Jacob Husseman

Management of synkinesis.

Facial synkinesis is one of the most distressing consequences of facial paralysis. Synkinesis refers to the abnormal involuntary facial movement that occurs with voluntary movement of a different facial muscle group. The pathophysiologic basis of facial synkinesis is likely multifactorial although the predominant mechanism appears to be aberrant regeneration of facial nerve fibers to the facial muscle groups after facial nerve injury. Patients experience hypertonic contractures and synkinetic movements such as eye closure with volitional movement of the mouth or midfacial movement during volitional or reflexive eye closure. Synkinesis can cause functional limitation with activities such as eating, drinking, smiling, and may even lead to social isolation. Evaluation of synkinesis is primarily subjective with facial grading scales such as the Sunnybrook scale. Objective measures of synkinesis using computerized video analysis show promise although no objective techniques are currently widely used. The most common therapeutic modalities for the treatment of facial synkinesis include (1) botulinum toxin type A (BTX-A) injections for selective chemodenervation of affected muscle groups and (2) facial neuromuscular retraining. Biofeedback using mirrors or electromyography has been used both for the treatment and prevention of facial synkinesis. Other treatment options include surgical therapies, such as selective neurolysis or myectomy, although these have been rendered nearly obsolete with the advent of BTX-A.

Increased ILC2s in the eosinophilic nasal polyp endotype are associated with corticosteroid responsiveness

Group 2 innate lymphoid cells (ILC2s) have recently been identified in human nasal polyps, but whether numbers of ILC2s differ by polyp endotype or are influenced by corticosteroid use is unknown. Here, we show that eosinophilic nasal polyps contained double the number of ILC2s vs. non-eosinophilic polyps. Polyp ILC2s were also reduced by 50% in patients treated with systemic corticosteroids. Further, using a fungal allergen challenge mouse model, we detected greatly reduced Th2 cytokine-producing and Ki-67+ proliferating lung ILC2s in mice receiving dexamethasone. Finally, ILC2 Annexin V staining revealed extensive apoptosis after corticosteroid treatment in vivo and in vitro. Thus, ILC2s are elevated in the eosinophilic nasal polyp endotype and systemic corticosteroid treatment correlated with reduced polyp ILC2s. Finally, allergen-challenged mice showed reduced ILC2s and increased ILC2 apoptosis after corticosteroid treatment suggesting that ILC2 may be responsive to corticosteroids in eosinophilic respiratory disease.

Gene Therapy in the Inner Ear Using Adenovirus Vectors

Therapies for the protection and regeneration of auditory hair cells are of great interest given the significant monetary and lifestyle impact of hearing loss. The past decade has seen tremendous advances in the use of adenoviral vectors to achieve these aims. Preliminary data demonstrated the functional capacity of this technique as adenoviral-induced expression of neurotrophic and growth factors protected hair cells and spiral ganglion neurons from ototoxic insults. Subsequent efforts confirmed the feasibility of adenoviral transfection of cells in the auditory neuroepithelium via cochleostomy into the scala media. Most recently, efforts have focused on regeneration of depleted hair cells. Mammalian hearing loss is generally considered a permanent insult as the auditory epithelium lacks a basal layer capable of producing new hair cells. Recently, the transcription factor Atoh1 has been found to play a critical role in hair cell differentiation. Adenoviral-mediated overexpression of Atoh1 in culture and in vivo have shown the ability to regenerate auditory and vestibular hair cells by causing transdifferentiation of neighboring epithelial-supporting cells. Functional recovery of both the auditory and vestibular systems has been documented following adenoviral induced Atoh1 overexpression.

TNFA deletion alters apoptosis as well as caspase 3 and 4 expression during otitis media

BackgroundTumor necrosis factor (TNFA) is the canonical member of the TNF superfamily, which plays a major role in both inflammation and apoptosis. To evaluate the role of TNFs in otitis media (OM), the most common disease of childhood, we evaluated middle ear (ME) expression of genes encoding the TNF and TNF receptor superfamilies during bacterial OM in the mouse, characterized OM in TNFA-deficient mice, and assessed apoptosis during OM in normal versus TNF-deficient MEs.ResultsTNFs and TNF receptors were broadly regulated during OM, with TNFA showing the highest level of up-regulation. TNF deficient mice exhibited mucosal hyperplasia even in the absence of infection and exuberant growth of the mucosa during OM, including the formation of mucosal polyps. Mucosal recovery during OM was also delayed, in parallel with a delay in mucosal apoptosis and reduced caspase gene expression.ConclusionsThe TNF and TNF receptor superfamilies mediate both inflammation and apoptosis during OM. TNF appears to be critical for the maintenance of mucosal architecture in both the normal and infected ME, since excessive accumulation of mucosal tissue is seen in TNFA-/- MEs both before and after bacterial inoculation of the ME. TNFA is also required for appropriate regulation of caspase genes.

Use of a sprayed fibrin hemostatic sealant after laser therapy for hereditary hemorrhagic telangiectasia epistaxis.

Background Hereditary hemorrhagic telangiectasia (HHT) is a relatively common autosomal dominant condition. Epistaxis is a frequent manifestation, often occurring daily and requiring iron and blood transfusions. Surgery often is bloody and difficult. The aim of this study was to evaluate the effectiveness of a sprayed fibrin, hemostatic sealant in preventing postoperative epistaxis after laser treatment of nasal mucosa in HHT. Fibrin sealant was compared with nasal packing for likelihood of postoperative epistaxis and financial impact including material costs and hospitalization fees. Methods Retrospective review was performed of 64 individual laser treatments for epistaxis in HHT patients at the University of California, San Diego, Medical Center between 2002 and 2005. Nasal packing was used in 30 procedures and fibrin sealant was used in 34 procedures. Results Six of 30 (20%) procedures using postoperative nasal packing required admission with an average hospital expense of

A Review of Hard Palate Fracture Repair Techniques

5914. One of 34 patients (3%) in the fibrin sealant group required hospitalization (p = 0.04). Conclusion Aerosolized fibrin sealant prevents postoperative epistaxis after nasal laser treatment in HHT patients. Compared with traditional nasal packing we found improved patient comfort and recovery with substantial cost savings.

The Role of Vascular Endothelial Growth Factors and Fibroblast Growth Factors in Angiogenesis during Otitis Media

PURPOSE Hard palate trauma is a relatively infrequent occurrence compared with other craniofacial injuries. Several techniques of hard palate fracture repair have been described. To date, there is no consensus on the optimal management of this type of fracture. The purpose of this study was to compile and analyze studies describing hard palate fracture repair techniques with outcomes data. MATERIALS AND METHODS A systematic review of the Medline, Scopus, and Web of Science databases was performed for articles describing hard palate fracture repair techniques. RESULTS Eight articles were ultimately included in the review. Of the collective 310 fractures reported, postoperative malocclusion occurred in 21 of 235 cases (8.9%) and other complications occurred in 13 of 299 cases (4.3%). The most important variability in technique was the method of palatal vault stabilization. Three studies described wiring techniques, 3 described internal fixation techniques, and 2 described external fixation techniques. Studies describing internal fixation techniques reported higher rates of wound complications. Proponents of rigid internal fixation believe that this technique provides better fracture reduction. External fixation techniques appear to impart low rates of wound complications, but their overall effectiveness remains in question. CONCLUSIONS Hard palate fractures are associated with high rates of malocclusion and wound complications. The most established methods of palatal vault stabilization are closed reduction with wiring and internal plate fixation. Depending on the fracture type, patient comorbidities, and associated injuries, either technique might be preferable in a given circumstance.

Impact of Humanitarian Experiences on Otolaryngology Trainees: A Follow-up Study of Travel Grant Recipients

The middle ear response to otitis media includes transformation and hyperplasia of the mucosal epithelium and subepithelial connective tissue. Significant neovascularization is also noted, which occurs both to support the hypertrophied mucosa and to mediate the increased trafficking of leukocytes. We investigated the role of two known potent angiogenic growth factor families, the fibroblast growth factors (FGFs) and vascular endothelial growth factors (VEGFs), in middle ear mucosal angiogenesis. DNA microarrays were used to evaluate the expression of FGFs and VEGFs, as well as their receptors and unique signaling proteins, in the middle ears of mice undergoing a complete course of acute bacterial otitis media. In addition, a member of each family was introduced to the middle ear submucosal compartment of the normal middle ears of guinea pigs, by a continuous-release osmotic minipump system over 1 week. During the course of bacterial otitis media, a significant regulation of a number of genes important for angiogenesis was identified. Histologic evaluation of middle ear mucosa following micropump infusion of both FGF1 and VEGF-A showed significant angiogenesis at the site of infusion in comparison to control saline infusion. These results support a role for FGFs and VEGFs in the neovascularization of the middle ear mucosa during otitis media, and offer a potential avenue for therapeutic intervention.

Active Transport of Peptides Across the Intact Human Tympanic Membrane

In this study, we seek (1) to determine the impact of humanitarian experiences on otolaryngology trainee recipients of the American Academy of Otolaryngology—Head and Neck Surgery Foundation humanitarian travel grant (2001-2015); (2) to better understand trainee and trip characteristics, as well as motivations and attitudes toward future volunteerism; and (3) and to identify potential barriers to participation. An anonymous 30-question survey was distributed to 207 individuals, and 52 (25.1%) responded. Respondents viewed the trip as very worthwhile (score = 98 of 100), expressed improved cultural understanding (75.0%), and continued participation in humanitarian activities (75.0%). Competency-based evaluation results suggest a positive impact on systems-based practice and professionalism. Respondents commented on the trip’s positive value and shared concerns regarding expense. Despite potential barriers, Foundation-supported humanitarian trips during training are perceived as worthwhile; they may enhance cultural understanding and interest in future humanitarian efforts; and they may positively affect competency-based metrics. Based on the potential benefits, continued support and formalization of these experiences should be considered.

Chronic sialadenitis with sialolithiasis associated with parapharyngeal fistula and tonsillolith

We previously identified peptides that are actively transported across the intact tympanic membrane (TM) of rats with infected middle ears. To assess the possibility that this transport would also occur across the human TM, we first developed and validated an assay to evaluate transport in vitro using fragments of the TM. Using this assay, we demonstrated the ability of phage bearing a TM-transiting peptide to cross freshly dissected TM fragments from infected rats or from uninfected rats, guinea pigs and rabbits. We then evaluated transport across fragments of the human TM that were discarded during otologic surgery. Human trans-TM transport was similar to that seen in the animal species. Finally, we found that free peptide, unconnected to phage, was transported across the TM at a rate comparable to that seen for peptide-bearing phage. These studies provide evidence supporting the concept of peptide-mediated drug delivery across the intact TM and into the middle ears of patients.