• Jillian W Bonaroti, Mehves Ozel, Tianmeng Chen, Jennifer L Darby, Xuejing Sun, Hamed Moheimani, Katherine M Reitz, Upendra K Kar, Brian S Zuckerbraun, Jishnu Das, David O Okonkwo, and Timothy R Billiar.
• From the Department of Surgery (Bonaroti, Ozel, Chen, Darby, Sun, Moheimani, Reitz, Kar, Zuckerbraun, Billiar), University of Pittsburgh, Pittsburgh, PA.
• J. Am. Coll. Surg. 2024 May 1; 238 (5): 924941924-941.

BackgroundMajor surgery triggers trauma-like stress responses linked to age, surgery duration, and blood loss, resembling polytrauma. This similarity suggests elective surgery as a surrogate model for studying polytrauma immune responses. We investigated stress responses across age groups and compared them with those of polytrauma patients.Study DesignPatients undergoing major spinal reconstruction surgery were divided into older (age >65 years, n = 5) and young (age 18 to 39 years, n = 6) groups. A comparison group consisted of matched trauma patients (n = 8). Blood samples were collected before, during, and after surgery. Bone marrow mononuclear cells and peripheral blood mononuclear cells were analyzed using cellular indexing of transcriptomes and epitopes sequencing or single-cell RNA sequencing. Plasma was subjected to dual-platform proteomic analysis (SomaLogic and O-link).ResultsResponse to polytrauma was highest within 4 hours. By comparison, the response to surgery was highest at 24 hours. Both insults triggered significant changes in cluster of differentiation 14 monocytes, with increased inflammation and lower major histocompatibility complex-class 2 expression. Older patient's cluster of differentiation 14 monocytes displayed higher inflammation and less major histocompatibility complex-class 2 suppression; a trend was also seen in bone marrow mononuclear cells. Although natural killer cells were markedly activated after polytrauma, they were suppressed after surgery, especially in older patients. In plasma, innate immunity proteins dominated at 24 hours, shifting to adaptive immunity proteins by 6 weeks with heightened inflammation in older patients. Senescence-associated secretory phenotype proteins were higher in older patients at baseline and further elevated during and after surgery.ConclusionsAlthough both major surgery and polytrauma initiate immune and stress responses, substantial differences exist in timing and cellular profiles, suggesting major elective surgery is not a suitable surrogate for the polytrauma response. Nonetheless, distinct responses in young vs older patients highlight the utility of elective spinal in studying patient-specific factors affecting outcomes after major elective surgery.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Surgeons.

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