Faculty Bibliography

BACKGROUND:Computerized surgical planning (CSP) in osseous reconstruction of head and neck cancer defects has become a mainstay of treatment. However, the consequences of CSP-designed titanium plating systems on planning adjuvant radiation remains unclear. METHODS:Two patients underwent head and neck cancer resection and maxillomandibular free fibula flap reconstruction with CSP-designed plates and immediate placement of osseointegrated dental implants. Surgical treatment was followed by adjuvant intensity modulated radiation therapy (IMRT). RESULTS:Both patients developed osteoradionecrosis (ORN), and one patient had local recurrence. The locations of disease occurred at the areas of highest titanium plate burden, possibly attributed to IMRT dosing inaccuracy caused by the CSP-designed plating system. CONCLUSION/CONCLUSIONS:Despite proven benefits of CSP-designed plates in osseous free flap reconstruction, there may be an underreported risk to adjuvant IMRT treatment planning leading to ORN and/or local recurrence. Future study should investigate alternative plating methods and materials to mitigate this debilitating outcome.

OBJECTIVES:The current study aimed to identify and map the available evidence surrounding cochlear implantation (CI) in older adults. Five outcomes were evaluated: speech perception scores, perioperative complications, neurocognitive outcomes, quality of life outcomes and vestibular dysfunction and fall rates after surgery. METHODS:A scoping review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews and included patients over the age of 60. RESULTS:Ninety-seven studies met inclusion criteria, encompassing 7,182 patients. Mean (SD) speech perception scores in quiet and in noise pre-and postoperatively were 7.9% (6.7) and 52.8% (14.3) and 8.0% (68.1) and 68.1% (15.9) respectively. Postoperative cardiac arrhythmias, urinary retention, and delirium occurred slightly more frequently in older adults. In terms of cognition, most studies noted stability or improvement one year after implantation. A majority of studies indicated better quality of life post-CI. Rates of fall after surgery were rarely reported, and there was a general paucity of data surrounding vestibular function changes after CI. DISCUSSION:This scoping review identifies many positive outcomes linked to CI in older adults. No findings suggest a single patient characteristic that would warrant refusal to consider evaluation for cochlear implantation.

Background/Purpose: Using whole exome sequencing (WES), we identified a de novo mutation in DYSF encoding dysferlin in 2 unrelated patients with systemic inflammation and sterile pulmonary abscesses. Unlike dysferlin mutations that cause muscular dystrophies, the patients have no muscle disease, but a robust clinical response to IL-1 blockade suggested inflammasome activation and the presentation with sterile pulmonary abscess formation raised questions about an efferocytosis defect Methods: We characterized monocytes and neutrophil activation and function to assess the mechanism of the IL-1 dependent inflammation by flowcytometry, immunofluoroscence, ELISA, cytokine array, survival assay and we developed an efferocytosis assay. U937 cells expressing mutant cell line was used to further understand the mutation.
Result(s): Monocyte and monocyte-derived M1 and M2 macrophages (MDM) stimulated with LPS and ATP-released high IL-1 serum levels, that was higher in the DYSF patients' monocytes and M1 and M2 MDM compared to healthy controls (HC), and was comparable to the augmented IL-1 production in NOMID. Dysferlin colocalizes with NLRP3 in LPS activated monocyte and in M1 and M2 MDMs. Expression levels of ASC, and Caspase-1 were increased in the DYSF patients monocytes. M2-MDMs from both patients expressed proinflammatory mediators, high CXCL1(P< 0.05), CCL2, IL-6 and IL-8. We observed LPS and ATP activation-induced altered nucleur integrity in M2-MDMs from both patients (70% and 50% respectively) compared to healthy controls. In neutrophils, LPS and ATP activation did not increase IL-1b was not upregulated although MIF, IL-16 and IL-8 levels were observed. We hypothesized that either delayed neutrophil apoptosis or clearence contribute to the lung abscess formation. While neutrophil apoptosis was normal, patients' M2 MDM ability to clear healthy control neutrophils by efferocytosis was significantly impaired. Coculturing patients' neutrophils with macrophages from healthy donors didn't result in abnormal effereocytosis, thus suggesting an efferocytosis defect caused by mutant monocyte derived macrophages. The abnormal efferocyutosis was reproduced in dysferlin nutant U937 cells which showed a defect in phagosome maturation.
Conclusion(s): The de novo GOF mutation in dysferlin in two patients with systemic inflammation and sterile lung abscesses reveal a novel role of dysferlin in regulating inflammasome activation in monocytes and macrophage maturation and in neutriophil efferocytosis. Our data expand on a previously unidentified role of dysferlin in regulating M2-macrophage efferocytosis of neutrophils as a mechanisms for lung abscess formation

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Non-squamous cell carcinoma (SCC) malignancies are rare, but well described laryngeal pathologies. However, the epidemiology and clinical behavior of these tumors is not well studied. STUDY DESIGN/METHODS:Retrospective cohort study. METHODS:Patients diagnosed with non-squamous cell larynx cancer from 2004 to 2017 in the National Cancer Database were selected. Demographic, clinicopathologic factors, treatments, and survival were analyzed. Univariable and multivariable cox regression were performed. Survival was compared with a propensity score-matched (PSM) population of laryngeal SCC patients. RESULTS:A total of 136,235 cases of larynx cancer were identified. After excluding SCC variants, 2,172 (1.6%) patients met inclusion criteria. The most common histology was chondrosarcoma (374, 17.2%), followed by small cell (345, 15.9%), and spindle cell carcinoma (268, 12.3%). The most common treatment was surgery (683, 31.4%) followed by chemoradiation (409, 18.8%) and surgery and adjuvant radiation (288, 13.3%). Overall, 3- and 5-year survival was 67.9% and 59.4%, respectively. In multivariate analysis controlling for age, stage, comorbidity, histology, and treatment modality; chondrosarcoma had the best survival (hazard ratio [HR] 0.11, confidence interval [CI] 0.07-0.19, P < .001). In a PSM population, matched for age, stage, comorbidity, and treatments; non-SCC patients had significantly lower survival (51.5% vs. 59.9%, P < .001). CONCLUSION/CONCLUSIONS:A diverse range of non-squamous cell malignancies occur in the larynx. In general, these tumors have poor survival, with few exceptions such as chondrosarcoma. While the majority of these histologies undergo surgical-based treatments in other sites, only 53% of patients underwent surgical-based treatment in the larynx. These data could guide clinicians in determining the outcome of treatment in these patients. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2022.

This "How I Do It" report describes modifications made to the OSIA bone conduction hearing implant surgery in order to reduce wound complications. Laryngoscope, 2022.

OBJECTIVE:Stimulated Raman histology (SRH) offers efficient and accurate intraoperative neuropathological tissue analysis without procedural alteration to the diagnostic specimen. However, there are limited data demonstrating one-to-one tissue comparisons between SRH and traditional frozen sectioning. This study explores the non-inferiority of SRH as compared to frozen section on the same piece of tissue in neurosurgical patients. METHODS:Tissue was collected over a 1-month period from 18 patients who underwent resection of central nervous system lesions. SRH and frozen section analyses were compared for diagnostic capabilities as well as assessed for quality and condition of tissue via a survey completed by pathologists. RESULTS:SRH was sufficient for diagnosis in 78% of specimens as compared to 94% of specimens by frozen section of the same specimen. A Fisher's exact test determined there was no significant difference in diagnostic capability between the two groups. Additionally, both quality of SRH and condition of tissue after SRH were deemed to be non-inferior to frozen section. CONCLUSIONS:This study provides further evidence for the non-inferiority of SRH techniques. It is also the first study to demonstrate SRH accuracy using one-to-one tissue analysis in neuropathological specimens.

OBJECTIVE:Carcinosarcoma of the salivary gland is a rare malignant biphasic tumor. The present study investigates the epidemiology and clinical behavior of carcinosarcoma of the major salivary glands using the National Cancer Database (NCDB). STUDY DESIGN/METHODS:Historical cohort study. SETTING/METHODS:NCDB. METHODS:All tumors were selected between 2004 and 2018. Patient demographics, tumor characteristics, treatments, and survival were analyzed. Cox regression analysis was performed in surgically treated patients. RESULTS:= .008) remained significant. CONCLUSION/CONCLUSIONS:Carcinosarcoma is a rare salivary gland tumor that frequently presents at a locally advanced stage. Despite multimodality treatments, the outcomes are poor. In the absence of clinical trial data, these data from the NCDB could guide clinicians in the management of this rare disease.

OBJECTIVES/OBJECTIVE:To outline an expert-based consensus of recommendations for the diagnosis and management of pediatric patients with congenital tracheal stenosis. METHODS:Expert opinions were sought from members of the International Pediatric Otolaryngology Group (IPOG) via completion of an 18-item survey utilizing an iterative Delphi method and review of the literature. RESULTS:Forty-three members completed the survey providing recommendations regarding the initial history, clinical evaluation, diagnostic evaluation, temporizing measures, definitive repair, and post-repair care of children with congenital tracheal stenosis. CONCLUSION/CONCLUSIONS:These recommendations are intended to be used to support clinical decision-making regarding the evaluation and management of children with congenital tracheal stenosis. Responses highlight the diverse management strategies and the importance of a multidisciplinary approach to care of these patients.