Derivation and Validation of a Biomarker-Based Clinical Algorithm to Rule Out Sepsis From Noninfectious Systemic Inflammatory Response Syndrome at Emergency Department Admission: A Multicenter Prospective Study*

Mearelli, Filippo; Fiotti, Nicola; Giansante, Carlo; Casarsa, Chiara; Orso, Daniele; Helmersen, Marco De; Altamura, Nicola; Ruscio, Maurizio; Castello, Luigi Mario; Colonetti, Efrem; Marino, Rossella; Barbati, Giulia; Bregnocchi, Andrea; Ronco, Claudio; Lupia, Enrico; Montrucchio, Giuseppe; Muiesan, María Lorenza; Somma, Salvatore Di; Avanzi, Gian Carlo; Biolo, Gianni

doi:10.1097/ccm.0000000000003206

Cited by 41 publications

(39 citation statements)

References 28 publications

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“…However, it is not clear from the existing literature whether the biomarkers included in such panels should be selected based on pathophysiological or other criteria. The combination of a biomarker panel with clinical information may be particularly useful in the diagnosis of sepsis or in the risk strati cation of patients with sepsis [37].…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of sepsis: Time for a Reappraisal

Pierrakos

Velissaris

Bisdorff

et al. 2020

Preprint

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Introduction : Sepsis 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. Methods: Using 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. Results: We 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 C-reactive protein 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. Conclusions : The 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.

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Section: Discussionmentioning

confidence: 99%

Biomarkers of sepsis: Time for a Reappraisal

Pierrakos

Velissaris

Bisdorff

et al. 2020

Preprint

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“…The idea of a multimarker approach has been recently reclaimed by Mearelli et al in a multicenter prospective study comprising a large cohort of patients. They developed and validated a high-performing, reproducible, and cost-effective algorithm to assist physicians of the emergency department in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome (SIRS) [96]. Nowadays, it is becoming evident that the use of biomarkers in clinical procedures can be helpful and essential for a correct diagnosis, to discriminate noninfectious SIRS, sepsis, and septic shock patients, and to estimate the prognosis.…”

Section: An Open Window On Sepsismentioning

confidence: 99%

Gas6/TAM Axis in Sepsis: Time to Consider Its Potential Role as a Therapeutic Target

et al. 2019

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Tyrosine kinase receptors are transmembrane proteins involved in cell signaling and interaction. Among them, the TAM family (composed by Tyro 3, Axl, and Mer) represents a peculiar subgroup with an important role in many physiological and pathological conditions. Despite different mechanisms of activation (e.g., protein S and Galactin-3), TAM action is tightly related to their common ligand, a protein named growth arrest-specific 6 (Gas6). Since the expression of both TAM and Gas6 is widely distributed among tissues, any alteration of one of these components can lead to different pathological conditions. Moreover, as they are indispensable for homeostasis maintenance, in recent years a growing interest has emerged regarding their role in the regulation of the inflammatory process. Due to this involvement, many authors have demonstrated the pivotal role of the Gas6/TAM axis in both sepsis and the sepsis-related inflammatory responses. In this narrative review, we highlight the current knowledge as well as the last discoveries on TAM and Gas6 implication in different clinical conditions, notably in sepsis and septic shock. Lastly, we underline not only the feasible use of Gas6 as a diagnostic and prognostic biomarker in certain systemic acute conditions but also its potential therapeutic role in these life-threatening diseases.

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“…in a patient with signs and symptoms of sepsis (Comstedt et al 2009;Heffner et al 2010). Additionally, a noninfectious etiology, such as pancreatitis, cancer, autoimmune inflammatory disease, or burns or other trauma including surgery, is found for 18-38% of patients presenting with sepsis symptoms (Comstedt et al 2009;de Prost et al 2013;Heffner et al 2010), a diagnosis often referred to as the noninfectious systemic inflammatory response syndrome (niSIRS) (Cabrera et al 2017;Mearelli et al 2018;Watt et al 2015). Thus, identifying specific biomarkers for sepsis is an area of significant research interest.…”

Section: Introductionmentioning

confidence: 99%

New markers for sepsis caused by Pseudomonas aeruginosa during burn infection

et al. 2020

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Introduction Sepsis is a leading cause of mortality in burn patients. One of the major causes of sepsis in burn patients is Pseudomonas aeruginosa. We hypothesized that during dissemination from infected burn wounds and subsequent sepsis, P. aeruginosa affects the metabolome of the blood resulting in changes to specific metabolites that would serve as biomarkers for early diagnosis of sepsis caused by P. aeruginosa. Objectives To identify specific biomarkers in the blood after sepsis caused by P. aeruginosa infection of burns. Methods Gas chromatography with time-of-flight mass spectrometry was used to compare the serum metabolome of mice that were thermally injured and infected with P. aeruginosa (B-I) to that of mice that were neither injured nor infected, mice that were injured but not infected, and mice that were infected but not injured. Results Serum levels of 19 metabolites were significantly increased in the B-I group compared to controls while levels of eight metabolites were significantly decreased. Thymidine, thymine, uridine, and uracil (related to pyrimidine metabolism), malate and succinate (a possible sign of imbalance in the tricarboxylic acid cycle), 5-oxoproline (related to glutamine and glutathione metabolism), and trans-4-hydroxyproline (a major component of the protein collagen) were increased. Products of amino acid metabolism were significantly decreased in the B-I group, including methionine, tyrosine, indole-3-acetate, and indole-3-propionate. Conclusion In all, 26 metabolites were identified, including a unique combination of five metabolites (trans-4-hydroxyproline, 5-oxoproline, glycerol-3-galactoside, indole-3-acetate, and indole-3-propionate) that could serve as a set of biomarkers for early diagnosis of sepsis caused by P. aeruginosa in burn patients.

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Derivation and Validation of a Biomarker-Based Clinical Algorithm to Rule Out Sepsis From Noninfectious Systemic Inflammatory Response Syndrome at Emergency Department Admission: A Multicenter Prospective Study*

Abstract: We have developed and validated a high-performing, reproducible, and parsimonious algorithm to assist emergency department physicians in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome.

Cited by 41 publications

References 28 publications

Biomarkers of sepsis: Time for a Reappraisal

Biomarkers of sepsis: Time for a Reappraisal

Gas6/TAM Axis in Sepsis: Time to Consider Its Potential Role as a Therapeutic Target

New markers for sepsis caused by Pseudomonas aeruginosa during burn infection

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