The neutrophil-to-lymphocyte ratio(NLR)is considered a robust prognostic biomarker for predicting patient survival outcomes in many diseases.However,it remains unclear whether it can be used as a biomarker for amyotro...The neutrophil-to-lymphocyte ratio(NLR)is considered a robust prognostic biomarker for predicting patient survival outcomes in many diseases.However,it remains unclear whether it can be used as a biomarker for amyotrophic lateral sclerosis(ALS).To correlate NLR with disease progression and survival in sporadic ALS,1030 patients with ALS between January 2012 and December 2018 were included in this study.These patients were assigned into three groups according to their NLR values:Group 1(NLR<2,n=544[52.8%]),Group 2(NLR=2–3,n=314[30.5%]),and Group 3(NLR>3,n=172[16.7%]).All patients were followed up until April 2020.Patients in Group 3 had a significantly older onset age,a lower score on the Revised ALS Functional Rating Scale,and rapidly progressing disease conditions.Furthermore,faster disease progression rates were associated with higher NLR values(odds ratio=1.211,95%confidence interval[CI]:1.090–1.346,P<0.001)after adjusting for other risk factors.Compared with Groups 1 and 2,the survival time in Group 3 was significantly shorter(log-rank P=0.002).The NLR value was considered an independent parameter for the prediction of survival in ALS patients after normalizing for all other potential parameters(hazard ratio[HR]=1.079,95%CI:1.016–1.146,P=0.014).The effects on ALS survival remained significant when adjusted for treatment(HR=1.074,95%CI:1.012–1.141,P_(trend)=0.019)or when considering the stratified NLR value(HR=1.115,95%CI:1.009–1.232,P_(trend)=0.033).Thus,the NLR may help to predict the rate of disease progression and survival in patients with sporadic ALS.The study was approved by the Institutional Ethics Committee of West China Hospital of Sichuan University,China(approval No.2015(236))on December 23,2015.展开更多
Background： Mitochondrial dysfunction plays an important role in the pathogenesis of amyotrophic lateral sclerosis （ALS）. We aimed to demonstrate mitochondrial dysfunction in ALS using a lactate stress test and to ...Background： Mitochondrial dysfunction plays an important role in the pathogenesis of amyotrophic lateral sclerosis （ALS）. We aimed to demonstrate mitochondrial dysfunction in ALS using a lactate stress test and to examine the relationship between mitochondrial dysfunction with motor deterioration. Methods： We enrolled 116 patients and observed clinical variables, including the survival state. Results： Patients with a rapid slope of revised ALS functional rating scales （ALSFRS-r） （〉20 U/year） exhibited the slowest elimination rate （median -4.67 × 10^-3 mmol·L ^-1min ^-1, coefficient of variation, 590.15%）, the shortest duration （0.63 ± 0.28 years） and the worst ALSFRS-r （32.59±4.93）. Patients with a moderate slope ofALSFRS-r （1~20 U/year） showed a moderate elimination rate （median -11.33 × 10^-3 mmol·L ^-1min ^-1, coefficient of variation, 309.89%）, duration （1.16± 0.45 years）, and ALSFRS-r （34.83 ± 6.11）. The slower progressing （〈10 U/year group） patients exhibited a rapid elimination rate （median： - 12.00 × 10^-3 mmol·L ^-1min ^-1, coefficient of variation： 143.08%）, longer duration （median： 3 years, coefficient of variation： 193.33%）, and adequate ALSFRS-r values （39.58 ± 9.44）. Advanced-phase ALS patients also showed slower elimination rate （ER, quartiles - 17.33, -5.67, 4.00） and worse ALSFRS-r （34.88 ± 9.27）, while early-phase patients showed a more rapid ER （quartiles -25.17, -11.33, -3.50） and better ALSFRS-r （39.28 ± 7.59）. These differences were statistically significant. Multiple linear regression analysis revealed strong direct associations among ER, ALSFRS-r slope （standard beta = 0.33, P = 0.007）, and forced vital capacity （predict %） （standard beta = -0.458, P = 0.006, adjusted for ALSFRS-r, course and onset region）. However, the data obtained from 3 years of follow-up showed no statistically significant difference in the survival rates between the most rapid and slowest ER groups. Conclusion： There is a potential linear relationship between ER and motor deterioration in ALS. Slower ER might be associated with faster disease progression.展开更多
目的系统评价依达拉奉用于肌萎缩侧索硬化患者的有效性和安全性。方法检索PubMed、Cochrane library、CNKI、万方电子数据库,同时进行手工检索,收集国内外1994年1月至2017年12月公开发表的关于依达拉奉用于治疗肌萎缩侧索硬化的随机对...目的系统评价依达拉奉用于肌萎缩侧索硬化患者的有效性和安全性。方法检索PubMed、Cochrane library、CNKI、万方电子数据库,同时进行手工检索,收集国内外1994年1月至2017年12月公开发表的关于依达拉奉用于治疗肌萎缩侧索硬化的随机对照研究。依据纳入和排除标准筛选文献,对纳入文献进行质量评估,并采用Rev Man 5.3软件统计学分析。结果共纳入6个研究(共609例)。Meta分析结果表明,依达拉奉与对照组相比,可改善患者肌萎缩侧索硬化功能等级评分(SMD=0.80,95%CI:0.62~0.98,P<0.00001),但不能减少患者死亡率(RR=0.73,95%CI:0.36~1.46,P=0.37)。与对照组相比,依达拉奉不增加不良反应的发生率(RR=0.91,95%CI:0.70~1.19,P=0.10)。结论依达拉奉有较好的安全性,虽不能减少死亡率的发生,但能够改善ALS患者功能。展开更多
基金supported by the Science and Technology Bureau Fund of Sichuan Province of China,No.2020YFS0220the China Postdoctoral Science Foundation,No.2019M653427+1 种基金Postdoctoral Research Project,West China Hospital,Sichuan University of China,No.2019HXBH029Health Commission of Sichuan Province of China,No.20PJ038(all to QQW)。
文摘The neutrophil-to-lymphocyte ratio(NLR)is considered a robust prognostic biomarker for predicting patient survival outcomes in many diseases.However,it remains unclear whether it can be used as a biomarker for amyotrophic lateral sclerosis(ALS).To correlate NLR with disease progression and survival in sporadic ALS,1030 patients with ALS between January 2012 and December 2018 were included in this study.These patients were assigned into three groups according to their NLR values:Group 1(NLR<2,n=544[52.8%]),Group 2(NLR=2–3,n=314[30.5%]),and Group 3(NLR>3,n=172[16.7%]).All patients were followed up until April 2020.Patients in Group 3 had a significantly older onset age,a lower score on the Revised ALS Functional Rating Scale,and rapidly progressing disease conditions.Furthermore,faster disease progression rates were associated with higher NLR values(odds ratio=1.211,95%confidence interval[CI]:1.090–1.346,P<0.001)after adjusting for other risk factors.Compared with Groups 1 and 2,the survival time in Group 3 was significantly shorter(log-rank P=0.002).The NLR value was considered an independent parameter for the prediction of survival in ALS patients after normalizing for all other potential parameters(hazard ratio[HR]=1.079,95%CI:1.016–1.146,P=0.014).The effects on ALS survival remained significant when adjusted for treatment(HR=1.074,95%CI:1.012–1.141,P_(trend)=0.019)or when considering the stratified NLR value(HR=1.115,95%CI:1.009–1.232,P_(trend)=0.033).Thus,the NLR may help to predict the rate of disease progression and survival in patients with sporadic ALS.The study was approved by the Institutional Ethics Committee of West China Hospital of Sichuan University,China(approval No.2015(236))on December 23,2015.
文摘Background： Mitochondrial dysfunction plays an important role in the pathogenesis of amyotrophic lateral sclerosis （ALS）. We aimed to demonstrate mitochondrial dysfunction in ALS using a lactate stress test and to examine the relationship between mitochondrial dysfunction with motor deterioration. Methods： We enrolled 116 patients and observed clinical variables, including the survival state. Results： Patients with a rapid slope of revised ALS functional rating scales （ALSFRS-r） （〉20 U/year） exhibited the slowest elimination rate （median -4.67 × 10^-3 mmol·L ^-1min ^-1, coefficient of variation, 590.15%）, the shortest duration （0.63 ± 0.28 years） and the worst ALSFRS-r （32.59±4.93）. Patients with a moderate slope ofALSFRS-r （1~20 U/year） showed a moderate elimination rate （median -11.33 × 10^-3 mmol·L ^-1min ^-1, coefficient of variation, 309.89%）, duration （1.16± 0.45 years）, and ALSFRS-r （34.83 ± 6.11）. The slower progressing （〈10 U/year group） patients exhibited a rapid elimination rate （median： - 12.00 × 10^-3 mmol·L ^-1min ^-1, coefficient of variation： 143.08%）, longer duration （median： 3 years, coefficient of variation： 193.33%）, and adequate ALSFRS-r values （39.58 ± 9.44）. Advanced-phase ALS patients also showed slower elimination rate （ER, quartiles - 17.33, -5.67, 4.00） and worse ALSFRS-r （34.88 ± 9.27）, while early-phase patients showed a more rapid ER （quartiles -25.17, -11.33, -3.50） and better ALSFRS-r （39.28 ± 7.59）. These differences were statistically significant. Multiple linear regression analysis revealed strong direct associations among ER, ALSFRS-r slope （standard beta = 0.33, P = 0.007）, and forced vital capacity （predict %） （standard beta = -0.458, P = 0.006, adjusted for ALSFRS-r, course and onset region）. However, the data obtained from 3 years of follow-up showed no statistically significant difference in the survival rates between the most rapid and slowest ER groups. Conclusion： There is a potential linear relationship between ER and motor deterioration in ALS. Slower ER might be associated with faster disease progression.
文摘目的系统评价依达拉奉用于肌萎缩侧索硬化患者的有效性和安全性。方法检索PubMed、Cochrane library、CNKI、万方电子数据库,同时进行手工检索,收集国内外1994年1月至2017年12月公开发表的关于依达拉奉用于治疗肌萎缩侧索硬化的随机对照研究。依据纳入和排除标准筛选文献,对纳入文献进行质量评估,并采用Rev Man 5.3软件统计学分析。结果共纳入6个研究(共609例)。Meta分析结果表明,依达拉奉与对照组相比,可改善患者肌萎缩侧索硬化功能等级评分(SMD=0.80,95%CI:0.62~0.98,P<0.00001),但不能减少患者死亡率(RR=0.73,95%CI:0.36~1.46,P=0.37)。与对照组相比,依达拉奉不增加不良反应的发生率(RR=0.91,95%CI:0.70~1.19,P=0.10)。结论依达拉奉有较好的安全性,虽不能减少死亡率的发生,但能够改善ALS患者功能。
