Noninvasive monitoring of the vagus nerve during thyroid surgery using cutaneous adhesive and needle electrodes: What is the optimal configuration?

OBJECTIVE: Endotracheal tube (ETT) surface electrodes are used to monitor the vagus nerve (VN), recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve (EBSLN) during thyroid and parathyroid surgery. Alternative nerve monitoring methods are desirable when intubation under general anesthesia is not desirable or possible. In this pilot study, we compared the performance of standard ETT electrodes to four different noninvasive cutaneous recording electrode types (two adhesive electrodes and two needle electrodes) in three different orientations. METHODS: The VN was stimulated directly during thyroid and parathyroid surgery using a Prass stimulator probe. Electromyographic (EMG) responses for each patient were recorded using an ETT plus one of the following four cutaneous electrode types: large-foot adhesive, small-foot adhesive, long-needle and short-needle. Each of the four electrode types was placed in three orientations: (1) bilateral, (2) ipsilateral mediolateral, and (3) ipsilateral craniocaudal. RESULTS: Four surgical cases were utilized for data collection with the repetitive measures obtained in each subject. Bilateral electrode orientation was superior to ipsilateral craniocaudal and ipsilateral mediolateral orientations. Regardless of electrodes type, all amplitudes in the bilateral orientation were >100 µV. When placed bilaterally, the small-foot adhesive and the long-needle electrodes obtained the highest EMG amplitudes as a percentage of ETT amplitudes. CONCLUSION: Cutaneous electrodes could potentially be used to monitor the VN during thyroid and parathyroid procedures. Different electrode types vary in their ability to record amplitudes and latencies. Bilateral orientation improves EMG responses in all electrode types. Additional validation of cutaneous electrodes as an alternative noninvasive method to monitor the VN is needed.

Assessing the Accuracy of Otomatch.com Data for Individuals Applying to Otolaryngology Residency.

OBJECTIVES: Otomatch.com is an online forum for residency applicants to discuss the otolaryngology match process including academic metrics. The purpose of this study is to assess the accuracy of self-reported match data on Otomatch relative to official data reported by the National Residency Match Program (NRMP) and the Association of American Medical Colleges (AAMC). METHODS: Data was collected from publicly editable Otomatch forums (2017-2018, 2018-2019, 2019-2020) and curated Otomatch survey responses (2018-2019, 2019-2020) whose results are released after Match Day. Aggregated data was collected from the NRMP 2018 and 2020 Charting Outcomes in the Match and AAMC Report on Residents (2017-2018, 2018-2019). Measures of interest included Step 1 scores, Step 2 CK scores, publications, number of interview invitations, number of interviews attended, and AOA status. ANOVA and 2 tailed T tests were performed to compare variables within each match year. RESULTS: Average Step 2 CK score was significantly higher on publicly editable Otomatch forums than AAMC in 2017-2018 (257vs 253, P < .05) and 2018-2019 (258vs 252, P < .05). Interviews attended were significantly higher on Otomatch survey responses than the publicly editable forum in 2019-2020 (13vs 9, P-value < .05). Step 1 scores, interview invitations, and AOA status were not statistically significantly different when data was available. CONCLUSION: Applicant statistics from online forums, online surveys, NRMP, and AAMC are consistent, except for Step 2 CK scores. Self-reported data on the Otomatch forum is an accurate estimate of academic metrics of otolaryngology residency applicants.

Surgical and Biochemical Outcomes in Nerve Monitored Reoperation Surgery for Recurrent Papillary Thyroid Carcinoma.

OBJECTIVE: To study the surgical and biochemical outcomes in nerve-monitored reoperation or revision surgery for recurrent thyroid cancers. STUDY DESIGN: A single-center retrospective study. SETTING: Tertiary center. METHODS: We identified patients with recurrent papillary thyroid carcinoma (PTC) who underwent reoperation/revision surgery. Study outcomes were surgical complications frequency, recurrence, distant metastasis, and biological complete response (BCR) by comparing preoperative and postoperative thyroglobulin (Tg) levels. RESULTS: Out of 227 patients, 33.9% presented for ≥2 reoperation surgeries. Nineteen (8.4%) had permanent preoperative hypoparathyroidism while 22 patients (9.7%) had preoperative vocal cord paralysis (VCP). Following reoperation surgery, there were 12 cases (5.3%) of permanent hypocalcemia and no cases of unexpected postoperative VCP. BCR was achieved in 31 patients (35.2%) with complete Tg data. Mean preoperative Tg was 47.7 ng/mL and was 19.7 ng/mL postoperatively (p = .003). The cervical nodal recurrence rate after final surgery was 7.0% (n = 16). CONCLUSION: Reoperation surgery for recurrent PTC may help achieve biochemical remission regardless of age or the number of prior surgeries.

A multicenter evaluation of near-infrared autofluorescence imaging of parathyroid glands in thyroid and parathyroid surgery.

BACKGROUND: The usefulness of incorporating near-infrared autofluorescence into the surgical workflow of endocrine surgeons is unclear. Our aim was to develop a prospective registry and gather expert opinion on appropriate use of this technology. METHODS: This was a prospective multicenter collaborative study of patients undergoing thyroidectomy and parathyroidectomy at 7 academic centers. A questionnaire was disseminated among 24 participating surgeons. RESULTS: Overall, 827 thyroidectomy and parathyroidectomy procedures were entered into registry: 42% of surgeons found near-infrared autofluorescence useful in identifying parathyroid glands before they became apparent; 67% correlated near-infrared autofluorescence pattern to normal and abnormal glands; 38% of surgeons used near-infrared autofluorescence, rather than frozen section, to confirm parathyroid tissue; and 87% and 78% of surgeons reported near-infrared autofluorescence did not improve the success rate after parathyroidectomy or the ability to find ectopic glands, respectively. During thyroidectomy, 66% of surgeons routinely used near-infrared autofluorescence to rule out inadvertent parathyroidectomy. However, only 36% and 45% felt near-infrared autofluorescence decreased inadvertent parathyroidectomy rates and improved ability to preserve parathyroid glands during central neck dissections, respectively. CONCLUSION: This survey study identified areas of greatest potential use for near-infrared autofluorescence, which can form the basis of future objective trials to document the usefulness of this technology.

Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis.

Importance: There is epidemiologic evidence that the increasing incidence of thyroid cancer is associated with subclinical disease detection. Evidence for a true increase in thyroid cancer incidence has also been identified. However, a true increase in disease would likely be heralded by an increased incidence of thyroid-referable symptoms in patients presenting with disease. Objectives: To evaluate whether modes of detection (MODs) used to identify thyroid nodules for surgical removal have changed compared with historic data and to determine if MODs vary by geographic location. Design, Setting, and Participants: This was a retrospective analysis of pathology and medical records of 1328 patients who underwent thyroid-directed surgery in 16 centers in 4 countries: 4 centers in Canada, 1 in Denmark, 1 in South Africa, and 12 in the US. The participants were the first 100 patients (or the largest number available) at each center who had thyroid surgery in 2019. The MOD of the thyroid finding that required surgery was classified using an updated version of a previously validated tool as endocrine condition, symptomatic thyroid, surveillance, or without thyroid-referable symptoms (asymptomatic). If asymptomatic, the MOD was further classified as clinician screening examination, patient-requested screening, radiologic serendipity, or diagnostic cascade. Main Outcomes and Measures: The MOD of thyroid nodules that were surgically removed, by geographic variation; and the proportion and size of thyroid cancers discovered in patients without thyroid-referable symptoms compared with symptomatic detection. Data analyses were performed from April 2021 to February 2022. Results: Of the 1328 patients (mean [SD] age, 52 [15] years; 993 [75%] women; race/ethnicity data were not collected) who underwent thyroid surgery that met inclusion criteria, 34% (448) of the surgeries were for patients with thyroid-related symptoms, 41% (542) for thyroid findings discovered without thyroid-referable symptoms, 14% (184) for endocrine conditions, and 12% (154) for nodules with original MOD unknown (under surveillance). Cancer was detected in 613 (46%) patients; of these, 30% (183 patients) were symptomatic and 51% (310 patients) had no thyroid-referable symptoms. The mean (SD) size of the cancers identified in the symptomatic group was 3.2 (2.1) cm (median [range] cm, 2.6 [0.2-10.5]; 95% CI, 2.91-3.52) and in the asymptomatic group, 2.1 (1.4) cm (median [range] cm, 1.7 [0.05-8.8]; 95% CI, 1.92-2.23). The MOD patterns were significantly different among all participating countries. Conclusions and Relevance: This retrospective analysis found that most thyroid cancers were discovered in patients who had no thyroid-referable symptoms; on average, these cancers were smaller than symptomatic thyroid cancers. Still, some asymptomatic cancers were large, consistent with historic data. The substantial difference in MOD patterns among the 4 countries suggests extensive variations in practice.

Severe Versus Very Severe Pediatric Obstructive Sleep Apnea Outcomes After Adenotonsillectomy.

OBJECTIVES/HYPOTHESIS: Adenotonsillectomy (AT) is generally considered the first line treatment for pediatric patients with obstructive sleep apnea (OSA). Pediatric patients with severe OSA have worse outcomes after AT than patients with milder OSA. It is currently unclear if this group of higher morbidity patients should be subdivided further. This study investigates patients with severe pediatric OSA to determine if there are differences in postsurgical outcomes based on initial severity of sleep disordered breathing, medical comorbidities, or demographic factors. STUDY DESIGN: Retrospective cohort study at a single tertiary referral center. METHODS: Patients aged 2-18 who underwent polysomnogram (PSG) from October 2012 to January 2019, had an apnea-hypopnea index (AHI) >10, and subsequently underwent AT were identified using a filter through electronic medical record. A total of 112 patients underwent both pre- and postoperative PSG. Bivariate analysis was conducted via Pearson chi-square test. Univariate and multivariate analyses via binary logistic and multinomial linear regressions were performed using SPSS. RESULTS: Of the 112 patients included in this study, 68 patients were identified as having severe OSA (AHI = 10-20) and 44 as having very severe OSA (AHI > 20). Very severe OSA patients were significantly less likely to be cured of sleep disordered breathing or have their OSA reduced to mild OSA. Obese patients were found to have less reduction in AHI after AT. CONCLUSIONS: The postsurgical outcomes of patients with severe and very severe OSA are significantly different indicating that patients traditionally categorized as having severe OSA may need to be further subcategorized. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1855-1860, 2022.

Socioeconomic variables as a predictor of indication for pediatric adenotonsillectomy.

OBJECTIVES: Adenotonsillectomy (AT) is a common pediatric procedure performed for sleep disordered breathing (SDB) or chronic/recurrent tonsillitis. A better understanding of factors associated with clinical indications for AT would positively contribute to patient-centered care of these conditions. Our objective is to assess the relationships between race, ethnicity, and socioeconomic status (SES) and indications for adenotonsillectomy in pediatric patients. METHODS: A retrospective chart review was conducted for pediatric patients between the ages 0-18 years who underwent adenotonsillectomy between October 2012 and October 2017 at Boston Medical Center. Indication for surgery was categorized as sleep disordered breathing (SDB), tonsillitis, or other. Age, race, ethnicity, gender, language, distance to hospital and insurance type were collected as demographic variables. 9-Digit patient zip codes were matched to a corresponding area deprivation index (ADI) which combines 17 neighborhood level socioeconomic markers. Logistic regression analysis was performed to assess for association between demographic variables and indication for adenotonsillectomy. RESULTS: 1315 children were included in this study (mean age = 6.4 years, 0-18 years). African American (OR = 3.90, p-value <0.0001), Latino (OR = 2.602, p-value < 0.0001), and Asian American (OR = 4.439, p-value = 0.0146) patients were more likely to have SDB as an indication than Caucasian patients. Among children undergoing AT for SDB, patients who received pre-operative polysomnogram were more likely to be under 2 years old, African American, Asian American, or of Hispanic ethnicity and have higher BMI than patients who were diagnosed clinically prior to surgery. There was no statistically significant association between indications for adenotonsillectomy and ADI, distance to hospital, insurance status or language. Males were more likely have to have SDB as an indication than females (OR = 1.67, p-value = 0.0014). Younger patients under two years of age were more likely to have SDB as an indication for surgery when compared to older patients. CONCLUSION: We found significant relationships between indications for adenotonsillectomy and race and ethnicity as well as gender and age. Additionally, our study showed that indication for AT was not associated with either ADI or insurance status. This suggests that race and ethnicity are predictors of indication independent of SES. Knowledge of predictive factors of adenotonsillectomy indications may help to improve patient centered care.

Characteristics and Outcomes of Pediatric Vestibular Schwannomas.

OBJECTIVE: To review the demographics, treatment modalities, and survival of children with vestibular schwannomas. STUDY DESIGN: Analysis using the Surveillance, Epidemiology, and End Results (SEER) database. SUBJECTS AND METHODS: Pediatric patients from birth to 18 years in the SEER database were included from 2004 to 2014 based on a diagnosis of vestibular schwannoma using the primary site International Classification of Diseases (ICD) O-3 code of C72.4: acoustic nerve and the ICD O-3 histology codes of 9540/1: neurofibromatosis, Not Otherwise Specified (NOS); 9560/0: neurilemoma, NOS; or 9570/0: neuroma, NOS. RESULTS: One hundred forty-eight pediatric vestibular schwannomas (VSs) cases were identified. The mean age at diagnosis was 13.9 years (range, 4.0-18.0). Eighty-five (57.4%) patients were women. Seventy-seven (52.0%) patients had isolated unilateral VSs while 71 (48.0%) patients had either bilateral VSs or unilateral VSs with other brain, spinal cord, or cranial nerve tumors. Eighty two (55.4%) patients received surgical resection only, 45 (30.4%) received no treatment, 6 (4.1%) received radiation only, and 12 (8.1%) received surgery and radiation. The median tumor size for patients who received no treatment was 9.5 mm (interquartile range [IQR]: 8.0) compared with 33.5 mm (IQR: 23.0) for patients who received surgical care and 41.0 mm (IQR: 1.5) for patients who received both surgery and radiation (p < 0.001). The 5-year overall survival rate was 97%. CONCLUSION: Pediatric VSs tend to be diagnosed in adolescence. No men or women predominance was appreciated. Treatment varied according to tumor size. Survival rates for children with vestibular schwannomas are excellent. These data may assist healthcare providers when counseling children with vestibular schwannomas and their families.

A review of pediatric middle ear tumors and analysis of the demographics, management, and survival of pediatric rhabdomyosarcomas of the middle ear.

OBJECTIVE: To examine the types of pediatric middle ear tumors and review the demographics, management, and survival of pediatric patients with rhabdomyosarcoma (RMS) of the middle ear. METHODS: Pediatric patients in the Surveillance, Epidemiology, and End Results (SEER) database were included from 1973 to 2014 based on a diagnosis of middle ear tumors using the ICD O-3 code: C30.1: Middle ear primary site. Patients were included from ages 0-18 years. RESULTS: Forty pediatric middle ear tumor cases were identified. Twenty patients were female (50%). Twenty-seven (67.5%) cases were rhabdomyosarcomas (RMS). Pediatric RMS patients tended to be diagnosed in early childhood (mean age 5.30 years, standard deviation 2.9, range 1.00-13.00, 59.3% of patients were ages 5 or below). Most pediatric RMS patients received chemotherapy and radiation therapy as part of the treatment regimen (88.8%). Finally, the 5-year overall and disease-specific survival rates were 59% and 63% respectively. CONCLUSIONS: Pediatric middle ear tumors are rare. Females and male pediatric patients are both at risk for middle ear tumors. RMS is the most common malignant middle ear tumor affecting pediatric patients. Despite the use of multimodality therapies, survival rates for pediatric patients with RMS of the middle ear are low. Physicians may consider including middle ear tumors on the differential diagnosis for pediatric patients with symptoms presenting similarly to non-resolving otitis media.

Dominant-negative Gα subunits are a mechanism of dysregulated heterotrimeric G protein signaling in human disease.

Auriculo-condylar syndrome (ACS), a rare condition that impairs craniofacial development, is caused by mutations in a G protein-coupled receptor (GPCR) signaling pathway. In mice, disruption of signaling by the endothelin type A receptor (ET(A)R), which is mediated by the G protein (heterotrimeric guanine nucleotide-binding protein) subunit Gα(q/11) and subsequently phospholipase C (PLC), impairs neural crest cell differentiation that is required for normal craniofacial development. Some ACS patients have mutations inGNAI3, which encodes Gα(i3), but it is unknown whether this G protein has a role within the ET(A)R pathway. We used a Xenopus model of vertebrate development, in vitro biochemistry, and biosensors of G protein activity in mammalian cells to systematically characterize the phenotype and function of all known ACS-associated Gα(i3) mutants. We found that ACS-associated mutations in GNAI3 produce dominant-negative Gα(i3) mutant proteins that couple to ET(A)R but cannot bind and hydrolyze guanosine triphosphate, resulting in the prevention of endothelin-mediated activation of Gα(q/11) and PLC. Thus, ACS is caused by functionally dominant-negative mutations in a heterotrimeric G protein subunit.

Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease.

Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase that is increasingly implicated in various neurodegenerative diseases. Deregulated Cdk5 activity has been associated with neuronal death, but the underlying mechanisms are not well understood. Here we report an unexpected role for Cdk5 in the regulation of induced autophagy in neurons. We have identified endophilin B1 (EndoB1) as a Cdk5 substrate, and show that Cdk5-mediated phosphorylation of EndoB1 is required for autophagy induction in starved neurons. Furthermore, phosphorylation of EndoB1 facilitates EndoB1 dimerization and recruitment of UVRAG (UV radiation resistance-associated gene). More importantly, Cdk5-mediated phosphorylation of EndoB1 is essential for autophagy induction and neuronal loss in models of Parkinson's disease. Our findings not only establish Cdk5 as a critical regulator of autophagy induction, but also reveal a role for Cdk5 and EndoB1 in the pathophysiology of Parkinson's disease through modulating autophagy.

Endophilin B1 as a novel regulator of nerve growth factor/ TrkA trafficking and neurite outgrowth.

Neurotrophins and their cognate receptors Trks are important regulators of neuronal survival and differentiation. Recent studies reveal that internalization and trafficking of Trks play a critical role in neurotrophin-mediated signaling. At present, little is known of the molecular events that mediate this process. In the current study, we show that endophilin B1 is a novel regulator of nerve growth factor (NGF) trafficking. We found that endophilin B1 interacts with both TrkA and early endosome marker EEA1. Interestingly, knockdown of endophilin B1 results in enlarged EEA1-positive vesicles in NGF-treated PC12 cells. This is accompanied by increased lysosomal targeting of NGF/TrkA and TrkA degradation, and reduced total TrkA levels. In addition, knockdown of endophilin B1 attenuates Erk1/2 activation in the endosomal fraction after NGF treatment. This is accompanied by a marked inhibition of NGF-induced gene transcription and neurite outgrowth in endophilin B1-knocked down cells. Our observations implicate endophilin B1 as a novel regulator of NGF trafficking, thereby affecting TrkA levels and downstream signaling on endosomes to mediate biological functions of NGF.