Magnetic Resonance Imaging as a Diagnostic and Research Tool in Patients with Olfactory Dysfunction: A Systematic Review.

BACKGROUND: Patients with acquired, idiopathic olfactory dysfunction (OD) commonly undergo magnetic resonance imaging (MRI) evaluation to rule out intracranial pathologies. This practice is highly debated given the expense of MRI relative to the probability of detecting a treatable lesion. This, combined with the increasing use of MRI in research to investigate the mechanisms underlying OD, provided the impetus for this comprehensive review. OBJECTIVE: The purpose of this systematic review was to both assess the utility of MRI in diagnosis of idiopathic OD and to describe MRI findings among mixed OD etiologies to better understand its role as a research tool in this patient population. METHODS: A literature search of PubMed, Embase, Cochrane, Web of Science, and Scopus for studies with original MRI data for patients with OD was completed. Studies exclusively investigating patients with neurocognitive deficits or those studying traumatic or congenital etiologies of OD were excluded. RESULTS: From 1758 candidate articles, 33 studies were included. Four studies reviewed patients with idiopathic OD for structural pathologies on MRI, of which 17 of 372 (4.6%) patients had a potential central cause identified, and 3 (0.8%) had an olfactory meningioma or olfactory neuroblastoma. Fourteen studies (42.4%) reported significant correlation between olfactory bulb volume and olfactory outcomes, and 6 studies (18.8%) reported gray matter volume reduction, specifically in the orbitofrontal cortex, anterior cingulate cortex, insular cortex, parahippocampal, and piriform cortex areas, in patients with mixed OD etiologies. Functional MRI studies reported reduced brain activation and functional connectivity in olfactory network areas. CONCLUSION: MRI uncommonly detects intracranial pathology in patients with idiopathic OD. Among patients with mixed OD etiologies, reduced olfactory bulb and gray matter volume are the most common abnormal findings on MRI. Further research is required to better understand the role of MRI and its cost-effectiveness in patients with acquired, idiopathic OD.

Taste receptors in chronic rhinosinusitus, what is the evidence? A systematic review.

BACKGROUND: Bitter and sweet taste receptors (T2Rs and T1Rs), respectively, are involved in the innate immune response of the sinonasal cavity and associated with chronic rhinosinusitis (CRS). Growing evidence suggests extraoral TRs as relevant biomarkers, but the current understanding is incomplete. This systematic review synthesizes current evidence of extraoral taste receptors in CRS. METHODS: PubMed, Embase, Cochrane, Web of Science, and Scopus were reviewed in accordance with Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines and included studies of genotypic and phenotypic T2R/T1R status in CRS patients. RESULTS: Twenty-two studies with 3845 patients were included. Seventeen studies evaluated genotype and 10 evaluated taste phenotypes. Four of 6 studies examining the haplotype distribution of the T2R, TAS2R38, demonstrated increased AVI/AVI haplotype ("nontaster") frequency in CRS. Meanwhile, 2 studies demonstrated decreased bitter sensitivity in CRS with nasal polyposis (CRSwNP), whereas 3 other studies reported decreased bitter sensitivity only in CRS without nasal polyposis (CRSsNP). Findings regarding sweet sensitivity were mixed. Three studies with cystic fibrosis patients (n = 1393) were included. Studies investigating the association between clinical outcomes and TAS2R38 alleles were limited, but the nonfunctional combination of AVI/AVI was associated with increased utilization of sinus surgery and, in CRSsNP patients, with poorer improvement of symptoms postoperatively. CONCLUSION: Both genotypic and phenotypic assessments of T2Rs suggest a potential association with CRS, particularly CRSsNP. However, limited evidence and mixed conclusions cloud the role of T2Rs in CRS. Future investigations should aim to increase diverse populations, broaden institutional diversity, examine T1Rs, and utilize uniform assessments.

Impact of Routine Endoscopic Skull Base Surgery on Subjective Olfaction and Gustation Outcomes.

BACKGROUND: As endoscopic endonasal skull base surgery (EESBS) for sellar pathology has become routine, there is increasing awareness of quality-of-life (QOL) outcomes related to this approach. Similarly, there is a growing interest in postoperative chemosensory function, with notable emphasis on olfaction and the corresponding psychosocial implications of olfactory dysfunction. Meanwhile, there has been minimal direct investigation into gustatory outcomes, and the association between these 2 chemosensory functions remains poorly understood. OBJECTIVE: To investigate patient-reported chemosensory function and rhinologic-specific QOL following EESBS for routine sellar pathologies. METHODS: Comprehensive clinical characteristics and sinonasal QOL assessments, measured using Anterior Skull Base Nasal Inventory-12 (ASK Nasal-12), were collected from 46 patients undergoing EESBS for sellar pathology. RESULTS: Forty-six patients were included: 65.2% female, average age 52.8 yr (range: 27-89). The most common pathology was nonfunctioning pituitary adenoma (n = 28). Preoperative ASK Nasal-12 scores (mean = 0.81) demonstrated postoperative worsening at 2 wk (mean = 2.52, P < .0001) and 1 mo (mean = 1.33, P = .0031), with no difference at 3 mo postoperatively (mean = 0.89, P = .92). Meanwhile, there was significant worsening of preoperative subjective smell (mean = 0.62) and taste function (mean = 0.42) at 2 wk (mean = 3.48, P < .0001; mean = 2.69, P < .0001) and 1 mo (mean = 2.40, P < .0001; mean = 2.03, P < .0001) postoperatively, which persisted at approximately 3 mo postoperatively (mean = 1.26, P = .04; mean = 1.15, P = .0059). CONCLUSION: Patients undergoing EESBS for sellar pathologies experience anticipated, temporary disruptions in sinonasal QOL but may have longer lasting perturbations in subjective olfaction and gustation. Given the increasing use of the endoscopic endonasal corridor, further investigation in postoperative chemosensory function is essential.

Predictors of Completion of Sublingual Immunotherapy.

OBJECTIVES: Sublingual immunotherapy (SLIT) has emerged as an effective treatment alternative to subcutaneous immunotherapy (SCIT) given its improved safety profile and more convenient dosing. However, SLIT still relies on daily dosing for many years to optimize effectiveness. This study sought to investigate factors that influence patient completion of SLIT. METHODS: We performed an institutional retrospective review of patients who received SLIT (2008-2020). Completion was defined as completing at least 36 months of SLIT. Patient demographics and characteristics, including the number of allergens treated, history of asthma and sinus surgery, number of clinic visits, and total time undergoing SLIT, were documented. Multivariate models were used to analyze predictors of SLIT completion. Subgroup analysis was performed among pediatric patients and patients who discontinued SLIT. RESULTS: Of the 404 total patients, 249 (61.6%) discontinued, 47 (11.6%) completed, and 108 (26.7%) were currently undergoing SLIT. The mean duration of therapy was 11.2 months for those who discontinued and 49.4 months for patients who completed SLIT. The odds of SLIT completion were twice as high with each additional clinic visit (P < .001), and twice as high when the dosage was increased during therapy (P = .06). Pediatric patients younger than age 12 with a history of asthma were over five times more likely to complete therapy (P = .045). Patients with more clinic visits (P < .001) and higher associated costs (P = .003) were less likely to be lost to follow-up. CONCLUSION: Increasing the frequency of clinic visits, improving therapy availability, and mitigating concerns about clinical efficacy may increase patient completion of SLIT. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2111-E2115, 2021.

Atypical Presentation of Silent Sinus Syndrome: A Case Report and Literature Review.

INTRODUCTION: Silent sinus syndrome (SSS) is a condition characterized by ophthalmologic features, such as spontaneous enophthalmos and hypoglobus with ipsilateral maxillary sinus atelectasis and an otherwise asymptomatic presentation. SSS has been documented secondary to a number of external causes, including trauma or surgery, but has less commonly been described in the setting of a potential mass in the deep masticator space. CASE PRESENTATION: A 56-year-old woman with a history of chronic headaches with normal prior sinonasal imaging presented with increasing right-sided facial pain and headaches that radiated to her occiput, subjective visual changes, sharp ear pain, and long-standing subjective diminished sense of smell. Physical examination was normal, while nasal endoscopy demonstrated lateral bowing of the medial maxillary wall on the right. Magnetic resonance imaging demonstrated a homogenous 2 × 2 × 2.4 cm T1- and T2-weighted, hyperintense mass lesion in the deep masticator space splaying the right medial and lateral pterygoid muscles concerning for a possible lipomatous lesion. Computed tomography revealed an atelectatic and opacified maxillary sinus with inward bowing of the posterior maxillary wall and increased orbital volume on that side. Endoscopic maxillary antrostomy was performed with biopsy of the retromaxillary space lesion and with near immediate resolution of the patient's symptoms. Histologic examination of the mass demonstrated mature adipose tissue with few aggregates of benign small vessels. DISCUSSION: This is an unusual presentation of SSS, with an accompanying enlargement of the retromaxillary fat pad. We herein review our clinical experience with SSS and provide a literature review of the presentation, management, and perioperative considerations for SSS.

Therapeutic efficacy of mesenchymal stem cells for the treatment of congenital and acquired corneal opacity.

Purpose: Maintenance of a transparent corneal stroma is imperative for proper vision. The corneal stroma is composed of primarily collagen fibrils, small leucine-rich proteoglycans (SLRPs), as well as sparsely distributed cells called keratocytes. The lattice arrangement and spacing of the collagen fibrils that allows for transparency may be disrupted due to genetic mutations and injuries. The purpose of this study is to examine the therapeutic efficacy of human umbilical cord mesenchymal stem/stromal cells (UMSCs) in treating congenital and acquired corneal opacity associated with the loss of collagen V. Methods: Experimental mice, i.e., wild-type, Col5a1f/f and Kera-Cre/Col5a1f/f (Col5a1∆st/∆st , collagen V null in the corneal stroma) mice in a C57BL/6J genetic background, were subjected to a lamellar keratectomy, and treated with or without UMSC (104 cells/cornea) transplantation via an intrastromal injection or a fibrin plug. In vivo Heidelberg retinal tomograph (HRT II) confocal microscopy, second harmonic generated (SHG) confocal microscopy, histology, and immunofluorescence microscopy were used to assess the corneal transparency of the regenerated corneas. Results: Col5a1∆st/∆st mice display a cloudy cornea phenotype that is ameliorated following intrastromal transplantation of UMSCs. Loss of collagen V in Col5a1∆st/∆st corneas augments the formation of cornea scarring following the keratectomy. UMSC transplantation with a fibrin plug improves the healing of injured corneas and regeneration of transparent corneas, as determined with in vivo HRT II confocal microscopy. Second harmonic confocal microscopy revealed the improved collagen fibril lamellar architecture in the UMSC-transplanted cornea in comparison to the control keratectomized corneas. Conclusions: UMSC transplantation was successful in recovering some corneal transparency in injured corneas of wild-type, Col5a1f/f and Col5a1∆st/∆st mice. The production of collagen V by transplanted UMSCs may account for the regeneration of corneal transparency, as exemplified by better collagen fiber organization, as revealed with SHG signals.

BMI-1 is a potential therapeutic target in diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine glioma (DIPG) is a poor-prognosis pediatric brain tumor. No effective curative therapy is currently available and no therapeutic advances have been made in several decades. BMI-1 is a member of the multimeric protein complex Polycomb repressor complex 1. It is highly expressed in a number of diseases and malignancies and has been implicated in self-renewal of normal and cancer cells, and in DNA damage signaling. The role of BMI-1 in DIPG is largely unknown. Here, we show that BMI-1 is highly expressed in tumor tissue samples of DIPG patients and in patient-derived cancer stem-like cells. BMI-1 downregulation leads to the inhibition of DIPG patient-derived neurosphere cell proliferation, cell cycle signaling, self-renewal, telomerase expression and activity, and suppresses DIPG cell migration. Moreover, targeted inhibition of BMI-1 sensitizes DIPG cells to radiomimetic drug-induced DNA damage. Together, our data validate BMI-1 as a potential therapeutic target to treat children with DIPG.