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Minerva Anestesiologica Oct 2021The 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... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
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.
EVIDENCE ACQUISITION
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 31, 2020. The risk of bias was assessed according to QUADAS-2 criteria.
EVIDENCE SYNTHESIS
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.
CONCLUSIONS
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.
Topics: Adrenomedullin; Area Under Curve; Biomarkers; Humans; Prognosis; Sepsis
PubMed: 34134460
DOI: 10.23736/S0375-9393.21.15585-3 -
Klinicheskaia Laboratornaia Diagnostika 2019A systematic search of literary sources in the abstract databases Scopus, Web of Science, MedLine, the Cochrane Library, CyberLeninka, RSCI for 2010-2018. The search...
A systematic search of literary sources in the abstract databases Scopus, Web of Science, MedLine, the Cochrane Library, CyberLeninka, RSCI for 2010-2018. The search queries were: acute pancreatitis and complications, acute pancreatitis and diagnosis, acute pancreatitis and diagnosis and complications, acute pancreatitis and compications, and sepsis. The results of search and analysis of selected literature sources are presented. It was revealed that the currently used set of laboratory and instrumental methods of diagnosis of infectious complications of acute pancreatitis does not fully meet the needs of clinical practice. The most common of them are the determination of blood concentrations Of C-reactive protein and procalcitonin. At the same time, a number of disadvantages of these methods are noted. In the last decade, many new markers of systemic infection have been introduced into clinical practice. Some of them are currently being investigated in order to diagnose systemic infection in General and infectious complications of acute pancreatitis in particular. The most promising are such as presepsin, MID-regional Pro-adrenomedullinum, CD64 neutrophil index and some others.
Topics: Acute Disease; Adrenomedullin; Biomarkers; C-Reactive Protein; Humans; Lipopolysaccharide Receptors; Pancreatitis; Peptide Fragments; Procalcitonin; Sepsis
PubMed: 31012552
DOI: 10.18821/0869-2084-2019-64-3-145-152 -
Open Heart 2018Biomarkers are important in the diagnosis, risk stratification and management of patients with heart failure (HF). The established biomarkers of myocardial stretch,...
BACKGROUND
Biomarkers are important in the diagnosis, risk stratification and management of patients with heart failure (HF). The established biomarkers of myocardial stretch, brain natriuretic peptide (BNP) and amino (N) portion of BNP (NT-proBNP) have been extensively studied, and early analyses have demonstrated response to exercise training. Several other biomarkers have been identified over the last decade and may provide valuable and complementary information which may guide treatment strategies, including exercise therapy.
METHODS
A systematic search of PubMed, EMBASE and Cochrane Trials Register to 31 October 2017 was conducted for exercise-based rehabilitation trials in HF. Randomised and controlled trials that reported biomarkers, BNP, NT-proBNP, soluble ST2, galectin-3, mid-regional atrial natriuretic peptide, mid-regional adrenomedullin and copeptin, were included.
RESULTS
Forty-three studies were included in the systematic review, with 27 studies suitable for meta-analyses. Data pooling was only possible for NT-proBNP and BNP. Meta-analyses of conventional training studies demonstrated a statistically significant improvement in NT-proBNP (pmol/L); mean difference (MD) -32.80 (95% CI -56.19 to -9.42), p=0.006 and in BNP (pmol/L); MD -17.17 (95% CI -29.56 to -4.78), p=0.007. Pooled data of non-conventional training failed to demonstrate any statistically significant improvements.
CONCLUSION
Pooled data indicated a favourable effect of conventional exercise therapy on the established biomarkers, NT-proBNP and BNP; however, this was in contrast to a number of studies that could not be pooled. Limited evidence exists as to the effect of exercise training on emerging biomarkers.
PubMed: 30018779
DOI: 10.1136/openhrt-2018-000819 -
Medicina Intensiva Oct 2018To ascertain the ability of adrenomedullin (ADM) and proadrenomedullin (proADM) to predict mortality in sepsis patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To ascertain the ability of adrenomedullin (ADM) and proadrenomedullin (proADM) to predict mortality in sepsis patients.
DESIGN
A systematic literature search was made of the PubMed, EMBASE, Cochrane and China National Knowledge Infrastructure (CNKI) databases before May 2017, supplemented by manual searches of references. A meta-analysis of high-quality clinical studies was subsequently performed to assess the association between ADM/proADM and mortality risk among patients with sepsis.
PATIENTS
Thirteen studies involving 2556 patients were included in the study.
INTERVENTIONS
Two reviewers independently identified articles, extracted data, assessed quality and cross-checked the results. The predictive values of ADM and proADM referred to mortality were assessed by relative risk (RR). The overall diagnostic accuracy of ADM and proADM in application to sepsis was pooled according to a bivariate model. Publication bias was assessed using Deek's funnel plot asymmetry test.
RESULTS
Elevated ADM or proADM levels were associated with increased mortality (pooled RR=3.31; 95%CI 2.31-4.75). Subgroup analyses indicated the pooled RRs were 3.12 (95%CI 1.75-5.56) and 3.43 (95%CI 2.21-5.31) for ADM and proADM, respectively. The pooled sensitivity and specificity were 0.72 (95%CI 0.64-0.78) and 0.77 (95%CI 0.69-0.83), respectively. The overall area under the summary receiver operating characteristic (SROC) curve was 0.80 (95%CI 0.77-0.84). Publication bias was not statistically significant.
CONCLUSIONS
Both ADM and proADM might serve as useful markers for predicting the prognosis of sepsis.
Topics: Adrenomedullin; Aged; Biomarkers; Humans; Middle Aged; Prognosis; Protein Precursors; ROC Curve; Risk; Sensitivity and Specificity; Sepsis
PubMed: 29246418
DOI: 10.1016/j.medin.2017.10.013 -
ESC Heart Failure May 2017Evidence accumulates for associations between hypertensive pregnancy disorders and increased cardiovascular risk later. The main goal of this study was to explore shared... (Review)
Review
Evidence accumulates for associations between hypertensive pregnancy disorders and increased cardiovascular risk later. The main goal of this study was to explore shared biomarkers representing common pathogenic pathways between heart failure with preserved ejection fraction (HFpEF) and pre-eclampsia where these biomarkers might be potentially eligible for cardiovascular risk stratification in women after hypertensive pregnancy disorders. We sought for blood markers in women with diastolic dysfunction in a first literature search, and through a second search, we investigated whether these same biochemical markers were present in pre-eclampsia.This systematic review and meta-analysis presents two subsequent systematic searches in PubMed and EMBASE. Search I yielded 3014 studies on biomarkers discriminating women with HFpEF from female controls, of which 13 studies on 11 biochemical markers were included. Cases had HFpEF, and controls had no heart failure. The second search was for studies discriminating women with pre-eclampsia from women with non-hypertensive pregnancies with at least one of the biomarkers found in Search I. Search II yielded 1869 studies, of which 51 studies on seven biomarkers were included in meta-analyses and 79 studies on 12 biomarkers in systematic review.Eleven biological markers differentiated women with diastolic dysfunction from controls, of which the following 10 markers differentiated women with pre-eclampsia from controls as well: C-reactive protein, HDL, insulin, fatty acid-binding protein 4, brain natriuretic peptide, N terminal pro brain natriuretic peptide, adrenomedullin, mid-region pro adrenomedullin, cardiac troponin I, and cancer antigen 125.Our study supports the hypothesis that HFpEF in women shares a common pathogenic background with pre-eclampsia. The biomarkers representing inflammatory state, disturbances in myocardial function/structure, and unfavourable lipid metabolism may possibly be eligible for future prognostic tools.
PubMed: 28451444
DOI: 10.1002/ehf2.12129 -
Breast (Edinburgh, Scotland) Dec 2016Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the... (Review)
Review
Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the biological basis of breast cancer osteotropism is not fully understood. This paper provides, for the first time, an integrative, systematic review of evidence of molecular factors that have functional roles in the homing of metastatic breast cancer to the bone. Pubmed, Web of Science and EBSCOhost were searched using keywords and synonyms for molecular, metastasis, breast cancer and bone to identify articles published between January 2004 and August 2016. 4491 potentially relevant citations were retrieved. 63 articles met the inclusion criteria, which were primary studies reporting evidence of molecular factors that have functional roles in predisposing breast cancer bone metastasis in vivo. 12 of those 63 articles that additionally met quality criteria were included in the review. Extracted data were tabulated and key findings that indicated biological mechanisms involved in breast cancer metastasis to bone were synthesised. 15 proteins expressed by breast cancer cells were identified as factors that mediate breast cancer bone metastasis: ICAM-1, cadherin-11, osteoactivin, bone sialoprotein, CCN3, IL-11, CCL2, CITED2, CXCR4, CTGF, OPN, CXCR1, TWIST1, adrenomedullin and Enpp1. Upregulation or overexpression of one or more of them by breast cancer cells resulted in increased breast cancer metastasis to bone in vivo, except for CCL2 where bone-metastatic cells showed a reduced expression of this factor. All factors identified, here expressed by breast cancer cells, are proteins that are normally expressed in the bone microenvironment and linked to physiologic bone functions. All have a functional role in one of more of the following: cell proliferation and differentiation, bone mineralization and remodelling, cell adhesion and/or chemokine signalling. Six of them (cadherin-11, ICAM-1, OPN, CXCR1, CCN3 and osteoactivin) have a reported function in cell adhesion and another eight (CCN3, osteoactivin, Enpp1, IL-11, CTGF, TWIST1, adrenomedullin and CITED2) are reported to be involved in cell proliferation and differentiation. This review collates and synthesises published evidence to increase our understanding of the biology of breast cancer osteomimicry in the development of bone metastasis. Findings of this review suggest that changes in expression of proteins in breast cancer cells that confer osteomimicry facilitate homing to bone to enable the development of bone metastasis.
Topics: Adrenomedullin; Animals; Bone Neoplasms; Breast Neoplasms; CX3C Chemokine Receptor 1; Cadherins; Cell Line, Tumor; Chemokine CCL2; Connective Tissue Growth Factor; Humans; Integrin-Binding Sialoprotein; Intercellular Adhesion Molecule-1; Interleukin-11; Membrane Glycoproteins; Neoplasm Metastasis; Nephroblastoma Overexpressed Protein; Osteopontin; Phosphoric Diester Hydrolases; Pyrophosphatases; Receptors, CXCR4; Receptors, Chemokine; Repressor Proteins; Trans-Activators; Twist-Related Protein 1
PubMed: 27750106
DOI: 10.1016/j.breast.2016.09.017 -
BMC Infectious Diseases May 2016The early identification of patients at risk of dying from community-acquired pneumonia (CAP) is critical for their treatment and for defining hospital resource... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The early identification of patients at risk of dying from community-acquired pneumonia (CAP) is critical for their treatment and for defining hospital resource consumption. Mid-regional pro-adrenomedullin (MR-proADM) has been extensively investigated for its prognostic value in CAP. However, the results are conflicting. The purpose of the present meta-analysis was to explore the diagnostic accuracy of MR-proADM for predicting mortality in patients suffering from CAP, particularly emergency department (ED) patients.
METHOD
We systematically searched the PubMed, Embase, Web of Knowledge and Cochrane databases. Studies were included if a 2 × 2 contingency table could be constructed based on both the MR-proADM level and the complications or mortality of patients diagnosed with CAP. The prognostic accuracy of MR-proADM in CAP was assessed using the bivariate meta-analysis model. We used the Q-test and I (2) index to evaluate heterogeneity.
RESULTS
MR-proADM displayed moderate diagnostic accuracy for predicting complications in CAP, with an overall area under the SROC curve (AUC) of 0.74 (95 % CI: 0.70-0.78). Eight studies with a total of 4119 patients in the emergency department (ED) were included. An elevated MR-proADM level was associated with increased risk of death from CAP (RR 6.16, 95 % CI 4.71-8.06); the I (2) value was 0.0 %, and a fixed-effects model was used to pool RR. The pooled sensitivity and specificity were 0.74 (95 % CI: 0.67-0.79) and 0.73 (95 % CI: 0.70-0.77), respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 2.8 (95 % CI, 2.3-3.3) and 0.36 (95 % CI, 0.29-0.45), respectively. In addition, the diagnostic odds ratio (DOR) was 8 (95 % CI, 5-11), and the overall area under the SROC curve was 0.76 (95 % CI, 0.72-0.80).
CONCLUSIONS
Our study has demonstrated that MR-proADM is predictive of increased complications and higher mortality rates in patients suffering from CAP. Future studies are warranted to determine the prognostic accuracy of MR-proADM in conjunction with severity scores or other biomarkers and to determine an optimal cut-off level.
Topics: Adrenomedullin; Biomarkers; Community-Acquired Infections; Emergency Service, Hospital; Humans; Pneumonia; Prognosis; Sensitivity and Specificity
PubMed: 27230573
DOI: 10.1186/s12879-016-1566-3 -
The Journal of Infection Mar 2016The pneumonia severity index and CURB-65 are risk assessment tools widely used in community-acquired pneumonia (CAP). However, limitations in these prognostic scores... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The pneumonia severity index and CURB-65 are risk assessment tools widely used in community-acquired pneumonia (CAP). However, limitations in these prognostic scores have led to increasing interest in finding biomarkers that might provide additional information. To date, the role of these biomarkers has not been fully elucidated.
METHODS
We systematically searched the Medline, Web of Knowledge, Science Direct, and LILACS databases. We included studies that assessed the accuracy of biomarkers for the prediction of in-hospital or ≤30-day mortality, in hospitalized adults with CAP. Two independent investigators extracted patient and study characteristics, which were thereafter pooled using a random effects model. Relationships between sensitivity and specificity of biomarkers and prognostic scores were plotter using the area under the receiver operator characteristic curve (AUC).
RESULTS
We included 24 articles and 2 databases from 1069 reviewed abstracts, which provided 10,319 patients for analysis. Reported mortality rates varied from 2.4% to 34.6%. The highest AUC values for predicting mortality were associated with pro-adrenomedullin (0.80) and prohormone forms of atrial natriuretic peptide (0.79), followed by cortisol (0.78), procalcitonin (0.75), copeptin (0.71), and C-reactive protein (0.62). There were no statistically significant differences between the AUCs of the studied biomarkers, other than for copeptin and C-reactive protein, which performed comparatively poorly. When compared with the CAP-specific scores, the AUCs were not significantly different from those of most biomarkers.
CONCLUSIONS
The identified biomarkers are able to predict mortality with moderate to good accuracy in CAP. However, biomarkers have no clear advantage over CAP-specific scores for predicting mortality.
Topics: Biomarkers; Community-Acquired Infections; Decision Support Techniques; Humans; Pneumonia; Prognosis; Sensitivity and Specificity; Survival Analysis
PubMed: 26777314
DOI: 10.1016/j.jinf.2016.01.002 -
Prenatal Diagnosis Jun 2015This overview provides insight into the underlying genetic mechanism of the high incidence of cardiac defects in fetuses with increased nuchal translucency (NT). Nuchal... (Review)
Review
This overview provides insight into the underlying genetic mechanism of the high incidence of cardiac defects in fetuses with increased nuchal translucency (NT). Nuchal edema, the morphological equivalent of increased NT, is likely to result from abnormal lymphatic development and is strongly related to cardiac defects. The underlying genetic pathways are, however, unknown. This study aims to present a systematic overview of genes involved in both cardiac and lymphatic development in mouse embryos. A search of PubMed and the Mammalian Phenotype Browser was performed. Fifteen candidate genes involved in both cardiac and lymphatic development were identified: Adrenomedullin; Chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TFII); Cyp51; Ephrin-B2; Forkhead box protein C2 (Foxc2); Nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1); Neurofibromatosis type 1 (Nf1); Phosphoinositide 3-kinase encoding isoform p110α (Pik3ca); Podoplanin; Prospero-related homeobox 1 (Prox1); T-box 1 (Tbx1); Tyrosine kinase with immunoglobulin-like and endothelial growth factor-like domains 1 (Tie1); vascular endothelial growth factor (Vegf)-A; Vegf receptor-3 (Vegfr-3); and Vascular endothelial zinc finger 1 (Vezf1). Mutations in all but one gene (Pik3ca) resulted in both a cardiac defect and nuchal edema. Candidate genes - mainly encoding for endothelium - are involved in both cardiac and lymphatic development. Alterations in candidate genes are associated with the strong relation between increased NT and cardiac defects.
Topics: Animals; Edema; Genes, Developmental; Heart; Heart Defects, Congenital; Lymphatic System; Mice; Nuchal Translucency Measurement
PubMed: 25728762
DOI: 10.1002/pd.4586 -
The American Journal of Cardiology Apr 2015We undertook this systematic review to determine the prognostic significance of adrenomedullin (ADM) in patients with heart failure and acute myocardial infarction... (Review)
Review
We undertook this systematic review to determine the prognostic significance of adrenomedullin (ADM) in patients with heart failure and acute myocardial infarction (AMI). Given the difficulty in measuring mature ADM, its surrogate, midregional proadrenomedullin (MRproADM) has been used in most studies. Systematic search of original published studies through MEDLINE and the Cochrane Collaboration databases restricted to reports in English from January 1, 1993, to June 30, 2014, in humans was undertaken. Heterogeneity of studies prohibited a meta-analysis. In patients with heart failure, the area under the curve for prediction of mortality by MRproADM ranged from 0.68 to 0.81 (95% confidence intervals [CI] 0.63 to 0.91) across studies. One nmol/l increase in MRproADM was associated with hazard ratios (HRs) ranging from 1.77 to 2.79 (95% CI 1.29 to 5.95) for death in patients with heart failure. In patients with AMI, the area under the curve for MRproADM predicting MACE ranged from 0.64 to 0.80 (CI 0.51 to 0.87) across studies and death 0.79 to 0.84 (CI 0.73 to 0.90). One nmol/l increase in MRproADM was associated with HR for MACE ranging from 1.78 to 4.10 (CI 1.20 to 10.12), whereas log10 of MRproADM had HRs of 3.63 to 9.75 (CI 1.48 to 26.16) for MACE and 4.86 to 16.68 (CI 4.56 to 60.99) for death across studies in patients with AMI. In conclusion, adrenomedullin is an independent predictor of death in patients with heart failure and of MACE and death in patients who have suffered an AMI. Quantification of this peptide might contribute to improved risk stratification in settings of heart failure and myocardial infarction.
Topics: Adrenomedullin; Biomarkers; Electrocardiography; Global Health; Heart Failure; Humans; Myocardial Infarction; Predictive Value of Tests; Prognosis; Survival Rate
PubMed: 25682438
DOI: 10.1016/j.amjcard.2015.01.027