None listed
Conditions
Brief summary
BACKGROUND: Sepsis represents an acute condition with high mortality. Endogenous anti-cytokine autoantibodies are present in healthy subjects and in a number of chronic inflammatory diseases. In autoimmune diseases, their role is detrimental as they cause dysfunction and worsen the illness. Their presence and role is sepsis is still not known. AIM OF THE STUDY: With this study we aim to demonstrate the presence and the prognostic role of autoantibodies and circulating mediators in the blood and urine of patients with sepsis and septic shock defined on the basis of the recently published new criteria.
Interventions
Patients will be divided into three groups according to the diagnosis: 1) infection with quick SOFA<2, 2) sepsis, and 3)septic shock, according to the new definitions (Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:801-10).
The definition of sepsis will be given according to an increase in SOFA equal or greater than 2; while the definition of septic shock will require the use of vasopressors to maintain a mean arterial press
Patients will be divided into three groups according to the diagnosis: 1) infection with quick SOFA<2, 2) sepsis, and 3)septic shock, according to the new definitions (Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:801-10). The definition of sepsis will be given according to an increase in SOFA equal or greater than 2; while the definition of septic shock will require the use of vasopressors to maintain a mean arterial pressure of 65 mmHg or greater and the presence of serum lactate level greater than 2 mmol/L in the absence of hypovolemia. We will enroll prospectively the first 200 patients meeting the three diagnostic groups that enter the Emergency Department of the Maggiore della Carita Hospital in Novara (this estimate will be refined on the basis of a pilot study). We will also study a group of 30 healthy volunteers matched for gender and age. With this study we aim to demonstrate the presence and the prognostic role of endogenous autoantibodies and circulating mediators in the blood of the three groups of patients studied and in a group of controls. Data and samples (blood and urine) collection will be carried out at enrollment (T0), after 24 hours (T1), after 48 hours (T2) and after 7 days from the enrollment or at discharge (T3). We will also perform a telephonic follow-up 1 and 6 months after the enrollment in order to assess mortality. Protein assays will be performed by using Enzyme-Linked Immunosorbent Assay (ELISA) in order to evaluate the blood or urine concentration of OPN and anti-OPN antibodies, IL-8 and anti-IL-8 IgM, , IL-6 and anti-IL-6, GAS6 and sMer, suPAR, NGAL and KIM1. Isolation and characterization of primary cultures of human kidney-derived endothelial cells will be carried out using typical endothelial markers (CD31, CD105, and von Willebrand factor). Plasma collected from septic patients will be incubated on these cells for specific in vitro assays: angiogenetic, apoptotic, quantification of nitric oxide (NO) generation and radical oxygen species (ROS) production assay.
Sponsors
University of Piemonte Oreintale "Amedeo Avogadro"
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria will be: suspected infection with at least two of the elements of the quick Sequential Organ Failure Assessment score (qSOFA)i.e., respiratory rate equal or more than 22/min, altered mental state with GCS less than 15, systolic arterial blood pressure equal or less than 100 mmHg. A written informed consent and age equal or more than 18 years and less than 85 years old will be mandatory as well. Healthy volunteers will be included if with an age equal or more than 18 years and less than 85 years old.
Exclusion criteria
Age equal or more than 18 years; age less than 85; lack of informed consent.
Outcome results
None listed