Sepsis biomarkers: a review.
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SUBMITTER: Pierrakos C
PROVIDER: S-EPMC2875530 | biostudies-literature | 2010
REPOSITORIES: biostudies-literature
Publications
Sepsis biomarkers: a review.
Pierrakos Charalampos C Vincent Jean-Louis JL
Critical care (London, England) 20100209 1
<h4>Introduction</h4>Biomarkers can be useful for identifying or ruling out sepsis, identifying patients who may benefit from specific therapies or assessing the response to therapy.<h4>Methods</h4>We used an electronic search of the PubMed database using the key words "sepsis" and "biomarker" to identify clinical and experimental studies which evaluated a biomarker in sepsis.<h4>Results</h4>The search retrieved 3370 references covering 178 different biomarkers.<h4>Conclusions</h4>Many biomarker ...[more]
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Project description:IntroductionA strong biologic rationale exists for targeting markers of endothelial cell (EC) activation as clinically informative biomarkers to improve diagnosis, prognostic evaluation or risk-stratification of patients with sepsis.MethodsThe objective was to review the literature on the use of markers of EC activation as prognostic biomarkers in sepsis. MEDLINE was searched for publications using the keyword 'sepsis' and any of the identified endothelial-derived biomarkers in any searchable field. All clinical studies evaluating markers reflecting activation of ECs were included. Studies evaluating other exogenous mediators of EC dysfunction and studies of patients with malaria and febrile neutropenia were excluded.ResultsSixty-one studies were identified that fulfilled the inclusion criteria. Overall, published studies report positive correlations between multiple EC-derived molecules and the diagnosis of sepsis, supporting the critical role of EC activation in sepsis. Multiple studies also reported positive associations for mortality and severity of illness, although these results were less consistent than for the presence of sepsis. Very few studies, however, reported thresholds or receiver operating characteristics that would establish these molecules as clinically-relevant biomarkers in sepsis.ConclusionsMultiple endothelial-derived molecules are positively correlated with the presence of sepsis in humans, and variably correlated to other clinically-important outcomes. The clinical utility of these biomarkers is limited by a lack of assay standardization, unknown receiver operating characteristics and lack of validation. Additional large-scale prospective clinical trials will be required to determine the clinical utility of biomarkers of endothelial activation in the management of patients with sepsis.
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Project description:We address the identification of optimal biomarkers for the rapid diagnosis of neonatal sepsis. We employ both canonical correlation analysis (CCA) and sparse support vector machine (SSVM) classifiers to select the best subset of biomarkers from a large hematological data set collected from infants with suspected sepsis from Yale-New Haven Hospital's Neonatal Intensive Care Unit (NICU). CCA is used to select sets of biomarkers of increasing size that are most highly correlated with infection. The effectiveness of these biomarkers is then validated by constructing a sparse support vector machine diagnostic classifier. We find that the following set of five biomarkers capture the essential diagnostic information (in order of importance): Bands, Platelets, neutrophil CD64, White Blood Cells, and Segs. Further, the diagnostic performance of the optimal set of biomarkers is significantly higher than that of isolated individual biomarkers. These results suggest an enhanced sepsis scoring system for neonatal sepsis that includes these five biomarkers. We demonstrate the robustness of our analysis by comparing CCA with the Forward Selection method and SSVM with LASSO Logistic Regression.
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Project description:The biological fingerprint of environmental adversity may be key to understanding health and disease, as it encompasses the damage induced as well as the compensatory reactions of the organism. Metabolic and hormonal changes may be an informative but incomplete window into the underlying biology. We endeavored to identify objective blood gene expression biomarkers for psychological stress, a subjective sensation with biological roots. To quantify the stress perception at a particular moment in time, we used a simple visual analogue scale for life stress in psychiatric patients, a high risk group. Then, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design, we were successful in identifying gene expression biomarkers that were predictive of high stress states, and of future psychiatric hospitalizations related to stress, more so when personalized by gender and diagnosis.
2019-03-15 | GSE125216 | GEO
Project description:IntroductionSepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers.MethodsUsing the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms "Biomarker" AND "Sepsis." There were no restrictions by age or language, and all studies, clinical and experimental, were included.ResultsWe retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis.ConclusionsThe number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.
| S-EPMC7273821 | biostudies-literature
Project description:BACKGROUND:Angiopoietin-1 (Ang-1) and 2 (Ang-2), high mobility group box 1 (HMGB1), soluble receptor for advanced glycation endproducts (sRAGE), soluble triggering receptor expressed on myeloid cells 1 (sTREM1), and soluble urokinase-type plasminogen activator receptor (suPAR) have shown promising results for predicting all-cause mortality in critical care patients. The aim of our systematic review and meta-analysis was to assess the prognostic value of these biomarkers for mortality in adult patients with sepsis. METHODS:A systematic literature search of the MEDLINE, PubMed, EMBASE, and Cochrane Library databases, for articles in English published from 01.01.1990 onwards, was conducted. The systematic review focused exclusively on observational studies of adult patients with sepsis, any randomized trials were excluded. For the meta-analysis, only studies which provide biomarker concentrations within 24 h of admission in sepsis survivors and nonsurvivors were included. Results are presented as pooled mean differences (MD) between nonsurvivors and survivors with 95% confidence interval for each of the six biomarkers. Studies not included in the quantitative analysis were narratively summarized. The risk of bias was assessed in all included studies using the Quality in Prognosis Studies (QUIPS) tool. RESULTS:The systematic literature search retrieved 2285 articles. In total, we included 44 studies in the qualitative analysis, of which 28 were included in the meta-analysis. The pooled mean differences in biomarker concentration (nonsurvivors - survivors), measured at onset of sepsis, are listed as follows: (1) Ang-1: -?2.9 ng/ml (95% CI -?4.1 to -?1.7, p?<?0.01); (2) Ang-2: 4.9 ng/ml (95% CI 2.6 to 7.1, p?<?0.01); (3) HMGB1: 1.2 ng/ml (95% CI 0.0 to 2.4, p?=?0.05); (4) sRAGE: 1003 pg/ml (95% CI 628 to 1377, p?<?0.01); (5) sTREM-1: 87 pg/ml (95% CI 2 to 171, p?=?0.04); (6) suPAR: 5.2 ng/ml (95% CI 4.5 to 6.0, p?<?0.01). CONCLUSIONS:Ang-1, Ang-2, and suPAR provide beneficial prognostic information about mortality in adult patients with sepsis. The further development of standardized assays and the assessment of their performance when included in panels with other biomarkers may be recommended. Trial registration This study was recorded on PROSPERO, prospective register of systematic reviews, under the registration ID: CRD42018081226.
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Project description:Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In 2017, almost 50 million cases of sepsis were recorded worldwide and 11 million sepsis-related deaths were reported. Therefore, sepsis is the focus of intense research to better understand the complexities of sepsis response, particularly the twin underlying concepts of an initial hyper-immune response and a counter-immunological state of immunosuppression triggered by an invading pathogen. Diagnosis of sepsis remains a significant challenge. Prompt diagnosis is essential so that treatment can be instigated as early as possible to ensure the best outcome, as delay in treatment is associated with higher mortality. In order to address this diagnostic problem, use of a panel of biomarkers has been proposed as, due to the complexity of the sepsis response, no single marker is sufficient. This review provides background on the current understanding of sepsis in terms of its epidemiology, the evolution of the definition of sepsis, pathobiology and diagnosis and management. Candidate biomarkers of interest and how current and developing point-of-care testing approaches could be used to measure such biomarkers is discussed.
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Project description:Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies.
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Project description:BackgroundCirculating biomarkers can facilitate sepsis diagnosis, enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers.Study objectivesTo define the discriminative value of PCT, interleukin-6 (IL-6), and C-reactive protein (CRP) for suspected sepsis.MethodsPCT, CRP, and IL-6 were correlated with infection likelihood, sepsis severity, and septicemia. Multivariable models were constructed for length-of-stay and discharge to a higher level of care.ResultsOf 336 enrolled subjects, 60% had definite infection, 13% possible infection, and 27% no infection. Of those with infection, 202 presented with sepsis, 28 with severe sepsis, and 17 with septic shock. Overall, 21% of subjects were septicemic. PCT, IL6, and CRP levels were higher in septicemia (median PCT 2.3 vs. 0.2 ng/mL; IL-6 178 vs. 72 pg/mL; CRP 106 vs. 62 mg/dL; p < 0.001). Biomarker concentrations increased with likelihood of infection and sepsis severity. Using receiver operating characteristic analysis, PCT best predicted septicemia (0.78 vs. IL-6 0.70 and CRP 0.67), but CRP better identified clinical infection (0.75 vs. PCT 0.71 and IL-6 0.69). A PCT cutoff of 0.5 ng/mL had 72.6% sensitivity and 69.5% specificity for bacteremia, as well as 40.7% sensitivity and 87.2% specificity for diagnosing infection. A combined clinical-biomarker model revealed that CRP was marginally associated with length of stay (p = 0.015), but no biomarker independently predicted discharge to a higher level of care.ConclusionsIn adult emergency department patients with suspected sepsis, PCT, IL-6, and CRP highly correlate with several infection parameters, but are inadequately discriminating to be used independently as diagnostic tools.
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2022-08-03 | GSE210335 | GEO
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