Table 2 Lipid metabolism marker findings from select TBI metabolomics sets

SMs

- Decreased SM 20:2 in a biosignature at 24 h and 4 days post injury predicting poorer GOSE outcomes at 3 months

sTBI (Serum)

Banoei et al. [30]

- Increased SM 16:1 in a biosignature at 24 h post injury predicting poorer GOSE outcomes at 12 months

- Decreasing levels of SMs (d38:2, (40:2)/(18:1/22:1), d40:1) within 24 h after injury predict increasing TBI severity

TBI (m/mod/s) (Serum)

Thomas et al. [31]

- Decreased SM(40:1) & SM(40:2), associated with positive CT findings

- Decreased SM (40:2)/(18:1/22:1), d40:1) predicts unfavorable GOSE outcomes at 6 months

LPCs

- Increased LPCs (16:0, 17:0, 18:0) in a biosignature at 24 h post injury predicting poorer GOSE outcomes at 3 months

sTBI (Serum)

Banoei et al. [30]

- Increased LPCs (14:0, 20:3 & 28:1) in a biosignature at 4 days post injury predicting poorer GOSE outcomes at 12 months

- Increased LPCs (28:1, 14:0) in a biosignature at 4 days post injury predicting poorer GOSE outcomes at 12 months

- Decreasing levels of LPCs (16:0, 18:0, 18:2, 20:5) within 24 h after injury predict increasing TBI severity

TBI (m/mod/s) (Serum)

Thomas et al. [31]

- Decreased LPC(18:2) & LPC(20:5) associated with positive CT findings (Serum)

- Decreased LPC (18:0, 18:2, 20:5) predicts unfavorable GOSE outcomes at 6 months

PCs

- Increased PC36:0 aa in a biosignature at 4 days post injury predicting poorer GOSE outcomes at 3 months

sTBI (Serum)

Banoei et al. [30]

- Increased PCs (38:0 aa, 40:6 ae) and O-phosphocholine at 24 h post injury predict 3-month mortality

- Increased PCs (38:0 aa, 36:00 aa) at 4 days post injury predict 3-month mortality

- Decreasing levels of O-PCs (34:3, 36:3) within 24 h after injury predict increasing TBI severity

TBI (m/mod/s) (Serum)

Thomas et al. [31]

- Decreased O-PC(34:2), O-PC(34:3), O-PC(36:3) associated with positive CT findings

- Decreased O-PC 3:3 predicts unfavorable GOSE outcomes at 6 months

Ketogenic AAs/BCAAs

- Increased leucine, tyrosine, threonine, phenylalanine, valine, 4-methyl-2-oxovaleric acid & propionylcarnitine associated with “healthier” metabolic state

sTBI (CMD)

Eiden et al. [46]

- Isoleucine among the top 10 most relevant metabolites for Therapy Intensity Level (TIL) prediction

- Decreased isoleucine, leucine, threonine phenylalanine & tyrosine in a biosignature at 24 h post injury predicting poorer GOSE outcomes at 3 months

sTBI (Serum)

Banoei et al. [30]

- Increased valine, lysine, tyrosine, isoleucine & leucine in a biosignature at 4 days post injury predicting poorer GOSE outcomes at 3 months

- Increased tyrosine, leucine & valine at 24 h and 4 days post injury predicting poorer GOSE outcomes at 12 months

- Decreased BCAAs at 24 h post injury predict 3-month mortality

- Increased BCAAs, tyrosine, ornithine tryptophan & threonine at 4 days post injury predict 3 month mortality

- Threonine and BCAA breakdown products decrease with increasing TBI severity and their downregulation within 24 h after injury predicts positive CT findings

- AAs including threonine, tryptophan & phenylalanine are decreased in sTBI patient sera (but not in mTBI patients) within 12 h after injury

TBI (m/mod/s) (Serum)

Orešič et al. [34]

- Decreased tryptophan and an unknown amino acid predict unfavorable GOSE outcomes at 6–12 (Serum) month

- Decreased serum 2-aminobutyric acid and an unknown amino acid within 12 h of admission for TBI predicted positive CT findings

TBI (m/mod/s) (Serum)

Dickens et al. [41]

Fatty acids

- Increased butyrylcarnitine associated with “healthier” metabolic state

sTBI (CMD)

Eiden et al. [46]

- Decreased medium straight chain fatty acids (decanoic acid and octanoic acid) associated with “healthier” metabolic state

- Butryrylcarnitine, 10-hydroxydecanoic acid (10-OH-C10), suberic acid, 8-hydroxyoctanoic acid (8- OHC8), 2-hydroxyoctanoic acid, dodecanoic acid are among the top 10 most relevant metabolites for TIL prediction

- Increased propionic, stearic, octadecanoic, myristic, oleic and linoleic acid in a biosignature at 24 h post injury predicting poorer GOSE outcomes at 3 months

sTBI (Serum)

Banoei et al. [30]

- Increased propionic acid, linoleic acid, valeric acid (C5) & medium-chain acylcarnitines in a biosignature at 24 h and 4 days post injury predicting poorer GOSE outcomes at 12 months

- Increased caproic acid (C6) & oleic acid in a biosignature at 4 days post injury predicting poorer GOSE outcomes at 12 months

- Increased acylcarnitines at 24 h post injury predict 3-month mortality

- Octanoic and decanoic acid levels within 24 h after injury increase with increasing TBI severity

TBI (m/mod/s) (Serum)

Thomas et al. [31]

- Octanoic and decanoic acid are increased in sTBI patient sera (and to a lesser degree in mTBI patients) within 12 h after injury and predict unfavorable GOSE outcomes at 6–12 months

TBI (m/mod/s) (Serum)

Orešič et al. [34]

- Increased decanoic acid is associated with mass lesion rather than diffuse lesion on CT

TBI (m/mod/s) (Serum)

Dickens et al. [41]

Ketone bodies

- Increased 3-hydroxybutyrate & 2-hydroxybutyrate associated with “healthier” metabolic state

sTBI (CMD)

Eiden et al. [46]

- 3-hydroxybutyrate & acetoacetate among the top 10 most relevant metabolites for TIL prediction

- 3-hydroxybutyric acid & 2-hydroxybutyric acid are upregulated in sTBI patients (and to a lesser degree in mTBI patients) within 12 h after injury

TBI (m/mod/s) (Serum)

Orešič et al. [34]

- Increased Acetoacetic acid (3-oxobutanoic acid) predicts poorer GOSE outcomes at 6–12 months

- Increased acetoacetic acid within 12 h of admission for TBI predicted positive CT findings

TBI (m/mod/s) (Serum)

Dickens et al. [41]

- Increased 2-hydroxybutyric acid is associated with mass lesion rather than diffuse injury on CT

NAA

- Increased NAA in a biosignature at 4 days post injury predicting poorer GOSE outcomes at 3 months

sTBI (Serum)

Banoei et al. [30]