The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination.

Growth factors of the gp130 family promote oligodendrocyte differentiation, and viability, and myelination, but their mechanisms of action are incompletely understood. Here, we show that these effects are coordinated, in part, by the transcriptional activator Krüppel-like factor-6 (Klf6). Klf6 is rapidly induced in oligodendrocyte progenitors (OLP) by gp130 factors, and promotes differentiation. Conversely, in mice with lineage-selective Klf6 inactivation, OLP undergo maturation arrest followed by apoptosis, and CNS myelination fails. Overlapping transcriptional and chromatin occupancy analyses place Klf6 at the nexus of a novel gp130-Klf-importin axis, which promotes differentiation and viability in part via control of nuclear trafficking. Klf6 acts as a gp130-sensitive transactivator of the nuclear import factor importin-α5 (Impα5), and interfering with this mechanism interrupts step-wise differentiation. Underscoring the significance of this axis in vivo, mice with conditional inactivation of gp130 signaling display defective Klf6 and Impα5 expression, OLP maturation arrest and apoptosis, and failure of CNS myelination.

Mild hypothermia is associated with improved outcomes in patients undergoing microvascular head and neck reconstruction.

OBJECTIVE: Microvascular free tissue transfer has become the standard for reconstruction for large defects. With long operative times and an increased surface area exposed, transient hypothermia is common, but it is unclear how this impacts surgical outcomes. This study evaluated the impact of core body temperature on free tissue flap outcomes in patients undergoing microvascular reconstruction. STUDY DESIGN: Retrospective data analysis. SETTING: Mount Sinai Hospital; NYC, NY; 2007-2016. SUBJECTS AND METHODS: Demographic information, mean/minimum/maximum body temperatures, and the presence of flap complications (venous thrombosis, arterial insufficiency, flap death, wound infection/dehiscence, fistula, chyle leak, hematoma/seroma) of 519 free tissue transfer patients were documented. Binomial logistic regression was used to examine associations between the presence of flap complications and mean temperature. Statistical analysis used SPSS, with p-values ≤0.05 deemed statistically significant. RESULTS: 393 soft-tissue and 125 osteocutaneous flaps were included. 19.8% (n = 103) patients had the presence of ≥1 flap complication, while 80.2% (n = 416) did not. Average temperature for all patients was 36.12 ±â€¯0.84 °C, with minimum at 34.43 ±â€¯0.97 °C and maximum at 37.24 ±â€¯1.23 °C. After controlling for several factors including: tumor stage, radiation, diabetes, BMI, age, sex, and flap type, there was a significant association between flap complications and mean intraoperative temperature (Exp(B) = 1.559, p = 0.004). CONCLUSION: Higher intraoperative temperatures were associated with worse outcomes. A mild relative hypothermia may improve flap outcomes in this population. This represents the largest study to date evaluating the impact of intraoperative temperature on free tissue transfer outcomes.

Understanding How Exercise Promotes Cognitive Integrity in the Aging Brain.

Alterations in the structure and organization of the aging central nervous system (CNS), and associated functional deficits, result in cognitive decline and increase susceptibility to neurodegeneration. Age-related changes to the neurovascular unit (NVU), and their consequences for cerebrovascular function, are implicated as driving cognitive impairment during aging as well as in neurodegenerative disease. The molecular events underlying these effects are incompletely characterized. Similarly, the mechanisms underlying effects of factors that reduce the impact of aging on the brain, such as physical exercise, are also opaque. A study in this issue of PLOS Biology links the NVU to cognitive decline in the aging brain and suggests a potential underlying molecular mechanism. Notably, the study further links the protective effects of chronic exercise on cognition to neurovascular integrity during aging.

Combinatorial actions of Tgfß and Activin ligands promote oligodendrocyte development and CNS myelination.

In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-ß (Tgfß) family and signal canonically via Smads 1/5/8. Tgfß ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfß ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgfß ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgfß1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgfß1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb(-/-) embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3(-/-) mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgfß ligands and ActB together support oligodendrocyte development and myelin formation.

Astrocytic TYMP and VEGFA drive blood-brain barrier opening in inflammatory central nervous system lesions.

In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood-brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood-brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood-brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood-brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood-brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood-brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an astrocyte-derived permeability factor, and suggest TYMP and VEGFA together promote blood-brain barrier breakdown.

Objective Comparison of White Light and Narrow-Band Imaging for Detecting Scars, Sulci and Nodules.

INTRODUCTION: Narrow-band imaging (NBI) can improve detection of lesions in the aerodigestive tract. However, its role in benign lesions of the larynx is unclear. This study aims to determine whether NBI improves the detection of scars, sulci, and nodules compared to panchromatic lighting using objective image analysis. METHODS: In total, 120 vocal folds (VFs) were analyzed with and without NBI (21 normal, 15 scars, 16 sulci, and 45 nodules). Each VF image had anterior, middle, and posterior thirds analyzed for brightness using an area morphometry software (Optimas 5.1a). The middle-third with the lesion was analyzed against surrounding VF segments for average and standard deviation (SD) in absolute grayscale. RESULTS: The use of panchromatic light resulted in greater illumination and grayscale values than NBI. All lesions tended to be in the mid-membranous fold. Under panchromatic light, change in brightness when comparing anterior versus middle (A-M) was +6.1% for normal, versus 6.5%, 8.1%, and 7.1% for sulci, nodules, and scars, respectively. Under NBI, they were 9.0% (normal), 12.3% (sulci), 13.7% (nodules), and 13.1% (scars). A greater SD of luminescence was observed at pathology sites (p < 0.05) when using NBI. The change in absolute grayscale at all lesion sites was greater when using NBI than when using panchromatic light (p < 0.05). CONCLUSION: NBI significantly enhanced the area of pathology in patients with nodules, sulci, and scars. Greater SD values in grayscale at pathologic sites were observed compared at normal sites. Thus, NBI may improve the detection of phonotraumatic lesions compared to panchromatic light. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:4066-4070, 2024.

Open Expansion Laryngoplasty for Combined Glottic and Subglottic Stenosis.

Expansion laryngoplasty is a new, combined procedure which can treat both glottic and subglottic stenosis simulataneously. This is a small case series showing how to perform this surgery as well as outcomes from a 15-year period. Laryngoscope, 2024.

Cellular and Molecular Effects of Steroid Sex Hormones on the Vocal Folds: A Scoping Review.

OBJECTIVE: Steroid sex hormones (SSH) target cell nuclei to affect transcription. Although laryngeal tissue is theorized to be hormonally responsive, SSH receptor presence and cellular effects on the vocal folds are not well-established. A scoping review of this literature might inform future research. DATA SOURCES: Medline, Embase, Scopus, and Web of Science were searched. REVIEW METHODS: This review followed JBI and PRISMA-ScR Guidelines. Two independent reviewers screened each title/abstract and full text according to eligibility criteria. Exclusion criteria included primary outcomes based on subjective interpretation and secondary effects on the vocal folds (e.g., voice). RESULTS: Three hundred and sixty one articles were screened at the title/abstract level, 83 at the full-text level, and 32 met inclusion criteria. Fourteen studies were performed in humans and 15 in animals; 3 were review articles. In studies directly examining receptors (n = 17), estrogen receptors (ER) were found in 10 of 15 studies, progesterone receptors (PR) in 6/10, and androgen receptors (AR) in 6/9. When the effects of SSH on vocal folds were studied (n = 16), estrogen had effects in 10/13, progesterone in 3/3, and androgens in 4/5. ER and PR were mostly identified in epithelium and fibroblasts of lamina propria (LP) while AR was found in muscle, lamina propria, and epithelium. CONCLUSIONS: Existing evidence variably supports the presence of SSH receptors in vocal fold tissue; therefore, further clarification is needed. Estrogen and progesterone were most identified in mucosal tissue, where they decrease fibrosis and help maintain the epithelial barrier. Androgens appear to be pro-fibrotic in epithelium and hypertrophic in muscle. Laryngoscope, 2024.

Outcomes of Supracricoid Partial Laryngectomy Performed in the United States: A Systematic Review.

OBJECTIVE: The primary objective of this study was to evaluate oncologic outcomes of all published cases of supracricoid partial laryngectomy (SCPL) performed in the United States. The secondary objective was to assess the functional outcomes associated with this procedure. REVIEW METHODS: A systematic review of PubMed, SCOPUS, and Embase for all English-language studies pertaining to SCPL performed in the United States was conducted until August 2021. Primary outcomes included disease-specific survival (DSS), overall survival, and local recurrence rate. Secondary outcomes included larynx preservation rate, gastrostromy tube dependency, days to gastrostomy tube removal, decannulation rate, and days to decannulation. RESULTS: A total of six studies were included in the analysis. A total of 113 patients (58.5%) underwent SCPL surgery as a primary treatment method whereas 80 patients (41.5%) underwent SCPL as salvage surgery. The 5-year DSS rates were 87.8% and 100% for primary and salvage procedures, respectively. Approximately 10.3% of patients undergoing a salvage SCPL procedure experienced a local recurrence whereas only 1.85% of primary SCPL procedures resulted in local recurrence. The rates of decannulation following primary and salvage SCPL were 92.7% and 88.1%, respectively. With regard to swallowing, primary and salvage SCPL procedures demonstrated comparably low postoperative gastrostomy tube dependency rates of 3.66% and 4.76%, respectively. CONCLUSIONS: SCPL performed in the United States is an effective surgical technique that produces excellent outcomes in qualifying patients, thus validating its viability as an organ-preserving surgical alternative. Laryngoscope, 134:3003-3011, 2024.

Microbial Composition of the Laryngotracheal Region: A Systematic Review.

INTRODUCTION: Microbiome research has predominantly focused on the oral cavity and oropharynx's role in disease, while the upper airway, specifically the larynx and trachea, has been relatively overlooked. Examining the microbial communities in these regions can shed light on how dysbiosis influences diseases and their management. This review evaluates laryngotracheal microbial compositions in both healthy and diseased patients. METHODS: We conducted a systematic review in EMBASE, MEDLINE, and Cochrane Central databases, yielding 1383 studies in the initial search. Inclusion criteria involved participants aged over 18 years and the use of next-generation 16s ribosomal sequencing methods. RESULTS: We included 10 studies-seven focused on larynx sequencing and four on trachea sequencing (one investigated both sites). In a healthy larynx, diverse species such as Streptococcus, Cloacibacterium, Prevotella, and Helicobacter were found. Benign laryngeal diseases exhibited reduced microbial diversity, mainly dominated by Streptococcus. Subglottic stenosis patients showed diminished diversity in both idiopathic and iatrogenic scars. Laryngeal squamous cell carcinoma displayed increased diversity, primarily featuring Fusobacterium. Among non-respiratory-compromised surgery patients, the tracheal microbiome was more diverse in diabetics and those later developing lower respiratory infections. Pneumonia patients exhibited an abundance of Prevotella and Streptococcus, linked to an increased 28-day survival rate, while Streptococcus and Haemophilus abundance correlated with successful extubation. CONCLUSIONS: The laryngotracheal region hosts a unique microbial community influenced by both benign and malignant conditions. Many lesions remain unexplored, underscoring the need for future studies encompassing diverse laryngotracheal conditions. Clinical trials assessing microbiome modifications may unveil novel therapeutic avenues. LEVEL OF EVIDENCE: NA Laryngoscope, 134:4167-4175, 2024.

High-Resolution Profiling of Human Vocal Fold Cellular Landscapes With Single-Nuclei RNA Sequencing.

INTRODUCTION: The function of the vocal folds (VFs) is determined by the phenotype, abundance, and distribution of differentiated cells within specific microenvironments. Identifying this histologic framework is crucial in understanding laryngeal disease. A paucity of studies investigating VF cellular heterogeneity has been undertaken. Here, we examined the cellular landscape of human VFs by utilizing single-nuclei RNA-sequencing. METHODS: Normal true VF tissue was excised from five patients undergoing pitch elevation surgery. Tissue was snap frozen in liquid nitrogen and subjected to cellular digestion and nuclear extraction. Nuclei were processed for single-nucleus sequencing using the 10X Genomics Chromium platform. Sequencing reads were assembled using cellranger and analyzed with the scanpy package in python. RESULTS: RNA sequencing revealed 18 global cell clusters. While many were of epithelial origin, expected cell types, such as fibroblasts, immune cells, muscle cells, and endothelial cells were present. Subcluster analysis defined unique epithelial, immune, and fibroblast subpopulations. CONCLUSION: This study evaluated the cellular heterogeneity of normal human VFs by utilizing single-nuclei RNA-sequencing. With further confirmation through additional spatial sequencing and microscopic imaging, a novel cellular map of the VFs may provide insight into new cellular targets for VF disease. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3193-3200, 2024.

Human Tracheal Transplantation.

Long-segment tracheal airway defects may be congenital or result from burns, trauma, iatrogenic intubation damage, or tumor invasion. Although airway defects <6 cm in length may be reconstructed using existing end-to-end reconstructive techniques, defects >6 cm continue to challenge surgeons worldwide. The reconstruction of long-segment tracheal defects has long been a reconstructive dilemma, and these defects are associated with significant morbidity and mortality. Many of these defects are not compatible with life or require a permanent extended-length tracheostomy that is fraught with complications including mucus plugging and tracheoesophageal fistula. Extensive circumferential tracheal defects require a reconstructive technique that provides a rigid structure able to withstand the inspiratory pressures, a structure that will biologically integrate, and contain functional ciliated epithelium to allow for normal mucociliary clearance. Tracheal transplantation has been considered the reconstructive "Holy Grail;" however, there has been a long-held scientific dogma that revascularization of the trachea was not possible. This dogma stifled research to achieve single-staged vascularized tracheal transplantation and prompted the introduction of many creative and inventive alternatives. Throughout history, alloplastic material, nonvascularized allografts, and homografts have been used to address this dilemma. However, these techniques have largely been unsuccessful. The recent introduction of a technique for single-staged vascularized tracheal transplantation may offer a solution to this dilemma and potentially a solution to management of the fatal tracheoesophageal fistula.

Transverse Cordotomy with Thyroarytenoid Myectomy for Bilateral Vocal Fold Immobility.

We propose a modification of the transverse cordotomy procedure which improves the predictable airway outcome and allows for better voice. Laryngoscope, 2023.

Case Report: Human Tracheal Transplantation Undergoes Progressive Reepithelialization Over Time.

OBJECTIVES: Tracheal transplantation is an ideal option for the reconstruction of long-segment circumferential tracheal defects. Our group performed the first successful vascularized single-staged tracheal transplantation in January 2021. Although a rigid biocompatible structure is necessary for a functioning tracheal replacement, the importance of ciliated epithelium, which allows for critical mucociliary clearance, is now being appreciated. Here, we examined the histological changes of the first single-staged human tracheal transplant from serial endoscopic biopsies. METHODS: Biopsies of the tracheal mucosa were serially obtained since the time of the tracheal transplantation. Samples were examined via hematoxylin and eosin, electron microscopy, and immunohistochemistry. RESULTS: One week after transplantation, there is loss of ciliated epithelium and seromucinous cells, with only a basal layer of epithelium remaining. By 2 weeks, however, the epithelium begins to recover, albeit differently depending on the location of the biopsy. Near the site of tracheal anastomosis, there is epithelial proliferation, with the appearance of early ciliated cells. However, in the midgraft, there appears to be evidence of squamous metaplasia. Over time, however, normal ciliated epithelium and mucous cells appear without signs of chronic inflammation. CONCLUSIONS: Critically, the tracheal allograft regained normal appearing respiratory epithelium after initial ischemic injury. The histologic differences at the midgraft versus anastomosis may suggest unique mechanisms of reepithelialization. At the recipient-donor interface, there may be a faster direct migration of recipient-derived epithelial cells, in line with preclinical studies. The midgraft, in contrast, responds with epithelial proliferation from the donor basal cells or dedifferentiated mucous cells. LEVEL OF EVIDENCE: N/A Laryngoscope, 2023.

Vascularized Tracheal Transplantation: A Twenty Month Follow Up.

BACKGROUND: Tracheal transplantation has been considered the ideal option for the reconstruction of long-segment circumferential tracheal defects. Our group developed a technique for vascularized single-staged tracheal transplantation. Twenty months ago, we performed the first-in-human tracheal transplantation. Herein, we report a twenty-month follow-up. METHODS: The recipient presented with a 9.0 cm airway tracheal stenosis and complete cricoid stenosis. The patient previously failed six major conventional surgical procedures. Prior to transplantation, the patient's airway was maintained with an extended tracheostomy and stent. The patient experienced repeated life-threatening airway obstruction because of mucous plugging and obstructive granulation tissue. In January 2020 the patient underwent a single-staged tracheal transplantation treated with triple-therapy immunosuppression. Organ rejection was monitored with endoscopic tracheoscopy, narrow-band imaging, free-cell DNA assessment, and histological and cytogenetic analysis of tracheal biopsies. Mucociliary function was assessed with dye motility studies. RESULTS: Twenty months following transplantation, there has been no evidence of acute or chronic rejection. Since day 60, there has been no detectable free cell DNA, a surrogate marker for immune-mediated allograft rejection. Fluorescence in situ hybridization (FISH) cytogenetics demonstrated that the donor trachea was repopulated with recipient epithelium establishing a chimeric allograft. Narrow-band imaging demonstrates a well-vascularized epithelial mucosa and bronchoscopic biopsies demonstrate normal ciliated epithelial architecture and viable epithelial lining with functional ciliated epithelium. The patient has resumed a normal life without a stent or tracheostomy and has returned to work. CONCLUSIONS: Twenty months after single-staged vascularized tracheal transplantation, the trachea is functional and the patient breathes without the need for a tracheostomy or stent. Single-staged long-segment tracheal transplantation is a viable option for tracheal defects that are not amenable to conventional reconstructive techniques. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1839-1845, 2023.

Intraoperative Use of Wide-Field Optical Coherence Tomography to Evaluate Tissue Microstructure in the Oral Cavity and Oropharynx.

Importance: Involvement of deep margins represents a significant challenge in the treatment of oropharyngeal cancer, and given practical limitations of frozen-section analysis, a need exists for real-time, nondestructive intraoperative margin analysis. Wide-field optical coherence tomography (WF-OCT) has been evaluated as a tool for high-resolution adjunct specimen imaging in breast surgery, but its clinical application in head and neck surgery has not been explored. Objective: To evaluate the utility of WF-OCT for visualizing microstructures at margins of excised oral and oropharyngeal tissue. Design, Setting, and Participants: This nonrandomized, investigator-initiated qualitative study evaluated the feasibility of the Perimeter Medical Imaging AI Otis WF-OCT device at a single academic center. Included participants were adults undergoing primary ablative surgery of the oral cavity or oropharynx for squamous cell carcinoma in 2018 and 2019. Data were analyzed in October 2019. Exposures: Patients were treated according to standard surgical care. Freshly resected specimens were imaged with high-resolution WF-OCT prior to routine pathology. Interdisciplinary interpretation was performed to interpret WF-OCT images and compare them with corresponding digitized pathology slides. No clinical decisions were made based on WF-OCT image data. Main Outcomes and Measures: Visual comparisons were performed between WF-OCT images and hematoxylin and eosin slides. Results: A total of 69 specimens were collected and scanned from 53 patients (mean [SD] age, 59.4 [15.2] years; 35 [72.9%] men among 48 patients with demographic data) undergoing oral cavity or oropharynx surgery for squamous cell carcinoma, including 42 tonsillar tissue, 17 base of the tongue, 4 buccal tissue, 3 mandibular, and 3 other specimens. There were 41 malignant specimens (59.4%) and 28 benign specimens (40.6%). In visual comparisons of WF-OCT images and hematoxylin and eosin slides, visual differentiation among mucosa, submucosa, muscle, dysplastic, and benign tissue was possible in real time using WF-OCT images. Microarchitectural features observed in WF-OCT images could be matched with corresponding features within the permanent histology with fidelity. Conclusions and Relevance: This qualitative study found that WF-OCT imaging was feasible for visualizing tissue microarchitecture at the surface of resected tissues and was not associated with changes in specimen integrity or surgical and pathology workflow. These findings suggest that formal clinical studies investigating use of WF-OCT for intraoperative analysis of deep margins in head and neck surgery may be warranted.

Long-term upper aerodigestive sequelae as a result of infection with COVID-19.

Objectives: Respiratory, voice, and swallowing difficulties after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may result secondary to upper airway disease from prolonged intubation or mechanisms related to the virus itself. We examined a cohort who presented with new laryngeal complaints following documented SARS-CoV-2 infection. We characterized their voice, airway, and/or swallowing symptoms and reviewed the clinical course of their complaints to understand how the natural history of these symptoms relates to COVID-19 infections. Methods: Retrospective review of patients who presented to our department with upper aerodigestive complaints as sequelae of prior infection with, and management of, SARS-CoV-2. Results: Eighty-one patients met the inclusion criteria. Median age was 54.23 years (±17.36). Most common presenting symptoms were dysphonia (n = 58, 71.6%), dysphagia/odynophagia (n = 16, 19.75%), and sore throat (n = 9, 11.11%). Thirty-one patients (38.27%) presented after intubation. Mean length of intubation was 16.85 days (range 1-35). Eighteen patients underwent tracheostomy and were decannulated after an average of 70.69 days (range 23-160). Patients with history of intubation were significantly more likely than nonintubated patients to be diagnosed with a granuloma (8 vs. 0, respectively, p < .01). Fifty patients (61.73%) were treated for SARS-CoV-2 without requiring intubation and were significantly more likely to be diagnosed with muscle tension dysphonia (19 vs. 1, p < .01) and laryngopharyngeal reflux (18 vs. 1, p < .01). Conclusion: In patients with persistent dyspnea, dysphonia, or dysphagia after recovering from SARS-CoV-2, early otolaryngology consultation should be considered. Accurate diagnosis and prompt management of these common underlying etiologies may improve long-term patient outcomes. Level of evidence: 4.

Multidisciplinary management of ventilator weaning and tracheostomies for COVID-19 patients at a major NYC public hospital: A blueprint for other institutions.

At the height of the coronavirus pandemic in New York City, at our hospital (NYC Health/Hospitals-Elmhurst) 95% of inpatients tested positive for COVID-19 and it operated at 500% surge ICU capacity-one of the greatest impacted centers in the nation. In the face of this we established a systematic multidisciplinary approach to manage ventilated ICU patients and select those appropriate for tracheostomy. Members from Pulmonary Critical Care, Anesthesiology, Surgery, Ethics, and Otolaryngology, created a protocolized way to assess all ICU patients in our hospital and, if deemed appropriate, help them towards weaning or tracheostomy and subsequent discharge. Given the climbing COVID numbers throughout the nation, and once again in NY, we believe sharing our protocol and brief outcomes will be very helpful for hospitals who are struggling with what we did, as it may serve as a blueprint for these institutions.