{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:22:42Z","timestamp":1791411762772,"version":"4.3.3"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100030902","name":"Martin-Luther-Universit\u00e4t Halle-Wittenberg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100030902","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    When retatrutide stimulates the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR), and the glucagon-like peptide-1 receptor (GLP-1R), then 3\u2032,5\u2032cyclic adenosine monophosphate (cAMP) is increased. We tested the hypothesis that retatrutide like the \u03b2-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically driven (1 Hz) left atrial preparations (LA) and exerts positive chronotropic effects (PCE) in isolated spontaneously beating right atrial preparations (RA) from adult CD1 mice. While 100 nM isoprenaline increased FOC, retatrutide (100 nM) failed to increase FOC in LA. In isolated mouse right atrial preparations (RA), retatrutide exerted PCE that were potentiated by 100 nM rolipram but that were antagonized by adomeglivant, a GCGR antagonist. The PCE of retatrutide but not the PCE of isoprenaline were attenuated by H89, an inhibitor of the cAMP-dependent protein kinase (PKA). The PCE of retatrutide were not weakened by the \u03b2-adrenoceptor antagonist propranolol (1 \u00b5M) but were blocked by 1 \u00b5M carbachol, an agonist at M\n                    <jats:sub>2<\/jats:sub>\n                    -cholinoceptor, and this effect was reversed by 1 \u00b5M atropine, a muscarinic receptor antagonist. Likewise, the PCE of retatrutide were blocked by 1 \u00b5M (-)-N\n                    <jats:sup>6<\/jats:sup>\n                    -phenylisopropyladenosine (PIA), an A\n                    <jats:sub>1<\/jats:sub>\n                    -adenosine receptor agonist, and this effect was reversed by 1 \u00b5M DPCPX, an adenosine A\n                    <jats:sub>1<\/jats:sub>\n                    -receptor antagonist. We conclude that retatrutide excites the beating rate in RA via GCGR, signalling via cAMP and PKA. Isoprenaline and retatrutide might increase cAMP in different compartments of the mouse sinus node.\n                  <\/jats:p>","DOI":"10.1007\/s00210-025-04335-0","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T06:33:47Z","timestamp":1749018827000},"page":"17147-17160","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Contractile effects of retatrutide in isolated mouse atrial preparations"],"prefix":"10.1007","volume":"398","author":[{"given":"Joachim","family":"Neumann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Undine","family":"Ahlrep","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Gergs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"4335_CR1","doi-asserted-by":"publisher","unstructured":"Ahlrep U, Neumann J, Hofmann B, Gergs U (2025) Effects of retatrutide in the mouse and human atrium. Naunyn-Schmiedeberg\u2019s Arch Pharmacol 398(Suppl 1):P042. https:\/\/doi.org\/10.1007\/s00210-025-03881-x","DOI":"10.1007\/s00210-025-03881-x"},{"key":"4335_CR2","doi-asserted-by":"publisher","unstructured":"Ali S, Ussher JR, Baggio LL, Kabir MG, Charron MJ, Ilkayeva O, Newgard CB, Drucker DJ (2014) Cardiomyocyte glucagon receptor signaling modulates outcomes in mice with experimental myocardial infarction. Mol Metab 4(2):132\u2013143. https:\/\/doi.org\/10.1016\/j.molmet.2014.11.005","DOI":"10.1016\/j.molmet.2014.11.005"},{"key":"4335_CR3","doi-asserted-by":"publisher","unstructured":"Baggio LL, Ussher JR, McLean BA, Cao X, Kabir MG, Mulvihill EE, Mighiu AS, Zhang H, Ludwig A, Seeley RJ, Heximer SP, Drucker DJ (2017) The autonomic nervous system and cardiac GLP-1 receptors control heart rate in mice. Mol Metab 6(11):1339\u20131349. https:\/\/doi.org\/10.1016\/j.molmet.2017.08.010","DOI":"10.1016\/j.molmet.2017.08.010"},{"key":"4335_CR4","doi-asserted-by":"publisher","unstructured":"Bode D, Pronto JRD, Schiattarella GG, Voigt N (2024) Metabolic remodelling in atrial fibrillation: manifestations, mechanisms and clinical implications. Nat Rev Cardiol 21(10):682\u2013700. https:\/\/doi.org\/10.1038\/s41569-024-01038-6","DOI":"10.1038\/s41569-024-01038-6"},{"key":"4335_CR5","doi-asserted-by":"publisher","unstructured":"Burnstock G (2017) Purinergic signaling in the cardiovascular system. Circ Res 120(1):207\u2013228. https:\/\/doi.org\/10.1161\/CIRCRESAHA.116.309726","DOI":"10.1161\/CIRCRESAHA.116.309726"},{"key":"4335_CR6","doi-asserted-by":"publisher","unstructured":"Coskun T, Urva S, Roell WC, Qu H, Loghin C, Moyers JS, O\u2019Farrell LS, Briere DA, Sloop KW, Thomas MK, Pirro V, Wainscott DB, Willard FS, Abernathy M, Morford L, Du Y, Benson C, Gimeno RE, Haupt A, Milicevic Z (2022) LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metab 34(9):1234-1247.e9. https:\/\/doi.org\/10.1016\/j.cmet.2022.07.013","DOI":"10.1016\/j.cmet.2022.07.013"},{"key":"4335_CR7","doi-asserted-by":"publisher","unstructured":"Cui X, Zhu Y, Zeng L, Zhang M, Uddin A, Gillespie TW, McCullough LE, Zhao S, Torres MA, Wan Y (2025) Pharmacological dissection identifies retatrutide overcomes the therapeutic barrier of obese TNBC treatments through suppressing the interplay between glycosylation and ubiquitylation of YAP. Adv Sci (Weinh) 27:e2407494. https:\/\/doi.org\/10.1002\/advs.202407494","DOI":"10.1002\/advs.202407494"},{"key":"4335_CR8","doi-asserted-by":"crossref","unstructured":"Farah A, Tuttle R (1960) Studies on the pharmacology of glucagon. J Pharmacol Exp Ther 129:49\u201355","DOI":"10.1016\/S0022-3565(25)25785-8"},{"key":"4335_CR9","doi-asserted-by":"publisher","unstructured":"Galindo-Tovar A, Vargas ML, Kaumann AJ (2016) Inhibitors of phosphodiesterases PDE2, PDE3, and PDE4 do not increase the sinoatrial tachycardia of noradrenaline and prostaglandin PGE\u2081 in mice. Naunyn Schmiedeberg\u00b4s Arch Pharmacol 389(2):177\u201386. https:\/\/doi.org\/10.1007\/s00210-015-1178-2","DOI":"10.1007\/s00210-015-1178-2"},{"key":"4335_CR10","doi-asserted-by":"publisher","first-page":"H788","DOI":"10.1152\/ajpheart.00691.2009","volume":"299","author":"U Gergs","year":"2010","unstructured":"Gergs U, Baumann M, B\u00f6ckler A, Buchwalow IB, Ebelt H, Fabritz L, G\u00fcnther S, Hauptmann S, Kirchhof P, Kl\u00f6ckner U, P\u00f6nicke K, R\u00fcckschlo\u00df U, Schmitz W, Schulz N, Werner F, Neumann J (2010) Cardiac overexpression of the human 5-HT4-receptor in mice. Am J Physiol Heart Circ Physio 299:H788\u2013H798","journal-title":"Am J Physiol Heart Circ Physio"},{"key":"4335_CR11","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1124\/jpet.118.255711","volume":"369","author":"U Gergs","year":"2019","unstructured":"Gergs U, Bernhardt G, Buchwalow IB, Edler H, Fr\u00f6ba J, Keller M, Kirchhefer U, K\u00f6hler F, Mi\u00dflinger N, Wache H, Neumann J (2019) Initial characterization of transgenic mice overexpressing human histamine H2 receptors. J Pharmacol Exp Ther 369:129\u2013141","journal-title":"J Pharmacol Exp Ther"},{"key":"4335_CR12","doi-asserted-by":"publisher","unstructured":"Gergs U, Jung F, Buchwalow IB, Hofmann B, Simm A, Treede H, Neumann J (2017) Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human hearts. Am J Physiol Heart Circ Physiol 313(6):H1087\u2013H1097. https:\/\/doi.org\/10.1152\/ajpheart.00350.2017","DOI":"10.1152\/ajpheart.00350.2017"},{"key":"4335_CR13","doi-asserted-by":"publisher","unstructured":"Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators (2022) Retatrutide once weekly for the treatment of obesity. N Engl J Med 387(3):205\u2013216. https:\/\/doi.org\/10.1056\/NEJMoa2206038","DOI":"10.1056\/NEJMoa2206038"},{"key":"4335_CR14","doi-asserted-by":"publisher","unstructured":"Jastreboff AM, Kaplan LM, Fr\u00edas JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML; Retatrutide phase 2 obesity trial investigators (2023) Triple-hormone-receptor agonist retatrutide for obesity - a phase 2 trial. N Engl J Med 389(6):514\u2013526. https:\/\/doi.org\/10.1056\/NEJMoa2301972","DOI":"10.1056\/NEJMoa2301972"},{"key":"4335_CR15","doi-asserted-by":"publisher","unstructured":"Kaumann AJ, Birnbaumer L (1974) Prostaglandin E1 action on sinus pacemaker and adenylyl cyclase in kitten myocardium. Nature 251(5475):515\u2013517. https:\/\/doi.org\/10.1038\/251515a0","DOI":"10.1038\/251515a0"},{"key":"4335_CR16","doi-asserted-by":"publisher","unstructured":"Kuchel O, Buu NT, Hamet P, Larochelle P (1985) Effect of metoclopramide on plasma catecholamine release in essential hypertension. Clin Pharmacol Ther 37(4):372\u2013375. https:\/\/doi.org\/10.1038\/clpt.1985.56","DOI":"10.1038\/clpt.1985.56"},{"key":"4335_CR17","unstructured":"Lewartowski B, Mackiewicz U (2015) The non-neuronal heart\u2019s acetylcholine in health and disease. J Physiol Pharmacol 66(6):773\u2013778\u00a0"},{"key":"4335_CR18","doi-asserted-by":"publisher","unstructured":"Ma J, Hu X, Zhang W, Tao M, Wang M, Lu W (2025) Comparison of the effects of liraglutide, tirzepatide, and retatrutide on diabetic kidney disease in db\/db mice. Endocrine 87(1):159\u2013169. https:\/\/doi.org\/10.1007\/s12020-024-03998-8","DOI":"10.1007\/s12020-024-03998-8"},{"key":"4335_CR19","doi-asserted-by":"publisher","unstructured":"Merino B, Quesada I, Hern\u00e1ndez-Cascales J (2015) Glucagon Increases beating rate but not contractility in rat right atrium. Comparison with Isoproterenol. Plos One 10(7):e0132884. https:\/\/doi.org\/10.1371\/journal.pone.0132884","DOI":"10.1371\/journal.pone.0132884"},{"key":"4335_CR20","unstructured":"National Research Council (2011) Guide for the care and use of laboratory animals: eighth edition. The National Academies Press, Washington, DC. http:\/\/www.nap.edu"},{"key":"4335_CR21","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/sj.bjp.0705012","volume":"138","author":"J Neumann","year":"2003","unstructured":"Neumann J, Boknik P, Matherne GP, Lankford A, Schmitz W (2003) Pertussis toxin sensitive and insensitive effects of adenosine and carbachol in murine atria overexpressing A1-adenosine receptors. Br J Pharmacol 138:209\u2013217","journal-title":"Br J Pharmacol"},{"key":"4335_CR22","doi-asserted-by":"crossref","unstructured":"Neumann J, Hu\u00dfler W, Hofmann B, Gergs U (2023a) Contractile effects of glucagon in atrial preparations from transgenic mice and men. American heart scientific sessions: Philadelphia November 11\u201313, 2023. Circulation 148:A14259","DOI":"10.1161\/circ.148.suppl_1.14259"},{"key":"4335_CR23","doi-asserted-by":"publisher","unstructured":"Neumann J, Hofmann B, Dhein S, Gergs U (2023b) Glucagon and its receptors in the mammalian heart. Int J Mol Sci 24(16):12829. https:\/\/doi.org\/10.3390\/ijms241612829","DOI":"10.3390\/ijms241612829"},{"key":"4335_CR24","doi-asserted-by":"publisher","unstructured":"Neumann J, Azatsian K, H\u00f6hm C, Hofmann B, Gergs U (2023c) Cardiac effects of ephedrine, norephedrine, mescaline and 3,4-methylenedioxymethamphetamine (MDMA) in mouse and human atrial preparations. Naunyn-Schmiedeberg\u00b4s Arch Pharmacol 396:275\u2013287.  https:\/\/doi.org\/10.1007\/s00210-022-02315-2","DOI":"10.1007\/s00210-022-02315-2"},{"key":"4335_CR25","doi-asserted-by":"publisher","unstructured":"Neumann J, Hu\u00dfler W, Hofmann B, Gergs U (2023d) Contractile effects of amphetamine, pseudoephedrine, nor-pseudoephedrine (cathine) and cathinone on atrial preparations of mice and humans. J Cardiovasc Pharmacol 83(3):243\u2013250. https:\/\/doi.org\/10.1097\/FJC.0000000000001536","DOI":"10.1097\/FJC.0000000000001536"},{"key":"4335_CR26","doi-asserted-by":"publisher","unstructured":"Neumann J, Hofmann B, Dhein S, Gergs U (2023e) Cardiac roles of serotonin (5-HT) and 5-HT-receptors in health and disease. Int J Mol Sci 24:4765. https:\/\/doi.org\/10.3390\/ijms24054765","DOI":"10.3390\/ijms24054765"},{"key":"4335_CR27","doi-asserted-by":"publisher","unstructured":"Neumann J, Hadova K, Klimas J, Hofmann B, Gergs U (2024a) Contractile effects of semaglutide in the human atrium. Pharmaceutics 16(9):1139. https:\/\/doi.org\/10.3390\/pharmaceutics16091139","DOI":"10.3390\/pharmaceutics16091139"},{"key":"4335_CR28","first-page":"p199","volume":"01\u201304","author":"J Neumann","year":"2024","unstructured":"Neumann J, Hofmann B, Gergs U (2024b) Positive inotropic effects of glucose-dependent insulinotropic polypeptide in the human atrium. Meeting of Deutsche Physiologische Gesellschaft 19.-21.09.2024 Wien. Abstractbook C 01\u201304:p199-200","journal-title":"Abstractbook C"},{"key":"4335_CR29","doi-asserted-by":"crossref","unstructured":"Neumann J, Schmidt F, Hofmann B, Gergs U (2025) Glucagon can increase force of contraction via glucagon receptors in the isolated human atrium. Int J Mol Sci 26:698","DOI":"10.3390\/ijms26020698"},{"key":"4335_CR30","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1038\/sj.bjp.0702963","volume":"128","author":"J Neumann","year":"1999","unstructured":"Neumann J, Vahlensieck U, Boknik P, Linck B, L\u00fcss H, M\u00fcller FU, Matherne GP, Schmitz W (1999) Functional studies in atrium overexpressing A1-adenosine receptors. Br J Pharmacol 128:1623\u20131629","journal-title":"Br J Pharmacol"},{"key":"4335_CR31","doi-asserted-by":"publisher","unstructured":"Ryan DH (2022) Drugs for treating obesity. Handb Exp Pharmacol 274:387\u2013414. https:\/\/doi.org\/10.1007\/164_2021_560","DOI":"10.1007\/164_2021_560"},{"key":"4335_CR32","doi-asserted-by":"publisher","unstructured":"Schmidt F, Neumann J, Kirchhefer U, Gergs U (2024) Contractile effects of glucagon in mouse atrial preparations. Naunyn-Schmiedeberg\u2019s Arch Pharmacol 397(Suppl 1):S34. https:\/\/doi.org\/10.1007\/s00210-024-02974-3","DOI":"10.1007\/s00210-024-02974-3"},{"key":"4335_CR33","doi-asserted-by":"publisher","unstructured":"Schwarz R, Hofmann B, Gergs U, Neumann J (2023) Cantharidin and sodium fluoride attenuate the negative inotropic effects of carbachol in the isolated human atrium. Naunyn-Schmiedeberg\u2019s Arch Pharmacol. https:\/\/doi.org\/10.1007\/s00210-023-02747-4","DOI":"10.1007\/s00210-023-02747-4"},{"key":"4335_CR34","doi-asserted-by":"publisher","unstructured":"Schwarz R, Hofmann B, Gergs U, Neumann J (2024) Cantharidin and sodium fluoride attenuate the negative inotropic effects of the adenosine A1 receptor agonist N6-(R)-phenylisopropyladenosine in isolated human atria. Naunyn-Schmiedeberg\u2019s Arch Pharmacol. https:\/\/doi.org\/10.1007\/s00210-024-03402-2","DOI":"10.1007\/s00210-024-03402-2"},{"key":"4335_CR35","doi-asserted-by":"publisher","unstructured":"Schwarz R, Hofmann B, Gergs U, Neumann J (2025) Inhibition of protein phosphatases attenuates A1-adenosine receptor-stimulation induced negative inotropic effects of cAMP-increasing agents in the isolated human atrium. Naunyn-Schmiedeberg\u00b4s Arch Pharmacol.  https:\/\/doi.org\/10.1007\/s00210-025-03854-0. Online ahead of print","DOI":"10.1007\/s00210-025-03854-0"},{"key":"4335_CR36","doi-asserted-by":"publisher","unstructured":"Stemmer P, Akera T (1986) Concealed positive force-frequency relationships in rat and mouse cardiac muscle revealed by ryanodine. Am J Physiol 251(6 Pt 2):H1106\u2013H1110. https:\/\/doi.org\/10.1152\/ajpheart.1986.251.6.H1106","DOI":"10.1152\/ajpheart.1986.251.6.H1106"},{"key":"4335_CR37","unstructured":"Surapaneni P, Vinales KL, Najib MQ, Chaliki HP (2011) Valvular heart disease with the use of fenfluramine-phentermine. Tex Heart Inst J 38(5):581\u20133"},{"key":"4335_CR38","doi-asserted-by":"publisher","unstructured":"Tamargo J, Caballero R, Delp\u00f3n E (2012) Drug-induced atrial fibrillation. Expert Opin Drug Saf 11(4):615\u2013634. https:\/\/doi.org\/10.1517\/14740338.2012.698609","DOI":"10.1517\/14740338.2012.698609"},{"key":"4335_CR39","doi-asserted-by":"publisher","unstructured":"Ussher JR, Campbell JE, Mulvihill EE, Baggio LL, Bates HE, McLean BA, Gopal K, Capozzi M, Yusta B, Cao X, Ali S, Kim M, Kabir MG, Seino Y, Suzuki J, Drucker DJ (2018) Inactivation of the glucose-dependent insulinotropic polypeptide receptor improves outcomes following experimental myocardial infarction. Cell Metab 27(2):450\u2013460.e6. https:\/\/doi.org\/10.1016\/j.cmet.2017.11.003","DOI":"10.1016\/j.cmet.2017.11.003"},{"key":"4335_CR40","doi-asserted-by":"publisher","unstructured":"Wallner M, Kolesnik E, Ablasser K, Khafaga M, Wakula P, Ljubojevic S, Thon-Gutschi EM, Sourij H, Kapl M, Edmunds NJ, Kuzmiski JB, Griffith DA, Knez I, Pieske B, von Lewinski D (2015) Exenatide exerts a PKA-dependent positive inotropic effect in human atrial myocardium: GLP-1R mediated effects in human myocardium. J Mol Cell Cardiol 89(Pt B):365\u2013375. https:\/\/doi.org\/10.1016\/j.yjmcc.2015.09.018","DOI":"10.1016\/j.yjmcc.2015.09.018"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04335-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-025-04335-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04335-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T04:29:19Z","timestamp":1764822559000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-025-04335-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,4]]},"references-count":40,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["4335"],"URL":"https:\/\/doi.org\/10.1007\/s00210-025-04335-0","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,4]]},"assertion":[{"value":"31 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Animals\n                      : The investigation conformed to the Guide for the Care and Use of Laboratory Animals as published by the National Research Council (\n                      \n                      ). The animals were handled and maintained according to the approved protocols of the Animal Welfare Committee of the University of Halle-Wittenberg, Halle, Germany (permission TS 10\u201324).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed written consent was obtained from all patients included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors declare that they have seen and approved the submitted version of this manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}