{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T21:19:02Z","timestamp":1781039942303,"version":"3.54.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"7-8","license":[{"start":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T00:00:00Z","timestamp":1703635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100013132","name":"Combat Casualty Care Research Program","doi-asserted-by":"publisher","award":["K_030_2020"],"award-info":[{"award-number":["K_030_2020"]}],"id":[{"id":"10.13039\/100013132","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013132","name":"Combat Casualty Care Research Program","doi-asserted-by":"publisher","award":["K_030_2020"],"award-info":[{"award-number":["K_030_2020"]}],"id":[{"id":"10.13039\/100013132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>If left untreated, burn injuries can deepen or progress in depth within the first 72\u2009hours after injury as a result of increased wound inflammation, subsequently worsening healing outcomes. This can be especially detrimental to warfighters who are constrained to resource-limited environments with delayed evacuation times to higher roles of care and more effective treatment. Preventing this burn progression at the point of injury has the potential to improve healing outcomes but requires a field-deployable therapy and delivery system. Subcutaneous therapies known to treat inflammation delivered local to the wound site may prove to be one such avenue for success.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>Seven Yorkshire-cross swine received partial-thickness burn injuries using a previously established contact burn model. Each animal received one of the seven therapies: (1) saline, (2) heparin, (3) ibuprofen, (4) erythropoietin, (5) resolvin, (6) rapamycin, and (7) placental extract, all of which are either currently employed or are experimental in field use and indicated to treat inflammation. Treatments were delivered subcutaneously on the day of injury and 24\u2009hours post-injury to simulate a prolonged field care scenario, before potential evacuation. Animals and wound development were observed for 28\u2009days before euthanasia. Throughout the course of the study, wounds were observed macroscopically via non-invasive imaging. Histological analyses provided the critical metric of burn progression. Treatment success criteria were designated as the ability to prevent burn progression past 80% of the dermal depth in two of the three treated wounds, a clinically relevant metric of burn progression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>It was determined that the applied model successfully created reproducible partial-thickness burn injuries in this porcine study. No significant differences with regard to lateral wound size or the rate of lateral wound closure were observed in any treatments. Several treatments including resolvin, rapamycin, ibuprofen, and erythropoietin successfully reduced burn progression to less than 80% of the dermal depth in two of the three wounds, 24\u2009hours after injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This report employs an established model of porcine contact burn injury in order to test the ability of local subcutaneous delivery of therapeutics to prevent burn progression at the point of injury, via what is believed to be the inhibition of inflammation. Several treatments successfully prevented burn progression to a full-thickness injury, potentially improving wound healing outcomes in a simulated battlefield scenario. Subcutaneously administered therapies combating burn-induced inflammation at the point of injury may serve as a field-deployable treatment modality to improve warfighter recovery and return to duty.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/milmed\/usad476","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T18:01:11Z","timestamp":1703700071000},"page":"1423-1431","source":"Crossref","is-referenced-by-count":3,"title":["Subcutaneous Anti-inflammatory Therapies to Prevent Burn Progression in\u00a0a Swine Model of\u00a0Contact Burn Injury"],"prefix":"10.1093","volume":"189","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6688-6770","authenticated-orcid":false,"given":"Marc A","family":"Thompson","sequence":"first","affiliation":[{"name":"Combat Wound Care, US Army Institute of Surgical Research , JBSA Fort Sam Houston, TX 78234,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Shaffer","sequence":"additional","affiliation":[{"name":"Combat Wound Care, US Army Institute of Surgical Research , JBSA Fort Sam Houston, TX 78234,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Larson","sequence":"additional","affiliation":[{"name":"Combat Wound Care, US Army Institute of Surgical Research , JBSA Fort Sam Houston, TX 78234,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Stavena-Holik","sequence":"additional","affiliation":[{"name":"Combat Wound Care, US Army Institute of Surgical Research , JBSA Fort Sam Houston, TX 78234,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Nail","sequence":"additional","affiliation":[{"name":"Combat Wound Care, US Army Institute of Surgical Research , JBSA Fort Sam Houston, TX 78234,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan","family":"Leatherman","sequence":"additional","affiliation":[{"name":"Combat Wound Care, US Army Institute of Surgical Research , JBSA Fort Sam Houston, TX 78234,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Tomblyn","sequence":"additional","affiliation":[{"name":"Plakous Therapeutics LLC , Winston-Salem, NC 27103,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Burnett","sequence":"additional","affiliation":[{"name":"Keranetics Inc. , Winston-Salem, NC 27101,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Trauma Research, Brooke Army Medical Center , JBSA Fort Sam Houston, TX 78234,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Christy","sequence":"additional","affiliation":[{"name":"Combat Wound Care, US Army Institute of Surgical Research , JBSA Fort Sam Houston, TX 78234,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine J","family":"Kowalczewski","sequence":"additional","affiliation":[{"name":"Combat Wound Care, US Army Institute of Surgical Research , JBSA Fort Sam Houston, TX 78234,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,27]]},"reference":[{"issue":"2","key":"2024122701013350800_R1","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.jss.2006.02.043","article-title":"Comparison of\u00a0combat and\u00a0non-combat burns from ongoing U.S. military operations","volume":"132","author":"Kauvar","year":"2006","journal-title":"J Surg Res"},{"issue":"6","key":"2024122701013350800_R2","doi-asserted-by":"publisher","DOI":"10.1097\/01.sla.0000219645.88867.b7","article-title":"Comparison between civilian burns and\u00a0combat burns from Operation Iraqi Freedom and\u00a0Operation Enduring Freedom","volume":"243","author":"Wolf","year":"2006","journal-title":"Ann Surg"},{"issue":"2","key":"2024122701013350800_R3","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1007\/s40719-017-0088-9","article-title":"Military resuscitation: lessons from recent battlefield experience","volume":"3","author":"Davis","year":"2017","journal-title":"Curr Trauma Rep"},{"key":"2024122701013350800_R4","first-page":"1","article-title":"Burns: dressings","volume":"2015","author":"Wasiak","year":"2015","journal-title":"BMJ Clin Evid"},{"issue":"6 Suppl 5","key":"2024122701013350800_R5","doi-asserted-by":"publisher","first-page":"S409","DOI":"10.1097\/TA.0b013e318275499f","article-title":"The US Army burn center: professional service during 10 years of\u00a0war","volume":"73","author":"Renz","year":"2012","journal-title":"J Trauma Acute Care Surg"},{"issue":"6","key":"2024122701013350800_R6","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1097\/BCR.0b013e3181f93571","article-title":"A review of\u00a0the local pathophysiologic bases of\u00a0burn wound progression","volume":"31","author":"Shupp","year":"2010","journal-title":"J Burn Care Res"},{"issue":"suppl_1","key":"2024122701013350800_R7","doi-asserted-by":"publisher","first-page":"S240","DOI":"10.1093\/jbcr\/iry006.457","article-title":"534 assessment of\u00a0the first 30 hours of\u00a0burn progression in\u00a0a porcine burn model","volume":"39","author":"Kowalczewski","year":"2018","journal-title":"J Burn Care Res"},{"issue":"1","key":"2024122701013350800_R8","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1097\/01.sap.0000252065.90759.e6","article-title":"The pathogenesis of\u00a0burn wound conversion","volume":"59","author":"Singh","year":"2007","journal-title":"Ann Plast Surg"},{"issue":"6","key":"2024122701013350800_R9","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1111\/j.1524-475X.2012.00847.x","article-title":"Histopathologic staining of\u00a0low temperature cutaneous burns: comparing biomarkers of\u00a0epithelial and\u00a0vascular injury reveals utility of\u00a0HMGB1 and\u00a0hematoxylin phloxine saffron","volume":"20","author":"Hirth","year":"2012","journal-title":"Wound Repair Regen"},{"issue":"7457","key":"2024122701013350800_R10","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1136\/bmj.329.7457.101","article-title":"Initial management of\u00a0a major burn: II\u2014assessment and\u00a0resuscitation","volume":"329","author":"Hettiaratchy","year":"2004","journal-title":"BMJ"},{"key":"2024122701013350800_R11","first-page":"509","article-title":"An electrospun poly-ethylene oxide\/cerium (III) nitrate dressing for\u00a0delayed debridement and\u00a0improved wound healing of\u00a0warfighter contact burns","volume":"2(6)","author":"Thompson","year":"2021","journal-title":"J ISSN"},{"issue":"5","key":"2024122701013350800_R12","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1093\/jbcr\/iraa111","article-title":"Enzymatic debridement of\u00a0porcine burn wounds via a novel protease, SN514","volume":"41","author":"Stone","year":"2020","journal-title":"J Burn Care Res"},{"issue":"3","key":"2024122701013350800_R13","doi-asserted-by":"publisher","first-page":"e176","DOI":"10.1097\/BCR.0000000000000131","article-title":"Treatment of\u00a0secondary burn wound progression in\u00a0contact burns\u2014a systematic review of\u00a0experimental approaches","volume":"36","author":"Schmauss","year":"2015","journal-title":"J Burn Care Res"},{"issue":"7","key":"2024122701013350800_R14","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1097\/00006534-199406000-00021","article-title":"Reduction of\u00a0burn injury by inhibiting CD18-mediated leukocyte adherence in\u00a0rabbits","volume":"93","author":"Bucky","year":"1994","journal-title":"Plast Reconst Surg"},{"issue":"1","key":"2024122701013350800_R15","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S0305-4179(96)00079-4","article-title":"Effects of\u00a0allopurinol, ibuprofen and\u00a0cyclosporin A on\u00a0local microcirculatory disturbances due to burn injuries","volume":"23","author":"Cetinkale","year":"1997","journal-title":"Burns"},{"issue":"4","key":"2024122701013350800_R16","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/0022-4804(92)90112-D","article-title":"Inhibition of\u00a0leukocyte-endothelial adherence following thermal injury","volume":"52","author":"Mileski","year":"1992","journal-title":"J Surg Res"},{"issue":"3","key":"2024122701013350800_R17","first-page":"123","article-title":"Low molecular weight heparin-induced pharmacological modulation of\u00a0burn wound healing","volume":"19","author":"Ravikumar","year":"2006","journal-title":"Ann Burn Fire Disasters"},{"key":"2024122701013350800_R18","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/B978-0-12-385061-4.00009-X","article-title":"Cardiovascular effects of\u00a0erythropoietin an update","volume":"60","author":"Santhanam","year":"2010","journal-title":"Adv Pharmacol"},{"issue":"4","key":"2024122701013350800_R19","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1097\/CCM.0b013e318275cee7","article-title":"Secondary burn progression decreased by erythropoietin","volume":"41","author":"Tobalem","year":"2013","journal-title":"Crit Care Med Apr"},{"issue":"9","key":"2024122701013350800_R20","doi-asserted-by":"publisher","first-page":"3513","DOI":"10.1073\/pnas.1214099110","article-title":"Alternative erythropoietin-mediated signaling prevents secondary microvascular thrombosis and\u00a0inflammation within cutaneous burns","volume":"110","author":"Bohr","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"2024122701013350800_R21","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/j.1524-475X.2012.00853.x","article-title":"Resolvin D2 prevents secondary thrombosis and\u00a0necrosis in\u00a0a mouse burn wound model","volume":"21","author":"Bohr","year":"2013","journal-title":"Wound Repair Regen"},{"issue":"1","key":"2024122701013350800_R22","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/cbin.10345","article-title":"Roles of\u00a0resolvins in\u00a0the resolution of\u00a0acute inflammation","volume":"39","author":"Qu","year":"2015","journal-title":"Cell Biol Int"},{"issue":"3","key":"2024122701013350800_R23","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.cmet.2014.01.001","article-title":"Rapamycin: one drug, many effects","volume":"19","author":"Li","year":"2014","journal-title":"Cell Metab"},{"issue":"6","key":"2024122701013350800_R24","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1111\/wrr.12090","article-title":"Rapamycin reduces burn wound progression by enhancing autophagy in\u00a0deep second-degree burn in\u00a0rats","volume":"21","author":"Xiao","year":"2013","journal-title":"Wound Repair Regen"},{"issue":"2","key":"2024122701013350800_R25","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1093\/jrr\/rrs105","article-title":"Placental extract protects bone marrow-derived stem\/progenitor cells against radiation injury through anti-inflammatory activity","volume":"54","author":"Kawakatsu","year":"2013","journal-title":"J Radiat Res"},{"issue":"3","key":"2024122701013350800_R26","doi-asserted-by":"publisher","first-page":"155","DOI":"10.5001\/omj.2010.49","article-title":"An overview of\u00a0clinical pharmacology of\u00a0ibuprofen","volume":"25","author":"Bushra","year":"2010","journal-title":"Oman Med J"},{"issue":"4","key":"2024122701013350800_R27","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/S0305-4179(99)00168-0","article-title":"Ibuprofen modulates tissue perfusion in\u00a0partial-thickness burns","volume":"26","author":"Barrow","year":"2000","journal-title":"Burns"},{"issue":"6","key":"2024122701013350800_R28","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1016\/j.burns.2015.03.001","article-title":"Utility of\u00a0spatial frequency domain imaging (SFDI) and\u00a0laser speckle imaging (LSI) to non-invasively diagnose burn depth in\u00a0a porcine model","volume":"41","author":"Burmeister","year":"2015","journal-title":"Burns"},{"issue":"2","key":"2024122701013350800_R29","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1177\/0300985811402846","article-title":"Swine as models in\u00a0biomedical research and\u00a0toxicology testing","volume":"49","author":"Swindle","year":"2012","journal-title":"Vet Pathol"},{"issue":"3","key":"2024122701013350800_R30","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1111\/jocd.12142","article-title":"The effect of\u00a0CO2 laser treatment on\u00a0skin tissue","volume":"14","author":"Baleg","year":"2015","journal-title":"J Cosmet Dermatol"},{"issue":"1","key":"2024122701013350800_R31","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/sj.cdd.4402060","article-title":"Caspase function in\u00a0programmed cell death","volume":"14","author":"Kumar","year":"2007","journal-title":"Cell Death Differ"},{"issue":"2","key":"2024122701013350800_R32","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","article-title":"Emerging roles of\u00a0caspase-3 in\u00a0apoptosis","volume":"6","author":"Porter","year":"1999","journal-title":"Cell Death Differ"},{"issue":"1","key":"2024122701013350800_R33","doi-asserted-by":"publisher","first-page":"40","DOI":"10.3390\/biology10010040","article-title":"Experimental study of\u00a0burn damage progression in\u00a0a human composite tissue model","volume":"10","author":"Hao","year":"2021","journal-title":"Biology"},{"issue":"2","key":"2024122701013350800_R34","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1111\/cts.12930","article-title":"Predicting resolvin D1 pharmacokinetics in\u00a0humans with physiologically-based pharmacokinetic modeling","volume":"14","author":"Yellepeddi","year":"2021","journal-title":"Clin Transl Sci"},{"issue":"4","key":"2024122701013350800_R35","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/BF00685908","article-title":"Dose-dependent pharmacokinetics of\u00a0rapamycin-28-N, N-dimethylglycinate in\u00a0the mouse","volume":"33","author":"Supko","year":"1994","journal-title":"Cancer Chemother Pharmacol"},{"key":"2024122701013350800_R36","doi-asserted-by":"publisher","first-page":"67","DOI":"10.2147\/JPR.S6993","article-title":"Intravenous ibuprofen: the first injectable product for\u00a0the treatment of\u00a0pain and\u00a0fever","volume":"3","author":"Bookstaver","year":"2010","journal-title":"J Pain Res"},{"issue":"2","key":"2024122701013350800_R37","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1345\/aph.1G425","article-title":"Erythropoietin dose requirements when converting from subcutaneous to intravenous administration among patients on\u00a0hemodialysis","volume":"40","author":"Moist","year":"2006","journal-title":"Ann Pharmacother"},{"issue":"5","key":"2024122701013350800_R38","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1016\/j.xphs.2018.01.007","article-title":"Challenges and\u00a0opportunities for\u00a0the subcutaneous delivery of\u00a0therapeutic proteins","volume":"107","author":"Turner","year":"2018","journal-title":"J Pharm Sci"},{"issue":"5","key":"2024122701013350800_R39","doi-asserted-by":"publisher","first-page":"222","DOI":"10.12968\/jowc.2006.15.5.26910","article-title":"Effect of\u00a0enzymatic debridement with collagenase on\u00a0acute and\u00a0chronic hard-to-heal wounds","volume":"15","author":"Marazzi","year":"2006","journal-title":"J Wound Care"},{"issue":"Sup5","key":"2024122701013350800_R40","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.12968\/bjcn.2003.8.Sup5.12607","article-title":"Understanding exudate management and\u00a0the role of\u00a0exudate in\u00a0the healing process","volume":"8","author":"Vowden","year":"2003","journal-title":"Br J Community Nurs"}],"container-title":["Military Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/milmed\/article-pdf\/189\/7-8\/1423\/58435522\/usad476.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/milmed\/article-pdf\/189\/7-8\/1423\/58435522\/usad476.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T01:01:38Z","timestamp":1735261298000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/milmed\/article\/189\/7-8\/1423\/7502679"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,27]]},"references-count":40,"journal-issue":{"issue":"7-8","published-online":{"date-parts":[[2023,12,27]]},"published-print":{"date-parts":[[2024,7,3]]}},"URL":"https:\/\/doi.org\/10.1093\/milmed\/usad476","relation":{},"ISSN":["0026-4075","1930-613X"],"issn-type":[{"value":"0026-4075","type":"print"},{"value":"1930-613X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,7]]},"published":{"date-parts":[[2023,12,27]]}}}