{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:38:41Z","timestamp":1791941921480,"version":"4.3.4"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Stress hyperglycemia (SHG) is associated with worse clinical outcomes in minor ischemic stroke. Hemorrhagic transformation (HT) represents a potential mechanism mediating this association, but clear characterization of this relationship is lacking. We therefore aimed to investigate whether HT mediates the effect of SHG on functional outcomes in patients with minor stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">This was a prospective international cohort study (5 comprehensive stroke centers, Italy\/United Kingdom). Individuals presenting with National Institutes of Health Stroke Scale \u22645, prestroke modified Rankin Scale \u22641, and without large vessel occlusion between January 2022 and December 2023 were included. SHG was assessed \u226424 hours using the glucose\u2010to\u2010glycated hemoglobin ratio. HT \u22647\u2009days was classified in hemorrhagic infarction and parenchymal hematoma. Causal mediation was used to estimate SHG effect on modified Rankin Scale \u22652 at 3 months mediated by HT. Effect modification of age, diabetes, C\u2010reactive protein, and intravenous thrombolysis was explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      There were 1316 patients included (mean age 69.6\u00b112.7\u2009years, 837 men [63.6%]). Higher glucose\u2010to\u2010glycated hemoglobin ratio quartiles were associated with modified Rankin Scale \u22652 (adjusted odds ratio [OR], 1.72 [95% CI, 1.24\u20132.40];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.001) and HT severity (adjusted OR, 2.32 [95% CI, 1.43\u20133.76];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.001). A significant proportion (14.8%) of the SHG effect on mRS was mediated by HT (average causal mediation effect, 0.014 [95% CI, 0.003\u20130.030];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.006). Effect modification was found for younger age (\u224860\u2009years old), higher C\u2010reactive protein (\u22487 mg\/L), and absence of diabetes, but not for intravenous thrombolysis use.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">In patients with minor stroke, HT significantly mediated the effect of SHG on unfavorable outcome. The mediating effect of HT was greater in patients either \u224860\u2009years old, without diabetes, or with high baseline C\u2010reactive protein levels. These initial results might inform patient selection for future interventional studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.046218","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:37:40Z","timestamp":1782211060000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Hemorrhagic Transformation Mediates Stress Hyperglycemia Effect on Functional Outcome in Minor Ischemic Stroke"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1725-1175","authenticated-orcid":false,"given":"Francesco","family":"Bax","sequence":"first","affiliation":[{"name":"Udine University Hospital","place":["Udine, Italy"]},{"name":"Massachusetts General Hospital and Harvard Medical School","place":["Boston, USA"]},{"name":"Udine University Hospital and DMED, University of Udine","place":["Udine, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6077-1315","authenticated-orcid":false,"given":"Mariarosaria","family":"Valente","sequence":"additional","affiliation":[{"name":"Udine University Hospital and DMED, University of Udine","place":["Udine, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Mazzacane","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0321-7155","authenticated-orcid":false,"given":"Matteo","family":"Foschi","sequence":"additional","affiliation":[{"name":"University of L\u2019Aquila","place":["L\u2019Aquila, Italy"]},{"name":"S. Maria delle Croci Hospital, AUSL Romagna","place":["Ravenna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9501-4031","authenticated-orcid":false,"given":"Raffaele","family":"Ornello","sequence":"additional","affiliation":[{"name":"University of L\u2019Aquila","place":["L\u2019Aquila, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9504-1794","authenticated-orcid":false,"given":"Alessandro","family":"Mar\u00e8","sequence":"additional","affiliation":[{"name":"Udine University Hospital and DMED, University of Udine","place":["Udine, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0076-193X","authenticated-orcid":false,"given":"Francesco","family":"Toraldo","sequence":"additional","affiliation":[{"name":"Udine University Hospital and DMED, University of Udine","place":["Udine, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0079-4487","authenticated-orcid":false,"given":"Caterina","family":"Del Regno","sequence":"additional","affiliation":[{"name":"Udine University Hospital and DMED, University of Udine","place":["Udine, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8048-1495","authenticated-orcid":false,"given":"Roberto","family":"Sperotto","sequence":"additional","affiliation":[{"name":"Udine University Hospital and DMED, University of Udine","place":["Udine, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1025-2545","authenticated-orcid":false,"given":"Antonio","family":"Taglialatela","sequence":"additional","affiliation":[{"name":"Udine University Hospital and DMED, University of Udine","place":["Udine, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5499-8342","authenticated-orcid":false,"given":"Beatrice","family":"Del Bello","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Spigariol","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Pavolucci","sequence":"additional","affiliation":[{"name":"S. 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