Search

MR1-restricted mucosal-associated invariant T (MAIT) cells play a unique role in the immune system. These cells develop intrathymically through a three-stage process, but the events that regulate this are largely unknown. Here, using bulk and single-cell RNA sequencing–based transcriptomic analysis in mice and humans, we studied the changing transcriptional landscape that accompanies transition through each stage. Many transcripts were sharply modulated during MAIT cell development, including SLAM (signaling lymphocytic activation molecule) family members, chemokine receptors, and transcription factors. We also demonstrate that stage 3 “mature” MAIT cells comprise distinct subpopulations including newly arrived transitional stage 3 cells, interferon-γ–producing MAIT1 cells and interleukin-17–producing MAIT17 cells. Moreover, the validity and importance of several transcripts detected in this study are directly demonstrated using specific mutant mice. For example, MAIT cell intrathymic maturation was found to be halted in SLAM-associated protein (SAP)–deficient and CXCR6-deficient mouse models, providing clear evidence for their role in modulating MAIT cell development. These data underpin a model that maps the changing transcriptional landscape and identifies key factors that regulate the process of MAIT cell differentiation, with many parallels between mice and humans.

BackgroundThe global myocardial stress response during cardiac surgery has not been systematically studied, nor is it known whether the response of the neonatal myocardium is intrinsically different from that of older children. To determine the age-related molecular basis of this response, we conducted microarray-based differential gene expression profiling on right ventricular tissue samples acquired in patients of varying ages with right ventricular outflow tract obstruction.MethodsWe studied gene expression profiles in 24 patients during operations for lesions involving right ventricular outflow tract obstruction age stratified into group I (7 patients, aged 5 to 66 days; mean, 30 days) and group II (17 patients, aged 4 months to 12.5 years; mean, 2.8 years). Myocardial samples were taken from the right ventricular outflow tract after aortic occlusion and archived in liquid nitrogen. RNA isolation, fluorescence labeling of complementary DNA, hybridization to spotted arrays containing 19,008 characterized or unknown human complementary DNAs, and quantitative fluorescence scanning of gene-expression intensity were performed at the University of Toronto Health Network Microarray Centre. Data were analyzed with the Significance Analysis for Microarrays program. Minimum Information About Microarray Experiments–compliant, log2-normalized data sets were compared to ascertain potential statistical differences in gene expression between patient groups.ResultsThere were no hospital deaths or major postoperative morbid events. We identified 50 transcripts differentially expressed in the neonatal group (the predicted false discovery rate was

In 1908, Alexander I. Ignatowski (1875-1955) published his pioneering work that first revealed a relationship between cholesterol-rich food and experimental atherosclerosis. This early experimental work paved a way to the metabolic study of the mechanism of atherosclerosis. Herein, we present a brief account of Ignatowski's work and life.

Papillary fibroelastomas are benign cardiac tumors that involve cardiac valves. These tumors are usually asymptomatic and are found incidentally during cardiac surgery or during echocardiographic evaluation in a patient who exhibits cardiac symptoms. However, these tumors may cause major thromboembolic complications. Herein, we describe the surgical management of a patient who had an unusual appearance and location of a papillary fibroelastoma that was attached to the interventricular septum.

Aortic valve replacement is the standard surgical procedure for severe aortic regurgitation. Due to advances over the past decade, there have been substantial improvements in aortic root graft design, in aortic valve repair techniques, and in the understanding of valvular function in the remodeled aortic root. Herein, we describe the case of a dyspneic patient with an asymmetric bicuspid aortic valve who underwent valve-sparing aortic root replacement and tricuspidization. The patient subsequently resumed strenuous physical activity and was asymptomatic 2 years after the operation.

Taussig-Bing anomaly is a rare congenital heart malformation that was first described in 1949 by Helen B. Taussig (1898–1986) and Richard J. Bing (1909–). Although substantial improvement has since been achieved in surgical results of the repair of the anomaly, management of the Taussig-Bing anomaly remains challenging. A history of the original description of the anomaly, the life stories of the individuals who first described it, and the current outcomes of its surgical management are reviewed herein.

Mitral valve repair has become an established treatment in adults, but there is limited experience with the procedure in children, in whom the avoidance of a valve prosthesis is particularly advantageous. Repair of the mitral valve in children who have Marfan syndrome is especially difficult due to the presence of generalized connective tissue disorder, which may lead to future elongation and rupture of chordae tendineae that were unaffected at the time of mitral valve repair. We performed a total augmentation of all segments of the mitral valve, using artificial chordae tendineae. Herein, we describe the procedure and the positive outcome in a 10-year-old girl.

A patient with healed prosthetic endocarditis, severe calcification of the mitral annulus, and multiple mitral periprosthetic leaks underwent double-valve replacement, with reconstruction of the intervalvular fibrous body. Placing sutures through healthy autologous tissues from outside the heart enabled secure replacement of the mitral prosthesis. This technique avoids extensive circumferential reconstruction of the mitral annulus.

We present a brief summary of the 10 greatest cardiologic developments and discoveries of the 20th century Described are electrocardiography; preventive cardiology and the Framingham Study; "lipid hypotheses" and atherosclerosis; coronary care units; echocardiography; thrombolytic therapy; cardiac catheterization and coronary angiography; open-heart surgery; automatic implantable cardiac defibrillators; and coronary angioplasty. These topics are the personal choices of the authors.

Yustin Y. Djanelidze is one of the little-known pioneers of cardiac surgery in the 20th century. He successfully sutured a penetrating injury of the ascending aorta in St. Petersburg, Russia, on 27 October 1913. To the best of our knowledge, this was the 1st case of ascending aorta repair described in the world medical literature.

ObjectivesThis study examined survival after surgical palliation in children with single-ventricle physiology.BackgroundContemporary surgical outcomes for the entire population of newborns undergoing single-ventricle palliation are unclear.MethodsIn a single-center review of 499 consecutive patients undergoing univentricular palliation from 1990 to 2008, predictors of mortality were determined using multivariate risk analysis, stratified for each post-operative stay and interim states.ResultsAfter 2000, the population comprised more patients with dominant right ventricle (66% vs. 36%) and hypoplastic left heart syndrome (HLHS) (47% vs. 13%). Median age at bidirectional cavopulmonary shunt (BCPS) decreased from 15 months (10 to 22 months) before 2000 to 4 months (3.3 to 9 months) thereafter. Survival rates at 1, 5, and 10 years were, respectively, 82% (95% confidence interval [CI]: 79% to 85%), 74% (95% CI: 70% to 78%), and 71% (95% CI: 67% to 75%). Throughout the study, atrioventricular valve regurgitation (hazard ratio [HR]: 1.8; p = 0.008), not having transposition (HR: 2.0; p = 0.013), and heterotaxia (HR: 2.0; p = 0.026) were predictors of mortality. The most potent risk factor was right ventricular (RV) dominance (HR: 2.2; p = 0.001) because of its impact before BCPS. HR for death in patients with RV dominance went from 2.8 (95% CI: 1.4 to 5.7; p = 0.005) before BCPS to 1.0 (95% CI: 0.5 to 2.1; p = 0.98) thereafter. Survival of patients with RV dominance, adjusted for the risk factors noted here, improved over the study period (p = 0.001).ConclusionsConsiderable mortality is still observed during the first years of life among patients with single ventricle. RV dominance is the most important risk factor for death but only before BCPS.

ObjectivesThe study sought to evaluate the late outcomes of a policy of transatrial repair delayed beyond the neonatal period.BackgroundLong-term outcomes of transatrial repair of tetralogy of Fallot are unknown.MethodsThe records of 675 consecutive patients undergoing a transatrial repair of tetralogy of Fallot between 1980 and 2005 were reviewed, their follow-up updated and survival confirmed from national death registries. One-third (220 of 675) had undergone previous palliation. Median age at repair was 2 years in the first 8 years, and 1 year from 1988 onward. A transannular incision was performed in 75% of cases and autologous pericardium was the material used to patch this incision in 92% of cases.ResultsThere were 7 hospital deaths (1%). Eight patients died during follow-up (2 sudden unexpected and 6 noncardiac deaths). Mean follow-up was 11.7 ± 6.3 years. Twenty-five years' survival was 97% (95% confidence interval [CI]: 95% to 98%). Twenty-five years' freedom from implantation of a valved conduit was 84.6% (95% CI: 77.8% to 89.5%). By multivariable analysis, prior palliation and younger age at repair were predictive of implantation of a valved conduit (hazard ratio: 2.4, 95% CI: 1.3 to 4.6, p = 0.008; hazard ratio: 0.70, 95% CI: 0.50 to 0.96, p = 0.03, respectively).ConclusionsDuring long-term follow-up, transatrial repair of tetralogy of Fallot was associated with a minimal risk of sudden death and low rate of reintervention for right ventricular dilation and residual outflow tract obstruction.