Otolaryngology Commons^™

Overview Of The Hecktor Challenge At Miccai 2022: Automatic Head And Neck Tumor Segmentation And Outcome Prediction In Pet/Ct, Vincent Andrearczyk, Valentin Oreiller, Moamen Abobakr, Azadeh Akhavanallaf, Panagiotis Balermpas, Sarah Boughdad, Leo Capriotti, Joel Castelli, Catherine Cheze Le Rest, Pierre Decazes, Ricardo Correia, Dina El-Habashy, Hesham Elhalawani, Clifton D Fuller, Mario Jreige, Yornna Khamis, Agustina La Greca, Abdallah Mohamed, Mohamed Naser, John O Prior, Su Ruan, Stephanie Tanadini-Lang, Olena Tankyevych, Yazdan Salimi, Martin Vallières, Pierre Vera, Dimitris Visvikis, Kareem Wahid, Habib Zaidi, Mathieu Hatt, Adrien Depeursinge

Faculty, Staff and Student Publications

This paper presents an overview of the third edition of the HEad and neCK TumOR segmentation and outcome prediction (HECKTOR) challenge, organized as a satellite event of the 25th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) 2022. The challenge comprises two tasks related to the automatic analysis of FDG-PET/CT images for patients with Head and Neck cancer (H&N), focusing on the oropharynx region. Task 1 is the fully automatic segmentation of H&N primary Gross Tumor Volume (GTVp) and metastatic lymph nodes (GTVn) from FDG-PET/CT images. Task 2 is the fully automatic prediction of Recurrence-Free Survival (RFS) …

Ambulatory Monitoring Of Subglottal Pressure Estimated From Neck-Surface Vibration In Individuals With And Without Voice Disorders, Juan P Cortés, Jon Z Lin, Katherine L Marks, Víctor M Espinoza, Emiro J Ibarra, Matías Zañartu, Robert E Hillman, Daryush D Mehta

Faculty, Staff and Student Publications

The aerodynamic voice assessment of subglottal air pressure can discriminate between speakers with typical voices from patients with voice disorders, with further evidence validating subglottal pressure as a clinical outcome measure. Although estimating subglottal pressure during phonation is an important component of a standard voice assessment, current methods for estimating subglottal pressure rely on non-natural speech tasks in a clinical or laboratory setting. This study reports on the validation of a method for subglottal pressure estimation in individuals with and without voice disorders that can be translated to connected speech to enable the monitoring of vocal function and behavior in …

Magnetic Resonance-Guided Radiation Therapy For Head And Neck Cancers, Danny Lavigne, Sweet Ping Ng, Brian O'Sullivan, Phuc Felix Nguyen-Tan, Edith Filion, Laurent Létourneau-Guillon, Clifton D Fuller, Houda Bahig

Faculty, Staff and Student Publications

Despite the significant evolution of radiation therapy (RT) techniques in recent years, many patients with head and neck cancer still experience significant toxicities during and after treatments. The increased soft tissue contrast and functional sequences of magnetic resonance imaging (MRI) are particularly attractive in head and neck cancer and have led to the increasing development of magnetic resonance-guided RT (MRgRT). This approach refers to the inclusion of the additional information acquired from a diagnostic or planning MRI in radiation treatment planning, and now extends to online high-quality daily imaging generated by the recently developed MR-Linac. MRgRT holds numerous potentials, including …

Adhering To Eat And Exercise Status During Radiotherapy For Oropharyngeal Cancer For Prevention And Mitigation Of Radiotherapy-Associated Dysphagia, Carly E A Barbon, Christine B Peterson, Amy C Moreno, Stephen Y Lai, Jay P Reddy, Ariana Sahli, Rosemary Martino, Faye M Johnson, Clifton David Fuller, Katherine A Hutcheson

Faculty, Staff and Student Publications

IMPORTANCE: Previously published work reported independent benefit of maintenance of oral intake (eat) and swallowing exercise adherence (exercise) during radiotherapy (RT) on diet and functional outcomes. The current study seeks to validate the authors' previously published findings in a large contemporary cohort of patients with oropharynx cancer (OPC) and address limitations of the prior retrospective study using prospective, validated outcome measures.

OBJECTIVE: To examine the longitudinal association of oral intake and swallowing exercise using validated, clinician-graded and patient-reported outcomes.

DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of a prospective OPC registry including patients who underwent primary RT/chemoradiotherapy (CRT) or primary transoral …

Automated Extraction Of Anatomical Measurements From Temporal Bone Ct Imaging, Andy S Ding, Alexander Lu, Zhaoshuo Li, Deepa Galaiya, Masaru Ishii, Jeffrey H Siewerdsen, Russell H Taylor, Francis X Creighton

Faculty, Staff and Student Publications

OBJECTIVE: Proposed methods of minimally invasive and robot-assisted procedures within the temporal bone require measurements of surgically relevant distances and angles, which often require time-consuming manual segmentation of preoperative imaging. This study aims to describe an automatic segmentation and measurement extraction pipeline of temporal bone cone-beam computed tomography (CT) scans.

STUDY DESIGN: Descriptive study of temporal bone measurements.

SETTING: Academic institution.

METHODS: A propagation template composed of 16 temporal bone CT scans was formed with relevant anatomical structures and landmarks manually segmented. Next, 52 temporal bone CT scans were autonomously segmented using deformable registration techniques from the Advanced Normalization Tools …

Swallowing After Primary Tors And Unilateral Or Bilateral Radiation For Low- To Intermediate-Risk Tonsil Cancer, Carly E A Barbon, Christopher M K Yao, Christine B Peterson, Amy C Moreno, Ryan P Goepfert, Faye M Johnson, Gregory M Chronowski, Clifton D Fuller, Neil D Gross, Katherine A Hutcheson

Faculty, Staff and Student Publications

Objective: The primary course of treatment for patients with low- to intermediate-risk tonsil cancer has evolved with a shift toward primary transoral robotic surgery (TORS) or radiation therapy (RT). While favorable outcomes have been reported after deintensification via unilateral TORS or RT (uniRT), comparisons of functional outcomes between these treatments are lacking. We compared clinical outcomes (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST] and feeding tube [FT]) and patient-reported swallowing outcomes (MD Anderson Dysphagia Inventory [MDADI]) based on primary treatment strategy: TORS, uniRT, or bilateral RT (biRT).

Study design: Secondary analysis of prospective cohort.

Setting: Single institution.

Methods: The study …

Changes In Apparent Diffusion Coefficient (Adc) In Serial Weekly Mri During Radiotherapy In Patients With Head And Neck Cancer: Results From The Predict-Hn Study, Sweet Ping Ng, Carlos E Cardenas, Houda Bahig, Baher Elgohari, Jihong Wang, Jason M Johnson, Amy C Moreno, Shalin J Shah, Adam S Garden, Jack Phan, G Brandon Gunn, Steven J Frank, Yao Ding, Lumine Na, Ying Yuan, Diana Urbauer, Abdallah S R Mohamed, David I Rosenthal, William H Morrison, Michael P Macmanus, Clifton D Fuller

Faculty, Staff and Student Publications

Background: The PREDICT-HN study aimed to systematically assess the kinetics of imaging MR biomarkers during head and neck radiotherapy.

Methods: Patients with intact squamous cell carcinoma of the head and neck were enrolled. Pre-, during, and post-treatment MRI were obtained. Serial GTV and ADC measurements were recorded. The correlation between each feature and the GTV was calculated using Spearman’s correlation coefficient. The linear mixed model was used to evaluate the change in GTV over time.

Results: A total of 41 patients completed the study. The majority (76%) had oropharyngeal cancer. A total of 36 patients had intact primary tumours that …

Muscle And Adipose Tissue Segmentations At The Third Cervical Vertebral Level In Patients With Head And Neck Cancer, Kareem A Wahid, Brennan Olson, Rishab Jain, Aaron J Grossberg, Dina El-Habashy, Cem Dede, Vivian Salama, Moamen Abobakr, Abdallah S R Mohamed, Renjie He, Joel Jaskari, Jaakko Sahlsten, Kimmo Kaski, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

The accurate determination of sarcopenia is critical for disease management in patients with head and neck cancer (HNC). Quantitative determination of sarcopenia is currently dependent on manually-generated segmentations of skeletal muscle derived from computed tomography (CT) cross-sectional imaging. This has prompted the increasing utilization of machine learning models for automated sarcopenia determination. However, extant datasets currently do not provide the necessary manually-generated skeletal muscle segmentations at the C3 vertebral level needed for building these models. In this data descriptor, a set of 394 HNC patients were selected from The Cancer Imaging Archive, and their skeletal muscle and adipose tissue was …

Glutathione Peroxidase 2 Is A Metabolic Driver Of The Tumor Immune Microenvironment And Immune Checkpoint Inhibitor Response, Kazi Mokim Ahmed, Ratna Veeramachaneni, Defeng Deng, Nagireddy Putluri, Vasanta Putluri, Maria F Cardenas, David A Wheeler, William K Decker, Andy I Frederick, Sawad Kazi, Andrew G Sikora, Vlad C Sandulache, Mitchell J Frederick

Faculty, Staff and Students Publications

BACKGROUND: The existence of immunologically 'cold tumors' frequently found across a wide spectrum of tumor types represents a significant challenge for cancer immunotherapy. Cold tumors have poor baseline pan-leukocyte infiltration, including a low prevalence of cytotoxic lymphocytes, and not surprisingly respond unfavorably to immune checkpoint (IC) inhibitors. We hypothesized that cold tumors harbor a mechanism of immune escape upstream and independent of ICs that may be driven by tumor biology rather than differences in mutational neoantigen burden.

METHODS: Using a bioinformatic approach to analyze TCGA (The Cancer Genome Atlas) RNA sequencing data we identified genes upregulated in cold versus hot …

Advances In Head And Neck Cancer Pain, Y Ye, D D Jensen, C T Viet, H L Pan, W M Campana, M Amit, M D Boada

Faculty, Staff and Student Publications

Head and neck cancer (HNC) affects over 890,000 people annually worldwide and has a mortality rate of 50%. Aside from poor survival, HNC pain impairs eating, drinking, and talking in patients, severely reducing quality of life. Different pain phenotype in patients (allodynia, hyperalgesia, and spontaneous pain) results from a combination of anatomical, histopathological, and molecular differences between cancers. Poor pathologic features (e.g., perineural invasion, lymph node metastasis) are associated with increased pain. The use of syngeneic/immunocompetent animal models, as well as a new mouse model of perineural invasion, provides novel insights into the pathobiology of HNC pain. Glial and immune …

Success And Outcomes Following A Second Salvage Attempt For Free Flap Compromise In Patients Undergoing Head And Neck Reconstruction, Allison A Slijepcevic, Gavin Young, Justin Shinn, Steven B Cannady, Matthew Hanasono, Matthew Old, Jeewanjot S Grewal, Tamer Ghanem, Yadranko Ducic, Joseph M Curry, Mark K Wax

Faculty, Staff and Student Publications

Importance: Incidence of perioperative free flap compromise is low, with successful salvage in up to 70%. When the flap is compromised a second time, the value of intervening is unknown.

Objective: To assess the outcomes of a second revascularization attempt for compromised free flaps.

Design, setting, and participants: This multicenter retrospective medical record review included patients undergoing head and neck reconstruction with free flaps at 6 US medical centers from January 1, 2000, through December 30, 2020. Patients were 18 years or older with a history of head and neck defects from cancer, osteoradionecrosis, or other wounds. Of 3510 flaps …

Knowledge-Based Planning For The Radiation Therapy Treatment Plan Quality Assurance For Patients With Head And Neck Cancer, Wenhua Cao, Mary Gronberg, Adenike Olanrewaju, Thomas Whitaker, Karen Hoffman, Carlos Cardenas, Adam Garden, Heath Skinner, Beth Beadle, Laurence Court

Faculty, Staff and Student Publications

This study aimed to investigate the feasibility of using a knowledge-based planning technique to detect poor quality VMAT plans for patients with head and neck cancer. We created two dose-volume histogram (DVH) prediction models using a commercial knowledge-based planning system (RapidPlan, Varian Medical Systems, Palo Alto, CA) from plans generated by manual planning (MP) and automated planning (AP) approaches. DVHs were predicted for evaluation cohort 1 (EC1) of 25 patients and compared with achieved DVHs of MP and AP plans to evaluate prediction accuracy. Additionally, we predicted DVHs for evaluation cohort 2 (EC2) of 25 patients for which we intentionally …

Outcomes After Definitive Surgery For Mandibular Osteoradionecrosis, Kevin J Contrera, Steven B Chinn, Randal S Weber, Dianna Roberts, Jeffery N Myers, Stephen Y Lai, Carol M Lewis, Amy C Hessel, Ann M Gillenwater, Collin F Mulcahy, Peirong Yu, Matthew M Hanasono, Clifton D Fuller, Mark S Chambers, Mark E Zafereo

Faculty, Staff and Student Publications

Objectives: To analyze charges, complications, survival, and functional outcomes for definitive surgery of mandibular osteoradionecrosis (ORN).

Materials and methods: Retrospective analysis of 76 patients who underwent segmental mandibulectomy with reconstruction from 2000 to 2009.

Results: Complications occurred in 49 (65%) patients and were associated with preoperative drainage (odds ratio [OR] 4.40, 95% confidence interval [CI] 1.01-19.27). The adjusted median charge was $343 000, and higher charges were associated with double flap reconstruction (OR 8.15, 95% CI 2.19-30.29) and smoking (OR 5.91, 95% CI 1.69-20.72). Improved swallow was associated with age <67 years (OR 3.76, 95% CI 1.16-12.17) and preoperative swallow (OR 3.42, 95% CI 1.23-9.51). Five-year ORN-recurrence-free survival was 93% while overall survival was 63% and associated with pulmonary disease (HR [hazard ratio] 3.57, 95% CI 1.43-8.94).

Conclusions: Although recurrence of ORN is rare, surgical complications are …

Integrative Genomic Analysis Reveals Low T-Cell Infiltration As The Primary Feature Of Tobacco Use In Hpv-Positive Oropharyngeal Cancer, Benjamin M Wahle, Paul Zolkind, Ricardo J Ramirez, Zachary L Skidmore, Sydney R Anderson, Angela Mazul, D Neil Hayes, Vlad C Sandulache, Wade L Thorstad, Douglas Adkins, Obi L Griffith, Malachi Griffith, Jose P Zevallos

Faculty, Staff and Students Publications

Although tobacco use is an independent adverse prognostic feature in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC), the biologic features associated with tobacco use have not been systematically investigated. We characterized genomic and immunologic features associated with tobacco use through whole exome sequencing, mRNA hybridization, and immunohistochemical staining in 47 HPV(+) OPSCC tumors. Low expression of transcripts in a T cell-inflamed gene expression profile (TGEP) was associated with tobacco use at diagnosis and lower overall and disease-free survival. Tobacco use was associated with an increased proportion of T > C substitutions and a lower proportion of expected mutational signatures, but not with …

Evaluation Of Programmed Death Ligand 1 Expression In Cytology To Determine Eligibility For Immune Checkpoint Inhibitor Therapy In Patients With Head And Neck Squamous Cell Carcinoma, Zhonghua Liu, Michelle Williams, John Stewart, Bonnie S Glisson, Clifton Fuller, Sinchita Roy-Chowdhuri

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway have recently emerged as a frontline treatment for head and neck squamous cell carcinoma (HNSCC). The evaluation of PD-L1 expression by immunohistochemistry in histologic samples is used to determine the eligibility of patients with HNSCC for immunotherapy. Patients with newly diagnosed HNSCC are frequently diagnosed by fine-needle aspiration (FNA) of lymph nodes with metastatic disease. However, the evaluation of PD-L1 expression with the proposed combined positive score (CPS) has not been well established in cytology specimens.

Methods: This study retrospectively identified 21 …

Metabolic Targeting, Immunotherapy And Radiation In Locally Advanced Non-Small Cell Lung Cancer: Where Do We Go From Here?, Annika Dhawan, Phillip M Pifer, Vlad C Sandulache, Heath D Skinner

Faculty, Staff and Students Publications

In the US, there are ~250,000 new lung cancer diagnoses and ~130,000 deaths per year, and worldwide there are an estimated 1.6 million deaths per year from this deadly disease. Lung cancer is the most common cause of cancer death worldwide, and it accounts for roughly a quarter of all cancer deaths in the US. Non-small cell lung cancer (NSCLC) represents 80-85% of these cases. Due to an enormous tobacco cessation effort, NSCLC rates in the US are decreasing, and the implementation of lung cancer screening guidelines and other programs have resulted in a higher percentage of patients presenting with …

Deep-Learning-Based Generation Of Synthetic 6-Minute Mri From 2-Minute Mri For Use In Head And Neck Cancer Radiotherapy, Kareem A Wahid, Jiaofeng Xu, Dina El-Habashy, Yomna Khamis, Moamen Abobakr, Brigid Mcdonald, Nicolette O' Connell, Daniel Thill, Sara Ahmed, Christina Setareh Sharafi, Kathryn Preston, Travis C Salzillo, Abdallah S R Mohamed, Renjie He, Nathan Cho, John Christodouleas, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

Background: Quick magnetic resonance imaging (MRI) scans with low contrast-to-noise ratio are typically acquired for daily MRI-guided radiotherapy setup. However, for patients with head and neck (HN) cancer, these images are often insufficient for discriminating target volumes and organs at risk (OARs). In this study, we investigated a deep learning (DL) approach to generate high-quality synthetic images from low-quality images.

Methods: We used 108 unique HN image sets of paired 2-minute T2-weighted scans (2mMRI) and 6-minute T2-weighted scans (6mMRI). 90 image sets (~20,000 slices) were used to train a 2-dimensional generative adversarial DL model that utilized 2mMRI as input and …

Proton Image-Guided Radiation Assignment For Therapeutic Escalation Via Selection Of Locally Advanced Head And Neck Cancer Patients [Pirates]: A Phase I Safety And Feasibility Trial Of Mri-Guided Adaptive Particle Radiotherapy, Lisanne V Van Dijk, Steven J Frank, Ying Yuan, Brandon Gunn, Amy C Moreno, Abdallah S R Mohamed, Kathryn E Preston, Yun Qing, Michael T Spiotto, William H Morrison, Anna Lee, Jack Phan, Adam S Garden, David I Rosenthal, Johannes A Langendijk, Clifton D Fuller

Faculty, Staff and Student Publications

Introduction: Radiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With "Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients" (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach.

Methods: The PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk …

Progression Free Survival Prediction For Head And Neck Cancer Using Deep Learning Based On Clinical And Pet/Ct Imaging Data, Mohamed A Naser, Kareem A Wahid, Abdallah S R Mohamed, Moamen Abobakr Abdelaal, Renjie He, Cem Dede, Lisanne V Van Dijk, Clifton D Fuller

Faculty, Staff and Student Publications

Determining progression-free survival (PFS) for head and neck squamous cell carcinoma (HNSCC) patients is a challenging but pertinent task that could help stratify patients for improved overall outcomes. PET/CT images provide a rich source of anatomical and metabolic data for potential clinical biomarkers that would inform treatment decisions and could help improve PFS. In this study, we participate in the 2021 HECKTOR Challenge to predict PFS in a large dataset of HNSCC PET/CT images using deep learning approaches. We develop a series of deep learning models based on the DenseNet architecture using a negative log-likelihood loss function that utilizes PET/CT …

Combining Tumor Segmentation Masks With Pet/Ct Images And Clinical Data In A Deep Learning Framework For Improved Prognostic Prediction In Head And Neck Squamous Cell Carcinoma, Kareem A Wahid, Renjie He, Cem Dede, Abdallah S R Mohamed, Moamen Abobakr Abdelaal, Lisanne V Van Dijk, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

PET/CT images provide a rich data source for clinical prediction models in head and neck squamous cell carcinoma (HNSCC). Deep learning models often use images in an end-to-end fashion with clinical data or no additional input for predictions. However, in the context of HNSCC, the tumor region of interest may be an informative prior in the generation of improved prediction performance. In this study, we utilize a deep learning framework based on a DenseNet architecture to combine PET images, CT images, primary tumor segmentation masks, and clinical data as separate channels to predict progression-free survival (PFS) in days for HNSCC …

Establishment And Validation Of Pre-Therapy Cervical Vertebrae Muscle Quantification As A Prognostic Marker Of Sarcopenia In Patients With Head And Neck Cancer, Brennan Olson, Jared Edwards, Catherine Degnin, Nicole Santucci, Michelle Buncke, Jeffrey Hu, Yiyi Chen, Clifton D Fuller, Mathew Geltzeiler, Aaron J Grossberg, Daniel Clayburgh

Faculty, Staff and Student Publications

Background: Sarcopenia is prognostic for survival in patients with head and neck cancer (HNC). However, identification of this high-risk feature remains challenging without computed tomography (CT) imaging of the abdomen or thorax. Herein, we establish sarcopenia thresholds at the C3 level and determine if C3 sarcopenia is associated with survival in patients with HNC.

Methods: This retrospective cohort study was conducted in consecutive patients with a squamous cell carcinoma of the head and neck with cross-sectional abdominal or neck imaging within 60 days prior to treatment. Measurement of cross-sectional muscle area at L3 and C3 levels was performed from CT …

Level I Nodal Positivity As A Factor For Involvement Of The Submandibular Gland In Oral Cavity Carcinoma: A Case Series Report, Hamdan Ahmed Pasha, Rahim Dhanani, Shayan Khalid, Kulsoom Ghias, Mumtaz Jamshed Khan

Section of Otolaryngology, Head & Neck Surgery

Introduction: The routine practice of neck dissection in the surgical management of oral carcinoma has evolved into a more functionally conservative approach. Over time, the rationale for removal of the submandibular gland has been questioned. Routine extirpation of the submandibular gland can aggravate the xerostomia experienced by many patients, significantly affecting their quality of life.
Objective: The objective of the present study was to determine the incidence of submandibular gland metastases in oral cavity carcinoma and to identify possible factors that may affect their involvement.
Methods: A total of 149 cases of oral carcinoma presenting at a private tertiary care …

Spliceosome-Targeted Therapies Trigger An Antiviral Immune Response In Triple-Negative Breast Cancer, Elizabeth A Bowling, Jarey H Wang, Fade Gong, William Wu, Nicholas J Neill, Ik Sun Kim, Siddhartha Tyagi, Mayra Orellana, Sarah J Kurley, Rocio Dominguez-Vidaña, Hsiang-Ching Chung, Tiffany Y-T Hsu, Julien Dubrulle, Alexander B Saltzman, Heyuan Li, Jitendra K Meena, Gino M Canlas, Srinivas Chamakuri, Swarnima Singh, Lukas M Simon, Calla M Olson, Lacey E Dobrolecki, Michael T Lewis, Bing Zhang, Ido Golding, Jeffrey M Rosen, Damian W Young, Anna Malovannaya, Fabio Stossi, George Miles, Matthew J Ellis, Lihua Yu, Silvia Buonamici, Charles Y Lin, Kristen L Karlin, Xiang H-F Zhang, Thomas F Westbrook

Faculty, Staff and Students Publications

Many oncogenic insults deregulate RNA splicing, often leading to hypersensitivity of tumors to spliceosome-targeted therapies (STTs). However, the mechanisms by which STTs selectively kill cancers remain largely unknown. Herein, we discover that mis-spliced RNA itself is a molecular trigger for tumor killing through viral mimicry. In MYC-driven triple-negative breast cancer, STTs cause widespread cytoplasmic accumulation of mis-spliced mRNAs, many of which form double-stranded structures. Double-stranded RNA (dsRNA)-binding proteins recognize these endogenous dsRNAs, triggering antiviral signaling and extrinsic apoptosis. In immune-competent models of breast cancer, STTs cause tumor cell-intrinsic antiviral signaling, downstream adaptive immune signaling, and tumor cell death. Furthermore, RNA …

Drug-Induced Sleep Endoscopy (Dise) With Simulation Bite To Predict The Success Of Oral Appliance Therapy In Treating Obstructive Sleep Apnea/Hypopnea Syndrome (Osahs), Pietro De Luca

Translational Medicine @ UniSa

Oral appliances have gained their place in the treatment of obstructive sleep apnea (OSA) where custom-made titratable mandibular advancement devices (MAD) have become the oral appliance of choice. This study aimed to asses the value of the drug-induced sleep endoscopy (DISE) using a MAD in the prediction of treatment outcome for OSAHS

This is a prospective, single-center cohort study that enrolled sixty-six consecutive patients with diagnosed OSA (5 events/h < apnea-hypopnea index (AHI) < 50 events/h) to be treated with a custom-made titratable MAD. The patients were evaluated polysomnographically with the MAD in situ after the adaptation and titration period of 3 months. The associations between findings during DISE and treatment outcome were assessed.

The subjects showed a wide range of severity of OSAHS pre-treatment: median AHI was 43.10 with a range from 20.13 to 66.07. The simulation bite was associated with a significant increase …

Head And Neck Surgery Residency During Covid-19 Pandemic. Lessons From Southern Italy, Pietro De Luca

Translational Medicine @ UniSa

A letter to the Editor from an otolaryngology-head and neck surgery resident.

Direct Delivery Of Antisense Oligonucleotides To The Middle And Inner Ear Improves Hearing And Balance In Usher Mice, Jennifer J. Lentz, Bifeng Pan, Abhilash Ponnath, Christopher M. Tran, Carl Nist-Lund, Alice Galvin, Hannah Goldberg, Katelyn N. Robillard, Francine M. Jodelka, Hamilton E. Farris, Jun Huang, Tianwen Chen, Hong Zhu, Wu Zhou, Frank Rigo, Michelle L. Hastings, Gwenaëlle S.G. Géléoc

School of Medicine Faculty Publications

Usher syndrome is a syndromic form of hereditary hearing impairment that includes sensorineural hearing loss and delayed-onset retinitis pigmentosa (RP). Type 1 Usher syndrome (USH1) is characterized by congenital profound sensorineural hearing impairment and vestibular areflexia, with adolescent-onset RP. Systemic treatment with antisense oligonucleotides (ASOs) targeting the human USH1C c.216G>A splicing mutation in a knockin mouse model of USH1 restores hearing and balance. Herein, we explore the effect of delivering ASOs locally to the ear to treat hearing and vestibular dysfunction associated with Usher syndrome. Three localized delivery strategies were investigated in USH1C mice: inner ear injection, trans-tympanic membrane …

A Developmental Study Of Apoptotic Markers And Histamine In Cephalopod Statocysts, Samantha Nicole Leef

Honors Theses and Capstones

Cephalopods can participate in complex navigation using landmarks that show context due to their statocysts. Statocysts are analogous to the vertebrate vestibular and auditory system encased in cartilage rather than bone making them more easily accessible. Age and anatomical dysfunctions are the reasons for many human vestibular malfunctions. Two of these sources are endolymph hydrops and aging. In the past, endolymph pressure changes were attributed to the ineffectual ion transport. Recent studies have illuminated the possibility of histamine receptors in the semicircular canal could be responsible for patients’ endolymph pressure changes rather than the previous belief that the pressure changes …

A Deafness Mechanism Of Digenic Cx26 (Gjb2) And Cx30 (Gjb6) Mutations: Reduction Of Endocochlear Potential By Impairment Of Heterogeneous Gap Junctional Function In The Cochlear Lateral Wall, Ling Mei, Jin Chen, Liang Zong, Yan Zhu, Chun Liang, Raleigh O. Jones, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Digenic Connexin26 (Cx26, GJB2) and Cx30 (GJB6) heterozygous mutations are the second most frequent cause of recessive deafness in humans. However, the underlying deafness mechanism remains unclear. In this study, we created different double Cx26 and Cx30 heterozygous (Cx26^+/−/Cx30^+/−) mouse models to investigate the underlying pathological changes and deafness mechanism. We found that double Cx26^+/−/Cx30^+/− heterozygous mice had hearing loss. Endocochlear potential (EP), which is a driving force for hair cells producing auditory receptor current, was reduced. However, unlike Cx26 homozygous knockout (Cx26^−/−) mice, the cochlea in Cx26 …

P2x2 Dominant Deafness Mutations Have No Negative Effect On Wild-Type Isoform: Implications For Functional Rescue And In Deafness Mechanism, Yan Zhu, Juline Beudez, Ning Yu, Thomas Grutter, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

The P2X2 receptor is an ATP-gated ion channel, assembled by three subunits. Recently, it has been found that heterozygous mutations of P2X2 V60L and G353R can cause autosomal dominant nonsyndromic hearing loss. However, the underlying mechanism remains unclear. The fact that heterozygous mutations cause deafness suggests that the mutations may have dominant-negative effect (DNE) on wild-type (WT) P2X2 isoforms and/or other partners leading to hearing loss. In this study, the effect of these dominant deafness P2X2 mutations on WT P2X2 was investigated. We found that sole transfection of both V60L and G353R deafness mutants could efficiently target to the plasma …

Progressive Age-Dependence And Frequency Difference In The Effect Of Gap Junctions On Active Cochlear Amplification And Hearing, Liang Zong, Jin Chen, Yan Zhu, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Mutations of Connexin 26 (Cx26, GJB2), which is a predominant gap junction isoform in the cochlea, can induce high incidence of nonsyndromic hearing loss. We previously found that targeted-deletion of Cx26 in supporting Deiters cells and outer pillar cells in the cochlea can influence outer hair cell (OHC) electromotility and reduce active cochlear amplification leading to hearing loss, even though there are no gap junction connexin expressions in the auditory sensory hair cells. Here, we further report that hearing loss and the reduction of active amplification in the Cx26 targeted-deletion mice are progressive and different at high and low …