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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">nogr</journal-id><journal-title-group><journal-title xml:lang="ru">Экспериментальная и клиническая гастроэнтерология</journal-title><trans-title-group xml:lang="en"><trans-title>Experimental and Clinical Gastroenterology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1682-8658</issn><publisher><publisher-name>«Global Media Technologies»</publisher-name></publisher></journal-meta><article-meta><article-id custom-type="elpub" pub-id-type="custom">nogr-637</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>КЛИНИЧЕСКАЯ ГАСТРОЭНТЕРОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>CLINICAL GASTROENTEROLOGY</subject></subj-group></article-categories><title-group><article-title>КАРДИАЛЬНАЯ ДИСФУНКЦИЯ У БОЛЬНЫХ АЛКОГОЛЬНЫМ ЦИРРОЗОМ ПЕЧЕНИ</article-title><trans-title-group xml:lang="en"><trans-title>CARDIAC DYSFUNCTION IN ALCOHOLIC LIVER CIRRHOSIS</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Иванов</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Ivanov</surname><given-names>A. S.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Романова</surname><given-names>В. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Romanova</surname><given-names>V. A.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Колесникова</surname><given-names>И. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kolesnikova</surname><given-names>I. A.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Аришева</surname><given-names>О. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Arisheva</surname><given-names>O. S.</given-names></name></name-alternatives><email xlink:type="simple">Olga.ariheva@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гармаш</surname><given-names>И. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Garmash</surname><given-names>I. V.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кобалава</surname><given-names>Ж. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Kobalava</surname><given-names>Z. D.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Федеральное государственное автономное образовательное учреждение высшего образования «Российский университет дружбы народов»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>“Peoples Friendship University of Russia”</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2018</year></pub-date><pub-date pub-type="epub"><day>20</day><month>06</month><year>2018</year></pub-date><volume>0</volume><issue>6</issue><fpage>52</fpage><lpage>57</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Иванов А.С., Романова В.А., Колесникова И.А., Аришева О.С., Гармаш И.В., Кобалава Ж.Д., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Иванов А.С., Романова В.А., Колесникова И.А., Аришева О.С., Гармаш И.В., Кобалава Ж.Д.</copyright-holder><copyright-holder xml:lang="en">Ivanov A.S., Romanova V.A., Kolesnikova I.A., Arisheva O.S., Garmash I.V., Kobalava Z.D.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.nogr.org/jour/article/view/637">https://www.nogr.org/jour/article/view/637</self-uri><abstract><p>Цель: изучить характер структурно-функциональных изменений сердца у больных в зависимости от тяжести алкогольного цирроза печени. Материалы и методы: Включено 80 пациентов с алкогольным циррозом печени (ЦП) без анамнеза заболеваний сердечно- сосудистой и дыхательной систем (средний возраст 53,1±12 лет), среди которых класс по Чайлд-Пью: А - 12 (14,8%), В - 22 (27,2%) и С - 46 (59,2%) больных. Всем больным выполнялась ЭКГ, эхокардиографическое исследование с оценкой фракции выброса левого желудочка (ФВ ЛЖ), диастолической функции ЛЖ, индекса массы миокарда ЛЖ, у 60 больных определялся уровень NT-proBNP. Результаты: У всех больных фракция выброса ЛЖ была удовлетворительной (65,3±5,8%). У 33 (40,7%) больных выявлена гипертрофия левого желудочка (ГЛЖ) (ИММЛЖ 149,8±20 г/м2). Нарушение диастолической функции ЛЖ наблюдалось у 58 пациентов (71,6%). Среднее значение уровня NT-proBNP у всех больных 621,5 пг/мл (min 33 пг/мл, max 3849 пг/мл), повышение NT-proBNP &gt; 125 пг/мл наблюдалось у 47 (58%) пациентов. Уровень NT-proBNP положительно коррелирует с количеством набранных баллов по Чайлд-Пью (R=0,27, p&lt;0,05) и MELD. Не было выявлено связи между тяжестью цирроза печени и структурно-функциональными. Заключение: У больных алкогольным ЦП наблюдаются структурно-функциональные изменения сердца в виде ГЛЖ, диастолической дисфункции ЛЖ. Более чем у половины больных наблюдалось повышение уровня NT-proBNP, прямо зависящее от тяжести цирроза печени.</p></abstract><trans-abstract xml:lang="en"><p>Objective: To evaluate structural and functional cardiac changes in patients with alcoholic cirrhosis in relation to the severity of liver disease. Methods: Study included 80 patients with alcoholic liver cirrhosis (LC) without history of cardiovascular and respiratory disease. ECG, echocardiography were performed. Plasma values of NT-proBNP were evaluated in 60 patients. Results: Left ventricular ejection fraction was normal in all patients (mean value 65,3 ± 5,8%). Left ventricular hypertrophy (LVH) (LVMI 149,8 ± 20 g/m 2) and LV diastolic dysfunction were observed in 33 (40,7%) and 58 (71,6%) patients, respectively. Median NT-proBNP value was 621,5 pg/ml (min 33 pg/ml; max 3849 pg/ml), NT-proBNP elevation (&gt; 125 pg/ml) was observed in 47 (58%) patients. NT-proBNP level positively correlated with the number of points on the Child-Pugh score (R =0,27, p &lt; 0,05). There was no relationship between the severity of cirrhosis and structural and functional cardiac changes. Conclusion: Patients with alcoholic LC frequently demostrate structural and functional cardiac changes such as left ventricular hypertrophy, diastolic dysfunction. NT-proBNP elevation was observed in more than half of the patients and directly correlated with the severity of cirrhosis.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>алкоголь</kwd><kwd>цирроз печени</kwd><kwd>кардиальная дисфункция</kwd><kwd>ремоделирование сердца</kwd></kwd-group><kwd-group xml:lang="en"><kwd>alcohol</kwd><kwd>liver liver</kwd><kwd>cardiac dysfunction</kwd><kwd>cardiac remodeling</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Klatsky A.L, Friedman G.D, Siegelaub A.B, et al: Alcohol consumption and blood pressure. N Engl J Med 1977; 296:1194-1200</mixed-citation><mixed-citation xml:lang="en">Klatsky A.L, Friedman G.D, Siegelaub A.B, et al: Alcohol consumption and blood pressure. N Engl J Med 1977; 296:1194-1200</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Kowalski H, Abelmann W.H. The cardiac output at rest in Laennec’s cirrhosis. J Clin Invest 1953;32:1025-1033.</mixed-citation><mixed-citation xml:lang="en">Kowalski H, Abelmann W.H. The cardiac output at rest in Laennec’s cirrhosis. J Clin Invest 1953;32:1025-1033.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Moller S, Henriksen J.H. Cardiovascular complications of cirrhosis. Gut 2008;57:268-278.</mixed-citation><mixed-citation xml:lang="en">Moller S, Henriksen J.H. Cardiovascular complications of cirrhosis. Gut 2008;57:268-278.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Sola E, Gines P. Renal and circulatory dysfunction in cirrhosis: current management and future perspectives. J Hepatol. 2010;53:1135-1145.</mixed-citation><mixed-citation xml:lang="en">Sola E, Gines P. Renal and circulatory dysfunction in cirrhosis: current management and future perspectives. J Hepatol. 2010;53:1135-1145.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Martell M, Coll M, Ezkurdia N, Raurell I, Genesca J. Physiopathology of splanchnic vasodilation in portal hypertension. World J Hepatol 2010;2:208-220.</mixed-citation><mixed-citation xml:lang="en">Martell M, Coll M, Ezkurdia N, Raurell I, Genesca J. Physiopathology of splanchnic vasodilation in portal hypertension. World J Hepatol 2010;2:208-220.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Limas C.J, Guiha N.H, Lekagul O, Cohn J.N. Impaired left ventricular function in alcoholic cirrhosis with ascites. Ineffectiveness of ouabain. Circulation 1974;49:754-760.</mixed-citation><mixed-citation xml:lang="en">Limas C.J, Guiha N.H, Lekagul O, Cohn J.N. Impaired left ventricular function in alcoholic cirrhosis with ascites. Ineffectiveness of ouabain. Circulation 1974;49:754-760.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Caramelo C, Fernandez-Munoz D, Santos J.C, Blanchart A, Rodriguez-Puyol D, Lopez-Novoa J.M, Hernando L: Effect of volume expansion expansion on hemodynamics, capillary permeability and renal function in conscious, cirrhotic rats. J Hepatol 1986;6:129-134.</mixed-citation><mixed-citation xml:lang="en">Caramelo C, Fernandez-Munoz D, Santos J.C, Blanchart A, Rodriguez-Puyol D, Lopez-Novoa J.M, Hernando L: Effect of volume expansion expansion on hemodynamics, capillary permeability and renal function in conscious, cirrhotic rats. J Hepatol 1986;6:129-134.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Ingles A.C, Hernandez I, Garcia-Estan J, Quesada T, Carbonell L.F. Limited cardiac preload reserve in conscious cirrhotic rats. Am J Physiol 1991;260: H1912-917.</mixed-citation><mixed-citation xml:lang="en">Ingles A.C, Hernandez I, Garcia-Estan J, Quesada T, Carbonell L.F. Limited cardiac preload reserve in conscious cirrhotic rats. Am J Physiol 1991;260: H1912-917.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Lee S.S, Marty J, Mantz J, Samain E, Braillon A, Lebrec D: Desensitization of myocardial β-adrenergic receptors in cirrhotic rats. J Hepatol 1990;12:481-485.</mixed-citation><mixed-citation xml:lang="en">Lee S.S, Marty J, Mantz J, Samain E, Braillon A, Lebrec D: Desensitization of myocardial β-adrenergic receptors in cirrhotic rats. J Hepatol 1990;12:481-485.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Donovan, C.L., et al. Two dimensional and dobutamine stress echocardiography in the prospective assessment of patients with end stage liver disease prior to orthotopic liver transplantation. Transplantation. 1996;61:1180-1188.</mixed-citation><mixed-citation xml:lang="en">Donovan, C.L., et al. Two dimensional and dobutamine stress echocardiography in the prospective assessment of patients with end stage liver disease prior to orthotopic liver transplantation. Transplantation. 1996;61:1180-1188.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Myers, R.P. and Lee, S.S. (2000) Cirrhotic cardiomyopathy and liver transplantation. Liver Transpl. 2000;6; S44-S52.</mixed-citation><mixed-citation xml:lang="en">Myers, R.P. and Lee, S.S. (2000) Cirrhotic cardiomyopathy and liver transplantation. Liver Transpl. 2000;6; S44-S52.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Therapondos G, Flapan A.D, Plevris J.N, Hayes P.C: Cardiac morbidity and mortality related to orthotopic liver transplantation. Liver Transpl 2004;10:1441-1453.</mixed-citation><mixed-citation xml:lang="en">Therapondos G, Flapan A.D, Plevris J.N, Hayes P.C: Cardiac morbidity and mortality related to orthotopic liver transplantation. Liver Transpl 2004;10:1441-1453.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Castell J, Margarit C, Esteban R, Guardia J, Genesca J: Cardiac alterations in cirrhosis: reversibility after liver transplantation. J Hepatol. 2005;42:68-74.</mixed-citation><mixed-citation xml:lang="en">Castell J, Margarit C, Esteban R, Guardia J, Genesca J: Cardiac alterations in cirrhosis: reversibility after liver transplantation. J Hepatol. 2005;42:68-74.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Fischer D.R, Mathews R.A, Neches W.H, Zuberbuhler J.R: Echocardiographic findings before and after liver transplantation. Am J Cardiol 1985;55:1373-1378.</mixed-citation><mixed-citation xml:lang="en">Fischer D.R, Mathews R.A, Neches W.H, Zuberbuhler J.R: Echocardiographic findings before and after liver transplantation. Am J Cardiol 1985;55:1373-1378.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Glauser F.L: Systemic hemodynamic and cardiac function changes in patients undergoing orthotopic liver transplantation. Chest 1990;98:1210-1215.</mixed-citation><mixed-citation xml:lang="en">Glauser F.L: Systemic hemodynamic and cardiac function changes in patients undergoing orthotopic liver transplantation. Chest 1990;98:1210-1215.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Singal A.K, Kamath P.S. Model for End-stage Liver Disease. J Hepatol. 2013;3(1):50-60.</mixed-citation><mixed-citation xml:lang="en">Singal A.K, Kamath P.S. Model for End-stage Liver Disease. J Hepatol. 2013;3(1):50-60.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Алкогольная болезнь. Поражение внутренних органов. Под редакцией акад. РАМН Моисеева В. С., 2014, 480 с.</mixed-citation><mixed-citation xml:lang="en">Алкогольная болезнь. Поражение внутренних органов. Под редакцией акад. РАМН Моисеева В. С., 2014, 480 с.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Гончаров А. С., Клинико-гемодинамические особенности и иммуновоспалительные изменения у больных хронической сердечной недостаточностью, злоупотребляющих алкоголем. Дисс. На соискание ученой степени кандидата медицинских наук. Москва, 2013, 115 с</mixed-citation><mixed-citation xml:lang="en">Гончаров А. С., Клинико-гемодинамические особенности и иммуновоспалительные изменения у больных хронической сердечной недостаточностью, злоупотребляющих алкоголем. Дисс. На соискание ученой степени кандидата медицинских наук. Москва, 2013, 115 с</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Keller H, Bezjak V, Stegaru B, Buss J, Holm E, Heene D.L. Ventricular function in cirrhosis and portosystemic shunt: a two-dimensional echocardiographic study. J Hepatol. 1988;8:658-662.</mixed-citation><mixed-citation xml:lang="en">Keller H, Bezjak V, Stegaru B, Buss J, Holm E, Heene D.L. Ventricular function in cirrhosis and portosystemic shunt: a two-dimensional echocardiographic study. J Hepatol. 1988;8:658-662.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Ahmed S.S, Howard M, Hove W.t, Leevy C.M, Regan T.J. Cardiac function in alcoholics with cirrhosis: absence of overt cardiomyopathy - myth or fact? J Am Coll Card 1984;3:696-702.</mixed-citation><mixed-citation xml:lang="en">Ahmed S.S, Howard M, Hove W.t, Leevy C.M, Regan T.J. Cardiac function in alcoholics with cirrhosis: absence of overt cardiomyopathy - myth or fact? J Am Coll Card 1984;3:696-702.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Sampaio F, Pimenta J, Bettencourt N, et al. Systolic and diastolic dysfunction in cirrhosis: a tissue-Doppler and speckle tracking echocardiography study. Liver Int. 2013;33:1158-65.</mixed-citation><mixed-citation xml:lang="en">Sampaio F, Pimenta J, Bettencourt N, et al. Systolic and diastolic dysfunction in cirrhosis: a tissue-Doppler and speckle tracking echocardiography study. Liver Int. 2013;33:1158-65.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Nazar A, Guevara M, Sitges M, et al. LEFT ventricular function assessed by echocardiography in cirrhosis: relationship to systemic hemodynamics and renal dysfunction. J Hepatol. 2012;58:51-7.</mixed-citation><mixed-citation xml:lang="en">Nazar A, Guevara M, Sitges M, et al. LEFT ventricular function assessed by echocardiography in cirrhosis: relationship to systemic hemodynamics and renal dysfunction. J Hepatol. 2012;58:51-7.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Wong F, Villamil A, Merli M, Romero G, Angeli P, Caraceni P, Steib C.J, Baik S.K, Spinzi G, Colombato L.A, Salerno F. Prevalence of diastolic dysfunction in cirrhosis and its clinical significance. J Hepatol. 2011;54(Suppl 1): A475-476.</mixed-citation><mixed-citation xml:lang="en">Wong F, Villamil A, Merli M, Romero G, Angeli P, Caraceni P, Steib C.J, Baik S.K, Spinzi G, Colombato L.A, Salerno F. Prevalence of diastolic dysfunction in cirrhosis and its clinical significance. J Hepatol. 2011;54(Suppl 1): A475-476.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Kazankov K, Holland-Fischer P, Andersen N.H, Torp P, Sloth E, Aagaard N.K, Vilstrup H. Resting myocardial dysfunction in cirrhosis quantified by tissue Doppler imaging. Liver Int 2011;31:534-540.</mixed-citation><mixed-citation xml:lang="en">Kazankov K, Holland-Fischer P, Andersen N.H, Torp P, Sloth E, Aagaard N.K, Vilstrup H. Resting myocardial dysfunction in cirrhosis quantified by tissue Doppler imaging. Liver Int 2011;31:534-540.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Lunseth J.H, Olmstead E.G, Abboud F. A study of heart disease in one hundred eight hospitalized patients dying with portal cirrhosis. Arch Intern Med 1958;102:405-413.</mixed-citation><mixed-citation xml:lang="en">Lunseth J.H, Olmstead E.G, Abboud F. A study of heart disease in one hundred eight hospitalized patients dying with portal cirrhosis. Arch Intern Med 1958;102:405-413.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Henriksen J.H, Gøtze J.P, Fuglsang S, Christensen E, Bendtsen F, Møller S. Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease. Gut. 2003;52(10):1511-7.</mixed-citation><mixed-citation xml:lang="en">Henriksen J.H, Gøtze J.P, Fuglsang S, Christensen E, Bendtsen F, Møller S. Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease. Gut. 2003;52(10):1511-7.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
