Prolonged operative time predicts postoperative deep venous thrombosis in head and neck cancer patients who undergo free flap reconstruction.

Objective: This study sought to quantify the deep venous thrombosis (DVT) incidence in head and neck cancer (HNC) patients undergoing free tissue transfer and to identify independent predictors of postoperative DVT. Materials and Methods: This is a cross-sectional study of the National Surgical Quality Improvement Program database from 2010 through 2020. The sample included all HNC surgical patients treated with free flap reconstruction. The study outcome was the presence of a DVT requiring treatment within 30 days of surgery. Univariate analyses were performed using chi-squared and independent t-tests. A multiple logistic regression model was created using all significant univariate predictors. Results: A total of 3954 patients were identified, of whom 53 (1.3%) experienced a postoperative DVT. The only medical comorbidity associated with DVT was COPD (RR = 2.7 [1.3, 5.4]; p < .01). Operative time longer than 9 hours (RR = 1.9 [1.0, 3.2]; p = .04) and length of stay longer than 10 days (RR = 1.9 [1.1, 3.2]; p = .02) were associated with greater DVT rates. In the multivariate analysis, only COPD (p < .01) and operative time (p = .02) were independently associated with DVT risk. The presence of a DVT was found to increase the relative risk of readmission (RR = 2.1 [1.2, 3.6]; p < .01) and non-home disposition (RR = 2.4 [1.7, 3.5]; p < .01). Conclusions: The incidence of DVT in HNC free flap patients was comparable to what has been reported in the general population of HNC surgery patients. Operative time >9 h and COPD history were independent risk factors for DVT in this subset of patients. Symptomatic DVTs necessitating treatment were accompanied by poorer post-hospitalization outcomes. Level of Evidence: Level 3.

Experimental Modeling of Host-Bacterial Interactions in Head and Neck Squamous Cell Carcinoma.

The microscopic species colonizing the human body, collectively referred to as the microbiome, play a crucial role in the maintenance of tissue homeostasis, immunity, and the development of disease. There is evidence to suggest associations between alterations in the microbiome and the development of head and neck squamous cell carcinomas (HNSCC). The use of two-dimensional (2D) modeling systems has made significant strides in uncovering the role of microbes in carcinogenesis; however, direct mechanistic links remain in their infancy. Patient-derived three-dimensional (3D) HNSCC organoid and organotypic models have recently been described. Compared to 2D models, 3D organoid culture systems effectively capture the genetic and epigenetic features of parent tissue in a patient-specific manner and may offer a more nuanced understanding of the role of host-microbe responses in carcinogenesis. This review provides a topical literature review assessing the current state of the field investigating the role of the microbiome in HNSCC; including in vivo and in vitro modeling methods that may be used to characterize microbiome-epithelial interactions.

Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma.

(1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating immune cell proportions with clinical, pathologic, and genomic data. (3) Results: We reliably deconvolved 22 immune cell subtypes in most patients and found that the most common immune cell types were M0 macrophages, M2 macrophages, and memory resting CD4 T cells. In the multivariable analysis, we identified advanced N stage and the presence of γδ T cells as independently predictive of poorer survival. (4) Conclusions: We uncovered that γδ T cells in the tumor microenvironment were a negative predictor of survival among patients with untreated HNSCC. Our findings underscore the need to better understand the role of γδ T cells in HNSCC, including potential pro-tumorigenic mechanisms, and whether their presence may predict the need for alternative therapy approaches.

Corrigendum: A review of the peripheral proprioceptive apparatus in the larynx.

[This corrects the article DOI: 10.3389/fnana.2023.1114817.].

A review of the peripheral proprioceptive apparatus in the larynx.

The larynx is an organ of the upper airway that participates in breathing, glutition, voice production, and airway protection. These complex functions depend on vocal fold (VF) movement, facilitated in turn by the action of the intrinsic laryngeal muscles (ILM). The necessary precise and near-instantaneous modulation of each ILM contraction relies on proprioceptive innervation of the larynx. Dysfunctional laryngeal proprioception likely contributes to disorders such as laryngeal dystonia, dysphagia, vocal fold paresis, and paralysis. While the proprioceptive system in skeletal muscle derived from somites is well described, the proprioceptive circuitry that governs head and neck structures such as VF has not been so well characterized. For over two centuries, researchers have investigated the question of whether canonical proprioceptive organs, muscle spindles, and Golgi tendon organs, exist in the ILM, with variable findings. The present work is a state-of-the-art review of the peripheral component of laryngeal proprioception, including current knowledge of canonical and possible alternative proprioceptive circuitry elements in the larynx.

Smoking and Head and Neck Cancer.

This Patient Page describes the association of tobacco use with head and neck cancer and provides suggested treatment and prevention measures.

Patient-derived three-dimensional culture techniques model tumor heterogeneity in head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) outcomes remain stagnant, in part due to a poor understanding of HNSCC biology. The importance of tumor heterogeneity as an independent predictor of outcomes and treatment failure in HNSCC has recently come to light. With this understanding, 3D culture systems, including patient derived organoids (PDO) and organotypic culture (OTC), that capture this heterogeneity may allow for modeling and manipulation of critical subpopulations, such as p-EMT, as well as interactions between cancer cells and immune and stromal cells in the microenvironment. Here, we review work that has been done using PDO and OTC models of HNSCC, which demonstrates that these 3D culture models capture in vivo tumor heterogeneity and can be used to model tumor biology and treatment response in a way that faithfully recapitulates in vivo characteristics. As such, in vitro 3D culture models represent an important bridge between 2D monolayer culture and in vivo models such as patient derived xenografts.

Multi-institutional search for patient factors associated with adverse events following tracheotomy.

BACKGROUND: Tracheotomy is a common procedure for otolaryngologists. The risk of complications is difficult to predict. This study aims to identify measurable preoperative indicators associated with adverse events following tracheotomy. METHODS: The charts of adults undergoing tracheotomy for respiratory failure at one of four university-affiliated hospitals between 1/2012 and 8/2018 were reviewed. Complications were analyzed in the context of demographics, physiologic parameters, and comorbidities. RESULTS: Among 507 tracheotomies performed, the most common complications included infection, bleeding, and cardiac arrest. Mortality was 39 % in patients with pulmonary hypertension, 42 % in those with ejection fraction ≤ 40 and 32 % in those with abnormal right ventricular function, double the rates in patients without each of these findings. CONCLUSION: Many critically ill tracheotomy patients experience significant rates of adverse events. Risk factors for mortality include ejection fraction ≤ 40, pulmonary hypertension, and abnormal ventricular function. These should be considered for use in preoperative counseling.

Healthy Human Laryngopharyngeal Sensory Innervation Density Correlates with Age.

OBJECTIVE: Somatosensory feedback from upper airway structures is essential for swallowing and airway defense but little is known about the identities and distributions of human upper airway neurons. Furthermore, whether sensory innervation modifies with aging is unknown. In this study, we quantify neuronal and chemosensory cell density in upper airway structures and correlate with age. METHODS: Participants underwent biopsies from base of tongue, lateral and midline pharyngeal wall, epiglottis, and arytenoids (N = 25 13 female/12 male; 20-80 years, mean 51.4 years without clinical diagnosis of dysphagia or clinical indication for biopsy). Tissue sections were labeled with antibodies for all neurons, myelinated neurons, and chemosensory cells. Densities of lamina propria innervation, epithelial innervation, solitary chemosensory cells, and taste buds were calculated and correlated with age. RESULTS: Arytenoid had the highest density of innervation and chemosensory cells across all measures compared to other sites. Taste buds were frequently observed in arytenoid and epiglottis. Base of tongue, lateral pharynx, and midline posterior pharynx had minimal innervation and few chemosensory cells. Epithelial innervation was present primarily in close proximity to chemosensory cells and taste buds. Overall innervation and myelinated fibers in the arytenoid lamina propria decline with aging. CONCLUSION: Findings establish the architecture of healthy adult sensory innervation and demonstrate the varied distribution of laryngopharyngeal innervation, necessary steps toward understanding the sensory basis for swallowing and airway defense. We also document age-related decline in arytenoid innervation density. These findings suggest that sensory afferent denervation of the upper airway may be a contributing factor to presbyphagia. LEVEL OF EVIDENCE: NA Laryngoscope, 133:773-784, 2023.

Practice of Telehealth in Otolaryngology: A Scoping Review in the Era of COVID-19.

OBJECTIVE: The COVID-19 pandemic has spurred widespread adoption and advancement in telehealth activities, representing a marked change in otolaryngology practice patterns. The present study undertakes a scoping review of research focused on telehealth in otolaryngology (teleotolaryngology) to identify key themes and commonly utilized outcome measures that will assist future development in this growing field. DATA SOURCES: PubMed, Embase, and Cochrane databases and reference review. REVIEW METHODS: Per guidelines of the PRISMA Extension for Scoping Reviews, we performed database queries using a comprehensive search strategy developed in collaboration with research librarians at the Columbia University Irving Medical Center. We identified 596 unique references to undergo title and abstract review by 2 independent reviewers, leaving 439 studies for full-text review. RESULTS: We included 285 studies for extraction of notable findings, leaving 262 unique studies after accounting for content overlap. We identified core outcome measures, including patient and provider satisfaction, costs and benefits, quality of care, feasibility, and access to care. Publication volume increased markedly over time, though only 4% of studies incorporated randomized study group assignment. Using an iterative approach to thematic development, we organized article content across 5 main themes: (1) exploration of teleotolaryngology evolution, (2) role in virtual clinical encounters, (3) applications in interdisciplinary care and educational initiatives, (4) emerging and innovative technologies, and (5) barriers to implementation. CONCLUSION: This scoping review of teleotolaryngology documents its evolution and identifies current use cases, limitations, and emerging applications, providing a foundation from which to build future studies, inform policy decision making, and facilitate implementation where appropriate.

Impingement of the Thyroid Cartilage on the Carotid Causing Clicking Larynx Syndrome and Stroke.

We present the case of a patient with a recent history of ischemic stroke who presented with clicking larynx syndrome, a condition in which clicking noises in the larynx can be provoked by movement of the head and neck. Diagnostic imaging revealed unusual development and posterior angulation of the superior horn of the thyroid cartilage that potentially was causing trauma to the left common carotid artery. We deduced that symptomatic impingement of the carotid artery by the thyroid cartilage was not only the cause of the patient's clicking larynx syndrome, but also suspected to be the cause of her prior strokes due to repetitive trauma resulting in thrombus. The patient was managed surgically with thyroplasty and transcervical resection of the left greater cornu of the thyroid cartilage with resolution of her symptoms. Anatomical displacement of the thyroid cartilage can manifest as clicking larynx syndrome as well as cause mechanical injury to the carotid artery, resulting in turbulent flow, possible thrombosis, and stroke. Laryngoscope, 132:1410-1413, 2022.

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids.

Esophageal squamous cell carcinoma (ESCC) is prevalent worldwide, accounting for 90% of all esophageal cancer cases each year, and is the deadliest of all human squamous cell carcinomas. Despite recent progress in defining the molecular changes accompanying ESCC initiation and development, patient prognosis remains poor. The functional annotation of these molecular changes is the necessary next step and requires models that both capture the molecular features of ESCC and can be readily and inexpensively manipulated for functional annotation. Mice treated with the tobacco smoke mimetic 4-nitroquinoline 1-oxide (4NQO) predictably form ESCC and esophageal preneoplasia. Of note, 4NQO lesions also arise in the oral cavity, most commonly in the tongue, as well as the forestomach, which all share the stratified squamous epithelium. However, these mice cannot be simply manipulated for functional hypothesis testing, as generating isogenic mouse models is time- and resource-intensive. Herein, we overcome this limitation by generating single cell-derived three-dimensional (3D) organoids from mice treated with 4NQO to characterize murine ESCC or preneoplastic cells ex vivo. These organoids capture the salient features of ESCC and esophageal preneoplasia, can be cheaply and quickly leveraged to form isogenic models, and can be utilized for syngeneic transplantation experiments. We demonstrate how to generate 3D organoids from normal, preneoplastic, and SCC murine esophageal tissue and maintain and cryopreserve these organoids. The applications of these versatile organoids are broad and include the utilization of genetically engineered mice and further characterization by flow cytometry or immunohistochemistry, the generation of isogeneic organoid lines using CRISPR technologies, and drug screening or syngeneic transplantation. We believe that the widespread adoption of the techniques demonstrated in this protocol will accelerate progress in this field to combat the severe burden of ESCC.

Postpartum length of stay and risk for readmission among women with preeclampsia.

Objective: How hospital length of stay after delivery for women with preeclampsia is associated with risk for readmission is unknown. The objective of this study was to evaluate risk for 60-day hypertension-related postpartum readmission based on length of stay after delivery.Methods: The 2014 Healthcare Cost and Utilization Project's (HCUP) Nationwide Readmissions Database was used to analyze risk for readmission for a hypertension-related diagnosis within 60 days from cesarean delivery hospitalization for women with preeclampsia who underwent cesarean delivery. Risk for readmission was evaluated based on postoperative length of stay as well as demographic, hospital, and other obstetric factors. Population weights were applied to create national estimates. Multivariable analyses were performed with adjusted risk ratios (aRR) and corresponding 95% confidence intervals as measures of effect. Mean and median hospital charges based upon postoperative length of stay were also evaluated. Time from delivery hospitalization to readmission was calculated.Results: In 2014, 65 401 women with preeclampsia underwent cesarean delivery. Of these, 1016 women (1.6%) were readmitted for a hypertension-related diagnosis. 921 of the 1016 readmissions occurred within 10 days of discharge (90.6%). In adjusted analyses, postoperative LOS 5-7 days and >7 days compared to LOS <3 days were associated with decreased risk of 60-day hypertension-related readmission (aRR 0.59 95% CI 0.45, 0.78; aRR 0.53 95% CI 0.29, 1.00, respectively). When the cohort was restricted to women with severe preeclampsia or eclampsia, LOS 5-7 days was associated with decreased risk of 60-day hypertension-related readmission in both unadjusted and adjusted analyses compared to LOS <3 days (risk ratios (RR) 0.34, 95% CI 0.18, 0.65; aRR 0.29, 95% 0.18, 0.46, respectively). Median delivery hospitalization charges were $26 512. Compared to LOS <3 days, mean and median charges increased significantly for patients with LOS 4, 5-7, and >7 days.Conclusion: Longer postoperative length of stay during cesarean delivery hospitalizations was associated with decreased risk for postpartum hypertension-related readmission. Most readmissions occurred soon after discharge. These findings support that post-delivery management may play a role in likelihood of women requiring subsequent readmission for complications related to preeclampsia after discharge.

Recurrent Laryngeal Nerve Reinnervation in Rats Posttransection: Neurotrophic Factor Expression over Time.

OBJECTIVE: Recurrent laryngeal nerve (RLN) injury causes vocal fold paralysis from which functional recovery is typically absent due to nonselective reinnervation. This study investigates expression of axon guidance cues and their modulators relative to the chronology of reinnervation by examining the expression of glial-derived neurotrophic factor (GDNF), netrin 1, and laminin 111 (LAMA1) in nonpooled laryngeal muscles. This study is the first to describe the post-RLN injury expression pattern of LAMA1, a target of particular interest as it has been shown to switch netrin 1-mediated growth cone attraction to repulsion. STUDY DESIGN: Animal experiment (rat model). SETTING: Basic science laboratory. METHODS: The right RLNs of 64 female Sprague-Dawley rats were transected, with sacrifice at 1, 3, 7, 21, 28, and 56 days postinjury (DPI). Single-animal messenger RNA was isolated from the ipsilateral posterior cricoarytenoid (PCA), lateral thyroarytenoid (LTA), and medial thyroarytenoid (MTA) for quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Immunostaining for LAMA1 expression was performed in the same muscles. RESULTS: LAMA1 was elevated in the PCA at 3 to 56 DPI, LTA at 7 DPI, and MTA at 14 and 28 DPI. This correlates with the chronology of laryngeal reinnervation. Using a new protocol, single-animal muscle qRT-PCR possible and expression results for GDNF and netrin 1 were similar to previous pooled investigations. CONCLUSION: Reliable qRT-PCR is possible with single rat laryngeal muscles. The expression of netrin 1 and LAMA1 is chronologically coordinated with muscle innervation in the LTA and MTA. This suggests that LAMA1 may influence netrin 1 to repel axons and delay LTA and MTA reinnervation.