No abstract

Palliative Potts shunt allows prolonged survival and dramatic, long-lasting improvement in functional capacities in children with severe, drug-refractory PAH. The Potts shunt might be considered as a first surgical or interventional step in the management of children with severe, drug-refractory PAH, leaving the door open for further lung transplantation, if needed.

Patients with SS have a high overall survival. Survival probability was lower in patients with associated CHDs and in patients with pulmonary hypertension. Surgical treatment of SS is beneficial in reducing symptoms, however, given the significant risk of post-operative scimitar drainage stenosis/occlusion, it should be tailored to a comprehensive haemodynamic evaluation and to the patient's age.

Objectives: Identification of variables influencing surgical outcome in patients treated for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. Methods: A total of 90 consecutive patients (median age, 12 months; range, 20 days to 35 years), who had primarily undergone either 1-stage unifocalization (n ¼ 69) or palliation to promote native pulmonary arterial development (n ¼ 21), were studied. Chromosome 22q11 deletion had occurred in 37% of the cases. Ventricular septal defect closure was accomplished in 70 patients (78%), with a mean postoperative right/left ventricular pressure ratio of 0.48 AE 0.14. Results: The rate of 14-year survival, freedom from conduit reintervention, and freedom from percutaneous intervention on the pulmonary arteries was 75%, 46%, and 52%, respectively. At a median interval of 95 months (range, 1.5-164 months), the right/left ventricular pressure ratio did not differ significantly from early postoperatively. Univariate analysis showed that an absence of confluent intrapericardial pulmonary arteries favorably affected the postoperative right/left ventricular pressure ratio after ventricular septal defect closure (P ¼ .04). Kaplan-Meier estimates showed age of 30 days or younger (P ¼ .0004) and weight of 3 kg or less (P ¼ .0004) at unifocalization and chromosome 22q11 deletion (P ¼ .001) significantly affected survival. Chromosome 22q11 deletion was significantly associated with mortality, even in the Cox regression model (hazard ratio, 8.26; P ¼ .003). Finally, ventricular septal defect closure during single-stage and single/multiple-stage procedures significantly correlated with both early (P ¼ .0013 and P < .00001, respectively) and overall (P ¼ .013 and P ¼ .0007, respectively) survival. Conclusions: The results of surgery were satisfactory and durable, despite the need for repeated percutaneous or surgical reinterventions. The outcomes were negatively affected by neonatal age and low body weight and positively affected by simultaneous or staged ventricular septal defect closure. Finally, chromosome 22q11 deletion remained an independent variable affecting survival.

The thymus plays a fundamental role in establishing and maintaining central and peripheral tolerance and defects in thymic architecture or AIRE expression result in the development of autoreactive lymphocytes. Patients with partial DiGeorge Syndrome (pDGS) and Down Syndrome (DS) present alterations in size and architecture of the thymus and higher risk to develop autoimmunity. We sought to evaluate thymic architecture and thymocyte development in DGS and DS patients and to determine the extent to which thymic defects result in immune dysregulation and T cell homeostasis perturbation in these patients. Thymi from pediatric patients and age-matched controls were obtained to evaluate cortex and medullary compartments, AIRE expression and thymocyte development. In the same patients we also characterized immunophenotype of peripheral T cells. Phenotypic and functional characterization of thymic and peripheral regulatory T (Treg) cells was finally assessed. Histologic analysis revealed peculiar alterations in thymic medulla size and maturation in DGS and DS patients. Perturbed distribution of thymocytes and altered thymic output was also observed. DGS patients showed lower mature CD4+ and CD8+ T cell frequency, associated with reduced proportion and function of Tregs both in thymus and peripheral blood. DS patients showed increased frequency of single positive (SP) thymocytes and thymic Treg cells. However, Tregs isolated both from thymus and peripheral blood of DS patients showed reduced suppressive ability. Our results provide novel insights on thymic defects associated with DGS and DS and their impact on peripheral immune dysregulation. Indeed, thymic abnormalities and defect in thymocyte development, in particular in Treg cell number and function could contribute in the pathogenesis of the immunodysregulation present in pDGS and in DS patients.

Specific types and subtypes of cardiac defects have been described in children with 22q11.2 deletion syndrome as well as in other genetic syndromes. The conotruncal heart defects occurring in patients with 22q11.2 deletion syndrome include tetralogy of Fallot, pulmonary atresia with ventricular septal defect, truncus arteriosus, interrupted aortic arch, isolated anomalies of the aortic arch, and ventricular septal defect. These conotruncal heart defects are frequently associated in this syndrome with additional cardiovascular anomalies of the aortic arch, pulmonary arteries, infundibular septum, and semilunar valves complicating cardiac anatomy and surgical treatment. In this review we describe the surgical anatomy, the operative treatment, and the prognostic results of the cardiac defects associated with 22q11.2 deletion syndrome. According to the current literature, in patients with tetralogy of Fallot with/without pulmonary atresia and truncus arteriosus, in spite of the complex cardiac anatomy, the presence of 22q11.2 deletion syndrome does not worsen the surgical prognosis. On the contrary in children with pulmonary atresia with ventricular septal defect and probably in those with interrupted aortic arch the association with 22q11.2 deletion syndrome is probably a risk factor for the operative treatment. The complex cardiovascular anatomy in association with depressed immunological status, pulmonary vascular reactivity, neonatal hypocalcemia, bronchomalacia and broncospasm, laryngeal web, and tendency to airway bleeding must be considered at the time of diagnosis and surgical procedure. Specific diagnostic, surgical, and perioperative protocols should be applied in order to provide appropriate treatment and to reduce surgical mortality and morbidity.

The population of neonates and children with congenital heart defects presents about a 30% prevalence of associated genetic syndrome or additional extracardiac anomalies and may show an increased risk of death or major complication at cardiac surgery. Since a well-defined pattern of combined cardiac and extracardiac anomalies may be found in relation to specific genetic defects, correct understanding of the genetic issues may help improving diagnosis, surgical approach and final outcome of these patients. Hereby we review the medical and surgical issues correlated to the genetic asset in patients with congenital heart defects and genetic syndromes, including trisomy 21, deletion 22q11, Noonan/LEOPARD, Turner, Marfan and Williams syndromes. Recognition of specific surgical risk factors can lead to the preparation of specific diagnostic and perioperative protocols in order to reduce operative mortality and morbidity.

Congenital heart diseases (CHDs) and cardiovascular abnormalities are one of the pillars of clinical diagnosis of 22q11.2 deletion syndrome (22q11.2DS) and still represent the main cause of mortality in the affected children. In the past 30 years, much progress has been made in describing the anatomical patterns of CHD, in improving their diagnosis, medical treatment, and surgical procedures for these conditions, as well as in understanding the underlying genetic and developmental mechanisms. However, further studies are still needed to better determine the true prevalence of CHDs in 22q11.2DS, including data from prenatal studies and on the adult population, to further clarify the genetic mechanisms behind the high variability of phenotypic expression of 22q11.2DS, and to fully understand the mechanism responsible for the increased postoperative morbidity and for the premature death of these patients. Moreover, the increased life expectancy of persons with 22q11.2DS allowed the expansion of the adult population that poses new challenges for clinicians such as acquired cardiovascular problems and complexity related to multisystemic comorbidity. In this review, we provide a comprehensive review of the existing literature about 22q11.2DS in order to summarize the knowledge gained in the past years of clinical experience and research, as well as to identify the remaining gaps in comprehension of this syndrome and the possible future research directions.