Local Anesthesia Round Window Plugging and Simultaneous Vibrant Soundbridge Implant for Superior Semicircular Canal Dehiscence

The aim of the present study is to report the outcomes of round window reinforcement surgery performed with the application of a Vibrant Soundbridge middle ear implant (VSB; MED-EL) in a patient with superior semicircular canal dehiscence (SSCD) who presented with recurrent vertigo, Tullio phenomenon, Hennebert's sign, bone conduction hypersensitivity, and bilateral moderate to severe mixed hearing loss. Vestibular evoked myogenic potentials (VEMPs) and high-resolution computed tomography (HRCT) confirmed bilateral superior semicircular canal dehiscence while this was not seen in magnetic resonance imaging. The surgical procedure was performed in the right ear as it had worse vestibular and auditory symptoms, a poorer hearing threshold, and greatly altered HRCT and VEMPs findings. With local-assisted anesthesia, round window reinforcement surgery (plugging) with perichondrium was performed with simultaneous positioning of a VSB on the round window niche. At the one and 3 months follow-up after surgery, VSB-aided hearing threshold in the right ear improved to mild, and loud sounds did not elicit either dizziness or pain in the patien

Effects on Posture of a Two-Diopter Horizontal Prism Base Out on the Non-Dominant Eye

Background/Objectives: Ocular proprioception is implicated in balance control and heterophoria is associated with abnormal posture, though previous research focused mainly on the role of vertical phoria and the use of vertical prisms. This study aims to evaluate whether ocular misalignment and prismatic correction of horizontal phoria affect posture. Methods: Sixty-nine (N = 69) young healthy subjects were included and equally divided by horizontal distance phoria: orthophoria (n = 23), esophoria (n = 23) and exophoria (n = 23). A prism of low power (two-diopter) was placed base out on the non-dominant eye, reducing misalignment in esophorics and increasing it in exophorics more than in orthophorics. Dynamic computerized posturography was performed with the sensory organization test protocol (SOT) of the EquiTest® NeuroCom® version 8 platform both without and with prism, always maintaining subjects unaware of prism use. A mixed model for repeated measures analysis of variance was run to evaluate the main effect of prism and the interaction effect of prism with baseline phoria. Results: Composite movement strategy score without prism was 88.1 ± 2.8% (ankle-dominant strategy) and slightly increased to 89.0 ± 3.1% with prism insertion (p = 0.004), further shifting toward ankle strategy. Composite equilibrium score without prism was 80.3 ± 6.5% and remained stable with prism insertion (81.3 ± 8.2%, p = 0.117), medio-lateral and antero-posterior projection of center of gravity did not displace significantly under prism insertion (p = 0.652 and p = 0.270, respectively). At baseline, posturographic parameters were statistically independent of individual phoria, and no significant interaction between prism insertion and individual phoria was documented for any parameters (p > 0.05 for all). Secondary analysis and pairwise comparisons confirmed that the effect of prism was strongly selective on condition SOT 5 (eyes-closed, platform sway-referenced) with improvement of equilibrium (70.4 ± 9.7% with prism vs. 65.7 ± 11.6% without) and more use of ankle strategy (81.6 ± 5.3% with prism vs. 78.2 ± 6.0% without), without any interaction of phoria and ocular dominance, while the other conditions were comparable with and without prism. Conclusions: A two-diopter prism base out on the non-dominant eye induces the body to use the ankle joint more independently of individual phoria, suggesting a small improvement in postural control, while maintaining oscillations of the center of gravity unaltered. Prism seems to enhance the function of vestibular system selectively. Phoria adjustments with prismatic correction enable intervention in postural behavior. Extraocular muscles could act as proprioceptors influencing postural stability

The incidence of vestibular neuritis in Italy

ObjectiveThis study aims to estimate the incidence of Vestibular neuritis (VN) in three different districts in Italy, its epidemiological features, and the prevalence of comorbidities associated with it. MethodsAn observational prospective study of 198 patients referred to ENT departments in Siena, Grosseto, and Cuneo was carried out over a 2-year period. Each patient underwent a complete otoneurologic examination in the first 48 h from the onset of symptoms and a brain MRI in the early stages of the disease. The follow-up lasted for 1 year. ResultsThe total VN incidence rate of the three municipalities was 48.497 (95% CI: 48.395-48.598) and its standardized value was 53.564 (95% CI: 53.463-53.666). The total VN incidence rate for the whole sample (municipality and district of the three centers) was 18.218 (95% CI: 18.164-18.272), and its standardized value was 20.185 (95% CI: 20.129-20.241). A significant difference was highlighted between patients living in the city compared to those living in the surrounding area (p < 0.000), this may be due to the ease of reaching the otoneurological referral center. ConclusionThe total incidence rate for the three municipalities was 48.497. This result is higher than previously reported studies

Frequency-dependent reduction of cybersickness in virtual reality by transcranial oscillatory stimulation of the vestibular cortex

Virtual reality (VR) applications are pervasive of everyday life, as in working, medical, and entertainment scenarios. There is yet no solution to cybersickness (CS), a disabling vestibular syndrome with nausea, dizziness, and general discomfort that most of VR users undergo, which results from an integration mismatch among visual, proprioceptive, and vestibular information. In a double-blind, controlled trial, we propose an innovative treatment for CS, consisting of online oscillatory imperceptible neuromodulation with transcranial alternating current stimulation (tACS) at 10 Hz, biophysically modelled to reach the vestibular cortex bilaterally. tACS significantly reduced CS nausea in 37 healthy subjects during a VR rollercoaster experience. The effect was frequency-dependent and placebo-insensitive. Subjective benefits were paralleled by galvanic skin response modulation in 25 subjects, addressing neurovegetative activity. Besides confirming the role of transcranially delivered oscillations in physiologically tuning the vestibular system function (and dysfunction), results open a new way to facilitate the use of VR in different scenarios and possibly to help treating also other vestibular dysfunctions

Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma

Background: The impact of the order of treatment with checkpoint inhibitors or BRAF/MEK inhibitors on the development of brain metastases in patients with metastatic unresectable BRAFV600-mutant melanoma is unknown. The SECOMBIT trial examined the impact of the order of receipt of these treatments in such patients. Methods: In this three-arm trial, we reviewed patients without brain metastases who received the BRAF/MEK inhibitors encorafenib and binimetinib until they had progressive disease followed by the immune checkpoint inhibitors ipilimumab and nivolumab (arm A); or treatment with ipilimumab and nivolumab until they had progressive disease followed by encorafenib and binimetinib (arm B); or treatment with encorafenib and binimetinib for 8 weeks followed by ipilimumab and nivolumab until they had progressive disease followed by retreatment with encorafenib arm binimetinib (arm C). Results: Brain metastases were discovered during the trial in 23/69 patients in arm A, 11/69 in arm B, and 9/68 in arm C. At a median follow-up of 56 months, the 60-month brain metastases-free survival rates were 56% for arm A, 80% for arm B (hazard ratio [HR] vs. A: 0.40, 95% confidence interval [CI] 0.23 to 0.58), and 85% for arm C (HR vs. A: 0.35, 95% CI 0.16 to 0.76). Conclusions: In patients with unresectable metastatic melanoma, the treatment sequence of immune checkpoint inhibition followed by BRAF/MEK inhibitors was associated with longer periods of new brain metastases-free survival than the reverse sequence. A regimen in which immune checkpoint inhibition was sandwiched between BRAF/MEK inhibition also appeared to be protective against brain metastases

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

Pathogen-sugar interactions revealed by universal saturation transfer analysis

Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an “end-on” manner. uSTA-guided modeling and a high-resolution cryo–electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)