The method of drug delivery directly into the cochlea with an implantable pump connected to a CI electrode array ensures long-term delivery and effective dose control, and also provides the possibility to use different drugs. The objective is to develop a model of inner ear pharmacokinetics of an implanted cochlea, with the delivery of FITC-Dextran, in the non-human primate model. A preclinical cochlear electrode array (CI Electrode Array HL14DD, manufactured by Cochlear Ltd.) attached to an implantable peristaltic pump filled with FITC-Dextran was implanted unilaterally in a total of 15 Macaca fascicularis (Mf). Three groups were created (5 Mf in each group), according to three different drug delivery times: 2 hours, 24 hours and 7 days. Perilymph (10 samples, 1μL each) was sampled from the apex of the cochlea and measured immediately after extraction with a spectrofluorometer. After scarifying the specimens, x-Rays and histological analysis were performed. Surgery, sampling and histological analysis were performed successfully in all specimens. FITC-Dextran quantification showed different patterns, depending on the delivery group. In the 2 hours injection experiment, an increase in FITC-Dextran concentrations over the sample collection time was seen, reaching maximum concentration peaks (420-964µM) between samples 5 and 7, decreasing in successive samples, without returning to baseline. The 24-hours and 7-days injection experiments showed even behaviour throughout the 10 samples obtained, reaching a plateau with mean concentrations ranging from 2144 to 2564 µM and from 1409 to 2502µM, respectively. Statistically significant differences between the 2 hours and 24 hours groups (p = 0.001) and between the 2 hours and 7 days groups (p = 0.037) were observed, while between the 24 hours and 7 days groups no statistical differences were found. This experimental study shows that a model of drug delivery and pharmacokinetics using an active pump connected to an electrode array is feasible in Mf. An infusion time ranging from 2 to 24 hours is required to reach a maximum concentration peak at the apex. It establishes then an even concentration profile from base to apex that is maintained throughout the infusion time in Mf. Flow mechanisms during injection and during sampling that may explain such findings may involve cochlear aqueduct flow as well as the possible existence of substance exchange from scala tympani to extracellular spaces, such as the modiolar space or the endolymphatic sinus, acting as a substance reservoir to maintain a relatively flat concentration profile from base to apex during sampling. Leveraging the learnings achieved by experimentation in rodent models, we can move to experiment in non-human primate with the aim of achieving a useful model that provides transferrable data to human pharmacokinetics. Thus, it may broaden clinical and therapeutic approaches to inner ear diseases.

Generalization of deep learning (DL) algorithms is critical for the secure implementation of computer-aided diagnosis systems in clinical practice. However, broad generalization remains to be a challenge in machine learning. This research aims to identify and study potential factors that can affect the internal validation and generalization of DL networks, namely the institution where the images come from, the image processing applied by the X-ray device, and the type of response function of the X-ray device. For these purposes, a pre-trained convolutional neural network (CNN) (VGG16) was trained three times for classifying COVID-19 and control chest radiographs with the same hyperparameters, but using different combinations of data acquired in two institutions by three different X-ray device manufacturers. Regarding internal validation, the addition of images from an external institution to the training set did not modify the algorithm’s internal performance, however, the inclusion of images acquired by a device from a different manufacturer decreased the performance up to 8% (p < 0.05). In contrast, generalization across institutions and X-ray devices with the same type of response function was achieved. Nonetheless, generalization was not observed across devices with different types of response function. This factor was the key impediment to achieving broad generalization in our research, followed by the device’s image-processing and the inter-institutional differences, which both reduced generalization performance to 18.9% (p < 0.05), and 9.8% (p < 0.05), respectively. Finally, clustering analysis with features extracted by the CNN was performed, revealing a substantial dependence of feature values extracted by the pre-trained CNN on the X-ray device which acquired the images.

Benign paroxysmal positional vertigo (BPPV) is one of the most common disorders that causes dizziness. The incidence of horizontal semicircular canal (HSC) BPPV ranges from 5% to 40.5% of the total number of BPPV cases diagnosed. Several studies have focused on establishing methods to treat BPPV caused by the apogeotropic variant of the HSC, namely, the Appiani maneuver (App). In 2016, a new maneuver was proposed: the Zuma e Maia maneuver (ZeM), based on inertia and gravity. The aim of this study is to analyze the efficacy of App versus ZeM in the resolution of episodes of BPPV produced by an affectation of the horizontal semicircular canal with apogeotropic nystagmus (Apo-HSC). A retrospective, quasi-experimental study was conducted. Patients attended in office (November 2014–February 2019) at a third-level hospital and underwent a vestibular otoneurology assessment. Those who were diagnosed with Apo-HSC, treated with App or ZeM, were included. To consider the efficacy of the maneuvers, the presence of symptoms and/or nystagmus at the first follow up was studied. Patients classified as “A” were those with no symptoms, no nystagmus; “A/N+”: no symptoms, nystagmus present during supine roll test; “S”: symptoms present. Previous history of BPPV and/or otic pathology and calcium levels were also compiled. From the 54 patients included, 74% were women. The average age was 69. Mean follow-up: 52.51 days. In those patients without previous history of BPPV (n = 35), the probability of being group “A” was 63% and 56% (p = 0.687) when treated with App and ZeM, respectively, while being “A/N+” was 79% and 87% for App and ZeM (p = 0.508). Of the 19 patients who had previous history of BPPV, 13% and 64% were group “A” when treated with App and ZeM (p = 0.043), and 25% and 82% were “A/N+” after App and ZeM, respectively (p = 0.021). In conclusion, for HSC cupulolithiasis, ZeM is more effective than App in those cases in which there is a history of previous episodes of BPPV (“A”: 64% (p = 0.043); “A/N+”: 82% (p = 0.021)).

Nystagmus induced by applying an intense vibratory stimulus to the skull (SVIN) indicates vestibular functional asymmetry. In unilateral vestibular loss, a 100 Hz bone-conducted vibration given to either mastoid immediately causes a primarily horizontal nystagmus. The test is performed in darkness to avoid visual fixation (VF) but there are no data about how much VF affects the often-intense SVIN. The aim is to analyze the amount of reduction in SVIN when VF is allowed during testing. Thus, all patients seen in a tertiary hospital for vertigo or dizziness with positive SVIN were included. SVIN was recorded for 10 s for each condition: without VF (aSVINwo) and with VF (aSVINw). We obtained an aSVINwo and an aSVINw as average slow-phase velocities (SPV) without and with VF. VF index (FI_SVIN) was calculated as the ratio of SPV. Among the 124 patients included, spontaneous nystagmus (SN) was found in 25% and the median slow phase velocity (mSPV) (without VF) of SN was 2.6 ± 2.4°/s. Mean FI_SVIN was 0.27 ± 0.29. FI_SVIN was 0 in 42 patients, and FI_SVIN between 0 and 1 was found in 82 (mean FI_SVIN 0.39 ± 0.02). Fixation suppression was found in all patients with SVIN in cases of peripheral vestibulopathy. FI_SVIN clearly delineates two populations of patients: with or without a complete visual reduction in nystagmus.