Autoimmune Lymphoproliferative Syndrome: an Update and Review of the Literature

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by immune dysregulation due to a defect in lymphocyte apoptosis. The clinical manifestations may be noted in multiple family members and include lymphadenopathy, splenomegaly, increased risk of lymphoma and autoimmune disease, which typically involve hematopoietic cell lines manifesting as multilineage cytopenias. Since the disease was first characterized in the early 1990s, there have been many advances in the diagnosis and management of this syndrome. The inherited genetic defect of many ALPS patients has involved (FAS) pathway signaling proteins, but there remain those patients who carry undefined genetic defects. Despite ALPS having historically been considered a primary immune defect presenting in early childhood, adult onset presentation is increasingly becoming recognized, and more so in genetically undefined patients and those with somatic FAS mutations. Thus, future research may identify novel pathways and/or regulatory proteins important in lymphocyte activation and apoptosis

Toll-like receptors (TLRs) and mannan-binding lectin (MBL): On constant alert in a hostile environment

In the beginning were neither B cells nor T cells nor antibodies, but innate immune defense alone. The primary functional theme of innate immunity is the distinction between self and non-self, which is maintained by a vast number of cellular and subcellular components. In this context, the immense importance of the Toll-like receptors (TLRs) is well established. Positive (Darwinian) selection seems to be acting on the ligand-binding domains of these molecules, suggesting a selection pattern similar to that previously observed in the MHC proteins. In sharp contrast to TLRs, the biological significance of mannan-binding lectin (MBL) is controversial, and, concerning humans, it has been suggested that low concentration of MBL in serum represents a selective advantage. In this mini-review, based on a doctoral thesis, evolutionary aspects of TLRs and MBL are discussed

Transcatheter pulmonary valve perforation using chronic total occlusion wire in pulmonary atresia with intact ventricular septum

Background: Perforation of pulmonary valve using radiofrequency ablation in pulmonary atresia with intact ventricular septum (PA IVS) is a treatment of choice. However, significant cost of the equipment limits its utility, especially in the developing economies. Objective: To assess the feasibility, safety, and efficacy of perforation of pulmonary valve using chronic total occlusion (CTO) wires in patients with PA IVS as an alternative to radiofrequency ablation. Methods: This is a single.center, nonrandomized, retrospective study conducted during June 2008 to September 2015. Twenty-four patients with PA IVS were selected for the procedure during the study period. The median age and weight of the study population were 8. days and 2.65 kg, respectively. Four patients were excluded after right ventricular angiogram as they showed right ventricular-dependent coronary circulation. The pulmonary valve perforation was attempted using various types of CTO wires based on the tip load with variable penetrating characteristics. Results: The procedure was successful in 16 of twenty patients using CTO wires: Shinobi in nine, Miracle in four, CROSS-IT in two, and Conquest Pro in one. Two patients had perforation of right ventricular outflow tract (RVOT). Pericardiocentesis was required in one patient to relieve cardiac tamponade. Later, the same patient underwent successful hybrid pulmonary valvotomy. The other patient underwent ductus arteriosus. (DA) stenting. Balloon atrial septostomy was needed in three cases with systemic venous congestion. Desaturation was persistent in five cases necessitating DA or RVOT stenting to augment pulmonary blood flow. There were two early and two late deaths. The mean follow-up was 22.66. ± 16 months. Three patients underwent one and half ventricle repair and one Blalock-Taussig shunt during follow-up. Conclusion: Perforation of the pulmonary valve can be done successfully using CTO wires in selected cases of pulmonary atresia with intact ventricular septum

Diagnosis and management of aorto-left ventricular tunnel

Background: Aorto-left ventricular tunnel (ALVT) is a rare congenital extracardiac channel with progressive left ventricular dilatation needs early correction. Materials and Methods: This is a report of diagnosis and management of aorto-left ventricular tunnel (ALVT) over a period of 11 years from a single institution. Seven patients (age range: 7 days-45 years) presented with heart failure. The diagnosis of ALVT was made by transthoracic echocardiogram in all cases. Results: Treatment was refused by two patients who died during follow-up. Surgical closure of the tunnel was done in four cases, of which one needed Bentall procedure. Two patients had residual leak after the surgery. Transcatheter closure using Amplatzer muscular device was performed in two cases (for postoperative residual leak in one and primary procedure in the other). Significant hemolysis developed in one of them, necessitating the removal of the device and closed surgically. This child underwent aortic valve replacement two years later. All the remaining patients were doing well during the median follow-up of 30 months (range: 1.5-9 years). Conclusion: ALVT is a rare and potentially fatal anomaly that is ideally managed surgically. Catheter closure has a limited role