Mid-regional Pro-adrenomedullin Research Articles

Mid-regional proadrenomedullin (MR-proADM), C-reactive protein (CRP) and other biomarkers in the early identification of disease progression in patients with COVID-19 in the acute NHS setting

AimsThere is a lack of biomarkers validated for assessing clinical deterioration in patients with COVID-19 on presentation to secondary or tertiary care. This evaluation looked at the potential clinical application...

Association of circulating MR-proADM with all-cause and cardiovascular mortality in the general population: Results from the KORA F4 cohort study.

Background and aimDespite its vasodilatory effect, adrenomedullin and its surrogate mid-regional pro-adrenomedullin (MR-proADM) have been found to be positively associated with all-cause and cardiovascular mortality. However, the underlying mechanisms thereof remain unclear and the associations were mostly shown in geriatric cohorts or in patients with chronic diseases. Therefore, we aimed to investigate the possible involvement of abdominal obesity, selected adipokines, and biomarkers of subclinical inflammation in the association of MR-proADM with mortality in a population based study cohort.MethodsProspective analysis of the KORA F4 study; median follow-up 9.1 (8.8–9.4) years. Complete data on MR-proADM and mortality was available for 1551 participants, aged 56.9±12.9 years (mean±SD). Correlation and regression analyses of MR-proADM with overall (BMI) and abdominal obesity (waist circumference), selected adipokines and biomarkers of subclinical inflammation. Cox proportional hazard models on the association of MR-proADM with all-cause and cardiovascular mortality with adjustment for cardiovascular risk factors and selected biomarkers in study subgroups (n = 603–1551).ResultsMR-proADM associated with all-cause (HR (95%CI): 2.37 (1.72–3.26) and 2.31 (1.67–3.20)) and cardiovascular mortality (4.28 (2.19–8.39) and 4.44 (2.25–8.76)) after adjustment for traditional cardiovascular risk factors including BMI or waist circumference, respectively. MR-proADM was further associated with four out of seven examined adipokines (leptin, retinol-binding protein-4, chemerin, and adiponectin) and with five out of eleven examined biomarkers of subclinical inflammation (high-sensitivity C-reactive protein, interleukin-6, myeloperoxidase, interleukin-22, and interleukin-1 receptor antagonist) after multivariable adjustment and correction for multiple testing. However, only IL-6 substantially attenuated the association of MR-proADM with all-cause mortality.ConclusionsWe found an association of MR-proADM with (abdominal) obesity, selected adipokines, and biomarkers of subclinical inflammation. However, the association of MR-proADM with mortality was independent of these parameters. Future studies should investigate the role of IL-6 and further characteristics of subclinical inflammation in the association between MR-proADM and all-cause mortality.

Mid-regional pro-adrenomedullin as apredictor of in-hospital mortality in adult patients with COVID-19: asingle-centre prospective study.

To determine the predictive value of mid-regional pro-adrenomedullin (MR-proADM) compared to routine clinical and laboratory parameters in patients with COVID-19. A total of 135 adult patients hospitalized with COVID-19 were included in a prospective single-centre study. In addition to routine parameters, the levels of MR-proADM in blood plasma were measured on the day of hospitalization. The patients were divided into 2 groups: those who survived and were discharged (n = 115, 85%) and those who did not survive (n = 20, 15%). Data are presented as median and interquartile range. The non-survivors had a statistically significantly greater age (73.4 [63.5-84.8] vs. 62.2 [50.3-71.4] years, P = 0.001), a lower level of haemoglobin oxygen saturation (91 [87-92] vs. 92 [92-93]%, P < 0.001), lower lymphocyte level (13 [7-30] vs. 21 [15-27]%, P = 0.03), higher lactate dehydrogenase (338 [273-480] vs. 280 [233-383] EU L-1, P = 0.04) and aspartate aminotransferase levels (49 [28-72] vs. 33 [23-47] EU L-1, P = 0.03), a higher National Early Warning (NEWS) score (7 [7- 8] vs. 6 [5-7] points, P < 0.001), and higher procalcitonin (0.16 [0.11-0.32] vs. 0.1 [0.07-0.18] ng mL-1, P = 0.006) and MR-proADM levels (1.288 [0.886-1.847] vs. 0.769 [0.6-0.955] nmol L-1, P < 0.001). MR-proADM had the highest predictive value for death during hospital stay (cut-off: 0.895 nmol L-1, AUC ROC 0.78 [95% CI: 0.66-0.90], sensitivity 75%, specificity 69%, OR 6.58 [95% CI: 2.22-19.51]). Compared with other indicators, MR-proADM has the highest predictive value for in-hospital mortality in patients with COVID-19.

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

BackgroundMid-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.MethodsAn 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.ResultsPatients 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.ConclusionsThis 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.

Mid-Regional Pro-Adrenomedullin, Methemoglobin and Carboxyhemoglobin as Prognosis Biomarkers in Critically Ill Patients with COVID-19: An Observational Prospective Study.

Mid-regional pro-adrenomedullin (MR-proADM), methemoglobin (MetHb), and carboxyhemoglobin (COHb) levels have been associated with sepsis. In this study, we assessed the role of this potential biomarkers in critically ill COVID-19 patients. Outcomes were mortality and a combined event (mortality, venous or arterial thrombosis, and orotracheal intubation (OTI)) during a 30-day follow-up. A total of 95 consecutive patients were included, 51.6% required OTI, 12.6% patients died, 8.4% developed VTE, and 3.1% developed arterial thrombosis. MetHb and COHb levels were not associated with mortality nor combined event. Higher MR-proADM levels were found in patients with mortality (median of 1.21 [interquartile range-IQR-0.84;2.33] nmol/L vs. 0.76 [IQR 0.60;1.03] nmol/L, p = 0.011) and combined event (median of 0.91 [IQR 0.66;1.39] nmol/L vs. 0.70 [IQR 0.51;0.82] nmol/L, p < 0.001); the positive likelihood ratio (LR+) and negative likelihood ratio (LR−) for mortality were 2.40 and 0.46, respectively. The LR+ and LR− for combined event were 3.16 and 0.63, respectively. MR-proADM ≥1 nmol/L was the optimal cut-off for mortality and combined event prediction. The predictive capacity of MR-proADM showed an area under the ROC curve of 0.73 (95% CI, 0.62–0.81) and 0.72 (95% CI, 0.62–0.81) for mortality and combined event, respectively. In conclusion, elevated on-admission MR-proADM levels were associated with higher risk of 30-day mortality and 30-day poor outcomes in a cohort of critically ill patients with COVID-19.

Mid-Regional Proadrenomedullin (MR-proADM) and Microcirculation in Monitoring Organ Dysfunction of Critical Care Patients With Infection: A Prospective Observational Pilot Study.

Introduction: Microvascular alterations are involved in the development of organ injury in critical care patients. Mid-regional proadrenomedullin (MR-proADM) may predict organ damage and its evolution. The main objective of this study was to assess the correlation between MR-proADM and microvascular flow index (MFI) in a small cohort of 20 adult critical care patients diagnosed with infection, sepsis, or septic shock. Further objectives were to evaluate the correlation between the clearance of MR-proADM and the variables of microcirculation and between MR-proADM and the Sequential Organ Failure Assessment (SOFA) score.Materials and Methods: This is a prospective observational pilot study. Inclusion criteria: consecutive adult patients admitted to intensive care unit (ICU) for or with infection-related illness. Daily measurement of MR-proADM and calculation of the SOFA score from admission in ICU to day 5. Repeated evaluations of sublingual microcirculation, collection of clinical data, and laboratory tests.Results: Primary outcome: MR-proADM was not significantly correlated to the MFI at admission in ICU. A clearance of MR-proADM of 20% or more in the first 24 h was related to the improvement of the MFIs and MFIt [percentual variation of the MFIs + 12.35 (6.01–14.59)% vs. +2.23 (−4.45–6.01)%, p = 0.005; MFIt +9.09 (4.53–16.26)% vs. −1.43 (−4.36–3.12)%, p = 0.002].Conclusion: This study did not support a direct correlation of MR-proADM with the MFI at admission in ICU; however, it showed a good correlation between the clearance of MR-proADM, MFI, and other microvascular variables. This study also supported the prognostic value of the marker. Adequately powered studies should be performed to confirm the findings.

Diagnostic Value of Mid Regional Proadrenomedullin as a Sepsis Biomarker in Pediatric Patients with Cancer-Related Chemotherapy

The aim of this study was to analyze the diagnostic value of mid regional proadrenomedullin as a sepsisbiomarker in pediatric patients with cancer-related chemotherapy. This cross-sectional observationalstudy was located in General Hospital Dr. Soetomo Surabaya from September until December 2020.International Pediatric Sepsis Consensus Conference criteria was used to define sepsis term on 2 studygroups. Serum mid regional proadrenomedullin has been drawn from 60 subjects (41 in-ward pediatricpatients) and measured on sandwich enzyme-linked immunosorbent assay from Elabscience® HumanMid Regional Proadrenomedullin. Humareader Single Plus® was used to measure the optical density.ROC analysis was used to find out cut off value, sensitivity, specificity, positive predictive value, negativepredictive value, negative likelihood ratio, positive likelihood ratio, and accuracy, respectively. Statisticsdeclared significant if p&lt;0.05 (95% CI). Between groups, temperature and heart rate were statisticallydifferent (p&lt;0.001; 95% CI). The median difference of mid regional proadrenomedullin between groupswas significant (p&lt;0.05; 95% CI). Cut off value 2,88 nmol/L, sensitivity 60.0%, specificity 56.67%,positive predictive value 58.06%, negative predictive value 58.62%, positive likelihood ratio 1.38,negative likelihood ratio 0.71 and diagnostic accuracy 59.33% was obtained while area under curvewas 0.707, respectively. Sepsis in children with cancer –related chemotherapy has not well diagnosedby serum mid regional proadrenomedullin.

Mid-regional pro-adrenomedullin and lactate dehydrogenase as predictors of left ventricular remodeling in patients with myocardial infarction treated with percutaneous coronary intervention.

The main impact of myocardial infarction (MI) is shifting from acute mortality to adverse remodeling, chronic left ventricular (LV) dysfunction, and heart failure. The aim of this study was to assess relationships between levels of circulating biomarkers and the function of LV after MI. This was a prospective study of 80 patients with MI treated with percutaneous coronary intervention. Novel biomarkers including mid‑regional pro‑adrenomedullin (MR‑proADM), Notch‑1, syndecan‑4, myeloperoxidase, S‑100 protein, soluble ST‑2, as well as markers of inflammatory response and tissue injury: galectin‑3, C‑reactive protein (CRP), lactate dehydrogenase (LDH), and interleukin‑6 (IL‑6) were assessed in the acute phase of MI. Echocardiography was performed at baseline and 6 month Results: Adverse remodeling, defined as more than 20% increase in LV end‑diastolic volume, occurred in 26% of patients. Reverse remodeling (>10% reduction in LV end‑systolic volume) was observed in 52% of patients. In the univariable analysis, higher levels of MR‑proADM and LDH were predictors of adverse remodeling and higher levels of MR ‑proADM, LDH, CRP, and IL ‑6 were negative predictors of reverse remodeling. In the multivariable model, LDH remained an independent predictor of adverse remodeling (odds ratio [OR], 3.13; 95% CI, 1.42-8.18; P = 0.003) and a negative predictor of reverse remodeling (OR, 0.37; 95% CI, 0.17-0.8; P = 0.005). LDH and MR ‑proADM seem to be promising biomarkers of adverse remodeling. On the other hand, higher levels of these biomarkers were associated with reduced chance of occurrence of favorable reverse remodeling in MI patients. However, further studies on larger groups of patients are necessary to confirm these data.

Prognostic Value of Biomarkers in Children and Adolescents With Orthostatic Intolerance.

Orthostatic intolerance (OI) refers to a series of symptoms that occur during upright standing, which can be relieved when returned to the supine position. OI is a common cause of syncope in children and adolescents. In recent years, more and more studies have been carried out to assess the prognosis of OI by using biomarkers, among which, flow-mediated vasodilation, left ventricular ejection fraction and fractional shortening, hemodynamic change during head-up tilt test, detection of 24-h urinary sodium excretion, body mass index, midregional pro-adrenomedullin, and erythrocytic H2S producing rate are relatively stable, inexpensive, and easy to obtain. With the help of biomarkers, individualized treatment can be carried out to improve the long-term prognosis of children and adolescents with OI. This article reviews the prognostic value of biomarkers in children and adolescents with OI.

Uncoupling between intravascular and distending pressures leads to underestimation of circulatory congestion in obesity.

Patients with obesity frequently present with dyspnoea. Biomarkers that reflect wall stress are often used to evaluate circulatory congestion and help determine whether dyspnoea is of cardiac causes. Patients with obesity display greater external restraint on the heart, which may alter relationships between intravascular pressures and stress markers. Subjects with unexplained dyspnoea (n= 212) underwent cardiac catheterization with simultaneous echocardiography. Blood sampling was performed in a subset (n= 58). Relationships between echocardiographic and blood biomarkers of circulatory congestion and directly-measured haemodynamics were compared between participants with severe obesity [body mass index (BMI) ≥35 kg/m2 , Group B) and those without (BMI <35 kg/m2 , Group A). Circulatory congestion was assessed by pulmonary capillary wedge pressure (PCWP), and vascular distending pressure was assessed by left ventricular transmural pressure (LVTMP). As compared to Group A, participants in Group B displayed higher PCWP relative to N-terminal pro-B-type natriuretic peptide, mid-regional pro-atrial natriuretic peptide, troponin T, and growth differentiation factor-15 (all p< 0.01). In contrast, the relationships between LVTMP and the biomarkers were superimposable. Echocardiographic biomarkers revealed the same pattern: PCWP was higher for any E/e' ratio in Group B compared to Group A, but the relationship between LVTMP and E/e' was similar. In contrast, levels of C-terminal pro-endothelin-1 and mid-regional pro-adrenomedullin were more robustly correlated with PCWP (r=0.67 and r=0.62, both p< 0.0001), with no differential relationship based upon BMI. Non-invasive haemodynamic markers underestimate circulatory congestion in patients with obesity, an effect that appears related to uncoupling between cardiac wall stress and intravascular pressures. This may lead to systematic under-recognition of congestion in patients with obesity.

Circulating biomarkers, echocardiographic parameters, and incident subclinical atrial fibrillation in patients with diabetes and hypertension.

Long-term rhythm monitoring (LTRM) can detect undiagnosed atrial fibrillation (AF) in patients at high risk of AF and stroke. Biomarkers and echocardiographic parameters could, however, help identify patients benefitting most from LTRM. The aim of this study was to investigate, whether circulating biomarkers of cardiac and vascular function (brain natriuretic peptide (BNP), cardiac troponin I (cTnI), copeptin, and mid-regional proadrenomedullin (MR-proADM)) and echocardiographic parameters were associated with incident subclinical AF (SCAF) in a population at high risk of stroke in the presence of AF. For this purpose, we investigated individuals ≥65 years of age with hypertension and diabetes mellitus, but no history or symptoms of AF or other cardiovascular disease (CVD). We included 82 consecutive patients (median age 71.3 years (IQR 67.4-75.1)). All patients received an insertable cardiac monitor (ICM) and were followed for a median of 588 days (IQR 453-712). On the day of ICM implantation, a comprehensive echocardiogram and blood samples were obtained. During a median follow-up of 588 days (IQR: 453-712 days), incident SCAF occurred in 17 patients (20.7%) with a median time to first-detected episode of 91 days (IQR 41-251 days). MR-proADM (median 0.87nmol/L (IQR 0.76-1.02) vs 0.78nmol/L (IQR 0.68-0.98)) and copeptin (median 13pmol/L (IQR 9-17) vs 8pmol/L (IQR 4-18)) levels were insignificantly higher in patients with incident SCAF. BNP and cTnI concentrations and echocardiographic parameters were similar in the two groups. MR-proADM, BNP, cTnI, copeptin, and several echocardiographic parameters were not associated with incident SCAF in this cohort of patients with hypertension and diabetes, but without any underlying CVD.

Mid-regional pro-adrenomedullin for diagnosing evolution after cardiac surgery in newborns: the PRONEW study.

Newborns are the most vulnerable patients after cardiac surgery. Although mortality risk scores before surgery may help predict the risk of poor outcome, new tools are required, and biomarkers could add objective data to these tools. The aim of this study was to assess the ability of mid-regional pro-adrenomedullin (pro-ADM) and pro-atrial natriuretic peptide (pro-ANP) to predict poor outcome after cardiac surgery. This is a pilot diagnostic accuracy study that includes newborns and infants under 2months admitted to an intensive care unit after cardiac surgery. Pro-ADM and pro-ANP were determined immediately upon admission. Poor outcome was defined as mortality, cardiac arrest, requiring extracorporeal support, requiring renal replacement therapy, or neurological injury. Forty-four patients were included. Twenty-six (59%) had a STAT category of ≥ 4. Ten patients (22.7%) presented a poor outcome, four of whom (9.1%) died. Pro-ADM was higher in patients with poor outcome (p = 0.024) and death (p = 0.012). Pro-ADM showed the best area under curve (AUC) for predicting poor outcome (0.735) and mortality alone (0.869). A pro-ADM of 2nmol/L had a Sn of 75% and a Sp of 85% for predicting mortality. Pro-ADM > 2nmol/L was independently associated with poor outcome (OR 5.8) and mortality (OR 14.1). Although higher pro-ANP values were associated with poor outcomes, no cut-off point were found. The combination of STAT ≥ 4 and the biomarkers did not enhance predictive power for poor outcome or mortality.Conclusion: Pro-ADM and pro-ANP determined immediately after surgery could be helpful for stratifying risk of poor outcome and mortality in newborns. What is Known: • Some congenital heart diseases must be corrected/palliated during the first days of life. A useful tool to predict the risk of severe complications has not been proposed. • Most unstable newborns would have higher values of biomarkers such as pro-ADM and pro-ANP related to shock and compensatory actions. What is New: • Pro-ADM and pro-ANP seem to be good biomarkers to predict poor outcome after cardiac surgery. A pro-ADM < 2 nmol/L would imply a low likelihood of a poor outcome. • Deepening the analysis of biomarkers can help in making decisions to prevent/treat complications.

Imaging and circulating biomarkers: a united approach for secondary tricuspid regurgitation

Abstract Background Secondary tricuspid regurgitation (STR) is frequent among patients with heart failure with reduced ejection fraction (HFrEF), however inheres considerable diagnostic challenges. The assessment of circulating biomarkers reflecting neurohumoral activation may constitute a valuable supplement to the currently imaging-based diagnostic process. This study therefore sought to investigate (i) the expression of a set of complementary biomarkers in STR, (ii) to evaluate their association with STR severity, and (iii) to analyse whether the combination of neurohormone measurement and echocardiographic grading improves the individual patient risk assessment. Methods We included 576 HFrEF patients under guideline-directed therapy recording functional, echocardiographic, invasive hemodynamic and biochemical measurements, i.e. N-terminal pro-B-type natriuretic peptide, mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin, C-terminal pro-endothelin-1 (CT-pro-ET1) and copeptin. Results Plasma levels of aforementioned neurohormones were significantly rising with increasing STR severity (for all P&amp;lt;0.001). Among all measured biomarkers, CT-pro-ET1 and MR-proANP were closest related to severe STR, even after multivariate adjustment for established clinical confounders (adj. OR 1.46; 95% CI 1.11–1.91, P=0.006 and adj. OR 1.45, 95% CI 1.13–1.87, P=0.004, respectively). By means of individual outcome in patients with moderate to severe STR, adding the selected biomarkers (i.e. CT-pro-ET1 and MR-proANP) resulted in a substantial improvement in the discriminatory power regarding long-term mortality (C-statistic: 0.54 vs. 0.65, P&amp;lt;0.001; continuous NRI 57%, P&amp;lt;0.001). Conclusions Circulating biomarkers closely relate to STR severity and correlate with hemodynamic and morphologic mechanisms of STR. Specifically, MR-proANP and CT-pro-ET1 are closely linked to the presence of severe STR and a combined assessment with the guideline recommended echocardiographic grading leads to a significant improvement of individual risk stratification. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): FWF - Austrian Science Fund Graphical AbstractNeurohumoral profiles of STR

Endothelial dysfunction and Mid-Regional proAdrenomedullin: What role in SARS-CoV-2 infected Patients?

BackgroundEndothelial dysfunction, a major complication of SARS-CoV-2 infectionplaying a key-role in multi-organ damage, carries high risk of mortality. AimTo investigate the potential role of Mid-Regional pro-Adrenomedullin (MR-proADM) in detecting endothelial damage with a view to stratifying the risk of adverse events (length of stay, death, admission in Intensive Care Unit) and/or disease resolution. Materials and MethodsIn 135 consecutive patients with SARS-CoV-2 infection, MR-proADM was measured in EDTA-K2 plasma samples using B.R.A.H.M.S. KRYPTOR® COMPACT Plus method (Thermo Fisher Scientific, Hennigsdorf, Germany) ResultsPatients were subdivided into three groups based on their MR-proADM value (nmol/L): 1 (n = 20, MR-proADM ≤ 0.55); 2 (n = 82, 0.55 < MR-proADM ≤ 1.50); 3 (n = 33, MR-proADM > 1.50). The higher the MR-proADM value, the greater the patients’ age, the more frequent the occurrence of pneumonia, the requiring of more aggressive treatment, the longer the hospitalization and the more frequent a fatal event. Significant differences were found between the three groups for MR-proADM, White-blood cell count, Neutrophil count, D-dimer, C-reactive Protein, Procalcitonin and hs-Troponin I. At logistic regression,it was found that MR-proADM and Log10D-dimer were the most significant predictors of adverse events. ConclusionThe findings made in the present study highlight the relevance of MR-proADM values in providing clinically useful information, particularly for stratifying COVID-19 patients according to the risk of a more severe form of disease and to the development of adverse events.

Diagnostic Accuracy and Prognostic Value of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Septic Patients outside the Intensive Care Unit

Background and Objectives: The aim of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios and to compare them with other biomarkers and clinical scores of sepsis outside the intensive care unit. Materials and methods: In this retrospective study, 251 patients with sepsis and 126 patients with infection other than sepsis were enrolled. NLR and PLR were calculated as the ratio between absolute values of neutrophils, lymphocytes, and platelets by complete blood counts performed on whole blood by Sysmex XE-9000 (Dasit, Italy) following the manufacturer’s instruction. Results: The best NLR value in diagnosis of sepsis was 7.97 with sensibility, specificity, AUC, PPV, and NPV of 64.26%, 80.16%, 0.74 (p < 0.001), 86.49%, and 53.18%, respectively. The diagnostic role of NLR significantly increases when PLR, C-reactive protein (PCR), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) values, as well as systemic inflammatory re-sponse syndrome (SIRS), sequential organ failure assessment (SOFA), and quick-sequential organ failure assessment (qSOFA) scores, were added to the model. The best value of NLR in predicting 90-day mortality was 9.05 with sensibility, specificity, AUC, PPV, and NPV of 69.57%, 61.44%, 0.66 (p < 0.0001), 28.9%, and 89.9%, respectively. Sensibility, specificity, AUC, PPV, and NPV of NLR increase if PLR, PCR, PCT, MR-proADM, SIRS, qSOFA, and SOFA scores are added to NLR. Conclusions: NLR and PLR represent a widely useful and cheap tool in diagnosis and in predict-ing 90-day mortality in patients with sepsis.

Activity of the adrenomedullin system to personalise post-discharge diuretic treatment in acute heart failure

BackgroundQuantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity.MethodsThis was a prospective multicentre study. AHF diagnosis and phenotype were centrally adjudicated by two independent cardiologists among patients presenting to the emergency department with acute dyspnoea. Adrenomedullin system activity was quantified using the biologically active component, bioactive adrenomedullin (bio-ADM), and a prohormone fragment, midregional proadrenomedullin (MR-proADM). Bio-ADM and MR-proADM concentrations were measured in a blinded fashion at presentation and at discharge. Interaction with specific treatments at discharge and the utility of these biomarkers on predicting outcomes during 365-day follow-up were assessed.ResultsAmong 1886 patients with adjudicated AHF, 514 patients (27.3%) died during 365-day follow-up. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/mL) derived disproportional benefit if treated with diuretics (interaction p values < 0.001). These findings were confirmed when quantifying adrenomedullin system activity using MR-proADM (n = 764) (interaction p values < 0.001). Patients with bio-ADM plasma concentrations above the median were at increased risk of death (hazard ratio 1.87, 95% CI 1.57–2.24; p < 0.001). For predicting 365-day all-cause mortality, both biomarkers performed well, with MR-proADM presenting an even higher predictive accuracy compared to bio-ADM (p < 0.001).ConclusionsQuantifying the adrenomedullin’s system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF.

Endothelium-associated biomarkers mid-regional proadrenomedullin and C-terminal proendothelin-1 have good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia: A prospective cohort study.

PurposeWe assessed the ability of mid-regional proadrenomedullin (MR-proADM) and C-terminal proendothelin-1 (CT-proET-1) to predict 28-day mortality in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.MethodsBiomarkers were collected during the first seven days in this prospective observational cohort study. We investigated the relationship between biomarkers and mortality in a multivariable Cox regression model adjusted for age and SOFA score.ResultsIn 105 critically ill patients with confirmed SARS-CoV-2 pneumonia 28-day mortality was 28.6%. MR-proADM and CT-proET-1 were significantly higher in 28-day non-survivors at baseline and over time. ROC curves revealed high accuracy to identify non-survivors for baseline MR-proADM and CT-proET-1, AUC 0.84, (95% CI 0.76–0.92), p < 0.001 and 0.79, (95% CI 0.69–0.89), p < 0.001, respectively. The AUC for prediction of 28-day mortality for MR-proADM and CT-proET-1 remained high over time. MR-proADM ≥1.57 nmol/L and CT-proET-1 ≥ 111 pmol/L at baseline were significant predictors for 28-day mortality (HR 6.80, 95% CI 3.12–14.84, p < 0.001 and HR 3.72, 95% CI 1.71–8.08, p 0.01).ConclusionBaseline and serial MR-proADM and CT-proET-1 had good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia.Trial registrationNEDERLANDS TRIAL REGISTER, NL8460.

Admission biomarkers among patients with acute myocardial-infarction related cardiogenic shock with or without out-of-hospital cardiac arrest an exploratory study

Background Acute myocardial infarction complicated by cardiogenic shock (AMICS) with or without out-of-hospital cardiac arrest (OHCA) have some pathophysiological differences and could potentially be considered as two individual clinical entities. Thus, there may also be differences in terms of blood borne biomarkers. Purpose To explore potential differences in concentrations of the biomarkers lactate, mid-regional proadrenomedullin (MRproADM), Copeptin, pro-atrial natriuretic peptide (proANP), Syndecan-1, soluble thrombomodulin (sTM), soluble suppression of tumorigenicity 2 (sST2) and neutrophil gelatinase-associated lipocalin (NGAL), in patients with AMICS with or without OHCA. Method Patients admitted for acute coronary angiography due to suspected ST-elevation myocardial infarction were enrolled during a 1-year period. In the present study 86 patients with confirmed AMICS at admission were included. Results In the adjusted analysis OHCA patients had higher levels of lactate (p = 0.008), NGAL (p = 0.03) and sTM (p = 0.011) while the level of sST2 was lower (p = 0.029). There was little difference in 30-day mortality between the OHCA and non-OHCA groups (OHCA 37% vs. non-OHCA 38%). Conclusion AMICS patients with or without OHCA had similar 30-day mortality but differed in terms of Lactate, NGAL, sTM and sST2 levels. These findings support that non-OHCA and OHCA patients with CS could be considered as two individual clinical entities.

Combination Biomarkers for Risk Stratification in Patients With Chronic Heart Failure Biomarkers Prognostication in HF

Current guidelines recommend measuring natriuretic peptide biomarkers to establish prognosis in patients with chronic heart failure with reduced ejection fraction (HFrEF). We assessed whether a combination biomarkers approach improve prognostication in patients with stable HFrEF. An observational cohort study recruited 202 patients with stable HFrEF at a single center, tertiary care hospital undergoing elective cardiac resynchronization therapy device placement from 2013 to 2015. Twenty-four biomarkers were analyzed individually and in combination using Cox proportion hazard regression model for major adverse cardiac events (ie, death, cardiac transplant, left ventricular assist device placement), and major adverse cardiac events plus HF hospitalizations. The single best biomarker for predicting major adverse cardiac events is peripheral mid-regional pro-adrenomedullin (C statistic = 0.771 ± 0.045) compared to current guideline recommended N-terminal pro b-type natriuretic peptide (C=0.668 ± 0.046). The best combined biomarkers for predicting major adverse cardiac events are blood urea nitrogen, coronary sinus C-reactive protein, peripheral mid-regional pro-atrial natriuretic peptide and peripheral soluble IL-1 receptor-like 1 (C = 0.767 ± 0.036). In this observational cohort, the combined biomarkers (blood urea nitrogen, C-reactive protein, mid-regional pro-atrial natriuretic peptide and soluble IL-1 receptor-like 1) or the single biomarker (mid-regional pro-adrenomedullin) was superior to N-terminal pro B-type natriuretic peptide, the current guideline recommended biomarker in predicting cardiovascular outcomes in patients with HFrEF. Larger studies are needed to validate these findings and examine whether single or combined biomarkers improve HFrEF prognostication.

The diagnostic accuracy of mid-regional pro-adrenomedullin for sepsis: a systematic review and meta-analysis.

The incidence and mortality of sepsis are high, and common biomarkers are not perfect. To identify a biomarker with high specificity and sensitivity for sepsis, we evaluated the current literature on the performance of mid-regional pro-adrenomedullin (MR-proADM) in the diagnosis of sepsis. According to appropriate eligibility and exclusion criteria, PubMed, EMBASE, Cochrane Library, China Journal full-text Database, Wanfang Database and Chinese Journal Full Text Database were searched for "mid-regional pro-adrenomedullin," "MR-proADM," "sepsis," "pyemia," "pyohemia," "septicemia," and "blood poisoning." The publication dates considered for the search were from inception until August 31st, 2020. The risk of bias was assessed according to QUADAS-2 criteria. Eleven studies involving 2038 cases were included. MR-proADM had high sensitivity and specificity in the diagnosis of sepsis, with values of 0.83 (95% CI: 0.79-0.87) and 0.90 (95% CI: 0.83-0.94), respectively. The odds ratio of a combined diagnosis was 41.35, and the area under the curve (AUC) was 0.91. The best cut-off value for MR-proADM diagnosis of sepsis is 1-1.5 nmol/L. MR-proADM may also have value in distinguishing pathogens and identifying sepsis severity and organ failure. MR-proADM is an excellent biomarker for the diagnosis of sepsis with high sensitivity and specificity. The best cut-off value for MR-proADM diagnosis of sepsis is 1-1.5 nmol/L.