Usher syndrome (USH), the most prevalent cause of hereditary deafness–blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1–3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods.

Functional and structural brain alterations in the absence of the auditory input have been described, but the observed structural brain changes in the deaf are not uniform. Some of the previous researchers focused only on the auditory areas, while others investigated the whole brain or other selected regions of interest. Majority of studies revealed decreased white matter (WM) volume or altered WM microstructure and preserved grey matter (GM) structure of the auditory areas in the deaf. However, preserved WM and increased or decreased GM volume of the auditory areas in the deaf have also been reported. Several structural alterations in the deaf were found also outside the auditory areas, but these regions differ between the studies. The observed differences between the studies could be due to the use of different single-analysis techniques, or the diverse population sample and its size, or possibly due to the usage of hearing aids by some participating deaf subjects. To overcome the aforementioned limitations four different image-processing techniques were used to investigate changes in the brain morphology of prelingually deaf adults who have never used hearing aids. GM and WM volume of the Heschl's gyrus (HG) were measured using manual volumetry, while whole brain GM volume, thickness and surface area were assessed by voxel-based morphometry (VBM) and surface-based analysis. The microstructural properties of the WM were evaluated by diffusion tensor imaging (DTI). The data were compared between 14 congenitally deaf adults and 14 sex- and age-matched normal hearing controls. Manual volumetry revealed preserved GM volume of the bilateral HG and significantly decreased WM volume of the left HG in the deaf. VBM showed increased cerebellar GM volume in the deaf, while no statistically significant differences were observed in the GM thickness or surface area between the groups. The results of the DTI analysis showed WM microstructural alterations between the groups in the bilateral auditory areas, including the superior temporal gyrus, the HG, the planum temporale and the planum polare, which were more extensive in the right hemisphere. Fractional anisotropy (FA) was significantly reduced in the right and axial diffusivity (AD) in the left auditory areas in the deaf. FA and AD were significantly reduced also in several other brain areas outside the auditory cortex in the deaf. The use of four different methods used in our study, although showing changes that are not directly related, provides additional information and supports the conclusion that in prelingually deaf subjects structural alterations are present both in the auditory areas and elsewhere. Our results support the findings of those studies showing that early deafness results in decreased WM volume and microstructural WM alterations in the auditory areas. As we observed WM microstructural alteration also in several other areas and increased GM volume in the cerebellum in the deaf, we can conclude that early deafness results in widespread structural brain changes. These probably reflect atrophy or degradation as well as compensatory cross-modal reorganisation in the absence of the auditory input and the use of the sign language.

The preparation of autologous platelet and extracellular vesicle-rich plasma (PVRP) has been explored in many medical fields with the aim to benefit from its healing potential. In parallel, efforts are being invested to understand the function and dynamics of PVRP that is complex in its composition and interactions. Some clinical evidence reveals beneficial effects of PVRP, while some report that there were no effects. To optimize the preparation methods, functions and mechanisms of PVRP, its constituents should be better understood. With the intention to promote further studies of autologous therapeutic PVRP, we performed a review on some topics regarding PVRP composition, harvesting, assessment and preservation, and also on clinical experience following PVRP application in humans and animals. Besides the acknowledged actions of platelets, leukocytes and different molecules, we focus on extracellular vesicles that were found abundant in PVRP.

Atypical skull-base osteomyelitis is a rare but fatal disease that usually involves infection of the ethmoid, sphenoid, occipital, or temporal bones that form the skull base. Unlike typical (so-called otogenic), atypical skull-base osteomyelitis has no otogenic cause. Instead, some authors call atypical skull-base osteomyelitis sinonasal, since the infection most often originates from the nose and paranasal sinuses. Diagnosing and treating this disease is challenging. To assist in managing atypical skull-base osteomyelitis, a review of the most recent literature, with patient cases and multidisciplinary perspectives from otolaryngologists, neurosurgeons, radiologists, infectious disease specialists, pathologists, and clinical microbiologists, is provided in this paper.

Purpose: To determine the efficacy of autologous platelet- and extracellular vesicle-rich plasma (PVRP) to treat chronic postoperative temporal bone cavity inflammation (CPTBCI) after exhausting surgical and standard conservative therapies.Materials and Methods: Patients were randomly allocated to treatment with PVRP (PVRP group) or standard conservative methods (control group) in a setting of four once-monthly checkups and subsequent follow-up. The treatment outcome was measured with the Chronic Otitis Media Questionnaire-12 (COMQ-12), CPTBCI focus surface area, and CPTBCI symptom-free time after the fourth checkup.Results: Eleven patients from each group completed the trial; 95% of patients suffered from chronically discharging mastoid cavity (the type of CPTBCI). Within four checkups, the COMQ-12 score decreased statistically significantly in the PVRP group (p< 0.001) but not in the control group (p= 0.339). The CPTBCI foci surface area decreased statistically significantly between the first and second checkups (p< 0.0005) but not between other checkups (p> 0.05) in the PVRP group. No statistically significant differences in CPTBCI foci surface area were detected between checkups in the control group (p= 0.152). Nine patients from the PVRP group and three patients from the control group were CPTBCI symptom-free at the fourth checkup. The median symptom-free time was 9.2 months (95% CI [7.4, 11.9]) in the PVRP group. Cumulatively, 49% of patients in the PVRP group remained CPTBCI symptom-free for 12.7 months after the fourth checkup.Conclusion: Autologous PVRP represents a novel additional and successful treatment modality for a chronically discharging radical mastoid cavity when the surgical and standard conservative treatment methods have been exhausted.Trial Number: https://clinicaltrials.gov(NCT04281901).