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There is mounting evidence that microbes residing in the human intestine contribute to diverse alcohol-associated liver diseases (ALD) including the most deadly form known as alcohol-associated hepatitis (AH). However, mechanisms by which gut microbes synergize with excessive alcohol intake to promote liver injury are poorly understood. Furthermore, whether drugs that selectively target gut microbial metabolism can improve ALD has never been tested. We used liquid chromatography tandem mass spectrometry to quantify the levels of microbe and host choline co-metabolites in healthy controls and AH patients, finding elevated levels of the microbial metabolite trimethylamine (TMA) in AH. In subsequent studies, we treated mice with non-lethal bacterial choline TMA lyase (CutC/D) inhibitors to blunt gut microbe-dependent production of TMA in the context of chronic ethanol administration. Indices of liver injury were quantified by complementary RNA sequencing, biochemical, and histological approaches. In addition, we examined the impact of ethanol consumption and TMA lyase inhibition on gut microbiome structure via 16S rRNA sequencing. We show the gut microbial choline metabolite TMA is elevated in AH patients and correlates with reduced hepatic expression of the TMA oxygenase flavin-containing monooxygenase 3 (FMO3). Provocatively, we find that small molecule inhibition of gut microbial CutC/D activity protects mice from ethanol-induced liver injury. CutC/D inhibitor-driven improvement in ethanol-induced liver injury is associated with distinct reorganization of the gut microbiome and host liver transcriptome. The microbial metabolite TMA is elevated in patients with AH, and inhibition of TMA production from gut microbes can protect mice from ethanol-induced liver injury.

Obesity has repeatedly been linked to reorganization of the gut microbiome, yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here, we show that gut microbe-targeted inhibition of the trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity (DIO) or leptin deficiency (Lepob/ob). Small molecule inhibition of the gut microbial enzyme choline TMA-lyase (CutC) does not reduce food intake but is instead associated with alterations in the gut microbiome, improvement in glucose tolerance, and enhanced energy expenditure. We also show that gut microbial CutC inhibition is associated with reorganization of host circadian control of both phosphatidylcholine and energy metabolism. This study underscores the relationship between microbe and host metabolism and provides evidence that gut microbe-derived trimethylamine (TMA) is a key regulator of the host circadian clock. This work also demonstrates that gut microbe-targeted enzyme inhibitors have potential as anti-obesity therapeutics.

Exposure to some environmental pollutants can have potent endocrine-disrupting effects, thereby promoting hormone imbalance and cardiometabolic diseases such as non-alcoholic fatty liver disease (NAFLD), diabetes, and cardiorenal diseases. Recent evidence also suggests that many environmental pollutants can reorganize the gut microbiome to potentially impact these diverse human diseases. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is among the most potent endocrine-disrupting dioxin pollutants, yet our understanding of how TCDD impacts the gut microbiome and systemic metabolism is incompletely understood. Here, we show that TCDD exposure in mice profoundly stimulates the hepatic expression of flavin-containing monooxygenase 3 (Fmo3), which is a hepatic xenobiotic metabolizing enzyme that is also responsible for the production of the gut microbiome-associated metabolite trimethylamine N-oxide (TMAO). Interestingly, an enzymatic product of FMO3 (TMAO) has been associated with the same cardiometabolic diseases that these environmental pollutants promote. Therefore, here, we examined TCDD-induced alterations in the gut microbiome, host liver transcriptome, and glucose tolerance in Fmo3+/+ and Fmo3−/− mice. Our results show that Fmo3 is a critical component of the transcriptional response to TCDD, impacting the gut microbiome, host liver transcriptome, and systemic glucose tolerance. Collectively, this work uncovers a previously underappreciated role for Fmo3 in integrating diet–pollutant–microbe–host interactions.

Radiotherapy (RT) and transoral robotic surgery (TORS) are both curative-intent treatment options for oropharyngeal squamous cell carcinoma (OPSCC). Herein, we report the final outcomes of the ORATOR trial comparing these modalities, 5 years after enrollment completion. We randomly assigned 68 patients with T1-2N0-2 OPSCC to RT (with chemotherapy if node-positive) versus TORS plus neck dissection (± adjuvant RT/chemoradiation). The primary end point was swallowing quality of life (QOL) assessed with the MD Anderson Dysphagia Inventory (MDADI). Secondary end points included overall and progression-free survival (OS, PFS), adverse events (AEs), and other QOL metrics. The primary end point has been previously reported (Nichols 2019). In this report, the median follow-up was 5.1 years (IQR, 5.0-5.3 years). MDADI total scores converged by 5 years and were not significantly different across the follow-up period ( P = .11). EORTC QLQ-C30 and H&N35 scores demonstrated differing profiles, including worse dry mouth in the RT arm ( P = .032) and worse pain in the TORS arm ( P = .002). Grade 2-5 AE rates did not differ between arms (91% [n = 31] v 97% [n = 33] respectively, P = .61), with more neutropenia and hearing loss in the RT arm, and more dysphagia and other pain in the TORS arm based on grades 2-5 (all P < .05). There were no differences in OS or PFS. In conclusion, toxicity and QOL profiles differ in some domains between RT and TORS, but oncologic outcomes were excellent in both arms. Choice of treatment should remain a shared decision between the patient and their providers.

Background: This ORATOR sub-study evaluated swallowing physiology in patients treated with transoral robotic surgery (TORS) versus radiotherapy (RT) for early-stage oropharynx cancer., Methods: Swallowing physiology was evaluated using videofluoroscopy and outcomes were compared across treatment arms and correlated with MDADI scores., Results: Of the 68 patients in the ORATOR trial, 21 participated in this sub-study (30.8%), including 15 RT Arm and six TORS Arm patients. Swallowing profiles were not significantly different between the arms. MBSImP pharyngeal scores for RT Arm versus TORS Arm patients were 4.8 (±2.1) versus 4.3 (±1.5) at baseline, 6.2 (±1.2) versus 9.6 (±4.8) at 6 months and 5.9 (±1.8) versus 8.0 (±4.7) at 12 months. MBSImP pharyngeal scores demonstrated weak associations with several MDADI subscales and PAS scores., Conclusions: To best describe swallowing outcomes in studies of RT and/or surgery, instrumental swallowing assessments should be strongly considered in addition to quality of life measures., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Objectives To determine the prevalence and specific modalities of complementary and alternative medicine (CAM) by professional voice users (PVUs) for vocal ailments and to examine the PVU's health care utilization. Methods A Canadian national cross-sectional survey was conducted. Surveys were distributed electronically to members of the Alliance of Canadian Cinema, Television, and Radio Artists; the National Association of Teachers of Singing; the Canadian Actors Equity Association; and the Department of Vocal Performance at Western University. Participants were asked about the products/therapies they use to improve vocal health. Frequency of use, health care utilization, and general influencers in treatment choice were also collected. Results Two hundred eighty-eight participants completed the survey. 86% of participants claimed to have taken at least one form of CAM when experiencing voice loss or a negative voice change. Of the respondents, 18% claimed to use products/therapies for vocal health routinely in the absence of vocal ailments. The most common CAMs used were hot drinks with honey and/or lemon, lozenges, and inhaling steam. When vocally ill, PVUs were significantly more likely to use CAMs than any other treatment method. Voice teachers and medical doctors most commonly influenced the choice of the treatment. Conclusion This study illustrated the substantial prevalence of CAMs in the PVU community. Understanding the utilization of CAMs can help clinicians navigate treatment strategies for this patient population., (Copyright © 2021. Published by Elsevier Inc.)

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations., Competing Interests: Declaration of interests All authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: We aimed to analyze and compare the timing and patterns of treatment failure, and survival after progression between HPV-positive (HPV+) and HPV-negative (HPV-) patients undergoing chemoradiation for oropharyngeal squamous cell carcinomas (OPSCC)., Methods: A retrospective review was performed of all patients undergoing primary chemoradiation for OPSCC between 2008 and 2021. Demographic and clinical data were collected. Kaplan-Meier estimates for overall survival (OS), and time to recurrence/metastases (TTR) were compared using the log-rank test, with Cox regression used for multivariable modeling comparing HPV+ and HPV- patients., Results: HPV- patients developed recurrence or metastases at earlier time points than HPV+ patients (8.8 vs. 15.2 months, p < 0.05), due to earlier local/locoregional recurrence and distant metastases, but not isolated regional recurrences. HPV- distant metastases exclusively occurred in a single organ, most commonly the lungs or bone, while HPV+ metastases frequently had multi-organ involvement in a wide variety of locations (p < 0.05). Once progression (recurrence/metastases) was diagnosed, HPV+ patients experienced superior survival to HPV- patients on univariate and multivariate analysis, largely due to improved outcomes after treatment of local/locoregional recurrences (p < 0.05). There were no differences in survival after isolated regional recurrences or distant metastases., Conclusion: HPV+ OPSCC patients relapse later compared to HPV- patients in local/locoregional and distant sites. HPV+ patients with local/locoregional recurrence experience superior survival after recurrence, which does not hold true for isolated regional recurrences or distant metastases. These data can be useful to inform prognosis and guide treatment decisions in patients with recurrent OPSCC., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) is associated with a poor prognosis and short survival duration. There is an urgent need to identify personalized predictors of drug response to guide the selection of the most effective therapy for each individual recurrence. We tested the feasibility of patient-derived xenografts (PDX) for guiding their RMHNSCC salvage treatment. Fresh tumor samples from eligible, consented patients were implanted into mice. Established tumors were expanded in mouse PDX cohorts to identify responses to candidate salvage drug treatments in parallel testing. Patients alive and suitable for chemotherapy were treated based on responses determined by PDX testing. Nine patient tumors were successfully engrafted in mice with an average time of 89.2±41.7 days. Four patients' PDX models underwent parallel drug testing. Two patients received PDX-guided therapy. In one of these patients, single agents of cetuximab and paclitaxel demonstrated the best responses in the PDX model, and this patient exhibited sequential partial responses to each drug, including a 17-month clinical response to cetuximab. The main limitation of PDX testing for RMHNSCC was the time delay in obtaining testing results. Despite this, parallel PDX testing may be feasible for a subset of patients and appears to correlate with clinical benefit., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Black et al.)

Objectives: Ultrasound-guided wire (USGW) localisation for small non-palpable tumours before a revision head and neck surgery is an attractive pre-operative option to facilitate tumour identification and decrease potential complications. We describe five cases of pre-operative USGW localisation of non-palpable head and neck lesions to facilitate surgical localisation and resection., Methods: All patients undergoing pre-operative USGW localisation for non-palpable tumours of the head and neck region at London Health and Sciences Center, London, Ontario, Canada, were included. All the USGW localisations were performed by the same interventional radiologist, and the surgeries were performed by fellowship trained head and neck surgeons., Results: Five patients were included. All patients were undergoing revision surgery for recurrent or persistent disease. All successfully underwent a pre-operative USGW localisation of the non-palpable lesion before revision surgery. All lesions were localised intra-operatively with no peri-operative complications., Conclusions: USGW localisation is a safe and effective pre-operative technique for the identification of small non-palpable head and neck tumours., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Introduction: Although concern related to conflicts within health care teams has been discussed in the literature, most studies have focused on individuals' personal conflict management style identification or on managers resolving workplace conflicts between parties. The purpose of this review was to identify significant components in the field of conflict with particular attention to conceptual findings that may be integrated into understanding interprofessional health care team conflict and its resolution., Methods: A critical review of the conflict literature across many fields was undertaken using the method identified by Grant and Booth, incorporating literature-search, appraisal, synthesis, and analysis., Results: This critical review explored existing models and schools of thought to provide an overview of how conflict is conceptualized, its focus on interpersonal and workplace issues, team conflict application and training in team conflict resolution, and finally a summary of this review's contribution to interprofessional health care team conflict and its resolution., Conclusions: Team conflict is comprised of three forms-relationship, task, and process. When team building occurs that incorporates training in the use of an adapted constructive controversy approach, there is a greater opportunity to enhance the quality of a cooperative approach to patients' care planning. Training in team conflict resolution is needed as a key ingredient to ensure all team members can enhance the effectiveness and quality of interprofessional client-centered collaborative practice. This benefits not only the health providers in the team, but also their clients/patients who are recipients of their shared teamwork., Competing Interests: Disclosures: The authors declare no conflict of interest., (Copyright © 2023 The Alliance for Continuing Education in the Health Professions, the Association for Hospital Medical Education, and the Society for Academic Continuing Medical Education.)

Purpose: Head and neck cancer (HNCa) presents numerous challenges secondary to treatment. While there is substantial clinical awareness to the range of challenges demonstrated in this population, information on the impact of post-treatment fatigue is limited. This study investigated the degree of perceived fatigue in those treated for HNCa., Methods: The study was a cross-sectional, self-report, survey design. Adult participants (n = 47) completed a series of three questionnaires; two validated fatigue measures - the Fatigue Screening Inventory (FSI) and the Multidimensional Fatigue Inventory (MFI-20) and a general health-related quality of life measure the European Organisation of Research on the Treatment of Cancer - Quality of Life Questionnaire (EORTC-QLQC30) and the head and neck site specific module (QLQ - H&N 35) were administered., Results: Of the 47 participants, more than half (55%) were identified as having clinically significant self-reported levels of fatigue. Correlational analysis revealed an inverse relationship between fatigue and overall health-related quality of life (HRQOL) implying that as fatigue increases, one's perceived HRQOL decreases., Conclusions: These data suggest that efforts to proactively screen for and index fatigue and seek anticipatory interventions may benefit both short- and long-term HRQOL outcomes in those diagnosed with HNCa., Level of Evidence: IV., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We aimed to analyze risk factors associated with poor survival outcomes for metastatic cutaneous head-and-neck SCC to the parotid., Methods: All patients undergoing surgery for metastatic cutaneous SCC to the parotid with curative intent between 2011 and 2018, were reviewed. Demographic and clinical characteristics were evaluated. Histopathological data including tumor size and histology, tumor grade, TNM stage, resection margins, lymphovascular invasion, and perineural invasion, were analyzed. Overall survival (OS), disease-specific survival (DSS), and freedom from locoregional recurrence (LRR) were assessed., Results: Ninety patients were included (mean age, 77 years; 75 men [83.3%]). A total parotidectomy was performed in 48 patients (53.3%), and 42 (46.7%) underwent a superficial parotidectomy. Seventy patients (77.8%) underwent adjuvant RT. The median follow-up was 31 months (20-39 months). Tumor volume ≥ 50 cm 3 and a shorter RT duration (<20 days) were associated with reduced OS (p = 0.002 and p = 0.01, p = 0.02 and p = 0.009, respectively), and DSS (p = 0.004 and p = 0.02, p = 0.04 and p = 0.02, respectively) on univariable and multivariable analysis, respectively. Only a shorter RT duration was associated with worse freedom from LRR on univariable and multivariable analysis, (p = 0.04 and p < 0.001, respectively). However, with death as a competing risk, a shorter duration of RT was not significantly associated with freedom from LRR., Conclusion: A shorter duration of adjuvant RT, and excised tumor volume ≥50 cm 3 were predictive factors of reduced OS and DSS, and a shorter duration of RT was also associated with reduced freedom from LRR in patients with metastatic SCC to the parotid gland., Level of Evidence: 4 Laryngoscope, 133:1163-1168, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Airway fires are a rare but devastating complication of airway surgery. Although protocols for managing airway fires have been discussed, the ideal conditions for igniting airway fires remain unclear. This study examined the oxygen level required to ignite a fire during a tracheostomy., Study Design: Porcine Model., Setting: Laboratory., Methods: Porcine tracheas were intubated with a 7.5 air-filled polyvinyl endotracheal tube. A tracheostomy was performed. Monopolar and bipolar cautery were used in independent experiments to assess the ignition capacity. Seven trials were performed for each fraction of inspired oxygen (FiO 2 ): 1.0, 0.9, 0.7, 0.6, 0.5, 0.4, and 0.3. The primary outcome was ignition of a fire. The time was started once the cautery function was turned on. The time was stopped when a flame was produced. Thirty seconds was used as the cut-off for "no fire.", Results: The average time to ignition for monopolar cautery at FiO 2 of 1.0, 0.9, 0.8, 0.7, and 0.6 was found to be 9.9, 6.6, 6.9, 9.6, and 8.4 s, respectively. FiO 2  ≤ 0.5 did not produce a flame. No flame was created using the bipolar device. Dry tissue eschar shortened the time to ignition, whereas moisture in the tissue prolonged the time to ignition. However, these differences were not quantified., Conclusion: Dry tissue eschar, monopolar cautery, and FiO 2  ≥ 0.6 are more likely to result in airway fires., Competing Interests: Competing interests: The authors declare no conflicts of interest., (© 2023 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objectives: Online patient forums have become a platform for patient education and advocacy in many areas of medicine. The anonymity provided by such forums may encourage honest, candid responses. Using patient online reviews, this study sought to explore themes that arose from negatively perceived care interactions with American otolaryngologists using the Accreditation Council for Graduate Medical Education (ACGME) competency framework., Study Design: Qualitative thematic analysis., Methods: Through an iterative multistep process, a qualitative thematic analysis was conducted on negative reviews (defined as ratings of two or less out of five) of all American otolaryngologists found on a popular online physician-rating website (RateMDs.com)., Results: A systematic search through the RateMDs website revealed 2950 separate comments of negative reviews. Of these negative reviews, 350 were randomly selected for thematic analysis. The predominant themes that emerged aligned closely with the Accreditation Council for Graduate Medical Education (ACGME) competencies, in particularly with professionalism and interprofessional skills and communication., Conclusions: The negative reviews of American otolaryngologists revealed a number of areas where improvements could be made to quality of care. Patients value evidence-based medicine delivered by compassionate and respectful physicians. Isolating and aligning predominant themes within the ACGME framework proved a productive method to collect and organize pertinent patient feedback and integrate teaching into the post-graduate training and continuing professional development in order to avoid such negatively perceived interactions in the future., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To illustrate variations of the vascular anatomy of the subscapular system highlighting practical implications on surgical access, patient positioning, and strategies to maximize the exposure of vascular pedicle., Methods: A retrospective review of patients undergoing reconstruction with a scapular tip free flap over a 2-year period at a tertiary referral center., Results: Forty patients were included. In 25 (62.5%) cases, the thoracodorsal artery (TD) ended bifurcating into latissimus dorsi (LD) and angular branch (AB), with the serratus artery branch arising from the LD pedicle; this vascular pattern was defined as "LD-dominant." In 10 (25%) cases, the TD bifurcated into LD and AB, with the serratus artery branch arising from the latter vessel, defined as "AB-dominant." Lastly, there was a trifurcation pattern in 5 (12.5%) patients. There was considerable variability in the distal branching pattern. Twenty-two (55%) patients had 2 LD branches; in 11 (27.5%) cases, there was only 1 LD branch, and 7 (17.5%) cases had 3. Thirty-seven patients (92.5%) had 1 AB; in the remaining three cases (7.5%), there were 2. The entry point of AB was located 4.86 cm (mean) ± 0.75 cm from the fibrous tip. The arm positioning and scapular retraction were the key maneuvers to facilitate pedicle exposure and dissection, with the shoulder abducted and scapula retracted away from the body., Conclusion: The subscapular vascular anatomy is highly variable. Knowledge of anatomic variability alongside surgical pearls to harvest STFF could facilitate the introduction of this flap into the toolkit of head and neck reconstructive teams., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: There is significant interest in treatment de-escalation for human papillomavirus-associated (HPV + ) oropharyngeal squamous cell carcinoma (OPSCC) patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to risk stratify HPV + OPSCC patients., Methods: We created an immune score (UWO3) associated with survival outcomes in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes., Findings: A three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival compared to the immune desert (HR = 9.0, 95% CI: 3.2-25.5, P = 3.6 × 10 -5 ) and mixed (HR = 6.4, 95% CI: 2.2-18.7, P = 0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two small treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation., Interpretation: With additional prospective validation, the UWO3 score could enable biomarker-driven clinical decision-making for patients with HPV + OPSCC based on robust outcome prediction across six independent cohorts. Prospective de-escalation and intensification clinical trials are currently being planned., Funding: CIHR, European Union, and the NIH., Competing Interests: Declaration of interests PYFZ, JWB, PCB, JSM and ACN have a US patent pending for the UWO3 score. All other authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

The molecular mechanisms by which dietary fruits and vegetables confer cardiometabolic benefits remain poorly understood. Historically, these beneficial properties have been attributed to the antioxidant activity of flavonoids. Here, we reveal that the host metabolic benefits associated with flavonoid consumption hinge, in part, on gut microbial metabolism. Specifically, we show that a single gut microbial flavonoid catabolite, 4-hydroxyphenylacetic acid (4-HPAA), is sufficient to reduce diet-induced cardiometabolic disease (CMD) burden in mice. The addition of flavonoids to a high fat diet heightened the levels of 4-HPAA within the portal plasma and attenuated obesity, and continuous delivery of 4-HPAA was sufficient to reverse hepatic steatosis. The antisteatotic effect was shown to be associated with the activation of AMP-activated protein kinase α (AMPKα). In a large survey of healthy human gut metagenomes, just over one percent contained homologs of all four characterized bacterial genes required to catabolize flavonols into 4-HPAA. Our results demonstrate the gut microbial contribution to the metabolic benefits associated with flavonoid consumption and underscore the rarity of this process in human gut microbial communities.

Objective: To implement a quality improvement initiative to achieve an institutional targeted discharge summary distribution metric of 50% within 48 hours of patient discharge from hospital within an academic tertiary care otolaryngology-head and neck surgery department., Methods: A pre- and postintervention study was conducted. Process mapping was performed. Interventions included education and engagement, implementation of auto-authentication (distribution immediately following transcription without review by the most responsible physician), and audit and feedback. The percentage of discharge summaries dictated with the auto-authentication code was evaluated. Process measures were collected for 12 months pre- and postimplementation. Balancing measures included workload and revisions to auto-authenticated notes. Analysis included summary statistics, statistical process control charting, and unpaired t tests., Results: The mean ± SD percentage of discharge summaries distributed within 48 hours increased from 19% ± 6.4% preintervention to 54% ± 20% postintervention ( P < .0001). Seventy-four percent of discharge summaries were dictated via the auto-authentication code. The target metric was met in 71% of discharges with the auto-authentication codes as compared with 26% with non-auto-authentication. The interventions did not result in any change to perceived workload, and the incidence of auto-authentication revisions was <1%. The results were sustained with an increase of 72% the following quarter. For fiscal year 2021-2022, performance remained sustained with an 85% completion rate., Discussion: Our surgical department exceeded and sustained the targeted metric for timely discharge summary distribution using a quality improvement approach., Implications for Practice: Timely distribution of discharge summaries optimizes patients' transitions of care and can be achieved through stakeholder education and engagement, auto-authentication, and audit with feedback., (© The Author(s) 2022.)

Objective: The aim of this study was to report the incidence and clinical course of a series of patients who were misdiagnosed with Bell's palsy and were eventually proven to have occult neoplasms., Methods: Two hundred forty patients with unilateral facial paralysis who were assessed at the facial nerve reanimation clinic, Victoria Hospital, London Health Science Centre, from 2008 through 2017 were reviewed. Persistent paralysis without recovery was the presenting complaint., Results: Nine patients (3.8%) who were proven to have occult neoplasms initially presented with a diagnosis of Bell's palsy. The mean diagnostic delay was 43.5 months. Four patients were proven to have skin cancers, 3 patients had parotid cancers, and 2 patients had facial nerve schwannomas as a final diagnosis. Initial magnetic resonance imaging (MRI) was performed in all 9 patients and 8 underwent a follow-up MRI. An occult tumor was identified upon review of the original MRI in one patient and at follow-up MRI in 8 patients. The mean time interval between the initial and follow-up imaging was 30.8 months. The disease status at most recent follow-up were no evidence of disease in 2 patients (22%) and alive with disease in 7 patients (78%). An irreversible, progressive pattern of facial paralysis combined with pain, multiple cranial neuropathies or history of skin cancer were predictable risk factors for occult tumors. Seven out of the 9 patients (77.8%) underwent at least one type of facial reanimation surgery, and the final subjective results by the surgeon were available for 5 patients. Three out of the 5 (60%) patients who were available for final subjective analysis were reported as Grade III according to the modified House-Brackmann scale., Conclusion: Occult facial nerve neoplasm should be suspected in patients with progressive and irreversible facial paralysis but the diagnosis may only become evident with follow-up imaging. Facial reanimation surgery is a satisfactory option for these patients., (© 2022. The Author(s).)

Background: Squamous cell carcinoma is the most common malignancy of the oral cavity. Primary treatment involves surgical resection of the tumour with a surrounding margin. Historically, the most commonly accepted margin clearance is 5 mm. This distance is controversial, with recent publications suggesting closer margins do not impact local recurrence and survival. The objective of this study is to determine the closest surgical margin that does not impact local recurrence and overall survival., Methods: A retrospective review of the London Health Sciences Centre Head and Neck Multidisciplinary Clinic between 2010 and 2018 was performed. Demographic data, subsite, tumour staging, treatment modality, margins, and survival outcomes were analyzed. The primary endpoint was local recurrence free survival. Secondary endpoints included recurrence-free survival and overall survival. Descriptive statistics, as well as univariable and multivariable Cox proportional hazards regression modelling were performed for all patients., Results: Four-hundred and twelve patients were included in the study, with a median follow-up of 3.3 years. On univariable analysis, positive margins and margins < 1 mm were associated with significantly worse local recurrence-free survival, recurrence-free survival, and overall survival (p < 0.05), compared to margins > 5 mm. Patients with surgical margins > 1 mm experienced similar outcomes to those with margins > 5 mm. Multivariable analysis identified age of diagnosis, alcohol consumption, pathological tumour and nodal category as predictors of local recurrence free survival., Conclusions: Although historical margins for head and neck surgery are 5 mm, similar outcomes were observed for margins greater than 1 mm in our cohort. These findings require validation through multi-institutional collaborative efforts., (© 2022. The Author(s).)

Objective: To compare pathologic and survival outcomes between primary muscle invasive (pMIBC) and secondary muscle invasive (sMIBC) bladder cancer patients who were treated with or without cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC)., Methods: We reviewed cT2-T4/N0 MIBC patients at our institution between 2010-2019. pMIBC was defined as presenting with > cT2 disease on initial or restaging TURBT with no prior history of bladder cancer. sMIBC was defined as prior history of NMIBC that was treated with at least one induction course of BCG that progressed to MIBC. Outcomes analyzed included pathologic downstaging rates defined as pT2 and N+ disease were predictors of poorer CSS and OS. Separate analysis of sMIBC patients whom underwent RC only (N = 61), demonstrated inferior oncologic outcomes to other cohorts (P < .01)., Conclusion: There were no differences in pathologic response or survival between pMIBC and sMIBC patients when managed with NAC and RC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Recent reports have suggested that fluid restriction as part of Enhanced Recovery after Surgery (ERAS) pathways may increase the risk of AKI in radical cystectomy (RC) patients. We sought to evaluate the impact of ERAS initiation on AKI incidence at a high-volume tertiary care center., Materials and Methods: We performed a retrospective review of our IRB approved database to identify patients receiving RC from 2010 to 2019. ERAS was initiated at our institution in October 2016. Acute kidney injuries were graded according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria and must have occurred within 7 days of indexed RC. Estimated glomerular filtration rate (eGFR) was captured at baseline, 1, 3, 6, and 12 months respectively. Categorical variables were compared with the Pearson-Chi square test. Quantitative variables were analyzed with the Wilcoxon-Rank sum test. Multivariable binary logistic regression and interaction analysis was used to identify predictors of AKI., Results: Twelve hundred patients were included. Twenty-two percent of patients experienced an AKI within 7 days. Patients in the ERAS cohort experienced less AKIs after RC (18% vs. 25%, P = 0.003). When adjusting for year of surgery, ERAS was not a significant predictor for AKI on multivariable analysis (OR: 0.87, P = 0.73). On interaction analysis, during the ERAS era, intracorporeal robot-assisted radical cystectomy (iRARC) was associated with decreased odds of AKI (OR: 0.39, P = 0.034). There were no significant differences in eGFR at 12 months postoperatively (P = 0.16)., Conclusion: Unlike previous reports, ERAS initiation was not associated with increased risk of AKI at a tertiary care high-volume center., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: The current study aims to quantify the growth rate of p16-negative oral cavity squamous cell carcinoma, characterize causative relationships between demographic risk factors and tumor growth, and examine pathologic findings associated with the tumor growth rate at a tertiary care institution. It is hypothesized that causative relationships will be drawn between the individual sociodemographic and pathologic factors and oral cavity p16-negative squamous cell carcinoma growth rate., Methods: Prospectively recruited participants, receiving surgical intervention only, were followed from initial staging CT scan to surgical resection. Interval growth was calculated in cm 3 /week. Demographic information including age, sex, smoking history, alcohol consumption history, previous all-type malignancy, previous chemotherapy treatment, previous head or neck radiation exposure, and time interval elapsed between diagnosis and surgery was collected from each participant, and regression analysis was applied to determine causality., Results: Summary statistics revealed a mean growth rate for the study sample of 1.385cm 3 /week. Statistically significant regression correlations were detected between tumor growth and alcohol consumption, origination at the retromolar trigone, and clinical nodal stage., Conclusions: Through a small prospective cohort sample, the current study suggests clinical associations between alcohol consumption, origination at the retromolar trigone, and clinical nodal stage with rate of tumor growth. Future work will validate these relationships in a larger patient cohort, and against stronger modeling techniques., Level of Evidence: Prospective non-random cohort design., Competing Interests: The authors of this paper have no competing interests nor conflicts of interest to disclose., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Introduction: Increases in publication quantity and the onset of open access have increased the complexity of conducting a literature search. Bibliometric markers, like impact factor (IF), have traditionally been used to help identify high-quality research. These markers exist amongst a variety of other factors, which poses the following question: what factors are examined when considering articles for clinical and academic research?, Objective: To determine what factors are involved when authors choose citations to include in their publications., Methods: A voluntary and anonymous questionnaire-based survey was distributed to medical students, residents, and faculty from multiple medical schools across Canada during the 2020/2021 academic year. Survey ratings were scored on a 5-point Likert scale and open word response., Results: The study collected 156 complete sets of responses including 78 trainees (61 medical students and 17 residents), and 78 faculty. Language of the article (3.93) and availability on PubMed/Medline (3.77) were found more important than country of origin (2.14), institution (2.26), and IF (2.97). Trainees found the following factors more important than faculty: year of publication (3.94 vs 3.47, p = 0.0016), availability on Google/Google Scholar (2.51 vs 1.88, p = 0.0013), Open-access (2.46 vs 1.87, p = 0.0011), and Free access (2.73 vs 2.31, p = 0.049)., Conclusion: Our study identified differences in faculty and trainee literature search preferences, bias towards English language publications, and the movement towards online literature sources. This knowledge provides insight into what biases individuals may be exposed to based on their language and literature search preferences. Future areas of research include how trainees' opinions change over time, identifying trainee ability to recognize predatory journals, and the need for better online journal article translators to mitigate the language bias. We believe this will lead to higher quality evidence and optimal patient care amongst healthcare workers., Competing Interests: Dr Amanda Hu reports grants from Michael Smith Foundation, grants from American Academy of Otolaryngology – Head & Neck Surgery, Advisory Board from Pentax Medical, Honorarium for educational product on chronic cough from Merck Inc., outside the submitted work. The authors report no other conflicts of interest in this work., (© 2022 Wiens et al.)

Purpose: Primary radiation therapy with or without chemotherapy (RT/CRT) is the most common treatment for oropharyngeal squamous cell carcinomas (OPSCC), but there has been an increase in transoral surgery (TOS) for T1-2 tumors. Because only a subset of T1-2 tumors are TOS-favorable, nonrandomized comparisons between RT/CRT and TOS could be confounded by indication. We aimed to compare outcomes of potential TOS-candidates versus non-TOS candidates, among patients who underwent RT/CRT for early T-stage OPSCC., Methods and Materials: For patients treated with RT/CRT for early-stage human papilloma virus positive OPSCC between 2014 and 2018, pretreatment imaging was reviewed by 3 head and neck surgeons, blinded to outcomes, to assess primary-site appropriateness for TOS, and extracapsular extension (ECE) was scored by a head and neck neuroradiologist. We compared outcomes based on surgical favorability pertaining to (1) the primary site tumor alone and (2) the primary site and an absence of ECE. Kaplan-Meier estimates for overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared using the log-rank test, with Cox regression used for multivariable modeling., Results: One hundred and forty-three patients were evaluated, of which 121 were male (84.6%), the median age was 59.4 years, and all of them were p16 positive (100%). The primary site was TOS-favorable in 115 of 143 (80.4%). Patients with TOS-favorable primary site experienced superior 5-year OS (89.8% vs 71.2%, P = .017), DSS (90.4% vs 63.4%, P = .022), and RFS (83% vs 49.4%, P = .04) compared with TOS-unfavorable patients. Similarly, patients with a TOS-favorable primary site and no ECE on imaging 101 of 143 (70.6%), had improved OS, DSS, and RFS (P < .05) compared with TOS-unfavorable patients., Conclusions: In this first study to assess surgical favorability as a prognostic factor among patients with T1/2 p16+ OPSCC, patients with TOS-favorable early-stage OPSCC have better outcomes than TOS-unfavorable patients. This provides valuable prognostic information for patients, and also suggests the risk of confounding by indication in nonrandomized comparisons of treatment modalities., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Postoperative respiratory failure (PRF) contributes significantly to morbidity and mortality. We sought to identify patient characteristics and perioperative risk factors associated with PRF in patients undergoing elective abdominal surgery to improve patient outcomes., Methods: We retrospectively reviewed patients undergoing elective abdominal surgery from 2011 to 2016 at our institution. An experimental group consisting of adult patients with the Patient Safety Indicator 11 diagnosis of PRF was compared with a time-matched control group., Results: Each group consisted of 233 patients. Comorbidities associated with PRF included ascites, coronary artery disease, chronic kidney disease, chronic obstructive pulmonary disease, diabetes mellitus type II, hypertension, and hypoalbuminemia (P < 0.05). American Society of Anesthesiologists score IV (20.2% versus 3.95%; P < 0.001), operative time (4.13 versus 2.55 h; P < 0.001), laparotomy with open operation (77.7% versus 45.5%; P < 0.001), and net intraoperative fluid balance (3635 versus 2410 mL; P < 0.001) were higher in patients with PRF. On multivariate analysis, age, American Society of Anesthesiologists score, chronic obstructive pulmonary disease, diabetes mellitus type II, laparotomy, and net intraoperative fluid balance maintained significance (P < 0.05)., Conclusions: We identified contributing pre- and intra-operative risk factors for PRF undergoing elective abdominal surgery. These findings may help identify those at increased risk for respiratory failure and mitigate complications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown., Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC., Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up., Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings)., Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects., Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively)., Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes., Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.

Background: Neck carcinoma of unknown primary (CUP) is a frequent scenario. Transoral robotic mucosectomies (TORM) of pharynx have increased rate of primary identification, but come with cost of treatment delay., Methods: We reviewed patients who underwent CUP protocol from 2014 to 2020. Patients with cervical nodes carcinoma and failure to localize a primary source were classified as CUP. We determined primary identification rate and postoperative complications., Results: We included 65 patients underwent TORM. Surgical approach consisted of lingual and/or palatine tonsillectomies. The primary detection rate was 49.2%. Average weight reduction was 2.5 ± 4.3 kg. The average number of days from consultation to definitive treatment was 52.2 ± 18.3., Conclusion: A systematic approach to patients with CUP showed a promising primary identification rate compared to panendoscopy alone. TORM carries a small risk of complications. The benefits of primary identification must be weighed with the morbidity and delay to definitive treatment., (© 2022 Wiley Periodicals LLC.)

Background: Numerous studies of head and neck squamous cell carcinoma (HNSCC) have demonstrated disparate outcomes by race and ethnicity. Beyond known associations with socioeconomic variables, whether these are also associated with differences in tumor molecular composition has thus far been poorly explored., Methods: We downloaded clinical and multiplatform molecular data from The Cancer Genome Atlas and other published studies. These were compared between non-Hispanic Black (n = 43) and White (n = 354) patients with non-HPV-related tumors, using multivariable models. Publicly available validation cohorts were used., Results: Black patients had poorer progression-free survival than White patients. Tumors of Black patients had greater copy number aberrations, and increased SFRP1 methylation and miRNA-mediated PRG4 silencing associated with poor survival. PI3K/AkT/mTOR pathway proteins were differentially expressed., Conclusions: There are molecular differences between tumors of Black and White patients that may partially account for differences in survival. These may inform targeted treatment decisions to achieve equitable outcomes., (© 2022 Wiley Periodicals LLC.)

Purpose: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking., Methods: We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial., Results: Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time ( P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years ( P = .015). Dry mouth scores were higher in RT patients over time ( P = .041)., Conclusion: On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355)., Competing Interests: Anthony C. NicholsResearch Funding: Novartis Canada Pharmaceuticals Inc (Inst) Eric BertheletResearch Funding: Eisai Eric WinquistConsulting or Advisory Role: Merck, Bayer, Eisai, Amgen, Roche, IpsenResearch Funding: Roche/Genentech (Inst), Merck (Inst), Pfizer (Inst), Eisai (Inst), Ayala Pharmaceuticals (Inst) David A. PalmaThis author is a member of the Journal of Clinical Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Employment: London Health Sciences Centre (LHSC)Patents, Royalties, Other Intellectual Property: US patent: a method for analyzing a three-dimensional computed tomography image, US patent application no. 61/896349 (not licensed, no commercial or financial impact)No other potential conflicts of interest were reported.

Anaplastic thyroid cancer (ATC) is a rare, aggressive form of undifferentiated thyroid cancer, which exhibits rapid progression and is almost universally fatal. At least a subset of ATC is thought to arise from pre-existing well-differentiated thyroid cancer, most frequently papillary thyroid cancer (PTC). While PIK3CA mutations are rare in PTC, they are common in ATC and tend to co-occur with BRAF mutations. This provided the rationale for our study to identify the potential role of PIK3CA mutations in the progression from well-differentiated to undifferentiated thyroid cancer. We introduced PIK3CA E545K into the LAM1 PTC cell line, which carries a BRAF V600E mutation. In culture, the engineered cell line (LAM1:PIK3CA E545K ) proliferated faster and demonstrated increased clonogenic potential relative to the parental line carrying an empty vector (LAM1 EV ). Both the LAM1 EV and LAM1:PIK3CA E545K edited lines were implanted into hind flanks of athymic nude mice for in vivo determination of disease progression. While tumour weights and volumes were not significantly higher in LAM1:PIK3CA E545K mice, there was a decrease in expression of thyroid differentiation markers TTF-1, thyroglobulin, PAX8 and B-catenin, suggesting that introduction of PIK3CA E545K led to dedifferentiation in vivo. Collectively, this study provides evidence of a role for PIK3CA E545K in driving disease progression from a well-differentiated to an undifferentiated thyroid cancer; however, over-expression was not a determinant of an accelerated growth phenotype in ATC., (© 2022. The Author(s).)

Loss of the 3p chromosome arm has previously been reported to be a biomarker of poorer outcome in both human papillomavirus (HPV)-positive and HPV-negative head and neck cancer. However, the precise operational measurement of 3p arm loss is unclear and the mutational profile associated with the event has not been thoroughly characterized. We downloaded the clinical, single nucleotide variation (SNV), copy number aberration (CNA), RNA sequencing, and reverse phase protein assay (RPPA) data from The Cancer Genome Atlas (TCGA) and The Cancer Proteome Atlas HNSCC cohorts. Survival data and hypoxia scores were downloaded from published studies. In addition, we report the inclusion of an independent Memorial Sloan Kettering cohort. We assessed the frequency of loci deletions across the 3p arm separately in HPV-positive and -negative disease. We found that deletions on chromosome 3p were almost exclusively an all or none event in the HPV-negative cohort; patients either had <1% or >97% of the arm deleted. 3p arm loss, defined as >97% deletion in HPV-positive patients and >50% in HPV-negative patients, had no impact on survival ( p > 0.05). However, HPV-negative tumors with 3p arm loss presented at a higher N-category and overall stage and developed more distant metastases ( p < 0.05). They were enriched for SNVs in TP53, and depleted for point mutations in CASP8, HRAS, HLA-A, HUWE1, HLA-B, and COL22A1 (false discovery rate, FDR < 0.05). 3p arm loss was associated with CNAs across the whole genome (FDR < 0.1), and pathway analysis revealed low lymphoid-non-lymphoid cell interactions and cytokine signaling (FDR < 0.1). In the tumor microenvironment, 3p arm lost tumors had low immune cell infiltration (FDR < 0.1) and elevated hypoxia (FDR < 0.1). 3p arm lost tumors had lower abundance of proteins phospho-HER3 and ANXA1, and higher abundance of miRNAs hsa-miR-548k and hsa-miR-421, which were all associated with survival. There were no molecular differences by 3p arm status in HPV-positive patients, at least at our statistical power level. 3p arm loss is largely an all or none phenomenon in HPV-negative disease and does not predict poorer survival from the time of diagnosis in TCGA cohort. However, it produces tumors with distinct molecular characteristics and may represent a clinically useful biomarker to guide treatment decisions for HPV-negative patients.

Objective: Detection of circulating tumor DNA (ctDNA) in cancer patients can potentially serve as a noninvasive, sensitive test of disease status. The purpose of this study was to determine the ability to detect BRAF (V600E) mutations in the plasma of patients with thyroid nodules, with the goal of distinguishing between benign and malignant nodules., Methods: Consecutive patients with thyroid nodules who consented for surgery were recruited. Plasma samples were obtained preoperatively and one month postoperatively. Quantitative PCR was used to determine the levels of the BRAF (V600E) mutation preoperatively and postoperatively., Results: A total of 109 patients were recruited. On final pathology, 38 (32.8%) patients had benign thyroid nodules, 45 (38.8%) had classical papillary thyroid cancer (PTC), 23 (19.8%) had nonclassical PTC, and 3 (2.6%) had follicular thyroid cancer. 15/109 patients had detectable BRAF (V600E) ctDNA in their preoperative samples-all of them having classical PTC. Higher T-stage and extrathyroidal extension in PTC were associated with positive BRAF (V600E) ctDNA ( p < 0.05). Eighty-eight pairs of preoperative and postoperative plasma samples were collected and analyzed. Of these eighty-eight paired samples, a total of 13/88 (14.8%) patients had detectable BRAF (V600E) ctDNA in their preoperative samples-all of them having classical PTC. 12 of these 13 patients had no detectable BRAF (V600E) postoperatively, while one remaining patient had a significant decline in his levels ( p < 0.05)., Conclusion: BRAF (V600E) circulating thyroid tumor DNA can be detected in plasma and is correlated with a final diagnosis of the classical variant of PTC. Given that a postoperative drop in BRAF (V600E) ctDNA levels was observed in all cases suggests its utility as a tumor marker., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Krupal B. Patel et al.)

Objective: To evaluate the impact of a high efficiency rapid standardized OR (RAPSTOR) for hemithyroid/parathyroid surgery using standardized equipment sets (SES) and consecutive case scheduling (CCS) on turnover times (TOT), average case volumes, patient outcomes, hospital costs and OR efficiency/stress., Methods: Patients requiring hemithyroidectomy (primary or completion) or unilateral parathyroidectomy in a single surgeon's practice were scheduled consecutively with SES. Retrospective control groups were classified as sequential (CS) or non-sequential (CNS). A survey regarding OR efficiency/stress was administered. Phenomenography and descriptive statistics were conducted for time points, cost and patient outcome variables. Hospital cost minimization analysis was performed., Results: The mean TOT of RAPSTOR procedures (16 min; n = 27) was not significantly different than CS (14 min, n = 14) or CNS (17 min, n = 6). Mean case number per hour was significantly increased in RAPSTOR (1.2) compared to both CS (0.9; p < 0.05) and CNS (0.7; p < 0.05). Average operative time was significantly reduced in RAPSTOR (32 min; n = 28) compared to CNS (48 min; p < 0.05) but not CS (33 min; p = 0.06). Time to discharge was reduced in RAPSTOR (595 min) compared to CNS (1210 min, p < 0.05). There was no difference in complication rate between all groups (p = 0.27). Survey responses suggested improved efficiency, teamwork and workflow. Furthermore, there is associated decrease in direct operative costs for RAPSTOR vs. CS., Conclusion: A high efficiency standardized OR for hemithyroid and parathyroid surgery using SES and CCS is associated with improved efficiency and, in this study, led to increased capacity at reduced cost without compromising patient safety., Level of Evidence: Level 2.

Purpose: Individuals with head and neck cancer (HNCa) face myriad biopsychosocial challenges. Even after treatment completion, these challenges may cause continued disablement and diminished quality of life (QoL). Resilience may serve to minimize the disabling impact of HNCa and, in turn, maximize QoL. The purpose of this study was to formally assess resilience in HNCa survivors and explore its relationship with QoL., Methods: A cross-sectional descriptive study was conducted. Forty HNCa survivors completed three validated, self-report questionnaires pertaining to the collection of resilience and QoL data. Descriptive and correlational analyses were performed., Results: Resilience was identified in HNCa survivors and a positive correlation was found between resilience and QoL., Conclusions: Data suggest that resilience may buffer the influence of HNCa on QoL. Thus, screening for reduced levels of resilience may proactively facilitate identification of those who are most vulnerable to the psychosocial impact of HNCa. Interventions that foster resilience may ameliorate the challenges of HNCa and maximize QoL.

Objective: To describe the successes and challenges associated with developing an otolaryngology-head and neck surgery (OHNS) medical education app and website., Design: From 2010 to 2018, OHNS faculty across Canada contributed to the development of a smartphone app, LearnENT. LearnENT 1.0, was initially launched in 2012 using the Apple iOS 6 platform. The app utilized a novel user interface and interactive features to help learners develop approaches to OHNS clinical problems, review relevant anatomy, history, and physical examination skills. However, the release of iOS 7 necessitated a redesign and relaunch of LearnENT which occurred from 2015 to 2018 to produce the final version of the app, LearnENT 2.0. Through the relaunching process, the LearnENT team redesigned the app's interface, produced a web version of the app, and created a new content management system., Setting: OHNS departments across Canada., Participants: OHNS faculty members, residents, and medical students., Results: Through this approach, a sustainable, widely accessible, open access OHNS e-Learning resource was developed. Since the relaunch, the LearnENT app has 2728 user accounts and has been widely used across the globe with users in 36 countries outside of North America. LearnENT is currently the official learning app of the Canadian Society of OHNS, has been featured on several different medical education platforms and incorporated into medical school curricula at various institutions., Conclusions: The authors successfully created a novel e-Learning resource with the goal of improving OHNS medical education both nationally and internationally., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives/hypothesis: Free flap transfer offers a versatile option for reconstruction in head and neck surgery, with success rates over 95%. There remains a substantial re-exploration rate of roughly 5% to 15%, with early recognition of compromise essential to flap survival. Monitoring techniques are highly desirable, with the gold standard being clinical monitoring. The Cook-Swartz Doppler (CSD) probe utilizes Doppler technology to inform clinicians about real-time flow. We aim to describe our adoption of this technology in 100 consecutive free flaps., Study Design: Prospective case series., Methods: Prospective data were collected from July 2014 to June 2015 on 100 consecutive free flaps performed at a head and neck unit in London, Ontario. All patients had a CSD inserted for arterial and venous monitoring., Results: A total of 100 free flaps were performed on 99 patients. Sensitivity was 87.1% and specificity was 85.7%. Positive predictive value was 98.8% and negative predictive value was 33.3%. False-negative and false-positive rate were 1.0% and 12.0%, respectively. The exploration rate was 12%, with no flap loss and two partial debridements. The CSD was helpful in management in 9% of cases and was clinically unhelpful in 11% of cases, with 10 of 11 abnormal signals ignored. There were three unique CSD complications; one retained wire, one pedicle laceration during extraction, and one clot around the probe interrupting signal., Conclusions: The CSD is a helpful adjunct to clinical monitoring but has unique complications, which were not previously described. Pros and cons must be considered for new centers adopting this technology., Level of Evidence: 4 Laryngoscope, 131:E1854-E1859, 2021., (© 2021 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Gut microbe-derived metabolites influence human physiology and disease. However, establishing mechanistic links between gut microbial metabolites and disease pathogenesis in animal models remains challenging. The major route of absorption for microbe-derived small molecules is venous drainage via the portal vein to the liver. In the event of presystemic hepatic metabolism, the route of metabolite administration becomes critical. To our knowledge, we describe here a novel portal vein cannulation technique using a s.c. implanted osmotic pump to achieve continuous portal vein infusion in mice. We first administered the microbial metabolite trimethylamine (TMA) over 4 weeks, during which increased peripheral plasma levels of TMA and its host liver-derived cometabolite, trimethylamine-N-oxide, were observed when compared with a vehicle control. Next, 4-hydroxyphenylacetic acid (4-HPAA), a microbial metabolite that undergoes extensive presystemic hepatic metabolism, was administered intraportally to examine effects on hepatic gene expression. As expected, hepatic levels of 4-HPAA were elevated when compared with the control group while peripheral plasma 4-HPAA levels remained the same. Moreover, significant changes in the hepatic transcriptome were revealed by an unbiased RNA-Seq approach. Collectively, to our knowledge this work describes a novel method for administering gut microbe-derived metabolites via the portal vein, mimicking their physiologic delivery in vivo.

Purpose: Head and neck squamous cell carcinoma (HNSCC) affects various anatomical sites, which often dictates whether the cancer is managed with primary surgery or radiation. This study aimed to assess differences in single nucleotide variation (SNV), copy number, mRNA abundance, methylation, and tumor microenvironment (TME) between HPV-negative oral cavity (OC), oropharyngeal (OPC), hypopharyngeal (HPC), and laryngeal (LC) cancers within The Cancer Genome Atlas (TCGA)., Methods: We downloaded the clinical information and molecular data for the TCGA HNSCC cohort from the data portal and published literature. The TME was estimated using mRNA abundance data. We conducted our analyses within the Bioconductor statistical framework in the R environment. CNA and mRNA abundance results were correlated and grouped with SNV results for downstream pathway analysis., Results: LC had a higher mutational burden than OC and OPC (p <10 -4 ). LC tumors were enriched in CSMD3, NSD1, DCHS2 and ANK2 SNVs, while OC tumors were enriched in CASP8 SNVs (FDR < 0.1). LCs were enriched for neuronal and glycosylation pathways, while OCs were enriched for extracellular matrix pathways. B cells and endothelial cells were more abundant in LC while monocytes were more abundant in OC (FDR < 0.1). OPC was the most hypoxic, followed by OC then LC (FDR < 0.05). OC had greater methylation of Hox genes than LC. Subsite analysis revealed that oral tongue cancers had fewer CASP8 and FBN2 mutations and higher dendritic cell abundance than other oral cavity cancers., Conclusions: We identified significant genomic, transcriptional, and microenvironmental differences between HPV-negative HNSCC. Further study is warranted to determine if these findings portend differential response to specific treatment modalities., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: This article reports on a unique cohort of patients with idiopathic subglottic stenosis spilt fairly equally between endoscopic and open surgical approaches. Patients' sequence of operations and reinterventions over time are outlined, offering insight to improve surgical counseling and allow for informative, autonomous patient decision making., Study Design: Retrospective cohort study., Setting: Tertiary care academic center., Methods: Cases of consecutive adults with idiopathic subglottic stenosis managed surgically over a 12-year period (January 2006-December 2017) were retrospectively reviewed. Surgical workflow, complications, and outcomes, including reinterventions and tracheotomy dependence, are reported., Results: Seventy-two patients (71 women; mean age, 50.4 years) with idiopathic subglottic stenosis requiring surgical airway intervention were identified. Six patients underwent tracheotomy prior to attempt at airway stenosis surgery. Initial surgical approach thereafter included endoscopic (73.5%, n = 53) and open (26.4%, n = 19) procedures. Thirty-one patients underwent cricotracheal resection; the reintervention rate was 22.5%. Sixty patients underwent 147 endoscopic procedures; the reintervention rate was 75.5%, and the mean time between dilations was 83 weeks (range, 5-402). Two (2.8%) patients remain tracheotomy dependent. Adverse events were significantly higher in the cricotracheal group, especially with respect to dysphonia and temporary gastrostomy tube placement ( P < .01)., Conclusions: Endoscopic and open surgical airway intervention can be employed successfully to avoid tracheotomy dependence and maintain airway patency; however, multiple procedures are usually required, regardless of surgical approach. Cricotracheal reintervention rates are lower than endoscopic dilation but with increased morbidity. Quality-of-life outcomes should be clearly discussed with patients before deciding on a surgical management strategy.

Background: Radiotherapy, along with laser surgery, is considered a standard treatment option for patients with early glottic squamous cell cancer (SCC). Historically, patients have received complete larynx radiotherapy (CL-RT) due to fear of swallowing and respiratory laryngeal motion and this remains the standard approach in many academic institutions. Local control (LC) rates with CL-RT have been excellent, however this treatment can carry significant toxicities include adverse voice and swallowing outcomes, along with increased long-term risk of cerebrovascular morbidity. A recent retrospective study reported improved voice quality and similar local control outcomes with focused vocal cord radiotherapy (VC-RT) compared to CL-RT. There is currently no prospective evidence on the safety of VC-RT. The primary objective of this Bayesian Phase II trial is to compare the LC of VC-RT to that of CL-RT in patients with T1N0 glottic SCC., Methods: One hundred and fifty-five patients with T1a-b N0 SCC of the true vocal cords that are n ot candidate or declined laser surgery, will be randomized in a 1:3 ratio the control arm (CL-RT) and the experimental arm (VC-RT). Randomisation will be stratified by tumor stage (T1a/T1b) and by site (each site will be allowed to select one preferred radiation dose regimen, to be used in both arms). CL-RT volumes will correspond to the conventional RT volumes, with the planning target volume extending from the top of thyroid cartilage lamina superiorly to the bottom of the cricoid inferiorly. VC-RT volumes will include the involved vocal cord(s) and a margin accounting for respiration and set-up uncertainty. The primary endpoint will be LC at 2-years, while secondary endpoints will include patient-reported outcomes (voice impairment, dysphagia and symptom burden), acute and late toxicity radiation-induced toxicity, overall survival, progression free survival, as well as an optional component of acoustic and objective measures of voice analysis using the Consensus Auditory-Perceptual Evaluation of Voice., Discussion: This study would constitute the first prospective evidence on the efficacy and safety of VC-RT in early glottic cancer. If positive, this study would result in the adoption of VC-RT as standard approach in early glottic cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT03759431 Registration date: November 30, 2018.

Competing Interests: The authors have no conflicts of interest to declare.