The Tobacco Industry Has No Business Funding Continuing Medical Education.

This Viewpoint explores tobacco industry­funded continuing medical education and concerns regarding the precedents this funding sets in relation to commercial bias and influence and conflicts of interest.

Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs.

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.

Flavour spectrum of the Puff family of disposable e-cigarettes.

BACKGROUND: In January 2020, the US Food and Drug Administration prohibited the sale of flavours (except for menthol and tobacco) in prefilled pod devices such as JUUL to decrease youth vaping. Excluded from the prohibition were disposable devices. OBJECTIVES: To determine the scope and scale of flavours marketed by Puff Bar, a leading disposable brand, and related products. METHODS: Disposable e-cigarette flavours were identified via online searches encompassing vendor websites, wholesale distributors, manufacturers (eg, made-in-china.com), and social media channel, Instagram, between June and August 2020. RESULTS: The 'Puff' brand name and iconic cloud logo appear on a variety of products of differing sizes and nicotine e-liquid volumes. Among Puff Bar and its copycats (Puff-a-Likes), 139 flavours were identified. Fruit flavours predominated comprising 82.2% of the flavour varieties (fruit 50%, fruit and menthol/mint 23.6%, and fruity drinks 8.6%). A prevalent new flavour category which combines fruit with menthol/mint (Ice) was offered in 33 varieties such as Lychee Ice, Lush Ice and Banana Ice. Disposable e-cigarette brands are undertaking measures to escape tobacco regulation (eg, non-tobacco-sourced nicotine) and flavour limitations via post-market flavour additions to unflavoured nicotine e-liquid. CONCLUSIONS: The proliferation of flavoured disposable e-cigarette products, many of which are designed to emulate popular pod devices, illustrates that narrowly limited flavour regulations covering only a single category are destined to fail. To be effective in youth protection, flavour regulations need to apply to all recreational nicotine-containing products and need to include measures to counter post-market flavour addition.

Combined transpetrosal approach for giant petroclival meningioma: 2-dimensional operative video.

Petroclival meningiomas are extremally challenging lesions due to their deep location and close relation to critical neurovascular structures. Several approaches have been described to achieve gross-total resection with low morbidity and mortality. In this 2-dimensional operative video, the authors show a simultaneous combined transpetrosal approach. The patient is a 44-year-old woman with an 8-month history of gait imbalance with evidence of a giant petroclival meningioma on neuroimaging. She underwent a combined middle fossa approach with anterior petrosectomy and retrosigmoid/retrolabyrinthine approach to achieve gross-total tumor resection. The postoperative course was characterized by trigeminal neuralgia, and neuroimaging showed gross-total resection of the tumor. The video can be found here: https://stream.cadmore.media/r10.3171/2022.1.FOCVID21248.

Early phase clinical studies of AR-42, a histone deacetylase inhibitor, for neurofibromatosis type 2-associated vestibular schwannomas and meningiomas.

OBJECTIVES: Two pilot studies of AR-42, a pan-histone deacetylase inhibitor, in human neurofibromatosis type 2 (NF2), vestibular schwannomas (VS), and meningiomas are presented. Primary endpoints included safety, and intra-tumoral pharmacokinetics (PK) and pharmacodynamics (PD). METHODS: Pilot 1 is a subset analysis of a phase 1 study of AR-42 in solid tumors, which included NF2 or sporadic meningiomas. Tumor volumes and treatment-related adverse events (TRAEs) are reported (NCT01129193).Pilot 2 is a phase 0 surgical study of AR-42 assessing intra-tumoral PK and PD. AR-42 was administered for 3 weeks pre-operatively. Plasma and tumor drug concentrations and p-AKT expression were measured (NCT02282917). RESULTS: Pilot 1: Five patients with NF2 and two with sporadic meningiomas experienced a similar incidence of TRAEs to the overall phase I trial. The six evaluable patients had 15 tumors (8 VS, 7 meningiomas). On AR-42, tumor volume increased in six, remained stable in eight, and decreased in one tumor. The annual percent growth rate decreased in eight, remained stable in three, and increased in four tumors. Pilot 2: Four patients with sporadic VS and one patient with meningioma experienced no grade 3/4 toxicities. Expression of p-AKT decreased in three of four VS. All tumors had higher AR-42 concentrations than plasma. CONCLUSIONS: AR-42 is safe. Tumor volumes showed a mixed response, but most slowed growth. On a 40-mg regimen, drug concentrated in tumors and growth pathways were suppressed in most tumors, suggesting this may be a well-tolerated and effective dose. A phase 2 study of AR-42 for NF2-associated tumors appears warranted. LEVEL OF EVIDENCE: 1b, 4.

Tumor Control Following Stereotactic Radiosurgery in Patients with Vestibular Schwannomas - A Retrospective Cohort Study.

BACKGROUND: To better counsel vestibular schwannoma patients, it is necessary to understand the tumor control rates of stereotactic radiosurgery (SRS). OBJECTIVES: To determine tumor control rates, factors determining control and complication rates following SRS. METHODS: Tertiary hospital retrospective cohort. RESULTS: 579 tumors (576 patients) were treated with SRS. 477 tumors (474 patients, 82%) had ≥1 year follow up and 60% (344) ≥3 years follow up. 88% of tumors had primary SRS and 6.7% salvage SRS. Median follow up time was 4.6 years. At 3 years, the tumor control rate of primary SRS was 89% (258 of 290) in sporadic tumors compared to 43% in Neurofibromatosis type II (3 of 17) (p < 0.01). Our bivariable survival data analysis showed that Neurofibromatosis type II, documented pre-SRS growth, tumor measured by maximum dimension, SRS given as nonprimary treatment increased hazard of failure to control. There was one case of malignancy and another of rapid change following intra-tumoral hemorrhage. For tumors undergoing surgical salvage (25 of 59), 56% had a total or near-total resection, 16% had postoperative CSF leak, with 12% new facial paralysis (House-Brackmann grade VI) and worsening of facial nerve outcomes (House-Brackmann grade worse in 59% at 12 mo). CONCLUSIONS: Control of vestibular schwannoma after primary SRS occurs in the large majority. Salvage surgical treatment was notable for higher rates of postoperative complications compared to primary surgery reported in the literature.

The risk of ergonomic injury across surgical specialties.

Lack of ergonomic training and poor ergonomic habits during the operation leads to musculoskeletal pain and affects the surgeon's life outside of work. The objective of the study was to evaluate the severity of ergonomic hazards in the surgical profession across a wide range of surgical subspecialties. We conducted intraoperative observations using Rapid Entire Body Assessment (REBA) score system to identify ergonomic hazards. Additionally, each of the ten surgical subspecialty departments were sent an optional 14 question survey which evaluated ergonomic practice, environmental infrastructure, and prior ergonomic training or education. A total of 91 surgeons received intraoperative observation and were evaluated on the REBA scale with a minimum score of 0 (low ergonomic risk <3) and a maximum score of 10 (high ergonomic risk 8-10). And a total of 389 surgeons received the survey and 167 (43%) surgeons responded. Of the respondents, 69.7% reported suffering from musculoskeletal pain. Furthermore, 54.9% of the surgeons reported suffering from the highest level of pain when standing during surgery, while only 14.4% experienced pain when sitting. Importantly, 47.7% stated the pain impacted their work, while 59.5% reported pain affecting quality of life outside of work. Only 23.8% of surgeons had any prior ergonomic education. Both our subjective and objective data suggest that pain and disability induced by poor ergonomics are widespread among the surgical community and confirm that surgeons rarely receive ergonomic training. Intraoperative observational findings identified that the majority of observed surgeons displayed poor posture, particularly a poor cervical angle and use of ergonomic setups, both of which increase ergonomic risk hazards. This data supports the need for a comprehensive ergonomic interventional program for the surgical team and offers potential targets for future intervention.

Stereotactic Radiosurgery for Vestibular Schwannoma Outcomes in Patients With Perfect Word Recognition-A Retrospective Cohort Study.

OBJECTIVES: To investigate tumor control rate and hearing outcomes following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) cases with perfect (100%) word recognition score (WRS). STUDY DESIGN: A retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Inclusion criteria were receiving primary SRS, a pretreatment WRS of 100%, and availability of both pre- and posttreatment audiometric data for evaluation. INTERVENTION: SRS delivered by Cyberknife. MAIN OUTCOME MEASURES: Tumor growth rates and audiological outcomes after SRS. RESULTS: The cohort consisted of 139 patients, with more than 1-year follow-up (mean 6.1 yrs). SRS tumor control rate was 87% for the whole cohort. Growth before SRS was documented in 24% (n = 34 of 139). The proportion of sporadic VS cases who maintained hearing (decline <10 dB of pure-tone audiometry or <20% of WRS) at 3 years was 50%, at 5 years was 45%, and at 10 years was 42%. In multivariate analysis, increased age was found to be predictive of increased hearing loss (p = 0.03), while the following factors were shown not to be significant: sex (p = 0.5), tumor size (p = 0.2), pre-SRS tumor growth (p = 0.5), and target volume (p = 0.42). CONCLUSIONS: Among patients with VS who had perfect WRS and underwent SRS, the overall tumor control rate was 87% comparable to observation. Hearing maintenance and preservation of "serviceable" hearing rates after 5 years in VS patients with perfect WRS treated by SRS is less than that when comparing to similar observation cohorts. Given this finding we do not advocate using SRS to preserve hearing, over observation, in tumors with perfect WRS.

Promoting Tobacco Use Among Students: The U.S. Smokeless Tobacco Company College Marketing Program.

OBJECTIVES/HYPOTHESIS: From the 1970s-1990s the U.S. Smokeless Tobacco Company (USST) conducted aggressive campaigns to solicit college students to buy their smokeless tobacco (ST) products. The scope, scale, methods, and impact of this youth marketing campaign have yet to be analyzed in the academic literature. STUDY DESIGN: Historical research study. METHODS: Internal industry documents describing the USST campaigns were obtained via the University of California, San Francisco's repository of tobacco company records. Marketing materials were obtained from Stanford University's Research Into the Impact of Tobacco Advertising (SRITA) collection of 657 USST advertisements. RESULTS: USST's College Marketing Program (1978-mid 1980s) sponsored events in some 350 campuses and hired student representatives in at least 175 colleges and universities across America. College representatives were trained to provide free samples to fellow students. Over a typical school year approximately a quarter million Happy Days, Skoal, and Skoal Bandits samples were handed out to undergraduates. USST paid their student representatives well and offered them a variety of incentives based upon sales growth. During the 1990s, USST's Skoal Music program engaged students on campuses and at "spring break" venues such as Daytona Beach. CONCLUSIONS: Targeting of college students on campus was a common tobacco industry practice between the 1940s and early 1960s. From the 1970s through 1990s USST resurrected the method and pursued it with vigor including: distribution of free samples; sponsored events and concerts, branded intramural teams; visits by sports celebrities; logo wearables and merchandise; contests and incentives; and displays and promotions in stores on and surrounding campuses. Laryngoscope, 131:E1860-E1872, 2021.

American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Foundation Guide to Enhance Otologic and Neurotologic Care During the COVID-19 Pandemic.

: This combined American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Surgery Foundation document aims to provide guidance during the coronavirus disease of 2019 (COVID-19) on 1) "priority" of care for otologic and neurotologic patients in the office and operating room, and 2) optimal utilization of personal protective equipment. Given the paucity of evidence to inform otologic and neurotologic best practices during COVID-19, the recommendations herein are based on relevant peer-reviewed articles, the Centers for Disease Control and Prevention COVID-19 guidelines, United States and international hospital policies, and expert opinion. The suggestions presented here are not meant to be definitive, and best practices will undoubtedly change with increasing knowledge and high-quality data related to COVID-19. Interpretation of this guidance document is dependent on local factors including prevalence of COVID-19 in the surgeons' local community. This is not intended to set a standard of care, and should not supersede the clinician's best judgement when managing specific clinical concerns and/or regional conditions.Access to otologic and neurotologic care during and after the COVID-19 pandemic is dependent upon adequate protection of physicians, audiologists, and ancillary support staff. Otolaryngologists and associated staff are at high risk for COVID-19 disease transmission based on close contact with mucosal surfaces of the upper aerodigestive tract during diagnostic evaluation and therapeutic procedures. While many otologic and neurotologic conditions are not imminently life threatening, they have a major impact on communication, daily functioning, and quality of life. In addition, progression of disease and delay in treatment can result in cranial nerve deficits, intracranial and life-threatening complications, and/or irreversible consequences. In this regard, many otologic and neurotologic conditions should rightfully be considered "urgent," and almost all require timely attention to permit optimal outcomes. It is reasonable to proceed with otologic and neurotologic clinic visits and operative cases based on input from expert opinion of otologic care providers, clinic/hospital administration, infection prevention and control specialists, and local and state public health leaders. Significant regional variations in COVID-19 prevalence exist; therefore, physicians working with local municipalities are best suited to make determinations on the appropriateness and timing of otologic and neurotologic care.

Prevalence and significance of cranial nerve imaging abnormalities in patients with hereditary neuropathies: Clinical implications at the skull base.

OBJECTIVE: To estimate the prevalence and significance of cranial nerve (CN) imaging abnormalities in patients with hereditary neuropathy and discuss clinical implications. METHODS: We retrospectively analyzed data from patients at four tertiary academic medical centers with hereditary neuropathy diagnoses who had undergone gadolinium-enhanced magnetic resonance imaging (MRI) of the brain or skull base between 2004 and 2018. MRI scans, as well as computed tomography imaging when available, were reviewed and bivariable analysis was performed to identify predictors of CN abnormalities on imaging. RESULTS: Among 39 patients meeting study criteria, 11 had clinical CN deficits (28%) and 8 had CN abnormalities on imaging (21%). Of the patients with CN abnormalities on imaging, half had CN deficits (4/8) and only a quarter had imaging abnormalities of the CNs with the deficits (2/8). Imaging abnormalities were found in varied CNs, including CNs III, V, VII, and the VII/VIII complex in the internal auditory canal. MRI obtained for the purpose of evaluating CN deficits had a statistically significant increased likelihood of containing CN imaging abnormalities. However, CN deficits themselves were not predictive of imaging abnormalities. CONCLUSION: Thickening and enhancement of CNs on MRI may be found in approximately 1/5 of patients with hereditary neuropathies and are inconsistently associated with clinical deficits. These imaging findings should not be mistaken for neoplastic and infectious processes as they may be manifestations of the patients' underlying genetic neuropathy. LEVEL OF EVIDENCE: 4.

A multimodal assessment of tobacco use on a university campus and support for adopting a comprehensive tobacco-free policy.

Many college campuses now prohibit tobacco use. At a private U.S. university, the current study assessed cigarette and e-cigarette use and characterized the climate for adopting a comprehensive tobacco-free policy. Data were gathered January-August 2018 via an: environmental scan; cigarette-urn audit; and representative surveys with campus community members. Despite low prevalence of tobacco (0.5%-8%) and e-cigarette use (0.9%-6%) among all groups, campus cigarette clean-up costs exceeded $114,000 for an estimated >1 million butts left on campus annually. A majority of respondents (63% of N = 2218) favored a campus-wide tobacco-free policy, 16% opposed, and 21% abstained. Most respondents endorsed benefits of supporting health (93%), ensuring tobacco-free air to breathe (92%), reducing litter (88%), preventing tobacco use (84%) and fires (83%), and helping tobacco users quit (65%). Identified challenges included policy enforcement (69%) and stigmatization of smoking (57%); 30% viewed a policy as compromising personal freedoms. In a model explaining 35% of variance in policy support, those more likely to favor comprehensive tobacco-free campus policy were Asian respondents; diagnosed with asthma; exposed to secondhand smoke on campus; who viewed campus cigarette butt litter as problematic; and identified health, prevention, and cessation benefits of a tobacco-free campus. Those less likely in favor were students, those who smoke, and those perceiving impingement upon personal freedoms, stigmatization, and broader (slippery slope) implications. Findings indicate low tobacco use prevalence among the campus community, yet a large volume of butt litter and high tobacco clean-up costs. Predictors of policy support can inform campus outreach efforts.

Outcomes of Overlapping Surgery in Otolaryngology.

OBJECTIVE: To compare outcomes in otolaryngology between overlapping and nonoverlapping surgeries. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. SUBJECTS AND METHODS: All patients undergoing otolaryngologic procedures at Stanford University Hospital between January 2009 and June 2016 were included (n = 13,479). Cases were divided into 2 cohorts: overlapping (n = 1806, 13.4%) vs nonoverlapping (n = 11,673, 86.6%). Variables reviewed were type of operation performed, multidisciplinary team involvement, complications, reoperations, readmissions, and deaths. RESULTS: The total complication rate over 7.5 years studied was 3.3% (n = 450). Complication rates were lower for overlapping cases (0.77%) compared to nonoverlapping cases (3.73%) with an odds ratio of 0.2014, which was statistically significant (P < .0001). When examined by subspecialty, the complication rate for rhinology and endoscopic skull base procedures was approximately 10 times lower when overlapping (0.30%) was compared to nonoverlapping (3.15%), with an odds ratio of 0.094 (P = .0001). There was no difference in complication rates for other surgical subspecialties. There were no deaths associated with overlapping surgery. The rate of major complications requiring reoperation was similarly lower for overlapping procedures (0.276%) compared to nonoverlapping procedures (1.35%) with an odds ratio of 0.2023 (P = .0004). Readmission rates were lower for overlapping cases (0.49%) when compared to nonoverlapping cases (1.09%), with an odds ratio of 0.4553 (P = .0229). CONCLUSIONS: Patients undergoing overlapping surgery had lower overall complication rates, lower reoperation rates, lower readmission rates, and no mortalities. The institutional experience presented provides evidence that with appropriate patient and case selection, otolaryngologists may safely perform overlapping surgery without increased risk of adverse patient outcomes.