Pancreatic stone protein as a novel marker for neonatal sepsis

Abstract

Background: Most clinical trials of sepsis treatment modalities fail at their primary objective of establishing superiority over placebo when added to background standard of care. While there is no definitive explanation for the high failure rate, it might be stated that our attempts to insert a new therapeutic agent into standard of care encounters severe problems with definition of exactly what stage is ongoing, and what are the criteria for progression or resolution from that time point onwards. Clearly there is need for a means of defining steps in the septic process that would apply to individuals, and to better define the course of sepsis in each patient after they are enrolled in a trial. Methods: For core model development, 30 septic patients were studied for time-related progression in relation to biomarkers, employing a Load Model in a neural net algorithm in MatLab. Causative bacterial infections were linked to primary infection sites. In order to minimize overparameterization, the model was allowed to estimate outputs using the best three input parameters. Bacterial load was tracked from origin using clinical and microbiologic data to provide an estimate at the start of sepsis. The bacterial load as well as clinical and laboratory parameters were model inputs with the output parameter being organ failures and/ or mortality. Results: At onset of sepsis, human bacterial load estimates ranged from between 10 8 and 10 11 CFU, which is consistent with inocula in animal models of sepsis. Sepsis proceeds to organ failures and mortality in a series of steps that are initially linked to bacterial load and inflammatory response, followed by coagulopathy, ischemia, oxygen deprivation in organs and tissues, and culminating in organ failures. The later stages of sepsis are all driven by metabolic parameters, and there seems to be little benefit to blocking inflammation at later stages. Substrate and oxygen deficiencies must be addressed first. Conclusion: Neural net progression models based on biomarkers and physiological markers are able to describe the evolution of sepsis to septic shock, organ failures, and provide some evidence that mortality may be a consequence of the stages of sepsis. Overall, these models appear useful to the task of sorting out organ failure endpoints and mechanisms in individual patients with sepsis progression across sepsis to septic shock. P2Extracellular matrix turnover, angiogenesis and endothelial function in acute lung injury: relationship to pulmonary dysfunction and outcome S Sayed * , N Idriss, H Sayyed Faculty of Medicine, Assuit University, Assuit, Egypt E-mail: 1@bmc.com Critical Care 2012, 16(Suppl 3):P2 Background: Acute lung injury (ALI) is a syndrome with a diagnostic criteria based on hypoxemia and a classical radiological appearance, with acute respiratory distress syndrome at the severe end of the disease. Facts recommended the occurrence of rupture of the basement membranes and interstitial matrix remodeling during ALI. Matrix metalloproteinases (MMPs) participate in...

Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a meta-analysis

“…This is consistent with existing studies on healthy neonates [14, 29]. It is important that in future studies on EOS the diagnostic value of age-adjusted PCT cut-offs will be assessed in association with other serum biomarkers [46, 53]. …”

Plasma Levels of Macrophage Migration Inhibitory Factor and d-Dopachrome Tautomerase Show a Highly Specific Profile in Early Life

“…In humans, MIF is present in the amniotic fluid and is expressed in the fetal membranes of the placenta and in the fetal and neonatal lungs (28–31). Interestingly, circulating levels of MIF are at least 10-fold higher in healthy term newborns than in adults (30, 32, 33). We recently reported that high expression levels of MIF sustain innate immune responses of newborn monocytes and counter-regulate the activity of adenosine and prostaglandin E2, two immunosuppressive mediators produced at high levels by the placenta (33).…”

Prognostic Value of High-Sensitivity C-Reactive Protein, Procalcitonin and Pancreatic Stone Protein in Pediatric Sepsis

“…Pancreatic stone protein (PSP) belongs to the family of lectin-binding proteins, and is constitutively secreted by pancreatic acinar cells into pancreatic juice along with zymogens. PSP is a relatively novel marker and research related to it is sparse [26,27]. Palmiere et al reported that PSP and PCT were positively correlated with mortality in patients with or without sepsis, and that the PSP levels were distinctly higher than in sepsis [28].…”

“…Peng et al observed a significant positive correlation between PSP and WBC, as well as serum PCT levels [7]. Schlapbach et al also used combined testing of PSP and PCT to diagnose early-onset sepsis [27]. The levels of PSP were closely related to the degree of infection.…”