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

• ClinicalTrials.gov Identifier: NCT04718623
• Recruitment Status: Unknown
• First Posted: January 22, 2021
• Last Update Posted: January 22, 2021
• Sponsor: Alexandria University
• Information provided by (Responsible Party): hossam abousamra, Alexandria University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Sepsis Following A Procedure; Diagnoses, Syndromes, and Conditions	Diagnostic Test: Quantitative determination of serum Presepsin (sCD-14), and Syndecan-1 concentrations

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 Design

• Study Type: Observational
• Estimated Enrollment: 30 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Evaluation of Presepsin and Syndecan-1 as Biomarkers for Early Diagnosis and Prognosis of Sepsis Following Major Surgeries
• Estimated Study Start Date: February 2021
• Estimated Primary Completion Date: March 2022
• Estimated Study Completion Date: April 2022

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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

Biospecimen Retention:   Samples Without DNA

Venous sample will be withdrawn:

This will be assayed to all patients by enzyme-linked immune sorbent assay (ELISA) kit using double-antibody Sandwich-ELISA as the method.

After collection of the whole blood, the blood will be left undisturbed at room temperature. This usually takes 10-20 minutes. After which the serum will be separated by centrifugation at 2000-3000 rpm for 20 minutes. Samples will be stored at -20℃ till assayed.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes 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.

Criteria

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

Contacts and Locations

Contacts

Contact: HOSSAM A HASSAN; +201026100724; drhossam@gmail.com

Contact: Assem A Abd Rabbih, Prof; +201222154828

Sponsors and Collaborators

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

More Information

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• Responsible Party: hossam abousamra, specialist of anaesthesia and intensive care, Alexandria University
• ClinicalTrials.gov Identifier: NCT04718623
• Other Study ID Numbers: presepsin,syndecan-1,sepsis
• First Posted: January 22, 2021
• Last Update Posted: January 22, 2021
• Last Verified: January 2021

Keywords provided by hossam abousamra, Alexandria University:

presepsin; syndecan-1; sepsis biomarkers; following major surgeries

Additional relevant MeSH terms:

Sepsis; Toxemia; Disease; Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation