{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:53:21Z","timestamp":1781877201862,"version":"3.54.5"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171129"],"award-info":[{"award-number":["82171129"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Laryngoscope Investig Oto"],"published-print":{"date-parts":[[2026,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objectives<\/jats:title>\n To examine the types and characteristics of acid\u2010free reflux in vocal cord granuloma (VCG).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A retrospective analysis was conducted on the VCG patients and those with benign unilateral vocal cord lesions between October 2017 and January 2025. Prior to treatment, all patients underwent 24\u2010h hypopharyngeal\u2010esophageal multichannel intraluminal impedance\u2010pH (HEMII\u2010pH) monitoring, high\u2010resolution esophageal manometry assessment, and electronic laryngoscopy examination. Furhermore, granuloma tissue samples from the VCG patients were obtained for detection of pepsin, pepsinogen A, pepsinogen C and trypsin, using immunohistochemical analysis.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The proportion of the VCG group experiencing acid\u2010free reflux was significantly higher than that observed in the benign lesion group (65.57%\u2009\u00b1\u200923.26% vs. 30.43%\u2009\u00b1\u200918.53%,\n t<\/jats:italic>\n \u2009=\u20094.134,\n p<\/jats:italic>\n \u2009<\u20090.001). Furthermore, the lower esophageal sphincter (LES) length in the VCG group was significantly shorter than that in the benign lesion group (2.25\u2009cm vs. 2.60\u2009cm,\n Z<\/jats:italic>\n \u2009=\u2009\u22121.977,\n p<\/jats:italic>\n \u2009=\u20090.047). Additionally, no pepsin expression was detected in any granuloma tissue samples. However, both pepsinogen A and pepsinogen C were positively expressed. Notably, the percentage of pepsinogen A\u2010positive cells in granuloma tissue exhibited a significant positive correlation with the size of the granulomas in the\n VCG<\/jats:styled-content>\n patients (\n r<\/jats:italic>\n \u2009=\u20090.691,\n p<\/jats:italic>\n \u2009=\u20090.027).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Acid\u2010free reflux could potentially play a significant role in the development of granulomas in VCG patients.<\/jats:p>\n <\/jats:sec>\n \n Level of Evidence<\/jats:title>\n 4.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/lio2.70409","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:46:36Z","timestamp":1776235596000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Acid\u2010Free Reflux on Vocal Cord Granuloma"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2706-7817","authenticated-orcid":false,"given":"Xiao\u2010Hong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery The Second Affiliated Hospital of Xi'an Jiao Tong University Xi'an China"},{"name":"Shaanxi Provincial Key Laboratory for Precision Diagnosis and Treatment of Otorhinolaryngology Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Qiang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery The Second Affiliated Hospital of Xi'an Jiao Tong University Xi'an China"},{"name":"Shaanxi Provincial Key Laboratory for Precision Diagnosis and Treatment of Otorhinolaryngology Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery The Second Affiliated Hospital of Xi'an Jiao Tong University Xi'an China"},{"name":"Shaanxi Provincial Key Laboratory for Precision Diagnosis and Treatment of Otorhinolaryngology Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery The Second Affiliated Hospital of Xi'an Jiao Tong University Xi'an China"},{"name":"Shaanxi Provincial Key Laboratory for Precision Diagnosis and Treatment of Otorhinolaryngology Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Xi","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery The Second Affiliated Hospital of Xi'an Jiao Tong University Xi'an China"},{"name":"Shaanxi Provincial Key Laboratory for Precision Diagnosis and Treatment of Otorhinolaryngology Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Wen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery The Second Affiliated Hospital of Xi'an Jiao Tong University Xi'an China"},{"name":"Shaanxi Provincial Key Laboratory for Precision Diagnosis and Treatment of Otorhinolaryngology Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Le","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery The Second Affiliated Hospital of Xi'an Jiao Tong University Xi'an China"},{"name":"Shaanxi Provincial Key Laboratory for Precision Diagnosis and Treatment of Otorhinolaryngology Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6950-2354","authenticated-orcid":false,"given":"Hua\u2010Nan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery The Second Affiliated Hospital of Xi'an Jiao Tong University Xi'an China"},{"name":"Shaanxi Provincial Key Laboratory for Precision Diagnosis and Treatment of Otorhinolaryngology Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/lio2.969"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0022215122000457"},{"issue":"10","key":"e_1_2_10_4_1","first-page":"1048","article-title":"Analysis of the Efficacy of Vocal Cord Botulinum Toxin Injection for Refractory Laryngeal Contact Granuloma","volume":"59","author":"Wang J. 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