{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:56:18Z","timestamp":1792166178257,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Prolonged antibiotic therapy in ventilator\u2010associated pneumonia (VAP) contributes to antimicrobial resistance. Inhaled heparin has pleiotropic anti\u2010inflammatory and mucolytic properties. This trial evaluated whether adjunctive nebulized heparin reduces antibiotic duration in VAP using a procalcitonin (PCT)\u2010guided discontinuation algorithm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this single\u2010center, double\u2010blind, randomized controlled trial, 82 mechanically ventilated adults with VAP (CPIS\u2009\u2265\u20096) were assigned to standard care plus nebulized heparin (10,000 IU every 6\u2009h) or placebo (sterile distilled water). Both groups followed a PCT\u2010guided antibiotic discontinuation algorithm (\u2264\u20090.2\u2009\u00b5g\/L or \u2265\u200990% reduction from peak, plus clinical stability). Primary outcome: antibiotic duration (days). Secondary outcomes: duration of mechanical ventilation, ICU\/hospital length of stay (LOS), serial CPIS, CRP, PCT, SOFA, APACHE II, adverse events, and 28\u2010day mortality rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Antibiotic duration was significantly shorter with heparin (mean difference \u22123.2 days; 95% CI: \u22124.8 to \u22121.6;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Baseline characteristics were similar except for higher mean APACHE II in the control group (18.8 vs. 15.2). After adjusting for baseline APACHE II imbalance, the treatment effect remained significant (adjusted mean difference \u22122.9 days; 95% CI: \u22124.5 to \u22121.3;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001). Heparin also reduced duration of mechanical ventilation (mean difference \u22121.47 days;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01), ICU LOS (\u2212\u20093.5 days;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02), and hospital LOS (\u2212\u20094.1 days;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01). CPIS and CRP improved more rapidly in the heparin group (group\u00d7time interaction\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). No major bleeding or heparin\u2010related adverse events occurred.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Adjunctive nebulized heparin (40,000 IU\/day) significantly shortens antibiotic duration and improves clinical recovery in VAP without increasing adverse events. However, given the single\u2010center design and modest sample size, our results require confirmation in future multicenter trials with optimum heparin doses and comprehensive biomarker panels to better elucidate the mechanisms of action and establish the definitive role of inhaled heparin in antimicrobial stewardship.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hsr2.73334","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:05:47Z","timestamp":1791183947000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhaled Heparin to Shorten Antibiotic Duration in Ventilator\u2010Associated Pneumonia: A Randomized Double\u2010Blind Controlled Trial"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9855-8402","authenticated-orcid":false,"given":"Anoush Dehnadi","family":"Moghadam","sequence":"first","affiliation":[{"name":"Guilan Road Trauma Research Center Poursina University Hospital, Guilan University of Medical Sciences Rasht Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Saeedinia","sequence":"additional","affiliation":[{"name":"Guilan Road Trauma Research Center Poursina University Hospital, Guilan University of Medical Sciences Rasht Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh Dehnadi","family":"Moghadam","sequence":"additional","affiliation":[{"name":"Aachen Faculty of Medicine Uniklinik RWTH Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"Textbook of Critical Care E\u2010Book","author":"Vincent J.\u2010L.","year":"2017"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0000000000000365"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70081-1"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/1547691X.2013.839587"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000201882.23917.B8"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/39.4.527"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2017.08.23"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3010525"},{"issue":"7","key":"e_1_2_12_10_1","first-page":"523","article-title":"Inhaled Unbruised Heparin a New Way to Improve Lung Function: A Review","volume":"8","author":"Dr.babitha M.","year":"2019","journal-title":"World Journal of Pharmaceutical Research"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1751143717740804"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/143.5_Pt_1.1121"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00582-2017"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2018.01.006"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc9269"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10198-011-0296-0"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.19.2588"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc13775"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.4103\/1687-8426.184374"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-016-0138-4"},{"key":"e_1_2_12_21_1","article-title":"Inhaled Anticoagulants for Mechanically Ventilated Patients: An Individual Patient Data Meta\u2010Analysis of Randomized Trials","volume":"12","author":"Glas G. 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