A Pilot Study Assessing the Prognostic Value of CK18 and nDNA Biomarkers in Severe Sepsis Patients

Moore, David; Greystoke, Alastair; Butt, Fouziah; Würthner, Jens U.; Growcott, Jim; Hughes, Andrew; Dive, Caroline

doi:10.2165/11598610-000000000-00000

Cited by 27 publications

(17 citation statements)

References 35 publications

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“…Other approaches involving ccfDNA analysis were taken into consideration in regard to prognosis, such as presence of methylated DNA as independent prognostic factors in mCRC (18). Note that the prognostic value of ccfDNA in severe sepsis (39) and out-of-hospital cardiac arrest patients (40) are under investigation. Prognostic value of quantitative analysis of ccfDNA might be synergistically empowered by analysis of mitochondrial DNA, exosomal RNA, or specific proteins in a "liquid profiling" approach.…”

Section: Discussionmentioning

confidence: 99%

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Messaoudi

Moulière

Manoir

et al. 2016

Clinical Cancer Research

140

106

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Purpose: Circulating cell-free DNA (ccfDNA) is a valuable source of tumor material obtained from a simple blood sampling that enables noninvasive analysis of the tumor genome. Our goal was to carry out a multiparametric analysis of ccfDNA and evaluate its prognostic value by investigating the overall survival (OS) of 97 metastatic colorectal cancer patients (mCRC).Experimental Design: Qualitative parameters (determination of the main KRAS exon2 and BRAF V600E mutations) and quantitative parameters (total ccfDNA concentration, mutant ccfDNA concentration, the proportion of mutant ccfDNA, and ccfDNA integrity index) were determined simultaneously in a single run using a unique Q-PCR multimarker approach (100% success rate).Results: The median follow-up time was 36 months and median OS was 22 months. Patients showing high ccfDNA levels had significantly shorter OS (18.07 months vs. 28.5 months, P ¼ 0.0087). Moreover, multivariate analysis revealed that a high ccfDNA level is an independent prognostic factor (P ¼ 0.034). All ccfDNA parameters were of prognostic interest: patients with higher levels of mutant ccfDNA and higher mutation loads for the detected mutations had shorter OS (P ¼ 0.0089 and P ¼ 0.05, respectively). In addition, the level of ccfDNA fragmentation correlated positively with decreased OS in the exclusive KRAS/ BRAF-mutant cohort of patients (P ¼ 0.0052) and appeared as a strong independent prognostic factor (P ¼ 0.0072), whereas it was not significant in the exclusive KRAS/BRAF WT cohort of patients (P ¼ 0.67).Conclusions: Our data provide for the first time qualitative and quantitative evidence in favor of multiparametric ccfDNA analysis in mCRC patients for prognostic assessment.

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Section: Discussionmentioning

confidence: 99%

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Messaoudi

Moulière

Manoir

et al. 2016

Clinical Cancer Research

140

106

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“…The measurement of cCK-18 concentration conduce the dimension of apoptosis in critically ill patients [112][113][114] . There is a correlation between persisting high concentrations of cCK-18 in the early treatment of sepsis and 28 d mortality [115] . Several trials showed higher concentration of cCK-18 in septic patients than in trauma patients or healthy individuals [116,117] .…”

Section: Cytokeratin 18mentioning

confidence: 99%

Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

Kojic

Siegler

Uhle

et al. 2015

WJEM

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Beside many efforts to improve outcome, sepsis is still one of the most frequent causes of death in critically ill patients. It is the most common condition with high mortality in intensive care units. The complexity of the septic syndrome comprises immunological aspects -i.e. , sepsis induced immunosuppression -but is not restricted to this fact in modern concepts. So far, exact mechanisms and variables determining outcome and mortality stay unclear. Since there is no typical risk profile, early diagnosis and risk stratification remain difficult, which hinders rapid and effective treatment initiation. Due to the heterogeneous nature of sepsis, potential therapy options should be adapted to the individual. Biomarkers like C-reactive protein and procalcitonin are routinely used as complementary tools in clinical decision-making. Beyond the acute phase proteins, a wide bunch of promising substances and non-laboratory tools with potential diagnostic and prognostic value is under intensive investigation. So far, clinical decision just based on biomarker assessment is not yet feasible. However, biomarkers should be considered as a complementary approach. Core tip: Sepsis is a complex continuum of disturbed systems. Despite the presence of clinical consensus criteria, the early diagnosis especially in the perioperative setting is challenging. A magnitude of potential new biomarkers is tested for this purpose, but evidence is mounting that due to the complex nature of the syndrome, biomarkers are rather complementary tools for clinical decision making than "magic bullets". Moreover, biomarkers are also evaluated for therapy guidance, linking diagnostic results to an individual therapeutic regime. This review summarizes the developments in the biomarker field, aiming to provide an overview about current targets and their limitations.

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“…Nucleosome concentration has been shown to indicate the presence of sepsis, organ dysfunction and survival in human patients . This biomarker has also been shown to be indicative of the need for renal support treatment in human sepsis patients . Nucleosome concentrations have also been shown to differentiate between patients with variable severities of sepsis …”

Section: Discussionmentioning

confidence: 99%

Plasma HMGB‐1 and Nucleosome Concentrations in Horses with Colic and Healthy Horses

Bauquier

Forbes

Nath

et al. 2015

Veterinary Internal Medicne

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BackgroundAcute gastrointestinal disease occurs commonly in horses. Novel biomarkers might improve the understanding of SIRS and aid diagnosis and determination of prognosis.HypothesesIncreased plasma concentrations of the biomarkers HMGB‐1 and nucleosomes are associated with severity of gastrointestinal lesions in horses; concentrations of these biomarkers will be greater in horses with lesions more likely to cause SIRS; and will provide additional information compared with standard biomarkers fibrinogen and SAA.AnimalsThirty horses with gastrointestinal disease, 22 healthy horses.MethodsProspective study. Plasma samples taken on admission were used for measurement of HMGB‐1, nucleosomes, fibrinogen, and SAA. Values were compared between healthy horses and those with gastrointestinal disease, and between horses with gastrointestinal disease grouped by lesion type (inflammatory, strangulating, and nonstrangulating). Correlations between biomarkers were assessed.ResultsPlasma concentrations of all biomarkers were significantly higher in horses with gastrointestinal disease compared to healthy horses (P ≤ .001). HMGB‐1 and nucleosomes were significantly higher in inflammatory and strangulating groups compared to healthy horses (3.5‐fold and 5.4‐fold increases, respectively, for HMGB‐1 (P < .05) and 4.8‐fold and 5.6‐fold increases for nucleosomes (P < .05)), but concentrations in the group with nonstrangulating disease did not differ from healthy horses. There was significant correlation between HMGB‐1 and nucleosomes (Spearman's r = 0.623; P < .001), and fibrinogen and SAA (Spearman's r = 0.801; P < .001) but not between other biomarkers.Conclusions and Clinical ImportanceHigh mobility group box‐1 and nucleosomes might have use as biomarkers for horses with gastrointestinal disease. Further studies are required to determine kinetics and prognostic value of serial measurements of these biomarkers in horses.

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A Pilot Study Assessing the Prognostic Value of CK18 and nDNA Biomarkers in Severe Sepsis Patients

Cited by 27 publications

References 35 publications

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

Plasma HMGB‐1 and Nucleosome Concentrations in Horses with Colic and Healthy Horses

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