Impact of the COVID-19 Global Pandemic on the Otolaryngology Fellowship Application Process

On March 11, 2020, the World Health Organization declared coronavirus disease 2019 a global pandemic. In addition to massive social disruption, this pandemic affected the traditional fellowship interview season for otolaryngology subspecialties, including head and neck surgical oncology, facial plastic and reconstructive surgery, laryngology, rhinology, neurotology, and pediatric otolaryngology. The impact on the fellowship interview process, from the standpoint of the institution and the applicant, necessitated the use of alternative interview processes. This change may alter the future of how interviews and the match proceed for years to come, with nontraditional methods of interviewing becoming a mainstay. While the impact this pandemic has on the fellowship match process is not yet fully realized, this commentary aims to discuss the challenges faced on both sides of the equation and to offer solutions during these unprecedented times

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Peri-operative factors predisposing to pharyngocutaneous fistula after total laryngectomy: analysis of a large multi-institutional patient cohort

BACKGROUND: Pharyngocutaneous fistula (PCF) is a problematic complication following total laryngectomy. Disagreement remains regarding predisposing factors. This study examines perioperative factors predicting PCF following total laryngectomy using a large multicenter data registry. METHODS: Retrospective cohort analysis was performed using patients undergoing total laryngectomy in the ACS-NSQIP database for 2006-2014. Sub-analysis was performed based on reconstruction type. Outcome of interest was PCF development within 30 days. RESULTS: Multivariate analysis of 971 patients was performed. Three variables showed statistical significance in predicting PCF: wound classification of 3 and 4 vs. 1-2 (OR 6.42 P \u3c 0.0004 and OR 8.87, P \u3c 0.0042), pre-operative transfusion of \u3e 4 units of packed red blood cells (OR 6.28, P = 0.043), and free flap versus no flap reconstruction (OR 2.81, P = 0.008). CONCLUSIONS: This study identifies important risk factors for development of PCF following total laryngectomy in a large, multi-institutional cohort of patients, thereby identifying a subset of patients at increased risk

Does metformin usage improve survival in head and neck squamous cell carcinoma? A population-based study

Abstract Background We sought to expand upon preliminary data suggesting that metformin confers a survival benefit to patients with head and neck squamous cell carcinoma (HNSCC). Methods A large-scale retrospective cohort study of all patients in Ontario diagnosed with squamous cancer of the larynx, hypopharynx, and nasopharynx between Dec 1st 2007 to Dec 1st 2012 was undertaken. The Institute for Clinical and Evaluative Sciences was accessed to obtain patient demographic, treatment and outcome information. We included patients on metformin at the time of diagnosis. Kaplan Meier methods and Cox Regression models were used. Results Patients taking metformin at the time of diagnosis had a higher comorbid status but were otherwise similar to patients without metformin usage. Using multivariate analysis, neither overall survival nor disease specific survival was improved in patients on metformin (OS: HR 1.123, p = .338; DSS: HR 1.048, p = .792). Conclusions No survival advantage was observed in patients with HNSCC taking metformin at the time of diagnosis

Droplet Exposure Risk to Providers From In-Office Flexible Laryngoscopy: A COVID-19 Simulation

To provide data on risk of respiratory droplets from common otolaryngologic procedures during the COVID-19 pandemic, a novel simulation of droplet exposure from flexible laryngoscopy was performed. After completion of a nasal symptom questionnaire, topical fluorescein spray was administered into the nasal and oropharynx of 10 healthy volunteers, who then underwent flexible laryngoscopy under 2 conditions: routine without provoked response and with prompted sneeze/cough. After each, droplets on the proceduralist and participant were counted under ultraviolet A light. Droplets were observed on 1 of 10 volunteers after routine laryngoscopy and 4 of 10 during laryngoscopy with sneeze/cough. A nasal symptom score based on congestion and rhinorrhea was significantly elevated among droplet producers after sneeze/cough (P = .0164). No droplets were observed on the provider. Overall, with adequate personal protective equipment, flexible laryngoscopy poses minimal droplet risk to providers. Nasal symptoms can identify patients more likely to produce droplets after sneeze/cough

Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study.

BACKGROUND: There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh-the most important blood groups-cannot be done with SNP typing alone. We aimed to develop a novel method based on whole-genome sequencing to identify RBC and platelet antigens. METHODS: This whole-genome sequencing study is a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial (NCT01736566) with no measured patient outcomes. We created a database of molecular changes in RBC and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis-trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30 × depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons. FINDINGS: We iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99·5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99·8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage). INTERPRETATION: By enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine. FUNDING: National Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust