{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T06:19:02Z","timestamp":1783059542575,"version":"3.54.6"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis is a life-threatening condition with persistently high mortality in the ICU, highlighting an urgent need for effective pharmacological interventions. Statins have been proposed as potential adjunctive therapies owing to their pleiotropic properties, but evidence specifically supporting the use of pravastatin\u2014a hydrophilic statin with distinct pharmacokinetics\u2014in this critically ill population remains insufficient.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study utilized data from the MIMIC-IV database (version 3.1). Adult patients with sepsis at their first ICU admission who received pravastatin within the first 24 hours of ICU admission were included, while those using other statins were excluded. Propensity score matching (PSM) was performed at a 1:1 ratio to balance baseline characteristics between the pravastatin and non\u2013pravastatin groups. The primary outcome was 28\u2013day all\u2013cause mortality. Secondary outcomes included in\u2013hospital mortality, in\u2013ICU mortality, and the incidence of acute kidney injury (AKI) and continuous renal replacement therapy (CRRT). Cox regression models were employed, and pre-specified subgroup analyses were conducted. Sensitivity analyses, including an expanded Cox model, overlap\u2013weighted regression, and E\u2013value analysis, were performed to assess the robustness of the findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From 546,028 admissions, 25,573 septic patients were identified. After PSM, 1,106 patients (553 per group) were included. The 28\u2013day mortality rate was 11.6% (64\/553) in the pravastatin group vs. 17.2% (95\/553) in the non\u2013pravastatin group. In the overall matched cohort, pravastatin use was associated with significantly lower 28\u2013day mortality in both unadjusted (HR, 0.66; 95% CI, 0.48\u20130.90; P\u00a0=\u00a00.009) and fully adjusted models (HR, 0.69; 95% CI, 0.50\u20130.95; P\u00a0=\u00a00.025). Pravastatin was associated with reduced in-hospital mortality, while in\u2013ICU mortality did not reach statistical significance after full adjustment. No significant differences were observed in AKI (79.6% vs. 81.7%; adjusted OR, 0.79; 95% CI, 0.57\u20131.10; P\u00a0=\u00a00.170) or CRRT use (4.0% vs. 5.8%; adjusted OR, 0.65; 95% CI, 0.32\u20131.30; P\u00a0=\u00a00.221). Subgroup analyses showed consistent associations across most strata, with no significant interactions (all P &amp;gt; 0.05). Timing analysis showed that in patients with pre-existing pravastatin use who continued treatment after ICU admission, continuation of pre-existing pravastatin was associated with reduced 28-day mortality (adjusted HR, 0.35; 95% CI, 0.17\u20130.73; P\u00a0=\u00a00.005). In patients with\n                      <jats:italic>de novo<\/jats:italic>\n                      initiation of pravastatin within 24 hours of ICU admission, no statistically significant association with 28-day mortality was observed after full adjustment (adjusted HR, 0.80; 95% CI, 0.57\u20131.13; P\u00a0=\u00a00.198). Sensitivity analyses yielded consistent results (expanded Cox: HR, 0.66; OW: HR, 0.70; E-value: 2.26 with lower bound 1.29).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In this retrospective analysis of septic ICU patients, continuation of pre-existing pravastatin use after ICU admission was associated with lower 28-day and in-hospital mortality, without an increased risk of AKI or CRRT use.\n                      <jats:italic>De novo<\/jats:italic>\n                      pravastatin initiation within 24 hours of ICU admission was not associated with reduced 28-day mortality. These hypothesis\u2013generating findings warrant confirmation in future prospective studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1814760","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:38:10Z","timestamp":1783057090000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between pravastatin use and short-term mortality in ICU patients with sepsis: a retrospective propensity score-matched cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Bo","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Cardiology, Chengdu Integrated TCM & Western Medicine Hospital","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Chengdu Integrated TCM & Western Medicine Hospital","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Personalized Drug Research and Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jiao","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1056\/NEJMra1208623","article-title":"Severe sepsis and septic shock","volume":"369","author":"Angus","year":"2013","journal-title":"N. 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