8 research outputs found
Community-based dispute resolution processes in Bamiyan province / Deborah J. Smith; Shelly Manalan
No full textCommunity-based dispute resolution processes in Bamiyan province
No full textDeborah J. Smith; Shelly Manala
Ranolazine as an Alternative Therapy to Flecainide for SCN5A V411M Long QT Syndrome Type 3 Patients
Get PDF[EN] The prolongation of the QT interval represents the main feature of the long QT syndrome (LQTS), a life-threatening genetic disease. The heterozygous SCN5A V411M mutation of the human sodium channel leads to a LQTS type 3 with severe proarrhythmic effects due to an increase in the late component of the sodium current (INaL). The two sodium blockers flecainide and ranolazine are equally recommended by the current 2015 ESC guidelines to treat patients with LQTS type 3 and persistently prolonged QT intervals. However, awareness of pro-arrhythmic effects of flecainide in LQTS type 3 patients arose upon the study of the SCN5A E1784K mutation. Regarding SCN5A V411M individuals, flecainide showed good results albeit in a reduced number of patients and no evidence supporting the use of ranolazine has ever been released. Therefore, we ought to compare the effect of ranolazine and flecainide in a SCN5A V411M model using an in-silico modeling and simulation approach. We collected clinical data of four patients. Then, we fitted four Markovian models of the human sodium current (INa) to experimental and clinical data. Two of them correspond to the wild type and the heterozygous SCN5A V411M scenarios, and the other two mimic the effects of flecainide and ranolazine on INa. Next, we inserted them into three isolated cell action potential (AP) models for endocardial, midmyocardial and epicardial cells and in a one-dimensional tissue model. The SCN5A V411M mutation produced a 15.9% APD90 prolongation in the isolated endocardial cell model, which corresponded to a 14.3% of the QT interval prolongation in a one-dimensional strand model, in keeping with clinical observations. Although with different underlying mechanisms, flecainide and ranolazine partially countered this prolongation at the isolated endocardial model by reducing the APD90 by 8.7 and 4.3%, and the QT interval by 7.2 and 3.2%, respectively. While flecainide specifically targeted the mutation-induced increase in peak INaL, ranolazine reduced it during the entire AP. Our simulations also suggest that ranolazine could prevent early afterdepolarizations triggered by the SCN5A V411M mutation during bradycardia, as flecainide. We conclude that ranolazine could be used to treat SCN5A V411M patients, specifically when flecainide is contraindicated.This work was partially supported by Fondo Europeo de Desarrollo Regional (FEDER, "Union Europea, Una forma de hacer Europa") with the Ministerio de Economia y Competitividad (DPI2015-69125-R), Direccion General de Politica Cientifica de la Generalitat Valenciana (PROMETEO/2020/043) and Instituto de Salud Carlos III (La Fe Biobank PT17/0015/0043), as well as by Vicerrectorado de Investigacion, Innovacion y Transferencia de la Universitat Politecnica de Valencia with Ayuda a Primeros Proyectos de Investigacion (PAID-06-18), and by Memorial Nacho Barbera.Cano, J.; Zorio, E.; Mazzanti, A.; Arnau, MÁ.; Trenor Gomis, BA.; Priori, SG.; Saiz Rodríguez, FJ.... (2020). Ranolazine as an Alternative Therapy to Flecainide for SCN5A V411M Long QT Syndrome Type 3 Patients. Frontiers in Pharmacology. 11:1-19. https://doi.org/10.3389/fphar.2020.580481S11911Abdelsayed, M., Peters, C. H., & Ruben, P. C. (2015). Differential thermosensitivity in mixed syndrome cardiac sodium channel mutants. The Journal of Physiology, 593(18), 4201-4223. doi:10.1113/jp270139Ackerman, M. J., Priori, S. G., Willems, S., Berul, C., Brugada, R., Calkins, H., … Zipes, D. P. (2011). HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies. Heart Rhythm, 8(8), 1308-1339. doi:10.1016/j.hrthm.2011.05.020Aliot, E., Capucci, A., Crijns, H. J., Goette, A., & Tamargo, J. (2010). Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation. Europace, 13(2), 161-173. doi:10.1093/europace/euq382Andrikopoulos, G. K. (2015). Flecainide: Current status and perspectives in arrhythmia management. World Journal of Cardiology, 7(2), 76. doi:10.4330/wjc.v7.i2.76Belardinelli, L., Liu, G., Smith-Maxwell, C., Wang, W.-Q., El-Bizri, N., Hirakawa, R., … Shryock, J. C. (2012). A Novel, Potent, and Selective Inhibitor of Cardiac Late Sodium Current Suppresses Experimental Arrhythmias. Journal of Pharmacology and Experimental Therapeutics, 344(1), 23-32. doi:10.1124/jpet.112.198887Bengel, P., Ahmad, S., & Sossalla, S. (2017). Inhibition of Late Sodium Current as an Innovative Antiarrhythmic Strategy. Current Heart Failure Reports, 14(3), 179-186. doi:10.1007/s11897-017-0333-0Blich, M., Khoury, A., Suleiman, M., Lorber, A., Gepstein, L., & Boulous, M. (2019). Specific Therapy Based on the Genotype in a Malignant Form of Long QT3, Carrying the V411M Mutation. International Heart Journal, 60(4), 979-982. doi:10.1536/ihj.18-705Bohnen, M. S., Peng, G., Robey, S. H., Terrenoire, C., Iyer, V., Sampson, K. J., & Kass, R. S. (2017). Molecular Pathophysiology of Congenital Long QT Syndrome. Physiological Reviews, 97(1), 89-134. doi:10.1152/physrev.00008.2016Britton, O. J., Bueno-Orovio, A., Van Ammel, K., Lu, H. R., Towart, R., Gallacher, D. J., & Rodriguez, B. (2013). Experimentally calibrated population of models predicts and explains intersubject variability in cardiac cellular electrophysiology. Proceedings of the National Academy of Sciences, 110(23), E2098-E2105. doi:10.1073/pnas.1304382110Caballero, R., Dolz-Gaiton, P., Gomez, R., Amoros, I., Barana, A., Gonzalez de la Fuente, M., … Delpon, E. (2010). Flecainide increases Kir2.1 currents by interacting with cysteine 311, decreasing the polyamine-induced rectification. Proceedings of the National Academy of Sciences, 107(35), 15631-15636. doi:10.1073/pnas.1004021107Carrasco, J. I., Izquierdo, I., Medina, P., Arnau, M. Á., Salvador, A., & Zorio, E. (2012). Flecainide, a Therapeutic Option in a Patient With Long QT Syndrome Type 3 Caused by the Heterozygous V411M Mutation in the SCN5A Gene. Revista Española de Cardiología (English Edition), 65(11), 1058-1059. doi:10.1016/j.rec.2012.03.013Chadda, K. R., Jeevaratnam, K., Lei, M., & Huang, C. L.-H. (2017). Sodium channel biophysics, late sodium current and genetic arrhythmic syndromes. Pflügers Archiv - European Journal of Physiology, 469(5-6), 629-641. doi:10.1007/s00424-017-1959-1Chang, K. C., Dutta, S., Mirams, G. R., Beattie, K. A., Sheng, J., Tran, P. N., … Li, Z. (2017). Uncertainty Quantification Reveals the Importance of Data Variability and Experimental Design Considerations for in Silico Proarrhythmia Risk Assessment. Frontiers in Physiology, 8. doi:10.3389/fphys.2017.00917Chorin, E., Hu, D., Antzelevitch, C., Hochstadt, A., Belardinelli, L., Zeltser, D., … Viskin, S. (2016). Ranolazine for Congenital Long-QT Syndrome Type III. Circulation: Arrhythmia and Electrophysiology, 9(10). doi:10.1161/circep.116.004370Colquhoun, D., Dowsland, K. A., Beato, M., & Plested, A. J. R. (2004). How to Impose Microscopic Reversibility in Complex Reaction Mechanisms. Biophysical Journal, 86(6), 3510-3518. doi:10.1529/biophysj.103.038679Crumb, W. J., Vicente, J., Johannesen, L., & Strauss, D. G. (2016). An evaluation of 30 clinical drugs against the comprehensive in vitro proarrhythmia assay (CiPA) proposed ion channel panel. Journal of Pharmacological and Toxicological Methods, 81, 251-262. doi:10.1016/j.vascn.2016.03.009Dutta, S., Chang, K. C., Beattie, K. A., Sheng, J., Tran, P. N., Wu, W. W., … Li, Z. (2017). Optimization of an In silico Cardiac Cell Model for Proarrhythmia Risk Assessment. Frontiers in Physiology, 8. doi:10.3389/fphys.2017.00616Elkins, R. C., Davies, M. R., Brough, S. J., Gavaghan, D. J., Cui, Y., Abi-Gerges, N., & Mirams, G. R. (2013). Variability in high-throughput ion-channel screening data and consequences for cardiac safety assessment. Journal of Pharmacological and Toxicological Methods, 68(1), 112-122. doi:10.1016/j.vascn.2013.04.007Ficker, E., Jarolimek, W., Kiehn, J., Baumann, A., & Brown, A. M. (1998). Molecular Determinants of Dofetilide Block of HERG K
+
Channels. Circulation Research, 82(3), 386-395. doi:10.1161/01.res.82.3.386Grandi, E., Pasqualini, F. S., & Bers, D. M. (2010). A novel computational model of the human ventricular action potential and Ca transient. Journal of Molecular and Cellular Cardiology, 48(1), 112-121. doi:10.1016/j.yjmcc.2009.09.019Guo, D., & Jenkinson, S. (2019). Simultaneous assessment of compound activity on cardiac Nav1.5 peak and late currents in an automated patch clamp platform. Journal of Pharmacological and Toxicological Methods, 99, 106575. doi:10.1016/j.vascn.2019.04.001Hegyi, B., Bányász, T., Izu, L. T., Belardinelli, L., Bers, D. M., & Chen-Izu, Y. (2018). β-adrenergic regulation of late Na+ current during cardiac action potential is mediated by both PKA and CaMKII. Journal of Molecular and Cellular Cardiology, 123, 168-179. doi:10.1016/j.yjmcc.2018.09.006Horne, A. J., Eldstrom, J., Sanatani, S., & Fedida, D. (2011). A novel mechanism for LQT3 with 2:1 block: A pore-lining mutation in Nav1.5 significantly affects voltage-dependence of activation. Heart Rhythm, 8(5), 770-777. doi:10.1016/j.hrthm.2010.12.041Horvath, B., Banyasz, T., Jian, Z., Hegyi, B., Kistamas, K., Nanasi, P. P., … Chen-Izu, Y. (2013). Dynamics of the late Na+ current during cardiac action potential and its contribution to afterdepolarizations. Journal of Molecular and Cellular Cardiology, 64, 59-68. doi:10.1016/j.yjmcc.2013.08.010Horváth, B., Hézső, T., Szentandrássy, N., Kistamás, K., Árpádffy-Lovas, T., Varga, R., … Nánási, P. P. (2020). Late sodium current in human, canine and guinea pig ventricular myocardium. Journal of Molecular and Cellular Cardiology, 139, 14-23. doi:10.1016/j.yjmcc.2019.12.015KAUFMAN, E. S. (2008). Use of Ranolazine in Long-QT Syndrome Type 3. Journal of Cardiovascular Electrophysiology, 19(12), 1294-1295. doi:10.1111/j.1540-8167.2008.01255.xLancaster, M. C., & Sobie, E. (2016). Improved Prediction of Drug-Induced Torsades de Pointes Through Simulations of Dynamics and Machine Learning Algorithms. Clinical Pharmacology & Therapeutics, 100(4), 371-379. doi:10.1002/cpt.367Li, Z., Dutta, S., Sheng, J., Tran, P. N., Wu, W., Chang, K., … Colatsky, T. (2017). Improving the In Silico Assessment of Proarrhythmia Risk by Combining hERG (Human Ether-à-go-go-Related Gene) Channel–Drug Binding Kinetics and Multichannel Pharmacology. Circulation: Arrhythmia and Electrophysiology, 10(2). doi:10.1161/circep.116.004628Liu, H., Atkins, J., & Kass, R. S. (2003). Common Molecular Determinants of Flecainide and Lidocaine Block of Heart Na+ Channels. Journal of General Physiology, 121(3), 199-214. doi:10.1085/jgp.20028723Liu, H., Tateyama, M., Clancy, C. E., Abriel, H., & Kass, R. S. (2002). Channel Openings Are Necessary but not Sufficient for Use-dependent Block of Cardiac Na+ Channels by Flecainide. Journal of General Physiology, 120(1), 39-51. doi:10.1085/jgp.20028558Lu, H. R., Vlaminckx, E., & Gallacher, D. J. (2008). Choice of cardiac tissue in vitro plays an important role in assessing the risk of drug-induced cardiac arrhythmias in human: Beyond QT prolongation. Journal of Pharmacological and Toxicological Methods, 57(1), 1-8. doi:10.1016/j.vascn.2007.06.005Makielski, J. C. (2016). Late sodium current: A mechanism for angina, heart failure, and arrhythmia. Trends in Cardiovascular Medicine, 26(2), 115-122. doi:10.1016/j.tcm.2015.05.006Makita, N., Behr, E., Shimizu, W., Horie, M., Sunami, A., Crotti, L., … Roden, D. M. (2008). The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome. Journal of Clinical Investigation. doi:10.1172/jci34057Maltsev, V. A., Sabbah, H. N., Higgins, R. S. D., Silverman, N., Lesch, M., & Undrovinas, A. I. (1998). Novel, Ultraslow Inactivating Sodium Current in Human Ventricular Cardiomyocytes. Circulation, 98(23), 2545-2552. doi:10.1161/01.cir.98.23.2545Moreno, J. D., & Clancy, C. E. (2012). Pathophysiology of the cardiac late Na current and its potential as a drug target. Journal of Molecular and Cellular Cardiology, 52(3), 608-619. doi:10.1016/j.yjmcc.2011.12.003Moreno, J. D., Lewis, T. J., & Clancy, C. E. (2016). Parameterization for In-Silico Modeling of Ion Channel Interactions with Drugs. PLOS ONE, 11(3), e0150761. doi:10.1371/journal.pone.0150761Moreno, J. D., Yang, P.-C., Bankston, J. R., Grandi, E., Bers, D. M., Kass, R. S., & Clancy, C. E. (2013). Ranolazine for Congenital and Acquired Late I
Na
-Linked Arrhythmias. Circulation Research, 113(7). doi:10.1161/circresaha.113.301971Moreno, J. D., Zhu, Z. I., Yang, P.-C., Bankston, J. R., Jeng, M.-T., Kang, C., … Clancy, C. E. (2011). A Computational Model to Predict the Effects of Class I Anti-Arrhythmic Drugs on Ventricular Rhythms. Science Translational Medicine, 3(98). doi:10.1126/scitranslmed.3002588Moss, A. J., Windle, J. R., Hall, W. J., Zareba, W., Robinson, J. L., McNitt, S., … Manalan, A. S. (2005). Safety and Efficacy of Flecainide in Subjects with Long QT-3 Syndrome (DeltaKPQ Mutation): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Annals of Noninvasive Electrocardiology, 10(s4), 59-66. doi:10.1111/j.1542-474x.2005.00077.xMOSS, A. J., ZAREBA, W., SCHWARZ, K. Q., ROSERO, S., MCNITT, S., & ROBINSON, J. L. (2008). Ranolazine Shortens Repolarization in Patients with Sustained Inward Sodium Current Due to Type-3 Long-QT Syndrome. Journal of Cardiovascular Electrophysiology, 19(12), 1289-1293. doi:10.1111/j.1540-8167.2008.01246.xO’Hara, T., Virág, L., Varró, A., & Rudy, Y. (2011). Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation. PLoS Computational Biology, 7(5), e1002061. doi:10.1371/journal.pcbi.1002061Paul, A. A., Witchel, H. J., & Hancox, J. C. (2002). Inhibition of the current of heterologously expressed HERG potassium channels by flecainide and comparison with quinidine, propafenone and lignocaine. British Journal of Pharmacology, 136(5), 717-729. doi:10.1038/sj.bjp.0704784Penniman, J. R., Kim, D. C., Salata, J. J., & Imredy, J. P. (2010). Assessing use-dependent inhibition of the cardiac Na± current (INa) in the PatchXpress automated patch clamp. Journal of Pharmacological and Toxicological Methods, 62(2), 107-118. doi:10.1016/j.vascn.2010.06.007Postema, P. G., De Jong, J. S. S. G., Van der Bilt, I. A. C., & Wilde, A. A. M. (2008). Accurate electrocardiographic assessment of the QT interval: Teach the tangent. Heart Rhythm, 5(7), 1015-1018. doi:10.1016/j.hrthm.2008.03.037Priori, S. G., Blomström-Lundqvist, C., Mazzanti, A., Blom, N., Borggrefe, M., Camm, J., … Van Veldhuisen, D. J. (2015). 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. European Heart Journal, 36(41), 2793-2867. doi:10.1093/eurheartj/ehv316Rivolta, I., Abriel, H., Tateyama, M., Liu, H., Memmi, M., Vardas, P., … Kass, R. S. (2001). Inherited Brugada and Long QT-3 Syndrome Mutations of a Single Residue of the Cardiac Sodium Channel Confer Distinct Channel and Clinical Phenotypes. Journal of Biological Chemistry, 276(33), 30623-30630. doi:10.1074/jbc.m104471200Romero, L., Cano, J., Gomis-Tena, J., Trenor, B., Sanz, F., Pastor, M., & Saiz, J. (2018). In Silico QT and APD Prolongation Assay for Early Screening of Drug-Induced Proarrhythmic Risk. Journal of Chemical Information and Modeling, 58(4), 867-878. doi:10.1021/acs.jcim.7b00440Romero, L., Trenor, B., Yang, P.-C., Saiz, J., & Clancy, C. E. (2015). In silico screening of the impact of hERG channel kinetic abnormalities on channel block and susceptibility to acquired long QT syndrome. Journal of Molecular and Cellular Cardiology, 87, 271-282. doi:10.1016/j.yjmcc.2015.08.015Rudy, Y., & Silva, J. R. (2006). Computational biology in the study of cardiac ion channels and cell electrophysiology. Quarterly Reviews of Biophysics, 39(1), 57-116. doi:10.1017/s0033583506004227Saint, D. A. (2008). The cardiac persistent sodium current: an appealing therapeutic target? British Journal of Pharmacology, 153(6), 1133-1142. doi:10.1038/sj.bjp.0707492Smallwood, J., Robertson, D., & Steinberg, M. (1989). Electrophysiological effects of flecainide enantiomers in canine Purkinje fibres. Naunyn-Schmiedeberg’s Archives of Pharmacology, 339(6). doi:10.1007/bf00168654Sobie, E. A. (2009). Parameter Sensitivity Analysis in Electrophysiological Models Using Multivariable Regression. Biophysical Journal, 96(4), 1264-1274. doi:10.1016/j.bpj.2008.10.056Soltis, A. R., & Saucerman, J. J. (2010). Synergy between CaMKII Substrates and β-Adrenergic Signaling in Regulation of Cardiac Myocyte Ca2+ Handling. Biophysical Journal, 99(7), 2038-2047. doi:10.1016/j.bpj.2010.08.016Trenor, B., Cardona, K., Gomez, J. F., Rajamani, S., Ferrero, J. M., Belardinelli, L., & Saiz, J. (2012). Simulation and Mechanistic Investigation of the Arrhythmogenic Role of the Late Sodium Current in Human Heart Failure. PLoS ONE, 7(3), e32659. doi:10.1371/journal.pone.0032659Yang, P.-C., DeMarco, K. R., Aghasafari, P., Jeng, M.-T., Dawson, J. R. D., Bekker, S., … Clancy, C. E. (2020). A Computational Pipeline to Predict Cardiotoxicity. Circulation Research, 126(8), 947-964. doi:10.1161/circresaha.119.316404Yang, P.-C., El-Bizri, N., Romero, L., Giles, W. R., Rajamani, S., Belardinelli, L., & Clancy, C. E. (2016). A computational model predicts adjunctive pharmacotherapy for cardiac safety via selective inhibition of the late cardiac Na current. Journal of Molecular and Cellular Cardiology, 99, 151-161. doi:10.1016/j.yjmcc.2016.08.011Yang, P., Moreno, J. D., Miyake, C. Y., Vaughn‐Behrens, S. B., Jeng, M., Grandi, E., … Clancy, C. E. (2015). In silico
prediction of drug therapy in catecholaminergic polymorphic ventricular tachycardia. The Journal of Physiology, 594(3), 567-593. doi:10.1113/jp271282Zhu, W., Mazzanti, A., Voelker, T. L., Hou, P., Moreno, J. D., Angsutararux, P., … Silva, J. R. (2019). Predicting Patient Response to the Antiarrhythmic Mexiletine Based on Genetic Variation. Circulation Research, 124(4), 539-552. doi:10.1161/circresaha.118.31405
Evaluation of serum inflammatory biomarkers as predictors of treatment outcome in pulmonary tuberculosis
Get PDFObjective: To evaluate C-reactive protein (CRP), globulin and white blood cell (WBC) count as predictors of treatment outcome in pulmonary tuberculosis (PTB).Methods: An observational study of patients with active PTB was conducted at a tertiary centre. All patients had serum CRP, globulin and WBC measured at baseline and at 2 months following commencement of treatment. The outcome of interest was requirement for extension of treatment beyond 6 months.Results: There were 226 patients included in the study. Serum globulin 45 g/l was the only baseline biomarker evaluated that independently predicted requirement for treatment extension (OR 3.42, 95%CI 1.597.32, P 0.001). An elevated globulin level that failed to normalise at 2 months was also associated with increased requirement for treatment extension (63.9% vs. 5.1%, P 0.001), and had a low negative likelihood ratio (0.07) for exclusion of requirement for treatment extension. On multivariable analysis, an elevated globulin that failed to normalise at 2 months was independently associated with requirement for treatment extension (OR 6.13, 95%CI 2.2316.80, P 0.001).Conclusions: Serum globulin independently predicts requirement for treatment extension in PTB and outperforms CRP and WBC as a predictive biomarker. Normalisation of globulin at 2 months following treatment commencement is associated with low risk of requirement for treatment extension.</p
Factors associated with reattendance to emergency services following COVID‐19 hospitalization
No full textSafety and Efficacy of Flecainide in Subjects with Long QT‐3 Syndrome (ΔKPQ Mutation): A Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial
No full textМетодика оценки легочной перфузии у пациентов с ранее перенесенной COVID-19 пневмонией: клиническое контролируемое нерандомизированное исследование
Get PDFINTRODUCTION: Evaluating pulmonary lung perfusion in patients with previously treated COVID-19 infection may lead to a better understanding of long-term consequences of the disease, as well as may identify the changes determined by their symptoms. Further research is required for optimization of lung perfusion’s design parameters’ methods in order to implement those in clinical practice.OBJECTIVE: To determine the possibilities of an alternative method for evaluation of relative lung perfusion using three-dimensional ultrafast contrast-enhanced MRI on patients with previously treated COVID-19 pneumonia.MATERIALS AND METHODS: We examined 100 patients (28 male and 72 female, aged 22 to 70) who had laboratory-confirmed COVID-19 infection. The research was conducted using the three-dimensional ultrafast dynamic contrast-enhanced MRI based on 3D T1-weighted images. During the postprocessing, we received the values of rPBF (relative pulmonary blood flow), rPBV (relative pulmonary blood volume), and rMTT (relative mean transit time).Statistics. For non-linear dependence modelling we used natural spline transformation for time and interaction effect with a group. Intergroup comparison on integral measures was based on Kruskall-Wallis test (χ2), pair comparisons were based on Conover’s test (Δ). For multiple hypothesis testing correction, we used the false discovery rate (FDR). Comparisons were determined as statistically significant when p<0.05.RESULTS: The differences in obtained values of lung perfusion among patient groups were confirmed both quantitatively (by rMTT, rPBV, rPBF) and qualitatively (by building the curves of contrast agent accumulation). Patients with previously treated COVID-19 demonstrate slower contrast agent transit and increased relative lung blood volume. Their accumulation curves have qualitative differences as well.DISCUSSION: We suggest a new method of evaluation of lung perfusion indicators in patients with previously treated COVID-19. We conducted an intergroup analysis based on the degree of lung damage during the acute phase of COVID-19 (with no infiltrativechanges, with minor lung damage, and major lung damage). The intergroup differences found are more significant for patients with lung damage (both minor and major) than for patients with no infiltrative lung changes during the acute phase of COVID-19.CONCLUSION: This method of evaluation of pulmonary perfusion is able to adequately characterize the functional lung conditions in patients with previously treated COVID-19 pneumonia. The chosen model is the most optimal.ВВЕДЕНИЕ: Оценка перфузии легких у людей с перенесенным COVID-19 может дать более четкое представление о долгосрочных последствиях болезни и выявить изменения, которые могут обусловливать их симптомы. Необходимы дальнейшие исследования с целью оптимизации методов расчета параметров легочной перфузии для внедрения их в клиническую практику.ЦЕЛЬ: Определить возможности альтернативного способа оценки относительной легочной перфузии с использованием трехмерной сверхбыстрой динамической контрастной магнитно-резонансной томографии у пациентов с ранее перенесенной COVID-19 пневмонией.МАТЕРИАЛЫ И МЕТОДЫ: Проведено обследование 100 пациентов (28 мужчин и 72 женщин в возрасте от 22 до 70 лет), перенесших лабораторно подтвержденный COVID-19, с использованием трехмерной сверхбыстрой динамической контрастной магнитно-резонансной томографии на базе градиентных 3D-Т1-взвешенных изображений. В ходе постпроцессинговой обработки изображений получены значения rPBF (относительная скорость кровотока), rPBV (относительный объем кровотока) и rMTT (относительное среднее время пассажа).Статистика. Для моделирования нелинейной зависимости использовалась натуральная сплайн-трансформация от времени с эффектом взаимодействия с групповой принадлежностью. Межгрупповое сравнение по интегральным показателям осуществлялось критерием Краскела–Уоллиса (χ2), попарные сравнения — критерием Коновера (Δ). Для коррекции множественного тестирования гипотез использовалась средняя доля ложных отклонений (FDR). Статистически значимыми различия признавались при p<0,05.РЕЗУЛЬТАТЫ: Различия показателей легочной перфузии между группами пациентов были подтверждены как количественно по параметрам rMTT, rPBV, rPBF, так и качественно при построении кривых накопления контрастного препарата. У пациентов с перенесенным COVID-19 наблюдается замедление пассажа контрастного препарата и увеличение относительного объема легочной крови, а кривые накопления контрастного препарата имеют качественные отличия.ОБСУЖДЕНИЕ: Предложен новый способ для оценки показателей легочной перфузии у пациентов с перенесенным COVID-19, проведен межгрупповой анализ групп в зависимости от степени поражения легких во время острой фазы COVID-19 (без инфильтративных изменений, с поражением легких легкой и тяжелой степени). Выявленные межгрупповые различия наиболее показательны для групп пациентов с поражением легких (как легкой, так и тяжелой степени) по сравнению с группой пациентов без инфильтративных изменений легких во время острой фазы COVID-19.ЗАКЛЮЧЕНИЕ: Данный способ оценки относительной легочной перфузии способен адекватно охарактеризовать функциональное состояние легких у пациентов с ранее перенесенной COVID-19 пневмонией, а выбранная модель является оптимальной
Abstracts of International Conference on Scholarly Communication, Open-Access Publishing and Ethics
Get PDFAcademic education, research, and development intensify the nation socially and fiscally competitive. Institutions have a greater role to enhance their intellectual infrastructure facilitations to help in the process of building an institutional academic and research culture through means of scholarly communication and publication. This book covers Abstracts of various peer-reviewed papers presented in the International Conference on Scholarly Communication, Open-access Publishing and Ethics (SCOPE-2018) held at SPA Vijayawada during 25 -26 October 2018. Indeed, these papers are divided into four important subject areas viz. academic research and development; scholarly communication; open access publishing, copyright and ethics; and academic library, preservation facilitations
