UMSARS Versus Laryngoscopy-Based Assessment of Dysphagia.

Background: Multiple System Atrophy (MSA) dysphagia is routinely assessed by the Unified Multiple System Atrophy Rating Scale (UMSARS) part I-item 2. Objective: To compare the UMSARS part I-item 2 with an ear/nose/throat (ENT) expert physician assessment. Methods: We retrospectively analyzed the data of MSA patients who underwent an ENT assessment (nasofibroscopic and radioscopic exam) and an annual UMSARS assessment. Deglutition Handicap Index (DHI) and pulmonary/nutrition complications were collected. Results: Seventy-five MSA patients were included. The ENT assessment revealed more severe dysphagia compared to the UMSARS part I-item 2 score (P = 0.003). A higher proportion of patients with impaired protective mechanisms showed severe UMSARS-based dysphagia (P = 0.005). Patients with choking and oral/pharyngeal transit defects and nutritional complications were equally distributed across UMSARS part I-item 2 scores. Worse UMSARS part I-item 2 scores had worse DHI scores. Conclusions: The UMSARS-based assessment of dysphagia does not capture key aspects of pharyngo-laryngeal dysfunction reflecting swallowing efficiency.

Evolution in the management of vestibular schwannoma: a single-center 15-year experience.

PURPOSE: To highlight the changes in the management of vestibular schwannoma (VS) since 2004 with a focus on small- to middle-size VS. METHODS: Retrospective analysis of the decisions made in skull base tumor board between 2004 and 2021. RESULTS: 1819 decisions were analyzed (average age 59.25, 54% females). Overall, 850 (47%) cases were allocated to a Wait and Scan (WS) approach, 416 (23%) received radiotherapy and 553 (30%) were treated surgically (MS). All stages considered WS increased from 39% before 2010 to 50% after 2010. Similarly, Stereotactic Radio Therapy (SRT) increased from 5 to 18%. MS decreased from 46 to 25%. It was more commonly proposed to younger patients and larger tumors, p < 0.001. For Koos stages 1, 2, and 3 there was a statistically significant increase in SRT, and a decrease in MS, p < 0.001. WS also increased for stages 1 and 2. However, such a trend was not observed for stage 3. MS remained the primary treatment modality for stage 4 tumors throughout the study period, p = 0.057. The significance of advanced age as a factor favoring SRT decreased over time. The opposite is true for serviceable hearing. There was also a decrease in the percentage of the justification "young age" in the MS category. CONCLUSION: The is a continuing trend towards non-surgical treatment. Small- to medium-sized VS witnessed an increase in both WS and SRT. There is only an increase in SRT for moderately large VS. Physicians are less and less considering young age as a factor favoring MS over SRT. There is a tendency towards favoring SRT when hearing is serviceable.

Exploration of the relationship between cumulative exposure to tobramycin and ototoxicity in patients with cystic fibrosis.

BACKGROUND: Aminoglycosides (AGs), such as tobramycin, are essential antibiotics in the management of pulmonary infections in patients with cystic fibrosis (CF). They induce ototoxicity without the relationship being clearly described in the literature. Our aim is to propose a mathematical and statistical model describing the relationship between the estimated cumulative exposure (Area Under the Curve, AUC) to tobramycin and ototoxicity with audiogram interpretation in young patients with CF. METHODS: Cumulative AUCs were estimated for each course of tobramycin, for the 106 individuals with CF (between 4 and 22 years of age) enrolled in this retrospective study (35 who had received IV tobramycin, 71 controls). Mean hearing loss was calculated for each audiogram and a statistical model was developed to predict hearing loss. RESULTS: The model confirms a significant relationship between cumulative tobramycin exposure and changes in hearing acuity: Meanhearingloss=2.7+(3×10-5)×AUC_tobramycin+individual_susceptibility However, the ototoxic effect is not clinically perceptible (mean hearing loss: 3.8 dB). The impact of AUC on hearing loss is minor in these subjects who received a limited number of courses of tobramycin (median: 5 courses). CONCLUSION: A significant relationship between cumulative exposure to tobramycin and ototoxicity was demonstrated. Individual treatment susceptibility should not be overlooked. As ototoxicity is not clinically perceptible in the study subjects, hearing tests should be continued during adulthood to provide individualized medical guidance and to obtain a lifetime analysis of the relationship between exposure and hearing loss.

Productive HIV-1 infection of tissue macrophages by fusion with infected CD4+ T cells.

Macrophages are essential for HIV-1 pathogenesis and represent major viral reservoirs. Therefore, it is critical to understand macrophage infection, especially in tissue macrophages, which are widely infected in vivo, but poorly permissive to cell-free infection. Although cell-to-cell transmission of HIV-1 is a determinant mode of macrophage infection in vivo, how HIV-1 transfers toward macrophages remains elusive. Here, we demonstrate that fusion of infected CD4+ T lymphocytes with human macrophages leads to their efficient and productive infection. Importantly, several tissue macrophage populations undergo this heterotypic cell fusion, including synovial, placental, lung alveolar, and tonsil macrophages. We also find that this mode of infection is modulated by the macrophage polarization state. This fusion process engages a specific short-lived adhesion structure and is controlled by the CD81 tetraspanin, which activates RhoA/ROCK-dependent actomyosin contractility in macrophages. Our study provides important insights into the mechanisms underlying infection of tissue-resident macrophages, and establishment of persistent cellular reservoirs in patients.

Can Swallowing Cerebral Neurophysiology Be Evaluated during Ecological Food Intake Conditions? A Systematic Literature Review.

Swallowing is a complex function that relies on both brainstem and cerebral control. Cerebral neurofunctional evaluations are mostly based on functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), performed with the individual laying down; which is a non-ecological/non-natural position for swallowing. According to the PRISMA guidelines, a review of the non-invasive non-radiating neurofunctional tools, other than fMRI and PET, was conducted to explore the cerebral activity in swallowing during natural food intake, in accordance with the PRISMA guidelines. Using Embase and PubMed, we included human studies focusing on neurofunctional imaging during an ecologic swallowing task. From 5948 unique records, we retained 43 original articles, reporting on three different techniques: electroencephalography (EEG), magnetoencephalography (MEG) and functional near infra-red spectroscopy (fNIRS). During swallowing, all three techniques showed activity of the pericentral cortex. Variations were associated with the modality of the swallowing process (volitional or non-volitional) and the substance used (mostly water and saliva). All techniques have been used in both healthy and pathological conditions to explore the precise time course, localization or network structure of the swallowing cerebral activity, sometimes even more precisely than fMRI. EEG and MEG are the most advanced and mastered techniques but fNIRS is the most ready-to-use and the most therapeutically promising. Ongoing development of these techniques will support and improve our future understanding of the cerebral control of swallowing.

Safety of office-based flexible endoscopic procedures of the pharynx and larynx under topical anesthesia.

INTRODUCTION: Flexible endoscopic procedures (FEP) using a working channel allowed otolaryngologists to perform more procedures on the pharynx and the larynx under local anesthesia. The purpose of this work is to demonstrate the feasibility and safety of this technique by studying the adverse effects of this practice in an office-based setting. METHODS: This is a monocentric retrospective cohort study. We searched the database using the French procedural code for FEP performed in an outpatient setting between January 2005 and December 2020. Data regarding the patient's characteristics, indications, and periprocedural complications were extracted. RESULTS: In total, we included 231 patients with a total of 308 FEP: 36% biopsy, 20% hyaluronic acid injection (including 3.5% at the level of the cavum), 20% injection of other substances (in descending order: botulinum toxin, cidofovir, physiological serum, cortisone), 20% exploration for an occult tumor, 3% samples for microbiological analysis, 1% other procedures. Of the 308 FEP included in this study, 24 patients (10.3%) had complications corresponding to 7.8% of the procedures performed. During the procedures, reported complications include minor laryngeal bleeding (n = 5), vasovagal syncope (n = 5), laryngospasm (n = 1) or nausea (n = 3), dysphagia (n = 3), and voice disorders (n = 3). Post-procedural complications were hypertensive crisis (n = 1), asthma attack (n = 1), pneumonia (n = 1), laryngitis (n = 1). Using the Clavien-Dindo classification system, these complications could be defined as grade I (laryngeal bleeding, vasovagal syncope, laryngospasm, dysphagia, nausea, voice disorders, and laryngitis) and grade II (hypertensive crisis, asthma attack, pneumonia) in 9.1% and 1.2% of cases, respectively. Most of these complications were self-limiting, while asthma attacks, pneumonia, laryngitis, and voice disorders required a medical intervention. All complications were managed without sequelae. There was no serious complication grade (no grade III, IV or V). CONCLUSIONS: FEP, which is now well standardized in our institution, makes it possible to carry out a wide range of interventions with little morbidity. These results are in line with those of literature but this technique remains out of nomenclature in France. Our experience led to the development of an evidence-based standard of care that can serve as a framework for practitioners on a nationwide level, while the work to establish official guidelines by the French society of phoniatrics and laryngology is in progress.

Stapedotomy Versus Hearing Aids in the Management of Conductive Hearing Loss Caused by Otosclerosis: A Prospective Comparative Study.

OBJECTIVE: To compare the outcomes of patients with unilateral otosclerosis treated consecutively by a hearing aid then stapedotomy. STUDY DESIGN: Monocentric, nonrandomized, prospective, longitudinal, cohort study. SETTING: Tertiary university hospital. PATIENTS: Adult patients with a unilateral conductive hearing loss of at least 30 dB caused by otosclerosis. INTERVENTIONS: Consecutive treatment by an external hearing aid followed by stapedotomy. MAIN OUTCOME MEASURES: Differences between hearing aids and stapedotomy in quality of life, pure-tone audiometry, binaural hearing, tinnitus severity, and patient satisfaction. RESULTS: Twenty-two patients were included, of which 20 (91%) underwent stapedotomy. Stapedotomy demonstrated increased quality of life according to Glasgow Health Status Inventory scores versus hearing aids (+10.4 ± 9.4 [p = 0.0001]). Stapedotomy versus hearing aids showed improved pure-tone averages (-11.1 ± 11.0 dB [p = 0.002]) and air-bone gaps (-11.8 ± 10.7 dB [p = 0.0006]). Stapedotomy was superior to hearing aids for speech-in-noise recognition in the reverse dichotic condition (-8.4 ± 26.9 dB [p = 0.004]) and showed improved sound localization accuracy in root mean square error (-14.5 ± 24.5 degrees [p = 0.02]). Stapedotomy, but not hearing aids, showed improved patient self-evaluated tinnitus after baseline adjustment according to the Tinnitus Handicap Inventory (-8.0 ± 13.4 [p = 0.02]) and visual analog scale for tinnitus intensity (-28.7 ± 34.1 [p = 0.006]). Overall, patients were more satisfied with surgery versus hearing aids. CONCLUSIONS: Stapedotomy remains more effective compared with hearing aids with greater improvements in quality of life, patient satisfaction, hearing outcomes, and self-evaluated tinnitus.

Functional Reorganization of the Central Auditory System in Children with Single-Sided Deafness: A Protocol Using fNIRS.

In children, single-sided deafness (SSD) affects the development of linguistic and social skills and can impede educational progress. These difficulties may relate to cortical changes that occur following SSD, such as reduced inter-hemispheric functional asymmetry and maladaptive brain plasticity. To investigate these neuronal changes and their evolution in children, a non-invasive technique is required that is little affected by motion artifacts. Here, we present a research protocol that uses functional near-infrared spectroscopy (fNIRS) to evaluate the reorganization of cortical auditory asymmetry in children with SSD; it also examines how the cortical changes relate to auditory and language skills. The protocol is designed for children whose SSD has not been treated, because hearing restoration can alter both brain reorganization and behavioral performance. We propose a single-center, cross-sectional study that includes 30 children with SSD (congenital or acquired moderate-to-profound deafness) and 30 children with normal hearing (NH), all aged 5-16 years. The children undergo fNIRS during monaural and binaural stimulation, and the pattern of cortical activity is analyzed using measures of the peak amplitude and area under the curve for both oxy- and deoxyhemoglobin. These cortical measures can be compared between the two groups of children, and analyses can be run to determine whether they relate to binaural hearing (speech-in-noise and sound localization), speech perception and production, and quality of life (QoL). The results could be of relevance for developing individualized rehabilitation programs for SSD, which could reduce patients' difficulties and prevent long-term neurofunctional and clinical consequences.

Using Classical Test Theory to Determine the Psychometric Properties of the Deglutition Handicap Index.

The Deglutition Handicap Index (DHI) is a self-report measure for patients at risk of oropharyngeal dysphagia on deglutition-related aspects of functional health status (FHS) and health-related quality of life (HR-QoL). The DHI consists of 30 items which are subsumed within the Symptom, Functional and Emotional subscales. The purpose of this study was to evaluate the psychometric properties of the DHI using Classic Test Theory according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. A total of 453 patients with dysphagia with different aetiologies were recruited concurrently at two academic hospitals. Dysphagia was confirmed by fiberoptic endoscopic and/or videofluoroscopic evaluation of swallowing. In addition, a healthy control group of 132 participants were recruited. Structural validity was determined using exploratory and confirmatory factor analyses and internal consistency by calculating Cronbach's alpha coefficients. Hypothesis testing was evaluated using Mann-Whitney U-tests, linear regression analysis and correlations analysis. Diagnostic performance and receiver operating characteristic curves analysis were calculated. Factor analyses indicated that the DHI is a unidimensional measure. The DHI has good internal consistency with some indication of item redundancy, weak to moderate structural validity and strong hypothesis testing for construct validity. The DHI shows high diagnostic performance as part of criterion validity. These findings support that the DHI is an appropriate choice as a patient self-report measure to evaluate FHS and HR-QoL in dysphagia. Ongoing validation to assess the measure for possible item redundancy and to examine the dimensionality of the DHI using item response theory is recommended.

Surgical treatments of superior semicircular canal dehiscence: A single-centre experience in 63 cases.

OBJECTIVE: Different procedures have been described to treat superior canal dehiscence. The present study aims to describe the results obtained with middle fossa approach, transmastoid approach, and round window reinforcement in a large series of patients. METHODS AND DESIGN: In this single-center retrospective study, we report the results of the procedures performed between 2006 and 2019 using the three main surgical approaches, middle fossa approach (MFA), transmastoid approach (TMA), and round window reinforcement (RWR). The outcome on cardinal cochlear and vestibular symptoms, audiometric results, and changes in cervical vestibular evoked myogenic potentials (cVEMPs) were analyzed. The patients were also interviewed 12 months to 13 years post-treatment to establish their overall satisfaction following surgery. RESULTS: Sixty-three patients were divided into three groups: 42 MFA; 12 RWR; 9 TMA. Postsurgical control rates exceeded 80% for the majority of symptoms in the MFA and TMA groups, and ranged from 11.1% to 83.3% for the RWR group. Over 90% of MFA or TMA patients and 60% of the RWR cohort were satisfied overall with their treatment. Hearing thresholds were intact following surgery in the MFA and TMA groups. There was one case of profound postoperative deafness in the RWR group. CONCLUSION: MFA and TMA are both safe and effective techniques in the treatment of disabling SSCD. Since MFA is the more invasive technique, we suggest that TMA should be proposed as first-line treatment, temporal bone anatomy permitting. RWR outcomes are more variable in term of symptomatic control, and this option could be offered to patients at risk under general anesthesia. LEVEL OF EVIDENCE: Level 4 evidence.

Intensity patterns at the peaks of brain activity in fMRI and PET are highly correlated with neural models of spatial integration.

Spatial integration during the brain's cognitive activity prompts changes in energy used by different neuroglial populations. Nevertheless, the organisation of such integration in 3D -brain activity remains undescribed from a quantitative standpoint. In response, we applied a cross-correlation between brain activity and integrative models, which yielded a deeper understanding of information integration in functional brain mapping. We analysed four datasets obtained via fundamentally different neuroimaging techniques (functional magnetic resonance imaging [fMRI] and positron emission tomography [PET]) and found that models of spatial integration with an increasing input to each step of integration were significantly more correlated with brain activity than models with a constant input to each step of integration. In addition, marking the voxels with the maximal correlation, we found exceptionally high intersubject consistency with the initial brain activity at the peaks. Our method demonstrated for the first time that the network of peaks of brain activity is organised strictly according to the models of spatial integration independent of neuroimaging techniques. The highest correlation with models integrating an increasing at each step input suggests that brain activity reflects a network of integrative processes where the results of integration in some neuroglial populations serve as an input to other neuroglial populations.

Multicentric phase II trial of TI-CE high-dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors.

BACKGROUND: High-dose chemotherapy (HDCT) with TI-CE regimen is a valid option for the treatment of relapsed advanced germ cell tumors (GCT). We report a phase II trial with therapeutic drug monitoring of carboplatin for optimizing area under the curve (AUC) of this drug. METHODS: Patients with unfavorable relapsed GCT were treated according to TI-CE regimen: two cycles combining paclitaxel and ifosfamide followed by three cycles of HD carboplatin plus etoposide administered on 3 days. Carboplatin dose was adapted on day 3 based on carboplatin clearance (CL) at day 1 in order to reach a target AUC of 24 mg.min/mL per cycle. The primary endpoint was the complete response (CR) rate. RESULTS: Eighty-nine patients who received HDCT were included in the modified intent-to-treat (mITT) analysis. Measured mean AUC was 24.4 mg.min/mL per cycle (22.4 and 26.8 mg.min/mL for 10th and 90th percentiles). Thirty-five (44.3%) patients achieved a CR with or without surgery of residual masses and 20 patients achieved a partial response with negative tumor markers. With a median follow-up of 44 months (m), median PFS was 12.3 m (95% CI: 7.5-25.9) and OS was 46.3 m (95% CI: 18.6-not reached). For high- and very high-risk patients, according to the International Prognostic Score at first relapse or treated after at least one salvage treatment (n = 51), 2-year PFS rate was 41.1%. CONCLUSION: The rates of complete and favorable responses were clinically relevant in this very poor risk population. Individual monitoring of carboplatin plasma concentration permitted to control more accurately the target AUC and avoided both underexposure and overexposure to the drug.

Quality of life of children treated for unilateral hearing loss: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the treatments' consequences for unilateral hearing loss in children. DESIGN: Systematic review and meta-analysis (CRD42018109417). The MEDLINE, CENTRAL, ISRCTN and ClinicalTrials databases were searched between September 2018 and May 2019. Articles were screened and data were collected independently by two authors following the Cochrane and Preferred Reporting Items for Systematic review and Meta-Analysis guidelines. The risk of bias was evaluated using the Cochrane tool, the Newcastle-Ottawa Scale, the National Institute of Health, USA tool and considering the risk of confounding. In the studies with the lowest risk of bias, a meta-analysis was conducted. INTERVENTIONS: Validated hearing rehabilitation devices. PATIENTS: 6-15 years old children with moderate to profound unilateral hearing loss. MAIN OUTCOME MEASURES: The primary study outcome was children's quality of life. Academic performances were studied as an additional outcome. RESULTS: 731 unique articles were identified from the primary search. Of these, 18 articles met the Population, Intervention, Control, Outcomes and Study design selection criteria. In the eight studies with the lowest risk of bias, two meta-analysis were conducted. There was not enough data on academic results to conduct a meta-analysis. In 73 children included in a fixed effect meta-analysis (two studies), no effect of treatment could be shown (g=-0.20, p=0.39). In 61 children included in a random-effect meta-analysis (six studies), a strong positive effect of hearing treatment on quality of life was demonstrated (g=1.32, p<0.05). CONCLUSIONS: The treatment of unilateral hearing loss seems to improve children's quality of life. Further research is needed to identify the most effective treatment and its corresponding indications.

Nontuberculous lymphadenitis in children: What management strategy?

OBJECTIVES: Nontuberculous mycobacterial (NTM) lymphadenitis is a rare disease of children under 5 years. Its treatment is not standardized, even a "wait-and-see" approach is shown to be effective in the literature. Here, we discuss the diagnostic and therapeutic strategies employed in our departments. METHODS: Records of pediatric patients treated for NTM cervical lymphadenitis from 2010 to 2015 in our tertiary center were retrospectively reviewed. Patients underwent cervical echotomography and/or CT scan. Every patient but one had microbiological explorations (NTM polymerase chain reaction [PCR] and culture) on fine needle aspiration of pus and/or adenitis biopsy. Differential diagnoses (tuberculosis, cat scratch disease) were excluded with serologies, chest X-Ray, and PCR on adenitis samples. Patients were classified as "proven diagnosis" (NTM detected), "highly probable" (suggestive clinical and anatomopathological aspect) or "possible" infection (suggestive adenitis alone). Treatments, follow-up and adverse events were reviewed. RESULTS: Thirty-one patients were treated for NTM, median age 2.40 years (Interquartile Range IQR = [1.85-3.16]). Twenty-nine patients (96.77%) had an isolated cervico-facial localization. Median follow-up was 8.00 months (IQR = [4.20-13.43]). We found 17 "proven diagnosis" (58.62%), 5 "highly probable" (17.24%) and 7 "possible" infections (24.14%). "Proven" infections were due to: Mycobacterium avium (n = 12, 66.67%) and M. intracellulare (n = 5, 27.78%). All 29 patients received antibiotics, which were effective for 10 (34.48%, group 1); 10 underwent surgical excision for a poor outcome with antibiotics (34.48%, group 2); spontaneous or surgical drainage occurred in 9 on antibiotics (31.03%, group 3). The median times to resolution for group 1, 2 and 3 were respectively 6.33 months, 6.22 months and 9.53 months. Antibiotics treatment was mostly clarithromycin (n = 27, 93.10%) and/or rifampicin (n = 19, 65.52%); 18 patients (62.07%) received both. Median antibiotics duration was 6.23 months (IQR = [5.17-7.46]), with good compliance (79.31%). The observed adverse effects were 3 (13.04%) isolated transient transaminase elevations, 1 case (4.35%) of minor creatinine elevation, and 1 case (4.35%) of transient diarrhea. Surgical drainage caused 1 transient marginal mandibular nerve palsy, resolutive after 1 month. CONCLUSION: Antibiotics in NTM adenitis lead to resolution in 7 months, with good tolerance and compliance. The efficacy of "wait-and-see" attitude in the literature make excision surgery a second line treatment.

Association of the Duration of Antibiotic Therapy With Major Surgical Site Infection in Cochlear Implantation.

Importance: Infection after cochlear implantation is a rare but serious event that can lead to meningitis. There is no consensus on prevention of infection in these patients, and each center applies its own strategy. Objective: To describe the rates of major surgical site infection for patients undergoing cochlear implantation who receive prolonged antibiotic treatment compared with those who receive a single perioperative dose of antibiotic prophylaxis. Design, Setting, and Participants: Retrospective cohort study of patients who underwent cochlear implantation between January 1, 2011, and July 8, 2015, with a postoperative follow-up of 1 to 3 years. In this multicenter study at 8 French university centers, 1180 patients (509 children and 671 adults) who underwent cochlear implantation during this period were included. Interventions: Prolonged antibiotic treatment vs single-dose antibiotic prophylaxis. Main Outcomes and Measures: Major infection and explantation. Results: Among 1180 patients (509 children [51.7% female] with a mean [SD] age of 4.6 [3.8] years and 671 adults [54.9% female] with a mean [SD] age of 54.8 [17.0] years), 12 patients (1.0%) developed a major infection, with 4 infections occurring in the prolonged antibiotic treatment group and 8 infections occurring in the antibiotic prophylaxis group (odds ratio, 2.45; 95% CI, 0.73-8.17). Children (9 of 509 [1.8%]) were more likely to develop infection than adults (3 of 671 [0.4%]). Among children, 4 infections occurred in the prolonged antibiotic group (n = 344), and 5 infections occurred in the antibiotic prophylaxis group (n = 158) (odds ratio, 2.78; 95% CI, 0.74-10.49). Among adults, 3 infections occurred in the antibiotic prophylaxis group (n = 365), whereas no infections occurred in the prolonged antibiotic treatment group (n = 290). Conclusions and Relevance: After cochlear implantation, infection was rare, was less common among those who received prolonged antibiotic treatment, and was less likely to occur in adults than in children.