Orthopaedic Hand Surgical Simulation Training: A Review.

In recent years, new orthopaedic surgical simulation and virtual reality (VR) training models have emerged to provide unlimited education medium to an unlimited number of trainees with no time limit, especially in response to trainee work-hour restrictions. Surgical simulators range from simple wooden boxes to animal and cadaver models to three-dimensional-printed and VR simulators. The coronavirus disease 2019 pandemic further highlighted the need for at-home learning tools for orthopaedic surgical trainees. Advancement in simulating shoulder and knee arthroscopies using VR simulators surpasses the other fields in orthopaedic surgery. Despite the high degree of precision needed to operate at a microscopic level involving vessels, nerves, and the small bones of the hand, the simulation tools have limited advancement in the field of orthopaedic hand surgery. This narrative review summarizes the status of surgical simulation and training techniques available to orthopaedic hand surgical trainees, factors affecting their application, and areas in hand surgery that still lag behind their surgical subspecialty counterparts.

Multimodal Imaging of Pre-Descemet Corneal Dystrophy Associated With X-Linked Ichthyosis and Deletion of the STS Gene.

PURPOSE: To investigate the presence of pre-Descemet corneal dystrophy (PDCD) in association with X-linked ichthyosis (XLI) in an 11-year-old boy using multimodal imaging and genetic analysis. METHODS: Corneal opacities were examined and imaged with slit-lamp biomicroscopy, anterior segment optical coherence tomography, noncontact specular microscopy, and in vivo confocal microscopy. Cytogenomic array analysis was performed using genomic DNA isolated from the patient. RESULTS: Corneal opacities characteristic of PDCD located in the posterior corneal stroma just anterior to Descemet membrane were identified by slit-lamp biomicroscopy. A pre-Descemet hyper-reflective line, consistent with these opacities, was seen with anterior segment optical coherence tomography. Scheimpflug tomography revealed a bimodal peak light scattering. In vivo confocal microscopy findings were unremarkable. Copy number analysis identified a 4389 kbp hemizygous deletion on the X chromosome (chr. X: 6,540,898-8,167,604), resulting in the deletion of 4 genes, including the known locus of XLI, the STS gene. CONCLUSIONS: This report demonstrates that PDCD-associated XLI may present in children and that the diagnosis may be confirmed through multimodal imaging in conjunction with genetic analysis.

Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion.

The advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. Expansion by continuous passaging induced replicative cell senescence. Transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion.

ZEB1 insufficiency causes corneal endothelial cell state transition and altered cellular processing.

The zinc finger e-box binding homeobox 1 (ZEB1) transcription factor is a master regulator of the epithelial to mesenchymal transition (EMT), and of the reverse mesenchymal to epithelial transition (MET) processes. ZEB1 plays an integral role in mediating cell state transitions during cell lineage specification, wound healing and disease. EMT/MET are characterized by distinct changes in molecular and cellular phenotype that are generally context-independent. Posterior polymorphous corneal dystrophy (PPCD), associated with ZEB1 insufficiency, provides a new biological context in which to understand and evaluate the classic EMT/MET paradigm. PPCD is characterized by a cadherin-switch and transition to an epithelial-like transcriptomic and cellular phenotype, which we study in a cell-based model of PPCD generated using CRISPR-Cas9-mediated ZEB1 knockout in corneal endothelial cells (CEnCs). Transcriptomic and functional studies support the hypothesis that CEnC undergo a MET-like transition in PPCD, termed endothelial to epithelial transition (EnET), and lead to the conclusion that EnET may be considered a corollary to the classic EMT/MET paradigm.