Post-approval upper airway stimulation predictors of treatment effectiveness in the ADHERE registry.

Upper airway stimulation (UAS) has been shown to reduce severity of obstructive sleep apnoea. The aim of this study was to identify predictors of UAS therapy response in an international multicentre registry.Patients who underwent UAS implantation in the United States and Germany were enrolled in an observational registry. Data collected included patient characteristics, apnoea/hypopnoea index (AHI), Epworth sleepiness scale (ESS), objective adherence, adverse events and patient satisfaction measures. Post hoc univariate and multiple logistic regression were performed to evaluate factors associated with treatment success.Between October 2016 and January 2018, 508 participants were enrolled from 14 centres. Median AHI was reduced from 34 to 7 events·h-1, median ESS reduced from 12 to 7 from baseline to final visit at 12-month post-implant. In post hoc analyses, for each 1-year increase in age, there was a 4% increase in odds of treatment success. For each 1-unit increase in body mass index (BMI), there was 9% reduced odds of treatment success. In the multivariable model, age persisted in serving as statistically significant predictor of treatment success.In a large multicentre international registry, UAS is an effective treatment option with high patient satisfaction and low adverse events. Increasing age and reduced BMI are predictors of treatment response.

Association between REM sleep and obstructive sleep apnea in obese and overweight adolescents.

PURPOSE: Overweight and obese children have demonstrated reduced rapid eye movement (REM) sleep, affecting energy balance regulation and predisposition to weight gain. Obstructive sleep apnea (OSA) is a known cause of decreased REM sleep. The purpose of this study is to examine the association between the percentage of REM sleep, BMI z-score, and OSA severity in overweight and obese adolescents. METHODS: We performed a cross-sectional study of 92 (43% female) overweight and obese adolescents (13-17 years old) who underwent overnight polysomnography (PSG) at Children's Hospital Los Angeles between 2010 and 2017. RESULTS: The average Body Mass Index (BMI) z-score was 2.27 ± 0.47, with 71% having BMI z-score ≥ 2. REM% during PSG was 15.6 ± 6.8, and obstructive apnea-hypopnea index was 17.1 ± 24.3. The distribution across categories of OSA severity was 27% none (≤ 1.5 events/h), 24% mild (> 1.5-5 events/h), 8% moderate (> 5-10 events/h), and 41% severe (> 10 events/h). REM% was not associated with BMI z-score, either on univariate or multivariate regression with adjustment for age, gender, and apnea-hypopnea index (AHI). When subdivided into OSA categories, a 1-unit increase in BMI z-score was associated with a 5.96 (p = 0.03) increase in REM% in mild OSA and an 8.86 (p = 0.02) decrease in REM% in severe OSA. There was no association between BMI z-score and REM% in none and moderate OSA. CONCLUSION: Among overweight and obese adolescents, BMI z-score was associated with decreased REM% in severe OSA and unexpectedly increased REM% in mild OSA, but there was no association in none or moderate OSA.

Society of Anesthesia and Sleep Medicine Guidelines on Preoperative Screening and Assessment of Adult Patients With Obstructive Sleep Apnea.

The purpose of the Society of Anesthesia and Sleep Medicine guideline on preoperative screening and assessment of adult patients with obstructive sleep apnea (OSA) is to present recommendations based on the available clinical evidence on the topic where possible. As very few well-performed randomized studies in this field of perioperative care are available, most of the recommendations were developed by experts in the field through consensus processes involving utilization of evidence grading to indicate the level of evidence upon which recommendations were based. This guideline may not be appropriate for all clinical situations and all patients. The decision whether to follow these recommendations must be made by a responsible physician on an individual basis. Protocols should be developed by individual institutions taking into account the patients' conditions, extent of interventions and available resources. This practice guideline is not intended to define standards of care or represent absolute requirements for patient care. The adherence to these guidelines cannot in any way guarantee successful outcomes and is rather meant to help individuals and institutions formulate plans to better deal with the challenges posed by perioperative patients with OSA. These recommendations reflect the current state of knowledge and its interpretation by a group of experts in the field at the time of publication. While these guidelines will be periodically updated, new information that becomes available between updates should be taken into account. Deviations in practice from guidelines may be justifiable and such deviations should not be interpreted as a basis for claims of negligence.

Coblation endoscopic lingual lightening (CELL) for obstructive sleep apnea.

This study investigated the feasibility, safety and efficacy of Coblation endoscopic lingual lightening (CELL) surgery for obstructive sleep apnea (OSA). This study was a retrospective case series in a tertiary referral sleep center. Twenty-five adults with moderate to severe OSA and determined to have retropalatal and tongue base obstruction based on Friedman tongue position III and fiberoptic endoscopy underwent CELL in combination with modified uvulopalatopharyngoplasty, known as relocation pharyngoplasty. CELL involves transoral resection of tongue base muscle tissue and lingual tonsil using Coblation under endoscopic guidance. The mean operation time for CELL was 42.6 ± 13.7 min. Total blood loss for CELL plus relocation pharyngoplasty was <50 ml in all patients. Mean postoperative pain score (sum of total pain scores/sum of total hospitalization day, visual analog scale, 0-10) was 2.6 ± 0.6. Postoperative bleeding and taste disturbance extending beyond 3 months occurred in one patient (4 %) individually. No patients reported tongue weakness or speech dysfunction. Epworth sleepiness scale improved from 9.6 ± 4.9 to 7.5 ± 4.3 (p = 0.023). Apnea-hypopnea index decreased from 45.7 ± 21.7 to 12.8 ± 8.2 events/hour (p < 0.001) 6 months after surgery. The overall response rate was 80 %. CELL is feasible, safe and effective in treating tongue base obstruction in OSA patients who underwent simultaneous relocation pharyngoplasty.

Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes.

Reduced upper airway muscle activity during sleep is a key contributor to obstructive sleep apnea pathogenesis. Hypoglossal nerve stimulation activates upper airway dilator muscles, including the genioglossus, and has the potential to reduce obstructive sleep apnea severity. The objective of this study was to examine the safety, feasibility and efficacy of a novel hypoglossal nerve stimulation system (HGNS; Apnex Medical, St Paul, MN, USA) in treating obstructive sleep apnea at 12 months following implantation. Thirty-one subjects (35% female, age 52.4 ± 9.4 years) with moderate to severe obstructive sleep apnea and unable to tolerate positive airway pressure underwent surgical implantation and activation of the hypoglossal nerve stimulation system in a prospective single-arm interventional trial. Primary outcomes were changes in obstructive sleep apnea severity (apnea-hypopnea index, from in-laboratory polysomnogram) and sleep-related quality of life [Functional Outcomes of Sleep Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 ± 16% of nights for 5.4 ± 1.4 h per night. There was a significant improvement (P < 0.001) from baseline to 12 months in apnea-hypopnea index (45.4 ± 17.5 to 25.3 ± 20.6 events h(-1) ) and Functional Outcomes of Sleep Questionnaire score (14.2 ± 2.0 to 17.0 ± 2.4), as well as other polysomnogram and symptom measures. Outcomes were stable compared with 6 months following implantation. Three serious device-related adverse events occurred: an infection requiring device removal; and two stimulation lead cuff dislodgements requiring replacement. There were no significant adverse events with onset later than 6 months following implantation. Hypoglossal nerve stimulation demonstrated favourable safety, feasibility and efficacy.

Advanced Diagnostic Techniques in Obstructive Sleep Apnea.

Optimal surgical and medical management of obstructive sleep apnea requires clinically reliable identification of patterns and sites of upper airway obstruction. A wide variety of modalities have been used to evaluate upper airway obstruction. Drug-induced sleep endoscopy (DISE) and cine MRI are increasingly used to identify upper airway obstruction sites, to characterize airway obstruction patterns, to determine optimum medical and surgical treatment, and to plan individualized surgical management. Here, we provide an overview of the applications of DISE and cine MRI in assessing upper airway obstruction in children and adults with obstructive sleep apnea.

Advanced Diagnostic Techniques in Obstructive Sleep Apnea.

Optimal surgical and medical management of obstructive sleep apnea (OSA) requires clinically reliable identification of patterns and sites of upper airway obstruction. A wide variety of modalities has been used to evaluate upper airway obstruction. Drug-induced sleep endoscopy (DISE) and cine MRI are increasingly used to identify upper airway obstruction sites, to characterize airway obstruction patterns, to determine optimum medical and surgical treatment, and to plan individualized surgical management. Here, the authors provide an overview of the applications of DISE and cine MRI in assessing upper airway obstruction in children and adults with OSA.

Palate shape is associated with Unilateral Hypoglossal Nerve Stimulation Outcomes.

OBJECTIVE: The aim was to determine the potential association between palate shape and unilateral hypoglossal nerve stimulation (HNS) outcomes. METHODS: Preoperative drug-induced sleep endoscopy (DISE) videos were reviewed and scored by 3 blinded reviewers to determine airway narrowing at the hard-soft palate junction (HP), soft palate genu, and inferior velum, as described by Woodson (2014). Scoring was as follows: 1-open airway, 2-narrow, 3-severe narrowing. Overall palate shape (oblique, intermediate, or vertical) was determined based on prior criteria. Successful surgical treatment was defined by the HNS titration polysomnogram as a reduction of ≥50% in the apnea-hypopnea index (AHI) to <15 events/h. RESULTS: Of 332 adults, the majority was male (77%) with an average BMI of 29.2 ± 3.6 kg/m2 . Overall success rate was 73%. Success rate was lower in patients with vertical palate shape compared with the other shapes (56% vs. 75%, p = 0.029). HP score 3 compared with scores 2 and 1 was associated with lower success rates (60% vs. 76%, p = 0.028), but genu and velum scores were not associated with outcomes. Patients with both HP score 3 and complete oropharyngeal lateral wall-related obstruction had notably worse outcomes (22% vs. 74%, p = 0.026). HP score 3 (OR 0.45, 95%CI 0.22-0.92) and vertical palate shape (OR 0.33, 95%CI 0.15-0.78) were independently associated with lower odds of surgical response after adjustment for DISE findings, age, gender, and BMI. CONCLUSION: Vertical palate shape and narrowing at the hard-soft palate junction are independently associated with lower HNS surgical success rates. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:981-986, 2024.

Reprogramming human B cells with custom heavy-chain antibodies.

The immunoglobulin locus of B cells can be reprogrammed by genome editing to produce custom or non-natural antibodies that are not induced by immunization. However, current strategies for antibody reprogramming require complex expression cassettes and do not allow for customization of the constant region of the antibody. Here we show that human B cells can be edited at the immunoglobulin heavy-chain locus to express heavy-chain-only antibodies that support alterations to both the fragment crystallizable domain and the antigen-binding domain, which can be based on both antibody and non-antibody components. Using the envelope protein (Env) from the human immunodeficiency virus as a model antigen, we show that B cells edited to express heavy-chain antibodies to Env support the regulated expression of B cell receptors and antibodies through alternative splicing and that the cells respond to the Env antigen in a tonsil organoid model of immunization. This strategy allows for the reprogramming of human B cells to retain the potential for in vivo amplification while producing molecules with flexibility of composition beyond that of standard antibodies.

Palate Shape, Drug-Induced Sleep Endoscopy Findings, and Obstructive Sleep Apnea Pharyngeal Surgery Outcomes.

OBJECTIVE: Pharyngeal surgery is a treatment option for patients with obstructive sleep apnea (OSA) unable to tolerate positive pressure therapy. This study aims to determine the association between palate shape as described by Woodson and pharyngeal surgical outcomes. STUDY DESIGN: Exploratory analysis of retrospective cohort. SETTING: Multicenter. METHODS: Three blinded reviewers assessed palate shape using drug-induced sleep endoscopy (DISE) videos from a previously-assembled cohort of adults undergoing pharyngeal surgery. Palate shape scores were examined for association with surgical outcomes with univariate and multivariate analyses. Multivariate analyses included adjustment for consensus DISE findings determined previously. RESULTS: Two hundred nine study subjects were included from 13 centers. Age was 53.7 ± 11.5 years, body mass index (BMI) was 30.3 ± 5.0 kg/m2, and 21% were female. In isolated soft palate surgery, greater GenuAP narrowing was associated with lesser odds of surgical response, whereas greater GenuLW narrowing was associated with greater odds of surgical response. These findings largely persisted after adjustment for key DISE findings, age, gender, OSA severity, BMI, and tonsil size. Other palate-shape findings were not clearly associated with surgical outcomes, although some palate-shape findings demonstrated trends toward an association with outcomes (P < .10). CONCLUSION: Greater GenuAP narrowing and GenuLW narrowing were associated with lesser and greater, respectively, odds of surgical response after isolated soft palate surgery. Palate shape and other palate shape level scores were not clearly associated with surgical outcomes. Larger studies may determine more precisely the association between palate shape and pharyngeal surgery outcomes.

Reprogramming human B cells with custom heavy chain antibodies.

We describe a genome editing strategy to reprogram the immunoglobulin heavy chain (IgH) locus of human B cells to express custom molecules that respond to immunization. These heavy chain antibodies (HCAbs) comprise a custom antigen-recognition domain linked to an Fc domain derived from the IgH locus and can be differentially spliced to express either B cell receptor (BCR) or secreted antibody isoforms. The HCAb editing platform is highly flexible, supporting antigen-binding domains based on both antibody and non-antibody components, and also allowing alterations in the Fc domain. Using HIV Env protein as a model antigen, we show that B cells edited to express anti-Env HCAbs support the regulated expression of both BCRs and antibodies, and respond to Env antigen in a tonsil organoid model of immunization. In this way, human B cells can be reprogrammed to produce customized therapeutic molecules with the potential for in vivo amplification.

Reprogramming human B cells with custom heavy chain antibodies.

We describe a genome editing strategy to reprogram the immunoglobulin heavy chain (IgH) locus of human B cells to express custom molecules that respond to immunization. These heavy chain antibodies (HCAbs) comprise a custom antigen-recognition domain linked to an Fc domain derived from the IgH locus and can be differentially spliced to express either B cell receptor (BCR) or secreted antibody isoforms. The HCAb editing platform is highly flexible, supporting antigen-binding domains based on both antibody and non-antibody components, and also allowing alterations in the Fc domain. Using HIV Env protein as a model antigen, we show that B cells edited to express anti-Env HCAbs support the regulated expression of both BCRs and antibodies, and respond to Env antigen in a tonsil organoid model of immunization. In this way, human B cells can be reprogrammed to produce customized therapeutic molecules with the potential for in vivo amplification.

Developing a Social Media Ontology Across Otolaryngology and its Subspecialties.

OBJECTIVE: To determine how social media is used in the dissemination of new information within otolaryngology, and to emphasize the importance of standardizing Twitter hashtag use. METHODS: Based on the 2019 SCImago journal rankings, the Twitter posts from the accounts of the top three journals covering each otolaryngology subspecialty were reviewed from August 1, 2020 to May 1, 2021. Twitter posts from the primary otolaryngology-related academic societies were also reviewed during this timeframe. A list of hashtags was generated based on a combination of the most common otolaryngologic procedures and most commonly used hashtags in the social media space. This list was then crowd-sourced with 10 fellowship-trained otolaryngologists for each subspecialty. RESULTS: Hashtag use among key stakeholders in the otolaryngology social media space varies considerably. For instance, #HNSCC, #HeadAndNeckSquamousCellCarcinoma, #HeadAndNeckCancer, #HeadAndNeckCancers, #OropharyngealCancer, #OropharynxCancer, #OralCancer, and #OPSCC were all commonly used hashtags to identify posts discussing oropharyngeal squamous cell carcinoma. #HeadAndNeckCancer and #HNSCC were most popular and used in a total of 85 and 65 tweets, respectively. #HeadAndNeckCancer was found alone in 32 out of 85 tweets (38%), whereas #HNSCC was found alone in 27 out of 65 tweets (42%). A standardized hashtag ontology covering all subspecialties within otolaryngology is proposed herein. CONCLUSIONS: Adoption of a standardized social media ontology within otolaryngology will improve information dissemination across all key stakeholders. Laryngoscope, 133:1595-1599, 2023.

Drug-induced sleep endoscopy: the VOTE classification.

The surgical evaluation of obstructive sleep apnea is designed to characterize the pattern of upper airway obstruction in order to develop an effective treatment plan for an individual patient. Drug-induced sleep endoscopy (DISE) is one evaluation technique that involves assessment of individuals under pharmacologic sedation designed to simulate natural sleep, utilizing fiberoptic endoscopy to examine the upper airway. Developed in multiple centers throughout Europe, DISE was first described in 1991 and is performed widely around the world. Although multiple studies support a potential role for DISE in evaluation for treatment with surgery and mandibular repositioning appliances, important clinical questions remain unanswered. A major limitation in advancing our understanding of drug-induced sleep endoscopy has been the multiplicity and, in many cases, the complexity of classification systems that prevent the comparison of results across the studies and centers. We present the VOTE classification, a method for characterizing DISE findings that focuses on its core feature, the specific structures that contribute to obstruction.

Altered regional cerebral blood flow in obstructive sleep apnea is associated with sleep fragmentation and oxygen desaturation.

Altered cerebral perfusion has been reported in obstructive sleep apnea (OSA). Using dynamic susceptibility contrast MRI, we compared cerebral perfusion between male OSA patients and male healthy reference subjects and assessed correlations of perfusion abnormalities of OSA patients with sleep parameters and neuropsychological deficits at 3 T MRI, polysomnography and neuropsychological tests in 68 patients with OSA and 21 reference subjects. We found lower global and regional cerebral blood flow and cerebral blood volume, localized mainly in bilateral parietal and prefrontal cortices, as well as multiple focal cortical and deep structures related to the default mode network and attention network. In the correlation analysis between regional hypoperfusion and parameters of polysomnography, different patterns of regional hypoperfusion were distinctively associated with parameters of intermittent hypoxia and sleep fragmentation, which involved mainly parietal and orbitofrontal cortices, respectively. There was no association between brain perfusion and cognition in OSA patients in areas where significant association was observed in reference subjects, largely overlapping with nodes of the default mode network and attention network. Our results suggest that impaired cerebral perfusion in important areas of functional networks could be an important pathomechanism of neurocognitive deficits in OSA.

Comparison of Traditional Upper Airway Surgery and Upper Airway Stimulation for Obstructive Sleep Apnea.

OBJECTIVE: To compare patients with moderate-severe obstructive sleep apnea (OSA) undergoing traditional single and multilevel sleep surgery to those undergoing upper airway stimulation (UAS). STUDY DESIGN: Case control study comparing retrospective cohort of patients undergoing traditional sleep surgery to patients undergoing UAS enrolled in the ADHERE registry. SETTING: 8 multinational academic medical centers. SUBJECTS AND METHODS: 233 patients undergoing prior single or multilevel traditional sleep surgery and meeting study inclusion criteria were compared to 465 patients from the ADHERE registry who underwent UAS. We compared preoperative and postoperative demographic, quality of life, and polysomnographic data. We also evaluated treatment response rates. RESULTS: The pre and postoperative apnea hypopnea index (AHI) was 33.5 and 15 in the traditional sleep surgery group and 32 and 10 in the UAS group. The postoperative AHI in the UAS group was significantly lower. The pre and postoperative Epworth sleepiness scores (ESS) were 12 and 6 in both the traditional sleep surgery and UAS groups. Subgroup analysis evaluated those patients undergoing single level palate and multilevel palate and tongue base traditional sleep surgeries. The UAS group had a significantly lower postoperive AHI than both traditional sleep surgery subgroups. The UAS group had a higher percentage of patients reaching surgical success, defined as a postoperative AHI <20 with a 50% reduction from preoperative severity. CONCLUSION: UAS offers significantly better control of AHI severity than traditional sleep surgery. Quality life improvements were similar between groups.

Drug-Induced Sleep Endoscopy and Hypoglossal Nerve Stimulation Outcomes: A Multicenter Cohort Study.

OBJECTIVES/HYPOTHESIS: To determine the association between findings of blinded reviews of preoperative drug-induced sleep endoscopy (DISE) and outcomes of hypoglossal nerve stimulation (HNS) for obstructive sleep apnea (OSA). STUDY DESIGN: Cohort study. METHODS: A retrospective, multicenter cohort study of 343 adults who underwent treatment of OSA with HNS from 10 academic medical centers was performed. Preoperative DISE videos were scored by four blinded reviewers using the VOTE Classification and evaluation of a possible primary structure contributing to airway obstruction. Consensus DISE findings were examined for an association with surgical outcomes based on therapy titration polysomnogram (tPSG). Treatment response was defined by a decrease of ≥50% in the apnea-hypopnea index (AHI) to <15 events/hour. RESULTS: Study participants (76% male, 60.4 ± 11.0 years old) had a body mass index of 29.2 ± 3.6 kg/m2 . AHI decreased (35.6 ± 15.2 to 11.0 ± 14.1 events/hour; P < .001) on the tPSG, with a 72.6% response rate. Complete palate obstruction (vs. none) was associated with the greatest difference in AHI improvement (-26.8 ± 14.9 vs. -19.2 ± 12.8, P = .02). Complete (vs. partial/none) tongue-related obstruction was associated with increased odds of treatment response (78% vs. 68%, P = .043). Complete (vs. partial/none) oropharyngeal lateral wall-related obstruction was associated with lower odds of surgical response (58% vs. 74%, P = .042). CONCLUSIONS: The DISE finding of primary tongue contribution to airway obstruction was associated with better outcomes, whereas the opposite was true for the oropharyngeal lateral walls. This study suggests that the role for DISE in counseling candidates for HNS extends beyond solely for excluding complete concentric collapse related to the velum. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1676-1682, 2021.

Obstructive Sleep Apnoea: From pathogenesis to treatment: Current controversies and future directions.

Obstructive sleep apnoea (OSA) is a common disease, recognized as an independent risk factor for a range of clinical conditions, such as hypertension, stroke, depression and diabetes. Despite extensive research over the past two decades, the mechanistic links between OSA and other associated clinical conditions, including metabolic disorders and cardiovascular disease, remain unclear. Indeed, the pathogenesis of OSA itself remains incompletely understood. This review provides opinions from a number of leading experts on issues related to OSA and its pathogenesis, interaction with anaesthesia, metabolic consequences and comorbidities, cardiovascular disease, genetics, measurement and diagnosis, surgical treatment and pharmacotherapeutic targets.

Methodological Quality of Systematic Reviews and Meta-analyses Published in High-Impact Otolaryngology Journals.

OBJECTIVE: To assess the methodological quality of intervention-focused systematic reviews (SRs) and meta-analyses (MAs) published in high-impact otolaryngology journals. DATA SOURCES: Ovid Medline, Embase, and Cochrane Library. REVIEW METHODS: A comprehensive search was performed for SR and MA citations from 2012 to 2017 in the 10 highest impact factor otolaryngology journals. Abstracts were screened to identify published manuscripts in which the authors indicated clearly that they were performing an SR or MA. Applying a modified typology of reviews, 4 reviewers characterized the review type as SR, MA, or another review type. A simplified version of the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews 2) tool was used to assess the reporting and methodological quality of the SRs and MAs that were focused on interventions. RESULTS: Search and abstract screening generated 499 manuscripts that identified themselves as performing an SR or MA. A substantial number (85/499, 17%) were review types other than SRs or MAs, including 34 (7%) that were literature reviews. In total, 236 SRs and MAs focused on interventions. Over 50% of these SRs and MAs had weaknesses in at least 3 of the 16 items in the AMSTAR 2, and over 40% had weaknesses in at least 2 of the 7 critical domains. Ninety-nine percent of SRs and MAs provided critically low confidence in the results of the reviews. CONCLUSION: Intervention-focused SRs and MAs published in high-impact otolaryngology journals have important methodological limitations that diminish confidence in the results of these reviews.