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In the present study, 126 patients were enrolled (23 control, 38 non-septic and 65 septic patients). Blood samples were collected from septic patients at the intensive care unit (ICU) at three time points (T1-3): T1: within 12h after admission; T2: second day morning; T3: third day morning. Sampling points for non-septic ICU patients were T1 and T3. Exclusion criteria were patients under 18 years of age, unobtainable consent, end-stage renal disease requiring chronic dialysis or kidney transplantation and patients with malignancies needing palliative care. Not more than one sample (venous blood) was collected from control patients. Plasma presepsin levels were determined by an automated chemiluminescence-based Point of Care instrument while serum gelsolin levels were measured using an automated immune turbidimetric assay. Plasma presepsin concentrations were expressed as pg/mL, while serum gelsolin levels were expressed as mg/L. Data were compared with laboratory and clinical parameters. Patients were categorized by the Sepsis-3 definitions and 10-day mortality data were investigated. Presepsin:gelsolin ratio was evaluated in major sepsis-related organ dysfunctions including hemodynamic disturbances, respiratory insufficiency and acute kidney injury (AKI).
Presepsin is the 13-kDa soluble N-terminal fragment of the 55-kDa cluster of differentiation (CD) marker protein CD14, which is the receptor for lipopolysaccharide (LPS) and LPS-binding protein complexes. CD14 is a glycoprotein expressed mostly on the membrane surface of macrophages, monocytes and granulocytes which is released and degraded during inflammation after the recognition of pathogen-associated molecular patterns (PAMP), thus probably resulting in earlier elevation of plasma presepsin (PSEP) levels than the conventional sepsis biomarkers (C-reactive protein, procalcitonin). There is a growing body of evidence indicating increasing PSEP levels as kidney function decreases (e.g. during chronic kidney disease or sepsis-related AKI). Gelsolin (GSN) is a multifunctional protein existing in three different isoforms. Secreted or plasma GSN (MW = 83 kDa) is an essential component of the so-called extracellular actin scavenger system, therefore, decreasing serum GSN levels were reported in various clinical conditions (e.g. severe sepsis, multiple organ dysfunction syndrome (MODS), extensive trauma, acute liver failure, myocardial infarction). As albumin levels also tend to decrease in severe catabolic conditions, the simultaneous measurement of PSEP and GSN could prove to be useful regarding the diagnosis and prognosis of sepsis and sepsis-related organ dysfunction. Therefore, a new potential marker was investigated: the presepsin:gelsolin (PSEP:GSN) ratio. The main focuses of this study were analyzing the time course of PSEP:GSN ratio in non-septic and septic patients, while also investigating its diagnostic and prognostic utility in various sepsis-related organ dysfunctions in contrast to the conventional sepsis markers and clinical prognostic scores.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Non-sepsis | Non-septic patients receive supportive treatment at the ICU. |
| |
| Sepsis | Patients receive sepsis therapy. |
| |
| Sepsis-related organ dysfunction | Patients receive sepsis therapy and advanced supportive treatment based on the occurrence of specific sepsis-related organ dysfunctions. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Supportive therapy at the ICU | Other | Non-septic ICU patients received adequate supportive treatment (fluid resuscitation, respiratory, anticoagulation, antimicrobial and vasopressor therapy along with sedation, ulcer prophylaxis and nutrition. Blood sampling for non-septic patients were the first (T1) and third (T3) postoperative morning at the ICU. Besides, 23 healthy outpatients were documented without sepsis or sepsis-related organ dysfuntion as a control group. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Presepsin concentrations | Plasma samples were centrifuged (10 min, 1500 g), then sample aliquots were stored without preservatives at -70 °C until analysis. Plasma presepsin levels were measured using an automated Point of Care instrument (PATHFAST; LSI Medience Corporation, Tokyo, Japan) based on a chemiluminescent enzyme immunoassay. | 3 days |
| Serum gelsolin concentrations | Clotted blood samples were centrifuged (10 min, 1500 g), then sample aliquots were stored without preservatives at -70 °C until analysis. Serum gelsolin levels were determined with an automated immune turbidimetric assay (Cobas 8000/c502 module (Roche Diagnostics GmbH, Mannheim, Germany)). | 3 days |
| Measure | Description | Time Frame |
|---|---|---|
| Presepsin:gelsolin ratios | Plasma presepsin levels were determined by an automated Point of Care instrument, while serum gelsolin concentrations were measured using an immune turbidimetric assay, therefore Presepsin:gelsolin ratios could be calculated. | 5 days |
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Inclusion Criteria:
Exclusion Criteria:
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Healthy control individuals (n=23), non-septic ICU patients (n=38) and septic patients (n=65) were enrolled, while the septic group was also investigated based on the occurrence of sepsis-related organ dysfunction (e.g. acute kidney injury, hemodynamic instability, acute respiratory distress syndrome)
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| Name | Affiliation | Role |
|---|---|---|
| Dániel Ragán, MD | Department of Laboratory Medicine, Medical School, University of Pécs | Principal Investigator |
| Péter Kustán, MD, PhD | Department of Laboratory Medicine, Medical School, University of Pécs | Principal Investigator |
| Zoltán Horváth-Szalai, MD, PhD | Department of Laboratory Medicine, Medical School, University of Pécs | Principal Investigator |
| Balázs Szirmay, MD | Department of Laboratory Medicine, Medical School, University of Pécs | Principal Investigator |
| Attila Miseta, MD, Dsc | Department of Laboratory Medicine, Medical School, University of Pécs | Principal Investigator |
| Gábor Woth, MD, PhD | Department of Anesthesiology and Intensive Therapy, Medical School, University of Pécs | Principal Investigator |
| Tamás Kőszegi, MD, PhD | Department of Laboratory Medicine, Medical School, University of Pécs | Principal Investigator |
| Diána Mühl, MD, PhD | Department of Anesthesiology and Intensive Therapy, Medical School, University of Pécs | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Anesthesiology and Intensive Therapy, Medical School, University of Pécs | Pécs | Baranya | 7624 | Hungary |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37215727 | Derived | Ragan D, Kustan P, Horvath-Szalai Z, Szirmay B, Miseta A, Woth G, Koszegi T, Muhl D. Presepsin: gelsolin ratio, as a promising marker of sepsis-related organ dysfunction: a prospective observational study. Front Med (Lausanne). 2023 May 5;10:1126982. doi: 10.3389/fmed.2023.1126982. eCollection 2023. |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| D012772 | Shock, Septic |
| D012128 | Respiratory Distress Syndrome |
| C537459 | Meretoja syndrome |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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Blood (Serum; Plasma)
|
| Sepsis therapy | Other | Patients receiving sepsis therapy followed the international guidelines of the 2016 Surviving Sepsis Campaign (SSC) regarding respiratory, antimicrobial, anticoagulation, vasopressor and hydrocortisone therapy, along with adequate fluid resuscitation, sedation, ulcer prophylaxis and nutrition. Blood samples were collected at the ICU from this patient group at three time points (T1-3): T1: within 12 hours after admission; T2: second day morning; T3: third day morning of follow-up. |
|
| Sepsis-related organ dysfunction therapy | Other | Patient management of sepsis and sepsis-related organ dysfunction followed the international guidelines of the 2016 Surviving Sepsis Campaign (SSC) regarding respiratory, antimicrobial, anticoagulation, vasopressor and hydrocortisone therapy, along with adequate fluid resuscitation, sedation, ulcer prophylaxis, nutrition and renal replacement therapy (if needed). In this patient group, blood sampling was performed at three time points (T1-3): T1: within 12 hours after admission; T2: second day morning; T3: third day morning of follow-up. |
|
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |