scholarly journals Prognostic value of circulating markers of neutrophil activation, neutrophil extracellular traps, coagulation and fibrinolysis in patients with terminal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Axel Rosell ◽  
Katherina Aguilera ◽  
Yohei Hisada ◽  
Clare Schmedes ◽  
Nigel Mackman ◽  
...  
Keyword(s):  
Advanced Cancer ◽  
Prognostic Value ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Activation ◽  
Terminal Cancer ◽  
Extracellular Traps ◽  
Terminal Cancer Patients ◽  
Future Care ◽  
Circulating Markers ◽  
Coagulation And Fibrinolysis

AbstractPredicting survival accurately in patients with advanced cancer is important in guiding interventions and planning future care. Objective tools are therefore needed. Blood biomarkers are appealing due to their rapid measurement and objective nature. Thrombosis is a common complication in cancer. Recent data indicate that tumor-induced neutrophil extracellular traps (NETs) are pro-thrombotic. We therefore performed a comprehensive investigation of circulating markers of neutrophil activation, NET formation, coagulation and fibrinolysis in 106 patients with terminal cancer. We found that neutrophil activation and NET markers were prognostic in terminal cancer patients. Interestingly, markers of coagulation and fibrinolysis did not have a prognostic value in this patient group, and there were weak or no correlations between these markers and markers of neutrophil activation and NETs. This suggest that NETs are linked to a poor prognosis through pathways independent of coagulation. Additional studies are needed to determine the utility of circulating neutrophil activation and NET markers, alone or in concert with established clinical parameters, as objective and reliable prognostic tools in advanced cancer.

scholarly journals Synthetic Siglec-9 Agonists Inhibit Neutrophil Activation Associated with COVID-19

2020 ◽  
Author(s):  
Corleone Delaveris ◽  
Aaron Wilk ◽  
Nicholas Riley ◽  
Jessica Stark ◽  
Samuel Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Therapeutic Strategy ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Activation ◽  
Signaling Cascade ◽  
Peripheral Inflammation ◽  
Pulmonary Tissue ◽  
Extracellular Traps ◽  
Cell Death Pathway ◽  
Key Factor

Severe cases of coronavirus disease 2019 (COVID-19), caused by infection with SARS-Cov-2, are characterized by a hyperinflammatory immune response that leads to numerous complications. Production of proinflammatory neutrophil extracellular traps (NETs) has been suggested to be a key factor in inducing a hyperinflammatory signaling cascade, allegedly causing both pulmonary tissue damage and peripheral inflammation. Accordingly, therapeutic blockage of neutrophil activation and NETosis, the cell death pathway accompanying NET formation, could limit respiratory damage and death from severe COVID-19. Here, we demonstrate that synthetic glycopolymers that activate the neutrophil checkpoint receptor Siglec-9 suppress NETosis induced by agonists of viral toll-like receptors (TLRs) and plasma from patients with severe COVID-19. Thus, Siglec-9 agonism is a promising therapeutic strategy to curb neutrophilic hyperinflammation in COVID-19.<br>

scholarly journals Autoantibodies stabilize neutrophil extracellular traps in COVID-19

2021 ◽  
Author(s):  
Yu Zuo ◽  
Srilakshmi Yalavarthi ◽  
Sherwin Navaz ◽  
Claire Hoy ◽  
Hui Shi ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Neutrophil Extracellular Traps ◽  
Healthy Controls ◽  
Oxygen Supplementation ◽  
Dna Complexes ◽  
Extracellular Traps ◽  
Circulating Markers ◽  
Clinical Associations ◽  
Antibody Levels ◽  
D Dimer

The release of neutrophil extracellular traps (NETs) by hyperactive neutrophils is recognized to play an important role in the thromboinflammatory milieu inherent to severe presentations of COVID-19. At the same time, a variety of functional autoantibodies have been observed in individuals with severe COVID-19 where they likely contribute to immunopathology. Here, we aimed to determine the extent to which autoantibodies might target NETs in COVID-19 and, if detected, to elucidate their potential functions and clinical associations. We measured global anti-NET activity in 171 individuals hospitalized with COVID-19 alongside 48 healthy controls. We found high anti-NET activity in the IgG and IgM fractions of approximately 40% and 50% of patients, respectively. There was a strong correlation between anti-NET IgG and anti-NET IgM, with high anti-NET antibody levels in general associating with circulating markers of NETs such as myeloperoxidase-DNA complexes and calprotectin. Clinically, anti-NET antibodies tracked with impaired oxygenation efficiency and elevated levels of circulating D-dimer. Furthermore, patients who required mechanical ventilation had higher levels of anti-NET antibodies than those who did not require oxygen supplementation. Mechanistically, anti-NET antibodies of the IgG isotype impaired the ability of DNases in healthy serum to degrade NETs. In summary, these data reveal high levels of anti-NET antibodies in individuals hospitalized with COVID-19, where they likely impair NET clearance and thereby potentiate SARS-CoV-2 mediated thromboinflammation.

scholarly journals Alterations in neutrophil extracellular traps is associated with the degree of decompensation of liver cirrhosis

2016 ◽  
Vol 10 (05) ◽  
pp. 512-517 ◽  
Author(s):  
Juan M Agraz-Cibrian ◽  
Jorge E Segura-Ortega ◽  
Vidal Delgado-Rizo ◽  
Mary Fafutis-Morris
Keyword(s):  
Liver Cirrhosis ◽  
Bacterial Infections ◽  
Causes Of Death ◽  
Serum Levels ◽  
Study Groups ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Activation ◽  
Neutrophil Extracellular Trap ◽  
Activation Markers ◽  
Extracellular Traps

Introduction: Liver cirrhosis (LC) constitutes one of the main 10 causes of death worldwide. LC has a characteristic asymptomatic compensated phase followed by a progressive decompensated phase, in which diverse complications are presented. LC patients are highly prone to bacterial infections. The neutrophils in these patients present defects in the production of oxygen radicals, which are essential for bacteria elimination as in the activation of neutrophil extracellular traps (NETs). The main objective of this work was to determine the NETs and neutrophil activation markers in LC patients. Methodology: Neutrophil purification was done with Ficoll Histopaque from a sample of the peripheral blood of patients with compensated and decompensated LC. Neutrophils were activated with Phorbol 12-myristate 13-acetate to evaluate the release of NETs by means of fluorescence microscopy and fluorometry, while expression of activation markers (CD69, CD80, perforin, and CAP-18) was evaluated by flow cytometry. Results: A significant decrease in the release capability of NETs was observed as the level of LC in the patient increased. When comparing serum levels in inflammatory cytokines among the different study groups, significant differences were observed. No significant differences were detected on neutrophil activation markers; nevertheless, there was a correlation between diminution of CD69 and CD80 expression in decompensated patients. Conclusions: We demonstrated that LC patients with neutrophil extracellular trap release deficiencies could have an increased rate of complications.

scholarly journals Neutrophil extracellular traps: diagnostic and prognostic value in COVID-19

2020 ◽  
Vol 48 ◽  
pp. 43-50
Author(s):  
D. V. Kassina ◽  
I. A. Vasilenko ◽  
A. S. Gur’ev ◽  
A. Yu. Volkov ◽  
V. B. Metelin
Keyword(s):  
Healthy Volunteers ◽  
Whole Blood ◽  
Prognostic Value ◽  
Acute Infection ◽  
Invasive Mechanical Ventilation ◽  
Neutrophil Extracellular Traps ◽  
Control Group ◽  
Risk Of Death ◽  
Extracellular Traps ◽  
Diagnostic And Prognostic Value

Rationale: An important element of antiviral defense in the pathophysiology of COVID-19 is the innate cell immunity including polymorphonuclear neutrophils prone to netotic transformation. Neutrophils can be not only a marker of acute infection, but, being a source of neutrophil extracellular traps (NET), can play a key role in the development of thrombotic complications leading to acute respiratory insufficiency in COVID-19.Aim: To determine the diagnostic and prognostic value of NET levels in patients with COVID-19.Materials and methods: We monitored NET levels in peripheral blood of 34 patients with COVID-19 (mean age, 67 ± 15.8 years), admitted to MONIKI hospital. The control group consisted of 54 healthy volunteers (mean age, 52 ± 11.5 years). Whole blood samples of 2 pL each were used for the preparation of monolayer smears (Giemsa stain) and calculation of at least 200 cell structures including native intact and transformed neutrophils (MECOS-C2 microscope, Medical computer systems).Results: Patients with COVID-19 had higher NET levels, compared to those in healthy controls: 14.5% (2.9-28.6%) vs. 5.0% (1.8-11.9%, p < 0.0001). The patients who were on non-invasive respiratory support (23.5%) had a NET level of 12% (8.122.3%), whereas those on invasive mechanical ventilation (17.6%) had a 1.5-fold higher NET level of 17.9% (12.3-28.2%) (p < 0.05). In the patients who died (11.8% of the cases), the NET level amounted to 19% (16.5-26%, p < 0.05). Monitoring of blood NET levels was performed in 9 patients from the day of admittance to the day of their transfer to the intensive care unit / discharge / death. It was shown that a decrease of NET levels mirrors an improvement of the patient's clinical condition and efficacy of his/hers treatment. On the opposite, an increase of NET levels can indicate a deterioration and risk of unfavorable course.Conclusion: We have identified some pathophysiological mechanisms in COVID-19, related to the neutrophil compartment. Patients with coronavirus infection are characterized by high NET levels which is at least 3-fold higher than that in healthy volunteers. This indicates an abnormality in immune host defense and development of an inadequate inflammatory response. An increase of NET in whole blood smears of more than 16% can be a criterion of an unfavorable prognosis of the disease course and the risk of death.

scholarly journals Prognostic value of quality of life scores in terminal cancer patients

1996 ◽  
Vol 11 (1) ◽  
pp. 32-41 ◽  
Author(s):  
Marcello Tamburini ◽  
Ciozia Brunelli ◽  
Stefano Rosso ◽  
Vittorio Ventafridda
Keyword(s):  
Quality Of Life ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Terminal Cancer ◽  
Terminal Cancer Patients
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