{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:01Z","timestamp":1792787581328,"version":"4.5.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Oxford NIHR Biomedical Research Centre"},{"name":"Oxford NIHR Biomedical Research Centre"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Sonographic septations are assumed to be important clinical predictors of outcome in pleural infection, but the evidence for this is sparse. The inflammatory and fibrinolysis-associated intrapleural pathway(s) leading to septation formation have not been studied in a large cohort of pleural fluid (PF) samples with confirmed pleural infection matched with ultrasound and clinical outcome data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the presence and severity of septations against baseline PF PAI-1 (Plasminogen-Activator Inhibitor-1) and other inflammatory and fibrinolysis-associated proteins as well as to correlate these with clinically important outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 214 pleural fluid samples from PILOT (Pleural Infection Longitudinal Outcome Study), a prospective observational pleural infection study, for inflammatory and fibrinolysis-associated proteins using the Luminex platform. Multivariate regression analyses were used to assess the association of pleural biological markers with septation presence and severity (on ultrasound) and clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>PF PAI-1 was the only protein independently associated with septation presence (P\u2009&amp;lt;\u20090.001) and septation severity (P\u2009=\u20090.003). PF PAI-1 concentrations were associated with increased length of stay (P\u2009=\u20090.048) and increased 12-month mortality (P\u2009=\u20090.003). Sonographic septations alone had no relation to clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In a large and well-characterized cohort, this is the first study to associate pleural biological parameters with a validated sonographic septation outcome in pleural infection. PF PAI-1 is the first biomarker to demonstrate an independent association with mortality. Although PF PAI-1 plays an integral role in driving septation formation, septations themselves are not associated with clinically important outcomes. These novel findings now require prospective validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202206-1084oc","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T15:34:13Z","timestamp":1664811253000},"page":"731-739","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":46,"title":["The Biological Role of Pleural Fluid PAI-1 and Sonographic Septations in Pleural Infection: Analysis of a Prospectively Collected Clinical Outcome Study"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9196-3934","authenticated-orcid":false,"given":"Eihab O.","family":"Bedawi","sequence":"first","affiliation":[{"name":"Oxford Pleural Unit, Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom"},{"name":"Oxford Respiratory Trials Unit"},{"name":"National Institute for Health Research Oxford Biomedical Research Centre"},{"name":"Department of Infection, Immunity, and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos I.","family":"Kanellakis","sequence":"additional","affiliation":[{"name":"Oxford Pleural Unit, Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom"},{"name":"Oxford Respiratory Trials Unit"},{"name":"National Institute for Health Research Oxford Biomedical Research Centre"},{"name":"Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine"},{"name":"Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Corcoran","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Derriford Hospital, University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8768-6548","authenticated-orcid":false,"given":"Maged","family":"Hassan","sequence":"additional","affiliation":[{"name":"Oxford Pleural Unit, Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom"},{"name":"Chest Diseases Department, Alexandria University Faculty of Medicine, Alexandria, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachelle","family":"Asciak","sequence":"additional","affiliation":[{"name":"Queen Alexandra Hospital, Portsmouth Hospitals NHS Trust, Portsmouth, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.","family":"Mercer","sequence":"additional","affiliation":[{"name":"Queen Alexandra Hospital, Portsmouth Hospitals NHS Trust, Portsmouth, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Sundaralingam","sequence":"additional","affiliation":[{"name":"Oxford Pleural Unit, Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom"},{"name":"Oxford Respiratory Trials Unit"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh N.","family":"Addala","sequence":"additional","affiliation":[{"name":"Oxford Pleural Unit, Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom"},{"name":"Oxford Respiratory Trials Unit"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F.","family":"Miller","sequence":"additional","affiliation":[{"name":"Institute for Global Health, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Dong","sequence":"additional","affiliation":[{"name":"Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, and"},{"name":"Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M.","family":"Condliffe","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity, and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najib M.","family":"Rahman","sequence":"additional","affiliation":[{"name":"Oxford Pleural Unit, Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom"},{"name":"Oxford Respiratory Trials Unit"},{"name":"National Institute for Health Research Oxford Biomedical Research Centre"},{"name":"Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine"},{"name":"Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"2026012204465102600_bib1","doi-asserted-by":"crossref","first-page":"L757","DOI":"10.1152\/ajplung.00501.2017","article-title":"Fibrin turnover and pleural organization: bench to bedside","volume":"314","author":"Komissarov","year":"2018","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026012204465102600_bib2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1164\/ajrccm\/144.1.187","article-title":"Abnormalities of pathways of fibrin turnover in the human pleural space","volume":"144","author":"Idell","year":"1991","journal-title":"Am Rev Respir Dis"},{"key":"2026012204465102600_bib3","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1056\/NEJMoa1012740","article-title":"Intrapleural use of tissue plasminogen activator and DNase in pleural infection","volume":"365","author":"Rahman","year":"2011","journal-title":"N Engl J Med"},{"key":"2026012204465102600_bib4","doi-asserted-by":"crossref","first-page":"L389","DOI":"10.1152\/ajplung.00171.2016","article-title":"Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models","volume":"311","author":"Komissarov","year":"2016","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026012204465102600_bib5","doi-asserted-by":"crossref","first-page":"837","DOI":"10.7863\/jum.2000.19.12.837","article-title":"Sonographic septation: a useful prognostic indicator of acute thoracic empyema","volume":"19","author":"Chen","year":"2000","journal-title":"J Ultrasound Med"},{"key":"2026012204465102600_bib6","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1016\/j.ultrasmedbio.2009.04.021","article-title":"Transthoracic ultrasonography in predicting the outcome of small-bore catheter drainage in empyemas or complicated parapneumonic effusions","volume":"35","author":"Chen","year":"2009","journal-title":"Ultrasound Med Biol"},{"key":"2026012204465102600_bib7","doi-asserted-by":"crossref","first-page":"2000130","DOI":"10.1183\/13993003.00130-2020","article-title":"Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study","volume":"56","author":"Corcoran","year":"2020","journal-title":"Eur Respir J"},{"key":"2026012204465102600_bib8","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jri.2005.03.005","article-title":"Validation and comparison of luminex multiplex cytokine analysis kits with ELISA: determinations of a panel of nine cytokines in clinical sample culture supernatants","volume":"66","author":"dupont","year":"2005","journal-title":"J Reprod Immunol"},{"key":"2026012204465102600_bib9","doi-asserted-by":"crossref","first-page":"e000171","DOI":"10.1136\/bmjresp-2016-000171","article-title":"Assessment of patient-reported outcome measures in pleural interventions","volume":"4","author":"Psallidas","year":"2017","journal-title":"BMJ Open Respir Res"},{"key":"2026012204465102600_bib10","year":"2017"},{"key":"2026012204465102600_bib11","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1378\/chest.13-1558","article-title":"A clinical score (RAPID) to identify those at risk for poor outcome at presentation in patients with pleural infection","volume":"145","author":"Rahman","year":"2014","journal-title":"Chest"},{"key":"2026012204465102600_bib12","doi-asserted-by":"crossref","first-page":"567","DOI":"10.3390\/medicina55090567","article-title":"PAI-1 level differences in malignant plural effusion, parapneumonic pleuritis, and cardiac hydrothorax","volume":"55","author":"Zentina","year":"2019","journal-title":"Medicina (Kaunas)"},{"key":"2026012204465102600_bib13","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40169-016-0097-2","article-title":"Organizing empyema induced in mice by Streptococcus pneumoniae: effects of plasminogen activator inhibitor-1 deficiency","volume":"5","author":"Tucker","year":"2016","journal-title":"Clin Transl Med"},{"key":"2026012204465102600_bib14","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/CPM.0000000000000216","article-title":"Precision-guided, personalized intrapleural fibrinolytic therapy for empyema and complicated parapneumonic pleural effusions: the case for the fibrinolytic potential","volume":"24","author":"Idell","year":"2017","journal-title":"Clin Pulm Med"},{"key":"2026012204465102600_bib15","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.2174\/138945011797635803","article-title":"Effects of altered plasminogen activator inhibitor-1 expression on cardiovascular disease","volume":"12","author":"Ploplis","year":"2011","journal-title":"Curr Drug Targets"},{"key":"2026012204465102600_bib16","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1055\/s-0034-1387883","article-title":"Role of plasminogen activator inhibitor-1 in senescence and aging","volume":"40","author":"Eren","year":"2014","journal-title":"Semin Thromb Hemost"},{"key":"2026012204465102600_bib17","doi-asserted-by":"crossref","first-page":"653655","DOI":"10.3389\/fcvm.2021.653655","article-title":"A serpin with a finger in many PAIs: PAI-1\u2019s central function in thromboinflammation and cardiovascular disease","volume":"8","author":"Morrow","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"2026012204465102600_bib18","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1164\/rccm.201911-2169OC","article-title":"Pleural fluid suPAR levels predict the need for invasive management in parapneumonic effusions","volume":"201","author":"Arnold","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204465102600_bib19","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40560-017-0238-8","article-title":"Usefulness of plasminogen activator inhibitor-1 as a predictive marker of mortality in sepsis","volume":"5","author":"Hoshino","year":"2017","journal-title":"J Intensive Care"},{"key":"2026012204465102600_bib20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13613-019-0499-6","article-title":"Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study","volume":"9","author":"Schmitt","year":"2019","journal-title":"Ann Intensive Care"},{"key":"2026012204465102600_bib21","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.21037\/atm-20-6022","article-title":"The effect of Cyclic-di-GMP on biofilm formation by Pseudomonas aeruginosa in a novel empyema model","volume":"8","author":"Zhang","year":"2020","journal-title":"Ann Transl Med"},{"key":"2026012204465102600_bib22","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1111\/resp.13881","article-title":"Pleural effusions and pneumothorax. Beyond simple plumbing: expert opinions on knowledge gaps and essential next steps","volume":"25","author":"Thomas","year":"2020","journal-title":"Respirology"},{"key":"2026012204465102600_bib23","first-page":"865","year":"2019"},{"key":"2026012204465102600_bib24","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/S1470-2045(18)30294-8","article-title":"Development and validation of response markers to predict survival and pleurodesis success in patients with malignant pleural effusion (PROMISE): a multicohort analysis","volume":"19","author":"Psallidas","year":"2018","journal-title":"Lancet Oncol"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/207\/6\/731\/66437259\/ajrccm_207_6_731.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/207\/6\/731\/66437259\/ajrccm_207_6_731.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T09:47:09Z","timestamp":1769075229000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/207\/6\/731\/8428168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3]]},"references-count":24,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3,15]]},"published-print":{"date-parts":[[2023,3,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.202206-1084oc","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742349094.793596391","asserted-by":"object"}]},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,3]]},"published":{"date-parts":[[2023,3]]},"assertion":[{"value":"2022-06-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}