Supplementary Material for: Integrative Psychological Support and PNI-Guided Early Enteral Nutrition Enhance Sleep, Nutritional Recovery, and Quality of Life After Curative Colorectal Cancer Surgery: A Randomized Controlled Trial

Background: Despite advances in enhanced recovery after surgery (ERAS), many colorectal cancer (CRC) patients continue to experience sleep disturbance, nutritional decline, pain, and psychological distress. Evidence on integrated psychobehavioral and immunonutritional strategies remains limited. Methods: In this single-center randomized controlled trial, 260 patients with stage I–III CRC undergoing elective curative resection were randomized (1:1) to receive standard ERAS care or an integrative program. The intervention comprised five structured sessions of resilience-oriented psychological support (two preoperatively, three postoperatively) and prognostic nutritional index (PNI)-guided early enteral nutrition (standard formula for PNI ≥45; ω-3/probiotic-enriched immunonutrition for PNI <45). The primary endpoint was global Pittsburgh Sleep Quality Index (PSQI) score at postoperative day (POD) 15. Secondary endpoints included nutritional biomarkers, pain, anxiety and depression, and health-related quality of life (HRQoL). Exploratory endpoints were C-reactive protein (CRP) and interleukin-6 (IL-6). Results: Of 298 screened, 260 were randomized and 240 completed per protocol. Adherence exceeded 90% with no serious adverse events. At POD15, the intervention group had lower PSQI scores (adjusted mean difference –2.4; 95% CI –3.2 to –1.6; p<0.001), with improvements in latency, disturbance, and daytime dysfunction. Nutritional recovery was enhanced (albumin +2.8 g/L, prealbumin +20.4 mg/L, transferrin +0.3 g/L, PⅢNP +15.2 ng/mL; all p<0.05). Pain and opioid use were reduced (VAS POD3 –1.5; opioids –30 mg, both p<0.001). Anxiety and depression scores improved (SAS –5.8, SDS –6.1; p<0.001), alongside clinically meaningful HRQoL gains in global health (+8.7), physical (+7.2), and emotional functioning (+6.5). Subgroup analyses confirmed consistent benefits, while CRP (–4.8 mg/L) and IL-6 (–3.1 pg/mL) were lower in the intervention group. Conclusions: Integrative perioperative care combining psychological support with PNI-guided early enteral nutrition is safe, feasible, and effective in improving sleep, nutritional recovery, pain control, psychological well-being, and quality of life after CRC surgery.