Publications by authors named "Bradley J Goldstein"

Article Synopsis
  • Olfactory neuroblastoma (ONB) is a rare cancer type from olfactory nerve cells, and a recent review focuses on its diagnosis and treatment challenges.
  • New research highlights advancements in genomic profiling and the use of targeted therapies, such as somatostatin analogs and PD-L1 inhibitors, along with insights from genetically engineered mouse models.
  • These advancements aim to improve diagnosis and personalize treatment for ONB, potentially enhancing patient outcomes through better imaging, targeted therapies, and collaborative research efforts.
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We developed a culture model of a human olfactory ensheathing cell tumor. Cultured organoids resemble normal ensheathing cells. Assays suggest that this model provides a tool for studying the roles of these glial cells in the maintenance of the peripheral olfactory system.

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An acute loss of smell emerged as a striking symptom present in roughly half of the people infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in the early phases of the COVID-19 pandemic. In most COVID-19 patients, olfaction recovers over the course of a few weeks. However, a lasting partial or complete loss of smell, often associated with distorted olfactory perceptions termed parosmia, has emerged as a widespread problem impacting at least 5%-10% of those who experience anosmia due to COVID-19.

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The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare tumor of unclear origins. Employing alterations in Rb1/Trp53/Myc (RPM), we establish a genetically engineered mouse model of high-grade metastatic ONB exhibiting a NEUROD1 immature neuronal phenotype. We demonstrate that globose basal cells (GBCs) are a permissive cell of origin for ONB and that ONBs exhibit cell fate heterogeneity that mimics normal GBC developmental trajectories.

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Adult neurogenesis occurs in the mammalian olfactory epithelium to maintain populations of neurons that are vulnerable to injury yet essential for olfaction. Multipotent olfactory basal stem cells are activated by damage, although mechanisms regulating lineage decisions are not understood. Using mouse lesion models, we focused on defining the role of Polycomb repressive complexes (PRCs) in olfactory neurogenesis.

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The olfactory mucosa, lining a portion of the nasal cavity, houses the primary olfactory sensory neurons responsible for odor transduction, along with supporting cell populations. Tremendous advances have come from studying the peripheral olfactory system in animal models, especially the mouse. However, acquired human olfactory disorders lack effective therapies, and many of these conditions involve pathology in the olfactory mucosa.

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Unlabelled: Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Because of the low incidence of this tumor, as well as an absence of established cell lines and murine models, understanding the mechanisms driving olfactory neuroblastoma pathobiology has been challenging. Here, we sought to apply advances from research on the human olfactory epithelial neurogenic niche, along with new biocomputational approaches, to better understand the cellular and molecular factors in low- and high-grade olfactory neuroblastoma and how specific transcriptomic markers may predict prognosis.

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Background: With a rising incidence of cerebrospinal fluid (CSF) leaks, endoscopic endonasal CSF leak repair is increasingly performed. Current approaches utilize a variety of materials including free mucosal grafts and vascularized flaps, but post-op leaks continue to be reported. Steroid-eluting bioabsorbable stents (SES) are used during functional endoscopic sinus surgery for chronic rhinosinusitis to reduce inflammation and scarring while maintaining patency of sinus ostia.

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Article Synopsis
  • Unilateral cleft lip nasal deformity (uCLND) leads to olfactory dysfunction, but the reasons behind it are not well understood.
  • A study analyzed uCLND patients over 16, focusing on how nasal structure affects sense of smell through tests like airflow simulations and biopsy analysis.
  • Results showed that all five subjects experienced significant nasal obstruction and varying levels of smell loss, particularly on the cleft side, suggesting that the olfactory dysfunction is mainly due to conductive issues related to changes in nasal anatomy.
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  • * In a study of olfactory tissue from patients with long-lasting smell loss, researchers found a persistent inflammatory response characterized by T cell infiltration and changes in myeloid cell populations.
  • * The findings suggest that even after the virus is cleared, inflammation in the olfactory epithelium may cause ongoing dysfunction of smell receptors, potentially explaining why some patients continue to struggle with olfactory issues post-COVID-19.
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In vitro tissue models hold great promise for modeling diseases and drug responses. Here, we used emulsion microfluidics to form micro-organospheres (MOSs), which are droplet-encapsulated miniature three-dimensional (3D) tissue models that can be established rapidly from patient tissues or cells. MOSs retain key biological features and responses to chemo-, targeted, and radiation therapies compared with organoids.

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Background: Endoscopic sinus surgery (ESS) offers excellent outcomes for patients with chronic rhinosinusitis (CRS) in the general population. It is unclear whether older patients with significant medical comorbidities experience similar benefits.

Objective: The purpose of this study is to evaluate whether increasing medical comorbidity is associated with worse sinonasal quality of life outcomes after ESS in older patients.

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Here, we provide an overview of olfactory dysfunction associated with COVID-19. We provide background regarding the organization and function of the peripheral olfactory system. A review of the relevant literature on anosmia and parosmia due to infection with SARS-CoV-2, the virus causing COVID-19, is provided.

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Most human subjects infected by SARS-CoV-2 report an acute alteration in their sense of smell, and more than 25% of COVID patients report lasting olfactory dysfunction. While animal studies and human autopsy tissues have suggested mechanisms underlying acute loss of smell, the pathophysiology that underlies persistent smell loss remains unclear. Here we combine objective measurements of smell loss in patients suffering from post-acute sequelae of SARS-CoV-2 infection (PASC) with single cell sequencing and histology of the olfactory epithelium (OE).

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Background: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O).

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Article Synopsis
  • Presbyosmia, or age-related loss of smell, impacts many individuals over 65 and is linked to damage in the olfactory epithelium, though its mechanisms remain unclear and lack treatment options.
  • The study utilized various methods, including biopsies and single-cell RNA sequencing, to investigate cellular changes in the olfactory epithelium of older adults, revealing inflammation-related alterations in stem cells that affect their ability to function properly.
  • Findings suggest that these inflammatory changes in olfactory epithelium stem cells could be a key factor in the development of presbyosmia, indicating they may serve as a potential target for therapeutic interventions to restore sense of smell.
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Background: Endoscopic sinus surgery is a well-established treatment for chronic rhinosinusitis in patients with cystic fibrosis, though its benefits seem to be limited to improving sinonasal symptoms rather than affecting lung function.

Objective: This study aims to identify clinical and demographic factors that may influence sinonasal and pulmonary outcomes after surgery.

Methods: This is a six-year retrospective analysis of adult cystic fibrosis patients who underwent endoscopic sinus surgery at a tertiary care center.

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Objective: To assess olfactory outcomes as measured by an olfactory-specific quality of life (QOL) questionnaire in patients undergoing EESBS for sellar lesions.

Design: Retrospective case series.

Setting: Tertiary academic medical center.

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Objectives: Mesenchymal stem cells (MSCs), classically expanded in culture from bone marrow, are of broad interest to the regenerative medicine community. Human nasal turbinate mesenchymal-like stem cell cultures have also been described, defined by an in vitro phenotype similar to bone marrow MSCs. Nonetheless, the identity in vivo of the cells that give rise to nasal MSC-like cultures remains unclear, and these cells are often suggested to be related to olfactory lineages.

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Background: Endoscopic sinus surgery (ESS) is an effective intervention for patients with medically refractory chronic rhinosinusitis. Frontal sinusotomy is the most challenging part of ESS, with one of the key outcomes being access for topical irrigations.

Objective: The purpose of this study is to compare irrigation penetration into the frontal sinus following Draf IIa versus modified Draf IIa frontal sinusotomy.

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Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) - the causal agent in COVID-19 - affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules.

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Background: Exposure to cigarette smoke has been associated with a higher incidence of postoperative complications across a variety of surgical specialties. However, it is unclear if smoking increases this risk after endoscopic sinus surgery (ESS). Because complication rates after ESS are relatively low, a large national database allows for a statistically meaningful study of this topic.

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The chemical senses of taste and smell play a vital role in conveying information about ourselves and our environment. Tastes and smells can warn against danger and also contribute to the daily enjoyment of food, friends and family, and our surroundings. Over 12% of the US population is estimated to experience taste and smell (chemosensory) dysfunction.

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The presence of active neurogenic niches in adult humans is controversial. We focused attention to the human olfactory neuroepithelium, an extracranial site supplying input to the olfactory bulbs of the brain. Using single-cell RNA sequencing analyzing 28,726 cells, we identified neural stem cell and neural progenitor cell pools and neurons.

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