{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T11:53:47Z","timestamp":1766490827744,"version":"3.48.0"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/4255\/2020"],"award-info":[{"award-number":["UIDB\/4255\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"RISE, Associated Laboratory","award":["LA\/P\/0053\/2020"],"award-info":[{"award-number":["LA\/P\/0053\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Interleukin-6 (IL-6) is a key inflammatory cytokine implicated in atherosclerotic plaque progression and carotid vulnerability. Although elevated IL-6 levels have been linked to cerebrovascular risk, its prognostic value in patients undergoing carotid endarterectomy (CEA) remains undefined. This systematic review aimed to investigate the available evidence on the relationship between IL-6 levels, surgical outcomes and mechanistic evidence in CEA patients. Materials and Methods: The review followed the PRISMA statement and AMSTAR-2 critical appraisal guidelines, with the protocol registered on PROSPERO (CRD420251120023). PubMed\/MEDLINE, Scopus, and Web of Science were systematically searched up to July 2025 using the terms \u201cinterleukin-6\u201d and \u201ccarotid endarterectomy\u201d. Original studies in humans assessing IL-6 in relation to clinical outcomes after CEA or mechanistic evidence were included without language or date restrictions. Study quality was evaluated using the Cochrane Risk of Bias 2 and NHLBI tools, and evidence certainty was appraised using the GRADE framework. Given the heterogeneity of studies, only a qualitative synthesis was performed. Results: From 1232 records identified, 13 studies encompassing 1396 patients met the inclusion criteria. Most were prospective observational cohorts, with a mean participant age of 68.52 years and 81.16% male predominance. Perioperative stroke and mortality rates were uniformly low (\u22642%), consistent with contemporary registry data. Across studies, elevated IL-6 levels\u2014whether systemic or plaque-derived\u2014were consistently associated with symptomatic carotid disease, plaque vulnerability, and adverse long-term outcomes. However, not all studies presented quantitative data on IL-6 levels, limiting the ability to draw definitive prognostic conclusions. Conclusions: Current evidence supports a mechanistic link between IL-6\u2013mediated inflammation and carotid plaque instability, yet robust clinical validation in surgical populations is lacking. Future large-scale, prospective studies incorporating IL-6 measurement are warranted to establish its prognostic utility, guide anti-inflammatory therapeutic strategies, and refine postoperative risk stratification in patients undergoing CEA.<\/jats:p>","DOI":"10.3390\/medsci13040325","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:15:21Z","timestamp":1766049321000},"page":"325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-6 and Surgical Outcomes in Carotid Endarterectomy: A Systematic Review"],"prefix":"10.3390","volume":"13","author":[{"given":"Ant\u00f3nia","family":"Rocha-Melo-Sousa","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"M\u00e1rcio","family":"Brazuna","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Biomedical Science, University of Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8298-3352","authenticated-orcid":false,"given":"Carmen","family":"Tavares","sequence":"additional","affiliation":[{"name":"Nova Medical School, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8906-0641","authenticated-orcid":false,"given":"Sai","family":"Guduru","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Mosaic Life Care, University of Missouri\u2013Kansas City, St. Joseph, MO 64506, USA"}]},{"given":"Mariana","family":"Frag\u00e3o-Marques","sequence":"additional","affiliation":[{"name":"Department of Immuno-Physiology and Pharmacology, ICBAS School of Medicine and Biomedical Sciences, University of Porto, 4150-180 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2656-8935","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Rocha-Neves","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Unit of Anatomy, Faculty of Medicine of University of Porto, 4200-319 Porto, Portugal"},{"name":"RISE-Health, Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Department of Vascular Surgery, Unidade Local de Sa\u00fade\u2013Alto Ave, 4835-044 Guimar\u00e3es, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/S0140-6736(10)61197-X","article-title":"10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): A multicentre randomised trial","volume":"376","author":"Halliday","year":"2010","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0140-6736(03)12228-3","article-title":"Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis","volume":"361","author":"Rothwell","year":"2003","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa0912321","article-title":"Stenting versus endarterectomy for treatment of carotid-artery stenosis","volume":"363","author":"Brott","year":"2010","journal-title":"N. 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