OBJECTIVE: The burn victim's inherent state of hyperinflammation frequently camouflages septic events delaying the initiation of targeted intensive care therapy. Accurate biomarkers are urgently needed to support sepsis detection before patients' clinical deterioration. SUMMARY OF BACK-GROUND DATA: Evidence on the usefulness of pancreatic stone protein (PSP) as a powerful diagnostic and prognostic marker in critically ill patients has recently accumulated. METHODS: Analysis of biomarker kinetics (PSP, routine markers) was performed on 90 patients admitted to the Zurich Burn Center between May 2015 and October 2018 with burns 15% total body surface area with regard to infection and sepsis (Sepsis-3) over a 14-day time course. RESULTS: PSP differentiated between sepsis, infection and sterile inflammation from day 3 onward with an area under the curve of up to 0.89 (P < 0.001), therefore, competing with procalcitonin (area under the curve = 0.86, P < 0.001). Compared to routine inflammatory biomarkers, only PSP demonstrated a significant interaction between time and presence of sepsis -signifying a steeper increase in PSP levels in septic patients as opposed to those exhibiting a nonseptic course (interaction P < 0.001). Event-related analysis demonstrated tripled PSP serum levels within 72 hours and doubled levels within 48 hours before a clinically apparent sepsis. CON-CLUSION: PSP is able to differentiate between septic and nonseptic patients during acute burn care. Its steep rise up to 72 hours before clinically overt deterioration has the potential for physicians to timely initiate treatment with reduced mortality and costs.

Background: Diagnosis of sepsis in burn patients remains difficult for various reasons. One major problem is the definition of sepsis itself. Therefore, previous and current sepsis definitions are a matter of ongoing validation, but a well-defined consensus on which clinical and laboratory parameters to incorporate in such a definition is lacking. The aim of the present study was to compare the incidence and time-related occurrence of septic events according to different definitions as well as their accompanying time course of pro-inflammatory biomarkers. Methods: Across the first 14 days after admission, the incidence and time point of sepsis according to three different definitions (Sepsis-3, Sepsis American Burns Association [ABA] 2007, Sepsis Zurich Burn Center) were assessed on a daily basis in adult burn patients with total body surface area (TBSA) ≥15% admitted to the Zurich Burn Center between May 2015 and October 2018. In order to investigate how well daily drawn proinflammatory biomarkers (white blood cells (WBCs), C-reactive protein (CRP), procalcitonin (PCT), and novel pancreatic stone protein (PSP)) reflect the progression of sepsis depending on its type of definition, a longitudinal mixed model analysis was performed across the first 14 days for septic and non-septic patients. Additionally, the relative increase of biomarker levels 24, 48, and 72 h prior to a septic event was analyzed for each definition used. Results: In our cohort of 90 severely burned patients, Sepsis-3 identified 46 patients (51.1%) as septic, while ABA 2007 and the Zurich Burn Center definition counted 33 patients (36.7%) and 24 patients (26.6%), respectively. Sepsis-3 detected sepsis about 1 day earlier than Sepsis ABA 2007 (p < 0.001) and about 0.5 days earlier than Sepsis Zurich Burn Center (p = 0.04). The course of pro-inflammatory biomarkers was largely unaffected by the type of sepsis definition. Irrespective of the sepsis definition, PSP was the only marker to demonstrate a highly significant interaction between time and group (sepsis versus no sepsis) (p < 0.001) with a 3.3–5.5-fold increase within 72 h before the event of sepsis, whereas CRP, PCT, and WBC showed only mild undulations. Conclusions: Despite the ongoing dilemma of how to define sepsis in burn patients, a continually calculated SOFA score as used in Sepsis-3 is advantageous to early identify a patient’s detrimental progression to sepsis. Inclusion of biomarkers, such as PSP, may help support the burn specialist’s diagnosis of sepsis and could improve the diagnostic performance of current and future definitions in burn patients.

Background Altered levels of pro-inflammatory markers secondary to trauma or surgery present a major problem to physicians in being prone to interfere with the clinical identification of infectious events. Methods Patients admitted to Zurich Burn Center between May 2015 and October 2018 with burns C10% total body surface area (TBSA) and without infection. Longitudinal analysis of the time course of PSP and routine inflammatory biomarkers [procalcitonin (PCT), C-reactive protein (CRP) and white blood cells (WBC)] over two days after (a) trauma with initial debridement and (b) subsequent burn surgeries was performed. The influence of TBSA, abbreviated burn severity index (ABSI), age and length of operation was investigated using a linear mixed effect regression model. Results Sixty-six patients (15 female) were included with a mean age of 45.5 ± 18.3 years, median TBSA of 22% (IQR 17) and mean ABSI score 6.8 ± 2.7. PSP was the only biomarker that showed no association with any of the baseline characteristics. Additionally, PSP serum levels did not change over time neither after the burn trauma (p = 0.832) nor after secondary procedures (p = 0.113), while PCT levels increased significantly after the trauma (p \ 0.001). Similarly, CRP serum levels were elevated significantly after both trauma and surgery (p \ 0.001), whereas WBC values demonstrated a significant decline after the trauma (p \ 0.001). Conclusion Established biomarkers (WBC, CRP and PCT) demonstrate decisive alterations after tissue destruction caused by burn injuries and subsequent surgical interventions. The robustness of PSP serum levels toward these inflammatory insults is a quality criterion for an upcoming sepsis biomarker.

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