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Table 1 Cohort studies of pathobiology-driven patient phenotypic classification

From: Heterogeneity in sepsis: new biological evidence with clinical applications

Endotypes

Cohort type (n)

Key biomarkers

Transcriptomic profiling

 Subclass A–C [13]

Pediatric septic shock (98)

44-gene classifier

 SRS1 and SRS2 [14]

CAP (265)

7-gene classifier: IDYRK2, DDNB1IP1, TDRD9, ZAP70, ARL14EP, MDC1 ADGRE3

 SRS1_FP and SRS2_FP [15]

Fecal peritonitis (117)

6-gene classifier: CD163, CDHHC19, MME, FAM89A, ZBP1, B3GNT2

 Mars1–4 [16]

All-cause sepsis (306)

2-gene ratios: Mars1: BPGM:TAP2, Mars2: GADD45A:PCGF5, Mars3: AHNAK:PDCD10, Mars4: IFIT5:GLTSCR2

 Inflammopathic, adaptive, coagulopathic [17]

Bacterial sepsis (700)

33-gene classifier

 Neutrophil pathways [18]

Sepsis with (29) and without ARDS (28)

OLFM4, LCN2 2, CD24, BPI

Metabolomics

 Energy metabolism [27]

Septic shock (39), ICU controls (20)

↑Glucose, 3-hydroxybutyrate, O-acetylcarnitine, succinate, creatine, creatine phosphate

↓Branched-chain amino acids and arginine

 Lipid homeostasis and tryptophan catabolism [28]

Septic shock (20)

↓Unsaturated long-chain PC and LPC, kynurenine

 Defect in fatty acid-β-oxidation [29]

Community-acquired sepsis survivors (119) and nonsurvivors (31)

Acylcarnitine esters, amino/nucleic acid catabolites, glycolysis/citric acid cycle components

 Lipid metabolism [30]

SIRS (29), Sepsis (30), sepsis-induced ARDS (31)

γ-glutamylphenylalanine, γ-glutamyltyrosine, 1-arachidonoyl-GPC (20:4), taurochenodeoxycholate, 3-(4-hydroxyphenyl) lactate, sucrose, kynurenine

 Lipid metabolism [31]

SIRS (42), CAP (67), IAI (60), UTI (73) BSI (26)

SM C22:3 and, lysoPCaC24:0, lysoPCaC26:1, putrescine, lysoPCaC18:0, SM C16:1

Cellular function

 Immunophenotype [34]

Sepsis (148)

Neutrophil, monocyte, and Treg phenotypes

 Immunophenotype [35]

Sepsis (22)

Lymphocyte PD-1/PD-L1 expression

 Immunophenotype [36]

Sepsis (505)

Monocyte and CD3, CD4, CD8 Tcell phenotypes

 Endothelial permeability [37]

Sepsis (35)

Supernatants from whole blood treated with LPS

 Endothelial permeability [38]

Primary (12) and secondary (6) sepsis

Neutrophils treated with fMLP

  1. CAP community-acquired pneumonia, PC phosphatidylcholines, LPC lysophosphatidylcholines, IAI intraabdominal infection, UTI urinary tract infection, BSI bloodstream infection, PD programmed death, LPS lipopolysaccharide, fMLP formyl, methionyl-leucyl-phenylalanine, SIRS systemic inflammatory response syndrome