{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:59:48Z","timestamp":1790780388532,"version":"4.1.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["82303376"],"award-info":[{"award-number":["82303376"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Sailing Program","award":["22YF1440400"],"award-info":[{"award-number":["22YF1440400"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Braak\u2019s hypothesis suggests that \u03b1-synuclein may enter the central nervous system through the enteric nervous system and contribute to the pathogenesis of Parkinson\u2019s disease (PD). The appendix, enriched in \u03b1-synuclein, has been proposed as a possible entry point in PD pathogenesis. This systematic review and meta-analysis aimed to assess the association between appendectomy and PD risk using newly available data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A literature search was conducted in PubMed and Embase through September 10, 2024, to identify studies on appendectomy and PD risk. Two independent reviewers screened and assessed articles for eligibility with a third reviewer involved in cases of disagreement. Study quality was assessed using the Newcastle-Ottawa Scale. Data for meta-analysis were pooled using a random-effects model and analyzed in Review Manager 5.4. Meta-regression, subgroup, and sensitivity analyses were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nine studies met inclusion criteria. Meta-analysis indicated no significant association between appendectomy and PD risk (RR: 1.01, 95% CI: 0.90\u20131.12,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.89). Subgroup analyses showed similar findings. Sensitivity analyses did not change the estimate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This analysis suggests no association between appendectomy and PD risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2025.1619236","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T14:49:48Z","timestamp":1753109388000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Appendectomy and risk of Parkinson\u2019s disease: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Hok Leong","family":"Chin","sequence":"first","affiliation":[{"name":"Section of Neurology, Department of Pediatrics, University of Chicago Medicine","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiu Sing","family":"Tsang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University","place":["Shanghai, China"]},{"name":"Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson's disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"612","DOI":"10.3389\/fnins.2018.00612","article-title":"Parkinson's disease: biomarkers, treatment, and risk factors","volume":"12","author":"Emamzadeh","year":"2018","journal-title":"Front Neurosci"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s00702-002-0808-2","article-title":"Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen","volume":"110","author":"Braak","year":"2003","journal-title":"J Neural Transm (Vienna)"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1111\/j.1365-2990.2007.00874.x","article-title":"Parkinson's disease: a dual-hit hypothesis","volume":"33","author":"Hawkes","year":"2007","journal-title":"Neuropathol Appl 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emergence of Parkinson's disease: a meta-analysis","volume":"87","author":"Ishizuka","year":"2021","journal-title":"Am Surg"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"776847","DOI":"10.3389\/fpubh.2021.776847","article-title":"Global trends in the incidence, prevalence, and years lived with disability of Parkinson's disease in 204 countries\/territories from 1990 to 2019","volume":"9","author":"Ou","year":"2021","journal-title":"Front Public Health"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1002\/mds.26670","article-title":"Appendectomy in mid and later life and risk of Parkinson's disease: a population-based study","volume":"31","author":"Marras","year":"2016","journal-title":"Mov 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tonsillectomy and Parkinson's disease risk: a Swedish register-based study","volume":"11","author":"Liu","year":"2020","journal-title":"Front Neurol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e268","DOI":"10.1016\/j.bja.2021.12.046","article-title":"Risk of Parkinson's disease after anaesthesia and surgery","volume":"128","author":"Jain","year":"2022","journal-title":"Br J Anaesth"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1136\/gutjnl-2023-329685","article-title":"Gastrointestinal syndromes preceding a diagnosis of Parkinson's disease: testing Braak's hypothesis using a nationwide database for comparison with Alzheimer's disease and cerebrovascular diseases","volume":"72","author":"Konings","year":"2023","journal-title":"Gut"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1002\/mdc3.14031","article-title":"Appendectomy and the risk of Parkinson's disease: a Korean Nationwide study","volume":"11","author":"Park","year":"2024","journal-title":"Mov Disord Clin Pract"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e10","DOI":"10.1136\/gutjnl-2024-332353","article-title":"Association between appendectomy and Parkinson's disease from the UK biobank","volume":"74","author":"Wang","year":"2024","journal-title":"Gut"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1111\/j.1365-2990.2007.00923.x","article-title":"The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson's disease: a critical analysis of alpha-synuclein staging","volume":"34","author":"Kalaitzakis","year":"2008","journal-title":"Neuropathol Appl Neurobiol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1007\/s00401-008-0346-6","article-title":"Applicability of current staging\/categorization of alpha-synuclein pathology and their clinical relevance","volume":"115","author":"Parkkinen","year":"2008","journal-title":"Acta Neuropathol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1002\/ana.24648","article-title":"Pathological \u03b1-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients","volume":"79","author":"Stokholm","year":"2016","journal-title":"Ann Neurol"}],"updated-by":[{"DOI":"10.3389\/fneur.2026.1773653","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000}}],"container-title":["Frontiers in 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