Sepsis, commonly known as blood poisoning, is a complex disease during which the body abnormally reacts to an infection (bacterial, fungal, viral). During the years, the death rate in sepsis syndromes has increased and has even become higher than in acute myocardial infarctions. There are diverse phenotypes of sepsis regarding both the infectious origin as well as short-/long-term presentations and outcomes. For example, the infected host may mount an excessive immune-inflammatory response or remain immunosuppressed (or most typically feature both types of responses). Simultaneously, organs and tissues may be under-supplied with the blood, cells fail to take up sufficient oxygen from the blood and are undergo damage from self and non-self biologically active mediators circulating in the blood and lymph (so-called Pathogen Activated Molecular Patterns, PAMPs). In the clinical context, such diverse causes and phenotypes mean that the disease is difficult to diagnose and even harder to treat.
Shock, although of different pathogenesis (hypovolemic, cardiogenic, obstructive, distributive), is associated with minor perfusion and consequently oxygen deficiency of vital organs and tissue hypoxia. Hemorrhages resulting in hypovolemic shock are the common cause of microcirculatory disturbances and oxygenation deficiency in trauma patients. Trauma also triggers a production/release of multiple biologically active mediators (so-called Damage Associated Molecular Patterns; DAMPs) with a capacity to both heal and damage. This fine response balance requires an in-depth understanding so that precise diagnostic, prediction and treatment characteristics could be established for patients with various types of traumas.
Our team investigates pathological processes that underlie sepsis, shock states and acute traumas. Thereby, various molecular mechanisms are examined that cause inflammatory responses and organ failure as well as functional changes and damage in cells and subcellular organelles occurring in those critical care conditions. Further research emphasis is put on:
- Characterizing various biomarkers and their application for prognostication of developing sepsis syndromes and predicting outcomes in septic in trauma patients
- Modeling of the influence of comorbidities (e.g. diabetes), age and/or gender in acute states
- Refinement and standardization of pre-clinical models for Sepsis-Trauma-Shock research
One ultimate aim is to enhance the pathophysiological understanding of the Sepsis-Trauma-Shock states. This consequently allows development and testing of targeted therapeutic strategies beneficially modulating the genomic, humoral and cellular signaling in in those states. This is a challenging task not only to our lab but the entire scientific community focused on the intensive care research. For example, no EMEA/FDA-approved sepsis drug specifically modulating the deranged immune-inflammatory responses in sepsis has been developed yet.
In the context of pre-clinical modeling improvements, our Wiggers-Bernard Initiative platform (coordinated by LBI Trauma) has published new guidelines for animal-based sepsis studies in 2018. A large quality gap and confusion with conflicting data, reflecting the variations found in different labs, substantially hampered an efficient translation of research into the clinic. By implementing the MQTiPSS (Minimum Quality Threshold in Pre-Clinical Sepsis Studies) as Expert Consensus Guidelines, an enhanced standardization can implemented to pre-clinical models of sepsis worldwide. Such an improvement has a high potential to improve translation of pre-clinical findings into clinics.
The videos were produced by, and are provided with the written permission of ESICM (European Society of Intensive Care Medicine). The MQTiPSS guidelines are openly accessible in the journals Intensive Care Medicine Experimental (link to the article), Infection and Shock.
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