Puccia, Giuseppe

Introduction:Deep Vein Thrombosis (DVT) of both lower and upper limbs is increasingly being recognized as a clinical entity in patients with chronic diseases hospitalized for several comorbidities. The occurrence of DVT in sites other than lower limbs is an emerging clinical presentation in a setting of a Department of Medicine. The relationship between score models, based on risk factors, symptoms and clinical signs of lower limbs DVT, and circulating biomarkers is not well studied. Hypothesis:We hypothesized to give an additional value to score models using circulating biomarkers in the prediction of DVT in patients hospitalized in Internal Medicine Department. Methods:We prospectively recruited 178 consecutive patients who presented a D-dimer value >500 ng/ml. In each patient Wells modified score for DVT, Hamilton score, Kahn score and St. André Hospital score were applied. We measured serum levels of albumin (%) and protein S (%). Diagnosis of DVT was made by Extended Compression Ultra-Sonography (ECUS) standardized procedure. All patients underwent also an angiographic-CT-scan Results:In 85 (48%) patients the diagnosis of DVT was confirmed. Sites of DVT were as follows: Lower limbs venous thrombosis n=71 (84%); Upper limb venous thrombosis n=8 (9%); portal vein thrombosis n=6 (7%). Patients with DVT had significantly lower albumin levels as compared with controls (mean ± SD 47.6 ± 7.9 vs 55.4 ± 4.6 %, respectively, P<0.001) and lower Protein S (60.7 ± 26.3 vs. 87.6 ± 11.9 %, P<0.001). In this setting, the use of clinical risk scores based on symptoms and clinical signs showed low accuracy (AUC 0.690). We gave an additional value to these scores by testing in combination biomarkers and two of the best items of all clinical score models used to predict DVT: we evaluated a ROC curve analysis including value of Albumin (%), Protein S (%), previous DVT and cancer obtaining a higher accuracy (AUC 0.901, Positive Likelihood Ratio (LR+) 12.97 and Negative Likelihood Ratio (LR-) 0.17). Conclusions:This study demonstrates that biomarkers improve the prediction of clinical scores in the diagnosis of DVT of all sites in hospitalized patients.

Introduction: Blood pressure (BP) control remains low despite combination therapy in resistant hypertension (RH). Thus, there is an unmet need for novel strategies targeting RH. Recently we have reported that M-ANP, a novel Mayo engineered ANP-based peptide, possesses greater and more sustained biological actions compared to ANP and is more resistant to neprilysin degradation. The current study was designed to investigate for the first time the efficacy of a single daily subcutaneous (SQ) injection of M-ANP using a chronic canine model of hypertension induced by angiotensin II (Ang-II). Hypothesis: We hypothesize that a daily SQ M-ANP injection would have potent BP lowering and renal enhancing properties in our chronic hypertensive canine model. Methods: We induced hypertension in canines (n=5) by continuous Ang II (80 ng/kg/min) osmotic mini-pump administration for 24 days. Continuous 24 hour mean BP (MBP) was measured by telemetry and a 24 hour urine collection was used to assess urinary volume, sodium (Na) and cGMP, the second messenger for the ANP system. M-ANP was administered SQ for 5 days (10μg/kg/day). Data are mean±SE. ΨP<0.05 Ang II Day 16 vs. baseline; *P<0.05 Ang II Day 16 vs. M-ANP (Table 1). Results: Chronic Ang II administration resulted in model of severe hypertension, with an increase in MBP from 112±2 to 157±2 mmHg (day 16). As seen in Table 1, M-ANP significantly reduced MBP, significantly increased plasma cGMP as well as urinary cGMP excretion, urinary volume rate (UV) and urinary Na excretion (UNa), without significant changes in heart rate (HR). Furthermore, there was a trend for plasma ANP to increase and plasma aldosterone to decrease with SQ M-ANP injection. Conclusions: This study demonstrates for the first time that chronic SQ administration of M-ANP reduces BP, activates plasma cGMP, and increases UV and UNa, without significant changes in HR in an experimental model of chronic hypertension.