Carla Wunderle, Elisabeth Martin, Alma Wittig, Pascal Tribolet, Thomas A Lutz, Christina Köster-Hegmann, Zeno Stanga, Beat Mueller, Philipp Schuetz
{"title":"比较炎症生物标志物IL- 6、TNF-α和CRP预测营养治疗对有营养不良风险的医疗患者死亡率的影响：对随机临床试验EFFORT的二次分析","authors":"Carla Wunderle, Elisabeth Martin, Alma Wittig, Pascal Tribolet, Thomas A Lutz, Christina Köster-Hegmann, Zeno Stanga, Beat Mueller, Philipp Schuetz","doi":"10.1186/s12950-025-00442-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov as NCT02517476 (registered 7 August 2015).</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"22 1","pages":"16"},"PeriodicalIF":4.4000,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023447/pdf/","citationCount":"0","resultStr":"{\"title\":\"Comparison of the inflammatory biomarkers IL- 6, TNF-α, and CRP to predict the effect of nutritional therapy on mortality in medical patients at risk of malnutrition : A secondary analysis of the randomized clinical trial EFFORT.\",\"authors\":\"Carla Wunderle, Elisabeth Martin, Alma Wittig, Pascal Tribolet, Thomas A Lutz, Christina Köster-Hegmann, Zeno Stanga, Beat Mueller, Philipp Schuetz\",\"doi\":\"10.1186/s12950-025-00442-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov as NCT02517476 (registered 7 August 2015).</p>\",\"PeriodicalId\":56120,\"journal\":{\"name\":\"Journal of Inflammation-London\",\"volume\":\"22 1\",\"pages\":\"16\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2025-04-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023447/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inflammation-London\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12950-025-00442-0\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inflammation-London","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12950-025-00442-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Comparison of the inflammatory biomarkers IL- 6, TNF-α, and CRP to predict the effect of nutritional therapy on mortality in medical patients at risk of malnutrition : A secondary analysis of the randomized clinical trial EFFORT.
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).
期刊介绍：
Journal of Inflammation welcomes research submissions on all aspects of inflammation.
The five classical symptoms of inflammation, namely redness (rubor), swelling (tumour), heat (calor), pain (dolor) and loss of function (functio laesa), are only part of the story. The term inflammation is taken to include the full range of underlying cellular and molecular mechanisms involved, not only in the production of the inflammatory responses but, more importantly in clinical terms, in the healing process as well. Thus the journal covers molecular, cellular, animal and clinical studies, and related aspects of pharmacology, such as anti-inflammatory drug development, trials and therapeutic developments. It also considers publication of negative findings.
Journal of Inflammation aims to become the leading online journal on inflammation and, as online journals replace printed ones over the next decade, the main open access inflammation journal. Open access guarantees a larger audience, and thus impact, than any restricted access equivalent, and increasingly so, as the escalating costs of printed journals puts them outside University budgets. The unrestricted access to research findings in inflammation aids in promoting dynamic and productive dialogue between industrial and academic members of the inflammation research community, which plays such an important part in the development of future generations of anti-inflammatory therapies.
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