Association of Baseline Inflammation With Effectiveness of Nutritional Support Among Patients With Disease-Related Malnutrition: A Secondary Analysis of a Randomized Clinical Trial | Nutrition | JAMA Network Open | JAMA Network
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    Original Investigation
    Nutrition, Obesity, and Exercise
    March 10, 2020

    Association of Baseline Inflammation With Effectiveness of Nutritional Support Among Patients With Disease-Related Malnutrition: A Secondary Analysis of a Randomized Clinical Trial

    Author Affiliations
    • 1Medical University Department, University of Basel, Kantonsspital Aarau, Aarau, Switzerland
    • 2University of Basel, Basel, Switzerland
    • 3Department of Health Professions, Bern University of Applied Sciences, Bern, Switzerland
    • 4Internal Medicine, Kantonsspital Muensterlingen, Muensterlingen, Switzerland
    • 5New York Academy of Sciences, New York
    • 6Internal Medicine and Endocrinology/Diabetes, Kantonsspital St Gallen, St Gallen, Switzerland
    • 7Internal Medicine, Kantonsspital Luzern, Luzern, Switzerland
    • 8Internal Medicine, Kantonsspital Solothurn, Solothurn, Switzerland
    • 9Internal Medicine, Kantonsspital Baselland, Baselland, Switzerland
    • 10Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
    • 11Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
    • 12Division of General Internal Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
    • 13Division of Diabetology, Endocrinology, Nutritional Medicine, and Metabolism, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland
    JAMA Netw Open. 2020;3(3):e200663. doi:10.1001/jamanetworkopen.2020.0663
    Key Points español 中文 (chinese)

    Question  Does nutritional support have a similar effect on 30-day mortality among patients with high inflammation compared with patients with low or moderate inflammation?

    Findings  In this secondary analysis of a Swiss multicenter trial, including 1950 patients at risk of malnutrition, patients with high levels of inflammation based on their levels of C-reactive protein at admission were not associated with a beneficial effect of nutritional support on 30-day mortality compared with the overall population, suggesting that inflammation has a significant modifying association.

    Meaning  Based on this secondary analysis of a multicenter randomized trial, patients’ inflammatory status at admission was associated with their response to nutritional support and may be considered when individualizing the nutritional management of medical inpatients.


    Importance  Inflammation is a key driver of malnutrition during illness and is often accompanied by metabolic effects, including insulin resistance and reduction of appetite. However, it still remains unclear if inflammation influences the response to nutritional support among patients with disease-related malnutrition.

    Objective  To examine whether patients’ baseline inflammatory status is associated with the effect of nutritional support on 30-day mortality.

    Design, Setting, and Participants  This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized clinical trial conducted in 8 Swiss hospitals from April 2014 to February 2018. A total of 1950 participants who had C-reactive protein measurements at the time of admission were included in this secondary analysis. Data analysis was conducted between June and July 2019.

    Interventions  Hospitalized patients at risk for malnutrition were randomly assigned to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or standard hospital food (control group).

    Main Outcomes and Measures  The primary end point was 30-day mortality. Based on C-reactive protein levels at admission, patients were stratified into groups with low, moderate, or high inflammation (<10 mg/L, 10-100 mg/L, and >100 mg/L, respectively).

    Results  A total of 1950 patients (median [interquartile range] age, 75 [65-83] years; 1025 [52.6%] men) were included; 533 (27.3%) had low levels of inflammation, 894 (45.9%) had moderate levels of inflammation, and 523 (26.8%) had high levels of inflammation. Compared with the control group, patients receiving nutritional support showed a significant reduction in 30-day mortality, regardless of C-reactive protein level (adjusted odds ratio, 0.61; 95% CI, 0.43-0.86; P = .005). In the subgroup of patients with high inflammation, there was no beneficial effect of nutritional support (adjusted odds ratio, 1.32; 95% CI, 0.70-2.50; P = .39), providing evidence that inflammation has a significant modifying association (P for interaction = .005).

    Conclusions and Relevance  Based on this secondary analysis of a multicenter randomized trial, a patient’s admission inflammatory status was associated with their response to nutritional support. If validated in future clinical trials, nutritional support may need to be individualized based on a patient’s initial presentation and markers of inflammation. These results may also help to explain some of the heterogeneity in treatment effects of nutrition seen in previous critical care trials.

    Trial Registration Identifier: NCT02517476