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.

Acute upper airway responses to hypoglossal nerve stimulation during sleep in obstructive sleep apnea.

RATIONALE: Hypoglossal nerve stimulation (HGNS) recruits lingual muscles, reduces pharyngeal collapsibility, and treats sleep apnea. OBJECTIVES: We hypothesized that graded increases in HGNS relieve pharyngeal obstruction progressively during sleep. METHODS: Responses were examined in 30 patients with sleep apnea who were implanted with an HGNS system. Current (milliampere) was increased stepwise during non-REM sleep. Frequency and pulse width were fixed. At each current level, stimulation was applied on alternating breaths, and responses in maximal inspiratory airflow (V(I)max) and inspiratory airflow limitation (IFL) were assessed. Pharyngeal responses to HGNS were characterized by the current levels at which V(I)max first increased and peaked (flow capture and peak flow thresholds), and by the V(I)max increase from flow capture to peak (ΔV(I)max). MEASUREMENTS AND MAIN RESULTS: HGNS produced linear increases in V(I)max from unstimulated levels at flow capture to peak flow thresholds (215 ± 21 to 509 ± 37 ml/s; mean ± SE; P < 0.001) with increasing current from 1.05 ± 0.09 to 1.46 ± 0.11 mA. V(I)max increased in all patients and IFL was abolished in 57% of patients (non-IFL subgroup). In the non-IFL compared with IFL subgroup, the flow response slope was greater (1241 ± 199 vs. 674 ± 166 ml/s/mA; P < 0.05) and the stimulation amplitude at peak flow was lower (1.23 ± 0.10 vs. 1.80 ± 0.20 mA; P < 0.05) without differences in peak flow. CONCLUSIONS: HGNS produced marked dose-related increases in airflow without arousing patients from sleep. Increases in airflow were of sufficient magnitude to eliminate IFL in most patients and IFL and non-IFL subgroups achieved normal or near-normal levels of flow, suggesting potential HGNS efficacy across a broad range of sleep apnea severity.

Comparison of Free Flap Outcomes at a University Hospital versus County Hospital Setting for Head and Neck Reconstruction.

Introduction Patients at public county hospitals often have poorer access to healthcare with advanced disease on presentation. These factors, along with limited resources at county hospitals, may have an impact on outcomes for patients requiring complex head and neck reconstruction. Objective To delineate differences in the frequency of complications in two different care settings, a public county hospital and a private university hospital. Methods Retrospective review of otolaryngology patients at a university hospital compared with a publicly-funded county hospital. The main outcome measure was major complications including total flap loss or unplanned reoperation in 30 days. Secondary outcome measures included medical complications, partial flap loss, and unplanned hospital readmission in 30 days. Results In the county hospital sample ( n = 58) free flap failure or reoperation occurred in 20.7% of the patients, and minor complications, in 36.2% of the patients. In the university hospital sample ( n = 65) flap failure or reoperation occurred in 9.2% of the patients, and minor complications, in 12.3% of the patients. Patients at the private hospital who had surgery in the oropharynx were least likely to have minor complications. Conclusion Patients at the county hospital had a higher but not statistically significant difference in flap failure and reoperation than those at a university hospital, although the county hospital experienced more minor postoperative complications. This is likely multifactorial, and may be related to poorer access to primary care preoperatively, malnutrition, poorly controlled or undiagnosed medical comorbidities, and differences in hospital resources.

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.

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.

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.

Transoral Robotic Surgery (TORS) Versus Non-TORS Tongue Resection for Obstructive Sleep Apnea.

OBJECTIVE: To compare transoral robotic surgery (TORS) versus non-TORS tongue resection procedures performed for obstructive sleep apnea from January 2010 to September 2015 using a national database, focusing on patient characteristics, performance of concurrent procedures, operative time, length of hospital stay, and postoperative complications. METHODS: A cohort of adults undergoing TORS and non-TORS tongue resection procedures was identified in the Nationwide Inpatient Sample, a publicly-available national administrative database incorporating a stratified sample of hospital discharge records. Outcomes were annual case volumes, prolonged (≥3 days) hospital stay, and complications. Statistical analyses examined potential associations between TORS and prolonged hospital stay and complications. RESULTS: From 2010 to 2015, 5709 hospital discharges included tongue resection surgery to treat obstructive sleep apnea. There was a gradual decline and stabilization in overall volumes, with the proportion of TORS use showing an initial increase, followed by a decrease and rebound increase. TORS patients were less likely to undergo concurrent nasal surgery (15% vs. 44%, P < .01), but there was no association between the use of TORS and concurrent palatal surgery. TORS use was not associated with concurrent hypopharyngeal surgery overall, but it was associated with specific types of hypopharyngeal surgery. TORS use was associated with patient age, payor, and certain hospital characteristics. TORS use was associated with an increased risk of prolonged hospital stay (33% vs. 25%, P = .045) but was not associated with complications. CONCLUSION: This study provides insight into TORS use in tongue resection surgery for obstructive sleep apnea during this period of early TORS adoption. LEVEL OF EVIDENCE: Level 3 (cohort study). Laryngoscope, 131:E1735-E1740, 2021.

Wavelet-based CNN for Predicting PAP Adherence Using Overnight Polysomnography Recordings: a Pilot Study.

Obstructive sleep apnea (OSA) is a common sleep disorder. Positive airway pressure (PAP) therapy is the first-line treatment, while its effectiveness is significantly limited by incomplete adherence in many patients. This work aims to find a predictive association between data from in-laboratory sleep studies during treatment (PAP titration polysomnogram, or PSG) and PAP adherence. Based on a PAP titration PSG database, we present a pipeline to develop a wavelet-based deep learning model and address two challenges. First, to tackle the problem of extremely long overnight PSG signals, it randomly draws segments and extracts features locally. The global representation for the entire signal is achieved by local feature P-norm pooling. Second, to tackle the problem of limited dataset size, the pre-trained EfficienNet-B7 is used as an unsupervised feature extractor to transfer ImageNet knowledge to PSG signals in the wavelet domain. The trained pipeline achieves 78% balanced accuracy and 83% AUC on the test set using airflow and frontal EEG signals, which, we believe, is a compelling result as a pilot study.

Upper Airway Classification in Sleep Endoscopy Examinations using Convolutional Recurrent Neural Networks.

Assessing the upper airway (UA) of obstructive sleep apnea patients using drug-induced sleep endoscopy (DISE) before potential surgery is standard practice in clinics to determine the location of UA collapse. According to the VOTE classification system, UA collapse can occur at the velum (V), oropharynx (O), tongue (T), and/or epiglottis (E). Analyzing DISE videos is not trivial due to anatomical variation, simultaneous UA collapse in several locations, and video distortion caused by mucus or saliva. The first step towards automated analysis of DISE videos is to determine which UA region the endoscope is in at any time throughout the video: V (velum) or OTE (oropharynx, tongue, or epiglottis). An additional class denoted X is introduced for times when the video is distorted to an extent where it is impossible to determine the region. This paper is a proof of concept for classifying UA regions using 24 annotated DISE videos. We propose a convolutional recurrent neural network using a ResNet18 architecture combined with a two-layer bidirectional long short-term memory network. The classifications were performed on a sequence of 5 seconds of video at a time. The network achieved an overall accuracy of 82% and F1-score of 79% for the three-class problem, showing potential for recognition of regions across patients despite anatomical variation. Results indicate that large-scale training on videos can be used to further predict the location(s), type(s), and degree(s) of UA collapse, showing potential for derivation of automatic diagnoses from DISE videos eventually.