{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:02:07Z","timestamp":1787806927358,"version":"build-2784847793"},"reference-count":118,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Sepsis is a critical condition characterized by an abnormal immune response to infection, resulting in systemic inflammation, organ failure, and high mortality rate. Postoperative sepsis, accounting for nearly one-third of all sepsis cases, predominantly affects the elderly and individuals with pre-existing conditions, with fatality rates between 30 and 50%. Surgical stress induces immune, hormonal, and metabolic disturbances, heightening susceptibility to immune dysregulation and sepsis. Neurocognitive disorders related to postoperative sepsis, which share pathophysiological similarities with sepsis-associated encephalopathy, involve neuroinflammation, blood\u2013brain barrier disruption, and mitochondrial dysfunction. Cognitive impairments, such as delirium, are frequent postoperative complications that vary in severity depending on the surgical complexity. This review examined the underlying mechanisms of these dysfunctions, the influence of different surgical procedures, and predictive and therapeutic strategies, including machine learning models, aimed at improving patient outcomes.<\/jats:p>","DOI":"10.3389\/fmed.2025.1513833","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T14:40:18Z","timestamp":1748961618000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Postoperative sepsis-associated neurocognitive disorder: mechanisms, predictive strategies, and treatment approaches"],"prefix":"10.3389","volume":"12","author":[{"given":"Zijing","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41590-023-01660-5","article-title":"The pathophysiology of Sepsis and precision-medicine-based immunotherapy","volume":"25","author":"Giamarellos-Bourboulis","year":"2024","journal-title":"Nat Immunol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and National Sepsis Incidence and mortality, 1990-2017: analysis for the global burden of disease 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dysfunction","volume":"264","author":"Goldblum","year":"1993","journal-title":"Am J Phys"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/s0140-6736(09)61158-2","article-title":"Systemic infection and delirium: when cytokines and acetylcholine collide","volume":"375","author":"van Gool","year":"2010","journal-title":"Lancet"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/s0891-5849(98)00216-0","article-title":"Mitochondrial damage induced by conditions of oxidative stress","volume":"26","author":"Kowaltowski","year":"1999","journal-title":"Free Radic Biol Med"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"102968","DOI":"10.1016\/j.redox.2023.102968","article-title":"Restoring the infected powerhouse: mitochondrial quality control in Sepsis","volume":"68","author":"Lira Chavez","year":"2023","journal-title":"Redox 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