Objective To explore the associations between serum creatinine and creatine kinase (CK) levels with survival in male and female ALS patients. Methods A prospective cohort study was carried out including 346 ALS patients with repeated serum creatinine and CK measurements. Kaplan Meier analysis and multivariable Cox regression were used to perform survival analysis. Results There were 218 male and 128 female patients, and the males had significantly higher baseline serum creatinine and CK levels than females. After multivariable Cox regression analysis, lower baseline serum creatinine levels were associated with a short survival in both male (≤61 μmol/L, HR: 1.629; 95%CI: 1.168–2.273) and female ALS patients (≤52 μmol/L, HR: 1.677; 95%CI: 1.042–2.699), whereas, the serum CK levels were not correlated with survival. Besides, creatinine levels were positively associated with ALSFRS‐R scores, and inversely with the decline rate of ALSFRS‐R per month. During follow‐up, serum creatinine levels tended to be decreased along with the disease progression, and the higher decline rate of creatinine per month (>1.5) showed significantly shorter survival, compared to the lower group (≤1.5) (30.0 months vs. 65.0 months, Chi square = 28.25, P < 0.0001). Interpretation Serum creatinine could be a reliable and easily accessible prognostic chemical marker for ALS, and decreased baseline creatinine levels could predict a poor prognosis and a short survival in both male and female ALS patients.

Objective: Amyotrophic lateral sclerosis (ALS) is an adult-onset fatal neurodegenerative disease which lacks identified biological markers. A label-free plasma surface-enhanced Raman spectroscopy (SERS) method was developed to explore a simple and noninvasive test for ALS. Methods: ALS patients were enrolled serially and plasma samples were collected at the time of diagnosis prior to the start of ALS treatment. SERS spectra were recorded using a Renishaw micro-Raman system. Results: To exclude the interference by varying disease severity, we enrolled three groups of ALS patients, including ALS-1 (n = 60; ALSFRS-R ≥ 42 and time interval ≤ 12 months), ALS-2 (n = 61; ALSFRS-R < 42 and time interval ≤ 12 months), and ALS-3 (n = 61; ALSFRS-R ≥ 38 and time interval> 12 months). The SERS spectra were analyzed using principal component analysis (PCA), which showed that ALS-1, ALS-2, ALS-3, and control groups were separated significantly. Then, decision tree (DT) models and receiver operating characteristic curves were employed and identified that bands at 722 and 739 cm À1 , and ratios of 635-722 cm À1 and 635-739 cm À1 were able to distinguish ALS from controls significantly. Finally, we highlighted six metabolism pathways correlated with ALS, including phenylalanine-tyrosine-tryptophan biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine metabolism, pantothenate and CoA biosynthesis, porphyrin and chlorophyll metabolism, and pyrimidine metabolism. Interpretation: Plasma SERS could be a promising tool for the detection of ALS. The bands at 722 and 739 cm À1 , and the ratios of 635-722 cm À1 and 635-739 cm À1 could serve as potential indicator for ALS.

This study aims to explore the association between median nerve-neurophysiological index (NI) and survival of patients with amyotrophic lateral sclerosis (ALS). Methods: A retrospective case series with a prospective follow-up study was performed in 238 patients with ALS. Their clinical profiles and NI were recorded. Kaplan-Meier curves and Cox regression were adopted to perform survival analysis. Results: The median survival time of all ALS cases was 33.0 months. Multivariate analysis showed that older age of onset, shorter diagnostic delay, higher ALSFRS-R, and faster progression {NI ≤ 2.15; hazard ratio [HR] = 1.543 [95% confidence interval (CI), 1.136-2.094]} were associated with short survival. NI was correlated with ALSFRS-R at baseline (r s = 0.3153; p < 0.0001) and ALSFRS-R at different time points of follow-up (r s = 0.5127; p < 0.0001). The higher NI slope of decline (> 0.25) showed shorter survival compared with the lower group (≤ 0.25; 34.0 vs. 52.0 months; p = 0.0003). A predictive model was constructed based on the age of onset, diagnostic delay, median nerve NI, and ALSFRS-R. The higher predictive score (> 14) showed significantly shorter survival compared with the lower group (≤ 14; HR = 3.907, 95% CI, 2.857-5.342). Conclusion: Median nerve NI and its slope of decline were predictive of survival of ALS.

Background Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease; most ALS patients die within 3 to 5 years after symptom onset, usually as a consequence of respiratory failure. In the present study, we aim to screen the survival-related pulmonary function parameters, and to explore the predictive value of peak expiratory flow (PEF) in disease severity and prognosis in patients with ALS. Methods The discovery cohort included 202 ALS patients, and the demographic and clinical characteristics of eligible patients were collected and pulmonary function tests were performed using MS-PFT spirometer. In the validation cohort, 62 newly diagnosed ALS patients performed the pulmonary function test by MS-PFT spirometer and household peak flow meter (KOKA) simultaneously. Results Among 12 pulmonary function parameters, FVC, FEV1, PEF, MEF75%, and MVV were identified to be independent predictive factors for survival. PEF was highly correlated with FVC (r = 0.797), MVV (r = 0.877), FEV1 (r = 0.847), and MEF75% (r = 0.963). Besides, the values of PEF were positively associated with disease severity (ALSFRS-R score, rs = 0.539, P < 0.0001), and negatively associated with progression rate (ΔALSFRS-R, rs = -0.316, P < 0.0001). Finally, we also confirmed that the values of KOKA-measured PEF were highly correlated with the ones measured using MS-PFT spirometer (r = 0.9644, p < 0.0001). Conclusions Our work emphasizes the critical role of PFTs in predicting prognosis of ALS patients. PEF is an easily available pulmonary function index, which is also a promising indicator in predicting disease severity and survival for ALS patients.

Background: Links between alterations in gut microbiota composition and amyotrophic lateral sclerosis (ALS) have previously been reported. This study aimed to examine the microbiota in the nasal cavity of ALS. Methods: Sixty-six ALS patients and 40 healthy caregivers who live in close proximity with patients were enrolled. High throughput metagenomic sequencing of the 16S ribosomal deoxyribonucleic acid (rDNA) gene V3–V4 region of nasal microbiota was used to characterize the alpha and beta diversity and relative abundance of bacterial taxa, predict function, and conduct correlation analysis between specific taxa and clinical features. Results: The nasal microbiome of ALS patients showed lower alpha diversity than that of corresponding healthy family members. Genera Gaiella, Sphingomonas, Polaribacter_1, Lachnospiraceae_NK4A136_group, Klebsiella, and Alistipes were differentially enriched in ALS patients compared to controls. Nasal microbiota composition in ALS patients significantly differed from that in healthy subjects (unweighted UniFrac P = 0.001), while LEfSe analysis indicated that Bacteroidetes and Firmicutes dominated healthy nasal communities at the phylum level, whereas Actinobacteria was the predominant phylum and Thermoleophilia was the predominant class in ALS patients. Genus Faecalibacterium and Alistipes were positively correlated with ALS functional rating scale revised (ALSFRS-R; r s = 0.349, P = 0.020 and r s = 0.393, P = 0.008), while Prevotella-9 and Bacteroides operational taxonomic units (OTUs) were positively associated with lung function (FVC) in ALS patients (r s = 0.304, P = 0.045, and r s = 0.300, P = 0.048, respectively). Prevotella-1 was positively correlated with white blood cell counts (WBC, r s = 0.347, P = 0.021), neutrophil percentage (Neu%, r s = 0.428, P = 0.004), and neutrophil-to-lymphocyte ratio (NLR, r s = 0.411, P = 0.006), but negatively correlated with lymphocyte percentage (Lym%, r s = –0.408, P = 0.006). In contrast, Streptococcus was negatively associated with Neu% (r s = –0.445, P = 0.003) and NLR (r s = –0.436, P = 0.003), while positively associated with Lym% (r s = 0.437, P = 0.003). No significant differences in nasal microbiota richness and evenness were detected among the severe and mild ALS patients. Conclusions: ALS is accompanied by altered nasal microbial community composition and diversity. The findings presented here highlight the need to understand how dysbiosis of nasal microbiota may contribute to the development of ALS.