Early Diagnosis and Prognosis of Postoperative Sepsis by Presepsin and Syndecan-1

January 20, 2021 updated by: hossam abousamra, Alexandria University

Evaluation of Presepsin and Syndecan-1 as Biomarkers for Early Diagnosis and Prognosis of Sepsis Following Major Surgeries

The aim of the present work is to study: Persepsin (sCD-14) and Syndecan-1 as biomarkers following major surgeries for early diagnosis and prognosis of sepsis Primary aim: early diagnosis and prognosis of sepsis Secondary aim: correlate them with SOFA and qSOFA scores.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Millions of patients die around the world every year because of sepsis. 1%-2% of patients admitted to hospital and 25% of Intensive Care Units (ICU) patients suffer from sepsis. One of the most important principles of sepsis management is early diagnosis and treatment as Surviving Sepsis Campaign recommends Hour-1 bundle use.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and organ dysfunction can be identified as an acute change in total Sepsis related Organ Failure Assessment (SOFA) score ≥ 2 points consequent to the infection.

The baseline SOFA score can be zero in patients not known to have pre-existing organ dysfunction. A SOFA score 2 reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection. Patients with suspected infection who are likely to have a prolonged ICU stay or die in the hospital can be promptly identified at the bedside with quick SOFA score (qSOFA) i.e. (HAT ie, Hypotension with systolic blood pressure ≤100 mm Hg, Alteration in mental status, or Tachypnea with respiratory rate ≥22/min.

Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. Patients with septic shock can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain mean arterial blood pressure (MAP) ≥65 mm Hg and having a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation. With these criteria, hospital mortality is in excess of 40%.

As blood culture is needed to confirm diagnosis of sepsis it requires 48-72 hours to be performed, and positive rate is low. No single clinical or biological marker indicative of sepsis has been approved.

There is a need for biomarkers with a high sensitivity and specificity for early diagnosis and prognosis. They also should be positively correlating with Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores.

Many known reported old biological markers as Procalcitonin (PCT), Interleukins, Pro-Vasopressin and C-Reactive Protein (CRP) have been studied and new markers were detected as Presepsin [(soluble CD14 (sCD-14)] and Syndecan-1 from Glycocalyx shedding.

One of the key molecular causes of gram-negative septicemia is a component of the outer membrane of gram-negative bacteria, lipopolysaccharide (LPS). It binds with high affinity to LPS-binding glycoproteins and activates Toll-like receptor (TLR)-4 and co-receptor cluster of differentiation 14 (CD14) expressed on monocytes/macrophages and endothelial cells to induce the secretion of proinflammatory cytokines. This is not the only main pathogenic mechanism of lipopolysaccharide (LPS). An alternative intracellular LPS-sensing pathway, bypassing TLR4, that activates caspases 4 and 5 in humans resulting in inflammasome(it is an intracellular multimeric protein complex that contains (1) a pattern recognition receptor (PRR), (2) an adaptor protein and (3) an effector enzyme (caspase), and catalyses a cellular reaction to protect against an immediate danger via cytokine secretion and cell death) induced pyroptosis has been considered to be the main pathogenic mechanism of sepsis.

Presepsin is an N-terminal fragments of 13kDa of soluble CD14 (sCD14). subtype (sCD14-ST). sCD14 is seen in plasma, and is produced by membrane-bound CD14 (mCD14) fall-off or cell secretion. Cluster of Differentiation 14 (CD14) is the receptor of lipopolysaccharide-lipopolysaccharide binding protein (LPS-LBP) complexes. CD14 has two forms: membrane-bound CD14 (mCD14) and soluble CD14 (sCD14). Presepsin is released after the binding of lipopolysaccharides (LPS) to monocytes, causing an enhanced immune response. mCD14 has a high affinity to LPS, and is mainly expressed on the cell surface of monocytes/macrophages or distributed a little bit on the cell surface of neutrophils. Two kinds of sCD14 could be detected in the plasma of healthy people at microgram level: 49KD and 55KD. sCD14 plays an important role in mediating the immune responses to LPS of CD14-negative cells such as endothelial cells and epithelial cells. sCD14 is cleaved by Cathepsin D and other proteases in plasma.

Since presepsin is produced immediately after the onset of an infection it can be detected early in the development of sepsis.its value as sepsis biomarker was shown in the diagnosis and evaluation of sepsis.

Syndecan-1 is one of components of Glycocalyx layer. This is a layer lining luminal surface of the vascular endothelium, which acts as a protective layer to maintain its permeability and a key factor in leukocyte migration and preventing intravascular coagulation.This is made of glycoproteins, proteoglycans, glycosaminoglycans and other plasma proteins especially hyaluronan and syndecans (a proteoglycan) are the principle component for its integrity.

Early pathophysiologic changes in sepsis concern the endothelium including degradation of the glycocalyx through proteinases produced by pathogens that lead to increase permeability to plasma proteins and fluids subsequently tissue edema formation and organ failure. The damaged glycocalyx layer becomes thinner and releases its components (such as syndecan-1, heparan sulfate, hyaluronan, chondroitin sulfates) into the plasma via enzymes including heparanase that cleaves the heparan sulfate and matrix metalloproteinase (MMPs) A disintegrin and metalloproteases (ADAMs). ADAM17 is inducible, cleaves syndecan-4,while ADAM10 is expressed constitutively, sheds syndecan-1 from proteoglycans. which could be used as a sepsis biomarker.

Study Type

Observational

Enrollment (Anticipated)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Adult patients aged ≥18 years, of either sex, after full recovery from anaesthesia and extubated, following scheduled major abdominal, abdomino-pelvic or vascular surgeries who develop an evident source of infection whether clinical, laboratory manifestation or radiological signs of infection and/or criteria of quick SOFA (qSOFA) after admission to ICU will be included in the study.

Description

Inclusion Criteria:

  • Adult patients aged ≥18 years, of either sex, after full recovery from anaesthesia and extubated, following scheduled major abdominal, abdomino-pelvic or vascular surgeries who develop an evident source of infection whether clinical, laboratory manifestation or radiological signs of infection and/or criteria of quick SOFA (qSOFA) after admission to ICU will be included in the study.

Exclusion Criteria:

  1. Patients aged <18 years old.
  2. Patients with terminal stage of malignancy of any type.
  3. Immune-compromised patients e.g., on immune-suppressive therapy, acquired immunodeficiency syndrome
  4. Patients with end-stage liver or renal disease.
  5. Patients with existing infection before surgery.
  6. Patients with emergency surgeries.
  7. Pregnancy.
  8. Chronic inflammatory disorders e.g., sarcoidosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Sepsis group (SG)
with source of infection and SOFA Score more than or equal 2
Diagnostic test: Quantitative determination of serum Presepsin (sCD-14), and Syndecan-1 concentrations
Quantitative determination of serum Presepsin (sCD-14), and Syndecan-1 concentrations by ELISA technique
Non-Sepsis Group (NSG)
with SOFA score less than 2
Diagnostic test: Quantitative determination of serum Presepsin (sCD-14), and Syndecan-1 concentrations
Quantitative determination of serum Presepsin (sCD-14), and Syndecan-1 concentrations by ELISA technique

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate Presepsin (sCD-14) and Syndecan-1 as biomarkers following major surgeries for early diagnosis and prognosis of sepsis
Time Frame: baseline
measure quantitative concentrations of Persepsin (sCD-14) and Syndecan-1 as biomarkers for early diagnosis and predict outcome
baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
correlate Persepsin (sCD-14) and Syndecan-1 with SOFA and qSOFA scores.
Time Frame: baseline
evaluation of level of Persepsin (sCD-14) and Syndecan-1 with SOFA and qSOFA scores to find if there is relationship between them
baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexandria University

Investigators

  • Study Director: Hesham F Shaaban, Prof, University of Alexandria
  • Study Director: Rania Sh Swelem, Prof, University of Alexandria
  • Study Director: Hussien W Hussein, PHD, University of Alexandria

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

February 1, 2021

Primary Completion (ANTICIPATED)

March 1, 2022

Study Completion (ANTICIPATED)

April 1, 2022

Study Registration Dates

First Submitted

January 18, 2021

First Submitted That Met QC Criteria

January 20, 2021

First Posted (ACTUAL)

January 22, 2021

Study Record Updates

Last Update Posted (ACTUAL)

January 22, 2021

Last Update Submitted That Met QC Criteria

January 20, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • presepsin,syndecan-1,sepsis

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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