The prefabricated supraclavicular artery flap in high-risk tracheal stenosis patients.

OBJECTIVES/HYPOTHESIS: Primary tracheal resection in appropriately selected patients with tracheal stenosis achieves >90% success rate. Risk factors for complications have been identified, making some patients high risk for this procedure. Herein is a review and discussion of a novel treatment method for tracheal stenosis utilizing a prefabricated composite auricular cartilage graft embedded in a supraclavicular artery island flap (pSCAIF) for tracheal reconstruction in high-risk patients. STUDY DESIGN: Retrospective case series. METHODS: After institutional review board approval, cases were analyzed after data collection. Between 2014 and 2016, eight patients underwent airway reconstruction using an auricular cartilage graft prefabricated within a supraclavicular artery island flap reconstruction; all of these were included in the study. Each case was reviewed, and relevant details of patient and disease characteristics, operative course, postoperative course, decannulation, and status at last follow-up were isolated and reported. RESULTS: Seven of eight patients were female. The most common cause of stenosis was iatrogenically induced multilevel stenosis (7/8 patients). All patients had undergone prior airway procedures, were high risk based on comorbid conditions, and underwent grafting and reconstruction with a composite supraclavicular island flap. All patients continue to follow up in a multidisciplinary clinic, and at last follow-up, eight of eight patients were successfully decannulated. CONCLUSIONS: The pSCAIF is a novel method for tracheal reconstruction. The analysis of the prefabricated locoregional approach cohort supports its utility for tracheal reconstruction in patients with complicated multilevel stenosis and adverse comorbidities and characteristics. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:641-648, 2020.

The impact of a head and neck microvascular fellowship program on otolaryngology resident training.

OBJECTIVE: To assess the impact of a microvascular head and neck (H&N) fellowship on senior residents' surgical experience. STUDY DESIGN: Retrospective review of Accreditation Council for Graduate Medical Education-generated operative case log reports, retrospective chart review, and electronic survey. METHODS: A retrospective review of one institution's residents' H&N operative case logs and free flap operative reports was performed to determine changes in key indicator cases (KICs) after the addition of a H&N fellowship. An electronic survey was distributed to senior residents at all U.S. otolaryngology residency programs to determine residents' perceptions of a H&N fellow's impact on their surgical experience. An electronic survey was distributed to senior medical students applying to surgical residencies to explore the perceived impact that a fellowship has on the desirability of a residency program. RESULTS: The average number of each postgraduate year (PGY)5's H&N KIC before and after the addition of the fellowship were: parotidectomy, 19 versus 17.8; neck dissection, 33.2 versus 40.6; oral cavity resection, 15.3 versus 12.6; thyroid/parathyroid, 45.5 versus 45.6; and flaps/grafts, 56.7 versus 42. PGY5 participation as first assistant in free flaps dropped from 78% to 17%; however, residents still participated in some aspect of 45% of the cases. Seventy percent of senior residents reported a positive perception of the H&N fellow on their H&N operative experience. Eighty-nine percent of senior medical student respondents reported a nonnegative perception of a fellowship in their applied field. CONCLUSION: The addition of a H&N fellowship did not decrease senior residents' H&N KIC, and most senior residents at programs with fellowships report that the fellow has a positive impact on their H&N operative experience. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:52-56, 2018.

Post-operative MRSA infections in head and neck surgery.

PURPOSE: Surgical site infection (SSI) with methicillin-resistant Staphylococcus aureus (MRSA) is a serious post-operative complication, with head and neck cancer patients at greater risk due to the nature of their disease. Infection with MRSA has been shown to be costly and impart worse outcomes on patients who are affected. This study investigates incidence and risks for MRSA SSIs at a tertiary medical institution. MATERIALS AND METHODS: This study reviewed 577 head and neck procedures from 2008 to 2013. Twenty-one variables (i.e. tumor characteristics, patient demographics, operative course, cultures) were analyzed with SPSS to identify trends. A multivariate analysis controlled for confounders (age, BMI, ASA class, length of stay) was completed. RESULTS: We identified 113 SSIs of 577 procedures, 24 (21.23%) of which were MRSA. Of all analyzed variables, hospital exposure within the preceding year was a significant risk factor for MRSA SSI development (OR 2.665, 95% CI: 1.06-6.69, z statistic 2.086, p=0.0369). Immunosuppressed patients were more prone to MRSA infections (OR 14.1250, 95%CI: 3.8133-52.3217, p<0.001), and patients with a history of chemotherapy (OR 3.0268, 95% CI: 1.1750-7.7968, p=0.0218). Furthermore, MRSA SSI resulted in extended post-operative hospital stays (20.8±4.72days, p=0.031). CONCLUSIONS: Patients who have a history of chemotherapy, immunosuppression, or recent hospital exposure prior to their surgery are at higher risk of developing MRSA-specific SSI and may benefit from prophylactic antibiotic therapy with appropriate coverage. Additionally, patients who develop MRSA SSIs are likely to have an extended postoperative inpatient stay.

Outcomes of microvascular free tissue transfer in twice-irradiated patients.

BACKGROUND: Patients may require microvascular free tissue transfer (MFTT) following re-irradiation for recurrent cancer or radiation complications. The objective of this study was to describe the indications for and outcomes of free flaps performed in twice-radiated patients. METHODS: A retrospective chart review identified the indications for and outcomes of 36 free flaps performed on 29 twice-irradiated patients. RESULTS: The free flap success rate was 92%. The most common indications requiring MFTT were cancer recurrence and osteoradionecrosis. Sixty-one percent experienced postoperative complications, most commonly wound infection (33%). Twenty-five percent of the procedures required return to the operating room due to postoperative complication. CONCLUSIONS: MFTT can be successfully performed in the twice-irradiated patient population with a success rate comparable to singly-radiated patients. Despite a high success rate, there is also a high rate of surgical site complications, especially infection.

A mouse model validates the utility of electrocochleography in verifying endolymphatic hydrops.

Endolymphatic hydrops (ELH) is a disorder of the inner ear that causes tinnitus, vertigo, and hearing loss. An elevated ratio of the summating potential (SP) to the action potential (AP) measured by electrocochleography has long been considered to be the electrophysiological correlate of ELH-related clinical conditions, such as Meniere's disease, but in vivo confirmation and correlation between an elevated SP/AP ratio and ELH has not yet been possible. Confirming this relationship will be important to show that elevated SP/AP ratio is indeed diagnostic of ELH. Here, we sought to confirm that an elevated SP/AP ratio is associated with ELH and test the hypothesis that severity of ELH and hearing loss would also correlate with the SP/AP ratio in vivo using the Phex(Hyp-Duk)/Y mouse model of postnatal ELH. In addition, we describe a minimally invasive approach for electrocochleography in mice. Auditory brainstem responses and electrocochleography data were collected from controls and Phex(Hyp-Duk)/Y mutants at postnatal day 21 and the mice (all male) were euthanized immediately for cochlear histology. Our results show that (1) the SP/AP ratio was significantly elevated in mice with histological ELH compared to controls, (2) the SP/AP ratio was not correlated with the severity of histological ELH or hearing loss, and (3) the severity of hearing loss correlated with the severity of histological ELH. Our study demonstrates that an elevated SP/AP ratio is diagnostic of ELH and that the severity of hearing loss is a better predictor of the severity of ELH than is the SP/AP ratio.

The mechanosensory structure of the hair cell requires clarin-1, a protein encoded by Usher syndrome III causative gene.

Mutation in the clarin-1 gene (Clrn1) results in loss of hearing and vision in humans (Usher syndrome III), but the role of clarin-1 in the sensory hair cells is unknown. Clarin-1 is predicted to be a four transmembrane domain protein similar to members of the tetraspanin family. Mice carrying null mutation in the clarin-1 gene (Clrn1(-/-)) show loss of hair cell function and a possible defect in ribbon synapse. We investigated the role of clarin-1 using various in vitro and in vivo approaches. We show by immunohistochemistry and patch-clamp recordings of Ca(2+) currents and membrane capacitance from inner hair cells that clarin-1 is not essential for formation or function of ribbon synapse. However, reduced cochlear microphonic potentials, FM1-43 [N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] loading, and transduction currents pointed to diminished cochlear hair bundle function in Clrn1(-/-) mice. Electron microscopy of cochlear hair cells revealed loss of some tall stereocilia and gaps in the v-shaped bundle, although tip links and staircase arrangement of stereocilia were not primarily affected by Clrn1(-/-) mutation. Human clarin-1 protein expressed in transfected mouse cochlear hair cells localized to the bundle; however, the pathogenic variant p.N48K failed to localize to the bundle. The mouse model generated to study the in vivo consequence of p.N48K in clarin-1 (Clrn1(N48K)) supports our in vitro and Clrn1(-/-) mouse data and the conclusion that CLRN1 is an essential hair bundle protein. Furthermore, the ear phenotype in the Clrn1(N48K) mouse suggests that it is a valuable model for ear disease in CLRN1(N48K), the most prevalent Usher syndrome III mutation in North America.

A multi-institutional analysis of tracheotomy complications.

OBJECTIVES/HYPOTHESIS: To define the prevalence of tracheotomy tube complications and evaluate risk factors (RFs) associated with their occurrence. STUDY DESIGN: Multi-institution historical cohort. METHODS: Data regarding tracheotomy tube complications from consecutive surgeries performed across eight participating institutions between January 1, 2008 and December 31, 2009 were retrospectively collected. Patient demographics, comorbidities, physician specialty, and surgical technique were recorded and statistically analyzed to identify the incidence of surgical complications following tracheotomy and associated RFs. RESULTS: The charts of 1,175 tracheotomy procedures were reviewed from eight academic institutions. Otolaryngologists performed 66.2% of the tracheotomies. Intraoperative, early (<1 week), and late complication rates were 1.4%, 5.6%, and 7.1%, respectively. Postoperative bleeding was identified as the most common early complication (2.6%), whereas airway stenosis was the most common late complication (1.7%). The use of outer flange security sutures to anchor the tracheostomy tube was negatively associated with the incidence of early complication (P<.0001). The use of large endotracheal tubes (size>7.5) and obesity were associated with the development of airway stenosis (P<.05).Twenty-two percent of patients undergoing tracheotomy died during hospitalization. CONCLUSIONS: Perioperative tracheotomy complications are rare; however, the rate of death for all causes is high (22%) in this population. Obesity and the use of endotracheal tubes over 7.5 in size are major risk factors for the development of airway stenosis. Although percutaneous tracheotomy resulted in a significantly higher rate of postoperative bleeding (6.6%) than the open method (1.9%) (P<.05), the use of outer flange tracheostomy tube sutures may reduce this complication.

Hearing preservation in Guinea pigs with long-standing endolymphatic hydrops.

HYPOTHESIS: Interruption of the excitotoxic and inflammatory pathways implicated in endolymphatic hydrops (ELH)-associated hearing loss (HL) should afford hearing protection at the neuronal level. BACKGROUND: Previous work in our laboratory in the mouse model of ELH shows that dimethyl sulfoxide (DMSO), an anti-inflammatory solvent, can slow the progression of HL before neuronal degeneration occurs. Riluzole, a glutamate release inhibitor, may provide synergistic benefit. This study was designed to quantify the effects of DMSO and riluzole in a long-term model. METHODS: Guinea pigs with surgically induced ELH were sorted into 3 groups: riluzole+DMSO (Group 1), DMSO alone (Group 2), and untreated controls (Group 3). Animals in Groups 1 and 2 received daily injections of the study drug(s). All animals underwent auditory-evoked brainstem response evaluation every 4 weeks until 24 weeks, when they were sacrificed. Cochleae were preserved; spiral ganglion density was quantified. Animals without hydrops were excluded from the study as surgical failures. RESULTS: Animals from all groups developed unilateral HL. At the end of the experiment, HL was significantly lower in Group 1 relative to Group 3 (p = 0.049) and trended toward lower in Group 2 relative to Group 3 (p = 0.097). Groups 1 and 2 were not different (p = 0.311). At the cellular level, there is no evidence of neuronal degeneration in either treated group, whereas there is a significant neuronal degeneration in the untreated group. CONCLUSION: These results confirm the hearing protection observed with DMSO in short-term studies. However, unlike the previous study, which showed no additive benefit to riluzole, the combined treatment group in this study showed a hearing-protective effect at 24 weeks. This indicates a potential additive benefit conferred by riluzole toward long-term hearing protection. The study also finds evidence of statistically significant neuronal protection with both treatment groups. Overall, study provides additional evidence that DMSO and riluzole may preserve or slow the long-term progression of ELH-associated HL.

Pharmacological protection of hearing loss in the mouse model of endolymphatic hydrops.

OBJECTIVES/HYPOTHESIS: Excitotoxic and related inflammatory injury are implicated in the spiral ganglion degeneration seen with Meniere's disease and endolymphatic hydrops (ELH). Excitotoxicity is initiated with glutamate elevation and associated with downstream increases in reactive oxygen species resulting in inflammation-mediated neuronal degeneration. This study tests the hypothesis that interruption of the initial and/or downstream aspects of excitotoxicity should provide hearing protection in ELH-associated hearing loss. STUDY DESIGN: This study tests whether riluzole, a glutamate release inhibitor, and dimethylsulfoxide (DMSO), an anti-inflammatory and antioxidant solvent with favorable properties at the level of glutamate receptors, can protect against early-stage hearing loss in a mouse model of ELH. METHODS: The Phex(Hyp-Duk) mouse spontaneously develops ELH and postnatal hearing loss. Starting at postnatal day 6 (P6), daily injections of riluzole + DMSO or just DMSO were administered. Untreated mutants served as controls. At P21, P25, and P30, hearing function was assessed by recording auditory brainstem responses. A cochlear function index was developed to assess global cochlear function at each time point. RESULTS: Compared to no treatment, DMSO provided significant hearing protection (P < .05). The riluzole + DMSO also showed protection, but it was statistically indistinguishable from DMSO alone; a synergistic increase in protection with riluzole was not observed. CONCLUSIONS: This study demonstrates pharmacological hearing protection in an animal model of ELH. The results support the assertion that inflammatory (reactive oxygen species) injury, which is part of the excitotoxic pathway, contributes to the development of ELH-associated hearing loss.

Surgical induction of endolymphatic hydrops by obliteration of the endolymphatic duct.

Surgical induction of endolymphatic hydrops (ELH) in the guinea pig by obliteration and obstruction of the endolymphatic duct is a well-accepted animal model of the condition and an important correlate for human Meniere's disease. In 1965, Robert Kimura and Harold Schuknecht first described an intradural approach for obstruction of the endolymphatic duct (Kimura 1965). Although effective, this technique, which requires penetration of the brain's protective covering, incurred an undesirable level of morbidity and mortality in the animal subjects. Consequently, Andrews and Bohmer developed an extradural approach, which predictably produces fewer of the complications associated with central nervous system (CNS) penetration.(Andrews and Bohmer 1989) The extradural approach described here first requires a midline incision in the region of the occiput to expose the underlying muscular layer. We operate only on the right side. After appropriate retraction of the overlying tissue, a horizontal incision is made into the musculature of the right occiput to expose the right temporo-occipital suture line. The bone immediately inferio-lateral the suture line (Fig 1) is then drilled with an otologic drill until the sigmoid sinus becomes visible. Medial retraction of the sigmoid sinus reveals the operculum of the endolymphatic duct, which houses the endolymphatic sac. Drilling medial to the operculum into the area of the endolymphatic sac reveals the endolymphatic duct, which is then packed with bone wax to produce obstruction and ultimately ELH. In the following weeks, the animal will demonstrate the progressive, fluctuating hearing loss and histologic evidence of ELH.

Spiral ganglion loss outpaces inner hair cell loss in endolymphatic hydrops.

OBJECTIVES/HYPOTHESIS: Neuronal toxicity is thought to be important in Meniere's disease and experimental endolymphatic hydrops (ELH). This study quantifies the relationship between neuronal degeneration and hair cell degeneration in ELH to evaluate the hypothesis that a primary neural insult would yield greater loss in the spiral ganglion than at the inner hair cell level. STUDY DESIGN: Following induction and histopathologic confirmation of endolymphatic hydrops in guinea pigs, the degree of hydrops, spiral ganglion loss, and hair cell degeneration were quantified and compared. METHODS: Guinea pigs with surgically induced unilateral hydrops were sacrificed and their cochleas preserved. Hydrops severity and spiral ganglion density were quantified using automated methods. Hair cells were counted manually. Values were normalized against the contralateral ear to create loss indexes. RESULTS: Inner hair cell (IHC) loss at the apex is significantly lower than corresponding neuronal loss. IHC loss at the base is also lower than neuron loss, although not significantly. Regression analysis shows a significant, positive correlation between neuron loss severity and IHC loss severity at the apex, but not at the base. There is no correlation between hydrops severity and inner hair cell loss. CONCLUSIONS: By confirming that spiral ganglion loss is more severe than hair cell loss, and that hair cell loss appears to worsen with neuronal degeneration, this study supports the theory that neuronal toxicity is the primary insult in ELH-related disorders, such as Meniere's disease, and may provide the basis for designing treatment strategies.

Usher syndrome IIIA gene clarin-1 is essential for hair cell function and associated neural activation.

Usher syndrome 3A (USH3A) is an autosomal recessive disorder characterized by progressive loss of hearing and vision due to mutation in the clarin-1 (CLRN1) gene. Lack of an animal model has hindered our ability to understand the function of CLRN1 and the pathophysiology associated with USH3A. Here we report for the first time a mouse model for ear disease in USH3A. Detailed evaluation of inner ear phenotype in the Clrn1 knockout mouse (Clrn1(-/-)) coupled with expression pattern of Clrn1 in the inner ear are presented here. Clrn1 was expressed as early as embryonic day 16.5 in the auditory and vestibular hair cells and associated ganglionic neurons, with its expression being higher in outer hair cells (OHCs) than inner hair cells. Clrn1(-/-) mice showed early onset hearing loss that rapidly progressed to severe levels. Two to three weeks after birth (P14-P21), Clrn1(-/-) mice showed elevated auditory-evoked brainstem response (ABR) thresholds and prolonged peak and interpeak latencies. By P21, approximately 70% of Clrn1(-/-) mice had no detectable ABR and by P30 these mice were deaf. Distortion product otoacoustic emissions were not recordable from Clrn1(-/-) mice. Vestibular function in Clrn1(-/-) mice mirrored the cochlear phenotype, although it deteriorated more gradually than cochlear function. Disorganization of OHC stereocilia was seen as early as P2 and by P21 OHC loss was observed. In sum, hair cell dysfunction and prolonged peak latencies in vestibular and cochlear evoked potentials in Clrn1(-/-) mice strongly indicate that Clrn1 is necessary for hair cell function and associated neural activation.