Article Figures & Data
Figures
- Figure 1 Estimated Functional Form of the Association Between Neutrophils and Survival
Plots show the estimated functional form of the association between neutrophils and survival (the larger the value on the y axis, the higher the hazard) for (A) all participants (model 1), (B) male participants (model 2), and (C) female participants (model 2). (A) Model 1 shows an overall flat line between the 2 × 106/mL and 4 × 106/mL neutrophil counts with an upward sloping line on either side, therefore justifying the cutoffs at <2 × 106/ml, 2–4 × 106/mL, and >4 × 106/mL. Similar trends in the functional form of neutrophils and survival were observed for males (B) and females (C). Each tick mark at the bottom of the graph represents a single participant sample. As illustrated, the decreased risk for the highest neutrophil count is driven by 1 participant.
- Figure 2 Neutrophil Impact on ALS Survival in Male and Female Participants
Estimated survival curves using 2 separate models for analysis. (A) In model 1, survival curves were adjusted for age, sex, onset segment, El Escorial criteria at diagnosis, and time between symptom onset and diagnosis. Study ALS participants were categorized into 3 neutrophil groups (<2, 2–4, and >4 × 106 neutrophils/mL of blood). Survival curves were generated by creating a pseudopopulation with identical population characteristics as the study participants for each neutrophil group and calculating their expected survival based on model 1 (table 3). Dashed lines indicate the median survival for each neutrophil group. (B) In model 2, female and male survival curves were displayed separately after adjusting for age, onset segment, El Escorial criteria at diagnosis, and time between symptom onset and diagnosis were estimated from the interaction model. Male and female data sets were categorized into 3 neutrophil groups per sex (<2, 2–4, and >4 × 106 neutrophils/mL of blood). Survival curves were generated by creating a pseudopopulation with identical population characteristics as the study participants for each neutrophil and sex group and calculating their expected survival based on model 2 (table 4). Dashed lines indicate the median survival for each neutrophil and sex group. ALS = amyotrophic lateral sclerosis.
- Figure 3 Accumulation of Neutrophils in the CNS During ALS
(A) Spinal cord tissue from control and ALS participants (cervical sections, collected postmortem) was analyzed for neutrophils using flow cytometry. (B) Total neutrophils were quantified in postmortem tissue of the cervical, thoracic, and lumbar spinal cord sections from control and ALS participants. Mean neutrophil counts were: cervical cord, ALS = 10.9 × 103/g, control = 1.6 × 103/g, p = 0.049; thoracic cord, ALS = 3.8 × 103/g, control = 0.7 × 103/g, p = 0.002; and lumbar cord, ALS = 8.4 × 103/g, control = 1.5 × 103/g, p = 0.194. (C) Neutrophil accumulation in the CNS of male and female ALS study participants is compared in the cervical, thoracic, and lumbar sections of the spinal cord. Mean neutrophil counts were: cervical cord, males 12.2 × 103/g, females 9.7 × 103/g, p = 0.686; thoracic cord, males 4.9 × 103/g, females 2.6 × 103/g, p = 0.343; lumbar cord, males 10.6 × 103/g, females 6.2 × 103/g, p = 0.314. *p < 0.05. ALS = amyotrophic lateral sclerosis; FSC = forward scatter.
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