Bio


Dr. Iram Ahmad received her MD from the University of Michigan Medical School. She then completed Otolaryngology residency program at the University of Iowa. At Iowa, she was an NIH- sponsored T32 research resident in the Department of Otolaryngology. During her residency training she also gained expertise in education and graduated with a Master in Medical Education from the University of Iowa Carver College of Medicine. After residency, Dr. Ahmad continued at Iowa for her fellowship in Pediatric Otolaryngology.

Dr. Ahmad is an Assistant Professor of Otolaryngology- Head and Neck Surgery in the Pediatric Division. Her clinical expertise is in Pediatric Otology and hearing loss. She is focused on children with hearing loss, cochlear implantation, cholesteatoma, and general pediatric Otolaryngology. Her research interests are in children with congenital hearing loss and microstructure changes of the brain.

Clinical Focus


  • Pediatric cochlear implants
  • Pediatric hearing loss
  • cholesteatoma
  • Otolaryngology
  • congenital hearing loss
  • conductive hearing loss
  • Genetic hearing loss
  • pediatric sleep apnea
  • endoscopic ear surgery
  • Ototoxicity

Academic Appointments


Boards, Advisory Committees, Professional Organizations


  • Well-Being Director, Stanford School of Medicine (2019 - Present)
  • Resident member, ACGME- Residency Review Committee (2014 - 2016)
  • Member, American Academy of Otolaryngology-Head and Neck Surgery (2009 - Present)

Professional Education


  • Board Certification: American Board of Otolaryngology, Pediatric Otolaryngology (2021)
  • Fellowship: University of Iowa Dept of Otolaryngology (2017) IA
  • Residency: University of Iowa Dept of Otolaryngology (2016) IA
  • Board Certification: American Board of Otolaryngology, Otolaryngology (2017)
  • MME, University of Iowa College of Medicine, Master in Medical Education (2012)
  • Medical Education: University of Michigan Medical School (2009) MI

All Publications


  • Microstructural Changes in the Brainstem Auditory Pathway in Children With Hearing Loss. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Moon, P. K., Ward, K. M., Din, T. F., Saki, S., Cheng, A. G., Yeom, K. W., Ahmad, I. N. 2024; 45 (3): e170-e176

    Abstract

    To assess the utility of diffusion tensor imaging of the auditory pathway in children with sensorineural hearing loss (SNHL).Retrospective cohort study.A single academic tertiary children's hospital.Sixteen pediatric patients with bilateral SNHL of at least moderate severity in the poorer ear (eight male; mean age, 5.3 ± 4.9 yrs). Controls consisted of age- and sex-matched children with normal hearing who were imaged for nonotologic, non-neurologic medical concerns and found to have normal magnetic resonance imaging (MRI).Three Tesla MRI scanners were used for diffusion tensor imaging.Quantitative diffusion tensor metrics were extracted from the superior olivary nucleus (SON), inferior colliculus (IC), and ipsilateral fiber tracts between the SON and IC delineated by tractography.We identified differences in fractional anisotropy of the SON between the SNHL cohort and controls (0.377 ± 0.056 vs. 0.422 ± 0.052; p = 0.009), but not in the IC. There were no differences in the mean diffusivity (MD) values in the IC and SON. Among younger children (≤5 yrs), MD was decreased in the SNHL cohort compared with controls in the IC (0.918 ± 0.051 vs. 1.120 ± 0.142; p < 0.001). However, among older children (>5 yrs), there were no differences in MD (1.124 ± 0.198 vs. 0.997 ± 0.103; p = 0.119). There were no differences in MD or fractional anisotropy in the white matter fibers of the IC-SON tract.Our results suggest abnormal neural tracts along the central auditory pathway among children with SNHL. Longitudinal studies should assess the prognostic value of these MRI-based findings for assessing long-term outcomes and determining intervention efficacy.

    View details for DOI 10.1097/MAO.0000000000004129

    View details for PubMedID 38361295

  • The safety and efficacy of radiofrequency ablation in benign pediatric thyroid disease in the US: An initial case series. Laryngoscope investigative otolaryngology Kim, G. S., Seeley, H., Noel, J., Ahmad, I., Meister, K. 2024; 9 (1): e1198

    Abstract

    To evaluate the efficacy and safety of radiofrequency ablation (RFA) for benign nonfunctional thyroid nodules or functional lingual thyroid gland in a pediatric population.Four pediatric patients (four female; mean age 13.50 ± 4.04, range 8-17 years) with either benign thyroid nodules or mildly obstructive lingual thyroid glands were treated with RFA from 2020 to 2021 were evaluated. The inclusion criteria for RFA therapy were (i) age < 18 years; (ii) benign cytopathological results on ultrasound guided fine needle aspiration; (iii) pressure or pain symptoms caused by the thyroid nodules; (iv) dysphagia or obstruction caused by the lingual thyroid tissue; (v) follow up for >6 months with otolaryngology or endocrinology.Two patients had benign non-functioning thyroid nodules and two had mildly obstructive functioning lingual thyroid glands. Mean follow up was 10.75 ± 4.79 months. Each patient underwent one RFA session with no complications. For the patients with thyroid nodules, there was >74% reduction in nodule size at last follow up with improvement in neck swelling and pain. For the patients with lingual thyroid glands, both did not have any other functional thyroid gland identified. Both had visible decrease in size of the gland as visualized transorally with improvement in dysphagia and obstructive symptoms when lying flat.RFA is a safe and effective option for managing benign thyroid nodules and lingual thyroid glands in a pediatric patient population.4.

    View details for DOI 10.1002/lio2.1198

    View details for PubMedID 38362180

    View details for PubMedCentralID PMC10866600

  • Canal wall up versus canal wall down mastoidectomy techniques in the pediatric population with cholesteatoma: A systematic review and meta-analysis of comparative studies. International journal of pediatric otorhinolaryngology Solis-Pazmino, P., Siepmann, T., Scheffler, P., Ali, N. E., Lincango-Naranjo, E., Valdez, T. A., Prokop, L. J., Min-Woo Illigens, B., Ponce, O. J., Ahmad, I. N. 2023; 173: 111658

    Abstract

    The optimal surgical management of cholesteatoma remains controversial. Within pediatric otolaryngology, one of the most vital points of contention is the selection of canal wall-up (CWU) versus canal wall-down (CWD) procedures. Pediatric cholesteatoma has high rates of recurrence (16%-54%). In adults, there is evidence that the selection of surgical techniques affects recurrence rates. This has not been shown in children.1. To systematically review the literature on recurrent and residual cholesteatoma after CWU and CWD in children and perform a meta-analysis of the data. 2. To assess the rates of recurrent and residual cholesteatoma between CWU and CWD techniques in pediatric patients. 3. To assess hearing outcomes by evaluating postoperative differences in the air-bone gap (ABG) between CWU and CWD techniques.A systematic search of PubMed, Embase, Scopus, and Cochrane Collaboration was performed from inception to May 1st, 2020, to identify studies that compared CWU and CWD procedures for acquired cholesteatoma in children.Search records were screened in duplicate by four reviewers. Inclusion criteria consisted of comparative randomized clinical trials and observational studies assessing outcomes of CWU and CWD techniques in the pediatric population. Studies involving patients with congenital cholesteatoma were excluded.Four reviewers working independently and in duplicate systematically reviewed and extracted study data. Dichotomous variables were analyzed as risk ratios (RR), while continuous variables were compared using weighted mean differences (MD). The risk of bias was assessed using the CLARITY Scale.The outcomes were recurrence, residual disease, air-bone gap (ABG), and air conductive (AC) thresholds.After screening 1036 publications, 17 retrospective cohort studies were selected. 1333 children were included; the overall mean age was ten years (SD 7.9), and the overall mean follow-up time was 5.9 years (SD 6.6). CWU and CWD techniques were performed in 60% (796) and 40% (537) cases. We did not find differences in cholesteatoma recurrence (RR: 1.50, 95% CI 0.94; 2.40; n = 544; I2 0%; Tau [2]: 0.00), or rates of residual cholesteatoma (RR 1.51, 95% CI 0.96; 2.38, n = 506; I2: 0%; Tau [2]: 0.00) in patients who underwent CWU and CWD mastoidectomy. The mean air-bone gap was lower with CWU than CWD (mean difference: 7.60, 95% CI -10.65; -4.54; n = 242; I2: 71%; Tau [2]: 5.98).and relevance: We show similar rates of recurrence and residual disease after either CWU or CWD tympanoplasty. Our results challenge the fundamental principle of CWD surgery as a standard technique, as there is no difference in rates of recurrence and residual disease in CWU and CWD. Moreover, audiometric results support CWU with improved hearing outcomes.PROSPERO identifier: CRD42020184029.

    View details for DOI 10.1016/j.ijporl.2023.111658

    View details for PubMedID 37666040

  • Imaging guidance for cholesteatoma surgery using tissue autofluorescence. Journal of biomedical optics Yang, S., Farrell, J., Ye, S., Ahmad, I., Valdez, T. A. 2023; 28 (6): 066003

    Abstract

    Cholesteatoma is an expansile destructive lesion of the middle ear and mastoid, which can result in significant complications by eroding adjacent bony structures. Currently, there is an inability to accurately distinguish cholesteatoma tissue margins from middle ear mucosa tissue, causing a high recidivism rate. Accurately differentiating cholesteatoma and mucosa will enable a more complete removal of the tissue.Develop an imaging system to enhance the visibility of cholesteatoma tissue and margins during surgery.Cholesteatoma and mucosa tissue samples were excised from the inner ear of patients and illuminated with 405, 450, and 520 nm narrowband lights. Measurements were made with a spectroradiometer equipped with a series of different longpass filters. Images were obtained using a red-green-blue (RGB) digital camera equipped with a long pass filter to block reflected light.Cholesteatoma tissue fluoresced under 405 and 450 nm illumination. Middle ear mucosa tissue did not fluoresce under the same illumination and measurement conditions. All measurements were negligible under 520 nm illumination conditions. All spectroradiometric measurements of cholesteatoma tissue fluorescence can be predicted by a linear combination of emissions from keratin and flavin adenine dinucleotide. We built a prototype of a fluorescence imaging system using a 495 nm longpass filter in combination with an RGB camera. The system was used to capture calibrated digital camera images of cholesteatoma and mucosa tissue samples. The results confirm that cholesteatoma emits light when it is illuminated with 405 and 450 nm, whereas mucosa tissue does not.We prototyped an imaging system that is capable of measuring cholesteatoma tissue autofluorescence.

    View details for DOI 10.1117/1.JBO.28.6.066003

    View details for PubMedID 37334207

    View details for PubMedCentralID PMC10275381

  • Prevalence of Cochlear Nerve Deficiency and Hearing Device Use in Children With Single-Sided Deafness OTOLARYNGOLOGY-HEAD AND NECK SURGERY Ward, K. M., Coughran, A. J., Lee, M., Fitzgerald, M. B., Cheng, A. G., Chang, K. W., Ahmad, I. N. 2023

    View details for DOI 10.1002/ohn.255

    View details for Web of Science ID 000928877200001

  • Prevalence of Cochlear Nerve Deficiency and Hearing Device Use in Children With Single-Sided Deafness. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Ward, K. M., Coughran, A. J., Lee, M., Fitzgerald, M. B., Cheng, A. G., Chang, K. W., Ahmad, I. N. 2023

    Abstract

    This study aimed to assess the prevalence of cochlear nerve deficiency (CND) in a cohort of pediatric patients with single-sided deafness (SSD). A secondary objective was to investigate trends in intervention and hearing device use in these children.Case series with chart review.Pediatric tertiary care center.Children ages 0 to 21 years with SSD (N = 190) who underwent computerized tomography (CT) and/or magnetic resonance imaging (MRI) were included. Diagnostic criteria for SSD included unilateral severe-to-profound sensorineural hearing loss with normal hearing sensitivity in the contralateral ear. Diagnostic criteria for CND included neuroradiologist report of an "aplastic or hypoplastic nerve" on MRI or a "stenotic cochlear aperture" on CT.The prevalence of CND was 42% for children with CT only, 76% for children with MRI only, and 63% for children with both MRI and CT. Of the children with MRI and CT, there was a 90% concordance across imaging modalities. About 36% of children with SSD had hearing devices that routed sound to the normal hearing ear (ie, bone conduction hearing device/contralateral routing of signal), while only 3% received a cochlear implant. Approximately 40% did not have a hearing device. Hearing device wear time averaged 2.9 hours per day and did not differ based on cochlear nerve status.There is a high prevalence of CND in children with SSD. Cochlear nerve status should be confirmed via MRI in children with SSD. The limited implementation and use of hearing devices observed for children with SSD reinforce the need for increased support for early and continuous intervention.

    View details for DOI 10.1002/ohn.255

    View details for PubMedID 36939463

  • Updates in Eustachian Tube Dysfunction. Otolaryngologic clinics of North America Maddineni, S., Ahmad, I. 2022; 55 (6): 1151-1164

    Abstract

    Eustachian tube dysfunction (ETD) is a common middle ear disorder in children that can have a significant impact on the quality of life. This review aims to provide an updated understanding of ETD and its clinical management. We will discuss the pathophysiology and diagnosis of ETD, as well as the medical and surgical treatment of ETD. We will also review studies of both adults and children with ETD, although special attention will be paid to children with ETD.

    View details for DOI 10.1016/j.otc.2022.07.010

    View details for PubMedID 36371132

  • Artificial intelligence and tele-otoscopy: A window into the future of pediatric otology. International journal of pediatric otorhinolaryngology Ezzibdeh, R., Munjal, T., Ahmad, I., Valdez, T. A. 2022; 160: 111229

    Abstract

    Telehealth in otolaryngology is gaining popularity as a potential tool for increased access for rural populations, decreased specialist wait times, and overall savings to the healthcare system. The adoption of telehealth has been dramatically increased by the COVID-19 pandemic limiting patients' physical access to hospitals and clinics. One of the key challenges to telehealth in general otolaryngology and otology specifically is the limited physical examination possible on the ear canal and middle ear. This is compounded in pediatric populations who commonly present with middle ear pathologies which can be challenging to diagnose even in the clinic. To address this need, various otoscopes have been designed to allow patients, their parents, or primary care providers to image the tympanic membrane and middle ear, and send data to otolaryngologists for review. Furthermore, the ability of these devices to capture images in digital format has opened the possibility of using artificial intelligence for quick and reliable diagnostic workup. In this manuscript, we provide a concise review of the literature regarding the efficacy of remote otoscopy, as well as recent efforts on the use of artificial intelligence in aiding otologic diagnoses.

    View details for DOI 10.1016/j.ijporl.2022.111229

    View details for PubMedID 35816971

  • Infectious Complications Following Cochlear Implant: Risk Factors, Natural History, and Management Patterns. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Moon, P. K., Qian, Z. J., Ahmad, I. N., Stankovic, K. M., Chang, K. W., Cheng, A. G. 2022: 1945998221082530

    Abstract

    OBJECTIVE: To describe the natural history, detail the treatment patterns, and identify the risk factors for cochlear implant (CI) infections in a large US cohort.STUDY DESIGN: Retrospective study based on insurance claims.SETTING: Optum Data Mart database: 6101 patients who received CIs from 2003 to 2019.METHODS: Infections, treatments patterns, and timelines were described. A multivariable logistic regression model was used to assess the association between postoperative oral antibiotics and CI infection.RESULTS: The cohort includes 4736 (77.6%) adults and 1365 (22.4%) children. Between adult and pediatric patients, rates of CI infection (5.1% vs 4.5%, P = .18) and explantation (1.2% vs 0.8%, P = .11) were not significantly different. Infections typically occurred within 5 months of surgery. Children were diagnosed with CI infection earlier than adults (median difference, -1.5 months; P = .001). Postoperative oral antibiotic supply was not associated with lower risk of CI infection in either children or adults. However, among adults, otitis media was associated with higher odds of CI infection (odds ratio, 1.41; P < .001), while higher income was associated with lower odds of CI infection (odds ratio, 0.71; P = .03).CONCLUSIONS: Postoperative oral antibiotics were not associated with lower risk of infection or interventions. Otitis media episodes and lower income were associated with increased risk of infection among adults as well as intervention overall. Infection typically presented within the first 6 months after surgery, with children presenting earlier than adults. Overall, our findings serve as a resource for providers to consider in their care of patients with CIs.

    View details for DOI 10.1177/01945998221082530

    View details for PubMedID 35192408

  • MRI Correlates of Ototoxicity in the Auditory Pathway in Children Treated for Medulloblastoma. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Moon, P., Theruvath, J., Chang, J., Song, Y., Shpanskaya, K., Maleki, M., Cheng, A. G., Ahmad, I. N., Yeom, K. W. 2021

    Abstract

    OBJECTIVE: To assess diffusion and perfusion changes of the auditory pathway in pediatric medulloblastoma patients exposed to ototoxic therapies.STUDY DESIGN: Retrospective cohort study.SETTING: A single academic tertiary children's hospital.PATIENTS: Twenty pediatric medulloblastoma patients (13 men; mean age 12.0 ± 4.8 yr) treated with platinum-based chemotherapy with or without radiation and 18 age-and-sex matched controls were included. Ototoxicity scores were determined using Chang Ototoxicity Grading Scale.INTERVENTIONS: Three Tesla magnetic resonance was used for diffusion tensor and arterial spin labeling perfusion imaging.MAIN OUTCOME MEASURES: Quantitative diffusion tensor metrics were extracted from the Heschl's gyrus, auditory radiation, and inferior colliculus. Arterial spin labeling perfusion of the Heschl's gyrus was also examined.RESULTS: Nine patients had clinically significant hearing loss, or Chang grades more than or equal to 2a; 11 patients had mild/no hearing loss, or Chang grades less than 2a. The clinically significant hearing loss group showed reduced mean diffusivity in the Heschl's gyrus (p = 0.018) and auditory radiation (p = 0.037), and decreased perfusion in the Heschl's gyrus (p = 0.001). Mild/no hearing loss group showed reduced mean diffusivity (p = 0.036) in Heschl's gyrus only, with a decrease in perfusion (p = 0.008). There were no differences between groups in the inferior colliculus. There was no difference in fractional anisotropy between patients exposed to ototoxic therapies and controls.CONCLUSIONS: Patients exposed to ototoxic therapies demonstrated microstructural and physiological alteration of the auditory pathway. The present study shows proof-of-concept use of diffusion tensor imaging to gauge ototoxicity along the auditory pathway. Future larger cohort studies are needed to assess significance of changes in diffusion tensor imaging longitudinally, and the relationship between these changes and hearing loss severity and longitudinal changes of the developing auditory white matter.

    View details for DOI 10.1097/MAO.0000000000003336

    View details for PubMedID 34739428

  • Trends and Healthcare Use Following Different Cholesteatoma Surgery Types in a National Cohort, 2003-2019. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Qian, Z. J., Tran, E. D., Alyono, J. C., Cheng, A. G., Ahmad, I. N., Chang, K. W. 2021

    Abstract

    OBJECTIVE: To describe national trends in cholesteatoma management.STUDY DESIGN AND SETTING: Retrospective analysis Optum Clinformatics Database from 2003 to 2019.PATIENTS: 16,179 unique adult and pediatric patients who received cholesteatoma surgery.INTERVENTIONS AND MAIN OUTCOME MEASURES: Patients were categorized into three groups by initial surgical modality: canal wall down (CWD), canal wall up (CWU), and tympanoplasty without mastoidectomy (TnoM). Three major comparisons between groups were performed: 1) temporal trends, 2) clinical and sociodemographic determinants, and 3) healthcare use in terms of total costs and incidence of postoperative imaging and subsequent surgery.RESULTS: Overall, 23.2% received initial CWD surgery, 44.3% CWU, and 32.5% TnoM. 1) The incidence of initial CWD surgery decreased (odds ratios [OR] = 0.98, 95% confidence intervals [CI] [0.97,0.99]), while CWU increased (OR = 1.02, 95% CI [1.01,1.03]), and TnoM remained stable over the study period (OR = 0.99, 95% CI [0.98,1.00]). 2) Relative to CWU, TnoM surgery was less likely in adults, patients with prior complications, and non-White patients, while being more likely in patients with higher household income. CWD was more likely than CWU in adults, patients with prior complications, and non-White patients, while income had no effect. 3) Postoperative costs for CWU and CWD were similar. In 2 years following initial surgery, postoperative imaging and/or subsequent surgery was performed in 45.48% of CWD, 57.42% of CWU, and 41.62% of TnoM patients.CONCLUSIONS: Incidence of initial CWD surgery decreased and social disparities in cholesteatoma management were observed. Postoperative imaging or second-look surgery were performed in less than 60% of patients with initial CWU surgery and over 40% of patients with initial CWD.

    View details for DOI 10.1097/MAO.0000000000003284

    View details for PubMedID 34310551

  • Shortwave infrared otoscopy for diagnosis of middle ear effusions: a machine-learning-based approach. Scientific reports Kashani, R. G., Mlynczak, M. C., Zarabanda, D., Solis-Pazmino, P., Huland, D. M., Ahmad, I. N., Singh, S. P., Valdez, T. A. 2021; 11 (1): 12509

    Abstract

    Otitis media, a common disease marked by the presence of fluid within the middle ear space, imparts a significant global health and economic burden. Identifying an effusion through the tympanic membrane is critical to diagnostic success but remains challenging due to the inherent limitations of visible light otoscopy and user interpretation. Here we describe a powerful diagnostic approach to otitis media utilizing advancements in otoscopy and machine learning. We developed an otoscope that visualizes middle ear structures and fluid in the shortwave infrared region, holding several advantages over traditional approaches. Images were captured in vivo and then processed by a novel machine learning based algorithm. The model predicts the presence of effusions with greater accuracy than current techniques, offering specificity and sensitivity over 90%. This platform has the potential to reduce costs and resources associated with otitis media, especially as improvements are made in shortwave imaging and machine learning.

    View details for DOI 10.1038/s41598-021-91736-9

    View details for PubMedID 34131163

  • The risk of ergonomic injury across surgical specialties. PloS one Aaron, K. A., Vaughan, J., Gupta, R., Ali, N., Beth, A. H., Moore, J. M., Ma, Y., Ahmad, I., Jackler, R. K., Vaisbuch, Y. 2021; 16 (2): e0244868

    Abstract

    Lack of ergonomic training and poor ergonomic habits during the operation leads to musculoskeletal pain and affects the surgeon's life outside of work. The objective of the study was to evaluate the severity of ergonomic hazards in the surgical profession across a wide range of surgical subspecialties. We conducted intraoperative observations using Rapid Entire Body Assessment (REBA) score system to identify ergonomic hazards. Additionally, each of the ten surgical subspecialty departments were sent an optional 14 question survey which evaluated ergonomic practice, environmental infrastructure, and prior ergonomic training or education. A total of 91 surgeons received intraoperative observation and were evaluated on the REBA scale with a minimum score of 0 (low ergonomic risk <3) and a maximum score of 10 (high ergonomic risk 8-10). And a total of 389 surgeons received the survey and 167 (43%) surgeons responded. Of the respondents, 69.7% reported suffering from musculoskeletal pain. Furthermore, 54.9% of the surgeons reported suffering from the highest level of pain when standing during surgery, while only 14.4% experienced pain when sitting. Importantly, 47.7% stated the pain impacted their work, while 59.5% reported pain affecting quality of life outside of work. Only 23.8% of surgeons had any prior ergonomic education. Both our subjective and objective data suggest that pain and disability induced by poor ergonomics are widespread among the surgical community and confirm that surgeons rarely receive ergonomic training. Intraoperative observational findings identified that the majority of observed surgeons displayed poor posture, particularly a poor cervical angle and use of ergonomic setups, both of which increase ergonomic risk hazards. This data supports the need for a comprehensive ergonomic interventional program for the surgical team and offers potential targets for future intervention.

    View details for DOI 10.1371/journal.pone.0244868

    View details for PubMedID 33561117

  • Modeling human adaptive immune responses with tonsil organoids. Nature medicine Wagar, L. E., Salahudeen, A. n., Constantz, C. M., Wendel, B. S., Lyons, M. M., Mallajosyula, V. n., Jatt, L. P., Adamska, J. Z., Blum, L. K., Gupta, N. n., Jackson, K. J., Yang, F. n., Röltgen, K. n., Roskin, K. M., Blaine, K. M., Meister, K. D., Ahmad, I. N., Cortese, M. n., Dora, E. G., Tucker, S. N., Sperling, A. I., Jain, A. n., Davies, D. H., Felgner, P. L., Hammer, G. B., Kim, P. S., Robinson, W. H., Boyd, S. D., Kuo, C. J., Davis, M. M. 2021

    Abstract

    Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.

    View details for DOI 10.1038/s41591-020-01145-0

    View details for PubMedID 33432170

  • Use of Diagnostic Testing and Intervention for Sensorineural Hearing Loss in US Children From 2008 to 2018. JAMA otolaryngology-- head & neck surgery Qian, Z. J., Chang, K. W., Ahmad, I. N., Tribble, M. S., Cheng, A. G. 2020

    Abstract

    Importance: Early detection and intervention of pediatric hearing loss is critical for language development and academic achievement. However, variations in the diagnostic workup and management of pediatric sensorineural hearing loss (SNHL) exist.Objective: To identify patient and clinician factors that are associated with variation in practice on a national level.Design, Setting, and Participants: This cross-sectional study used the Optum claims database to identify 53 711 unique children with SNHL between January 1, 2008, and December 31, 2018.Main Outcomes and Measures: National use rates and mean costs for diagnostic modalities (electrocardiogram, cytomegalovirus testing, magnetic resonance imaging, computed tomography, and genetic testing) and interventions (speech-language pathology, billed hearing aid services, and cochlear implant surgery) were reported. The associations of age, sex, SNHL laterality, clinician type, race/ethnicity, and household income with diagnostic workup and intervention use were measured in multivariable analyses.Results: Of 53 711 patients, 23 735 (44.2%) were girls, 2934 (5.5%) were Asian, 3797 (7.1%) were Black, 5626 (10.5%) were Hispanic, 33 441 (62.3%) were White, and the mean (SD) age was 7.3 (5.3) years. Of all patients, 32 200 (60.0%) were seen by general otolaryngologists, while 7573 (14.10%) were seen by pediatric otolaryngologists. Diagnostic workup was received by 14 647 patients (27.3%), while 13 482 (25.1%) received intervention. Use of genetic testing increased (odds ratio, 1.22 per year; 95% CI, 1.20-1.24), whereas use of computed tomography decreased (odds ratio, 0.93 per year; 95% CI, 0.92-0.94) during the study period. After adjusting for relevant covariables, children who were seen by pediatric otolaryngologists and geneticists had the highest odds of receiving workup and intervention. Additionally, racial/ethnic and economic disparities were observed in the use of most modalities of diagnostic workup and intervention for pediatric SNHL.Conclusions and Relevance: This cross-sectional study identified factors associated with disparities in the diagnostic workup and intervention of pediatric SNHL, thus highlighting the need for increased education and standardization in the management of this common sensory disorder.

    View details for DOI 10.1001/jamaoto.2020.5030

    View details for PubMedID 33377936

  • Direct laryngoscopy assisted fiberoptic intubation: A novel technique for the pediatric airway. International journal of pediatric otorhinolaryngology Ahmad, I. N., Ali, N., Liming, B. J. 2020; 137: 110232

    Abstract

    OBJECTIVE: To introduce a novel intubation technique for difficult pediatric airways.METHODS: This two-provider technique requires a direct laryngoscope and a flexible fiberoptic laryngoscope. One provider performs direct laryngoscopy which allows for introduction of the flexible laryngoscope. The second provider inserts the flexible laryngoscope with the endotracheal tube loaded, through the oropharynx in to the subglottis.RESULTS: We report three pediatric patients that were initially unable to be intubated by conventional methods. We were ultimately able to successfully intubate these patients with difficult airways using our novel technique.CONCLUSIONS: We found that this technique of direct laryngoscopy assisted flexible fiberoptic intubation is a useful adjunct in select pediatric difficult airway patients.

    View details for DOI 10.1016/j.ijporl.2020.110232

    View details for PubMedID 32896347

  • Cerebral volume and diffusion MRI changes in children with sensorineural hearing loss. NeuroImage. Clinical Moon, P. K., Qian, J. Z., McKenna, E. n., Xi, K. n., Rowe, N. C., Ng, N. N., Zheng, J. n., Tam, L. T., MacEachern, S. J., Ahmad, I. n., Cheng, A. G., Forkert, N. D., Yeom, K. W. 2020; 27: 102328

    Abstract

    Sensorineural hearing loss (SNHL) is the most prevalent congenital sensory deficit in children. Information regarding underlying brain microstructure could offer insight into neural development in deaf children and potentially guide therapies that optimize language development. We sought to quantitatively evaluate MRI-based cerebral volume and gray matter microstructure children with SNHL.We conducted a retrospective study of children with SNHL who obtained brain MRI at 3 T. The study cohort comprised 63 children with congenital SNHL without known focal brain lesion or structural abnormality (33 males; mean age 5.3 years; age range 1 to 11.8 years) and 64 age-matched controls without neurological, developmental, or MRI-based brain macrostructure abnormality. An atlas-based analysis was used to extract quantitative volume and median diffusivity (ADC) in the following brain regions: cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, brain stem, and cerebral white matter. SNHL patients were further stratified by severity scores and hearing loss etiology.Children with SNHL showed higher median ADC of the cortex (p = .019), thalamus (p < .001), caudate (p = .005), and brainstem (p = .003) and smaller brainstem volumes (p = .007) compared to controls. Patients with profound bilateral SNHL did not show any significant differences compared to patients with milder bilateral SNHL, but both cohorts independently had smaller brainstem volumes compared to controls. Children with unilateral SNHL showed greater amygdala volumes compared to controls (p = .021), but no differences were found comparing unilateral SNHL to bilateral SNHL. Based on etiology for SNHL, patients with Pendrin mutations showed higher ADC values in the brainstem (p = .029, respectively); patients with Connexin 26 showed higher ADC values in both the thalamus (p < .001) and brainstem (p < .001) compared to controls.SNHL patients showed significant differences in diffusion and volume in brain subregions, with region-specific findings for patients with Connexin 26 and Pendrin mutations. Future longitudinal studies could examine macro- and microstructure changes in children with SNHL over development and potential predictive role for MRI after interventions including cochlear implant outcome.

    View details for DOI 10.1016/j.nicl.2020.102328

    View details for PubMedID 32622314

  • Montelukast and Nasal Corticosteroids to Treat Pediatric Obstructive Sleep Apnea: A Systematic Review and Meta-analysis. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Liming, B. J., Ryan, M., Mack, D., Ahmad, I., Camacho, M. 2018: 194599818815683

    Abstract

    OBJECTIVE: To systematically review the literature on anti-inflammatory medications for treating pediatric obstructive sleep apnea and perform meta-analysis of the available data.DATA SOURCES: PubMed/MEDLINE and 4 additional databases.REVIEW METHODS: Three authors independently and systematically searched through June 28, 2018, for studies that assessed anti-inflammatory therapy for treatment of pediatric obstructive sleep apnea (OSA). Data were compiled and analyzed using Review Manager 5.3 (Nordic Cochrane Centre).RESULTS: After screening 135 studies, 32 were selected for review with 6 meeting inclusion criteria. In total, 668 patients aged 2 to 5 years met inclusion criteria for meta-analysis. Of these, 5 studies (166 children) that evaluated montelukast alone as treatment for pediatric OSA found a 55% improvement in the apnea-hypopnea index (AHI) (mean [SD] 6.2 [3.1] events/h pretreatment and 2.8 [2.7] events/h posttreatment; mean difference [MD] of -2.7 events/h; 95% confidence interval [CI], -5.6 to 0.3) with improvement in lowest oxygen saturation (LSAT) from 89.5 (6.9) to 92.1 (3.6) (MD, 2.2; 95% CI, 0.5-4.0). Two studies (502 children) observing the effects of montelukast with intranasal corticosteroids on pediatric OSA found a 70% improvement in AHI (4.7 [2.1] events/h pretreatment and 1.4 [1.0] events/h posttreatment; MD of -4.2 events/h; 95% CI, -6.3 to -2.0), with an improvement in LSAT from 87.8 (3.1) to 92.6 (2.2) (MD, 4.8; 95% CI, 4.5-5.1).CONCLUSIONS: Treatment with montelukast and intranasal steroids or montelukast alone is potentially beneficial for short-term management of mild pediatric OSA.

    View details for PubMedID 30513051

  • Nf2 Mutation in Schwann Cells Delays Functional Neural Recovery Following Injury. Neuroscience Truong, K., Ahmad, I., Jason Clark, J., Seline, A., Bertroche, T., Mostaert, B., Van Daele, D. J., Hansen, M. R. 2018; 374: 205-213

    Abstract

    Merlin is the protein product of the NF2 tumor suppressor gene. Germline NF2 mutation leads to neurofibromatosis type 2 (NF2), characterized by multiple intracranial and spinal schwannomas. Patients with NF2 also frequently develop peripheral neuropathies. While the role of merlin in SC neoplasia is well established, its role in SC homeostasis is less defined. Here we explore the role of merlin in SC responses to nerve injury and their ability to support axon regeneration. We performed sciatic nerve crush in wild-type (WT) and in P0SchΔ39-121 transgenic mice that express a dominant negative Nf2 isoform in SCs. Recovery of nerve function was assessed by measuring mean contact paw area on a pressure pad 7, 21, 60, and 90 days following nerve injury and by nerve conduction assays at 90 days following injury. After 90 days, the nerves were harvested and axon regeneration was quantified stereologically. Myelin ultrastructure was analyzed by electron microscopy. Functional studies showed delayed nerve regeneration in Nf2 mutant mice compared to the WT mice. Delayed neural recovery correlated with a reduced density of regenerated axons and increased endoneurial space in mutants compared to WT mice. Nevertheless, functional and nerve conduction measures ultimately recovered to similar levels in WT and Nf2 mutant mice, while there was a small (∼17%) reduction in the percent of regenerated axons in the Nf2 mutant mice. The data suggest that merlin function in SCs regulates neural ultrastructure and facilitates neural regeneration, in addition to its role in SC neoplasia.

    View details for DOI 10.1016/j.neuroscience.2018.01.054

    View details for PubMedID 29408605

    View details for PubMedCentralID PMC5841622

  • Ectopic Thymic Cyst of the Subglottis: Considerations for Diagnosis and Management ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Ahmad, I., Kirby, P., Liming, B. 2018; 127 (3): 200–204

    Abstract

    To share the diagnostic and management challenges created by an extremely rare airway lesion-the subglottic ectopic thymic cyst.Case report and literature review.We review the presentation, management, and clinical course of an infant who presented with a subglottic mass that was histologically confirmed as a thymic cyst. A brief literature review supplements the case presentation Results: We present the third described case of an ectopic thymic cyst presenting as a subglottic mass. The differential diagnosis of subglottic masses in neonates consists primarily of subglottic hemangioma and mucous retention cysts. Otolaryngologists must be prepared for unexpected findings when dealing with critical airways. We compare the presentation and management of our patient with the 2 previously described cases. We propose an embryologic theory for the origin of these rare lesions.An ectopic thymic cyst is a rare and unexpected cause of neonatal stridor. Management of pediatric airway lesions must allow for unexpected findings at the time of diagnostic and therapeutic endoscopy. The appropriate management of subglottic thymic cysts is poorly defined, but close surveillance for recurrence is mandatory.

    View details for PubMedID 29291277

  • Merlin status regulates p75(NTR) expression and apoptotic signaling in Schwann cells following nerve injury. Neurobiology of disease Ahmad, I., Fernando, A., Gurgel, R., Jason Clark, J., Xu, L., Hansen, M. R. 2015; 82: 114-122

    Abstract

    After nerve injury, Schwann cells (SCs) dedifferentiate, proliferate, and support axon regrowth. If axons fail to regenerate, denervated SCs eventually undergo apoptosis due, in part, to increased expression of the low-affinity neurotrophin receptor, p75(NTR). Merlin is the protein product of the NF2 tumor suppressor gene implicated in SC tumorigenesis. Here we explore the contribution of merlin to SC responses to nerve injury. We find that merlin becomes phosphorylated (growth permissive) in SCs following acute axotomy and following gradual neural degeneration in a deafness model, temporally correlated with increased p75(NTR) expression. p75(NTR) levels are elevated in P0SchΔ39-121 transgenic mice that harbor an Nf2 mutation in SCs relative to wild-type mice before axotomy and remain elevated for a longer period of time following injury. Replacement of wild-type, but not phospho-mimetic (S518D), merlin isoforms suppresses p75(NTR) expression in primary human schwannoma cultures which otherwise lack functional merlin. Despite elevated levels of p75(NTR), SC apoptosis following axotomy is blunted in P0SchΔ39-121 mice relative to wild-type mice suggesting that loss of functional merlin contributes to SC resistance to apoptosis. Further, cultured SCs from mice with a tamoxifen-inducible knock-out of Nf2 confirm that SCs lacking functional merlin are less sensitive to p75(NTR)-mediated cell death. Taken together these results point to a model whereby loss of axonal contact following nerve injury results in merlin phosphorylation leading to increased p75(NTR) expression. Further, they demonstrate that merlin facilitates p75(NTR)-mediated apoptosis in SCs helping to explain how neoplastic SCs that lack functional merlin survive long-term in the absence of axonal contact.

    View details for DOI 10.1016/j.nbd.2015.05.021

    View details for PubMedID 26057084

    View details for PubMedCentralID PMC4641051

  • The Need for a Leadership Curriculum for Residents. Journal of graduate medical education Jardine, D., Correa, R., Schultz, H., Nobis, A., Lanser, B. J., Ahmad, I., Crowder, A., Kim, M. B., Hinds, B. 2015; 7 (2): 307-9

    View details for DOI 10.4300/JGME-07-02-31

    View details for PubMedID 26221472

    View details for PubMedCentralID PMC4512827

  • p75NTR is highly expressed in vestibular schwannomas and promotes cell survival by activating nuclear transcription factor κB. Glia Ahmad, I., Yue, W. Y., Fernando, A., Clark, J. J., Woodson, E. A., Hansen, M. R. 2014; 62 (10): 1699-712

    Abstract

    Vestibular schwannomas (VSs) arise from Schwann cells (SCs) and result from the loss of function of merlin, the protein product of the NF2 tumor suppressor gene. In contrast to non-neoplastic SCs, VS cells survive long-term in the absence of axons. We find that p75(NTR) is overexpressed in VSs compared with normal nerves, both at the transcript and protein level, similar to the response of non-neoplastic SCs following axotomy. Despite elevated p75(NTR) expression, VS cells are resistant to apoptosis due to treatment with proNGF, a high affinity ligand for p75(NTR) . Furthermore, treatment with proNGF protects VS cells from apoptosis due to c-Jun N-terminal kinase (JNK) inhibition indicating that p75(NTR) promotes VS cell survival. Treatment of VS cells with proNGF activated NF-κB while inhibition of JNK with SP600125 or siRNA-mediated knockdown reduced NF-κB activity. Significantly, proNGF also activated NF-κB in cultures treated with JNK inhibitors. Thus, JNK activity appears to be required for basal levels of NF-κB activity but not for proNGF-induced NF-κB activity. To confirm that the increase in NF-κB activity contributes to the prosurvival effect of proNGF, we infected VS cultures with Ad.IκB.SerS32/36A virus, which inhibits NF-κB activation. Compared with control virus, Ad.IκB.SerS32/36A significantly increased apoptosis including in VS cells treated with proNGF. Thus, in contrast to non-neoplastic SCs, p75(NTR) signaling provides a prosurvival response in VS cells by activating NF-κB independent of JNK. Such differences may contribute to the ability of VS cells to survive long-term in the absence of axons.

    View details for DOI 10.1002/glia.22709

    View details for PubMedID 24976126

    View details for PubMedCentralID PMC4150679

  • Abnormal transsulfuration and glutathione metabolism in the micropig model of alcoholic liver disease. Alcoholism, clinical and experimental research Villanueva, J. A., Esfandiari, F., Wong, D. H., Ahmad, I., Melnyk, S., James, S. J., Halsted, C. H. 2006; 30 (7): 1262-70

    Abstract

    Alcoholic liver disease is associated with abnormalities of methionine metabolic enzymes that may contribute to glutathione depletion. Previously, we found that feeding micropigs a combination of ethanol with a folate-deficient diet resulted in the greatest decreases in S-adenosylmethionine and glutathione and increases in liver S-adenosylhomocysteine and oxidized disulfide glutathione.To study the mechanisms of glutathione depletion, we analyzed the transcripts and activities of enzymes involved in its synthesis and metabolism in liver and plasma specimens that were available from the same micropigs that receive folate-sufficient or folate-depleted diets with or without 40% of energy as ethanol for 14 weeks.Ethanol feeding, folate deficiency, or their combination decreased liver and plasma glutathione and the activities of hepatic copper-zinc superoxide dismutase and glutathione peroxidase and increased the activity of manganese superoxide dismutase and glutathione reductase. Hepatic levels of cysteine and taurine were unchanged while plasma cysteine was increased in the combined diet group. Cystathionine beta-synthase transcripts and activity were unaffected by ethanol feeding, while the activities of other transsulfuration enzymes involved in glutathione synthesis were increased. Glutathione transferase transcripts were increased 4-fold and its mean activity was increased by 34% in the combined ethanol and folate-deficient diet group, similar in magnitude to the observed 36% reduction in hepatic glutathione.Chronic ethanol feeding and folate deficiency acted individually or synergistically to affect methionine metabolism in the micropig by depleting glutathione pools and altering transcript expressions and activities of enzymes involved in its synthesis, utilization, and regeneration. The data suggest that the observed decrease in hepatic glutathione during ethanol feeding reflects its increased utilization to meet increased antioxidant demands, rather than reduction in its synthesis.

    View details for DOI 10.1111/j.1530-0277.2006.00147.x

    View details for PubMedID 16792574