Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

Abstract: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. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients

Gentamicin Rapidly Inhibits Mitochondrial Metabolism in High-Frequency Cochlear Outer Hair Cells

Aminoglycosides (AG), including gentamicin (GM), are the most frequently used antibiotics in the world and are proposed to cause irreversible cochlear damage and hearing loss (HL) in 1/4 of the patients receiving these life-saving drugs. Akin to the results of AG ototoxicity studies, high-frequency, basal turn outer hair cells (OHCs) preferentially succumb to multiple HL pathologies while inner hair cells (IHCs) are much more resilient. To determine if endogenous differences in IHC and OHC mitochondrial metabolism dictate differential sensitivities to AG-induced HL, IHC- and OHC-specific changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH) fluorescence during acute (1 h) GM treatment were compared. GM-mediated decreases in NADH fluorescence and succinate dehydrogenase activity were observed shortly after GM application. High-frequency basal turn OHCs were found to be metabolically biased to rapidly respond to alterations in their microenvironment including GM and elevated glucose exposures. These metabolic biases may predispose high-frequency OHCs to preferentially produce cell-damaging reactive oxygen species during traumatic challenge. Noise-induced and age-related HL pathologies share key characteristics with AG ototoxicity, including preferential OHC loss and reactive oxygen species production. Data from this report highlight the need to address the role of mitochondrial metabolism in regulating AG ototoxicity and the need to illuminate how fundamental differences in IHC and OHC metabolism may dictate differences in HC fate during multiple HL pathologies

Management of epistaxis in patients with ventricular assist device: a retrospective review

Abstract Background Patients with a ventricular assist device (VAD) are at risk for epistaxis due to the need for anticoagulation. Additionally, these patients develop acquired von Willebrand syndrome (AvWS) due to these devices. Management is complicated by the risk of thrombosis if anticoagulation is reversed. This study sought to characterize the clinical features and management of epistaxis in this high-risk population. Methods Retrospective review of adults with VAD and epistaxis necessitating inpatient consultation with the otolaryngology service were included. Results 49 patients met inclusion criteria. All patients had a presumed diagnosis of AvWS. An elevated INR (> 2.0) was present in 18 patients (36.7%). Anticoagulation was held in 14 (28.6%) patients, though active correction was not necessary. Multiple encounters were required in 16 (32.7%) patients. Spontaneous epistaxis was associated with multiple encounters (p = 0.02). The use of hemostatic material was associated with a lower likelihood of bleeding recurrence (p = 0.05), whereas cauterization with silver nitrate alone was associated with a higher likelihood of re-intervention (p = 0.05). Surgery or embolization was not required urgently for any patient. Endoscopy under general anesthesia was performed for one patient electively. Mean follow up time was 16.6 months (σ = 6.3). At six months, 18 (36.7%) patients were deceased. Conclusion While these patients are at risk for recurrent spontaneous epistaxis, nonsurgical treatment without active correction of INR or AvWS was largely successful. Placement of hemostatic material, as opposed to cautery with silver nitrate, should be considered as a first-line treatment in this group. Multidisciplinary collaboration is critical for successful management

Single-stage total endoscopic resection of a plexiform neurofibroma of the maxillary sinus in a child with type 1 neurofibromatosis

Plexiform neurofibromas are peripheral nerve sheath tumors associated with neurofibromatosis type 1. The maxillary sinus is an extremely rare location of the plexiform neurofibroma and only two adult cases have been previously reported. We report the first case of plexiform neurofibroma of the maxillary sinus occurring in a child with neurofibromatosis type 1. This unusual location presents a management challenge considering the infiltrative nature and the potential malignant degeneration of this type of tumor. MRI is highly valuable to diagnose and plan the surgical approach of the plexiform neurofibroma of the maxillary sinus. Due to the location of the tumor and the patient's age, conservative surgery is highly recommended. We performed an endoscopic total en-bloc resection of the tumor with no recurrence after nine months of follow-up

Endoscopic Anterior Skull Base Resection for Olfactory Neuroblastoma

Background: This study reports our experience with endoscopic endonasal anterior skull base resection for olfactory neuroblastoma. Study Design: This study is a retrospective chart review at a tertiary medical center from 1996 to 2013. Methods: A total of 22 patients underwent anterior total ( n  = 19) or hemi ( n  = 3) skull base resection for olfactory neuroblastoma. The outcomes measured include demographics, operative details, postoperative course, and oncological outcomes including Kaplan–Meier analysis. Results: Mean age was 59.9 years; mean follow-up was 43.3 months (range, 1–203 months). The modified kadish staging at presentation was stage A in six patients, B in nine patients, C in six, and D in one patient. All cases were primary, four patients had major complications including cranial, orbital, or pulmonary embolism and three had minor complications. All patients underwent skull base reconstruction using acellular dermal allograft either as single layer ( n  = 19) or double layer ( n  = 2) or in a combination with a nasoseptal flap ( n  = 1). One patient had a postoperative cerebrospinal fluid leak which required revision skull base reconstruction using a second layer of acellular dermal allograft and lumbar drain placement. One patient had positive final margins and one patient developed local recurrence on long-term follow-up. Conclusion: Endoscopic anterior skull base resection for olfactory neuroblastoma and reconstruction using single layer acellular dermal allograft provides good oncological outcomes and low-postoperative morbidity

Middle Ear Irrigations Decrease the Density of Mucosal Biofilms in an Animal Model of Acute Otitis Media

Objective: Bacteria in biofilms are extremely resistant to antibiotics. Recurrent acute otitis media appears to be a disease related to biofilm formation. The goal of this study is to determine if middle ear irrigations with saline or baby shampoo could eradicate mucosal biofilms in a chinchilla model of acute otitis media. Method: After a baseline ABR, middle ears of 10 chinchillas were inoculated with Haemophilus influenzae. On day 5, the ears were irrigated with saline or 1% baby shampoo using a syringe or hydrodebrider. A final ABR was obtained before the animals were euthanized and middle ear mucosa were harvested for SEM analysis. Results: Biofilm formation on middle ear mucosa in chinchillas was in nonuniform distribution. SEM analysis by a blinded microscopist showed a statistically significant decrease in biofilm densities of middle ear mucosa after normal saline or 1% baby shampoo irrigations when compared with nonirrigated ears using Wilcoxon/Kruskal-Wallis Tests ( P < .01). No statistically significant difference in biofilm densities between normal saline and 1% baby shampoo irrigations was seen. The hearing thresholds on auditory brainstem responses (ABR) at frequencies 16 kHz, 4 kHz, 1 kHz, and 500 Hz were unchanged two days after normal saline or 1% baby shampoo irrigations. Conclusion: Middle ear irrigations with 1% baby shampoo or normal saline lead to a statistically significant decrease in biofilm densities. One percent baby shampoo or normal saline are non-ototoxic and can be safely used for middle ear irrigations. Future work in our laboratory will study the effect of a hydrodebrider prototype

Endoscopic Reconstruction of Large Anterior Skull Base Defects using Single Layer of Acellular Dermal Allograft

Background: Endoscopic repair of large skull base defects following endoscopic anterior skull base resection using free grafts or pedicled vascular flaps in a single or multilayer technique have been well described. Objective: The purpose of this study is to review our experience in endoscopic reconstruction of large anterior skull base defects following endoscopic anterior skull base resection using a single layer of acellular dermal allograft. Study Design: This study is retrospective chart review at a tertiary medical center from 1996 to 2014. Materials and Methods: Of 69 patients, 46 patients met these criteria. All repair of skull base defects were performed by a transnasal, endoscopic approach using a single layer of acellular dermal allograft. The main outcome measured was the success of graft take. Comparison with the group reconstructed using different techniques was performed. Results: Mean patient age was 58 years. Of the 69 patients, 17 patients underwent endoscopic hemi skull base resection and 29 patients underwent endoscopic total skull base resection. The most common tumor was olfactory neuroblastoma. Three patients (6.5%) had postoperative cerebrospinal fluid leak. Of these three patients, two were repaired using a second layer of acellular dermal allograft and one patient using a nasoseptal flap. Two patients had a lumbar drain placed. Six patients underwent reconstruction in a different bilayer technique using acellular dermal allograft and either a nasoseptal flap or an on-lay free mucosal graft. None of these patients had postoperative cerebrospinal leak. Conclusion: Single layer acellular dermal allograft can be used successfully to reconstruct large defects following endoscopic anterior skull base resection