The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology

Alder, Matthew N.; Lindsell, Christopher J.; Wong, Hector R.

doi:10.1586/14787210.2014.912131

Cited by 31 publications

(24 citation statements)

References 58 publications

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“…Both the pediatric and adult versions of PERSEVERE outperform commonly used prognostic scoring systems based on laboratory and physiological parameters. A comparison of the two models may provide some insight regarding the influence of age and development on the biology of sepsis [47]. …”

Section: Combination Biomarkersmentioning

confidence: 99%

Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment

Sandquist

Wong²

2014

Expert Review of Clinical Immunology

Self Cite

144

129

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Biomarkers have great potential to improve the diagnosis and treatment of sepsis. The available literature supports the potential utility of sTREM-1, IL-27, suPAR, neutrophil CD64, presepsin, cfDNA and miRNAs as novel diagnostic, prognostic and treatment response biomarkers. The future of sepsis biomarkers lies in extensive validation studies of such novel biomarkers across heterogeneous populations and exploration of their power in combination. Furthermore, the use of a companion diagnostics model may augment the ability of investigators to identify novel sepsis biomarkers and develop specific therapeutic strategies based on biomarker information.

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Section: Combination Biomarkersmentioning

confidence: 99%

Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment

Sandquist

Wong²

2014

Expert Review of Clinical Immunology

Self Cite

144

129

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“…ASSIST includes biomarker information that reflects the underlying biology while APACHE II reflects symptoms and clinical risk factors [2, 3, 5, 11, 12]. As such, enrichment using ASSIST may better stratify patients according to pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

“…As such, enrichment using ASSIST may better stratify patients according to pathophysiology. We note that the ASSIST biomarkers reflect inflammation and immune function [3, 6]. It is possible that an anti-tumor necrosis factor strategy could modify the biology reflected by these biomarkers, and hence modify outcome.…”

Section: Discussionmentioning

confidence: 99%

“…For example, patients at low risk of an event might be exclude as being unlikely to benefit from a treatment, while patients at extremely high risk of an event might be excluded if their poor outcome is likely unalterable by the treatment under study. We have developed a stratification tool called Adult Septic Shock Information and Stratification Technology (ASSIST) [2, 3]. ASSIST incorporates a panel of biomarkers, age, lactate, and chronic health status to estimate a baseline 28-day mortality probability for adults with septic shock.…”

Section: Introductionmentioning

confidence: 99%

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An Enrichment Strategy For Sepsis Clinical Trials

Wong

Lindsell

2016

Shock

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Introduction Selecting participants for research based on their risk is an enrichment strategy with potential for enhancing clinical trials in sepsis. Adult Septic Shock Information and Stratification (ASSIST) is a tool for estimating mortality risk that incorporates a panel of biomarkers, age, lactate, and chronic health status. We assessed the utility of ASSIST as an enrichment strategy in a clinical trial testing the efficacy of a polyclonal anti-tumor necrosis factor-α fragment antibody (AZD9773) in adults with severe sepsis or septic shock. We hypothesized that the effects of AZD9773 are dependent on baseline mortality risk, as estimated by ASSIST. Methods This was a post hoc analysis of a recently completed trial of 300 subjects, randomized to placebo, low dose AZD9773, or high dose AZD9773. The study’s primary endpoint was number of ventilator free days. There were 286 subjects with available plasma samples from study entry. We measured the ASSIST biomarkers and assigned each subject to low, intermediate, and high risk strata based on their ASSIST mortality probability. To mirror the study’s original statistical plan, we estimated the least squares mean ventilator free days for each study arm within risk strata. Results The effect of study arm within ASSIST-based risk strata was significant (p = 0.017). Within the low risk group, there was an increase in ventilator free days for both drug arms. Within the intermediate risk group, there was an increase in ventilator free days among those in the low dose arm, but a decrease in the high dose arm. Among high risk patients, there was a decrease of ventilator free days in both drug arms. Analogous associations were observed when modeling 28-day mortality. Conclusions In this study, a beneficial effect of AZD9773 might have been observed if the trial selected low to intermediate risk patients. ASSIST has the potential to serve as an enrichment tool for sepsis clinical trials.

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“…Recent studies reported on the derivation and validation of the Pediatric Sepsis Biomarker Risk Model (PEREVERE) (67–69). PERSEVERE is a multi-biomarker-based risk model that assigns a baseline mortality risk for children with septic shock.…”

Section: The Emerging Role Of Sepsis Biomarkersmentioning

confidence: 99%

Sepsis in Pediatric Cardiac Intensive Care

Wheeler

Wong

2016

Pediatric Critical Care Medicine

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Objectives In this review we will discuss risk factors for developing sepsis; the role of biomarkers in establishing an early diagnosis, monitoring therapeutic efficacy, stratification, and for the identification of sepsis endotypes; and the pathophysiology and management of severe sepsis and septic shock, with an emphasis on the impact of sepsis on cardiovascular function. Data Source MEDLINE, PubMed Conclusion There is a lot of excitement in the field of sepsis research today. Scientific advances in the diagnosis and clinical staging of sepsis, as well as a personalized approach to the treatment of sepsis, offer tremendous promise for the future. However, at the same time, it is also evident that sepsis mortality has not improved enough, even with progress in our understanding of the molecular pathophysiology of sepsis.

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The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology

Cited by 31 publications

References 58 publications

Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment

Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment

An Enrichment Strategy For Sepsis Clinical Trials

Sepsis in Pediatric Cardiac Intensive Care

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