Exosomal CD63 in critically ill patients with sepsis

AbstractCD63 is one of the tetraspanin protein family members that is ubiquitously expressed on exosomes and is involved in the signal transduction of various types of immune cells. It may thus contribute to immunometabolic mechanisms of cellular and organ dysfunction in sepsis. Nonetheless, the association of exosomal CD63 with the severity and mortality of sepsis is not well known. Therefore, in the present study, the overall levels of exosomal CD63 were evaluated to ascertain whether they were associated with organ failure and mortality in patients with sepsis. Exosomal CD63 was measured from prospectively enrolled critically-ill patients with sepsis (n = 217) and healthy control (n = 20). To detect and quantify exosomes in plasma, a commercially available enzyme-linked immunosorbent assay kit was used according to the manufacturer’s protocol. The total number of exosomal CD63 was determined by quantifying the immunoreactive CD63. The association between plasma levels of exosomal CD63 and sequential organ failure assessment (SOFA) score was assessed by a linear regression method. The best cut-off level of exosomal CD63 for 28-day mortality prediction was determined by Youden’s index. Among 217 patients with sepsis, 143 (66%) patients were diagnosed with septic shock. Trends of increased exosomal CD63 levels were observed in control, sepsis, and septic-shock groups (6.6 µg/mL vs. 42 µg/mL vs. 90 µg/mL, p < 0.001). A positive correlation between exosomal CD63 and SOFA scores was observed in patients with sepsis (r value = 0.35). When patients were divided into two groups according to the best cut-off level, the group with higher exosomal CD63 levels (more than 126 µg/mL) was significantly associated with 28-day and in-hospital mortality. Moreover, the Kaplan–Meier survival method showed a significant difference in 90-day survival between patients with high- and low-exosomal CD63 levels (log-rank p = 0.005). Elevated levels of exosomal CD63 were associated with the severity of organ failure and predictive of mortality in critically ill patients with sepsis.

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Faculty Opinions recommendation of Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718312921.793493679 ◽

2014 ◽

Author(s):

Niranjan Kissoon ◽

Srinivas Murthy

Keyword(s):

Septic Shock ◽

Severe Sepsis ◽

New Zealand ◽

Critically Ill ◽

Critically Ill Patients ◽

Sepsis And Septic Shock

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Diagnostic and Prognostic Value of Presepsin in Patients with Non-Infectious Organ Failure, Sepsis, and Septic Shock: A Prospective Observational Study According to the Sepsis-3 Definitions

10.21203/rs.3.rs-413686/v1 ◽

2021 ◽

Author(s):

Sukyo Lee ◽

Juhyun Song ◽

Dae Won Park ◽

Hyeri Seok ◽

Jae-hyung Cha ◽

...

Keyword(s):

Septic Shock ◽

Observational Study ◽

Organ Failure ◽

Prospective Observational Study ◽

Survival Curve ◽

Curve Analysis ◽

Roc Curve Analysis ◽

Kaplan Meier ◽

Sepsis And Septic Shock ◽

Meier Survival Curve

Abstract Background: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. Early diagnosis of sepsis is challenging due to unknown sources of infection, and mortality prediction is usually complex. We aimed to investigate the clinical value of presepsin for discriminating sepsis from non-infectious organ failure and predicting mortality among sepsis patients in the emergency department (ED).Methods: This prospective observational study included 420 patients divided into three groups according to the Sepsis-3 definitions: non-infectious organ failure (n=142), sepsis (n=141), and septic shock (n=137). Blood samples for biomarker measurement of presepsin, procalcitonin, and C-reactive protein were drawn in the ED and biomarker levels were compared between the groups. Optimal cut-off values for presepsin to discriminate between the three clinical diagnoses were evaluated using receiver operating characteristic (ROC) curve analysis. We also performed ROC curve analysis for each biomarker as a predictor of mortality. After excluding non-infectious organ failure, we extracted the optimal cut-off value of presepsin to predict mortality associated with sepsis and septic shock and performed Kaplan–Meier survival curve analysis according to the cut-off value.Results: Presepsin levels (median [IQR]) were significantly higher in sepsis than in non-infectious organ failure (792 [450–1273] vs. 286 [170–417], p <0.001) and significantly higher in septic shock than in sepsis (1287 [589–2365] vs. 792 [450–1273], p=0.002). The optimal cut-off value for presepsin to discriminate between sepsis and non-infectious organ failure was 582 pg/mL (sensitivity, 70.1; specificity, 89.4; AUC, 0.877; p <0.001) and to discriminate between sepsis and septic shock was 1285 pg/mL (sensitivity, 50.4; specificity, 76.6; AUC, 0.618; p <0.001). The optimal cut-off value for presepsin for predicting 30-day mortality was 821 pg/mL (sensitivity, 68.9; specificity, 50.5; AUC, 0.605; p=0.005) in patients with sepsis and septic shock. Kaplan-Meier survival curve analysis showed that patients with higher presepsin levels (≥821 pg/mL) had significantly higher mortality than patients with lower presepsin levels (<821 pg/mL) (log-rank test; p=0.004). Conclusions: Presepsin levels could effectively differentiate sepsis from non-infectious organ failure and septic shock from sepsis. Presepsin levels could help clinicians predict mortality in patients with sepsis and septic shock.

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Circulating myeloperoxidase is elevated in septic shock and is associated with systemic organ failure and mortality in critically ill patients

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2019.11.004 ◽

2020 ◽

Vol 152 ◽

pp. 462-468 ◽

Cited By ~ 4

Author(s):

Anitra C. Carr ◽

Emma Spencer ◽

Teagan S. Hoskin ◽

Patrice Rosengrave ◽

Anthony J. Kettle ◽

...

Keyword(s):

Septic Shock ◽

Organ Failure ◽

Critically Ill ◽

Critically Ill Patients

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Chronically critically ill patients: different behavior in severe sepsis and septic shock?

Intensive Care Medicine Experimental ◽

10.1186/2197-425x-3-s1-a83 ◽

2015 ◽

Vol 3 (S1) ◽

Author(s):

DH Prevedello ◽

A Rea-Neto ◽

HA Teive ◽

LA Tannous ◽

RAO Deucher ◽

...

Keyword(s):

Septic Shock ◽

Severe Sepsis ◽

Critically Ill ◽

Critically Ill Patients ◽

Chronically Critically Ill ◽

Sepsis And Septic Shock

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Population Pharmacokinetics and Monte Carlo Dosing Simulations of Meropenem during the Early Phase of Severe Sepsis and Septic Shock in Critically Ill Patients in Intensive Care Units

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04166-14 ◽

2015 ◽

Vol 59 (6) ◽

pp. 2995-3001 ◽

Cited By ~ 30

Author(s):

Sutep Jaruratanasirikul ◽

Suriyan Thengyai ◽

Wibul Wongpoowarak ◽

Thitima Wattanavijitkul ◽

Kanyawisa Tangkitwanitjaroen ◽

...

Keyword(s):

Septic Shock ◽

Monte Carlo ◽

Severe Sepsis ◽

Critically Ill ◽

Critically Ill Patients ◽

Early Phase ◽

Volume Of Distribution ◽

Therapeutic Success ◽

Altered Pharmacokinetic ◽

Sepsis And Septic Shock

ABSTRACTPathophysiological changes during the early phase of severe sepsis and septic shock in critically ill patients, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors influencing therapeutic success. The aims of this study were (i) to reveal the population PK parameters and (ii) to assess the probability of target attainment (PTA) for meropenem. The PK studies were carried out following administration of 1 g of meropenem every 8 h during the first 24 h of severe sepsis and septic shock in nine patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the free plasma drug concentration remains above the MIC (fT>MIC) and 80%fT>MIC. The volume of distribution (V) and total clearance (CL) of meropenem in these patients were 23.7 liters and 7.82 liters/h, respectively. For pathogens with MICs of 4 μg/ml, the PTAs of 40%fT>MICfollowing administration of meropenem as a 1-h infusion of 1 g every 8 h and a 4-h infusion of 0.5 g every 8 h were 92.52% and 90.29%, respectively. For pathogens with MICs of 2 μg/ml in immunocompromised hosts, the PTAs of 80%fT>MICfollowing administration of 1-h and 4-h infusions of 2 g of meropenem every 8 h were 84.32% and 94.72%, respectively. These findings indicated that theVof meropenem was greater and the CL of meropenem was lower than the values obtained in a previous study with healthy subjects. The maximum recommended dose, i.e., 2 g of meropenem every 8 h, may be required for treatment of life-threatening infections in this patient population.

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