Massimo Villella

Skeletal involvement in female acromegalic subjects : The effects of growth hormone excess in amenorrheal and menstruating patients

Bone involvement is a common clinical feature in acromegalic patients, though previous studies gave divergent results possibly because of the different gonadal status of the patients studied. To study the influence of estrogen milieu in these patients, we evaluated 23 acromegalic patients with active disease, subdivided into two groups: menstruating and amenorrheal patients, comparable for duration and activity of disease. Forty‐two matched women served as controls. Skeletal involvement was studied by measuring: (a) the main biomarkers of bone turnover: serum alkaline phosphatase total activity (AP), bone GLA protein (BGP), serum carboxy‐terminal propeptide of type I collagen (PICP), serum type I cross‐linked N‐telopeptide (ICTP), and urinary pyridinoline and deoxypyridinoline corrected for creatinine (Pyr/Cr, D‐Pyr/Cr) and urinary calcium/creatinine ratio (Ca/Cr); (b) bone mineral density (BMD), as measured by quantitative computed tomography both at lumbar spine and distal radius, and by dual X‐ray absorptiometry both at lumbar spine and at three femoral sites (Wards triangle, femoral neck, and great trochanter). AP, BGP, ICTP, Pyr/Cr, D‐Pyr/Cr were significantly higher in patients than in controls, independent of the menstrual pattern. Higher PICP levels were found in the whole group and in menstruating acromegalics when compared with control women; no difference was found in amenorrheal patients, who in turn showed higher urinary Ca/Cr values. When patients were considered all together, BMD at spine, femoral neck, and trochanter was higher than in controls. In contrast, when the gonadal status was taking into account and, menstruating and amenorrheal subjects were considered separately, BMD at spine, but not in other sites, was significantly higher in menstruating patients than in controls. In contrast, no difference of BMD values at any site was observed between amenorrheal patients and controls. The mean BMD Z scores allowed us to detect an unequal involvement of different skeletal sites. Our results show that bone turnover is increased in acromegalic women and suggest that GH anabolic effect on bone is more evident in the presence of estrogens and that different skeletal sites may be affected differently by hormone excess.

Prognostic significance of double product and inadequate double product response to maximal symptom-limited exercise stress testing after myocardial infarction in 6296 patients treated with thrombolytic agents

BACKGROUND The aim of this study was to evaluate the prognostic significance of the pressure-rate product (PRP) obtained during exercise stress testing and of its change from rest to maximal exercise (dPRP) in a population of survivors of acute myocardial infarction treated with thrombolytic agents. METHODS AND RESULTS Survivors of acute myocardial infarction (n = 6251) from the GISSI-2 database, who underwent a maximal symptom-limited exercise test with either bicycle ergometer or treadmill, were followed up for 6 months. PRP and dPRP values were dichotomized (</=21,700 and >21,700, </=11, 600 and >11,600, respectively) and analyzed in a multivariate Cox model individually and simultaneously with other ergometric variables. Six-month mortality rate was 0.8% in the high PRP group and 2.0% in the low PRP group. Low PRP was an independent predictor of 6-month mortality rate (relative risk [RR] 1.97, 95% confidence interval [CI] 1.24 to 3.13). Patients with low dPRP had mortality rates higher than patients with high dPRP (2.1% vs 0.8%). At the multivariate analysis, low dPRP showed negative predictive value (RR 1.97, 95% CI 1.23 to 3.16). A further multivariate analysis was performed with PRP and dPRP, also adjusting for low work capacity, abnormal systolic blood pressure response to exercise, and symptomatic-induced ischemia. The results showed that low work capacity, low PRP, and symptomatic exercise-induced ischemia were still significantly associated with higher 6-month mortality rate (P =.04,.02, and.05; RR = 1.68, 1.71, and 1.78 respectively). CONCLUSIONS PRP is a predictive index to assess prognosis in survivors of acute myocardial infarction treated with thrombolytic agents able to perform an exercise test after acute myocardial infarction, but its usefulness appears to be limited, considering that these patients were at low risk.

Influence of Pentraxin 3 (PTX3) Genetic Variants on Myocardial Infarction Risk and PTX3 Plasma Levels

PTX3 is a long pentraxin of the innate immune system produced by different cell types (mononuclear phagocytes, dendritic cells, fibroblasts and endothelial cells) at the inflammatory site. It appears to have a cardiovascular protective function by acting on the immune-inflammatory balance in the cardiovascular system. PTX3 plasma concentration is an independent predictor of mortality in patients with acute myocardial infarction (AMI) but the influence of PTX3 genetic variants on PTX3 plasma concentration has been investigated very little and there is no information on the association between PTX3 variations and AMI. Subjects of European origin (3245, 1751 AMI survivors and 1494 controls) were genotyped for three common PTX3 polymorphisms (SNPs) (rs2305619, rs3816527, rs1840680). Genotype and allele frequencies of the three SNPs and the haplotype frequencies were compared for the two groups. None of the genotypes, alleles or haplotypes were significantly associated with the risk of AMI. However, analysis adjusted for age and sex indicated that the three PTX3 SNPs and the corresponding haplotypes were significantly associated with different PTX3 plasma levels. There was also a significant association between PTX3 plasma concentrations and the risk of all-cause mortality at three years in AMI patients (OR 1.10, 95% CI: 1.01–1.20, p = 0.02). Our study showed that PTX3 plasma levels are influenced by three PTX3 polymorphisms. Genetically determined high PTX3 levels do not influence the risk of AMI, suggesting that the PTX3 concentration itself is unlikely to be even a modest causal factor for AMI. Analysis also confirmed that PTX3 is a prognostic marker after AMI.

Assessment of ultrasound acoustic artifacts in patients with acute dyspnea: a multicenter study

Background Recent reports indicate that numerical assessment of B-lines during transthoracic ultrasound may aid the differential diagnosis of acute diffuse pleuropulmonary disorders. Purpose To determine whether B-lines are different in normal and diseased lungs and whether they can be used to discriminate between different types of pulmonary disorders in acutely ill patients. Material and Methods In this multicenter study, transthoracic ultrasonography was performed on 193 patients with acute dyspnea, 193 healthy non-smokers, and 58 patients who had undergone pneumonectomy for lung cancer. Examinations were done with a low–medium frequency (3.5–5.0 MHz) convex probe and a high-frequency (8–12.5 MHz) linear probe. Video recordings were re-examined by a second set of examiners. In each participant, we measured the number of B-lines observed per scan. Results B-lines counts were higher in dyspnoic patients (means: 3.11 per scan per linear probe scan vs. 1.93 in healthy controls and 1.86 in pneumonectomized patients; P < 0.001 for all); all counts were higher when convex probes were used (5.4 in dyspnoic patients and 2 in healthy controls; P < 0.001 vs. the linear probe). Subgroups of dyspnoic patients defined by cause of dyspnea displayed no significant differences in the number of B-lines. Conclusion Our results demonstrate that there are a significant higher number of B-lines in the lungs of patients with dyspnea compared to healthy subjects and to pneumonectomized patients. Nevertheless, the quantification of B-lines does not make any significant contribution to the differential diagnosis of dyspnea.

Exercise and cardiovascular diseases.

Exercise is a physiologic stressor that has multiple beneficial effects on cardiovascular system. Currently exercise training is a class I intervention as part of a multifactorial long-term process that includes: clinical assistance, assessment of global cardiovascular risk, identification of specific objective for each cardiovascular risk factor, formulation of an individual treatment plan with multiple intervention aimed at reduction of the risk, educational programs, planning of long term follow-up. This paper reviews the evidences of benefit of exercise in the most common heart diseases and describes the role of exercise training in the cardiac rehabilitation programs.

Self-expanding stent for spontaneous coronary artery dissection: a rational choice.

&NA; Spontaneous coronary artery dissection (SCAD) is a rare and poorly understood cause of acute coronary syndrome in relatively young patients. Nowadays, the optimal treatment of SCAD is uncertain. A conservative approach seems to be preferable, but in particular conditions, an invasive strategy is necessary. The poor rate of procedural success, the high risk of procedural complications and the uncertain long and mid-term results make the interventional treatment of SCAD a challenge. We report a case of a young male patient presenting with SCAD successfully treated with a sirolimus-eluting self-expanding coronary stent. To our knowledge, the use of self-expanding coronary stent for SCAD has never been described yet and we discuss about the rationale of a possible larger use in clinical practice.