ACTA ENDOCRINOLOGICA (BUC)

Background. Risk stratification and an appropriate therapeutic approach could be lifesaving in acute pulmonary embolism (PE). Echocardiographic (ECHO) acute right ventricular dysfunction (RVD) is the actual &#8220;gold standard&#8221; in risk evaluation of PE. We previously demonstrated that plasma BNP levels were significantly higher in patients with PE and acute RVD on ECHO vs. patients with normal RV function on ECHO.\r\nAim. Evaluation of the limits of plasma BNP in signalling acute RVD in PE. \r\nMethods. 70 patients with PE were prospectively investigated: 42(60.0%) men, mean ? SD(standard deviation) age 52.51?8.82. BNP was measured on admission using a quantitative fluorescence immunoassay (TriageBNP). ECHO evaluation of the RV function was performed in the first hour after admission. Study protocol was approved by local Ethical Committee. Patients were divided into two groups: group 1-with acute RVD on ECHO, n=24(34.3%) patients; group 2 - without acute RVD on ECHO, n=46(65.7%).Patients from group 1 were further divided into two subgroups: subgroup 1A-admitted in <12 hours after their PE symptoms onset, n=12(50.0%) patients, and subgroup 1B-admitted in >12 hours after the onset of PE symptoms, n=12(50.0%) patients.\r\nResults. BNP proved good in discriminating between patients with and without acute RVD (AUC=0.88, P<0.0001). The cut-off level of plasma BNP=50 pg/mL showed the best sensitivity=0.86 and specificity=0.82 in identifying acute RVD. BNP levels were significantly lower in subgroup 1A (admitted soon) compared to subgroup 1B (admitted later than 12 hours): medians 45.25 pg/mL vs. 344.50 pg/mL, P<0.0001. Eight patients from subgroup 1A, all admitted soon after the onset of their PE symptoms, and all experiencing at least one syncopal episode showed BNP under the cut-off level. In subgroup 1A BNP did not correlate with RV end-diastolic diameter (R=0.23, P=NS), while in subgroup 1B BNP and RV end-diastolic diameter showed a consistent positive correlation (R=0.91, P<0.0001). In subgroup 1A BNP correlated significantly, but negatively, with RV systolic pressure (R=-0.64, P<0.01). In subgroup 1B BNP was significantly positively correlated with RV systolic pressure (R=0.76, P<0.001).\r\nConclusions. BNP higher than a cut-off level of 50 pg/mL could predict acute RVD in patients with PE with a good sensitivity and specificity. Exception of this rule was found in some patients with recent (<12 hours) PE symptoms onset and poor clinical condition.

Context. Aromatase is a key enzyme in local estrogen production by androgen conversion, especially in women post-menopause. There have been controversies concerning aromatase localization in breast carcinomas and its association with current histopathological variables. Material and Methods. Using polyclonal antibody immunohistochemistry we assessed (by intensity and percentage scores) the immunolocalization of aromatase in 70 tissue samples, and described particularities within the molecular subtypes of breast cancer. Results. Aromatase was found in all tissue compartments: tumor (95.7%), stroma (58.6%) and adipose tissue (94.3%). Aromatase expression in tumor cells correlated inversely with tumor grading (p=-0.361, p=0.027), and positively with estrogen receptor status (ER, p=0.143, p<0.001). Dividing the study group by intrinsic subtypes, a strongly inversely association between tumor aromatase and grading (p=-0.486, p<0.001), and between stromal aromatase and Ki67-index (p=-0.448, p=0.048) was observed in luminal A breast cancer. Tumor aromatase and ER percentage scores had stronger correlations in luminal B HER2 negative (p=0.632, p=0.002), and positive (p=0.324, p=0.026) tumors. In contrast, in triple negative tumors, a positive association stromal aromatase and Ki67 index (p=- 0.359, p=0.007) was observed. Conclusion. Local aromatase was linked to better tumor differentiation and proliferation in luminal breast subtypes, and not in triple negative cases, suggesting a potential prognostic role of aromatase in breast carcinomas.

Background. Early prediction of anticancer therapy cardiotoxicity is essential for applying proper preventive and supporting therapeutic strategies. Objective. To evaluate plasma N-terminal fragment of pro-brain natriuretic peptide(NT-proBNP) related to cardiac dysfunction assessed by transthoracic 2 D echocardiography (2D-TTE) in patients with cancer and early onset asymptomatic anthracycline-induced cardiomyopathy(AIC). Methods. Prospective study of 68 patients with cancer treated with anthracyclines, followed up for 6 months. Diagnosis of AIC was set at 6 months by decreasing of left ventricular ejection fraction(LVEF) below 50% or with more than 10 units or 20% from baseline. NT-proBNP and 2D-TTE were assessed at enrollment, and thereafter at 3 and 6 months. Results. Fifteen(22.1%) patients developed AIC at 6 months of anthracycline treatment (group 1), and 53(77.95%) patients did not evolve with AIC (group 2). At 3 months, in patients from group 1 NT pro-BNP was significantly higher compared to group 2 [121.0 (119.8;140.8) pg/mL vs. 97.7(75.5;111.7) pg/mL, P=0.0001, values expressed as median (25th; 75th percentiles)]. Left ventricular(LV) diastolic dysfunction was significantly more frequent in group 1(93.3%) vs. group 2(37.7%), P=0.0002. NT-proBNP at 3 months proved accurate in predicting asymptomatic AIC at 6 months [area under the receiver operating characteristic curve(AUC)=0.845, 95%Confidence Interval(CI): 0.735-0.954, P=0.0001]. Newinstalled diastolic dysfunction at 3 months had a sensitivity of 60 %, a specificity of 77% in predicting AIC at 6 months. NT-proBNP assessed at 3 months above a cut-off=118.5pg/ mL was an independent predictor of AIC at 6 months. Conclusions. Plasma NT-proBNP at 3 months of anthracycline therapy proved to be an early independent predictor of asymptomatic anthracycline-induced cardiomyopathy.

Right ventricular dysfunction (RVD) is critical for risk stratification of patients with pulmonary embolism (PE). Evaluation can be made by echocardiography or biological markers among which plasma levels of brain natriuretic peptide (BNP). The aim of our study is assessment of BNP levels in patients with PE associating or not RVD as diagnosed by classic echocardiographic criteria. We prospectively assessed 40 patients with deep venous thrombosis and confirmed PE (age range 52.5 ? 9.14 years, 22 men and 18 women), with (14) or without (26) RVD on echocardiography. Plasma BNP levels were significantly higher in RVD patients (190 ? 171.2 pg/mL vs. 15.75 ? 18.85 pg/mL, P < 0.0001). A cut-off level of plasma BNP = 50 pg/mL had a sensitivity, specificity, positive and negative predictive value for the diagnosis of RVD of 84% (C.I. 79% - 88%), 80% (C.I. 75% - 85%), 83% (C.I. 77% - 87%) and 79% (C.I. 75% - 84%), respectively. There was a significant correlation between plasma BNP levels and end-diastolic RV diameter (r = 0.56, P < 0.0001), RV systolic pressure (r = 0.50, P < 0.001) and the presence of a Qr complex in V1-lead on ECG (r = 0.55, P < 0.05). Four patients with RVD on echocardiography and syncope, all admitted relatively soon after the onset of their symptoms, had BNP in normal range. In conclusion, PE should be considered in the differential diagnosis of patients with dyspnoea and increased plasma BNP levels. A cut-off level of 50 pg/mL could identify the RVD in patients with PE with a good sensitivity and specificity. Normal range plasma BNP levels do not exclude even a severe PE and should be interpreted with caution, especially in highly symptomatic patients with recent symptom onset.