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, 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, 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, 2024.

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.

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.

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.

Virtual Reality as Distraction Analgesia and Anxiolysis for Pediatric Otolaryngology Procedures.

OBJECTIVES/HYPOTHESIS: While virtual reality (VR) has been used as analgesia and anxiolysis for invasive procedures, no literature exists on the use of VR in the pediatric otolaryngology setting. The purpose of this study was to determine the efficacy of VR in reducing pain and anxiety for pediatric otolaryngology patients. STUDY DESIGN: Randomized controlled trial. METHODS: A total of 53 patients aged 7-17 undergoing in-office nasal endoscopies were included. Patients were randomized to receive VR or standard of care. Procedural pain, anxiety, and satisfaction scores were recorded from patients and caregivers. The physician filled out a childhood emotional manifestation scale (CEMS). RESULTS: Patients in VR group reported a significant decrease in pain (0.80 ± 1.06 vs. 2.26 ± 2.38, P = .018) and anxiety (9.50 ± 12.48 vs. 38.48 ± 29.83, P = .0002) and increase in procedural satisfaction (6.40 ± 0.77 vs. 4.74 ± 1.74, P = .0002) compared to patients in control group. CEMS scores were significantly reduced in VR group (5.15 ± 0.46 vs. 9.64 ± 5.66, P = .0001) and caregiver anxiety levels were significantly reduced in VR group (11.50 ± 17.67 vs. 27.39 ± 30.48, P = .041) compared to control group. There were no reported side effects. Procedural time did not significantly differ between groups. CONCLUSIONS: For pediatric otolaryngology patients undergoing in-office nasal endoscopies, VR is a safe and effective form of distraction analgesia and anxiolysis, significantly reducing pain and increasing procedural satisfaction for patients. In addition, VR significantly reduces anxiety for both patients and caregivers without disrupting procedural efficiency and workflow. LEVEL OF EVIDENCE: 2. Laryngoscope, 131:E1714-E1721, 2021.

US Medical Trainees' Knowledge of Human Papilloma Virus and Head and Neck Cancer.

Given the increasing incidence of human papilloma virus (HPV)-positive head and neck cancers (HNCs), discussion of this oncologic outcome should be incorporated into HPV vaccine counseling practices. Yet, preliminary evidence shows that knowledge of the association between HPV and HNC is lacking among most medical trainees. To better characterize this deficit, we nationally assessed knowledge of HPV's association with HNC among medical students and residents across 4 specialties (pediatrics, obstetrics and gynecology, family medicine, and otolaryngology). A total of 3141 responses from 46 states were obtained (n = 402 pediatric residents, n = 346 obstetrics/gynecology residents, n = 260 family medicine residents, n = 87 otolaryngology residents, and n = 2045 medical students). Only 40.3% of surveyed medical students and 56.1% of surveyed obstetrics/gynecology, pediatrics, and family medicine residents identified associations between persistent HPV infection and HNC. When counseling on the vaccine, nonotolaryngology residents more often discussed cervical cancer (99.8%) as compared with HNC (39.7%), commonly because of less HNC knowledge (61.5%). These results suggest that it is imperative to develop educational interventions targeted at medical students and resident trainees on the front line of HPV vaccine counseling and administration.

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.

The Use of the Exoscope in Lateral Skull Base Surgery: Advantages and Limitations.

OBJECTIVE: We describe our experience using the extracorporeal video microscope, the "exoscope" for various applications within the field of lateral skull base surgery. STUDY DESIGN: A retrospective case series was performed investigating patient demographics, indications for surgery, procedure type, operative time, approach to the skull base, complications, adequacy of visualization, and surgeon comfortability. PATIENTS: Six cases were performed with a three dimensional surgical exoscope, obviating the use of a traditional binocular microscope. SETTING: Academic, tertiary referral center. MAIN OUTCOME MEASURES: Type of surgical approach, operative time, patient demographics, surgical complications, and surgeon comfortability. RESULTS: The following procedures were performed; four vestibular schwannoma resections via suboccipital craniotomy and two combined transmastoid and transtemporal approaches for temporal lobe encephalocele repairs. The average operative time was 227 and 577 minutes for temporal lobe encephalocele repairs and vestibular schwannoma cases, respectively. No intraoperative complications were encountered during these cases. None of the procedures required abandonment of the exoscope in favor of the microscope during the procedure. Advantages include high-resolution three-dimensional visualization, increased degrees of freedom for exoscope adjustment, and reduced surgeon fatigue in a fixed, unnatural posture. Limitations include decreased depth perception and increased operative time. CONCLUSION: The exoscope system is a safe and effective alternative or adjunct to the existing binocular operating microscope for lateral skull based procedures. The exoscope provides the surgeon with a comfortable, high-resolution visualization without compromising surgical exposure and patient safety. LEVEL OF EVIDENCE: 4.

Assessment of the NSQIP Surgical Risk Calculator in Predicting Microvascular Head and Neck Reconstruction Outcomes.

OBJECTIVE: This study evaluated the accuracy of the Surgical Risk Calculator (SRC) of the ACS NSQIP (American College of Surgeons National Surgical Quality Improvement Program) in predicting head and neck microvascular reconstruction outcomes. STUDY DESIGN: Retrospective analysis. SETTING: Tertiary medical center. SUBJECTS AND METHODS: A total of 561 free flaps were included in the analysis. The SRC-predicted 30-day rates of postoperative complications, hospital length of stay (LOS), and rehabilitation discharge were compared with the actual rates and events. The SRC's predictive value was examined with Brier scores and receiver operating characteristic area under the curve. RESULTS: A total of 425 myocutaneous, 134 osseous (84 fibula, 47 scapula, and 3 iliac crest), and 2 omental free flaps were included in this study. All perioperative complications evaluated had area under the curve values ≤0.75, ranging from 0.480 to 0.728. All but 2 postoperative complications had Brier scores >0.01. SRC-predicted LOS was 9.4 ± 2.38 days (mean ± SD), which did not strongly correlate with the actual LOS of 11.98 ± 9.30 days ( r = 0.174, P < .0001). CONCLUSION: The SRC is a poor predictor for surgical outcome among patients undergoing microvascular head and neck reconstruction.

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.