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Somatic mutations that perturb Parkin ubiquitin ligase activity and the misregulation of iron homeostasis have both been linked to Parkinson's disease. Lactotransferrin (LTF) is a member of the family of transferrin iron binding proteins that regulate iron homeostasis, and increased levels of LTF and its receptor have been observed in neurodegenerative disorders like Parkinson's disease. Here, we report that Parkin binds to LTF and ubiquitylates LTF to influence iron homeostasis. Parkin-dependent ubiquitylation of LTF occurred most often on lysines (K) 182 and 649. Substitution of K182 or K649 with alanine (K182A or K649A, respectively) led to a decrease in the level of LTF ubiquitylation, and substitution at both sites led to a major decrease in the level of LTF ubiquitylation. Importantly, Parkin-mediated ubiquitylation of LTF was critical for regulating intracellular iron levels as overexpression of LTF ubiquitylation site point mutants (K649A or K182A/K649A) led to an increase in intracellular iron levels measured by ICP-MS/MS. Consistently, RNAi-mediated depletion of Parkin led to an increase in intracellular iron levels in contrast to overexpression of Parkin that led to a decrease in intracellular iron levels. Together, these results indicate that Parkin binds to and ubiquitylates LTF to regulate intracellular iron levels. These results expand our understanding of the cellular processes that are perturbed when Parkin activity is disrupted and more broadly the mechanisms that contribute to Parkinson's disease.

Short-rib polydactyly syndromes (SRPS) arise from mutations in genes involved in retrograde intraflagellar transport (IFT) and basal body homeostasis, which are critical for cilia assembly and function. Recently, mutations in WDR34 or WDR60 (candidate dynein intermediate chains) were identified in SRPS. We have identified and characterized Tctex1d2, which associates with Wdr34, Wdr60 and other dynein complex 1 and 2 subunits. Tctex1d2 and Wdr60 localize to the base of the cilium and their depletion causes defects in ciliogenesis. We propose that Tctex1d2 is a novel dynein light chain important for trafficking to the cilium and potentially retrograde IFT and is a new molecular link to understanding SRPS pathology.

Historically, comprehensive surgical resection for olfactory neuroblastoma has included the bilateral olfactory epithelium, cribriform plate, overlying dura, olfactory bulbs and tracts. This results in postoperative anosmia that may significantly impact a patient's quality of life without definitive added benefit in survival. The prevalence of occult intracranial disease is low, especially for Hyams grade I and II tumors. A unilateral approach sparing the contralateral cribriform plate and olfactory system can be considered for select cases of early stage, low‐grade tumors when the disease does not cross midline to involve the contralateral olfactory cleft or septal mucosa and when midline dural margins can be cleared with frozen pathology. Approximately half of patients who undergo unilateral resection may have residual olfaction even with adjuvant unilateral radiation. Early data suggest favorable disease‐free survival and overall survival for patients who underwent the unilateral approach; however, larger sample studies are needed to confirm comparability to bilateral resections regarding oncologic outcomes. [ABSTRACT FROM AUTHOR]

Objective: Post-tracheotomy swallowing function has not been well described in the pediatric population. This study aims to (1) determine differences in swallowing functioning pre- and post-tracheotomy and (2) examine the association between postoperative dysphagia and indication for tracheotomy, age at the time of tracheotomy, and time between tracheotomy and modified barium swallow (MBS). Methods: A retrospective chart review was performed on 752 patients who underwent a tracheotomy from 2003 to 2018 and had adequate documentation for review. Patients were included if they received a post-operative MBS. Descriptive statistics, logistic regression, and Fisher's exact test were used to analyze the data. Results: The cohort included 233 patients. The mean age at the time of tracheotomy was 25 months (±50.5). The indications for the tracheotomy were upper airway obstruction (110/233, 47.2%), chronic respiratory failure (104/233, 44.6%), and neurologic disease (19/233, 8.2%). The mean time from tracheotomy to post-operative MBS was 224 days (±297.7). Of the patients who had documented pre- and post-tracheotomy diets, nearly half of patients had improvement in their swallowing function after tracheotomy placement (82/195; 42.1%). Post-tracheotomy MBS recommended thickened liquids in 30.9% of the patients (72/233) and 42.5% (99/233) were recommended thin liquids. The remainder (62/233, 26.6%) remained nothing by mouth (NPO). Patients with neurological disease as the indication for the tracheotomy were more likely to remain NPO (P =.039). Conclusion: A tracheotomy can functionally and anatomically affect swallowing in pediatric patients. The majority of our studied cohort was able to resume some form of an oral diet postoperatively based on MBS. This study highlights the need for objective measurements of swallowing in the postoperative tracheotomy patient to allow for safe and timely commencement of an oral diet. Level of Evidence: Level 3. [ABSTRACT FROM AUTHOR]

Objective: To analyze trends in otolaryngology consultations and provide algorithms to guide management during the COVID-19 pandemic. Methods: A retrospective cohort study at a single institution tertiary care hospital. A total of 95 otolaryngology consultations were performed from March 1, 2020 to April 26, 2020 (COVID-era) and 363 were performed from September 1, 2019 to February 29, 2020 (pre-COVID-era) at the UPMC Oakland campus. Data collected included patient demographics, COVID-19 status, reason for consult, location of consult, type of consult, procedures performed, need for surgical intervention, length of hospital stay and recommended follow up. Results: Patient populations in the pre-COVID-era and COVID-era were similar in terms of their distribution of demographics and chief complaints. Craniofacial trauma was the most common reason for consultation in both periods, followed by vocal fold and airway-related consults. We saw a 21.5% decrease in the rate of consults seen per month during the COVID-era compared to the 6 months prior. Review of trends in the consult workflow allowed for development of several algorithms to safely approach otolaryngology consults during the COVID-19 pandemic. Conclusions: Otolaryngology consultations provide valuable services to inpatients and patients in the emergency department ranging from evaluation of routine symptoms to critical airways. Systematic otolaryngology consult service modifications are required in order to reduce risk of exposure to healthcare providers while providing comprehensive patient care. [ABSTRACT FROM AUTHOR]

Objective: (1) Review a multidisciplinary vascular anomalies center's practice regarding periprocedural anticoagulation for venous malformations (VM) and the associated risk of thromboembolic and disseminated intravascular coagulation (DIC) events. (2) Compare the risk of thromboembolic events and DIC post‐procedure between head and neck (H&N) and extremity VM patients. Methods: An Institutional Review Board (IRB)‐approved, retrospective chart review was performed on 120 VM patients. A thromboembolic event was defined as a thrombus formation post‐sclerotherapy or post‐surgery within 2 months in a distant or local venous structure not directly addressed by the procedure. Results: There were 39 cases involving the H&N and 81 cases based at the extremities. There were eight cases of post‐procedure thrombus formation within the extremity VM group (8/71; 11.3%) as opposed to 0 cases in the H&N group (OR: 0, 95% CI.00–.09), p =.049. There was no difference in incidence of post‐procedure thromboembolic events between those with elevated D‐dimer (H&N: 0%, extremity: 22.7%, 5/22) and normal D‐dimer values (H&N: 0%, extremity: 6.3% [1/16], P =.370). There was no difference in incidence of post‐procedure thromboembolic events between those who received periprocedural anticoagulation (H&N: 0%, extremity: 21%, 4/19) and those who did not (H&N: 0%, extremity: 8.2%, 4/49), (Extremity: OR: 3.00,.67–13.50, P =.206). Conclusion: Post‐procedure thromboembolism is rare in the treatment of venous malformations, especially in the head and neck subsite. Regardless of anticoagulation use, there were no thromboembolic events for H&N VM patients. Such events are rare, and the odds may approach zero, especially with small sample size. Level of Evidence: 4 Laryngoscope, 131:1163–1167, 2021 [ABSTRACT FROM AUTHOR]

Objective: During the COVID-19 era, a reliable method for tracing aerosols and droplets generated during otolaryngology procedures is needed to accurately assess contamination risk and to develop mitigation measures. Prior studies have not investigated the reliability of different fluorescent tracers for the purpose of studying aerosols and small droplets. Objectives include (1) comparing vitamin B2, fluorescein, and a commercial fluorescent green dye in terms of particle dispersion pattern, suspension into aerosols and small droplets, and fluorescence in aerosolized form and (2) determining the utility of vitamin B2 as a fluorescent tracer coating the aerodigestive tract mucosa in otolaryngology contamination models. Methods: Vitamin B2, fluorescein, and a commercial fluorescent dye were aerosolized using a nebulizer and passed through the nasal cavity from the trachea in a retrograde-intubated cadaveric head. In another scenario, vitamin B2 was irrigated to coat the nasal cavity and nasopharyngeal mucosa of a cadaveric head for assessment of aerosol and droplet generation from endonasal drilling. A cascade impactor was used to collect aerosols and small droplets ≤14.1 µm based on average aerodynamic diameter, and the collection chambers were visualized under UV light. Results: When vitamin B2 was nebulized, aerosols ≤5.4 µm were generated and the collected particles were fluorescent. When fluorescein and the commercial water tracer dye were nebulized, aerosols ≤8.61 µm and ≤2.08 µm respectively were generated, but the collected aerosols did not appear visibly fluorescent. Endonasal drilling in the nasopharynx coated with vitamin B2 irrigation yielded aerosols ≤3.30 µm that were fluorescent under UV light. Conclusion: Vitamin B2's reliability as a fluorescent tracer when suspended in aerosols and small droplets ≤14.1 µm and known mucosal safety profile make it an ideal compound compared to fluorescein and commercial water-based fluorescent dyes for use as a safe fluorescent tracer in healthcare contamination models especially with human subjects. [ABSTRACT FROM AUTHOR]

Objective: To define the aerosol and droplet risks associated with endonasal drilling and to identify mitigation strategies. Study Design: Simulation series with fluorescent 3-dimensional (3D) printed sinonasal models and deidentified cadaveric heads. Settings: Dedicated surgical laboratory. Subjects and Methods: Cadaveric specimens irrigated with fluorescent tracer and fluorescent 3D-printed models were drilled. A cascade impactor was used to collect aerosols and small droplets of various aerodynamic diameters under 15 µm. Large droplet generation was measured by evaluating the field for fluorescent debris. Aerosol plumes through the nares were generated via nebulizer, and mitigation measures, including suction and SPIWay devices, nasal sheaths, were evaluated regarding reduction of aerosol escape from the nose. Results: The drilling of cadaveric specimens without flexible suction generated aerosols ≤3.30 µm, and drilling of 3D sinonasal models consistently produced aerosols ≤14.1 µm. Mitigation with SPIWay or diameter-restricted SPIWay produced same results. There was minimal field contamination in the cadaveric models, 0% to 2.77% field tarp area, regardless of drill burr type or drilling location; cutting burr drilling without suction in the 3D model yielded the worst contamination field (36.1%), followed by coarse diamond drilling without suction (19.4%). The simple placement of a flexible suction instrument in the nasal cavity or nasopharynx led to complete elimination of all aerosols ≤14.1 µm, as evaluated by a cascade impactor positioned immediately at the nares. Conclusion: Given the findings regarding aerosol risk reduction, we strongly recommend that physicians use a suction instrument in the nasal cavity or nasopharynx during endonasal surgery in the COVID-19 era. [ABSTRACT FROM AUTHOR]