Alkynyl nicotinamides show antileukemic activity in drug-resistant acute myeloid leukemia.

Activating mutations of FLT3 contribute to deregulated hematopoietic stem and progenitor cell (HSC/Ps) growth and survival in patients with acute myeloid leukemia (AML), leading to poor overall survival. AML patients treated with investigational drugs targeting mutant FLT3, including Quizartinib and Crenolanib, develop resistance to these drugs. Development of resistance is largely due to acquisition of cooccurring mutations and activation of additional survival pathways, as well as emergence of additional FLT3 mutations. Despite the high prevalence of FLT3 mutations and their clinical significance in AML, there are few targeted therapeutic options available. We have identified 2 novel nicotinamide-based FLT3 inhibitors (HSN608 and HSN748) that target FLT3 mutations at subnanomolar concentrations and are potently effective against drug-resistant secondary mutations of FLT3. These compounds show antileukemic activity against FLT3ITD in drug-resistant AML, relapsed/refractory AML, and in AML bearing a combination of epigenetic mutations of TET2 along with FLT3ITD. We demonstrate that HSN748 outperformed the FDA-approved FLT3 inhibitor Gilteritinib in terms of inhibitory activity against FLT3ITD in vivo.

Facility Volume and Changing Facilities for Postoperative Radiotherapy in Salivary Gland Cancer.

OBJECTIVES: Changing location of postoperative radiotherapy (PORT) after treatment at a high-volume facility (HVF) is associated with worse survival in various head and neck cancers. Our study investigates this relationship in salivary gland cancer (SGC). METHODS: The 2004-2016 National Cancer Database was queried for all cases of adult SGC treated with surgery and PORT with or without adjuvant chemotherapy. Patients with multiple cancer diagnoses, metastatic disease, or unknown PORT facility were excluded. Reporting facilities with >95th percentile annual case volume were classified as HVFs, the remainder were classified low-volume facilities (LVFs). RESULTS: A total of 7885 patients met inclusion criteria, of which 418 (5.3%) were treated at an HVF. Patients treated at an HVF had higher rates clinical nodal positivity (18.2% vs. 14.0%, p < 0.001) and clinical T3/T4 (27.3% vs. 20.7%, p = 0.001) disease. Patients at HVFs changed facility for PORT at lower rates (18.9% vs. 24.5%, p = 0.009). Patients treated at an HVF had higher 5-year overall survival (5-OS) than those treated at an LVF (79.0% vs. 72.0%, p = 0.042). Patients treated at an HVF that changed PORT facility had worse 5-OS (60.8% vs. 83.2%, p < 0.001). Radiation facility change was an independent predictor of worse survival in patients treated at an HVF (HR: 8.99 [3.15-25.67], p < 0.001) but not for patients treated at a LVF (HR: 1.11 [0.98-1.25], p = 0.109). CONCLUSIONS: Patients treated at an HVF changing facility for PORT for SGC experience worse survival. Our data suggest patients treated surgically at an HVF should be counseled to continue their PORT at the same institution. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Evaluation of Rhinology Fellowship Program Websites.

Objectives: Applicants for rhinology fellowship often utilize program websites to make informed application decisions. Although the American Rhinologic Society (ARS), the professional organization of rhinologists in the United States, maintains a directory of rhinology fellowships that includes basic information for each program, the ARS discloses that the information is provided directly by program directors and may therefore be inconsistent, inaccurate, or outdated. Methods: Our study evaluates the content and comprehensiveness of rhinology fellowship program websites in 31 areas related to either clinical training, research, application process, incentives, or administrative communications. Results: Of 32 unique rhinology fellowship programs, 29 of 32 (90.6%) had websites. On average program websites included 12.1 of the 31 items analyzed (39.0%). Information related to clinical training (mean 54.2%) and research (mean 60.9%) was included more often than information related to application process (mean 50.6%), and incentives (mean 14.9%). Programs with [Formula: see text] 5 dedicated physician faculty included more items than smaller programs (15.3 vs. 11.7 items, P = 0.015). Conclusion: Websites included information on clinical training and research more often than on incentives, even though these factors are important to many applicants. Few programs detailed past or ongoing research opportunities, which if included could help applicants identify mentors with similar research interests. Most websites had less than half of factors analyzed, emphasizing need for continued improvement.

Topical Application of 5-Fluorouracil for the Treatment of Sinonasal Adenocarcinoma and Inverted Papilloma.

BACKGROUND: Sinonasal tumors represent a rare and heterogeneous group of rhinologic neoplasms. Even with advancements in surgical approaches, mortality rates of patients with sinonasal adenocarcinoma (SNAC) have not significantly improved and persistently high rates of recurrence in certain patients with inverted papilloma (IP) are seen. The use of 5-fluorouracil (5-FU) has been successfully described as an adjuvant treatment of SNAC and in the prevention of IP recurrence. OBJECTIVE: This review aims to present the current evidence on the management of SNAC and IP with topical 5-FU. METHODS: A three-author independent literature review was conducted to identify research involving the use of topical 5-FU for the treatment of SNAC and IP. A total of nine papers on the treatment of SNAC and IP were collected. RESULTS: The earliest study looking at the combination of adjuvant low-dose radiation and topical 5-FU for adenocarcinoma of the ethmoid sinus showed a 5-year survival rate of 100%. A follow-up study evaluating a similar protocol reported adjusted disease-free survival at 2, 5, and 10 years of 96%, 87%, and 74%, respectively. Similar results have been demonstrated for adjuvant 5-FU use following endoscopic resection and have even been described in the novel setting of transcutaneous 5-FU delivery following frontal trephination. Topical 5-FU has also been described in the treatment of aggressive IP. The largest case series described the use of 5-FU for eighteen cases and demonstrated only a single recurrence. CONCLUSION: The use of topical 5-FU currently represents an underutilized therapeutic modality within the treatment of rhinologic neoplasms. Available literature suggests that neoadjuvant use of topical 5-FU can improve survival and decrease recurrence for SNAC and IP. However, the small sample sizes prevent advocation for routine use in the general population and further research on 5-FU is necessary.

Retracted Publications in Otolaryngology-Head and Neck Surgery: What Mistakes Are Being Made?

Objectives: Retraction of publications is critical to maintaining scientific integrity, yet there is a lack of research on its occurrence in Otolaryngology. This study investigates characteristics, trends, and reasons for retraction of publications in otolaryngology journals. Study Design: Bibliometric analysis. Setting: PubMed, Scopus, Web of Science. Methods: A PubMed search for publications retracted during 1990 to 2022 from the top 60 journals with the subject "Otorhinolaryngology" using Scopus' CiteScore was performed. Publications were excluded if they were not in English, had missing information or did not have available abstracts or full-text. Publication and retraction dates, journal, country of origin, citation counts, journal impact factor (JIF), topic, and reason for retraction were recorded. Pearson correlation coefficients were calculated to identify potential associations in the data. Results: Fifty-three publications were included. The 2020s had the highest number of retractions per year (4.33), with publications being retracted on average, 35 months after initial publication. The most common retracted topic and country of origin were head and neck (26.4%) and China (17.0%), respectively. Most publications were retracted because of plagiarism or duplicate publication (52.8%). Mean citation count was 6.92 ± 8.32 and mean JIF was 2.80 ± 1.35. Citation count was positively associated with months until retraction (r = .432, P = .001). There was no significant correlation between months to retraction and JIF (r = .022, P = .878). Conclusion: The most cited reasons for retraction were plagiarism and duplicate publication. An understanding of the reasons for retraction can better position journals to enforce more meticulous review standards and reduce such publications from being published. Level of Evidence: Level 4.

Broadly protective bispecific antibodies that simultaneously target influenza virus hemagglutinin and neuraminidase.

Monoclonal antibodies (mAbs) are an attractive therapeutic platform for the prevention and treatment of influenza virus infection. There are two major glycoproteins on the influenza virion surface: hemagglutinin (HA), which is responsible for viral attachment and entry, and neuraminidase (NA), which mediates viral egress by enzymatically cleaving sialic acid to release budding particles from the host cell surface. Broadly neutralizing antibodies (bNAbs) that target the conserved HA central stalk region, such as CR9114, can inhibit both viral entry and egress. More recently, broadly binding mAbs that engage and inhibit the NA active site, such as 1G01, have been described to prevent viral egress. Here, we engineered bispecific antibodies (bsAbs) that combine the variable domains of CR9114 and 1G01 into a single molecule and evaluated if simultaneous targeting of two different glycoproteins improved antiviral properties in vitro and in vivo. Several CR9114/1G01 bsAbs were generated with various configurations of the two sets of the variable domains ("bsAb formats"). We found that combinations employing the addition of a single-chain variable fragment in the hinge region of an IgG scaffold had the best properties in terms of expression, stability, and binding. Further characterization of selected bsAbs showed potent neutralizing and egress-inhibiting activity. One such bsAb ("hSC_CR9114_1G01") provided higher levels of prophylactic protection from mortality and morbidity upon challenge with H1N1 than either of the parental mAbs at low dosing (1 mg/kg). These results highlight the potential use of bsAbs that simultaneously target HA and NA as new influenza immunotherapeutics. IMPORTANCE: Infection by the influenza virus remains a global health burden. The approaches utilized here to augment the activity of broadly protective influenza virus antibodies may lead to a new class of immunotherapies with enhanced activity.

Sex-Stratified Predictors of Prolonged Operative Time and Hospital Admission in Outpatient Parathyroidectomy.

Our retrospective database study investigates sex-stratified predictors of prolonged operative time (POT) and hospital admission following parathyroidectomy for primary hyperparathyroidism (PHPT). The 2016 to 2018 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) was queried for patients with PHPT undergoing parathyroidectomy. Cases analyzed were all outpatient status, arrived from home, coded as non-emergent, and elective. POT was defined by the 75th percentile. Hospital admission was defined as LOS ≥ 1 day. Univariate and multivariable binary logistic regressions were utilized. Of 7442 cases satisfying inclusion criteria, the majority were female (78.0%) and White (78.5%). Median OT (IQR) for females and males was 77 (58-108) and 81 (61-109) minutes, respectively (P = 0.003). 1965 (33.9%) females and 529 (32.3%) males required hospital admission. Independent predictors of POT included ASA class III/IV (aOR 1.342, 95% CI 1.007-1.788) and obesity (aOR 1.427, 95% CI 1.095-1.860) for males (P < 0.05). Independent predictors of hospital admission included age (aOR 1.008, 95% CI 1.002-1.014), ASA class III/IV (aOR 1.490, 95% CI 1.301-1.706), obesity (aOR 1.309, 95% CI 1.151-1.489), dyspnea (aOR 1.394, 95% CI 1.041-1.865), chronic steroid use (aOR 1.674, 95% CI 1.193-2.351), and COPD (aOR 1.534, 95% CI 1.048-2.245) for females (P < 0.05); and ASA class III/IV (aOR 1.931, 95% CI 1.483-2.516) and bleeding disorder (aOR 2.752, 95% CI 1.443-5.247) for males (P < 0.005). In conclusion, predictors of POT and hospital admission following parathyroidectomy for PHPT differed by patient sex. Identifying patients at risk for POT and hospital admission may optimize healthcare resource utilization. Level of Evidence: IV. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04444-3.

Elective Neck Dissection in cT1-4 N0M0 Head and Neck Basaloid Carcinoma.

OBJECTIVE: To investigate the survival benefit of elective neck dissection (END) over neck observation in surgically resected cT1-4 N0M0 head and neck basaloid carcinoma (HNBC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2006 to 2017 hospital-based National Cancer Database. METHODS: Patients with surgically resected cT1-4 N0M0 HNBC were selected. Linear, binary logistic, Kaplan-Meier, and Cox proportional hazards regression models were implemented. RESULTS: Of 857 patients satisfying inclusion criteria, the majority were male (77.0%) and white (88.1%) with disease of the oral cavity (21.5%) or oropharynx (42.9%) classified as high grade (76.9%) and cT1-2 (72.9%). 389 (45.4%) patients underwent END. END utilization between 2006 and 2017 increased for cT1-2 disease (33.3% vs 56.9%, R2 = .699) but remained relatively constant for cT3-4 disease (66.7% vs 57.9%, R2 = .062). One-hundred and fifteen (29.6%) ENDs detected occult nodal metastases (ONMs). The 5-year overall survival (OS) of patients undergoing neck observation and END was 65.6% and 66.8%, respectively (P = .652). END was not associated with improved OS in survival analyses stratified by patient demographics, clinicopathologic features, and adjuvant therapy. Compared with surgery alone, adjuvant radiotherapy (adjusted hazard ratio: 0.74, 95% confidence interval [CI]: 0.57-0.97, P = .031) was associated with improved OS. END (hazard ratio [HR]: 0.96, 95% CI: 0.71-1.28, P = .770) and ONM (HR: 1.12, 95% CI: 0.78-1.61, P = .551) were not associated with OS. CONCLUSION: END is performed in nearly half of patients with HNBC but is not associated with improved OS, even after stratifying survival analyses by patient demographics, clinicopathologic features, and adjuvant therapy. The rate of ONM approaching 30%, however, justifies inclusion of END in the surgical management of HNBC.

Design and characterization of protective pan-ebolavirus and pan-filovirus bispecific antibodies.

Monoclonal antibodies (mAbs) are an important class of antiviral therapeutics. MAbs are highly selective, well tolerated, and have long in vivo half-life as well as the capacity to induce immune-mediated virus clearance. Their activities can be further enhanced by integration of their variable fragments (Fvs) into bispecific antibodies (bsAbs), affording simultaneous targeting of multiple epitopes to improve potency and breadth and/or to mitigate against viral escape by a single mutation. Here, we explore a bsAb strategy for generation of pan-ebolavirus and pan-filovirus immunotherapeutics. Filoviruses, including Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV), cause severe hemorrhagic fever. Although there are two FDA-approved mAb therapies for EBOV infection, these do not extend to other filoviruses. Here, we combine Fvs from broad ebolavirus mAbs to generate novel pan-ebolavirus bsAbs that are potently neutralizing, confer protection in mice, and are resistant to viral escape. Moreover, we combine Fvs from pan-ebolavirus mAbs with those of protective MARV mAbs to generate pan-filovirus protective bsAbs. These results provide guidelines for broad antiviral bsAb design and generate new immunotherapeutic candidates.

Dry and liquid formulations of IBT-V02, a novel multi-component toxoid vaccine, are effective against Staphylococcus aureus isolates from low-to-middle income countries.

Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs) in the U.S. as well as more serious invasive diseases, including bacteremia, sepsis, endocarditis, surgical site infections, osteomyelitis, and pneumonia. These infections are exacerbated by the emergence of antibiotic-resistant clinical isolates such as methicillin-resistant S. aureus (MRSA), highlighting the need for alternatives to antibiotics to treat bacterial infections. We have previously developed a multi-component toxoid vaccine (IBT-V02) in a liquid formulation with efficacy against multiple strains of Staphylococcus aureus prevalent in the industrialized world. However, liquid vaccine formulations are not compatible with the paucity of cold chain storage infrastructure in many low-to-middle income countries (LMICs). Furthermore, whether our IBT-V02 vaccine formulations are protective against S. aureus isolates from LMICs is unknown. To overcome these limitations, we developed lyophilized and spray freeze-dried formulations of IBT-V02 vaccine and demonstrated that both formulations had comparable biophysical attributes as the liquid formulation, including similar levels of toxin neutralizing antibodies and protective efficacy against MRSA infections in murine and rabbit models. To enhance the relevancy of our findings, we then performed a multi-dimensional screen of 83 S. aureus clinical isolates from LMICs (e.g., Democratic Republic of Congo, Palestine, and Cambodia) to rationally down-select strains to test in our in vivo models based on broad expression of IBT-V02 targets (i.e., pore-forming toxins and superantigens). IBT-V02 polyclonal antisera effectively neutralized toxins produced by the S. aureus clinical isolates from LMICs. Notably, the lyophilized IBT-V02 formulation exhibited significant in vivo efficacy in various preclinical infection models against the S. aureus clinical isolates from LMICs, which was comparable to our liquid formulation. Collectively, our findings suggested that lyophilization is an effective alternative to liquid vaccine formulations of our IBT-V02 vaccine against S. aureus infections, which has important implications for protection from S. aureus isolates from LMICs.

Smoking impacts outcomes in transcervical Zenker's diverticulectomy.

PURPOSE: There is sparse literature discussing the impact of smoking on postoperative outcomes following surgical treatment of Zenker's diverticulum. In this study, we seek to characterize differences in the management and outcomes of open Zenker's diverticulectomy based on patient smoking status. METHODS AND MATERIALS: This paper is a retrospective cohort review. The 2005-2018 American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) database was queried for patients undergoing open Zenker's diverticulectomy. Chi-square and multivariable logistic regression were performed to determine statistical associations between postoperative outcomes and smoking status. RESULTS: Of the 715 identified patients, 70 (9.8 %) were smokers and 645 (91.2 %) were non-smokers. Smokers were younger than non-smokers (mean 63.9 vs. 71.7 years, p < 0.001) and more likely to have a prolonged operative time (20.0 % vs. 11.6 %, p = 0.044). On multivariable regression analysis controlling for demographics and comorbidities, smokers had greater odds than non-smokers for developing overall postoperative complications (OR: 2.776, p = 0.013), surgical infections (OR: 3.194, p = 0.039), medical complications (OR: 3.563, p = 0.011), and medical infections (OR: 1.247, p = 0.016). Smokers also had greater odds for requiring ventilation/intubation (OR: 8.508, p = 0.025) and having a prolonged postoperative stay (OR: 2.425, p = 0.030). CONCLUSION: In a cohort of patients undergoing transcervical Zenker's diverticulectomy, smokers are at increased risk for overall complications, medical complications, medical infections, surgical infections, prolonged postoperative stay, and ventilation/intubation.

Extranodal extension in laryngeal squamous cell carcinoma.

Objective: Although large retrospective database studies have associated extranodal extension (ENE) with worse survival in several head and neck cancers, the prognostic significance of ENE in laryngeal squamous cell carcinoma (LSCC) remains unclear. Our study examines ENE and overall survival (OS) in LSCC. Methods: The 2006-2017 National Cancer Database was queried for patients with LSCC undergoing surgical resection and neck dissection, with or without adjuvant therapy. Kaplan-Meier and multivariable Cox regression survival analyses were implemented to identify the independent impacts of pathologic nodal (pN) classification and ENE on OS. Results: Of 4208 patients satisfying inclusion criteria, 2343 (55.7%) were pN0/ENE-negative, 1059 (25.2%) were pN1-2/ENE-negative, and 806 (19.2%) were pN1-2/ENE-positive. The 5-year OS of pN0/ENE-negative, pN1-2/ENE-negative, and pN1-2/ENE-positive patients was 62.8%, 56.7%, and 32.9%, respectively (p < .001). Among pN1-2/ENE-positive patients undergoing no adjuvant therapy, adjuvant radiotherapy alone, and adjuvant chemoradiotherapy, 5-year OS was 24.1%, 30.7%, and 36.7%, respectively (p < .001). After adjusting for patient demographics, clinicopathologic features, and adjuvant therapy, ENE-positivity was associated with worse OS than ENE-negativity (adjusted hazard ratio [aHR] 1.76, 95% confidence interval [CI] 1.53-2.02, p < .001). pN1/ENE-positivity (aHR 1.82, 95% CI 1.31-2.54) and pN2/ENE-positivity (aHR 1.89, 95% CI 1.49-2.40) were associated with worse OS than pN1/ENE-negativity (p < .001). Microscopic (aHR 1.83, 95% CI 1.54-2.18) and macroscopic ENE-positivity (aHR 1.75, 95% 1.35-2.26) were associated with worse OS than ENE-negativity (p < .001). Conclusion: ENE-positivity has prognostic significance in LSCC and is associated with worse OS than ENE-negativity. pN classification did not have prognostic significance independent of ENE. ENE should be carefully considered when determining the prognosis of LSCC and selecting adjuvant therapy. Level of Evidence: 4.

Managing the low carbon transition pathways through solid waste electricity.

The potential of solid waste as an energy source is clear, owing to its wide availability and renewable properties, which provide a critical answer for energy security. This can be especially effective in reducing the environmental impact of fossil fuels. Countries that rely heavily on coal should examine alternatives such as electricity from solid waste to provide a constant energy supply while also contributing to atmospheric restoration. In this regards, Low Emissions Analysis Platform (LEAP) is used for simulation the entire energy system in Pakistan and forecasted its capital cost and future CO2 emissions in relation to the use of renewable and fossil fuel resources under the different growth rates of solid waste projects like 20%, 30% and 40% for the study period 2023-2053. The results revealed that, 1402.97 TWh units of energy are generated to meet the total energy demand of 1193.93 TWh until 2053. The share of solid waste based electricity in total energy mix is increasing from a mere 0.81% in 2023 to around 9.44% by 2053 under the 20% growth rate, which then increase to 39.67% by 2053 under the 30% growth rate and further increases to 78.33% by 2053 under the 40% growth rate. It is suggested that 40% growth rate for solid waste based electricity projects is suitable for Pakistan until 2053 because under this condition, renewable sources contributes 95.2% and fossil fuels contributed 4.47% in the total energy mix of Pakistan. Hence, CO2 emissions are reduced from 148.26 million metric tons to 35.46 million metric tons until 2053 but capital cost is increased from 13.23 b$ in 2023 to 363.11 b$ by 2053.

Surgical Resection Improves Overall Survival in cT4b Major Salivary Gland Cancer.

OBJECTIVE: To compare surgical and nonsurgical definitive treatment in cT4b major salivary gland cancer (MSGC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2004 to 2019 National Cancer Database. METHODS: The NCDB was queried for patients with cT4b MSGC (N = 976). Patients undergoing definitive treatment with (1) surgical resection + adjuvant therapy, (2) radiotherapy (RT) alone, or (3) chemoradiotherapy (CRT) were included in Kaplan-Meier and Cox survival analyses. RESULTS: Of 219 patients undergoing definitive treatment, 148 (67.6%) underwent surgical resection + adjuvant therapy and 71 (32.4%) underwent RT or CRT. There were no documented mortalities within 90 days of surgical resection. Tumor diameter and nodal metastasis were associated with decreased odds of undergoing definitive treatment (P < 0.025). Patients with positive surgical margins (PSM) had higher 5-year overall survival (OS) than those undergoing definitive RT or CRT (48.5% vs 30.1%, P = 0.018) and similar 5-year OS as those with negative margins (48.5% vs 54.0%, P = 0.205). Surgical resection + adjuvant therapy (adjusted hazard ratio: 0.55, 95% confidence interval [CI]: 0.37-0.84) was associated with higher OS than definitive RT or CRT (P < 0.025). A separate cohort of 961 patients with cT4a tumors undergoing surgical resection + adjuvant therapy was created; cT4a and cT4b (hazard ratio: 1.02, 95% CI: 0.80-1.29, P = 0.896) tumors had similar OS. CONCLUSION: A minority of patients with cT4b MSGC undergo definitive treatment. Surgical resection + adjuvant therapy was safe and associated with higher OS than definitive RT or CRT, despite high rate of PSM. In the absence of clinical trial data, appropriately selected patients with cT4b MSGC may benefit from surgical resection.

Patterns and Trends in Adjuvant Therapy for Major Salivary Gland Cancer.

OBJECTIVE: To investigate adjuvant therapy indications, utilization, and associated survival disparities in major salivary gland cancer (MSGC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2006 to 2017 National Cancer Database. METHODS: Patients with surgically resected MSGC were included (N = 11,398). pT3-4 classification, pN2-3 classification, lymphovascular invasion, pathologic extranodal extension (pENE), and positive surgical margin (PSM) were considered indications for adjuvant radiotherapy (aRT). pENE and PSM were considered possible indications for adjuvant chemotherapy. Multivariable logistic and Cox regression models were implemented. RESULTS: Among 6694 patients with ≥ $\ge $ 1 indication for aRT, 1906 (28.5%) received no further treatment and missed aRT. Age, race, comorbidity status, facility type, and distance to reporting facility were associated with missed aRT (P < .025). Among 4003 patients with ≥1 possible indication for adjuvant chemoradiotherapy (aCRT), 914 (22.8%) received aCRT. Patients with pENE only (38.5%) and both pENE and PSM (44.0%) received aCRT more frequently than those with PSM only (17.0%) (P < .001). Academic facility was associated with aCRT utilization (P < .05). aCRT utilization increased between 2006 and 2017 in both academic (14.8% vs 23.9%) and nonacademic (8.8% vs 13.5%) facilities (P < .05). Among 2691 patients with ≥1 indication for aRT alone, missed aRT portended poorer OS (hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.28-2.03, P < .001). Among 4003 patients with ≥1 possible indication for aCRT, aRT alone (HR: 1.02, 95% CI: 0.89-1.18, P = .780) and aCRT were associated with similar OS. CONCLUSION: Missed aRT in MSGC occurs frequently and portends poorer OS. Further studies clarifying indications for aCRT are required.

Factors Associated with Research Productivity and National Institutes of Health Funding in Academic Otology.

OBJECTIVES: Bibliometrics, such as the Hirsch index (h-index) and the more recently developed relative citation ratio (RCR), are utilized to evaluate research productivity. Our study evaluates demographics, research productivity, and National Institutes of Health (NIH) funding in academic otology. METHODS: Academic otologists were identified, and their demographics were collected using institutional faculty profiles (N = 265). Funding data were obtained using the NIH Research Portfolio Online Reporting Tools Expenditures and Reports Database. The h-index was calculated using Scopus and mean (m-RCR) and weighted RCR (w-RCR) were calculated using the NIH iCite tool. RESULTS: H-index (aOR 1.18, 95% CI 1.10-1.27, p < 0.001), but not m-RCR (aOR 1.50, 95% CI 0.97-2.31, p = 0.069) or w-RCR (aOR 1.00, 95% CI 0.99-1.00, p = 0.231), was associated with receiving NIH funding. Men had greater h-index (16 vs. 9, p < 0.001) and w-RCR (51.8 vs. 23.0, p < 0.001), but not m-RCR (1.3 vs. 1.3, p = 0.269) than women. Higher academic rank was associated with greater h-index and w-RCR (p < 0.001). Among assistant professors, men had greater h-index than women (9.0 vs. 8.0, p = 0.025). At career duration 11-20 years, men had greater h-index (14.0 vs. 8.0, p = 0.009) and w-RCR (52.7 vs. 25.8, p = 0.022) than women. CONCLUSION: The h-index has a strong relationship with NIH funding in academic otology. Similar h-index, m-RCR, and w-RCR between men and women across most academic ranks and career durations suggests production of similarly impactful research. The m-RCR may correct some deficiencies of time-dependent bibliometrics and its consideration in academic promotion and research funding allocation may promote representation of women in otology. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:3786-3794, 2024.

Production and Purification of Filovirus Glycoproteins.

Ebola (EBOV) and Marburg (MARV) viruses cause hemorrhagic fever disease in humans and non-human primates (NHPs) with case-fatality rates as high as 90%. The 2013-2016 Ebola virus disease (EVD) outbreak led to over 28,000 cases and 11,000 deaths and took an enormous toll on the economy of West African nations, in the absence of any vaccine or therapeutic options. Like EVD, there have been at least 6 outbreaks of MVD with ~88% case-fatality and the most recent cases emerging in Equatorial Guinea in February 2023. These outbreaks have spurred an unprecedented global effort to develop vaccines and therapeutics for EVD and MVD and led to an approved vaccine (ERVEBO™) and two monoclonal antibody (mAb) therapeutics for EBOV. In contrast to EVD, therapeutic options against Marburg and another Ebola-relative Sudan virus (SUDV) are lacking. The filovirus glycoprotein (GP), which mediates host cell entry and fusion, is the primary target of neutralizing antibodies. In addition to its pre- and post-fusion trimeric states, the protein is highly glycosylated making production of pure and homogeneous trimers on a large scale, a requirement for subunit vaccine development, a challenge. In efforts to address this roadblock, we have developed a unique combination of structure-based design, selection of expression system, and purification methods to produce uniform and stable EBOV and MARV GP trimers at scales appropriate for vaccine production.

Choice of Adjuvant Radiotherapy Facility in Major Salivary Gland Cancer.

OBJECTIVE: Undergoing surgery and adjuvant radiotherapy (aRT) at the same facility has been associated with higher overall survival (OS) in head and neck squamous cell carcinoma. Our study investigates whether undergoing surgery and aRT at the same academic facility is associated with higher OS in major salivary gland cancer (MSGC). METHODS: The 2006-2018 National Cancer Database was queried for patients with MSGC undergoing surgery at an academic facility and then aRT. Multivariable binary logistic and Cox proportional hazards regression models were implemented. RESULTS: Of 2801 patients satisfying inclusion criteria, 2130 (76.0%) underwent surgery and aRT at the same academic facility. Residence in a less populated area (adjusted odds ratio [aOR] 1.69, 95% confidence interval [CI] 1.16-2.45), treatment without adjuvant chemotherapy (aOR 1.97, 95% CI 1.41-2.76), and aRT duration (aOR 1.02, 95% CI 1.01-1.04) were associated with undergoing surgery and aRT at different facilities on multivariable logistic regression adjusting for patient demographics, clinicopathologic features, and adjuvant therapy (p < 0.01). Five-year OS was higher in patients undergoing surgery and aRT at the same academic facility (68.8% vs. 61.9%, p < 0.001). Undergoing surgery and aRT at different facilities remained associated with worse OS on multivariable Cox regression (aHR 1.41, 95% CI 1.10-1.81, p = 0.007). CONCLUSION: Undergoing surgery and aRT at the same academic facility is associated with higher OS in MSGC. Although undergoing surgery and aRT at the same academic facility is impractical for all patients, academic physicians should consider same-facility treatment for complex patients who would most benefit from clear multidisciplinary communication. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3620-3632, 2024.