2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T83d,Background: Pulmonary fibrosis is a progressive and often irreversible condition that can develop following acute lung injury (ALI), particularly in patients requiring prolonged mechanical ventilation. Antifibrotic agents such as pirfenidone and nintedanib slow fibrosis progression in idiopathic pulmonary fibrosis, but their role in post-ALI fibrosis remains unclear. This meta-analysis aimed to evaluate the effects of antifibrotic therapy on mortality and secondary outcomes in patients with ALI. Methods: We searched Embase, PubMed, and Cochrane up to 17 March 2025 for randomized controlled trials and observational studies comparing antifibrotic therapy to standard care in patients with ALI. The primary outcome was all-cause mortality at the longest follow-up available. Secondary outcomes were length of hospital stay and radiological and functional findings. Results: We identified six studies (two randomized, two propensity matched and two case control studies) for a total of 697 COVID-19 patients and no study performed on non-COVID-19 patients. Antifibrotic therapy was associated with a significant reduction in all-cause mortality compared to the control group (16.1% vs. 23.9%, OR 0.61, 95% CI 0.40–0.93, p = 0.02, I2 = 40%). The number needed to treat to prevent one death was 13. There was no significant difference in length of hospital stay between the antifibrotic and control groups. Individual studies reported improvements in computed tomography severity scores and pulmonary function parameters in the antifibrotic group. Conclusions: This meta-analysis suggests that antifibrotic therapy might reduce mortality in patients with ALI. Improvements in radiological and functional outcomes indicate a potential role for antifibrotic agents in modifying disease progression. Further well-designed randomized controlled trials are necessary to confirm these results and determine the optimal use of antifibrotic therapy in post-ALI fibrosis. The PROSPERO Registration: The study protocol was prospectively registered in PROSPERO (registration number CRD420251001885).31:T795,Patients with sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) commonly suffer from severe pulmonary thrombosis, but clinical trials of anticoagulant therapies in patients with sepsis and ARDS have failed. Patients with ARDS plus thrombocytopenia also exhibit increased mortality, and widespread pulmonary thrombosis is often seen in patients with COVID-19 ARDS. Different amounts of microbeads were administered intravenously to adult mice to induce various levels of pulmonary thrombosis. ALI was induced by either intraperitoneal lipopolysaccharide or cecal ligation and puncture. Endothelial cell (EC)-targeted nanoparticles were used to deliver plasmid DNA expressing the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) system for EC-specific gene knockout of Alox15 (arachidonate 15-lipoxygenase) or plasmid DNA expressing Alox15 for EC-specific overexpression. Lipidomic profiling and in vivo rescue studies with the identified Alox15-regulated lipids were performed. In addition, thrombocytopenia was induced by genetic depletion of platelets using We show that although severe pulmonary thrombosis or thrombocytopenia augments sepsis-induced ALI, the induction of mild pulmonary thrombosis conversely reduces EC apoptosis, ALI, and mortality via sustained expression of endothelial Alox15. Endothelial We have demonstrated that moderate levels of lung thrombosis protect against sepsis-induced inflammatory lung injury via endothelial Alox15. Overexpression of endothelial Alox15 inhibits severe pulmonary thrombosis-induced increases in ALI. Thus, upregulation of ALOX15 expression or treatment with ALOX15-dependent protective lipid(s) represents a promising therapeutic strategy for treatment of ARDS, especially in subpopulations of patients with thrombocytopenia or widespread pulmonary thrombosis.32:T1040, BACKGROUND: Patients with sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) commonly suffer from severe pulmonary thrombosis, but clinical trials of anticoagulant therapies in patients with sepsis and ARDS have failed. Patients with ARDS plus thrombocytopenia also exhibit increased mortality, and widespread pulmonary thrombosis is often seen in patients with COVID-19 ARDS. METHODS: Different amounts of microbeads were administered intravenously to adult mice to induce various levels of pulmonary thrombosis. ALI was induced by either intraperitoneal lipopolysaccharide or cecal ligation and puncture. Endothelial cell (EC)–targeted nanoparticles were used to deliver plasmid DNA expressing the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat–associated 9) system for EC-specific gene knockout of Alox15 (arachidonate 15-lipoxygenase) or plasmid DNA expressing Alox15 for EC-specific overexpression. Lipidomic profiling and in vivo rescue studies with the identified Alox15-regulated lipids were performed. In addition, thrombocytopenia was induced by genetic depletion of platelets using DTR Pf4Cre mice, and the effects of restoration of pulmonary thrombosis were assessed. RESULTS: We show that although severe pulmonary thrombosis or thrombocytopenia augments sepsis-induced ALI, the induction of mild pulmonary thrombosis conversely reduces EC apoptosis, ALI, and mortality via sustained expression of endothelial Alox15. Endothelial Alox15 knockout in adult mice abolished the protective impact of mild lung thrombosis. Conversely, overexpression of endothelial Alox15 inhibited the increases in ALI caused by severe pulmonary thrombosis. Treatment of the endothelial Alox15 knockout mice with 1-palmitoyl-2-oleoyl-3-arachidonoyl-rac-glycerol (C 57 H 100 O 6 ), a top candidate of the 32 Alox15-regulated lipids identified by lipidomic profiling, markedly reversed the defective phenotype, suggesting that Alox15 protects from lung injury via protective lipids. The clinical relevance of the findings was supported by the observation of reduced ALOX15-expressing ECs in lung autopsy samples of patients with ARDS. In addition, restoration of pulmonary thrombosis in thrombocytopenic mice normalized endotoxemia-induced ALI. CONCLUSIONS: We have demonstrated that moderate levels of lung thrombosis protect against sepsis-induced inflammatory lung injury via endothelial Alox15. Overexpression of endothelial Alox15 inhibits severe pulmonary thrombosis-induced increases in ALI. Thus, upregulation of ALOX15 expression or treatment with ALOX15-dependent protective lipid(s) represents a promising therapeutic strategy for treatment of ARDS, especially in subpopulations of patients with thrombocytopenia or widespread pulmonary thrombosis. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Acute Lung Injury: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Acute Lung Injury (condition). Clinician-written summaries and actionable practice insights. 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AVDS-related vascular pathology should be considered when evaluating unexplained hypoxemia in these patients."}},{"doi":"10.1152/ajplung.00066.2026","pmid":"42030197","title":"Engineering function in lung biology: integrating imaging, regenerative constructs, and functional biodesign","journal_title":"American Journal of Physiology-Lung Cellular and Molecular Physiology","journal_issn":"1040-0605","published_at":"2026-04-24T00:00:00.000Z","url":"https://doi.org/10.1152/ajplung.00066.2026","source_score":2,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-02T13:27:31.733Z","updated_at":"2026-06-02T13:27:31.733Z","tags":[{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"condition","value":"Acute Lung Injury","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"condition","value":"Lung Disease","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"modality","value":"Cell-Based Therapy","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"modality","value":"Induced Pluripotent Stem Cell-Derived Models","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"modality","value":"Organ-on-Chip","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"modality","value":"Tissue Engineering","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"warning","value":"No original data presented; all conclusions are expert opinion from a narrative review. Level of evidence is assigned as 7 (expert opinion/narrative review).","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"warning","value":"No specific patient population, sample size, or comparator group exists; age_group tag 'mixed' is inferred from the broad scope of the review rather than explicit reporting.","value_numeric":null},{"paper_doi":"10.1152/ajplung.00066.2026","tag_type":"warning","value":"The paper is dated April 2026 and references technologies that may still be preclinical or in early validation stages—clinical applicability is prospective.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates emerging technologies for functional biodesign in lung regeneration, focusing on platforms that couple engineered constructs (whole lung scaffolds, iPSC-derived models, organ-on-chip systems) with measurement tools—including dynamic imaging like crystal ribcage approaches—that assess native mechanics, perfusion, and immune dynamics under physiological load.","key_result":"The authors identify a central bottleneck: the field lacks broadly adopted platforms to test whether engineered or regenerative constructs restore lung *function* under physiological conditions, and argue that success should be judged by physiological performance rather than molecular or structural endpoints alone.","limitations":"This is a narrative review without systematic methods or meta-analysis, so conclusions reflect expert opinion rather than pooled evidence. No original experimental data are presented, and clinical translation benchmarks discussed (durability, infection resistance, mechanical integrity) remain aspirational rather than validated.","practice_takeaway":"Clinicians and researchers designing lung repair strategies should evaluate constructs against functional benchmarks—alveolar mechanics, capillary perfusion, immune surveillance—rather than relying solely on molecular or histological markers. Lessons from medical device translation (durability, infection resistance) should be incorporated as non-negotiable standards for regenerative therapies."}},{"doi":"10.22514/sv.2025.163","pmid":null,"title":"Antifibrotic therapy in patients with acute lung injury: a systematic review and meta-analysis","journal_title":"Signa Vitae","journal_issn":"1334-5605","published_at":"2025-12-08T00:00:00.000Z","url":"https://doi.org/10.22514/sv.2025.163","source_score":9,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-12-12","doi":"10.22514/sv.2025.163","days":"30","issn":"1334-5605","rank":"4","field":"Clinical Medicine","score":"9","category":"Emergency Medicine","categories":["Emergency Medicine"],"_categories":["Emergency Medicine"]},"pubmed":null,"crossref":{"DOI":"10.22514/sv.2025.163","URL":"https://doi.org/10.22514/sv.2025.163","ISSN":["1334-5605","1845-206X"],"page":"4","type":"journal-article","issue":null,"score":1,"title":["Antifibrotic therapy in patients with acute lung injury: a systematic review and meta-analysis"],"author":[{"given":"Nora Di","family":"Tomasso","sequence":"first","affiliation":[]}],"issued":{"date-parts":[[2025,12,8]]},"member":"26027","prefix":"10.22514","source":"Crossref","volume":null,"created":{"date-time":"2025-10-28T09:15:29Z","timestamp":1761642929000,"date-parts":[[2025,10,28]]},"indexed":{"date-time":"2025-12-09T07:26:49Z","timestamp":1765265209051,"date-parts":[[2025,12,9]]},"subject":[],"abstract":"$30","relation":{},"resource":{"primary":{"URL":"https://www.signavitae.com/articles/10.22514/sv.2025.163"}},"subtitle":[],"deposited":{"date-time":"2025-12-09T07:22:12Z","timestamp":1765264932000,"date-parts":[[2025,12,9]]},"issn-type":[{"type":"print","value":"1334-5605"},{"type":"electronic","value":"1845-206X"}],"published":{"date-parts":[[2025,12,8]]},"publisher":"MRE Press","reference":null,"short-title":[],"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["Signa Vitae"],"published-print":{"date-parts":[[2025,12,8]]},"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2025,12,8]]},"references-count":0,"short-container-title":["SV"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.22514/sv.2025.163","is_oa":true,"title":"Antifibrotic therapy in patients with acute lung injury: a systematic review and meta-analysis","updated":"2025-12-11T01:31:13+00:00","published_date":"2025-10-28","best_oa_location":{"url":"https://doi.org/10.22514/sv.2025.163","pmh_id":null,"url_for_pdf":null,"url_for_landing_page":"https://doi.org/10.22514/sv.2025.163"}}},"created_at":"2026-01-11T11:19:33.869Z","updated_at":"2026-01-11T11:19:33.869Z","tags":[{"paper_doi":"10.22514/sv.2025.163","tag_type":"category","value":"Emergency Medicine","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"condition","value":"Acute Lung Injury","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"condition","value":"COVID-19","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"generic","value":"nintedanib","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"generic","value":"pirfenidone","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"modality","value":"Antifibrotic","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"sample_size","value":"n=697","value_numeric":697},{"paper_doi":"10.22514/sv.2025.163","tag_type":"study_design","value":"Systematic Review and Meta-analysis","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"warning","value":"All included studies enrolled COVID-19 patients only; applicability to non-COVID ALI/ARDS is unclear.","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"warning","value":"All studies were rated high risk of bias and the GRADE certainty for mortality was low.","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"warning","value":"Designs were mixed (randomized and observational), and one study had imbalance in co-interventions (tocilizumab).","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"warning","value":"Radiologic and functional outcomes varied across studies and were not meta-analyzed.","value_numeric":null}],"summaries":{"what_studied":"Systematic review and meta-analysis of 6 studies (2 randomized, 2 propensity-matched, 2 case-control; total n=697) of antifibrotic therapy (pirfenidone or nintedanib) versus standard care in acute lung injury, all in COVID-19 patients, with searches through March 17, 2025. The primary outcome was all-cause mortality at the longest follow-up; secondary outcomes included length of stay and radiologic/functional measures.","key_result":"Across 4 studies reporting mortality (n=612), antifibrotics reduced deaths: 48/298 (16.1%) vs 75/314 (23.9%); OR 0.61 (95% CI 0.40–0.93), p=0.02; I2=40%; number needed to treat=13. Length of stay showed no difference (mean difference −0.98 days, 95% CI −7.36 to 5.39; p=0.57; I2=65%); individual studies reported improvements in CT scores, SpO2/FiO2, and spirometry with antifibrotics.","limitations":"All included studies were at high risk of bias, with mixed randomized and observational designs and low certainty of evidence for mortality. The evidence was limited to COVID-19 ALI, reducing generalizability to non-COVID ALI/ARDS. Radiologic and functional outcomes were heterogeneous and not pooled; one study had imbalance in tocilizumab use despite matching.","practice_takeaway":"In COVID-19–related acute lung injury, antifibrotic therapy was associated with lower mortality (NNT 13) but the certainty is low and all studies were high risk of bias; routine use should await well-designed randomized trials. No reduction in length of stay was seen; radiologic and functional improvements were reported only in individual small studies."}},{"doi":"10.1161/circresaha.125.326357","pmid":"41235428","title":"The Unexpected Protective Role of Thrombosis in Lung Injury via Endothelial Alox15","journal_title":"Circulation Research","journal_issn":"0009-7330","published_at":"2025-11-14T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12724588/","source_score":39,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-06","doi":"10.1161/circresaha.125.326357","days":"30","issn":"0009-7330","rank":"9","field":"Clinical Medicine","score":"39","category":"Hematology","categories":["Hematology"],"_categories":["Hematology"]},"pubmed":{"doi":"10.1161/CIRCRESAHA.125.326357","title":"The Unexpected Protective Role of Thrombosis in Lung Injury via Endothelial Alox15.","journal":"Circulation research","methods":"","results":"We show that although severe pulmonary thrombosis or thrombocytopenia augments sepsis-induced ALI, the induction of mild pulmonary thrombosis conversely reduces EC apoptosis, ALI, and mortality via sustained expression of endothelial Alox15. Endothelial ","abstract":"$31","keywords":["acute lung injury","endothelial cells","inflammation","lipids","sepsis","thrombosis"],"pubmed_id":"41235428","conclusions":"","publication_date":"2025-11-14T00:00:00"},"crossref":{"DOI":"10.1161/circresaha.125.326357","URL":"https://doi.org/10.1161/circresaha.125.326357","ISSN":["0009-7330","1524-4571"],"link":[{"URL":"https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.125.326357","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":"1","score":1,"title":["The Unexpected Protective Role of Thrombosis in Lung Injury via Endothelial Alox15"],"author":[{"given":"Colin E.","family":"Evans","sequence":"first","affiliation":[{"name":"Program for Lung and Vascular Biology (C.E.E., S.P.B., X.Z., N.M., K.D.A., Y.-Y.Z.), Ann & Robert H. Lurie Children’s Hospital of Chicago, IL."},{"name":"Section for Injury Repair and Regeneration Research, Stanley Manne Children’s Research Institute (C.E.E., S.P.B., X.Z., N.M., K.D.A., Y.-Y.Z.), Ann & Robert H. Lurie Children’s Hospital of Chicago, IL."},{"name":"Division of Critical Care, Department of Pediatrics (C.E.E., S.P.B., X.Z., N.M., K.D.A., Y.-Y.Z.), Northwestern University Feinberg School of Medicine, Chicago, IL."},{"name":"Now with Department of Cell Biology and Anatomy, Cardiovascular Translational Research Center, University of South Carolina School of Medicine, Columbia, SC (C.E.E.)."}]},{"given":"Sushreesangita P.","family":"Behera","sequence":"additional","affiliation":[{"name":"Program for Lung and Vascular Biology (C.E.E., S.P.B., X.Z., N.M., K.D.A., Y.-Y.Z.), Ann & Robert H. Lurie Children’s Hospital of Chicago, IL."},{"name":"Section for Injury Repair and Regeneration Research, Stanley Manne Children’s Research Institute (C.E.E., S.P.B., X.Z., N.M., K.D.A., Y.-Y.Z.), Ann & Robert H. Lurie Children’s Hospital of Chicago, IL."},{"name":"Pediatric Genetic Medicine and Nanotechnology Development Center (GeneMeNDer), Stanley Manne Children’s Research Institute (S.P.B., X.Z., N.M., K.D.A., Y.-Y.Z.), Ann & Robert H. Lurie Children’s Hospital of Chicago, IL."}]},{"given":"Xianming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Program for Lung and Vascular Biology (C.E.E., S.P.B., X.Z., N.M., K.D.A., Y.-Y.Z.), Ann & Robert H. Lurie Children’s Hospital of Chicago, IL."},{"name":"Section for Injury Repair and Regeneration Research, Stanley Manne Children’s Research Institute (C.E.E., S.P.B., X.Z., N.M., K.D.A., Y.-Y.Z.), Ann & Robert H. Lurie Children’s Hospital of Chicago, IL."},{"name":"Pediatric Genetic Medicine and Nanotechnology Development Center (GeneMeNDer), Stanley Manne Children’s Research Institute (S.P.B., X.Z., N.M., K.D.A., Y.-Y.Z.), Ann & Robert H. Lurie Children’s Hospital of Chicago, IL."},{"name":"Division of Critical Care, Department of Pediatrics (C.E.E., S.P.B., X.Z., N.M., K.D.A., Y.-Y.Z.), Northwestern University Feinberg School of Medicine, Chicago, IL."}]},{"given":"Narsa","family":"Machireddy","sequence":"additional","affiliation":[{"name":"Program for Lung and Vascular Biology (C.E.E., S.P.B., X.Z., N.M., K.D.A., Y.-Y.Z.), Ann & Robert H. Lurie Children’s Hospital of Chicago, IL."},{"name":"Section for Injury Repair and Regeneration Research, Stanley Manne Children’s Research Institute (C.E.E., S.P.B., X.Z., N.M., K.D.A., Y.-Y.Z.), Ann & Robert H. 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Endothelial-targeted nanoparticles delivered CRISPR/Cas9 or Alox15 plasmids for endothelial cell–specific Alox15 knockout or overexpression; lipidomic profiling and in vivo rescue with Alox15-regulated lipids were performed, and thrombocytopenia was modeled by genetic platelet depletion.","key_result":"Mild pulmonary thrombosis reduced endothelial apoptosis, acute lung injury, and mortality via sustained endothelial Alox15 expression, whereas severe thrombosis or thrombocytopenia worsened sepsis-induced lung injury. Endothelial Alox15 overexpression attenuated the increase in lung injury caused by severe thrombosis.","limitations":"Findings are from mouse models (microbead thrombosis, LPS/CLP sepsis, genetic thrombocytopenia) and may not generalize to humans. 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