PORTFOLIO

Sepsis is a life-threatening condition due to untreated or severe infections, leading to an uncontrollable inflammatory response throughout the body and eventually organ failure. Sepsis often occurs in patients with an impaired immune system, including post-operative cases and in the presence of pre-existing diseases. Early detection of infection and development of sepsis is important to initiate adequate life-supporting therapy. Unfortunately, early markers of sepsis are not available or not reliable. Thus, there is an ongoing need for better diagnostic tests.

In animal experiments, we observed that pancreatic stone protein (PSP), a protein produced by the pancreas during pancreatitis, is also markedly increased in the serum during inflammatory events affecting other organs. Therefore, we hypothesize that serum levels of PSP act as a biomarker for infection and sepsis. To test this hypothesis, we developed an assay able to accurately measure PSP levels in human serum and quantified PSP values in a study of accident patients that required emergency treatment. In this study, we showed that patients developing sepsis had highly increased PSP values, even before the clinical diagnosis of the disease. We concluded that PSP is a useful diagnostic test with a better diagnostic efficacy than currently established serum markers such as C-reactive protein (CRP), Interleukin 6 (IL-6) and procalcitonin (PCT). To further confirm the validity of this marker, we planned and initiated several clinical trials under different clinical situations.

The prevalence of a disease in the population has an important influence on the positive predictive value of a diagnostic test. Thus, we aim to compare the accuracy of the PSP test with the current serum markers in two stages of trials that include cohorts with high (stage 1) and low (stage 2) incidence of sepsis. In addition, we plan a prospective randomized trial that uses PSP values as a basis for a clinical decision (stage 3).

With these clinical studies we will be able to validate PSP as a marker of infection and sepsis. We perceive a number of potential clinical applications: earlier and patient tailored administration of antibiotics, interventions during intensive care including ventilation and hemofiltration, and the indication for operation or re-operation. In conjunction with currently established serum markers, clinical decisions based on PSP may lead to a reduction of morbidity, mortality and costs.

This project evaluates a new biomarker which has not been recognized by physicians and surgeons dealing with infection and sepsis. Validation under various clinical situations will provide recommendations for its use in clinical practice. The assay should reach commercial applicability in a few years. Establishing an alternative biomarker available for clinical diagnosis and therapy monitoring will increase the chances for better care of severely ill patients.

We have concluded and published clinical evaluation of PSP under different conditions, particularly in the setting of postoperative intensive care. Studies still under way are focusing on postoperative outcome after abdominal surgery, evaluation of PSP as a diagnostic tool for appendectomy, the evaluation of PSP in septic complications during pregnancy and in patients with severe burns.

Several of our studies evaluated the potential of PSP in combination with other serum markers (e.g. PCT) to increase the diagnostic power. This would be an interesting approach in a ‘point-of-care’ situation in the intensive care unit, where results should be quickly available for decision making.

Proper timing for the application of antibiotics is an important issue in several diseases, e.g. severe burns. Here, PSP might be a good diagnostic tool to help initiate antibiotic therapy.

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