{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:40:33Z","timestamp":1790350833677,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UID\/50016\/2025"],"award-info":[{"award-number":["UID\/50016\/2025"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"award":["UID\/50016\/2025"],"award-info":[{"award-number":["UID\/50016\/2025"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Postoperative complications following adult cardiac surgery are biologically interrelated, yet most machine learning models predict single outcomes. We developed an explainable multi-output model integrating routinely collected clinical variables and patient blood management (PBM) biomarkers to predict multiple postoperative outcomes simultaneously, with complementary mono-output analyses for selected endpoints. Methods: This retrospective single-center cohort included 1414 adults undergoing cardiac surgery. In total, 513 complete cases were analyzed. Thirteen outcomes were modeled, including major binary complications and ICU\/ward length of stay. An initial 80:20 train\u2013test split was used only for algorithm screening across six candidate multi-output regressors and training-set-defined feature subsets. The selected regressor was then evaluated across five random states, and global permutation feature importance was used for multi-output explainability. Mono-output binary analyses using the selected regressor and the same training-set-only feature-selection workflow were evaluated along with accuracy, precision, recall\/sensitivity, and F1-scores. Results: The Decision Tree Regressor was selected. Across five random states, global multi-output performance was R2 = 0.83, MSE = 1.296, RMSE = 1.132, MAE = 0.298, and MAPE = 0.128. Based on global multi-output permutation importance, creatinine, ferritin, platelet count, estimated glomerular filtration rate, preoperative red blood cell units, and EuroSCORE II were ranked the highest. Atrial fibrillation had the lowest mono-output F1-score (0.719), whereas acute kidney injury, postoperative bleeding, infection, and 1-year hospital readmission yielded F1-scores of 0.928, 0.970, 0.963, and 0.975, respectively. Conclusions: This proof-of-concept study shows the feasibility of explainable multi-output modeling for postoperative outcomes after adult cardiac surgery using clinical and PBM variables. However, external validation is required prior to clinical use.<\/jats:p>","DOI":"10.3390\/jcm15114221","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T17:36:18Z","timestamp":1780076178000},"page":"4221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multi-Output Machine Learning for Prediction of Postoperative Outcomes After Cardiac Surgery Using Patient Blood Management Biomarkers"],"prefix":"10.3390","volume":"15","author":[{"given":"Henrique","family":"Coelho","sequence":"first","affiliation":[{"name":"CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2014Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Universidade Cat\u00f3lica Portuguesa, 4169-005 Porto, Portugal"},{"name":"Servi\u00e7o de Hematologia, Unidade Local de Sa\u00fade de Vila Nova de Gaia e Espinho, 4434-502 Vila Nova de Gaia, Portugal"},{"name":"Departamento de Ci\u00eancias M\u00e9dicas, Universidade de Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0060-4253","authenticated-orcid":false,"given":"Diana","family":"Paup\u00e9rio","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Anestesiologia, Unidade Local de Sa\u00fade de Vila Nova de Gaia e Espinho, 4434-502 Vila Nova de Gaia, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7818-5661","authenticated-orcid":false,"given":"Fernando","family":"Silva","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias M\u00e9dicas, Universidade de Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Servi\u00e7o de Hematologia, Unidade Local de Sa\u00fade da Regi\u00e3o de Aveiro, 3814-501 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria In\u00eas","family":"Barbosa","sequence":"additional","affiliation":[{"name":"CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2014Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Universidade Cat\u00f3lica Portuguesa, 4169-005 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8236-2563","authenticated-orcid":false,"given":"Pedro","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2014Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Universidade Cat\u00f3lica Portuguesa, 4169-005 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5040-735X","authenticated-orcid":false,"given":"Marta","family":"Correia","sequence":"additional","affiliation":[{"name":"CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2014Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Universidade Cat\u00f3lica Portuguesa, 4169-005 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5381-6615","authenticated-orcid":false,"given":"Pedro Miguel","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2014Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Universidade Cat\u00f3lica Portuguesa, 4169-005 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13613-023-01165-2","article-title":"Angiopoietin-2 is associated with capillary leak and predicts complications after cardiac surgery","volume":"13","author":"Wollborn","year":"2023","journal-title":"Ann. 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