A novel activation-induced cytidine deaminase (AID) mutation in Brazilian patients with hyper-IgM type 2 syndrome.

Activation-induced cytidine deaminase (AID) is a DNA editing protein that plays an essential role in three major events of immunoglobulin (Ig) diversification: somatic hypermutation, class switch recombination and Ig gene conversion. Mutations in the AID gene (AICDA) have been found in patients with autosomal recessive Hyper-IgM (HIGM) syndrome type 2. Here, two 9- and 14-year-old Brazilian sisters, from a consanguineous family, were diagnosed with HIGM2 syndrome. Sequencing analysis of the exons from AICDA revealed that both patients are homozygous for a single C to G transversion in the third position of codon 15, which replaces a conserved Phenylalanine with a Leucine. To our knowledge, this is a new AICDA mutation found in HIGM2 patients. Functional studies confirm that the homologous murine mutation leads to a dysfunctional protein with diminished intrinsic cytidine deaminase activity and is unable to rescue CSR when introduced in Aicda(-/-)stimulated murine B cells. We briefly discuss the relevance of AICDA mutations found in patients for the biology of this molecule.

The Anaortic Technique with Bilateral Internal Thoracic Artery Grafting - Filling the Gap in Coronary Artery Bypass Surgery.

Coronary artery bypass grafting (CABG) has consolidated its role as the most effective procedure for treating patients with advanced atherosclerotic coronary artery disease, reducing the long-term risk of myocardial infarction and death compared to other therapies and relieving angina. Despite the recognized benefits afforded by surgical myocardial revascularization, a subset of higher-risk patients bears a more elevated risk of perioperative stroke. Stroke remains the drawback of conventional CABG and has been strongly linked to aortic manipulation (cannulation, cross-clamping, and side-biting clamping for the performance of proximal aortic anastomoses) and the use of cardiopulmonary bypass. Adoption of off-pump CABG (OPCAB) is demonstrated to lower the risk of perioperative stroke, as well as reducing the risk of short-term mortality, renal failure, atrial fibrillation, bleeding, and length of intensive care unit stay. However, increased risk persists owing to the need for the tangential ascending aorta clamping to construct the proximal anastomosis. The concept of anaortic (aorta no-touch) OPCAB (anOPCAB) stems from eliminating ascending aorta manipulation, virtually abolishing the risk of embolism caused by aortic wall debris into the brain circulation. The adoption of anOPCAB has been shown to further decrease the risk of postoperative stroke, especially in higher-risk patients, entailing a step forward and a refinement of outcomes provided by the primeval OPCAB technique. Therefore, anOPCAB has been the recommended technique in patients with cerebrovascular disease and/or calcification or atheromatous plaque in the ascending aorta and should be preferred in patients with high-risk factors for neurological damage and stroke.

The Anaortic Technique with Bilateral Internal Thoracic Artery Grafting - Filling the Gap in Coronary Artery Bypass Surgery

Abstract Coronary artery bypass grafting (CABG) has consolidated its role as the most effective procedure for treating patients with advanced atherosclerotic coronary artery disease, reducing the long-term risk of myocardial infarction and death compared to other therapies and relieving angina. Despite the recognized benefits afforded by surgical myocardial revascularization, a subset of higher-risk patients bears a more elevated risk of perioperative stroke. Stroke remains the drawback of conventional CABG and has been strongly linked to aortic manipulation (cannulation, cross‐clamping, and side-biting clamping for the performance of proximal aortic anastomoses) and the use of cardiopulmonary bypass. Adoption of off-pump CABG (OPCAB) is demonstrated to lower the risk of perioperative stroke, as well as reducing the risk of short-term mortality, renal failure, atrial fibrillation, bleeding, and length of intensive care unit stay. However, increased risk persists owing to the need for the tangential ascending aorta clamping to construct the proximal anastomosis. The concept of anaortic (aorta no-touch) OPCAB (anOPCAB) stems from eliminating ascending aorta manipulation, virtually abolishing the risk of embolism caused by aortic wall debris into the brain circulation. The adoption of anOPCAB has been shown to further decrease the risk of postoperative stroke, especially in higher-risk patients, entailing a step forward and a refinement of outcomes provided by the primeval OPCAB technique. Therefore, anOPCAB has been the recommended technique in patients with cerebrovascular disease and/or calcification or atheromatous plaque in the ascending aorta and should be preferred in patients with high-risk factors for neurological damage and stroke.