Immune Modulation by Personalized vs Standard Prehabilitation Before Major Surgery: A Randomized Clinical Trial.

Summary

This single-blinded randomized trial shows that personalized prehabilitation improved preoperative physical function and reduced moderate-to-severe postoperative complications compared with a standard program. Mass cytometry revealed dampened inflammatory signaling across specific innate and adaptive immune cell subsets only in the personalized group, suggesting a biologically meaningful effect.

Key Findings

• Personalized prehabilitation improved 6MWT performance (median 496 to 546; P=.03).
• Moderate-to-severe postoperative complications were fewer with personalized prehabilitation (4 vs 11; P=.04).
• Mass cytometry showed dampened inflammatory signaling (e.g., phosphorylated ERK1/2 after IL-2/4/6; reduced pCREB in Th1) only in the personalized group (AUROC 0.88; P<.001).

Clinical Implications

Personalized prehabilitation should be considered for integration into perioperative pathways, with potential for immune-based monitoring to tailor intensity. Programs may reduce complications while improving surgical readiness.

Limitations

• Single-center study with modest sample size.
• Blinding limited to single-blind; durability of effects beyond the immediate postoperative period not reported.

Future Directions

Multicenter RCTs with larger samples to validate clinical benefits, define optimal components/intensity, and test immune-based monitoring for adaptive personalization.