Identification of COVID-19 patients at risk of hospital admission and mortality: a European multicentre retrospective analysis of mid-regional pro-adrenomedullin.

BACKGROUND: Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. METHODS: An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. RESULTS: Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02 nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2 mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score < 2 if MR-proADM was ≤ 0.83 nmol/L regardless of age. Those at an increased risk of mortality could be identified upon presentation to secondary care with an MR-proADM value of > 0.85 nmol/L, in combination with a SOFA score ≥ 2 and LDH > 720 U/L, or in combination with a CRP > 29.26 mg/L and age ≤ 64, when MR-proADM was > 1.02 nmol/L. CONCLUSIONS: This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient's SOFA score could identify patients at low risk where outpatient treatment may be safe.

Circulating MR-proADM levels, as an indicator of endothelial dysfunction, for early risk stratification of mid-term mortality in COVID-19 patients.

OBJECTIVES: Thromboinflammation, resulting from a complex interaction between thrombocytopathy, coagulopathy, and endotheliopathy, contributes to increased mortality in COVID-19 patients. MR-proADM, as a surrogate of adrenomedullin system disruption, leading to endothelial damage, has been reported as a promising biomarker for short-term prognosis. We evaluated the role of MR-proADM in the mid-term mortality in COVID-19 patients. METHODS: A prospective, observational study enrolling COVID-19 patients from August to October 2020. A blood sample for laboratory test analysis was drawn on arrival in the emergency department. The primary endpoint was 90-day mortality. The area under the curve (AUC) and Cox regression analyses were used to assess discriminatory ability and association with the endpoint. RESULTS: A total of 359 patients were enrolled, and the 90-day mortality rate was 8.9%. ROC AUC for MR-proADM predicting 90-day mortality was 0.832. An optimal cutoff of 0.80 nmol/L showed a sensitivity of 96.9% and a specificity of 58.4%, with a negative predictive value of 99.5%. Circulating MR-proADM levels (inverse transformed), after adjusting by a propensity score including eleven potential confounders, were an independent predictor of 90-day mortality (HR: 0.162 [95% CI: 0.043-0.480]) CONCLUSIONS: Our data confirm that MR-proADM has a role in the mid-term prognosis of COVID-19 patients and might assist physicians with risk stratification.

Characteristics and laboratory findings on admission to the emergency department among 2873 hospitalized patients with COVID-19: the impact of adjusted laboratory tests in multicenter studies. A multicenter study in Spain (BIOCOVID-Spain study).

Identification of predictors for severe disease progression is key for risk stratification in COVID-19 patients. We aimed to describe the main characteristics and identify the early predictors for severe outcomes among hospitalized patients with COVID-19 in Spain. This was an observational, retrospective cohort study (BIOCOVID-Spain study) including COVID-19 patients admitted to 32 Spanish hospitals. Demographics, comorbidities and laboratory tests were collected. Outcome was in-hospital mortality. For analysis, laboratory tests values were previously adjusted to assure the comparability of results among participants. Cox regression was performed to identify predictors. Study population included 2873 hospitalized COVID-19 patients. Nine variables were independent predictors for in-hospital mortality, including creatinine (Hazard ratio [HR]:1.327; 95% Confidence Interval [CI]: 1.040-1.695, p = .023), troponin (HR: 2.150; 95% CI: 1.155-4.001; p = .016), platelet count (HR: 0.994; 95% CI: 0.989-0.998; p = .004) and C-reactive protein (HR: 1.037; 95% CI: 1.006-1.068; p = .019). This is the first multicenter study in which an effort was carried out to adjust the results of laboratory tests measured with different methodologies to guarantee their comparability. We reported a comprehensive information about characteristics in a large cohort of hospitalized COVID-19 patients, focusing on the analytical features. Our findings may help to identify patients early at a higher risk for an adverse outcome.

Prognostic performance of pancreatic stone protein in critically ill patients with sepsis.

Aim: To assess the prognostic value for 28-day mortality of PSP in critically ill patients with sepsis. Material & methods: 122 consecutive patients with sepsis were enrolled in this study. Blood samples were collected on admission and day 2. Results: On admission, the combination of PSP and lactate achieved an area under the receiver operating characteristic (AUC-ROC) of 0.796, similar to sequential organ failure assessment score alone (AUC-ROC: 0.826). On day 2, PSP was the biomarker with the highest performance (AUC-ROC: 0.844), although lower (p = 0.041) than sequential organ failure assessment score (AUC-ROC: 0.923). Conclusion: The combination of PSP and lactate and PSP alone, on day 2, have a good performance for prognosis of 28-day mortality and could help to identify patients who may benefit most from tailored intensive care unit management.

Analyzing the capability of PSP, PCT and sCD25 to support the diagnosis of infection in cancer patients with febrile neutropenia.

Background Early diagnosis of infection is essential for the initial management of cancer patients with chemotherapy-associated febrile neutropenia (FN). In this study, we have evaluated two emerging infection biomarkers, pancreatic stone protein (PSP) and soluble receptor of interleukin 2, known as soluble cluster of differentiation 25 (sCD25), for the detection of an infectious cause in FN, in comparison with other commonly used infection biomarkers, such as procalcitonin (PCT). Methods A total of 105 cancer patients presenting to the emergency department were prospectively enrolled. We observed 114 episodes of chemotherapy-associated FN. At presentation, a blood sample was collected for the measurement of PCT, PSP and sCD25. In order to evaluate the discriminatory ability of these markers for the diagnosis of infection, the area under the curve (AUC) of the receiver operating characteristic curves was calculated. Results Infection was documented in 59 FN episodes. PCT, PSP and sCD25 levels were significantly higher in infected patients. PCT was the biomarker with the highest diagnostic accuracy for infection (AUC: 0.901), whereas PSP and sCD25 showed a similar performance, with AUCs of 0.751 and 0.730, respectively. In a multivariable analysis, PCT and sCD25 were shown to be independently associated with infection. Conclusions Two novel biomarkers, PSP and sCD25, correlated with infection in cancer patients with chemotherapy-associated FN, but neither PSP nor sCD25 improved the performance of PCT. Based on the results obtained, the introduction of these novel biomarkers as a tool for the diagnosis of infection in this patient group is not recommended.

Prognostic value of procalcitonin and lipopolysaccharide binding protein in cancer patients with chemotherapy-associated febrile neutropenia presenting to an emergency department.

INTRODUCTION: Cancer patients with chemotherapy-induced febrile neutropenia are a heterogeneous group with a significant risk of serious medical complications. In these patients, the Multinational Association for Supportive Care in Cancer (MASCC) score is the most widely used tool for risk-stratification. The aim of this prospective study was to analyse the value of procalcitonin (PCT) and lipopolysaccharide binding protein (LBP) to predict serious complications and bacteraemia in cancer patients with febrile neutropenia, compared with MASCC score. MATERIALS AND METHODS: Data were collected from 111 episodes of febrile neutropenia admitted consecutively to the emergency department. In all of them, MASCC score was calculated and serum samples were collected for measurement of PCT and LBP by well-established methods. The main and secondary outcomes were the development of serious complications and bacteraemia, respectively. RESULTS: A serious complication occurred in 20 (18%) episodes and in 16 (14%) bacteraemia was detected. Areas under the receiver operating characteristic curve (ROC AUC) of MASCC score, PCT and LBP to select low-risk patients were 0.83 (95% confidence interval (CI): 0.74 - 0.89), 0.85 (95% CI: 0.77 - 0.91) and 0.70 (95% CI: 0.61 - 0.78), respectively. For bacteraemia, MASCC score, PCT and LBP showed ROC AUCs of 0.74 (95% CI: 0.64 - 0.82), 0.86 (95% CI: 0.78 - 0.92) and 0.76 (95% CI: 0.67 - 0.83), respectively. CONCLUSION: A single measurement of PCT performs similarly as MASCC score to predict serious medical complications in cancer patients with febrile neutropenia and can be a useful tool for risk stratification. Besides, low PCT concentrations can be used to rule-out the presence of bacteraemia.

No additional value of conventional and high-sensitivity cardiac troponin over clinical scoring systems in the differential diagnosis of type 1 vs. type 2 myocardial infarction.

BACKGROUND: The distinction of type 1 and type 2 myocardial infarction (MI) is of major clinical importance. Our aim was to evaluate the diagnostic ability of absolute and relative conventional cardiac troponin I (cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) in the distinction between type 1 and type 2 MI in patients presenting at the emergency department with non-ST-segment elevation acute chest pain within the first 12 h. METHODS: We measured cTnI (Dimension Vista) and hs-cTnT (Cobas e601) concentrations at presentation and after 4 h in 200 patients presenting with suspected acute MI. The final diagnosis, based on standard criteria, was adjudicated by two independent cardiologists. RESULTS: One hundred and twenty-five patients (62.5%)were classified as type 1 MI and 75 (37.5%) were type 2 MI. In a multivariable setting, age (relative risk [RR]=1.43, p=0.040), male gender (RR=2.22, p=0.040), T-wave inversion (RR=8.51, p<0.001), ST-segment depression (RR=8.71, p<0.001) and absolute delta hs-cTnT (RR=2.10, p=0.022) were independently associated with type 1 MI. In a receiver operating characteristic curve analysis, the discriminatory power of absolute delta cTnI and hs-cTnT was significantly higher compared to relative c-TnI and hs-cTnT changes. The additive information provided by cTnI and hs-cTnT over and above the information provided by the "clinical" model was only marginal. CONCLUSIONS: The diagnostic information provided by serial measurements of conventional or hs-cTnT is not better than that yielded by a simple clinical scoring model. Absolute changes are more informative than relative troponin changes.

Diagnostic accuracy of lipopolysaccharide-binding protein for sepsis in patients with suspected infection in the emergency department.

Background Biomarkers can facilitate the diagnosis of sepsis, enabling early management and improving outcomes. Lipopolysaccharide-binding protein (LBP) has been reported as a biomarker for the detection of infection, but its diagnostic value is controversial. In this study, we assessed the diagnostic accuracy of LBP for sepsis in the emergency department (ED) patients, comparing it with more established biomarkers of sepsis, including procalcitonin (PCT) and C-reactive protein (CRP). Methods LBP and other sepsis biomarkers, including PCT and CRP, were measured on admission in 102 adult patients presenting with suspected infection . Classification of patients was performed using the recently updated definition for sepsis (Sepsis-3). The diagnostic accuracy of LBP, CRP and PCT for sepsis was evaluated by using receiver operating characteristic curve (ROC) analysis. Results A total of 49 patients were classified as having sepsis. In these patients, median (interquartile range) LBP (41.8 [41.1] µg/dL vs. 26.2 [25] µg/dL), CRP (240 [205] mg/L vs. 160 [148] mg/dL) and PCT (5.19 [13.68] µg/L vs. 0.39 [1.09] µg/L) were significantly higher than in patients classified as not having sepsis ( P < 0.001 for all three biomarkers). ROC curve analysis and area under curve (AUC) revealed a value of 0.701 for LBP, similar to CRP (0.707) and lower than that for PCT (0.844) ( P = 0.012). Conclusion In adult ED patients with suspected infection, the diagnostic accuracy for sepsis of LBP is similar to that of CRP but lower than that of PCT.

Pancreatic stone protein and soluble CD25 for infection and sepsis in an emergency department.

BACKGROUND: Infection is a common problem in emergency departments (EDs) and is associated with high mortality, morbidity and costs. Identifying infection in ED patients can be challenging. Biomarkers can facilitate its diagnosis, enabling an early management and improving outcomes. In the critical care setting, two emerging biomarkers, pancreatic stone protein (PSP) and soluble CD25 (sCD25), have demonstrated to be useful for diagnosis of sepsis. We aimed to assess the diagnostic value of these biomarkers, in comparison with procalcitonin (PCT), for infection and sepsis in an ED population with suspected infection. MATERIALS AND METHODS: Through a prospective, observational study, we investigated the utility of serum PCT, PSP and sCD25 levels, measured on admission, for diagnosis of infection and sepsis, defined according to the recently updated for sepsis (Sepsis-3), in patients presenting to the ED for suspected infection. Diagnostic accuracy was evaluated by using receiver operating characteristic curves (ROC) analysis. RESULTS: Of the 152 patients enrolled in this study, 129 had a final diagnosis of infection, including 82 with noncomplicated infection and 47 with sepsis. Median PCT, PSP and sCD25 levels were significantly higher in patients with infection and sepsis. The ROC curve analysis revealed a similar diagnostic accuracy for infection (ROC area under the curve (AUC) PCT: 0·904; sCD25: 0·869 and PSP: 0·839) and for sepsis (ROC AUC: PCT: 0·820; sCD25: 0·835 and PSP: 0·872). CONCLUSIONS: Pancreatic stone protein and sCD25 perform well as infection and sepsis biomarkers, with a similar performance than PCT, in ED patients with suspected infection. Further larger studies investigating use of PSP and sCD25 are needed.

Value of lipopolysaccharide binding protein as diagnostic marker of infection in adult cancer patients with febrile neutropenia: comparison with C-reactive protein, procalcitonin, and interleukin 6.

PURPOSE: Early detection of infection is essential for initial management of cancer patients with chemotherapy-associated febrile neutropenia in the emergency department. In this study, we evaluated lipopolysaccharide binding protein (LBP) as predictor for infection in febrile neutropenia and compared with other biomarkers previously studied: C-reactive protein (CRP), procalcitonin (PCT), and interleukin (IL)-6. METHODS: A total of 61 episodes of chemotherapy-associated febrile neutropenia in 58 adult cancer patients were included. Serum samples were collected on admission at emergency department and CRP, LBP, PCT, and IL-6 were measured. Patients were classified into fever of unknown origin and infection, including microbiologically and clinically documented infection, groups. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker for the diagnosis of infection. RESULTS: Thirty-two of the 61 episodes were classified as infection. On admission, CRP, PCT, IL-6, and LBP were significantly increased in patients with infection compared to fever of unknown origin group. Area under the ROC curve (AUC ROC) of CRP, PCT, IL-6, and LBP for discriminating both groups was 0.77, 0.88, 0.82, and 0.82, respectively, without significant difference between them. The combination of IL-6 and PCT or LBP did not lead to a significant improvement of the diagnostic accuracy of PCT or LBP alone. CONCLUSIONS: On admission, LBP has a similar diagnostic accuracy than PCT or IL-6 for the diagnosis of infection and might be used as additional diagnostic tool in adult cancer patients with chemotherapy-associated febrile neutropenia.