Investigation into the 3D structure of the developing human fetal heart

Investigating the developmental processes of the human fetal heart is a challenging task. Few reports describe the morphological features during the first stage of heart maturation and consecutive developmental periods after cardiogenesis. Reasons for this include the difficulty of collecting suitable samples and the limitations of investigating modalities. This research was proposed to clarify the detailed morphological features of normal human fetal hearts in early-stage maturation, using post-mortem samples. These samples were analysed using high-resolution episcopic microscopy (HREM), and compared with the latest clinical imaging taken by 3D fetal echocardiography and compared with mouse samples. HREM, a newly-developed high-quality image modality, produces a computerbased 3D reconstruction which enables us to visualize detailed spatial structures of small specimens. HREM includes several procedural steps, which may affect the histological or morphological structures of samples, so I explored the potential effects. I found 12% shrinkage due to dehydration and polymerization. Therefore, while the general appearance of 3D reconstructed images looked identical to the pictures of the original heart samples, it is important to consider the effects of shrinkage when interpreting the morphological assessment by HREM. Normal human fetal hearts from the 9th to 11th weeks of postmenstrual gestation demonstrated unique morphological findings. Ventricular walls and trabeculations showed thick and random cellular structures. Atrioventricular and semilunar valves were also thick but histological maturation was observed within a few weeks after cardiogenesis. The great arterial walls were thick and comprised of dense cellular matrix. Morphologically, several characteristic findings, such as large atrial appendages, the developmental process of formation of the membranous ventricular septum and prominent coronary arteries, were recognised during this period. Heart size increased linearly with gestation. Normal human fetal hearts demonstrate geometrical development and histological and morphological maturation after the period of cardiogenesis. In comparison with human fetal hearts, mouse hearts demonstrate dramatic morphological alterations during a short maturation period. Fetal mouse hearts show some similar morphological findings to the human fetal heart, such as large atrial appendages, lack of formation of the membranous septum, and thickened great arterial walls. This suggests a shared mechanism of fetal heart maturation in mammals. Detailed clinical information regarding cardiac morphology is vital for accurate prenatal heart diagnosis in the first trimester. Fetal echocardiography in early gestation has become routine practice. However, the technical limitations of image acquisition and picture resolution make it difficult to visualize clear 3D images for fetal cardiac diagnosis. Current modalities for clinical investigation by 3D echocardiography do not have sufficient resolution to enable detailed morphological investigation of the human fetal heart between 10th to 12th weeks of postmenstrual gestation. Only the original data of the four-chamber view demonstrated no offsetting of the atrioventricular valves as seen on HREM. Further technical advances in 3D echocardiography will be required to enable precise cardiac diagnosis in the first trimester. This thesis describes morphological development in normal human fetal hearts for the first few weeks after cardiogenesis and contributes to a better understanding of the normal appearances in the first trimester which is vital for future investigation into the origin of congenital heart disease

Bilateral diaphragm paralysis after simultaneous cardiac surgery and Nuss procedure in the infant

AbstractThe case of a 15-month-old boy with bilateral diaphragm paralysis after simultaneous cardiac surgery for tetralogy of Fallot, and Nuss procedure for pectus excavatum, is presented. Extubated one day after his first operation, the boy suffered severe respiratory distress soon after, due to bilateral diaphragmatic paralysis. Diaphragm paralysis restricted abdominal respiration, while thoracic respiration was inhibited by metallic bar after the Nuss Procedure, which combined prevented extubation for 47 days. Thoracoplasty, such as the Nuss Procedure, should not be performed simultaneously with cardiac surgery because abdominal and thoracic respiration can be restricted in infants, causing prolonged, severe, post-surgical respiratory failure

Case report: Autonomic and endocrine response in the process of brain death in a child with hypoxic-ischemic brain injury

BackgroundThe causes of brain death include cerebral herniation and brainstem ischemia. Neuroendocrine failure or a series of autonomic nervous system disorders are clinically recognized in the transition to brain death among patients with critical brain injuries. An accurate evaluation of these physiologic instabilities and biomarkers is essential to assess the severity and prognosis of pediatric brain injury as well as to initiate supportive care. This case report presents a detailed evaluation of the autonomic nervous system and endocrine function during the transition to brain death in infantile hypoxic-ischemic brain injury by analyzing the heart rate variability and endocrine status.Case PresentationA 1-year-old previously healthy boy went into cardiac arrest after choking on a toy at home. Although spontaneous circulation returned 60 min after cardiopulmonary resuscitation, no cerebral activity or brainstem reflexes were observed after 18 hospital days. The heart rate variability was assessed by analyzing the generic electrocardiogram data. Rapid spikes or drops in the total power of the heart rate variability, accompanied by a cortisol surge, as well as an alternating surge of high- and low-frequency domain variables were detected in the process of brain death.ConclusionThe heart rate variability assessment combined with endocrine provides a better understanding of the clinical course of patients undergoing brain death. It accurately detects the loss of brainstem function, which allows physicians to provide the appropriate supportive care

Over-investigation and overtreatment in pediatrics: a survey from the European Academy of Paediatrics and Japan Pediatric Society

IntroductionAvoiding over-investigation and overtreatment in health care is a challenge for clinicians across the world, prompting the international Choosing Wisely campaign. Lists of recommendations regarding medical overactivity are helpful tools to guide clinicians and quality improvement initiatives. We aimed to identify the most frequent and important clinical challenges related to pediatric medical overactivity in Europe and Japan. Based on the results, we aim to establish a (European) list of Choosing Wisely recommendations.MethodsIn an online survey, clinicians responsible for child health care in Europe and Japan were invited to rate 18 predefined examples of medical overactivity. This list was compiled by a specific strategic advisory group belonging to the European Academy of Paediatrics (EAP). Participants were asked to rate on a Likert scale (5 as the most frequent/important) according to how frequent these examples were in their working environment, and how important they were considered for change in practice.ResultsOf 2,716 physicians who completed the survey, 93% (n = 2,524) came from 17 countries, Japan (n = 549) being the largest contributor. Pediatricians or pediatric residents comprised 89%, and 51% had 10–30 years of clinical experience. Cough and cold medicines, and inhaled drugs in bronchiolitis were ranked as the most frequent (3.18 and 3.07 on the Likert scale, respectively), followed by intravenous antibiotics for a predefined duration (3.01), antibiotics in uncomplicated acute otitis media (2.96) and in well-appearing newborns. Regarding importance, the above-mentioned five topics in addition to two other examples of antibiotic overtreatment were among the top 10. Also, IgE tests for food allergies without relevant medical history and acid blockers for infant GER were ranked high.ConclusionOvertreatment with antibiotics together with cough/cold medicines and inhaled drugs in bronchiolitis were rated as the most frequent and important examples of overtreatment across countries in Europe and Japan