Rosa Lucci

Revised Guidelines for Neonatal Screening Programmes for Primary Congenital Hypothyroidism

Since the first guidelines for neonatal screening for congenital hypothyroidism (CH) were issued by ESPE in 1993 [1], there have been considerable advances in our understanding of CH and our appreciation of the various geographical and logistic difficulties involved. Therefore, an updating of the guidelines is overdue. Experience from countries where screening began in the late 1970s and early 1980s has indicated that treatment should be started no later than the first 2 weeks of life using a ‘high’ dosage regime of L-thyroxine (10–15 Ìg/kg/day). It has also been shown that the quality of long-term outcome is closely related to the quality of follow-up. In Eastern Europe, screening programmes for CH have either been started or will start soon in almost all countries, and although many programmes are operating satisfactorily, it is important to standardise screening procedures and management of suspected cases as much as possible in order to optimise outcome. A degree of uniformity throughout Europe would not only facilitate early detection and treatment of individual patients but give insight into the economic and epidemiological aspects of the screening programmes as well as the epidemiological aspect of CH.

Power Doppler Improves the Diagnostic Accuracy of Color Doppler Ultrasonography in Cold Thyroid Nodules: Follow-Up Results

The usefulness of a recent color Doppler (CD) ultrasonography technique, named power Doppler (PD), was evaluated in the diagnosis of thyroid nodules showing low or absent uptake of 99mTc-pertechnetate, in order to investigate the possibility to improve the diagnostic accuracy of ultrasonography. The rationale was the evidence that at PD the color map displays the total integrated Doppler power in color, while CD generally displays an estimate of the mean Doppler shift. The vascular patterns recorded at PD and CD evaluation of 322 thyroid nodules were compared to the results of cytology and/or histology, when surgery was performed. In respect to the results of cytology, PD has a higher sensitivity (100 vs. 91%) and specificity (95.1 vs. 86.2%) than CD. A similar result was found when PD and CD were compared to the results of histology, sensitivity being 100 vs. 89% and specificity 98.1 vs. 93.7%, respectively. During the follow-up the 2 nodules considered false positive at PD resulted to be tumoral lesions. On this basis, the final specificity of PD in our series was 100%. In conclusion, in the current series including 322 thyroid nodules characterized by a low or absent uptake of 99mTc-pertechnetate, PD seems to provide a better characterization of thyroid nodules, possibly allowing a more accurate selection of the patients to subject to fine-needle biopsy.

Long-term effects of cardiac rehabilitation on end-exercise heart rate recovery after myocardial infarction.

Background Heart rate recovery (HRR) is a marker of vagal tone that is a powerful predictor of mortality in patients with coronary artery disease. Design This study aims at evaluating the effects of long-term exercise training on HRR after acute myocardial infarction (AMI), in order to clarify whether prolonged exercise training could maintain a long-term improvement of HRR. Methods Forty-four patients after AMI were enrolled in a 3-month hospital-based exercise training programme. At the end, patients were subdivided into two groups: group A (n = 22), patients discharged with a specific home-based exercise training programme and instructions for improving leisure-time physical activity; group B (n = 22), patients discharged with generic instructions to maintain physical activity. All patients underwent a cardiopulmonary exercise test before, at the end of 3 months exercise training and at 6 months follow-up. Results At the end of the hospital-based exercise training programme we observed an increase in peak oxygen consumption [VO2peak; from 13.9 ± 3.6 to 18 ± 2.7 ml/kg per min (A) and from 14.1 ± 3.9 to 17.9 ± 2.1 ml/kg per min (B), P<0.001] and in HRR [from 17.1 ± 1.8 to 23.4 ± 1.4 beats/min (A), and from 18.8 ± 2.1 to 24.3 ± 1.9 beats/min (B), P<0.001]. At 6 months’ follow-up we observed a further improvement in VO2peak (from 18.0 ± 2.7 to 20.3 ± 2.7 ml/kg per min, P<0.001) and in HRR (from 23.4 ± 1.4 to 27.8 ± 2.1 beats/min, P<0.001) in group A, but a significant decrease in VO2peak and in HRR in group B (P<0.001). Conclusion Long-term exercise training is useful for maintaining or improving the beneficial results of the standard 3-month exercise training programme on cardiovascular capacity and HRR. This observation may bear beneficial prognostic effects on patients after AMI.

Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide.

Aims To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. Methods Sixty-one postinfarction patients were randomized into two groups: group T [n = 30, LV ejection fraction (EF) 41.6 ± 11.3%, mean ± SD] entered a 6-month ET programme, whereas group C (n = 31, EF 42.0 ± 7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. Results At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; −9%, P<0.001), a reduction in NT-proBNP (−71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (−40%, P<0.001; T vs. C group, P<0.001). Conclusions Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.

Hormone levels and tumour size response to quinagolide and cabergoline in patients with prolactin‐secreting and clinically non‐functioning pituitary adenomas: predictive value of pituitary scintigraphy with 123I‐methoxybenzamide

BACKGROUND Dopamine agonists are indicated as primary therapy for PRL‐secreting pituitary adenomas, while controversial results have been reported in nonfunctioning adenomas (NFA).

Reduction of N terminal-pro-brain (B-type) natriuretic peptide levels with exercise-based cardiac rehabilitation in patients with left ventricular dysfunction after myocardial infarction.

Introduction N-terminal-pro-brain (B-type) natriuretic peptide (NT-pro-BNP) is a peptide hormone released from ventricles in response to myocyte stretch. The aim of the study was to investigate the influence of exercise training on plasma NT-pro-BNP to verify if this parameter could be used as a biological marker of left ventricular remodelling in myocardial infarction patients undergoing an exercise training programme. Methods Forty-four patients after myocardial infarction were enrolled into a cardiac rehabilitation programme, and were randomized in two groups of 22 patients each. Group A patients followed a 3-month exercise training programme, while group B patients received only routine recommendations. All patients underwent NT-pro-BNP assay, and cardiopulmonary exercise test before hospital discharge and after 3 months. Results In Group A, exercise training reduced NT-pro-BNP levels (from 1498 ± 438 to 470 ± 375 pg/ml, P = 0.0026), increased maximal (V O2peak + 4.3 ± 2.9 ml/kg per min, P<0.001; Powermax + 38 ± 7, P<0.001) exercise parameters and work efficiency (Powermax/V O2peak + 1.3 ± 0.4 Power/ml per kg per min, P<0.001); there was also an inverse correlation between changes in NT-pro-BNP levels and in V O2peak (r = −0.72, P<0.001), E-wave (r = −0.51, P<0.001) and E/A ratio (r = 0.59, P<0.001). In group B, at 3 months, no changes were observed in NT-pro-BNP levels, exercise and echocardiographic parameters. Conclusion Three months exercise training in patients with moderate left ventricular systolic dysfunction after myocardial infarction induced a reduction in NT-pro-BNP levels, an improvement of exercise capacity and early left ventricular diastolic filling, without negative left ventricular remodelling. Whether the reduction of NT-pro-BNP levels could be useful as a surrogate marker of favourable left ventricular remodelling at a later follow-up remains to be further explored.

Two-year multicomprehensive secondary prevention program: favorable effects on cardiovascular functional capacity and coronary risk profile after acute myocardial infarction.

Background Cardiac rehabilitation includes interventions aimed at facilitating physical, psychological and emotional recovery following the acute phase of myocardial infarction (AMI). To date, optimal cardiac rehabilitation program duration and frequency of patient contact has yet to be identified. Objective The present study was performed to evaluate the effects of two different strategies of secondary prevention (2 years, multifactorial continued educational and behavioral intervention versus usual care) implemented into a cardiac rehabilitation setting on several cardiovascular endpoints indicating cardiovascular functional exercise capacity and coronary risk profile in patients with recent AMI. Methods This was a prospective randomized study including 52 postinfarction patients. Initially, all patients were enrolled in a 3-month outpatient cardiac rehabilitation program. Thereafter, they were randomly subdivided into two groups (I = intervention group; C = control group), each composed of 26 patients, and followed for 24 months. Results At the end of the 3-month outpatient cardiac rehabilitation program, both groups showed a significant (P < 0.05) improvement in cardiopulmonary parameters (maximal oxygen consumption, maximal workload) and in cardiovascular risk profile (BMI, lipid profile). During the 24-month study period, group I showed stabilization or even improvement (P < 0.05) of both cardiopulmonary parameters and cardiovascular risk profile, whereas group C patients showed a deterioration or significant impairment (P < 0.05) of the same parameters. Clinical events occurred in 27% of patients in the control group (n = 7) and in 11% in the training group (n = 3) (P < 0.05). Conclusion Long-term, multifactorial educational and behavioral intervention maintained for 2 years in a multicomprehensive cardiac rehabilitation setting represents a valid strategy for improving long-term cardiovascular functional capacity and cardiovascular risk profile in postinfarction patients.

Favourable effects of exercise-based Cardiac Rehabilitation after acute myocardial infarction on left atrial remodeling

BACKGROUND Left atrial enlargement is an important predictor of cardiovascular outcomes in patients after acute myocardial infarction. While the favourable effect of exercise exercise-based Cardiac Rehabilitation (CR) on postinfarction LV remodeling has been well documented, those on LA remodeling have yet to be defined. This study investigated the effects of CR on LA remodeling in postinfarction patients with moderate left ventricular (LV) dysfunction. METHODS Sixty postinfarction patients were randomised randomized into two groups, each composed of 30 patients: group T (LV ejection fraction (EF) 43.7+/-4.2%, mean+/-SD) entered a 6-month CR program, whereas group C (EF 44.7+/-4.4%, P=ns) did not. Doppler echocardiography and cardiopulmonary exercise test were performed upon enrolment and at 6-month. RESULTS At 6-month, trained patients showed a significant (P<0.001) improvement in peak oxygen consumption (DeltaVO(2peak)=+5.2+/-2.1 ml/kg/min) and a reduction in LA (DeltaLAV(MAX)=-1.9+/-3.7 ml/m(2)) and in LV volumes (DeltaLVEDV=-3.6+/-4.4 ml/m(2)). At 6-month, untrained patients showed LAV(MAX) (+3.6+/-4.4 ml/m(2), P<0.001) and LV dilation (+4.2+/-5.1 ml/m(2), P<0.001; group T vs. C, P<0.001); whereas no significant changes in VO(2peak) were observed. Multiple linear regression analysis showed that age (beta=0.442, P<0.001), inclusion in the training group (beta=-0.599, P<0.001), E/A ratio (beta=-0.210, P=0.038), LVEDV (beta=0.376, P<0.001), and LVEF (beta=-0.279, P=0.007) are significant predictors of LA remodeling. CONCLUSIONS Six-month exercise-based CR in postinfarction patients with mild to moderate LV dysfunction induced a favourable LA remodeling.

Autonomic dysfunction is associated with high mobility group box-1 levels in patients after acute myocardial infarction

BACKGROUND High mobility group box-1 (HMGB1) protein, a critical mediator of inflammatory processes, is a novel predictor of adverse post-infarction clinical outcomes, being involved in the healing process after MI. Heart rate recovery (HRR), a marker of autonomic function defined as the fall in heart rate during the first minute after exercise, is a powerful predictor of mortality in post-infarction patients. The present study was designed to test the hypothesis that HMGB1 is associated with autonomic dysfunction in post-infarction patients. METHODS Sixty-seven consecutive patients (mean age 59.3 years, 84% males) recovering from acute MI were included in the study protocol. All patients underwent Doppler-echocardiography, cardiopulmonary exercise and HMGB1 assay. RESULTS HMGB1 levels were inversely correlated with peak oxygen consumption (VO(2peak)) (r=-0.449, P<0.001), with left ventricular ejection fraction (LVEF) (r=-0.360, P=0.003), and with HRR (r=-0.387, P<0.001). In a linear regression analysis adjusted for multiple confounders, we found a significant inverse association between HMGB1 levels and HRR independent of age, gender, body mass index, VO(2peak), slope of increase in ventilation over carbon dioxide output (VE/VCO(2slope)), and presence of diabetes (beta=-0.377, P=0.034). CONCLUSIONS This study provided the first evidence for a significant association between increased HMGB1 levels and autonomic dysfunction expressed by post-exercise slower HRR in post-infarction patients. The prognostic implication of such association needs to be explored as well as whether HMGB1 could represent a valid marker for risk stratification either during the acute phase or long-term after MI.

Effects of exercise-based cardiac rehabilitation on high mobility group box-1 levels after acute myocardial infarction: rationale and design.

Background High-mobility group box-1 (HMGB1) is a ubiquitous nuclear protein recently recognized as a critical mediator of inflammatory processes. HMGB1 is a novel predictor of adverse postinfarction clinical outcomes, playing a crucial role in the appropriate healing process after myocardial infarction (MI). The present trial is designed in order to reveal the postinfarction HMGB1 expression pattern and its relationship with cardiac remodeling. The effects of an exercise-based cardiac rehabilitation program on HMGB1 expression pattern will be addressed as well. Design Single-center, randomized, controlled study carried out at a university hospital. Methods Postinfarction patients are randomized into a training group (enrolled in a 6-month exercise-based cardiac rehabilitation program) and into a control group. HMGB1 levels are evaluated by enzyme-linked immunosorbent assay. Results Postinfarction patients are enrolled from September 2008 through December 2009. Results will be available in mid-2010. Conclusion Despite the importance of the inflammatory response and healing process in postinfarction left ventricular remodeling, the mechanisms that initiate and control these processes remain to be elucidated. The rationale and design of the present study is designed to test the postinfarction HMGB1 expression pattern and its relationship with cardiac remodeling as well as the effects of an exercise-based cardiac rehabilitation program.