Browsing by Author "Nelson, Rick F."
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Item Aerosol generation during cadaveric simulation of otologic surgery and live cochlear implantation(Wiley, 2021-02) Sharma, Dhruv; Campiti, Vincent J.; Ye, Michael J.; Saltagi, Mohamad; Carroll, Aaron E.; Ting, Jonathan Y.; Illing, Elisa A.; Park, Jae Hong; Nelson, Rick F.; Burgin, Sarah J.; Otolaryngology -- Head and Neck Surgery, School of MedicineObjective The risk of SARS‐CoV‐2 transmission to healthcare workers through airborne aerosolization during otologic surgery has not been characterized. The objective of this study was to describe and quantify the aerosol generation during common otologic procedures in both cadaveric surgical simulation and live patient surgery. Methods The number concentrations of generated aerosols in the particle size range of 0.30 to 10.0 μm were quantified using an optical particle sizer during both a cadaveric simulation of routine otologic procedures as well as cochlear implant surgery on live patients in the operating room. Results In the cadaveric simulation, temporalis fascia graft harvest using cold techniques (without electrocautery) (n = 4) did not generate aerosols above baseline concentrations. Tympanoplasty (n = 3) and mastoidectomy (n = 3) both produced statistically significant increases in concentrations of aerosols (P < 0.05), predominantly submicron particles (< 1.0 μm). High‐speed, powered drilling of the temporal bone during mastoidectomy with a Multi Flute cutting burr resulted in higher peak concentrations and greater number of spikes in aerosols than with a diamond burr. In the operating room, spikes in aerosols occurred during both cochlear implant surgeries. Conclusion In the cadaveric simulation, temporalis fascia graft harvest without electrocautery did not generate aerosol levels above baseline, while significant aerosol levels were generated during mastoidectomy and to a much less degree during tympanoplasty. Aerosol spikes were appreciated during cochlear implantation surgery in live patients.Item Association of Intracranial Hypertension With Calvarial and Skull Base Thinning(Wolters Kluwer, 2019-07) Rabbani, Cyrus C.; Patel, Janaki M.; Nag, Amit; Schueth, Elizabeth; Saltagi, Mohamad Z.; Kao, Richard; Nelson, Rick F.; Otolaryngology -- Head and Neck Surgery, School of MedicineObjective: Determine if patients with increased opening pressure (OP) on lumbar puncture (LP) have thinner calvaria and skull bases. Study Design: Retrospective cohort study. Setting: Tertiary referral center. Patients: Patients (≥18 yr of age) who had a recorded OP on LP and high-resolution computed tomography imaging of the head. Patient age, sex, body mass index were calculated. Intracranial hypertension (IH) was defined with an OP≥25 cm-H2O and low intracranial pressure with an OP<15 cm-H2O. Intervention: Measurement of calvarial, zygoma, and skull base thickness when blinded to OP with three-dimensional slicer and radiologic calipers. Main Outcome Measures: Association of calvarial, skull base, and zygoma thickness with OP and age. Results: Fifty-eight patients were included with a mean (SD) age of 53.1 (16.2) years and average (SD) body mass index of 30.1 (9.1) kg/m2. Patients with IH had thinner mean (SD) calvaria (3.01 [0.81] versus 2.70 [0.58] mm; p = 0.036) and skull bases (5.17 [1.22] versus 4.60 [1.42] mm; p = 0.043) when compared with patients without IH. The mean (SD) extracranial zygoma thickness was similar between the two groups (5.09 [0.76] versus 5.00 [0.73] mm; p = 0.56). General linear model regression demonstrated advancing age was associated with increasing calvarial thickness in patients without IH and calvarial thinning in patients with IH (p = 0.038). Conclusion: IH is independently associated with intracranial bone (calvaria and skull base) thinning and not extracranial (zygoma) thinning. Skull thinning occurs with IH and advancing age. These findings support a possible role of increased ICP in the pathophysiologic development of spontaneous cerebrospinal fluid leaks.Item Association of Obstructive Sleep Apnea With Calvarial and Skull Base Thinning(American Medical Association, 2018-06-01) Rabbani, Cyrus; Saltagi, Mohamad Z.; Ye, Michael J.; Patel, Janaki M.; Manchanda, Shalini; Nelson, Rick F.; Otolaryngology -- Head and Neck Surgery, School of MedicineImportance: Spontaneous cerebrospinal fluid leaks (sCSF-L) of the temporal bone are associated with obesity, calvarial thinning, and obstructive sleep apnea (OSA), and the incidence has doubled in the past decade. It is currently unknown if OSA is independently associated with skull thinning. Objective: To determine if patients with OSA have thinner skulls than patients without OSA. Design, Setting, and Participants: A retrospective cohort study of patients who underwent a level 1 polysomnogram (PSG) and also had high-resolution computed tomographic (CT) imaging of the head from January 2010 to March 2017 at Indiana University was carried out. Patients with moderate to severe OSA (apnea-hypopnea index [AHI]≥25/h) and without OSA (AHI<5/h) were matched for age and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared). Interventions: Measurement of calvarial thickness, extracranial zygoma thickness, skull base height and tegmen dehiscence (>4 mm) when blinded to OSA status. Main Outcomes and Measures: Primary outcomes were calvarial, skull base, and zygoma thickness differences between patients with OSA vs those without OSA. Results: A total of 22 933 patients had a PSG and 1012 also had head CT imaging. Of the 1012 patients with both PSG and CT, the mean (SD) age was 50.8 (16.2) years and 624 (61.7%) were women. Those patients with moderate to severe OSA (56) and without OSA (58) were matched for mean (SD) age (50.3 [6.5] vs 49.8 [6.1] years]) and BMI (37.4 [8.1] vs 38.6 [6.8]). Patients with OSA had thinner mean (SD) calvaria (2.73 [0.67] vs 2.47 [0.52] mm; difference, -0.26 mm; 95% CI, -0.49 to -0.04; Cohen d, 0.44) and thinner skull bases (5.03 [1.40] vs 4.32 [1.28] mm; difference, -0.71; 95% CI, -1.23 to -0.19; Cohen d, 0.53). The mean (SD) extracranial zygoma thickness was the same (4.92 [0.87] vs 4.84 [0.84] mm; difference, -0.07 mm; 95% CI, -0.39 to 0.24). The tegmen mastoideum was dehiscent in nearly twice as many patients with OSA as those without (37% vs 20%; difference, 17%; 95% CI, 0.4-32). Conclusions and Relevance: Obstructive sleep apnea was independently associated with intracranial bone (calvaria and skull base) thinning and not with extracranial (zygoma) thinning. These findings support a possible role of OSA in the pathophysiologic development of sCSF-L.Item Biallelic Loss-of-Function Variants in BICD1 Are Associated with Peripheral Neuropathy and Hearing Loss(MDPI, 2023-05-17) Hirsch, Yoel; Chung, Wendy K.; Novoselov, Sergey; Weimer, Louis H.; Rossor, Alexander; LeDuc, Charles A.; McPartland, Amanda J.; Cabrera, Ernesto; Ekstein, Josef; Scher, Sholem; Nelson, Rick F.; Schiavo, Giampietro; Henderson, Lindsay B.; Booth, Kevin T. A.; Otolaryngology -- Head and Neck Surgery, School of MedicineHearing loss and peripheral neuropathy are two clinical entities that are genetically and phenotypically heterogeneous and sometimes co-occurring. Using exome sequencing and targeted segregation analysis, we investigated the genetic etiology of peripheral neuropathy and hearing loss in a large Ashkenazi Jewish family. Moreover, we assessed the production of the candidate protein via western blotting of lysates from fibroblasts from an affected individual and an unaffected control. Pathogenic variants in known disease genes associated with hearing loss and peripheral neuropathy were excluded. A homozygous frameshift variant in the BICD1 gene, c.1683dup (p.(Arg562Thrfs*18)), was identified in the proband and segregated with hearing loss and peripheral neuropathy in the family. The BIDC1 RNA analysis from patient fibroblasts showed a modest reduction in gene transcripts compared to the controls. In contrast, protein could not be detected in fibroblasts from a homozygous c.1683dup individual, whereas BICD1 was detected in an unaffected individual. Our findings indicate that bi-allelic loss-of-function variants in BICD1 are associated with hearing loss and peripheral neuropathy. Definitive evidence that bi-allelic loss-of-function variants in BICD1 cause peripheral neuropathy and hearing loss will require the identification of other families and individuals with similar variants with the same phenotype.Item Calvarium Thinning in Patients with Spontaneous Cerebrospinal Fluid Leaks of the Anterior Skull Base(Wiley, 2021-06) Sharma, Dhruv; Tucker, Brady J.; Millay, David S.; Rubel, Kolin E.; Saltagi, Mohamad; Nelson, Rick F.; Illing, Elisa A.; Ting, Jonathan Y.; Otolaryngology -- Head and Neck Surgery, School of MedicineObjectives/Hypothesis Patients with spontaneous cerebrospinal fluid leaks (sCSF-L) of the temporal bone have isolated calvarial and skull base thinning that is independent of obesity. This study determines if anterior skull base (ASB) sCSF-L patients also have calvarial thinning. Study Design Retrospective Cohort Study. Methods This was a retrospective cohort study of ASB sCSF-L patients compared to nonobese (body mass index [BMI] < 30 kg/m2) and obese (BMI ≥ 30) control groups. Twenty-one patients in the ASB sCSF-L group and 25 patients in each control group were included. Calvarium and extracranial zygoma thicknesses were measured bilaterally with blinded, standardized, volumetric analysis. Results ASB sCSF-L patients had a mean (SD) age of 50.43 (10.19) years, an average (SD) BMI of 38.81 (8.92) kg/m2, and most were female (85.71%). The calvarium in patients with ASB sCSF-L was significantly thinner than the nonobese (2.55 mm [0.77] vs. 2.97 [0.67] mm; P = .006; 95% confidence intervals [CI], 0.12–0.30; Cohen d, 0.58) and obese control groups (2.55 [0.77] vs. 2.92 [0.76] mm; P = .02; 95% CI, 0.05–0.34; Cohen d, 0.66). The calvarium thickness of the nonobese patients was not significantly different from the obese patient controls (2.97 [0.67] vs. 2.92 [0.76] mm, P = .9). The extracranial zygoma was not significantly different among the groups (analysis of variance, P = .33). Conclusions ASB sCSF-L patients have isolated calvarial thinning that is independent of obesity. Like lateral skull base sCSF-L patients, these data suggest that the additional obesity-associated intracranial process contributes to skull thinning.Item Centralized Otolaryngology Research Efforts: Stepping‐stones to Innovation and Equity in Otolaryngology–Head and Neck Surgery(Wiley, 2022-06) Brenner, Michael J.; Nelson, Rick F.; Valdez, Tulio A.; Moody-Antonio, Stephanie A.; Nathan, Cherie-Anne O.; St John, Maie A.; Francis, Howard W.; Otolaryngology -- Head and Neck Surgery, School of MedicineThe Centralized Otolaryngology Research Efforts (CORE) grant program coordinates research funding initiatives across the subspecialties of otolaryngology-head and neck surgery. Modeled after National Institutes of Health study sections, CORE grant review processes provide comprehensive reviews of scientific proposals. The organizational structure and grant review process support grant-writing skills, attention to study design, and other components of academic maturation toward securing external grants from the National Institutes of Health or other agencies. As a learning community and a catalyst for scientific advances, CORE evaluates clinical, translational, basic science, and health services research. Amid the societal reckoning around long-standing social injustices and health inequities, an important question is to what extent CORE engenders diversity, equity, and inclusion for the otolaryngology workforce. This commentary explores CORE's track record as a stepping-stone for promoting equity and innovation in the specialty. Such insights can help maximize opportunities for cultivating diverse leaders across the career continuum.Item Cerebrospinal Fluid Leaks From the Lateral Ventricle: A Case Series(Wolters Kluwer, 2021-09) Saltagi, Mohamad Z.; Fraser, Amy L.; Alwani, Mohamedkazim M.; Mosier, Kristine M.; Nelson, Rick F.; Otolaryngology -- Head and Neck Surgery, School of MedicineOBJECTIVES: Describe the diagnosis and management of lateral skull base (LSB) cerebrospinal fluid (CSF) leaks originating from the lateral ventricle. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral academic center. PATIENTS: Patients with CSF leaks with direct communication to the lateral ventricle on preoperative imaging. INTERVENTION: Surgical repair via the middle cranial fossa (MCF) approach. MAIN OUTCOME MEASURES: CSF leak patient characteristics (age, sex, body mass index [BMI]) and postoperative course (complications and CSF leak resolution) were collected. RESULTS: Three patients had CSF leaks from the lateral ventricle and all patients demonstrated encephalomalacia of the temporal lobe on preoperative imaging. Encephalomalacia resulted from trauma in one case (age 5) and neurodegeneration in two cases (age 77 and 84). BMI ranged from 16.3 to 26.6 mg/kg2 and follow-up ranged from 4 to 21 months. Two patients presented with preoperative meningitis and all patients had resolution of CSF leaks after MCF repair. With the exception of the higher rate of meningitis, patient presentations did not differ from other spontaneous CSF leaks through middle fossa defects. There were no minor or major postoperative complications. CONCLUSIONS: CSF leaks from the lateral ventricle represent a rare subset of LSB CSF leaks and can occur in non-obese patients secondary to temporal lobe encephalomalacia. The MCF approach allows for repair of the dura and skull base in this cohort of patients with high-flow CSF leaks and loss of brain parenchyma.Item Cochlear Implantation in US Military Veterans: A Single Institution Study(Sage, 2023-05-12) Totten, Douglas J.; Saltagi, Abdul; Libich, Karen; Pisoni, David B.; Nelson, Rick F.; Otolaryngology -- Head and Neck Surgery, School of MedicineObjective: Military veterans have high rates of noise-induced hearing loss (NIHL) which is associated with more significant spiral ganglion neuronal loss. This study explores the relationship between NIHL and cochlear implant (CI) outcomes in veterans. Study design: Retrospective case series of veterans who underwent CI between 2019 and 2021. Setting: Veterans Health Administration hospital. Methods: AzBio Sentence Test, Consonant-Nucleus-Consonant (CNC) scores, and Speech, Spatial, and Qualities of Hearing Scale (SSQ) were measured pre- and postoperatively. Linear regression assessed relationships between outcomes and noise exposure history, etiology of hearing loss, duration of hearing loss, and Self-Administered Gerocognitive Exam (SAGE) scores. Results: Fifty-two male veterans were implanted at an average (standard deviation) age of 75.0 (9.2) years without major complications. The average duration of hearing loss was 36.0 (18.4) years. The average time of hearing aid use was 21.2 (15.4) years. Noise exposure was reported in 51.3% of patients. Objectively, AzBio and CNC scores 6 months postoperatively showed significant improvement of 48% and 39%, respectively. Subjectively, average 6-month SSQ scores showed significant improvement by 34 points (p < .0001). Younger age, SAGE score ≥17, and shorter duration of amplification were associated with higher postoperative AzBio scores. Greater improvement in AzBio and CNC scores was associated with lower preoperative scores. Noise exposure was not associated with any difference in CI performance. Conclusion: Despite high levels of noise exposure and advanced age, veterans derive substantial benefits from cochlear implantation. SAGE score ≥17 may be predictive of overall CI outcomes. Noise exposure does not impact CI outcomes.Item Comment on Liu et al. Aberrant Expression of FBXO2 Disrupts Glucose Homeostasis Through Ubiquitin-Mediated Degradation of Insulin Receptor in Obese Mice. Diabetes 2017;66:689–698(American Diabetes Association, 2020-02) Wong, Siauyen; Nelson, Rick F.; Lu, Peiran; Paulson, Henry; Lin, Dingbo; Otolaryngology -- Head and Neck Surgery, School of MedicineItem Deafness-in-a-dish: modeling hereditary deafness with inner ear organoids(Springer, 2022) Romano, Daniel R.; Hashino, Eri; Nelson, Rick F.; Otolaryngology -- Head and Neck Surgery, School of MedicineSensorineural hearing loss (SNHL) is a major cause of functional disability in both the developed and developing world. While hearing aids and cochlear implants provide significant benefit to many with SNHL, neither targets the cellular and molecular dysfunction that ultimately underlies SNHL. The successful development of more targeted approaches, such as growth factor, stem cell, and gene therapies, will require a yet deeper understanding of the underlying molecular mechanisms of human hearing and deafness. Unfortunately, the human inner ear cannot be biopsied without causing significant, irreversible damage to the hearing or balance organ. Thus, much of our current understanding of the cellular and molecular biology of human deafness, and of the human auditory system more broadly, has been inferred from observational and experimental studies in animal models, each of which has its own advantages and limitations. In 2013, researchers described a protocol for the generation of inner ear organoids from pluripotent stem cells (PSCs), which could serve as scalable, high-fidelity alternatives to animal models. Here, we discuss the advantages and limitations of conventional models of the human auditory system, describe the generation and characteristics of PSC-derived inner ear organoids, and discuss several strategies and recent attempts to model hereditary deafness in vitro. Finally, we suggest and discuss several focus areas for the further, intensive characterization of inner ear organoids and discuss the translational applications of these novel models of the human inner ear.