{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T12:20:02Z","timestamp":1764937202991,"version":"3.37.3"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T00:00:00Z","timestamp":1599523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T00:00:00Z","timestamp":1599523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2016YFC1300504"],"award-info":[{"award-number":["2016YFC1300504"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81622017","81601017"],"award-info":[{"award-number":["81622017","81601017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science Technology Department of Zhejiang Province","award":["2018C04011"],"award-info":[{"award-number":["2018C04011"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl. Stroke Res."],"published-print":{"date-parts":[[2021,8]]},"DOI":"10.1007\/s12975-020-00846-5","type":"journal-article","created":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T23:09:57Z","timestamp":1599520197000},"page":"530-539","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Iodinated Contrast Agents Reduce the Efficacy of Intravenous Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke Patients: a Multicenter Cohort Study"],"prefix":"10.1007","volume":"12","author":[{"given":"Zhicai","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wansi","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxian","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haitao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongyu","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuojian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6627-064X","authenticated-orcid":false,"given":"Min","family":"Lou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,9,8]]},"reference":[{"key":"846_CR1","doi-asserted-by":"publisher","first-page":"e46","DOI":"10.1161\/STR.0000000000000158","volume":"49","author":"WJ Powers","year":"2018","unstructured":"Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the american heart association\/american stroke association. Stroke. 2018;49:e46\u2013e110.","journal-title":"Stroke"},{"key":"846_CR2","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1161\/CIRCRESAHA.116.309278","volume":"120","author":"L Catanese","year":"2017","unstructured":"Catanese L, Tarsia J, Fisher M. Acute ischemic stroke therapy overview. Circ Res. 2017;120:541\u201358.","journal-title":"Circ Res"},{"key":"846_CR3","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1148\/radiology.206.1.9423675","volume":"206","author":"A Doerfler","year":"1998","unstructured":"Doerfler A, Engelhorn T, von Kummer R, Weber J, Knauth M, Heiland S, et al. Are iodinated contrast agents detrimental in acute cerebral ischemia? An experimental study in rats. Radiology. 1998;206:211\u20137.","journal-title":"Radiology."},{"key":"846_CR4","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1161\/STROKEAHA.112.651737","volume":"43","author":"I Dzialowski","year":"2012","unstructured":"Dzialowski I, Puetz V, Buchan AM, Demchuk AM, Hill MD, Calgary SP. Does the application of x-ray contrast agents impair the clinical effect of intravenous recombinant tissue-type plasminogen activator in acute ischemic stroke patients? Stroke. 2012;43:1567\u201371.","journal-title":"Stroke"},{"key":"846_CR5","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1136\/jnis.2009.000794","volume":"2","author":"R Khatri","year":"2010","unstructured":"Khatri R, Khatri P, Khoury J, Broderick J, Carrozzella J, Tomsick T. Microcatheter contrast injections during intra-arterial thrombolysis increase intracranial hemorrhage risk. J Neurointerv Surg. 2010;2:115\u20139.","journal-title":"J Neurointerv Surg"},{"key":"846_CR6","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1016\/0735-1097(94)00528-X","volume":"25","author":"GJ Dehmer","year":"1995","unstructured":"Dehmer GJ, Gresalfi N, Daly D, Oberhardt B, Tate DA. Impairment of fibrinolysis by streptokinase, urokinase and recombinant tissue-type plasminogen activator in the presence of radiographic contrast agents. J Am Coll Cardiol. 1995;25:1069\u201375.","journal-title":"J Am Coll Cardiol"},{"key":"846_CR7","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1016\/S0735-1097(98)00326-X","volume":"32","author":"S Pislaru","year":"1998","unstructured":"Pislaru S, Pislaru C, Szilard M, Arnout J, Van de Werf F. In vivo effects of contrast media on coronary thrombolysis. J Am Coll Cardiol. 1998;32:1102\u20138.","journal-title":"J Am Coll Cardiol"},{"key":"846_CR8","doi-asserted-by":"publisher","first-page":"170","DOI":"10.3174\/ajnr.A1782","volume":"31","author":"KA Dani","year":"2010","unstructured":"Dani KA, Muir KW. Do iodinated contrast agents impair fibrinolysis in acute stroke? A systematic review. AJNR Am J Neuroradiol. 2010;31:170\u20134.","journal-title":"AJNR Am J Neuroradiol"},{"key":"846_CR9","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1161\/STROKEAHA.113.003268","volume":"45","author":"MM McDonald","year":"2014","unstructured":"McDonald MM, Archeval-Lao JM, Cai C, Peng H, Sangha N, Parker SA, et al. Iodinated contrast does not alter clotting dynamics in acute ischemic stroke as measured by thromboelastography. Stroke. 2014;45:462\u20136.","journal-title":"Stroke."},{"key":"846_CR10","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1056\/NEJMoa1813046","volume":"380","author":"H Ma","year":"2019","unstructured":"Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med. 2019;380:1795\u2013803.","journal-title":"N Engl J Med"},{"key":"846_CR11","doi-asserted-by":"publisher","first-page":"2276","DOI":"10.1161\/STROKEAHA.111.613273","volume":"42","author":"A Bruno","year":"2011","unstructured":"Bruno A, Akinwuntan AE, Lin C, Close B, Davis K, Baute V, et al. Simplified modified Rankin scale questionnaire: reproducibility over the telephone and validation with quality of life. Stroke. 2011;42:2276\u20139.","journal-title":"Stroke."},{"key":"846_CR12","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S0140-6736(18)32823-X","volume":"393","author":"Collaboration FT","year":"2019","unstructured":"Collaboration FT. Effects of fluoxetine on functional outcomes after acute stroke (focus): a pragmatic, double-blind, randomised, controlled trial. Lancet (London, England). 2019;393:265\u201374.","journal-title":"Lancet (London, England)"},{"key":"846_CR13","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/S1474-4422(13)70130-3","volume":"12","author":"group ISTc","year":"2013","unstructured":"group ISTc. Effect of thrombolysis with alteplase within 6 h of acute ischaemic stroke on long-term outcomes (the third international stroke trial [ist-3]): 18-month follow-up of a randomised controlled trial. Lancet Neurol. 2013;12:768\u201376.","journal-title":"Lancet Neurol"},{"key":"846_CR14","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1161\/01.STR.32.2.438","volume":"32","author":"V Larrue","year":"2001","unstructured":"Larrue V, von Kummer RR, Muller A, Bluhmki E. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the european-australasian acute stroke study (ecass ii). Stroke. 2001;32:438\u201341.","journal-title":"Stroke."},{"key":"846_CR15","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/0031-9384(74)90111-5","volume":"12","author":"PM Groves","year":"1974","unstructured":"Groves PM, Boyle RD, Welker RL, Miller SW. On the mechanism of prepulse inhibition. Physiol Behav. 1974;12:367\u201375.","journal-title":"Physiol Behav"},{"key":"846_CR16","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1002\/ana.25269","volume":"84","author":"G Tsivgoulis","year":"2018","unstructured":"Tsivgoulis G, Katsanos AH, Mavridis D, Gdovinova Z, Karlinski M, Macleod MJ, et al. Intravenous thrombolysis for ischemic stroke patients on dual antiplatelets. Ann Neurol. 2018;84:89\u201397.","journal-title":"Ann Neurol"},{"key":"846_CR17","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1148\/radiology.162.3.3809474","volume":"162","author":"HJ Robertson","year":"1987","unstructured":"Robertson HJ. Blood clot formation in angiographic syringes containing nonionic contrast media. Radiology. 1987;162:621\u20132.","journal-title":"Radiology."},{"key":"846_CR18","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.thromres.2003.09.031","volume":"112","author":"CI Jones","year":"2003","unstructured":"Jones CI, Goodall AH. Differential effects of the iodinated contrast agents ioxaglate, iohexol and iodixanol on thrombus formation and fibrinolysis. Thromb Res. 2003;112:65\u201371.","journal-title":"Thromb Res"},{"key":"846_CR19","doi-asserted-by":"publisher","first-page":"167","DOI":"10.3233\/CH-170261","volume":"66","author":"E Voros","year":"2017","unstructured":"Voros E, Deres L, Halmosi R, Varady E, Toth K, Battyani I. Interactions between iodinated contrast media and tissue plasminogen activator: in vitro comparison study. Clin Hemorheol Microcirc. 2017;66:167\u201374.","journal-title":"Clin Hemorheol Microcirc"},{"key":"846_CR20","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1161\/01.RES.68.3.881","volume":"68","author":"DA Gabriel","year":"1991","unstructured":"Gabriel DA, Jones MR, Reece NS, Boothroyd E, Bashore T. Platelet and fibrin modification by radiographic contrast media. Circ Res. 1991;68:881\u20137.","journal-title":"Circ Res"},{"key":"846_CR21","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1023\/A:1015283210156","volume":"12","author":"PM Farrehi","year":"2001","unstructured":"Farrehi PM, Zhu Y, Fay WP. An analysis of mechanisms underlying the antifibrinolytic properties of radiographic contrast agents. J Thromb Thrombolysis. 2001;12:273\u201381.","journal-title":"J Thromb Thrombolysis"},{"key":"846_CR22","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1097\/00004424-199407000-00007","volume":"29","author":"A Schilvold","year":"1994","unstructured":"Schilvold A, Bjornsen S, Ing C, Brosstad F. The effect of various contrast media on the activation of plasminogen by streptokinase or recombinant tissue plasminogen activator in vitro. Investig Radiol. 1994;29:705\u20138.","journal-title":"Investig Radiol"},{"key":"846_CR23","doi-asserted-by":"publisher","first-page":"2170","DOI":"10.1161\/STROKEAHA.111.618777","volume":"42","author":"NJ Macdougall","year":"2011","unstructured":"Macdougall NJ, McVerry F, Baird S, Baird T, Teasdale E, Muir KW. Iodinated contrast media and cerebral hemorrhage after intravenous thrombolysis. Stroke. 2011;42:2170\u20134.","journal-title":"Stroke"},{"key":"846_CR24","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1161\/STROKEAHA.110.578245","volume":"41","author":"Y Kurosawa","year":"2010","unstructured":"Kurosawa Y, Lu A, Khatri P, Carrozzella JA, Clark JF, Khoury J, et al. Intra-arterial iodinated radiographic contrast material injection administration in a rat middle cerebral artery occlusion and reperfusion model: possible effects on intracerebral hemorrhage. Stroke. 2010;41:1013\u20137.","journal-title":"Stroke."},{"key":"846_CR25","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.3174\/ajnr.A3953","volume":"35","author":"H Morales","year":"2014","unstructured":"Morales H, Lu A, Kurosawa Y, Clark JF, Leach J, Weiss K, et al. Decreased infarct volume and intracranial hemorrhage associated with intra-arterial nonionic iso-osmolar contrast material in an mca occlusion\/reperfusion model. AJNR Am J Neuroradiol. 2014;35:1885\u201391.","journal-title":"AJNR Am J Neuroradiol"},{"key":"846_CR26","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1097\/00004424-199112000-00012","volume":"26","author":"AJ Wilson","year":"1991","unstructured":"Wilson AJ, Evill CA, Sage MR. Effects of nonionic contrast media on the blood-brain barrier. Osmolality versus chemotoxicity. Investig Radiol. 1991;26:1091\u20134.","journal-title":"Investig Radiol"},{"key":"846_CR27","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1111\/j.1440-1681.2011.05503.x","volume":"38","author":"MM Sendeski","year":"2011","unstructured":"Sendeski MM. Pathophysiology of renal tissue damage by iodinated contrast media. Clin Exp Pharmacol Physiol. 2011;38:292\u20139.","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"846_CR28","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.mvr.2008.05.002","volume":"76","author":"RP Franke","year":"2008","unstructured":"Franke RP, Fuhrmann R, Hiebl B, Jung F. Influence of various radiographic contrast media on the buckling of endothelial cells. Microvasc Res. 2008;76:110\u20133.","journal-title":"Microvasc Res"},{"key":"846_CR29","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.3174\/ajnr.A4421","volume":"36","author":"TA Tomsick","year":"2015","unstructured":"Tomsick TA, Foster LD, Liebeskind DS, Hill MD, Carrozella J, Goyal M, et al. Outcome differences between intra-arterial iso- and low-osmolality iodinated radiographic contrast media in the interventional management of stroke iii trial. AJNR Am J Neuroradiol. 2015;36:2074\u201381.","journal-title":"AJNR Am J Neuroradiol"},{"key":"846_CR30","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1259\/bjr.74.885.740811","volume":"74","author":"AD Blann","year":"2001","unstructured":"Blann AD, Adams R, Ashleigh R, Naser S, Kirkpatrick U, McCollum CN. Changes in endothelial, leucocyte and platelet markers following contrast medium injection during angiography in patients with peripheral artery disease. Br J Radiol. 2001;74:811\u20137.","journal-title":"Br J Radiol"},{"key":"846_CR31","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.vph.2012.10.004","volume":"58","author":"E Scoditti","year":"2013","unstructured":"Scoditti E, Massaro M, Montinari MR. Endothelial safety of radiological contrast media: why being concerned. Vasc Pharmacol. 2013;58:48\u201353.","journal-title":"Vasc Pharmacol"},{"key":"846_CR32","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.3174\/ajnr.A4803","volume":"37","author":"QQ Ni","year":"2016","unstructured":"Ni QQ, Chen GZ, Schoepf UJ, Klitsie MAJ, De Cecco CN, Zhou CS, et al. Cerebral cta with low tube voltage and low contrast material volume for detection of intracranial aneurysms. AJNR Am J Neuroradiol. 2016;37:1774\u201380.","journal-title":"AJNR Am J Neuroradiol"},{"key":"846_CR33","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.2214\/ajr.136.6.1151","volume":"136","author":"LA Hayman","year":"1981","unstructured":"Hayman LA, Evans RA, Bastion FO, Hinck VC. Delayed high dose contrast ct: identifying patients at risk of massive hemorrhagic infarction. AJR Am J Roentgenol. 1981;136:1151\u20139.","journal-title":"AJR Am J Roentgenol"},{"key":"846_CR34","doi-asserted-by":"publisher","first-page":"225","DOI":"10.2214\/ajr.155.2.2115244","volume":"155","author":"BL McClennan","year":"1990","unstructured":"McClennan BL, Preston M. Hickey memorial lecture. Ionic and nonionic iodinated contrast media: evolution and strategies for use. AJR Am J Roentgenol. 1990;155:225\u201333.","journal-title":"AJR Am J Roentgenol"},{"key":"846_CR35","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1148\/radiology.175.3.2343107","volume":"175","author":"H Katayama","year":"1990","unstructured":"Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K. Adverse reactions to ionic and nonionic contrast media. A report from the japanese committee on the safety of contrast media. Radiology. 1990;175:621\u20138.","journal-title":"Radiology."},{"key":"846_CR36","doi-asserted-by":"publisher","first-page":"376","DOI":"10.5301\/JN.2010.5784","volume":"24","author":"HC Lee","year":"2011","unstructured":"Lee HC, Chang JG, Yen HW, Liu IH, Lai WT, Sheu SH. Ionic contrast media induced more apoptosis in diabetic kidney than nonionic contrast media. J Nephrol. 2011;24:376\u201380.","journal-title":"J Nephrol"},{"key":"846_CR37","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1097\/RLI.0b013e3181d77eed","volume":"45","author":"M Sendeski","year":"2010","unstructured":"Sendeski M, Patzak A, Persson PB. Constriction of the vasa recta, the vessels supplying the area at risk for acute kidney injury, by four different iodinated contrast media, evaluating ionic, nonionic, monomeric and dimeric agents. Investig Radiol. 2010;45:453\u20137.","journal-title":"Investig Radiol"},{"key":"846_CR38","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1002\/ccd.20670","volume":"67","author":"C Le Feuvre","year":"2006","unstructured":"Le Feuvre C, Batisse A, Collet JP, Batisse JP, Choussat R, Beygui F, et al. Cardiac events after low osmolar ionic or isosmolar nonionic contrast media utilization in the current era of coronary angioplasty. Catheter Cardiovasc Interv. 2006;67:852\u20138.","journal-title":"Catheter Cardiovasc Interv"},{"key":"846_CR39","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1148\/radiol.2353040726","volume":"235","author":"MC Heinrich","year":"2005","unstructured":"Heinrich MC, Kuhlmann MK, Grgic A, Heckmann M, Kramann B, Uder M. Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro. Radiology. 2005;235:843\u20139.","journal-title":"Radiology."}],"container-title":["Translational Stroke Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12975-020-00846-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12975-020-00846-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12975-020-00846-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T23:07:16Z","timestamp":1631056036000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12975-020-00846-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,8]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["846"],"URL":"https:\/\/doi.org\/10.1007\/s12975-020-00846-5","relation":{},"ISSN":["1868-4483","1868-601X"],"issn-type":[{"type":"print","value":"1868-4483"},{"type":"electronic","value":"1868-601X"}],"subject":[],"published":{"date-parts":[[2020,9,8]]},"assertion":[{"value":"30 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 August 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"The protocol was approved by human ethics committee of The Second Affiliated Hospital of Zhejiang University. The clinical investigation was conducted according to the principles expressed in the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Written informed consent was obtained from all of the patients.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}}]}}