Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Otolaryngology
Total Results:
7604
Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis
Vocal fold (VF) fibrosis is a major cause of intractable voice-related disability and reduced quality of life. Excision of fibrotic regions is suboptimal and associated with scar recurrence and/or further iatrogenic damage. Non-surgical interventions are limited, putatively related to limited insight regarding biochemical events underlying fibrosis, and downstream, the lack of therapeutic targets. YAP/TAZ integrates diverse cell signaling events and interacts with signaling pathways related to fibrosis, including the TGF-β/SMAD pathway. We investigated the expression of YAP/TAZ following vocal fold injury in vivo as well as the effects of TGF-β1 on YAP/TAZ activity in human vocal fold fibroblasts, fibroblast-myofibroblast transition, and TGF-β/SMAD signaling. Iatrogenic injury increased nuclear localization of YAP and TAZ in fibrotic rat vocal folds. In vitro, TGF-β1 activated YAP and TAZ in human VF fibroblasts, and inhibition of YAP/TAZ reversed TGF-β1-stimulated fibroplastic gene upregulation. Additionally, TGF-β1 induced localization of YAP and TAZ in close proximity to SMAD2/3, and nuclear accumulation of SMAD2/3 was inhibited by a YAP/TAZ inhibitor. Collectively, YAP and TAZ were synergistically activated with the TGF-β/SMAD pathway, and likely essential for the fibroplastic phenotypic shift in VF fibroblasts. Based on these data, YAP/TAZ may evolve as an attractive therapeutic target for VF fibrosis.
PMID: 34188130
ISSN: 2045-2322
CID: 4926502
Dopaminergic signaling supports auditory social learning
Explicit rewards are commonly used to reinforce a behavior, a form of learning that engages the dopaminergic neuromodulatory system. In contrast, skill acquisition can display dramatic improvements from a social learning experience, even though the observer receives no explicit reward. Here, we test whether a dopaminergic signal contributes to social learning in naïve gerbils that are exposed to, and learn from, a skilled demonstrator performing an auditory discrimination task. Following five exposure sessions, naïve observer gerbils were allowed to practice the auditory task and their performance was assessed across days. We first tested the effect of an explicit food reward in the observer's compartment that was yoked to the demonstrator's performance during exposure sessions. Naïve observer gerbils with the yoked reward learned the discrimination task significantly faster, as compared to unrewarded observers. The effect of this explicit reward was abolished by administration of a D1/D5 dopamine receptor antagonist during the exposure sessions. Similarly, the D1/D5 antagonist reduced the rate of learning in unrewarded observers. To test whether a dopaminergic signal was sufficient to enhance social learning, we administered a D1/D5 receptor agonist during the exposure sessions in which no reward was present and found that the rate of learning occurred significantly faster. Finally, a quantitative analysis of vocalizations during the exposure sessions suggests one behavioral strategy that contributes to social learning. Together, these results are consistent with a dopamine-dependent reward signal during social learning.
PMCID:8222360
PMID: 34162951
ISSN: 2045-2322
CID: 4934122
Complications associated with deep brain stimulation for Parkinson's disease: a MAUDE study
INTRODUCTION/UNASSIGNED:Deep brain stimulation (DBS) is a common surgical option for the treatment of medically refractory Parkinson's disease (PD). Manufacturer and User Facility Device Experience (MAUDE), a United States Food and Drug Administration (FDA)-compiled database of adverse event reports related to medical devices, is a public resource that can provide insight into the relative frequency of complications and patient complaints. MATERIALS AND METHODS/UNASSIGNED:We accessed the MAUDE database and queried for adverse reports for deep brain stimulators implanted for PD from January 1, 2009 to December 31, 2018. Complaints were classified into device malfunction, patient non-compliance, patient complaint, surgically managed complications (i.e. complications that are corrected via surgery), and death. Patient complaints were further stratified into ineffective stimulation, shock, overstimulation, battery-related problems, or pain at the pulse generator site. Surgically managed complications were classified as intraoperative complications, impedance, migration, erosion, infection, lead fracture, and lead disconnection. Each event could receive multiple classifications and subclassifications. RESULTS/UNASSIGNED:A total of 4,189 adverse event reports was obtained. These encompassed 2,805 patient complaints. Within this group, 797 (28%) events were classified as ineffective stimulation. There were 1,382 surgically managed complications, 104 (8%) of which were intraoperative complications, 757 (55%) documented impedance issues, 381 (28%) infections, and 413 (30%) lead-related issues. There were 53 documented deaths. CONCLUSIONS/UNASSIGNED:The MAUDE database has potential use as a real time monitor for elucidating the relative occurrence of complications associated with deep brain stimulation. It also allows for the analysis of device-related complications in specific patient populations. Although the database is useful in this endeavor, it requires improvements particularly in the standardization of reporting adverse events.
PMID: 34151665
ISSN: 1360-046x
CID: 4918142
The impact of the COVID-19 pandemic on otolaryngologic emergency department visits at two major NYC hospital systems
PURPOSE/OBJECTIVE:Since the COVID-19 pandemic began, emergency departments (ED) across the country have seen a significant decrease in patient visits. We aim to evaluate the impact of COVID-19 on ED visits for acute otolaryngologic complaints in New York City, one of the first epicenters of the pandemic in the US. MATERIALS AND METHODS/METHODS:We conducted a retrospective study of patients who presented to the ED with a primary diagnosis of an acute otolaryngologic complaint between March 1 and May 31 in 2019 and 2020. This was a multicenter study, including two tertiary care hospital systems encompassing Manhattan, Bronx, Queens, and Long Island. RESULTS:A total of 10,162 patients were identified. Significantly fewer patients presented to the ED for acute otolaryngologic complaints in 2020 (7332 vs 2830, p < 0.001). The rate of total otolaryngology-related ED visits was decreased by a factor of 0.635 (95% CI 0.6079 to 0.6634). In a subgroup analysis of each individual diagnosis, there was a significant decrease in rate of ED visits for 13 out of 18 diagnoses, including for life-threatening conditions, such as anaphylaxis. There was no significant difference based on which borough in New York City. Pediatric patients (age 0-17) were more significantly impacted by the pandemic compared to other age groups. CONCLUSION/CONCLUSIONS:The COVID-19 pandemic has led to a reduction in the utilization of ED for acute otolaryngologic complaints, including those requiring emergent management, and an even more significant reduction in the pediatric population. Healthcare providers should encourage patients to seek appropriate care, particularly for those illnesses with significant associated morbidity and mortality.
PMCID:8214322
PMID: 34186437
ISSN: 1532-818x
CID: 4926472
Cochlear implantation for single-sided deafness after COVID-19 hospitalization
INTRODUCTION/UNASSIGNED:Understanding the clinical manifestations of the coronavirus disease (COVID-19) has become an urgent objective in the research community. Amongst the emerging neurologic complications is sensorineural hearing loss. While several cases of hearing loss amongst COVID-19 patients have been reported, the management of these patients has yet to be discussed and determined. Herein we present cochlear implant outcomes for a patient who suffered from unilateral sensorineural hearing loss after a prolonged hospital course for COVID-19. METHODS/UNASSIGNED:A patient who was hospitalized for COVID-19 for one month and subsequently developed unilateral profound sensorineural hearing loss underwent cochlear implantation for single-sided deafness. His COVID-19 hospital course was reviewed in detail. Speech perception and audiometric assessments were used to evaluate cochlear implant outcomes. RESULTS/UNASSIGNED:After cochlear implantation, the patient demonstrated improved speech perception on the implanted side and decreased tinnitus within 1 month of activation. CONCLUSIONS/UNASSIGNED:Cochlear implantation may be an appropriate intervention for patients who suffer from severe sensorineural hearing loss following infection with COVID-19.
PMID: 34151741
ISSN: 1754-7628
CID: 4965542
Systematic review of submental artery island flap versus free flap in head and neck reconstruction
PURPOSE/OBJECTIVE:The aim of this systematic review is to compare the perioperative characteristics and outcomes of submental artery island flap (SAIF) to free tissue transfer (FTT) in head and neck reconstruction. MATERIALS AND METHODS/METHODS:Screening and data extraction were done with Pubmed, Embase, and Web of Science databases by two independent authors to identify randomized and observational studies that compared patient outcomes for SAIF vs. FTT for reconstruction head and neck cancer ablative surgery. Data were pooled with random-effects meta-analysis to determine pooled difference in means (DM), absolute risk differences, and 95% confidence intervals (CI). Heterogeneity was assessed with the I-squared statistic. RESULTS:(95% CI 6.5 to 38.4). SAIF had a 5% higher incidence of partial flap necrosis than FTT (95% CI, 1 to 10), but all other perioperative complications, including recurrence rate in malignant cases, were statistically comparable. CONCLUSIONS:The SAIF requires less operative time, hospital stay, and has comparable perioperative outcomes to FTT, but the area of flap harvest is significantly smaller. The findings of this study add to the growing body of evidence demonstrating the safety and reliability of SAIF in head and neck reconstruction.
PMID: 34174670
ISSN: 1532-818x
CID: 4925992
Peripheral Nerve Resident Macrophages and Schwann Cells Mediate Cancer-induced Pain
Although macrophages (MΦ) are known to play a central role in neuropathic pain, their contribution to cancer pain has not been established. Here we report that depletion of sciatic nerve resident MΦs (rMΦ) in mice attenuates mechanical/cold hypersensitivity and spontaneous pain evoked by intraplantar injection of melanoma or lung carcinoma cells. MΦ-colony stimulating factor (M-CSF) was upregulated in the sciatic nerve trunk and mediated cancer-evoked pain via rMΦ expansion, transient receptor potential ankyrin 1 (TRPA1) activation, and oxidative stress. Targeted deletion of Trpa1 revealed a key role for Schwann cell TRPA1 in sciatic nerve rMΦ expansion and pain-like behaviors. Depletion of rMΦs in a medial portion of the sciatic nerve prevented pain-like behaviors. Collectively, we identified a feed-forward pathway involving M-CSF, rMΦ, oxidative stress and Schwann cell TRPA1 that operates throughout the nerve trunk to signal cancer-evoked pain.
PMID: 33771895
ISSN: 1538-7445
CID: 4929522
Listening to speech with a guinea pig-to-human brain-to-brain interface
Nicolelis wrote in his 2003 review on brain-machine interfaces (BMIs) that the design of a successful BMI relies on general physiological principles describing how neuronal signals are encoded. Our study explored whether neural information exchanged between brains of different species is possible, similar to the information exchange between computers. We show for the first time that single words processed by the guinea pig auditory system are intelligible to humans who receive the processed information via a cochlear implant. We recorded the neural response patterns to single-spoken words with multi-channel electrodes from the guinea inferior colliculus. The recordings served as a blueprint for trains of biphasic, charge-balanced electrical pulses, which a cochlear implant delivered to the cochlear implant user's ear. Study participants completed a four-word forced-choice test and identified the correct word in 34.8% of trials. The participants' recognition, defined by the ability to choose the same word twice, whether right or wrong, was 53.6%. For all sessions, the participants received no training and no feedback. The results show that lexical information can be transmitted from an animal to a human auditory system. In the discussion, we will contemplate how learning from the animals might help developing novel coding strategies.
PMCID:8192924
PMID: 34112826
ISSN: 2045-2322
CID: 4924582
Global Impact of COVID-19 on Stroke Care and Intravenous Thrombolysis
OBJECTIVE:The objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods. METHODS:We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases. RESULTS:There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95%CI, -11.7 to - 11.3, p<0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95%CI, -13.8 to -12.7, p<0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95%CI, -13.7 to -10.3, p=0.001). Recovery of stroke hospitalization volume (9.5%, 95%CI 9.2-9.8, p<0.0001) was noted over the two later (May, June) versus the two earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS:The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
PMID: 33766997
ISSN: 1526-632x
CID: 4822932
B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma
Current immunotherapy paradigms aim to reinvigorate CD8+ T cells, but the contribution of humoral immunity to antitumor immunity remains understudied. Here, we demonstrate that in head and neck squamous cell carcinoma (HNSCC) caused by human papillomavirus infection (HPV+), patients have transcriptional signatures of germinal center (GC) tumor infiltrating B cells (TIL-Bs) and spatial organization of immune cells consistent with tertiary lymphoid structures (TLS) with GCs, both of which correlate with favorable outcome. GC TIL-Bs in HPV+ HNSCC are characterized by distinct waves of gene expression consistent with dark zone, light zone and a transitional state of GC B cells. Semaphorin 4a expression is enhanced on GC TIL-Bs present in TLS of HPV+ HNSCC and during the differentiation of TIL-Bs. Our study suggests that therapeutics to enhance TIL-B responses in HNSCC should be prioritized in future studies to determine if they can complement current T cell mediated immunotherapies.
PMCID:8184766
PMID: 34099645
ISSN: 2041-1723
CID: 5482242
