Management of Jugular Bulb Stenosis in Pediatric Vein of Galen Malformation: A Novel Management Paradigm.

INTRODUCTION: Pediatric vein of Galen malformations (VOGMs) are fistulous intracranial malformations arising congenitally within the choroidal fissure that can present with an array of neurological and cardiac sequelae. Associated venous stenosis may result in intracranial venous hypertension and ischemia leading to severe, irreversible cerebral injury. Management of neonatal VOGMs typically involves staged embolization and angioplasty/stenting for relief of venous stenosis. Rarely, jugular foraminal narrowing has been identified as causing jugular bulb stenosis. CASE PRESENTATION: We present the case of a 22-month-old female diagnosed with VOGM prenatally who displayed persistent intracranial venous hypertension despite multiple neuroembolization procedures during the neonatal period. Following initial reduction in arteriovenous shunting, she once again developed venous hypertension secondary to jugular bulb stenosis for which angioplasty was attempted. Failure of angioplasty to relieve the venous hypertension prompted skull base imaging, which revealed jugular foraminal ossification and stenosis. Microsurgical jugular foraminotomy followed by balloon angioplasty and stenting significantly reduced jugular pressure gradients. Restenosis requiring re-stenting developed postoperatively at 9 months, but the patient has remained stable with significant improvement in cortical venous congestion. DISCUSSION/CONCLUSION: This case demonstrates the efficacy of microsurgical decompression of the jugular foramen and endovascular angioplasty/stenting as a novel treatment paradigm for the management of intracranial venous hypertension in the setting of VOGM.

Subtemporalis Muscle Middle Cranial Fossa Bone-Island Craniotomy Technique for Placement of an Active Transcutaneous Bone-Conduction Implant.

OBJECTIVE: Placement of an active transcutaneous bone-conduction implant (BCI) requires drilling of a precise bone bed to accommodate the device and allow for fixation points to make appropriate contact with bone, which can be difficult even when lifts are used. We describe a subtemporalis muscle middle cranial fossa bone-island craniotomy technique that simplifies the procedure and obviates the need for lifts in securing the device. STUDY DESIGN: Prospective case series. SETTING: Tertiary academic medical center. PATIENTS: Seventeen patients underwent surgery for placement of 18 transcutaneous BCIs, 14 for conductive or mixed hearing loss, and 4 for single-sided deafness. INTERVENTIONS: Surgical placement of a transcutaneous BCI with a bone-island craniotomy technique. MAIN OUTCOME MEASURES: Functional gain in air-conduction thresholds, aided air-bone gap, frequency of need for lifts, and minor and major complications. RESULTS: For the conductive or mixed hearing loss cohort, with the transcutaneous BCI in place, there was a highly statistically significant mean functional gain of 35.4 dB hearing level (HL) (range, 16.7-50.25 dB HL; standard deviation, 12.4 dB HL) compared with the unaided condition (p < 0.0001; 95% confidence interval, 36.6-51.6 dB HL). Lifts were not needed in any case. There was one minor complication requiring a second procedure in a patient who had previously received radiation and no major complications. There was no device loss or failure. CONCLUSIONS: A subtemporalis muscle middle cranial fossa bone-island craniotomy technique eliminates the need for lifts and is a safe and effective method for placement of a transcutaneous BCI.

An Animal Model of Neonatal Intensive Care Unit Exposure to Light and Sound in the Preterm Infant.

According to the World Health Organization, ∼15 million children are born prematurely each year. Many of these infants end up spending days to weeks in a neonatal intensive care unit (NICU). Infants who are born prematurely are often exposed to noise and light levels that affect their auditory and visual development. Children often have long-term impairments in cognition, visuospatial processing, hearing, and language. We have developed a rodent model of NICU exposure to light and sound using the Mongolian gerbil (Meriones unguiculatus), which has a low-frequency human-like audiogram and is altricial. To simulate preterm infancy, the eyes and ears were opened prematurely, and animals were exposed to the NICU-like sensory environment throughout the gerbil's cortical critical period of auditory development. After the animals matured into adults, auditory perceptual testing was carried out followed by auditory brainstem response recordings and then histology to assess the white matter morphology of various brain regions. Compared to normal hearing control animals, NICU sensory-exposed animals had significant impairments in learning at later stages of training, increased auditory thresholds reflecting hearing loss, and smaller cerebellar white matter volumes. These have all been reported in longitudinal studies of preterm infants. These preliminary results suggest that this animal model could provide researchers with an ethical way to explore the effects of the sensory environment in the NICU on the preterm infant's brain development.

Superior semicircular canal dehiscence and subsequent closure induces reversible impaired decision-making.

Background: Vestibular loss and dysfunction has been associated with cognitive deficits, decreased spatial navigation, spatial memory, visuospatial ability, attention, executive function, and processing speed among others. Superior semicircular canal dehiscence (SSCD) is a vestibular-cochlear disorder in humans in which a pathological third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The primary symptoms include sound-induced dizziness/vertigo, inner ear conductive hearing loss, autophony, headaches, and visual problems; however, individuals also experience measurable deficits in basic decision-making, short-term memory, concentration, spatial cognition, and depression. These suggest central mechanisms of impairment are associated with vestibular disorders; therefore, we directly tested this hypothesis using both an auditory and visual decision-making task of varying difficulty levels in our model of SSCD. Methods: Adult Mongolian gerbils (n = 33) were trained on one of four versions of a Go-NoGo stimulus presentation rate discrimination task that included standard ("easy") or more difficult ("hard") auditory and visual stimuli. After 10 days of training, preoperative ABR and c+VEMP testing was followed by a surgical fenestration of the left superior semicircular canal. Animals with persistent circling or head tilt were excluded to minimize effects from acute vestibular injury. Testing recommenced at postoperative day 5 and continued through postoperative day 15 at which point final ABR and c+VEMP testing was carried out. Results: Behavioral data (d-primes) were compared between preoperative performance (training day 8-10) and postoperative days 6-8 and 13-15. Behavioral performance was measured during the peak of SSCD induced ABR and c + VEMP impairment and the return towards baseline as the dehiscence began to resurface by osteoneogenesis. There were significant differences in behavioral performance (d-prime) and its behavioral components (Hits, Misses, False Alarms, and Correct Rejections). These changes were highly correlated with persistent deficits in c + VEMPs at the end of training (postoperative day 15). The controls demonstrated additional learning post procedure that was absent in the SSCD group. Conclusion: These results suggest that aberrant asymmetric vestibular output results in decision-making impairments in these discrimination tasks and could be associated with the other cognitive impairments resulting from vestibular dysfunction.

Impact of Social Determinants of Health on Stereotactic Radiotherapy for Vestibular Schwannoma.

OBJECTIVES/HYPOTHESIS: Linear accelerator (LINAC) and Gamma Knife (GK) are common stereotactic radiation therapies for treating vestibular schwannoma (VS). There is currently limited literature examining specific demographic and socioeconomic factors, which influence the type of stereotactic radiation therapy a patient with VS receives. STUDY DESIGN: Retrospective database review. METHODS: The National Cancer Database was queried for cases of VS between 2004 and 2016. Patient demographic characteristics were compared using chi-squared and t-tests between GK and LINAC treated groups. Multivariate regression analysis was performed to assess predictors of stereotactic radiation therapy received. RESULTS: Of the 6,208 included patients, 5,306 (85.5%) received GK and 902 (14.5%) received LINAC. The mean age of GK patients was significantly lower than that of LINAC patients (58.0 vs. 59.7, P < .001). Individuals treated with GK had greater proportions of private insurance (P < .001) and incomes greater than $63,332 (P = .003). A greater proportion of GK patients were treated in academic centers (P < .001), in high-volume facilities (P < .001), in metropolitan areas (P < .001), and in the Northeastern United States (P < .001). On multivariate logistic regression analysis, region, metropolitan area, facility type, tumor size, and distance traveled by patients independently predict receipt of GK versus LINAC. CONCLUSION: Differences in patient demographics and other social determinants of health influence choice of GK versus LINAC therapy for VS patients. Future studies focused on addressing barriers to care, which may influence postprocedural quality of life and clinical outcomes associated with these two treatments are necessary to better understand the impact of these social differences. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:2232-2240, 2022.

New model of superior semicircular canal dehiscence with reversible diagnostic findings characteristic of patients with the disorder.

Background: Third window syndrome is a vestibular-cochlear disorder in humans in which a third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The nature and location of this third mobile window can occur at many different sites (or multiple sites); however, the most common third mobile window is superior semicircular canal dehiscence (SSCD). There are two essential objective diagnostic characteristics needed to validate a model of SSCD: the creation of a pseudoconductive hearing loss and cVEMP increased amplitude and decreased threshold. Methods: Adult Mongolian gerbils (n = 36) received surgical fenestration of the superior semicircular canal of the left inner ear. ABR and c+VEMP testing were carried out prior to surgery and over acute (small 1 mm SSCD, 1-10 days) or prolonged (large 2 mm SSCD, 28 days) recovery. Because recovery of function occurred quickly, condenser brightfield stereomicroscopic examination of the dehiscence site was carried out for the small SSCD animals post-hoc and compared to both ABRs and c+VEMPs. Micro-CT analysis was also completed with representative samples of control, day 3 and 10 post-SSCD animals. Results: The SSCD created a significant worsening of hearing thresholds of the left ear; especially in the lower frequency domain (1-4 kHz). Left (EXP)/right (CTL) ear comparisons via ABR show significant worsening thresholds at the same frequency representations, which is a proxy for the human pseudoconductive hearing loss seen in SSCD. For the c+VEMP measurements, increased amplitude of the sound-induced response (N1 2.5 ms and P1 3.2 ms) was observed in animals that received larger fenestrations. As the bone regrew, the c+VEMP and ABR responses returned toward preoperative values. For small SSCD animals, micro-CT data show that progressive osteoneogenesis results in resurfacing of the SSCD without bony obliteration. Conclusion: The large (2 mm) SSCD used in our gerbil model results in similar electrophysiologic findings observed in patients with SSCD. The changes observed also reverse and return to baseline as the SSCD heals by bone resurfacing (with the lumen intact). Hence, this model does not require a second surgical procedure to plug the SSCD.

Iatrogenic Cholesteatoma Presenting as Neck Mass.

We present a rare iatrogenic cholesteatoma of the neck in a ten year old male four years after tympanomastoidectomy, an entity that to our knowledge has not been published in the literature for over 30 years. Furthermore, we discuss the diagnostic uncertainty of typical magnetic resonance imaging protocols for pediatric neck lesions and the improved diagnostic specificity of diffusion weighted magnetic resonance imaging. En bloc surgical extirpation was performed. Laryngoscope, 131:E882-E884, 2021.

Gray-Scale Inversion on High Resolution Computed Tomography of the Temporal Bone: An Observational Study.

OBJECTIVES: This is a qualitative study to explore the utility of gray-scale inversion or the "invert" function of high-resolution computed tomography (HRCT) scans in the diagnosis of temporal bone anatomy and pathology. METHODS: This is a case series describing an innovative application of an existing image processing tool to visualize temporal bone anatomy and pathology. Illustrative patients at a tertiary referral center with otologic symptoms and findings leading to HRCT scans of the temporal bone were included. Diagnostic HRCT scans were evaluated utilizing the gray-scale inversion function (invert function). RESULTS: Nine illustrative cases which demonstrate conditions such as persistent stapedial artery, membranous stapes footplate, total ossicular prosthesis migration into the vestibule, third window syndrome such as superior semicircular canal dehiscence (SSCD) and cochlea-facial nerve dehiscence, otosclerosis, and ossicular chain discontinuity are included. The enhanced visualization was confirmed surgically in 3 cases, and 1 had physiological confirmation using cervical vestibular evoked myogenic potentials (cVEMP). CONCLUSIONS: Gray-scale inversion can be used to improve visualization of temporal bone anatomy and pathologic changes when diagnoses are in doubt. The invert function is a useful adjunct in the armamentarium of both radiologists and otologists when evaluating HRCT of the temporal bone.

Frailty as a Predictor of Postoperative Complications Following Skull Base Surgery.

OBJECTIVE/HYPOTHESIS: Frailty has emerged as a powerful risk stratification tool across surgical specialties; however, an analysis of the impact of frailty on outcomes following skull base surgery has not been published. The aim of this study was to assess the validity of the 5-factor modified frailty index (mFI-5) as a predictor of perioperative morbidity and mortality in patients undergoing skull base surgery. METHODS: A mFI-5 score was calculated for patients undergoing skull base surgeries using the National Surgical Quality Improvement Program (NSQIP) database from 2005 to 2018. Multivariate logistic regression analysis was used to evaluate the association of increasing frailty with complications in the 30-day postoperative period, with a subanalysis by operative location. RESULTS: A total of 17,912 patients who underwent skull base procedures were identified, with 45.5% of patients having a frailty score of one or greater; 44.9% were male and the mean age was 52.0 (±16.1 SD) years. Multivariable regression analysis revealed frailty to be an independent predictor of overall complications (odds ratio [OR]: 1.325, P < .001), life-threatening complications (OR: 1.428, P < .001), and mortality (OR: 1.453, P < .001). Higher frailty also correlated with increased length of stay. When procedures were stratified by operative location, frailty correlated significantly with overall complications for middle, posterior, and multiple-fossae operations but not the anterior fossa. CONCLUSIONS: Frailty demonstrates a significant and stepwise association with life-threatening postoperative morbidity, mortality, and length of stay following skull base surgeries. mFI-5 is an objective and easily calculable measure of preoperative risk, which may facilitate perioperative planning and counseling regarding outcomes prior to surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1977-1984, 2021.

Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction.

BACKGROUND: COVID-19 is a pandemic respiratory and vascular disease caused by SARS-CoV-2 virus. There is a growing number of sensory deficits associated with COVID-19 and molecular mechanisms underlying these deficits are incompletely understood. METHODS: We report a series of ten COVID-19 patients with audiovestibular symptoms such as hearing loss, vestibular dysfunction and tinnitus. To investigate the causal relationship between SARS-CoV-2 and audiovestibular dysfunction, we examine human inner ear tissue, human inner ear in vitro cellular models, and mouse inner ear tissue. RESULTS: We demonstrate that adult human inner ear tissue co-expresses the angiotensin-converting enzyme 2 (ACE2) receptor for SARS-CoV-2 virus, and the transmembrane protease serine 2 (TMPRSS2) and FURIN cofactors required for virus entry. Furthermore, hair cells and Schwann cells in explanted human vestibular tissue can be infected by SARS-CoV-2, as demonstrated by confocal microscopy. We establish three human induced pluripotent stem cell (hiPSC)-derived in vitro models of the inner ear for infection: two-dimensional otic prosensory cells (OPCs) and Schwann cell precursors (SCPs), and three-dimensional inner ear organoids. Both OPCs and SCPs express ACE2, TMPRSS2, and FURIN, with lower ACE2 and FURIN expression in SCPs. OPCs are permissive to SARS-CoV-2 infection; lower infection rates exist in isogenic SCPs. The inner ear organoids show that hair cells express ACE2 and are targets for SARS-CoV-2. CONCLUSIONS: Our results provide mechanistic explanations of audiovestibular dysfunction in COVID-19 patients and introduce hiPSC-derived systems for studying infectious human otologic disease.

Third Window Syndrome: Surgical Management of Cochlea-Facial Nerve Dehiscence.

Objective: This communication is the first assessment of outcomes after surgical repair of cochlea-facial nerve dehiscence (CFD) in a series of patients. Pre- and post-operative quantitative measurement of validated survey instruments, symptoms, diagnostic findings and anonymous video descriptions of symptoms in a cohort of 16 patients with CFD and third window syndrome (TWS) symptoms were systematically studied. Study design: Observational analytic case-control study. Setting: Quaternary referral center. Patients: Group 1 had 8 patients (5 children and 3 adults) with CFD and TWS who underwent surgical management using a previously described round window reinforcement technique. Group 2 had 8 patients (2 children and 6 adults) with CFD who did not have surgical intervention. Interventions: The Dizziness Handicap Inventory (DHI) and Headache Impact Test (HIT-6) were administered pre-operatively and post-operatively. In addition, diagnostic findings of comprehensive audiometry, cervical vestibular evoked myogenic potential (cVEMP) thresholds and electrocochleography (ECoG) were studied. Symptoms before and after surgical intervention were compared. Main outcome measures: Pre- vs. post-operative DHI, HIT-6, and audiometric data were compared statistically. The thresholds and amplitudes for cVEMP in symptomatic ears, ears with cochlea-facial nerve dehiscence and ears without CFD were compared statistically. Results: There was a highly significant improvement in DHI and HIT-6 at pre- vs. post-operative (p < 0.0001 and p < 0.001, respectively). The age range was 12.8-52.9 years at the time of surgery (mean = 24.7 years). There were 6 females and 2 males. All 8 had a history of trauma before the onset of their symptoms. The mean cVEMP threshold was 75 dB nHL (SD 3.8) for the operated ear and 85.7 dB (SD 10.6) for the unoperated ear. In contrast to superior semicircular canal dehiscence, where most ears have abnormal ECoG findings suggestive of endolymphatic hydrops, only 1 of 8 operated CFD ears (1 of 16 ears) had an abnormal ECoG study. Conclusions: Overall there was a marked improvement in DHI, HIT-6 and symptoms post-operatively. Statistically significant reduction in cVEMP thresholds was observed in patients with radiographic evidence of CFD. Surgical management with round window reinforcement in patients with CFD was associated with improved symptoms and outcomes measures.

Gamma Knife surgery of vestibular schwannomas: longitudinal changes in vestibular function and measurement of the Dizziness Handicap Inventory.

OBJECT: Gamma Knife surgery (GKS) is one of the methods available to treat vestibular schwannomas (VSs), in addition to microsurgical resection; however, clear information regarding balance function outcomes and the impact of treatment on patients' quality of life over time remains an important clinical need. The purpose of this study was to assess the longitudinal balance outcomes and Dizziness Handicap Inventory (DHI) following GKS for VSs. METHODS: This was a prospective clinical study of balance outcomes in all patients with VSs treated in the Acoustic Neuroma and Skull Base Surgery Program at a tertiary referral center by the senior author and the Gamma Knife team between June 2000 and May 2008. The main outcome measures included preoperative vestibular testing and postoperative caloric testing performed at 6-month intervals to determine vestibular function. The DHI questionnaires were administered retrospectively to assess the impact of GKS on self-perceived disability. RESULTS: Between June 2000 and May 2008, 55 sporadic VSs were treated. There was a >or= 60-month follow-up available in 27 of these patients, >or= 48 months in 32, >or= 36 months in 38, >or= 24 months in 43, >or= 12 months in 51, and >or= 6 months in 54 (1 patient was excluded from the analysis because the follow-up was < 6 months). Various patterns of changes in vestibular function were observed in either positive or negative directions. A significant difference in total DHI score was seen only in the elderly (> 65 years old) patients pre-GKS compared with post-GKS (t = 1.34, p = 0.05). CONCLUSIONS: Longitudinal changes in vestibular function occur over time, with the largest changes seen in the first 6 months after treatment. Potential for clinical intervention, such as vestibular rehabilitation therapy, exists during this interval; however, larger cohorts must be studied to determine the timing and efficacy of this intervention. The statistically significant improvement in the DHI score in the patient cohort > 65 years old treated with GKS suggests that this group may benefit from this option when considering the symptom of dizziness.

Distribution of two-pore-domain potassium channels in the adult rat vestibular periphery.

Constitutively active background or "leak" two-pore-domain potassium (K(+)) channels (Kcnk family), as defined by lack of voltage and time dependency are central to electrical excitability of cells by controlling resting membrane potential and membrane resistance. Inhibition of these channels by several neurotransmitters, e.g. glutamate, or acetylcholine, induces membrane depolarization and subsequent action potential firing as well as increases membrane resistance amplifying responses to synaptic inputs. In contrast, their opening contributes to hyperpolarization. Because of their central role in determining cellular excitability and response to synaptic stimulation, these channels likely play a role in the differential effects of vestibular efferent neurons on afferent discharge. Microarray data from previous experiments showed Kcnk 1, 2, 3, 6, 12 and 1 5 mRNA in Scarpa's ganglia. Real-time RT-PCR showed Kcnk 1, 2, 3, 6, 12 and 15 mRNA expression in Scarpa's ganglia and Kcnk 1, 2, 3, 6, 12 but not 15 mRNA expression in the crista ampullaris. We studied the distribution of two-pore-domain potassium channels K(2P)1.1, 2.1, 3.1 and 6.1 like immunoreactivity (corresponding to Kcnk genes 1, 2, 3 and 6) in the vestibular periphery. K(2P)1.1 (TWIK 1) immunoreactivity was detected along nerve terminals, supporting cells and blood vessels of the crista ampullaris and in the cytoplasm of neurons of the Scarpa's ganglia. K(2P)2.1 (TREK 1) immunoreactivity was detected in nerve terminals and transitional cells of the crista ampullaris, in the vestibular dark cells and in neuronal fibers and somata of neurons of Scarpa's ganglia. K(2P)3.1 (TASK 1) immunoreactivity was detected in supporting cells and transitional cells of the crista ampullaris, in vestibular dark cells and in neuron cytoplasm within Scarpa's ganglia. K(2P)6.1 (TWIK 2) immunoreactivity was detected in nerve terminals, blood vessels hair cells and transitional cells of the crista ampullaris and in the somata and neuron fibers of Scarpa's ganglia.

MUC2 expression in human middle ear epithelium of patients with otitis media.

OBJECTIVE: To compare levels of expression of mucin gene 2 (MUC2), a major secretory mucin, in the middle ear of patients with otitis media (OM) and control patients. DESIGN: Case-control study. SETTING: Children's Hospital of Wisconsin, Milwaukee. PATIENTS: Nineteen patients aged 6 months to 15 years undergoing routine ventilation tube insertion for recurrent OM or chronic OM with effusion and 8 controls with no history of OM undergoing cochlear implantation. INTERVENTIONS: Biopsy of middle ear epithelium for RNA extraction. MAIN OUTCOME MEASURE: Expression of MUC2 by real-time reverse transcription-polymerase chain reaction. RESULTS: Twenty-seven OM samples (17 recurrent and 10 with effusion) from 19 patients were analyzed and compared with 9 control samples from 8 patients. The mean MUC2 expression was 6.12 (95% confidence interval, 3.32-8.89) times that of the controls in the OM samples overall, 5.00 (95% confidence interval, 2.79-7.21) times that of controls in the recurrent OM samples, and 7.98 (95% confidence interval, 1.58-14.38) times that of controls in the OM with effusion samples. CONCLUSIONS: Levels of MUC2 expression in human middle ear epithelium are significantly increased in patients with OM overall, patients with recurrent OM, and patients with OM with effusion compared with controls. Mucins are fundamentally important in the middle ear, controlling viscoelastic properties of secretions and providing mucosal protection and bacterial clearance. Demonstration of these differences between patient groups highlights the need for greater understanding of molecular responses in OM, which may provide novel interventions for this common problem.

Quantitative analysis of electrically evoked auditory brainstem responses in implanted children with auditory neuropathy/dyssynchrony.

OBJECTIVE: Cochlear implantation is a common treatment approach for children with auditory neuropathy/dyssynchrony (AN/AD) who do not benefit from hearing aids. The auditory brainstem response (ABR) is a measure of neural synchrony along the auditory pathway up through the brainstem. By definition, acoustically evoked ABR is absent in AN/AD, however, ABR can be elicited by electrical stimulation through the cochlear implant (electrically evoked ABR [EABR]). Reports of EABR with AN/AD to date have been primarily descriptive in nature. The objective of this study was to quantify EABR wave V measures in implanted children with and without AN/AD. STUDY DESIGN: Retrospective analysis of EABR waveforms from March 2000 through February 2005. SETTING: Comprehensive Cochlear Implant Program/Tertiary Referral Center. PATIENTS: Pediatric cochlear implant users of two etiologic groups: congenital AN/AD (n = 5) and other congenital profound sensorineural hearing loss (n = 27). INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Intraoperative EABR wave V threshold, suprathreshold amplitude, and latency measures were compared between groups. RESULTS: The EABR threshold and suprathreshold amplitude measures across the population were variable regardless of etiology. With some exceptions, a trend was observed for the AN/AD group that included average or below-average thresholds and below-average suprathreshold response amplitudes. CONCLUSION: Cochlear implantation can provide synchronous neural responses to auditory stimulation in AN/AD, as previously known. The quantification of EABR measures in this study indicates that subjects with AN/AD have sufficient neural sensitivity to electrical stimulation, however, they may experience less robust neural responses at suprathreshold levels. Given the heterogeneity of potential causes of AN/AD, however, caution needs to be applied when grouping this population for analyses.

Tissue and fluid penetration of garenoxacin in surgical patients.

BACKGROUND AND PURPOSE: Garenoxacin is a novel des-F(6)-quinolone that exhibits broad-spectrum activity against a wide range of aerobic and anaerobic pathogens of clinical importance. This study examined the penetration of garenoxacin into sinus mucosa, incisional skin, subcutaneous tissue, bile, adipose tissue, striated muscle, bone, gallbladder wall, liver, small and large bowel mucosa, and mesenteric lymph nodes relative to the plasma concentration after an oral 600 mg dose. METHODS: A series of 30 patients, ages 20 to 83 years, undergoing elective surgery were enrolled. Patients received a single 600 mg oral dose of garenoxacin before surgery. Blood and tissue specimens were collected at surgery 3-5 h post-dose, and garenoxacin concentrations were determined using validated liquid chromatography/tandem mass spectrometry assays designed specifically for each tissue and biofluid. RESULTS: The mean plasma or bile (mcg/mL) and tissue (mcg/g) concentrations ( +/- standard deviation) were plasma 5.71 +/- 3.44, bile 7.59 +/- 9.96, adipose tissue 0.90 +/- 0.54, subcutaneous tissue 1.19 +/- 1.23, incisional skin 3.06 +/- 1.74, striated muscle 3.92 +/- 2.54, bone 2.82 +/- 2.42, sinus mucosa 5.26 +/- 3.84, liver 1.84 +/- 0.75, gallbladder 11.59 +/- 11.94, large intestine 12.13 +/- 9.34, small intestine 15.66 +/- 19.20, and mesenteric lymph node 3.10 +/- 2.44. CONCLUSION: After a single 600 mg oral dose, garenoxacin penetrates well into selected tissues and fluids. In addition, the tissue and fluid concentrations at 3-5 hours post-dose exceeded the minimum inhibitory concentration-90% of most targeted pathogens, suggesting that garenoxacin would be effective in the treatment of sinus, skin and skin structure, and intra-abdominal infections.

Progressive Consent and Specimen Accrual Models to Address Sustainability: A Decade's Experience at an Oregon Biorepository.

BACKGROUND: The Legacy Biorepository is a College of American Pathologists-accredited biorepository operating within a seven-hospital healthcare system, with a decade's experience in specimen accrual, storage, and distribution. While standardization of our practices through accreditation remains a priority, we along with others face challenges with regard to sustainability. Purposeful changes in our consent process, which we term "progressive consent," are expected to improve sustainability and operational flexibility while increasing our scientific impact. METHODS: Until 2015, informed consent was performed primarily by biorepository staff at an estimated time of 1 hour per case. After a process improvement exercise, we successfully changed our informed consent process to a modified front-door model, with use of material and data for research as an opt-in or opt-out selection on the institutional patient informed consent form provided to surgery patients in the healthcare system. Successful implementation of this change required the engagement and participation of multiple stakeholders in healthcare system leadership, hospital administration, research, legal, regulatory, and patient care levels. RESULTS: A modified front-door consent enabled us to collect an additional 38 specimens in the first two quarters of 2016, with a time commitment of 15.75 hours, a time savings per specimen increasing in Q2 over Q1. We estimate a potential savings of 43 hours in 2016. This progressive model allowed us to maintain our frozen sample collection while increasing the availability of paraffin-embedded tissue and bodily fluids. Augmenting our tissue collection added little expense per case (approximately half that of each frozen tissue aliquot) and increased the range of biospecimens collected. CONCLUSIONS: Biorepository financial sustainability is a critical issue. Thorough evaluation and modification of existing procedures and collection models, as well as cost recovery initiatives, can translate into savings. Sustainability, process improvement, and scientific impact broadly overlap and continue to require operational critique and implementation of strategic changes.

Comorbidities confounding the outcomes of surgery for third window syndrome: Outlier analysis.

Objective: Patients with third window syndrome and superior semicircular canal dehiscence (SSCD) symptoms whose surgical outcomes placed them as outliers were systematically studied to determine comorbidities that were responsible for their poor outcomes due to these confounding factors. Study Design: Observational analytic case-control study in a tertiary referral center. Methods: Twelve adult patients with clinical SSCD syndrome underwent surgical management and had outcomes that did not resolve all of their subjective symptoms. In addition to one of the neurotologists, 2 neurologists (one specializing in migraine and the other a neuro-ophthalmologist), and a psychologist clinician-investigator completed comprehensive evaluations. Neuropsychology test batteries included: the Millon Behavioral Medicine Diagnostic; Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Screener (GAD-7); Adverse Childhood Experiences Scale; the Wide Range Assessment of Memory and Learning, including the 3 domains of verbal memory, visual memory, and attention/concentration; Wechsler Adult Intelligence Scale; and the Delis-Kaplan Executive Function System. The control cohort was comprised of 17 participants who previously underwent surgery for third window syndrome that resulted in the expected outcomes of resolution of their third window syndrome symptoms and cognitive dysfunction. Results: There was a high rate of psychological comorbidity (n = 6) in the outlier cohort; multiple traumatic brain injuries were also a confounding element (n = 10). One patient had elevated cerebrospinal fluid (CSF) pressure requiring ventriculoperitoneal shunting to control the recurrence of dehiscence and one patient with a drug-induced Parkinson-like syndrome and idiopathic progressive neurological degenerative process. Conclusions: Components of the Millon Behavioral Medicine Diagnostic, PHQ-9 and GAD-7 results suggest that these instruments would be useful as screening tools preoperatively to identify psychological comorbidities that could confound outcomes. The identification of these comorbid psychological as well as other neurological degenerative disease processes led to alternate clinical management pathways for these patients. Level of Evidence: 2b.