Search Results (32)

Background: Suppression of Tumorigenicity 2 (ST2), a member of the interleukin-1 receptor family, plays a crucial role in immune regulation. Elevated sST2 levels are associated with poor prognosis in various inflammatory and cardiovascular diseases, including acute heart failure (AHF), sepsis and transplant rejection. Objectives and methods: This study aimed to evaluate the diagnostic and prognostic accuracy of sST2, along with other biomarkers, such as high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), procalcitonin (PCT) and mid-regional pro-adrenomedullin (MR-proADM), in patients with AHF, sepsis and AHF/sepsis overlap. Results: A cohort of 74 patients was analyzed, and comparison statistics revealed that sST2 levels were significantly higher in the AHF/sepsis group (113.88 ng/mL) compared to the AHF group (42.24 ng/mL, p = 0.024), while no significant difference was observed between sepsis and AHF groups (p = 0.10). Other biomarkers, including hs-CRP and PCT, showed significant differences between the AHF and AHF/sepsis groups. ROC curve analysis identified sST2 as a strong predictor of mortality and readmission, with high AUC values for 30-day readmission (0.821) and mortality (0.87). Conclusions: These findings suggest that combining biomarkers, including sST2, could improve the early diagnosis, risk stratification and management of critically ill patients with overlapping AHF and sepsis. Further studies with larger populations are needed to validate these findings and explore the potential of integrating these biomarkers into clinical practice. Full article

This study aimed to investigate the impact of long-term survival on cardiac serum biomarkers such as natriuretic peptides (mid-regional pro-atrial natriuretic peptide [MR-proANP], B-type natriuretic peptide [BNP], N-terminal prohormone BNP [NT-proBNP]), soluble ST2 (sST2), galectin-3 and mid-regional pro-adrenomedullin (MR-proAMD). Consecutive patients hospitalized in a tertiary center, undergoing echocardiographic and invasive left cardiac catheterization for diastolic dysfunction assessment were prospectively included in this study. Cardiac biomarkers were determined from pre-procedural peripheral venous blood samples. A total of 110 patients were included, with a median follow-up of 1.66 (1.23–2.16) years during which 16 (14.5%) patients died. A total of 45.4% (50) of patients had diastolic dysfunction. In the univariate Cox regression, long-term survival was predicted by BNP (p < 0.0001, HR = 0.39 [0.20–0.53]), NT-proBNP (p < 0.0001, HR = 0.40 [0.22–0.55]), MR-proANP (p = 0.001, HR = 0.30 [0.11–0.46]), sST2 (p < 0.0001, HR = 0.47 [0.30–0.60]), but not with MR-proAMD (p = 0.77) or galectin-3 (p = 0.76). In the final stepwise multivariable Cox regression non-invasive and invasive models, NT-proBNP and sST2 remained independent predictors of survival. Natriuretic peptides (BNP and NT-proBNP) and sST2 were predictors of long-term survival, while MR-proANP, MR-proADM and galectin-3 did not have predictive values. NT-proBNP and sST2 improved survival prediction in both a non-invasive scenario (including clinical, serum and echocardiographic parameters) and an invasive clinical scenario (including left heart catheterization parameters). The sST2 pathway could provide a target for therapeutic intervention. Full article

Background: Patent ductus arteriosus (PDA) in preterm infants presents a significant challenge in neonatal care, marked by ongoing debates about its definition, diagnosis, treatment options, and effects on patient outcomes. Plasma biomarkers assess mediators involved in PDA closure and hemodynamic responses, assisting in identifying newborns at higher risk of developing potentially serious neonatal conditions. The purpose of this review was to investigate the relationship between PDA and various plasma biomarkers used to evaluate and diagnose ductal patency during perinatal life, as outlined in the relevant literature. Methods: We conducted an electronic search of the National Library of Medicine (MEDLINE)/PubMed and Web of Science for relevant studies published up to December 2024, including prospective, retrospective, cohort, and cross-sectional studies, as well as reviews and meta-analyses. The keywords used in the search included “preterm infant”, “persistent ductus arteriosus”, “patent ductus arteriosus”, “PDA”, “neonatal biomarkers”, “cardiac biomarkers”, and “vasoactive biomarkers”. Results: Out of the 813 identified articles, 85 were included in our review of cardiac biomarkers: Natriuretic peptides (NPs), Cardiac troponin T (cTnT), vasoactive biomarkers (Mid-regional pro-adrenomedullin (MR-proADM), Endothelin-1 (ET-1), Copeptin, and Isoprostanes (IPs)), and inflammatory biomarkers (Interleukin-6 (IL-6), IL-8, IL-10, Growth Differentiation Factor 15 (GDF-15), Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), Macrophage Inflammatory Protein-1α (MIP-1α/CCL3)) in relation to PDA. Conclusions: Even if research shows a strong correlation between specific biomarkers and echocardiographic parameters in patients with PDA, clinical judgment must take these evaluations into account, particularly when determining whether to treat a PDA. Future research should focus on investigating new biomarkers associated with the underlying mechanisms of perinatal ductus arteriosus dynamics in preterm infants. Full article

Background/Objectives: Cardiovascular complications are a leading cause of premature mortality in patients with acromegaly. Copeptin (CPP) correlates strongly with plasma osmolality and is regulated by non-osmotic stimuli involved in the pathophysiology of cardiovascular disease. Mid-regional proadrenomedullin (MR-proADM), synthesized mainly in the adrenal medulla, vascular endothelial cells, and the heart, has vasodilatory effects. The study aimed to assess two cardiovascular biomarkers (CPP and MR-proADM) in acromegaly patients in relation to disease activity and compare findings with a control group. Methods: The study examined CPP and MR-proADM levels alongside hormonal and biochemical parameters and cardiovascular and metabolic disease prevalence in 53 acromegaly patients and 26 controls. Results: No significant differences in CPP or MR-proADM concentrations were observed between the two groups. However, a positive correlation occurred between growth hormone (GH) and CPP concentrations, and there was a negative correlation between fasting glucose and CPP concentrations in acromegaly patients. The study also found a positive correlation between low-density lipoprotein (LDL) cholesterol and MR-proADM concentrations and between high-density lipoprotein (HDL) cholesterol and MR-proADM levels in the study group. Moreover, atherogenic dyslipidemia was significantly more common in the active form of acromegaly and pituitary macroadenoma patients than in the control group. Acromegaly patients had significantly higher fasting glucose and fasting insulin levels compared to controls, and the homeostasis model assessment of the insulin resistance (HOMA-IR) index was significantly lower in the study group than in the controls. Conclusions: Neither CPP or MR-proADM are significant diagnostic or monitoring indicators of cardiovascular or metabolic complications in acromegaly. Full article

Background: In the era of personalized medicine, tools for risk stratification after cardiovascular interventions are crucial to reduce mortality and morbidity, especially in the aging population. Biomarker-based approaches, in particular, have gained significant importance. Mid-regional pro-adrenomedullin (MR-proADM) represents an easily assessable biomarker that mirrors cardiac function and fibrosis. Therefore, we aimed to investigate the prognostic potential of MR-proADM in patients undergoing elective cardiac surgery. Methods: Patients undergoing elective cardiac bypass and/or valve surgery were prospectively enrolled between May 2013 and August 2018. The primary endpoint was the composite of hospitalization for heart failure (HHF) or cardiovascular (CV) mortality. Results: In total, 500 patients (146 female [29.2%]; median age 69.8 years (IQR 60.6–75.5 years) were included. Individuals were stratified into risk categories based on their MR-proADM values (Low Risk ≤ 0.63 nmol/L, Intermediate Risk > 0.63 and ≤0.84, High Risk > 0.84). A significant increase in 5-year event rates for HHF/CV mortality in patients in the high-risk category (Low Risk 8.6% vs. High Risk 37.7%, p < 0.001) was observed. MR-pro ADM showed an independent association with HHF/ CV mortality (adjusted HR of 3.43, 95% CI 1.83–6.42; p < 0.001 comparing the High-Risk group to the Low-Risk group). Conclusions: MR-pro ADM was found to be a strong and independent predictor for HHF/CV mortality in patients undergoing elective cardiac surgery. Considering a personalized diagnostic and prognostic work-up, a standardized preoperative evaluation of MR-proADM levels might help to identify patients at risk for major adverse events and early re-hospitalization. Full article

Background: Complications in community-acquired pneumonia (CAP), including cardiovascular events (CVE), can occur during an acute episode and in the long term. We aimed to analyse the role of endothelial damage biomarkers (C-terminal endothelin-1 precursor fragment [CT-proET-1] and mid-regional pro-adrenomedullin [MR-proADM]), in contrast to classic inflammation markers (C Reactive Protein [CRP] and procalcitonin [PCT]) in patients admitted for CAP and their relationship with ICU admission, CVE and mortality in the short and long term; Methods: Biomarkers were analysed in 515 patients with CAP at day 1, 285 at day 5 and 280 at day 30. Traditional inflammatory biomarkers and endothelial damage biomarkers were measured. ICU admission, CVE and mortality (in-hospital and 1-year follow-up) were assessed using receiver operating characteristic (ROC) curve analysis and univariate logistic regression. Results: A statistically significant association was observed between initial, raised CT-proET-1 and MR-proADM levels, the need for ICU admission and the development of in-hospital CVE or in-hospital mortality. Both endothelial markers maintained a strong association at day 30 with 1-year follow-up CVE. At day 1, CRP and PCT were only associated with ICU admission. On day 30, there was no association between inflammatory markers and long-term CVE or death. The odds ratio (OR) and area under the curve (AUC) of endothelial biomarkers were superior to those of classic biomarkers for all outcomes considered. Conclusions: Endothelial biomarkers are better indicators than classic ones in predicting worse outcomes in both the short and long term, especially CVE. MR-proADM is the best biomarker for predicting complications in CAP. Full article

Adrenomedullin has emerged as a promising biomarker in the field of viral diseases. Numerous studies have demonstrated its potential in assessing disease severity, predicting clinical outcomes, and monitoring treatment response. Adrenomedullin (AM) is a multifaceted peptide implicated in vasodilation, hormone secretion, antimicrobial defense, cellular growth, angiogenesis, and, importantly, chronic pain. AM and related peptides interface with cytoskeletal proteins within neuronal contexts, influencing microtubule dynamics. AM has primarily been utilized in diagnosing diseases of bacterial origin, including sepsis. Nevertheless, there are reports suggesting its utility in diseases of viral origin, and this is the focus of the present study. Furthermore, adrenomedullin has been shown to be elevated in various viral infections, suggesting its role in immune response modulation. Furthermore, AM may contribute to neuronal dysfunction through mechanisms involving immune and inflammatory responses, apoptosis, and disruptions in calcium homeostasis. This review aims to consolidate current knowledge regarding AM and its potential implications in viral diseases, elucidating its diverse roles in neurological pathophysiology. This review highlights the growing importance of adrenomedullin as a biomarker in viral diseases and the need for further functional studies to understand the underlying mechanisms involved. Full article

Adrenomedullin (ADM) is a peptide hormone produced primarily in the adrenal glands, playing a crucial role in various physiological processes. As well as improving vascular integrity and decreasing vascular permeability, ADM acts as a vasodilator, positive inotrope, diuretic, natriuretic and bronchodilator, antagonizing angiotensin II by inhibiting aldosterone secretion. ADM also has antihypertrophic, anti-apoptotic, antifibrotic, antioxidant, angiogenic and immunoregulatory effects and antimicrobial properties. ADM expression is upregulated by hypoxia, inflammation-inducing cytokines, viral or bacterial substances, strength of shear stress, and leakage of blood vessels. These pathological conditions are established during systemic inflammation that can result from infections, surgery, trauma/accidents or burns. The ability to rapidly identify infections and the prognostic, predictive power makes it a valuable tool in severe viral and bacterial infections burdened by high incidence and mortality. This review sheds light on the pathophysiological processes that in severe viral or bacterial infections cause endothelitis up to the development of organ damage, the resulting increase in ADM levels dosed through its more stable peptide mid-regional proadrenomedullin (MR-proADM), the most significant studies that attest to its diagnostic and prognostic accuracy in highlighting the severity of viral or bacterial infections and appropriate therapeutic insights. Full article

Sepsis causes immune dysregulation and endotheliitis, with an increase in mid-regional pro-adrenomedullin (MR-proADM). The aim of the study is to determine an MR-proADM value that, in addition to clinical diagnosis, can identify patients with localized infection or those with sepsis/septic shock, with specific organ damage or with the need for intensive care unit (ICU) transfer and prognosis. The secondary aim is to correlate the MR-proADM value with the length of stay (LOS). In total, 301 subjects with sepsis (124/301 with septic shock) and 126 with localized infection were retrospectively included. In sepsis, MR-proADM ≥ 3.39 ng/mL identified acute kidney injury (AKI); ≥2.99 ng/mL acute respiratory distress syndrome (ARDS); ≥2.28 ng/mL acute heart failure (AHF); ≥2.55 ng/mL Glascow Coma Scale (GCS) < 15; ≥3.38 multi-organ involvement; ≥3.33 need for ICU transfer; ≥2.0 Sequential Organ Failure Assessment (SOFA) score ≥ 2; and ≥3.15 ng/mL non-survivors. The multivariate analysis showed that MR-proADM ≥ 2 ng/mL correlates with AKI, anemia and SOFA score ≥ 2, and MR-proADM ≥ 3 ng/mL correlates with AKI, GCS < 15 and SOFA score ≥ 2. A correlation between mortality and AKI, GCS < 15, ICU transfer and cathecolamine administration was found. In localized infection, MR-proADM at admission ≥ 1.44 ng/mL identified patients with AKI; ≥1.0 ng/mL with AHF; and ≥1.44 ng/mL with anemia and SOFA score ≥ 2. In the multivariate analysis, MR-proADM ≥ 1.44 ng/mL correlated with AKI, anemia, SOFA score ≥ 2 and AHF. MR-proADM is a marker of oxidative stress due to an infection, reflecting severity proportionally to organ damage. Full article

The rising prevalence of cardiovascular disease (CVD) and the impact of the SARS-CoV-2 pandemic have both led to increased mortality rates, affecting public health and the global economy. Therefore, it is essential to find accessible, non-invasive prognostic markers capable of identifying patients at high risk. One encouraging avenue of exploration is the potential of mid-regional proadrenomedullin (MR-proADM) as a biomarker in various health conditions, especially in the context of CVD and COVID-19. MR-proADM presents the ability to predict mortality, heart failure, and adverse outcomes in CVD, offering promise for improved risk assessment and treatment strategies. On the other hand, an elevated MR-proADM level is associated with disease severity and cytokine storms in patients with COVID-19, making it a predictive indicator for intensive care unit admissions and mortality rates. Moreover, MR-proADM may have relevance in long COVID, aiding in the risk assessment, triage, and monitoring of individuals at increased risk of developing prolonged cardiac issues. Our review explores the potential of MR-proADM as a predictor of enduring cardiovascular complications following COVID-19 infection. Full article

Background: It has been reported that mid-regional proadrenomedullin (MR-proADM) could be considered a useful tool to stratify the mortality risk in COVID-19 patients upon admission to the emergency department (ED). During the COVID-19 outbreak, computed tomography (CT) scans were widely used for their excellent sensitivity in diagnosing pneumonia associated with SARS-CoV-2 infection. However, the possible role of CT score in the risk stratification of COVID-19 patients upon admission to the ED is still unclear. Aim: The main objective of this study was to assess if the association of the CT findings alone or together with MR-proADM results could ameliorate the prediction of in-hospital mortality of COVID-19 patients at the triage. Moreover, the hypothesis that CT score and MR-proADM levels together could play a key role in predicting the correct clinical setting for these patients was also evaluated. Methods: Epidemiological, demographic, clinical, laboratory, and outcome data were assessed and analyzed from 265 consecutive patients admitted to the triage of the ED with a SARS-CoV-2 infection. Results and conclusions: The accuracy results by AUROC analysis and statistical analysis demonstrated that CT score is particularly effective, when utilized together with the MR-proADM level, in the risk stratification of COVID-19 patients admitted to the ED, thus helping the decision-making process of emergency physicians and optimizing the hospital resources. Full article

The development of multiple organ failure and septic complications increases the cumulative risk of mortality in children with severe injury. Clinically available biochemical markers have shown promise in assessing the severity and predicting the development of complications and outcomes in such cases. This study aimed to determine informative criteria for assessing the severity and outcome prediction of severe injury in children based on levels of mid-regional proadrenomedullin (MR-proADM) procalcitonin (PCT), neuron-specific enolase (NSE), and protein S100. Biomarker levels were measured in 52 children with severe injury (ISS ≥ 16) on the 1st, 3rd, 7th, and 14th days after admission to the ICU. The children were divided into groups based on their favorable (n = 44) or unfavorable (n = 8) outcomes according to the Severe Injury Outcome Scale, as well as their favorable (n = 35) or unfavorable (n = 15) outcomes according to the Glasgow Coma Outcome Scale (GOS). The study also evaluated the significance of biomarker levels in predicting septic complications (with SC (n = 16) and without SC (n = 36)) and diagnosing and stratifying multiple organ failure (with MOF (n = 8) and without MOF (n = 44)). A comprehensive assessment of MR-proADM and PCT provided the highest diagnostic and prognostic efficacy for early diagnosis, risk stratification of multiple organ failure, and outcome prediction in severe injury cases involving children. Additionally, the inclusion of the S100 protein in the study allowed for further assessment of brain damage in cases of traumatic brain injury (TBI), contributing to the overall prognostic model. Full article

Background: Identifying a panel of markers detecting kidney injury before the glomerular filtration rate reduction is a challenge to improving the diagnosis and management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase-2, insulin growth factor binding protein-7 (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in patients with AKI. Patients and Methods: This study was prospectively conducted in an intensive care unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 h of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7–36.5) hours after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 h in AKI patients (1.1 ± 0.4 mg/L vs. 0.08 ± 0.02 mg/L; p < 0.001). Its concentration > 2 mg/L increases AKI risk within the following 24 h, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/L (0.7–7.8 nmol/L), with the highest values observed in septic shock patients (5.6 nmol/L (3.2–18 nmol/L)) and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values > 5.1 nmol/L and urine TIMP2*IGBP7 levels > 2 mg/L showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. Conclusions: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement. Full article

Early diagnosis and appropriate treatments are crucial to reducing mortality risk in septic patients. Low SOFA scores and current biomarkers may not adequately discern patients that could develop severe organ dysfunction or have an elevated mortality risk. The aim of this prospective observational study was to evaluate the predictive value of the biomarkers mid-regional pro-adrenomedullin (MR-proADM), procalcitonin (PCT), C-reactive protein (CRP), and lactate for 28-day mortality in patients with sepsis, and patients with a SOFA score ≤6. 284 were included, with a 28-day all-cause mortality of 8.45% (n = 24). Non-survivors were older (p = 0.003), required mechanical ventilation (p = 0.04), were ventilated for longer (p = 0.02), and had higher APACHE II (p = 0.015) and SOFA (p = 0.027) scores. Lactate showed the highest predictive ability for all-cause 28-day mortality, with an area under the receiver-operating characteristic curve (AUROC) of 0.67 (0.55–0.79). The AUROC for all-cause 28-day mortality in patients with community-acquired infection was 0.69 (0.57–0.84) for SOFA and 0.70 (0.58–0.82) for MR-proADM. A 2.1 nmol/L cut-off point for this biomarker in this subgroup of patients discerned, with 100% sensibility, survivors from non-survivors at 28 days. In patients with community-acquired sepsis and initial SOFA score ≤ 6, MR-proADM could help identify patients at risk of 28-day mortality. Full article

Background: Acute heart failure (AHF) is a major cause of hospitalization and mortality worldwide. Early and accurate diagnosis, as well as effective risk stratification, are essential for optimizing clinical management and improving patient outcomes. In this context, biomarkers have gained increasing interest in recent years as they can provide important diagnostic and prognostic information in patients with AHF. Aim and Methods: The primary objective of the present study was to compare the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), and C-reactive protein (CRP) between patients diagnosed with acute heart failure (AHF) and those without AHF and sepsis. Furthermore, the study aimed to assess the diagnostic and prognostic value of the use of a multimarker approach in AHF patients. To achieve these objectives, a total of 145 patients with AHF and 127 patients without AHF and sepsis, serving as the control group, were consecutively enrolled in the study. Results: Levels of MR-proADM (median: 2.07; (25th–75th percentiles: 1.40–3.02) vs. 1.11 (0.83–1.71) nmol/L, p < 0.0001), and NT-proBNP (5319 (1691–11,874) vs. 271 (89–931.5) pg/mL, p < 0.0001) were significantly higher in patients with AHF compared to controls, whereas CRP levels did not show significant differences. The mortality rate in the AHF group during in-hospital stay was 12%, and the rate of new re-admission for AHF within 30 days after discharge was 10%. During in-hospital follow-up, Cox regression analyses showed that levels of NT-proBNP > 10,132 pg/mL (hazard ratio (HR) 2.97; 95% confidence interval (CI): 1.13–7.82; p = 0.0284) and levels of MR-proADM > 2.8 nmol/L (HR: 8.57; CI: 2.42–30.28; p = 0.0009) predicted mortality. The combined use of MR-proADM and NT-proBNP provided significant additive predictive value for mortality and new re-admission for AHF at 30 days after discharge. A logistic regression analysis showed that the presence of NT-proBNP pg/mL > 12,973 pg mL and/or MR-proADM > 4.2 nmol/L predicted hospital re-admission within 30 days (OR: 3.23; CI: 1.05–9.91; p = 0.041). Conclusion: The combined assay of MR-proADM and NT-proBNP could be helpful in accurately identifying AHF and in defining prognosis and re-admission for AHF. The complementary use of these biomarkers can provide a useful clinical evaluation of AHF while also orienting clinicians to the pathophysiology underlying heart damage and assisting them in tailoring therapy. Full article