{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T06:13:27Z","timestamp":1793168007308,"version":"4.5.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM","award":["Grant No. 2023IHM01050"],"award-info":[{"award-number":["Grant No. 2023IHM01050"]}]},{"name":"Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM","award":["2023IHM01052"],"award-info":[{"award-number":["2023IHM01052"]}]},{"name":"Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM","award":["2023IHM01054"],"award-info":[{"award-number":["2023IHM01054"]}]},{"DOI":"10.13039\/501100004000","name":"Guangzhou Municipal Science and Technology Program key projects","doi-asserted-by":"publisher","award":["2024B03J0436"],"award-info":[{"award-number":["2024B03J0436"]}],"id":[{"id":"10.13039\/501100004000","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec015\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute ischemic stroke (AIS) remains a leading cause of disability and death globally, with limited effective neuroprotective strategies beyond reperfusion therapies. Despite advances in reperfusion treatments, many patients still experience poor outcomes, highlighting the urgent need for additional therapeutic approaches. We investigated whether intra-arterial local therapeutic hypothermia (IA-LTH) combined with endovascular treatment could improve outcomes in patients with AIS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec016\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      We conducted a multicenter, randomized trial with blinded outcome assessment (ISOLATION trial), where outcome assessors and patients were blinded to treatment allocation while procedural staff could not be blinded, to test the effectiveness of IA-LTH for neuroprotection in AIS (registration number: ChiCTR2300074990). Between September 2023 and January 2024, we recruited 100 patients with anterior circulation large vessel occlusion within 24\u2009h of stroke onset from 18 stroke centers in China. Participants were randomly assigned (1:1) to receive either IA-LTH plus standard care (including endovascular treatment and guideline-recommended medical therapy; intervention;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200950) or standard care alone (control;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200950). The IA-LTH group received intra-arterial infusion of 4 \u00b0C saline during and following endovascular treatment. Primary outcome was favorable functional outcome (modified Rankin Scale 0\u20132) at 90 days. Using intention-to-treat analysis, among participants (median age 69 years, 64% [64\/100] male, median National Institutes of Health Stroke Scale score 14), the primary outcome did not reach statistical significance, with favorable outcome achieved in 58.0% (29\/50) of the IA-LTH group versus 40.0% (20\/50) of controls (adjusted relative risk [aRR] of 1.47 (95% CI [0.99, 2.16];\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.055)). This lack of statistical significance is primarily due to the limited sample size of this pilot study, which was designed to assess feasibility and safety rather than provide definitive efficacy evidence. Safety outcomes, including rates of symptomatic intracranial hemorrhage (8.0% [4\/50] versus 16.0% [8\/50]) and mortality (20.0% [10\/50] versus 22.0% [11\/50]), were not significantly different between groups. The main limitations include the insufficient sample size of this pilot study which limited statistical power to detect differences in the primary outcome, the inability to adjust for potentially important confounders beyond age and ASPECTS due to the small sample size, and the higher incidence of pulmonary infections in the IA-LTH group that may have resulted from hypothermia-induced immune suppression or sedation-related factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec017\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This pilot study provides preliminary insights suggesting that IA-LTH combined with endovascular therapy may be feasible and safe, with potential to improve functional outcomes in patients with AIS. The primary outcome did not reach statistical significance. However, the observed numerical differences suggest that IA-LTH warrants further investigation in larger trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec018\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Chinese Clinical Trial Registry (ChiCTR) ChiCTR2300074990<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004668","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T17:25:17Z","timestamp":1753377917000},"page":"e1004668","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Intra-arterial selective hypothermia for acute ischemic stroke neuroprotection: A multicenter pilot trial in China"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0705-1970","authenticated-orcid":true,"given":"Zhi-Xin","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1821-0534","authenticated-orcid":true,"given":"Miaomiao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6320-6987","authenticated-orcid":true,"given":"Pan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuying","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanlong","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4776-7228","authenticated-orcid":true,"given":"Ping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Luan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongyi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaolai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1873-8831","authenticated-orcid":true,"given":"Yongkun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongtao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dezhi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongkui","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiliang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jilong","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haike","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7460-0787","authenticated-orcid":true,"given":"Lizhi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinfeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7268-2085","authenticated-orcid":true,"given":"Wen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"For 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