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Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.
Assuntos
Autopsia/métodos , COVID-19/mortalidade , COVID-19/virologia , Bulbo Olfatório/virologia , Mucosa Olfatória/virologia , Mucosa Respiratória/virologia , Idoso , Anosmia , COVID-19/fisiopatologia , Endoscopia/métodos , Feminino , Glucuronosiltransferase/biossíntese , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Transtornos do Olfato , Neurônios Receptores Olfatórios/metabolismo , Sistema Respiratório , SARS-CoV-2 , OlfatoRESUMO
We present a protocol for the rapid postmortem bedside procurement of selected tissue samples using an endoscopic endonasal surgical technique that we adapted from skull base surgery. We describe steps for the postmortem collection of blood, cerebrospinal fluid, a nasopharyngeal swab, and tissue samples; the clean-up procedure; and the initial processing and storage of the samples. This protocol was validated with tissue samples procured postmortem from COVID-19 patients and can be applied in another emerging infectious disease. For complete details on the use and execution of this protocol, please refer to Khan et al. (2021)1 and Khan et al. (2022).2.
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Procedimentos de Cirurgia Plástica , Humanos , Base do Crânio/cirurgia , Endoscopia/métodos , Mucosa Olfatória/cirurgia , Lobo Frontal/cirurgiaRESUMO
Cochlear implantation initiates an inflammatory cascade in which both acute insertion trauma and chronic foreign body reaction lead to intracochlear fibrosis and loss of residual hearing. Several strategies have been proposed to attenuate the local reactive process after implantation, including intracochlear drug delivery. The present study gives an overview of what is being investigated in the field of inner ear therapeutics and cochlear implant surgery. The aim is to evaluate its potential benefit in clinical practice. A systematic search was conducted in PubMed, Embase, and Cochrane Library databases identifying comparative prospective studies examining the effect of direct inner ear drug application on mechanical cochlear trauma. Both animal and human studies were considered and all studies were assessed for quality according to the validated risk of bias tools. Intracochlear administration of drugs is a feasible method to reduce the local inflammatory reaction following cochlear implantation. In animal studies, corticosteroid use had a significant effect on outcome measures including auditory brainstem response, impedance, and histological changes. This effect was, however, only durable with prolonged drug delivery. Significant differences in outcome were predominantly seen in studies where the cochlear damage was extensive. Six additional reports assessing non-steroidal agents were found. Overall, evidence of anti-inflammatory effects in humans is still scarce.
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Implante Coclear , Implantes Cocleares , Orelha Interna , Animais , Orelha Interna/cirurgia , Audição , Estudos ProspectivosRESUMO
Background: Up to 40% of patients with chronic rhinosinusitis (CRS) remain uncontrolled despite guidelines of care being available, with an enormous socio-economic impact. The reasons for uncontrolled disease can be arbitrarily divided into disease-related, diagnosis-related, treatment-related, and patient-related factors. The relative contribution of each factor in uncontrolled CRS remains speculative. This explorative study aimed at determining the factors responsible for uncontrolled CRS in a tertiary care center, thereby identifying the most commons reasons for uncontrolled disease in CRS. Methods: Patients with uncontrolled CRS (n = 187) were asked to fill out a questionnaire and underwent a clinical examination at the outpatient clinic of the University Hospital of Leuven, Belgium. Two independent physicians evaluated the (multiple) reason(s) for uncontrolled disease. Results: In uncontrolled CRS, 66% of patients showed two or more reasons for uncontrolled disease according to the physicians' evaluation. Disease-related factors (70%) were most often considered the reason for uncontrolled disease, followed by treatment- (45%), patient- (42%), and diagnosis- (32%) related factors. Conclusion: In case of uncontrolled CRS, the different contributing factors to the uncontrolled nature need to be carefully addressed during diagnostic and therapeutic actions in order to define strategies to improve CRS care. Most uncontrolled CRS patients have multiple reasons contributing to their disease status, with disease-related factors being the most common factor.
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BACKGROUND: Recent data show uncontrolled disease in 35% of allergic rhinitis (AR) patients on medical treatment. The reasons for uncontrolled disease can arbitrarily be divided into disease-related, diagnosis-related, treatment-related, and patient-related factors. However, the relative importance of these factors in uncontrolled disease remains speculative. This explorative study aimed at determining the factors causing uncontrolled AR on four different continents worldwide, identifying the most common reasons for uncontrolled disease in AR. METHODS: Patients with uncontrolled AR (n = 430) were asked to fill out a questionnaire and underwent a clinical examination at the outpatient clinic in five university outpatient clinics (Leuven [Belgium], Beijing [China], Kinshasa [Congo], Bangalore [India], and Philadelphia [US]). Two independent physicians evaluated the reason or multiple reasons for uncontrolled disease. The study was coordinated from the University Hospital of Leuven. RESULTS: In uncontrolled AR patients, 76% of patients showed two or more reasons for uncontrolled disease according to the physicians' evaluation. Disease-related factors (64%) were considered most often the reason for uncontrolled disease, followed by treatment- (56%), patient- (54%), and diagnosis-related (47%) factors. There is limited variability in observations across different centers worldwide. CONCLUSION: We here define the multiple reasons for uncontrolled AR across different continents, with disease-related factors being most frequently associated with uncontrolled disease. A better understanding of uncontrolled disease will guide us in defining strategies to improve AR care.
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Rinite Alérgica , Alérgenos , China , República Democrática do Congo , Humanos , Índia , Rinite Alérgica/diagnóstico , Rinite Alérgica/epidemiologia , Rinite Alérgica/terapia , Inquéritos e QuestionáriosRESUMO
Posterior semicircular canal dehiscence is a rare condition and can cause a variety of symptoms. We report three cases of children between 5 and 12 years of age with a PSCD. They all presented with different complaints as follows: Tullio phenomenon in the first case, conductive hearing loss in the second and, conductive hearing loss and pulsatile tinnitus in the third. Imaging showed in all cases a PSCD on the right side, caused by a prominent jugular bulb (high riding bulb). We describe the clinical, audiometric and radiological findings, and discuss the management and therapy. A conservative "wait and see" approach is recommended, especially with children, because of the possible complications of surgery and the possibility that the symptoms will lessen with the skull base osseous maturation.