Serum S100A8/A9 Correlates to Surgery-Free Interval in Idiopathic Subglottic Stenosis.

Objective: Idiopathic subglottic stenosis (iSGS) is a progressive fibrotic condition of the subglottis that presents in women of northern European descent. Endoscopic dilation is a common surgical approach to management of iSGS. The surgery-free interval, or the time between endoscopic dilation procedures is considered an indicator of disease severity.

Evaluation and Treatment of Acute Laryngeal Injury at Time of Tracheostomy for Prolonged Intubation.

Objectives: The primary objective was to assess incidence and severity of acute laryngeal injury (ALgI) following intubation at time of tracheostomy using a proposed grading scale. The secondary objective was to evaluate what factors influence the rate of decannulation.

Methods: Single institution cohort study with review of prospectively maintained database including patients from October 2021 to October 2022 who underwent tracheostomy for prolonged intubation/critical illness.

Open laryngotracheal reconstruction for iatrogenic posterior glottic stenosis in adults: international multicenter experience.

Objective: Posterior glottic stenosis (PGS) has a significant impact on breathing and quality of life, and remains a challenging condition to manage. Literature does not provide a single optimal approach. In this study we aim to assess post-operative outcomes of adult patients with acquired PGS treated with open laryngotracheal reconstruction (LTR) with autologous or cadaveric rib grafting.

Oral Everolimus Following Dilation in Idiopathic Subglottic Stenosis: A Phase 1 Nonrandomized Clinical Trial.

Importance: Current medical therapies in idiopathic subglottic stenosis (iSGS) are insufficient in preventing the development and progression of scar tissue. An inhibitor of mammalian target of rapamycin, everolimus is an immunosuppressive medication shown to be effective in reducing fibrosis across a variety of fibroproliferative disorders, including preclinical models of iSGS.

Objective: To evaluate the effect of oral everolimus on postoperative recurrence of stenosis in iSGS.

An Ovine Model Yields Histology and Gene Expression Changes Consistent with Laryngotracheal Stenosis.

Objectives: Animal models for laryngotracheal stenosis (LTS) are critical to understand underlying mechanisms and study new therapies. Current animal models for LTS are limited by small airway sizes compared to human. The objective of this study was to develop and validate a novel, large animal ovine model for LTS.

A Comprehensive Flow Cytometry Panel for Analysis of Idiopathic Subglottic Stenosis.

Objective: To present a comprehensive flow cytometry panel for idiopathic subglottic stenosis (iSGS).

Study Design: Controlled ex vivo cohort study.

Setting: Tertiary care academic hospital in a metropolitan area.

Similarity Network Analysis of the Adaptive Immune Response in the Proximal Airway.

Objectives: Recent immunologic study of the adaptive immune repertoire in the subglottic airway demonstrated high-frequency T cell clones that do not overlap between individuals. However, the anatomic distribution and antigenic target of the T cell repertoire in the proximal airway mucosa remain unresolved.

Methods: Single-cell RNA sequencing of matched scar and unaffected mucosa from idiopathic subglottic stenosis patients (iSGS, n = 32) was performed and compared with airway mucosa from healthy controls (n = 10).

Post-extubation Assessment of Laryngeal Symptoms and Severity (PALSS) in the Intensive Care Unit: Protocol of a Prospective Cohort Study.

Aims: The Post-extubation Assessment of Laryngeal Symptoms and Severity (PALSS) study systematically evaluates patient symptoms related to endotracheal intubation with mechanical ventilation, assesses laryngeal injury and voice function after extubation, and develops a screening tool to identify patients with clinically important, post-extubation laryngeal injury.

Design: Single-center, prospective observational cohort study conducted in 6 intensive care units (ICU).

Methods: Patients ≥18 years old who are orally intubated and mechanically ventilated in an ICU and meet eligibility criteria will undergo flexible laryngoscopy, with a sample size goal of 300 completed laryngoscopies.

Automatic Root Length Estimation from Images Acquired In Situ without Segmentation.

Image-based root phenotyping technologies, including the minirhizotron (MR), have expanded our understanding of the in situ root responses to changing environmental conditions. The conventional manual methods used to analyze MR images are time-consuming, limiting their implementation. This study presents an adaptation of our previously developed convolutional neural network-based models to estimate the total (cumulative) root length (TRL) per MR image without requiring segmentation.

Medical concept embedding of real-valued electronic health records with application to inflammatory bowel disease.

Deep learning approaches are gradually being applied to electronic health record (EHR) data, but they fail to incorporate medical diagnosis codes and real-valued laboratory tests into a single input sequence for temporal modeling. Therefore, the modeling misses the existing medical interrelations among codes and lab test results that should be exploited to promote early disease detection. To find connections between past diagnoses, represented by medical codes, and real-valued laboratory tests, in order to exploit the full potential of the EHR in medical diagnosis, we present a novel method to embed the two sources of data into a recurrent neural network.

Characterizing the T Cell Repertoire in the Proximal Airway in Health and Disease.

Objectives: Recent translational scientific efforts in subglottic stenosis (SGS) support a disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. Given the observed immune cell infiltrate in SGS, we sought to test the hypothesis that SGS cases possessed a low diversity (highly clonal) adaptive immune response when compared with healthy controls.

Methods: Single cell RNA sequencing (scRNA-seq) of subglottic mucosal scar in iSGS (n = 24), iLTS (n = 8), and healthy controls (n = 7) was performed.

Murine Model of Airway Fibrosis has Anatomic, Physiologic, and Molecular Congruency to Human iSGS.

Objective: To narrow knowledge gaps in the pathophysiology of idiopathic subglottic stenosis (iSGS) through comparison of a murine subglottic stenosis model with iSGS.

Study Design: In vivo animal study.

Setting: Academic institution.

Recurrent laryngeal motor nerve conduction studies in a rat model: Establishing an objective measure for investigating laryngeal innervation.

Introduction/aims: Disease or injury can cause neuromuscular changes to the larynx that can affect voice, breathing, and swallowing. Motor nerve conduction studies have had limited use in the study of laryngeal neurophysiology, despite their importance in other anatomic sites. The aim of this study was to explore the feasibility of performing recurrent laryngeal motor nerve conduction studies (rlMNCS) in a rat model.

Dysfunctional Epithelial Barrier Is Characterized by Reduced E-Cadherin in Idiopathic Subglottic Stenosis.

Objectives: To aim of the study was to characterize the molecular profile and functional phenotype of idiopathic subglottic stenosis (iSGS)-scar epithelium.

Methods: Human tracheal biopsies from iSGS scar (n = 6) and matched non-scar (n = 6) regions were analyzed using single-cell RNA sequencing (scRNA-seq). Separate specimens were used for epithelial cell expansion in vitro to assess average growth rate and functional capabilities using transepithelial-electrical resistance (TEER), fluorescein isothiocyanate-dextran flux permeability assay, ciliary coverage, and cilia beating frequency (CBF).

Deep Convolutional Tables: Deep Learning Without Convolutions.

We propose a novel formulation of deep networks that do not use dot-product neurons and rely on a hierarchy of voting tables instead, denoted as convolutional tables (CTs), to enable accelerated CPU-based inference. Convolutional layers are the most time-consuming bottleneck in contemporary deep learning techniques, severely limiting their use in the Internet of Things and CPU-based devices. The proposed CT performs a fern operation at each image location: it encodes the location environment into a binary index and uses the index to retrieve the desired local output from a table.

Localizing Hormone Receptor Expression to Cellular Compartments in Idiopathic Subglottic Stenosis.

Objectives: Idiopathic subglottic stenosis (iSGS) is an unexplained progressive fibrosis of the upper airway. iSGS almost exclusively affects women; as a result, female hormones (estrogen and progesterone) have been proposed to participate in the pathogenesis of iSGS. Our aim was to localize cell-specific gene expression of estrogen receptors (ESR1 and ESR2) and progesterone receptor (PGR) using an established iSGS single-cell RNA sequencing (scRNAseq) cell atlas.

Idiopathic subglottic stenosis arises at the epithelial interface of host and pathogen.

Background: Idiopathic subglottic stenosis (iSGS) is a rare fibrotic disease of the proximal airway affecting adult Caucasian women nearly exclusively. Life-threatening ventilatory obstruction occurs secondary to pernicious subglottic mucosal scar. Disease rarity and wide geographic patient distribution has previously limited substantive mechanistic investigation into iSGS pathogenesis.

Sirolimus-eluting airway stent reduces profibrotic Th17 cells and inhibits laryngotracheal stenosis.

Laryngotracheal stenosis (LTS) is pathologic fibrotic narrowing of the larynx and trachea characterized by hypermetabolic fibroblasts and CD4+ T cell-mediated inflammation. However, the role of CD4+ T cells in promoting LTS fibrosis is unknown. The mTOR signaling pathways have been shown to regulate the T cell phenotype.

Mapping Genetic Susceptibility to Stenosis in the Proximal Airway.

Objectives: Recent translational scientific efforts in subglottic stenosis (SGS) support a disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. Yet despite recent advances, the genetic basis of SGS remains poorly understood. We sought to identify candidate risk genes associated with an SGS phenotype, investigate their biological function, and identify the cell types enriched for their expression.

Comparative Treatment Outcomes for Idiopathic Subglottic Stenosis: 5-Year Update.

The North American Airway Collaborative (NoAAC) previously published a 3-year multi-institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re-enrolled for 2 additional years and followed using the prespecified published protocol.

Human Leukocyte Antigen Genotyping of Idiopathic Subglottic Stenosis.

Objective: Despite recent scientific inquiry, idiopathic subglottic stenosis (iSGS) remains an enigmatic disease. The consistent demographics of the affected population suggest genetic factors may contribute to disease susceptibility. Given the inflammation observed in the affected proximal airway mucosa, we interrogated disease association with human leukocyte antigen (HLA) polymorphisms.