{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T13:48:54Z","timestamp":1762264134783,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the U.S. Army Medical Research and Development Command, Military Infection Disease Research Programs","award":["MI220039"],"award-info":[{"award-number":["MI220039"]}]},{"name":"an appointment to the Department of Defense (DOD) Research Participation Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Background\/Objectives: Extremity trauma represents a significant proportion of battlefield injuries and is prevalent in polytraumatized patients from accidents. Delayed antibiotic treatment and surgical intervention can lead to wound infections, contributing to preventable mortality. This preliminary study aimed to develop a conscious swine model of complex extremity trauma that induces systemic inflammatory response syndrome (SIRS). Methods: All surgical procedures were conducted under anesthesia with sufficient analgesia. All swine were instrumented with a telemetry device and catheters at least 3 days prior to any injury. In phase 1 of model development, a complex extremity injury was performed that consisted of skin and muscle loss, bone defect, severe hemorrhage, and 2 h tourniquet application. In phase 2, multi-drug resistant Gram-positive and Gram-negative bacteria were inoculated topically at the injury site to exacerbate pathophysiological changes towards SIRS. Post-injury, conscious animals were assessed a minimum of twice daily, including pain assessment, neurological response, and vital signs. Blood samples were collected for microbiological testing, complete blood cell counts, and biochemical analysis. Results: After establishing SIRS criteria for Sinclair swine, we developed a model of severe extremity trauma leading to SIRS. During phase 1, resuscitative fluids were reduced and discontinued, with animals surviving 24 h and maintaining SIRS for up to 4 h post-recovery. Phase 2 showed that Gram-negative and Gram-positive pathogens can exacerbate and prolong SIRS. After 72 h, localized infection at the injury site was observed in all animals. Conclusions: We established a new swine model of complex extremity trauma with SIRS. Our model is consistent, reproducible, and relevant to prolonged care scenarios, providing a platform for future research into the evaluation of preventative and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/pathophysiology32040059","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T12:13:08Z","timestamp":1762258388000},"page":"59","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polymicrobial Infection (Gram-Positive and Gram-Negative) Exacerbates Systemic Inflammatory Response Syndrome in a Conscious Swine Extremity Trauma Model"],"prefix":"10.3390","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9116-2838","authenticated-orcid":false,"given":"Catharina C.","family":"Gaeth","sequence":"first","affiliation":[{"name":"Combat Wound Care, United States Army Institute of Surgical Research, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0182-1949","authenticated-orcid":false,"given":"Travis R.","family":"Madaris","sequence":"additional","affiliation":[{"name":"Combat Wound Care, United States Army Institute of Surgical Research, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamila M.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Combat Wound Care, United States Army Institute of Surgical Research, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber M.","family":"Powers","sequence":"additional","affiliation":[{"name":"Combat Wound Care, United States Army Institute of Surgical Research, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina M.","family":"Sandoval","sequence":"additional","affiliation":[{"name":"Combat Wound Care, United States Army Institute of Surgical Research, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie M.","family":"Shiels","sequence":"additional","affiliation":[{"name":"Combat Wound Care, United States Army Institute of Surgical Research, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6000-3524","authenticated-orcid":false,"suffix":"II","given":"Randolph","family":"Stone","sequence":"additional","affiliation":[{"name":"Combat Wound Care, United States Army Institute of Surgical Research, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e107","DOI":"10.1097\/BOT.0b013e3182703188","article-title":"The nature and incidence of musculoskeletal combat wounds in Iraq and Afghanistan (2005\u20132009)","volume":"27","author":"Belmont","year":"2013","journal-title":"J. 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