E-ABR in patients with cochlear implant: A comparison between patients with malformed cochlea and normal cochlea

OBJECTIVES: This study aims to compare the electrical auditory brainstem response (EABR) following cochlear implant (CI) surgery in pediatric subjects with cochlear malformation and a normal cochlea, in order to assess the sensitivity of EABR and to evaluate the surgery outcome. MATERIALS and METHODS: A total of 26 pediatric subjects who were deaf and scheduled for CI surgery were enrolled into this case control study. Group A (n=20) included subjects with a normo-conformed cochlea. Group B (n=6) included subjects with cochlear malformation. Subjects were evaluated with EABR immediately (T0) and 6 months (T1) post-CI surgery. The EABR Waves III and V average amplitude and latency were compared across time, separately for each group, and across groups, separately for each time. RESULTS: Auditory brainstem response (ABR) could only be recorded in Group A. We were able to record EABR from all subjects at T0 and T1, and waves III and V were present in all the recorded signals. There were no statistically significant differences between T0 and T1 in EABR Waves III and V in terms of average amplitude and latency in neither group. When comparing Groups A and B, the only statistically significant difference was the average amplitude of wave V, both at T0 and T1. CONCLUSION: EABR is a valid tool to measure the auditory nerve integrity after CI surgery in patients with a normal and malformed cochlea, as shown by its ability to measure waves III and V when ABR is absent. The EABR testing should be performed before and after CI surgery, and EABR should be used as a measure of outcome, especially in patients with a malformed cochlea

Cooperation between Prostaglandin E2 and Epidermal Growth Factor Receptor in Cancer Progression: A Dual Target for Cancer Therapy

It is recognized that prostaglandin E2 (PGE2) is one key lipid mediator involved in chronic inflammation, and it is directly implicated in tumor development by regulating cancer cell growth and migration, apoptosis, epithelial–mesenchymal transition, angiogenesis, and immune escape. In addition, the expression of the enzymes involved in PGE2 synthesis, cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES1), positively correlates with tumor progression and aggressiveness, clearly indicating the crucial role of the entire pathway in cancer. Moreover, several lines of evidence suggest that the COX2/mPGES1/PGE2 inflammatory axis is involved in the modulation of epidermal growth factor receptor (EGFR) signaling to reinforce the oncogenic drive of EGFR activation. Similarly, EGFR activation promotes the induction of COX2/mPGES1 expression and PGE2 production. In this review, we describe the interplay between COX2/mPGES1/PGE2 and EGFR in cancer, and new therapeutic strategies that target this signaling pathway, to outline the importance of the modulation of the inflammatory process in cancer fighting. © 2023 by the authors

Patient Perceptions of Effectiveness in Treatments for Menière's Disease: a National Survey in Italy

Objective: The aim of this study was to investigate current treatment practices and self-reported effectiveness in Menière's disease. Materials and Methods: Members of two Italian Menière's disease support (n=170) with ≥6-month history of Menière's disease were administered an online survey about recent treatments. Vertigo episode count, work absenteeism, and limitations in family life, social life,work or travel, as included in the Social Life and Work Impact of Dizziness (SWID) Questionnaire before and after recent treatments were queried. Results: Twenty-four different treatments were reported for Menière's disease, with dietary modifications (55%), diuretics (47%), and betahistine (41%) being most common. The majority (71%) received multiple simultaneous treatments. Prior to the most recent treatments 78-89% of respondents indicated limitations in family or social life, work or traveling. After their most recent treatment, respondents reported improvements in mean vertigo episode counts (5.7±7.6 vs. 2.6 ±4.6, p<0.001), days off work per month (10.1 ±9.2 vs. 4.2 ±6.7, p<0.001), and proportions indicating limitations in any functional measure assessed (p<0.05). These findings were consistent regardless of treatment approach (all p<0.05). Intratympanic gentamicin provided the greatest reductions in vertigo count, functional limitations, and work absenteeism (all p<0.01) as well as the fewest respondents reporting post-treatment functional limitations (16-37%). Conclusions: Despite numerous treatment approaches targeting different proposed pathophysiology for Menière's disease in this cross-sectional survey, all treatments are reported as effective by patients. These findings support a prominent placebo effect in Menière's disease and highlight challenges in studying treatment outcomes; there is a critical need to better understand Menière's disease

A Multicenter Clinical Evaluation of Data Logging in Cochlear Implant Recipients Using Automated Scene Classification Technologies

Currently, there are no studies assessing everyday use of cochlear implant (CI) processors by recipients by means of objective tools. The Nucleus 6 sound processor features a data logging system capable of real-time recording of CI use in different acoustic environments and under various categories of loudness levels. In this study, we report data logged for the different scenes and different loudness levels of 1,366 CI patients, as recorded by SCAN. Monitoring device use in cochlear implant recipients of all ages provides important information about the listening conditions encountered in recipients' daily lives that may support counseling and assist in the further management of their device settings. The findings for this large cohort of active CI users confirm differences between age groups concerning device use and exposure to various noise environments, especially between the youngest and oldest age groups, while similar levels of loudness were observed

Bidimentional in vitro angiogenic assays to study CCM pathogenesis: Endothelial cell proliferation and migration

Cerebral cavernous malformation (CCM) is a cerebrovascular disorder of proven genetic origin characterized by abnormally dilated and leaky capillaries occurring mainly in the central nervous system, with a prevalence of 0.3–0.5% in the general population. Genetic studies have identified three genes associated to CCMs: KRIT1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3), which account for about 50%, 20%, and 10% of the cases, respectively. The great advances in the knowledge of the physiopathological functions of CCM genes, such as their involvement in the angiogenic process, have allowed to propose distinct putative therapeutic compounds, which showed to be effective at least in limiting some pathological phenotypes in cellular and animal models of the disease. However, despite numerous efforts, targeted pharmacological therapies that improve the outcome of CCM disease are currently lacking. Here we describe simply and low-cost assays as in vitro endothelial cell proliferation and migration assays that can be used to better understand the role of CCM genes on endothelial cell functions and to screen potential new compounds for CCM therapy

Disease models in cerebral cavernous malformations

Cerebral cavernous malformation (CCM) is a rare disease of genetic origin characterized by dilated and leaky capillaries occurring mainly in the central nervous system. CCM can arise sporadically or may be inherited as an autosomal dominant condition with incomplete penetrance and variable clinical expressivity. The sporadic form accounts for up to 80% of cases, whereas the familial form accounts for at least 20% of cases. Genetic studies have identified three genes associated with CCMs: KRIT1 (CCM1), MGC4607 (CCM2) and PDCD10 (CCM3). Recently, great advances in understanding the pathophysiology of CCM disease have been obtained thanks to the use of animal and cellular models displaying all or some of the pathological characteristics that are observed in the human disease. Despite interspecies differences and the difficulty in creating animal models that completely recapitulate the human CCM disease onset and progression, these models have been helpful in identifying new molecular mechanisms underlying CCM development and in testing novel pharmacological therapies