{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:46:41Z","timestamp":1785732401953,"version":"3.56.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"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. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Minimally invasive hematoma evacuation with local thrombolysis is increasingly used for spontaneous intracerebral hemorrhage (ICH), yet comparative data on thrombolytic agents across early time windows remain limited. Whether the thrombin-activatable fibrinolysis inhibitor (TAFI) Thr325Ile polymorphism modulates thrombolytic efficacy in this setting is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective comparative cohort study involving 120 patients with supratentorial ICH. Following minimally invasive hematoma aspiration, patients were treated with either rt-PA (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f60) or urokinase (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f60). Each group was stratified by onset-to-surgery time into ultra-acute (3 to 6\u202fh), acute (6 to 24\u202fh), and subacute (24 to 72\u202fh) subgroups. Neurological and functional outcomes, hematoma clearance, perihematomal edema, and TAFI genotypes were analyzed. Pre-specified exploratory subgroup analyses by dominant hemisphere and by hematoma volume stratum (30\u201350\u202fmL vs. 51\u201380\u202fmL) were also performed. Effect sizes with 95% confidence intervals (CIs) are reported alongside\n                      <jats:italic>p-<\/jats:italic>\n                      values, and the Bonferroni method was applied to control the family-wise error rate for primary between-group comparisons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      rt-PA was associated with better neurological and functional outcomes than urokinase from discharge onward across all three time windows (all Bonferroni-adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.017), with higher hematoma clearance and lower perihematomal edema. The difference in 3-month NIHSS score within the ultra-acute subgroup was 5.24 points (95% CI: 4.30\u20136.18; Cohen\u2019s\n                      <jats:italic>d<\/jats:italic>\n                      \u202f=\u202f4.06). Ultra-acute treatment produced the most favorable outcomes regardless of agent. The TAFI Ile325 (TT) genotype was enriched in the ultra-acute rt-PA subgroup (80.00% vs. 22.22% acute and 29.63% subacute;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.009; odds ratio for TT carriage vs. urokinase in the ultra-acute subgroup\u202f=\u202f10.00 [95% CI: 1.80\u201355.71]) and positively correlated with hematoma clearance in that window (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f0.670,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.006). No genotype\u2013outcome association was observed with urokinase.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>rt-PA was associated with more favorable outcomes than urokinase for minimally invasive ICH evacuation in this retrospective cohort, with the ultra-acute window conferring the greatest benefit. The TAFI Ile325 genotype may represent a candidate pharmacogenomic marker for enhanced rt-PA response during this early period. These hypothesis-generating findings require validation in prospective, multicenter studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1830505","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:26:01Z","timestamp":1785731161000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of rt-PA versus Urokinase in early time windows for minimally invasive intracerebral hemorrhage evacuation and exploratory TAFI pharmacogenomics"],"prefix":"10.3389","volume":"17","author":[{"given":"Yonggang","family":"Jiao","sequence":"first","affiliation":[{"name":"Department of Neurology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yangshan Hospital of the Affiliated Guangdong Second Provincial General Hospital of Jinan University","place":["Yangshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongpeng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yangshan Hospital of the Affiliated Guangdong Second Provincial General Hospital of Jinan University","place":["Yangshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Health Management, The Affiliated Guangdong Second Provincial General Hospital of Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yangshan Hospital of the Affiliated Guangdong Second Provincial General Hospital of Jinan University","place":["Yangshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1056\/NEJMra2201449","article-title":"Spontaneous intracerebral hemorrhage","volume":"387","author":"Sheth","year":"2022","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"123329","DOI":"10.1016\/j.jns.2024.123329","article-title":"Recent and future advances in intracerebral hemorrhage","volume":"467","author":"Puy","year":"2024","journal-title":"J Neurol Sci"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.1186\/s12889-024-19923-7","article-title":"Global, regional, and national burden of intracerebral hemorrhage and its attributable risk factors from 1990 to 2021: results from the 2021 global burden of disease study","volume":"24","author":"Xu","year":"2024","journal-title":"BMC Public Health"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1016\/S0140-6736(24)00702-5","article-title":"Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial","volume":"403","author":"Beck","year":"2024","journal-title":"Lancet"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s41016-022-00288-y","article-title":"Conventional craniotomy versus conservative treatment in patients with minor spontaneous intracerebral hemorrhage in the basal ganglia","volume":"8","author":"Wang","year":"2022","journal-title":"Chin Neurosurg J"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/S0140-6736(13)60986-1","article-title":"Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial","volume":"382","author":"Mendelow","year":"2013","journal-title":"Lancet"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1097\/CRD.0000000000000335","article-title":"Minimally invasive treatment options for managing spontaneous intracerebral hemorrhage","volume":"29","author":"Kim","year":"2021","journal-title":"Cardiol Rev"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e24213","DOI":"10.1097\/MD.0000000000024213","article-title":"Efficacy of minimally invasive surgery for the treatment of hypertensive intracerebral hemorrhage: a protocol of randomized controlled trial","volume":"100","author":"Liu","year":"2021","journal-title":"Medicine (Baltimore)"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/S0140-6736(19)30195-3","article-title":"Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded 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intracerebral haemorrhage","volume":"5","author":"Cao","year":"2020","journal-title":"Stroke Vasc Neurol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1001\/jama.2024.23480","article-title":"Intra-arterial Urokinase after endovascular reperfusion for acute ischemic stroke: the POST-UK randomized clinical trial","volume":"333","author":"Liu","year":"2025","journal-title":"JAMA"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/s10571-020-00985-1","article-title":"Hemorrhagic transformation after tissue plasminogen activator treatment in acute ischemic stroke","volume":"42","author":"Liu","year":"2022","journal-title":"Cell Mol Neurobiol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"5262","DOI":"10.3390\/ijms23095262","article-title":"The role of fibrinolytic system in health and disease","volume":"23","author":"Kwaan","year":"2022","journal-title":"Int J Mol 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