Dataset Information

The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis - a secondary analysis of a large randomised controlled trial.

ABSTRACT: BACKGROUND:This study assessed the ability of mid-regional proadrenomedullin (MR-proADM) in comparison to conventional biomarkers (procalcitonin (PCT), lactate, C-reactive protein) and clinical scores to identify disease severity in patients with sepsis. METHODS:This is a secondary analysis of a randomised controlled trial in patients with severe sepsis or septic shock across 33 German intensive care units. The association between biomarkers and clinical scores with mortality was assessed by Cox regression analysis, area under the receiver operating characteristic and Kaplan-Meier curves. Patients were stratified into three severity groups (low, intermediate, high) for all biomarkers and scores based on cutoffs with either a 90% sensitivity or specificity. RESULTS:1089 patients with a 28-day mortality rate of 26.9% were analysed. According to the Sepsis-3 definition, 41.2% and 58.8% fulfilled the criteria for sepsis and septic shock, with respective mortality rates of 20.0% and 32.1%. MR-proADM had the strongest association with mortality across all Sepsis-1 and Sepsis-3 subgroups and could facilitate a more accurate classification of low (e.g. MR-proADM vs. SOFA: N = 265 vs. 232; 9.8% vs. 13.8% mortality) and high (e.g. MR-proADM vs. SOFA: N = 161 vs. 155; 55.9% vs. 41.3% mortality) disease severity. Patients with decreasing PCT concentrations of either ??20% (baseline to day 1) or ??50% (baseline to day 4) but continuously high MR-proADM concentrations had a significantly increased mortality risk (HR (95% CI): 19.1 (8.0-45.9) and 43.1 (10.1-184.0)). CONCLUSIONS:MR-proADM identifies disease severity and treatment response more accurately than established biomarkers and scores, adding additional information to facilitate rapid clinical decision-making and improve personalised sepsis treatment.

SUBMITTER: Elke G

PROVIDER: S-EPMC5863464 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis - a secondary analysis of a large randomised controlled trial.

Elke Gunnar G Bloos Frank F Wilson Darius Cameron DC Brunkhorst Frank Martin FM Briegel Josef J Reinhart Konrad K Loeffler Markus M Kluge Stefan S Nierhaus Axel A Jaschinski Ulrich U Moerer Onnen O Weyland Andreas A Meybohm Patrick P

Critical care (London, England) 20180321 1

<h4>Background</h4>This study assessed the ability of mid-regional proadrenomedullin (MR-proADM) in comparison to conventional biomarkers (procalcitonin (PCT), lactate, C-reactive protein) and clinical scores to identify disease severity in patients with sepsis.<h4>Methods</h4>This is a secondary analysis of a randomised controlled trial in patients with severe sepsis or septic shock across 33 German intensive care units. The association between biomarkers and clinical scores with mortality was ...[more]

PMID: 29562917

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Project description:BACKGROUND:A reduction in duration of antibiotic therapy is crucial in minimizing the development of antimicrobial resistance, drug-related side effects and health care costs. The minimal effective duration of antimicrobial therapy for febrile urinary tract infections (fUTI) remains a topic of uncertainty, especially in male patients, those of older age or with comorbidities. Biomarkers have the potential to objectively identify the optimal moment for cessation of therapy. METHODS:A secondary analysis of a randomized placebo-controlled trial among 35 primary care centers and 7 emergency departments of regional hospitals in the Netherlands. Women and men aged ?18?years with a diagnosis of fUTI were randomly assigned to receive antibiotic treatment for 7 or 14?days. Patients indicated to receive antimicrobial treatment for more than 14?days were excluded from randomization. The biomarkers procalcitonin (PCT), mid-regional proadrenomedullin (MR-proADM), and C-reactive protein (CRP) were compared in their ability to predict clinical cure or failure through the 10-18?day post-treatment visit. RESULTS:Biomarker concentrations were measured in 249 patients, with a clinical cure rate of 94% in the 165 randomized and 88% in the 84 non-randomized patients. PCT, MR-proADM and CRP concentrations did not differ between patients with clinical cure and treatment failure, and did not predict treatment outcome, irrespective of 7 or 14?day treatment duration (ROCAUC 0.521; 0.515; 0.512, respectively). PCT concentrations at presentation were positively correlated with bacteraemia (? =?0.33, p <?0.001) and presence of shaking chills (? =?0.25, p?<?0.001), and MR-proADM levels with length of hospital stay (? =?0.40, p?<?0.001), bacteraemia (? =?0.33, p?<?0.001), initial intravenous treatment (? =?0.22, p?<?0.001) and time to defervescence (? =?0.21, p?<?0.001). CRP did not display any correlation to relevant clinical parameters. CONCLUSIONS:Although the biomarkers PCT and MR-proADM were correlated to clinical parameters indicating disease severity, they did not predict treatment outcome in patients with community acquired febrile urinary tract infection who were treated for either 7 or 14?days. CRP had no added value in the management of patients with fUTI. TRIAL REGISTRATION:The study was registered at ClinicalTrials.gov [ NCT00809913 ; December 16, 2008] and trialregister.nl [ NTR1583 ; December 19, 2008].

Project description:BackgroundAlthough there is increasing understanding of the changes in the laboratory parameters of Coronavirus disease 2019 (COVID-19), the correlation between circulating Mid-regional Proadrenomedullin (MR-proADM) and mortality of patients with COVID-19 is not fully understood. In this study, we conducted a systematic review and meta-analysis to evaluate the prognostic value of MR-proADM in patients with COVID-19.MethodsThe PubMed, Embase, Web of Science, Cochrane Library, Wanfang, SinoMed and Chinese National Knowledge Infrastructure (CNKI) databases were searched from 1 January 2020 to 20 March 2022 for relevant literature. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess quality bias, STATA was employed to pool the effect size by a random effects model, and potential publication bias and sensitivity analyses were performed.Results14 studies comprising 1822 patients with COVID-19 met the inclusion criteria, there were 1145 (62.8%) males and 677 (31.2%) females, and the mean age was 63.8 ± 16.1 years. The concentration of MR-proADM was compared between the survivors and non-survivors in 9 studies and the difference was significant (P < 0.01), I2 = 46%. The combined sensitivity was 0.86 [0.73-0.92], and the combined specificity was 0.78 [0.68-0.86]. We drew the summary receiver operating characteristic (SROC) curve and calculated the area under curve (AUC) = 0.90 [0.87-0.92]. An increase of 1 nmol/L of MR-proADM was independently associated with a more than threefold increase in mortality (odds ratio (OR) 3.03, 95% confidence interval (CI) 2.26-4.06, I2 = 0.0%, P = 0.633). The predictive value of MR-proADM for mortality was better than many other biomarkers.ConclusionMR-proADM had a very good predictive value for the poor prognosis of COVID-19 patients. Increased levels of MR-proADM were independently associated with mortality in COVID-19 patients and may allow a better risk stratification.

Project description:Background/objectivesPatients affected by obesity and Coronavirus disease 2019, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appear to have a higher risk for intensive care (ICU) admission. A state of low-grade chronic inflammation in obesity has been suggested as one of the underlying mechanisms. We investigated whether obesity is associated with differences in new inflammatory biomarkers mid-regional proadrenomedullin (MR-proADM), C-terminal proendothelin-1 (CT-proET-1), and clinical outcomes in critically ill patients with SARS-CoV-2 pneumonia.Subjects/methodsA total of 105 critically ill patients with SARS-CoV-2 pneumonia were divided in patients with obesity (body mass index (BMI) ≥ 30 kg/m2, n = 42) and patients without obesity (BMI < 30 kg/m2, n = 63) and studied in a retrospective observational cohort study. MR-proADM, CT-proET-1 concentrations, and conventional markers of white blood count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) were collected during the first 7 days.ResultsBMI was 33.5 (32-36.1) and 26.2 (24.7-27.8) kg/m2 in the group with and without obesity. There were no significant differences in concentrations MR-proADM, CT-proET-1, WBC, CRP, and PCT at baseline and the next 6 days between patients with and without obesity. Only MR-proADM changed significantly over time (p = 0.039). Also, BMI did not correlate with inflammatory biomarkers (MR-proADM rho = 0.150, p = 0.125, CT-proET-1 rho = 0.179, p = 0.067, WBC rho = -0.044, p = 0.654, CRP rho = 0.057, p = 0.564, PCT rho = 0.022, p = 0.842). Finally, no significant differences in time on a ventilator, ICU length of stay, and 28-day mortality between patients with or without obesity were observed.ConclusionsIn critically ill patients with confirmed SARS-CoV-2 pneumonia, obesity was not associated with differences in MR-proADM, and CT-proET-1, or impaired outcome.Trial registrationNetherlands Trial Register, NL8460.

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The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis - a secondary analysis of a large randomised controlled trial.

Publications

The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis - a secondary analysis of a large randomised controlled trial.

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