New approach to establish a surgical planning in infantile vallecular cyst synchronous with laryngomalacia based on aerodynamic analysis.

BACKGROUND AND OBJECTIVES: A large proportion of infants with vallecular cyst (VC) have coexisting laryngomalacia (LM). Feeding difficulties, regurgitation, occasional cough, and sleep-disordered breathing are the common symptoms in moderate to severe cases. The surgical management of these cases is more challenging and remains controversial. The purpose of this study is to help surgeons select the effective surgical strategies by computer-aided design (CAD) and computational fluid dynamics (CFD) simulations of the upper airway flow characteristics. METHODS: The three dimensional (3D) geometric model of the upper airway was reconstructed based on two dimensional (2D) medical images of the patient with VC accompanied with LM. Virtual surgeries were carried out preoperatively to simulate three possible post-operative states in silico. The different outcomes of virtual surgical strategies were predicted based on computational evaluations of airway fluid dynamics including pressure, resistance, velocity, and wall shear stress (WSS). RESULTS: The CFD results of this study suggested the importance of the angle between the rim of epiglottis and arytenoid epiglottic (AE) fold. There was a small impact on the upper airway flow field while the VC was removed and the angle of epiglottis was unchanged. The partial lifting of epiglottis can further improve the flow field. With performing supraglottoplasty (SGP) and the marsupialization of VC, epiglottis was completely recovered, and the flow field was significantly improved. The clinical symptoms of this patient improved greatly after surgeries and no recurrence or growth retardation were noted during 1-year follow-up. The clinical prognosis was consistent with the prediction of the CFD results. CONCLUSIONS: The state of epiglottis needs to be carefully checked to evaluate the necessity of performing further SGP in the patients with VC accompanied with LM. CFD and CAD could be developed as a new approach to help surgeons predict the post-operative outcomes through quantification of the airflow dynamics, and make the optimal and individualized surgical approaches for patients with airway obstruction.

Differential developmental blueprints of organ-intrinsic nervous systems.

The organ-intrinsic nervous system is a major interface between visceral organs and the brain, mediating important sensory and regulatory functions in the body-brain axis and serving as critical local processors for organ homeostasis. Molecularly, anatomically, and functionally, organ-intrinsic neurons are highly specialized for their host organs. However, the underlying mechanism that drives this specialization is largely unknown. Here, we describe the differential strategies utilized to achieve organ-specific organization between the enteric nervous system (ENS) 1 and the intrinsic cardiac nervous system (ICNS) 2 , a neuronal network essential for heart performance but poorly characterized. Integrating high-resolution whole-embryo imaging, single-cell genomics, spatial transcriptomics, proteomics, and bioinformatics, we uncover that unlike the ENS which is highly mobile and colonizes the entire gastrointestinal (GI) tract, the ICNS uses a rich set of extracellular matrix (ECM) genes that match with surrounding heart cells and an intermediate dedicated neuronal progenitor state to stabilize itself for a 'beads-on-the-necklace' organization on heart atria. While ICNS- and ENS-precursors are genetically similar, their differentiation paths are influenced by their host-organs, leading to distinct mature neuron types. Co-culturing ENS-precursors with heart cells shifts their identity towards the ICNS and induces the expression of heart-matching ECM genes. Our cross-organ study thus reveals fundamental principles for the maturation and specialization of organ-intrinsic neurons.