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BMC Infectious Diseases May 2023The early diagnosis of sepsis is hampered by the lack of reliable laboratory measures. There is growing evidence that presepsin and Mid-regional pro-adrenomedullin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The early diagnosis of sepsis is hampered by the lack of reliable laboratory measures. There is growing evidence that presepsin and Mid-regional pro-adrenomedullin (MR-proADM) are promising biomarkers in the diagnosis of sepsis. This study was conducted to evaluate and compare the diagnostic value of MR-proADM and presepsin in sepsis patients.
METHODS
We searched Web of Science, PubMed, Embase, China national knowledge infrastructure, and Wanfang up to 22th July, 2022, for studies evaluating the diagnosis performance of presepsin and MR-proADM in adult sepsis patients. Risk of bias was assessed using quadas-2. Pooled sensitivity and specificity were calculated using bivariate meta-analysis. Meta-regression and subgroup analysis were used to find source of heterogeneity.
RESULTS
A total of 40 studies were eventually selected for inclusion in this meta-analysis, including 33 for presepsin and seven for MR-proADM. Presepsin had a sensitivity of 0.86 (0.82-0.90), a specificity of 0.79 (0.71-0.85), and an AUC of 0.90 (0.87-0.92). The sensitivity of MR-proADM was 0.84 (0.78-0.88), specificity was 0.86 (0.79-0.91), and AUC was 0.91 (0.88-0.93). The profile of control group, population, and standard reference may be potential sources of heterogeneity.
CONCLUSIONS
This meta-analysis demonstrated that presepsin and MR-proADM exhibited high accuracy (AUC ≥ 0.90) in the diagnosis of sepsis in adults, with MR-proADM showing significantly higher accuracy than presepsin.
Topics: Adult; Humans; Shock, Septic; Adrenomedullin; Prognosis; Protein Precursors; Sepsis; Biomarkers; Peptide Fragments; Lipopolysaccharide Receptors
PubMed: 37147598
DOI: 10.1186/s12879-023-08262-4 -
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 -
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 -
International Journal of Molecular... Apr 2023Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between... (Review)
Review
Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between fibroids and infertility has been established, especially if the fibroid protrudes in the uterine cavity. Hormonal therapy is associated with side-effects and as well as hysterectomy, which is incompatible with a desire to conceive. To improve treatment, it is essential to unravel the etiology of fibroid-related symptoms. We aim to evaluate endometrial angiogenesis in women with fibroids, with and without AUB, and the influence of pharmaceutical therapies in these patients. Furthermore, we explore the possible role of altered angiogenesis in patients with fibroids and infertility. We performed a systematic review according to PRISMA-guidelines (PROSPERO: CRD42020169061), and included 15 eligible studies. Endometrial expression of vascular endothelial growth factor (VEGF) and adrenomedullin was increased in patients with fibroids. This suggests aberrant angiogenesis, potentially involving disturbed vessel maturation, resulting in immature and fragile vessels. Treatment with gonadotropin-releasing hormone agonist, ulipristal acetate, and continuous oral contraception pills reduced several angiogenic parameters, including VEGF. If infertile and fertile patients with fibroids were compared, a significant decreased expression of the bone morphogenetic protein/Smad-protein pathway was found, possibly caused by the increased expression of transforming growth factor-beta. For future therapeutic development, these different angiogenic pathways could be of interest as possible targets to treat fibroid-related symptoms.
Topics: Humans; Female; Vascular Endothelial Growth Factor A; Uterine Neoplasms; Leiomyoma; Infertility; Uterine Hemorrhage
PubMed: 37108180
DOI: 10.3390/ijms24087011 -
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 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 -
Respiratory Medicine Nov 2014The initial prognostic assessment of patients with community-acquired pneumonia( CAP) has important clinical implications. We hypothesized that midregional... (Meta-Analysis)
Meta-Analysis Review
The initial prognostic assessment of patients with community-acquired pneumonia( CAP) has important clinical implications. We hypothesized that midregional proadrenomedullin(MR-proADM) is a valuable test for the prediction of outcomes in patients with CAP.Methods: We performed a systemic review of the literature and a meta-analysis to evaluate the prognostic value of MR-proADM for short and long-term mortality in patients with CAP.Results: Twelve studies were included in the systematic review. Elevated MR-proADM was associated with an increase in short-term mortality (OR Z 6.8; 95% CI: 4.65-10.13; P value < 0.001) and complications (OR = 5.0; 95% CI: 3.86-6.49; P value < 0.001). The pooled analysis of 4 studies showed an improvement in the discriminant ability by 8% (95% CI: 2%e14%)when MR-proADM was added to CURB-65/CRB-65. Studies that reported long-term prognosis indicated an increased risk of death in patients with elevated MR-proADM.Conclusion: Elevated level of MR-proADM is significantly associated with both short-term mortality and complications in patients with CAP. Studies also indicate that MR-proADM has prognostic value for prediction of long-term mortality in these patients. The addition of MR-proADM improves the discriminant ability of CURB-65/CRB-65.
Topics: Adrenomedullin; Bias; Biomarkers; Community-Acquired Infections; Humans; Pneumonia; Prognosis; Protein Precursors; Risk Assessment; Sensitivity and Specificity
PubMed: 25448309
DOI: 10.1016/j.rmed.2014.09.018 -
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 -
BMC Pediatrics Apr 2022Invasive bacterial infections (IBI) in children present a difficult clinical challenge. They are often life-threatening, however in the early stages they can be hard to...
BACKGROUND
Invasive bacterial infections (IBI) in children present a difficult clinical challenge. They are often life-threatening, however in the early stages they can be hard to differentiate from benign viral infections. This leaves clinicians with the risk of missing a serious IBI diagnosis or inappropriately using antimicrobials in a child with a viral infection- contributing to the ongoing development of increased antimicrobial resistance. Hence, biomarkers which could aid in early detection of IBI and differentiation from viral infections are desirable. Mid-Regional pro-Adrenomedullin (MR-proADM) is a biomarker which has been associated with IBI. The aim of this systematic review was to determine its diagnostic accuracy in identifying children with IBI.
METHODS
A strategy was devised to search online databases MEDLINE, Embase, Web of Science and Scopus for human clinical trials reporting the accuracy of MR-proADM in children. Against predesigned inclusion and exclusion criteria full texts were selected for inclusion and data extraction. True positives, false positives, true negatives and false negatives were extracted from each included study to fill 2 × 2 tables. Using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool methodological quality of each study was assessed.
RESULTS
A total of 501 articles were initially identified. After the removal of duplicates and abstract screening 11 texts were fully reviewed and four texts (totaling 1404 patients) were included in the systematic analysis. Only one study was of a high quality and that study accounted for the vast majority of patients. A single study reported the diagnostic accuracy of MR-proADM for invasive bacterial infection reporting an Area under the Curve of 0.69. The paucity of available studies made meta-analysis and studies of heterogeneity impossible.
CONCLUSION
There is a paucity of research regarding the diagnostic accuracy of MR-proADM in the diagnosis of invasive bacterial infections in children. Initial results would suggest that MR-proADM testing alone is poor at identifying IBI in young children. It remains unclear if MR-proADM performs differently in older children or in children with signs and symptoms of IBI.
TRIAL REGISTRATION
PROSPERO CRD42018096295 .
Topics: Adrenomedullin; Anti-Infective Agents; Bacterial Infections; Biomarkers; Child; Child, Preschool; Early Diagnosis; Humans
PubMed: 35379203
DOI: 10.1186/s12887-022-03255-9 -
Annals of Medicine Dec 2023Mid-regional pro-adrenomedullin (MR-proADM) is useful for risk stratification in patients with sepsis and respiratory infections. The study's purpose was to assess the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mid-regional pro-adrenomedullin (MR-proADM) is useful for risk stratification in patients with sepsis and respiratory infections. The study's purpose was to assess the available data and determine the association between MR-proADM levels and mortality in COVID-19 participants.
METHODS
A comprehensive literature search of medical electronic databases was performed including PubMed, Web of Science, Scopus, Cochrane, and grey literature for relevant data published from 1 January 2020, to 20 November 2022. Mean differences (MD) with 95% confidence intervals (CI) were calculated.
RESULTS
Fourteen studies reported MR-proADM levels in survivors vs. non-survivors of COVID-19 patients. Pooled analysis showed that MR-proADM level in the survivor group was 0.841 ± 0.295 nmol/L for patients who survive COVID-19, compared to 1.692 ± 0.761 nmol/L for non-survivors (MD = -0.78; 95%CI: -0.92 to -0.64; < 0.001).
CONCLUSIONS
The main finding of this study is that mortality of COVID-19 is linked to MR-proADM levels, according to this meta-analysis. The use of MR-proADM might be extremely beneficial in triaging, assessing probable therapy escalation, predicting potential complications during therapy or significant clinical deterioration of patients, and avoiding admission which may not be necessary. Nevertheless, in order to confirm the obtained data, it is necessary to conduct large prospective studies that will address the potential diagnostic role of MR-proADM as a marker of COVID-19 severity.KEY MESSAGESSeverity of COVID-19 seems to be linked to MR-proADM levels and can be used as a potential marker for predicting a patient's clinical course.The use of MR-proADM might be beneficial in triaging, assessing probable therapy escalation, predicting potential complications during therapy or significant clinical deterioration of patients, and avoiding admission which may not be necessary.For patients with COVID-19, MR-proADM may be an excellent prognostic indicator because it is a marker of endothelial function that may predict the precise impact on the equilibrium between vascular relaxation and contraction and lowers platelet aggregation inhibitors, coagulation inhibitors, and fibrinolysis activators in favor of clotting factors.
Topics: Humans; Prognosis; Biomarkers; Prospective Studies; Protein Precursors; Adrenomedullin; Clinical Deterioration; COVID-19
PubMed: 36607317
DOI: 10.1080/07853890.2022.2162116