Yuri van der Does

BACKGROUND: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. METHODS: An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days. RESULTS: One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0-207.6], 23.4 [11.1-49.3] and 32.6 [9.4-113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities. CONCLUSIONS: In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.

BACKGROUND: Patients with a severe COVID-19 infection often require admission at an intensive care unit (ICU) when they develop acute respiratory distress syndrome (ARDS). Hyperinflammation plays an important role in the development of ARDS in COVID-19. Procalcitonin (PCT) is a biomarker which may be a predictor of hyperinflammation. When patients with COVID-19 are in the emergency department (ED), elevated PCT levels could be associated with severe COVID-19 infections. The goal of this study is to investigate the association between PCT levels and severe COVID-19 infections in the ED. METHODS: This was a retrospective cohort study including patients with a confirmed COVID-19 infection who visited the ED of Erasmus Medical Center in Rotterdam, the Netherlands, between March and December 2020. The primary outcome was a severe COVID-19 infection, which was defined as patients who required ICU admission, all cause in-hospital mortality and mortality within 30 days after hospital discharge. PCT levels were measured during the ED visit. We used logistic regression to calculate the odds ratio (OR) with 95% confidence interval (95% CI) and corresponding area under the curve (AUC) of PCT on a severe COVID-19 infection, adjusting for bacterial coinfections, age, sex, comorbidities, C-reactive protein (CRP) and D-dimer. RESULTS: A total of 332 patients were included in the final analysis of this study, of which 105 patients reached the composite outcome of a severe COVID-19 infection. PCT showed an unadjusted OR of 4.19 (95%CI: 2.52-7.69) on a severe COVID-19 infection with an AUC of 0.82 (95% CI: 0.76-0.87). Corrected for bacterial coinfection, the OR of PCT was 4.05 (95% CI: 2.45-7.41). Adjusted for sex, bacterial coinfection, age any comorbidity, CRP and D-dimer, elevated PCT levels were still significantly associated with a severe COVID-19 infection with an adjusted OR of 2.11 (95% CI: 1.36-3.61). The AUC of this multivariable model was 0.85 (95%CI: 0.81-0.90). CONCLUSION: High PCT levels are associated with high rates of severe COVID-19 infections in patients with a COVID-19 infection in the ED. The routine measurement of PCT in patients with a COVID-19 infection in the ED may assist physicians in the clinical decision making process regarding ICU disposition.

BACKGROUND: Sepsis can be detected in an early stage in the emergency department (ED) by biomarkers and clinical scoring systems. A combination of multiple biomarkers or biomarker with clinical scoring system might result in a higher predictive value on mortality. The goal of this systematic review is to evaluate the available literature on combinations of biomarkers and clinical scoring systems on 1-month mortality in patients with sepsis in the ED. METHODS: We performed a systematic search using MEDLINE, EMBASE and Google Scholar. Articles were included if they evaluated at least one biomarker combined with another biomarker or clinical scoring system and reported the prognostic accuracy on 28 or 30 day mortality by area under the curve (AUC) in patients with sepsis. We did not define biomarker cut-off values in advance. RESULTS: We included 18 articles in which a total of 35 combinations of biomarkers and clinical scoring systems were studied, of which 33 unique combinations. In total, seven different clinical scoring systems and 21 different biomarkers were investigated. The combination of procalcitonin (PCT), lactate, interleukin-6 (IL-6) and Simplified Acute Physiology Score-2 (SAPS-2) resulted in the highest AUC on 1-month mortality. CONCLUSION: The studies we found in this systematic review were too heterogeneous to conclude that a certain combination it should be used in the ED to predict 1-month mortality in patients with sepsis. Future studies should focus on clinical scoring systems which require a limited amount of clinical parameters, such as the qSOFA score in combination with a biomarker that is already routinely available in the ED.