{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T03:18:58Z","timestamp":1794107938485,"version":"4.8.0"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    There is a pressing clinical need for thrombolytic agents that can effectively disaggregate arterial thrombi in acute ischemic stroke without significantly increasing the risk of bleeding. This pilot study aimed to investigate the safety and efficacy of\n                    <jats:italic>N<\/jats:italic>\n                    -acetylcysteine (NAC) as an adjunctive therapy to intravenous recombinant tissue plasminogen activator (rtPA or alteplase). A randomized, open-label, blinded assessor pilot study was conducted. Patients presenting with an\u00a0acute ischemic stroke within 4.5\u00a0h from onset were randomized into two groups: intravenous NAC and rtPA or rtPA alone. Primary outcomes included intracerebral hemorrhage, symptomatic intracerebral hemorrhage, extracranial bleeding, and adverse reactions. Secondary outcomes comprised major neurological improvement assessed by (National Institute of Health Stroke Scale) NIHSS at 24\u00a0h, recanalization on first run of angiography in patients who underwent thrombectomy or on repeat vascular imaging at 24\u00a0h, modified Rankin scale, and three-month mortality. Forty patients were enrolled, with 21 receiving only rtPA and 19 receiving NAC with rtPA. Baseline characteristics were comparable among groups. No significant differences were observed in adverse events (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.99), intracranial hemorrhage (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.21), symptomatic intracerebral hemorrhage (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.47), or extracranial bleeding (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.21). Median NIHSS at 24\u00a0h was significantly lower in the intervention group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03). Functional outcomes and three-month mortality were similar between groups (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.85 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.99 respectively). The co-administration of\n                    <jats:italic>N<\/jats:italic>\n                    -acetylcysteine with alteplase did not significantly alter safety profiles, morbidity, or mortality at 3\u00a0months. While no substantial differences were noted, a slightly improved early neurological outcome was observed\u00a0in the intervention arm. The study's findings were constrained by a small sample size, emphasizing the necessity for future large-scale trials to comprehensively evaluate the safety and efficacy of\n                    <jats:italic>N<\/jats:italic>\n                    -acetylcysteine as a thrombolytic agent in acute ischemic stroke.\n                  <\/jats:p>\n                  <jats:p>Trial Registration Clinical Trials Registry India\u2014CTRI\/2019\/05\/019305.<\/jats:p>","DOI":"10.1038\/s41598-023-49054-9","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T07:01:54Z","timestamp":1704956514000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Safety and efficacy of N-acetylcysteine (NAC) as an adjunct to standard treatment in patients with acute ischemic stroke: a randomized controlled pilot trial (NACTLYS)"],"prefix":"10.1038","volume":"14","author":[{"given":"Snigdha","family":"Komakula","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Bhatia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhil","family":"Sahib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Upadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leve Joseph","family":"S","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Garg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishnu V","family":"Y","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awadh Kishor","family":"Pandit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepti","family":"Vibha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamta Bhushan","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjari","family":"Tripathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. V. Padma","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"issue":"1","key":"49054_CR1","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1161\/01.STR.0000196957.55928.ab","volume":"37","author":"JL Saver","year":"2006","unstructured":"Saver, J. L. Time is brain\u2014quantified. Stroke 37(1), 263\u2013266 (2006).","journal-title":"Stroke"},{"issue":"10","key":"49054_CR2","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.1161\/STROKEAHA.110.592535","volume":"41","author":"R Bhatia","year":"2010","unstructured":"Bhatia, R. et al. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: Real-world experience and a call for action. Stroke 41(10), 2254\u20132258 (2010).","journal-title":"Stroke"},{"issue":"7","key":"49054_CR3","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1161\/STROKEAHA.114.008247","volume":"46","author":"YD Kim","year":"2015","unstructured":"Kim, Y. D. et al. Time-dependent thrombus resolution after tissue-type plasminogen activator in patients with stroke and mice. Stroke 46(7), 1877\u20131882 (2015).","journal-title":"Stroke"},{"issue":"7","key":"49054_CR4","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1161\/CIRCULATIONAHA.117.027290","volume":"136","author":"S de Martinez Lizarrondo","year":"2017","unstructured":"de Martinez Lizarrondo, S. et al. Potent thrombolytic effect of N-acetylcysteine on arterial thrombi. 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