Dataset Information

Prospective validation of a transcriptomic severity classifier among patients with suspected acute infection and sepsis in the emergency department.

ABSTRACT:

Background and importance

mRNA-based host response signatures have been reported to improve sepsis diagnostics. Meanwhile, prognostic markers for the rapid and accurate prediction of severity in patients with suspected acute infections and sepsis remain an unmet need. IMX-SEV-2 is a 29-host-mRNA classifier designed to predict disease severity in patients with acute infection or sepsis.

Objective

Validation of the host-mRNA infection severity classifier IMX-SEV-2.

Design, settings and participants

Prospective, observational, convenience cohort of emergency department (ED) patients with suspected acute infections.

Outcome measures and analysis

Whole blood RNA tubes were analyzed using independently trained and validated composite target genes (IMX-SEV-2). IMX-SEV-2-generated risk scores for severity were compared to the patient outcomes in-hospital mortality and 72-h multiorgan failure.

Main results

Of the 312 eligible patients, 22 (7.1%) died in hospital and 58 (18.6%) experienced multiorgan failure within 72 h of presentation. For predicting in-hospital mortality, IMX-SEV-2 had a significantly higher area under the receiver operating characteristic (AUROC) of 0.84 [95% confidence intervals (CI), 0.76-0.93] compared to 0.76 (0.64-0.87) for lactate, 0.68 (0.57-0.79) for quick Sequential Organ Failure Assessment (qSOFA) and 0.75 (0.65-0.85) for National Early Warning Score 2 (NEWS2), ( P = 0.015, 0.001 and 0.013, respectively). For identifying and predicting 72-h multiorgan failure, the AUROC of IMX-SEV-2 was 0.76 (0.68-0.83), not significantly different from lactate (0.73, 0.65-0.81), qSOFA (0.77, 0.70-0.83) or NEWS2 (0.81, 0.75-0.86).

Conclusion

The IMX-SEV-2 classifier showed a superior prediction of in-hospital mortality compared to biomarkers and clinical scores among ED patients with suspected infections. No improvement for predicting multiorgan failure was found compared to established scores or biomarkers. Identifying patients with a high risk of mortality or multiorgan failure may improve patient outcomes, resource utilization and guide therapy decision-making.

SUBMITTER: Galtung N

PROVIDER: S-EPMC9432813 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prospective validation of a transcriptomic severity classifier among patients with suspected acute infection and sepsis in the emergency department.

Galtung Noa N Diehl-Wiesenecker Eva E Lehmann Dana D Markmann Natallia N Bergström Wilma H WH Wacker James J Liesenfeld Oliver O Mayhew Michael M Buturovic Ljubomir L Luethy Roland R Sweeney Timothy E TE Tauber Rudolf R Kappert Kai K Somasundaram Rajan R Bauer Wolfgang W

European journal of emergency medicine : official journal of the European Society for Emergency Medicine 20220421 5

<h4>Background and importance</h4>mRNA-based host response signatures have been reported to improve sepsis diagnostics. Meanwhile, prognostic markers for the rapid and accurate prediction of severity in patients with suspected acute infections and sepsis remain an unmet need. IMX-SEV-2 is a 29-host-mRNA classifier designed to predict disease severity in patients with acute infection or sepsis.<h4>Objective</h4>Validation of the host-mRNA infection severity classifier IMX-SEV-2.<h4>Design, settin ...[more]

PMID: 35467566

Similar Datasets

Project description:ObjectiveTo derive and validate a new clinical prediction rule to risk-stratify emergency department (ED) patients admitted with suspected sepsis.DesignRetrospective prognostic study of prospectively collected data.SettingED.ParticipantsPatients aged ≥18 years who met two Systemic Inflammatory Response Syndrome criteria or one Red Flag sepsis criteria on arrival, received intravenous antibiotics for a suspected infection and admitted.Primary outcome measureIn-hospital all-cause mortality.MethodThe data were divided into derivation and validation cohorts. The simplified-Mortality in Severe Sepsis in the ED score and quick-SOFA scores, refractory hypotension and lactate were collectively termed 'component scores' and cumulatively termed the 'Risk-stratification of ED suspected Sepsis (REDS) score'. Each patient in the derivation cohort received a score (0-3) for each component score. The REDS score ranged from 0 to 12. The component scores were subject to univariate and multivariate logistic regression analyses. The receiver operator characteristic (ROC) curves for the REDS and the components scores were constructed and their cut-off points identified. Scores above the cut-off points were deemed high-risk. The area under the ROC (AUROC) curves and sensitivity for mortality of the high-risk category of the REDS score and component scores were compared. The REDS score was internally validated.Results2115 patients of whom 282 (13.3%) died in hospital. Derivation cohort: 1078 patients with 140 deaths (13%). The AUROC curve with 95% CI, cut-off point and sensitivity for mortality (95% CI) of the high-risk category of the REDS score were: derivation: 0.78 (0.75 to 0.80); ≥3; 85.0 (78 to 90.5).Validation0.74 (0.71 to 0.76); ≥3; 84.5 (77.5 to 90.0). The AUROC curve and the sensitivity for mortality of the REDS score was better than that of the component scores. Specificity and mortality rates for REDS scores of ≥3, ≥5 and ≥7 were 54.8%, 88.8% and 96.9% and 21.8%, 36.0% and 49.1%, respectively.ConclusionThe REDS score is a simple and objective score to risk-stratify ED patients with suspected sepsis.

Project description:ObjectivesIncrease of nucleated RBCs in peripheral blood has been shown to be predictive of mortality in ICU patients. The aim of this study was to explore the prognostic value of nucleated RBCs in the first blood sample taken at admission to the emergency department from patients with suspected sepsis.DesignSingle-center prospective cohort study.SettingEmergency department.PatientsOne-thousand two-hundred thirty-one consecutive adult patients with suspected sepsis were included in a prospective quality register-based cohort study. Inclusion criteria were as follows: patients received in rapid response team with blood cultures taken and immediate antibiotics given in the emergency department.InterventionNot applicable.Measurement and main resultsNucleated RBCs, Sequential Organ Failure Assessment score, Quick Sequential Organ Failure Assessment, Charlson Comorbidity Index, and commonly used laboratory tests measured in the emergency department were compared with 30-day mortality. Nvaucleated RBC counts were divided into five groups, called "Nucleated RBC score," according to nucleated RBC count levels and analyzed with logistic regression together with the Sequential Organ Failure Assessment score and Charlson Comorbidity Index. Of the 262 patients with nucleated RBCs equal to or higher than the detection limit (0.01 × 109/L), 26% died within 30 days, compared with 12% of the 969 patients with nucleated RBCs below the detection limit (p < 0.0001). Mortality was significantly higher for each increase in Nucleated RBC score, except from score 2 to 3, and was 62% in the highest group. In multivariate logistic regression, odds ratios for 30-day mortality were as follows: Nucleated RBC score: 1.33 (95% CI, 1.13-1.56), Sequential Organ Failure Assessment score: 1.32 (1.29-1.56), and Charlson Comorbidity Index: 1.17 (1.09-1.25).ConclusionsMost patients with suspected sepsis in emergency department had undetectable nucleated RBCs at admission to the emergency department. However, increased nucleated RBCs significantly predicted 30-day mortality. Nucleated RBCs may provide additional prognostic information to Sequential Organ Failure Assessment score and other laboratory tests.

Project description:ImportanceProfessional guidelines recommend noninvasive cardiac testing (NIT) within 72 hours of an emergency department (ED) evaluation for suspected acute coronary syndrome. However, there is inexact evidence that this strategy reduces the risk of future death or acute myocardial infarction (MI).ObjectiveTo evaluate the effectiveness of early NIT in reducing the risk of death or acute MI within 30 days.Design, setting, and participantsThis retrospective, multicenter cohort study within the Kaiser Permanente Southern California integrated health care delivery system compared the effectiveness of early noninvasive cardiac testing vs no testing in patients with chest pain and in whom acute MI was ruled out who presented to an ED from January 2015 to December 2017. Patients were followed up for up to 30 days after emergency department discharge.ExposuresNoninvasive cardiac testing performed within 3 days of an ED evaluation for suspected acute coronary syndrome.Main outcomes and measuresThe primary outcome was composite risk of death or acute MI, within 30 days of an ED discharge.ResultsA total of 79 040 patients were evaluated in this study, of whom 57.7% were female. The mean (SD) age of the cohort was 57 (16) years, and 16 164 patients (21%) had completed early NIT. The absolute risk of death or MI within 30 days was low (<1%). Early NIT had the minor benefit of reducing the absolute composite risk of death or MI (0.4% [95% CI, -0.6% to -0.3%]), and, separately, of death (0.2% [95% CI, -0.2% to -0.1%]), MI (-0.3% [95% CI, -0.5% to -0.1%]), and major adverse cardiac event (-0.5% [95% CI, -0.7% to -0.3%]). The number needed to treat was 250 to avoid 1 death or MI, 500 to avoid 1 death, 333 to avoid 1 MI, and 200 to avoid 1 major adverse cardiovascular event within 30 days. Subgroup analysis revealed a number needed to treat of 14 to avoid 1 death or MI in the subset of patients with elevated troponin.Conclusions and relevanceEarly NIT was associated with a small decrease in the risk of death or MI in patients admitted to the ED with suspected acute coronary syndrome, but this clinical strategy may not be optimal for most patients given the large number needed to treat.

Project description:PURPOSE:Sepsis is a common acute life-threatening condition that emergency physicians routinely face. Diagnostic options within the Emergency Department (ED) are limited due to lack of infrastructure, consequently limiting the use of invasive hemodynamic monitoring or imaging tests. The mortality rate due to sepsis can be assessed via multiple scoring systems, for example, mortality in emergency department sepsis (MEDS) score and sepsis patient evaluation in the emergency department (SPEED) score, both of which quantify the variation of mortality rates according to clinical findings, laboratory data, or therapeutic interventions. This study aims to improve the management processes of sepsis patients by comparing SPEED score and MEDS score for predicting the 28-day mortality in cases of emergency sepsis. METHODS:The study is a cross-sectional, prospective study including 61 sepsis patients in ED in Suez Canal University Hospital, Egypt, from August 2017 to June 2018. Patients were selected by two steps: (1) suspected septic patients presenting with at least one of the following abnormal clinical findings: (a) body temperature higher than 38 °C or lower than 36 °C, (b) heart rate higher than 90 beats/min, (c) hyperventilation evidenced by respiratory rate higher than 20 breaths/min or PaCO2 lower than 32 mmHg, and (d) white blood cell count higher than 12,000/μL or lower than 4000/μL; (2) confirmed septic patients with at least a 2-point increase from the baseline total sequential organ failure assessment (SOFA) score following infection. Other inclusion criteria included adult patients with an age ≥18 years regardless of gender and those who had either systemic inflammatory response syndrome or suspected/confirmed infection. Patients were shortly follow-up for the 28-day mortality. Each patient was subject to SPEED score and MEDS score and then the results were compared to detect which of them was more effective in predicting outcome. The receiver operating characteristic curves were also done for MEDS and SPEED scores. RESULTS:Among the 61 patients, 41 died with the mortality rate of 67.2%. The mortality rate increased with a higher SPEED and MEDS scores. Both SPEED and MEDS scores revealed significant difference between the survivors and nonsurvivors (p = 0.004 and p < 0.001, respectively), indicating that both the two systems are effective in predicting the 28-day mortality of sepsis patients. Thereafter, the receiver operating characteristic curves were plotted, which showed that SPEED was better than the MEDS score when applied to the complete study population with an area under the curve being 0.87 (0.788-0.963) as compared with 0.75 (0.634-0.876) for MEDS. Logistic regression analysis revealed that the best fitting predictor of 28-day mortality for sepsis patients was the SPEED scoring system. For every one unit increase in SPEED score, the odds of 28-day mortality increased by 37%. CONCLUSION:SPEED score is more useful and accurate than MEDS score in predicting the 28-day mortality among sepsis patients. Therefore SPEED rather than MEDS should be more widely used in the ED for sepsis patients.

Dataset Information

Prospective validation of a transcriptomic severity classifier among patients with suspected acute infection and sepsis in the emergency department.

Background and importance

Objective

Design, settings and participants

Outcome measures and analysis

Main results

Conclusion

Publications

Prospective validation of a transcriptomic severity classifier among patients with suspected acute infection and sepsis in the emergency department.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets