{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:27:31Z","timestamp":1786940851652,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Hypoglossal nerve stimulation (HNS) is an established surgical therapy for adults with moderate-to-severe obstructive sleep apnea (OSA) who are intolerant to positive airway pressure. Although aggregate response rates of ~70\u201380% have been reported, substantial variability across clinical settings remains poorly understood. Prior meta-analyses have largely emphasized pooled continuous outcomes, limiting interpretation of responder-based endpoints and drivers of between-study heterogeneity. Methods: A PRISMA-compliant systematic review and meta-analysis was performed. MEDLINE, Embase, and Cochrane CENTRAL were searched from inception through 31 December 2025. Eligible studies enrolled adults with OSA treated with implantable HNS, reported Sher-defined response (\u226550% AHI reduction and residual AHI &lt; 20 events\/hour), and\/or continuous outcomes, and included \u226520 patients. Random-effects models (REML) were applied. Heterogeneity was quantified using I2 and \u03c42, with prediction intervals. Meta-regression assessed baseline AHI, BMI, and follow-up duration. Subgroup analyses examined device laterality, stimulation modality, sleep assessment method, and follow-up. Results: Thirty-eight studies (39 cohorts; n = 3220) were included. The pooled Sher response rate was 74.0% (95% CI 67.6\u201379.5%). Heterogeneity was substantial. HNS significantly improved all continuous outcomes (AHI \u221223.3 events\/hour; ESS \u22124.5 points; ODI \u221214.5 events\/hour). Comparative analyses favored HNS over surgical comparators, inactive stimulation, and delayed treatment. Revision and explantation rates were 5% and 4%, respectively. Meta-regression showed no significant effects of baseline AHI, BMI, or follow-up, explaining negligible variance. Subgroups suggested numerically higher response with breathing-synchronized stimulation, but heterogeneity remained high. Conclusions: HNS achieves Sher response in approximately three-quarters of appropriately selected CPAP-intolerant OSA patients, with durable clinical benefits and a favorable safety profile. Persistent unexplained heterogeneity highlights limitations of conventional predictors and underscores the need for more granular response determinants.<\/jats:p>","DOI":"10.3390\/jcm15135180","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:51:25Z","timestamp":1783003885000},"page":"5180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis on Responder-Based Outcomes and Between-Study Heterogeneity"],"prefix":"10.3390","volume":"15","author":[{"given":"Clemens","family":"Heiser","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Klinikum Rechts Der ISAR, Technical University Munich, 81675 Munich, Germany"},{"name":"ENT Center Mangfall-Inn, 83043 Bad Aibling, Germany"},{"name":"Faculty of Medicine, Translational Neurosciences, University of Antwerp, B-2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8101-3465","authenticated-orcid":false,"given":"Marcel","family":"Braun","sequence":"additional","affiliation":[{"name":"Center for Sleep & Telemedicine, Faculty of Medicine, University Duisburg-Essen, 45239 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Huntley","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hutz","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Section of Sleep Surgery, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8411-6806","authenticated-orcid":false,"given":"Thomas Michael","family":"Kaffenberger","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurits","family":"Boon","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1152\/physrev.00043.2008","article-title":"Pathophysiology of sleep apnea","volume":"90","author":"Dempsey","year":"2010","journal-title":"Physiol. 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