Effect of Different Therapeutic Strategies on Olfactory Outcomes in Patients With Chronic Rhinosinusitis With Nasal Polyps: A Systematic Review.

INTRODUCTION: Olfactory impairment is one of the cardinal symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the effect of currently available therapeutic options on the recovery of the sense of smell is not well defined. The aim of this systematic review was to compile evidence on the impact of medical, surgical, and biological treatment on olfactory outcomes in patients with CRSwNP. METHODS: This review was conducted by 2 reviewers according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of evidence of all the studies included in the qualitative synthesis was evaluated using the Critical Appraisal Skills Programme (CASP). RESULTS: Forty-four studies were included in the qualitative synthesis. These assessed sinonasal surgery (n=23), biologics (n=15), and conventional medical treatment (n=6). The methodological quality was moderate-to-high in most. Overall, significant improvements in the sense of smell were detected with all the interventions analyzed and measured using an objective tool, a subjective tool, or both. However, most studies used different outcome measures, thus hindering comparisons between interventions, and data on clinically relevant changes were missing. CONCLUSION: Oral corticosteroids, biologics, and sinonasal surgery improve the olfactory impairment associated with CRSwNP. However, the heterogeneous nature of existing studies does not allow accurate comparisons.

SNOT-22 in general population, a Spanish cohort study with an updated meta-analysis.

BACKGROUND: Olfactory loss (OL) has emerged as one of the most prevalent and debilitating symptoms of SARS-CoV-2 infection and long-COVID-19. The present prospective observational study aimed to evaluate the efficacy of olfactory training (OT) on orthonasal and retronasal olfactory function in a cohort of individuals with persistent post-COVID-19 OL. METHODOLOGY: Participants with post-COVID-19 olfactory impairment underwent 4 months of OT, self-assessing their smell perception and undergoing comprehensive psychophysical evaluation of orthonasal and retronasal olfaction at baseline and after training. Orthonasal olfactory function was assessed using the extended Sniffin' Sticks test battery. Retronasal olfactory function was tested with powdered aromas. RESULTS: Among 114 participants with post-COVID-19 olfactory loss, adherence to OT was 60%. In adherents, the average increase in composite TDI score was 6.0 points compared to 2.6 points in non-adherents. Fifty-seven percent of adherent participants achieved a clinically significant improvement in TDI score (≥5.5 points), compared to 22% of non-adherents. In retronasal olfactory identification, 56% of adherents achieved a clinically significant improvement (≥4 points), compared to 16% of non-adherents. CONCLUSION: Adherence to a 4-month OT regimen can yield clinically meaningful improvements in both orthonasal and retronasal olfactory function among individuals with persistent post-COVID-19 olfactory dysfunction.

Low levels of miR-143-3p are associated with severe chronic rhinosinusitis with nasal polyps.

microRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules that regulate post-transcriptional gene expression. Accumulating evidence suggests their involvement in regulating various biological and pathological processes, including inflammation. Studies have revealed distinct expression patterns of miRNAs in Chronic Rhinosinusitis with (CRSwNP) and without (CRSsNP) nasal polyps (1). Specifically, miR-155 and miR-21 have been observed to be upregulated in CRSwNP, increasing and attenuating the expression of pro-inflammatory cytokines, respectively (2,3). Conversely, the downregulation of miR-34, miR-449, and members of the miR-200 family has been associated with impaired ciliogenesis and the regulation of epithelial-mesenchymal transition, respectively (4,5). Nonetheless, the direct role of miRNAs in CRSwNP is still being investigated.

Prevalence of chronic rhinosinusitis without/with nasal polyps according to severity in Spain.

BACKGROUND: The worldwide prevalence range of chronic rhinosinusitis (CRS) is 5-12%; from this, 20 % have nasal polyps. Due to the little epidemiological data about CRS in the Spanish population, this study analyses the prevalence and severity of CRS with (CRSwNP) or without (CRSsNP) nasal polyps, and their connection with other coexisting type 2 inflammatory diseases in Spain. METHODOLOGY: This is a retrospective, large-scale, nationwide, epidemiological study based on the electronic medical records from the BIG-PAC® database. Patients diagnosed of CRSsNP and CRSwNP were identified using specific disease codes. The severe form of the disease was defined as patients who received at least a long course of antibiotics in CRSsNP or ≥2 short courses of systemic corticosteroids in CRSwNP in ≤12 months during the last 2 years, and/or had previous sinus surgery. Physician diagnosed prevalence, sociodemographic and clinical characteristics, and disease severity were assessed. RESULTS: Out of a cohort of 1,012,257 patients (≤18 years old), 42,863 and 7,550 patients with diagnosed CRSsNP and CRSwNP, respectively, were analysed. The overall prevalence of diagnosed CRS was 5.1%, being 4.3% and 0.8% for CRSsNP and CRSwNP, respectively. Patients with CRSwNP and severe forms of the disease were older and had higher levels of type 2 inflammatory biomarkers than CRSsNP patients and non-severe disease. CONCLUSIONS: Although CRSsNP was more prevalent than CRSwNP, the severe forms of CRS were more frequent in patients with CRSwNP. In addition, CRSwNP patients had a higher incidence of coexisting type 2 inflammatory diseases.

Validation of Visual Analogue Scale for loss of smell as a quick test in chronic rhinosinusitis with nasal polyps.

BACKGROUND AND OBJECTIVE: Diagnostic criteria of chronic rhinosinusitis with nasal polyps (CRSwNP) include, among others, olfactory dysfunction (OD). We hypothesize that patients suffering with CRSwNP are good at self-assessing their sense of smell through visual analogue scale (VAS) compared to smell tests. METHODS: A controlled cross-sectional study was planned. Adults diagnosed with severe CRSwNP waiting for endoscopic sinus surgery were included. A cohort of healthy controls was also studied. All participants performed Barcelona smell test (BAST-24), sinonasal outcomes test 22 (SNOT-22), and VAS for loss of smell. CRSwNP underwent blood test (eosinophils count, total serum IgE), CT scan (Lund-Mackay Score), and nasal endoscopy. RESULTS: 138 severe CRSwNP and 40 controls subjects were included. The BAST-24 identification score was strongly correlated with the VAS score in the CRSwNP group (rho=-0.79, p<0.001) but not in the control group (rho=-0.14; p=0.39), this difference between groups being statistically significant (p<0.001). A significant correlation of SNOT-22 item 21 (loss of smell) was also found with BAST-24 identification (rho=-0.65, p<0.001), this difference being statistically significant (Z=-2.43; p=0.015). In the ROC curve, the area under the curve (AUC) was 0.85 with 72.5% sensitivity and 93.1% specificity. CONCLUSION: This study demonstrates a potential role of the VAS score for the screening of OD in severe CRSwNP in daily clinical practice.

Spanish Consensus on the Management of Chronic Rhinosinusitis With Nasal Polyps (POLIposis NAsal/POLINA 2.0).

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly prevalent and burdensome disease for both individuals and health systems. Its management involves many specialties, including otorhinolaryngology, allergology, pulmonology, primary care, pharmacy, and pediatrics. A multidisciplinary approach and the participation of the patient in decision-making are essential, both for diagnosis and for therapy. The authors of the consensus aim to translate current knowledge into an easy-to-read practical guide and emphasize those aspects requiring further discussion or with unmet needs owing to the lack of appropriate scientific evidence. An iterative approach for the development of an evidence-based systematic review with recommendations was followed using a standard quality assessment approach (Scottish Intercollegiate Guidelines Network [SIGN] and National Institute for Health and Care Excellence [NICE]). The guideline was critically evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) and Recommendation Excellence (AGREE REX) instruments. Consequently, POLINA has been considered a high-quality guideline by an independent agency. The POLINA consensus provides new definitions of control, therapeutic management (including surgery and evaluation of severity), indications for use of biologics, and response. Finally, this guideline focuses on unmet research needs in CRSwNP.

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Septoplasty and/or inferior turbinoplasty produce significant improvements of the sense of smell.

BACKGROUND: Patients with septal deviation and/or turbinal hypertrophy may experience olfactory disfunction (OD). The aim of this study was to analyse the effect of septoplasty and/or turbinoplasty on both lateralized and bilateral olfactory function. METHODOLOGY: Prospective study of 47 patients with nasal obstruction secondary to septal deviation and/or turbinal hypertrophy and 20 healthy controls. The Barcelona Olfactory test (BOT-8), a new supraliminal orthonasal subjective olfactometry, was applied 3 times in a row (in each nostril separately and in both simultaneously). The 8 items were applied randomly to minimize the possible risk of learning. The test has not established the minimal clinically important difference (MCID). Anterior rhinomanometry and acoustic rhinometry were performed. All participants self-assessed smell loss and nasal obstruction using a visual analogue scale (VAS) and completed questionnaires for nasal obstruction (Nasal Obstruction Symptom Evaluation, NOSE) and for quality of life (QoL), using disease-specific (SinoNasal Outcome Test-22, SNOT-22) and generic (Short Form-12 Health Survey, SF-12) questionnaires. Nasal measurements and questionnaires were performed preoperatively and 12 months after surgery. RESULTS: Before surgery, patients reported worse VAS on smell loss and on nasal obstruction compared to controls. Patients scored lower BOT-8 than controls. Lateralized preoperative olfactory function showed that all BOT-8 characteristics were lower at the narrow side than the wider one. Smell function and QoL improved significantly one year after surgery. CONCLUSIONS: Nasal septal deviation and turbinal hypertrophy lead to an olfactory impairment on the obstructed nostril. Nasal surgery provides a positive outcome on olfactory function, as well as on subjective and objective outcomes.

Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

The 8-Odorant Barcelona Olfactory Test (BOT-8): Validation of a New Test in the Spanish Population During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVE: Most smell tests are difficult to implement in daily clinical practice owing to their long duration. The aim of the present study was to develop and validate a short, easy-to-perform, and reusable smell test to be implemented during the COVID-19 pandemic. METHODS: The study population comprised 120 healthy adults and 195 patients with self-reported olfactory dysfunction (OD). The 8-Odorant Barcelona Olfactory Test (BOT-8) was used for detection, memory/recognition, and forced-choice identification. In addition, a rose threshold test was performed, and a visual analog scale was applied. The Smell Diskettes Olfaction Test (SDOT) was used for correlation in healthy volunteers, and the University of Pennsylvania Smell Identification Test (UPSIT) was used for patients with OD to establish cut-offs for anosmia and hyposmia. In order to take account of the COVID-19 pandemic, disposable cotton swabs with odorants were compared with the original test. RESULTS: In healthy persons, the mean (SD) BOT-8 score was 100% for detection, 94.5% (1.07) for memory/recognition, and 89.6% (0.86) for identification. In patients with OD, the equivalent values were 86% (32.8), 73.2% (37.9), and 77.1% (34.2), respectively. BOT-8 demonstrated good test-retest reliability, with agreement of 96.7% and a quadratic k of 0.84 (P<.001). A strong correlation was observed between BOT-8 and SDOT (r=0.67, P<.001) and UPSIT (r=0.86, P<.001). Agreement was excellent for disposable cotton swabs, with a k of 0.79 compared with the original test. The cut-off point for anosmia was ≤3 (area under the curve, 0.83; sensitivity, 0.673; specificity, 0.993). CONCLUSION: BOT-8 offers an efficient and fast method for assessment of smell threshold, detection, memory, and identification in daily clinical practice. Disposable cotton swabs with odorants proved to be useful and safe during the COVID-19 pandemic.

Twelve-year long-term postoperative outcomes in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Evidence regarding long-term postoperative follow-up of chronic rhinosinusitis with nasal polyps (CRSwNP) patients is scarce in the literature. The objective of the present study was to report long-term 12-year postoperative outcomes for CRSwNP patients. METHODS: CRSwNP patients were prospectively followed after endoscopic sinus surgery. Sinonasal symptoms, nasal polyp score (NPS), Barcelona Smell Test 24 (BAST-24), Lund-Mackay Score (LMS), and Medical Outcome Study Short Form-36 (SF-36) questionnaire were assessed before and 12 years after surgery. RESULTS: At long-term follow-up (median, 12 years), a strong improvement was noted for all patients (N=76) in nasal symptoms score, NPS, BAST-24, and LMS scores compared with baseline. No long-term improvement in SF-36 was found. CONCLUSION: Patients with CRSwNP have a long-term 12-year postoperative improvement in nasal symptoms, polyp size, computed tomography, and olfaction.

Twelve-year long-term postoperative outcomes in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Evidence regarding long-term postoperative follow-up of chronic rhinosinusitis with nasal polyps (CRSwNP) patients is scarce in the literature. The objective of the present study was to report long-term 12-year postoperative outcomes for CRSwNP patients. METHODS: CRSwNP patients were prospectively followed after endoscopic sinus surgery. Sinonasal symptoms, nasal polyp score (NPS), Barcelona Smell Test 24 (BAST-24), Lund-Mackay Score (LMS), and Medical Outcome Study Short Form-36 (SF-36) questionnaire were assessed before and 12 years after surgery. RESULTS: At long-term follow-up (median, 12 years), a strong improvement was noted for all patients (N=76) in nasal symptoms score, NPS, BAST-24, and LMS scores compared with baseline. No long-term improvement in SF-36 was found. CONCLUSION: Patients with CRSwNP have a long-term 12-year postoperative improvement in nasal symptoms, polyp size, computed tomography, and olfaction.

Sinonasal mucosal melanomas: defining profiles for better survival outcomes.

BACKGROUND: Sinonasal mucosal melanoma is an aggressive malignancy with a 5-year survival rate ranging from 20% to 39%. Despite the evolving surgical and radiotherapy techniques, and introduction of immune-checkpoint inhibitor therapy, overall survival rates remain poor. METHODOLOGY: A retrospective cohort study was conducted at the Hospital Clinic de Barcelona and the Hospital de la Santa Creu i Sant Pau between 1984 and 2020; primary outcome measures were 3 and 5-year melanoma-specific survival (MSS). Kaplan-Meier survival analysis and Cox proportional hazards model were performed to identify predictors of survival. RESULTS: Fifty patients were included, the mean age was 70.4, MSS at 3 and 5 years was 51.2%, and 29.5%, respectively. The median follow-up was 39.6 months during which 46% presented locoregional recurrence and 36%, metastasis. The univariate and multivariate analyses found as survival predictors the N category, the treatment received, the surgical margins and the mitotic index. CONCLUSIONS: We found an overall 5-year MSS of 29.5%. Those patients with intention-to-cure (stages III and IVa) treated by surgery that were N0 at diagnosis, with < 10 mitoses per HPF showed a 5-year MSS rate of 74.1%. More studies will be needed to adequately define the patients' profiles that will benefit from a better survival outcome.

Direct Costs of Acute Rhinosinusitis in Spain: A Prospective and Observational Study (PROSINUS).

BACKGROUND AND OBJECTIVES: The incidence of acute rhinosinusitis (ARS) is high throughout the world. Although diagnosis is clinical and disease course is mostly self-limiting, diagnostic tools and medications are overused by physicians, thus increasing the direct medical costs of the disease. Objective: The aim of the PROSINUS study was to quantify the direct medical costs of management of ARS in Spain. METHODS: We performed a prospective observational study of 1610 patients with a clinical diagnosis of nonbacterial, uncomplicated ARS. According to the duration of symptoms by the European Position Paper on Rhinosinusitis and Nasal Polyps, patients were classified as having viral or postviral ARS with different levels of severity. Direct medical costs were calculated based on medical visits, use of diagnostic tools, and medications prescribed. RESULTS: Overall, the mean (SD) direct medical costs per episode were €322.3 (301.2) vs €441.1 (344.3) for viral and postviral ARS episodes, respectively (P<.001). When viral and postviral disease were compared, the medical costs per episode were €245.0 (265.4) vs €328.4 (301.9) for medical visits (P<.001), €38.1 (64.0) vs €61.9 (78.8) for diagnostic tools (P<.001), and €39.2 (25.9) vs €50.8 (25.3) for medications prescribed (P<.001). CONCLUSION: The direct medical costs of postviral ARS episodes were higher than those of viral episodes (common cold). Uncomplicated nonbacterial ARS represents an important socioeconomic burden owing to the excessive number of medical visits, use of diagnostic tools, and medications prescribed.

High Frequency of Smell and Taste Dysfunction in Health Care Professionals With COVID-19 Working in Allergy Departments.

INTRODUCTION AND OBJECTIVE: Since the early stages of the novel coronavirus 2019 (SARS-CoV-2) outbreak, smell and/or taste dysfunction (STD) has been reported in 5% to 88% of COVID-19 patients. Objective: We aimed to assess STD in health care professionals (HCPs), mainly allergists, affected by COVID-19. We carried out a survey to evaluate the association between STD and its severity and demographic characteristics, symptoms, comorbidities, and hospital admission. METHODS: We designed a 15-item questionnaire comprising various sections, as follows: demographics, diagnostic characteristics, STD patterns, medication use, and comorbidities. The questionnaire was developed using Google forms. It was distributed to members of the Spanish Society of Allergology and Clinical Immunology (SEAIC) and sent via social media to be completed by HCPs with COVID-19. RESULTS: The survey was completed by HCPs (n=234), of whom 76.5% were aged ≤55 years and 73.5% were female. STD was detected in 74.4% of respondents, of whom 95.6% reported moderate-severe impairment. Mean time until recovery of taste dysfunction was 21.6 (24.0) days in HCPs aged ≤55 years and 33.61±26.2 days in those aged >55 years (P=.019). Analysis stratified by severity of STD showed that more than a half of COVID-19 patients presented severe loss of smell. Older age (>55 years) was associated with fever, anorexia, lower frequency of headache, and longer persistence of taste dysfunction. CONCLUSION: STD is a common symptom in COVID-19, even as a unique or preceding symptom. HCPs who reported smell dysfunction were younger than those not affected with STD. Taste dysfunction may imply more systemic involvement in COVID-19-positive HCPs.

Functional Examination of the Upper and Lower Airways in Asthma and Respiratory Allergic Diseases: Considerations in the Post-SARS-CoV-2 Era.

Airway examination procedures can potentially transmit infectious diseases to patients and to the health care professionals who perform them via various mechanisms. The COVID-19 pandemic has halted most of the activity of the clinics and laboratories involved in assessment of lung and nasal function, and clear recommendations in this regard have been made. Today, we still do not know for sure what its consequences will be in the short or long term, since important gaps remain in our knowledge of aspects as fundamental as virus transmission mechanisms, pathophysiology, immune response, and diagnosis. In this review, we study the examination techniques used to assess patients with respiratory allergy, asthma, and associated diseases during this period and highlight their possible advantages and disadvantages. Therefore, we focus on exploring the entire upper and lower airways, from the perspective of the safety of both health professionals and patients and their specific characteristics. We also analyze the intrinsic value of these interventions in terms of diagnosis and patient management. The changing situation of COVID-19 may mean that some of the assertions presented in this review will have to be modified in the future. While we seek to ensure a consistently broad approach, some differences in operational details may apply owing to local regulations.

Change in olfactory function after septoplasty. A systematic review and meta-analysis.

BACKGROUND: Septoplasty is one of the most frequently performed surgeries. However, there remains a question as to the effect of such intervention on the sense of smell. This study aims to examine the available evidence regarding the effect of septoplasty on the sense of smell. METHODS: A database search was performed using PubMed, ScienceDirect, Google Scholar and The Cochrane Library databases from January 1990 to February 2020. Search terms included smell, olfaction, odor, septum, septoplasty, and septorhinoplasty. A meta-analysis was performed with 12 studies that provided sufficient data on change in olfaction. RESULTS: 14 studies met the inclusion criteria, and 2 additional studies were included manually; comprising a total of 996 patients and 25 controls. Significant improvement in olfactory test scores was observed in all tests. Pre- and postoperative differences in means were 0.63 for BSIT, 0.80 for CCCRC test, 1.16 for odor threshold, 1.43 for odor discrimination, and 1.18 for odor identification. CONCLUSIONS: Septoplasty seems to improve olfactory function. However, the outcome of this intervention is discrete and not equal for all patients, so further randomized trials are needed to confirm current findings.

Endoscopic endonasal surgery to treat intrinsic brainstem lesions: correlation between anatomy and surgery.

OBJECTIVE: The endoscopic endonasal approach (EEA) has been proposed as an alternative in the surgical removal of ventral brainstem lesions. However, the feasibility and limitations of this approach to treat such pathologies are still poorly understood. This study aimed to report our experience in five consecutive cases of intrinsic brainstem lesions that were managed via an EEA, as well as the specific anatomy of each case. METHODS: All patients were treated in a single center by a multidisciplinary surgical team between 2015 and 2019. Before surgery, a dedicated anatomical analysis of the brainstem safe entry zone was performed, and proper surgical planning was carried out. Neurophysiological monitoring was used in all cases. Anatomical dissections were performed in three human cadaveric heads using 0° and 30° endoscopes, and specific 3D reconstructions were executed using Amira 3D software. RESULTS: All lesions were located at the level of the ventral brainstem. Specifically, one mesencephalic cavernoma, two pontine ca- vernomas, one pontine gliomas, and one medullary diffuse midline glioma were reported. Cerebrospinal fluid leak was the major complication that occurred in one case (medullary diffuse midline glioma). From an anatomical standpoint, three main safe entry zones were used, namely the anterior mesencephalic zone (AMZ), the peritrigeminal zone (PTZ, used in two cases), and the olivar zone (OZ). Reviewing the literature, 17 cases of various brainstem lesions treated using an EEA were found. CONCLUSIONS: To our knowledge, this was the first preliminary clinical series of intrinsic brainstem lesions treated via an EEA presented in the literature. The EEA can be considered a valid surgical alternative to traditional transcranial approaches to treat selected intra-axial brainstem lesions located at the level of the ventral brainstem. To achieve good results, surgery must involve comprehensive anatomical knowledge, meticulous preoperative surgical planning, and intraoperative neurophysiological moni- toring.

Olfactory Dysfunction in the COVID-19 Outbreak.

The first cases of coronavirus 2019 disease (COVID-19) occurred in Wuhan, China, and the disease rapidly become a public health emergency of international proportions. COVID-19 can cause mild-to-severe acute respiratory syndrome (SARS) and is caused by the SARS-CoV-2 coronavirus. The clinical manifestations of COVID-19 include fever, dry cough, fatigue, sputum production, shortness of breath, sore throat, and headache. We performed this narrative review to analyze the current literature on postviral olfactory dysfunction related to the SARSCoV- 2 pandemic. Since the initial anecdotal reports from China, increasingly frequent international reports on COVID-19 indicate that 5% to 85% of affected patients lose their sense of smell, thus highlighting the very heterogeneous nature of the literature in this area. Therefore, we advise home isolation measures and/or social distancing, as well as tests to detect SARS-CoV-2 when possible, in patients with sudden and severe loss of smell who cannot be promptly evaluated.