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The use of selectable markers (ecogpt) and selection pressures to aid in detection of poxvirus (Vaccinia, VV) recombinants has been implicated in the unintended introduction of second site mutations. We have reinvestigated the use of the helper virus system described by Scheiflinger et al. [1] and adapted by Yao and Evans [2] which produces recombinants at a high frequency in the absence of any selection, at a rate of 6–100%. Our system uses fowlpox virus (FPV) as the infectious helper virus which in infected cells provides the enzymatic apparatus for transcription and replication of a purified, transfected VV genome and for recombination with a second transfected PCR generated DNA fragment. To optimize the system, a PCR DNA fragment was generated that contained poxvirus promoter driven gfp and lacZ genes inserted within the coding sequences of the viral thymidine kinase gene. This PCR fragment was co-transfected together with VV genomic DNA. Recombinant VV was identified by plaquing the mixture on cells non-permissive for FPV and selection of green fluorescent or LacZ positive recombinant vaccinia plaques. The system was optimized using FPV permissive cells (CEF) and non-permissive cells (A549, CV-1) for both the initial infection/transfection and the subsequent selection. Up to 70% of the progeny vaccinia virus contained the gfp/LacZ insertion. In order to test for the presence of FPV/VV intertypic recombinants or other unintended mutations, recombinant wtVV (RwtVV) was regenerated from the gfp/LacZ viruses and evaluated by RFLP analysis and pathogenesis in animals. While all RwtVVs were viable in cell culture, in many of the RwtVV isolates, RFLP differences were noted and while some recombinant viruses exhibited wild type behavior in mice, a wide range of virulence indicative of unintended changes suggests that mutants created by “rescue” systems require careful analysis particularly before use for in vivo studies employing animal models.

CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Previously, we demonstrated the efficacy of CMX001 in protecting New Zealand White rabbits from mortality following intradermal infection with rabbitpox virus as a model for smallpox, monkeypox and for treatment of adverse reactions to smallpox vaccination. Here we extend these studies by exploring different dosing regimens and performing randomized, blinded, placebo-controlled studies. In addition, because rabbitpox virus can be transmitted via naturally generated aerosols (animal to animal transmission), we report on studies to test the efficacy of CMX001 in protecting rabbits from lethal rabbitpox virus disease when infection occurs by animal to animal transmission. In all cases, CMX001 treatment was initiated at the onset of observable lesions in the ears to model the use of CMX001 as a treatment for symptomatic smallpox. The results demonstrate that CMX001 is an effective treatment for symptomatic rabbitpox virus infection. The rabbitpox model has key similarities to human smallpox including an incubation period, generalized systemic disease, the occurrence of lesions which may be used as a trigger for initiating therapy, and natural animal to animal spread, making it an appropriate model.

There are mounting concerns regarding inherent bias, safety, and tendency toward misinformation of large language models (LLMs), which could have significant implications in health care. This study sought to determine whether generative artificial intelligence (AI)-based simulations of physicians making life-and-death decisions in a resource-scarce environment would demonstrate bias. Thirteen questions were developed that simulated physicians treating patients in resource-limited environments. Through a random sampling of simulated physicians using OpenAI’s generative pretrained transformer (GPT-4), physicians were tasked with choosing only 1 patient to save owing to limited resources. This simulation was repeated 1000 times per question, representing 1000 unique physicians and patients each. Patients and physicians spanned a variety of demographic characteristics. All patients had similar a priori likelihood of surviving the acute illness. Overall, simulated physicians consistently demonstrated racial, gender, age, political affiliation, and sexual orientation bias in clinical decision-making. Across all demographic characteristics, physicians most frequently favored patients with similar demographic characteristics as themselves, with most pairwise comparisons showing statistical significance (P

Surgical residents may have limited experience with grant writing even though it is an important skill for academic physicians. We describe a novel curriculum on the conduct of research and grant literacy delivered at a single otolaryngology training program over 5 years. This workshop series included preparing a draft grant and conducting a mock grant review committee. In a survey of past participants (71% response rate), 91% found the workshops useful for grant writing or reviewing, and many used or planned to use the draft grants for real grant applications. The average number of American Academy of Otolaryngology–Head and Neck Surgery Foundation CORE grants submitted and successfully funded increased among residents at this program in the 4 years after the introduction of the workshop series as compared with the 4 years before. Further improvements continue to be made to the curriculum based on resident feedback.

Abstract Competency‐based medical education (CBME) is an outcomes‐focused approach to educating medical professionals that will be central to future efforts to improve resident training in otolaryngology. The transition to CBME for otolaryngology in the United States will require the development of specialty‐specific assessments and benchmarks, the financial and administrative support for implementation, the professional development of faculty and learners, and the cooperation of all major stakeholders in graduate medical education. In this article, we describe the need for evidence‐based innovation in surgical training, the history of CBME in the United States, and the progress towards defining “entrustable professional activities” as the building blocks of assessments for CBME. We explore what such a paradigm shift in surgical education could mean for academic otolaryngologists by examining innovative educational practices in other surgical specialties and discussing foreseeable challenges in implementation for the American healthcare system.

Abstract A paired surgical educator curriculum on adult learning was designed for residents and faculty at a large otolaryngology residency program. In its first year of implementation, 12 core faculty and 20 residents attending the workshops, with positive feedback from all participants and measurable improvements in their understanding of basic terms in adult cognitive learning theory. The curriculum enabled faculty and residents to practice applying educational theories to their every day clinical teaching activities and is adaptable for use in other surgical training programs. Level of Evidence IV.

Abstract Objectives A paucity of literature exists about childbearing during otolaryngology residency. Pregnancy is a common part of many physician life cycles, but the timing of residency and the rigors of surgical training amplify the challenges. This study was designed to understand the experiences of childbearing otolaryngology residents and support them during this major life event. Unique challenges include long training, shortage of role models, combination surgical and clinical work, and higher rates of infertility. Study Design Qualitative research. IRB exempt. Setting United States. Methods To capture modern perspectives, 16 current and former otolaryngology residents that experienced pregnancy and childbirth during residency in all four geographic regions of the United States in the past 10 years were recruited to participate in individual structured qualitative interviews. Results Although there was significant training program and personal anxiety reported by childbearing otolaryngology residents, many surgeons experienced healthy pregnancies and postpartum recoveries with minimal disruption to clinical productivity and minimal disruption to their training programs. Multiple recurring themes were identified among the participants spanning the entire childbearing process: increased incidence of pregnancy complications and preterm labor, pregnancy stigma from leadership and coresidents, scheduling logistics regarding call and parental leave, and challenging transitions back to clinical work while navigating breastfeeding and childcare. Conclusion There are actional recommendations that programs can address to make childbearing during residency accessible and acceptable. Understanding these challenges is an important step to encouraging childbearing residents to prosper in academic otolaryngology, increasing the diversity at the highest levels of the field. Level of Evidence 4.

Abstract Objective Surgical education is changing in an era of new regulations and evolving training cultures. We sought to understand the factors that affect operative experiences during otolaryngology residency. Methods From December 2019 to December 2020, five otolaryngology training programs used the SIMPL OR smartphone application to evaluate residents after each operation. Residents and attendings rated the trainee's autonomy on a 4‐level Zwisch scale, performance on a 5‐level scale, and case complexity on a 3‐level scale. We examined associations between ratings of autonomy and performance with variables including postgraduate year (PGY), case complexity, gender, week of the academic year (AY), and whether multiple procedures were logged. Results 78 attendings and 92 residents logged 2984 evaluations. PGY level and week of the AY were positively associated with attending ratings of autonomy and performance (PGY3 vs. PGY2: B = 0.63, p

Abstract Objective We surveyed otolaryngology program directors (PDs) and recent otolaryngology residency graduates on the operative autonomy of graduating residents and their comfort with independent practice. Methods An anonymous survey was sent to otolaryngology PDs and recent graduates of training programs (members of the Young Physicians Section [YPS] of the American Academy of Otolaryngology‐Head and Neck Surgery Foundation). Questions were developed around the 14 key indicator procedures (KIPs) defined by the Accreditation Council for Graduate Medical Education. Results Fifty PDs (43% of PDs) and 152 recent graduates (6% of YPS members) responded. Over 90% of participating PDs felt their graduating residents were either somewhat or extremely comfortable performing 12 out of 14 KIPs. Among the 12 procedures PDs felt their graduating residents were comfortable performing, 57% to 95% of recent graduates also felt either somewhat or extremely comfortable performing them by graduation. Similarly, at least 90% of responding PDs felt their residents achieved meaningful autonomy in the last 2 months of residency prior to graduation for 11 of 14 KIPs. For these same 11 procedures, 74% to 95% of recent graduates indicated they achieved meaningful autonomy. The procedures that PDs and recent graduates felt required the most surgical assistance were ossiculoplasty/stapedectomy, rhinoplasty, and mastoidectomy. All PDs agreed or strongly agreed that graduating residents are comfortable operating and taking call as general otolaryngologists, compared to 86% and 93% of recent graduates. Conclusion Most PDs and recent graduates agree that residents are well‐prepared for general otolaryngology practice with the exception of select KIPs. Level of evidence: 4.

Abstract Objective Otolaryngology residency applicants face challenges finding accurate information about training programs. Social media platforms are not verified, and official training program websites are not standardized. Currently, the American Medical Association's Fellowship and Residency Electronic Interactive Database (FREIDA) is the most comprehensive sanctioned and verified otolaryngology residency program database. However, the exact amount of information shared by individual programs included is not presently known. Methods Herein, we analyzed the available data on all 124 otolaryngology residency programs in FREIDA to assess the completeness of the database. Results While every program listed an address, contact email, and the name of the program director, more than half of programs (n = 65, 52.4%) did not provide additional information. Most programs (70.2%) did not include a one‐paragraph program description. Conclusion Our findings suggest that while FREIDA is the only sanctioned online database for residency programs, it is inadequately populated with detailed program information. Level of Evidence N/A

Abstract Objectives To determine preference patterns for topical anesthesia in patients undergoing endoscopy pre‐coronavirus (2019 coronavirus disease [COVID‐19]) pandemic and analyze outcomes based on preference, using a decision aid format. Methods A decision aid was developed with expert and patient input. New patients presenting to subspecialty clinics over a 2‐month pre‐COVID‐19 period completed a pre‐procedure survey about their priorities, then were asked to choose between topical oxymetazoline/lidocaine spray or none. A post‐procedure outcome survey followed. Results Of 151 patients, 90.1% patients elected to have topical anesthesia. Top patient priorities were “I want the scope to be easy for the doctor” and “I want to be as comfortable as possible.” Patients who strongly wanted to avoid medication (P = .002) and bad taste (P = .003) were more likely to select no spray, whereas those who wanted to avoid pain received anesthetic (P = .011). According to the post‐procedure assessment, 95.4% of patients were satisfied or strongly satisfied their choice, and this did not correlate with anesthetic vs none. Conclusions Patient preferences are easily elicited and correlate with treatment choices. Most patients chose to have topical anesthetic and were willing to tolerate side effects; however, both patients with and without topical anesthetic were satisfied with their choices. This decision aid can be used to optimize shared decision making in the otolaryngology clinic. Given the aerosolizing potential of both spray and no spray conditions, this insight may be consequential when devising office protocols for post‐COVID‐19 practice. Level of evidence II.

Abstract Objectives Aspirin‐exacerbated respiratory disease (AERD) is a chronic respiratory condition characterized by a triad of symptoms: asthma, chronic rhinosinusitis with nasal polyposis, and a respiratory reaction to aspirin and other cyclooxygenase‐1 inhibitors, also known as nonsteroidal anti‐inflammatory drugs. The objective of this review is to provide otolaryngologists with an overview of the pathophysiology, diagnosis, and treatment of this under‐recognized condition. Data sources and methods Foundational papers on AERD were reviewed, focusing on the clinical otolaryngology and allergy/immunology literature and other high impact journals or trials. Results AERD results from increased production of pro‐inflammatory leukotrienes and a decrease in production of anti‐inflammatory prostaglandins associated with the dysregulation of multiple enzymes influencing eicosanoid metabolism. Diagnosis hinges on a high index of suspicion, careful history, and confirmatory testing for all three elements. Treatments include endoscopic sinus surgery; topical, inhaled, or oral corticosteroids; aspirin desensitization; leukotriene modifying drugs; and the new class of biologics such as dupilumab. Conclusion AERD is an under‐recognized disease associated with substantial patient‐reported morbidity. We expect rapid progress in the pathophysiological understanding of this disease and available treatments in the coming decades. Level of evidence 5

Abstract Objective Repair of cerebrospinal fluid (CSF) leaks of the lateral recess of the sphenoid (LRS) sinus can be challenging to accomplish via an endoscopic transphenoidal approach. The endoscopic transpterygoid approach can improve surgical access to the lateral recess but requires more extensive surgical dissection. We review our experience with LRS CSF leak repair via both techniques to determine whether preoperative radiologic data can help predict the most appropriate surgical approach. Methods Electronic medical records of patients with LRS CSF leaks were retrospectively reviewed at a single tertiary referral center. Radiographic measurements from preoperative computed tomography images were reviewed. Results Twenty‐two LRS CSF leaks were identified. The transphenoidal and transpterygoid approach were used in 6 (27.3%) and 16 (72.7%) cases, respectively. The mean vidian canal to foramen rotundum angle of the repairs accessed transphenoidally as compared to the transptyergoid approach were not significantly different (41.93° ±10.91, 40.72° ±19.49, respectively; P = .63). However, the mean volume of the LRS accessed by the transpterygoid approach was significantly greater compared to those accessed through the transphenoidal approach (0.97 cm3 ± 0.48, 0.39 cm3 ± 0.40, respectively; P = .04). A LRS volume of 0.400 cm3 or greater predicted the use of the transpterygoid approach with 93.3% sensitivity and 60.0% specificity. Conclusion This study demonstrated that LRS CSF leaks that necessitated repair by the transpterygoid approach, rather than transphenoidal approach, were in the context of significantly larger lateral recess. Assessment of the LRS volume is a quantifiable parameter to aid in preoperative surgical planning. Level of Evidence Level 4.

The extent to which medical management of chronic rhinosinusitis (CRS) may improve health utility value (HUV) remains unknown. We conducted a prospective pilot study to longitudinally assess HUV via the EQ-5D-5L questionnaire in patients with CRS who were receiving medical therapy but did not undergo sinus surgery. The primary study outcome was HUV at 12-month follow-up; secondary end points included HUV at baseline and 3- and 24-month follow-up. Our study enrolled 115 patients who received the following medical treatments: saline irrigations (n = 83, 72.2%), steroid sprays (n = 93, 80.9%), antihistamines (n = 64, 55.7%), steroid irrigations (n = 29, 25.2%), and oral antibiotics (n = 58, 50.4%). There was a statistically significant improvement (mean, +0.073; P = .003) in HUV at 12 months (minimum clinically important difference, 0.055) as compared with baseline. However, there was no statistically significant trend in HUV over time between baseline and 24-month follow-up ( P = .3033). These findings can inform cost-effectiveness research as new medical therapies for CRS emerge.

Abstract Background In the era of duty hour restrictions, otolaryngology residents may not gain the operative experience necessary to function autonomously by the end of training. This study quantifies residents' autonomy during key indicator cases, defined by the Accreditation Council for Graduate Medical Education. Study Design Prospective cohort study. Methods Faculty and residents at a large academic institution were surveyed on the surgical autonomy trainees should achieve for otolaryngology key indicator surgeries at each training level. Residents and faculty used the mobile application “System for Improving and Measuring Procedural Learning” (SIMPL) between December 2017 and July 2018 to log trainees' operative autonomy during cases on a validated four‐level Zwisch scale, from “show and tell” to “supervision only.” Results The study included 40 participants (23 residents and 17 attendings). The survey response rate was 83%. In surveys, residents overestimated the autonomy PGY5 residents should achieve for parotidectomy, rhinoplasty, thyroid/parathyroidectomy, and airway procedures compared with faculty (P

Objective Online resources may provide an ideal forum for expert presentation of surgical techniques. The purpose of this study was to investigate utilization patterns of a sinus surgery website, SinusVideos.com , to gain insight into the needs of viewers. Study Design Retrospective analysis. Setting Surgical teaching website. Subjects and Methods The website’s anonymized analytic database was queried from 2009 to 2014. Quantified data included user demographics, geographic location, viewing device, page visits, and time spent on the website. Results A total of 428,691 website pages were viewed during the study period. Growth in viewership was observed each successive year since the site was launched. The mean time spent viewing webpages was 96.1 seconds for desktop computer users, 98.0 for tablet users, and 103.8 for mobile users. The percentage of mobile devices used to view the site increased significantly between 2009 and 2014 (2.1% vs 25.4%, respectively; P < .0001). The website’s viewership expanded globally, with a significant increase in site views from outside North America over this same period (18.4% vs 51.7%, P < .0001). Conclusion The observed increase in global participation and mobile device usage may reflect new areas of growth for surgical education.

Abstract Objectives To describe the presentation, work-up, and management of patients with metastatic renal cell carcinoma (RCC) to the sinonasal cavity and skull base, and to describe our current treatment algorithm of endoscopic surgical resection followed by radiation therapy. Design Retrospective review of two recent cases from our institution over a 1-year period, with a relevant review of the literature. Setting A large regional tertiary care facility. Participants Consecutive cases of RCC with metastases to the sinonasal cavity presenting to our institution. Main Outcome Measures Preoperative and postoperative sinonasal outcome test (SNOT)-22 scores, duration of hospital stay, complications, and local disease control Results Patients in this series underwent preoperative embolization followed by endoscopic resection without complication. Postoperatively they were treated with radiation therapy. They experienced improvement in their SNOT-22 scores and are currently free of local disease. Conclusion Metastatic RCC to the sinonasal cavity can be safely treated with preoperative embolization followed by endoscopic surgical resection and radiation therapy, which can result in improvement in sinonasal quality of life and is a potential adjunct for local control of disease.

Evaluation of resident operative skills is challenging in the fast-paced operating room environment and limited by lack of validated assessment metrics. We describe a smartphone-based app that enables rapid assessment of operative skills. Accreditation Council for Graduate Medical Education (ACGME) otolaryngology taxonomy surgical procedures (n = 593) were uploaded to the software platform. The app was piloted over 1 month. Outcomes included (1) completion of evaluation, (2) time spent completing the evaluation, and (3) quantification of case complexity, operative autonomy, and performance. During the study, 12 of 12 procedures, corresponding to 3 paired evaluated by the resident/attending dyad. Mean ± SD time of evaluation completion was 98.0 ± 24.2 and 123.0 ± 14.0 seconds for the resident and attending, respectively. Mean time between resident and attending evaluation completion was 27.9 ± 26.8 seconds. Resident and attending scores for case complexity, operative autonomy, and performance were strongly correlated ( P < .0001). Rapid evaluation of resident intraoperative performance is feasible using smartphone-based technology.

Background Sphenoid sinus fungal balls (SSFB) are rare entities that can result in serious orbital and intracranial complications. There are few published reports of complications that result from SSFB. Objective To review the incidence of skull base erosion and orbital or intracranial complications in patients who present with SSFB. Methods A retrospective review was performed of all the patients with SSFB who were treated at the Massachusetts Eye and Ear Infirmary from 2006 to 2014. Presenting clinical data, radiology, operative reports, pathology, and postoperative course were reviewed. Results Forty-three patients with SSFB were identified. Demographic data were compared between patients with (39.5%) and those without (61.5%) skull base erosion. Two patients underwent emergent surgery for acute complications of SSFB (one patient with blindness, one patient who had a seizure). Both patients with acute complications had evidence of skull base erosion, whereas no patients with an intact skull base developed an orbital or intracranial complication (p = 0.15). All the patients were surgically managed via an endoscopic approach. Conclusion SSFBs are rare but may cause significant skull base erosion and potentially severe orbital and intracranial complications if not treated appropriately. Endoscopic sphenoidotomy is effective in treating SSFB and should be performed emergently in patients who presented with associated complications.

Abstract Background Schwannomas of the vidian canal are an extremely rare type of intracranial tumor that can have variable clinical presentations including headache, facial pain, facial muscle paralysis, decreased lacrimation, or nasal dryness. We present an atypical case of an incidentally identified asymptomatic vidian canal schwannoma. Case Description A 49-year-old woman with a history of multiple sclerosis presented for routine surveillance magnetic resonance imaging that detected an ovoid mass originating in the vidian canal. Given the unusual location of the lesion, an endoscopic endonasal biopsy was performed and confirmed the diagnosis of a vidian canal schwannoma, for which the patient chose to receive fractionated radiation therapy. Conclusion When a vidian canal tumor is identified, endoscopic endonasal biopsy can be used to confirm the diagnosis before pursuing either surgical or radiotherapy treatment. In particular, fractionated radiation therapy offers a radiobiologically safe means of delivering radiation when there is concern for late radiation-related side effects following treatment completion.