Hospital exposome and physiological resilience are associated with postoperative delirium, major complications, and long-term cognitive decline in older adults undergoing cancer surgery: A prospective multidomain cohort study.

BACKGROUND: Postoperative delirium (POD) and long-term cognitive decline remain frequent and incompletely explained complications in older adults undergoing cancer surgery. Hospital environmental exposures (exposomes) may be associated with age-related physiological vulnerability, yet prospective evidence integrating ward-level exposome data with multidomain physiological resilience is limited. OBJECTIVE: To examine the associations of hospital environmental burden and physiological resilience with POD, major complications, cognitive trajectories, and long-term oncologic outcomes. DESIGN: Prospective observational cohort study (hypothesis-generating; prespecified statistical analysis plan provided). SETTING: Tertiary academic hospital gastrointestinal surgical wards. PATIENTS: A total of 420 patients aged ≥60 years undergoing elective gastrointestinal cancer surgery. EXPOSURES: Bed-level nocturnal environmental exposures (noise, light, and care interruptions) and multidomain physiological measures integrating sleep-circadian regulation, autonomic variability, inflammatory reactivity, and gut microbial-metabolic profiles. MAIN OUTCOME MEASURES: POD, clinically significant postoperative complications, longitudinal cognitive trajectories, assessed at predefined follow-up time points, and disease-free and overall survival up to 36 months. RESULTS: POD occurred in 21.4% of patients. Higher hospital environmental burden was independently associated, after multivariable adjustment, with increased odds of delirium [adjusted odds ratio (OR) 1.78 per standard deviation (SD) increase, 95% confidence interval (CI) 1.35 to 2.34] and postoperative complications, whereas higher physiological resilience was associated with lower risk of these outcomes (adjusted OR 0.62, 95% CI 0.48 to 0.81 for POD). Exploratory analyses further showed graded associations of the integrated exposome-resilience profile with delirium incidence, longitudinal cognitive decline, and disease-free survival. Mediation analyses were statistically consistent with partial mediation of the associations between environmental burden and postoperative outcomes by physiological resilience; these findings are exploratory and do not imply causal or mechanistic relationships. CONCLUSIONS: In this single-centre prospective observational cohort study, hospital environmental burden and multidomain physiological resilience were associated with postoperative vulnerability in older adults undergoing cancer surgery. These findings support a conceptual framework linking ward-level environmental exposures and physiological regulatory capacity to postoperative brain health but should be considered hypothesis-generating and require external validation.