Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics.

Hearing impairment is the most common sensory disorder in humans, and yet hardly any medications are licensed for the treatment of inner ear pathologies. Intricate pharmacokinetic examinations to better understand drug distribution within this complex organ could facilitate the development of novel therapeutics. For such translational research projects, animal models are indispensable, but differences in inner ear dimensions and other anatomical features complicate the transfer of experimental results to the clinic. The gap between rodents and humans may be bridged using larger animal models such as non-human primates. However, their use is challenging and impeded by administrative, regulatory, and financial hurdles. Other large animal models with more human-like inner ear dimensions are scarce. In this study, we analyzed the inner ears of piglets as a potential representative model for the human inner ear and established a surgical approach for intracochlear drug application and subsequent apical sampling. Further, controlled intracochlear delivery of fluorescein isothiocyanate-dextran (FITC-d) was carried out after the insertion of a novel, clinically applicable CE-marked cochlear catheter through the round window membrane. Two, six, and 24 hours after a single injection with this device, the intracochlear FITC-d distribution was determined in sequential perilymph samples. The fluorometrically assessed concentrations two hours after injection were compared to the FITC-d content in control groups, which either had been injected with a simple needle puncture through the round window membrane or the cochlear catheter in combination with a stapes vent hole. Our findings demonstrate not only significantly increased apical FITC-d concentrations when using the cochlear catheter but also higher total concentrations in all perilymph samples. Additionally, the concentration decreased after six and 24 hours and showed a more homogenous distribution compared to shorter observation times.

Combined Open Surgical and Endoscopic Approach for Management of a Meningoencephalocele After Iatrogenic Perforation of the Anterior Skull Base in a Young Infant.

Traumatic iatrogenic perforation of the anterior skull base is a rare complication following endonasal intubation in preterm infants. Subsequent meningoencephaloceles with concomitant cerebrospinal fluid (CSF) fistulas bear the risk of severe complications, therefore early diagnosis and closure of the skull defect are crucial. However, there is no consensus on the management of such cases of meningoencephaloceles. This case report presents a sophisticated approach of open brain surgery in combination with endonasal endoscopy. A 15-month-old girl presented with a meningoencephalocele and a CSF fistula due to iatrogenic perforation of the left anterior skull base during attempted endonasal intubation after birth. Difficult nasal breathing and an increasing diameter of the skull base defect on imaging controls indicated surgical management. Close multidisciplinary collaboration was essential for diagnosis and decision upon treatment. Open neurosurgical resection and CSF fistula closure combined with endonasal endoscopic removal of the excised meningoencephalocele was performed. Our case report shows that this combined open surgical and endonasal endoscopic approach is a safe procedure in favor of the postoperative outcome and follow-up of the patient.

Intranasal application of adeno-associated viruses: a systematic review.

Adeno-associated viruses (AAVs) represent some of the most commonly employed vectors for targeted gene delivery and their extensive study has resulted in the approval of multiple gene therapies to treat human diseases. The intranasal route of vector application in gene therapy offers several advantages over traditional ways of administration. In addition to targeting local tissue like the olfactory epithelium, it provides minimally invasive access to various organ systems, including the central nervous system and the respiratory tract. Through a systematic literature review, a total of 53 articles that investigated the intranasal application of AAVs were identified, included, and summarized in this manuscript. Within these studies, AAV-based gene therapy was mainly investigated for its application in various infectious, pulmonary, or neurologic and/or psychiatric diseases. This review gives a comprehensive overview of the current technological state of the art regarding the intranasal application of AAVs for gene transfer and discusses remaining hurdles, which still have to be resolved before this approach can effectively be implemented in the routine clinical setting.

Peaks in online inquiries into pharyngitis-related symptoms correspond with annual incidence rates.

OBJECTIVE: To assess whether web-based public inquiries into pharyngitis-related search terms follow annual incidence peaks of acute pharyngitis in various countries from both hemispheres. METHODS: Google Trends (GT) was utilized for systematic acquisition of pharyngitis-related search terms (sore throat, cough, fever, cold). Six countries from both hemispheres including four English (United Kingdom, United States, Canada, and Australia) and two non-English speaking countries (Austria and Germany) were selected for further analysis. Time series data on relative search interest for pharyngitis-related search terms, covering a timeframe between 2004 and 2019 were extracted. Following reliability analysis using the intra-class correlation coefficient, the cosinor time series analysis was utilized to determine annual peaks in public-inquiries. RESULTS: The extracted datasets of GT proved to be highly reliable with correlation coefficients ranging from 0.83 to 1.0. Graphical visualization showed annual seasonal peaks for pharyngitis-related search terms in all included countries. The cosinor time series analysis revealed these peaks to be statistically significant during winter months (all p < 0.001). CONCLUSION: Our study revealed seasonal variations for pharyngitis-related terms which corresponded to winter incidence peaks of acute pharyngitis. These results highlight the need for easily accessible information on diagnosis, therapy, and red-flag symptoms for this common disease. Accurately informed patients might contribute to a reduction of unnecessary clinic visits and potentially cutback the futile antibiotic overuse.