The multisystem nature of isomerism: left isomerism complicated by Abernethy malformation and portopulmonary hypertension.

Isomerism, also referred to as "heterotaxy" is a complex set of anatomic and functional perturbations. One of the most obvious manifestations of isomerism is the disturbance of organ arrangement, such that the thoracic organs are no longer asymmetric on the left and right. We report the case of a 14-year-old female in whom exercise-induced dyspnea led to a late diagnosis of left isomerism complicated by Abernethy malformation and portopulmonary hypertension. A comprehensive evaluation revealed two anatomic left lungs and hyparterial bronchi, bilateral left atria, an interrupted inferior caval vein with azygos continuation, multiple spleens, sinus node dysfunction, hepatic hypertrophy with focal nodular hyperplasia, and absence of the portal vein. Pulmonary vasodilator therapy was initiated resulting in clinical improvement. This case exhibits unique features including a late diagnosis of isomerism with Abernethy malformation and portopulmonary hypertension. The patient's presentation, medical workup, and future treatment emphasise the importance of multidisciplinary care in children with complex multisystem disease. We review the multiple cardiac and extracardiac manifestations of isomerism.

Preoperative Management of Neonates With Congenital Heart Disease.

Clinicians caring for neonates with congenital heart disease encounter challenges in clinical care as these infants await surgery or are evaluated for further potential interventions. The newborn with heart disease can present with significant pathophysiologic heterogeneity and therefore requires a personalized therapeutic management plan. However, this complex field of neonatal-cardiac hemodynamics can be simplified. We explore some of these clinical quandaries and include specific sections reviewing the anatomic challenges in these patients. We propose this to serve as a primer focusing on the hemodynamics and therapeutic strategies for the preoperative neonate with systolic dysfunction, diastolic dysfunction, excessive pulmonary blood flow, obstructed pulmonary blood flow, obstructed systemic blood flow, transposition physiology, and single ventricle physiology.

Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum.

Although most causes of death and morbidity in premature infants are related to immune maladaptation, the premature immune system remains poorly understood. We provide a comprehensive single-cell depiction of the neonatal immune system at birth across the spectrum of viable gestational age (GA), ranging from 25 weeks to term. A mass cytometry immunoassay interrogated all major immune cell subsets, including signaling activity and responsiveness to stimulation. An elastic net model described the relationship between GA and immunome (R=0.85, p=8.75e-14), and unsupervised clustering highlighted previously unrecognized GA-dependent immune dynamics, including decreasing basal MAP-kinase/NFκB signaling in antigen presenting cells; increasing responsiveness of cytotoxic lymphocytes to interferon-α; and decreasing frequency of regulatory and invariant T cells, including NKT-like cells and CD8+CD161+ T cells. Knowledge gained from the analysis of the neonatal immune landscape across GA provides a mechanistic framework to understand the unique susceptibility of preterm infants to both hyper-inflammatory diseases and infections.

Functional, quality of life, and neurodevelopmental outcomes after congenital cardiac surgery.

Throughout the past few decades, advances in cardiology, neonatal intensive care, and surgical techniques have resulted in a growing cohort of thriving school-aged children with previously lethal complex congenital heart diseases. While survival has increased, there remains significant morbidity following repair including neurodevelopmental sequelae. Compared to children with a structurally normal heart, these infants and children have a higher frequency of abnormalities in tone, feeding, and delayed developmental milestones, as well as challenges with speech and learning disabilities, while a higher proportion of adolescents suffer from problems with processing speed, executive function, and a unique set of medical hardships related to exercise intolerance and obesity, medication burden, and mental health comorbidities. Innovative perioperative techniques and early psychosocial intervention in these young survivors has shown that despite the obstacles, the majority of these children can grow to have fulfilling lives with intelligence and social skills in the normal range. Additionally, a comprehensive medical home aids in optimizing the quality of life for these children and their families.