ABSTRACT
The specialty of otolaryngology and head and neck surgery involves various subspecialties, encompassing clinical conditions ranging from medical to surgical issues in infections, noninfectious benign conditions and various benign and malignant tumors. Drug repurposing has proven to be significant in multiple fields and is still investigational in many promising possible solutions to different clinical challenges in this specialty. We discuss some classes of drugs that have been successfully repurposed for ENT pathologies. We also discuss the novel research goals that are being pursued in our department in the context of drug repurposing for airway infectious diseases including COVID-10 and mucormycosis. There has been a silent and underappreciated rise in drug-resistant invasive fungal infections (IFIs). Emerging Mucorales are difficult to diagnose and tolerant to many of the frontline antifungal therapies. There is an urgent need to combat these emerging pathogens and investigate the molecular mechanisms underlying their potentiated virulence traits to identify potential therapeutic targets susceptible to anti-fungal compounds. The drug development process for IFIs remains largely expensive, and is inherently risky. These challenges declare an urgent need for discovery of new antifungal drugs and encourage drug repurposing as alternative approach to fungal control. The understanding of molecular underpinnings behind fungi and human host continue to grow, however, further research endeavors are underway to fully explore the fungal pathogenesis, (including the role of iron) to gather new insights to achieve improved therapeutics. Above all, creative screening tools and out-of-the-box ideas aimed at increasing the possibility of identifying potential first-in-class antifungals are highly encouraged. The recently emerging fungal co-infections in the COVID-19 disease patients has revived the interest in the pathophysiology and clinical management of the IFIs, and identification of potential druggable nodes in olfactory niche to inhibit the spread of COVID-19 and associated co-infections by leveraging in vitro-disease models of host-pathogen interaction. We employed our recently established COVID-19 disease model to decipher potential anti-metabolic molecules that can be repurposed as novel bilateral drugs having anti-fungal and host-directed features with extended applicability in diabetes, COVID-19, and mucormycosis with and without COVID-19. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.
ABSTRACT
Interaction with the world around us requires extracting meaningful signals to guide behaviour. The mammalian senses of olfaction, vision, somatosensation, hearing, balance and taste facilitate extraction of sense-specific information. Most sensory organs in the vertebrate head originate from cranial placodes (CPs). CPs are formed embryonically through a series of differentiation steps arising at the boundary between neural and non-neural ectoderm, and they can be divided into anterior, posterior and intermediate groups depending on their place of origin in the developing embryonic head. Anterior CPs include adenohypophyseal, olfactory and lens placodes;intermediate CPs include the trigeminal placode, which gives rise to the sensory neurons of the ophthalmic and maxilla-mandibular divisions of the trigeminal ganglion;posterior CPs are comprised of the otic, lateral line placode and the epibranchial placodes that give rise to the inner ear, lateral line organs (in fish and amphibian) and sensory neurons of the geniculate, petrosal and nodose ganglia, respectively. The complexity of neural plate border specification in vitro poses a major limitation to gain deeper mechanistic insights into the developmental cues driving efficient placodal differentiation;hence generation and establishment of in vitro cellular models with improved cranial placode differentiation are challenging. Our group is interested in the establishment of cranial/sensory placodes in vitro using novel cellular stress stem cell reprogramming models with translational implications in sensorineural hearing loss regeneration and modelling COVID-19-associated anosmia. We are primarily interested in building the otic placodes that can form viable otic vesicles in vitro, which can be further directed to generate cochlear/vestibular systems of inner ear and the sensory neurons of its associated vestibulocochlear ganglion. Given the copious involvement of serine proteases in COVID-19 pathogenesis, we are also encouraged to leverage our proteolytic stress cellular models towards establishment and characterization of novel olfactory epithelial neurospheres housing supporting cells, progenitor cells and sensory neurons for investigating cellular and molecular targets of COVID-19-associated anosmia. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.
ABSTRACT
Background: Long-term postsurgical follow-up in chronic otitis media (COM) is crucial in otologic practice for outcome assessment. Validated questionnaires for the same are robust alternatives when physical visits are not feasible such as the current COVID-19 pandemic and we present our findings of outcome assessment using COM outcome test (COMOT)-15 questionnaire through nonphysical mode. Material(s) and Method(s): A retrospective analysis of a cohort of 112 patients of COM who underwent surgery by the single senior otology surgeon between 2009 and 2019 was done using COMOT 15 questionnaire through telephonic methods to circumvent the need of office visits. Result(s): Fifty out of 112 patients could be contacted and consented for the assessment and their COMOT-15 scores were obtained. The numbers of patients with any otologic symptoms and their need for consultations, except hearing loss were significantly less. One-third of the patients had mild to moderate residual hearing loss and its quality of life impacts, although the same neither was statistically significant nor required increased numbers of consultations. Conclusion(s): Bothering symptoms and the need for a frequent visit to the doctor is significantly less with adequate clearance of disease and mastoid obliteration in cases of canal wall down procedures. The residual mild-to-moderate hearing loss are not significant and manageable with day-to-day activities. Successful outcome of COM surgery needs long-term follow-up and evaluation by all practicing otologic departments and surgeons which can well be done through nonphysical modes in unprecedented situations like the current times. Copyright © 2022 Indian Journal of Otology Published by Wolters Kluwer-Medknow.