Long-Term Generator Replacement Experience in Hypoglossal Nerve Stimulator Therapy Recipients With CPAP-Intolerant Obstructive Sleep Apnea.

OBJECTIVE: In the last decade, hypoglossal nerve stimulation (HNS) has emerged as a therapeutic alternative for patients with obstructive sleep apnea. The original clinical trial cohorts are entering the phase of expected battery depletion (8-12 years). This study aimed to examine the surgical experience with implantable pulse generator (IPG) replacements and the associated long-term therapy outcomes. STUDY DESIGN: Retrospective analysis of patients from the original clinical trial databases (STAR, German post-market) who were followed in the ongoing ADHERE registry. SETTING: International multicenter HNS registry. METHODS: The ADHERE registry and clinical trial databases were cross-referenced to identify the serial numbers of IPGs that were replaced. Data collection included demographics, apnea-hypopnea index (AHI), therapy use, operative times, and adverse events. RESULTS: Fourteen patients underwent IPG replacement 8.3 ± 1.1 years after their initial implantation. Body mass index was unchanged between the original implant and IPG replacement (29 ± 4 vs 28 ± 2 kg/m2 , p = .50). The mean IPG replacement operative time was shorter than the original implant (63 ± 50 vs 154 ± 58 minutes, p < .002); however, 2 patients required stimulation lead replacement which significantly increased operative time. For patients with available AHI and adherence data, the mean change in AHI from baseline to latest follow-up (8.7 ± 1.1 years after de novo implant) was -50.06%, and the mean therapy use was 7.2 hours/night. CONCLUSION: IPG replacement surgery was associated with low complications and shorter operative time. For patients with available outcomes data, adherence and efficacy remained stable after 9 years of follow-up.

The Role of Isolated Nasal Surgery in Obstructive Sleep Apnea Therapy-A Systematic Review.

Nasal obstruction is believed to play a significant role in the pathophysiology and management of obstructive sleep apnea (OSA). However, controversy remains about the ability of isolated nasal surgery to improve OSA. The objective of this systematic review is to give an updated overview of the literature on whether isolated nasal surgery can improve OSA subjectively (Epworth Sleepiness Scale (ESS)) and/or objectively (polysomnography (PSG)). Methods: A systematic review was performed searching the electronic databases PubMed, Embase.com (accessed on 20 June 2022) Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials (CENTRAL) up to 20 June 2022. Eligible studies were reviewed for methodological quality using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: Twenty-one studies met the inclusion criteria. The majority of the included studies reported no significant reduction in the apnea-hypopnea index (AHI) after isolated nasal surgery in patients with OSA. The meta-analysis suggests that the AHI slightly decreases after nasal surgery. The ESS was significantly lower after nasal surgery in eighteen studies. Conclusion: Based on the present analysis of objective outcomes, isolated nasal surgery did not improve the AHI significantly in the majority of the studies. The meta-analysis suggests a slight decrease in AHI after nasal surgery, but this reduction is not clinically relevant in terms of treatment success. Isolated nasal surgery should therefore not be recommended as a first-line treatment for OSA. Because of high study heterogeneity, these results should be interpreted with caution. Isolated nasal surgery can possibly improve OSA subjectively. Perhaps only OSA patients with complaints of nasal obstruction or OSA patients experiencing difficulty with continuous positive airway pressure (CPAP) compliance would benefit from isolated nasal surgery.

Novel Positional Devices for the Treatment of Positional Obstructive Sleep Apnea, and How This Relates to Sleep Surgery.

If untreated, obstructive sleep apnea (OSA) develops as a gradual progressive disease. In the early stage of the disease most patients with OSA are positional. The archetypical patient might progress from simple positional snoring via positional early-stage mild disease to less positional moderate and finally nonpositional severe OSA. At first, the apnea-hypopnea index (AHI) is high only in the supine position, and later is high in all sleeping positions. The phenomenon is reversible. After partial effective treatment, patients with severe OSA can reverse to less severe positional OSA or, in other words, the AHI drops more in the lateral position than in supine position. This has been shown for palatal surgery, multilevel surgery, bimaxillary osteotomies, and bariatric surgery. The absence or presence of positional dependency has a great influence on sleep surgery. First, the results of sleep surgery might be worse in positional patients. Second, the addition of positional therapy to sleep surgery might improve the overall outcome and, as such, enhance the indication of sleep surgery as an alternative to continuous positive airway pressure and mandibular advancement device treatment.

Advances in the Diagnosis of Obstructive Sleep Apnea: Drug-Induced Sleep Endoscopy.

Drug-induced sleep endoscopy was introduced in 1991 and has recently evolved into a pivotal instrument for patients in whom obstructive sleep apnea surgery is considered. Here, we discuss the indications, contraindications, technique, anesthesia, scoring systems, validity, and insights of the literature.

Delivery of tumor associated antigens to antigen presenting cells using penetratin induces potent immune responses.

Cytoplasmic delivery of proteins or CTL epitopes is crucial for the presentation of antigen for the generation of CTL. We previously described the use of the 16-amino acid peptide penetratin from the Drosophila Antennapedia domain (Int) to transport CTL epitopes into cells. Here we show that, Int, incorporating MUC1 CTL epitopes in tandem is able to facilitate their rapid uptake by macrophages and dendritic cells (DC) in an energy-dependent endocytic pathway. We also demonstrate for the first time that Int conjugated proteins are also able to be efficiently taken up by DC. Furthermore, C57BL/6 and HLA-A2 transgenic mice immunized with the Int-peptides or Int-proteins induce strong IFN-gamma secreting T cells and weak IgG1 antibodies. Immunized C57BL/6 mice were protected against the growth of a MUC1(+) tumor cell line.