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Article Abstract

Background: Inflammation is a key driver of disease-related malnutrition and patients with high inflammation may not show the same benefits from nutritional therapy as other patients. We compared in an exploratory manner the prognostic ability of interleukin- 6 (IL- 6), tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) to predict outcome and response to nutritional therapy, respectively, within a large cohort of patients from a previous nutritional trial.

Methods: This is a secondary analysis of the Swiss-wide, multicenter, randomized controlled Effect of early nutritional therapy on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) trial comparing individualized nutritional support with usual care nutrition in medical inpatients. The primary endpoint was 30-day all-cause mortality.

Results: We included 996 patients with an overall mortality rate of 6% within 30 days. Compared to patients with low IL- 6 level < 11.2pg/mL, patients with high levels had a more than 3-fold increase in mortality at 30-days (adjusted HR 3.5, 95% CI 1.95-6.28, p < 0.001), but tended to have a less pronounced mortality benefit from individualized nutritional therapy as compared to usual nutritional care (hazard ratio 0.82 vs. 0.32). CRP and TNF-α were not associated with mortality, but patients with increased CRP levels > 100 mg/dl also showed a trend towards a diminished response to nutritional intervention (hazard ratio 1.25 vs. 0.47).

Conclusion: Our findings support the thesis that a high inflammatory state is linked to reduced benefits from nutritional therapy. Apparently, CRP and IL- 6 effectively predict treatment response, but IL- 6 may additionally serve as a prognostic marker for increased mortality. This finding might help to develop improved treatment strategies for patients with elevated inflammatory profiles.

Trial Registration: Clinicaltrials.gov as NCT02517476 (registered 7 August 2015).

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023447PMC
http://dx.doi.org/10.1186/s12950-025-00442-0DOI Listing

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