A genomic mutational constraint map using variation in 76,156 human genomes.

The depletion of disruptive variation caused by purifying natural selection (constraint) has been widely used to investigate protein-coding genes underlying human disorders1-4, but attempts to assess constraint for non-protein-coding regions have proved more difficult. Here we aggregate, process and release a dataset of 76,156 human genomes from the Genome Aggregation Database (gnomAD)-the largest public open-access human genome allele frequency reference dataset-and use it to build a genomic constraint map for the whole genome (genomic non-coding constraint of haploinsufficient variation (Gnocchi)). We present a refined mutational model that incorporates local sequence context and regional genomic features to detect depletions of variation. As expected, the average constraint for protein-coding sequences is stronger than that for non-coding regions. Within the non-coding genome, constrained regions are enriched for known regulatory elements and variants that are implicated in complex human diseases and traits, facilitating the triangulation of biological annotation, disease association and natural selection to non-coding DNA analysis. More constrained regulatory elements tend to regulate more constrained protein-coding genes, which in turn suggests that non-coding constraint can aid the identification of constrained genes that are as yet unrecognized by current gene constraint metrics. We demonstrate that this genome-wide constraint map improves the identification and interpretation of functional human genetic variation.

Indications and Short-Term Outcomes for In-Office Therapeutic Superior Laryngeal Nerve Block.

OBJECTIVE: Superior laryngeal nerve (SLN) block consists of injection of steroid and anesthetic at the internal branch of the SLN entry site. Prior case series have demonstrated beneficial effects on neurogenic cough. SLN blocks have also recently shown benefit for paralaryngeal pain. We describe short-term outcomes for multiple symptoms of irritable larynx syndrome (ILS) including neurogenic cough, dysphonia related to laryngeal hypersensitivity, inducible laryngeal obstruction (ILO), paralaryngeal pain, and isolated globus. METHODS: Retrospective review from 2 institutions of patients undergoing a single SLN block for the indications listed. Variables include age, sex, indication(s), known vagus neuropathy, and patient-reported outcomes at short-term follow-up. RESULTS: A total of 209 patients were included (59 males, 150 females; age: 58 ± 13 years). Twenty-six patients (12%) had a history of a vagus nerve injury. Indications included neurogenic cough (n = 149), dysphonia related to laryngeal hypersensitivity (n = 66), paralaryngeal pain (n = 50), ILO (n = 23), and isolated globus (n = 3). Some patients had multiple indications. Significant improvements in patient-reported measures occurred after a single SLN block within 2 to 4 weeks for neurogenic cough (cough severity index; 25.2 ± 11.2 to 19.0 ± 12.8; P < .001), dysphonia (voice handicap index-10; 22.1 ± 12.2-18.0 ± 13.3; P = .005), and ILO (dyspnea index; 21.0 ± 14.9-14.7 ± 15.7; P = .017). Subjective pain improved in 23 of 39 patients with paralaryngeal pain. There was no observed improvement for isolated globus. Presence of known vagal neuropathy or therapy around the time of SLN block did not affect outcome. CONCLUSION: SLN block can be an effective component of treatment for a variety of ILS symptoms. Patients may experience some improvement after 1 injection. LAY SUMMARY: Symptoms of irritable larynx syndrome, such as neurogenic cough, paralaryngeal pain, inducible laryngeal obstruction, and dysphonia related to laryngeal hypersensitivity can be challenging to manage. In-office Superior Laryngeal Nerve blocks can serve as a quick, well tolerated, adjunctive treatment with positive short-term outcomes. LEVEL OF EVIDENCE: 4.

Tracheal invasion and perforation from advanced primary thyroid lymphoma: a case report and literature review.

OBJECTIVE: We report a case of an elderly female with primary diffuse large B-cell thyroid lymphoma causing an extensive tracheal defect that was managed expectantly with good results. METHOD: Case report RESULTS: This is the only known reported case of a patient with tracheal invasion and perforation caused by primary thyroid lymphoma who has subsequently survived. CONCLUSION: Due to the rarity of invasive primary thyroid lymphoma there is currently no standard surgical management of the airway. We propose that expectant management with temporary airway protection is an alternative to invasive procedures such as tracheotomy or tracheal stent placement, even in the scenario of serious airway defects.

Predictors of Mortality in Patients With COVID-19 Undergoing Tracheotomy.

OBJECTIVE: To identify factors predictive of 30-day mortality following tracheotomy in patients with COVID-19. METHODS: A retrospective chart review of patients with COVID-19 who underwent tracheotomy at a tertiary medical center between March 2020 and October 2021 was conducted. Univariate and multivariable analyses of factors correlated with 30-day post-tracheotomy mortality were performed. The outcomes of tracheotomies performed in the operating room and at bedside were compared with t-tests and multivariable analysis. RESULTS: One hundred-twenty patients met inclusion criteria, with 48 female patients (40%). Mean age was 59.8 [12.6] years, and the 30-day mortality rate was 18.3%. On univariate analysis, age (odds ratio (OR) = 1.06; P = .015), FiO2 at the time of tracheotomy (OR = 1.06; P < .001), and bedside tracheotomy (OR = 3.21; P = .019) were associated with increased risk of 30-day mortality. After including control variables, increased FiO2 continued to predict increased odds of 30-day mortality (OR = 1.08; P = .02); specifically, patients with FiO2 > 65% were significantly more likely to pass within 30 days than those with FiO2 ≤ 40% (OR = 28.24; P < .001). There was a significant difference in the 30-day mortality rate of bedside tracheotomies (31%) and OR tracheotomies (12%; P = .02), but this association was eliminated on multivariable analysis (OR = 0.95; P = .96). CONCLUSION: Intubated patients with COVID-19 undergoing tracheotomy with FiO2 > 65% have 25 times greater odds of 30-day mortality than those with FiO2 ≤ 40%. There were no differences in outcomes between bedside and OR tracheotomies.

Characteristics of Idiopathic Subglottic Stenosis in the Elderly.

OBJECTIVE: To compare characteristics of patients ≥65 years presenting with idiopathic subglottic stenosis (iSGS) to patients diagnosed at <65 years. We hypothesize that the groups have similar comorbidities and disease courses. DATA SOURCES: Medical records of patients treated for iSGS at a tertiary care institution from January 2005-September 2022. REVIEW METHODS: Patient demographics, time from symptom onset to diagnosis, medical history and comorbidities, and treatment modalities/intervals were recorded and analyzed. Characteristics of patients ≥65 and <65 years at presentation were compared using Chi-square analysis for non-numeric values and the Mann-Whitney U-test for numeric values. RESULTS: One hundred seven patients with iSGS were identified and 16 (15%) were aged ≥65 years (mean age 72.6, 15 female) at presentation. These patients were compared to 91 patients aged <65 years (mean age = 47.6, 90 female). Patients ≥65 years had higher rates of type 2 diabetes mellitus (T2DM) (p = 0.004) and tobacco use (p = 0.004). There were no significant differences in body mass index, gastroesophageal reflux disease, hormone replacement therapy, time from symptom onset to presentation, or length of operative treatment intervals. CONCLUSION: Patients ≥65 years with iSGS have higher rates of tobacco use, suggesting that alterations in wound healing may play a role in the development of iSGS in this age group. Although rates of T2DM were higher in the elderly group, clinical significance may be limited given the overall higher rate of diabetes mellitus in the elderly population. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:3075-3079, 2023.

In-Office Superior Laryngeal Nerve Block for Paralaryngeal Pain and Odynophonia.

OBJECTIVES: Pain localized to the thyrohyoid region may be due to neuralgia of the superior laryngeal nerve (SLN), inflammation of the thyrohyoid complex, or a voice disorder. We present outcomes of treatment of paralaryngeal pain and odynophonia with SLN block. STUDY DESIGN: Retrospective Review. METHODS: A retrospective chart review of patients undergoing in-office SLN block for paralaryngeal pain between 2015 and 2018 at two tertiary care centers was conducted. Patient demographics, indications, and response to treatment were analyzed. RESULTS: Thirty-eight patients underwent blockade of the internal branch of the SLN for paralaryngeal pain, with 10 excluded for incomplete medical records. Eighty-two percent (23/28) reported an improvement in their symptoms. Patients underwent an average of 2.5 blocks (SD = 1.88, range 1-8), with 10 patients (36%) undergoing a single procedure. Of the 18 patients who underwent multiple blocks, nine had eventual cessation of symptoms (50%) compared to resolution in 6/10 undergoing a single injection. Eleven patients (39%) noted odynophonia related to vocal effort, and all of these patients had improvement in or resolution of their symptoms and were more likely to improve compared to those without odynophonia (P = .006). Of the four patients who had a vocal process granuloma (VPG) at presentation, three had complete resolution of the lesion at follow-up. CONCLUSION: In-office SLN block is effective in the treatment of paralaryngeal pain. It may be used as an adjunct in the treatment of vocal process granulomas, as well as voice disorders where odynophonia is a prominent symptom. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:401-405, 2022.

Characteristics and outcomes of young patients with laryngeal cancer: National hospital-based retrospective cohort analysis.

BACKGROUND: The relative incidence of laryngeal cancer is rising in young patients, yet their characteristics, risk factors, and outcomes relative to older patients are poorly understood. METHODS: Retrospective cohort analysis of the National Cancer Database from 2006 to 2015. RESULTS: Among 25 029 total patients, 923 (3.7%) were young (<45 years old) and 3266 underwent tumor HPV testing. Compared to older patients, a greater proportion of young patients were female (30.3%, 23.3%; p < 0.001) and seen with high-risk HPV-positive tumors (29.9%, 12.4%; p < 0.001). In subset analyses of young patients, females with higher income (≥$38 000) exhibited a decreased risk of overall mortality compared to all other sex-income subcategories (adjusted hazard ratio [aHR]: 0.43, 95% confidence interval [CI]: 0.25-0.72). In subset analyses of patients of all ages with known tumor HPV status, patients with high-risk HPV-positive tumors exhibited a reduced risk of all-cause mortality (aHR: 0.74, 95%CI: 0.60-0.92, p = 0.007). CONCLUSION: The interdependent associations between age, sex, tumor HPV status, and income on laryngeal cancer outcomes warrant further investigation.

Clinical and Biologic Characteristics and Outcomes in Young and Middle-Aged Patients With Laryngeal Cancer: A Retrospective Cohort Analysis.

OBJECTIVE: To describe the clinical and biologic characteristics and outcomes of young and middle-aged (YMA; <65 years) patients according to the presence or absence of traditional risk factors for laryngeal cancer. STUDY DESIGN: Retrospective cohort analysis. SETTING: Single-institution academic medical center. METHODS: Patients without a history of clinically significant tobacco use or heavy alcohol use were defined as "nontraditional": ≤5 pack-years, ≤5 years smoked, ≤14 alcoholic drinks per week, and ≥15-year interval from last tobacco abuse use to diagnosis. Remaining patients were categorized as "traditional." Select tumor samples were evaluated for bacterial and viral DNA by multiplex polymerase chain reaction. RESULTS: Seventy-eight YMA patients with primary laryngeal squamous cell carcinoma were identified, 23% (n = 18) of whom were nontraditional. Nontraditional patients were younger than traditional patients (median age, 51 vs 59 years; P < .001). Twenty-eight tumors were prospectively tested for human papillomavirus (HPV), and nontraditional patients were more likely to exhibit high-risk HPV (57% vs 5%, P < .01). Among 17 select tumors (nontraditional, n = 8; traditional, n = 9), 35% exhibited HPV16 (nontraditional, 63%; traditional, 11%; P = .05). Other viruses were identified but did not differ according to risk status: herpesviruses (40%) and Merkel cell polyomavirus (7%). Chlamydia, ß-HPV, and γ-HPV DNA was not detected in any samples. Median length of follow-up was 42 months. On adjusted analyses, nontraditional patients exhibited nonsignificantly improved overall survival (hazard ratio, 0.24 [95% CI, 0.03-1.82]; P = .17) and disease-free survival (hazard ratio, 0.34 [95% CI, 0.10-1.23]; P = .08) as compared with traditional patients. CONCLUSION: Almost one-quarter of YMA patients lacked characteristic risk factors for laryngeal squamous cell carcinoma, and their tumors exhibited a higher prevalence of high-risk HPV. The significance of HPV16 and other tumor viruses with outcomes in nontraditional patients should be evaluated further.

Impact of Patient Factors and Management Strategies on Outcomes After Transverse Posterior Cordotomy.

OBJECTIVES/HYPOTHESIS: Carbon dioxide laser transverse posterior cordotomy (TPC) aims to improve airway aperture in patients with glottic obstruction. Postoperative complications may worsen airway compromise and necessitate additional interventions. We sought to identify factors impacting outcomes after TPC. STUDY DESIGN: Retrospective chart review. METHODS: Medical records of patients who underwent TPC for glottic airway obstruction at a tertiary-care medical center between 2008 and 2018 were reviewed. Demographics, comorbidities, and intra- and postoperative management strategies were analyzed. RESULTS: Twenty patients who underwent TPC for glottic airway obstruction met inclusion criteria. The mean age was 57 years, and 13 patients were female. Mean follow-up time was 442 days. Seven patients had posterior glottic stenosis, and 13 had bilateral vocal fold paralysis. Twelve patients developed postoperative complications including granuloma formation (four patients), hospital readmission for dyspnea due to glottic edema (five patients), need for revision surgery (nine patients), or failure to decannulate tracheotomy (five patients). Eight patients had an uncomplicated recovery with improved dyspnea, with two patients with tracheotomies decannulated. Patients with a history of smoking tobacco were more likely to experience complications (P = .035). There were no significant differences in outcomes with respect to history of head and neck radiation or gastroesophageal reflux disease. Steroid injection at the surgical site and postoperative medications did not significantly impact outcomes. With respect to granuloma formation, none of the variables analyzed reached significance. CONCLUSIONS: History of tobacco use increases complication rates after TPC. Other patient comorbidities and intra- and postoperative management strategies do not impact outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1066-1070, 2021.

Is the gender gap closing in otolaryngology subspecialties? An analysis of research productivity.

OBJECTIVE: The proportion of women specializing in otolaryngology-head and neck surgery (Oto-HNS) and seeking fellowship training has steadily increased over the last several years. In academic Oto-HNS, gender differences exist in research productivity, scholarly impact, and funding. This study aims to evaluate gender differences in academic productivity between otolaryngologists in early, mid-, and later careers stages and within various subspecialties. METHODS: Departmental websites for all Oto-HNS residency programs were accessed, and data including gender, academic rank, and fellowship training/subspecialty field was collected. Bibliometric data including h-index, publication years, number of citations, documents, and coauthors was obtained from the Scopus database. Career groups were defined as early (1-5 years), mid- (6-15 years), and later (16+ years). Continuous data was compared using the t test. RESULTS: Data was collected on 1,754 academic otolaryngologists (412 women, 1,342 men). Overall, men exhibited significantly higher h-indices, number of documents, citations, and coauthors and actively published for more years compared to women (P < 0.0001 for all variables). Similar trends persisted across all subspecialties. When authors were broken down into career groups, women and men showed similar research productivity across all career groups in the subspecialties of otology, facial plastics, and rhinology; however, in head and neck, laryngology, and pediatrics, women continued to lag behind men. CONCLUSION: This study suggests that female otolaryngologists within certain subspecialties are keeping pace with their male counterparts in publication productivity in the early career time frame. This represents a change from prior studies which have shown women to be less productive in the early career period. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1144-1150, 2020.

Primary odynophonia: When pain is out of proportion to dysphonia.

OBJECTIVES/HYPOTHESIS: Odynophonia is generally regarded as a symptom of a voice disorder. However, a subset of patients with odynophonia have debilitating pain out of proportion to the relatively mild degree of dysphonia and are not responsive to voice therapy. The goals of this study were to 1) describe the symptomatology of this subset of patients and differentiate it from typical odynophonia, 2) propose alternate models to explain this phenomenon of primary odynophonia, and 3) present a new treatment paradigm based on the proposed models. STUDY DESIGN: Case series. METHODS: Inclusion criteria were complaint of persistent pain associated with voicing, normal vocal fold mobility, complete glottic closure, and limited or lack of response of pain to voice therapy. Presenting symptoms, voice evaluation, and treatment outcomes were reviewed. RESULTS: Eleven patients fit the inclusion criteria. The degree of pain did not follow the trajectory of vocal improvement with therapy. The pain was stagnant or worsened with voice exercises. The most dramatic improvement came about in one patient who received false vocal fold Botox injections, and another who received thyrohyoid lidocaine/triamcinolone injection. We propose that these patients had developed primary odynophonia, in which the pain had become self-sustaining and no longer responded to correction of hyperfunctional vocal behavior. The mechanism of pain persistence may involve superior laryngeal neuralgia, cartilaginous or ligamentous inflammation, and/or central sensitization. CONCLUSIONS: A minority of patients have primary odynophonia distinct from typical odynophonia. Direct treatment of pain may be advisable prior to or in conjunction with voice therapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E183-E189, 2020.

Histopathologic predictors of pilocytic astrocytoma event-free survival.

Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. Most arise in the cerebellum, but they also can develop in the brainstem and optic nerve, where gross total resection (GTR) is not possible. In the absence of GTR, significant variability in both clinical behavior and histology exists. To identify potential markers associated with poor clinical outcome, we retrospectively assessed pathological features in 107 patients with PAs. We identified four pathological features (necrosis, oligodendroglioma-like features, vascular hyalinization, and calcification) that showed a significant correlation with decreased event-free survival (EFS). Similar to previous reports, we also found that PAs involving the optic pathway were associated with worse EFS compared with those arising in other locations. In contrast, mitotic index, p53 immunoreactivity and hyperactivation of several mitogenic signaling pathways (MAPK, CREB, mTOR) did not demonstrate a statistically significant relationship with EFS. Lastly, we did find a statistical trend between EFS and the number of CD68+ cells, suggesting that non-neoplastic elements of the tumor microenvironment may influence subsequent growth and clinical recurrence. Collectively, the identification of specific histopathologic features associated with clinical outcome may improve our ability to determine which PAs are more likely to exhibit clinical progression and require more vigilant observation.

Office-Based 532-Nanometer Pulsed Potassium-Titanyl-Phosphate Laser Procedures in Laryngology.

With fiber-based lasers that may be passed via the working channel of a flexible laryngoscope, in-office laser laryngeal surgery has become possible. The potassium-titanyl-phosphate laser has several features that make it ideal for laryngeal surgery, and it is now the laser of choice for in-office management of a variety of laryngeal lesions. Its applications have expanded significantly since its introduction, with reports of new indications continuing to appear in the literature. This article provides a comprehensive review of the indications and technical details of in-office potassium-titanyl-phosphate laser laryngeal surgery, and a summary of the existing literature regarding outcomes of these procedures.

Shar Pei Larynx: Supraglottic and Postcricoid Mucosal Redundancy and Its Association With Medical Comorbidities.

OBJECTIVES:: The aim of this study is to describe a clinical entity the authors term "Shar Pei larynx," characterized by redundant supraglottic and postcricoid mucosa that the authors hypothesize coexists in patients with obstructive sleep apnea, laryngopharyngeal reflux, and obesity. By exploring this hypothesis, the authors hope to set the foundation for future research with the goal of identifying whether Shar Pei larynx is a marker for untreated sleep apnea or other diseases. STUDY DESIGN:: Retrospective chart review. SETTING:: Two tertiary care academic institutions. METHODS:: Data were collected from a 5-year period by querying for patients described to have "Shar Pei larynx" or "posterior supraglottic and/or postcricoid mucosal redundancy" on laryngoscopic findings. Relevant demographic and clinical characteristics were analyzed, with a focus on associations with obesity, sleep apnea, and laryngopharyngeal reflux. RESULTS:: Thirty-two patients were identified with physical findings consistent with Shar Pei larynx. Twenty-six patients (81.3%) were obese; 16 (50%) were morbidly obese. Twenty-two patients (68.8%) either had an existing diagnosis of obstructive sleep apnea or were diagnosed on polysomnography performed after initial evaluation. Sixteen patients (50%) had type 2 diabetes mellitus, and 87.5% of these patients were obese. Twenty-eight patients (87.5%) noted histories of reflux, with a median reflux symptom index of 27 of 45. Five patients underwent procedures to reduce mucosal redundancy related to Shar Pei larynx. CONCLUSIONS:: This pilot study confirms that the majority of patients diagnosed with Shar Pei larynx also had diagnoses of obesity, obstructive sleep apnea, and reflux disease. The demonstrated association is strong enough to warrant further study.

Gene expression profiling of NF-1-associated and sporadic pilocytic astrocytoma identifies aldehyde dehydrogenase 1 family member L1 (ALDH1L1) as an underexpressed candidate biomarker in aggressive subtypes.

Pilocytic astrocytomas (PAs) are World Health Organization Grade I gliomas; they most often affect children and young adults and occur in patients with neurofibromatosis type 1 (NF1). To identify genes that are differentially expressed in sporadic (S-PA) versus NF1-associated PAs (NF1-PAs) and those that might reflect differences in clinical behavior, we performed gene expression profiling using Affymetrix U133 Plus2.0 GeneChip arrays in 36 S-PAs and 11 NF1-PAs. Thirteen genes were overexpressed, and another 13 genes were underexpressed in NF1-PAs relative to S-PAs. Immunohistochemical studies performed on 103 tumors, representing 2 independently generated tissue microarrays, confirmed the differential expression of CUGBP2 (p = 0.0014), RANBP9 (p = 0.0075), ITGAV1 (p = 0.0001), and INFGR1 (p = 0.024) proteins. One of the underexpressed genes, aldehyde dehydrogenase 1 family member L1 (ALDH1L1), was also reduced in clinically aggressive compared with typical PAs (p = 0.01) and in PAs with increased cellularity and necrosis. Furthermore, in an additional independent set of tumors, weak to absent ALDH1L1 expression was found in 13 (72%) of 18 clinically aggressive PAs, in 8 (89%) of 9 PAs with pilomyxoid features, in 7 (70%) of 10 PAs with anaplastic transformation, and in 16 (76%) of 21 diffusely infiltrating astrocytomas of various grades. In summary, we have identified a molecular signature that distinguishes NF1-PA from S-PA and found that ALDH1L1 underexpression is associated with aggressive histology and/or biologic behavior.

Impact of Perioperative Voice Therapy on Outcomes in the Surgical Management of Vocal Fold Cysts.

INTRODUCTION: Vocal fold cysts are benign mid-membranous lesions of the true vocal fold, classified as mucus retention or epidermal inclusion cysts. Treatment is surgical excision with or without postoperative voice therapy. METHODS: A retrospective review was performed of the demographics, treatment approach, and outcomes of patients treated for vocal fold cysts between 2009 and 2014. Voice Handicap Index (VHI)-10 scores before and after treatment were compared using the Wilcoxon Rank-Sum test and the two-tailed Student's t test. Videostroboscopy examinations were reviewed for posttreatment changes in vibratory characteristics of the vocal folds. RESULTS: Twenty-five patients were identified, and one was excluded for incomplete records. Mean age was 41.9 years (66.7% female), and mean follow-up time was 5.58 months. Microflap excision was pursued by 21/24 (87.5%) patients, with 14 patients (58.3%) undergoing perioperative voice therapy. One cyst recurred. Two patients elected for observation, and their cysts persisted. VHI-10 decreased from 23.8 to 6.6 (P < 0.001) overall. There was a statistically significant reduction in VHI-10 in patients undergoing surgery with and without postoperative voice therapy (P < 0.004 and 0.001), but there was no significant difference between these two groups. Mucosal wave was classified as normal or improved in the majority. Cysts were characterized as mucus retention cysts in 19/21 (90%) and as epidermal inclusion cysts in 2/21 (10%). CONCLUSIONS: Vocal fold cysts impact mucosal wave and glottic closure. Surgical excision resulted in low rates of recurrence, and in improvement in the mucosal wave and VHI-10. Perioperative voice therapy did not offer a significant benefit. Mucus retention cysts were the majority, in contrast to other published studies.

Treatment of chronic neurogenic cough with in-office superior laryngeal nerve block.

OBJECTIVES: Neurogenic cough is believed to result from a sensory neuropathy involving the internal branch of the superior laryngeal nerve (SLN). We present our outcomes for the treatment of neurogenic cough with localized blockade of the internal branch of the SLN. METHODS: A retrospective chart review of patients who underwent in-office percutaneous SLN block for treatment of neurogenic cough between 2015 and 2017 was conducted. Patient demographics, indications for injection, and response to treatment were recorded and analyzed. Cough severity index (CSI) scores before and after treatment were compared. RESULTS: Twenty-three patients underwent percutaneous blockade of the internal branch of the SLN in the clinic setting, and five patients were excluded for incomplete records. The indication was neurogenic cough as a diagnosis of exclusion. The injectable substance used was a 1:1 mixture of a long-acting particulate corticosteroid and a local anesthetic. Unilateral injections were performed in 13 patients, and five patients underwent bilateral injections. Of the unilateral injections, 10 were left-sided. Patients underwent an average of 2.4 SLN block procedures (range 1-7). Mean follow-up time postinjection was 85.4 days (7-450 days). Cough severity index scores decreased significantly from an average of 26.8 pretreatment to 14.6 posttreatment (P < 0.0001). CONCLUSION: The SLN block is an effective treatment for neurogenic cough, with average CSI scores significantly improved following injection. Further study is necessary to determine the characteristics of patients' responses to treatment, long-term outcomes, and efficacy of the procedure when compared to placebo and other accepted treatments for neurogenic cough. LEVEL OF EVIDENCE: 4. Laryngoscope, 1898-1903, 2018.

Inflammatory reaction to hyaluronic acid: A newly described complication in vocal fold augmentation.

OBJECTIVES/HYPOTHESIS: To establish the rate of inflammatory reaction to hyaluronic acid (HA) in vocal fold injection augmentation, determine the most common presenting signs and symptoms, and propose an etiology. STUDY DESIGN: Retrospective chart review. METHODS: Patients injected with HA over a 5-year period were reviewed to identify those who had a postoperative inflammatory reaction. Medical records were reviewed for patient demographic information, subjective complaints, Voice Handicap Index-10 (VHI-10) scores, medical intervention, and resolution time. Videolaryngostroboscopy examinations were also evaluated. RESULTS: A total of 186 patients (245 vocal folds) were injected with HA over a 5-year period, with a postoperative inflammatory reaction rate of 3.8%. The most common complaints in these patients were odynophagia, dysphonia, and dyspnea with vocal fold erythema, edema, and loss of pliability on videolaryngostroboscopy. All patients were treated with corticosteroids. Return of vocal fold vibration ranged from 3 weeks to 26 months, with VHI-10 scores normalizing in 50% of patients. CONCLUSIONS: This reaction may be a form of hypersensitivity related to small amounts of protein linked to HA. Alternatively, extravascular compression from the HA could lead to venous congestion of the vocal fold. The possibility of equipment contamination is also being investigated. Further studies are needed to determine the etiology and best treatment. LEVEL OF EVIDENCE: 4 Laryngoscope, 2016 127:445-449, 2017.