Secondary prophylaxis of hepatocellular carcinoma: the comparison of direct-acting antivirals with pegylated interferon and untreated cohort.

During the past two decades, several studies showed reduced rates of hepatocellular carcinoma recurrence in patients with HCV-related cirrhosis after interferon-based antiviral therapies respect to untreated controls, even without reaching viral clearance. The recent development of new all-oral regimens with direct-acting antivirals has radically improved the therapeutic management of hepatitis C. Nevertheless, paradoxical, or at least unexpected, high rates of both occurrence and recurrence of hepatocellular carcinoma after a treatment with direct-acting antivirals, have been reported in the recent literature. These findings generated a strong rebound in the hepatology community and are at present still controversial. We sought to compare the hepatocellular carcinoma recurrence-free survival of a historical cohort treated with pegylated interferon/ribavirin and an untreated cohort with a cohort treated with direct-acting antivirals.

The department of psychology within a pediatric cardiac transplant unit.

In 1979, the department of Psychology started its activity to provide psychological support to patients and their families during the course of treatment and during the follow-up period. Since 1986, a transplantation program was initiated in the cardiology and pediatric cardiac surgery departments, performing 179 cardiac, 3 heart-kidney, 18 heart-lung 14 both lung, 1 heart-lung-liver, and 1 single lung transplantation. From 1993, to September 2010 the kidney transplant program has performed. 218 cases. Since 2008, we performed (32 liver and 1 intestinal transplantations). We examined the quality of life and coping with transplantation attitudes because there is recent evidence of high levels of family anxiety and depression related to a child's poor response to the disease and compliance. Our work associated post-traumatic stress disorder (PTSD) with anxiety and with these clinical variables: gender pathology, rejection, number of drugs frequency of hospital visits, number of hospitalizations, as well as age at and time from transplantation. We examined 56 parents (25 fathers and 31 mothers) of cardiac transplant recipients. Our most relevant data demonstrated the presence of PTSD among 52% of mothers and 40% of fathers. Significant correlations were observed within the trait of anxiety. No correlations were noted between PTSD and other variables. Testing anxiety levels of parents is considered to be basic to provide psychological support to parents, encourage personal skills, and avoid PTSD symptoms.

Accuracy of VirtualTouch Acoustic Radiation Force Impulse (ARFI) imaging for the diagnosis of cirrhosis during liver ultrasonography.

PURPOSE: VirtualTouch is a new technique recently proposed to evaluate liver stiffness during B-mode ultrasonography. The goal of the present study was to analyze the diagnostic accuracy of VirtualTouch in the diagnosis of cirrhosis and its correlation with transient elastography (Fibroscan). MATERIALS AND METHODS: A total of 133 patients with chronic liver disease were enrolled. 90 of 133 underwent VirtualTouch and transient elastography and 70 patients assessed with VirtualTouch were submitted to liver biopsy. Stiffness was assessed by both techniques in the right liver lobe. The diagnostic accuracy for cirrhosis was first assessed in the 90 patients submitted to transient elastography with > 13 kPa (47 % of patients) as diagnostic for cirrhosis values. The best cut-off for cirrhosis with VirtualTouch was then tested in the 70 patients with biopsy (cirrhosis in 38 % of patients). 41 patients were assessed by VirtualTouch by two different operators. RESULTS: The VirtualTouch values in controls, chronic hepatitis and cirrhosis were respectively 113, 147 and 255 cm/sec. The AUROC of liver VirtualTouch for the diagnosis of cirrhosis (reference Fibroscan) was 0.941 with 175 cm/sec as the best cut-off (sensitivity 93.0 %; specificity 85.1 %). VirtualTouch confirmed good performance also in patients with bioptic diagnosis of cirrhosis (AUROC 0.908, sensitivity 81.5 %, specificity 88.4 %,). The correlation of VirtualTouch with transient elastography was strict (r = 0.891) and the correlation in VirtualTouch measurements between two operators was also good (r = 0.874). CONCLUSION: VirtualTouch is able to identify the presence of cirrhosis with good accuracy, shows good interobserver reproducibility and the correlation of its values with those obtained by transient elastography with Fibroscan is good.

Immunological modifications during treatment with thymosin alpha1 plus antiviral therapy in chronic hepatitis C.

The current standard therapy for the treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin, although many patients fail to clear the virus and their retreatment options are still unsatisfactory. Thymosin alpha1 (Talpha1) is an immunomodulating agent that has been proposed as complementary therapy for chronic HCV, especially in the setting of difficult-to-treat patients. The aim of this study was to evaluate, in patients nonresponsive to previous Peg-based therapy, the effect of standard antiviral therapy with or without Talpha1 on peripheral lymphocyte subsets. Twenty-four patients, 12 receiving Talpha1 and 12 standard therapy, were enrolled. Peripheral subpopulations were analyzed by flow cytometry. Although the addition of Talpha1 did not seem to significantly modify the T-lymphocyte subpopulations, as comparable behaviors were observed in the CD4 and CD8 longitudinal evaluation, Talpha1 produced an earlier increase of natural killer cells. An accurate selection of HCV patients who can benefit from immunomodulation is needed.

Thymoglobuline use in pediatric heart transplantation.

The literature has few data regarding the use of polyclonal anti-thymocyte globulin in pediatric cardiac transplantation. We describe our single-center, retrospective study of the use of Thymoglobuline in a pediatric population. We included in the study 31 consecutive heart transplant recipients (mean age, 7.8 years; median age, 9 years; range, 4 months-17 years), who all survived surgery. To induce immunosuppression, all patients received Thymoglobuline therapy at age-dependent doses (1-1.5 mg/kg/day between 0 and 1 year; 1.5-2 mg/kg/day from 1 year to 8 years; and 2.5 mg/kg/day >8 years). Duration of treatment was 1 to 7 days. In patients <1 year, the total number of lymphocytes was maintained at >500/mm(3). Thirty of 31 patients are alive at the end of follow-up. During the first 3 months, 3 Grade 3A and 10 Grade 1A (Working Formulation grading system) rejection episodes occurred. All reversed after steroid treatment. Eleven viral infections, 2 bacterial infections, and 1 fungal infection occurred. Not all patients with infection were symptomatic but all responded successfully to treatment. One episode of post-transplantation lymphoproliferative disease regressed after decreasing immunosuppression therapy and after acyclovir therapy. At the end of follow-up, 19 patients are without steroids. Immunosuppression therapy with Thymoglobuline is safe in the pediatric age group if the number of lymphocytes is monitored strictly.

Numerical simulation of a realistic total cavo-pulmonary connection: effect of unbalanced pulmonary resistances on hydrodynamic performance.

Total cavo pulmonary connection (TCPC) is one of the surgical techniques adopted to compensate the failure of the right heart in pediatric patients. The main goal of this procedure is the realization of a configuration for the caval veins and for the pulmonary arteries that can guarantee as low as possible pressure losses and appropriate lung perfusion. Starting from this point of view, a realistic TCPC with extracardiac conduit (TECPC) is investigated by means of Computational Fluid Dynamics (CFD) to evaluate the pressure loss under different pressure conditions, simulating different vessel resistances, on the pulmonary arteries. A total flow of 3 L/min, with a distribution between the inferior vena cava (IVC) and the superior vena cava (SVC) equal to 6/4, was investigated; three different boundary conditions for the pressure were imposed, resulting in three simulations in steady-state conditions, to the right pulmonary artery (RPA) and to the left pulmonary artery (LPA), simulating a balanced (deltaP(LPA-RPA) = 0 mmHg) and two unbalanced pulmonary resistances to blood flow (a pressure difference deltaP(LPA-RPA) = +/- 2 mmHg, respectively). The geometry for the TECPC was realized according to MRI derived physiological values for the vessels and for the configuration adopted for the anastomosis (the extra-cardiac conduit was inclined 22 degrees towards the left pulmonary artery with respect to the IVC axis). The computed power losses agree with previous in vitro Particle Image Velocimetry investigations. The results show that a higher resistance on the LPA causes the greater pressure loss for the TECPC under study, while the minimum pressure loss can be achieved balancing the pulmonary resistances, subsequently obtaining a balanced flow repartition towards the lungs.

Does chronic pacing affect exercise capacity after Mustard operation for transposition of the great arteries?

Late survival after Mustard repair of transposition of the great arteries is generally good but is often characterized by progressive deterioration of ventricular function and by late postsurgical arrhythmias, thus imposing the need for permanent pacing. To evaluate how chronic pacing affects long-term exercise capacity, we compared two groups of these patients: group 1, comprising 12 patients, aged 9.0 +/- 2.6 years, without pacemaker; and group 2, comprising 18 patients, aged 9.3 +/- 2.0 years, with pacemaker. Patient evaluation included history, physical examination electrocardiograph, Holter monitoring, and echocardiography. Pacing modes were as follows: AAI (6 patients), AAIR (9 patients), VVI (2 patients), and VVIR (1 patient). At exercise test we evaluated exercise tolerance, maximum heart rate, blood pressure, oxygen consumption, and cardiac output at rest and at peak exercise. The two groups were comparable for all variables examinated. All pacemakers showed normal function. During the exercise, 11 of 12 patients in group 1 showed sinus rhythm, and in group 2, 11 patients showed sinus rhythm, 5 junctional rhythm, and 2 continuous pacing. There were no significant differences between groups. Chronically paced Mustard patients but with restoration of spontaneous rhythm during the exercise test do not show reduced exercise tolerance in comparison with nonpaced Mustard patients.

Pulmonary atresia with ventricular septal defect: prevalence of deletion 22q11 in the different anatomic patterns.

BACKGROUND: Pulmonary atresia with ventricular septal defect (PA-VSD) is one of the most common cardiac defects associated with DiGeorge syndrome. The pattern of the pulmonary circulation determines the complexity of this type of heart disease. The aim of this study was to establish the prevalence of DiGeorge syndrome with deletion 22q11 in patients with simple and complex PA-VSD. METHODS: Since 1993 we have studied 128 consecutive patients affected by PA-VSD. In 90 of our patients the PA-VSD was considered "simple" (group I), because it was not associated with any other cardiac defects. In the other 38 children the PA-VSD was considered "complex" (group II) owing to the presence of heterotaxia, tricuspid atresia, a double-inlet left ventricle, transposition of the great arteries and congenitally corrected transposition of the great arteries. RESULTS: In group I, 38 patients (42%) had genetic syndromes or major extracardiac anomalies; deletion 22q11 was detected in 31% of cases. Major aortopulmonary collateral arteries were present in 50% of group I patients and in 57% of those with deletion 22q11. In group II, 10 patients (26%) had genetic syndromes or major extracardiac anomalies but none had deletion 22q11 (p < 0.005); in no case was the presence of major aortopulmonary collateral arteries observed (p < 0.005). CONCLUSIONS: PA-VSD is an anatomically and morphogenetically heterogeneous disease: in the setting of DiGeorge syndrome or velocardiofacial syndrome, PA-VSD is associated with a peculiar cardiac pattern and is due to deletion 22, whereas in case of nonsyndromic PA-VSD or when this disease is associated with different syndromes or with other types of cardiac defects, it is due to other morphogenetic mechanisms.

A mathematical model of the fetal cardiovascular system based on genetic algorithms as identification technique.

The development of fetal cardiac surgery, considered the ultimate goal in the treatment of congenital cardiac malformations, needs to be supported by detailed knowledge of the blood circulation in the fetal cardiovascular system. The hemodynamic behavior in distal territories is usually inferred from vessel resistance indices, which give limited physiological information. This study presents a mathematical model of the human fetal global cardiovascular system, developed to clarify the relationships and differences existing between upper and lower body circulation. We modelled the heart with two time-varying capacitances, each representing the respective ventricle's pressure-volume relationship. The fetal vascular system was represented using two six-element Windkessel models, for the upper and lower body respectively. We obtained the identification of the set of circuital and elastance function parameters of the model using Genetic Algorithms (GAs), which follow the laws of evolutionary theory. We compared the results of our numerical study on the model identified with data collected from measurements and literature, to validate the proposed global cardiovascular system model of the human fetus. This model is intended as an instrument to investigate the differences in blood distribution between the different vascular districts in the upper and lower fetal body and the role of the aortic isthmus, the small tract of vessel connecting upper and lower fetal vascular beds; it may also represent a useful tool in the assessment of dynamic balance during mechanical assistance of circulation.

Transposition with absent pulmonary valve syndrome: early repair of a rare case.

The congenital absence of the pulmonary valve cusps can occur either isolated or in association with other heart lesions. We report a very rare case of a 40-day-old infant with transposition of the great arteries, ventricular septal defect, pulmonary annular stenosis, absent pulmonary valve and aneurysmal dilation of the central pulmonary arteries, who received surgical treatment at our institution.

Minimally invasive or interventional repair of atrial septal defects in children: experience in 171 cases and comparison with conventional strategies.

OBJECTIVES: The goal of this study was to evaluate percutaneous interventional and minimally invasive surgical closure of secundum atrial septal defect (ASD) in children. BACKGROUND: Concern has surrounded abandoning conventional midline sternotomy in favor of the less invasive approaches pursuing a better cosmetic result and a more rational resource utilization. METHODS: A retrospective analysis was performed on the patients treated from June 1996 to December 1998. RESULTS: One hundred seventy-one children (median age 5.8 years, median weight 22.1 kg) underwent 52 device implants, 72 minimally invasive surgical operations and 50 conventional sternotomy operations. There were no deaths and no residual left to right shunt in any of the groups. The overall complication rate causing delayed discharge was 12.6% for minimally invasive surgery, 12.0% for midline sternotomy and 3.8% for transcatheter device closure (p < 0.01). The mean hospital stay was 2.8 +/- 1.0 days, 6.5 +/- 2.1 days and 2.1 +/- 0.5 days (p < 0.01); the skin-to-skin time was 196 +/- 43 min, 163 +/- 46 min and 118 +/- 58 min, respectively (p < 0.001). Extracorporeal circulation time was 49.9 +/- 10.1 min in the minithoracotomy group versus 37.2 +/- 13.8 min in the sternotomy group (p < 0.01) but without differences in aortic cross-clamping time. Sternotomy was the most expensive procedure (15,000 EUR +/- 1,050 EUR vs. 12,250 EUR +/- 472 EUR for minithoracotomy and 13,000 EUR +/- 300 EUR for percutaneous devices). CONCLUSIONS: While equally effective compared with sternotomy, the cosmetic and financial appeal of the percutaneous and minimally invasive approaches must be weighed against their greater exposure to technical pitfalls. Adequate training is needed if a strategy of surgical or percutaneous minimally invasive closure of ASD in children is planned in place of conventional surgery.

Aortopulmonary window coexisting with tetralogy of Fallot.

Aortopulmonary window is a rare cardiac malformation presenting either in the isolated form, or in association with other cardiac anomalies. The isolated form usually presents an increased pulmonary blood flow as the main clinical feature, but if associated with other cardiac anomalies the clinical findings change according to the additional defect. Only 19 cases of aortopulmonary window associated with tetralogy of Fallot have been reported. Five of them have associated pulmonary atresia. We report two neonatal cases of aortopulmonary window and tetralogy of Fallot, one of them presenting an associated pulmonary atresia.

Particle image velocimetry analysis of the flow field in the total cavopulmonary connection.

The total cavopulmonary connection (TCPC) is a common operation, meant to restore a proper pulmonary blood flow in heart defects with only one functional ventricle. It consists of the direct connection of the venae cavae to the pulmonary arteries in a cross-shaped disposition which entails a peculiar hemodynamics: Side effects can occur, such as recirculation zones and pressure drop across the connection. Our study is aimed at the quantitative investigation of the flow field of a successful Fontan-type operation, in view of the clinical importance of assuring a nearly physiological pulmonary blood flow, especially if one considers that many pediatric patients are eligible for this operation. A glass-blown TCPC phantom, realized according to nuclear magnetic resonance data, was employed in a steady-flow loop. Thus, a realistic model of this Fontan-type operation was realized using materials which enable advanced measurement techniques such as particle image velocimetry (PIV). The mean flow rates at each branch of the cavopulmonary shunt could be independently varied with a vertical shift of the corresponding upstream reservoir. The PIV technique was used successfully in identifying the flow field characteristics. The flow field in this TCPC topology was shown to be well organized and regulated by the presence of a vortex at the confluence of the venae cavae. The effect of different loading conditions, which realistically can be found in vivo, is studied with a high spatial resolution, showing the possibility to use pulmonary resistance as a parameter in designing the surgical geometry.

Right submammary minithoracotomy for repair of congenital heart defects.

OBJECTIVE: The initial experience with the right submammary minithoracotomy incision for correction of intracardiac congenital defects is reported. METHODS: Between March 1997 and March 1999, 100 children underwent repair of congenital heart disease through this approach. Their mean age and weight were 4.6 years and 20 kg, respectively. Diagnosis included: atrial septal defect (78), ventricular septal defect (7), tetralogy of Fallot (6), partial atrioventricular canal (5), double-chambered right ventricle (3) and single ventricle with dextrocardia (1). The standard technique entailed a 5 to 6 cm right submammary incision, entering the chest through the third or fourth intercostal space (depending on the body weight), direct aortic and bicaval cannulation and aortic cross-clamping with cardioplegic protection. RESULTS: There were no hospital deaths. Postoperative morbidity included bleeding in two cases, recurrent atrial septal defect in one, spleen injury in one. The average hospital stay was 3.5 days. All patient are currently free of symptoms and medications. CONCLUSIONS: (1) This approach for repair of selected congenital cardiac malformations is technically feasible, safe and effective; (2) younger age is a facilitating factor; (3) hospital stays are effectively reduced.

Elevated plasma homocysteine concentrations after pediatric heart transplantations.

Graft coronary artery vasculopathy is the main cause of late morbidity and mortality in cardiac allograft recipients. A high plasma homocysteine (hcy) concentration is now generally accepted as a risk factor for coronary arteriosclerosis, but little information exists for the pediatric age group. We therefore explored the potential role of hcy and antioxidants in 31 pediatric allograft recipients. We found hcy concentrations to be significantly higher in recipients than in control. Hcy continued to rise within the first 2 postoperative years. Vitamin A and E concentrations were significantly lower in transplant patients. Hyperhomocysteinemia was significantly more common in patients with complications than in those without. Our findings suggest that pediatric allograft recipients experience oxidant stress, as highlighted by the high plasma levels of Hcy and the low concentrations of vitamins A and E. Nutritional supplementation may be indicated to lower plasma hcy and to reduce oxidant stress.