Airway protection and outcomes after staged versus concurrent bilateral neck dissections with transoral base of tongue cancer resection.

OBJECTIVES: To assess airway, safety, and resource utilization outcomes between transoral base of tongue (BOT) surgery with staged versus concurrent bilateral neck dissections (BND). METHODS: A retrospective cohort study of patients with human papilloma virus (HPV)-related BOT cancer who underwent transoral surgery and BND from January 2015 through June 2022 was conducted. Free flap patients were excluded. RESULTS: Of 126 patients (46 [37%] staged and 80 [63%] concurrent BND), there were no significant differences in rates of postoperative intubation, tracheostomy, intensive care admission, operative takebacks, gastrostomy, and 30-day readmission. Total operative time (median difference 1.4 [95% CI 0.9-1.8] hours), length of stay (1.0 [1.0-1.0] day), and time between primary surgery and adjuvant therapy initiation (4.0 [0.0-8.0] days) were lower in the concurrent BND cohort. CONCLUSION: Concurrent BND alongside transoral BOT resection is safe with similar airway outcomes and lower total operative time, length of stay, and time to adjuvant therapy initiation compared to staged BND.

Neighborhood socioeconomic status and race are associated with incidence disparities in oral cavity cancers.

OBJECTIVES: To determine the association between neighborhood socioeconomic status (nSES), race and incidence rate trends of oral cavity cancer (OCC). MATERIALS AND METHODS: We used data from the SEER (Surveillance, Epidemiology, and End Results) 18 Census Tract-level SES and Rurality Database (2006-2018) database of the National Cancer Institute to create cohorts of OCC patients between 2006 and 2018. Annual incidence rates were calculated and trends in rates were estimated using joinpoints regression. RESULTS: The incidence of OCC is the highest among low nSES White Americans (2.86 per 100 000 persons) and the lowest among high nSES Black Americans (1.17 per 100 000 persons). Incidence has significantly increased among Asian Americans (annual percent change [APC]: low nSES-2.4, high nSES-2.6) and White Americans (APC: low nSES-1.4, high nSES-1.6). Significant increases in the incidence of oral tongue cancer in these groups primarily drive this increase. Other increases were noted in alveolar ridge cancer among White Americans and hard palate cancer among Asian Americans. OCC incidence decreased significantly in Hispanic Americans of high nSES (APC: -2.5) and Black Americans of low nSES (APC: -2.7). Floor of mouth cancer incidence decreased among most groups. CONCLUSION: Despite the overall decreasing incidence of OCC, these trends are inconsistent among all OCC subsites. Differences are seen by race, nSES, and subsite, indicating intersectional barriers that extend beyond nSES and race and ethnicity alone. Further research on risk factors and developing interventions targeting vulnerable groups is needed.

Eight Tales of Cervical Necrotizing Fasciitis and Free Tissue Transfer.

OBJECTIVES: Aggressive surgical debridement is required in cervical necrotizing fasciitis, and in severe defects, subsequent free tissue transfer might be necessary. However, there is concern that the inflammatory environment of the infection site may threaten free flap viability, particularly with concerns for thrombosis of feeding vessels and compromised tissue integration. Cases in the head and neck area are rare, so there are limited data regarding outcomes of free tissue transfer in these patients. METHODS: A retrospective chart review assessed patients with cervical necrotizing fasciitis treated at an academic tertiary hospital between 2015 and 2021. Twenty-five patients were identified, and eight required free tissue transfer after adequate surgical debridement. Treatment, hospital course, and demographic data were collected on these eight patients. RESULTS: All flaps had full survival at follow up (median follow up 3 months, range 1-39 months) without concerns for vascular compromise. CONCLUSION: These data suggest that in patients with large soft tissue defects due to cervical necrotizing fasciitis, free tissue transfer may be a safe treatment modality.

Risk Factors for Functional Outcomes in Advanced Laryngeal Squamous Cell Carcinoma.

OBJECTIVE: Chemoradiation for patients with laryngeal squamous cell carcinoma (SCC) may achieve organ preservation, but appropriate patient selection remains unknown. This study investigates pre-treatment risk factors associated with functional and survival outcomes after radiation-based therapy in patients with advanced laryngeal SCC. METHODS: A retrospective cohort study was performed on 75 adult patients with stage III or IV laryngeal SCC receiving definitive radiation-based therapy from 1997 to 2016 at a tertiary care center. Tracheostomy and gastrostomy dependence were the primary functional outcomes. Multivariable logistic regressions were performed to evaluate relationships between pre-treatment factors and tracheostomy and gastrostomy dependence. Time-to-event analyses were performed to determine risk factors associated with overall survival. RESULTS: Among 75 patients included in the analysis, 30 (40%) patients were tracheostomy dependent and 31 (41%) were gastrostomy tube dependent. The median length of follow-up was 31 months (range = 1 to 142 months). Pre-treatment tracheostomy was a significant predictor of post-treatment tracheostomy (aOR = 13.9, 95% CI = 3.35 to 57.5) and moderate-severe comorbidity was a significant predictor of post-treatment gastrostomy dependence (aOR = 2.96, 95% CI = 1.04 to 8.43). The five-year overall survival was 51% (95% CI = 38 to 64%). Pre-treatment gastrostomy tube dependence was associated with an increased risk of death (aHR = 2.45, 95% CI = 1.09 to 5.53). CONCLUSIONS: Baseline laryngeal functional status and overall health in advanced laryngeal SCC are associated with poor functional outcomes after radiation-based therapy, highlighting the importance of patient selection when deciding between surgical and non-surgical treatment plans. Laryngoscope, 133:594-600, 2023.

Infection Control With Topical Antimicrobial Prophylaxis for Mucosal Head and Neck Surgery: A Meta-analysis.

OBJECTIVE: To assess for differences in surgical site infection (SSI) rates and bacterial load after major mucosal head and neck surgery between patients who received topical antimicrobial prophylaxis and those who did not. DATA SOURCES: Ovid Medline, Embase, SCOPUS, Cochrane Library, and ClinicalTrials.gov from inception to May 20, 2021, with cross-referencing of retrieved studies per PRISMA guidelines. REVIEW METHODS: Inclusion criteria captured clinical trials, cohort studies, and case-control studies with infectious outcomes of adults who underwent major mucosal head and neck surgery and received perioperative topical antimicrobial therapy to the oral cavity and/or pharynx. Studies of dental procedures were excluded. The primary outcome was SSI rate, and the secondary outcome was bacterial load. Two blinded investigators screened each text. RESULTS: Of 265 unique citations, 9 studies of 470 total patients were included. Topical treatments included numerous antibiotics and antiseptics directly applied over mucosa. Pooled SSI rates of 252 patients in the intervention cohort and 218 in the control cohort were 8% (95% CI, 3%-14%; I 2 = 61.2%) and 29% (95% CI, 16%-43%; I 2 = 79.5%), respectively. A meta-analysis of 7 comparative studies totaling 192 patients receiving topical therapy and 218 control patients revealed a pooled relative risk of 0.44 (95% CI, 0.28-0.68; I 2 = 0.0%) in favor of the treatment group. The studies demonstrated a short-term decrease in bacterial counts after topical antimicrobial prophylaxis. CONCLUSION: Patients who underwent prophylactic topical antimicrobial therapy had less than half the risk of developing SSI after mucosal head and neck surgery when compared with those who received no topical prophylaxis.

Development and Psychometric Validation of the Olfactory Dysfunction Outcomes Rating.

Importance: Olfactory dysfunction (OD) is an increasingly common and morbid condition, especially given the ongoing COVID-19 pandemic. Thus, the ability to reproducibly measure smell loss-associated quality of life (QOL) and its response to treatment is paramount. Objective: To develop and validate a concise and visually appealing smell loss-associated QOL patient-reported outcome measure for OD. Design, Setting, and Participants: A secondary analysis of comments to an online survey by 1000 patients with olfactory dysfunction published in 2013 was used as the primary source to generate items of the Olfactory Dysfunction Outcomes Rating (ODOR). In addition, 30 patients with OD enrolled in 2 clinical studies at a tertiary care medical center (Washington University) were asked to identify their main concerns associated with smell loss. And finally, 4 otolaryngologists reviewed the items generated from the online survey and the patients' interviews to identify any additional items. Prospective study design was used for data collection from the 30 patients and 4 otolaryngologists. Prospective study design was used for survey validation. Validation of the ODOR was performed with 283 patients enrolled in several prospective studies at a single institution that completed the ODOR as an outcome measure. Main Outcomes and Measures: Item generation and selection were the outcomes of ODOR development. The psychometric and clinimetric measures evaluated for validation were internal consistency, test-retest reliability, face and content validity, concurrent validity, and discriminant validity. Minimal clinically important difference was also determined. Results: The ODOR is a 28-item instrument with each item scored as either no difficulty or very rarely bothered (0) to complete difficulty or very frequently bothered (4) with a total instrument score range of 0 to 112 points. Higher scores indicate higher degree of dysfunction and limitation. Validation in the cohort of 283 patients (mean [SD] age, 47.0 [14.4] years; 198 female participants [73%]; 179 White participants [80%]) revealed that the instrument has high internal consistency (Cronbach α = 0.968), test-retest reliability (r = 0.90 [95% CI, 0.81-0.95]), face validity, content validity, concurrent validity (r = 0.87 [95% CI, 0.80-0.91] compared with the Questionnaire of Olfactory Disorders-Negative Statements; ρ = -0.76 [95% CI, -0.81 to -0.71] compared with a patient-reported symptom severity scale), and divergent validity (mean score difference, -33.9 [95% CI, -38.3 to -29.6] between normosmic patients and hyposmic/anosmic patients). The minimal clinically important difference was 15 points. The estimated time for survey completion was approximately 5 minutes. Conclusions and Relevance: In this survey creation and validation study, the ODOR was shown to be a novel, concise, reliable, and valid patient-reported outcome measure of OD-associated QOL. It can be used to measure physical problems, functional limitations, and emotional consequences associated with OD and how they change after a given intervention, which is clinically applicable and particularly pertinent given the growing burden of OD associated with COVID-19.

Efficacy and Safety of Saline Nasal Irrigation Plus Theophylline for Treatment of COVID-19-Related Olfactory Dysfunction: The SCENT2 Phase 2 Randomized Clinical Trial.

Importance: Recent studies suggest that theophylline added to saline nasal irrigation (SNI) can be an effective treatment for postviral olfactory dysfunction (OD), a growing public health concern during the COVID-19 pandemic. Objective: To evaluate the efficacy and safety of theophylline added to SNI compared with placebo for COVID-19-related OD. Design, Setting, and Participants: This triple-blinded, placebo-controlled, phase 2 randomized clinical trial was conducted virtually between March 15 and August 31, 2021. Adults residing in Missouri or Illinois were recruited during this time period if they had OD persisting for 3 to 12 months following suspected COVID-19 infection. Data analysis was conducted from October to December 2021. Interventions: Saline sinus rinse kits and bottles of identical-appearing capsules with either 400 mg of theophylline (treatment) or 500 mg of lactose powder (control) were mailed to consenting study participants. Participants were instructed to dissolve the capsule contents into the saline rinse and use the solution to irrigate their nasal cavities in the morning and at night for 6 weeks. Main Outcomes and Measures: The primary outcome was the difference in the rate of responders between the treatment and the control arms, defined as a response of at least slightly better improvement in the Clinical Global Impression-Improvement scale posttreatment. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT), the Questionnaire for Olfactory Disorders, the 36-Item Short Form Health Survey on general health, and COVID-19-related questions. Results: A total of 51 participants were enrolled in the study; the mean (SD) age was 46.0 (13.1) years, and 36 (71%) participants were women. Participants were randomized to SNI with theophylline (n = 26) or to SNI with placebo (n = 25). Forty-five participants completed the study. At the end of treatment, 13 (59%) participants in the theophylline arm reported at least slight improvement in the Clinical Global Impression-Improvement scale (responders) compared with 10 (43%) in the placebo arm (absolute difference, 15.6%; 95% CI, -13.2% to 44.5%). The median difference for the UPSIT change between baseline and 6 weeks was 3.0 (95% CI, -1.0 to 7.0) for participants in the theophylline arm and 0.0 (95% CI, -2.0 to 6.0) for participants in the placebo arm. Mixed-model analysis revealed that the change in UPSIT scores through study assessments was not statistically significantly different between the 2 study arms. Eleven (50%) participants in the theophylline arm and 6 (26%) in the placebo arm had a change of 4 or more points in UPSIT scores from baseline to 6 weeks. The difference in the rate of responders as measured by the UPSIT was 24% (95% CI, -4% to 52%) in favor of theophylline. Conclusions and Relevance: This randomized clinical trial suggests that the clinical benefit of theophylline nasal irrigations on olfaction in participants with COVID-19-related OD is inconclusive, though suggested by subjective assessments. Larger studies are warranted to investigate the efficacy of this treatment more fully. Trial Registration: ClinicalTrials.gov Identifier: NCT04789499.

Development and Validation of a Novel At-home Smell Assessment.

IMPORTANCE: Current tools for diagnosis of olfactory dysfunction (OD) are costly, time-consuming, and often require clinician administration. OBJECTIVE: To develop and validate a simple screening assessment for OD using common household items. DESIGN, SETTING, AND PARTICIPANTS: This fully virtual diagnostic study included adults with self-reported OD from any cause throughout the US. Data were collected from December 2020 to April 2021 and analyzed from May 2021 to July 2021. MAIN OUTCOMES AND MEASURES: Participants with self-reported olfactory dysfunction took a survey assessing smell perception of 45 household items and completed the Clinical Global Impression-Severity (CGI-S) smell questionnaire, the University of Pennsylvania Smell Identification Test (UPSIT), and the 36-item Short Form Survey (SF-36). Psychometric and clinimetric analyses were used to consolidate 45 household items into 2 short Novel Anosmia Screening at Leisure (NASAL) assessments, NASAL-7 (range, 0-14; lower score indicating greater anosmia) and NASAL-3 (range, 0-6; lower score indicating greater anosmia). RESULTS: A total of 115 participants were included in the study, with a median (range) age of 42 (19-70) years, 92 (80%) women, and 97 (84%) White individuals. There was a moderate correlation between the UPSIT and NASAL-7 scores and NASAL-3 scores (NASAL-7: ρ = 0.484; NASAL-3: ρ = 0.404). Both NASAL-7 and NASAL-3 had moderate accuracy in identifying participants with anosmia as defined by UPSIT (NASAL-7 area under the receiver operating curve [AUC], 0.706; 95% CI, 0.551-0.862; NASAL-3 AUC, 0.658; 95% CI, 0.503-0.814). Scoring 7 or less on the NASAL-7 had 70% (95% CI, 48%-86%) sensitivity and 53% (95% CI, 43%-63%) specificity in discriminating participants with anosmia from participants without. Scoring 2 or less on the NASAL-3 had 57% (95% CI, 36%-76%) sensitivity and 78% (95% CI, 69%-85%) specificity in discriminating participants with anosmia from participants without. There was moderate agreement between UPSIT-defined OD categories and those defined by NASAL-7 (weighted κ = 0.496; 95% CI, 0.343-0.649) and those defined by NASAL-3 (weighted κ = 0.365; 95% CI, 0.187-0.543). The agreement with self-reported severity of olfactory dysfunction as measured by CGI-S and the NASAL-7 and NASAL-3 was moderate, with a weighted κ of 0.590 (95% CI, 0.474-0.707) for the NASAL-7 and 0.597 (95% CI, 0.481-0.712) for the NASAL-3. CONCLUSION AND RELEVANCE: The findings of this diagnostic study suggest that NASAL-7 and NASAL-3, inexpensive and brief patient-reported assessments, can be used to identify individuals with OD. As the burden of COVID-19-associated OD increases, these assessments may prove beneficial as screening and diagnostic tools. Future work will explore whether the NASAL assessments are sensitive to change and how much of a change is clinically important.

Curbing the Cough: Multimodal Treatments for Neurogenic Cough: A Systematic Review and Meta-Analysis.

OBJECTIVES/HYPOTHESIS: Neurogenic cough affects 11% of Americans and causes significant detriment to quality of life. With the advent of novel therapies, the objective of this review is to determine how procedural therapies (e.g., superior laryngeal nerve block) compare to other established pharmacologic and non-pharmacologic treatments for neurogenic cough. METHODS: With the assistance of a medical librarian, a systematic review was performed using PICOS (patients, interventions, comparator, outcome, study design) format: adults with neurogenic cough receiving any pharmacologic or non-pharmacologic treatment for neurogenic cough compared to adults with neurogenic cough receiving any other relevant interventions, or treated as single cohorts, assessed with cough-specific quality of life outcomes, in all study designs and case series with ≥ 10 cases. Case reports, review articles, non-human studies, non-English language articles, and unavailable full-text articles were excluded. RESULTS: There were 2408 patients with neurogenic cough in this review, treated with medical therapy (77%), speech therapy (19%), both medical and speech therapy (1%), and procedural therapy (3%). The included studies ranged from low to intermediate quality. Overall, most interventions demonstrated successful improvement in cough. However, the heterogeneity of included study designs precluded direct comparisons between intervention types. CONCLUSION: This meta-analysis compared various treatments for neurogenic cough. Procedural therapy should be considered in the armamentarium of neurogenic cough treatments, particularly in patients refractory to, or intolerant of, the side effects of medical therapy. Lastly, this review illuminates key areas for improving neurogenic cough diagnosis, such as strict adherence to diagnostic and treatment guidelines, sophisticated reflux testing, and standardized, consistent outcome reporting. Laryngoscope, 132:107-123, 2022.

Chronic rhinosinusitis as a risk factor for intracranial and extracranial complications after endoscopic transsphenoidal surgery.

PURPOSE: To elucidate whether chronic rhinosinusitis (CRS), usually an inflammatory-mediated rather than infectious process, is a risk factor for extracranial and intracranial complications after elective endoscopic transsphenoidal surgery (ETSS). MATERIALS AND METHODS: A single-center retrospective cohort study of consecutive patients who underwent ETSS between January 2015 and July 2019 was performed, which included chart review and computed tomography assessment. CRS was defined by symptomatology and concurrent endoscopic or radiographic findings. RESULTS: Of 292 subjects, 11% (n = 33) met criteria for CRS. Median difference in Lund-Mackay scores between the CRS and non-CRS groups was 3.0 (95% CI 2.0-4.0). Complications included acute rhinosinusitis requiring antibiotics (23%, 68/292), epistaxis (10%, 28/292), meningitis (1%, 3/292), cerebrospinal fluid (CSF) leak (7%, 20/292), revision sinonasal procedures (10%, 28/292), and frequent in-office debridement (13%, 39/292). CRS was strongly associated with postoperative acute rhinosinusitis (aRR 1.85, 95% CI 1.18-2.90) and frequent debridement (aRR 1.96, 95% CI 1.00-3.83). Conversely, CRS was not associated with epistaxis (aRR 1.52, 95% CI 0.62-3.72), postoperative CSF leak (aRR 0.91, 95% CI 0.24-3.44), or additional sinonasal procedures (aRR 0.70, 95% CI 0.21-2.29). The rate of meningitis was not significantly higher in the CRS cohort (difference 2.2%, 95% CI -1.0% to 14.5%). CONCLUSIONS: CRS was a strong risk factor for acute rhinosinusitis and need for frequent in-office debridement after ETSS. It was not associated with other postoperative complications including epistaxis, CSF leak, or revision sinonasal procedures. CRS patients had a slightly higher rate of meningitis, which is likely not clinically meaningful.

Management of Flap Failure After Head and Neck Reconstruction: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically review management of flap loss in head and neck construction with free tissue transfer as compared with locoregional flap or conservative management. DATA SOURCES: Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov were searched up to October 2019. REVIEW METHODS: Candidate articles were independently reviewed by 2 authors. Articles were considered eligible if they included adequate reporting of flap management after flap loss and outcomes for survival of reconstruction, length of hospitalization, and perioperative complications. RESULTS: A total of 429 patients had acute flap failure in the perioperative period. The overall success with a secondary free flap was 93% (95% CI, 0.89-0.97; n = 26 studies, I2 = 12.8%). There was no difference in hospitalization length after secondary reconstruction between free tissue transfer and locoregional flaps or conservative management (relative risk of hospitalization ≥2 weeks, 96%; 95% CI, 0.80-1.14; n = 3 studies, I2 = 0). The pooled relative risk of perioperative complications following free tissue transfer was 0.60 when compared with locoregional flap or conservative management (95% CI, 0.40-0.92; n = 5 studies, I2 = 0). CONCLUSION: Salvage reconstruction with free tissue transfer has a high success rate. Second free flaps following flap failure had a similar length of hospitalization and lower overall complication rate than locoregional reconstruction or conservative management. A second free tissue transfer, when feasible, is likely a more reliable and effective procedure for salvage reconstruction.

Smell Changes and Efficacy of Nasal Theophylline (SCENT) irrigation: A randomized controlled trial for treatment of post-viral olfactory dysfunction.

OBJECTIVE: To evaluate the efficacy and safety of intranasal theophylline saline irrigation on olfactory recovery in patients with post-viral olfactory dysfunction (PVOD). METHODS: Between May 2019 and April 2020, we conducted a double-blinded, placebo-controlled randomized clinical trial of adults with 6-36 months of PVOD. Patients were randomized to nasal theophylline saline irrigation or placebo saline irrigation twice a day for 6 weeks. The primary outcome was the Global Rating of Smell Change. Secondary outcomes were changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). RESULTS: Twenty-two patients (n = 12, theophylline; n = 10, placebo) completed the study. Slightly more patients in the theophylline group (33%) reported improved smell compared to the placebo group (30%, difference 3.3%, 95% CI -35.6% to 42.3%). The median differences in pre- and post-treatment UPSIT and QOD-NS change between the two groups were 1 (95% CI -3 to 5) and -10 (95% CI -15 to -4), respectively in favor of theophylline. Three patients receiving theophylline and 2 receiving placebo had clinically meaningful improvements on the UPSIT (difference 5%, 95% CI -30% to 40%). There were no adverse events, and serum theophylline levels were undetectable in 10/10 patients. CONCLUSIONS: While safe, there were no clinically meaningful differences in olfactory change between the two groups except for olfaction-related quality of life, which was better with theophylline. The imprecise estimates suggest future trials will need substantially larger sample sizes or treatment modifications, such as increasing the theophylline dose, to observe larger treatment effects.

Endonasal Free Flap Reconstruction Combined With Draf Frontal Sinusotomy for Complex Cerebrospinal Fluid Leak: A Technical Report & Case Series.

BACKGROUND: Frontal sinus cranialization with closure via bifrontal pericranial flaps is the gold standard for separating the nasofrontal recess from the intracranial cavity for posterior table defects. Despite the high success rate, cerebrospinal fluid (CSF) leak may persist and is particularly challenging when vascularized reconstructive options from the bicoronal incision are exhausted. OBJECTIVE: To assess a novel endonasal technique using an adipofascial radial forearm free flap delivered to the frontal recess through a Draf sinusotomy to repair complex CSF leaks from the frontal sinus. METHODS: A retrospective review of 3 patients (all male; ages 42, 43, and 69 yr) with persistent CSF leak despite frontal sinus cranialization and repair with bifrontal pericranium was performed. Etiology of injury was traumatic in 2 patients and iatrogenic in 1 patient after anaplastic meningioma treatment. To create space for the flap and repair the nasofrontal ducts, endoscopic Draf III (Case 1, 3) or Draf IIb left frontal sinusotomy (Case 2) was performed. The forearm flap was harvested, passed through a Caldwell-Luc exposure, and placed within the Draf frontal sinustomy. The flap vessels were tunneled to the left neck and anastomosed to the facial vessels by the mandibular notch. RESULTS: Intraoperatively, the flaps were well-seated and provided a watertight seal. Postoperative hospital courses were uncomplicated. There were no new CSF leaks or flap necrosis at 12, 14, and 16 mo. CONCLUSION: Endoscopic endonasal free flap reconstruction through a Draf procedure is a novel viable option for persistent CSF leak after failed frontal sinus cranialization.

Endoscopic Adipofascial Radial Forearm Free Flap Reconstruction of the Skull Base: A Technical Update.

Objective While most defects after endoscopic endonasal resections can be closed with local or locoregional options, rare cases require free tissue transfer. In this setting, while minimally invasive techniques have been described, the essential procedural details are lacking. The objective of this report is to describe several key technical modifications to free flap harvest and endoscopic-assisted inset which decrease morbidity and improve reliability and efficiency. Methods A retrospective chart review was performed of consecutive patients treated at Washington University in St. Louis with endoscopic free flap reconstruction through a Caldwell-Luc/transbuccal approach between January 2016 and September 2019. Results A total of six patients underwent adipofascial radial forearm free flap with this technique, five for recalcitrant cerebrospinal fluid leak or pneumocephalus and one for osteoradionecrosis. All flaps survived and there were no flap-related complications. Five patients (83%) achieved successful healing and separation of the sinonasal cavity and intracranial space. One patient developed recurrent pneumocephalus. Three key technical modifications were identified that improve efficiency and reliability of flap delivery and inset: (1) use of an adipofascial radial forearm flap, without skin paddle; (2) wide resection of the anterior and lateral maxillary face to facilitate flap delivery; and (3) precise defect measurement and flap contouring prior to inset to prevent any need to debulk the flap in situ. Conclusion Endoscopic adipofascial radial forearm free flap delivered to the skull base through a Caldwell-Luc/transbuccal corridor is a feasible option with a high success rate and low morbidity when other reconstructive attempts have failed.

Computed Tomography as a Predictor of Sinonasal Inverted Papilloma Origin, Skull Base Involvement, and Stage.

Objective To investigate the diagnostic performance of computed tomography (CT) to determine the origin, skull base involvement, and stage of sinonasal inverted papilloma (IP). Design This is a retrospective cohort study. Setting This is set at a tertiary care medical center. Participants Patients with preoperative CT imaging who underwent extirpative surgery for histologically confirmed sinonasal IP between January 2005 and October 2019. Main Outcome Measures The likely sites of tumor origin, skull base involvement, and radiographic tumor stage were determined by two board-certified neuroradiologists after re-reviewing preoperative CT imaging. These radiologic findings were then compared with intraoperative and pathologic findings. Results Of 86 patients, 74% (64/86) had IP lesions with correctly classified sites of origin on CT. CT was not sensitive for diagnosing ethmoid sinus origin (48%, 52%), frontal sinus origin (80%, 40%), and skull base origin (17%, 17%). CT was not sensitive (62%, 57%) but specific (86%, 98%) for identifying any skull base involvement. There was substantial-to-near perfect agreement between radiographic and pathologic Cannady stages (weighted κ = 0.61 for rater 1; weighted κ = 0.81 for rater 2). Interrater agreement was substantial for identifying tumor origin (κ = 0.75) and stage (weighted κ = 0.62) and moderate for identifying skull base involvement (κ = 0.43). Conclusion Interrater agreement on CT findings was substantial except on skull base involvement. CT correctly predicted site of tumor origin in up to 74% of subjects. CT was not sensitive for diagnosing skull base involvement but had substantial-to-near perfect agreement with pathologic tumor staging. CT is a useful but albeit limited adjunct for tumor localization and surgical planning for sinonasal IP.

The Impact of Treatment Delay on Malunion and Nonunion After Open Reduction of Mandible Fractures.

Importance: Time to surgical intervention is an oft-investigated potentially modifiable risk factor for complications after mandible fracture. Objective: To identify novel risk factors for malunion/nonunion after mandible fracture and determine the impact of treatment delay on malunion and nonunion after open reduction of mandible fractures. Design: Retrospective cohort. Setting and Participants: Encounter billing records from the New York State Inpatient Databases, State Emergency Department Databases, and State Ambulatory Surgery Databases. Patients aged 18 years and older with isolated mandible fracture in the emergency department or inpatient setting from January 1, 2006 to September 30, 2015. Main Outcomes and Measures: Mandibular Malunion/Nonunion. Results: A total of 19,152 adults were diagnosed with isolated mandible fracture. After fracture, 247 patients (1.3%) developed mandibular malunion or nonunion. In multivariable analysis, patients with open fractures (odds ratio [OR] 1.93, confidence interval [95% CI] 1.40-2.65), body fractures (OR 2.00, 1.50-2.65), alcohol abuse (OR 1.61, 1.22-2.11), diabetes mellitus (OR 1.57, 1.02-2.42), and Medicaid insurance (OR 1.46, 1.03-2.07) had increased risk, whereas patients with subcondylar fractures had reduced risk (OR 0.45, 0.28-0.72) of mandibular malunion/nonunion. The risk of mandibular malunion/nonunion after open reduction increased with treatment delay until 6-7 days after presentation (OR 1.84, 1.11-3.06). Conclusion and Relevance: Although treatment delay is often unavoidable, these findings suggest that physicians should consider early intervention in patients requiring open reduction of mandible fractures when able.

Orphan nuclear receptor COUP-TFII enhances myofibroblast glycolysis leading to kidney fibrosis.

Recent studies demonstrate that metabolic disturbance, such as augmented glycolysis, contributes to fibrosis. The molecular regulation of this metabolic perturbation in fibrosis, however, has been elusive. COUP-TFII (also known as NR2F2) is an important regulator of glucose and lipid metabolism. Its contribution to organ fibrosis is undefined. Here, we found increased COUP-TFII expression in myofibroblasts in human fibrotic kidneys, lungs, kidney organoids, and mouse kidneys after injury. Genetic ablation of COUP-TFII in mice resulted in attenuation of injury-induced kidney fibrosis. A non-biased proteomic study revealed the suppression of fatty acid oxidation and the enhancement of glycolysis pathways in COUP-TFII overexpressing fibroblasts. Overexpression of COUP-TFII in fibroblasts also induced production of alpha-smooth muscle actin (αSMA) and collagen 1. Knockout of COUP-TFII decreased glycolysis and collagen 1 levels in fibroblasts. Chip-qPCR revealed the binding of COUP-TFII on the promoter of PGC1α. Overexpression of COUP-TFII reduced the cellular level of PGC1α. Targeting COUP-TFII serves as a novel treatment approach for mitigating fibrosis in chronic kidney disease and potentially fibrosis in other organs.

Free vascularized parascapular fat flap for parotidectomy reconstruction.

OBJECTIVE: The contour defect resulting after parotidectomy can be cosmetically unappealing. Multiple reconstructive efforts have been reported to mitigate this problem. We describe a novel technique of vascularized parascapular fat reconstruction based on the circumflex scapular vessels and evaluate its outcomes. METHODS: Consecutive patients who underwent parotidectomy with or without additional resections and vascularized parascapular fat flap reconstruction in 2020 were included. Demographic, morphologic, intraoperative, and postoperative data were assessed. RESULTS: Eight patients (3 female) were included. Median cut-to-close time was 247 (range 209-298) minutes, including tumor ablation. None of the patients had any wound complications, and all except one was discharged on postoperative day 1. Flap monitoring was not performed. None reported any significant donor site morbidity except scar formation. At last follow up, all patients reported satisfactory facial contour. CONCLUSION: Vascularized parascapular fat flap reconstruction of parotidectomy contour defects has satisfactory cosmetic outcomes with minimal morbidity and short hospitalization courses.

Association of Olfactory Training With Neural Connectivity in Adults With Postviral Olfactory Dysfunction.

Importance: Viral upper respiratory tract infections are a major cause of olfactory loss. Olfactory training (OT) is a promising intervention for smell restoration; however, a mechanistic understanding of the changes in neural plasticity induced by OT is absent. Objective: To evaluate functional brain connectivity in adults with postviral olfactory dysfunction (PVOD) before and after OT using resting-state functional magnetic resonance imaging. Design, Setting, and Participants: This prospective cohort study, conducted from September 1, 2017, to November 30, 2019, recruited adults with clinically diagnosed or self-reported PVOD of 3 months or longer. Baseline olfaction was measured using the University of Pennsylvania Smell Identification Test (UPSIT) and the Sniffin' Sticks test. Analysis was performed between December 1, 2020, and July 1, 2020. Interventions: Participants completed 12 weeks of OT using 4 essential oils: rose, eucalyptus, lemon, and clove. The resting-state functional magnetic resonance imaging measurements were obtained before and after intervention. Main Outcome and Measures: The primary outcome measure was the change in functional brain connectivity before and after OT. Secondary outcome measures included changes in UPSIT and Sniffin' Sticks test scores, as well as patient-reported changes in treatment response as measured by subjective changes in smell and quality-of-life measures. Results: A total of 16 participants with PVOD (11 female [69%] and 14 White [88%]; mean [SD] age, 60.0 [10.5] years; median duration of smell loss, 12 months [range, 3-240 months]) and 20 control participants (15 [75%] female; 17 [85%] White; mean [SD] age, 55.0 [9.2] years; median UPSIT score, 37 [range, 34-39]) completed the study. At baseline, participants had increased connectivity within the visual cortex when compared with normosmic control participants, a connection that subsequently decreased after OT. Furthermore, 4 other network connectivity values were observed to change after OT, including an increase in connectivity between the left parietal occipital junction, a region of interest associated with olfactory processing, and the cerebellum. Conclusions and Relevance: The use of OT is associated with connectivity changes within the visual cortex. This case-control cohort study suggests that there is a visual connection to smell that has not been previously explored with OT and that further studies examining the efficacy of a bimodal visual and OT program are needed.