Proteomic biomarkers for early diagnosis and prognosis in pediatric sepsis

Table 2 Comparative characteristics of the four included studies

Ref.	Wong et al[20]	Luo et al[21]	Pilar-Orive et al[22]	Shubin et al[23]
Setting/design	17-center PICU; prospective observational diagnostic biomarker study	Single-center; nested case-control; pneumonia-derived sepsis	Single-center; analytical observational case-control study	Single-center PICU/cardiac intensive care unit; prospective observational, proteomics
Number (analyzed) and age	231 (vs 61 control group); noted multicenter; ≤ 10 years	90 discovery samples pooled (20 controls); enzyme-linked immunosorbent assays validation (n = 35). Age strata: Infants (7-12 months), toddlers (13-36 months)	40 septic children (vs 24 healthy donors); 1 month to 16 years	35 sepsis (vs 28 control); 1 sepsis outlier removed 34 sepsis analyzed, 1-8 years
Specimen and timing	Serum; within first 24 hours	Plasma; processed ≤ 24 hours; -80 °C storage; top-12 depletion	Serum; single draw (study baseline)	Serum; day-1 post-presentation/CPB (per cohort definitions)
Comparators	Systemic inflammatory response syndrome (culture-neg) vs sepsis/septic shock (culture-pos)	Within-age outcome groups (improved vs no-improve vs non-survivors)	Healthy donors	Post-CPB infection-negative systemic inflammation (non-infectious systemic inflammation)
Sepsis marker	Interleukin-27	Haptoglobin, thrombospondin 1, SAA1/2	Soluble CD25, SAA1, leucine-rich alpha-2-glycoprotein 1	Signal transducer and activator of transcription 3
Response time	Rises within 4-6 hours	Rises within 2-4 hours	Rises within 4-6 hours	Rises within 2-4 hours
Clinical significance	Early diagnosis of sepsis; monitoring post-surgery recovery	Early diagnosis of sepsis; optimizing antibiotic treatment	Diagnosis of specific pathogens; prognosis of sepsis severity	Early diagnosis of sepsis; prognosis for severe sepsis
Strengths	High specificity for bacterial infection; rapid response	Good specificity for bacterial infections; rapid biomarker rise	Targeted multi-marker approach; provides pathogen-specific diagnostic cues	High specificity for sepsis; useful for early prognosis
Limitations	Low sensitivity in localized infections (false negatives)	False positives in non-bacterial inflammation; expensive test	Limited generalizability; potential for false positives in specific cases	Expensive; limited accessibility

CPB: Cardiopulmonary bypass; PICU: Pediatric intensive care unit; SAA: Serum amyloid A.