Mid-Regional Pro-Adrenomedullin Can Predict Organ Failure and Prognosis in Sepsis?

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.

Mid-Regional Pro-Adrenomedullin and N-Terminal Pro-B-Type Natriuretic Peptide Measurement: A Multimarker Approach to Diagnosis and Prognosis in Acute Heart Failure.

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.

Pleomorphicskin eruptions in a COVID-19 affected patient: Case report and review of the literature.

The coronavirus disease (COVID-19), during its course, may involve several organs, including the skin with a petechial skin rash, urticaria and erythematous rash, or varicella-like eruption, representing an additional effect of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as commonly observed in other viral diseases. Considering that symptomatic patients with COVID-19 generally undergo multidrug treatments, the occurrence of a possible adverse drug reaction presenting with cutaneous manifestations should be contemplated. Pleomorphic skin eruptions occurred in a 59-year-old Caucasian woman, affected by a stable form of chronic lymphocytic leukemia, and symptomatic SARS-CoV-2 infection, treated with a combination of hydroxychloroquine sulfate, darunavir, ritonavir, sarilumb, omeprazole, ceftriaxone, high-flow oxygen therapy devices, filgrastim (Zarzio®) as a single injection, and enoxaparin. The patient stopped all treatment but oxygen and enoxaparin were continued and the patient received a high-dose Desametasone with complete remission of dermatological impairment in 10 days. It is very important to differentially diagnose COVID-19 disease-related cutaneous manifestations, where is justified to continue the multidrug antiviral treatment, from those caused by an adverse drug reaction, where it would be necessary to identify the possible culprit drug and to start appropriate antiallergic treatment.

Anabolic Hormones Deficiencies in Heart Failure With Preserved Ejection Fraction: Prevalence and Impact on Antioxidants Levels and Myocardial Dysfunction.

Purpose: In heart failure with reduced ejection fraction, catabolic mechanisms have a strong negative impact on mortality and morbidity. The relationship between anabolic hormonal deficiency and heart failure with preserved ejection fraction (HFpEF) has still been poorly investigated. On the other hand, oxidative stress is recognized as a player in the pathogenesis of HFpEF. Therefore, we performed a cohort study in HFpEF aimed to (1) define the multi-hormonal deficiency prevalence in HFpEF patients; (2) investigate the relationships between hormonal deficiencies and echocardiographic indexes; (3) explore the modulatory activity of anabolic hormones on antioxidant systems. Methods: 84 patients with diagnosis of HFpEF were enrolled in the study. Plasma levels of N-terminal pro-brain natriuretic peptide, fasting glucose, insulin, lipid pattern, insulin-like growth factor-1, dehydroepiandrosterone-sulfate (DHEA-S), total testosterone (T, only in male subjects) were evaluated. Hormonal deficiencies were defined according to T.O.S.C.A. multi-centric study, as previously published. An echocardiographic evaluation was performed. Plasma total antioxidant capacity (TAC) was measured using the system metmyoglobin -H2O2 and the chromogen ABTS, whose radical form is spectroscopically revealed; latency time (LAG) in the appearance of ABTS• is proportional to antioxidants in sample. Results: Multiple deficiencies were discovered. DHEA-S deficiency in 87% of patients, IGF-1 in 67% of patients, T in 42%. Patients with DHEA-S deficiency showed lower levels of TAC expressed by LAG (mean ± SEM 91.25 ± 9.34 vs. 75.22 ± 4.38 s; p < 0.05). No differences between TAC in patients with or without IGF-1 deficiency were found. A trend toward high level of TAC in patients without hormonal deficiencies compared with patients with one or multiple deficiencies was found. Regarding echocardiographic parameters, Left Atrial and Left Atrial Volume Index were significantly higher in patients with low IGF-1 values (mean ± SD 90.84 ± 3.86 vs. 72.83 ± 3.78 mL; 51.03 ± 2.33 vs. 40.56 ± 2.46 mL/m2, respectively; p < 0.05). Conclusions: Our study showed high prevalence of anabolic deficiencies in HFpEF. DHEA-S seems to influence antioxidant levels; IGF-1 deficiency was associated with alteration in parameters of myocardial structure and dysfunction. These data suggest a role of anabolic hormones in the complex pathophysiological mechanisms of HFpEF and could represent the basis for longitudinal studies and investigations on possible benefits of replacement therapy.