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European Journal of Clinical... Apr 2024Midregional-proAdrenomedullin (MR-proADM) has been recently proposed as a tool in patients with sepsis and septic shock. Our aim was to evaluate the prognostic role of... (Review)
Review
BACKGROUND
Midregional-proAdrenomedullin (MR-proADM) has been recently proposed as a tool in patients with sepsis and septic shock. Our aim was to evaluate the prognostic role of MR-proADM in hospitalized patients with sepsis and septic shock.
METHODS
PRISMA guideline was followed. MEDLINE and EMBASE were searched up to June 2023. Primary outcome was mean difference in MR-proADM among survivors and nonsurvivors, secondary outcome mean difference in MR-proADM according to infection severity and type. Risk of bias was evaluated using Newcastle-Ottawa scale for observational studies and Cochrane tool for randomized trials. Pooled mean differences (MD) with corresponding 95% confidence intervals (CIs) were calculated in a random-effects model.
RESULTS
Twenty-four studies included 6730 adult patients (1208 nonsurvivors and 5522 survivors) and three studies included 195 paediatric patients (30 nonsurvivors and 165 survivors). A total of 10, 4 and 13 studies included, respectively, patients with sepsis (3602 patients), septic shock (386 patients) and a mixed population (2937 patients). Twenty-one studies included patients with different source of infection, three with pneumonia and one with a catheter-related infection. Most studies (n = 12) had a follow-up of 28 days. In adult cohort, pooled mean difference between nonsurvivors and survivors of MR-proADM was 2.55 mmol/L (95% CI: 1.95-3.15) with higher values in patients with septic shock (4.25 mmol/L; 95% CI, 2.23-6.26 mmol/L) than in patients with sepsis (1.77 mmol/L; 95% CI: 1.11-2.44 mmol/L). In paediatric cohort, pooled mean difference was 3.11 mmol/L (95% CI: -0.02-6.24 mmol/L).
CONCLUSIONS
Higher values of MR-proADM are detectable in nonsurvivors adult and paediatric-hospitalized patients with sepsis or septic shock.
PubMed: 38632681
DOI: 10.1111/eci.14225 -
International Journal of Molecular... Feb 2024Overhydration (OH) is a prevalent medical problem that occurs in patients with kidney failure, but a specific marker has still not been found. Patients requiring kidney... (Review)
Review
Overhydration (OH) is a prevalent medical problem that occurs in patients with kidney failure, but a specific marker has still not been found. Patients requiring kidney replacement therapy suffer from a water imbalance, which is correlated with mortality rates in this population. Currently, clinicians employ techniques such as bioimpedance spectroscopy (BIS) and ultrasound (USG) markers of overhydration or markers of heart and kidney function, namely NT-pro-BNP, GFR, or creatinine levels. New serum markers, including but not limited to Ca-125, galectin-3 (Gal-3), adrenomedullin (AMD), and urocortin-2 (UCN-2), are presently under research and have displayed promising results. Ca-125, which is a protein mainly used in ovarian cancer diagnoses, holds great potential to become an OH marker. It is currently being investigated by cardiologists as it corresponds to the volume status in heart failure (HF) and ventricular hypertrophy, which are also associated with OH. The need to ascertain a more precise marker of overhydration is urgent mainly because physical examinations are exceptionally inaccurate. The signs and symptoms of overhydration, such as edema or a gradual increase in body mass, are not always present, notably in patients with chronic kidney disease. Metabolic disruptions and cachexia can give a false picture of the hydration status. This review paper summarizes the existing knowledge on the assessment of a patient's hydration status, focusing specifically on kidney diseases and the role of Ca-125.
Topics: Humans; Biomarkers; Kidney Failure, Chronic; Renal Dialysis; Renal Insufficiency, Chronic; Water Intoxication; CA-125 Antigen
PubMed: 38396869
DOI: 10.3390/ijms25042192 -
BMC Infectious Diseases May 2023Although there is increasing understanding of the changes in the laboratory parameters of Coronavirus disease 2019 (COVID-19), the correlation between circulating... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although 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.
METHODS
The 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.
RESULTS
14 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), I = 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, I = 0.0%, P = 0.633). The predictive value of MR-proADM for mortality was better than many other biomarkers.
CONCLUSION
MR-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.
Topics: Female; Male; Humans; Middle Aged; Aged; COVID-19; Adrenomedullin; Area Under Curve; Asian People
PubMed: 37158819
DOI: 10.1186/s12879-023-08275-z -
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 -
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 -
Reviews in Medical Virology Jul 2023Numerous studies have linked coronavirus disease 2019 (COVID-19) with endothelial dysfunction and reported elevated levels of endothelial biomarkers in this disease. We... (Meta-Analysis)
Meta-Analysis Review
Numerous studies have linked coronavirus disease 2019 (COVID-19) with endothelial dysfunction and reported elevated levels of endothelial biomarkers in this disease. We conducted a systematic review and meta-analysis of the published evidence in this respect. A systematic literature search of PubMed and Scopus databases was performed to find studies investigating biomarkers of endothelial dysfunction in COVID-19 patients. Pooled standardized mean differences and their 95% confidence intervals were calculated for each biomarker using random effect model. 74 studies with 7668 patients were included. In comparison to patients with good outcome, those with poor outcome had higher levels of von Willebrand factor (vWF) (SMD: 0.83, 95% CI: 0.59-1.07, p < 0.00001), vWF:ADAMTS13 (1.23, (0.77-1.7), p < 0.00001), angiopoietin-2 (Ang-2) (1.06 (0.6-1.51), p < 0.0001), E-selectin (1.09 (0.55-1.63), p < 0.0001), P-selectin (0.59 (0.24-0.94), p = 0.001), syndecan-1 (0.99 (0.6-1.37), p < 0.00001), mid-regional pro-adrenomedullin (MR-proADM) (1.52 (1.35-1.68), p < 0.00001), vascular endothelial growth factor (0.27 (0.02-0.53), p = 0.03), soluble fms-like tyrosine kinase-1 (sFLT-1) (1.93 (0.65-3.21), p = 0.03) and lower levels of ADAMTS13 antigen (-0.69 (-0.9 to -0.47) p < 0.00001) and activity (-0.84 (-1.06 to -0.61) p < 0.0000). Plasminogen activator inhibitor-1 and tissue plasminogen activator levels were not different between the two groups (p < 0.05). There were elevated levels of endothelial dysfunction biomarkers in COVID-19 patients with poor outcome, indicating their possible role in disease severity and prognosis. In particular, MR-proADM, vWF, syndecan-1 and sFLT-1 showed a significant association with poor outcome in these patients.
Topics: Humans; Tissue Plasminogen Activator; Syndecan-1; COVID-19; Vascular Endothelial Growth Factor A; von Willebrand Factor; Biomarkers
PubMed: 36943015
DOI: 10.1002/rmv.2442 -
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 -
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 -
Current Medicinal Chemistry 2022Several studies have revealed the link between Coronavirus Disease 2019 (COVID-19) and endothelial dysfunction. To better understand the global pattern of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several studies have revealed the link between Coronavirus Disease 2019 (COVID-19) and endothelial dysfunction. To better understand the global pattern of this relationship, we conducted a meta-analysis on endothelial biomarkers related to COVID-19 severity.
METHODS
We systematically searched the literature up to March 10, 2021, for studies investigating the association between COVID-19 severity and the following endothelial biomarkers: Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), E-selectin, P-selectin, Von Willebrand Factor Antigen (VWFAg), soluble Thrombomodulin (sTM), Mid-regional pro-adrenomedullin (MR-proADM), and Angiopoietin-2 (Ang-2). Pooled estimates and mean differences (PMD) for each biomarker were reported.
RESULTS
A total of 27 studies (n=2213 patients) were included. Critically ill patients presented with higher levels of MR-proADM (PMD: 0.71 nmol/L, 95% CI: 0.22 to 1.20 nmol/L, p=0.02), E-selectin (PMD: 13,32 pg/ml, 95% CI: 4,89 to 21,75 pg/ml, p=0.008), VCAM-1 (PMD: 479 ng/ml, 95% CI: 64 to 896 ng/ml, p=0.03), VWF-Ag (PMD: 110.5 IU/dl, 95% CI: 44.8 to 176.1 IU/dl, p=0.04) and Ang-2 (PMD: 2388 pg/ml, 95% CI: 1121 to 3655 pg/ml, p=0.003), as compared to non-critically ill ones. ICAM-1, P-selectin and thrombomodulin did not differ between the two groups (p>0.05).
CONCLUSION
Endothelial biomarkers display significant heterogeneity in COVID-19 patients, with higher MR-proADM, E-selectin, VCAM-1, VWF-Ag, and Ang-2 levels being associated with increased severity. These findings strengthen the evidence on the key role of endothelial dysfunction in disease progress.
Topics: Biomarkers; COVID-19; E-Selectin; Endothelium, Vascular; Humans; Intercellular Adhesion Molecule-1; Thrombomodulin; Vascular Cell Adhesion Molecule-1; Vascular Diseases; von Willebrand Factor
PubMed: 34702152
DOI: 10.2174/0929867328666211026124033 -
Proadrenomedullin and neonatal sepsis: a systematic review and meta-analysis of diagnostic accuracy.European Journal of Pediatrics Jan 2022The association of proadrenomedullin and neonatal sepsis has been examined in numerous studies. The object of our meta-analysis is to evaluate differences in... (Meta-Analysis)
Meta-Analysis Review
The association of proadrenomedullin and neonatal sepsis has been examined in numerous studies. The object of our meta-analysis is to evaluate differences in proadrenomedullin among neonates with sepsis and health neonates. We systematically searched the following databases: MEDLINE, Clinicaltrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, and WHO (International Clinical Trials Register Platform) using a structured algorithm. Statistical analysis was conducted using Revman 5.3 and R software. Included studies in the meta-analysis were assessed using the Newcastle-Ottawa scale. Proadrenomedullin levels were found significantly higher in neonates with sepsis than healthy neonates with an SMD equal with 3.07 [95% CI 1.71, 4.42 (p < 10, I = 98%)]. The optimal cutoff point of pro-ADM was calculated at 17.559 with a sensitivity of 0.879 (0.458; 0.984) and a specificity of 0.994 (0.820; 1.000), and an AUC of 0.905. Subgroup analysis, leave-one-out meta-analysis, and meta-regression were performed in an effort to lower inter-study heterogeneity. Sensitivity analysis was conducted by excluding high risk of bias studies and those contributing to the overall heterogeneity shown by the Baujat plot. Publication bias was assessed using a funnel plot and the trim-and-fill method. Certainty assessment was evaluated using the GRADE score.Conclusion: The findings of our meta-analysis suggest that proadrenomedullin is elevated in neonates with sepsis. However, future prospective cohort studies need to be conducted in order to assess its diagnostic accuracy. What is Known: • Proadrenomedullin has been found increased in adult patients with infectious diseases such as community acquired pneumonia. • Proadrenomedullin plays a major role in the pathophysiology of sepsis in adults. What is New: • Proadrenomedullin is increased in neonates with sepsis. • Future cohort studies need to be conducted in order to elucidate the value of proadrenomedullin in a safer way.
Topics: Adrenomedullin; Humans; Infant, Newborn; Neonatal Sepsis; Prospective Studies; Protein Precursors; Sepsis
PubMed: 34342678
DOI: 10.1007/s00431-021-04214-9