Sepsis is a life-threatening syndrome caused by a dysregulated host response to an infection leading to organ dysfunction. The COVID-19 pandemic profoundly increased the incidence of sepsis, which was already extremely high before, as sepsis affects 50 million people per year and causes one in five deaths. Despite attempts to unravel its complex pathogenesis, exact mechanisms driving the extreme heterogenic clinical course remain unknown.
Early recognition of sepsis and prediction of the clinical course is difficult as signs and symptoms may be nonspecific and are highly variable. In spite of timely initiation of adequate care, clinical deterioration occurs in about one in four patients within 24 hours and approximately one in five patients die in hospital. Survivors of sepsis have a reduced quality of life for months to years after sepsis and are at major risk for chronic kidney disease and (fatal) cardiovascular events.
Current treatment is limited to antibiotics and supportive care, rather than targeting the molecular causes of organ dysfunction. We aim to improve early recognition and develop precision medicine to improve outcome of this common, potentially fatal disease.
Every year, more people die of sepsis than of any type of cancer, myocardial infarction or traffic accidents in the Netherlands. To improve recognition and treatment of early sepsis, we follow two main research lines.
To improve early recognition and monitor response to treatment in individual patients, we have initiated a large data-biobank in acute care: Acutelines. We collect health data from pre-hospital up to long after discharge, which is combined with vital parameters and electrophysiologic waveforms from wearable devices and biomarkers. By comprehensively analysing the clinical course over time in patients acutely admitted to the hospital, we aim to identify early risk markers (i.e. biomarkers, physiological patterns) predictive of the clinical response to treatment with relevance to both short- and long-term outcome. These risk markers will be exploited to predict response to treatment in individual patients and support clinical decisions, by integrating the full set of clinical, physiological and molecular data and developing pattern recognition using machine-learning approaches. The identified biomarkers and patterns will be exploited in collaboration with private partners to develop assays and medical software that can be used to facilitate early recognition, predict response to treatment and support clinical decisions.
As the precise mechanisms that lead to organ dysfunction and death are largely unknown, current treatment is limited to antibiotics and supportive care, rather than targeting molecular derangements. To optimize outcome from sepsis, novel approaches to improve early recognition, treatment and prediction of treatment response are needed. Risk markers associated with the clinical course in patients with early sepsis, will be exploited in pre-clinical models of sepsis (i.e. cells, mice, fruit flies) to identify novel therapeutic targets to feed drug discovery, with a specific focus on preservation of mitochondrial function, which is considered to be the culprit in the induction of organ failure in sepsis. An effective solution to prevent organ failure during physiological extreme conditions is found in nature: hibernation, which is associated with resistance to metabolic stress and longevity. Despite a profound reduction in blood flow and body temperature, hibernators maintain mitochondrial homeostasis and preclude organ injury. The protective mechanisms of hibernation can in part be mimicked by caloric restriction, modulation of energy sensing pathways (i.e. Sirtuins, AMPK) or augmenting hydrogen sulphide (H2S) levels, which might reveal to be a novel cornerstone to preserve mitochondrial function and thereby cellular homeostasis in the treatment of sepsis.
University Medical Center Groningen (UMCG)
Early sepsis research group
PO Box 30.001
9700 RB Groningen
The Netherlands
Visiting address
University Medical Center Groningen (UMCG)
Early sepsis research group
Hanzeplein 1
9713 GZ Groningen
The Netherlands
