比较炎症生物标志物白细胞介素-6、肿瘤坏死因子-α和C反应蛋白以预测营养治疗对有营养不良风险的内科患者死亡率的影响：随机临床试验EFFORT的二次分析
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.
作者信息
Wunderle Carla, Martin Elisabeth, Wittig Alma, Tribolet Pascal, Lutz Thomas A, Köster-Hegmann Christina, Stanga Zeno, Mueller Beat, Schuetz Philipp
机构信息
Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Tellstrasse 25, Aarau, 5001, Switzerland.
Medical Faculty, University of Basel, Basel, 4056, Switzerland.
出版信息
J Inflamm (Lond). 2025 Apr 24;22(1):16. doi: 10.1186/s12950-025-00442-0.
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).
背景
炎症是疾病相关性营养不良的关键驱动因素，炎症水平高的患者可能无法像其他患者一样从营养治疗中获益。我们在前一项营养试验的大量患者队列中，以探索性方式比较了白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和C反应蛋白（CRP）分别预测营养治疗结局和反应的能力。
方法
这是一项对瑞士范围内多中心随机对照试验——早期营养治疗对营养不良内科住院患者虚弱、功能结局及恢复的影响试验（EFFORT）的二次分析，该试验比较了内科住院患者个体化营养支持与常规护理营养。主要终点是30天全因死亡率。
结果
我们纳入了996例患者，30天内总死亡率为6%。与IL-6水平低（<11.2pg/mL）的患者相比，IL-6水平高的患者30天死亡率增加了3倍多（校正风险比3.5，95%置信区间1.95 - 6.28，p < 0.001），但与常规营养护理相比，个体化营养治疗对其死亡率的益处往往不那么明显（风险比0.82对0.32）。CRP和TNF-α与死亡率无关，但CRP水平升高（>100mg/dl）的患者对营养干预的反应也有减弱趋势（风险比1.25对0.47）。
结论
我们的研究结果支持高炎症状态与营养治疗获益减少相关的论点。显然，CRP和IL-6能有效预测治疗反应，但IL-6还可作为死亡率增加的预后标志物。这一发现可能有助于为炎症水平升高的患者制定改进的治疗策略。
试验注册
Clinicaltrials.gov，注册号为NCT02517476（2015年8月7日注册）。
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