Paediatric sepsis continues to be a significant contributor to child morbidity and mortality worldwide, with disproportionate impact in resource-constrained environments. Early and accurate prognostication of disease trajectory supports timely triage and management, but existing biomarkers and clinical scoring systems can lack specificity, be operationally complex, or have limited applicability across diverse clinical settings. Investigating novel biomarkers may improve early risk stratification.
Cereblon (CRBN) is a multifunctional protein implicated in immune modulation. Studies in adult sepsis populations have reported variable associations between CRBN expression and outcomes, but the role of CRBN in paediatric sepsis has not been evaluated. This study protocol describes a prospective observational approach to determine whether CRBN expression at admission correlates with clinical outcomes in children with sepsis and therefore could serve as an early prognostic biomarker.
Primary objective:
Secondary objectives:
This is a prospective observational study conducted in a paediatric intensive care unit (PICU). The protocol specifies consecutive non-probability sampling to recruit eligible participants. The study will enroll a total of 240 children aged between 2 months and 15 years presenting with sepsis.
Children meeting clinical criteria for sepsis and within the specified age range (2 months to 15 years) will be approached for inclusion. Enrollment will use consecutive non-probability sampling in the PICU to capture eligible cases. Details of specific inclusion and exclusion criteria were not reported in the source beyond age and sepsis diagnosis.
Clinical data collection will include Pediatric Sequential Organ Failure Assessment (pSOFA) scores recorded at admission and repeated at 24 hours. At admission, blood samples will be collected for laboratory assessment of CRBN expression. Two complementary laboratory approaches will be used:
Other laboratory data will include inflammatory markers such as C-reactive protein (CRP), which will be used in secondary analyses comparing biomarker levels and clinical severity.
Primary outcome:
Secondary outcomes:
Comparisons of CRBN levels will be made between survivors and non-survivors, and associations with clinical and laboratory markers will be quantified.
Descriptive comparisons of CRBN levels between survivors and non-survivors will be performed. Correlation analyses with continuous clinical scores and laboratory markers will use Pearson's or Spearman's correlation tests as appropriate based on data distribution.
Prognostic performance of CRBN to predict 28-day mortality will be assessed with Receiver Operating Characteristic (ROC) curves and the area under the curve (AUC). Youden-derived cut-offs will be used to identify operating points for sensitivity and specificity.
Multivariable regression analyses will be conducted to adjust for key confounders when evaluating the independent prognostic value of CRBN; specific confounders planned for adjustment were not detailed in the source document.
Ethical approval for the study was obtained from the Institutional Ethics Committee, All India Institute of Medical Sciences, Raebareli (IEC Code-2024-4-EMP-EXP-9). Written informed consent will be obtained from parents or legal guardians prior to enrollment and sample collection.
Study findings will be disseminated through peer-reviewed journal publications and presentations at scientific conferences.
The investigators plan to report study results in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines to promote transparency and completeness of reporting.