Published on January 31, 2023   30 min

A selection of talks on Immunology & Inflammation

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Hello. This talk is on sepsis. I'm John Kellum from the University of Pittsburgh.
The term sepsis dates back to antiquity when it was understood to be the process by which flesh rots, wounds fester, and swamps produce foul odors. In the 19th century, thanks to the work by Pasteur, Pfeiffer, Koch, and others, germ theory took hold, and sepsis was understood to be due to systemic infections, and terms like blood poisoning and septicemia were also invoked. In the modern era, thanks to the work by Beutler, Hoffman, and many others, molecular biology has unraveled many of the mysteries of sepsis. Pathogen-associated molecular patterns, or PAMPs, and damage-associated molecular patterns, or DAMPs, were discovered to signal the immune system through pattern recognition receptors, most notably Toll-like receptors. Furthermore, consensus definitions, though still evolving, have come to view sepsis as an uncontrolled host response to infection.
The clinical criteria for sepsis, according to the most recent definition of sepsis the Sepsis-3 Criteria, which were derived by international consensus, defines sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection. This can be operationalized using organ failure scores such as the Sequential Organ Failure Assessment score, SOFA. The change of 2 or more points is considered to fulfill the definition. Importantly, this change in organ function should be consequent to infection and not caused by something else. It should be remote from the site of infection so that local infection itself causing organ failure is not evidence of a dysregulated systemic hos response. For example, respiratory failure, secondary to pneumonia does not in and of itself fulfill the criteria for sepsis.