Admission Cell Free DNA Levels Predict 28-Day Mortality in Patients with Severe Sepsis in Intensive Care

Avriel, Avital; Wiessman, Maya; Almog, Yaniv; Perl, Yael; Novack, Victor; Galante, Ori; Klein, Moti; Pencina, Michael J.; Douvdevani, Amos

doi:10.1371/journal.pone.0100514

Cited by 71 publications

(71 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell-free DNA (cfDNA) Measurements cfDNA was measured directly in sera using SYBR Gold Nucleic Acid Gel Staining, according to the fluorometric method published before [32,33]. Briefly, samples were added to a black 96-well plate (Greiner Bio-One).…”

Section: Measurement Of Serum Alt Ast Tbil Tnfα Il-1β and Il-10mentioning

confidence: 99%

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

et al. 2018

View full text Add to dashboard Cite

Macrophages play essential roles in the generation and resolution of inflammation. Ischemia-reperfusion injury (IRI) triggers a systemic inflammatory response and leads to cellular injury and organ failure.During surgical procedures of the liver, such as hepatic resection and liver transplantation, IRI leads to the dysfunction of the liver. Rho-associated protein kinase (ROCK) inhibitors were reported protecting the liver from IRI. However, the systematic administration of ROCK inhibitors causes severe hypotension.Here, using Fasudil carried liposomes, we specifically inhibited the ROCK-II expression in Kupffer cells and blood monocytes. Through this macrophage/monocyte specific treatment of Fasudil, we successfully protected the liver from IRI by shifting Kupffer cells/monocytes from M1/classical to M2/patrolling phenotype in the liver and peripheral blood. Our finding provides novel insights into the macrophage/monocyte-specific drug delivery and the treatment of liver IRI.

show abstract

Section: Measurement Of Serum Alt Ast Tbil Tnfα Il-1β and Il-10mentioning

confidence: 99%

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Furthermore, new diagnostic strategies have been currently under evaluation for potential clinical application including measurement of mitochondrial or cell free DNA by qRT-PCR or by direct fluorescence assays (90,91). Recent studies highlighted the key role of epigenetics in sepsis-associated immune dysfunction, in particular DNA methylation and histone acetylation of inflammatory genes (92,93).…”

Section: Resultsmentioning

confidence: 99%

Immune Cell Phenotype and Function in Sepsis

Rimmelé

Payen²,

Cantaluppi³

et al. 2016

Shock

150

119

View full text Add to dashboard Cite

Cells of the innate and adaptive immune systems play a critical role in the host response to sepsis. Moreover, their accessibility for sampling and their capacity to respond dynamically to an acute threat increases the possibility that leukocytes might serve as a measure of a systemic state of altered responsiveness in sepsis. The working group of the 14th Acute Dialysis Quality Initiative (ADQI) conference sought to obtain consensus on the characteristic functional and phenotypic changes in cells of the innate and adaptive immune system in the setting of sepsis. Techniques for the study of circulating leukocytes were also reviewed and the impact on cellular phenotypes and leukocyte function of non extracorporeal treatments and extracorporeal blood purification therapies proposed for sepsis was analyzed. A large number of alterations in the expression of distinct neutrophil and monocyte surface markers have been reported in septic patients. The most consistent alteration seen in septic neutrophils is their activation of a survival program that resists apoptotic death. Reduced expression of HLA-DR is a characteristic finding on septic monocytes but monocyte antimicrobial function does not appear to be significantly altered in sepsis. Regarding adaptive immunity, sepsis-induced apoptosis leads to lymphopenia in patients with septic shock and it involves all types of T cells (CD4, CD8 and Natural Killer) except T regulatory cells, thus favoring immunosuppression. Finally, numerous promising therapies targeting the host immune response to sepsis are under investigation. These potential treatments can have an effect on the number of immune cells, the proportion of cell subtypes and the cell function.

show abstract

“…Even though it is difficult to isolate the relationship between cfDNA levels and inflammation from a noninfectious etiology, exclusion of patients with sepsis or pneumonia increased the specificity of this marker for assessing COPDE. In our previous work,24 no association was observed between cfDNA levels and microorganisms or source of sepsis. In the present study, cfDNA was found to be a good clinical marker during a COPDE as observed in other medical conditions 17,19.…”

Section: Discussionmentioning

confidence: 61%

“…Thus, studying cfDNA during a COPDE is an important area of research given that exacerbations are marked by an increased inflammatory response11,12 that is characterized by cell damage and apoptosis 11,13,14. Recently, cfDNA has been investigated as a reliable, novel prognostic marker in a number of disease states such as cancer, trauma, myocardial infarction and sepsis 15–24…”

Section: Introductionmentioning

confidence: 99%

Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations

Avriel¹,

Rozenberg²,

Raviv³

et al. 2016

COPD

Self Cite

View full text Add to dashboard Cite

BackgroundChronic obstructive pulmonary disease exacerbations (COPDEs) are associated with increased morbidity and mortality. Cell-free DNA (cfDNA) is a novel biomarker associated with clinical outcomes in several disease states but has not been studied in COPD. The objectives of this study were to assess cfDNA levels during a COPDE, to evaluate the association of cfDNA with clinical parameters and to explore the prognostic implications of cfDNA levels on long-term survival.MethodsThis was an observational study that assessed cfDNA levels in patients admitted to hospital for a COPDE. Plasma cfDNA levels of COPDE patients were compared to those of matched stable COPD patients and healthy controls. Multivariable and Cox regression analyses were used to assess the association of cfDNA levels with blood gas parameters and long-term survival.ResultsA total of 62 patients (46 males, forced expiratory volume in 1 second [FEV1] 38%±13%) were included. The median cfDNA levels on admission for COPDE patients was 1,634 ng/mL (interquartile range [IQR] 1,016–2,319) compared to 781 ng/mL (IQR 523–855) for stable COPD patients, matched for age and disease severity, and 352 ng/mL (IQR 209–636) for healthy controls (P<0.0001, for both comparisons). cfDNA was correlated with partial arterial pressure of carbon dioxide (PaCO2, r=0.35) and pH (r=−0.35), P=0.01 for both comparisons. In a multivariable analysis, PaCO2 was the only independent predictor of cfDNA. Using a cfDNA level of 1,924 ng/mL (threshold for abnormal PaCO2), those with high levels had a trend for increased 5-year mortality risk adjusted for age, sex and FEV1% (hazard ratio 1.92, 95% confidence interval 0.93–3.95, P=0.08).ConclusionPlasma cfDNA might offer a novel technique to identify COPD patients at increased risk of poor outcomes, but the prognostic utility of this measurement requires further study.

show abstract

Admission Cell Free DNA Levels Predict 28-Day Mortality in Patients with Severe Sepsis in Intensive Care

Cited by 71 publications

References 33 publications

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

Immune Cell Phenotype and Function in Sepsis

Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations

Contact Info

Product

Resources

About