{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T07:57:06Z","timestamp":1793606226718,"version":"4.5.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100031566","name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante","doi-asserted-by":"crossref","award":["2023\/0278"],"award-info":[{"award-number":["2023\/0278"]}],"id":[{"id":"10.13039\/100031566","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Radiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate vascular attenuation (VA) in conventional and low-energy virtual monoenergetic images (LEVMI), volumetric lung iodine density (VID) and quality of CT pulmonary angiography (CTPA) in dual-layer detector spectral CT using three iodinated contrast medium (ICM) administration protocols.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>A prospective randomized single-center study including patients with CTPA to rule out pulmonary embolism (PE) was performed. Examinations were randomized to one of three ICM administration protocols: A, 40\u2009mL at 4\u2009mL\/s; B, 30\u2009mL at 3\u2009mL\/s; and C, 20\u2009mL of ICM diluted with 20\u2009mL of saline at 4\u2009mL\/s. Two radiologists evaluated the presence of PE, VA in conventional images and LEVMI, lung VID, perfusion defects detection, and quality of Z-effective maps. Statistical comparisons were performed between protocols.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty patients were randomized to each protocol. In conventional images, VA in pulmonary arteries was above 200 HU in more than 90% in protocols A and B, but only in 70% in protocol C. VA increased in LEVMI, with a minimum value of 269 HU. Differences in pulmonary VA with protocol C were statistically significant. At LEVMI, aortic attenuation was above 100 HU in most examinations. Protocol C presented the worst quality of iodine map and the lowest VID; however, it detected perfusion defects in all PE cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The use of LEVMI provides diagnostic VA levels in pulmonary arteries in all the protocols, and a minimum aortic enhancement in most cases. Even the lowest ICM dose maintains diagnostic iodine maps, although with lower quality and VID.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic>Question<\/jats:italic>\n                      <\/jats:bold>\n                      <jats:italic>Do low doses of iodinated contrast medium for spectral CT pulmonary angiography achieve diagnostic vascular attenuation, and do they allow detection of perfusion defects in pulmonary embolism?<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic>Findings<\/jats:italic>\n                      <\/jats:bold>\n                      <jats:italic>All three protocols achieved diagnostic pulmonary artery attenuation in low-energy virtual monoenergetic images and detected perfusion defects in all pulmonary embolism cases<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic>Clinical relevance<\/jats:italic>\n                      <\/jats:bold>\n                      <jats:italic>Spectral CT pulmonary angiography enables diagnostic pulmonary vascular enhancement and reliable perfusion defect detection with reduced contrast material doses, supporting safer and more efficient pulmonary embolism imaging protocols<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00330-025-12309-2","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:33:24Z","timestamp":1769733204000},"page":"4801-4811","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Vascular attenuation and volumetric lung iodine density in dual-layer spectral CT pulmonary angiography: a randomized controlled trial comparing three contrast doses"],"prefix":"10.1007","volume":"36","author":[{"given":"David","family":"Ferr\u00e1ndez-Ferr\u00e1ndez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5044-0173","authenticated-orcid":false,"given":"Juan Jos\u00e9","family":"Arenas-Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almudena","family":"Ure\u00f1a Vacas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Sirera Matilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elo\u00edsa","family":"Feliu Rey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Marquina Arribas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Trigueros Buil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Garc\u00eda-Garrig\u00f3s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"12309_CR1","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1093\/eurheartj\/ehz405","volume":"41","author":"SV Konstantinides","year":"2020","unstructured":"Konstantinides SV, Meyer G, Bueno H et al (2020) 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European respiratory society (ERS). Eur Heart J 41:543\u2013603","journal-title":"Eur Heart J"},{"key":"12309_CR2","doi-asserted-by":"publisher","first-page":"e243833","DOI":"10.1148\/radiol.243833","volume":"315","author":"FA Klok","year":"2025","unstructured":"Klok FA, Barco S, Bertoletti L et al (2025) Optimal approach to performing and reporting computed tomography angiography for suspected acute pulmonary embolism: a clinical consensus statement of the ESC Working Group on Pulmonary Circulation & Right Ventricular Function, the Fleischner Society, the Association for Acute Cardiovascular Care (ACVC) and the European Association of Cardiovascular Imaging (EACVI) of the ESC, Endorsed by European Respiratory Society (ERS), Asian Society of Thoracic Radiology (ASTR), European Society of Thoracic Imaging (ESTI), and Society of Thoracic Radiology (STR). Radiology 315:e243833","journal-title":"Radiology"},{"key":"12309_CR3","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1007\/s00330-023-10101-8","volume":"34","author":"T Sch\u00f6nfeld","year":"2024","unstructured":"Sch\u00f6nfeld T, Seitz P, Krieghoff C et al (2024) High-pitch CT pulmonary angiography (CTPA) with ultra-low contrast medium volume for the detection of pulmonary embolism: a comparison with standard CTPA. Eur Radiol 34:1921\u20131931","journal-title":"Eur Radiol"},{"key":"12309_CR4","doi-asserted-by":"publisher","first-page":"e0167214","DOI":"10.1371\/journal.pone.0167214","volume":"11","author":"A Meier","year":"2016","unstructured":"Meier A, Higashigaito K, Martini K et al (2016) Dual energy CT pulmonary angiography with 6g iodine\u2014a propensity score-matched study. PLoS One 11:e0167214","journal-title":"PLoS One"},{"key":"12309_CR5","doi-asserted-by":"publisher","first-page":"4649","DOI":"10.1007\/s00330-025-11420-8","volume":"35","author":"CH Kristiansen","year":"2025","unstructured":"Kristiansen CH, Thomas O, Nyquist AB et al (2025) A randomised controlled trial comparing three clinical administration strategies in spectral detector CT pulmonary angiography with low contrast medium dose. Eur Radiol 35:4649\u20134660","journal-title":"Eur Radiol"},{"key":"12309_CR6","doi-asserted-by":"publisher","first-page":"195","DOI":"10.5152\/dir.2019.17498","volume":"25","author":"P Rajiah","year":"2019","unstructured":"Rajiah P, Ciancibello L, Novak R, Sposato J, Landeras L, Gilkeson R (2019) Ultra-low dose contrast CT pulmonary angiography in oncology patients using a high-pitch helical dual-source technology. Diagn Interv Radiol 25:195\u2013203","journal-title":"Diagn Interv Radiol"},{"key":"12309_CR7","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s11547-019-01098-6","volume":"125","author":"M Silva","year":"2020","unstructured":"Silva M, Milanese G, Cobelli R et al (2020) CT angiography for pulmonary embolism in the emergency department: investigation of a protocol by 20 ml of high-concentration contrast medium. Radiol Med 125:137\u2013144","journal-title":"Radiol Med"},{"key":"12309_CR8","doi-asserted-by":"publisher","first-page":"20190995","DOI":"10.1259\/bjr.20190995","volume":"93","author":"H Alobeidi","year":"2020","unstructured":"Alobeidi H, Alshamari M, Widell J, Eriksson T, Lid\u00e9n M (2020) Minimizing contrast media dose in CT pulmonary angiography with high-pitch technique. Br J Radiol 93:20190995","journal-title":"Br J Radiol"},{"key":"12309_CR9","doi-asserted-by":"publisher","first-page":"112172","DOI":"10.1016\/j.ejrad.2025.112172","volume":"189","author":"R Varga","year":"2025","unstructured":"Varga R, Weiss F, Raudner M, Prosch H, Schernthaner RE (2025) Personalized high pitch CTPA facilitates a reduction of contrast agent volume. Eur J Radiol 189:112172","journal-title":"Eur J Radiol"},{"key":"12309_CR10","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1161\/CIRCINTERVENTIONS.109.910638","volume":"3","author":"JR Brown","year":"2010","unstructured":"Brown JR, Robb JF, Block CA et al (2010) Does safe dosing of iodinated contrast prevent contrast-induced acute kidney injury? Circ Cardiovasc Interv 3:346\u2013350","journal-title":"Circ Cardiovasc Interv"},{"key":"12309_CR11","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1097\/RCT.0000000000001674","volume":"49","author":"GV Toia","year":"2025","unstructured":"Toia GV, Ananthakrishnan L (2025) The environmental impact of iodinated contrast media: strategies for optimized use and recycling. J Comput Assist Tomogr 49:203\u2013214","journal-title":"J Comput Assist Tomogr"},{"key":"12309_CR12","unstructured":"Yee KM (2025) ISCT: 2022 ICM shortage was a \u2018wake-up call.\u2019 Did we listen? Available via https:\/\/www.auntminnie.com\/clinical-news\/ct\/article\/15754564\/isct-2022-icm-shortage-was-a-wakeup-call-did-we-listen. Accessed 2 Nov 2025"},{"key":"12309_CR13","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1148\/rg.2016150185","volume":"36","author":"H Machida","year":"2016","unstructured":"Machida H, Tanaka I, Fukui R et al (2016) Dual-energy spectral CT: various clinical vascular applications. Radiographics 36:1215\u20131232","journal-title":"Radiographics"},{"key":"12309_CR14","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.3348\/kjr.2020.1512","volume":"22","author":"YJ Hong","year":"2021","unstructured":"Hong YJ, Shim J, Lee SM, Im DJ, Hur J (2021) Dual-energy CT for pulmonary embolism: current and evolving clinical applications. Korean J Radiol 22:1555\u20131568","journal-title":"Korean J Radiol"},{"key":"12309_CR15","doi-asserted-by":"publisher","first-page":"775","DOI":"10.2214\/AJR.19.21818","volume":"214","author":"EG Kikano","year":"2020","unstructured":"Kikano EG, Rajdev M, Salem KZ et al (2020) Utility of iodine density perfusion maps from dual-energy spectral detector CT in evaluating cardiothoracic conditions: a primer for the radiologist. AJR Am J Roentgenol 214:775\u2013785","journal-title":"AJR Am J Roentgenol"},{"key":"12309_CR16","doi-asserted-by":"publisher","first-page":"144","DOI":"10.2214\/AJR.08.1653","volume":"193","author":"SF Thieme","year":"2009","unstructured":"Thieme SF, Johnson TRC, Lee C et al (2009) Dual-energy CT for the assessment of contrast material distribution in the pulmonary parenchyma. AJR Am J Roentgenol 193:144\u2013149","journal-title":"AJR Am J Roentgenol"},{"key":"12309_CR17","doi-asserted-by":"publisher","first-page":"6658","DOI":"10.1002\/mp.15227","volume":"48","author":"K Li","year":"2021","unstructured":"Li K, Li Y, Qi Z, Garrett JW, Grist TM, Chen GH (2021) Quantitative lung perfusion blood volume using dual energy CT\u2013based effective atomic number (Zeff) imaging. Med Phys 48:6658\u20136672","journal-title":"Med Phys"},{"key":"12309_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20254-y","volume":"8","author":"M Meyer","year":"2018","unstructured":"Meyer M, Haubenreisser H, Schabel C et al (2018) CT pulmonary angiography in patients with acute or chronic renal insufficiency: evaluation of a low dose contrast material protocol. Sci Rep 8:1995","journal-title":"Sci Rep"},{"key":"12309_CR19","doi-asserted-by":"publisher","first-page":"6544","DOI":"10.1007\/s00330-024-10724-5","volume":"34","author":"M Remy-Jardin","year":"2024","unstructured":"Remy-Jardin M, Oufriche I, Guiffault L et al (2024) Diagnosis of acute pulmonary embolism: when photon-counting-detector CT replaces energy-integrating-detector CT in daily routine. Eur Radiol 34:6544\u20136555","journal-title":"Eur Radiol"},{"key":"12309_CR20","doi-asserted-by":"publisher","first-page":"734","DOI":"10.2214\/AJR.17.18537","volume":"210","author":"K Bae","year":"2018","unstructured":"Bae K, Jeon KN, Cho SB et al (2018) Improved opacification of a suboptimally enhanced pulmonary artery in chest CT: experience using a dual-layer detector spectral CT. AJR Am J Roentgenol 210:734\u2013741","journal-title":"AJR Am J Roentgenol"},{"key":"12309_CR21","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.21037\/qims-21-229","volume":"12","author":"JR Kroeger","year":"2022","unstructured":"Kroeger JR, Z\u00f6llner J, Gerhardt F et al (2022) Detection of patients with chronic thromboembolic pulmonary hypertension by volumetric iodine quantification in the lung\u2014a case control study. Quant Imaging Med Surg 12:1121\u20131129","journal-title":"Quant Imaging Med Surg"},{"key":"12309_CR22","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1016\/j.crad.2015.06.094","volume":"70","author":"A Meier","year":"2015","unstructured":"Meier A, Wurnig M, Desbiolles L, Leschka S, Frauenfelder T, Alkadhi H (2015) Advanced virtual monoenergetic images: improving the contrast of dual-energy CT pulmonary angiography. Clin Radiol 70:1244\u20131251","journal-title":"Clin Radiol"},{"key":"12309_CR23","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1097\/RLI.0000000000000176","volume":"50","author":"W Stiller","year":"2015","unstructured":"Stiller W, Skornitzke S, Fritz F et al (2015) Correlation of quantitative dual-energy computed tomography iodine maps and abdominal computed tomography perfusion measurements. Invest Radiol 50:703\u2013708","journal-title":"Invest Radiol"},{"key":"12309_CR24","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.ejrad.2014.09.009","volume":"84","author":"M Okada","year":"2015","unstructured":"Okada M, Kunihiro Y, Nakashima Y et al (2015) Added value of lung perfused blood volume images using dual-energy CT for assessment of acute pulmonary embolism. Eur J Radiol 84:172\u2013177","journal-title":"Eur J Radiol"},{"key":"12309_CR25","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1148\/radiol.2018180594","volume":"289","author":"EK Weidman","year":"2018","unstructured":"Weidman EK, Plodkowski AJ, Halpenny DF et al (2018) Dual-energy CT angiography for detection of pulmonary emboli: incremental benefit of iodine maps. Radiology 289:546\u2013553","journal-title":"Radiology"},{"key":"12309_CR26","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.2214\/AJR.06.1104","volume":"188","author":"C Wittram","year":"2007","unstructured":"Wittram C (2007) How I do it: CT pulmonary angiography. AJR Am J Roentgenol 188:1255\u20131261","journal-title":"AJR Am J Roentgenol"},{"key":"12309_CR27","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1097\/RLI.0b013e31821a2142","volume":"47","author":"JW Nance","year":"2012","unstructured":"Nance JW, Henzler T, Meyer M et al (2012) Optimization of contrast material delivery for dual-energy computed tomography pulmonary angiography in patients with suspected pulmonary embolism. Invest Radiol 47:78\u201384","journal-title":"Invest Radiol"},{"key":"12309_CR28","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1186\/s13244-025-02037-y","volume":"16","author":"EJI Hoeijmakers","year":"2025","unstructured":"Hoeijmakers EJI, Martens B, Wildberger JE, Flohr TG, Jeukens CRLPN (2025) Objective assessment of diagnostic image quality in CT scans: what radiologists and researchers need to know. Insights Imaging 16:154","journal-title":"Insights Imaging"},{"key":"12309_CR29","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1093\/bjr\/tqaf008","volume":"98","author":"K Yasaka","year":"2025","unstructured":"Yasaka K, Saigusa H, Abe O (2025) Iodine concentration in the lung parenchyma in relation to different inspiratory depths during CT pulmonary angiography. Br J Radiol 98:556\u2013561","journal-title":"Br J Radiol"},{"key":"12309_CR30","doi-asserted-by":"publisher","first-page":"2944","DOI":"10.1007\/s00330-023-10337-4","volume":"34","author":"RJ Gertz","year":"2024","unstructured":"Gertz RJ, Gerhardt F, Pienn M et al (2024) Dual-layer dual-energy CT-derived pulmonary perfusion for the differentiation of acute pulmonary embolism and chronic thromboembolic pulmonary hypertension. Eur Radiol 34:2944\u20132956","journal-title":"Eur Radiol"},{"key":"12309_CR31","doi-asserted-by":"publisher","first-page":"835732","DOI":"10.3389\/fcvm.2022.835732","volume":"9","author":"RJ Gertz","year":"2022","unstructured":"Gertz RJ, Gerhardt F, Kr\u00f6ger JR et al (2022) Spectral detector CT-derived pulmonary perfusion maps and pulmonary parenchyma characteristics for the semiautomated classification of pulmonary hypertension. Front Cardiovasc Med 9:835732","journal-title":"Front Cardiovasc Med"},{"key":"12309_CR32","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1590\/0100-3984.2021.0063","volume":"55","author":"RR Borges","year":"2022","unstructured":"Borges RR, Morato TN, Bezerra ASA et al (2022) Evaluation of intravascular contrast media transit times in coronary computed tomography angiography. Radiol Bras 55:161\u2013166","journal-title":"Radiol Bras"},{"key":"12309_CR33","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s13244-016-0524-3","volume":"8","author":"A Chaturvedi","year":"2017","unstructured":"Chaturvedi A, Oppenheimer D, Rajiah P, Kaproth-Joslin KA, Chaturvedi A (2017) Contrast opacification on thoracic CT angiography: challenges and solutions. Insights Imaging 8:127\u2013140","journal-title":"Insights Imaging"},{"key":"12309_CR34","doi-asserted-by":"publisher","first-page":"340.e9","DOI":"10.1016\/j.crad.2016.11.018","volume":"72","author":"J Zhu","year":"2017","unstructured":"Zhu J, Wang Z, Kim Y et al (2017) Analysis of contrast time\u2013enhancement curves to optimise CT pulmonary angiography. Clin Radiol 72:340.e9\u2013340.e16","journal-title":"Clin Radiol"},{"key":"12309_CR35","doi-asserted-by":"publisher","first-page":"e2330154","DOI":"10.2214\/AJR.23.30154","volume":"222","author":"P Pannenbecker","year":"2024","unstructured":"Pannenbecker P, Heidenreich JF, Grunz JP et al (2024) Image quality and radiation dose of CTPA with iodine maps: a prospective randomized study of high-pitch mode photon-counting detector CT versus energy-integrating detector CT. AJR Am J Roentgenol 222:e2330154","journal-title":"AJR Am J Roentgenol"}],"container-title":["European Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-025-12309-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00330-025-12309-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-025-12309-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T12:25:32Z","timestamp":1779798332000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00330-025-12309-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["12309"],"URL":"https:\/\/doi.org\/10.1007\/s00330-025-12309-2","relation":{},"ISSN":["1432-1084"],"issn-type":[{"value":"1432-1084","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]},"assertion":[{"value":"26 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 December 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2026","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 scientific guarantor of this publication is Juan Jos\u00e9 Arenas-Jim\u00e9nez.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Guarantor"}},{"value":"The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"One of the authors has significant statistical expertise.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statistics and biometry"}},{"value":"Written informed consent was obtained from all subjects (patients) in this study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Institutional Review Board approval was obtained.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"No cohort overlap.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Study subjects or cohorts overlap"}},{"order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Methodology"}}]}}