An immune-endocrine approach to identify biomarkers of outcomes following major burn injury in adults

Altarrah, Khaled S Y M (2020). An immune-endocrine approach to identify biomarkers of outcomes following major burn injury in adults. University of Birmingham. Ph.D.

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Abstract

Severe thermal injury induces a profound immune-inflammatory, endocrine and hypermetabolic response associated with poor outcomes including delayed wound healing, sepsis, multiorgan failure (MOF) and mortality. One urgent clinical need is to understand the mechanisms mediating the systemic response in order to identify prognostic biomarkers of outcome and develop new therapies.

This thesis analysed stored serum samples from a large observational study of severely burned patients (≥20% TBSA) at the Queen Elizabeth Hospital Birmingham. The HPA/HPG, Vitamin D, inflammatory, immune and adipokine responses were characterized from day of injury to 12 months post-injury and related to clinical outcomes including sepsis, MOF, wound healing, scarring and mortality.

Low DHEA, DHEAS, Testosterone and Vitamin D (25D3, Free 25D3, Bioavailable 25D3) status showed significant associations with poor outcomes including delayed wound healing, sepsis and mortality independent of age, gender and injury severity. Higher levels of DHEA, DHEAS, testosterone, Vitamin D and adiponectin were associated with improved scarring. Current burn treatments with potential influence on the endocrine system were also assessed. Corticosteroid use was associated with poor prognosis including sepsis, MOF and mortality, whereas Oxandrolone use was associated with improved outcomes. The data reveal several novel biomarkers of outcome that could also have therapeutic value.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):