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Open Access Publications from the University of California

This series is automatically populated with publications deposited by UC Davis Department of Otolaryngology researchers in accordance with the University of California’s open access policies. For more information see Open Access Policy Deposits and the UC Publication Management System.

The Status of Dysphagia Clinics During the COVID-19 Pandemic.

(2021)

The study aimed to determine the status of dysphagia clinics and procedures applied in dysphagia clinics during the COVID-19 pandemic. Clinicians working in an outpatient dysphagia clinic were included. A 30-question survey inquiring about the descriptive information of the participants and their clinics, their clinical practice, and the tele-health applications during the COVID-19 pandemic. The survey was administered via Google forms. The participants were asked to fill out the survey on behalf of their clinics. One survey was completed per dysphagia clinic. Twenty-three clinicians responded on behalf of their clinics. The number of patients and dysphagia evaluations decreased during the COVID-19 pandemic (p < 0.05). The COVID-19 screening procedures mostly performed before dysphagia evaluations were temperature check (n = 14, 60.9%), nasopharyngeal swab test (n = 9, 39.1%), anamnestic risk assessment (n = 6, 26.1%), and saturation test (n = 6, 26.1%). Protective equipments mostly used while dysphagia evaluations were surgical mask, FFP3 mask, standard gloves, glasses, and face shield. It was found that 69.6% (n = 16) of the dysphagia clinics were reported to be suitable for working under pandemic conditions, and 30.4% (n = 7) were reported to be unsuitable. The use of tele-health applications significantly increased from 13.0% (n = 3) to 52.2% (n = 12) (p = 0.003). The present study provides a general overview of the status of dysphagia clinics and procedures applied in dysphagia clinics during the COVID-19 pandemic period. The study showed that working conditions, the number of patients, and the total number of evaluations have changed throughout the pandemic, and the use of tele-health applications increased.

The Impact of COVID-19 on Head and Neck Cancer Treatment: Before and During the Pandemic.

(2021)

Objectives

To describe the impact that the coronavirus disease 2019 (COVID-19) pandemic had on the presentation of patients with head and neck cancer in a single tertiary care center.

Study design

Retrospective cohort study.

Setting

Academic institution.

Methods

We performed a retrospective review of patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC) who presented as new patients between September 10, 2019, and September 11, 2020. Patients presenting during the 6 months leading up to the announcement of the pandemic (pre-COVID-19 period) on March 11, 2020, were compared to those presenting during the first 6 months of the pandemic (COVID-19 period). Demographics, time to diagnosis and treatment, and tumor characteristics were analyzed.

Results

There were a total of 137 patients analyzed with newly diagnosed malignancies. There were 22% fewer patients evaluated during the COVID-19 timeframe. The groups were similar in demographics, duration of symptoms, time to diagnosis, time to surgery, extent of surgery, and adjuvant therapy. There was a larger proportion of tumors classified as T3/T4 (61.7%) in the COVID-19 period vs the pre-COVID-19 period (40.3%) (P = .024), as well as a larger median tumor size during the COVID-19 period (P = .0002). There were no differences between nodal disease burden (P = .48) and distant metastases (P = .42).

Conclusion

Despite similar characteristics, time to diagnosis, and surgery, our findings suggest that there was an increase in primary tumor burden in patients with HNSCC during the early COVID-19 pandemic.

Cover page of Inflammatory Effects of Thickened Water on the Lungs in a Murine Model of Recurrent Aspiration.

Inflammatory Effects of Thickened Water on the Lungs in a Murine Model of Recurrent Aspiration.

(2021)

Objective

Liquid thickeners are commonly recommended in individuals with dysphagia and recurrent aspiration as a strategy for pneumonia prevention. The goal of this study was to examine the effects of small amounts of aspirated liquid thickener on the lungs.

Study design

Animal model. Prospective small animal clinical trial.

Methods

Adult Sprague Dawley rats (n = 19) were divided into two groups and underwent three intratracheal instillations of either xanthan gum-based nectar-thick water (0.1-0.25 mL/kg) or water-only control over the course of 8 days. Blood was collected from a peripheral vein on days 1 and 8 and submitted for complete blood count (CBC) analysis. Rats were euthanized 10 days after the last instillation, and the lungs were harvested. Histopathology was conducted on lung specimens by a blinded licensed veterinary pathologist and scored for evidence of lung injury and pneumonia.

Results

Fifteen animals (8 nectar-thickener group, 7 control group) survived until the endpoint of the study (day 18). Serum CBC did not show abnormalities at any timepoint in either group. Histological evidence of lung inflammation and edema were significantly greater in the nectar-thick group compared to controls (P < .05). Signs of inflammation included aggregates of foamy macrophages, expansion of bronchiolar lymphoid tissue, and large numbers of eosinophilic intraalveolar crystals. Histiocytic and neutrophilic pneumonia was noted in one animal that received thickened liquids.

Conclusion

Recurrent aspiration of small amounts of thickened water resulted in significant pulmonary inflammation in a murine model of aspiration. Results of this study support the need for further investigation of liquid thickener safety and its efficacy in reducing the pulmonary complications of swallowing disorders.

Level of evidence

NA Laryngoscope, 131:1223-1228, 2021.

Genetic analysis of sinonasal undifferentiated carcinoma discovers recurrent SWI/SNF alterations and a novel PGAP3-SRPK1 fusion gene.

(2021)

Background

Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown.

Methods

We evaluated survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. We performed exome sequencing to characterize a series of SNUC tumors (n = 5) and cell line (MDA8788-6) to identify high confidence mutations, copy number alterations, microsatellite instability, and fusions. Knockdown studies using siRNA were utilized for validation of a novel PGAP3-SRPK1 gene fusion.

Results

Overall survival analysis revealed no significant difference in outcomes between patients treated with surgery +/- CRT and CRT alone. Tobacco use was the only significant predictor of survival. We also confirmed previously published findings on IDH and SMARC family mutations and identified novel recurrent aberrations in the JAK/STAT and PI3K pathways. We also validated a novel PGAP3-SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling.

Conclusion

Collectively, these data demonstrate recurrent alterations in the SWI/SNF family as well as IDH, JAK/STAT, and PI3K pathways and discover a novel fusion gene (PGAP3-SRPK1). These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease.

Cover page of Liquid Biopsies in Head and Neck Cancer: Current State and Future Challenges.

Liquid Biopsies in Head and Neck Cancer: Current State and Future Challenges.

(2021)

Head and neck cancers are the seventh most frequent malignancy worldwide, consisting of a heterogeneous group of cancers that develop in the oral cavity, pharynx, and larynx, with head and neck squamous cell carcinoma (HNSCC) being the most common pathology. Due to limitations with screening and physical examination, HNSCC often presents in advanced disease states and is thus associated with poor survival. In this setting, liquid biopsies, or obtaining patient bodily fluid samples for cancer diagnosis and prognosis, may play a dramatic role in optimizing care for HNSCC patients. In recent years, there have been dramatic advancements in investigations focused on optimizing and implementing liquid biopsies in general, and specifically for HNSCC patients. Moving forward, there remain significant challenges in liquid biopsy technological development, as well as opportunities for the development of HNSCC liquid biopsy clinical trials and treatment paradigms. In this review, we discuss the current state of liquid biopsy technologies via circulating tumor cells, circulating tumor DNA and exosomes, approaches in head and neck cancer, challenges to optimization and application of liquid biopsies for clinical study, and future prospects for this field of research as it applies to head and neck cancer.

An in vivo Cell-Based Delivery Platform for Zinc Finger Artificial Transcription Factors in Pre-clinical Animal Models.

(2021)

Zinc finger (ZF), transcription activator-like effectors (TALE), and CRISPR/Cas9 therapies to regulate gene expression are becoming viable strategies to treat genetic disorders, although effective in vivo delivery systems for these proteins remain a major translational hurdle. We describe the use of a mesenchymal stem/stromal cell (MSC)-based delivery system for the secretion of a ZF protein (ZF-MSC) in transgenic mouse models and young rhesus monkeys. Secreted ZF protein from mouse ZF-MSC was detectable within the hippocampus 1 week following intracranial or cisterna magna (CM) injection. Secreted ZF activated the imprinted paternal Ube3a in a transgenic reporter mouse and ameliorated motor deficits in a Ube3a deletion Angelman Syndrome (AS) mouse. Intrathecally administered autologous rhesus MSCs were well-tolerated for 3 weeks following administration and secreted ZF protein was detectable within the cerebrospinal fluid (CSF), midbrain, and spinal cord. This approach is less invasive when compared to direct intracranial injection which requires a surgical procedure.

Cover page of Diagnosis and Management of Depression in CRS: A Knowledge, Attitudes and Practices Survey.

Diagnosis and Management of Depression in CRS: A Knowledge, Attitudes and Practices Survey.

(2021)

Introduction  Comorbid major depressive disorder (MDD) is present in up to 25% of chronic rhinosinusitis (CRS) cases and provides prognostic information for patients undergoing endoscopic sinus surgery (ESS). Clinical visits offer an opportunity to identify at-risk patients. Objective  The purpose of the present study is to evaluate practice patterns among members of the American Rhinologic Society (ARS) in screening for/diagnosing MDD. Methods  A 21-question survey was distributed to 1,206 members of the ARS from May 26, 2018 to June 12, 2018. The impact of demographic factors, including hospital setting, fellowship status, and experience were assessed through chi-squared analysis. Results  A total of 80 members of the ARS completed the survey, yielding a response rate of 7%. Half of the respondents worked in academic settings and 43% had completed a rhinology fellowship. Twenty percent of the participants felt comfortable diagnosing or managing MDD, while only 10% of participants screened for MDD in patients with CRS. Respondents cited a lack of training (76%) and unfamiliarity with diagnostic criteria (76%) as barriers to the routine assessment of MDD. Most respondents (95%) considered comorbid psychiatric illness to negatively impact outcomes following ESS. Fellowship-trained respondents were significantly more likely to implement screening tools in their practice ( p  = 0.05), and believe in the negative impact of MDD on postoperative outcomes ( p  = 0.007), cost of care ( p  = 0.04) and quality of life ( p  = 0.047). Conclusion  Amongst ARS members, 95% of the respondents consider comorbid MDD to negatively impact patient outcomes following ESS. Regardless, a large proportion of surgeons neither screen nor feel comfortable diagnosing MDD.

Cover page of Challenges facing otolaryngologists in low- and middle-income countries during the COVID-19 pandemic.

Challenges facing otolaryngologists in low- and middle-income countries during the COVID-19 pandemic.

(2020)

The COVID-19 pandemic poses significant challenges for otolaryngologists practicing in low- and middle-income countries (LMICs). This commentary highlights some of the particular challenges in low resource settings, including limited testing, insufficient personal protective equipment, small numbers of surgeons, and competing socio-economic demands. The commentary focuses on specific examples from around the world to draw attention to these challenges and also highlight examples of success and innovation. Amidst the crisis an opportunity exists for otolaryngologists from around the world to share resources, ideas, and innovations to best serve patients and improve the health system globally for the future.

Cover page of Prognostic Significance of Oxidation Pathway Mutations in Recurrent Laryngeal Squamous Cell Carcinoma.

Prognostic Significance of Oxidation Pathway Mutations in Recurrent Laryngeal Squamous Cell Carcinoma.

(2020)

Organ preservation protocols are commonly used as first line therapy for advanced laryngeal cancer. Recurrence thereafter is associated with poor survival. The aim of this study is to identify genetic alterations associated with survival among patients with recurrent laryngeal cancer undergoing salvage laryngectomy. Sixty-two patients were sequenced using a targeted panel, of which twenty-two also underwent transcriptome sequencing. Alterations were grouped based on biologic pathways and survival outcomes were assessed using Kaplan-Meier analysis and multivariate cox regression. Select pathways were evaluated against The Cancer Genome Atlas (TCGA) data. Patients with mutations in the Oxidation pathway had significantly worse five-year disease specific survival (1% vs. 76%, p = 0.02), while mutations in the HN-Immunity pathway were associated with improved five-year disease specific survival (100% vs. 62%, p = 0.02). Multivariate analysis showed mutations in the Oxidation pathway remained an independent predictor of disease specific survival (HR 3.2, 95% CI 1.1-9.2, p = 0.03). Transcriptome analysis of recurrent tumors demonstrated that alterations in the Oxidation pathway were associated a positive Ragnum hypoxia signature score, consistent with enhanced pathway activity. Further, TCGA analyses demonstrated the prognostic value of oxidation pathway alterations in previously untreated disease. Alterations in the Oxidation pathway are associated with survival among patients with recurrent laryngeal cancer. These prognostic genetic biomarkers may inform precision medicine protocols and identify putatively targetable pathways to improve survival in this cohort.

Cover page of International Society for Extracellular Vesicles and International Society for Cell and Gene Therapy statement on extracellular vesicles from mesenchymal stromal cells and other cells: considerations for potential therapeutic agents to suppress coronavirus disease-19.

International Society for Extracellular Vesicles and International Society for Cell and Gene Therapy statement on extracellular vesicles from mesenchymal stromal cells and other cells: considerations for potential therapeutic agents to suppress coronavirus disease-19.

(2020)

Statement

The International Society for Cellular and Gene Therapies (ISCT) and the International Society for Extracellular Vesicles (ISEV) recognize the potential of extracellular vesicles (EVs, including exosomes) from mesenchymal stromal cells (MSCs) and possibly other cell sources as treatments for COVID-19. Research and trials in this area are encouraged. However, ISEV and ISCT do not currently endorse the use of EVs or exosomes for any purpose in COVID-19, including but not limited to reducing cytokine storm, exerting regenerative effects or delivering drugs, pending the generation of appropriate manufacturing and quality control provisions, pre-clinical safety and efficacy data, rational clinical trial design and proper regulatory oversight.