Local budesonide therapy in the management of persistent hyposmia in suspected non-severe COVID-19 patients: Results of a randomized controlled trial.

OBJECTIVES: Consequences of COVID-19 on olfactory functions remained unclear during the pandemic. We assessed the efficacy of local budesonide in addition to olfactory rehabilitation when managing non-severe COVID-19 patients with persistent hyposmia. METHODS: A multicentric, randomized, superiority trial was conducted (ClinicalTrials.gov NCT04361474). The experimental group (EG) received budesonide and physiological saline nasal irrigations administered via three syringes of 20 ml in each nasal cavity in the morning and evening for 30 days. The control group (CG) received a similar protocol without budesonide. Patients were included if they were >18 years old, with a SARS-CoV-2 infection and presenting an isolated hyposmia persisting 30 days after symptom onset. The primary endpoint was the percentage of patients with improvement of more than two points on the ODORATEST score after 30 days of treatment. RESULTS: In total, 123 patients were included and randomized (EG: 62 vs CG: 61). Two patients from the EG met the primary endpoint with no statistical difference between the two groups (P = 0.5). CONCLUSION: To our knowledge, this is the first study evaluating local budesonide for COVID-19 related hyposmia treatment even though previous trials were performed with other local corticosteroids. Local budesonide efficacy was not demonstrated for persistent hyposmia related to COVID-19.

Infliximab for the Treatment of Inflammatory Labyrinthitis: A Retrospective Cohort Study.

Inflammatory labyrinthitis is defined as a fluctuant vestibulo-cochlear syndrome associated with an impairment of the blood-labyrinthine barrier (BLB) on delayed FLAIR MRI sequences. Systemic and intratympanic corticosteroids are the gold standard treatment but their effect is frequently insufficient. The objective is here to determine whether infliximab could be of value in the treatment of bilateral inflammatory labyrinthitis. A retrospective monocentric study was conducted between January 2013 and December 2021. All patients included in the study were affected with a bilateral vestibulo-cochlear syndrome associated with bilateral blood-labyrinthine barrier impairment. Patients were administered infliximab at the dose of 5 mg/kg every 6 weeks for 6 months. Audiometry, MRI with delayed FLAIR sequences on the labyrinth, and corticosteroid doses still required were assessed both before and after treatment with infliximab was completed. Pure-tone average (PTA) was the primary outcome. The secondary outcomes were the speech recognition threshold (SRT), the Dizziness Handicap Inventory (DHI) score, and the corticosteroid (CS) dose. A total of nine patients including five men and four women were enrolled in the study. Thirteen ears were analyzed. After a 6-month period of treatment, the mean PTA (54 ± 24 db versus 66 ± 22 db; p = 0.027), SRT (54 ± 37 db versus 66 ± 32 db; p = 0.041) and DHI score (27 ± 15 versus 9 ± 2; p = 0.032) significantly improved. After the 6-month treatment period, the mean CS dose decreased from 38 ± 33 to 6 ± 5 mg/day (p = 0.003). We conclude that infliximab substantially improves the vestibulo-cochlear function in patients with bilateral inflammatory labyrinthitis and could be of value in corticosteroid-dependent cases.

Results of watchful waiting of unruptured intracranial aneurysms in a Western patient population: a single-center cohort.

BACKGROUND: The natural history of unruptured intracranial aneurysms (UIAs) in Western populations is still debated, especially for those <7 mm. Reporting data of a large single-center cohort managed with watchful waiting is therefore interesting. METHODS: From January 2011 to June 2019, 662 UIAs were followed up by yearly MR angiography. Morphologically stable UIAs were managed conservatively while unstable UIAs were offered treatment. The patients' clinical and radiological data were analyzed retrospectively. RESULTS: UIAs were ≤4 mm in 60%, 4.1-7.0 mm in 33%, and >7 mm in 7%. They were located on the anterior circulation in 90% of cases. The mean follow-up duration was 51.32 months for a total of 2831 aneurysm-years. During follow-up, 37 UIAs (5.5%) were treated because of an increase in size, and 8 UIAs were treated because of patient decision. Three aneurysms ruptured during follow-up for an annual risk of rupture of 0.1% (95% CI 0% to 0.24%). No risk factors for rupture were identified. The three ruptured cases made an excellent recovery. During follow-up, annual mortality from unrelated causes was 0.8% (95% CI 0.51% to 1.18%). CONCLUSIONS: This single-center cohort evaluated our watchful waiting policy applied in two-thirds of all incidental UIAs. Morphological change of UIAs during follow-up led to treatment in 5.5% of cases. With such a management paradigm, we found a low rupture rate in these selected UIAs and the mortality was unrelated to aneurysms.

Patterns of recurrences in sinonasal cancers undergoing an endoscopic surgery-based treatment: Results of the MUSES* on 940 patients: *MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers.

OBJECTIVES: The improvements in survival with expansion of the survivors' population, along with evolution of endoscopically-based treatment modalities, have contributed to emphasize the clinical relevance of recurrences in sinonasal cancers. However, at present, literature is scant regarding the pattern of recurrences and the therapeutic strategies available to manage long survivors who experienced single or multiple failures. The aim of the present study was to analyze sinonasal cancers recurrences to provide data regarding rates and patterns of relapse, predictors of failure and prognostic impact of the recurrence. MATERIALS AND METHODS: All patients receiving multimodal treatments including endoscopic surgery between 1995 and 2021 in three European referral centers were included. Statistical analysis of survival was performed through univariable, multivariable and unidirectional multistate models. Survival after recurrence analysis was implemented for patients experiencing at least one recurrence. RESULTS: The 5- and 10-year recurrence free survival rates were 34.1% and 38.4% for the whole population. With a mean follow-up time of 60 months, a global recurrence rate of 32.9% was observed. The 5- and 10-year survival after recurrence rates were 27.2% and 21.7%, respectively. Incidence and rates of recurrences were significantly associated with histology subtypes. CONCLUSION: This study provides valuable oncologic outcomes regarding a large homogenous cohort of patients affected by sinonasal malignances treated within a multimodal framework, emphasizing the strong correlation of histologic type with prognosis, as well as with pattern of recurrences.

The MUSES∗: a prognostic study on 1360 patients with sinonasal cancer undergoing endoscopic surgery-based treatment: ∗MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers.

BACKGROUND: Over the last 2 decades, transnasal endoscopic surgery (TES) has become the most frequently employed surgical technique to treat sinonasal malignancies. The rarity and heterogeneity of sinonasal cancers have hampered large non-population-based analyses. METHODOLOGY: All patients receiving TES-including treatment between 1995 and 2021 in 5 referral hospitals were included. A prognostic study was performed, and multivariable models were transformed into nomograms. Training and validation sets were based on results from 3 European and 2 non-European centres, respectively. RESULTS: The training and validation set included 940 and 420 patients, respectively. The mean age at surgery, primary-versus-recurrent presentation, histology distribution, type of surgery, T category and type of adjuvant treatment were differently distributed in the training and validation set. In the training set, 5-year overall survival and recurrence-free survival with a 95%-confidence interval were 72.7% (69.5-76.0%) and 66.4% (63.1-69.8%), respectively, significantly varying with histology. At multivariable analyses, age, gender, previous treatment, the extent of resection on the cranial, lateral and posterolateral axes, grade/subtype, T category, nodal status, margin status and adjuvant treatment were all associated with different prognostic outcomes, displaying a heterogeneous significance and effect size according to histology. The internal and external validation of nomograms was satisfactory (optimism-corrected C-index >0.7 and cumulative area under curve >0.7) for all histologies but mucosal melanoma. CONCLUSIONS: Outcomes of TES-based treatment of sinonasal cancers vary substantially with histology. This large, non-population-based study provides benchmark data on the prognosis of sinonasal cancers that are deemed suitable for treatment including TES.

Carotid artery webs in embolic stroke of undetermined source with large intracranial vessel occlusion.

BACKGROUND: Whether carotid artery web can be considered as a potential source of arterial thromboembolism in ischemic stroke remains uncertain. AIMS: In a large sample of individuals with large intracranial artery occlusion, we compared the prevalence of carotid artery webs between patients with and without embolic stroke of undetermined source. METHODS: In a single-center study of consecutive patients with anterior circulation ischemic stroke referred for mechanical thrombectomy, the presence of carotid artery web was systematically assessed by two independent readers. Thereafter, its prevalence was compared between patients with and without embolic stroke of undetermined source. RESULTS: Among 466 patients of whom 12% were considered to have had an embolic stroke of undetermined source, ipsilateral carotid artery web was detected in 1.9% (confidence interval 95% = 0.7-3.1). Ipsilateral carotid artery web was more frequent in embolic stroke of undetermined source than in the rest of the sample (10.7% (confidence interval 95% = 2.7-18.7] vs. 0.7% (0-1.5), P < 0.001). This difference remains significant after adjustment for sex, age, and vascular risk factor (odds ratio: 12.5 (2.1-72), P = 0.005) or after exclusion of patients with any other bulb wall thickening (P = 0.025). In contrast, the difference of prevalence of contralateral carotid artery web between the two groups did not reach statistical significance (2.4% vs. 1.9%, P = 0.6). CONCLUSIONS: Our results suggest that the presence of a carotid artery web might be considered as a potential source of large intracranial artery embolism. Longitudinal studies are needed to assess the exact risk of recurrence associated with these lesions.

Study of the Comorbidity Between Cases of Acute Peripheral Vestibulopathies and COVID-19.

IMPORTANCE: An infective etiology of acute peripheral vestibulopathy (APV) has long been hypothesized. In the context of coronavirus disease 2019 (COVID-19), we examined the possible comorbidity between these two entities. OBJECTIVES: APV is the second most common cause of vestibular disorders and results from a sudden and unilateral loss of vestibular inputs. The characteristic signs and symptoms include sudden and prolonged vertigo, absence of auditory symptoms, and absence of other neurological symptoms. An infective etiology of APV has long been hypothesized on the basis of its association with respiratory tract infections and its frequent occurrence in epidemics. Possible comorbidity with herpes simplex virus type 1 reactivation or influenza virus infection has also been proposed. This study was designed to assess the possible comorbidity between APV and COVID-19. DESIGN/SETTING/PARTICIPANTS: Quantification of the number of hospital admissions for APV over the period from February to May 2020 was carried out in 5 French hospitals. A comparison with 2018 and 2019 entries over the same period was made. Comorbidity between APV and COVID-19 infection was investigated. RESULTS: No significant increase in admission for APV was noticed over the examination period. No significant difference was noticed among hospitals located in COVID-19 high- and low-risk zones for SARS-CoV-2. No significant increase in the severity of the APV cases was noticed. No case of comorbidity between APV and SARS-CoV-2 infection was reported. Based on our observations, no correlation was made between APV and COVID-19. CONCLUSION: Based on our observations, COVID-19 is not statistically correlated with APV.

Embolization of Internal Carotid Artery Branches in Juvenile Nasopharyngeal Angiofibroma.

OBJECTIVE: Preoperative embolization of juvenile nasopharyngeal angiofibroma (JNA) is usually performed by the occlusion of branches of the external carotid artery (ECA). However, a significant proportion of JNAs also receive blood from the internal carotid artery (ICA). The objective of this study was to report on the feasibility and clinical impact of superselective embolization of ICA branches in complex cases of JNA. METHODS: This was a single-center retrospective study of all patients operated on for JNA between 2000 and 2018. The patients treated with embolization of branches of the ICA were identified. The results in terms of complications, intraoperative blood loss, and rate of residual disease were analyzed and compared to those of a control group of patients treated only with embolization of ECA branches and matched by age, stage, angiographic pattern, surgical approach, and previous surgery. RESULTS: Ninety-two patients were included. Embolization of branches of the ICA was attempted in 14 cases of advanced or recurrent tumors and was ultimately possible in nine cases. There were no complications after embolization. The mean intraoperative blood loss was 1428 mL. Residual disease was found in three cases (33%). There was no significant difference compared with the control group (mean intraoperative blood loss = 1355 mL, residual disease = 4 (44%); all P > .05). CONCLUSION: In this retrospective study, we report the feasibility of superselective embolization of ICA branches in selected cases of JNA. There was no observed benefit of this technique in terms of intraoperative bleeding or decreased risk of residual disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E775-E780, 2021.

Loss of smell in patients with COVID-19: MRI data reveal a transient edema of the olfactory clefts.

OBJECTIVE: To assess the physiopathology of olfactory function loss (OFL) in patients with coronavirus disease 2019 (COVID-19), we evaluated the olfactory clefts (OC) on MRI during the early stage of the disease and 1 month later. METHODS: This was a prospective, monocentric, case-controlled study. Twenty severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-infected patients with OFL were included and compared to 20 age-matched healthy controls. All infected patients underwent olfactory function assessment and 3T MRI, performed both at the early stage of the disease and at the 1-month follow-up. RESULTS: At the early stage, SARS-CoV2-infected patients had a mean olfactory score of 2.8 ± 2.7 (range 0-8), and MRI displayed a complete obstruction of the OC in 19 of 20 patients. Controls had normal olfactory scores and no obstruction of the OC on MRI. At the 1 month follow-up, the olfactory score had improved to 8.3 ± 1.9 (range 4-10) in patients, and only 7 of 20 patients still had an obstruction of the OC. There was a correlation between olfactory score and obstruction of the OC (p = 0.004). CONCLUSION: OFL in SARS-CoV2-infected patients is associated with a reversible obstruction of the OC.

Association of spontaneous cerebrospinal fluid rhinorrhea with transverse venous sinus stenosis: a retrospective matched case-control study.

BACKGROUND: A significant proportion of spontaneous cerebrospinal fluid (sCSF) leaks are associated with idiopathic intracranial hypertension (IIH). The aim of this study was to assess the association between sCSF rhinorrhea and transverse venous sinus stenosis (VSS), a feature commonly observed in IIH with a proposed role in its pathophysiology. METHODS: In this single-center, retrospective, matched case-control study, venous and pituitary imaging data of consecutive patients undergoing endoscopic surgery for sCSF rhinorrhea over the last 10 years were retrospectively reviewed. Measurement of the height of the pituitary gland was used to assess empty sella and VSS was quantified as the ratio between the minimal area of the transverse sinus and the cross-sectional area of the sigmoid sinus. VSS was considered significant when it was ≥50% and bilateral. Cases were compared with 1:1 age- and sex-adjusted controls explored for causes other than IIH, intracranial mass effect, or venous thrombosis. RESULTS: Twenty-nine patients were included (median age 56 years, females 69%, body mass index [BMI] 33.8 kg/m2 ). Cases had a significantly lower height of the pituitary gland than controls (2.5 mm vs 6.6 mm, p < 0.001). Bilateral VSS was found in 23 of 29 cases (79%; 95% confidence interval [CI], 65% to 94%) vs 3 of 29 controls (10%; 95% CI, 0% to 21%), with p < 0.001. CONCLUSION: In this retrospective study, sCSF leaks were strongly associated with VSS. This novel finding provides a rationale for further investigation of the role of VSS in the onset of sCSF leaks and of the potential interest in venous stenting after the surgical repair of leaks.

Efficacy of local budesonide therapy in the management of persistent hyposmia in COVID-19 patients without signs of severity: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To assess the efficacy of local intranasal treatment with budesonide (nasal irrigation), in addition to olfactory rehabilitation, in the management of loss of smell in COVID-19 patients without signs of severity and with persistent hyposmia 30 days after the onset of symptoms. To search for an association between the presence of an obstruction on MRI and the severity of olfactory loss, at inclusion and after 30 days of treatment. TRIAL DESIGN: Two center, open-label, 2-arm (1:1 ratio) parallel group randomized controlled superiority trial. PARTICIPANTS: Inclusion criteria - Patient over 18 years of age; - Patient with a suspected SARS-CoV-2 infection, whether or not confirmed by PCR, or close contact with a PCR-confirmed case, typical chest CT scan (unsystematic frosted glass patches with predominantly sub-pleural appearance, and at a later stage, alveolar condensation without excavation or nodules or masses) or positive serology ; - Patient with isolated sudden onset hyposmia persisting 30 days after the onset of symptoms of CoV-2 SARS infection; - Affiliate or beneficiary of a social security scheme; - Written consent to participate in the study. Non-inclusion criteria - Known hypersensitivity to budesonide or any of the excipients; - Hemostasis disorder or epistaxis; - Oral-nasal and ophthalmic herpes virus infection; - Long-term corticosteroid treatment; - Treatment with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone and HIV protease inhibitors); - Severe forms of SARS-CoV-2 with respiratory or other signs; - Hyposmia persisting for more than 90 days after the onset of symptoms - Other causes of hyposmia found on interrogation or MRI; - Patient benefiting from a legal protection measure; - Pregnant or breastfeeding women. The participants will be recruited from: Hôpital Fondation Adolphe de Rothschild and Hôpital Lariboisière in Paris, France INTERVENTION AND COMPARATOR: Intervention: Experimental group: Nasal irrigation with budesonide and physiological saline (Budesonide 1mg/2mL diluted in 250mL of physiological saline 9°/00): 3 syringes of 20mL in each nasal cavity, morning and evening, for 30 days, in addition to olfactory rehabilitation twice a day. CONTROL GROUP: Nasal irrigation with physiological saline 9°/00 only: 3 syringes of 20cc in each nasal cavity, morning and evening, for 30 days, in addition to olfactory rehabilitation twice a day. MAIN OUTCOMES: Percentage of patients with an improvement of more than 2 points on the ODORATEST score after 30 days of treatment. RANDOMISATION: Patients will be randomized (1:1) between the experimental and control groups, using the e-CRF. The randomization list will be stratified by centre. BLINDING (MASKING): Participants and caregivers are aware of the group assignment. People assessing the outcomes are blinded to the group assignment Numbers to be randomised (sample size) 120 patients are planned to be randomized into two groups of 60 patients. TRIAL STATUS: MDL_2020_10. Version number 2, May 22, 2020. Recruitment started on May 22, 2020. The trial will finish recruiting by August 2020. TRIAL REGISTRATION: EUDRACT number: 2020-001667-85; date of trial registration: 15 May 2020 Protocol registered on ClinicalTrial.gov, registration number: NCT04361474 ; date of trial registration: 24 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Relationship between video head impulse test, ocular and cervical vestibular evoked myogenic potentials, and compartmental magnetic resonance imaging classification in menière's disease.

OBJECTIVES/HYPOTHESIS: Currently, it is possible to assess in vivo the morphology of each compartment of the endolymphatic spaces 4 hours after an intravenous administration of gadolinium on magnetic resonance imaging (MRI). The aim of this study was to assess the correlation between otolithic and ampullar functions (cervical vestibular evoked myogenic potential [cVEMP], ocular vestibular evoked myogenic potential [oVEMP], video head impulse test [VHIT]) and delayed inner ear MRI based on a compartmental, anatomically based classification that included the cochlea, the saccule, the utricle, and the ampullas. STUDY DESIGN: Retrospective case-control study. METHODS: In this retrospective study, we performed three-dimensional fluid-attenuated inversion recovery sequences with delayed acquisition in 26 healthy subjects and 31 definite Menière's disease (MD) patients. Each subject was then graded on MRI on the basis on cochlear, saccular, utricular, and ampullar hydrops in MD patients. All patients underwent pure-tone audiometry, VHIT, cVEMP, and oVEMP testing. RESULTS: Cochlear, saccular, utricular, and ampullar hydrops were found on MRI in 88%, 91%, 50%, and 8.5% respectively. We found no significant correlation between the presence of saccular hydrops versus cVEMP, utricular hydrops versus oVEMP, and ampullar hydrops versus VHIT. However, the severity of endolymphatic hydrops on MRI was correlated to the degree of hearing loss. CONCLUSIONS: We proposed a compartmental, anatomically based classification for endolymphatic hydrops on MRI, which included the whole vestibular compartment. Using this classification, we observed increasing morphological changes as the disease evolved, affecting first the saccule, then the utricle, and finally the ampullas. The severity of vestibular endolymphatic hydrops is only correlated to hearing loss severity. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:E444-E452, 2020.

Multimodal strategy for the management of sphenoid osteoradionecrosis: Preliminary results.

OBJECTIVE: Osteoradionecrosis (ORN) of the sphenoid is a rare but potentially lethal complication that can occur after irradiation of nasopharyngeal and clival malignancies. The objective of this study was to describe a multimodal treatment strategy tailored to the clinical signs and to the radiological extent of the disease, and to report on its preliminary results. METHODS: Retrospective monocentric study at a tertiary skull base center. Patients treated for a sphenoid ORN from January 2014 to August 2018 were identified and charts were retrospectively reviewed for demographics, histologic tumor type, previous treatments of the tumor, clinical signs at presentation, radiological data, treatment, and outcomes. Sphenoid ORN was treated by a combination of medical therapy, endovascular treatment, and/or surgery. The use of each of these therapeutic modalities was based on the extent of ORN and on the presenting signs. RESULTS: Seven patients were included: four patients underwent endovascular treatment with occlusion of the internal carotid artery, five patients underwent surgical debridement, and covering of the exposed bone by a local flap, seven patients received antibiotics (in combination with pentoxyphilline, tocopherol, and clodronate in one case). Three patients died after progression of the ORN. The global survival rate was 57% (4/7) with a mean follow-up of 24 months. In one case, ORN was treated successfully by medical treatment only, with a combination of antibiotics, pentoxyphilline, tocopherol, and clodronate. CONCLUSION: This retrospective study describes the results of a management strategy adapted to the extent of the disease in sphenoid ORN and based on medical therapy only, or on a combination of medical therapy, interventional radiology, and/or surgery. LEVEL OF EVIDENCE: 4.

Olfactory and Gustatory Dysfunction as An Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study.

OBJECTIVE: Evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in COVID-19 patients Study Design: Multicenter Case Series Setting: 5 tertiary care hospitals (3 in China, 1 in France, 1 in Germany) Subjects and Methods: 394 PCR confirmed COVID-19 positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and Visual Analogue Scale (VAS) were used to quantify olfactory and gustatory dysfunction respectively. All subjects at one hospital (Shanghai) without subjective olfactory complaints underwent objective testing. RESULTS: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n=239), German (n=39) and French (n=116) cohorts were 32%, 69%, and 49% 138 respectively. The median age of included subjects was 39 years old, 92/161 (57%) were male, and 10/161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10/90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. 43% (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. CONCLUSIONS: Olfactory and/or gustatory disorders may represent early or isolated symptoms of SARS-CoV-2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

Olfactory and Gustatory Dysfunction as an Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study.

OBJECTIVE: To evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in coronavirus disease 2019 (COVID-19) patients. STUDY DESIGN: Multicenter case series. SETTING: Five tertiary care hospitals (3 in China, 1 in France, 1 in Germany). SUBJECTS AND METHODS: In total, 394 polymerase chain reaction (PCR)-confirmed COVID-19-positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and visual analog scale (VAS) were used to quantify olfactory and gustatory dysfunction, respectively. All subjects at 1 hospital (Shanghai) without subjective olfactory complaints underwent objective testing. RESULTS: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n = 239), German (n = 39), and French (n = 116) cohorts was 32%, 69%, and 49%, respectively. The median age of included subjects was 39 years, 92 of 161 (57%) were male, and 10 of 161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10 of 90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. Forty-three percent (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. CONCLUSIONS: Olfactory and/or gustatory disorders may represent early or isolated symptoms of severe acute respiratory syndrome coronavirus 2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

Pharmacoepigenomics of opiates and methadone maintenance treatment: current data and perspectives.

Current treatments of opioid addiction include primarily maintenance medications such as methadone. Chronic exposure to opiate and/or long-lasting maintenance treatment induce modulations of gene expression in brain and peripheral tissues. There is increasing evidence that epigenetic modifications underlie these modulations. This review summarizes published results on opioid-induced epigenetic changes in animal models and in patients. The epigenetic modifications observed with other drugs of abuse often used by opiate abusers are also outlined. Specific methadone maintenance treatment induced epigenetic modifications at different treatment stages may be combined with the ones resulting from patients' substance use history. Therefore, research comparing groups of addicts with similar history and substances use disorders but contrasting for well-characterized treatment phenotypes should be encouraged.