Proteomic and Genomic Methylation Signatures of Idiopathic Subglottic Stenosis.

OBJECTIVE: Idiopathic subglottic stenosis (iSGS) is a chronic inflammatory condition that causes dyspnea and affects middle-aged women of White race and non-Latino or Hispanic ethnicity. To better characterize its phenotype and pathogenesis, we assessed the proteomic and genomic methylation signatures of subglottic tissue collected from iSGS patients compared to controls. STUDY DESIGN: Molecular analysis of clinical biospecimens. METHODS: We collected subglottic tissue biopsies from 12 patients during direct laryngoscopy, immediately prior to surgical treatment of iSGS; as well as from 4 age-, sex-, and race/ethnicity-matched control patients undergoing other direct laryngoscopic procedures. We isolated protein and genomic DNA, acquired proteomic data using label-free quantitative mass spectrometry techniques, and acquired genome-wide methylation data using bisulfite conversion and a microarray platform. We compared molecular profiles across the iSGS and control groups, and with respect to clinical course in the iSGS group. Eight of the 12 iSGS patients underwent subsequent blood collection and plasma isolation for further assessment. RESULTS: Proteomic analysis revealed 42 differentially abundant proteins in the iSGS biopsies compared to controls, inferring enrichment of biological pathways associated with early wound healing, innate immunity, matrix remodeling, and metabolism. Proteome-based hierarchical clustering organized patients into two iSGS and one control subgroups. Methylation analysis revealed five hypermethylated genes in the iSGS biopsies compared to controls, including the biotin recycling enzyme biotinidase (BTD). Follow-up analysis showed elevated plasma BTD activity in iSGS patients compared to both controls and published normative data. CONCLUSION: iSGS exhibits distinct proteomic and genomic methylation signatures. These signatures expand current understanding of the iSGS phenotype, support the possibility of disease subgroups, and should inform the direction of future experimental studies. LEVEL OF EVIDENCE: Not applicable Laryngoscope, 131:E540-E546, 2021.

Sulcus Vocalis.

Sulcus vocalis, defined as a type of groove along the free edge of the vocal fold, disrupts the normal, pliable vocal fold cover, causing alterations in the intrinsic mucosal wave. The primary symptom is breathy, effortful dysphonia. Diagnosis may be challenging, and this classically has led to difficulties with identification and management. Treatment options, although often promising, have been notoriously unreliable. Current understanding, considerations for management, and future treatment options are explored.

The Influence of Occupation on Self-perceived Vocal Problems in Patients With Voice Complaints.

OBJECTIVE: This study aimed to examine the relationships among patient occupation, laryngeal diagnosis, perceptual dysphonia severity, and patient-perceived voice impairment. METHODS: Adult patients presenting with a chief complaint of dysphonia over a 20-month period at a tertiary care, interdisciplinary voice center were included in this retrospective cohort study. Patients were categorized by profession: vocal performers, high occupational voice demand, low or no occupational voice demand, and retired. Associations between professional voice demand and clinician rating of dysphonia severity using the "Grade" score from the Grade, Roughness, Breathiness, Asthenia, and Strain scale and patient ratings of voice impairment using the Voice Handicap Index-10 (VHI-10) were tested using standard descriptive statistical methods. RESULTS: One hundred and sixty-three patients with a presenting complaint of dysphonia were evaluated. Significant associations were found on univariate and multivariable analysis among a patient's occupational voice demand, Grade, Roughness, Breathiness, Asthenia, and Strain grade, and VHI-10 score (P = 0.007 and P < 0.001, respectively). Patients subject to greater vocal demands as a result of their occupation had a greater perception of impairment, regardless of acoustic-perceptual severity, when compared with those with low or no occupational voice demand. Although voice diagnosis was significantly associated with VHI-10 score on univariate analysis, it failed to reach significance on multivariable analysis. Demographic measures such as gender and age also did not correlate with perceived vocal impairment. CONCLUSION: Patient-perception of voice impairment is influenced by occupational demand, independent of acoustic-perceptual dysphonia. Performers and people with high occupational voice needs demonstrate a unique sensitivity to subtle voice changes.

The Role of Occupational Voice Demand and Patient-Rated Impairment in Predicting Voice Therapy Adherence.

OBJECTIVE: Examine the relationship among the severity of patient-perceived voice impairment, perceptual dysphonia severity, occupational voice demand, and voice therapy adherence. Identify clinical predictors of increased risk for therapy nonadherence. METHODS: A retrospective cohort study of patients presenting with a chief complaint of persistent dysphonia at an interdisciplinary voice center was done. The Voice Handicap Index-10 (VHI-10) and the Voice-Related Quality of Life (V-RQOL) survey scores, clinician rating of dysphonia severity using the Grade score from the Grade, Roughness Breathiness, Asthenia, and Strain scale, occupational voice demand, and patient demographics were tested for associations with therapy adherence, defined as completion of the treatment plan. Classification and Regression Tree (CART) analysis was performed to establish thresholds for nonadherence risk. RESULTS: Of 166 patients evaluated, 111 were recommended for voice therapy. The therapy nonadherence rate was 56%. Occupational voice demand category, VHI-10, and V-RQOL scores were the only factors significantly correlated with therapy adherence (P < 0.0001, P = 0.018, and P = 0.008, respectively). CART analysis found that patients with low or no occupational voice demand are significantly more likely to be nonadherent with therapy than those with high occupational voice demand (P < 0.001). Furthermore, a VHI-10 score of ≤29 or a V-RQOL score of >40 is a significant cutoff point for predicting therapy nonadherence (P < 0.011 and P < 0.004, respectively). CONCLUSION: Occupational voice demand and patient perception of impairment are significantly and independently correlated with therapy adherence. A VHI-10 score of ≤9 or a V-RQOL score of >40 is a significant cutoff point for predicting nonadherence risk.

Does Even Low-Grade Dysphonia Warrant Voice Center Referral?

OBJECTIVE: Data regarding the referral of dysphonic patients to specialty voice clinics are limited. The objective of this study is to examine the relationship between low perceptual dysphonia severity and subtle laryngeal findings to discern if this can help guide referral. STUDY DESIGN: This is a retrospective chart review. METHODS: The charts of 94 patients presenting with a primary complaint of hoarseness to a single laryngologist over a 1-year period at a tertiary care, interdisciplinary voice center were analyzed. Patients were stratified by clinician perceptual rating of dysphonia severity using the overall Grade score from the GRBAS (grade, roughness, breathiness, asthenia, strain) scale, and this was compared to their laryngeal findings on stroboscopy. RESULTS: Forty-one patients had a Grade score of 0 or 1, of whom 85% had relatively subtle findings on stroboscopy, including vocal fold paresis, muscle tension dysphonia, and spasmodic dysphonia. CONCLUSION: Patients with a primary complaint of hoarseness but absent or only mild perceptual dysphonia may have subtle or occult laryngeal findings that may be easily missed. These patients may benefit from early referral to a specialty voice center.

Treatment of Chronic Cough.

Objective Chronic cough remains a challenging condition, especially in cases where it persists despite comprehensive medical management. For these particular patients, there appears to be an emerging role for behavior modification therapy. We report a series of patients with refractory chronic cough to assess if there is any benefit of adding behavioral therapy to their treatment regimen. Study Design A case series with planned chart review of patients treated for chronic cough. Setting The review was performed with an outpatient electronic health record system at a tertiary care center. Subjects and Methods The charts of all patients treated for chronic cough by a single laryngologist over a 30-month period were analyzed. Patients' response to treatment and rate of cough improvement were assessed for those with refractory chronic cough who underwent behavior modification therapy. Results Thirty-eight patients with chronic cough were initially treated empirically for the most common causes of cough, of which 32% experienced improvement. Nineteen patients who did not significantly improve with medical management underwent behavior modification therapy with a speech-language pathologist. Of these patients, 84% experienced resolution or marked improvement of their symptoms. Conclusion Behavioral therapy may be underutilized in practice and could lead to improvement of otherwise recalcitrant cough.

Endoscopic excision of a tympanic paraganglioma: Training the next generation of ear surgeons.

Tympanic paragangliomas are uncommon vascular tumors of neural crest origin. Classically these lesions have been surgically managed via a transcanal or transmastoid approach using binocular microscopy. We describe a case in which a tympanic paraganglioma was removed via a transcanal approach, using the endoscope exclusively. Endoscopic ear surgery enhances visualization, helping to ensure complete tumor removal, while reducing unnecessary dissection and its associated morbidity. For small middle ear neoplasms, a purely endoscopic approach is feasible, with excellent results. Resident education in ear surgery has also been enhanced by the use of endoscopes. The wide field of view provided by the endoscope helps trainees understand the intricate three-dimensional anatomy of the middle ear cleft.

Sinonasal extramedullary plasmacytoma: a systematic review of 175 patients.

BACKGROUND: This study reviews the published literature related to extramedullary sinonasal plasmacytomas. Clinical presentation, demographics, treatment, and outcomes of this uncommon disease are reported. METHODS: A systematic review of studies for sinonasal plasmacytomas from 1950 to 2012 was conducted. A PubMed database search, both for articles related to this condition along with bibliographies of those selected articles, was performed. Articles were examined for patient data that reported disease outcome. RESULTS: Sixty-seven journal articles were included in this analysis, comprising a total of 175 cases. Radiotherapy was the most common treatment modality, used in 89 cases, followed by a combination of surgery and radiotherapy, and surgery alone. A total of 71.8% of patients were alive after a median follow-up of 39 months, independent of treatment modality. A combination of radiotherapy and chemotherapy was rarely used but had the best treatment outcome, with 88.9% of patients (8/9 patients) alive. Of the 3 most common treatment modalities, a combination of radiotherapy and surgery had the most favorable outcomes. Sixteen patients (9.1%) converted to multiple myeloma, with the majority of these patients (75.0%) receiving radiotherapy alone as their treatment modality. CONCLUSION: This review contains the largest pool of sinonasal plasmacytoma patients to date and suggests aggressive radiotherapy is the most common treatment modality for this condition. Of the 3 most common treatment modalities, a combination of surgery and radiotherapy was shown to have the best survival outcomes.

From above or below: the controversy and historical evolution of tuberculum sellae meningioma resection from open to endoscopic skull base approaches.

In the early 20th century, the first successful surgical removal of a tuberculum sellae meningioma (TSM) was performed and described by Harvey Cushing. It soon became recognized that TSM pose a formidable challenge for skull base surgeons because of their deep and sensitive location, proximity to critical neurovascular elements, and often dense and fibrous nature. Because of this, over the next several decades controversy transpired regarding their optimal method of resection. Early attempts involved utilization of open transcranial routes. This included classic bilateral and unilateral frontal approaches, followed by pterional or frontotemporal approaches, which have evolved to incorporate skull base modifications, such as the supraorbital, orbitozygomatic, and orbitopterional approaches. Minimally invasive supraorbital keyhole approaches through eyebrow incisions have also been adopted. Over the past 25 years, the microsurgical transsphenoidal approach, classically used for pituitary and parasellar tumors, was modified to resect suprasesllar TSM via the extended transsphenoidal approach. More recently, with the evolution of endoscopic techniques, resection of TSM has been achieved using purely endoscopic endonasal transplanum transtuberculum approaches. Although each of these techniques has been successfully described for the treatment of TSM, the question still remains: is it better to access and operate on these lesions via a traditional, transcranial avenue, or are they better treated via endoscopic endonasal techniques? We outline the surgical management of TSM through history, from early transcranial and transsphenoidal approaches to modern extended endoscopic endonasal procedures. We briefly explore the arguments favoring each of the methods and the advancements which have emerged to further optimize surgical resection.

Postoperative cerebrospinal fluid leak after septoplasty: A potential complication of occult anterior skull base encephalocele.

Postoperative cerebrospinal fluid (CSF) rhinorrhea after septoplasty is a known entity resulting from errors in surgical technique and improper handling of the perpendicular plate of the ethmoid bone. When these occur, urgent management is necessary to prevent deleterious sequelae such as meningitis, intracranial abscess, and pneumocephalus. Encephaloceles are rare occurrences characterized by herniation of intracranial contents through a skull base defect that can predispose patients to CSF rhinorrhea. In this report, we present a case of CSF rhinorrhea occurring 2 weeks after septoplasty likely from manipulation of an occult anterior skull base encephalocele. To our knowledge, no previous similar case has been reported in the literature. Otolaryngologists should be aware of the possibility of occult encephaloceles while performing septoplasties because minimal manipulation of these entities may potentially result in postoperative CSF leakage.

Celebrating the golden anniversary of anterior skull base surgery: reflections on the past 50 years and its historical evolution.

With its inception nearly half a century ago through the pioneering work of Dandy, McLean, and Smith, anterior skull base (ASB) surgery is a relatively young discipline. It became a distinct entity in 1963 when Ketcham popularized the combined transcranial transfacial approach for en bloc resection of tumors of the paranasal sinuses extending into the anterior cranial fossa. However, because these procedures resulted in major morbidities and mortalities, alternative modes of treatment were sought. Since the 1970s, the introduction and promotion of the surgical endoscope by Messerklinger, Stammberger, and Kennedy, commenced the era of endoscopic sinus surgery. Thaler and colleagues described the utility of the endoscope for ASB surgery at the turn of the century. This allowed direct visualization and safer, more accurate removal of tumors. In 2001, Casiano reported the first purely endoscopic endonasal ASB resection, a novel technique that has been adopted by major skull base centers. The success of ASB surgery can be attributed to both the development of the skull base team as well as improvements in surgical techniques, instrumentation, and visualization technology. In this article, we review the historical evolution of ASB surgery as we approach the 50th anniversary since its recognition as a distinct entity.