{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:26:51Z","timestamp":1791498411891,"version":"4.3.4"},"reference-count":26,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011033","name":"Thermo Fisher Scientific","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011033","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Mid-regional pro-adrenomedullin (MR-proADM) is a biomarker of endothelial dysfunction in sepsis. Its relationship with real-time microcirculatory alterations in critically ill patients remains insufficiently characterised. Methods: In a prospective cohort of 59 ICU patients with sepsis, serial sublingual microcirculation assessments were performed using sidestream dark field (SDF) imaging. Serum MR-proADM concentrations were measured with BRAHMS Kryptor assays. Automated software quantified microvascular structure and flow. Associations with disease severity and outcomes were evaluated using correlation, regression, and receiver operating characteristic (ROC) analyses (ClinicalTrials.gov Identifier: NCT05357339). Results: Higher MR-proADM concentrations at ICU admission were modestly associated with impaired microvascular perfusion (perfused number of crossings [PNOC]: \u03c1 = \u22120.32; perfused De Backer density [PDBD]: \u03c1 = \u22120.32; consensus proportion of perfused vessels [CPPV]: \u03c1 = \u22120.26; all p &lt; 0.05). Rising MR-proADM levels over time were strongly associated with worsening perfusion (\u0394PDBD: \u03c1 = 0.52; \u0394PNOC: \u03c1 = 0.54). MR-proADM correlated with SOFA and APACHE II scores and predicted the need for renal replacement therapy (AUC = 0.799, p = 0.041), but not ICU length of stay or hospital mortality. Conclusions: MR-proADM correlates with in vivo microcirculatory dysfunction in sepsis. Its dynamic association with microvascular impairment supports its potential role as a translational biomarker for monitoring endothelial and microcirculatory failure in critically ill patients.<\/jats:p>","DOI":"10.3390\/medsci14010117","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:24:34Z","timestamp":1772447074000},"page":"117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mid-Regional Pro-Adrenomedullin as a Translational Biomarker of Microcirculatory Dysfunction in Sepsis: A Prospective Observational Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Rachael","family":"Cusack","sequence":"first","affiliation":[{"name":"Multidisciplinary Intensive Care Research Organisation (MICRO), Department of Intensive Care Medicine, St. James\u2019 Hospital, D08 NHY1 Dublin, Ireland"},{"name":"Trinity College Dublin, School of Medicine, College Green, D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Garduno","sequence":"additional","affiliation":[{"name":"Trinity College Dublin, School of Medicine, College Green, D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Cumpf","sequence":"additional","affiliation":[{"name":"Biochemistry Department, St. James\u2019s Hospital, James\u2019s Street, D08 NHY1 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramila","family":"Reyes-Morales","sequence":"additional","affiliation":[{"name":"Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3097-758X","authenticated-orcid":false,"given":"Marc","family":"Leone","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care, Nord Hospital, Assistance Publique H\u00f4pitaux Universitaires de Marseille, Aix Marseille University, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso Blanco","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8828-5984","authenticated-orcid":false,"given":"Alejandro","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Rovira & Virgili University, 43002 Tarragona, Spain"},{"name":"Critical Care Department, Hospital Universitari de Tarragona Joan XXIII, Mallafr\u00e9 Guasch 4, 43007 Tarragona, Spain"},{"name":"IISPV (Instituto de Investigaci\u00f3n Sanitaria Pere Virgili), 43005 Tarragona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5834-4063","authenticated-orcid":false,"given":"Ignacio","family":"Martin-Loeches","sequence":"additional","affiliation":[{"name":"Multidisciplinary Intensive Care Research Organisation (MICRO), Department of Intensive Care Medicine, St. James\u2019 Hospital, D08 NHY1 Dublin, Ireland"},{"name":"Trinity College Dublin, School of Medicine, College Green, D02 PN40 Dublin, Ireland"},{"name":"Centre for Biomedical Research Network Respiratory Diseases (CIBERES), 43005 Tarragona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"i1585","DOI":"10.1136\/bmj.i1585","article-title":"Sepsis: Pathophysiology and clinical management","volume":"353","author":"Gotts","year":"2016","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.bjid.2020.09.004","article-title":"Molecular mechanisms of organ damage in sepsis: An overview","volume":"24","author":"Sygitowicz","year":"2020","journal-title":"Braz. 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