Zhu Yahui, Zhang Ying, Li Mao, Bai Jiongming, Wang Hongfen, Pang Xinyuan, Du Rongrong, Wang Jiao, Huang Xusheng
Department of Neurology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
J Cachexia Sarcopenia Muscle. 2024 Dec;15(6):2743-2755. doi: 10.1002/jcsm.13618. Epub 2024 Oct 24.
Nutritional status, systemic inflammatory responses and muscle mass are associated with the prognosis of patients with amyotrophic lateral sclerosis (ALS). However, the optimal biomarker for predicting prognosis remains unclear. This study aimed to identify the optimal indicators of survival among the nutrition-based, inflammation-based and muscle mass-related markers for ALS patients.
We enrolled ALS patients from January 2014 to December 2019. Experienced neurologists followed up with the participants until January 2022. This study included a total of 17 nutritional, systemic inflammatory or muscle mass-related indicators. Maximally selected rank statistics determined the cut-off points for these indicators. Kaplan-Meier estimation was used to assess survival. Uni- and multivariate Cox proportional hazards models were used to determine the effects of indicators on survival. Finally, time-dependent receiver operating characteristic (time-ROC) curves and the C-index were calculated to evaluate the predictive efficacy of different indicators.
A total of 506 patients with ALS were enrolled in this study, including 288 males (56.9%) and 218 females (43.1%), with a mean age of 54.2 ± 10.5 years. Among these ALS patients, 334 cases (68.0%) either died or underwent tracheotomy. In univariate Cox proportional hazards regression, 11 indicators were significantly associated with ALS survival (p < 0.05). And systemic immune inflammation (SII), platelet-to-lymphocyte ratio (PLR), modified geriatric nutritional risk index (mGNRI), creatinine and sarcopenia index (SI, (creatinine/cystatin C) × 100) were determined as independent predictors (p < 0.05) in multivariate Cox proportional hazards regression. A higher SI predicted longer survival (hazard ratio, 0.59; 95% confidence interval [CI], 0.46-0.76; p < 0.001). The results of time-ROC and C-index analyses indicated that SI had the best predictive efficacy for ALS survival, with a C-index of 0.65 (95% CI, 0.54-0.75) for 1-year, 0.61 (95% CI, 0.57-0.65) for 3-year and 0.59 (95% CI, 0.55-0.62) for 5-year survival. Across different subgroups, SI had the highest C-index in men and women, limb onset and aged < 60 year ALS patients, compared with other indicators. However, cystatin C was the best indicator for predicting the survival of ALS patients with bulbar onset, whereas the prognostic nutritional index (PNI) was the best for those aged ≥60 years.
The serum SI demonstrates superior prognostic ability compared to other inflammation-based, nutrition-based and muscle mass-related indicators for patients with ALS. Given its simplicity and availability, it is well suited for clinical use in evaluating the prognosis of ALS patients.
营养状况、全身炎症反应和肌肉质量与肌萎缩侧索硬化症（ALS）患者的预后相关。然而，用于预测预后的最佳生物标志物仍不明确。本研究旨在确定基于营养、炎症和肌肉质量的标志物中预测ALS患者生存的最佳指标。
我们纳入了2014年1月至2019年12月的ALS患者。经验丰富的神经科医生对参与者进行随访直至2022年1月。本研究共纳入17项与营养、全身炎症或肌肉质量相关的指标。最大选择秩统计确定这些指标的截断点。采用Kaplan-Meier估计法评估生存情况。单因素和多因素Cox比例风险模型用于确定指标对生存的影响。最后，计算时间依赖性受试者工作特征（time-ROC）曲线和C指数以评估不同指标的预测效能。
本研究共纳入506例ALS患者，其中男性288例（56.9%），女性218例（43.1%），平均年龄54.2±10.5岁。在这些ALS患者中，334例（68.0%）死亡或接受了气管切开术。在单因素Cox比例风险回归中，11项指标与ALS生存显著相关（p<0.05）。在多因素Cox比例风险回归中，全身免疫炎症（SII）、血小板与淋巴细胞比值（PLR）、改良老年营养风险指数（mGNRI）、肌酐和肌少症指数（SI，（肌酐/胱抑素C）×100）被确定为独立预测因素（p<0.05）。较高的SI预测生存时间更长（风险比，0.59；95%置信区间[CI]，0.46-0.76；p<0.001）。time-ROC和C指数分析结果表明，SI对ALS生存的预测效能最佳，1年生存的C指数为0.65（95%CI，0.54-0.75），3年生存的C指数为0.61（95%CI，0.57-0.65），5年生存的C指数为0.59（95%CI，0.55-0.62）。在不同亚组中，与其他指标相比，SI在男性和女性、肢体起病和年龄<60岁的ALS患者中C指数最高。然而，胱抑素C是预测延髓起病的ALS患者生存的最佳指标，而预后营养指数（PNI）是年龄≥60岁患者的最佳指标。
与其他基于炎症、营养和肌肉质量的指标相比，血清SI对ALS患者具有更好的预后预测能力。鉴于其简单易行且可获得，它非常适合临床用于评估ALS患者的预后。
