Biomarkers of cell damage, neutrophil and macrophage activation associated with in-hospital mortality in geriatric COVID-19 patients.

BACKGROUND: The risk for symptomatic COVID-19 requiring hospitalization is higher in the older population. The course of the disease in hospitalised older patients may show significant variation, from mild to severe illness, ultimately leading to death in the most critical cases. The analysis of circulating biomolecules involved in mechanisms of inflammation, cell damage and innate immunity could lead to identify new biomarkers of COVID-19 severity, aimed to improve the clinical management of subjects at higher risk of severe outcomes. In a cohort of COVID-19 geriatric patients (n= 156) who required hospitalization we analysed, on-admission, a series of circulating biomarkers related to neutrophil activation (neutrophil elastase, LL-37), macrophage activation (sCD163) and cell damage (nuclear cfDNA, mithocondrial cfDNA and nuclear cfDNA integrity). The above reported biomarkers were tested for their association with in-hospital mortality and with clinical, inflammatory and routine hematological parameters. Aim of the study was to unravel prognostic parameters for risk stratification of COVID-19 patients. RESULTS: Lower n-cfDNA integrity, higher neutrophil elastase and higher sCD163 levels were significantly associated with an increased risk of in-hospital decease. Median (IQR) values observed in discharged vs. deceased patients were: 0.50 (0.30-0.72) vs. 0.33 (0.22-0.62) for n-cfDNA integrity; 94.0 (47.7-154.0) ng/ml vs. 115.7 (84.2-212.7) ng/ml for neutrophil elastase; 614.0 (370.0-821.0) ng/ml vs. 787.0 (560.0-1304.0) ng/ml for sCD163. The analysis of survival curves in patients stratified for tertiles of each biomarker showed that patients with n-cfDNA integrity < 0.32 or sCD163 in the range 492-811 ng/ml had higher risk of in-hospital decease than, respectively, patients with higher n-cfDNA integrity or lower sCD163. These associations were further confirmed in multivariate models adjusted for age, sex and outcome-related clinical variables. In these models also high levels of neutrophil elastase (>150 ng/ml) appeared to be independent predictor of in-hospital death. An additional analysis of neutrophil elastase in patients stratified for n-cfDNA integrity levels was conducted to better describe the association of the studied parameters with the outcome. CONCLUSIONS: On the whole, biomarkers of cell-free DNA integrity, neutrophil and macrophage activation might provide a valuable contribution to identify geriatric patients with high risk of COVID-19 in-hospital mortality.

Diagnosis and treatment of hypertensive emergencies and urgencies among Italian emergency and intensive care departments. Results from an Italian survey: Progetto GEAR (Gestione dell'Emergenza e urgenza in ARea critica).

Hypertensive emergencies (HE) and urgencies (HU) are frequent causes of patients referral to Emergency Department (ED) and the approach may be different according to local clinical practice. Our aim was to explore awareness, management, treatment and counselling after discharge of HE and HU in Italy, by mean of an on-line survey. The young investigator research group of the Italian Society of Hypertension developed a 23-item questionnaire spread by e-mail invitation to the members of Italian Scientific societies in the field of Hypertension. 665 questionnaires were collected from EDs, Emergency and Urgency Medicine, Cardiology or Coronary Units, Internal Medicines, Intensive care, Stroke units. Symptoms considered suspicious of acute organ damage were: chest pain (89.0%), visual disturbances (89.8%), dyspnoea (82.7%), headache (82.1%), dizziness (52.0%), conjunctival haemorrhages (41.5%), tinnitus (38.2%) and epistaxis (34.4%). Exams more frequent prescribed were: electrocardiogram (97.2%), serum creatinine (91.4%), markers of cardiomyocyte necrosis (66.2%), echocardiography (65.1%). The use of intravenous or oral medications to treat HEs was 94.7% and 3.5%, while for HUs 24.4% and 70.8% respectively. Of note, a surprisingly high percentage of physicians (22 % overall, 24.5% in North Italy) used to prescribe sublingual nifedipine. After discharge, home blood pressure monitoring and general practitioner re-evaluation were more frequently suggested, while ambulatory blood pressure monitoring and hypertension specialist examination were less prescribed. The differences observed across the different macro-areas, regarded prescription of diagnostic test and drug administration. This survey depicts a complex situation of shades and lights in the real-life management of HE and HU in Italy.

N-terminal pro B-Type natriuretic peptide is inversely correlated with low density lipoprotein cholesterol in the very elderly.

BACKGROUND AND AIMS: Laboratory studies on human adipose tissue and differentiated adipocytes indicate that natriuretic peptides (NPs) affect lipid metabolism and plasma cholesterol. Few previous clinical studies in non-elderly populations found associations between NPs in the physiological range and cholesterol. AIM: evaluate the association between NT-proBNP and lipid profile in very elderly hospitalized patients characterized by a wide range of NT-proBNP levels. METHODS AND RESULTS: Cross-sectional study on 288 very elderly patients hospitalized for medical conditions, in which increased NT-proBNP levels are very common. NT-proBNP, total cholesterol (TC), HDL cholesterol (HDLc) and triglycerides were collected just few days before discharge. Patients taking lipid-lowering drugs and patients with an admission diagnosis of acute heart failure were excluded. Calculated LDL-cholesterol (LDLc) was used for the analyses. Mean age: 87.7 ± 6.2 years; female prevalence (57.3%). Median NT-proBNP: 2949 (1005-7335) pg/ml; mean TC: 145.1 ± 40.3 mg/dl; mean HDLc: 38.4 ± 18.6 mg/dl; median triglycerides: 100 (75-129) mg/dl; mean LDLc: 84.0 ± 29.5 mg/dl. We found negative correlations between NT-proBNP and both TC and LDLc (Rho = -0.157; p = 0.008 and Rho = -0.166; p = 0.005, respectively), while no correlations emerged between NT-proBNP and HDLc (Rho = -0.065; p = 0.275) or triglycerides (Rho = -0.009; p = 0.874). These associations were confirmed considering NT-proBNP tertiles. The inverse association between NT-proBNP and LDLc was maintained even after adjusting for confounding factors. CONCLUSION: Our real-life clinical study supports the hypothesis that NPs play a role on cholesterol metabolism, given the association found between LDLc and NT-proBNP even in very elderly patients where NT-proBNP values are often in the pathological range.