Voice as a Biomarker in Health-Tech: Mapping the Evolving Landscape of Voice Biomarkers in the Start-Up World.

OBJECTIVE: The vocal biomarkers market was worth $1.9B in 2021 and is projected to exceed $5.1B by 2028, for a compound annual growth rate of 15.15%. The investment growth demonstrates a blossoming interest in voice and artificial intelligence (AI) as it relates to human health. The objective of this study was to map the current landscape of start-ups utilizing voice as a biomarker in health-tech. DATA SOURCES: A comprehensive search for start-ups was conducted using Google, LinkedIn, Twitter, and Facebook. A review of the research was performed using company website, PubMed, and Google Scholar. REVIEW METHODS: A 3-pronged approach was taken to thoroughly map the landscape. First, an internet search was conducted to identify current start-ups focusing on products relating to voice as a biomarker of health. Second, Crunchbase was utilized to collect financial and organizational information. Third, a review of the literature was conducted to analyze publications associated with the identified start-ups. RESULTS: A total of 27 start-up start-ups with a focus in the utilization of AI for developing biomarkers of health from the human voice were identified. Twenty-four of these start-ups garnered $178,808,039 in investments. The 27 start-ups published 194 publications combined, 128 (66%) of which were peer reviewed. CONCLUSION: There is growing enthusiasm surrounding voice as a biomarker in health-tech. Academic drive may complement commercialization to best achieve progress in this arena. More research is needed to accurately capture the entirety of the field, including larger industry players, academic institutions, and non-English content.

Impact of BMI on Dyspnea and Need for Surgical Intervention in Bilateral Vocal Fold Immobility.

OBJECTIVE: Bilateral vocal fold paralysis (BVFP) and posterior glottic stenosis (PGS) are causes of bilateral vocal fold immobility (BVFI) and may cause shortness of breath, stridor, and need for surgical intervention. Although increased body mass index (BMI) is associated with restrictive breathing patterns in patients with normal upper airways, it is unclear how BMI impacts dyspnea and need for surgical intervention in BVFI patients. STUDY DESIGN: Retrospective cohort study. SETTING: Three tertiary academic centers in the United States. METHODS: Demographics, BMI, Dyspnea Index (DI), etiology, presence of tracheostomy and surgical intervention (dilation, tracheostomy, cordotomy, arytenoidectomy, open reconstruction) were collected. Primary outcomes included dyspnea measured by DI and need for surgery to improve airway. Linear regressions were performed to assess continuous outcomes. Mann-Whitney U-test was utilized to assess categorical outcomes. RESULTS: Among 121 patients, 52 presented with BVFP and 69 with PGS. Previous neck surgery was the most common cause of BVFI (40.2%). 44.3% of patients received a tracheostomy. Through multivariate linear regression, increased BMI was significantly associated with increased DI in the entire cohort (ß = .43, P = .016). Increased BMI was also associated with need for any surgical intervention (odds ratio [OR] = 1.07, 95% confidence interval [CI] = [1.01-1.13]) in the overall cohort. When stratifying our data, BMI was only significantly associated with DI in BVFP (ß = .496) and need for surgical intervention in PGS (OR = 1.11, 95% CI = [1.01-1.21]), although a positive trend was seen in all analyses. CONCLUSION: Increased BMI may correlate with worsening dyspnea symptoms and need for surgical intervention in patients with BVFI. Weight-loss-related counseling may benefit symptom management.

Voice as an AI Biomarker of Health-Introducing Audiomics.

This Viewpoint discusses the need to create standards for audiomics to identify unique audio biomarkers of health and disease­now possible because of more efficient voice data analysis available through the use of artificial intelligence (AI)­and to improve patient care.

Decision-Making in the Treatment of Idiopathic Subglottic Stenosis: A Survey of Laryngologists.

OBJECTIVE: Idiopathic subglottic stenosis (iSGS) is a rare condition involving the subglottic larynx and upper trachea, commonly affecting Caucasian females between 30 and 50 years of age. Despite its homogeneous presentation, clinical management for iSGS is yet to be standardized, leading to variability in outcomes between predominant interventions. In recognition of the heterogenicity in iSGS treatment and the need to improve patient outcomes, this study aimed to survey laryngologists to understand the factors influencing clinical decision-making and the incorporation of new treatment modalities for iSGS. METHODS: An online survey was sent to 145 academic laryngologists. The survey assessed respondents' professional backgrounds, experience treating iSGS, treatment algorithms, and how various patient factors affect management. RESULTS: Of the 87 (60%) laryngologists who responded to the survey, the most common clinical assessments were tracheoscopy/bronchoscopy (96.8%) and pulmonary function tests (43.6%). Endoscopic dilation (ED) was the most common primary treatment offered (97.5%): 28.7% of surveyed laryngologists offer SISI as a primary treatment, and 74.7% perform SISI as a planned postoperative treatment. The most common SISI protocol was repeated injections every 4-6 weeks for a series of 1-3 total injections. Notably, 9.2% perform the Maddern procedure. Routine algorithms of care involving surgery were most often based on prior experience and prior patient outcomes (75.9%) and conversations with colleagues (64.4%). Only 31% report using the same protocol learned during their fellowship training. CONCLUSION: This survey highlights significant variation in the management of patients with iSGS. Understanding the factors that influence decision-making may lead to potential standardization in heterogeneous treatment approaches and may improve clinical outcomes. LEVEL OF EVIDENCE: 5 Laryngoscope, 134:865-872, 2024.

Machine Learning Analysis of Physical Activity Data to Classify Postural Dysfunction.

BACKGROUND: Machine learning (ML) analysis of biometric data in non-controlled environments is underexplored. OBJECTIVE: To evaluate whether ML analysis of physical activity data can be employed to classify whether individuals have postural dysfunction in middle-aged and older individuals. METHODS: A 1 week period of physical activity was measured by a waist-worn uni-axial accelerometer during the 2003-2004 National Health and Nutrition Examination Survey sampling period. Features of physical activity along with basic demographic information (42 variables) were paired with ML models to predict the success or failure of a standard 30 s modified Romberg test during which participants had their eyes closed and stood upon a 3-inch compliant surface. Model performance was evaluated by area under the receiver operating characteristic curve (AUC-ROC), balanced accuracy, and F1-score. RESULTS: The cohort was comprised of 1625 participants ≥40 years (median age 61, IQR 51-71). Approximately half (47%) were diagnosed with postural dysfunction having failed the binarized (pass/fail) scoring mechanism of the modified Romberg exam. Five ML models were trained on the classification task, achieving AUC values ranging from 0.67 to 0.73. The support vector machine (SVM) and a gradient-boosted model, XGBoost, achieved the highest AUC of 0.73 (SD 0.71-0.75). Age was the most important variable for SVM classification, followed by four features that evaluated accelerometer counts at various thresholds, including those delineating total, moderate, and moderate-vigorous activity. CONCLUSIONS: ML analysis of accelerometer-derived physical activity data to classify postural dysfunction in middle-aged and older individuals is feasible in real-world environments such as the home. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3529-3533, 2023.

Factors Associated With Dysphagia in Patients Undergoing Tracheal Resection.

Importance: Patients undergoing tracheal resection commonly experience dysphagia postoperatively, and the patient factors that predict severity and duration of symptoms are currently unclear. Objective: To determine the association of patient and surgical factors on postoperative dysphagia in adult patients undergoing tracheal resection. Design, Setting, and Participants: This was a retrospective cohort study of patients undergoing tracheal resection at 2 tertiary academic centers from February 2014 to May 2021. The centers included LAC+USC (Los Angeles County + University of Southern California) Medical Center and Keck Hospital of USC, both tertiary care academic institutions. Patients involved in the study underwent a tracheal or cricotracheal resection. Exposures: Tracheal or cricotracheal resection. Main Outcomes and Measures: The main outcome was dysphagia symptoms as measured by the functional oral intake scale (FOIS) on postoperative days (PODs) 3, 5, and 7, on the day of discharge, and at the 1-month follow-up visit. Demographics, medical comorbidities, and surgical factors were evaluated for association with FOIS scores at each time period using Kendall rank correlation and Cliff delta. Results: The study cohort consisted of 54 patients, with a mean (SD) age of 47 (15.7) years old, of whom 34 (63%) were male. Length of resection segment ranged from 2 to 6 cm, with a mean (SD) length of 3.8 (1.2) cm. The median (range) FOIS score was 4 (1-7) on PODs 3, 5, 7. On the day of discharge and at 1-month postoperative follow-up, the median (range) FOIS score was 5 (1-7) and 7 (1-7), respectively. Increasing patient age was moderately associated with decreasing FOIS scores at all measured time points (τ = -0.33; 95% CI, -0.51 to -0.15 on POD 3; τ = -0.38; 95% CI, -0.55 to -0.21 on POD 5; τ = -0.33; 95% CI, -0.58 to -0.08 on POD 7; τ = -0.22; 95% CI, -0.42 to -0.01 on day of discharge; and τ = -0.31; 95% CI, -0.53 to -0.09 at 1-month follow-up visit). History of neurological disease, including traumatic brain injury and intraoperative hyoid release, was not associated with FOIS score at any of the measured time points (δ = 0.03; 95% CI, -0.31 to 0.36 on POD 3; δ = 0.11; 95% CI, -0.28 to 0.47 on POD 5, δ = 0.3; 95% CI, -0.25 to 0.70 on POD 7; δ = 0.15; 95% CI, -0.24 to 0.51 on the day of discharge, and δ = 0.27; 95% CI, -0.05 to 0.53 at follow-up). Resection length was also not correlated with FOIS score with τ ranging from -0.04 to -0.23. Conclusions and Relevance: In this retrospective cohort study, most patients undergoing tracheal or cricotracheal resection experienced full resolution of dysphagia symptoms within the initial follow-up period. During preoperative patient selection and counseling, physicians should consider that older adult patients will experience greater severity of dysphagia throughout their postoperative course and delayed resolution of symptoms.

Artificial Intelligence and Laryngeal Cancer: From Screening to Prognosis: A State of the Art Review.

OBJECTIVE: This state of the art review aims to examine contemporary advances in applications of artificial intelligence (AI) to the screening, detection, management, and prognostication of laryngeal cancer (LC). DATA SOURCES: Four bibliographic databases were searched: PubMed, EMBASE, Cochrane, and IEEE. REVIEW METHODS: A structured review of the current literature (up to January 2022) was performed. Search terms related to topics of AI in LC were identified and queried by 2 independent reviewers. Citations of selected studies and review articles were also evaluated to ensure comprehensiveness. CONCLUSIONS: AI applications in LC have encompassed a variety of data modalities, including radiomics, genomics, acoustics, clinical data, and videomics, to support screening, diagnosis, therapeutic decision making, and prognosis. However, most studies remain at the proof-of-concept level, as AI algorithms are trained on single-institution databases with limited data sets and a single data modality. IMPLICATIONS FOR PRACTICE: AI algorithms in LC will need to be trained on large multi-institutional data sets and integrate multimodal data for optimal performance and clinical utility from screening to prognosis. Out of the data types reviewed, genomics has the most potential to provide generalizable models thanks to available large multi-institutional open access genomic data sets. Voice acoustic data represent an inexpensive and accurate biomarker, which is easy and noninvasive to capture, offering a unique opportunity for screening and monitoring of LA, especially in low-resource settings.

Intractable Bleeding Following an Awake Bedside Injection Laryngoplasty in a Patient on KVAD ECMO.

INTRODUCTION: Awake injection laryngoplasty (IL) is becoming increasingly utilized in the inpatient setting, especially as a therapeutic option for patients with vocal fold immobility immediately following cardiothoracic surgery. While prior studies consistently demonstrate complication rates below 3%, significant bleeding has not been reported as a major complication in any awake IL case series. The objective of this report is to highlight a case of intractable bleeding following awake inpatient bedside IL in a patient on KVAD (Koji Takeda Ventricular Assist Device) extracorporeal membrane oxygenation (ECMO). METHODS: Case Report. RESULTS: A 24-year-old female admitted to the cardiac ICU for asystole was placed on KVAD ECMO for heart failure of unknown etiology. She was extubated and listed for cardiac transplant. On postoperative day 14, she underwent a left vocal fold injection at bedside to treat fold paralysis with a large glottic gap causing her complete aphonia, dysphagia, and chronic aspiration. Seven hours post procedure, the patient had to be reintubated due to intractable bleeding. A direct laryngoscopy was performed at bedside and continuous trickle of blood from the injection site at the superior posterior lateral surface of the vocal fold was stopped using a combination of epi-pledgets and hemostatic matrix. The same procedure had to be performed again due to further bleeding 2 days later and permanent hemostasis was achieved. During the week post injection, the patient required transfusion of 5 units of pRBC's. One month later the patient underwent successful orthotopic heart transplantation and was transferred from the ICU to a stepdown unit, and then a rehabilitation unit. No further IL hemorrhage occurred. CONCLUSION: Although a few studies have discussed the safety of IL in patients receiving anticoagulation, this case report demonstrates intractable bleeding requiring intubation and intervention to achieve hemostasis in a patient on KVAD ECMO. This report highlights the importance of weighing the risks and benefits of vocal fold injection in this patient population.

A Comparison of an Artificial Intelligence Tool to Fundamental Frequency as an Outcome Measure in People Seeking a More Feminine Voice.

OBJECTIVES/HYPOTHESIS: An artificial intelligence (AI) tool was developed using audio clips of cis-male and cis-female voices based on spectral analysis to assess %probability of a voice being perceived as female (%Prob♀). This program was validated with 92% accuracy in cisgender speakers. The aim of the study was to assess the relationship of fo on %Prob♀ by a validated AI tool in a cohort of trans females who underwent intervention to feminize their voice with behavioral modification and/or surgery. STUDY DESIGN: Cohort study. METHODS: Fundamental frequency (fo ) from prolonged vowel sounds (fo /a/) and fo from spontaneous speech (fo -sp) were measured using the Kay Pentax Computerized Speech Lab (Montvale, NJ) in trans females postintervention. The same voice samples were analyzed by the AI tool for %Prob♀. Chi-square analysis and regression models were performed accepting >50% Prob♀ as female voice. RESULTS: Forty-two patients were available for analysis after intervention. fo -sp post-treatment was positively correlated with %Prob♀ (R = 0.645 [P < .001]). Chi-square analysis showed a significant association between AI %Prob♀ >50% for the speech samples and fo -sp >160 Hz (P < .01). Sixteen of 42 patients reached an fo -sp >160 Hz. Of these, the AI program only perceived nine patients as female (>50 %Prob♀). CONCLUSION: Patients with fo -sp >160 Hz after feminization treatments are not necessarily perceived as having a high probability of being female by a validated AI tool. AI may represent a useful outcome measurement tool for patients undergoing gender affirming voice care. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2567-2571, 2021.

In-Office Endoscopic Laryngeal Laser Procedures: A Patient Safety Initiative.

Objective To review complications of in-office endoscopic laryngeal laser procedures after implementation of standardized safety protocol. Methods A retrospective review was conducted of the first 2 years of in-office laser procedures at St Michaels Hospital after the introduction of a standardized safety protocol. The protocol included patient screening, procedure checklist with standardized reporting of processes, medications, and complications. Primary outcomes measured were complication rates of in-office laryngeal laser procedures. Secondary outcomes included hemodynamic changes, local anesthetic dose, laser settings, total laser/procedure time, and incidence of sedation. Results A total of 145 in-office KTP procedures performed on 65 patients were reviewed. In 98% of cases, the safety protocol was fully implemented. The overall complication rate was 4.8%. No major complications were encountered. Minor complications included vasovagal episodes and patient intolerance. The rate of patient intolerance resulting early termination of anticipated procedure was 13.1%. Total local anesthetic dose averaged 172.9 mg lidocaine per procedure. The mean amount of laser energy dispersed was 261.2 J, with mean total procedure time of 48.3 minutes. Sixteen percent of patients had preprocedure sedation. Vital signs were found to vary modestly. Systolic blood pressure was lower postprocedure in 13.8% and symptomatic in 4.1%. Discussion The review of our standardized safety protocol has revealed that in-office laser treatment for laryngeal pathology has extremely low complication rates with safe patient outcomes. Implications for Practice The trend of shifting procedures out of the operating room into the office/clinic setting requires new processes designed to promote patient safety.

In-office laryngeal procedures (IOLP) in Canada: current safety practices and procedural care.

BACKGROUND: The advent of chip tip technology combined with advanced endoscopy has revolutionized the field of laryngology in the past decade. Procedures such as transnasal esophagoscopy, site-specific steroid injections, injection laryngoplasty and laryngeal laser treatment can now be performed in the office setting under local anaesthesia. Although In-Office Laryngeal Procedures (IOLPs) have become standard-of-care in many American and several Canadian centers, there are no guidelines regulating the practice of these procedures. The goal of this report was to evaluate the current method of IOLP delivery in Canada. METHODS: An electronic survey was dispersed to 22 practicing Canadian laryngologists to assess safety and procedural care measures undertaken when performing IOLP. The survey consisted of 37 questions divided into 6 categories; 1) Demographic data 2) Facilities 3) Staff/personnel 4) Patient screening/monitoring 5) Procedure and emergency equipment 6) Reporting of adverse events. RESULTS: Data was collected for 16/22 laryngologists (72.7% response rate). Only 1 respondent did not perform IOLP. All performed injection augmentation laryngoplasty. Most performed laryngeal biopsies, intramuscular injection and/or electromyography guided injection for the treatment of spasmodic dysphonia and glottic/subglottic steroid injections. Only 4 respondents performed in-office KTP laser. Significant variation was found in procedural processes including intra procedural monitoring, anticoagulation screening, access to emergency equipment and documentation. CONCLUSION: Our survey demonstrates that the delivery of IOLP in Canada varies considerably. The construct of IOLP practice guidelines based on the evidence with consistent documentation would promote safe, efficient and quality care for patient with voice disorders.