asurgeryАмбулаторная хирургияAmbulatornaya khirurgiya = Ambulatory Surgery (Russia)2712-87412782-2591ООО «ГРУППА РЕМЕДИУМ»10.21518/akh2024-002asurgery-423Research ArticleФЛЕБОЛОГИЯPHLEBOLOGYВозможные осложнения, обусловленные применением цианоакрилатного клея у пациентов с варикозной болезньюPossible complications associated with the use of cyanoacrylate obliteration in patients with varicose veinshttps://orcid.org/0000-0003-4488-9123БолдинБ. В.BoldinB. V.

Болдин Борис Валентинович - д.м.н., профессор, заведующий кафедрой факультетской хирургии № 2.

117997, Москва, ул. Островитянова, д. 1

Boris V. Boldin - Dr. Sci. (Med.), Professor, Head of the Department of Faculty Surgery No.2.

1, Ostrovityanov St., Moscow, 117997

facultysurgery@gmail.comhttps://orcid.org/0000-0002-3940-0787БогачевВ. Ю.BogachevV. Yu.

Богачев Вадим Юрьевич - д.м.н., профессор кафедры факультетской хирургии №2.

117997, Москва, ул. Островитянова, д. 1

Vadim Yu. Bogachev - Dr. Sci. (Med.), Professor of the Department of Faculty Surgery No.2.

1, Ostrovityanov St., Moscow, 117997

vadim.bogachev63@gmail.comРодионовС. В.RodionovS. V.

Родионов Сергей Васильевич - д.м.н., профессор кафедры факультетской хирургии №2.

117997, Москва, ул. Островитянова, д. 1

Sergey V. Rodionov - Dr. Sci. (Med.), Professor of the Department of Faculty Surgery No.2.

1, Ostrovityanov St., Moscow, 117997

rodionov.51@mail.ruhttps://orcid.org/0000-0002-6262-4770ТуркинП. Ю.TurkinP. Yu.

Туркин Павел Юрьевич - к.м.н., доцент кафедры факультетской хирургии №2, РНИМУ имени Н.И. Пирогова; врач-хирург операционного блока, ЦКБ Святителя Алексия Митрополита Московского.

117997, Москва, ул. Островитянова, д. 1; 119071, Москва, Ленинский проспект, д. 27

Pavel Yu. Turkin - Cand. Sci. (Med.), Associate Professor of the Department of Faculty Surgery No.2, Pirogov RNRMU; Doctor-Surgeon of the Operating Unit, CCH of the Moscow Patriarchate of St Alexy.

1, Ostrovityanov St., Moscow, 117997; 27, Leninsky Ave., Moscow, 119071

pavelturkin@gmail.comhttps://orcid.org/0009-0003-8165-7230СлесареваА. А.SlesarevaA. A.

Слесарева Анна Андреевна - ассистент кафедры факультетской хирургии №2.

117997, Москва, ул. Островитянова, д. 1

Anna A. Slesareva - Аssistant of the Department of Faculty Surgery No.2

1, Ostrovityanov St., Moscow, 117997

byann_lin@mail.ruhttps://orcid.org/0000-0002-6976-7678ГолосницкийП. Ю.GolosnitskiyP. Yu.

Голосницкий Павел Юрьевич - к.м.н., доцент кафедры факультетской хирургии №2, РНИМУ имени Н.И. Пирогова; руководитель центра сосудистой хирургии, ЦКБ Святителя Алексия Митрополита Московского.

117997, Москва, ул. Островитянова, д. 1; 119071, Москва, Ленинский проспект, д. 27

Pavel Yu. Golosnitskiy - Cand. Sci. (Med.), Associate Professor of the Department of Faculty Surgery No.2, Pirogov RNRMU; Head of the Vascular Surgery Center, CCH of the Moscow Patriarchate of St Alexy.

1, Ostrovityanov St., Moscow, 117997; 27, Leninsky Ave., Moscow, 119071

hirurg1978@mail.ruhttps://orcid.org/0000-0003-4298-950XДизенгофИ. М.DizengofI. M.

Дизенгоф Игорь Михайлович - к.м.н., ассистент кафедры факультетской хирургии №2, РНИМУ имени Н.И. Пирогова; заместитель главного врача по хирургии, ЦКБ Святителя Алексия Митрополита Московского.

117997, Москва, ул. Островитянова, д. 1; 119071, Москва, Ленинский проспект, д. 27

Igor M. Dizengof - Cand. Sci. (Med.), Аssistant of the Department of Faculty Surgery No.2, Pirogov RNRMU; Deputy Chief Physician for Surgery, CCH of the Moscow Patriarchate of St Alexy.

1, Ostrovityanov St., Moscow, 117997; 27, Leninsky Ave., Moscow, 119071

idizengof@yandex.ruhttps://orcid.org/0000-0002-3574-6190ВаричГ. А.VarichG. A.

Варич Георгий Александрович - к.м.н., доцент кафедры факультетской хирургии №2, РНИМУ имени Н.И. Пирогова; заместитель главного врача по хирургии, Химкинская ОБ.

117997, Москва, ул. Островитянова, д. 1; 141407, Московская обл., Химки, Куркинское шоссе, д. 11

George A. Varich - Cand. Sci. (Med.), Associate Professor of the Department of Faculty Surgery No.2, Pirogov RNRMU; Deputy Chief Physician for Surgery, Khimki RH.

1, Ostrovityanov St., Moscow, 117997; 11, Kurkinskoe Shosse, Khimki, Moscow Region, 141407

geravarich@mail.ruРоссийский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияPirogov Russian National Research Medical UniversityRussian FederationРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова; Центральная клиническая больница Святителя Алексия Митрополита МосковскогоРоссияPirogov Russian National Research Medical University; Central Clinical Hospital of the Moscow Patriarchate of St. AlexyRussian FederationРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова; Химкинская областная больницаРоссияPirogov Russian National Research Medical University; Khimki Regional HospitalRussian Federation2024170520242114854Copyright © Болдин Б.В., Богачев В.Ю., Родионов С.В., Туркин П.Ю., Слесарева А.А., Голосницкий П.Ю., Дизенгоф И.М., Варич Г.А., 20242024Болдин Б.В., Богачев В.Ю., Родионов С.В., Туркин П.Ю., Слесарева А.А., Голосницкий П.Ю., Дизенгоф И.М., Варич Г.А.Boldin B.V., Bogachev V.Y., Rodionov S.V., Turkin P.Y., Slesareva A.A., Golosnitskiy P.Y., Dizengof I.M., Varich G.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.a-surgeon.ru/jour/article/view/423

Проблема поиска идеального метода ликвидации вертикального венозного рефлюкса при варикозной болезни нижних конечностей крайне актуальна ввиду стремительного развития технологий и появления новых способов лечения, в т. ч. мини-инвазивных. По мнению многих исследователей, главными параметрами выбора оптимальной оперативной методики должны быть низкая травматичность, соответствие анатомической, в т. ч. ультразвуковой, картине, возможность использования местных анестезиологических пособий, учет сопутствующей патологии и индивидуальной непереносимости пациентом различных препаратов, эффективность облитерации венозного сосуда, минимальный риск возможных осложнений. В обзоре рассматривается сравнительная характеристика эндовазальных методов лечения варикозной болезни, а также перечислены основные возможные осложнения каждого из них. С точки зрения эффективности облитерации и наименьшей выраженности осложнений лидирующую позицию занимает метод цианоакрилатной облитерации. В литературе появляется все больше информации об использовании цианоакрилатного композита в лечении варикозной болезни нижних конечностей. Так как этот метод является относительно новым, увеличивается количество публикаций, посвященных осложнениям данной процедуры. Мы описываем ряд специфичных нежелательных явлений, возникающих при проведении этой операции (экстравазация цианоакрилатного композита с образованием асептических гранулем и в ряде случаев их инфицированием, флебитоподобные явления, формирование ригидных подкожных тяжей, ограничивающих подвижность в коленном суставе, миграция цианоакрилата в систему глубоких вен нижних конечностей), возможные механизмы их возникновения и различные подходы к лечению. Особое внимание уделяется проксимальной миграции цианоакрилатного композита в область сафено-феморального соустья с описанием конкретного клинического случая и обсуждением дальнейшей тактики ведения данной категории пациентов.

The problem of finding an ideal method for the correction of vertical venous reflux in lower extremity varicose disease is highly relevant due to the rapid development of technologies and the opening of new treatment methods, including minimally invasive ones. According to many researchers, the main parameters for choosing the optimal surgical technique should be low invasiveness, compliance with the anatomical, including ultrasound, picture, the possibility of using local anesthesia, taking into account concomitant pathology and individual intolerance of various drugs by patients, effectiveness of venous vessel obliteration, and minimal risk of possible complications. The review considers a comparative characterization of endovascular treatment methods for varicose disease, as well as lists the main possible complications of each of them. In terms of obliteration effectiveness and the least pronounced complications, the leading position is occupied by the method of cyanoacrylate obliteration. There is an increasing amount of information in the literature about the use of cyanoacrylate composite in the treatment of lower extremity varicose disease. Since this method is relatively new, the number of publications describing complications of this procedure is increasing. We describe a number of specific adverse events that occur during this surgery (extravasation of cyanoacrylate composite with the formation of aseptic granulomas and, in some cases, phlebitis-like phenomena, formation of rigid subcutaneous bands limiting mobility in the knee joint, migration of cyanoacrylate into the deep venous system of the lower extremities), possible mechanisms of their occurrence, and various approaches to treatment. Special attention is paid to proximal migration of cyanoacrylate composite into the area of the saphenofemoral junction, with a description of a specific clinical case and a discussion of further management tactics for this category of patients.

варикозная болезнь нижних конечностеймини-инвазивные методыцианоакрилатная облитерацияпроксимальная миграция цианоакрилатного композитаосложненияvaricose disease of the lower extremitiesminimally invasive methodscyanoacrylate obliterationproximal migration of the cyanoacrylate compositecomplicationsReferencesGalanopoulos G, Lambidis C. Minimally invasive treatment of varicose veins: Endovenous laser ablation (EVLA). Int J Surg. 2012;10(3):134–139. https://doi.org/10.1016/j.ijsu.2012.02.013.Galanopoulos G, Lambidis C. Minimally invasive treatment of varicose veins: Endovenous laser ablation (EVLA). Int J Surg. 2012;10(3):134–139. https://doi.org/10.1016/j.ijsu.2012.02.013.Gao RD, Qian SY, Wang HH, Liu YS, Ren SY. Strategies and challenges in treatment of varicose veins and venous insufficiency. World J Clin Cases. 2022;10(18):5946–5956. https://doi.org/10.12998/wjcc.v10.i18.5946.Gao RD, Qian SY, Wang HH, Liu YS, Ren SY. Strategies and challenges in treatment of varicose veins and venous insufficiency. World J Clin Cases. 2022;10(18):5946–5956. https://doi.org/10.12998/wjcc.v10.i18.5946.Kolluri R, Chung J, Kim S, Nath N, Bhalla BB, Jain T et al. Network meta-analysis to compare VenaSeal with other superficial venous therapies for chronic venous insufficiency. J Vasc Surg Venous Lymphat Disord. 2020;8(3):472–481.e3. https://doi.org/10.1016/j.jvsv.2019.12.061.Kolluri R, Chung J, Kim S, Nath N, Bhalla BB, Jain T et al. Network meta-analysis to compare VenaSeal with other superficial venous therapies for chronic venous insufficiency. J Vasc Surg Venous Lymphat Disord. 2020;8(3):472–481.e3. https://doi.org/10.1016/j.jvsv.2019.12.061.Lim C, Hsu J, Vo T, Behseresht J, Tayyarah M, Andacheh I. A Comparison of Venaseal Versus Radiofrequency Ablation Outcomes Within a Managed Care Organization. Ann Vasc Surg. 2024;99:75–81. https://doi.org/10.1016/j.avsg.2023.09.088.Lim C, Hsu J, Vo T, Behseresht J, Tayyarah M, Andacheh I. A Comparison of Venaseal Versus Radiofrequency Ablation Outcomes Within a Managed Care Organization. Ann Vasc Surg. 2024;99:75–81. https://doi.org/10.1016/j.avsg.2023.09.088.Ширинбек О, Мнацаканян ГВ, Одинокова СН. Цианоакрилатная клеевая облитерация варикозных вен в реальной клинической практике: двухлетние результаты лечения. Амбулаторная хирургия. 2022;19(1):132–139. https://doi.org/10.21518/1995-1477-2022-19-1-132-139.Shirinbek O, Mnatsakanyan GV, Odinokova SN. Cyanoacrylate Adhesive Closure in the Real-World Practice: 2-Year Results of Varicose Vein Treatment. Ambulatornaya Khirurgiya. 2022;19(1):132–139. (In Russ.) https://doi.org/10.21518/1995-1477-2022-19-1-132-139.Hamann SAS, Giang J, De Maeseneer MGR, Nijsten TEC, van den Bos RR. Editor’s choice – five year results of great saphenous vein treatment: a meta-analysis. Eur J Vasc Endovasc Surg. 2017;54(06):760–770. https://doi.org/10.1016/j.ejvs.2017.08.034.Hamann SAS, Giang J, De Maeseneer MGR, Nijsten TEC, van den Bos RR. Editor’s choice – five year results of great saphenous vein treatment: a meta-analysis. Eur J Vasc Endovasc Surg. 2017;54(06):760–770. https://doi.org/10.1016/j.ejvs.2017.08.034.O’Banion LAA, Siada S, Cutler B, Kochubey M, Collins T, Ali A, Tenet M et al. Thrombotic complications after radiofrequency and cyanoacrylate endovenous ablation: Outcomes of a multicenter real-world experience. J Vasc Surg Venous Lymphat Disord. 2022;10(6):1221–1228. https://doi.org/10.1016/j.jvsv.2022.05.009.O’Banion LAA, Siada S, Cutler B, Kochubey M, Collins T, Ali A, Tenet M et al. Thrombotic complications after radiofrequency and cyanoacrylate endovenous ablation: Outcomes of a multicenter real-world experience. J Vasc Surg Venous Lymphat Disord. 2022;10(6):1221–1228. https://doi.org/10.1016/j.jvsv.2022.05.009.Chan SSJ, Yap CJQ, Tan SG, Choke ETC, Chong TT, Tang TY. The utility of endovenous cyanoacrylate glue ablation for incompetent saphenous veins in the setting of venous leg ulcers. J Vasc Surg Venous Lymphat Disord. 2020;8(6):1041–1048. https://doi.org/10.1016/j.jvsv.2020.01.013.Chan SSJ, Yap CJQ, Tan SG, Choke ETC, Chong TT, Tang TY. The utility of endovenous cyanoacrylate glue ablation for incompetent saphenous veins in the setting of venous leg ulcers. J Vasc Surg Venous Lymphat Disord. 2020;8(6):1041–1048. https://doi.org/10.1016/j.jvsv.2020.01.013.Proebstle TM, Alm J, Dimitri S, Rasmussen L, Whiteley M, Lawson J et al. The European multicenter cohort study on cyanoacrylate embolization of refluxing great saphenous veins. J Vasc Surg Venous Lymphat Disord. 2015;3(1):2–7. https://doi.org/10.1016/j.jvsv.2014.09.001.Proebstle TM, Alm J, Dimitri S, Rasmussen L, Whiteley M, Lawson J et al. The European multicenter cohort study on cyanoacrylate embolization of refluxing great saphenous veins. J Vasc Surg Venous Lymphat Disord. 2015;3(1):2–7. https://doi.org/10.1016/j.jvsv.2014.09.001.Joh JH, Lee T, Byun SJ, Cho S, Park HS, Yun WS et al. A multicenter randomized controlled trial of cyanoacrylate closure and surgical stripping for incompetent great saphenous veins. J Vasc Surg Venous Lymphat Disord. 2022;10(2):353–359. https://doi.org/10.1016/j.jvsv.2021.08.012.Joh JH, Lee T, Byun SJ, Cho S, Park HS, Yun WS et al. A multicenter randomized controlled trial of cyanoacrylate closure and surgical stripping for incompetent great saphenous veins. J Vasc Surg Venous Lymphat Disord. 2022;10(2):353–359. https://doi.org/10.1016/j.jvsv.2021.08.012.Langridge BJ, Onida S, Weir J, Moore H, Lane TR, Davies AH. Cyanoacrylate glue embolisation for varicose veins – a novel complication. Phlebology. 2020;35(7):520–523. https://doi.org/10.1177/0268355520901662.Langridge BJ, Onida S, Weir J, Moore H, Lane TR, Davies AH. Cyanoacrylate glue embolisation for varicose veins – a novel complication. Phlebology. 2020;35(7):520–523. https://doi.org/10.1177/0268355520901662.Almeida JI, Min RJ, Raabe R, McLean DJ, Madsen M. Cyanoacrylate adhesive for the closure of truncal veins. Vasc Endovascular Surg. 2011;45(7):631–635. https://doi.org/10.1177/1538574411413938.Almeida JI, Min RJ, Raabe R, McLean DJ, Madsen M. Cyanoacrylate adhesive for the closure of truncal veins. Vasc Endovascular Surg. 2011;45(7):631–635. https://doi.org/10.1177/1538574411413938.Gracé J, Connor D, Bester L, Rogan C, Parsi K. Polymerisation of cyanoacrylates: The effect of sclero-embolic and contrast agents. Phlebology. 2024;39(2):114–124. https://doi.org/10.1177/02683555231214343.Gracé J, Connor D, Bester L, Rogan C, Parsi K. Polymerisation of cyanoacrylates: The effect of sclero-embolic and contrast agents. Phlebology. 2024;39(2):114–124. https://doi.org/10.1177/02683555231214343.Parsi K, Kang M, Yang A, Kossard S. Granuloma formation following cyanoacrylate glue injection in peripheral veins and arteriovenous malformation. Phlebology. 2020;35(2):115–123. https://doi.org/10.1177/0268355519856756.Parsi K, Kang M, Yang A, Kossard S. Granuloma formation following cyanoacrylate glue injection in peripheral veins and arteriovenous malformation. Phlebology. 2020;35(2):115–123. https://doi.org/10.1177/0268355519856756.Lew PS, Tan YK, Chong TT, Tang TY. VenasealTM cyanoacrylate glue rejection following endovenous ablation – another new complication. Biomed J Sci Tech Res. 2019;17:12993–12994. https://doi.org/10.26717/BJSTR.2019.17.003040.Lew PS, Tan YK, Chong TT, Tang TY. VenasealTM cyanoacrylate glue rejection following endovenous ablation – another new complication. Biomed J Sci Tech Res. 2019;17:12993–12994. https://doi.org/10.26717/BJSTR.2019.17.003040.Chan YC, Cheung GC, Ting AC, Cheng SW. Modification of protocol with one extra drop of endovascular cyanoacrylate improved closure rates in incompetent great saphenous veins. Phlebology. 2022;37(6):425–431. https://doi.org/10.1177/02683555221082358.Chan YC, Cheung GC, Ting AC, Cheng SW. Modification of protocol with one extra drop of endovascular cyanoacrylate improved closure rates in incompetent great saphenous veins. Phlebology. 2022;37(6):425–431. https://doi.org/10.1177/02683555221082358.Tang TY, Tiwari A. The VenaSeal™ abnormal red skin reaction: Looks like but is not phlebitis! Eur J Vasc Endovasc Surg. 2018;55:841. https://doi.org/10.1016/j.ejvs.2018.02.003.Tang TY, Tiwari A. The VenaSeal™ abnormal red skin reaction: Looks like but is not phlebitis! Eur J Vasc Endovasc Surg. 2018;55:841. https://doi.org/10.1016/j.ejvs.2018.02.003.Hirsch T. Non-thermal endovenous treatment: acrylate adhesion of varicose saphenous veins. Phlebologie. 2017;46:143–147. https://doi.org/10.12687/phleb2363-3-2017.Hirsch T. Non-thermal endovenous treatment: acrylate adhesion of varicose saphenous veins. Phlebologie. 2017;46:143–147. https://doi.org/10.12687/phleb2363-3-2017.Park I, Jeong MH, Park CJ, Park WI, Park DW, Joh JH. Clinical Features and Management of “Phlebitis-like Abnormal Reaction” After Cyanoacrylate Closure for the Treatment of Incompetent Saphenous Veins. Ann Vasc Surg. 2019;55:239–245. https://doi.org/10.1016/j.avsg.2018.07.040.Park I, Jeong MH, Park CJ, Park WI, Park DW, Joh JH. Clinical Features and Management of “Phlebitis-like Abnormal Reaction” After Cyanoacrylate Closure for the Treatment of Incompetent Saphenous Veins. Ann Vasc Surg. 2019;55:239–245. https://doi.org/10.1016/j.avsg.2018.07.040.Gibson K, Minjarez R, Rinehardt E, Ferris B. Frequency and severity of hypersensitivity reactions in patients after VenaSeal™ cyanoacrylate treatment of superficial venous insufficiency. Phlebology. 2020;35(5):337–344. https://doi.org/10.1177/0268355519878618.Gibson K, Minjarez R, Rinehardt E, Ferris B. Frequency and severity of hypersensitivity reactions in patients after VenaSeal™ cyanoacrylate treatment of superficial venous insufficiency. Phlebology. 2020;35(5):337–344. https://doi.org/10.1177/0268355519878618.Sumarli SA, Lee QWS, Yap HY, Tay HTL, Chong TT, Tang TY. Exit site complications following cyanoacrylate glue endovenous ablation of incompetent truncal veins for chronic venous insufficiency. J Vasc Surg Cases Innov Tech. 2020;6(4):500–504. https://doi.org/10.1016/j.jvscit.2020.08.010.Sumarli SA, Lee QWS, Yap HY, Tay HTL, Chong TT, Tang TY. Exit site complications following cyanoacrylate glue endovenous ablation of incompetent truncal veins for chronic venous insufficiency. J Vasc Surg Cases Innov Tech. 2020;6(4):500–504. https://doi.org/10.1016/j.jvscit.2020.08.010.Athavale A, Thao M, Sassaki VS, Lewis M, Chandra V, Fukaya E. Cyanoacrylate glue reactions: A systematic review, cases, and proposed mechanisms. J Vasc Surg Venous Lymphat Disord. 2023;11(4):876–888.e1. https://doi.org/10.1016/j.jvsv.2023.03.018.Athavale A, Thao M, Sassaki VS, Lewis M, Chandra V, Fukaya E. Cyanoacrylate glue reactions: A systematic review, cases, and proposed mechanisms. J Vasc Surg Venous Lymphat Disord. 2023;11(4):876–888.e1. https://doi.org/10.1016/j.jvsv.2023.03.018.Tang TY, Rathnaweera HP, Kam JW, Chong TT, Choke EC, Tan YK. Endovenous cyanoacrylate glue to treat varicose veins and chronic venous insufficiency – experience gained from our first 100+ truncal venous ablations in a multi-ethnic Asian population using the Medtronic VenaSeal™ Closure System. Phlebology. 2019;34:543–551. https://doi.org/10.1177/0268355519826008.Tang TY, Rathnaweera HP, Kam JW, Chong TT, Choke EC, Tan YK. Endovenous cyanoacrylate glue to treat varicose veins and chronic venous insufficiency – experience gained from our first 100+ truncal venous ablations in a multi-ethnic Asian population using the Medtronic VenaSeal™ Closure System. Phlebology. 2019;34:543–551. https://doi.org/10.1177/0268355519826008.Chan SSJ, Chan YC, Walsh SR, Chong TT, Choke ETC, Tiwari A, Tang TY. Endovenous cyanoacrylate ablation for chronic venous insufficiency and varicose veins among Asians. Ann Acad Med Singap. 2021;50(3):241–249. https://doi.org/10.47102/annals-acadmedsg.2020346.Chan SSJ, Chan YC, Walsh SR, Chong TT, Choke ETC, Tiwari A, Tang TY. Endovenous cyanoacrylate ablation for chronic venous insufficiency and varicose veins among Asians. Ann Acad Med Singap. 2021;50(3):241–249. https://doi.org/10.47102/annals-acadmedsg.2020346.Eysenbach LM, Koo KSH, Monroe EJ, Reis J, Perkins JA, Shivaram GM. Migration of n-BCA glue as a complication of venous malformation treatment in children. Radiol Case Rep. 2021;16(11):3526–3533. https://doi.org/10.1016/j.radcr.2021.07.065.Eysenbach LM, Koo KSH, Monroe EJ, Reis J, Perkins JA, Shivaram GM. Migration of n-BCA glue as a complication of venous malformation treatment in children. Radiol Case Rep. 2021;16(11):3526–3533. https://doi.org/10.1016/j.radcr.2021.07.065.

The authors declare that there are no conflicts of interest present.