{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:59:17Z","timestamp":1785473957454,"version":"3.56.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Postoperative delirium (POD) is a common complication in elderly patients undergoing hip or knee arthroplasty, and neuroinflammation plays a critical role in its pathogenesis. In addition to its antifibrinolytic properties, tranexamic acid (TXA) also exhibits anti-inflammatory effects. However, whether there is an association among TXA, inflammation, and POD remains poorly investigated. Therefore, this study aimed to investigate the effect of intravenous TXA on the incidence of POD in elderly patients undergoing hip or knee arthroplasty and to analyze the potential mediating role of inflammatory markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This single-center, retrospective cohort study included 1,234 elderly patients (aged \u226565\u202fyears) undergoing hip or knee arthroplasty at our institution between January 2017 and January 2026. Patients were divided into the TXA group (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f651) and the control group (n\u202f=\u202f583) based on the intraoperative administration of intravenous TXA. Outcomes included POD incidence within 7\u202fdays and 48-h postoperative markers: neutrophil-to-lymphocyte ratio (NLR), systemic inflammation response index (SIRI), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6). Multivariable logistic regression, linear regression, and subgroup analyses were performed to evaluate the associations, while mediation analysis was conducted to assess the potential role of inflammatory markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The incidence of POD was significantly lower in the TXA group than in the control group (26.0% vs. 41.9%,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Additionally, postoperative levels of all inflammatory markers (NLR, SIRI, MLR, SII, PLR, hs-CRP, and IL-6) were significantly reduced in the TXA group (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Adjusting for confounders, TXA remained an independent protective factor against POD (OR\u202f=\u202f0.415, 95% CI: 0.305, 0.563,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Exploratory mediation analysis showed that NLR, SIRI, SII, hs-CRP, and IL-6 may partially mediate the association between TXA and a reduced risk of POD, with mediation proportions of 18.17, 9.88, 14.75, 14.23, and 5.56%, respectively. Subgroup analyses confirmed that intravenous TXA remained a protective factor against POD across various patient strata.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Intravenous TXA administration is significantly associated with a reduced incidence of POD in elderly patients undergoing hip or knee arthroplasty. This association may be partially mediated by inflammatory markers, including NLR, SIRI, SII, hs-CRP, and IL-6. These findings contribute to the development of more effective strategies to improve the quality of postoperative recovery in elderly patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1865593","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:24:13Z","timestamp":1785471853000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between tranexamic acid and postoperative delirium in elderly patients: a mediation analysis of inflammatory markers following hip and knee arthroplasty"],"prefix":"10.3389","volume":"13","author":[{"given":"Junyang","family":"Chu","sequence":"first","affiliation":[{"name":"Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Department of Anesthesiology and Pain Medicine, Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Gao","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Department of Anesthesiology and Pain Medicine, Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xie","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushun","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Department of Anesthesiology and Pain Medicine, Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Jiaxing University","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1016\/s0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1016\/s0140-6736(18)31777-x","article-title":"Hip Replacement","volume":"392","author":"Ferguson","year":"2018","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1016\/s0140-6736(18)32344-4","article-title":"Knee 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