HEPARIN-BINDING PROTEIN LEVELS PREDICT UNFAVORABLE OUTCOME IN COVID-19 PNEUMONIA: A POST HOC ANALYSIS OF THE SAVE TRIAL.

ABSTRACT: We aimed to evaluate heparin-binding protein (HBP) as a marker of prognosis of unfavorable outcome in COVID-19 pneumonia. This was a post hoc analysis of the SAVE clinical trial investigating anakinra treatment, guided by suPAR (soluble urokinase plasminogen activator receptor) levels ≥6 ng/mL, for the prevention of severe respiratory failure in hospitalized patients with COVID-19 pneumonia. Baseline HBP plasma levels were measured in 534 patients by fluorescence dry quantitative immunoassay using the Jet-iStar 800 analyzer. Concentrations higher than 35 ng/mL predicted 30-day mortality with a moderate specificity of 53.3% and negative predictive value 78.1%; sensitivity was low (29.0%). After multivariate Cox analysis, HBP higher than 35 ng/mL was an independent predictor of 30-day unfavorable outcome (adjusted hazard ratio, 1.77; 95% CI, 1.06-2.94; P = 0.028) and these patients were also at greater risk of death after 90 days (hazard ratio, 1.85; 95% CI, 1.25-2.74; P = 0.002). The cutoff was not predictive of development of severe respiratory failure, septic shock or acute kidney injury. Among patients with baseline HBP levels higher than 35 ng/mL, anakinra treatment was associated with decreased mortality (7.2%) versus comparators (18.1%; P < 0.001). Results confirm that HBP may be an early biomarker of poor outcome among preselected patients at risk from COVID-19 pneumonia.ClinicalTrials.gov registration NCT04357366.

Early Occurrence of Adverse Events in Hospitalized Patients With COVID-19 and Beneficial Effect of Anticoagulation.

BACKGROUND/AIM: This study analyzed the characteristics of patients with COVID-19 with major events during the first days of hospitalization. PATIENTS AND METHODS: This is a retrospective analysis of prospectively collected data from consecutive patients admitted to two hospitals in Athens, Greece. The characteristics of patients with COVID-19 who suffered the primary endpoint (venous thromboembolic events, intubation, and death) during the first days of hospitalization were analyzed. RESULTS: Among 95 patients included in the analysis, 21 presented with major adverse events during a median follow-up of 13 days. More than 50% of these patients presented with a major event during the first 3 days. Anticoagulation treatment was inversely associated with the cumulative incidence of the primary endpoint [hazard ratio=0.16 (95% confidence interval=0.06-0.47)]. Patients with major events were older, with lower baseline SatO2, and higher number of Wells' criteria and Charlson comorbidity index. Among these patients, those with hypertension were at higher risk for early occurrence of events (≤ first three days of hospitalization). CONCLUSION: Major adverse events may occur early in hospitalized patients with COVID-19 with a high-risk profile. Anticoagulation treatment appears to reduce this risk and thus prompt thromboprophylaxis should be employed in these patients.

Integration of heparin-binding protein and interleukin-6 in the early prediction of respiratory failure and mortality in pneumonia by SARS-CoV-2 (COVID-19).

Recent publications on the probable role of heparin-binding protein (HBP) as a biomarker in sepsis prompted us to investigate its diagnostic and prognostic performance in severe COVID-19. HBP and IL-6 were measured by immunoassays at admission and on day 7 in 178 patients with pneumonia by SARS-CoV-2. Patients were classified into non-sepsis and sepsis as per the Sepsis-3 definitions and were followed up for the development of severe respiratory failure (SRF) and for outcome. Results were confirmed by multivariate analyses. HBP was significantly higher in patients classified as having sepsis and was negatively associated with the oxygenation ratio and positively associated with creatinine and lactate. Logistic regression analysis evidenced admission HBP more than 18 ng/ml and IL-6 more than 30 pg/ml as independent risk factors for the development of SRP. Their integration prognosticated SRF with respective sensitivity, specificity, positive predictive value, and negative predictive 59.1%, 96.3%, 83.9%, and 87.8%. Cox regression analysis evidenced admission HBP more than 35 ng/ml and IL-6 more than 30 pg/ml as independent risk factors for 28-day mortality. Their integration prognosticated 28-day mortality with respective sensitivity, specificity, positive predictive value, and negative predictive value 69.2%, 92.7%, 42.9%, and 97.5%. HBP remained unchanged over-time course. A prediction score of the disposition of patients with COVID-19 is proposed taking into consideration admission levels of IL-6 and HBP. Using different cut-offs, the score may predict the likelihood for SRF and for 28-day outcome.

Beneficial Effects of Intermediate Dosage of Anticoagulation Treatment on the Prognosis of Hospitalized COVID-19 Patients: The ETHRA Study.

BACKGROUND/AIM: To investigate the efficacy (prognosis, coagulation/inflammation biomarkers) and safety (bleeding events) of different anticoagulation dosages in COVID-19 inpatients. PATIENTS AND METHODS: COVID-19 inpatients (Athens, Greece) were included. The "Enhanced dose THRomboprophylaxis in Admissions (ETHRA)" protocol was applied in certain Departments, suggesting the use of intermediate anticoagulation dosage. The primary endpoint was a composite of intubation/venous thromboembolism/death. Inflammation/coagulation parameters were assessed. RESULTS: Among 127 admissions, 95 fulfilled the inclusion criteria. Twenty-one events (4 deaths, 17 intubations) were observed. Regression analysis demonstrated significant reduction of events with intermediate or therapeutic dosage [HR=0.16 (95%CI=0.05-0.52) p=0.002; HR=0.17 (0.04-0.71) p=0.015, respectively]. D-Dimer values were higher in those who met the composite endpoint. Intermediate dosage treatment was associated with decreased values of ferritin. Three patients (3%) had minor hemorrhagic complications. CONCLUSION: Anticoagulation treatment (particularly intermediate dosage) appears to have positive impact on COVID-19 inpatients' prognosis by inhibiting both coagulation and inflammatory cascades.

Salmonella enteritidis Infection Complicated by Acute Myocarditis: A Case Report and Review of the Literature.

Salmonella spp. is the cause of commonly encountered infections, with seasonal pattern of occurrence and worldwide distribution. Some of the clinical manifestations such as gastroenteritis and bacteremia are common, whereas others like mycotic aneurysms and osteomyelitis are infrequent especially in immunocompetent patients. Salmonella has been rarely described as a cause of myocarditis in the literature. We describe a case of an 18-year-old previously healthy male patient with myocarditis after Salmonella enteritidis infection. Clinical manifestations and diagnostic approach of this severe complication are discussed with a review of the literature.

Home blood pressure is as reliable as ambulatory blood pressure in predicting target-organ damage in hypertension.

BACKGROUND: Our objective was to assess the value of home blood pressure (BP) monitoring in comparison to office BP measurements and ambulatory monitoring in predicting hypertension-induced target-organ damage. METHODS: Sixty-eight untreated patients with hypertension with at least two routine prestudy office visits were included (mean age, 48.6 +/- 9.1 [SD] years; 50 men). Office BP was measured in two study visits, home BP was measured for 6 workdays, and ambulatory BP was monitored for 24 h. All BP measurements were obtained using validated electronic devices. Target-organ damage was assessed by measuring the echocardiographic left-ventricular mass index (LVMI), urinary albumin excretion rate (AER) in two overnight urine collections, and carotid-femoral pulse-wave velocity (PWV) (Complior device; Colson, Garges-les-Gonesse, Paris, France). RESULTS: The correlation coefficients of LVMI with office BP were 0.24/0.15 (systolic/diastolic), with home BP 0.35/0.21 (systolic, P < .01), and with 24-h ambulatory BP 0.23/0.19, awake 0.21/0.16, and asleep 0.28/0.26 (asleep, both P < .05). The correlation coefficients of AER with office BP were 0.24/0.31 (diastolic, P < .05), with home BP 0.28/0.26 (both P < .05), and with 24-h ambulatory BP 0.25/0.24, awake 0.24/0.25 (diastolic, P < .05), and asleep 0.26/0.18 (systolic, P < .05). There was a trend for negative correlations between PWV and diastolic BP measurements (not significant). In multiple-regression models assessing independent predictors of each of the three indices of target-organ damage, systolic home BP and age were the only independent predictors of increased LVMI that reached borderline statistical significance. CONCLUSIONS: These data suggest that home BP is as reliable as ambulatory monitoring in predicting hypertension-induced target-organ damage, and is superior to carefully taken office measurements.

Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients.

PURPOSE: To evaluate the predictive and prognostic value of peripheral blood cytokeratin-19 (CK-19) mRNA-positive cells in axillary lymph node-negative breast cancer patients. PATIENTS AND METHODS: Peripheral blood was obtained from 167 node-negative breast cancer patients before the initiation of any systemic adjuvant therapy, and was analyzed for the presence of CK-19 mRNA-positive cells using a real time polymerase chain reaction assay. The association with known prognostic factors and the effect of CK-19 mRNA-positive cells on patients' prognosis was investigated. RESULTS: CK-19 mRNA-positive cells were detected in the blood of 36 (21.6%) of the 167 patients. There was no correlation between the detection of CK-19 mRNA-positive cells in the peripheral blood and the various known pathologic and clinical prognostic factors; only overexpression of HER2 receptor (score 2+/3+) on the primary tumor was associated with a higher incidence of CK-19 mRNA-positive cell detection (P = .033). Multivariate analysis revealed that detection of peripheral blood CK-19 mRNA-positive cells was associated with early clinical relapse (P < .00001) and disease-related death (P = .008). CONCLUSION: Detection of peripheral-blood CK-19 mRNA-positive cells is an independent predictive and prognostic factor for reduced disease-free interval and overall survival, respectively, in node-negative breast cancer patients.

Determinants of arterial stiffness in Greek and French hypertensive men.

The aim of the present study was to assess the main determinants of arterial stiffness in Greek and French middle-aged, hypertensive men, by using pulse wave velocity (PWV) measurements, which is an established method of quantification of arterial stiffness. The study was performed in 83 consecutive Greek and 79 consecutive French untreated male hypertensive outpatients aged 45-65 years. French subjects were examined in Paris at the "Centre d'Investigations Préventives et Cliniques" (the IPC Center). Greek patients were examined in Athens at the hypertension outpatient clinic in Sotiria Hospital (University of Athens). In both Greek and French hypertensive subjects, aortic stiffness was determined by the same parameters: age, blood pressure and heart rate (HR) explained approximately 40% of the aortic PWV variations, whereas lipids, triglycerides and tobacco smoking were not significant associated with aortic stiffness. After multivariate adjustments, Greek hypertensives had higher aortic stiffness as compared to the French patients by 1.2 m/s (approximately 10%); p < 0.001. Greek hypertensive subjects had also a higher body weight, waist, HR and prevalence of smoking. However, among all these factors only HR had a significant effect on PWV. Also after adjustment for HR, the difference in PWV between the two populations persisted. In conclusion, in two different populations, stiffness seems to be regulated by the same major factors. The higher aortic stiffness found in Greek hypertensives may be explained by the presence of other non-evaluated risk factors and/or patient selection differences.