No abstract

Aim: Transcriptomic biomarkers originating from reticulocytes measured in dried blood spots (DBSs) may be reliable indicators of blood doping. Methods/results: Here, we examined changes in the expression levels of the erythropoiesis-related ALAS2, CA1 and SLC4A1 genes in DBS samples from elite athletes and volunteers of clinical study with recombinant erythropoietin dose. Conclusion: By comparing the mean intraday coefficients of variation for ALAS2L, ALASLC, CA1 and SLC4A1 between manual and automated RNA extractions, an average improvement was observed, whereas the assessment of interday variability provided comparable results for both manual and automated approaches. Our results confirmed that RNA biomarkers on DBS support are efficient to detect blood doping.

The aim of this study was to evaluate the effects of Sacubitril/Valsartan (S/V) on clinical, laboratory and echocardiographic parameters and outcomes in a real-world population with heart failure with reduced ejection fraction (HFrEF). This was a prospective observational study enrolling patients with HFrEF undergoing treatment with S/V. The primary outcome was the composite of cardiac death and HF rehospitalization at 12 months follow-up; secondary outcomes were all-cause death, cardiac death and the occurrence of rehospitalization for worsening HF. The clinical outcome was compared with a retrospective cohort of 90 HFrEF patients treated with standard medical therapy. The study included 90 patients (66.1 ± 11.7 years) treated with S/V. The adjusted regression analysis showed a significantly lower risk for the primary outcome (HR:0.31; 95%CI, 0.11-0.83; p = 0.019) and for HF rehospitalization (HR:0.27; 95%CI, 0.08-0.94; p = 0.039) in S/V patients as compared to the control group. A significant improvement in NYHA class, left ventricular ejection fraction, left ventricular end systolic volume and systolic pulmonary arterial pressure was observed up to 6 months. S/V did not affect negatively renal function and was associated with a significantly lower dose of furosemide dose prescribed at 6-and 12-month follow-up. In this study, S/V reduced the risk of HF rehospitalization and cardiac death at 1 year in patients with HFrEF. S/V improved NYHA class, echocardiographic parameters and need of furosemide, and preserved renal function.Despite the improvements in clinical management and medical therapy of heart failure (HF), the outcome of patients with HF and reduced ejection fraction (HFrEF) remains poor 1 . If compared to the other HF entities, this category shows distinct demographic characteristics, comorbidities, response to therapy, and a substantially higher risk of mortality secondary to sudden cardiac death (SCD) and rehospitalization for worsening HF 2 . Many HFrEF patients are still undertreated and several drugs, such as beta-blockers and ACE inhibitors (ACEi), are under-dosed. This issue is also related to the incorrect risk evaluation by clinicians, who are likely to consider the absence or paucity of symptoms as an indicator of HF stability 3 . In fact, HFrEF is a progressive disorder that, despite the improvement of patient's clinical status achieved with conventional medications, may be associated with a high risk of adverse events at short and long-term follow-up 4 .Current European guidelines 5 recommend the use Sacubitril/Valsartan (S/V), an angiotensin receptorneprilysin inhibitor (ARNI), in replacement of the renin-angiotensin-aldosterone system (RAAS) inhibition in ambulatory HFrEF patients still symptomatic despite optimal medical therapy (OMT). This recommendation comes from a single randomized study named PARADIGM-HF trial 6 , which showed the superiority of S/V compared to Enalapril in reducing the incidence of cardiovascular death or hospitalizations for HF. Few studies have so far investigat...

The aim of this study was to evaluate and correlate the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS) and tumour cellular differentiation on histopathology. Patients underwent hepatic CEUS, performed with SonoVue and contrast pulse sequencing. The correlation between enhancement time and enhancement level of the lesions in different vascular phases and tumour cellular differentiation was determined. The tumours were graded according to the Edmondson grading system. Then, diagnosis was obtained by histopathological examination following surgery or percutaneous ultrasound-guided biopsy. 189 patients with HCC were examined with CEUS and histopathological examination between 2003 and 2009: 159 had a solitary lesion (85 %), 24 had 2 lesions (12 %) and 6 had multiple lesions (3 %). The final histological grading of the tumours was as follows: 22, 114, 49, 4 grade I-IV, respectively. Significant differences were shown between the time that HCC become hypoenhancing or remained echogenic in late phase and tumour cellular differentiation (p = 0.006, p = 0.036). The timing of HCC becoming hypoenhancing was correlated with tumour cellular differentiation, with better differentiated HCCs washing out more slowly than poorly differentiated ones (p = 0.164, p = 0.113; p = 0.186, p = 0.070). The enhancement pattern of HCC by CEUS correlates with the cellular differentiation. In late phases, hyperechoic lesions are likely to be better differentiated, whereas hypoechoic lesion is more likely to be poorly differentiated.