Cholinergic depolarization recruits a persistent Ca2+ current in Aplysia bag cell neurons.

Many behaviors and types of information storage are mediated by lengthy changes in neuronal activity. In bag cell neurons of the hermaphroditic sea snail Aplysia californica, a transient cholinergic synaptic input triggers an ∼30-min afterdischarge. This causes these neuroendocrine cells to release egg laying hormone and elicit reproductive behavior. When acetylcholine is pressure-ejected onto a current-clamped bag cell neuron, the evoked depolarization is far longer than the current evoked by acetylcholine under voltage clamp, suggesting recruitment of another conductance. Our earlier studies found bag cell neurons to display a voltage-dependent persistent Ca2+ current. Hence, we hypothesized that this current is activated by the acetylcholine-induced depolarization and sought a selective Ca2+ current blocker. Rapid Ca2+ current evoked by 200-ms depolarizing steps in voltage-clamped cultured bag cell neurons demonstrated a concentration-dependent sensitivity to Ni2+, Co2+, Zn2+, and verapamil but not Cd2+ or ω-conotoxin GIVa. Leak subtraction of Ca2+ current evoked by 10-s depolarizing steps using the IC100 (concentration required to eliminate maximal current) of Ni2+, Co2+, Zn2+, or verapamil revealed persistent Ca2+ current, demonstrating persistent current block. Only Co2+ and Zn2+ did not suppress the acetylcholine-induced current, although Zn2+ appeared to impact additional channels. When Co2+ was applied during an acetylcholine-induced depolarization, the amplitude was reduced; furthermore, protein kinase C activation, previously established to enhance the persistent Ca2+ current, extended the depolarization. Therefore, the persistent Ca2+ current sustains the acetylcholine-induced depolarization and may translate brief cholinergic input into afterdischarge initiation. This could be a general mechanism of triggering long-term change in activity with a short-lived input.NEW & NOTEWORTHY Ionotropic acetylcholine receptors mediate brief synaptic communication, including in bag cell neurons of the sea snail Aplysia. However, this study demonstrates that cholinergic depolarization can open a voltage-gated persistent Ca2+ current, which extends the bag cell neuron response to acetylcholine. Bursting in these neuroendocrine cells results in hormone release and egg laying. Thus, this emphasizes the role of ionotropic signaling in reaching a depolarized level to engage Ca2+ influx and perpetuating the activity necessary for behavior.

Patterns of Care and Outcomes of Primary Adenoid Cystic Carcinoma of the Trachea.

OBJECTIVE: Primary tracheal malignancies are relatively rare cancers, representing 0.1% to 0.4% of all malignancies. Adenoid cystic carcinoma (ACC) is the second most common histology of primary tracheal malignancy, after squamous cell carcinoma. This study aims to analyze demographic characteristics and potential influencing factors on survival of tracheal ACC (TACC). METHODS: This was a retrospective cohort study utilizing the National Cancer Database (NCDB). The NCDB was queried for all cases of TACC diagnosed from 2004 to 2016 (n = 394). Kaplan-Meier (KM) and Cox proportional-hazards models were used to determine clinicopathological and treatment factors associated with survival outcomes. RESULTS: Median age of diagnosis was 56 (IQR: 44.75-66.00). Females were affected slightly more than males (53.8% vs 46.2%). The most prevalent tumor diameter range was 20 to 39 mm (34.8%) followed by greater than 40 mm in diameter (17.8%). Median overall survival (OS) was 9.72 years with a 5- and 10-year OS of 70% and 47.5%, respectively. Localized disease was not associated with a survival benefit over invasive disease (P = .388). The most common intervention was surgery combined with radiation therapy (RT) at 46.2%, followed by surgery alone (16.8%), and standalone RT (8.9%). When adjusting for confounders, surgical resection was independently associated with improved OS (HR 0.461, 95% CI 0.225-0.946). Tumor size greater than 40 mm was independently associated with worse OS (HR 2.808; 95% CI 1.096-7.194). CONCLUSION: Our data suggests that surgical resection, possibly in conjunction with radiation therapy, is associated with improved survival, and tumor larger than 40 mm are associated with worse survival.

The Relationship Between Open Access Article Publishing and Short-Term Citations in Otolaryngology.

OBJECTIVES: The purpose of this study is to compare the number of citations received by open access articles versus subscription access articles in subscription journals in the Otolaryngology literature. METHODS: Using the Dimensions research database, we examined articles indexed to PubMed with at least 5 citations published in 2018. Articles were included from Otolaryngology-Head and Neck Surgery, The Laryngoscope, JAMA Otolaryngology-Head and Neck Surgery, Annals of Otology, Rhinology, and Laryngology, and American Journal of Otolaryngology. Multivariate Poisson regression modeling was used to adjust for journal, article type, and topic. Practice guidelines, position statements, or retractions were excluded as potential outliers. RESULTS: 137 open access articles and 337 subscription access articles meeting inclusion criteria were identified, with a median citation number of 8 (IQR 6-11). The most common article type was original investigation (82.5%), and the most common study topic was head and neck (28.9%). Open access articles had a higher median number of citations at 9 (IQR 6-13) when compared to subscription access articles at 7 (IQR 6-10) (P = .032). Open access status was significantly associated with a higher number of citations than subscription access articles when adjusting for journal, article type, and topic (ß = .272, CI 0.194-0.500, P < .001). CONCLUSIONS: Although comprising a minority of articles examined in this study of subscription journals, open access articles were associated with a higher number of citations than subscription access articles. Open access publishing may facilitate the spread of novel findings in Otolaryngology.

Landscape of Centralized Otolaryngology Research Efforts Grant Recipients Over the Past Decade.

OBJECTIVE: To investigate the demographics of CORE grant recipients (Centralized Otolaryngology Research Efforts) over the last decade and evaluate disparity among recipients as compared with otolaryngology overall. To assess whether procurement of a grant predicts pursuit of an academic career. STUDY DESIGN: Analysis of grant recipients' bibliometrics. SETTING: Academic medical center. METHODS: The list of recipients of grants from 2010 to 2019 was obtained from the website of the American Academy of Otolaryngology-Head and Neck Surgery. Demographics of recipients were collected through an internet search, including gender, race, residency program, and h-index. Recipients from 2010 were searched to determine current academic faculty rank. Univariate and multivariate analyses were used to compare these factors with otolaryngology overall. RESULTS: The distribution of gender among recipients over the last decade remained nearly constant, with no significant difference versus residents in otolaryngology (P > .05). However, there were significantly more female recipients when adjusted for gender differences in the field overall (P < .01). Asians were relatively overrepresented, while Black and Hispanic residents were underrepresented (P < .01). Many recipients (52.6%) trained at institutions recognized as the best training programs with reputations for quality research output. The h-index of recipients decreased over the last decade (P < .01). The h-index of duplicate winners was significantly higher than those of nonduplicate winners (P < .01). After adjusting for gender and rank, recipients were significantly more likely to hold academic positions (P < .01). CONCLUSION: CORE grants are favorably distributed as related to gender and racial disparities, and recipients frequently go on to achieve high levels of academic success.

Understanding giant cell sarcoma of the head and neck: A population-based study.

BACKGROUND: Giant cell sarcomas (GCS) are rare head and neck neoplasms. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for all patients who have been diagnosed with GCS from 1973 to 2014. RESULTS: Four hundred and forty cases of GCS of the head and neck were identified. The average age at diagnosis was 74.4 years, 86.8% were white, 82.5% were male, 70.7% were insured, and 88.2% lived in an urban metropolitan region. Connective tissue was the most frequent primary site (42.5%). The 5Y-DSS rate was 91.1%, while the 5Y-OS was 54.6% for all cases. Patients treated with surgery alone had the highest 5Y-DSS rate of 94.5. T-classification odds ratio was a significant predictor of survival accounting for confounding variables on multivariate analysis. CONCLUSIONS: GCS presents most frequently in connective tissue of the head and neck with overall high probability of survival. The treatment of choice is surgery alone.

Evaluating YouTube as a Resource for Trigeminal Neuralgia Patient Education.

PURPOSE: The objective of this study was to examine the educational value of YouTube as a source of patient information regarding trigeminal neuralgia and its treatment. We also sought to determine the degree of bias that is present in the top videos regarding this condition. MATERIALS AND METHODS: We selected 6 search terms related to trigeminal neuralgia to examine on YouTube for quality and bias using the DISCERN criteria. Filtering by relevance and total view count, we determined the top 20 results for each search term and evaluated all videos for overall educational quality and creator bias. We categorized the type of content creator and compared overall DISCERN scores and bias scores between creator type and search term. RESULTS: There were 80 unique and 40 duplicate videos. There were 10,745,574 total views across all videos, with an average view count of 89,546. The mean DISCERN score for all videos was 1.7, and the mean bias score was 2.2. Based on individual search terms, the highest mean DISCERN score was for trigeminal neuralgia surgery (2.1) and the highest mean bias score was for tic douloureux (2.8). Among creator types, medical professionals had significantly higher overall (2.2) and bias (2.6) scores. CONCLUSIONS: Overall, YouTube is a relatively poor source of unbiased information about trigeminal neuralgia. Among the existing content, medical professionals provide educational material that is the highest quality and the most unbiased.

Helping Children with Special Needs: Who Receives Tympanostomy Tubes?

OBJECTIVES: Tympanostomy tubes can prevent sequelae of otitis media that adversely affect long term hearing and language development in children. These negative outcomes compound the existing difficulties faced by children who are already diagnosed with developmental disorders. This study aims to characterize this subset of children with developmental disorders undergoing myringotomy and tympanostomy tube insertion. METHODS: A retrospective review using the Kids' Inpatient Database (KID) was conducted, with codes from International Classification of Diseases, Ninth Revision used to query data from the years 2003 to 2012 to determine a study group of children with a diagnosis of a developmental disorder undergoing myringotomy and tympanostomy insertion. This group was compared statistically to patients undergoing these procedures who did not have a diagnosed developmental disorder. RESULTS: In total, 21 945 cases of patients with myringotomy with or without tympanostomy tube insertion were identified, of which 1200 (5.5%) had a diagnosis of a developmental disorder. Children with developmental disorders had a higher mean age (3.3 years vs 2.9 years, P = .002) and higher mean hospital charges ($43 704.77 vs $32 764.22, P = .003). This cohort also had higher proportions of black (17.6% vs 12.3%, P < .001) and Hispanic (23.9% vs 20.6%, P = .014) patients, and had lower rates of private insurance coverage (39.6% vs 49%, P < .001). CONCLUSION: The population of children with developmental disorders undergoing myringotomy or tympanostomy tube placement has a different demographic composition than the general population and faces distinct financial and insurance coverage burdens. Further study should be done to assess if these differences impact long term outcomes.

Analysis of Head and Neck Primary Cutaneous Mucinous Carcinoma: An Indolent Tumor of the Eccrine Sweat Glands.

BACKGROUND/OBJECTIVES: Primary cutaneous mucinous carcinoma (PCMC) of the head and neck is a rare pathologic entity that is an adenocarcinoma of the eccrine sweat glands. Though it has low metastatic potential, it does have a significant recurrence rate. Due to its rarity, its clinical features are not well-known. METHODS: The authors searched the National Cancer Database (NCDB) for all cases of PCMC with primary sites of the skin of the head and neck confirmed histologically diagnosed from 2004 to 2016. Those with missing survival information were excluded. Kaplan-Meier (KM) and Cox proportional-hazards models were used to analyze the epidemiology and survival outcomes of PCMC. RESULTS: The authors analyzed 289 cases. Females were more commonly affected (58.8%; P < 0.05) with the most common primary sites being the eyelid (41.9%) and scalp/neck (25.3%). The average age of diagnosis was 63.8 years (± SD 12.5). Almost all patients received surgery as standalone treatment (92.7%) with wide local excision being the common surgery performed (36.3%). Mohs surgery represented 15.2% of surgically treated cases. Mean overall survival (OS) was 11.4 years with 5-year and 10-year OS being 85.0% and 78.0%, respectively. Most cases were localized at diagnosis with only 2% metastatic at presentation. KM analysis indicated that surgical procedure type, age, tumor diameter, Charlson-Deyo Comorbidity Score, facility type, and stage were significant predictors of OS (P < 0.05). Cox proportional-hazards analysis did not reveal independent association of the aforementioned factors with OS. CONCLUSION: Primary cutaneous mucinous carcinoma has an excellent prognosis with 98% of cases being diagnosed in Stage I and Stage II. As most cases present in the eyelid, special attention should be given to surgical treatment to ensure optimal aesthetic outcomes in this sensitive region. This study represents the largest cohort of head and neck PCMC studied to date.

Time is Money: Relative Value Units and Operative Time in Otolaryngology.

OBJECTIVES: Physician compensation for procedures is typically rooted in the work relative value unit (wRVU) system. Operative time is one of the factors that goes into the determination of wRVU assignment. There should be consistency between the wRVU/hr rate, irrespective of average operative time required to perform certain procedures. We investigate if wRVU assignment for otolaryngology procedures adequately accounts for increased operative time. STUDY DESIGN: Retrospective analysis of a surgical database. METHODS: NSQIP was queried from 2015-2018 for the top 50 most frequently performed otolaryngology Current Procedural Terminology (CPT) codes completed as standalone procedures. Median operative time was determined for each CPT code, and wRVU/hr was calculated. Correlations between operative time, wRVU, and wRVU/hr were investigated using linear regression analysis. A secondary analysis using complication rate as an indicator for procedure complexity was performed to examine the relation between wRVUs and complication rates. RESULTS: Fifty CPT codes containing 64,084 patients where only one code was reported were included in this analysis. The median operative time was 84 minutes, median wRVU was 11.23, and median wRVU/hour was 7.96. Linear regression analysis demonstrated a strong positive correlation between operative time and wRVU assignment (R2 = 0.805, P < .001). Further analysis found no correlation between operative time and wRVU/hr (R2 = 0.008, P = .525). Linear regression of wRVU/hr and complication rate showed a statistically significant positive correlation (R2 = 0.113, P = .017). CONCLUSION: This analysis suggests that compensation for otolaryngology procedures is positively correlated with operative time. Surgeries where more than one code is reported could not be evaluated, thus excluding some common combination of procedures performed by otolaryngologists. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E395-E400, 2021.

Microcystic adnexal carcinoma of the head and neck: Characteristics, treatment, and survival statistics.

Studies on microcystic adnexal carcinoma (MAC) survival rates have been limited. This effort examines the association of patient demographics, treatment modalities, and tumor stage with overall survival (OS) in patients with MAC of the head and neck. All cases of MAC with primary sites of the skin of the head and neck, confirmed histologically, and diagnosed from 2004 to 2016 in the National Cancer Database, were analyzed. We utilized Kaplan-Meier and Cox proportional-hazard models to analyze the characteristics and survival outcomes of the 415 cases that met the criteria. The mean age of diagnosis was 63.8 years (SD ±15.8). Mean OS was 10.8 years with 5- and 10-year OS being 81.0% and 68.0%, respectively. Women were more frequently affected (59.0%; P < .001). Stand-alone primary site surgery was the most common treatment (81.4%): 15.9% of patients were treated with postexcision radiation therapy (RT). 18.3% were treated with RT with or without surgery and/or chemotherapy. RT was independently associated with a decreased hazard of death (HR = 0.23; P = .044). MAC of the head and neck disproportionately affects whites, is more common in women, and has the potential to metastasize. Surgical excision is the commonest treatment; our study shows benefit from judicious RT.

Analysis of Characteristics and Survival of Primary Cutaneous Adenoid Cystic Carcinoma of the Head and Neck.

BACKGROUND/OBJECTIVES: Primary cutaneous adenoid cystic carcinoma (PCACC) is a rare skin tumor. The head and neck (H&N) is the most common anatomical location. Due to limited published cases, its clinical course and management are not well understood. METHODS: The National Cancer Database (NCDB) was queried for all cases of H&N PCACC diagnosed from 2004 to 2016. Kaplan-Meier (KM) and Cox proportional hazards models were used to determine clinicopathological and treatment factors associated with survival outcomes. RESULTS: A total of 201 cases were analyzed. The average age of diagnosis was 57.7 years (± SD 15.8). There was a female predilection (57.7%; P < .05) with the most common primary site being the ear (58.2%). The average tumor size was 15.9 mm in diameter. The most common treatment was surgery alone (51.7%) with wide local excision being the common surgery performed (36.3%). 5-year and 10-year OS were 87.0% and 76.0%, respectively. A total of 65.8% of cases were localized (Stage I and II). KM analysis indicated that gender, age, insurance status, Charlson-Deyo Comobordity Score, and stage were significant predictors of OS (P < .05). Cox proportional hazards analysis revealed that patients with both private (HR 0.11, 95%CI [0.019-0.670]; P = .02) and government (HR 0.12, 95%CI [0.019-0.972]; P = .03) health insurance had a significantly decreased hazard of death than patients who were uninsured. Increasing age was associated with an increased hazard of death (HR 1.06, 95%CI [1.016-1.110]; P = .01). CONCLUSION: This study represents the largest cohort of H&N PCACC studied to date and provides important clinicopathologic information for this rare tumor. Additionally, our results emphasize the importance of health insurance as an independent predictor of survival in PCACC.

The Affordable Care Act: Implications for underserved populations with head & neck cancer.

PURPOSE: This study was done to determine the direct impact implementation of the Affordable Care Act (ACA) on patients with Head and Neck Cancer (HNCA) in states that chose to expand Medicaid compared to in states that did not, as well as assess whether this impact varied among different demographic groups. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for cases of HNCA diagnosed from 2011 to 2014. Rates of uninsured status were compared before and after Medicaid expansion and contrasted between states that did and did not expand coverage, stratified by patient and tumor characteristics, and assessed via multivariate regression. RESULTS: Overall rates of uninsured status (UR) were decreased by 63.08% in states that expanded coverage (ES) but only by 2.6% in states that did not (NS). In NS, there was an increase in proportion of black patients who were uninsured over the study period (13.7%, p = 0.077) whereas in ES, this proportion decreased by 73.3%. When stratified by primary site, patients with laryngeal cancer had the highest UR with an increase by 16.7% in NS and a decrease by 70.5% in ES. Multivariate analysis yielded predictors of uninsured status including residence in a NS, Hispanic ethnicity, and black race. CONCLUSIONS: Implementation of the ACA resulted in expanded insurance coverage for patients diagnosed with HNCA concentrated mainly in states that expanded Medicaid coverage and for patients derived from vulnerable populations, including black and Hispanic patients. In states that did not expand Medicaid, vulnerable populations were disproportionately affected.

Perceptions of Orthopaedic Volunteers and Their Local Hosts in Low- and Middle-Income Countries: Are We on the Same Page?

OBJECTIVE: Our goal was to compare the perceptions of overseas orthopaedic volunteers and their hosts in low- and middle-income countries (LMICs) regarding the role of international volunteerism. We also sought to determine if differences in perception exist between trainee and fully trained orthoapedic surgeon volunteers. METHODS: Surveys with similar multiple-choice and open-ended questions were administered to 163 Health Volunteers Overseas orthopaedic volunteers (response rate 45%) and 53 members of the host orthopaedic staff (response rate 40%). Fifty-four volunteers and 20 hosts also contributed open-ended responses. Quantitative responses were analyzed for significance using Mantel-Haenzel χ tests. Open-ended responses were coded using thematic analysis. RESULTS: Both the international volunteers and their LMIC hosts agreed that volunteers learned new skills while volunteering. Both groups believed that international volunteerism had a positive overall impact on the local practice, but hosts viewed these benefits more favorably than volunteers did. LMIC staff believed that, besides altruistic reasons, volunteers were also motivated by professional gains, diverging from volunteer responses. In open-ended responses, hosts desired longer term commitments from volunteers and had some concerns regarding volunteers' qualifications. Between volunteer trainees and fully trained surgeons, trainees were more likely to be motivated by personal benefits. CONCLUSION: Efforts must be made to further align the expectations and goals of volunteers and their hosts in LMICs. Certain measures such as predeparture orientations for volunteers and developing a more longitudinal and bidirectional experience may enhance the impact of orthopaedic volunteerism in LMICs. Further studies are needed to explore the impact of international orthopaedic volunteerism on the host population.