eP803 - Generating Intervenable Markers of Frailty in Colorectal Surgery Patients

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Purpose/Background: Older colorectal surgical patients are a growing and heterogeneous population. Accumulation of vulnerabilities and impairments culminates in frailty, a complex condition of decline of reserve across multiple physiologic systems. Frailty is strongly associated with poor outcomes from colorectal surgery and can be modified with pre-habilitation. At the biologic level, preliminary data indicate that frailty can be studied as a metabolic phenomenon, reflecting the deterioration of multiple biochemical pathways. The overall goal of this pilot study is to identify postoperative metabolic pathway disruptions in frail colorectal surgical patients and analyze the effect of pre-habilitation on those pathways.Methods/Interventions: To test our central hypothesis that frail patients have unique and potentially modifiable postoperative metabolic derangements, we have created a prospective observational study of adults over age 69 undergoing elective intra-abdominal colorectal surgery. Patients are referred to established geriatric preoptimization clinic at the discretion of the surgeon. Participants are assessed for frailty using three metrics: electronic rapid fitness assessment (eRFA), G8 geriatric screening tool, and the Flemish Triage Risk Screening Tool (fTRST). These tools identify patients as frail versus robust for comparison. Plasma samples are collected at baseline, after pre-habilitation (if completed), at post-operative day two, and at post-operative weeks 3-6. Additionally, an intra-operative muscle biopsy is obtained. Untargeted plasma metabolomic analysis will be performed on these samples. Identified metabolites will be mapped to biochemical pathways and differences compared longitudinally and between frail and robust groups.Results/Outcomes: From study inception to January 1, 2024, 17 patients have been enrolled with an average age of 74. The most common diagnosis code being managed includes ascending colon cancer. Untargeted metabolomics analysis will be completed following recruitment of 30 patients. Of the enrolled patients, most (66%) are independent in their ADLs and iADLs, the average G8 score is 13, and the average fTRST is 2.Conclusion/

Discussion: Untargeted metabolomic analysis has the potential to identify unique post-operative metabolic pathway dysregulations in frail patients. This work unites longstanding research on the physiologic stress of surgery, elevated surgical risk in frail patients, and appreciation of frailty as a metabolic derangement. Outcomes could identify potential biomarkers and therapeutic targets. These innovations would help close the gap in outcomes between frail and robust older surgical patients.