[Show abstract][Hide abstract] ABSTRACT: Background
Heart transplantation is limited by severe donor organ shortage. Regardless of the changes made in the acceptance of marginal donors, any such mechanism cannot be considered successful unless recipient graft survival rates remain acceptable. A stress echo-driven selection of donors has proven successful in older donors with normal left ventricular resting function and in standard donors with reversible resting left ventricular dysfunction acutely improving during stress, or slowly improving (over hours) during intensive hormonal treatment. Aim of this study is to assess the medium-term outcome of recipients of marginal donor hearts selected with new echocardiographic techniques over standard criteria.
Methods and results
We enrolled 43 recipients of marginal donor hearts: age > 55 years, or < 55 years but with concomitant risk factors, n = 32; acutely improving during stress, n = 3; or slowly improving during hormonal treatment, n = 8. At follow-up (median, 30 months; interquartile range, 21–52 months), 37 of the recipients were still alive. One-year survival was 93%.
The strict use of new stress-echocardiographic techniques over standard criteria of marginal donor management, together with comprehensive monitoring of the donor, has the potential to substantially increase the number of donor hearts without adverse effects on recipient medium-term outcome.
[Show abstract][Hide abstract] ABSTRACT: Two centrifugal pumps, the RotaFlow (Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany) and Levitronix CentriMag (Levitronix LCC, Waltham, MA, USA), used in central or peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) support systems have been investigated, in terms of double-center experience, as treatment for patients with refractory cardiogenic shock (CS). Between January 2006 and December 2012, 228 consecutive adult patients were supported on RotaFlow (n = 213) or CentriMag (n = 15) ECMO, at our institutions (155 men; age 58.3 ± 10.5 years, range: 19–84 years). Indications for support were: failure to wean from cardiopulmonary bypass in the setting of postcardiotomy (n = 118) and primary donor graft failure (n = 37); postacute myocardial infarction CS (n = 27); acute myocarditis (n = 6); and CS on chronic heart failure (n = 40). A peripheral ECMO setting was established in 126 (55.2%) patients while it was established centrally in 102 (44.7%). Overall mean support time was 10.9 ± 9.7 days (range: 1–43 days). Eighty-four (36.8%) patients died on ECMO. Overall success rate, in terms of survival on ECMO (n = 144), weaning from mechanical support (n = 107; 46.9%), bridge to mid-long-term ventricular assist device (n = 6; 2.6%), and bridge to heart transplantation (n = 31; 13.5%), was 63.1%. One hundred twenty-two (53.5%) patients were successfully discharged. Stepwise logistic regression identified blood lactate level and MB isoenzyme of creatine kinase (CK-MB) relative index at 72 h after ECMO initiation, and number of packed red blood cells (PRBCs) transfused on ECMO as significant predictors of mortality on ECMO (P = 0.010, odds ratio [OR] = 2.94; 95% confidence interval [CI] = 1.10–3.14; P = 0.010, OR = 2.82, 95% CI = 1.014–3.721; and P = 0.011, OR = 2.69; 95% CI = 1.06–4.16, respectively). Central ECMO population had significantly higher rate of continuous veno-venous hemofiltration need and bleeding requiring surgery events compared with the peripheral ECMO setting population. No significant differences were seen by comparing the RotaFlow and CentriMag populations in terms of device performance. At follow-up, persistent heart failure with left ventricle ejection fraction (LVEF) ≤40% was a risk factor after hospital discharge. Patients with a poor hemodynamic status may benefit from rapid central or peripheral insertion of ECMO. The blood lactate level, CK-MB relative index, and PRBCs transfused should be strictly monitored during ECMO support. In addition, early ventricular assist device placement or urgent listing for heart transplant should be considered in patients with persistent impaired LVEF after ECMO.
[Show abstract][Hide abstract] ABSTRACT: Advanced age of patients (pts) is often considered to be a risk for morbidity and mortality in permanent Mechanical Circulatory Support (MCS). We investigated outcomes of aged vs younger pts implanted with Jarvik 2000 (intraventricular-axial-flow pump with novel power delivery system) and enrolled in the Italian Registry (IR) in terms of length of MCS out of hospital. Outcomes were also analyzed according to preoperative conditions and INTERMACS scale.Methods and MaterialsFrom June 2006 to September 2012, 79 consecutive end-stage heart failure adult pts (70 males, mean age 62 ±8 yrs, median 64 yrs, 52% ischemic cardiomyopathy, 95% ineligible for heart transplantation) were enrolled in the Jarvik 2000 IR. 36 pts were ≥65yr old (mean age 69 ±3 yrs, median 69 yrs, group A), 43 patients were <65 yr old (mean age 56 ±7 yrs, median 57 yrs, group B). Relevant pre-operative data and outcomes were analyzed by comparing long term survivors (subgroup A1, B1, on MCS >1 yr) and early deaths (subgroup A2, B2, on MCS <1 month).Results17/36 pts (subgroup A1) and 14/43 pts (subgroup B1) were on MCS > 1 year, all of them being discharged home. No significant difference in gender, etiology, pre-operative hemodynamics, pre-implant INTERMACS mean class (3.6 and 3.5 respectively) or mean time on MCS (699±241 and 865±311 days respectively) were found between the 2 groups. In 9 and 10 pts respectively MCS is ongoing. 5/36 pts (subgroup A2) and 9/43 pts (subgroup B2) were on MCS < 1 month: significant difference was found in pre-implant INTERMACS in subgroups A1 vs A2 (3.6 vs 2) and B1 vs B2 (3.5 vs 2.6).Conclusions
In our experience, elderly patients on permanent MCS have comparable outcomes to their younger counterparts. For both groups we confirmed that results are optimal when elective LVAD implantation is performed before development of inotropic dependency or cardiogenic shock. These results suggest that age need not be a limiting factor in the decision to implant MCS in end stage heart failure.
The Journal of Heart and Lung Transplantation 04/2013; 32(4):S284-S285. DOI:10.1016/j.healun.2013.01.750 · 6.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Non-functional recovery of the graft (primary graft failure, PGF) is still the major cause of early adverse outcome after heart transplantation (HT). While several donor- and recipient-related factors have been taken into account to explain PGF onset, few data are available analyzing how donor-recipient match may be optimized to reduce PGF occurrence. In this study, we explored PGF risk factors, aiming to identify specific donor-recipient matches associated with PGF onset.Methods and MaterialsWe reviewed data from all adult patients transplanted between 1999 and 2011 at our center, including those with pre-HT laboratory and hemodynamic data availability. Study endpoint was occurrence of PGF defined as need of mechanical circulatory support with ECMO/intra-aortic balloon pump, or cardiac index <2.5 l/min/m2 for three consecutive hours despite adequate filling pressure, during the first 24 post-HT hours.ResultsOut of 370 patients included, 63(17%) presented PGF. Among all clinical and laboratory variables analyzed, recipient female sex (P<0,01), transpulmonar gradient ≥12 mmHg (GTP) (P=0.02), and increasing calculated pulmonary arterial resistances (RVP) were associated with the risk of PGF (P=0.04). To analyze the interplay of donor features with recipient-related risk factors for PGF, we performed subgroup analyses revealing that recipient cerebral hemorrhage increased by 3.45 the odds for PGF only in recipients with high RVP, and that BMI mismatch increased by 2.91 the odds for PGF only in female recipients (all P<0.02). These donor-recipient matches accounted for 48% of all the PGF cases.Conclusions
Female gender and high GTP independently predicted PGF onset. Allocation of donors died of cerebral hemorrhage to recipients with high RVP, or of undersized donors to female recipients, markedly increased PGF risk. Underscoring the importance of strategies directed at controlling reactive pulmonary hypertension before HT, this study suggests that development of customized allocation algorythms may signifcantly improve post-HT outcomes.
The Journal of Heart and Lung Transplantation 04/2013; 32(4):S255-S256. DOI:10.1016/j.healun.2013.01.662 · 6.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to investigate the blood perfusion and the inflammatory response of the myocardial infarct area after transplanting a hyaluronan-based scaffold (HYAFF® 11) with bone marrow mesenchymal stem cells (MSCs). Nine-week-old female pigs were subjected to a permanent left anterior descending coronary artery ligation for 4 weeks. According to the kind of the graft, the swine subjected to myocardial infarction were divided into the HYAFF® 11, MSCs, HYAFF® 11/MSCs and untreated groups. The animals were killed 8 weeks after coronary ligation. Scar perfusion, evaluated by Contrast Enhanced Ultrasound echography, was doubled in the HYAFF® 11/MSCs group and was comparable with the perfusion of the healthy, non-infarcted hearts. The inflammation score of the MSCs and HYAFF® 11/MSCs groups was near null, revealing the role of the grafted MSCs in attenuating the cell infiltration, but not the foreign reaction strictly localized around the fibres of the scaffold. Apart from the inflammatory response, the native tissue positively interacted with the HYAFF® 11/MSCs construct modifying the extracellular matrix with a reduced presence of collagene and increased amount of proteoglycans. The border-zone cardiomyocytes also reacted favourably to the graft as a lower degree of cellular damage was found. This study demonstrates that the transplantation in the myocardial infarct area of autologous MSCs supported by a hyaluronan-based scaffold restores blood perfusion and almost completely abolishes the inflammatory process following an infarction. These beneficial effects are superior to those obtained after grafting only the scaffold or MSCs, suggesting that a synergic action was achieved using the cell-integrated polymer construct.
Journal of Cellular and Molecular Medicine 03/2013; 17(4). DOI:10.1111/jcmm.12039 · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Splitting the liver for two adults to increase the donor pool is still a debated issue, especially for combined organ transplantation. We described a case of liver-splitting procedure for two adults, which was successful even in the presence of combined organ transplantation. Three adult combined organ transplantations from one deceased donor were performed, with, use of split liver grafts in two patients: a combined heart-right split liver, a left kidney-left split liver, and a right kidney-pancreas transplantation. Despite a not perfect match between the graft type and recipient, the prevention of small-for-size syndrome by ligature of the splenic artery, and/or hemiportocaval shunt in the patient receiving the left split liver, and the maximal reduction of ischemia time were the main factors contributing to the success of the procedure. This is the first report of combined heart and split liver in two adults which may suggest new strategies for organ transplantations.
[Show abstract][Hide abstract] ABSTRACT: Purpose: Atherosclerotic plaques progress in a highly individual manner. Plaque eccentricity has been associated with a rupture-prone phenotype and adverse coronary events in humans. Endothelial shear stress (ESS) critically determines plaque growth and low ESS leads to high-risk lesions. However, the factors responsible for rapid disease progression with increasing plaque eccentricity have not been studied. We investigated in vivo the effect of local hemodynamic and plaque characteristics on progressive luminal narrowing with increasing plaque eccentricity in humans.
Methods: Three-dimensional coronary artery reconstruction using angiographic and intravascular ultrasound data was performed in 374 patients at baseline (BL) and 6-10 months later (FU) to assess plaque natural history as part of the PREDICTION Trial. A total of 874 coronary arteries were divided into consecutive 3-mm segments. We identified 408 BL discrete luminal narrowings with a throat in the middle surrounded by gradual narrowing proximal and distal to the throat. Local BL ESS was assessed by computational fluid dynamics. The eccentricity index (EI) at BL and FU was computed as the ratio of max to min plaque thickness at the throat. Mixed-effects logistic regression was used to investigate the effect of BL variables on the combined endpoint of substantial worsening of luminal narrowing (decrease in lumen area >1.8 mm2 or >20%) with an increase in plaque EI.
Results: Lumen worsening with an increase in plaque EI was evident in 73 luminal narrowings (18%). Independent predictors of worsening lumen narrowing with plaque EI increase were low BL ESS (<1 Pa) distal to the throat (odds ratio [OR] =2.2 [95% CI: 1.3-3.7]; p=0.003) and large BL plaque burden (>51%) at the throat (OR=1.7 [95% CI: 1.0-2.8]; p=0.051). The incidence of worsening lumen narrowing with increasing plaque eccentricity was 30% in the presence of both predictors versus 15% in luminal narrowings without this combination of characteristics (OR=2.4 [95% CI: 1.4-4.3]; p=0.002).
Conclusions: Low local ESS independently predicts areas with rapidly progressive luminal narrowing and increasing plaque eccentricity. Coronary regions manifesting an abrupt anatomic change, i.e., at highest risk to cause an adverse event, can be identified early by assessment of ESS and plaque burden.
[Show abstract][Hide abstract] ABSTRACT: Aims:
Hereditary transthyretin (TTR)-related amyloidosis (ATTR) is mainly considered a neurologic disease. We assessed the phenotypic and genotypic spectra of ATTR in a Caucasian area and evaluated the prevalence, genetic background, and disease profile of cases with an exclusively cardiac phenotype, highlighting possible hints for the differential diagnosis with hypertrophic cardiomyopathy (HCM) and senile systemic amyloidosis (SSA).
Methods and results:
In this Italian multicentre study, 186 patients with ATTR were characterized at presentation. Thirty patients with SSA and 30 age-gender-matched HCM patients were used for comparison. Phenotype was classified as exclusively cardiac (n = 31, 17%), exclusively neurologic (n = 46, 25%), and mixed cardiac/neurologic (n = 109, 58%). Among the eight different mutations responsible for an exclusively cardiac phenotype, Ile68Leu was the most frequent. Five patients with an exclusively cardiac phenotype developed mild abnormalities at neurological examination, but no symptoms during a 36-month follow-up (range: 14-50). Exclusively cardiac phenotype was characterized by male gender, age >65 years, heart failure symptoms, symmetric left ventricular (LV) 'hypertrophy', and moderately depressed LV ejection fraction. This profile was similar to SSA, but relatively distinct from HCM. Compared with patients with a mixed phenotype, patients with an exclusively cardiac phenotype showed a more pronounced cardiac involvement on both echocardiogram and electrocardiogram (ECG).
A clinically relevant subset of Caucasian ATTR patients present with an exclusively cardiac phenotype, mimicking HCM or SSA. Echocardiographic and ECG findings are useful to differentiate ATTR from HCM but not from SSA. The role of liver transplantation in these patients should be reconsidered.
European Heart Journal 06/2012; 34(7). DOI:10.1093/eurheartj/ehs123 · 15.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Knowledge of the patterns of myocardial amyloid accumulation could improve the interpretation of electrocardiographic, echocardiographic and magnetic resonance imaging findings of amyloidosis. We assessed the extent and pattern of myocardial amyloid infiltration in explanted or autopsied hearts of patients with cardiomyopathy related to acquired monoclonal immunoglobulin light-chain (AL) or hereditary transthyretin (TTR) related amyloidosis (ATTR).
We analyzed nine explanted/autopsied hearts from patients with AL (n = 4) and ATTR (n = 5) cardiac amyloidosis. For each heart, a biventricular histological macrosection was obtained at mid-ventricular level and analyzed with both inspective and computer-assisted histologic and histomorphometric analysis aimed in particular at quantifying muscle cells, fibrosis and amyloid infiltration.
The extent of amyloid infiltration of the left ventricle (LV) ranged from 45 to 76% (median [interquartile range (IQR)] = 57% [51-64]) of the overall surface. Although LV trabecular and subendocardial were the most infiltrated layers (45-94%, median [IQR] = 73% [67-84] and from 44 to 71%, median [IQR] = 57% [49-59], respectively), intra- and inter-patient heterogeneity was high. Three main patterns of amyloid infiltration of the LV were identified: diffuse (five cases), mainly subendocardial (two cases), and mainly segmental (two cases). The extent of amyloid infiltration of the right ventricle ranged from 48 to 93% (median [IQR] = 61% [59-83]); contributions of parietal and trabecular layers ranged from 32 to 99% (median [IQR] = 63% [47-88]) and from 49 to 93% (median [IQR] = 74% [64-79]), respectively.
In amyloidotic cardiomyopathy, amyloid deposition is highly heterogeneous. Different patterns of infiltration are identifiable, including diffuse, mainly segmental and mainly subendocardial. Awareness of this variability can help the interpretation of ECGs, echocardiograms and magnetic resonance imaging.
Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 05/2012; 19(2):99-105. DOI:10.3109/13506129.2012.684810 · 2.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Permanence of grafted stem cells in the infarcted myocardial area has been suggested to be favored by tissue engineering strategies, including the application of a scaffold as a cell support. However, an estimation of how many cells remain localized in the site of transplantation has never been done. The aim of this work was to investigate the localization of mesenchymal stem cells (MSCs) grafted with a well cell-adhesive polymer in the scar region of the infarcted heart. MATERIALS AND METHODS: Rat MSCs were engineered in a hyaluronan-based scaffold (HYAFF(®)11) for 3 wk. The hearts of donor rats were also explanted, subjected to coronary artery ligation, and grafted into the abdomen of syngeneic rats. Two wk after coronary ligation a small dish of the HYAFF(®)11/MSC construct was introduced into a pouch created in the ventricular wall of the infarct area and left for 2 wk. RESULTS: Under ex vivo conditions, MSCs tightly adhered to the hyaluronan fibers and secreted abundant extracellular matrix. In contrast, HYAFF(®)11 was not more surrounded by the engrafted MSCs 2 wk after construct transplantation. Most MSCs migrated near the border zone of the infarcted area close to the coronary vessels. Moreover, the infarcted region of the heart was enriched in capillaries and the degree of fibrosis was attenuated. CONCLUSIONS: Two wk after transplantation most MSCs grafted in the infarcted myocardium with HYAFF(®)11 had left the scaffold and moved to the border zone. Nevertheless, this treatment increased the myocardial vascularization and reduced the degree of fibrosis in the scar area.
Journal of Surgical Research 03/2012; 179(1). DOI:10.1016/j.jss.2012.01.028 · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: In the last decade there was an expanding application of ventricular assist devices (VAD) due to a shortage of donor organs combined with the efficacy of these mechanical circulatory supports. The Jarvik 2000 is one of the most used worldwide.
We report our experience of in-hospital intensive phase cardiac rehabilitation (CR) in pts who underwent Jarvik 2000 VAD implantation as destination therapy.
Methods: In the period 2009-2011, 18 pts (3 females, mean age 66.6±5.8 yo) had been admitted to our CR unit, 65±52 [20-205] days after operation. They followed a structured rehabilitation programme that included 3 daily sessions on 6 days/week of respiratory exercises, aerobic training, calisthenics, plus physiotherapy and treatment of specific deficiencies, as well as psychological and dietary support. When possible, a six-minute walking test (6MWT) and a symptom limited cardiopulmonary exercise test (CPET) were performed at admission and at discharge. The Barthel scale (BI), measured at entry and at discharge, was used as autonomy index.
Results: During the CR stay (mean 19±7 [5-39] days) 2 pts suffered of major gastrointestinal bleedings, requiring repeated blood transfusions, and had to be transferred before completing the rehabilitation protocol (both pts in the first year); in the last 3 years no major complications occurred in the CR unit and all pts completed the program. A mild hemolytic anemia was recognized in all pts (mean Hb level at discharge 10.2±1.3 g/dl).
At the end of the CR period all pts enhanced independence and mobility (mean ?BI +11%) and were able to walk at least with the assistance of a stick.
A 6MWT could be performed in 72% of pts (after 8±8 days) with a mean increment in the distance walked of 70.2±21.3 mt (p<0.05). In the same pts, the CPET demonstrated that they were able to sustain a light intensity work load (35.7±11.9 W; range 20-54 W), with a low maximum O2 consumption (12.4±3.4 ml/kg/min; range 7.4-19.8), close to the anaerobic threshold (11,3±2,8 ml/kg/min).
Conclusions: Our experience with Jarvik 2000 VAD indicate that CR is feasible and safe in these patients allowing them to improve self autonomy and functional capacity; In this particular setting of patients, who usually have a lot of comorbidities and long periods of hospital stay before VAD implantation, It’s also a good tool to monitor the complications in the delicate phase after discharge from the acute departments.
European Journal of Cardiovascular Prevention and Rehabilitation 01/2012; 19((Suppl 1)):S126. · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The heart transplant is a treatment of the heart failure, which is not responding to medications. To counteract heart donor shortage, we should screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease, in order to exclude donors with a history of cardiac disease. A simple way to evaluate this should be stress echocardiography.
A marginal donor (a 57 year old woman meeting legal requirements for brain death) underwent a transesophageal (TE) dipyridamole stress echo (6 minutes accelerated protocol) to rule out moderate or severe heart and coronary artery disease. Wall motion was normal at baseline and at peak stress, without signs of stress inducible ischemia, and there was no latent myocardial dysfunction. The marginal donor heart was transplanted to a recipient marginal for co-morbidity (a 63 year old man with multiple myeloma and cardiac amyloidosis , chronic severe heart failure, NYHA class IV). The transplanted heart was assessed normal for dimensions and ventricular function at transthoracic (TT) echocardiography on post-transplant day 7. Coronary artery disease was ruled out at coronary angiography one month after transplant.
For the first time stress echo was successfully used for the selection of hearts "too good to die", representing a critical way to solve the mismatch between donor need and supply.
Recenti progressi in medicina 05/2011; 102(5):207-11. DOI:10.1701/659.7670
[Show abstract][Hide abstract] ABSTRACT: Because of the shortage of donor hearts, the criteria for acceptance have been considerably expanded. Abnormal results on pharmacologic stress echocardiography are associated with significant coronary artery disease and/or occult cardiomyopathy on verification by cardiac autopsy. The aim of this study was to establish the feasibility of an approach based on pharmacologic stress echocardiography as a gatekeeper for extended heart donor criteria.
From April 2005 to April 2010, 39 "marginal" candidate donors (mean age, 56 ± 6 years; 21 men) were initially enrolled. After legal declaration of brain death, marginal donors underwent rest echocardiography, and if the results were normal, dipyridamole (0.84 mg/kg over 6 min, n = 25) or dobutamine (up to 40 μg/kg/min, n = 3) stress echocardiography.
A total of 19 eligible hearts were found with normal findings. Of these, three were not transplanted because of the lack of a matching recipient, and verification by cardiac autopsy showed absence of significant coronary artery disease or cardiomyopathy abnormalities. The remaining 16 eligible hearts were uneventfully transplanted in marginal emergency recipients. All showed normal (n = 14) or nearly normal (minor single-vessel disease in two) angiographic, intravascular ultrasound, hemodynamic and ventriculographic findings at 1 month. At follow-up (median, 14 months; interquartile range, 4-31 months), 14 patients survived and two had died, one at 2 months from general sepsis and one at 32 months from allograft vasculopathy in recurrent multiple myeloma.
Pharmacologic stress echocardiography can safely be performed in candidate heart donors with brain death and shows potential for extending donor criteria in heart transplantation.
Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 04/2011; 24(4):353-62. DOI:10.1016/j.echo.2010.11.014 · 4.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: When a physiological (exercise) stress echo is scheduled, interest focuses on wall motion segmental contraction abnormalities to diagnose ischemic response to stress, and on left ventricular ejection fraction to assess contractile reserve. Echocardiographic evaluation of volumes (plus standard assessment of heart rate and blood pressure) is ideally suited for the quantitative and accurate calculation of a set of parameters allowing a complete characterization of cardiovascular hemodynamics (including cardiac output and systemic vascular resistance), left ventricular elastance (mirroring left ventricular contractility, theoretically independent of preload and afterload changes heavily affecting the ejection fraction), arterial elastance, ventricular arterial coupling (a central determinant of net cardiovascular performance in normal and pathological conditions), and diastolic function (through the diastolic mean filling rate). All these parameters were previously inaccessible, inaccurate or labor-intensive and now become, at least in principle, available in the stress echocardiography laboratory since all of them need an accurate estimation of left ventricular volumes and stroke volume, easily derived from 3 D echo.
Aims of this paper are: 1) to propose a simple method to assess a set of parameters allowing a complete characterization of cardiovascular hemodynamics in the stress echo lab, from basic measurements to calculations 2) to propose a simple, web-based software program, to learn and training calculations as a phantom of the everyday activity in the busy stress echo lab 3) to show examples of software testing in a way that proves its value.
The informatics infrastructure is available on the web, linking to http://cctrainer.ifc.cnr.it