Efficacy of expansion pharyngoplasty and hypoglossal nerve stimulation in treating sleep apnea.

OBJECTIVE: We investigated whether a palatal conversion procedure combined with a second-stage hypoglossal nerve stimulator (HGNS) insertion can be beneficial for those patients who have a complete concentric velopharyngeal collapse and may initially not meet the criteria for use of HGNS. METHODS: A retrospective chart review included all patients who underwent a planned multi-level sleep surgery including expansion sphincter pharyngoplasty (ESP) followed by HGNS. All patients had a complete concentric collapse (CCC) of the velopharynx (VP) on pre-intervention drug-induced sleep endoscopy (DISE) and were initially not a candidate for HGNS. These patients then underwent ESP followed by a DISE to confirm elimination of the CCC of the VP. They then went on to HGNS implantation several months later followed by a sleep study. RESULTS: A total of 20 patients were identified and included in the retrospective chart analysis. All patients who underwent ESP successfully converted their VP from CCC to an anterior-posterior collapse pattern and thus met inclusion criteria for HGNS. After the HGNS was implanted, patients showed a significant reduction of the mean AHI from 53.9 before ESP to 8.2 after ESP and HGNS and a decrease in the Epworth Sleep Score (ESS) from a mean of 13.3 to 5.7. CONCLUSION: ESP can be effective in eliminating the CCC of the VP thus making patients become HGNS candidates. In selected OSA patients, who have multilevel upper airway obstruction with complete concentric VP collapse, the combination of ESP and HGNS insertion should be considered as a planned 2-staged approach.

Inhibition of Mitochondrial Division Attenuates Cisplatin-Induced Toxicity in the Neuromast Hair Cells.

Cisplatin and other related platinum antineoplastic drugs are commonly used in the treatment of a variety of cancers in both adults and children but are often associated with severe side effects, including hearing loss. Cisplatin's ototoxic effects are multifaceted, culminating in irreversible damage to the mechanosensory hair cells in the inner ear. Platinum drugs act on cancerous cells by forming nuclear DNA adducts, which may initiate signaling leading to cell cycle arrest or apoptosis. Moreover, it was reported that cisplatin may induce mitochondrial DNA damage in non-cancerous cells. Therefore, protecting mitochondria may alleviate cisplatin-induced insult to non-proliferating cells. Thus, it is important to identify agents that shield the mitochondria from cisplatin-induced insult without compromising the anti-tumor actions of the platinum-based drugs. In this study we tested the protective properties of mitochondrial division inhibitor, mdivi-1, a derivative of quinazolinone and a regulator of mitochondrial fission. Interestingly, it has been reported that mdivi-1 increases the apoptosis of cells that are resistant to cisplatin. The ability of mdivi-1 to protect hair cells against cisplatin-induced toxicity was evaluated in a fish model. Wild-type (Tübingen strain), cdh23 mutant, and transgenic pvalb3b::GFP zebrafish stably expressing GFP in the hair cells were used in this study. Larvae at 5-6 days post fertilization were placed in varying concentrations of cisplatin (50-200 µM) and/or mdivi-1 (1-10 µM) for 16 h. To evaluate hair cell's viability the number of hair bundles per neuromast were counted. To assess hair cell function, we used the FM1-43 uptake assay and recordings of neuromast microphonic potentials. The results showed that mdivi-1 protected hair cells of lateral line neuromasts when they were challenged by 50 µM of cisplatin: viability of hair cells increased almost twice from 19% ± 1.8% to 36% ± 2.0% (p < 0.001). No protection was observed when higher concentrations of cisplatin were used. In addition, our data were in accord with previously reported results that functional mechanotransduction strongly potentiates cisplatin-induced hair cell toxicity. Together, our results suggest that mitochondrial protection may prevent cisplatin-induced damage to hair cells.