Using single-cell immune profiling, researchers identified delivery-specific differences in preoperative immune signaling that distinguished personalized from standard prehabilitation approaches, according to a recent randomized clinical trial published in JAMA Surgery.
Immune profiles collected before surgery differed significantly only among patients who received a personalized, remotely coached intervention, suggesting that how prehabilitation is delivered may shape biological readiness for surgery.
In the trial, patients assigned to personalized prehabilitation also demonstrated broader improvements in physical and cognitive function before surgery and experienced fewer moderate to severe postoperative complications than those who followed a standard, paper-based program. These functional and clinical outcomes were reported alongside immune findings showing cell type–specific modulation of intracellular signaling pathways implicated in perioperative inflammation.
The single-center, single-blinded trial enrolled 58 adults scheduled for major elective surgery and randomized them to standard prehabilitation (n = 30) or personalized prehabilitation (n = 28) delivered 2 to 6 weeks before surgery. Fifty-four patients completed the study and were included in paired preintervention and postintervention analyses. Standard prehabilitation consisted of a paper-based program addressing physical activity, nutrition, cognitive training, and stress reduction without individualized follow-up. The personalized intervention incorporated twice-weekly one-on-one remote coaching sessions tailored to individual progress across the same four domains.
Patients assigned to personalized prehabilitation demonstrated significant preoperative functional improvements. Median 6-minute walk test distance increased from 496 meters before prehabilitation to 546 meters after prehabilitation. Timed up-and-go performance improved from a median of 9 seconds to 6.9 seconds, and wall squat duration increased from 37.4 seconds to 66.2 seconds. Cognitive performance also improved, with median Quick Mild Cognitive Impairment scores increasing from 66 to 72. In contrast, patients in the standard group showed improvement only in 6-minute walk test distance, with no significant gains in other physical or cognitive measures.
Postoperative outcomes favored the personalized approach. Fewer patients in the personalized group experienced moderate to severe postoperative complications, defined as Clavien-Dindo grade greater than one, compared with the standard group (4 vs 11 patients). Hospital length of stay did not differ significantly between groups.
Peripheral immune modulation was assessed using a 47-parameter single-cell mass cytometry immunoassay. Multivariable machine learning models reliably distinguished immune profiles before and after prehabilitation in the personalized group but not in the standard group. Personalized prehabilitation was associated with cell type–specific dampening of proinflammatory intracellular signaling, including reduced protein kinase R-like endoplasmic reticulum kinase signaling in classical monocytes and myeloid-derived suppressor cells and altered phosphorylated cyclic adenosine monophosphate response–element binding protein signaling in multiple T-cell subsets.
The researchers noted several limitations. All patients received prehabilitation, precluding comparison with no intervention. The study was conducted at a single academic center with a modest sample size, and heterogeneity in surgical procedures may have introduced outcome variability despite randomization. In addition, the targeted mass cytometry approach required preselection of immune markers, potentially limiting detection of broader biological changes. Larger multicenter trials using complementary omics strategies are needed to validate these findings and inform scalable, biologically driven prehabilitation pathway design.
“Identification of cell-specific immune features reliably modulated in the personalized prehabilitation group provides a promising set of immune biomarkers that may form the foundation for immune-based diagnostics to identify high-risk patients most likely to benefit from personalized prehabilitation,” noted author Amélie Cambriel, MD, of the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University School of Medicine in California, and in the Department of Anesthesiology and Critical Care at Hôpital Saint-Antoine and the Centre de Recherche Saint-Antoine at Sorbonne Université–Inserm in Paris, France, and colleagues.
Disclosures can be found in the study.
Source: JAMA Surgery
