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"Lin, Vincent Y"
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Comprehensive Expression of Wnt Signaling Pathway Genes during Development and Maturation of the Mouse Cochlea
2016
In the inner ear Wnt signaling is necessary for proliferation, cell fate determination, growth of the cochlear duct, polarized orientation of stereociliary bundles, differentiation of the periotic mesenchyme, and homeostasis of the stria vascularis. In neonatal tissue Wnt signaling can drive proliferation of cells in the sensory region, suggesting that Wnt signaling could be used to regenerate the sensory epithelium in the damaged adult inner ear. Manipulation of Wnt signaling for regeneration will require an understanding of the dynamics of Wnt pathway gene expression in the ear. We present a comprehensive screen for 84 Wnt signaling related genes across four developmental and postnatal time points.
We identified 72 Wnt related genes expressed in the inner ear on embryonic day (E) 12.5, postnatal day (P) 0, P6 and P30. These genes included secreted Wnts, Wnt antagonists, intracellular components of canonical signaling and components of non-canonical signaling/planar cell polarity.
A large number of Wnt signaling molecules were dynamically expressed during cochlear development and in the early postnatal period, suggesting complex regulation of Wnt transduction. The data revealed several potential key regulators for further study.
Journal Article
Focused ultrasound-mediated drug delivery of bevacizumab in treating NF2-related schwannomatosis in an animal model
2025
Neurofibromatosis type 2 (NF2)-related schwannomatosis is an autosomal dominant genetic disorder characterized by the development of cranial and peripheral nerve schwannomas, including bilateral vestibular schwannomas which are associated with substantial morbidity. Current therapeutic strategies comprise surgical resection, radiotherapy, and systemic administration of bevacizumab; however, these approaches are frequently limited by high recurrence rates and morbidity. In this study, a transgenic murine model (
Postn-Cre;Nf2
flox/flox
) was employed to investigate the combined effect of intraperitoneally administered human bevacizumab (5 mg/kg b. w.) and focused ultrasound (FUS) on drug delivery and tumor growth in DRG schwannomas. ELISA-based analysis demonstrated a 3.8-fold increase in intratumoral bevacizumab concentration following the combined application of human bevacizumab and FUS, compared to bevacizumab alone. Tumor growth was assessed using 7-T MRI of the spine with intravenous gadolinium contrast, and outcomes were compared across five experimental groups: (1) human bevacizumab alone, (2) murine bevacizumab alone, (3) human bevacizumab combined with FUS, (4) FUS alone, and (5) untreated controls. Treatments, including drug administration and FUS exposure, were performed three times at two-week intervals. Notably, the combined treatment group (human bevacizumab + FUS) exhibited a trend toward tumor size reduction.
Journal Article
Neural responses to naturalistic audiovisual speech are related to listening demand in cochlear implant users
by
Paul, Brandon T
,
Chen, Joseph M
,
Dimitrijevic, Andrew
in
Cochlea
,
Cochlear implants
,
Environmental effects
2022
There is a weak relationship between clinical and self-reported speech perception outcomes in cochlear implant (CI) listeners. Such poor correspondence may be due to differences in clinical and “real-world” listening environments and stimuli. Speech in the real world is often accompanied by visual cues, background environmental noise, and is generally in a conversational context, all factors that could affect listening demand. Thus, our objectives were to determine if brain responses to naturalistic speech could index speech perception and listening demand in CI users. Accordingly, we recorded high-density EEG while CI users listened/watched a naturalistic stimulus (i.e., the television show, “The Office”). We used continuous EEG to quantify “speech neural tracking” (i.e., TRFs, temporal response functions) to the show’s soundtrack and 8–12 Hz (alpha) brain rhythms commonly related to listening effort. Background noise at three different signal-to-noise ratios (SNRs), +5, +10, and +15 dB were presented to vary the difficulty of following the television show, mimicking a natural noisy environment. The task also included an audio-only (no video) condition. After each condition, participants subjectively rated listening demand and the degree of words and conversations they felt they understood. Fifteen CI users reported progressively higher degrees of listening demand and less words and conversation with increasing background noise. Listening demand and conversation understanding in the audio-only condition was comparable to that of the highest noise condition (+5 dB). Increasing background noise affected speech neural tracking at a group level, in addition to eliciting strong individual differences. Mixed effect modeling showed that listening demand and conversation understanding were correlated to early cortical speech tracking, such that high demand and low conversation understanding occurred with lower amplitude TRFs. In the high noise condition, greater listening demand was negatively correlated to parietal alpha power, where higher demand was related to lower alpha power. No significant correlations were observed between TRF/alpha and clinical speech perception scores. These results are similar to previous findings showing little relationship between clinical speech perception and quality-of-life in CI users. However, physiological responses to complex natural speech may provide an objective measure of aspects of quality-of-life measures like self-perceived listening demand.
Journal Article
The feasibility and safety of eustachian tube dilation with a standard endovascular balloon: a clinical pilot study
2023
BackgroundObstructive eustachian tube dysfunction is a common pathology, generally accepted as the underlying cause for chronic ear diseases. Eustachian tube dilation has shown promising results in randomized controlled trials, but is a costly procedure.The aim of the current study was to assess the feasibility of transnasal balloon dilatation of the eustachian tube with an endovascular balloon in the context of ease of use, maneuverability, and safety.MethodsClinical pilot study carried out at a university tertiary care facility. In total, twelve patients, were included over a period of 6 months. All patients underwent tympanoplasty or tympanomastoidectomy surgeries. Eustachian tube dilation was carried out transnasal using an endovascular balloon. A computed tomography was carried out after surgery to assess for any potential damages and compared to preoperative imaging studies. Postoperative endoscopy was performed intraoperatively and at follow up to assess for any potential damages.ResultsAll eustachian tube dilations were carried out successfully. No severe adverse events were noted during the procedure, in the postoperative period, or on imaging studies. Minor adverse events such as mild intraoperative bleeding was managed in a routine fashion.ConclusionsBalloon dilation of the eustachian tube with the endovascular balloon was feasible and safe in all cases. It is likely a more cost-effective alternative to commercially available balloons with similar designs and specifications.Trial registration The study was registered at clinicaltrials.gov; NCT04809753, initial release February 24th, 2021.
Journal Article
Using augmented reality to guide bone conduction device implantation
by
Irish, Jonathan C.
,
Chen, Joseph M.
,
Chan, Harley H. L.
in
692/698/1671/63
,
692/700/565/545
,
Accuracy
2023
Exact placement of bone conduction implants requires avoidance of critical structures. Existing guidance technologies for intraoperative placement have lacked widespread adoption given accessibility challenges and significant cognitive loading. The purpose of this study is to examine the application of augmented reality (AR) guided surgery on accuracy, duration, and ease on bone conduction implantation. Five surgeons surgically implanted two different types of conduction implants on cadaveric specimens with and without AR projection. Pre- and postoperative computer tomography scans were superimposed to calculate centre-to-centre distances and angular accuracies. Wilcoxon signed-rank testing was used to compare centre-to-centre (C-C) and angular accuracies between the control and experimental arms. Additionally, projection accuracy was derived from the distance between the bony fiducials and the projected fiducials using image guidance coordinates. Both operative time (4.3 ± 1.2 min. vs. 6.6 ± 3.5 min.,
p
= 0.030) and centre-to-centre distances surgery (1.9 ± 1.6 mm vs. 9.0 ± 5.3 mm,
p
< 0.001) were significantly less in augmented reality guided surgery. The difference in angular accuracy, however, was not significantly different. The overall average distance between the bony fiducial markings and the AR projected fiducials was 1.7 ± 0.6 mm. With direct intraoperative reference, AR-guided surgery enhances bone conduction implant placement while reduces operative time when compared to conventional surgical planning.
Journal Article
Is otologic surgery contributing to the opioid epidemic?
2021
Background
The opioid epidemic is a significant public health crisis challenging the lives of North Americans. Interestingly, this problem does not exist to the same extent in Europe. Surgeons play a significant role in prescribing opioids, especially in the context of post-operative pain management. The aim of this study was to compare the post-surgical prescribing patterns of otologists comparing Canada and Austria.
Methods
An online questionnaire was sent to 33 Canadian and 32 Austrian surgeons, who perform otologic surgery on a regular basis. Surgeons were asked to answer some questions about their background as well as typical prescribing patterns for postoperative pain medication for different ear surgeries (cochlear implant, stapedotomy, tympanoplasty). In addition, surgeons were asked about the typical use of local anesthetics for pain control at the end of a procedure. Otologists gave an estimate how confident they were that their therapy and prescriptions provide sufficient pain control to their patients.
Results
Analysis of the returned questionnaires showed that opioids are more commonly prescribed in Canada than in Austria. Nonsteroidal anti-inflammatory drugs are used for postoperative pain more regularly after ear surgery in Austria, as opposed to Canada. Some of the prescribed drugs by European otologists are not available in North America. The use of local anesthetics at the end of surgery is not common in Austria. Surgeons´ confidence that the prescribed pain medication was sufficient to control postoperative symptoms was higher in the group not prescribing opioids than in the group that did routinely prescribe opioids.
Conclusion
Prescribing patterns differ substantially between the two evaluated countries. This data suggests an opportunity to reduce opioid prescriptions after otologic surgeries. Studies to evaluate pain after these operations as well as efficacy of analgesics following ear surgery are an important next step.
Graphical abstract
Journal Article
How standardised are antibiotic regimens in otologic surgery?
by
Arnoldner, Christoph
,
Chen, Joseph M
,
Dahm, Valerie
in
Antibiotics
,
Antimicrobial agents
,
Bacterial infections
2023
BackgroundWithin otologic surgery, a paucity of well-controlled studies assessing the use of systemic antibiotic to reduce surgical site infections exists. Moreover, discrepancies in wound classification of procedures challenge consensus in antimicrobial prescribing patterns. We sought to compare surgeons from two different health systems to examine how surgeons’ prescribing habits compared to practice guidelines for numerous otologic procedures.MethodsAn online questionnaire was distributed to 33 Canadian and 32 Austrian surgeons who regularly perform otologic surgery. Current systemic antibiotic prescribing habits for cochlear implantation, cholesteatoma surgery, stapes surgery, and tympanoplasty ± ossiculoplasty were collected.ResultsEighteen of 33 (54.5%) Canadian surgeons provided responses, while 18 of 32 (56.3%) of Austrian surgeons answered. Clear consistency with clinical practice guidelines exists for pre-operative antibiotics use in cochlear implant surgery and infected cholesteatoma surgery. However, for stapes surgery and tympanoplasty ± ossiculoplasty, consensus is lacking for both pre- and post-operative antibiotic prescribing habits. Notable differences between the two countries include post-operative antibiotics for cochlear implant surgery (Austria: 36.4%, Canada: 71.4%) and uninfected cholesteatoma surgery (Austria: 33.3%, Canada: 77.8%). Across all procedures, both induction and post-operative antibiotic administration was not significantly associated with surgeon seniority when stratified by five-year increments.ConclusionThe lack of consensus among each country’s otologic surgeons underscores the uncertainty in wound classification and thus, adherence to clinical practice guidelines.
Journal Article
Predictors of round window accessibility for adult cochlear implantation based on pre-operative CT scan: a prospective observational study
2015
Background
Cochlear implantation has become a mainstream treatment option for patients with severe to profound sensorineural hearing loss. During cochlear implant, there are key surgical steps which are influenced by anatomical variations between each patient. The aim of this study is to determine if there are potential predictors of difficulties that may be encountered during the cortical mastoidectomy, facial recess approach and round window access in cochlear implant surgery based upon pre-operative temporal bone CT scan.
Methods
Fifty seven patients undergoing unilateral cochlear implantation were analyzed. Difficulty with 1) cortical mastoidectomy, 2) facial recess approach, and 3) round window access were scored intra-operatively by the surgeon in a blinded fashion (1 = “easy”, 2 = “moderate”, 3 = “difficult”). Pre-operative temporal bone CT scans were analyzed for 1) degree of mastoid aeration; 2) location of the sigmoid sinus; 3) height of the tegmen; 4) the presence of air cells in the facial recess, and 5) degree of round window bony overhang.
Results
Poor mastoid aeration and lower tegmen position, but not the location of sigmoid sinus, are associated with greater difficulty with the cortical mastoidectomy. Presence of an air cell around the facial nerve was predictive of easier facial recess access. However, the degree of round window bony overhang was not predictive of difficulty associated with round window access.
Conclusion
Certain parameters on the pre-operative temporal bone CT scan may be useful in predicting potential difficulties encountered during the key steps involved in cochlear implant surgery.
Journal Article
Vestibular function following unilateral cochlear implantation for profound sensorineural hearing loss
2016
Background
Many Canadians are affected by sensorineural hearing loss (SNHL) and those with severe or profound hearing loss may have poor hearing function despite optimized hearing aids. Cochlear implants (CI) offer effective hearing rehabilitation for these patients, however, concern continues to exist regarding possible effects of CI on the vestibular system and balance.
The objective of this study was to conduct a pilot study assessing the effects of unilateral cochlear implantation (CI) on balance and the vestibular system in post-lingually deafened adults.
Methods
Twelve patients were included in this pilot study and were assessed pre-operatively and at immediate, 1 week, and 1 month post-operative intervals. Assessments consisted of the dizziness handicap inventory (DHI), subjective visual vertical (SVV), and timed up-and-go testing (TUG). When applicable, testing was repeated with the CI on and off.
Results
Many patients were found to have deviated SVV at pre-operative and post-operative assessments. However, statistically significant changes were not seen when comparing pre-operative and post-operative SVV or when comparing SVV with the CI on and with the CI off. DHI was found to improve in five patients and worsen in two patients, however, no statistically significant change was found in DHI scores or with TUG testing.
Conclusions
This current pilot study does not indicate that CI surgery or implant activity influence vestibular or balance function, however, this pilot study is underpowered and greater numbers of patients would need be assessed to confirm these findings.
Journal Article
Mobile phone app Vs bucket test as a subjective visual vertical test: a validation study
2020
Background
The SVV tests the ability of a person to perceive the gravitational vertical. A tilt in SVV indicates vestibular imbalance in the roll plane, and thus injuries to the utricle or its connecting nerves. A validated bedside method (et, al., 2009, 72(19):1689–1692, Neurol, Zwergal) is the bucket method, in which the subject estimates the true vertical by attempting to properly align a straight line visible on the bottom of a bucket that is rotated at random by the examiner. In our study, the subjects need to align the plumb line on the Visual Vertical iOS app to the vertical direction.
Methods
Measurements of the SVV were made in 22 healthy subjects (16 females and 6 males). Each subject conducted 10 iterations of bucket test and 10 iterations of iOS app test. The reliability and validity of the iOS app was analyzed by SPSS21.
Results
Cronbach’s α for the plumb line method was 0.976, and the iOS app was 0.978. Statistical comparison of SVV values measured by the iOS app and the bucket method showed no significant difference in distribution (Mann Whitney U test U = 0.944).
Conclusion
The Visual Vertical iOS app is an effective and accessible substitute to the plumb line for the measurement of the validated bucket test.
Journal Article