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International audience; Background: Magnetic resonance imaging (MRI) is the gold standard in the etiological assessment of a persistent olfactory dysfunction (OD). While the utility of imaging in COVID-19-related OD has yet to be established, MRI is recommended in all patients with persistent OD. The high prevalence of the latter after SARS-CoV-2 infection means evaluating this strategy is an important public health matter.Methods:The main objective was to examine the impact of systematic MRI on the management of patients with OD. All adult patients consulting for persistent OD (>2 months) after primary SARS-COV-2 infection (PCR) between March 2020 and December 2021 were included (n = 67). The secondary objective was to evaluate the relationship between the severity of the OD as measured by psychophysical testing (ETOC) and the volume of the olfactory bulb (OB) measured by MRI.Results: All patients underwent MRI, and none led to a change in diagnosis or treatment. Among them, 82% (55/67) were considered normal by the radiologist on initial interpretation. There were no significant differences (visual analysis or OB volume) between groups (mild, moderate, and severe hyposmia).Conclusion: Systematic MRI may be unnecessary in patients whose persistent OD began soon (a few days) after confirmed SARS-CoV-2 infection.

Surveillance imaging is a valid management option for selected vestibular schwannomas (VS). An ideal protocol for radiologic monitoring would highlight growth-related risk factors and tailor management accordingly. This study aims to identify variables associated with the growth of sporadic VS to enhance surveillance imaging, enable early intervention, and optimize outcomes.The review was conducted according to the PRISMA guidelines. A systematic review of 5 databases (PubMed, Ovid, Cochrane Library, Web of Science, and Google Scholar) was performed to identify negative and positive growth predictors of sporadic vestibular schwannomas. The search was limited to studies reported between January 2015 and January 2020. We conducted an individual patient data meta-analysis using a 1-stage multivariate mixed-effect logistic regression model.A total of 437 studies were identified, of which 25 met our criteria for full-text analysis. Articles that measured VS with comparable methods were determined eligible for meta-analysis inclusion. The selected articles were highly heterogeneous in their use of grading scales and assessment of tumor size. Our review showed that size at diagnosis (odds ratio, 1.15; 95% confidence interval, 1.11-1.18; P0.0001) and intracanalicular localization (odds ratio, 0.49; 95% confidence interval, 0.26-0.90; P = 0.023) were associated with VS growth.The factors most frequently reported as being associated with growth within the literature were size of VS at diagnosis and localization of an intracanalicular component. Greater attention should be placed on these criteria within the surveillance imaging algorithm for VS.

ImportanceThere is no consensus on the benefits of routine magnetic resonance imaging (MRI) of the facial nerve in patients with suspected idiopathic peripheral facial palsy (PFP) (ie, Bell palsy [BP]).ObjectivesTo estimate the proportion of adult patients in whom MRI led to correction of an initial clinical diagnosis of BP; to determine the proportion of patients with confirmed BP who had MRI evidence of facial nerve neuritis without secondary lesions; and to identify factors associated with secondary (nonidiopathic) PFP at initial presentation and 1 month later.Design, Setting, and ParticipantsThis retrospective multicenter cohort study analyzed the clinical and radiological data of 120 patients initially diagnosed with suspected BP from January 1, 2018, to April 30, 2022, at the emergency department of 3 tertiary referral centers in France.InterventionsAll patients screened for clinically suspected BP underwent an MRI of the entire facial nerve with a double-blind reading of all images.Main Outcomes and MeasuresThe proportion of patients in whom MRI led to a correction of the initial diagnosis of BP (any condition other than BP, including potentially life-threating conditions) and results of contrast enhancement of the facial nerve were described.ResultsAmong the 120 patients initially diagnosed with suspected BP, 64 (53.3%) were men, and the mean (SD) age was 51 (18) years. Magnetic resonance imaging of the facial nerve led to a correction of the diagnosis in 8 patients (6.7%); among them, potentially life-threatening conditions that required changes in treatment were identified in 3 (37.5%). The MRI confirmed the diagnosis of BP in 112 patients (93.3%), among whom 106 (94.6%) showed evidence of facial nerve neuritis on the affected side (hypersignal on gadolinium-enhanced T1-weighted images). This was the only objective sign confirming the idiopathic nature of PFP.Conclusions and RelevanceThese preliminary results suggest the added value of the routine use of facial nerve MRI in suspected cases of BP. Multicentered international prospective studies should be organized to confirm these results.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a typical type-2 inflammation involving several cytokines and is associated with epithelial cell dysfunction. Oncostatin M (OSM) (belonging to the interleukin(IL)-6 family) could be a key driver of epithelial barrier dysfunction. Therefore, we investigated the presence of OSM and IL-6 and the expression pattern of tight junctions (TJs) in the nasal tissue of CRSwNP patients and controls using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Then, their potential role in the epithelial barrier was evaluated in vitro in 27 different primary cultures of human nasal epithelial cells (HNECs) by measuring TJ expression and transepithelial electric resistance (TEER) with or without OSM or IL-6 (1, 10, and 100 ng/mL). The effect on ciliary beating efficiency was evaluated by high-speed videomicroscopy and on repair mechanisms with a wound healing model with or without OSM. OSM and IL-6 were both overexpressed, and TJ (ZO-1 and occludin) expression was decreased in the nasal polyps compared to the control mucosa. OSM (100 ng/mL) but not IL-6 induced a significant decrease in TJ expression, TEER, and ciliary beating efficiency in HNECs. After 24 h, the wound repair rate was significantly higher in OSM-stimulated HNECs at 100 ng/mL. These results suggest that OSM could become a new target for monoclonal antibodies.

Background: Malaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories. There is therefore a need for an alternative route for malaria pre-referral treatment. The aim of this study was to assess the potential of intranasal route for malaria pre-referral treatment.Methods: The permeability of artesunate through human nasal mucosa was tested in vitro. The Transepithelial Electrical Resistance (TEER) of the nasal mucosa was followed during the permeation tests. Beside, regional deposition of artesunate powder was assessed with a unidose drug delivery device in each nostril of a nasal cast. Artesunate quantification was performed using Liquid Chromatography coupled to tandem Mass Spectrometry. Results: The experimental model of human nasal mucosa was successfully implemented. Using this model, artesunate powder showed a much better passage rate through human nasal mucosa than solution (26.8 ± 6.6% versus 2.1 ± 0.3%). More than half (62.3%) of the artesunate dose sprayed in the nostrils of the nasal cast was recovered in the olfactory areas (44.7 ± 8.6%) and turbinates (17.6 ± 3.3%) allowing nose-to-brain and systemic drug diffusion, respectively.Conclusion: Artesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment.

Background Malaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories. There is, therefore, a need for an alternative route for malaria pre-referral treatment. The aim of this study was to assess the potential of intranasal route for malaria pre-referral treatment. Methods The permeability of artesunate through human nasal mucosa was tested in vitro. The Transepithelial Electrical Resistance (TEER) of the nasal mucosa was followed during the permeation tests. Beside, regional deposition of artesunate powder was assessed with an unidose drug delivery device in each nostril of a nasal cast. Artesunate quantification was performed using Liquid Chromatography coupled to tandem Mass Spectrometry. Results The experimental model of human nasal mucosa was successfully implemented. Using this model, artesunate powder showed a much better passage rate through human nasal mucosa than solution (26.8 ± 6.6% versus 2.1 ± 0.3%). More than half (62.3%) of the artesunate dose sprayed in the nostrils of the nasal cast was recovered in the olfactory areas (44.7 ± 8.6%) and turbinates (17.6 ± 3.3%) allowing nose-to-brain and systemic drug diffusion, respectively. Conclusion Artesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment.

Surgery and hearing aids have similar outcomes in terms of hearing acuity but differ in terms of cost, aesthetics, and patient quality of life. The cost-effectiveness and budget impact of otosclerosis treatments have never been studied in Europe.To compare the estimated mean costs per patient over 10 years of surgery vs hearing aids for the treatment of otosclerosis and to estimate the budget impact of an increase in the proportion of patients receiving surgical treatment.This economic evaluation analyzed French and European epidemiological data on the surgical management of symptomatic otosclerosis and compared them with data from the literature to build economic models. The analysis was conducted in January 2021.Two care pathways were considered in the treatment of otosclerosis, either hearing aid or surgery.Costs were studied over 10 years using Markov models of the 2 care pathways (hearing aid vs surgery). The budget impact analysis was performed over 5 and 10 years, assuming a 1-percentage point yearly increase in the proportion of patients receiving surgical treatment.Over 10 years, the estimated mean cost per patient was significantly lower in the surgery group compared with the hearing aid group (€3446.9 vs €6088.4; mean difference, -€2641.5; 95% CI -€4064.8 to -€1379.4 [US $3913.4 vs US $6912.4; mean difference, -US $2999.0; 95% CI, -US $4614.9 to -US $1566.1]). Increasing surgical treatment by 1 percentage point per year for 10 years would lead to overall savings of €1 762 304 (US $2 000 798) in France, with an increase of €1 322 920 (US $1 501 952) at 10 years for the public health insurance system and a decrease of €3 085 224 (US $3 502 750) at 10 years for patients and private health insurers. Sensitivity analyses showed that these results were robust.These results suggest that in France, treating otosclerosis surgically is slightly less expensive over 10 years than using hearing aids, when considering all payers. The proposed models developed in this study could be adjusted to perform the same analysis in other countries.

Laryngeal mobility disorder after a pediatric heart surgery is common (between 5 and 10% of cases), and has important consequences on swallowing, breathing and speaking. After reviewing the literature, the recovery rate is variable and the postoperative follow-up is often done on a short time frame. The primary objective of the study is to describe the recovery from laryngeal mobility disorder with a follow-up time of at least 5 years. The secondary objective is to describe of the quality of life of the child in terms of phonation and swallowing, and to identify potential risk factors for a lasting laryngeal mobility disorder.We collected data (morphological characteristics and details of the procedures and medical care) on children who had undergone a heart surgery with risks of complications, between 2010 and 2015, and with a laryngeal mobility disorder detected after the surgery through nasal flexible laryngoscopy. During a follow-up consultation, carried at least 5 years after the surgery, we performed a nasal flexible laryngoscopy to assess whether or not the patient had recovered a full mobility of the larynx. Two questionnaires were also given to the patients, the pVHI and the PEDI EAT-10, to assess respectively the quality of their speech and of their swallowing function.The recovery rate for a laryngeal mobility disorder more than 5 years after surgery was found to be 65% (9 children out of the 14 included in the study). We identified a risk factor for the persistence of a laryngeal mobility disorder after surgery: the presence of an associated genetic syndrome, p = 0.025. Children with persistent laryngeal mobility disorder have an impaired quality of life score, using the pVHI scale, which correlates well with the flexible laryngoscopy findings, p = 0.033.Children with a lasting laryngeal mobility disorder have disabling respiratory and vocal symptoms in their daily lives. Nasal flexible laryngoscopy should therefore be systematically performed postoperatively after a surgery carrying risks. For improved patient management, early detection of these disorders by pharyngolaryngeal nasal flexible laryngoscopy in the aftermath of high-risk cardiac surgery is strongly advised, with prolonged follow-up.

International audience; FcRn plays a major role in regulating immune homeostasis, but it is also able to transport biologics across cellular barriers. The question of whether FcRn could be an efficient transporter of biologics across the nasal epithelial barrier is of particular interest, as it would allow a less invasive strategy for the administration of biologics in comparison to subcutaneous, intramuscular or intravenous administrations, which are often used in clinical practice. A focused systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It was registered on the international prospective register of systematic reviews PROSPERO, which helped in identifying articles that met the inclusion criteria. Clinical and preclinical studies involving FcRn and the nasal delivery of biologics were screened, and the risk of bias was assessed across studies using the Oral Health Assessment Tool (OHAT). Among the 12 studies finally included in this systematic review (out of the 758 studies screened), 11 demonstrated efficient transcytosis of biologics through the nasal epithelium. Only three studies evaluated the potential toxicity of biologics’ intranasal delivery, and they all showed that it was safe. This systematic review confirmed that FcRn is expressed in the nasal airway and the olfactory epithelium, and that FcRn may play a role in IgG and/or IgG-derived molecule-transcytosis across the airway epithelium. However, additional research is needed to better characterize the pharmacokinetic and pharmacodynamic properties of biologics after their intranasal delivery.

To evaluate hearing results and outcome using two different surgical techniques (microdrill and CORetrospective audiometric database and chart review from January 2005 until December 2016.Two tertiary referral hospitals MATERIALS AND METHODS: Seven-hundred forty-two primary stapedotomy have been reviewed retrospectively in two referral hospitals. This multicenter study compared 424 patients operated for otosclerosis with microdrill technique and 318 patients operated with COThere were no statistically significant differences in demographic data between the two groups and no statistically significant difference in hearing outcome between the two groups. COThe use of CO