train_dataset.jsonl

{"note": "\ufeffTitle: Functional outcomes in early (T1/T2) supraglottic cancer: a systematic review"}
{"note": "Abstract"}
{"note": "Objectives: Organ preserving surgery (OPS) and radiotherapy (RT) are both accepted treatment options for early stage supraglottic cancer (SGC). Radiation has supplanted surgery in most cases, because of the perception that surgery results in poorer functional outcomes. However, evidence suggests that OPS with a neck dissection may be associated with improved survival. Our objective was to conduct a systematic review of the literature to compare functional outcomes of OPS and RT for early SGC."}
{"note": "Methods: We searched Medline, EMBASE and Cochrane Central Register of Controlled Trials to identify studies. Studies were included if they reported functional outcomes on 10 or more patients with early stage SGC treated with radiation or OPS, including open partial laryngectomy, transoral laser microsurgery (TLM) or transoral robotic surgery (TORS). Two reviewers independently screened articles for relevance using pre-determined criteria."}
{"note": "Results: From 7720 references, we included 10 articles (n = 640 patients). 50% (n = 320) of patients were treated with surgery. Three head-to-head RT versus OPS papers were included, however different outcome measures were used for each group. Intractable aspiration management (including total laryngectomy or permanent tracheostomy) following OPS was reported in five papers representing 186 patients; the definitive intractable aspiration management rate was 2.6% (95% CI 1.0\u20136.8%). Four papers reported permanent G-tube rate for the surgical group (n = 198), calculating a rate of 5.3% (95% CI 2.6\u201310.5%), this was not reported for the RT group in any papers. One study reported quality of life. Two studies reported objective voice measures."}
{"note": "Conclusions: This systematic review revealed a paucity of objective measures and significant data heterogeneity, rendering the comparison of functional outcomes following OPS versus RT for early SGC limited. Future research should include objective measures of functional outcomes including laryngectomy rate, g-tube rate, tracheostomy dependence, quality of life, and voice quality measures."}
{"note": "Keywords: Early stage, Supraglottic squamous cell carcinoma, Supraglottic SCC, Outcomes, Systematic review, Functional outcomes"}
{"note": "Introduction"}
{"note": "Early stage supraglottic squamous cell carcinoma (SSCC) includes T1 tumours, isolated to one subsite of the supra- glottis with normal vocal cord function, or T2 tumours, involving more than one subsite of the supraglottis, glottis, or surrounding tissue, without evidence of regional disease spread [1]. A recent study of nearly 160,000 laryngeal can- cer SCC patients in the United States, found the incidence of SSCC to account for one third of laryngeal cancers [2]. Laryngeal cancers are the most common malignant lesions of the head and neck, with an estimated 13,150 new laryngeal cancers per year [3].The recommendations from the National Comprehensive Cancer Network (NCCN) guidelines for treatment of early stage SSCC include both organ preservation strategies \u2013 radiation (RT) or organ preservation surgery (OPS) with or without a neck dissection [3, 4]. Despite small tumour sizes, 5-year survival for early stage SSCC is 64%, and oncologic outcomes have not improved over the past 30 years [2, 5\u20138]. This is hypothesized to be a result of the robust lymphatic supply to the supraglottis leading to higher rates of occult metastases to regional and distant sites. When comparing the relative 5-year survival from 1985 to 1987 to 1994\u20131996, there was a decline from 52.2 to 47.3%. Reviewing the data from the National Cancer Database, the largest decline was identified in patients with T1 N0-T2 N0 disease. A recent meta-analysis by Patel et al. (2018) examining survival in early stage supraglottic SCC suggested that primary surgery may result in decreased disease specific survival (OR 0.43, 95% CI 0.31\u20130.60) and overall mortality (OR 0.40, 0.29\u20130.55) when compared with primary radiotherapy [9]. There are a limited number of studies, with no previ- ous meta-analysis, that have compared the functional outcomes between primary surgery and primary radio- therapy for early stage SSCC. Much of the available data focuses on survival outcomes for the two treatment modalities [7\u201317]. There are no prospective clinical trials, and the majority of the studies reported are small and retrospective in design. Our objectives were to systematically review the literature to find all the relevant studies about the functional outcomes for surgery and radiation for early stage SSSC, synthesize the results and perform meta-analyses where possible."}
{"note": "Methods"}
{"note": "A systematic review protocol was developed a priori to en- sure the objectives and aims were outlined from the outset. Computerized bibliographic databases: Medline, EMBASE and Cochrane Central Register of Controlled Trials were searched to identify studies. English language records were included from January 1990 to October 2018. The search strategy was designed by three authors (B.V.W., K.B.P. and S.D.M.) and an experienced librarian. Randomized controlled trials, head-to-head comparative studies, observational studies, and case series that included 10 or more patients were reviewed. Single arm studies that reported functional results of organ preserva- tion surgeries or radiotherapy as single modality therapy were included in the review. Studies on organ preserving surgeries, including open partial laryngectomy, transoral laser microsurgery (TLM) or transoral robotic surgery (TORS), with and without neck dissection were included. The study population was limited to patients aged 18 and older, diagnosed with early stage supraglottic SCC (Tis, T1 N0, T2 N0). We excluded studies where functional results for patients with advanced T stage or node positive disease were grouped into the results and could not be reliably differentiated. We also excluded studies where functional outcomes for patients with early supra- glottic cancers were combined with early glottic cancers. Included studies were assessed for the following functional outcomes: aspiration; gastrostomy tube dependence; objective voice outcomes; and quality of life measures. Titles, abstracts, and full texts of the studies were reviewed independently by two authors (B.V.W. and K.B.P.). Disagreements were resolved by consensus. Inter-observer agreement was analyzed with Cohen\u2019s kappa. Titles were screened for the keywords: \u201csquamous cell carcinoma\u201d and \u201csupraglottic\u201d, or \u201csupraglottis\u201d, or \u201cglottic\u201d, or \u201cglottis\u201d, or \u201clarynx\u201d, or \u201claryngeal\u201d. All study abstracts that met the eligibility criteria were then screened individu- ally. The full text of studies that met inclusion criteria were then reviewed. The Newcastle-Ottawa Quality Assessment Scale for Cohort Studies was used to determine the quality of the studies (Table 2) [18]. Relevant data was extracted using a standardized data extraction form. Not all studies contained data for each of the outcome measures.         Review Manager 5.3 and Comprehensive Meta-Analysis applications were used for statistical analysis. Dichotomous outcomes were compared using odds ratios (OR) or weighted incidence rates and 95% confidence intervals (CI). Heterogeneity across the studies was evaluated by the chi-square statistic and significance was set at p < 0.05. The I2 test was used to measure the extent of inconsist- ency across the results. A random effects model was used to allow for differences in the treatment effects from study to study. The Z statistic was used to test for overall pooled effect and significance was set at p < 0.05."}
{"note": "Results"}
{"note": "The search strategy produced 7720 records. After dupli- cate records were removed from the search, 5218 unique records remained. After reviewing the titles, 1187 abstracts were deemed appropriate for abstract review. Following abstract review, 115 studies were appropriate for full text review. Ten studies met the final inclusion criteria after reviewing the full text."}
{"note": "CONCLUSIONS:"}
{"note": "There is an overall paucity of literature available regarding functional outcomes in the treatment of early stage SSCC patients, the majority of which is moderate in overall quality and retrospective in nature. The majority of the data does not reflect the treatment algorithms of today, with the introduction of focused radiation therapies and endoscopic surgical approaches. Changes to treatment algorithms have not been reflected in head-to-head studies examining the functional outcomes. The outcome measures reported have significant heterogeneity in the current literature, which limits the ability to draw definitive conclusions. Moving forward, we propose that aspiration, intractable aspiration intervention, permanent gastrostomy tube requirements, and objective quality of life scales as objective measures that should be included in future research on this topic. Future studies and research should include well designed prospective trials with rigorous reporting of outcome measures."}
{"note": "Study characteristics and methodologic quality"}
{"note": "There were no randomized controlled trials comparing the functional outcomes of primary surgery versus radiation. Of the 10 studies included in the analysis, 6 were retrospective cohort studies, 4 were case series. There were no prospective studies included. There were 320 patients treated with OPS, including open partial laryngectomy, transoral laser microsurgery (TLM) or trans- oral robotic surgery (TORS). For the RT arm, there were 320 patients. Altogether, 640 patients were ana- lyzed from 10 studies. There were 6 patients with early SSCC where the treatment modality was not specified and could not be included in the analyses. Characteristics of the included studies are summarized in Table 1. Overall, the quality of the included studies was moder- ate, this was for a variety of reasons, including no reference group (surgery or radiation arm only), short or unreported length of follow up, and unaccounted for patients. Table 2 summarizes the quality of the individual studies."}
{"note": "Aspiration"}
{"note": "Aspiration was deemed a primary functional outcome measure of assessment. It was reported in 5 studies [11, 14, 19\u201321]. In one paper, this was evaluated under direct visualization with a functional endoscopic examination of swallowing, where the authors documented liquid penetration. The remainder of the papers reported patients with clinically evident late aspiration, and sequelae such as aspiration pneumonia. In the surgical arm, 9 out of 252 patients were reported to experience aspiration, for a pooled aspiration rate of 3.7% (95% CI 1.9\u20136.9%) (Fig. 2). In the RT arm, aspiration is reported in 15 out of 198 patients, for a pooled aspiration rate of 14.5% (95% CI 9.1\u201322.5%) (Fig. 3). The odds ratio is 1.23 (95% CI 0.14\u201310.86) (Fig. 4)."}
{"note": "Intractable aspiration management"}
{"note": "In many of the studies, rate of functional laryngectomy and permanent tracheostomy dependence was reported. These statistics included some, but not all, of the pa- tients who experienced late complications associated with aspiration events. This was reported in 5 studies, accounting for 186 surgical patients and 198 radiation patients. The pooled event rate for intractable aspiration management in the surgical arm is 2.6% (95% CI 1.0\u2013 6.8%) (Fig. 5). The pooled event rate for the RT arm is 16.8% (95% CI 10.8\u201325.0%) (Fig. 6). The odds ratio com- paring the two groups is 1.14 (95% CI 0.04\u201333.45) (Fig. 7)."}
{"note": "Permanent gastrostomy tube and swallowing dysfunction"}
{"note": "The rate of permanent gastrostomy tube was reported in four studies for the OPS group. This accounted for 198 patients. This outcome measure was not reported for the radiation group in any of the studies. The pooled event ratio for permanent gastrostomy tube dependence is 5.3% (95% CI 2.6\u201310.5%) (Fig. 8)."}
{"note": "Additionally, Chun et al. compared OPS to RT with respect to functional outcomes of swallowing and speech. To evaluate swallowing, patients underwent a functional endoscopic examination of swallowing (FEES) using videoesophagofluoroscopy. The researchers looked specifically for evidence of aspiration. Liquid aspiration was identified 6% of patients in the OPS group (n = 1). There was no identified liquid aspiration in the RT co- hort [11]."}
{"note": "Quality of life and voice outcomes"}
{"note": "Quality of life data was reported in one study. Another study reported objective voice outcome measures. Oridate et al. compared VRQOL, VHI-10, and GRBAS scores for T2 N0 SSCC against T1a, T1b, and T2 N0 glottic carcin- omas and found no significant differences in functional outcomes [22]."}
{"note": "Chun et al. used stroboscopy and acoustic waveform ana- lysis to objectively evaluate voice outcomes. Abnormalities were in mucosal waveforms were identified 13% of the OPS cohort (n = 2) and 20% of the RT group (n = 2). These find- ings were not statistically significant [11]."}
{"note": "Discussion"}
{"note": "To our knowledge, this is the first systematic review evaluating the functional outcomes of surgery versus radiother- apy for early-stage SSCC. All studies that met inclusion criteria were retrospective in design and there were 3 head-to-head comparisons of surgery versus radiation. Aspiration events, management of intractable aspiration, and permanent gastrostomy tubes are some of the major indications of laryngeal function. There was insufficient data to thoroughly meta-analyze the two modalities with respect to these outcome measures. Furthermore, object- ive voice outcomes were available in just two studies. Quality of life measures were only found in one included paper."}
{"note": "Aspiration events were reported, in many cases, with little additional information. In some studies, these were clinically evident respiratory events, such as aspiration pneumonias that occurred late in the post-operative course, others reported only the number patients that experienced aspiration. Aspiration events are reported in 50% of studies (n =5), 2 of which were head-to-head comparisons."}
{"note": "For intractable aspiration intervention, there was data from both the surgical and radiation cohorts from multiple studies. This was reported as permanent trache- ostomy dependence or conversion to a functional total laryngectomy. We calculated pooled event rates as well as pooled odds ratio. From the current data available, there is no strong evidence to suggest there is a differ- ence between the two modalities with respect to this outcome measure."}
{"note": "With respect to permanent gastrostomy tube rate, there was no available data for the radiation cohort. Four papers reported this outcome measure for the surgical group (n = 198 patients). As a result, we were unable to make comparisons across the two treatment modalities."}
{"note": "Subjective and objective measures of voice outcome were sparsely and inconsistently reported. Quality of life measures were found in just one study, which actually compared T2N0 supraglottic cancers to early glottic cancers."}
{"note": "Surgery and radiotherapy for early stage SSCC"}
{"note": "Several factors are important in considering treatment options for patients with early laryngeal cancer. Survival outcomes are obviously at the forefront. While there is no RCT data comparing survival outcomes of patients with early SSCC, a 2016 meta-analysis by Patel et al. studying early stage SSCC suggests that patients who undergo primary surgery have better survival than those who underwent primary radiotherapy [8]. Laryngectomy rate is another important consideration, as most patients with early stage laryngeal cancer are candidates for organ preservation treatment. Finally, in the presence of equivalent survival for two treatment modalities, functional outcomes are important to assess in comparing treatment options."}
{"note": "Over the last 40 years the treatment of early stage laryngeal cancer has evolved [23, 24]. Surgery, in the form of open partial laryngectomy, was initially popular how- ever many patients had poor functional outcomes including aspiration and impaired base of tongue and laryngeal movements leading to swallowing dysfunction [25]. Radiation then took over as the primary treatment modality for early stage laryngeal cancer, with the goal of mitigating many of the functional problems associated with open partial laryngectomy. However, radiation is not without its own side effects. In addition, minimally invasive surgical techniques including TORS and TLM are increasingly being used for early stage SSCC [23, 24], raising the question of whether the functional outcomes with TORS and TLM may be better than radiation. Unfortunately, there are very few studies reporting the functional outcomes of TORS and TLM for early stage supraglottic cancer."}
{"note": "There are several advantages of RT. It preserves the laryngeal structures, it is generally well tolerated by patients, and increases surgical exposure to achieve excellent oncologic outcomes [26\u201329]. Radiation provides an effective treatment modality for patients not considered candidates for OPS due to their comorbid medical conditions. One of the disadvantages in treating early stage SSCC with RT, is that these patients are at high risk for developing a second primary and local regional recurrence [5, 6, 30]. If radiation is used as the primary treatment modality, most patients can only be salvaged with surgery, and, in the case of recurrent or new laryngeal cancer, the treatment is almost always total laryngectomy."}
{"note": "Surgical approaches include open surgery or transoral surgical approaches, including laser (TLM) and robotic (TORS). Organ-preserving surgery, both open and endoscopic approaches, offer several advantages over RT. As mentioned, patients with SSCC have reasonable 5-year overall survival rates, albeit with an increased risk of developing second primary aerodigestive tract malignancy [5, 6, 30]. Surgery can therefore be utilized as the first line, and, in the setting of recurrence, radiation can be used as salvage therapy. An additional advantage of surgery is the cost benefit of surgical intervention over radiotherapy [31, 32]. Furthermore, surgical management with a neck dissection provides the opportunity to identify oc- cult metastasis; an important consideration given that up to 30% patients with SSCC may have occult nodal metastasis [32]. Identification of occult metastasis al- lows for accurate staging of patients, and subsequently treatment with multimodality therapies."}
{"note": "Dombree et al. analyzed the cost of open supraglottic laryngectomy, TLM, and TORS in a Belgian model. Their study suggests the cost of open supraglottic laryn- gectomy similar to that of TLM in upfront surgical costs [31]. TORS tends to be more expensive primarily due to purchase and maintenance costs [31]. This study did not account for in-hospital costs such as length of admis- sion, complications or readmission rates. With regard to glottic cancers, a cost analysis was carried out for a Canadian model comparing TLM to radiotherapy. This showed TLM to be a more cost-effective treatment option [33]."}
{"note": "There are also disadvantages of surgery, including risk of general anesthetic, particularly in patients with comor- bidities, bleeding, and infection. Pharyngocutaneous fis- tula, dysphagia and permanent tracheostomy dependence are specific risks of supraglottic laryngectomies. A criti- cism of OPS are the associated poor functional outcomes [25]. However, newer surgical techniques including TLM and TORS have gained popularity recently, and hold several advantages over open surgery and RT. In one study, TLM was compared to open surgery, resulting in reduced incidence of permanent gastrostomies and tracheostomies [20]. Since the introduction of TLM by Strong and Jako, there have been several reports investigating the role of TLM for supraglottic laryngectomy [34\u201348]. With respect to TORS, the majority of the stud- ies report on all stages of supraglottic SCC [20, 43, 48\u2013 59]. With that in mind, long-term tracheostomy and gastric feeding tube rates range from 0 to 20% in patients treated with TORS [49, 52, 55]. None of the studies included in this systematic review examined the functional outcomes of TORS."}
{"note": "Strengths"}
{"note": "There are several strengths to this review. To our know- ledge, this is the first comprehensive review of all available literature comparing functional outcomes between surgery versus radiation for patients with early stage SSCC. It was designed, conducted and reported in accordance with published guidelines (PRISMA) and the study protocol, as well as search strategy, was outlined a priori. A comprehensive search strategy was undertaken and led to the review of 5218 unique citations of which ten studies met our inclusion criteria. This resulted in the analysis of a large number of patients with early stage SSCC (n = 640)."}
{"note": "Limitations"}
{"note": "As with all systematic reviews, the strength of the conclu- sions that can be drawn from this study depend on the quality of the primary studies. The included studies were evaluated with the Newcastle-Ottawa Scale for Assessing Cohort Studies, most of which were of moderate in overall quality. Next, although we only included studies published from 1990 forward, some of the studies in our review included patients treated well before that time period. This broad recruitment period includes many patients where treatment algorithms may not reflect today\u2019s standards. Given the improvements in medical imaging, some patients may have had regional nodal disease which was not evident on the available scans, therefore reflecting more advanced disease. Furthermore, many of the current treatment options, such intensity modulated radiotherapy (IMRT), TLM, and TORS were not in clinical practice prior to 1990. The types of radiation and protocols used were not clearly outlined in the studies included. As well, given the broad recruitment periods for some of these studies, different radiotherapy protocols would have been offered to the patients according to the available therapies at that time."}
{"note": "All 10 studies that met the inclusion criteria were retrospective study designs and there were no randomized controlled trials. Retrospective studies have inherent biases including selection biases. Patient\u2019s with medical comorbidities may not have been deemed appropriate surgical candidates and only offered radiotherapy, which may not be reflected in the results."}
{"note": "Significant heterogeneity was noted between the out- come measures of the included studies. In the surgical group, not all patients may have received the same type or extent of surgery, including elective neck dissections, TLM, and TORS operations. We only considered English language studies for our systematic review, which limited the number of titles screened and studies included, how- ever, the effect of this would likely be small."}
{"note": "The heterogeneity of the functional outcomes reported limited our ability to meta-analyze the data. Additionally, many of the outcomes were sparsely reported or reported for only one of the arms of study, either OPS or RT. The overall paucity of data limits our ability to draw conclusions."}
{"note": "Given the lack of high level evidence guiding the opti- mal management of early stage supraglottic cancer and potential biases of retrospective studies, a head to head comparison between newer modalities such as TLM and TORS with RT is critical in determining the therapeutic algorithm that can yield better functional outcomes in early stage SSCC patient. Many studies were ruled out as part of our protocol due to the stratification of results with respect to laryngeal subsite and staging criteria (including advanced stage disease). The method in which functional results are reported, is often less rigorous than the report- ing of survival and locoregional control. The use of object- ive measures and validated tools was limited and not consistent across studies."}
{"note": "Traditionally, studies comparing surgery and radiation have been challenging to accrue patients to. Ongoing efforts comparing OPS to RT for oropharyngeal cancer are underway and actively accruing [60, 61], demonstrating that a head-to-head comparison of surgery and radiation is a possibility for patients with early stage supraglottic cancer. High level of evidence is important in the development of treatment guidelines for patients with early stage disease that have a surprisingly poor prognosis, compared to other early stage head and neck cancers. Traditionally, OPS has been seen as an option with poor functional outcomes. We did not find evidence to support one modality being better than another with respect to functional outcomes."}
{"note": "Conclusions"}
{"note": "There is an overall paucity of literature available regarding functional outcomes in the treatment of early stage SSCC patients, the majority of which is moderate in overall quality and retrospective in nature. The majority of the data does not reflect the treatment algorithms of today, with the introduction of focused radiation therapies and endoscopic surgical approaches. Changes to treatment algorithms have not been reflected in head-to-head studies examining the functional outcomes. The outcome mea- sures reported have significant heterogeneity in the current literature, which limits the ability to draw defini- tive conclusions."}
{"note": "Moving forward, we propose that aspiration, intract- able aspiration intervention, permanent gastrostomy tube requirements, and objective quality of life scales as objective measures that should be included in future re- search on this topic. Future studies and research should include well designed prospective trials with rigorous reporting of outcome measures.\n\u2014------------------------------"}
{"note": "Title: Cannabinoid Use in the Treatment of Laryngeal Dystonia and Vocal Tremor: A Pilot Investigation"}
{"note": "Abstract:"}
{"note": "Objectives/hypothesis. Laryngeal dystonia and vocal tremor can be debilitating conditions with\nsuboptimal treatment options. Botulinum toxin chemodenervation is typically the first-line treatment and is considered the gold standard. However, patient response to botulinum toxin varies widely. There is anecdotal evidence for the use of cannabinoids in treating laryngeal dystonia with a scarcity of research investigating this potential treatment option. The primary objective of this study is to survey patients with laryngeal dystonia and vocal tremor to gauge how some people are using cannabinoids to treat their condition and to ascertain patient perceptions of cannabinoid effectiveness."}
{"note": "Study Design. This is a cross-sectional survey study."}
{"note": "Methods. An eight-question anonymous survey was distributed to people with abductor spasmodic dysphonia adductor spasmodic dysphonia, vocal tremor, muscle tension dysphonia, and mixed laryngeal dystonia via the Dysphonia International (formerly National Spasmodic Dysphonia Association) email listserv."}
{"note": "Results. 158 responses: 25 males and 133 females, (mean [range] age, 64.9 [22\u201395] years). 53.8% of participants had tried cannabinoids for the purposes of treating their condition at some point, with 52.9% of this subset actively using cannabis as part of their treatment. Most participants who have used cannabinoids as a treatment rank their effectiveness as somewhat effective (42.4%) or ineffective (45.9%). Participants cited a reduction in voice strain and anxiety as reasons for cannabinoid effectiveness."}
{"note": "Conclusions. People with laryngeal dystonia and/or vocal tremor currently use or have tried using cannabinoids as a treatment for their condition. Cannabinoids were better received as a supplementary treatment than as a stand-alone treatment."}
{"note": "Key Words: Cannabinoids\u2013Laryngeal dystonia\u2013Muscle tension dysphonia\u2013Vocal tremor\u2013Spasmodic dysphonia\u2013Botox chemodenervation."}
{"note": "INTRODUCTION"}
{"note": "There is currently no curative treatment for laryngeal dystonia and vocal tremor. Laryngeal dystonia is a neurogenic condition that is categorized by spasms in the adductor muscles in the vocal folds, abductor muscles, or a mix of both muscle groups.1 Adductor spasmodic dysphonia is the most commonly diagnosed condition of the three, with abductor spasmodic dysphonia and mixed spasmodic dysphonia more rarely diagnosed.2,3 Muscle tension dysphonia (MTD) is a functional condition rather than dystonia, characterized by excessive tension of the laryngeal musculature during phonation.4 Vocal tremor is characterized by involuntary regular movements of the larynx and vocal tract during phonation, with many individuals also experiencing tremors elsewhere in the body.5 Existing treatments for laryngeal dystonia seek to minimize the symptoms associated with the condition but current medications and procedures have variable efficacy among the different conditions and the individual patients diagnosed with these conditions. Chemodenervation via botulinum neurotoxin (BTX) injection is considered the standard, first-line treatment for laryngeal dystonia and vocal tremor.6,7 However, treatment is imperfect and requires repeated treatment by a skilled clinician.6,8 Besides BTX injections, voice therapy and surgery are also used to treat laryngeal dystonia and vocal tremor with inconsistent results.4,7\u201310 Given the vast variability in responses to different treatments for laryngeal dystonia and vocal tremor, people with these conditions often seek alternative treatment options. Cannabinoids have been used in treating dystonic conditions with varying success.11\u201313 Their effectiveness in treating dystonia as a whole is yet to be confirmed as reports of their benefit have been constrained to a limited number of case studies and trials with statistically small sample sizes.12,13 A recent survey, however, has shown that a sizable number of patients with vocal conditions in general use cannabinoids to manage their symptoms.14 This study aimed to survey the patterns of cannabinoid product use among patients with laryngeal dystonia/vocal tremor as well as their perspectives of the efficacy of cannabinoid products in treating their vocal condition. This research study defines cannabinoid products or cannabinoids as products or substances derived from the cannabis plant, including but not limited to Marijuana, Tetrahydrocannabinol (THC) products, and cannabidiol products (CBD)."}
{"note": "MATERIALS AND METHODS"}
{"note": "This study was approved by the Institutional Review Board of the University of Southern California (UP-21-00354). This study used a cross-sectional survey methodology utilizing a responsive questionnaire composed of eight primary questions. This electronic survey was developed using skip logic, presenting varied questions depending on the participant\u2019s responses. The survey was created and hosted on REDCap, and distributed through the Dysphonia International (formerly the National Spasmodic Dysphonia Association) email listserv, a collection of approximately 5000 emails belonging to patients, doctors, and other healthcare professionals. The survey collected responses from December 29, 2021, to November 1, 2022. Participants were provided an informed consent instructional text before starting the survey. Participants: To be eligible to participate, participants required a diagnosis of spasmodic dysphonia or laryngeal dystonia, vocal tremor, and/or muscle tension dysphonia. To answer the survey in its entirety, participants must have reported using a cannabinoid product at least once in the past to manage their vocal symptoms specifically. Participants who had not tried a cannabinoid product at least once to treat their voice symptoms were ineligible to answer the remaining questions regarding cannabinoid use. Participation was voluntary and anonymous. Survey structure, content, and data collection The survey was composed of eight questions as well as an additional general comments box. The survey used branching conditional logic to guide participants through the questionnaire. The question format included multiple-choice, multiple-select, and open-ended written response. Participants who selected a response of \u201cother\u201d on any question were offered a short answer write-in text box for clarification. The first question asked participants if they had ever used cannabinoid products (Marijuana, THC products, CBD products) to treat their voice condition. If a participant selected \u201cno\u201d, the survey would close but would allow for participants to provide write-in responses in the general comment box. All other participants would be guided through the remaining seven primary questions with additional secondary subsections and clarification questions contingent on their responses. These participants were also able to provide write-in responses in the general comments box at the end of the survey. A facsimile of the survey can be reviewed in the supplementary section of this study (Supplementary 1). Bar graphs were created to reflect the number of responses for multiple-choice and multiple-select formatted questions. Write-in responses were reviewed for common motifs and coded for overall themes to reflect the various perspectives of the participant responses. Quotations were selected that best represented the coded themes. Demographic information was collected to gauge the diversity and overall composition of the sample population. This information included participant age, gender, and primary and ancillary dystonic diagnoses."}
{"note": "RESULTS"}
{"note": "Participant demographics The survey included a total of 158 participants comprised of responses from 133 cisgender female participants and 25 cisgender male participants with a mean age of 64.8 years old and participant age ranging from 22 years old to 95 years old (Figure 1). Adductor spasmodic dysphonia was the most common condition with 65 participants claiming this diagnosis (Figure 1). Mixed spasmodic dysphonia was found to be the second most common with 37 responses claiming this diagnosis, and abductor spasmodic dysphonia closely followed at 30 participant responses (Figure 1). Muscle tension dysphonia, vocal tremor, and vocal dystonia otherwise not specified were less common diagnoses for this survey population (Figure 1). A majority of the respondents were not diagnosed with dystonia or tremor elsewhere in their body, though 51 of the participants (32.3%) reported experiencing dystonia or tremor beyond their vocal symptoms (Figure 1). Participants using cannabinoid products to treat vocal dystonia Of the 85 (53.8%) participants who stated they had tried using cannabinoid products at least once in the past to treat their vocal condition (Figure 2A), 45 participants (52.9%) stated they currently use cannabinoid products as treatment (Figure 2A). Among these participants, 24 participants (53.3%) used cannabinoid products daily (Figure 2B). Eight participants used cannabinoid products once a week, six participants used cannabinoid products multiple times a week, and seven participants used cannabinoid products more sparingly at once or twice a month (Figure 2B). The majority of participants reported using cannabinoid products to treat their symptoms for at least 1 year (58.8%) with 28 of these participants (32.9%) reporting use for approximately 1\u20132 years and 22 of these participants (25.9%) reporting using for at least 3 years (Figure 2C). Seventeen respondents reported using cannabinoid products for less than a month and 12 respondents reported several months of use (Figure 2C). Respondents were most likely to use cannabinoid products containing CBD alone (32 of 85 participants) or CBD in combination with THC (39 of 85 participants) and were less likely to use THC products alone (12 of 85 participants) (Figure 3). Among participants who actively used cannabinoids to treat their vocal condition, the most frequently used formulation of cannabinoid products was edible products, with 29 respondents (64.4%) stating they used this preparation (Figure 3). Twelve participants who selected \u201cother\u201d specified that they used a tincture preparation of cannabinoids and one participant specified tablets, both of which are oral formularies that can also be classified as an edible cannabinoid product (Figure 3). The second most common mode of using cannabinoid products was via smoke inhalation, with 16 participants (35.6%) using this method (Figure 3). Vaping was another common method of using cannabinoid products with 10 participants (22.2%) stating they used this formulation (Figure 3). Topical cannabinoid products were the least commonly used product with eight participants (17.8%) stating they used this preparation; one participant who selected \u201cother\u201d specified that they used CBD patches, which can be reclassified as a topical preparation of cannabinoids (Figure 3). Participants who did not use cannabinoid products to treat vocal dystonia Of the 158 respondents in total, 73 (46.2%) had never tried using cannabinoid products to treat laryngeal dystonia/ vocal tremor/MTD (Figure 2). Additionally, 40 respondents stated they had tried cannabinoid products to treat their condition but had since discontinued cannabinoid use (Figure 2). The most commonly cited reason for discontinuing cannabinoid use among respondents was the ineffectiveness of these products in treating their underlying vocal condition, with 31 participants (77.5%) selecting this response (Figure 4). Cost, side effects, and other reasons for discontinuing use were less frequently selected (Figure 4). The role of cannabinoid products in treating vocal dystonia in context of current treatments Cannabinoid products are overwhelmingly taken outside the care of a medical professional with 36 of the 45 participants (80.4%) who actively use these products doing so as self-directed rather than as medically prescribed. Twenty-five respondents of the 45 (55.6%) who were currently using cannabinoid products reported them as a supplementary treatment alongside medications or treatments provided by a healthcare professional (Figure 5). Botox was the most commonly used treatment alongside cannabinoid products with 15 of the 25 participants (60%) reporting that they were using this combination (Figure 5). Five participants (20%) used voice therapy in combination with cannabinoid products (Figure 5). Surgery was the least commonly reported treatment being used in combination with cannabinoid products with one participant reporting this combination"}
{"note": "LIMITATIONS"}
{"note": "As an electronic survey, this study is limited to participants who have Internet access. The electronic link was distributed exclusively through the Dystonia International (previously National Spasmodic Dysphonia Association) listserv, limiting the diversity of the sample population. The intrinsic nature of online surveys can also predispose to self-selection bias as participants choose to participate in the survey potentially based on pre-existing bias. Patients with a positive response to cannabinoids may have been more likely to respond, while those who had never considered cannabinoids may have not had as pronounced interest in responding. This may be reflected in the low percentage response rate, with only 158 responses in a collection of 5000 total emails in the listserv. However, it would be inaccurate to attribute the low response rate to selection bias alone, as the listserv was comprised of not just patients, but also physicians and healthcare professionals. Without knowing the exact number of patients in the listserv, the true response rate is difficult to calculate. As this study required participants to retrospectively recall the extent of effectiveness after using cannabinoid products, there is likely recall bias that is affecting the collected data."}
{"note": "CONCLUSION"}
{"note": "A considerable number of patients with vocal dystonia have tried using cannabinoid products or currently use cannabinoids to treat their laryngeal dystonia, vocal tremor, and MTD. Most participants considered cannabinoids as either less effective or similarly effective to other treatments in treating their vocal dystonia. A select group of participants who used cannabinoids with Botox injections reported the combination as more effective than using Botox alone. A prospective study is warranted for further investigation to help clinicians counsel patients in their treatment journey.\n\n\n\u2014----------------------------------------------------------------------------"}
{"note": "Title: Safety of Platelet-Rich Plasma Subepithelial Infusion for Vocal Fold Scar, Sulcus, and Atrophy"}
{"note": "Abstract"}
{"note": "Objective: To demonstrate the safety profile of platelet-rich plasma (PRP) as an injectable therapeutic for the treatment of vocal fold scarring and atrophy."}
{"note": "Methods: Preliminary report on a prospective clinical trial of patients with vocal fold scar or atrophy undergoing unilateral vocal fold subepithelial infusion with autologous PRP. Enrolled patients underwent four sub- epithelial injections spaced 1 month apart. Adverse events were assessed peri and post-injection at each session. Patient-reported outcomes were collected at every visit using the Voice Handicap Index-10 (VHI-10) and Vocal Fatigue Index (VFI) questionnaires."}
{"note": "Results: Twelve patients underwent unilateral vocal fold injection with autologous PRP prepared according to Eclipse \u00ae"}
{"note": "Conclusion: This prospective study cohort demonstrated a favorable safety profile, with no adverse events or peri-procedural complications. Subjective improvements in vocal quality and reduction in vocal fatigue need to be clinically correlated with further study."}
{"note": "Key Words: platelet-rich plasma, vocal fold scar, superficial lamina propria, vocal fold atrophy. Level of Evidence: 4"}
{"note": "PRP system protocol. Forty-three injections were performed using a peroral or percutaneous approach. An average of 1.57 0.4 cc (range 0.6\u20132.0 cc) injectate was used. All patients tolerated the procedure without difficulty or peri-procedural complications. The average duration of follow-up was 3.6 1.8 months. No significant inflammatory reactions or adverse events were seen to date. There was statistically significant improvement in patient-reported outcomes at the 3 month follow up (n = 9) follow-up (mean \u0394VHI-10 = 10.8, p < 0.001, mean \u0394VFI = 18.9, p = 0.01, t test, paired two sample for means, two- tail). All nine patients who completed the series of four injections subjectively (yes/no) reported they were satisfied with the results."}
{"note": "INTRODUCTION"}
{"note": "Vocal fold atrophy and scar are causes of dysphonia that pose major treatment challenges for laryngologists.1 The etiology of vocal fold scar is diverse, potentially stemming from phonotrauma, phonomicrosurgery, iatrogenic injury, malignancy, and radiation therapy.2,3 Addition- ally, loss of hyaluronic acid, elastic fibers, and lubrication during the aging process can reduce viable tissue mass.4 Underlying alterations to the superficial lamina propria (SLP) of the vocal folds drastically alter compliance.5 Con- sequently, patients endure considerable dysphonia, vocal fatigue, decreased volume, and altered pitch. These changes can contribute to depression, reduced social interaction, and decreased quality of life.6"}
{"note": "The most common initial treatment for vocal fold atrophy condition is voice therapy administered by a specialized speech-language pathologist spaced out over multiple monthly sessions. Voice therapy introduces logistical strains in the elderly population, such as coordinating transportation across several sessions, and is limited by its inability to restore normal vocal fold volume and morphology.5 Alternatively, injectable filler materials (e.g., carboxymethylcellulose and micronized collagen) may be used to augment the vocal folds for patients with glottic insufficiency secondary to loss of the SLP.7 However, this treatment is temporary and fails to provide a durable effect.8 In addition, it carries the risk of worsening dysphonia due to filler inert mass effect or superficially misplaced injection.5"}
{"note": "For patients with vocal fold scar, a range of surgical procedures from augmentation laryngoplasty,9 angiolytic laser procedures,10 tissue grafting,11 and Gray\u2019s mini- thyrotomy12 have been described, which also provide inconsistent improvement.13 Recent experimental studies have explored the prospect of restoring normal SLP architecture via stem cell tissue engineering14 and growth fac- tor injections.15 Nevertheless, the paucity of controlled studies has left a void for a treatment modality that is safe, addresses the fundamental cause, and provides durable results for patients with vocal fold atrophy or scar."}
{"note": "Platelet-rich plasma (PRP) consists of platelets, growth factors, cytokines, and cell adhesion molecules derived from the patient\u2019s own blood.16 PRP is believed to activate tissue regeneration by introducing high concentrations of platelet-derived growth factors and fibrin into damaged or atrophied tissue.17 Studies in orthopedics and cosmetic surgery emphasize the breadth and safety of the therapeutic applications of PRP.18\u201320 Previ- ous work at our institution highlights the technical considerations for in-office PRP vocal fold injections.21 Hence, serial PRP vocal fold injections hold promise as a new treatment modality for vocal fold atrophy and scar."}
{"note": "This study aims to evaluate the safety profile of autologous PRP for use as an injectable therapeutic in the vocal fold. Secondarily, we aim to determine the clini- cal efficacy of serial PRP vocal fold injections regarding patient-reported outcome measures and longevity of clinical effects from serial PRP vocal fold injections."}
{"note": "MATERIALS AND METHODS"}
{"note": "Study Population: This study was approved by the University of Southern California Institutional Review Board. Patients were enrolled as part of an ongoing prospective clinical trial (clinicaltrials. gov APP-18-05224) consisting of a series of four unilateral vocal fold injections with autologous platelet-rich plasma. Vocal fold atrophy and lamina propria defects were diagnosed on laryngeal videostroboscopy by a fellowship-trained laryngologist. All participants were adults (age 18 years or older) with a baseline VHI-10 score \u2265 10. Patients with a his- tory of allergy or hypersensitivity to lidocaine, amide-based anesthetics, or bovine products were excluded from the trial. Patients who underwent recent laryngeal surgery or invasive procedures (e.g., vocal fold injection augmentation) within the last 3months were not permitted to enroll., Additionally, patients with active infection or inflammation in the larynx, underlying coagulopathy, thrombocytopenia, or platelet dys- function, autoimmune disease, cancer, liver disease, or respi- ratory compromise were excluded. Concomitant laryngeal conditions including but not limited to vocal tremor and laryn- geal dystonia that would otherwise warrant alternative inter- ventions for optimal treatment were also excluded. Finally, patients with a life expectancy of less than 6 months were excluded from this study."}
{"note": "Clinical Protocol: The clinical protocol for this clinical trial is outlined in Figure 1. As part of the initial intake, patients completed the Voice Handicap Index-10 (VHI-10) and Vocal Fatigue Index (VFI). During their initial visit, a complete history and physical examination were performed along with voice and laryngeal videostroboscopy recordings. The first PRP vocal fold injection (Day 0) was performed within 4 weeks of the decision to partici- pate. The patient was monitored for 1 h post procedure for any potential adverse events. The following day (Day 1), the patient was re-evaluated in clinic for any side effects or adverse events. One week following the initial injection the patient was re-evaluated in clinic and VHI-10 and VFI questionnaires were collected. Subsequently, the patient returned at monthly inter- vals for repeat evaluation and re-injection for a total of four uni- lateral vocal fold injections. The patient\u2019s subjective experience, patient-reported outcome measures, and stroboscopic examina- tion were collected at each visit. Patients continued follow-up visits at monthly intervals for 3 months following the fourth injection (Fig. 2)."}
{"note": "Drug/Device Information and Administration: The leukocyte poor platelet-rich plasma preparation was achieved via the Eclipse PRP\u00ae system manufactured by Eclipse\u00ae medical device (BK110035). Activation of PRP in our study is accomplished without exogenous substances by relying on shear force from injection and exposure to native collagen at the injection site.18 Patients underwent venipuncture to collect 11 ml of blood. The collected blood was placed in the Eclipse PRP centrifuge per product protocol."}
{"note": "Study Agent Administration system: Unilateral injection of 1.0\u20132.0 cc of PRP into the membra- nous vocal fold near the area of the scar on the pre-determined side was performed using a 23-gauge needle via previously described percutaneous methods for vocal fold injection (thyrohyoid, transoral approaches).8 Trans-cervical injections were carried out through the thyro-hyoid approach with no significant leakage of PRP noted during these injections. Injections were performed throughout this study taking care to place the needle superficially into the vocal fold. The PRP then tracks throughout the entire surface of the superficial vocal fold and bulges the epi- thelium. Once material begins to extrude, commonly between 1 and 1.5 cc, the injection is concluded. All injections were per- formed in an outpatient clinic setting under local and topical anesthesia apart from one patient who requested injection 2 be performed in the operating room due to intolerance of awake in- office vocal fold injection. Due to this patient\u2019s preference, accommodations were made to perform injections 3 and 4 in the operating room as well. The contralateral vocal fold did not undergo injection and served as an internal control. During interim periods between scheduled visits, subjects were instructed to call with any potential adverse event that may require in-person evaluation at the clinic or in an acute care setting for appropriate clinical care."}
{"note": "Evaluation Criteria and Endpoint Definitions: Study completion was achieved after patients received four unilateral PRP injections and completed all follow-up post- injection clinic visits. The main objective of this study is to define the safety profile of PRP for use with serial vocal fold injections to treat vocal fold atrophy and scar. As such, the focus will be on any treatment-related adverse events that are reported during the study. Previously cited adverse events in vocal fold injection include local tissue reactivity, hemorrhage, hematoma, granuloma         formation, and postprocedural airway compromise.22 Secondary endpoints included patient-reported outcome measures (VHI-10, VFI) from designated follow-up time points which are compared to baseline values prior to the first injection. Follow-up duration refers to the number of months since a patient\u2019s first injection and continues to accumulate after all four injections have been administered. For patients with vocal fold scars, we did not include specific etiology in our demographic information as many patients had longstanding scars of unknown etiology."}
{"note": "Statistical Analysis: Sample size calculations were performed based on data from prior studies for VHI-10 outcomes after vocal fold augmentation for vocal fold atrophy.23 These calculations were based on a planned comparison of VHI-10 scores before and after serial PRP injections via paired t-test statistics. All comparisons were made between baseline scores and individual post-injection time- point. The primary outcome of safety was focused on the incidence of serious adverse events related to the study material under investigation. We expected the risk of a serious adverse event to be exceedingly low and did not base our sample size calculation on that. The study cohort will be analyzed using descriptive statistics of the primary outcome. The incidence of both minor and major adverse events will be measured as a percent of total participants experiencing said adverse event. Comparison of patient-reported outcome measures from post-intervention time points to pre-intervention baseline were evaluated using parametric statistics (t-test, paired two samples for means, two-tail)."}
{"note": "RESULTS"}
{"note": "Twelve patients with vocal fold scar or atrophy under- went unilateral vocal fold injection with autologous PRP prepared according to Eclipse PRP system protocol. A total of 43 injections were performed using a peroral or percutaneous approach. An overview of study participant demo- graphics and pathology is outlined in Table I. An average of 1.57 0.4 cc (range 0.6\u20132.0 cc) of injectate was used. The average duration of follow-up was 3.6 1.8 months. Nine patients (75.0%) completed all four PRP injections, while two patients completed three injections and one patient received only one injection as part of the ongoing trial. At the one-month timepoint, one patient requested to receive the PRP injection in the operating room to better tolerate treatment. All other injections were per- formed in the outpatient clinic setting. No significant inflammatory reactions or adverse events were seen to date.                                                \nthe earliest significantly significant decrease in both questionnaires. This significant downtrend persisted through the two-month (VHI-10 score 19.9 11.3; VFI 31.1 14.9) and three-month (VHI-10 18.9 12.4; VFI 25.1 16.2) timepoints. At the four-month timepoint, one month after the fourth injection, the VHI-10 score was 16.4 14.8 (median \u0394VHI-10 = 8.4, p = 0.03) and the VFI score was 14.4 11.8 (mean \u0394VFI = 23.8, p = 0.08). All patients self-reported tolerating the procedure without difficulty or immediate complications. Some patients described discomfort associated with the laryngotracheal anesthetic and mild discomfort was noted on the side of injection in two patients 1 day after the initial injection. No safety events were reported from any of the injections (n = 43) throughout the duration of the trial."}
{"note": "All patients continued to experience subjectively improved voice outcomes, with the improved overall quality, loudness, vocal endurance, and less strain and breathiness at 1 month. Two patients noted that the improvements were sustained until 3 weeks following the first injection when they experienced a slight deteriora- tion but did not return to their baseline dysphonia. Eight patients continued to experience improved voice quality and resonance 1 month following the second injection. Two patients reported sustained voice quality at the level experienced after the initial injection with no notable improvement thereafter. All patients reported subjective improvement in their voice 1 month after the third injec- tion, of which three experienced their best overall voice enhancement. Two patients consistently experienced gradual deterioration in their voice quality and noted voice instability as they neared the one-month timepoint following each injection."}
{"note": "DISCUSSION"}
{"note": "While the application of regenerative medicine techniques in laryngology holds great promise there is a pau- city of human data on the use of PRP. This prospective cohort study demonstrated a favorable safety profile for the use of serial in-office vocal fold injections of autologous PRP among patients with vocal disturbances due to vocal fold atrophy and scar. There were no adverse events or peri-procedural complications across 43 PRP injections in 12 patients. The practicality of in-office procedures has been embraced in laryngology as they circumvent the use of general anesthesia and the need for an operating room and staff.24,25 The bioactive components in PRP such as growth factors, cytokines, and cell adhesion molecules are self-renewing. Moreover, the plasma derivative tissue product is reliably reproduced via routine blood draws and minimal subsequent manipulation. In this trial, blood collection and centrifugation added approximately 10\u201315 min of preparation time. Blood collection, PRP product preparation, and treatment can be completed in a timely manner rendering the process feasible for the ambulatory care setting."}
{"note": "Lamina propria defects found in vocal fold atrophy and scar represent challenging pathologies to treat.3 Therapeutic interventions include surgical and non-surgical options including tissue transplantation, angiolytic laser treatments, and voice therapy. Surgeons must consider the diverse roles of the larynx during respiration, phonation, and deglutination26,27 to preserve functional capacity fol- lowing treatment.2,28 Pathologic healing from scar tissue can lead to persistent dysphonia that impairs appropriate vocal fold approximation and natural dynamic oscillation required for clear resonant voice sounds.3 Moreover, there is no substance to replace the intricate framework of the SLP. Prior to trial enrollment, all patients underwent some form of previous treatment including steroid injections, injection augmentation, or surgical scar revision."}
{"note": "Despite these interventions, these patients continued to have residual vocal deficits despite temporary improve- ment seen in some instances. All participants expressed dissatisfaction with their vocal capabilities during the baseline evaluation. PRP is a biological material shown to stimulate host tissue rejuvenation without eliciting immune rejection as it is derived from the patient\u2019s own blood. The composi- tion of PRP consists primarily of a high concentration of platelets and growth factors but can also include white blood cells and other vasoactive and chemotactic agents.29 PRP releases growth factors that expedite wound healing via cell proliferation, matrix formation, osteoid produc- tion, connective tissue healing, angiogenesis, and collagen synthesis.30,31 PRP injections have been shown to have a broad range of applications in tissue sealing, stabiliza- tion, scar maturation, osteogenesis, and alopecia across various surgical specialties from orthopedics to cosmetic surgery with virtually no adverse side effects.32\u201334 In vivo studies revealed the effect of PRP in vocal fold healing in rabbit models following acute vocal fold injury.29 In oto- laryngology, the wound healing properties of PRP have previously been used to treat tympanic membrane perfo- ration.35 This prospective clinical report on the use of PRP in the human larynx is unique and builds on recent interest in commissioning bioactive components, includ- ing fibroblast growth factors and autologous bone marrow-derived mesenchymal stromal cells, to treat pathologies of the head and neck. Recently Woo et al. reported short-term voice improvements following in-office PRP injections with 11 patients receiving three injec- tions.26 While our preliminary work set out to show the safety and tolerability of PRP injections in an ambulatory care setting, many of the patients expressed subjective improvements occurring after a four-injection series. The standardized design of our prospective trial, formatted with consistent follow-up after four unilateral vocal fold injections, provides a unique and controlled study method. As a newly emerging therapeutic avenue in laryngology, our findings contribute to the scarcity of literature exploring the potential use of PRP injections as a suitable treatment modality for patients with vocal fold scar and atrophy. Our results are consistent with the safety of PRP injections described by Woo et al., and further support the use of PRP precisely because of their similarity."}
{"note": "All patients underwent treatment without difficulty or complications. There were no accounts of laryngeal edema, local inflammatory reaction, dysphagia, or dyspnea. Mild discomfort was noted on the side of injection in two patients 1 day after the initial injection. Patients in our trial expressed a variable range of voice improve- ment. Three patients described a mild roughness in the quality of their voice for 3\u20135 days following the first injec- tion which subsequently resolved. One patient went on to experience a similar occurrence at their second injection. Patient experiences reflected a general trend of improve- ment with consecutive PRP injections. Three accounts across two patients described sustained improvement for 3 weeks following treatment before perceiving remission in voice quality. Generally, patients experienced vocal quality and consistency that eventually spanned the month between injections. Interestingly, three subjects experienced their best overall voice improvement after injection number three. All patients who received four PRP injections were satisfied with the improvement of their voice and expressed interest in continued treatment beyond the completion of their trial participation."}
{"note": "VHI-10 and VFI scores mirror the trend of gradual improvement. At 1 week after the first PRP injection, the average VHI-10 and VFI scores began to downtrend to 27.5 10.2 and 42.9 16.4 but did not achieve the range of published minimally important clinical difference (MCID) for either questionnaire.36,37 However, by 1month, the change in the average VHI-10 and VFI scores reflected a significant decrease compared to baseline, beyond the MCID range of a four-to-six-point decrease in total score. With repeat monthly injections both the average VHI-10 and VFI scores continued to decrease significantly with sub- sequent follow-up evaluations at the two and three-month timepoints. Interestingly, at the four-month timepoint, both the VHI-10 and VFI scores continued to decrease, but only the VHI-10 score was significantly lower than baseline. It is important to note that only five patients have reached this point in the study. Therefore, it is perhaps too early to com- ment on the longevity of serial PRP injections in terms of their impact on these patient-reported outcomes."}
{"note": "Our preliminary work contains encouraging outcome trends that may point to positive outcome longevity regarding voice quality in patients treated with serial PRP injections. Continued patient follow-up and enroll- ment will further elucidate the therapeutic role of PRP in laryngology. Determining the safety of PRP treatment is a crucial step toward characterizing its use in patient care with respect to outpatient laryngeal procedures. While this work builds on earlier efforts from our institu- tion outlining the technical feasibility and safety of PRP injections, ongoing enrollment will continue to substantiate our early findings.21 While the contralateral vocal fold served as a control, incorporating a volume-occupying control such as saline or platelet-poor plasma could be beneficial in definitively attributing vocal improvements to the bioactive components in PRP."}
{"note": "The trial contains clear limitations. The subjective nature of patient-reported voice outcomes limits the scope of meaningful conclusions about the procedure\u2019s long- term efficacy. To that end, patient experiences need to be correlated to objective anatomical changes and voice parameters. By the current trial design, patients will be followed-up for a minimum of 12 months after the concluding injection. Future work will assess objective outcome measurement from video stroboscopic evaluation which will provide a functional clinical correlate to bolster the results thus far. More work is also needed to determine the optimal timing of PRP treatment and the number of injections needed to provide optimal effect."}
{"note": "CONCLUSION: The absence of any reported safety events during the application and follow-up period for 43 unilateral vocal fold injections using PRP indicates its safety for use in the ambulatory care setting. The standardized approach of PRP preparation and application to the vocal folds rep- resents a safe therapeutic approach for patients with vocal fold atrophy or scar. Subjective improvements in vocal quality were accompanied by significant decreases in VHI-10 and VFI questionnaire scores in patients included in this trial. The overall trend of the patient- reported outcome measures indicates voice improvements beyond the limits of the MCID for these measures. While these results persisted for most patients during the trial, a few did report a gradual decline in voice quality after receiving a PRP injection. Additional follow-up will deter- mine the true longevity and extent to which in-office PRP injections affect objective voice parameters. Ongoing enrollment in the clinical trial will continue to assess the safety and therapeutic benefits of serial PRP injections.\n\n\n\u2014--------------------------------------------"}
{"note": "Title: A Machine-Learning Algorithm for the Automated Perceptual Evaluation of Dysphonia Severity"}
{"note": "Summary: Objectives. Auditory-perceptual assessments are the gold standard for assessing voice quality."}
{"note": "This project aims to develop a machine-learning model for measuring perceptual dysphonia severity of audio samples consistent with assessments by expert raters."}
{"note": "Methods. The Perceptual Voice Qualities Database samples were used, including sustained vowel and Consensus Auditory-Perceptual Evaluation of Voice sentences, which were previously expertly rated on a 0\u2013100 scale. The OpenSMILE (audEERING GmbH, Gilching, Germany) toolkit was used to extract acoustic (Mel-Frequency Cepstral Coefficient-based, n = 1428) and prosodic (n = 152) features, pitch onsets, and recording duration. We utilized a support vector machine and these features (n = 1582) for automated assessment of dysphonia severity. Recordings were separated into vowels (V) and sentences (S) and features were extracted separately from each. Final voice quality predictions were made by combining the features extracted from the individual components with the whole audio (WA) sample (three file sets: S, V, WA)."}
{"note": "Results. This algorithm has a high correlation (r = 0.847) with estimates of expert raters. The root mean square error was 13.36. Increasing signal complexity resulted in better estimation of dysphonia, whereby combining the features outperformed WA, S, and V sets individually."}
{"note": "Conclusion. A novel machine-learning algorithm was able to perform perceptual estimates of dysphonia severity using standardized audio samples on a 100-point scale. This was highly correlated to expert raters. This suggests that ML algorithms could offer an objective method for evaluating voice samples for dysphonia severity."}
{"note": "Key Words: Machine learning\u2013Voice evaluation\u2013Perceptual voice evaluation\u2013Automation\u2013Artificial intelligence."}
{"note": "BACKGROUND: Structured voice evaluation is a critical component of assessing patients with dysphonia. Comprehensive assessment typically includes both perceptual and instrumental assessments. Auditory-perceptual analysis represents the gold standard for the assessment of dysphonia severity. It is inexpensive and robust. This method of voice assessment is widely accepted in clinical applications as well as research purposes. Despite the widespread use of perceptual evaluations, it remains a subjective assessment and raters will develop their own internal reference standards with inherent biases, which impact the judgment of future voice samples. These internal standards can vary across time and between different raters, highlighting one critique of this form of voice assessment, namely reliability. Through standardized scales, such as the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) tool, high levels of consistency within and across raters can be achieved. With tools such as this, small-scale changes from sample to sample can be reliably detected. Reliability of auditory-perceptual evaluations has been extensively researched and, when confounding variables are controlled, they have been proven a robust form of voice assessment. Expert raters are important in the reliability of these assessments. Speech pathology assessment is a time-limited resource and voice evaluations are limited to the times patients can provide voice samples. Furthermore, these assessments typically rely on in-person voice samples, though some research suggests that remote sample collection from non-optimized settings may be adequate for clinical assessment. These restrictions indicate a resource bottleneck in these evaluations. A computer-automated perceptual evaluation tool may provide an opportunity to relieve the resource limitations and objectively measure voice samples. This might allow for interval evaluations between in-person visits, which could increase the total number of assessments, and ultimately could allow for within-person normative values as targets for tracking therapeutic improvement or decline. Recent advancements in machine learning methods have led to many medical applications, including applications within otolaryngology\u2014head and neck surgery. With respect to voice assessments, researchers have developed tools to categorize samples according to gender and evaluate dysphonia using sustained vowel samples. However, the traditional auditory-perceptual assessment includes both sustained vowels and connected speech to evaluate voice parameters across a variety of laryngeal behaviors. To date, there are no machine-learning global assessments of dysphonia severity using both sustained vowels and sentence samples calibrated to known expert ratings. In this study, the authors seek to develop a machine-learning algorithm for evaluating dysphonia severity on a 100-point scale using previously collected and expertly rated voice samples of sustained vowels and connected speech."}
{"note": "METHODS This study was designed using a previously labeled data set to train a machine-learning model. The Perceptual Voice Qualities Database (PVQD) includes audio samples (n = 295) which were professionally captured at participating voice centers. These samples include sustained vowels and connected speech (CAPE-V sentences) segments. Furthermore, each sample was previously rated by three experts on a 0\u2013100 scale according to the standards of the CAPE-V. The labeled data set allows the computer to know how the samples are supposed to be rated and to fit different criteria for the prediction model result in similar estimates. The primary goal was to teach the model to categorize voice samples according to the same scale. To do this, we used the OpenSMILE open-source toolkit with the emobase2010 configuration to extract acoustic and prosodic features, as well as pitch onsets and recording duration. More explicitly, we extracted a base of 34 low-level descriptor (LLD) features (including Mel-Frequency Cepstral Coefficient features, logarithmic power of Mel-frequency bands, normalized intensity, etc) with 34 corresponding delta coefficients appended and applied 21 different statistical functions (such as standard deviation, arithmetic mean, skewness, kurtosis, etc) to these, which resulted in 1428 features. Next, 19 functionals were applied to four LLD features based on the pitch (F0final, jitterLocal, jitterDDP, and shimmerLocal) as well as their corresponding four delta coefficients, resulting in 152 features. Finally, we appended pitch onsets and recording duration features. All LLD features are extracted based on a frame-by-frame analysis, using windows of 25 ms with 10 ms frameshifts. In consideration of the nature and size of our dataset, we adopted a support vector machine (SVM) instead of a recursive neural network. An SVM is a method often adopted for categorization problems, looking to draw lines between categories that maximize the margin between the line and the closest data points in each category. Within the context of the SVM, different features were tried to achieve the highest correlation and lowest root mean square error (RMSE) to the expert raters\u2019 data. The features were analyzed separately for different parts of the voice recordings, and then combined to make the final predictions. Our feature set, extracted through OpenSmile, consists of descriptive statistics related to low-level characteristics. These are widely utilized in various speech-related tasks such as emotion recognition. The SVM model was implemented with Gaussian kernel, and we tried different configurations of the penalty parameter C and kernel coefficient. The optimal parameters were selected based on the five-fold cross-validation. This entails splitting the data set into five parts. The model is then trained and tested five times, each using a different part as the test data and the remainder as the training data. Since the data is limited, we selected the K best features using a univariate F test by the scikit-learn Python module, where K ranged from 50 to 1000. The F test measures the impact of each feature on the output. The features with the highest scores were selected for the model and the number of features selected was chosen from the set of values ranging from 50 to 1000. We separated the recordings into two segments: sustained vowels (V) and connected sentences (S). For each segment, we separately extracted features and also generated a third dataset by extracting features from the whole, unsegmented audio file (WA). To improve the predictive quality of the model, we concatenated the features from these three datasets before selecting the K best features. We selected the combined audio set as it had the best correlation and lowest RMSE. After feature selection, we found jitter-related features of the entire audio file were consistently selected. Jitter, influenced by both sustained vowels and connected sentences, is closely linked to overall voice quality. Extracting jitter features separately from these segments before combining them resulted in slightly lower accuracy, likely due to the short duration of some individual audio files."}
{"note": "RESULTS: The algorithm developed for this study was found to have a high correlation (r = 0.847) with estimates of expert raters when combining features of the three audio sets as shown in Table 1. The model showed enhanced performance when exposed to the augmented dataset that is comprised of combined features from (S, V, and WA). This was indicated by higher correlation coefficients and lower RMSE values. The sustained vowel segments alone showed Pearson\u2019s correlation coefficient of 0.767. The sentences segment alone had a correlation of 0.822, and unsegmented audio (WA) had a correlation of 0.846. Mean error when combining three sets of features (V, S, WA) was 10.22, with RMSE of 13.36 (Table 1). Increasing signal complexity resulted in better estimation of dysphonia, whereby combining the features outperformed WA, S, and V sets individually. The mean of the two combined data sets was 29.88 (standard deviation (SD) 21.24) for the algorithm and 29.32 (SD 25.17) for the expert raters. The intra-class correlation coefficient was 0.83 (95% CI (confidence interval) 0.79, 0.97, P < 0.001) between the two data sets, suggesting they are strongly aligned (Figure 1)."}
{"note": "DISCUSSION: Voice evaluations are a crucial part of evaluating laryngology patients. The current gold standard for voice evaluation is through auditory-perceptual assessments performed on recorded audio samples collected during the process of in-person office visits. Furthermore, expert voice raters are required for perceptual evaluations, representing a bottleneck in the scalability of ratings. These limitations expose a resource-intensive portion of the laryngology patient examinations. Automation using computers represents a potential pathway toward reducing the cost of voice evaluation and increasing potential measurement opportunities. Furthermore, machine learning techniques have been applied to tackle a wide variety of predictive tasks within medicine, including the identification of skin malignancies and disordered voices, as well as predicting binary gender from voice samples in gender-affirming voice care. Current-day computing power has led to innovation in voice assessments, particularly in the field of modern acoustic voice evaluations including spectral and cepstral analyses."}
{"note": "In this study, the authors have sought to develop an algorithm for automating portions of the auditory-perceptual evaluation of voice, namely Overall Severity. The high correlation coefficient and intra-class correlation with expert raters in the voice samples of the PVQD database indicate this algorithm is able to accurately estimate dysphonia severity. Moreover, the RMSE of 13.36 further attests to the accuracy of the algorithm. A low RMSE, a measure indicating the precision of the predicted versus observed values of a model, indicates a more accurate model. In this case, an RMSE of 13.36 further supports the utility of this algorithm for estimating dysphonia severity in clinical use."}
{"note": "As far as the selection of the features and data sets, this was determined during the training of the model. The 5-fold cross-validation process revealed that the combined audio set was the most highly correlated and had the lowest RMSE of the group (WA, V, and S). In more detail, after performing feature selection on the combined version, the authors observed that the jitter-related features of WA are consistently chosen. This is a result of the fact that jitter is a characteristic influenced by both V and S, and results in independently different measures. The measurement of jitter as part of the whole audio file was more closely linked to overall vocal quality. Should we have used the jitter features extracted from S and V individually before combining them, the measurement performed slightly less accurately, presumably because of the short duration of the individual audio files in some samples."}
{"note": "An area in that we saw the model stray from the experts was with the normal and severe ranges of the CAPE-V system. These edge cases were more likely to be classified as mildly or moderately dysphonic instead of normal and severe respectively. Further study of normal and severely dysphonic samples would be important to improve the validity of this tool. Until then, these limitations need to be recognized when evaluating the quality of this algorithm. For a tool like this to achieve maximal utility to clinicians, it would be applied to mobile and remotely collected voice samples. This study was performed on high-quality audio samples, but future studies should include non-optimized audio files for analysis. This algorithm performed very well with this data set and opens the doors for exciting opportunities to measure voice samples in an automated fashion, thereby reducing the resource requirements of perceptual voice. This could also lead to the opportunity of collecting measurements outside of traditional evaluation settings, such as clinical visits. If these possibilities can be achieved, within subject normative values and measurement trending could be used to objectively track voice quality throughout treatment courses and time. These types of remote assessments could provide a method for biofeedback-driven therapeutic approaches. Lastly, the predictive capabilities of an algorithm like this could eventually recommend in-person visits for patients with acute voice changes when compared to their own normal samples."}
{"note": "This study is limited by the development of this algorithm using the high-quality, professionally captured audio samples of the PVQD. This data set is small (n = 295), which represents one limitation of the study\u2019s generalizability and future studies should include a higher number of samples for assessment of the model. Secondly, the samples were vetted to be of high recording quality, which would not be representative of voice samples collected remotely or in non-optimized settings, and a secondary study should be completed before this can be applied to these settings. Finally, the data used to train and test the model were not prospectively captured as part of a clinical assessment or within subjects\u2019 measurements. The repeatability across time within individuals should be further studied."}
{"note": "CONCLUSIONS: This study represents a significant step toward the automation of dysphonia severity evaluations. The machine learning algorithm developed in this study has shown remarkable consistency with expert raters in evaluating the overall severity of dysphonia. The high correlation coefficient (r = 0.847), intra-class correlation (0.83), and small RMSE (13.36 points) between the algorithm's ratings and the expert raters\u2019 ratings suggest that this algorithm has the potential to become a reliable and objective tool for dysphonia evaluation. With respect to comprehensive voice evaluations, dysphonia severity represents one small part. Future studies should evaluate the same algorithm as it applies to other parts of the CAPE-V to fully automate a perceptual evaluation. This study represents a significant achievement toward building confidence in automated voice evaluations. Importantly, this evaluates voice samples similar to the way clinicians do in many prominent voice centers (100-point CAPE-V scale). Categorization in this manner is far more complicated than would be found in previous studies that performed a similar task utilizing the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale."}
{"note": "This algorithm was trained on a dataset consisting of previously rated voice samples of the CAPE-V sentences and sustained vowels from the PVQD. Although the results are encouraging, more work is necessary to confirm these findings in a larger clinical population. In particular, future studies should assess the repeatability of the measures and compare them with expert raters\u2019 ratings. Moreover, the algorithm's performance may vary depending on the voice samples\u2019 quality, as this study only used optimized voice samples. Therefore, future studies should evaluate the algorithm's performance using non-optimized voice samples."}
{"note": "The developed algorithm has the potential to automate remote evaluations of dysphonia, which can be particularly useful in areas where access to clinical experts is limited. Furthermore, the algorithm provides an objective estimation of dysphonia severity, which can aid in developing treatment plans and evaluating the effectiveness of interventions. By training a model on expected values from expert raters who utilized the CAPE-V scales, while it does not truly represent the full spectrum of the perceptual evaluation provided by a trained listener, it provides an objective estimation with contextual information of the CAPE-V scales. This number alone does not have meaning but provides a common nomenclature to communicate dysphonia severity by recognizing how the algorithm was trained to perform the estimation."}
{"note": "In conclusion, this study has demonstrated that automated perceptual evaluations of dysphonia severity are possible using current computing power and machine learning techniques. With further development and validation, this algorithm has the potential to become an important tool for clinical evaluations of dysphonia.\n\u2014-------------------------------------------------"}
{"note": "Title:  Robot-Automated Cartilage Contouring for Complex Ear Reconstruction: A Cadaveric Study"}
{"note": "Abstract: Objectives/Hypothesis: Auricular reconstruction requiring manual contouring of costal cartilage is complex and time-consuming, which could be facilitated by a robot in a fast and precise manner. This feasibility study evaluates the accuracy and speed of robotic contouring of cadaver costal cartilage."}
{"note": "Methods: An augmented robot with a spherical burr was used on cadaveric rib cartilage. Using a laser scanner, each rib section was converted to a three-dimensional model for preoperative planning. A model ear was also scanned to define a carving path for each piece of cartilage. After being contoured, each specimen was compared against the preoperative plan utilizing deviation maps to analyze topographic accuracy. Contouring times of the robot were compared with 13 retrospectively reviewed cases (2006\u20132017) by an experienced surgeon."}
{"note": "Results: Scanning the cartilage sections took 24.8 \u00b1 6.8 seconds. Preoperative processing took an additional 29.9 \u00b1 8.9 seconds for the preparation of the contouring path. Once the path was prepared, the robot contoured the specimens with a root mean square error of 0.54 mm and a mean absolute deviation of 0.40 mm. The average time to contour the specimens with the robot was 13 \u00b1 2 minutes compared to 71 \u00b1 6 minutes for the manual contouring in the reviewed cases."}
{"note": "Conclusions: The accuracy of the robotic system was high, with submillimeter deviations from the preoperative plan. The robot required <20% of the contouring time compared to the experienced surgeon. This represents a fast and accurate alternative to hand-contouring costal cartilage grafts for auricular reconstruction."}
{"note": "Key Words: Auricular reconstruction, robot, ear, cartilage, costal cartilage graft."}
{"note": "BACKGROUND: Auricular reconstruction is a complex procedure due to intricate topographic features of the cartilage. Previous research has indicated negative effects on psychological health secondary to inadequate reconstruction, and symmetry of the ears has important cosmetic implications, contributing to self-image and mental health. With consideration of these concerns, complex surgical techniques are used in auricular reconstruction, including the use of autologous cartilage grafts."}
{"note": "When reconstructing auricular defects, there are two major components: the hairless skin envelope and the cartilaginous framework. The complex shape of the ear from the cartilaginous framework has been reconstructed in many ways including alloplastic implants, homologous cartilage, and autologous cartilage. Several complications with alloplastic and homologous reconstructions have been reported, including extrusion of alloplastic implants and resorption of homologous cartilage. Furthermore, both types of implants have been shown to respond poorly to future trauma."}
{"note": "For these reasons, autologous cartilage has become the standard choice for auricular framework reconstruction. This is most commonly performed via composite reconstruction using costal cartilage harvested from the sixth to ninth ribs. Once harvested, the autologous cartilage is contoured into the intended shape, often using the contralateral ear for reference. However, the process of manually contouring costal cartilage is a time-consuming aspect of the operation, even when performed by experienced surgeons. Despite the time requirements of this procedure, reconstruction with autologous cartilage is reliable, and leads to favorable cosmetic outcomes."}
{"note": "The process of contouring the harvested cartilage is the rate-limiting step of the procedure. It necessitates contouring of the intricate topographic features of the contralateral ear, adding length to the surgical procedure. Previous studies have shown that prolonged operative time adds risk (e.g., venous thromboembolism) to the operation and is associated with complications (e.g., surgical site infections). Similar tasks have been automated outside of medicine and could represent an opportunity for innovation. Robot-automation for milling and contouring is a widely available process in other applications, providing high accuracy and precision for complex shaping. These processes rely on computer-derived milling paths, leading to intricately carved pieces. Additionally, robotics have become increasingly utilized in surgical applications in the past decades for orthopedics and neurosurgical procedures, and robot automation may offer an innovative solution to the complex shapes required of auricular reconstruction. In the present study, we report a novel, robot-automated approach to cartilage contouring for auricular reconstruction. The primary and secondary outcomes of this study are accuracy and speed, respectively."}
{"note": "MATERIALS AND METHODS: Materials: A cadaveric feasibility study was performed to test the accuracy (primary outcome) and timing (secondary outcome) of a robot-automated contouring process. Five ribs were harvested from fresh-frozen cadaveric specimens, and costal cartilage sections were excised, marked, and divided into 11 pieces that would be considered clinically acceptable for reconstructing a large peripheral one-third auricular defect. Each sectioned specimen was surface scanned with a handheld laser/optical scanner, and a three-dimensional (3D) solid computer model of the specimen was created. This process was timed, and the results were tabulated in a spreadsheet for analysis. An intact ear was surface scanned, and a 3D model generated, which would serve as the desired reconstruction target for all specimens. The 3D ear model was virtually overlaid onto each of the cartilage 3D models and aligned to maximize the surface area on each piece, while taking advantage of the natural shape of the cartilage. The desired ear model was virtually subtracted from each cartilage piece, leaving a negative volume representing the material to be removed from the cartilage. Computer numerical control software was then used to generate a contouring path, taking into account all the process parameters such as the diameter and shape of the carving bit, its rotation speed and direction, single-pass carving depth, approach angle, and robot velocity. All commands were encoded in G-code, the industry standard for material subtractive-type processes such as milling. Timing data were collected and documented for the above steps, including the postprocessing time, to generate a cutting path from the laser-scanned data."}
{"note": "Robot Methodology: The cartilage contouring was completed using a 4-mm spherical burr mounted on a six-axis custom Stewart Platform robot, designed with high stiffness and compact size, ideal in an operating room setting. This configuration is from a class of robots known as hexapods, having six servo-actuated struts, which is analogous to a Taylor spatial frame often used for external fracture fixation. The robot\u2019s moving platform was augmented with an orthopedic surgical burr stylus, and a custom cartilage specimen fixture was mounted to the robot\u2019s base. The robot-driven autonomous carving path was controlled in real time according to the G-code generated in the preoperative planning phase. The timing of the robotic carving process was recorded, and upon completion, the rib cartilage was removed from the mount and the excess cartilage trimmed from its perimeter. The robot was also augmented with a Force-Space Navigation system, which recorded six-axis motion to serve as a redundant real-time confirmation of the planned path. The Force-Space system\u2019s hardware consisted of a six-axis force sensor and two Nitinol metal bands tethering the robot\u2019s moving platform to its stationary base, without affecting the robot\u2019s freedom of movement. The preoperatively planned path was confirmed by measuring the reaction forces in the super-elastic Nitinol bands as a function of the robot\u2019s real-time positions, and thus achieving a redundant reliability check independent from the robot\u2019s position controller."}
{"note": "Surgeon Methodology: All charts from surgical cases with a similarly sized defect at London Health Sciences Centre from 2006 to 2017 were reviewed. During these cases, after the harvest of an adequately sized cartilaginous graft for the treated defect, a 15 blade was used to manually shape the graft for inset. To create a template, a clear acetate sheet was used to trace the contralateral auricle and mirror the image as a guide to achieve symmetry. The surgical carving times began after the harvest was completed until the graft was ready for inset. The timing data and methods of collection were recorded in the patient chart. The relevant data were extracted from the patient records and recorded in a spreadsheet."}
{"note": "Data Analysis: Each cartilage piece prepared by the robot was laser scanned, and a new 3D model was created for comparison with the original ear scan by superimposing the two 3D models. A global coregistration function was used to minimize misalignment errors. Following alignment, a surface deviation map was generated to represent the topographical difference between the preoperative plan versus the postoperative result. Using the surface deviation maps, the root mean squared (RMS) error and mean absolute deviation were calculated. Mean contouring times were compared between the robotic and manual methods, and descriptive statistics were generated."}
{"note": "RESULTS: Primary Outcome: Accuracy"}
{"note": "For all (n = 11) specimens, the RMS error was 0.54 \u00b1 0.05 mm. The mean absolute deviation was 0.40 \u00b1 0.05 mm (Fig. 5). The lowest mean absolute devia- tion was 0.28 mm and the highest mean absolute devia- tion was 0.47 mm. The maximum error tended to occur at the auricular tubercle, possibly due to the thicker skin of the helix, which is included in the model ear scan, but is not accounted for in the cartilage surface scan. Slightly increased errors also occurred at the antihelix and within the fossa of the helix; however, all errors were <0.50 mm. An example of a robotically prepared rib cartilage graft is presented in Figure 4A, with a deviation map sup- erimposed on the desired ear scan to illustrate topograph- ical error relative to the preoperative plan (Fig. 4B)."}
{"note": "Secondary Outcome: Speed"}
{"note": "For the purposes of this study, the contouring pro- cess consisted of multiple stages that were each timed. The surface scanning time for each cartilage specimen was 24.8 \u00b1 6.8 seconds, and the 3D-model generation time was 29.9 \u00b1 8.9 seconds. The robot contouring process had a mean time of 13 \u00b1 2 minutes (Fig. 6). Thirteen recent surgical cases with similarly sized defects were reviewed from 2006 to 2017. In these cases, the traditional manual carving process required 71 \u00b1 6 minutes (Fig. 6). Thus, the robot carving time was <20% of the average reported manual time in the reviewed cases."}
{"note": "DISCUSSION: Composite auricular reconstruction is a challenging reconstructive problem that commonly relies on autologous cartilage grafting. Harvested costal cartilage is manually contoured to create symmetry with the contralateral ear. This graft forms the basis of the cartilaginous framework, which recreates the topographic features of the ear. The process of manual contouring is time-consuming and represents the rate-limiting step of the procedure. For example, a review of patient charts from an experienced surgeon at our institution resulted in average contouring times in excess of 1 hour."}
{"note": "Outside of the medical field, robot-automated contouring systems have become increasingly available and have been successfully implemented in other surgical fields. This study evaluates the feasibility of robot-automated carving of cartilaginous grafts for auricular framework reconstruction with outcome metrics including preoperative planning time, carving accuracy, and carving time."}
{"note": "On average, the robotic carving process was over five times faster than the reviewed surgical cases, while maintaining submillimeter accuracy, thus achieving both the desired primary and secondary outcomes. The time saved on surgical carving alone represents a significant potential benefit from utilizing this existing technology for auricular reconstruction. Additional time savings can be realized by performing closure of the donor site while the robot carves the harvested cartilage on the benchtop. By working in parallel, this could further reduce operating room time. Moreover, the robotic carving time is known from the surgical planning phase, when the preoperative plan is converted into the robot\u2019s motion commands, thus providing a reliable surgical time estimate. This could also lead to decreased time under anesthetic, which may contribute to patient safety."}
{"note": "Handheld laser/optical scanners have been employed for creating anatomical 3D models in many studies, with fast and accurate results. For the present study, both a model ear (i.e., desired geometry) and the harvested cartilage were surface scanned. Collecting the scans and generating 3D models required less than 60 seconds on average. In practice, the patient\u2019s contralateral ear would serve as the desired model, which could be scanned prior to the surgery and virtually mirrored as part of the preoperative planning process. However, given the speed of this process, it could be performed intraoperatively, if required."}
{"note": "Patient and operator safety are important concerns with any autonomous robot, especially one with a rotating burr. The design presented here avoids patient safety matters by performing the cartilage contouring process on the benchtop away from the patient. The robot has a very small range of motion, only slightly larger than the cartilage graft itself, and its hexapod configuration provides extremely high stiffness that prevents unwanted movement due to accidental contact. Despite these design considerations, there is still the possibility for a servo motor or its position encoder to malfunction, causing the autonomous robot to proceed off course. To prevent this unlikely scenario, a Force-Space device, independent from any of the robot\u2019s systems, was employed to provide a redundant check. Any deviation from the planned pathway would halt the robot. This consideration could lead to destruction of the harvested cartilage, which may render it unsuitable for surgical implantation. The authors recognize that this could represent a serious intraoperative concern and further safety assessments would be required before widespread adoption of this technology could be recommended. In this study, no such deviation was detected."}
{"note": "A limitation of this study was that a true operative experience was not reproduced, and so logistics of bringing the robot into the operating room were not evaluated. Notwithstanding this limitation, practical logistics would likely be mitigated by the design of the robot, which is a small portable device made to function on a benchtop with a standard electrical power supply. Another limitation is that this was a cadaveric study, and little precaution was made to maintain a sterile environment. The robot was designed to utilize a standard orthopedic burring stylus and a cartilage fixture, which can both be autoclaved. Moreover, the fixturing was designed to accommodate a small plastic sterile sheath, often used to shield cables of surgical electronics, which would be tied tightly around the burring stylus neck to isolate the cartilage while allowing access for the burr. This design is meant to keep a sterile environment for the cartilage and to protect the robot so that its sterile maintenance requires only standard spraying and wiping procedures. Additionally, the small form factor of the robot used in this study would allow for a simple shield to encapsulate the device in an operating room, which would prevent the spray of cartilage and soft tissue debris removed by the burr in the course of contouring the graft. Nonetheless, specific sterilization protocols were not followed in this study, and so the true logistics cannot be commented on here, and future work should include an analysis of sterility."}
{"note": "CONCLUSION: The accuracy and speed of robot-automated contouring for auricular reconstruction observed in this study indicate an opportunity to improve surgical times and clinical outcomes. The complex shapes of the auricular framework are challenging and time-consuming to recreate by hand, but by using a surface scanner in combination with a hexapod robot, highly accurate results were achieved. Moreover, robotic carving is not surgeon-dependent, and even the preoperative planning process is largely automated and standardized by 3D modeling software functions. Thus, with the use of an autonomous robot in auricular framework reconstruction, accuracy and surgical time would not be affected by surgeon-dependent factors, thus improving consistency of final cosmetic outcomes. Robot-automated contouring represents an innovative approach to improving complex auricular framework reconstruction. The process was shown to be fast and accurate on cadaveric models and should be trialed in an operating room setting to confirm utility for future reconstructions.\n\u2014-----------------------------------------------------------------"}
{"note": "TITLE: Evaluation of Acoustic Analyses of Voice  in Nonoptimized Conditions"}
{"note": "ABSTRACT: Objectives: This study aimed to evaluate the fidelity and accuracy of a smartphone microphone and recording environment on acoustic measurements of voice. Method: A prospective cohort proof-of-concept study was conducted using two sets of prerecorded samples: (a) sustained vowels (/a/) and (b) Rainbow Passage sentences, played and recorded via the internal iPhone microphone and the Blue Yeti USB microphone in two environments\u2014a sound-treated booth and a quiet office setting. Recordings were presented using a calibrated mannequin speaker at a fixed intensity and distance. Acoustic measures, including fundamental frequency (fo), jitter, shimmer, harmonic-to-noise ratio (HNR), and cepstral peak prominence (CPP), were analyzed using Praat software. Data from both pathologic and normal voiced male and female speakers were compared using repeated measures analysis of variance. Results: Analysis indicated significant differences in jitter, shimmer, HNR, and CPP based on microphone choice, and differences in shimmer, HNR, and CPP based on recording environment. While significant, differences for certain measures fell within normative ranges, suggesting minimal clinical impact. Conclusions: Microphone type and recording setting significantly affected acoustic measurements, but differences in some measures were unlikely to influence clinical interpretation. This suggests smartphone microphones in non-sound-treated settings can still yield acceptable recordings for acoustic analysis."}
{"note": "INTRODUCTION: Acoustic analysis plays a pivotal role in the clinical assessment of voice disorders, offering baseline and diagnostic information along with objective measures for evaluating treatment outcomes. It serves as a noninvasive, objective method to detect vibratory abnormalities in voice production and to measure the extent of abnormalities within the vocal signal. The field of mobile health (mHealth) has seen rapid growth, with smartphones becoming a key tool in patient care due to their improved hardware, including microphones suitable for voice sample collection. This study addresses the challenges in voice sample collection for acoustic analysis, which traditionally requires a sound-treated environment, professional equipment, and a standardized setup. It explores the potential of using smartphone microphones in non-sound-treated settings for reliable acoustic voice analysis, considering the impact of recording environment and microphone quality on acoustic measurements. Despite potential challenges such as ambient noise and the lack of a trained practitioner for sample collection, previous research suggests that smartphone microphones can provide high-quality recordings for acoustic analysis. This study aims to systematically evaluate the effects of smartphone microphones and recording settings on the validity of acoustic voice measurements, proposing a mobile solution to increase accessibility to acoustic voice analysis by reducing costs and improving the efficiency of voice sample collection."}
{"note": "MATERIALS AND METHODS: Participants: High-quality prerecorded audio samples were utilized to assess the impact of microphone and recording environment on acoustic measurements. For vowel analysis, 20 sustained vowel samples (/a/) included both normal (n=10) and dysphonic (n=10) voices, with dysphonic samples ranging from mild-to-severe. Samples were chosen from an archival database, assessed for overall severity using a visual analogue scale by an experienced listener. The samples consisted of male (n=5) and female (n=15) speakers. Sentence stimuli used the second sentence of The Rainbow Passage, including both male (n=12) and female (n=12) voices, judged to range from normal to severely dysphonic."}
{"note": "Procedure: Two microphones were used: (a) an iPhone 7 Plus internal microphone and (b) a Blue Yeti Ultimate USB Microphone, recording in mono. The iPhone microphone, an omnidirectional transducer with a 44,100 Hz sampling rate, and the Blue Yeti, recording at 48,000 Hz with a cardioid pattern, were chosen for their quality and prevalence in voice analysis studies. Recordings were taken in both a soundproof room and a nonsoundproof room using a calibrated mannequin speaker at a fixed distance of 15 inches, with the output volume set to 69 dBA."}
{"note": "Data and Statistical Analysis: A power calculation determined 17 recordings per group were required. Recordings were time-windowed for consistent analysis. Praat software calculated fundamental frequency (fo), jitter, shimmer, harmonic-to-noise ratio (HNR), and cepstral peak prominence (CPP). HNR and CPP were analyzed for both sustained vowels and sentences, while fo, jitter, and shimmer were assessed for vowels only. A repeated-measures analysis of variance (ANOVA) evaluated the influence of microphone type and recording environment on these measures. Descriptive statistics were gathered for all acoustic values, with analyses performed using SPSS Version 23.0.0.0."}
{"note": "RESULTS: The analysis presented in the tables outlined the mean, median, standard deviation, and standard error for each acoustic measure across four different recording conditions. The repeated-measures ANOVA showed that there were no significant differences in the fundamental frequency (fo) across conditions, indicating the consistency of fo estimation regardless of microphone type or recording environment."}
{"note": "However, jitter measures were significantly affected by microphone type but not by the acoustic environment, with iPhone recordings showing higher jitter values than Yeti recordings in both settings. Both shimmer and harmonic-to-noise ratio (HNR) measures showed significant differences based on both the microphone type and recording environment, with greater discrepancies observed in the office setting compared to the sound booth when comparing Yeti and iPhone recordings."}
{"note": "For HNR derived from sentences and cepstral peak prominence (CPP) from both vowels and sentences, significant differences were noted for the main effects of both environment and microphone, highlighting better performance in sound booth conditions and with Yeti microphones. Scatter plots with linear regression fits visually represented these data comparisons, showing that the Yeti recordings in the sound booth served as a reliable reference, with regression fits explaining a high percentage of variance in most conditions. Notably, variability increased for shimmer and HNR measures with iPhone recordings in office environments, as evidenced by lower percentages of variance explained in these conditions."}
{"note": "DISCUSSION: This study investigated the impact of smartphone microphones and recording environments on voice sample collection, revealing statistically significant differences for most acoustic measurements between microphone types and recording environments. However, the absolute differences were generally small, suggesting that in many cases, these differences might not be clinically significant."}
{"note": "The fundamental frequency (fo) was consistent across recording conditions, indicating fo estimation is robust, with deviations primarily from a single outlier in severely disordered samples. This aligns with literature suggesting fo estimation is reliable across different acoustic analysis systems for voices that are not severely pathological."}
{"note": "Jitter differences between microphone types were statistically significant but minor in magnitude. Even with these differences, jitter values remained within published normative ranges, suggesting these variations might not impact clinical interpretations significantly."}
{"note": "Shimmer and harmonic-to-noise ratio (HNR) measures were affected by both the microphone type and the recording environment. Despite statistical significance, only the shimmer data from iPhone recordings in a nonsoundproof environment notably exceeded normative thresholds. This indicates that, while statistically significant, many of these differences may not alter clinical outcomes or interpretations, especially for measurements within the normative range."}
{"note": "The cepstral peak prominence (CPP) measures, which are increasingly considered important in dysphonia evaluation, showed differences that were within the range of clinical insignificance. This is encouraging, demonstrating the potential reliability of smartphone microphones for collecting voice samples outside of traditional clinical settings."}
{"note": "The cardioid pattern of the Yeti microphone seemed to mitigate environmental noise impacts, highlighting the importance of microphone selection in achieving reliable voice recordings. However, caution is advised due to potential proximity effects, which were minimized in this study by maintaining an appropriate distance between the source and the microphone."}
{"note": "In summary, while microphone type and recording environment influenced acoustic voice measures, the clinical significance of these differences is limited for many measures. This suggests that smartphone microphones, even in less controlled environments, can provide viable options for voice sample collection, expanding accessibility to voice analysis. However, certain conditions and measurements, such as shimmer and HNR in nonsoundproof environments, require careful consideration and interpretation. This study supports the feasibility of using smartphones for voice analysis, potentially democratizing access to voice assessment tools outside traditional clinical settings."}
{"note": "CONCLUSIONS: This study found statistically significant differences when using smartphone microphones and nonsound controlled environments for voice sample collection in acoustic voice analysis. However, the examination of these differences indicates a limited overall impact on certain acoustic measures, suggesting these factors might not result in clinically relevant changes. This underscores the complexity of balancing control in voice sample collection with the practicality and accessibility of using smartphones for this purpose."}
{"note": "Despite potential concerns about the validity of data obtained from less controlled environments and with consumer-grade technology, the findings suggest that the advantages of increasing accessibility to acoustic voice analysis may outweigh the minimal loss of accuracy in most clinical or monitoring scenarios. Notably, some acoustic measures, such as the mean fundamental frequency (fo) and cepstral peak prominence (CPP), showed a robustness that renders them clinically useful even under these less controlled conditions."}
{"note": "The study supports the feasibility of using smartphones as a reliable tool for voice sample collection, paving the way for their use in the assessment and ongoing monitoring of voice disorders. This aligns with the broader goals of mobile health (mHealth) applications in providing accessible, efficient, and patient-centered care solutions. Given these findings, smartphones may indeed represent a valuable first step towards the integration of mHealth applications in the field of voice disorder management, offering a promising avenue for expanding the reach and effectiveness of voice disorder assessments and interventions.\n\u2014-----------------------------------------------------------------"}
{"note": "TITLE: Parapharyngeal abscess following use of a laryngeal mask airway during open revision septorhinoplasty"}
{"note": "ABSTRACT: The laryngeal mask airway (LMA) is a widely used device to maintain the airway in patients undergoing surgery with general anesthesia, known for its safety and low complication rate. This report presents a rare case of a 50-year-old female who developed a parapharyngeal neck abscess after an uneventful septorhinoplasty performed with an LMA Classic. The patient experienced pain and difficulty swallowing post-operation. Imaging showed significant soft tissue edema involving multiple neck spaces, leading to the diagnosis of a parapharyngeal abscess. The abscess was successfully treated through incision and drainage, along with laryngoscopic evaluation of the infection site at the right pyriform fossa, resulting in full recovery. This case underscores the importance of prompt recognition and treatment of rare LMA-related complications, such as parapharyngeal abscess, to prevent severe outcomes like airway obstruction. The suspected cause of the abscess was pressure necrosis from LMA over-inflation, leading to perforation into the parapharyngeal space. This report aims to raise awareness of potential complications from routine airway management techniques in shared airway surgeries."}
{"note": "INTRODUCTION: The Laryngeal Mask Airway (LMA) is recognized for its efficacy in providing a secure artificial airway for both controlled and spontaneous ventilation by forming a low-pressure seal around the glottis. With a success rate of insertion at 99.81% among 11,910 patients and a critical incident rate of only 0.15%, the LMA's safety and effectiveness are well-documented. Complications, though rare, can range from minor issues such as coughing and sore throat to more serious conditions like arytenoid dislocation and vocal cord paralysis. Retropharyngeal and parapharyngeal abscesses following LMA use are exceedingly uncommon, with literature documenting only a handful of cases resulting from pharyngeal trauma. Such abscesses pose significant risks, including airway obstruction and sepsis, necessitating prompt surgical and antibiotic treatment. Despite the rarity, parapharyngeal space infections, if untreated, can progress to retropharyngeal spaces and further descend into the mediastinum, highlighting the gravity of managing such complications effectively. This report presents a case of a 50-year-old female developing a parapharyngeal neck abscess after an open revision septorhinoplasty using an LMA, underscoring the need for awareness and early intervention in such rare but serious complications."}
{"note": "CASE PRESENTATION: A 50-year-old female experienced right neck pain and odynophagia following an open revision septorhinoplasty, where a Number 4 LMA Classic\u2122 laryngeal mask airway was employed for airway management. The procedure and LMA insertion were uneventful, completed within two hours by an experienced anesthetist without laryngoscopy and with no air leak noted during surgery. Postoperatively, the patient reported pain with swallowing and right otalgia, managed initially with IV morphine and subsequently with Percocet due to codeine intolerance."}
{"note": "Persisting swallowing difficulties and insufficient pain relief from oxycodone led her to present to the emergency room five days post-surgery. Initial treatment included IV ceftriaxone, and imaging identified a significant abscess in the right neck. A CT scan detailed a loculated fluid and air collection extending from the right parapharyngeal space across to the retropharyngeal space, without mediastinal extension. Despite presenting tachycardic and febrile, the patient's airway remained uncompromised as confirmed by flexible endoscopy."}
{"note": "Surgical intervention at a community hospital involved incision and drainage of the abscess, confirmed by laryngoscopy, and a nasogastric tube placement for nutrition. Cultures identified multiple organisms, including Streptococcus anginosus group, anaerobic gram-positive cocci, and Prevotella species. Following transfer to a regional hospital for continued care, the patient showed significant improvement, managing a soft food diet upon discharge eight days later, eventually making a full recovery from the parapharyngeal abscess."}
{"note": "This case underscores the rarity yet potential severity of complications associated with LMA use, such as parapharyngeal abscess, which demands prompt recognition and intervention to prevent more serious outcomes. The patient's recovery highlights the importance of multidisciplinary management in addressing complex postoperative complications."}
{"note": "DISCUSSION: This case report illuminates a rare instance of parapharyngeal abscess following the use of a Laryngeal Mask Airway (LMA) in a surgical procedure. It's suspected that over-inflation of the LMA cuff led to soft tissue necrosis, forming a pathway for infection into the deep neck spaces, ultimately resulting in a neck abscess. This complication underscores the importance of monitoring cuff pressure, a practice not routinely performed at the reporting institution, suggesting a need for more stringent protocols. The LMA, a device celebrated for its ease of use and low complication rate, can, under certain conditions, pose a risk to patient safety. This case also emphasizes the significance of choosing the appropriate airway management device, considering the LMA's design and the procedure's duration as key factors."}
{"note": "CONCLUSION: Laryngeal mask airway-related injuries, while rare, can lead to severe complications, such as parapharyngeal abscesses. This report highlights the critical need for early detection and intervention to prevent complications from escalating to more serious conditions like retropharyngeal abscesses and airway obstruction. It raises awareness about the potential risks associated with seemingly routine airway management techniques and underscores the importance of considering alternative airway management strategies and routine monitoring of LMA cuff pressures to mitigate these risks. This case also serves as a reminder of the challenges in providing fully informed consent, as such rare complications are often not discussed during preoperative counseling.\n\u2014-----------------------------------------------------------------------------------"}
{"note": "TITLE:Sialocutaneous fistula to the external auditory canal repaired with superficial parotidectomy and temporoparietal flap: A case report"}
{"note": "ABSTRACT: This case report details the surgical management of a late-evolving sialocutaneous fistula to the external auditory canal, manifesting 27 years after the initial operation and 19 years following the onset of mild symptoms. The patient presented with left-sided clear otorrhea that was gustatory in nature, experiencing a significant increase in volume over 8 months, leading to social disruption. The diagnosis was a sialocutaneous fistula to the external auditory canal. Conservative therapies were unsuccessful, leading to a decision for surgical intervention. The chosen surgical method was a superficial parotidectomy combined with a temporoparietal flap to close the fistula. The patient had no postoperative complications and reported resolution of gustatory otorrhea at the one-year follow-up. This case underscores the possibility of late presentation and symptom evolution in postoperative complications, highlighting the need for awareness among clinicians. Despite its rarity, such a complication can significantly impact the patient's social life and can be managed effectively through both conservative medical approaches and various surgical techniques."}
{"note": "Keywords: auditory canal atresia, canaloplasty, external auditory canal, salivary fistula, sialocutaneous fistula"}
{"note": "INTRODUCTION: Sialocutaneous fistula, characterized by an abnormal connection between the salivary gland ducts and the skin, is an infrequent medical condition. While congenital instances have been documented, the majority of cases are attributed to facial trauma. The spectrum of management strategies ranges from non-invasive approaches\u2014such as watchful waiting, application of sclerosing agents, and botulinum toxin injections\u2014to more definitive surgical interventions like parotidectomy. This report delves into a unique case of a sialocutaneous fistula presenting at the external auditory canal (EAC), notable for its delayed onset and progressive symptomatology that emerged decades after the initial precipitating event. The narrative further explores the considerable social implications experienced by the patient, offering insights into the personal challenges posed by this rare condition. The preparation of this case report was conducted with the explicit consent of the patient, ensuring ethical compliance in the sharing of her medical history."}
{"note": "CASE REPORT:"}
{"note": "2.1. Patient Information: This case involves a 41-year-old female with an 18-year history of gustatory, left-sided clear otorrhea, which had significantly increased in volume over the last 8 months, causing social discomfort. She had a history of bilateral canaloplasty for congenital auditory canal atresia and had been under routine EAC debridement with no prior complications. Initial treatment with cephalexin by her family physician did not yield improvement. Notably, the patient reported no otalgia, vertigo, hearing loss, or tinnitus. The otorrhea was first mild in 1996 but worsened in 2015, leading to social withdrawal."}
{"note": "2.2. Physical Examination: The examination showed canals within normal limits following previous canaloplasty, intact tympanic membranes bilaterally, fluid presence in the left external canal, and a small punctum in the anteroinferior portion of her left external canal."}
{"note": "2.3. Diagnostic Assessment: Salivary amylase testing of the otorrhea returned a highly positive result (>33,000 u/L), suggesting a salivary origin. However, magnetic resonance imaging of the neck found no evidence of a parotid/EAC fistula or other abnormalities. An MR sialogram, which could have definitively identified the fistula tract, was not available."}
{"note": "2.4. Interventions: Initially considered as a potential case of Frey Syndrome in the EAC and treated with Botox injections without improvement, the patient was eventually referred for surgical treatment. Opting for a definitive solution, she underwent a superficial parotidectomy with a temporoparietal flap, chosen over more conservative fistula tract obliteration, to address her complex medical history and symptomatology."}
{"note": "2.5. Follow-up and Outcomes: Postoperatively, the patient reported cessation of otorrhea, with no facial weakness, First Bite syndrome, or Frey syndrome symptoms. The surgical incision healed well, with no hair loss, and the fistula tract site remained visible but dry."}
{"note": "This case underscores the challenges in diagnosing and managing late-presenting, evolving sialocutaneous fistulas, particularly when initial conservative treatments fail. Surgical intervention, tailored to the patient's specific condition and history, proved effective in resolving the symptoms and improving the patient's quality of life."}
{"note": "DISCUSSION:"}
{"note": "Sialocutaneous fistula to the external auditory canal (EAC) presents a diagnostic challenge due to its rarity, leading to potential misdiagnosis and inadequate treatment. The origins of such fistulas can be congenital or acquired, with the Foramen of Huschke and the Fissures of Santorini being potential congenital pathways, while iatrogenic trauma, infection, neoplasm, or chronic inflammation can serve as acquired causes. Particularly, iatrogenic causes are often seen as postoperative complications following head and neck surgeries. In this context, salivary gland tissue near the surgical site may continue secreting saliva, which then finds the path of least resistance, forming a fistula."}
{"note": "The reported incidence of sialocutaneous fistula to the EAC following surgical repair for congenital aural atresia is notably low, at 0.4%. The case presented here is distinguished by its delayed onset, with the patient initially experiencing mild symptoms that were not reported until 19 years post canaloplasty. The significant increase in otorrhea volume 19 years later prompted the search for definitive treatment, underscoring the evolving nature of this complication."}
{"note": "Conservative treatments such as observation, sclerosing agents, and anticholinergics (e.g., Botox or glycopyrrolate) have been mentioned in literature, along with pressure dressings and surgical options like fistula tract obliteration, direct fascial closure, and parotidectomy. The decision to pursue a more aggressive surgical intervention in this case was driven by the acute exacerbation of symptoms and the patient's considerable social discomfort, highlighted by the need to constantly carry a towel for the otorrhea."}
{"note": "The chosen surgical approach of superficial parotidectomy combined with temporoparietal flap aimed to not only address the fistula but also to prevent future salivary leakage by removing adjacent salivary tissue and creating a barrier. This method has proven to be a viable solution for resolving severe or refractory cases of gustatory otorrhea, offering a blend of efficacy and patient satisfaction by alleviating the symptoms and, importantly, the social disruptions caused by this condition."}
{"note": "CONCLUSION: Sialocutaneous fistula to the external auditory canal (EAC) represents a rare and challenging condition, with the case discussed herein exemplifying an unusually late manifestation following canaloplasty\u2014a scenario that extends well beyond typical postoperative complication timeframes. Highlighting the complexity and chronic nature of this condition, the case underscores the necessity for a definitive surgical intervention in instances where conservative management fails or is deemed unsuitable due to the severity and social implications of the symptoms. The successful resolution of this patient's symptoms through the surgical removal of salivary gland tissue and the strategic use of a temporoparietal flap to establish a durable physical barrier against recurrence demonstrates the efficacy of this approach. This case contributes valuable insights into the surgical management of late-presenting sialocutaneous fistulas, reinforcing the importance of considering patient-specific factors and the potential for delayed complications when planning postoperative care.\n\u2014---------------------------------------------------------------"}
{"note": "TITLE: Cricothyroid Muscle Botulinum Toxin Chemodenervation to Treat Recalcitrant High-Pitched Functional Dysphonia in an Adult Male"}
{"note": "ABSTRACT: Summary: Introduction: Functional dysphonia, characterized by voice disorders such as aphonia or inappropriate vocal pitch without any structural or neurologic abnormalities in the larynx, primarily receives voice therapy as the initial treatment modality. However, options for cases unresponsive to voice therapy remain underexplored in current literature."}
{"note": "Methods: This study involves a retrospective review of medical records alongside a detailed case report."}
{"note": "Results: We present a distinctive case of an adult male suffering from persistent high-pitched functional dysphonia, diagnosed in adulthood, who experienced significant improvement following a single botulinum toxin (Botox) chemodenervation injection into the cricothyroid muscle."}
{"note": "Conclusion: Cricothyroid muscle botulinum toxin chemodenervation emerges as a viable therapeutic option for treating stubborn cases of functional dysphonia, offering a potential avenue for patients who do not respond to conventional voice therapy."}
{"note": "Key Words: High-pitched functional dysphonia, Puberphonia, Dysphonia, Botulinum toxin injection, Cricothyroid muscle."}
{"note": "INTRODUCTION: Functional dysphonia is a voice disorder occurring without structural or neurological laryngeal abnormalities, often resulting from inappropriate laryngeal muscle tension during phonation. Various factors, including infections, intubation, or trauma, have been suggested as potential triggers, yet the precise underlying mechanisms remain a subject of ongoing debate. According to one theory, individuals with functional dysphonia may develop excessive laryngeal and surrounding muscle tension in response to psychological or physical stressors, leading to compensatory recruitment of additional musculature and thus perpetuating the cycle of inappropriate tension during voice use. This condition manifests in diverse voice symptoms, ranging from aphonia or a whispering voice to neck discomfort due to chronic muscular strain, significantly affecting patients' quality of life."}
{"note": "The primary management strategy for functional dysphonia involves specialized voice therapy conducted by skilled speech-language pathologists (SLPs), focusing on techniques like manual laryngeal manipulation to alleviate symptoms. Despite the general effectiveness of voice therapy, literature on alternative treatments for cases unresponsive to conventional approaches is scant. This report introduces a novel instance of adult-onset high-pitched functional dysphonia, reminiscent of puberphonia, yet distinct due to its acquisition in adulthood and resistance to standard voice therapy. Highlighted is the successful application of cricothyroid muscle botulinum toxin (Botox) chemodenervation in treating this unique presentation of functional dysphonia in a cisgender male, marking the first documented case of its kind."}
{"note": "CASE REPORT:"}
{"note": "A 49-year-old male with a history of high-pitched voice following right-sided anterior cervical discectomy and fusion reported a sudden onset of symptoms five years post-surgery. Initially presenting with a weak, breathy, high-pitched voice diagnosed as right vocal fold paralysis, his condition evolved to less breathy yet persistently high-pitched phonation despite the recovery of vocal fold function. This change in voice led to significant personal and professional difficulties, including job loss and social misgendering."}
{"note": "Despite undergoing two courses of voice therapy and vocal fold injection augmentation without success, the patient continued to experience voice-related challenges. An initial examination at our clinic showed reduced vocal intensity and high-pitched falsetto phonation, with a Voice Handicap Index-10 (VHI-10) score of 34/40, reflecting a significant daily impact. Videostroboscopy revealed falsetto phonation with elongated vocal folds but no structural abnormalities."}
{"note": "Diagnosed with functional dysphonia, puberphonia, and laryngeal spasm, the patient underwent an intensive day of voice therapy \"boot camp\" without sustaining improvement. Returning 14 months later, he consented to cricothyroid muscle botulinum toxin (Botox) chemodenervation, leading to a remarkable recovery of his natural voice pitch post-injection and sustained improvement over six months. His follow-up VHI-10 score dropped to 0/40, indicating a profound positive change in voice quality and its impact on his life."}
{"note": "This case underscores the potential of cricothyroid muscle Botox injection as an effective intervention for recalcitrant functional dysphonia when combined with specialized voice therapy. The patient's recovery highlights the importance of multidisciplinary approaches in managing complex voice disorders and the transformative impact such treatments can have on patient well-being."}
{"note": "DISCUSSION:"}
{"note": "Functional dysphonia, characterized by abnormal voice quality without identifiable laryngeal pathology, often results in significant discomfort and psychosocial impacts, manifesting in various forms, including, though rarely, high pitch in adult males. This high pitch is typically related to puberphonia or mutational falsetto, a condition where the voice does not transition from the pre-pubertal to the adult pitch post-puberty. However, a high-pitched voice emerging in adulthood, as seen in our case, without organic laryngeal abnormalities, is more accurately classified as functional dysphonia, possibly stemming from maladaptive laryngeal muscle tension following a physical insult."}
{"note": "Voice therapy led by a voice-specialized speech-language pathologist (SLP) stands as the primary treatment, effectively alleviating symptoms for most patients. Nonetheless, second-line treatments remain under-explored. Botulinum toxin (Botox) injections, known for their neuromuscular blockade effect, have found widespread use across various conditions, including spasmodic dysphonia in otolaryngology, by reducing acetylcholine release at neuromuscular junctions. Although Botox injections have been applied for conditions like bilateral vocal fold abductor paralysis and spasmodic dysphonia, their use in functional dysphonia, especially for non-high-pitched vocal qualities, lacks documentation."}
{"note": "Our case illustrated the successful application of Botox injection to the cricothyroid muscle in treating persistent high-pitched functional dysphonia, showcasing rapid symptom resolution and significant quality of life improvement. This outcome suggests that cricothyroid muscle Botox chemodenervation could disrupt the cycle of maladaptive laryngeal muscle tension, similar to the temporary relief observed with topical local anesthetics in functional dysphonia. This case opens avenues for future research to explore long-term outcomes of Botox treatment in functional dysphonia and to evaluate its efficacy across a broader range of vocal disorders beyond high pitch."}
{"note": "CONCLUSIONS:"}
{"note": "This case marks the first documentation of a puberphonia-like high-pitched manifestation of functional dysphonia in an adult male, which was effectively managed with cricothyroid muscle botulinum toxin chemodenervation after failing to respond to initial voice therapy sessions. For individuals experiencing functional dysphonia that persists despite traditional voice therapy approaches, particularly those presenting with high-pitched, puberphonia-like symptoms, botulinum toxin injections to the cricothyroid muscle present a viable, adjunctive treatment strategy. This intervention demonstrates potential for substantial improvement in voice quality and patient quality of life, expanding the therapeutic options available for complex cases of functional dysphonia.\n\u2014----------------------------------------------------------------------------"}
{"note": "TITLE: Cervicofacial Actinomycosis in the Pediatric Population: Presentation and Management        ABSTRACT:"}
{"note": "Background: Actinomyces species causing head and neck infections in children represent a rare but significant clinical challenge, characterized by chronic cervicofacial infection, localized swelling, abscess formation, sinus drainage, and potential osteomyelitis complications."}
{"note": "Methods: This report details two pediatric cases of secondary actinomycosis associated with congenital lesions: one involving a previously excised preauricular sinus and another associated with a persistent sublingual mass. A thorough literature review was conducted to identify reported pediatric cervicofacial actinomycosis cases."}
{"note": "Results: The two presented cases were effectively managed through comprehensive surgical removal of the lesions coupled with extended antibiotic treatment. In total, thirty-four pediatric cases of cervicofacial actinomycosis were reviewed, including the two described in this report and thirty-two from existing literature. The findings revealed an equal gender distribution with a median age of 7.5 years, and the submandibular region was identified as the most frequent infection site. Notably, four cases (12%) involved pre-existing congenital lesions. The majority of patients received penicillin-based antibiotics for an average of six months post-surgical excision or debridement."}
{"note": "Conclusions: Cervicofacial actinomycosis, particularly secondary infections stemming from head and neck congenital lesions, remains a rare condition. This report is the first to identify infections arising from a preauricular sinus excision and a sublingual dermoid cyst. Actinomycosis should be considered in the differential diagnosis for chronic draining sinuses in the head and neck area, with diagnosis confirmed via anaerobic culture. Given the risk of osteomyelitis, MR imaging is advisable. Treatment typically involves prolonged penicillin-based antibiotic therapy and surgical intervention."}
{"note": "Keywords: Infection, Anaerobic bacteria, Children, Intraoral excision, Common childhood external ear problems."}
{"note": "INTRODUCTION:"}
{"note": "Cervicofacial actinomycosis represents a rare yet significant cause of head and neck abscesses in children, marked by a slow, subacute, or chronic progression. The condition is attributed to the Actinomyces species, gram-positive, filamentous anaerobic bacteria known for producing characteristic sulfur granules. These organisms are naturally found colonizing the human oral cavity, gastrointestinal, and genitourinary tracts, with mucosal injury, poor oral hygiene, and immunosuppression being key factors in the disease's pathogenesis. The infections often present as polymicrobial and necessitate prolonged anaerobic culture, extending up to 15 days, for accurate identification. Although A. israelii is the species most frequently associated with human infections, over 25 other Actinomyces species have been identified through 16S ribosomal RNA sequencing, contributing to the disease's complexity."}
{"note": "Cervicofacial actinomycosis typically manifests as chronic submandibular swelling but can affect various head and neck areas, potentially leading to misdiagnoses as other granulomatous diseases or malignancies due to symptoms like pain, fever, and weight loss. Complications can include draining sinuses, osteomyelitis, and bacteremia, highlighting the infection's invasive nature and the substantial morbidity risk without long-term penicillin-based treatment. Diagnosing actinomycosis necessitates anaerobic cultures, particularly for atypical pediatric head or neck masses, emphasizing the importance of accurate identification and appropriate dual management involving penicillin-based antibiotics for the polymicrobial infection and surgical intervention for extensive or recurrent cases."}
{"note": "This introduction sets the stage for discussing two pediatric cases of secondary cervicofacial actinomycosis arising in atypical sites not previously documented, including the first reported case of A. turicensis cervicofacial infection in a child. These cases underscore the clinical challenge posed by actinomycosis and the necessity for heightened awareness and strategic treatment approaches in managing this rare infection in the pediatric population."}
{"note": "CASES:"}
{"note": "Case 1: A 10-year-old female with a history of a recurrently infected left pre-auricular sinus post-surgical debridement experienced a chronic infection post-operatively. Despite multiple oral antibiotics, the infection persisted with negative wound swabs. Re-exploration and re-excision were conducted, revealing purulence and a sinus tract extending to the cartilaginous helix. Anaerobic cultures grew Actinomyces turicensis, prompting a switch to amoxicillin-clavulanate based on polymicrobial findings. Despite a second surgical re-excision due to intermittent drainage, the patient ultimately responded well to a 6-month course of amoxicillin-clavulanate, with no recurrence observed at the 6-month follow-up."}
{"note": "Case 2: A 14-year-old male presenting with a sublingual mass, initially managed as a plunging ranula, experienced an increase in size following trauma. Despite initial decompression and marsupialization, recurrence led to aspiration, which grew Actinomyces spp. MRI excluded osteomyelitis. Persistent infection and swelling necessitated surgical excision of what was identified as a dermoid cyst. The patient underwent a 9-month course of high-dose amoxicillin-clavulanate, resulting in no signs of recurrence 2 months post-operatively."}
{"note": "These cases highlight the rare occurrence of cervicofacial actinomycosis secondary to congenital lesions in children, underscoring the importance of considering Actinomyces spp. in chronic draining sinuses of the head and neck region. Both cases emphasize the need for surgical excision coupled with prolonged antibiotic therapy for successful management."}
{"note": "METHODS:"}
{"note": "A comprehensive literature search was conducted using PubMed, EMBASE, and Medline databases up to March 28, 2020, employing infection-specific terms related to Actinomyces and actinomycosis, combined with condition-, site-, and age-specific phrases. Additional databases like Cochrane and Web of Science were searched, though no new relevant articles were found. The review focused on English-language reports of confirmed pediatric cervicofacial actinomycosis cases in patients under 18. Exclusion criteria included articles not specifically addressing pediatric cervicofacial actinomycosis, immunocompromised patients, or infections of the tonsils, thyroid, intracranial, or dental regions due to differing presentations. Data on demographics, clinical features, microbiology, management, and outcomes were systematically extracted."}
{"note": "RESULTS:"}
{"note": "From 149 English-language articles, 26 met the inclusion criteria after rigorous screening, contributing data on 32 pediatric patients. The gender distribution was nearly even, with a median age of 7.5 years. The mandibular region was the most common infection site (48%), followed by cervical (25%) and infra-auricular areas (6%). Congenital lesions were noted in 4 cases (12%), including the two presented in this study. The majority of infections manifested as cervicofacial masses (91%), with pain reported in 65% of cases with documented symptoms. Sinus tracts and osteomyelitis features were noted in 19% and 41% of cases, respectively. The predominant causative organisms were A. israelii (28%) and A. odontolyticus (13%), with some cases unspecified. Penicillin-based antibiotics were the mainstay of treatment (94%), supplemented with non-penicillin antibiotics in 23% of cases. Surgical intervention was common (75%), and antibiotic therapy duration varied widely, from 1 week to over 2 years. All reported cases resulted in infection resolution or loss to follow-up."}
{"note": "CONCLUSIONS:"}
{"note": "Cervicofacial actinomycosis in children is rare, with potential secondary infection in congenital lesions. The comprehensive review underscores the efficacy of combined surgical and prolonged penicillin-based antibiotic therapy. These findings highlight the importance of considering actinomycosis in persistent cervicofacial infections and the value of aggressive management to prevent morbidity."}
{"note": "DISCUSSION:"}
{"note": "This study presents two unique pediatric cases of cervicofacial actinomycosis arising from congenital lesions, marking the first reported instances of actinomycosis at each respective site. Actinomyces species, part of the normal oral flora, can lead to infection following mucosal injury or immune compromise, potentially explaining the sublingual infection observed. The pre-auricular sinus case is hypothesized to have become infected through oral secretions during sleep, showcasing the diverse pathways through which actinomyces can infect congenital lesions."}
{"note": "Actinomycosis, while rare in children and more prevalent in middle-aged individuals, mimics various diseases, making diagnosis difficult. It often presents as a cervicofacial mass, especially in the mandibular area, and can be complicated by draining sinuses and osteomyelitis. Diagnosis requires anaerobic cultures due to its polymicrobial nature, which can complicate the identification of the infection."}
{"note": "Pre-auricular sinuses, common congenital abnormalities, can become secondarily infected, highlighting the necessity for thorough surgical excision and consideration of actinomyces in chronic draining sinuses. Dermoid cysts in the head and neck region, representing another potential site for actinomycosis infection, emphasize the need for complete surgical management and prolonged antibiotic therapy in cases of recurrent or persistent infection."}
{"note": "Cervicofacial actinomycosis typically manifests as a painful mass or swelling, with osteomyelitis being a recognized complication, particularly affecting the mandible. Diagnosis and management require a comprehensive approach, including MRI to exclude bony involvement and cultures to guide targeted antibiotic therapy."}
{"note": "Treatment recommendations include prolonged penicillin-based antibiotics, potentially extended in cases complicated by osteomyelitis. Surgical debridement may be necessary, especially for congenital lesions with secondary infection. Alternative antibiotics should be considered for patients with penicillin allergies or in cases of coinfection with organisms like S. aureus."}
{"note": "CONCLUSIONS:"}
{"note": "Cervicofacial actinomycosis, though rare in children, primarily affects the mandibular region and poses significant management challenges due to its tendency to spread to adjacent tissues, including bone. Early and accurate diagnosis, facilitated by anaerobic culture of exudates, is critical for effective management. Long-term, targeted penicillin-based therapy, coupled with surgical intervention, is essential for treating these chronic infections. MR imaging is recommended to assess for possible complications such as osteomyelitis, underscoring the importance of a comprehensive approach to treatment that includes both medical and surgical strategies.\n\n\n\u2014---------------------------------------------------------------------------"}
{"note": "TITLE: Local Reaction Causing Airway Compromise Following Vocal Fold Injection Augmentation with Carboxymethylcellulose"}
{"note": "ABSTRACT: Summary: Objectives. This report highlights a rare case of local allergic reaction following vocal fold injection augmentation with carboxymethylcellulose, emphasizing the critical management of subsequent airway swelling. Introduction. Addressing glottic insufficiency, particularly arising from true vocal fold immobility, is essential for reducing aspiration risk and enhancing voice quality. Carboxymethylcellulose-based injection laryngoplasty is widely recognized as a safe and effective intervention for this condition. Methods. A retrospective review of medical records and detailed case analysis were conducted. Results. We describe a distinct incident involving an adult female treated for vocal fold immobility with carboxymethylcellulose injection laryngoplasty who experienced a severe local reaction necessitating emergency airway management, including intubation and tracheostomy. Conclusion. Otolaryngologists should be cognizant of the potential for this severe complication and discuss it with patients during the consent process. Immediate measures, including ICU monitoring, intravenous steroids, and, if required, intubation, are crucial for patients exhibiting signs of airway edema following this procedure. Key Words: Case report, Carboxymethylcellulose, Injection laryngoplasty, Adverse reaction, Renu Gel, Prolaryn Gel."}
{"note": "INTRODUCTION:"}
{"note": "Addressing glottic insufficiency, particularly stemming from true vocal fold immobility, is critical for mitigating the risk of aspiration and enhancing voice function. Treatment strategies involve vocal fold medialization through either permanent implant surgical insertion or temporary filler material injections. The choice of augmentation material hinges on its durability, impacting the duration of the effect. For individuals with permanent vocal fold immobility, who are either not candidates for surgery or prefer non-surgical options, longer-lasting materials like calcium hydroxyapatite or autologous fat are often recommended. Conversely, for patients with potential for vocal fold mobility recovery, shorter-lasting substances such as carboxymethylcellulose (CMC) and hyaluronic acid are preferred, providing a temporary solution while possibly allowing the vocal fold's condition to naturally resolve."}
{"note": "Among the temporary fillers, CMC-based gels like Prolaryn Gel and Renu Gel are commonly utilized due to their viscoelastic properties and transient durability. However, beyond these characteristics, the safety profile of these materials is paramount, especially given the critical anatomical location of the vocal folds. Any adverse effect in this region can significantly impact airway status, swallowing function, and voice quality. A retrospective analysis of 228 awake vocal fold augmentation procedures using CMC reported no airway complications, underscoring CMC's safety. Further investigations, including a review of the FDA\u2019s MAUDE Adverse Event Database, indicated minimal complications potentially associated with CMC, with existing reports often lacking detailed clinical information."}
{"note": "This case report highlights a rare but significant complication following vocal fold injection augmentation with carboxymethylcellulose, where a patient encountered a local allergic reaction leading to acute airway obstruction, necessitating immediate intubation and subsequent tracheostomy placement. This incident underscores the importance of recognizing the possibility of allergic reactions to vocal fold injection materials, understanding the signs of airway edema, and discussing the potential risks with patients during the consent process to ensure prompt and effective management should complications arise."}
{"note": "CASE:"}
{"note": "This case report discusses a 70-year-old female who underwent vocal fold injection augmentation with carboxymethylcellulose (CMC), known commercially as Renu Gel, to address right true vocal fold immobility and resultant glottic insufficiency. This procedure was performed following a right far lateral craniotomy with partial resection of a hemangioblastoma affecting cranial nerves CN VII-X. The injection was administered percutaneously over the thyrohyoid membrane using a clean technique and a disposable 23-gauge needle, with the injection site prepared with an alcohol pad."}
{"note": "On the first day after the injection, the patient experienced acute stridor, severe respiratory distress, and demonstrated tripoding. Initial interventions included oxygen administration via nasal cannula, nebulized albuterol, nebulized racemic epinephrine, and high-dose intravenous dexamethasone. Flexible nasolaryngoscopy revealed watery edema originating from the injection site, affecting the arytenoid cartilage without signs of hematoma, red discoloration, or coagulopathy."}
{"note": "Given the severe edema and rapid symptom onset, the patient was intubated for airway management and received continuous high-dose corticosteroids. Antibiotics were not administered due to the absence of infection indicators. Despite brief extubation on day 12 post-injection, the patient required re-intubation and ultimately underwent a tracheostomy due to persistent laryngeal edema and complications with swallowing and oxygenation. The tracheostomy was successfully decannulated at a skilled nursing facility within a month post-discharge, concluding a 33-day hospital stay."}
{"note": "Follow-up nasolaryngoscopy showed the swelling had resolved, but right vocal fold immobility persisted, with a small glottic gap evident. The patient reported mild dysphagia but managed a regular diet with some micro aspiration detected in a modified barium swallow study. While the patient's voice quality improved slightly from the immediate post-operative period, mild dysphonia remained. Medialization thyroplasty is planned as definitive treatment for the vocal fold immobility."}
{"note": "This case underscores the importance of recognizing potential rare but severe complications following vocal fold injection augmentation, including acute airway compromise necessitating intubation and tracheostomy, and emphasizes the need for vigilant post-procedural monitoring and prompt management of emergent airway edema."}
{"note": "DISCUSSION:"}
{"note": "Carboxymethylcellulose (CMC), an anionic water-soluble polymer derived from native cellulose, is broadly utilized across pharmaceutical, food, and cosmetic industries due to its FDA-approved status and general consideration as inert. Despite this, there have been multiple instances of hypersensitivity reactions to CMC documented in various applications. The case presented here marks the first instance where a local reaction to CMC, following vocal fold injection augmentation, resulted in significant airway compromise. Initially, a laryngeal hematoma was considered; however, subsequent flexible laryngoscopy exams did not support this diagnosis, as there was no discoloration typical of a hematoma, nor did the patient have predisposing factors such as coagulopathies."}
{"note": "The reaction experienced by the patient is likely a type one hypersensitivity to CMC, necessitating previous exposure for sensitization. Although direct exposure histories to CMC-containing products were not confirmed for this patient, it is speculated that previous medical treatments could have served as the initial sensitization source. It's crucial to note that while CMC is present in various injectables, its poor absorption when ingested makes dietary exposure an unlikely priming route for immune responses."}
{"note": "Comparatively, CMC's allergenic potential seems lower than other augmentation materials like hyaluronic acid (HA), which has a notable history of reactions. These reactions are often attributed to residual bacterial proteins from the Streptococcal bacteria used in HA production. Conversely, CMC's synthetic process, not involving bacterial cultures, ostensibly presents a lower allergy risk. Yet, this case, occurring closely following a COVID-19 vaccination, hints at the potential for exacerbated or novel allergic responses post-vaccination, echoing recent observations with HA."}
{"note": "Management improvements could have included histamine receptor antagonists alongside steroids for a more targeted approach to the suspected type I hypersensitivity reaction. Additionally, a thorough examination of the CMC product for recalls or contaminants might have elucidated the reaction's cause. This incident underscores the importance for otolaryngologists to be vigilant about this rare but severe complication of vocal fold augmentation. Prior to the procedure, a detailed history of recent vaccinations and known allergies should be taken to inform material choice and anticipate potential reactions."}
{"note": "Ultimately, should there be any indication of post-injection swelling, immediate flexible nasopharyngoscopy and, if necessary, ICU monitoring and treatment strategies should be employed. For patients with known CMC sensitivity, alternative augmentation materials such as hyaluronic acid or calcium hydroxyapatite may be considered to mitigate the risk of allergic reactions."}
{"note": "CONCLUSIONS: This represents the first reported case describing a local reaction to carboxymethylcellulose following vocal fold injection augmentation, leading to life-threatening laryngeal edema, intubation, and eventual tracheostomy placement. While rare, based on the existing literature, it appears most likely that our patient had a type I hypersensitivity reaction to CMC. Otolaryngologists should be aware of this potential complication, counsel patients accordingly, and if a reaction does occur, treat aggressively with intravenous steroids, histamine antagonists, traditional airway supportive measures, and potential intubation.\n\u2014----------------------------------------------------------------------------------"}
{"note": "TITLE: The Effect of Subglottic Steroid injection on Blood Glucose in a Cohort of Patients With Subglottic Stenosis"}
{"note": "ABSTRACT: Objective: The objective of this work was to assess the effect of a single intralesional subglottic steroid injection on fasting blood glucose over 7 days in a cohort of patients with subglottic stenosis. Methods: A prospective cohort study of patients undergoing intralesional steroid injections at a tertiary academic center. Patients had baseline bloodwork performed, including fasting blood glucose (FBG), and hemoglobin A1C levels. Demographic data and risk factors were collected. Fasting capillary glucose (FCG) was measured using a capillary glucometer and performed by patients daily from days 0 to 7 after a single injection of Triamcinolone into the subglottic airway. Data were analyzed using descriptive and comparative statistics. Results: Eleven patients were enrolled, and 10 completed data collection over 7 days. All were female, with a mean age of 52.6 years (SD 17.5). Two patients were diabetic (non-insulin dependent). There was a statistically significant increase in FCG on day 1 post-injection (mean = 122.4 mg/dl compared to 100.7 mg/dl) that normalized for all patients within 24\u201372 h. The mean increase in FCG was 21.5% (SD 22.5%) of the initial value for the cohort. The diabetic group had statistically significant higher glucose values on day 1 compared to the non-diabetic group (146.5 mg/dl compared to 117.0 mg/dl). Conclusion: A single subglottic steroid injection appears to cause a transient increase in FCG 1 day post injection, which resolves after 24\u201372 h and can be more pronounced in diabetic patients."}
{"note": "Key Words: blood glucose, steroid injection, subglottic stenosis, systemic effects."}
{"note": "INTRODUCTION Subglottic and tracheal stenosis remain challenging problems to treat for the otolaryngologist. Scarring of the upper airway can be iatrogenic (from prolonged intubation or traumatic intubation) or idiopathic (idiopathic subglottic stenosis). The standard of care for patients with subglottic stenosis that can be managed endoscopically can involve a combination of lysis or resection of the scar using a cold steel or CO2 laser, balloon dilation of the stenosis, and injection of steroids while the patient is under general anesthesia. Previous studies have reported wide ranges of recurrence rates of between 20%\u2013 80% within 3 to 4 years of surgery. The rate of recurrences and number of surgeries required can differ based on surgical technique and patient factors. In the last few years, awake serial intralesional steroid injections (SILSI) have been used by a growing number of laryngologists to reduce the number of operating room dilations by serially injecting steroids in the subglottis and are gaining popularity in the laryngology field. Most authors describe these awake injections as an adjunct to operating room dilation, while others describe cohorts of patients that can be managed with SILSI as the mainstay treatment. The principle consists of injecting the subglottic region with local steroids before the scar has the time to re-form completely and cause significant airway impairment. Although there is no standard protocol to guide the use of these injections, most studies report performing 2\u201310 injections of local steroid in the subglottic region at intervals ranging from 2 to 6 weeks. While injections of local steroids in the upper airway were thought to have minimal systemic effects, recent reports have raised concern about systemic absorption. A recent study by Woliansky et al. found a significant increase in blood cortisol levels 1 day after an in-office injection of steroids in the subglottis, which normalized after 7 days. Anecdotal cases of Cushing syndrome secondary to these serial injections have also been reported in the literature. In parallel, recent evidence from the orthopedic and musculoskeletal literature warns of the rise in blood glucose following intra-articular injection of steroids for diabetic patients. These findings raise concern about the systemic effects of these serial injections on blood glucose in our patient population, including those with diabetes. Understanding how these injections can impact blood glucose in diabetic and non-diabetic patients is crucial to guiding counseling and monitoring of patients receiving SILSI. The aim of this prospective study is to assess the effect of a single in-office subglottic steroid injection on blood glucose levels in a cohort of patients with subglottic stenosis."}
{"note": "METHODS This prospective observational study was approved by the Institutional Review Board of the University of South California (USC) Voice Center."}
{"note": "USC Protocol for Subglottic Stenosis"}
{"note": "At our tertiary academic center, all patients who present with subglottic stenosis and need an operating room procedure undergo an endoscopic CO2 laser procedure under general anesthesia with radial lysis of scar, balloon dilation, and triamcinolone (40 mg/cc) injection. This is followed by a series of SILSI consisting of three injections of triamcinolone 40 mg/cc at 1, 2, and 3 months post-operatively. The decision of further injections beyond the series of three are made by the clinicians based on patients\u2019 symptoms and severity of stenosis on laryngoscopy. The awake injections are performed in the clinic with no sedation. Local anesthesia is obtained using a transtracheal injection of 2 cc of lidocaine 4% or a nebulizer of 4 cc of lidocaine 4%. The injection is performed under fiberoptic visualization and 2 cc of triamcinolone 40 mg/cc (a total of 80 mg) is injected in the subglottic area through a transtracheal or trans-cricothyroid approach using a 25-gauge needle. For all patients in this study, the full 80 mg of triamcinolone was injected, and the methodology and analysis did not account for any small amount of triamcinolone lost in the airway."}
{"note": "Participants"}
{"note": "Participants were recruited from the outpatient clinic of the USC Voice Center on a voluntary basis from January 1, 2021 to September 30, 2021. All patients undergoing awake SILSI in the outpatient setting as per the USC protocol were offered to participate in the study. Inclusion criteria included patients having subglottic or tracheal stenosis and receiving one or more intralesional injections of steroids. Diabetic and non-diabetic patients were included in the study. Patients were excluded if they had received another source of exogenous steroids within 2 weeks of the injection or were planning to receive another source of exogenous steroids 10 days after the injection. Due to the slightly invasive nature of the capillary blood glucose daily self-test, patients who were deemed to be non-compliant were excluded from this study. A patient could decide to leave the study at any time before or during the data collection process."}
{"note": "Measurement of Blood Glucose"}
{"note": "The complete study protocol is summarized in Table I. Enrolled patients were asked to participate in only one of their injection visits. Patients were consented for this study prior to their injection visit and given a detailed protocol explaining the methodology. On the day of the injection, baseline bloodwork was collected, including glycated hemoglobin (HbA1c) and fasting blood glucose (FBG). Patients were asked to fast starting at midnight on the day of their injection and booked as the first morning appointment to reduce any inconvenience related to fasting. Demographic data were collected, including age, sex, past medical history with specific questions on history of diabetes, family history of diabetes, hypertension, cholesterol, and obesity. Medications were reviewed with a specific focus on hypoglycemic agents and insulin."}
{"note": "On the day of their injection, participants were given materials for at-home measurement of capillary blood glucose, including a glucometer device, test strips, and needles. They were provided with a data collection sheet (Supporting Information, Appendix S1) and instructed to take their fasting capillary blood glucose (FCG) every morning for 7 days after the day of the injection. Specific verbal and written instructions were provided regarding the use of the glucometer, fasting instructions, and the data collection methodology. The data collection for day 0 was performed in the office before the injection and supervised by the research assistant to confirm appropriate methodology and patient independence. Patients used the glucometer to take and record their fasting blood glucose at home at the same time in the morning for days 1\u20137. Patients were not asked to follow any specific diet during the data collection week but were instructed to make note of any significant deviation from their usual diet."}
{"note": "Statistical Analysis"}
{"note": "Descriptive statistics were used to present the mean and standard deviation. A Wilcoxon signed rank test was used to assess the significance of the change in FCG as measured by a capillary glucometer from baseline (day 0) to day 1. Mann\u2013Whitney U test was used to compare HbA1c levels across groups (diabetic vs. nondiabetic), and to assess significance of change in FCG levels from baseline (day 0) to day 1 across groups (diabetic vs. non-diabetic)."}
{"note": "RESULTS"}
{"note": "A total of 11 patients were enrolled in this study, and 10 completed data collection for the full 7 days post-injection, while one could only complete data collection up to post-injection day 2 due to equipment malfunction. This patient\u2019s data was included in data analysis until post-injection day 2. Patient\u2019s demographic data is detailed in Table II. All were female with a mean age of 52.6 years (SD 147.5). Two patients were diabetic (non-insulin dependent). From the non-diabetic cohort, 4/9 patients had a family history of diabetes and 1/9 had a BMI of >25. 8/11 (72.7%) of patients had idiopathic subglottic stenosis as the etiology, while the remaining 3/11 (27.3%) had auto-immune disease (GPA)."}
{"note": "Pre-Injection Laboratory Results"}
{"note": "Pre-injection laboratory results are summarized in Table III. Patients with diagnosed diabetes (n = 2) had statistically significantly higher HbA1c and serum fasting blood glucose (FBG) levels prior to injection compared to the non-diabetic patients (n = 9) (mean HbA1c = 7.7% compared to 5.4%, mean fasting serum glucose of 136.0 mg/dl compared to 95.6 mg/dl, U = 0.00, p = 0.033)."}
{"note": "Effect of Steroid Injection on Capillary Blood Glucose Over 7 Days"}
{"note": "Test results of FCG across time points are reported for each patient (Fig. 1). There was a statistically significant increase in FCG on day 1 post-injection (mean FCG = 122.4 mg/dl compared to 100.7 mg/dl, Z = 2.313, p = 0.021) that normalized for all patients within 24 to 72 h. Mean FCG on day 1 was 122.4 mg/dl, SD = 25.4, while the maximum value was 167 mg/dl in a non-insulin-dependent (NID) diabetes patient. 9/11 patients had an increase in their FCG from days 0 to 1, with a mean increase of 30.7% (SD 15.8%) of the initial value for the cohort."}
{"note": "Comparing Diabetic and Non-Diabetic Patients"}
{"note": "Two patients from this cohort were NID diabetics, while nine patients were non-diabetics. Using 99 mg/dl as the upper value for the normal range of FCG for non-diabetic patients, 6/9 (66.7%) patients had abnormal values (>99 mg/dl) on day 1 compared to 2/9 (22.2%) on day 0. Although both groups had an increase in FCG value on day 1, the two diabetic patients had statistically significant higher glucose values on day 1 compared to the non-diabetic patients (146.5 mg/dl compared to 117.0 mg/dl), U = 0.0, p = 0.033, although the percent increase in glucose value was lower for the diabetic patients (11.4% compared to 24.6%)."}
{"note": "DISCUSSION"}
{"note": "SILSI is becoming a common treatment for the laryngologist. First described in 2018 by Franco et al., they have been shown to be a safe alternative to operating room steroid injection and lengthen intervals between operating room dilations. Despite their growing use in the last 5 years, little is known about the effect of systemic absorption of the steroids and their impact on blood glucose and cortisol levels in diabetic and non-diabetic patients. This is the first study to specifically examine blood glucose levels after these injections, and the results are in keeping with the recent literature about local steroid injections."}
{"note": "A recent study by Woliansky et al. studied changes in cortisol and white blood cells in a cohort of 6 patients with idiopathic subglottic stenosis after a single injection of 40 to 200 mg of triamcinolone. They found a significant fall in serum cortisol from days 0 to 1 (284.0 61.4 nmol/L to 15.5 4.3 nmol/L, p = 0.03), which recovered 7 days post-injection. They found similar findings with salivary cortisol and white cell counts, suggesting an acute but transient hypothalamic\u2013pituitary\u2013adrenal (HPA) axis suppression. Our study suggests similar findings with a marked increase in FCG on post-procedure day 1, rapidly normalizing within 24 to 72 h."}
{"note": "Cumulative systemic side effects of these injections have recently been reported by a few authors. Neevel et al. reported systemic side effects of these injections as a secondary outcome of their prospective cohort study in patients receiving SILSI. From the 19 patients in the studied cohort, 6 (32%) developed systemic side effects from the SILSI, including Cushing Syndrome, increased intraocular pressure (IOP), central serous chorioretinopathy, new insulin requirement in the setting of diabetes, and acne, all within the course of the injections (1 to 4), with a mean of onset at 3.2 months (95% CI, 2.4\u20134.0) from the first injection. Another study by Franco et al. used a retrospective cohort of 49 patients receiving SILSI to assess systemic side effects using a questionnaire on 12 side effects of steroids. Fifty-five percent of the cohort reported systemic side effects, including menstrual irregularities, feeling joyful, and sleeping difficulties. Lastly, a case report by Silverstein et al. described the onset of Cushing Syndrome in a 55-year-old non-diabetic female undergoing SILSI after a total of 8 injections of triamcinolone over a 12 month interval, which resolved 6 months after the last injection. This case report includes the intralesional injection of triamcinolone in the operating room during a dilation, which could explain the excess steroid."}
{"note": "In our patient cohort, although the additive effect of the multiple injections was not studied, the two diabetic patients from this cohort reported a new diabetes diagnosis after they had started their injection series. This diagnosis was made by their family doctor or endocrinologist prior to the start of this study and is based on laboratory criteria. Both patients had a family history of diabetes. Although direct correlation cannot be assessed, this anecdotal evidence could be in keeping with the findings described in the literature."}
{"note": "Although the evidence of systemic absorption of SILSI is not commonly studied, the systemic effects of local steroid injections are well documented in the musculoskeletal literature. A systematic review by Chouhdry et al. looked at the effect of intra-articular steroid injections on blood glucose levels in diabetic patients. Seven studies were included in the analysis, totalling 72 diabetic patients. All studies found an increase in blood glucose levels after intra-articular injection, with peak values as high as 500 mg/dl and trends of hyperglycemia occurring within 24 to 72 h post-injection. The authors concluded that diabetic patients should be counseled on the risk of hyperglycemia after these injections. Uboldi et al. did a prospective study on 16 subjects (12 non-diabetic and 4 diabetic) undergoing intra-articular steroid injection for rheumatoid arthritis. Blood glucose was assessed over 24 h after the injection. Blood glucose increased for both groups, with a maximum increase of 2 h after injection for the non-diabetic group compared to a delayed increase of 12 h for diabetic patients. The elevation was also lower for the non-diabetic group (43% vs. baseline, p = 0.0025 compared to 70%, 12 h vs. baseline, p = 0.41)."}
{"note": "Study Limitations and Future Directions"}
{"note": "This study is limited by the size of its cohort and the very small number of diabetic patients enrolled. As the means of data collection were invasive (blood work and daily FCG for 7 days), recruitment was limited by voluntary participation."}
{"note": "Another limitation is the lack of control for diet in our patient cohort. Although diet was not controlled, patients were asked to report if they had any significant deviations from their normal diets, and no patients reported dietary changes."}
{"note": "We chose FCG as the primary outcome measure as it was simple to control in all patients without the need for calorie counting or a specific diet. Although our study demonstrates a mild transient elevation in fasting blood glucose, it is possible that this elevation could be accentuated by eating and become more pronounced on postprandial measures."}
{"note": "Two patients in the non-diabetic cohort also had elevated glucose on day 0 without having a diagnosis of diabetes and with normal HbA1c values. This could suggest these patients had pre-diabetes. Due to the small cohort, no comparisons between pre-diabetic and diabetic patients were made, but this could certainly represent a future direction for further work. As our study demonstrates that glucose elevation is mild and transient in non-diabetic patients, further work with insulin-dependent diabetic cohorts are needed to characterize the glucose increase in this patient group and could facilitate data collection due to the familiarity of the patients with the capillary glucose technique."}
{"note": "CONCLUSION"}
{"note": "A single intralesional injection of subglottic steroid seems to cause a transient increase in FCG in a cohort of patients with subglottic stenosis on day 1 post-injection that normalizes within 24\u201372 hours and can potentially be more pronounced in diabetic patients. As SILSI is becoming a common procedure for patients with subglottic stenosis (SGS), understanding the impact of these injections on blood glucose is key to counseling diabetic and non-diabetic patients and understanding potential side effects. This is the first prospective clinical study looking at the effect of these injections on blood glucose. Although our study described the effects after a single injection, further research is needed to understand the systemic cumulative effects of SILSI and complications for diabetic and non-diabetic patients.\n\u2014------------------------------------------------------------------"}
{"note": "Thesis Writing"}
{"note": "ABSTRACT:"}
{"note": "Background: Acoustic voice analysis typically requires a resource-intensive setup, including a soundproof booth. This project assesses the impact of smartphone microphones and recording environments on voice sample collection for acoustic voice analysis. A proprietary analysis algorithm is introduced and validated."}
{"note": "Methods: Microphone and recording environment were evaluated using previously collected voice samples presented in four conditions to test two microphones and two recording environments. Prospective samples were then used to test the proprietary algorithm, with samples analyzed using this algorithm and Praat."}
{"note": "Results: Microphone and recording environment had minimal, clinically insignificant impacts on most measurements. The proprietary algorithm reliably analyzed sustained vowels, showing strong correlation with Praat results. However, continuous speech analysis was less reliable."}
{"note": "Conclusion: Smartphone microphones are suitable for voice sample collection, and quiet, non-soundproof settings can be used. The proprietary algorithm offers a reliable method for analyzing sustained vowel samples, although improvements are needed for continuous speech analysis."}
{"note": "Lay Summary: Acoustic voice analysis is an important part of a comprehensive voice examination, aiding in objectively quantifying normal and abnormal voices. However, existing methods for voice sample collection and analysis are often resource-intensive, limiting access. This study investigated the use of smartphones for voice sample acquisition and on-device acoustic voice analysis. Phase one evaluated microphones and recording environments, finding minimal differences in most acoustic measures, suggesting that robust acoustic voice analysis is feasible on smartphones in non-soundproof conditions. Phase two compared a proprietary application with Praat for acoustic voice analysis, showing promise for future use of the proprietary algorithm. These findings suggest that the smartphone application could be reliably used by patients, healthcare providers, and researchers for acoustic voice analysis. Keywords: Voice; Acoustic Voice Analysis; Mobile Health; mHealth"}
{"note": "Introduction"}
{"note": "Voice disorders are prevalent and significant clinical concerns, affecting over 10% of the population, with a higher frequency among professional voice users. These users include individuals in occupations where the voice is of primary importance, such as teachers and salespeople, constituting 5-10% of the general population. Voice disorders arise from various benign and malignant conditions affecting the vocal folds, ranging from structural changes to neurological etiologies. Benign conditions, such as vocal fold nodules and polyps, often require treatment with behavioral voice therapy, where acoustic analysis plays a crucial role in assessing treatment efficacy. Conversely, laryngeal cancers, representing the most common malignant lesions of the head and neck, necessitate preservation of vocal function during treatment. Early detection of laryngeal tumors often relies on identifying voice changes."}
{"note": "Acoustic voice analysis, along with auditory-perceptual measures, is integral to the clinical assessment of voice disorders for diagnostic and treatment monitoring purposes. Acoustic measures provide objective quantification of normal and pathologic voices, including vibratory abnormalities. However, the current methods of voice sample collection and analysis are resource-intensive, requiring a soundproof booth, trained personnel, and expensive instrumentation. This limitation hampers regular use and comprehensive assessment of treatment outcomes."}
{"note": "The advent of mobile health (mHealth) technologies presents an opportunity to address these barriers by leveraging smartphones for voice sample acquisition and analysis. Mobile computing advancements have made smartphones equipped with adequate hardware accessible to clinicians and researchers, potentially overcoming the constraints of traditional voice analysis setups."}
{"note": "Voice evaluation encompasses various assessments, including acoustic analysis, aerodynamic measurements, auditory-perceptual analysis, and self-reported outcome measures. Acoustic analysis provides valuable objective data that can complement other assessment tools, contributing to a comprehensive evaluation of voice function. Reliable objective measures correlated with perceptual scores facilitate quantification of dysphonic voices and clinical voice disorders."}
{"note": "Clinical Voice Disorders"}
{"note": "Benign voice disorders encompass a range of etiologies, including structural pathologies, autoimmune disorders, and neurological conditions, each affecting voice production through different mechanisms. Structural changes, such as nodules and polyps, disrupt the quasi-periodic vibration required for normal voice production, leading to hoarseness, decreased volume, and breathiness. Hyperfunctional voice disorders result from the misuse of laryngeal musculature, causing repetitive trauma to the vocal folds and potentially irreversible changes requiring surgical intervention. Hypofunctional voice disorders, characterized by weak or insufficient voice production, may arise postoperatively or due to respiratory conditions, necessitating appropriate diagnosis for voice rehabilitation guidance."}
{"note": "Structure-based voice disorders involve the development of benign laryngeal masses or reactive lesions, impacting vocal fold vibration and resulting in aperiodic vocal signals with decreased quality. Neurological conditions affecting the larynx, such as peripheral nerve injuries and spasmodic dysphonia, lead to voice instability and coordination deficits. These conditions highlight the complex interplay between structural, functional, and neurological factors in voice production, emphasizing the importance of multidimensional assessment approaches, including acoustic analysis, for accurate diagnosis and treatment planning."}
{"note": "Current Approaches to Assessment and Diagnosis of Voice Disorders"}
{"note": "Patients presenting with voice disorders typically undergo assessment by an otolaryngologist and/or speech-language pathologist, including a comprehensive history and physical examination of the head and neck. Indirect assessments of the larynx, such as flexible nasopharyngoscopy and stroboscopy, allow visualization of the vocal folds and assessment of the mucosal waveform. Patient symptom scores, like the Voice Handicap Index and Reflux Symptom Index, provide insights into the severity of voice-related symptoms and their impact."}
{"note": "Auditory-perceptual evaluation of voice involves a multidimensional assessment of various perceptual elements using scaling methods. These methods, including prothetic and metathetic scaling, allow subjective assessment by either naive or trained listeners. Auditory-perceptual assessment is considered robust, although inter-judge variability may occur due to individual biases. However, it remains the gold standard for evaluating voices due to its simplicity, robustness, and cost-effectiveness."}
{"note": "Acoustic Voice Analysis"}
{"note": "Acoustic voice analysis quantifies normal and abnormal voices in a non-invasive manner, relying on established normative values for objective comparison. This method extracts periodic time intervals from the vocal signal and calculates microacoustic measures such as jitter, shimmer, and harmonic-to-noise ratio. However, acoustic measures may become unreliable with increasing aperiodicity in severely dysphonic voices. Despite its limitations, a battery of acoustic measures combining time- and spectral-based analyses has been proposed to overcome these challenges."}
{"note": "Auditory-perceptual Voice Analysis"}
{"note": "Auditory-perceptual evaluation is simple, robust, and inexpensive, making it the most common method of voice assessment. Judgments are based on perceptual elements of voice quality, which are intuitive and widely shared among listeners of varying expertise levels. While inter-judge variability exists, auditory-perceptual assessments remain reliable and provide a common language to describe voices. They offer a non-intrusive, repeatable measure to document clinically evident voice changes, making them indispensable in voice analysis."}
{"note": "Technological Advances and mHealth"}
{"note": "Smartphones have become a focus for health interventions due to their widespread availability and technological capabilities. They are utilized in various health-related applications, including text message interventions, habit-forming applications, and even assessing artery patency using the device camera. Smartphone microphones have been found useful in recording voice samples for microacoustic analysis, offering a feasible alternative to traditional methods."}
{"note": "The advantages of mobile analysis lie in its accessibility. With smartphones, standardized recording protocols can be implemented easily, reducing barriers to acoustic analysis such as specific recording setups and sound-controlled environments. Instructions for recording tasks can limit variability in sample collection by end-users. Although smartphone microphones may not match professional equipment, they still provide reliable recordings for analysis."}
{"note": "The wide availability of smartphones enables more frequent testing between formal follow-up visits, facilitating longitudinal assessment of voice changes. Within-subject comparisons become feasible, allowing for the establishment of patient-specific normative values and evaluation of clinical significance. Despite challenges like ambient noise and variability in sample collection, the benefits of mobile voice analysis outweigh the limitations."}
{"note": "Objectives"}
{"note": "The objectives of this project include:"}
{"note": "1. Confirming the iPhone microphone's ability to capture voice samples for microacoustic measurements in optimized settings."}
{"note": "2. Assessing the iPhone microphone's capacity to capture samples in non-optimized settings for acoustic analysis."}
{"note": "3. Determining the computational capabilities of the iPhone for immediate on-device voice analysis."}
{"note": "Review of the Literature"}
{"note": "In the literature, several well-researched acoustic measures have been identified, with five common ones selected for this project: fundamental frequency (F0), jitter, shimmer, harmonic-to-noise ratio, and cepstral peak prominence. Each measure plays a crucial role in assessing various aspects of voice quality and pathology."}
{"note": "Fundamental Frequency (F0)"}
{"note": "Vocal pitch, as measured by fundamental frequency (F0), is a fundamental aspect of voice evaluation. Traditionally, pitch assessment relied on subjective perceptual judgment, which lacked standardization and reliability. Objective measures like F0 were developed to introduce unbiased normative values, considering factors such as age and gender."}
{"note": "F0 represents the vibratory rate of a waveform repeated per time frame, measured in Hertz (Hz). As F0 increases, pitch also increases, although this relationship is not linear. Age and gender norms exist for F0, and normalization of values is essential for determining a speaker's functional range."}
{"note": "Various algorithms can extract F0, classified into event detection (peak picking, zero crossing) and averaging methods (waveform matching). Event detection methods, such as peak picking and zero crossing, rely on waveform properties to identify peaks or zero crossings per cycle. Averaging methods, like waveform matching, compare adjacent waveforms to calculate F0, providing robust results even in the presence of signal noise and amplitude variations."}
{"note": "Accurate determination of F0 is crucial for calculating measures of perturbation like jitter and shimmer. Waveform matching methods are particularly effective in dysphonic voice samples, ensuring reliable results for downstream calculations."}
{"note": "In summary, F0 serves as a vital acoustic measure for assessing vocal pitch, with established normative ranges and reliable calculation methods essential for accurate voice evaluation, especially in dysphonic conditions."}