Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study.

Preliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample. This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures). Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006). We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.

Association of air pollution with olfactory identification performance of São Paulo residents: a cross-sectional study.

OBJECTIVE: Exposure to particulate matter of 10 µm or less in diameter (PM10) has been implicated in pulmonary and cardiovascular diseases. However, the effect of PM10 on olfaction has not been well established. We estimated individual acute and chronic PM10 exposure levels in a large Brazilian cohort and related them to the ability to identify odors. METHODS: Adults from São Paulo (n = 1358) were recruited from areas with different levels of air pollution. To verify individual exposure to air pollution, the averages of 30, 60, 90, 180 and 364 days of PM10 were interpolated to subjects' zip codes using the kriging method. Olfactory identification performance was tested using the University of Pennsylvania Smell Identification Test (UPSIT®). Multiple linear regressions were used to calculate the effect of air pollution on olfactory identification performance, controlling for demographic and other variables that affect the sense of smell. RESULTS: Acute exposures to PM10 were related to worse UPSIT® scores, including 30- (ß = - 0.94, 95% Confidence Interval [CI] - 0.98, - 0.89), 60- (ß = - 1.09, 95% CI = - 1.13, - 1.04) and 90-day intervals (ß = - 1.06, 95% CI - 1.10, - 1.02) (reference for ß: 1 µm/m3 increase in PM10 exposure per point decrease in UPSIT® score). Chronic exposures were also associated with worse olfaction for both 180- (ß = - 1.06, 95% CI - 1.10, - 1.03) and 364-day (ß = - 0.87, 95% CI - 0.90, - 0.84) intervals. As in prior work, men, older, low-income, and low-schooling people demonstrated worse olfactory performance. CONCLUSION: Acute and chronic exposure to PM10 is strongly associated with olfactory identification performance in Brazilian adults. Understanding the mechanisms which underlie these relationships could help to improve chemosensory function with a large public health impact.

Olfaction in nasal polyp patients after Reboot surgery: an endotype-based prospective study.

PURPOSE: To report biomarkers present in the olfactory mucosa in chronic rhinosinusitis with nasal polyps (CRSwNP) in comparison with nasal polyps and to nasal mucosal tissues from control patients. To evaluate the kinetics of smell over 6 months in patients who underwent Reboot surgery. METHODS: Cohort study from May 2021 to May 2022. We collected samples of olfactory mucosa and nasal polyps from 16 CRSwNP patients and inferior turbinate samples from 20 control subjects. The study was not randomized for surgical and/or medical treatment. Samples were analyzed by Luminex and Unicap 100 to measure biomarkers of inflammation (IL1-ß, IL4, IL5, IL6, IL17, CCL3, CCL4, G-CSF, SE-IgE, total IgE and ECP). 12 of the CRSwNP patients underwent Extended Sniffin'tests at timepoints 1-4 days pre-surgery, and 1, 3 and 6 months after Reboot surgery. RESULTS: Type-2 markers were significantly elevated in OM and polyp tissue in CRSwNP (n = 16) vs. controls (n = 20), P < 0.05. TDI scores improved already 1 month (P < 0.05) after surgery and remained stable for 6 months. Type-2 inflammation in nasal polyps was associated with decreased sense of smell and taste before surgery, but improved after surgery (P = 0.048). Type-3 inflammation was present in the olfactory mucosa and was associated with a better sense of smell before surgery, but a smaller improvement of smell afterward. CONCLUSIONS: Type-2 inflammation is present in the olfactory mucosa in CRSwNP patients and is associated with smell loss. Reboot surgery, aiming to completely remove inflamed sinus mucosa, significantly improves the smell in this group of patients.

Reboot surgery for chronic rhinosinusitis with nasal polyposis: recurrence and smell kinetics.

OBJECTIVE: To evaluate the time for recovery of the sense of smell in patients with CRSwNP who underwent Reboot surgery compared to patients undergoing ESS in a long-term follow-up study. METHODS: Data were collected retrospectively from 168 patients with severe uncontrolled CRSwNP, who underwent revision surgery, either as Extended Endoscopic Sinus Surgery (Reboot, 140 patients) or as regular Endoscopic Sinus Surgery (ESS, 28 patients) between January 1, 2014, and December 31, 2015, aiming to compare the outcome of surgeries after 2 years of follow-up. Sense of smell was scored as judged by the patient using scores 0 to 3 reflecting a percentage estimate of remaining smell. RESULTS: Smell improved similarly in the Reboot and ESS groups over the first 9 months, which was maintained over 24 months in the Reboot, but not the ESS group (p = 0.007 after 18 months, p = 0.001 after 24 months). Furthermore, polyp recurrence rates were significantly lower in the Reboot group. CONCLUSION: Reboot surgery significantly improved olfactory function and significantly reduced nasal polyp recurrence rates over 2 years post-operatively. Therefore, Reboot should be considered for patients with uncontrolled severe CRSwNP, specifically when ESS failed, to offer long-term smell and a polyp-free status. LEVEL OF EVIDENCE: 3b.

Safety and efficacy of superior turbinate biopsies as a source of olfactory epithelium appropriate for morphological analysis.

PURPOSE: There is no standardized approach for preserving olfactory function in the side of the nose where biopsy of the olfactory epithelium (OE) is performed. Moreover, a gold standard technique for obtaining human OE in vivo is still lacking. We determined the efficacy of obtaining good-quality OE specimens suitable for pathological analysis from the lower half of the superior turbinate and verified the safety of this procedure in maintaining bilateral and unilateral olfactory function. METHODS: In 21 individuals without olfactory complaints and who had undergone septoplasty and inferior turbinectomy OE biopsy was made during septoplasty. Olfactory function, both unilateral and bilateral, was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) before and 1 month after the procedure. Specimens were marked with the olfactory marker protein for confirmation of OE presence. RESULTS: Ninety percent of the samples contained OE, although clear histological characterization was possible from only 62%. There was no deterioration of UPSIT scores either bilaterally or unilaterally on the side of the biopsy. Patients also maintained the ability to identify individual odorants. CONCLUSION: Biopsies of the lower half of the superior turbinate do not affect olfactory function and show strong efficacy in yielding OE tissue and moderate efficacy for yielding tissue appropriate for morphological analysis. Future studies are needed to assess the safety of this procedure in other OE regions.

Olfactory symptoms reported by migraineurs with and without auras.

OBJECTIVE: Olfaction-related symptoms accompany migraine attacks and some, such as osmophobia, may be useful in differentiating migraine from other types of headaches. However, the types and frequencies of olfactory symptoms associated with migraine have not been well characterized. The goal of this study was to better characterize the olfactory symptoms of migraine. METHODS: A cross-sectional study was devised. One hundred and thirteen patients who met the International Classification of Headache Disorders II criteria for migraine were administered a new 65-item questionnaire specifically focused on olfaction-related experiences (eg, odor-related triggers, osmophobia, cacosmia, phantosmia, olfactory hallucinations, olfactory hypersensitivity, and self-perceived olfactory function). Visual analog scale ratings and frequencies were computed and compared between migraineurs with and without auras using t-tests and chi-square analyses. RESULTS: While osmophobia was present in 95.5% of the patients, the prevalence of other olfaction-related symptoms was much lower (interictal olfactory hypersensitivity [IOH], 14.1%; olfactory hallucinations, 6.2%; phantosmia, 4.4%; cacosmia/euosmia, 2.6%). Migraine was commonly triggered by odors (90.2%), with perfume being the most common trigger (95.1%), followed by cleaning products (81.3%), cigarette smoke (71.5%), and motor vehicle exhaust (70.5%). No significant differences in symptom frequencies were apparent between migraineurs with or without auras (P > .40). Interestingly, patients with IOH reported being less likely to experience osmophobia and odor-triggered crisis than did those without this symptom (respective percentages: 75% vs. 99% and 69% vs. 94%, P ≤ .002). Osmophobia and odor triggered headache were associated with a mild decrease in self-reported olfactory acuity. CONCLUSION: Odor-related disturbances were common symptoms of the 113 migraineurs, with nearly all reporting osmophobia. Perfume odor was the most common trigger for the migraine. The reported symptoms did not differ between patients with and without auras. Patients who experienced IOH appeared to fundamentally differ from those who did not experience IOH in terms of the incidence of osmophobia and odor-triggered crisis. Subjects who reported experiencing osmophobia and odor-triggered headache reported having worse olfactory acuity.

Development of normative data for the Brazilian adaptation of the University of Pennsylvania Smell Identification Test.

It is well established that olfactory dysfunction has significant implications for safety, nutrition, and quality of life. The more reliable standardized tests of olfactory function, such as the University of Pennsylvania Smell Identification Test (UPSIT), assess odor identification ability. Unfortunately, cultural factors can influence such tests, as a number of odors are not universally recognized. In this study, a Portuguese language version of the UPSIT was administered to an age- and sex-stratified prospective sample of 1820 Brazilian subjects. Normative data were developed for a subset of 1578 subjects who reported having no difficulties smelling or tasting. Individuals with a history of head trauma or, in the case of those over the age of 64 years, Mini-Mental State Examination Scores <24, were excluded from analysis. As in other populations, the test scores were significantly influenced by age and sex. The median overall difference between the North American and Brazilian UPSIT scores was 2.2 points for men and 0.8 points for women, although subtle age-related differences were also apparent. This research represents that largest clinical study of olfaction ever performed in South America. Correction factors based upon age and sex are provided to allow for direct comparisons of Brazilian test scores to those based upon North American norms.

Immunoregulatory effects of bone marrow-derived mesenchymal stem cells in the nasal polyp microenvironment.

Nasal polyposis is a severe, chronic inflammatory condition of the paranasal sinuses and is frequently associated with asthma and aspirin sensitivity. Mesenchymal stem cells exhibit a potent immunosuppressive effect in several inflammatory conditions, and their role in nasal polyposis remains little explored. Hence, we investigated whether bone marrow-derived mesenchymal stem cells could modulate cell phenotype in the nasal polyp milieu. After coculture with mesenchymal stem cells, the frequency of these inflammatory cells was found to decrease. Furthermore, mesenchymal stem cells promoted strong inhibition of CD4+ and CD8+ T cell proliferation, increased the frequency of CD4+CD25+Foxp3 T cells, and changed the global cytokine profile from an inflammatory to an anti-inflammatory response. We believe that mesenchymal stem cells may be a very useful adjunct for investigation of the inflammatory process in nasal polyposis, contributing to better understanding of the inflammatory course of this condition.

Lateral sphenoid sinus recess cerebrospinal fluid leak: a case series.

The lateral recess of the sphenoid sinus is one of the most common sites of meningocele and spontaneous cerebrospinal fluid (CSF) leak. Despite the availability of several techniques for closure of skull base defects occurring in this location, recurrence still poses a major challenge. This report reviews the experience of surgical repair of lateral sphenoid sinus recess CSF leak at a tertiary referral center and provides a brief discussion of this rare lesion. Nine surgeries were performed for six cases of spontaneous lateral sphenoid sinus recess CSF leak (two revisions and one repair of a new defect). Two patients presented with intracranial hypertension (ICH) and four with meningocele or meningoencephalocele. The transpterygoid approach was used in two procedures. A multilayer graft was used in seven cases and a nasoseptal flap in two. Three patients received lumbar or ventricular shunts, and one received acetazolamide for ICH management. Two minor complications were recorded, and the overall surgical success rate was 78 %. We conclude that nasoseptal flaps are a valid option for repair of recurrent CSF leaks, particularly in the lateral sphenoid sinus recess. Furthermore, identification and correction of ICH plays an essential role in the success of treatment in this patient population.

Endoscopic Study of Ethmoidal Canals in Cadavers, Including a Histological Analysis of Their Contents.

Introduction The advent of the endoscope has enabled the use of the endonasal approach for a variety of diseases. Studying the ethmoidal canals is important for surgeries of the paranasal sinuses and the anterior base of the skull. Objective To investigate the ethmoidal canals and evaluate their structure, the presence of vessels and nerves, their location, and to perform an anatomopathological study of their contents. Methods We evaluated 20 cadavers (20 left and 20 right nasal cavities) through endoscopic dissection of the anterior base of the skull and exposure of the medial periorbita and dura mater; then, the ethmoidal canals were located and measured in relation to the anterior wall of the sphenoid sinus and between the ethmoidal canals, followed by removal of their content for histological analysis. Results Vessels were present in 75% of the left anterior ethmoidal canals, 70% of the left posterior ethmoidal canals, 75% of the left middle ethmoidal canals, 85% of the right anterior ethmoid canals, and 64.5% of the right posterior ethmoid canals; 50% of the right middle ethmoidal canals contained one vessel. Conclusion The ethmoidal canal does not necessarily contain an ethmoidal artery. Studies with a larger sample should be performed to quantify the correct proportion of arteries and ethmoidal canals.

Olfaction and Quality of Life in Patients with Eosinophilic CRS Undergoing Endoscopic Sinus Surgery.

Introduction Chronic rhinosinusitis (CRS) is a common inflammatory disease. This high prevalence leads to high direct and indirect public health costs, which include medical visits, laboratory tests and imaging, pharmacotherapy, hospitalizations, and surgical treatment. Furthermore, CRS has a substantial impact on patient quality of life, affecting productivity and being a common cause of absence from work CRS-associated olfactory dysfunction is highly prevalent, the actual effectiveness of surgical intervention remains inconsistent. Although there are studies evaluating the postoperative course of patients with eosinophilic Chronic rhinosinusitis (eCRS) treated with high-volume budesonide irrigation, there is little objective information regarding the impact of this intervention on olfactory status and quality of life. Objective To conduct a pre- and postoperative analysis of olfaction and quality of life in patients with eCRS treated with surgical intervention followed by high-volume budesonide nasal irrigation. Methods Prospective, descriptive, uncontrolled study of patients with eCRS. All patients underwent pre- and postoperative nasal endoscopy, SNOT-22 questionnaire, and the University of Pennsylvania Smell Identification Text (UPSIT), always by the same previously trained examiner. The SNOT-22 questionnaire and the UPSIT were readministered to all patients at 3 months, 6 months, and 1 year postoperatively, and scores compared with those obtained preoperatively. Results Twenty patients were included in the study, 13 males and 7 females, between the ages of 23 and 65; 8 patients had comorbid asthma. Quantitative evaluation using the UPSIT test showed a significant improvement in olfaction 3 months after surgery, which remained 6 months and 1 year after surgery (p = 0.0063). There was no significant association between eosinophil concentrations in polypoid tissue and postoperative SNOT-22 and UPSIT results. Patients with tissue eosinophils >50 had a lower preoperative UPSIT score. As early as 3 months postoperatively, a significant improvement in quality of life was already noticeable, as represented by a decrease in SNOT-22 values, which persisted through the 1-year postoperative follow-up evaluation (p = 0.0005). Quantitative evaluation using the UPSIT test showed a significant improvement in olfaction 3 months after surgery, which remained 6 months and 1 year after surgery (p = 0.0063). Conclusion Surgery effectively controlled eCRS in patients who adhered to high-volume budesonide nasal irrigation postoperatively. There were significant improvements in quality of life and olfaction, which persisted at least up to one year postoperatively.

Upper Airway Mucociliary Clearance is Impaired in Dyspneic COVID-19 Patients.

Covid-19 is transmitted mainly by respiratory droplets and as the upper airway mucosa is the first innate immune barrier, it is crucial to understand the effects of SARS-CoV-2 on this system. In the current study, we aimed to evaluate the nasal mucociliary clearance in patients with SARS-CoV-2 infection and their symptom development. Observational cross-sectional study. The nasal mucociliary clearance (NMC) time was evaluated by the saccharin test and the results were compared between patients with SARS-CoV-2 infection (group 1) and controls (group 2, asymptomatic patients with a negative polymerase chain reaction test). We also compared the NMC time for each specific symptom suffered by participants in group 1 with the NMC time of the control group as well as with the patients in group 1 who were asymptomatic. There was a significant increase in NMC time in group 1 with dyspnea when compared to the control group (p = 0.032) and also when compared to patients who were infected were not dyspneic (p = 0.04). There were no differences in the clearance times when considering other symptoms. COVID-19 patients with dyspnea present with altered nasal mucociliary clearance.

Computed Tomography Evaluation of the Paranasal Sinuses in Adults with Primary Ciliary Dyskinesia.

Introduction Primary ciliary dyskinesia is a rare inherited disease that results in a malfunction of mucociliary clearance and sinonasal complaints. Aplasia/hypoplasia of the frontal and sphenoid sinuses has been described as more frequent in this population. However, to date, no studies have provided a detailed description of computed tomography findings in adult patients with a diagnosis of this condition. Objective To describe the computed tomography (CT) findings of adult patients with primary ciliary dyskinesia. Methods Retrospective observational study of adult patients with primary ciliary dyskinesia who underwent CT. Results Twenty-one adults were included in the study. Aplasia occurred in 38.1% of frontal sinuses and in 14.3% of sphenoid sinuses. Likewise, hypoplasia occurred in 47.6% of the frontal sinuses, in 54.8% of the sphenoid sinuses and in 40.5% of the maxillary sinuses. Furthermore, trabecular loss was identified in 61.9% ethmoidal sinuses. The mean Lund-Mackay score was 13.5. In addition, 9.5% of the patients had concha bullosa, 47.6% had marked bilateral inferior turbinate hypertrophy, 38.1% had marked middle turbinate hypertrophy, and 47.6% had marked septal deviation. Finally, we identified images suggestive of fungus ball, mucocele, osteoma, a possible antrochoanal polyp, and frontal bone erosions. Conclusion The present study provides a detailed description of CT findings in patients with primary ciliary dyskinesia. We also describe abnormalities that must be identified for safer surgical planning and that suggest a diagnosis of primary ciliary dyskinesia if found in patients with a consistent clinical picture.

Outcomes of Endoscopic Sinus Surgery for Chronic Rhinosinusitis in Adults with Primary Ciliary Dyskinesia.

Introduction Primary ciliary dyskinesia (PCD) is a rare inherited disease associated with impairment of mucociliary transport and, consequently, with a high incidence of chronic rhinosinusitis. For patients with chronic rhinosinusitis who remain symptomatic despite medical treatment, endoscopic sinus surgery is a safe and effective therapeutic option. However, to date, no studies have been found evaluating the effect of surgery on the quality of life associated with the effect on olfaction and nasal endoscopy findings of patients with primary ciliary dyskinesia and chronic rhinosinusitis. Objective To describe the effect of endoscopic sinus surgery on the quality of life, on olfaction, and on nasal endoscopy findings of adults with PCD and chronic rhinosinusitis. Methods Four patients who underwent endoscopic sinus surgery were included. The Sinonasal Outcome Test-22 (SNOT-22) score, the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire, and the Lund-Kennedy score were collected preoperatively and at 3 and 6 months postoperatively. The olfaction as assessed with the University of Pennsylvania Smell Identification Test (UPSIT), which was administered preoperatively and 3 months postoperatively. Results A total of 4 patients with a mean age of 39.3 years old (3 men and 1 woman) completed the study. All patients showed clinically significant improvement in the SNOT-22, NOSE, and Lund-Kennedy scores at 3 months postoperatively, and this improvement was sustained throughout the follow-up period. However, olfaction did not improve after surgery. Conclusion The endoscopic sinus surgery treatment of chronic rhinosinusitis in adults with PCD was associated with improvement in quality of life and endoscopic findings. However, no improvement in olfaction was demonstrated. Studies with a larger number of patients and control groups should help confirm these findings.

Impact of Chronic Rhinosinusitis with Nasal Polyposis on IL-12 and IL-8.

Introduction: The pathophysiology of Chronic Rhinosinusitis is coordinated by distinct inflammatory reactions in different individuals. Inflammatory environments with a predominance of Th2 lymphocytes tend also to be rich in eosinophils. These environments are common during the formation of nasal polyps associated with aspirin intolerance, which is also marked by an increase in inflammatory mediators, especially IL-4, IL-5, and IL-13. Despite the significance of these inflammatory mediators, the relevance of IL-12 subunits' presence within eosinophilic nasal polyps, however, has been less studied. The current study aims to evaluate the presence of IL-12 subunits, IL-12p40 and IL-12p70, in eosinophilic nasal polyps and their correlations with IL-8 presence. Materials and Methods: We compared the concentrations of IL-8, IL12p40, and IL12p70 among samples of eosinophilic nasal polypoid tissue, eosinophilic nasal polypoid tissue associated with aspirin intolerance, and healthy nasal mucosa, using an indirect immunoassay (ELISA) kit. Results: When compared to healthy nasal mucosa, there was a lower concentration of IL-8 in Chronic Rhinosinusitis with Nasal Polyp (CRSwNP) tissue. Aspirin Intolerant polypoid tissue also presented a lower concentration of IL-12 subunits compared to healthy nasal mucosa. There was no significant correlation between IL-8 and IL-12 in the eosinophilic polypoid conditions. Conclusion: In CRSwNP, there is a reduction in IL-8 and IL-12 subunits compared to control, with a lack of correlation between IL-12 and IL-8. The lack of correlation can be justified by a type two inflammatory storm environment.

High prevalence of olfactory dysfunction detected in treatment-naive patients with head and neck cancer.

BACKGROUND: Previous studies demonstrated the difficulty of patients with Head and Neck Cancer (HNC) in sensing food taste, a function in which olfaction has a significant role. However, neither study employed psychophysical tests or control groups to establish the veracity of such complaints. AIMS/OBJECTIVES: In this study, we quantitatively tested the olfactory function of HNC individuals and compared their function to that of healthy controls. METHODS: Thirty-one HNC naïve treatment patients and thirty-one controls, matched for sex, age, schooling, and smoking, were tested with the University of Pennsylvania Smell Identification Test (UPSIT). RESULTS: The olfactory function was significantly worse among the patients diagnosed with head and neck cancer [UPSIT cancer = 22.9(CI 95%: 20.5-25.4) vs. UPSIT controls = 29.1(CI 95%: 26.9-31.3); p < .001]. Most patients with HNC had olfactory disorders (n = 29, 93.5%). The risk of olfactory loss was higher in the cancer group [OR: 10.5(CI 95%: 2.1-51.9; p = .001)]. CONCLUSION AND SIGNIFICANCE: Olfactory disorders can be detected in more than 90% of patients with head and neck cancer when evaluated using a well-validated olfactory test. Smell disorders may be a potential marker for early diagnosis of HNC.

Differential Angiogenic Induction Impacts Nasal Polyp Tissue Growth.

In chronic rhinosinusitis with nasal polyps, inflammatory edema drives tissue remodeling favoring anomalous growth of the nasal mucosa, but a proangiogenic contribution of nasal polyp in support of tissue growth is still controversial. The chorioallantoic membrane of chicken embryo model was employed to address the potentiality of nasal tissue fragments to modulate angiogenesis. Fifty-seven fertilized eggs were implanted with polyp or healthy nasal mucosa tissue or were kept as non-implanted controls. The embryos' size, length, and development stage, and chorioallantoic membrane vasculature morphology were evaluated after 48 h. Quantitative computer vision techniques applied to digital chorioallantoic membrane images automatically calculated the branching index as the ratio between the areas of the convex polygon surrounding the vascular tree and the vessels' area. Ethics approval and consent to participate: the study was approved by the Human Research Ethics Committee of the Federal University of São Paulo (CAAE number: 80763117.1.0000.5505) and by the Animal Research Ethics Committee of University of São Paulo (nº CEUA 602-2019). Mucosal, but not polyp tissue implants, hampered embryo development and induced underdeveloped chorioallantoic membranes with anastomosed, interrupted, and regressive vessels. Vessels' areas and branching indexes were higher among the chorioallantoic membranes with polyp implants and controls than among those with healthy mucosa implants. Nasal polyp presents differential angiogenic induction that impacts tissue growth.

Perivascular Innervation in the Nasal Mucosa and Clinical Findings in Patients with Allergic Rhinitis and Idiopathic Rhinitis.

Introduction The nonspecific hyperreactivity of rhinitis has been attributed to neurotrophins activating sensory nerves and inflammatory cells. The relationship between these markers and the intensity of the symptoms is not well established and few studies have evaluated individuals with idiopathic rhinitis. Objective The present study aims to evaluate whether perivascular innervation and nerve growth factor (NGF) are related to the intensity of the clinical conditions in allergic rhinitis (AR) and idiopathic rhinitis (IR). Methods A total of 15 patients with AR and 15 patients with IR with the indication for inferior turbinectomy (associated or not with septoplasty) were selected. The patients received a score according to their signs and symptoms. After the surgery, we quantified eosinophils, mast cells, NGF, and nerve fibers in the nasal turbinate. Results The score of the signs and symptoms was higher in the AR group. Nerve growth factor was found in the cytoplasm of inflammatory cells in the submucosa in greater quantity in the AR group. The nerve fibers were distributed throughout the tissue, mainly in the subepithelial, glandular, and vascular regions, and there was no difference between the groups. Greater perivascular innervation was associated with a higher signs and symptoms score. Conclusions We concluded that these findings suggest that the NGF produced by submucosal inflammatory cells stimulates increased perivascular innervation in rhinitis, thus directly reflecting in more intense clinical conditions, especially in AR.

Chemosensory Dysfunction 3-Months After COVID-19, Medications and Factors Associated with Complete Recovery.

OBJECTIVES: To examine the longitudinal prevalence and recovery of olfactory, gustatory, and oral chemesthetic deficits in a sizable cohort of SARS-CoV-2 infected persons using quantitative testing. To determine whether demographic and clinical factors, mainly the medications used after the COVID-19 diagnosis, influence the test measures. METHODS: Prospective cohort in a hospital with primary, secondary, tertiary, and quaternary care. Patients with confirmed COVID-19 were tested during the acute infection phase (within 15 days of initial symptom, n = 187) and one (n = 113) and 3 months later (n = 73). The University of Pennsylvania Smell Identification Test, the Global Gustatory Test, and a novel test for chemesthesis were administered at all visits. RESULTS: During the acute phase, 93% were anosmic or microsmic and 29.4% were hypogeusic. No one was ageusic. A deficit in oral chemesthesis was present in 13.4%. By 3 months, taste and chemesthesis had largely recovered, however, some degree of olfactory dysfunction remained in 54.8%. Remarkably, patients who had been treated with anticoagulants tended to have more olfactory improvement. Recovery was greater in men than in women, but was unrelated to disease severity, smoking behavior, or the use of various medications prior to, or during, COVID-19 infection. CONCLUSIONS: When using quantitative testing, olfactory disturbances were found in nearly all SARS-CoV-2 infected patients during the acute infection phase. Taste or chemesthetic deficits were low. Olfactory impairment persisted to some degree in over half of the patients at the 3-month follow-up evaluation, being more common in women and less common in those who had been treated earlier with anticoagulants. LEVEL OF EVIDENCE: 3.

New Nasopharyngeal Flap for Posterior Skull-base Reconstruction: The Upper-Tongue Flap.

Introduction Reconstructions of clival resection are still challenging, and additional reconstructive methods may be necessary to achieve full coverage of the skull-base defect in patients with middle- and lower-clivus disease. Objective To describe a new nasopharyngeal flap for the middle and lower clivus. Methods Using nasal endoscopy in a cadaver dissection, we demonstrated a new nasopharygeal flap to cover the lower and middle clival resection. Results We described a new nasopharyngeal flap capable of covering the lower and middle portion of the clivus. Discussion The new nasopharyngeal flap, called the upper-tongue flap, is particularly adequate as an alternative for the reconstruction of middle and lower clivus defects, and it is better used in association with a nasalseptal flap in cases in which the nasalseptal flap alone does not provide enough mucosal coverage. Conclusion The new nasopharyngeal flap can be used in the reconstruction of clival resection.