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Dr Z B Banoo Inkosi Albert Luthuli Central Hospital Paediatric ...

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<strong>Dr</strong> Z B <strong>Banoo</strong><br />

<strong>Inkosi</strong> <strong>Albert</strong> <strong>Luthuli</strong> <strong>Central</strong> <strong>Hospital</strong><br />

<strong>Paediatric</strong> Intensive Care Unit


Unwanted<br />

Persistent<br />

Ubiquitous<br />

Mysterious<br />

Leading cause of death


Pathophysiology<br />

Definition dilemmas<br />

Diagnostic Tools<br />

Clinical to Cultures<br />

Biomarkers to genomics<br />

Summary


Derived from the Greek word ŋΨις<br />

Decomposition of animal and vegetable<br />

organic matter<br />

100 years ago link between bacteria<br />

and sepsis<br />

sepsis synonymous with severe infection


Precise definition of the disease process<br />

in question<br />

Complex process, multiple sites, multiple<br />

organisms<br />

Multitude of symptoms & signs, varying<br />

over time, severity from mild to fatal<br />

Complexity and variation- single<br />

definition impossible


Microbiological markers<br />

Blood cultures<br />

Tracheal Aspirates<br />

Urine MCS<br />

Cerebral Spinal Fluid<br />

Pus Swabs


Clinical<br />

Manifestation<br />

Acute Phase<br />

Proteins<br />

Cytokines<br />

Cytokines<br />

Inflammatory<br />

Cells<br />

Inflammatory<br />

cells<br />

Orgs<br />

Organisms


Indicator of a biological state<br />

Measurable substance in an organism<br />

Molecular marker or signature molecule<br />

Diagnostic and/or prognostic utility<br />

Surrogate endpoint


Leucocytosis<br />

Leucopenia<br />

White Blood<br />

Count<br />

Insensitive<br />

Non-specific<br />

Marker of<br />

Inflammation<br />

Bandemia


Inflammatory stimuli marginalization,<br />

extravasation and activation of<br />

granulocytes and monocytes<br />

Release of pro-inflammatory cytokines<br />

TNF<br />

IL-1<br />

IL-6<br />

Production of acute phase proteins


Late<br />

Biomarker<br />

Serial<br />

Measurements<br />

C- reactive protein<br />

Low<br />

sensitivity<br />

and<br />

specificity<br />

Peak 2-3 days


APP produced in response to proinflammatory<br />

cytokines<br />

Direct measure of the cytokines earlier<br />

indication of infection<br />

IL-1, IL-6, TNF, sIL2R<br />

Initial reports of high sensitivity and<br />

specificity have not been borne out in<br />

clinical trials


Soluble triggering receptor expressed on<br />

myeloid cells<br />

Upregulated in neutrophils and<br />

monocytes during bacterial infection<br />

Limited value in neutropenia


Identification of resistant genes by<br />

molecular techniques<br />

Genomics – identification of genes<br />

upregulated in infection eg IL8 AND<br />

MCP-1 Mrna<br />

Proteonomics – mass spectrometry<br />

profiling technology to identify host<br />

response proteins<br />

Gelsolin, Copeptin, Endothelial-1…..


Sepsis – homogenous disease process<br />

inadequate<br />

Clinical variables – too sensitive,<br />

nonspecific<br />

Synthesis of clinical, physiological and<br />

laboratory features


Gut<br />

instinct<br />

Clinical<br />

features<br />

Sepsis<br />

Special<br />

Investigations<br />

Biomarkers

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