Background: Sepsis caused by complicated intra-abdominal infection is associated with high mortality. Loss of endothelial barrier integrity, inflammation, and impaired cellular oxygen have been shown to be primary contributors to sepsis. To date, little is known regarding the pathway for the mobilization of endothelial progenitor cells (EPCs) from the bone marrow in sepsis whereas stromal-cell-derived factor 1a (SDF-1a) and hypoxia inducible factor 1 (HIF-1) seem to have a role in the EPC response to hypoxic microenvironments. The aims of the study are: (a) to determine the time course of the levels of circulating EPCs (CD133/CD34), SDF-1a, and HIF-1 in septic patients undergoing major abdominal surgery (group S), (b) to investigate the relationship between CD133/CD34, HIF-1, and SDF-1a, and (c) to investigate the relationship of these factors with the outcome of group S patients treated with standard conventional therapy alone (CT) or with the addition of extracorporeal hemoperfusion therapy (HCT). Methods/design: Patients undergoing major abdominal surgery will be allocated into groups: postoperative non-septic patients in an emergency surgical ward (group C) and postoperative septic patients in an intensive care unit (group S). The latter will be randomized to receive CT alone (S1) or with HCT (S2). Healthy volunteers (group H) will be recruited at University Hospital Foggia. Peripheral blood (PB) samples will be collected preoperatively (T0), at 24 h (T1), 72 h (T2), 7 (T3), and 10 (T4) postoperative days in groups S and C, and at T0 in group H. The CD34/133 cells and HIF-1 counts will be determined by flow cytometer analysis. The concentration of SDF-1a in plasma will be calculated by enzyme-linked immunosorbent assay analysis (ELISA). Discussion: This prospective randomized clinical trial is designed to investigate circulating stem cells, levels of HIF-1 and SDF-1a, and their interrelationship in septic postoperative abdominal surgical patients treated with CT alone or with HCT. The rationale is that an integrated understanding of the role of hypoxia-related factors and EPCs in PB of septic patients could indicate which molecular processes need to be regulated to recover the innate immunity homeostasis. Understanding the function of EPCs in sepsis may provide innovative diagnostic and therapeutic approaches to improve the prognosis of this syndrome.

Circulating stem cells, HIF-1, and SDF-1 in septic abdominal surgical patients: Randomized controlled study protocol

Cotoia, Antonella
;
Mirabella, Lucia;Altamura, Sabrina;Villani, Rachele;Marchese, Flavia;Mariano, Karim;Livio, Tullo;Cinnella, Gilda
2018

Abstract

Background: Sepsis caused by complicated intra-abdominal infection is associated with high mortality. Loss of endothelial barrier integrity, inflammation, and impaired cellular oxygen have been shown to be primary contributors to sepsis. To date, little is known regarding the pathway for the mobilization of endothelial progenitor cells (EPCs) from the bone marrow in sepsis whereas stromal-cell-derived factor 1a (SDF-1a) and hypoxia inducible factor 1 (HIF-1) seem to have a role in the EPC response to hypoxic microenvironments. The aims of the study are: (a) to determine the time course of the levels of circulating EPCs (CD133/CD34), SDF-1a, and HIF-1 in septic patients undergoing major abdominal surgery (group S), (b) to investigate the relationship between CD133/CD34, HIF-1, and SDF-1a, and (c) to investigate the relationship of these factors with the outcome of group S patients treated with standard conventional therapy alone (CT) or with the addition of extracorporeal hemoperfusion therapy (HCT). Methods/design: Patients undergoing major abdominal surgery will be allocated into groups: postoperative non-septic patients in an emergency surgical ward (group C) and postoperative septic patients in an intensive care unit (group S). The latter will be randomized to receive CT alone (S1) or with HCT (S2). Healthy volunteers (group H) will be recruited at University Hospital Foggia. Peripheral blood (PB) samples will be collected preoperatively (T0), at 24 h (T1), 72 h (T2), 7 (T3), and 10 (T4) postoperative days in groups S and C, and at T0 in group H. The CD34/133 cells and HIF-1 counts will be determined by flow cytometer analysis. The concentration of SDF-1a in plasma will be calculated by enzyme-linked immunosorbent assay analysis (ELISA). Discussion: This prospective randomized clinical trial is designed to investigate circulating stem cells, levels of HIF-1 and SDF-1a, and their interrelationship in septic postoperative abdominal surgical patients treated with CT alone or with HCT. The rationale is that an integrated understanding of the role of hypoxia-related factors and EPCs in PB of septic patients could indicate which molecular processes need to be regulated to recover the innate immunity homeostasis. Understanding the function of EPCs in sepsis may provide innovative diagnostic and therapeutic approaches to improve the prognosis of this syndrome.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11369/366570
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