was performed using GraphPad Prism 8. We compared two methods using a Bland–Altman plot and per-vessel ROC curve analysis. Considering the abnormality of distribution by the Kolmogorov-Smirnov test, we have used Spearman’s rank correlation coefficient.Results:During data processing, three patients of the retrospective and 46 patients of the prospective group were excluded. The sensitivity of our method was 66.67% (95% CI: 46.71–82.03); the specificity was 78.95% (95% CI: 56.67–91.49), p = 0.0052, in the per-vessel analysis. In per-patient analysis, the sensitivity was 69.57% (95% CI: 49.13–84.40); the specificity was 87.50% (95% CI: 52.91–99.36), p = 0.0109. The area under the ROC curve in the per-vessel analysis was 77.52% (95% CI: 66.97–88.08), p < 0.0001.Conclusion:The obtained indices of sensitivity, specificity, PPV, and NPV are, in general, comparable to those in other studies. Moreover, the noninvasive values of FFR yielded a high correlation coefficient with the invasive values. However, the AUC was not high enough, 77.52 (95% CI: 66.97–88.08), p < 0.0001. The discrepancy is probably attributed to the initial data heterogeneity and low statistical power. 相似文献
102.
Galyna V. Grygoriv Dmitry A. Lega Valentin P. Chernykh Lucjusz Zaprutko Andrzej K. Gzella Anna Paweczyk Leonid A. Shemchuk 《RSC advances》2018,8(65):37295
The reactivity of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide was studied in multicomponent type reactions for the first time, namely, in a three-component interaction with active methylene nitriles and aromatic aldehydes in order to construct condensed 2-amino-4H-pyran derivatives. The reaction outcome strongly depended on the nature of an active methylene nitrile and an arenecarbaldehyde. Application of malononitrile resulted in novel 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carbonitrile 5,5-dioxides in most cases, whereas the utilization of ethyl cyanoacetate resulted in a complex mixture of products. In the last case, three different products were isolated depending on the arenecarbaldehyde used, namely ethyl 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carboxylate 5,5-dioxides, ethyl 2-cyano-3-arylacrylates, and salts of 3,3′-(arylmethylene)bis(4-hydroxybenzo[e][1,2]oxathiine 2,2-dioxides). Attempts to obtain separately ethyl 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carboxylate 5,5-dioxides enabled us to propose reaction pathways leading to these products. The salts were obtained for the first time. The preparative method for the synthesis of triethylammonium salts of 3,3′-(arylmethylene)bis(4-hydroxybenzo[e][1,2]oxathiine 2,2-dioxides) was proposed by the direct interaction of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide with arenecarbaldehydes. The application of ammonium acetate as a catalyst allowed us to synthesize 7-aryl-7,14-dihydrobenzo[5,6][1,2]oxathiino[4,3-b]benzo[5,6][1,2]oxathiino[3,4-e]pyridine 6,6,8,8-tetraoxides containing a novel heterocyclic system. These facts, combined with our past investigations, allowed us to assert that the reactivity of enol nucleophiles that include the COCH2SO2X fragment has not been reported previously.Reactivity of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide was for the first time studied in multicomponent type reactions involving active methylene nitriles and aromatic aldehydes. 相似文献
103.
With the rapid increase of reported COVID‐19 cases, German policymakers announced a 4‐week “shutdown light” starting on November 2, 2020. Applying mathematical models, possible scenarios for the evolution of the outbreak in Germany are simulated. The results indicate that independent of the effectiveness of the current restrictive measures they might not be sufficient to mitigate the outbreak. Repeated shutdown periods or permanently applied measures over the winter could be successful alternatives. 相似文献
104.
von Büdingen HC Hauser SL Fuhrmann A Nabavi CB Lee JI Genain CP 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(12):8207-8212
Myelin/oligodendrocyte glycoprotein (MOG) is a target antigen for myelin-destructive Abs in autoimmune central nervous system demyelinating disorders. Little is known about the molecular and structural basis of these pathogenic Ab responses. Here, we have characterized anti-MOG Ab specificities in the marmoset model of experimental allergic encephalomyelitis, by means of a combinatorial IgG-Fab library. We found that a diverse population of Ig genes encodes for auto-Abs that exclusively recognize conformation-dependent antigenic targets on MOG. These antigenic domains correspond to exposed epitopes in vivo, as the Fab fragments recognize native MOG in situ in marmoset brain tissue. The Ab fragments described here represent Ab specificities that are common constituents of the humoral immune repertoire against MOG in outbred populations, as demonstrated by their ability to displace native anti-MOG Abs present in sera from MOG-immune marmosets and patients with multiple sclerosis. Furthermore, neuropathological analysis and characterization of Ab epitope specificities in animals immunized with MOG or MOG-derived peptides revealed that only conformation-dependent Abs are associated with demyelinating activity, suggesting that epitope recognition is an important factor for Ab pathogenicity. Our findings provide novel and unexpected knowledge on the diversity of anti-MOG Ab responses in nonhuman primates and humans, and will permit the dissection of pathogenic auto-Ab properties in multiple sclerosis. 相似文献
105.
Sun Z Wu J Fujii H Wu J Li SH Porozov S Belleli A Fulga V Porat Y Li RK 《European journal of heart failure》2008,10(6):525-533
BACKGROUND: We recently isolated angiogenic cell precursors (ACPs) from human blood, which can induce angiogenesis in vitro. AIMS: In the present study, we used a nude rat model of ischaemic cardiomyopathy to compare the efficacy of intramyocardial and intracoronary ACP implantation, and to evaluate effects on cardiac function, scar size and angiogenesis. METHODS AND RESULTS: Adult nude rats underwent coronary artery ligation. Six days later, ACPs (characterized in vitro prior to implantation) or culture media were injected directly into the ischaemic myocardial region or into the coronary artery via the aorta. Cardiac function was measured by echocardiography prior to and at 2 and 4 weeks after implantation. Scar morphology, cell engraftment, and myocardial angiogenesis were evaluated at 4 weeks. Two and four weeks after implantation, cardiac function declined in both of the control groups but improved in both the intramyocardial and intracoronary ACP groups. Significant reductions in myocardial scar area were only observed in the intramyocardial ACP group, while increases in blood vessel density, which were observed in all ACP recipients, were greatest in the intracoronary ACP group. CONCLUSIONS: Human ACPs, delivered via intramyocardial or intracoronary injection, engrafted into damaged cardiac tissue and improved cardiac function within 4 weeks through effects on scar morphology and blood vessel formation. 相似文献
106.
We have investigated the interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis. Acidic FGF (aFGF) stimulated the proliferation of murine megakaryocytes and human erythroleukemia (HEL) cells in a concentration-dependent manner. The concentrations of aFGF required to elicit half-maximum and maximum effects were similar for HEL and megakaryocytic colony formation. The effect of aFGF was comparable to that of basic FGF (bFGF) in both cell types. The effect of both FGFs was found to be synergistic with interleukin-3 (IL-3), and was abrogated by a monoclonal anti-IL-6 antibody. A specific cell surface receptor complex of approximately 120 Kd was detected for FGF by crosslinking experiments on HEL cells and total bone marrow (BM) cells. Single-cell autoradiography of megakaryocytes in BM smears and BM cultures showed binding sites for 125I-aFGF. Northern blot analysis of messenger RNA (mRNA) from total BM and HEL cells showed a 4.4-kb mRNA specific for FGF receptors type 1 (flg) and type 2 (bek). This was confirmed by polymerase chain reaction, which also showed the presence of FGF receptor mRNA in megakaryocytic-like cells, normal megakaryocytes, and platelets. Together, these results indicate that FGF is involved in megakaryocytopoiesis and suggest that this interaction may be mediated via FGF receptor type 1 and type 2 located on the megakaryocytic lineage or on accessory cells responsible for the release of megakaryocytic growth-promoting activities. 相似文献
107.
Orsolya Balogh Valentin Brodszky László Gulácsi Emese Herédi Krisztina Herszényi Hajnalka Jókai Sarolta Kárpáti Petra Baji Éva Remenyik Andrea Szegedi Péter Holló 《The European journal of health economics》2014,15(1):101-109
Background
Despite the widespread availability of biological drugs in psoriasis, there is a shortage of disease burden studies.Objectives
To assess the cost-of-illness and quality of life of patients with moderate to severe psoriasis in Hungary.Methods
Consecutive patients with Psoriasis Area and Severity Index (PASI) > 10 and Dermatology Life Quality Index (DLQI) > 10, or treated with traditional systemic (TST) or biological systemic treatment (BST) were included. Demographic data, clinical characteristics, psoriasis related medication, health care utilizations and employment status in the previous 12 months were recorded. Costing was performed from the societal perspective applying the human capital approach. Quality of life was assessed using DLQI and EQ-5D measures.Results
Two-hundred patients were involved (females 32 %) with a mean age of 51 (SD 13) years, 103 (52 %) patients were on BST. Mean PASI, DLQI and EQ-5D scores were 8 (SD 10), 6 (SD 7) and 0.69 (SD 0.3), respectively. The mean total cost was €9,254/patient/year (SD 8,502) with direct costs accounting for 86 %. The main cost driver was BST (mean €7,339/patient/year). Total costs differed significantly across treatment subgroups, mean (SD): no systemic therapy €2,186 (4,165), TST €2,388 (4,106) and BST €15,790 (6,016) (p < 0,001). Patients with BST had better PASI and DLQI scores (p < 0.01) than the other two subgroups.Conclusions
Patients with biological treatment have a significantly better quality of life and higher total costs than patients with or without traditional systemic treatment. Our study is the largest in Europe and the first in the CEE region that provides cost-of-illness data in psoriasis involving patients with BST.108.
Nikola Y. Kolev Anton Y. Tonev Valentin L. Ignatov Aleksander K. Zlatarov Vasil M. Bojkov Tanya D. Kirilova Elitsa Encheva Krasimir Ivanov 《International surgery》2014,99(2):106-111
In the last 20 years, endorectal ultrasound (ERUS) has been one of the main diagnostic methods for locoregional staging of rectal cancer. ERUS is accurate modality for evaluating local invasion of rectal carcinoma into the rectal wall layers (T category). Adding the three-dimensional modality (3-D) increases the capabilities of this diagnostic tool in rectal cancer patients. We review the literature and report our experience in preoperative 3-D ERUS in rectal cancer staging. In the group of 71 patients, the staging of preoperative 3-D endorectal ultrasonography was compared with the postoperative morphologic examination. Three-dimensional ERUS preoperative staging was confirmed with morphologic evaluation in 66 out of 71 cases (92.9%). The detection sensitivities of rectal cancer with 3-D ERUS were as follows: T1, 92.8%; T2, 93.1%; T3, 91.6%; and T4, 100.0%; with specificity values of T1, 98.2%; T2, 95.4%; T3, 97.8%; and T4, 98.5%. Three-dimensional ERUS correctly categorized patients with T1, 97.1%; T2, 94.3%; T3, 95.7%; and T4, 98.5%. The percentage of total overstaged cases was 2.75% and that of understaged cases was 6.87%. The metastatic status of the lymph nodes was determined with a sensitivity of 79.1% (19 of 24), specificity of 91.4% (43 of 47), and diagnostic accuracy of 87.3% (62 of 71). In our experience, 3-D ERUS has the potential to become the diagnostic modality of choice for the preoperative staging of rectal cancer.Key words: Three-dimensional endorectal ultrasound, Rectal cancerEndorectal ultrasound (ERUS) has been used as a diagnostic tool for evaluation and staging of rectal cancer since the 1980s.1 According to the literature, in studies with more than 50 patients included, an overall accuracy of approximately 81.8% was reported.2 Most of the studies present data between 85% and 95%, but in the studies with more than 200 patients, the accuracy rates are relatively lower—63.3% and 69%, respectively.3,4 A common disadvantage of ERUS and magnetic resonance imaging (MRI) is the overstaging of T2 tumors owing to an irregular outer rectal wall resulting from transmural tumor extension or inflammation around the tumor. Another challenge for the ERUS, and especially the rigid probes, are the locally advanced, stenotic tumors, where the probe may not be able to pass above the lesion.5 The nodal staging accuracy of ERUS ranges from 70% to 75%.1,5,6 The metastatic lymph nodes are distinguished by hypoechoic appearance, round shape, peritumoral location, and size >5 mm.7,8 Lymph nodes >5 mm have a 50% to 70% chance of being malignant, while those <4 mm have only a 20% chance.9,10 A new modality of endorectal ultrasound represents a three-dimensional (3-D) ERUS that provides better visual images of the tumor volume and spatial relations to the adjacent organs and structures, even better than those of MRI, which leads to better diagnostic accuracy than MRI and standard ERUS.11–15 The unique 3-D–ERUS longitudinal scan can precisely assess the tumor size and location.16 The most important feature of this upgraded modality is the ability to reduce interpreter errors and offer potential predictive value. Three-dimensional ERUS provides the possibility to distinguish blood vessels from lymph nodes and allow precise fine needle aspiration (FNA) biopsies.13,17 The infiltration of circumferential margin has been proven to correlate with T category, lymph node metastasis histologic tumor differentiation, and lymphovascular invasion.13,17 Three-dimensional ERUS gives the possibility of multiplane evaluation of the tumor, allowing visualization of more subtle changes in the tumor characteristics and therefore better T and N categorizing.18 A review of 86 patients who underwent standard 3-D ERUS, ERUS and 4-channel detector computed tomography (CT) demonstrated T-category accuracy of 78%, 69%, and 57%, respectively.19 After analysis of the examiner''s error, the accuracy of 3-D ERUS for T category has reached 91% for 3-D ERUS and 88% for standard ERUS, and the N category accuracy improved to 90% and 76%, respectively. Also, ERUS can be used for diagnosis of premalignant lesions such as adenomas and polyps.20 The main goal is to properly identify any chance of tumor invasion in the primary lesion and involvement of the surrounding lymph nodes in case the absence of those alarming characteristics allows for endoscopic resection of the lesion. Using higher-resolution probes, ERUS can distinguish T0 from T1 lesions. According to a meta-analysis of 258 biopsy-negative tumors, ERUS identified tumor mass in 81% of the 24 lesions, which were found to be invasive tumors on morphologic examination.20 Another series of 60 patients with pT0/pT1 lesions demonstrated sensitivity and specificity of ERUS 89% and 88%, respectively.21 As with MRI, 3-D ERUS could provide an evaluation of the mesorectal fascia.14,22The reported data lead to the position that 3-D ERUS combines the high-resolution images of the rectal wall and cost-effectiveness of standard ERUS with the multiplanar and stereoscopic imaging capabilities of MRI. Three-dimensional ERUS may be the future premier imaging modality used in rectal cancer management. 相似文献
109.
110.