{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T22:22:36Z","timestamp":1767910956408,"version":"3.49.0"},"reference-count":22,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"unspecified","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Synapse Research Institute"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,2,28]]},"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The cause of ischaemic stroke at a young age remains unknown in 30% of cases, highlighting the need to identify hidden causes and risk factors in young patients. Transient and chronic risk factors may interact with the inflammatory and haemostatic systems, potentially driving key mechanisms in the pathogenesis. The \u2018Observational Dutch Young StrokE study\u2014Extended\u2019 (ODYSSEY-nEXT) aims to enhance our understanding of these complex interactions through detailed phenotyping of the immune and haemostatic system and explore their relationship with long-term prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>The ODYSSEY-nEXT is a multicentre prospective controlled cohort study of patients aged 18\u201350 years with a first neuroimaging-proven ischaemic stroke or transient ischaemic attack and healthy controls. We aim to include a total of 200 patients and 60 controls between January 2023 and January 2027. Blood samples will be collected within 72 hours after the index event and at 3\u2009months to assess inflammatory and haemostatic markers. In a subgroup of 20 patients, whole blood analysis will be performed to investigate ex vivo immune cell functionality, the capacity of platelets to release granules and thrombin generation. All patients will complete a questionnaire about trigger and risk factors. Advanced intracranial and extracranial vessel wall imaging with MRI will be performed within a week. Long-term prognosis will be monitored through annual questionnaires about recurrent events for ten years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study was approved by the Medical Ethical Committee region \u2018Oost-Nederland\u2019 (NL77518.091.21) and will adhere to the Declaration of Helsinki and its later amendments. Participants have to provide written informed consent, but in cases where the patient cannot sign due to physical limitations as a result of the stroke, such as paresis, verbal consent is obtained from the patient and a legal representative will be asked to sign the consent form on their behalf. The findings of this study will be disseminated to healthcare professionals and the scientific community through peer-reviewed publications and to participants through accessible formats such as summary reports or newsletters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05853796\">NCT05853796<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-096330","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T23:45:07Z","timestamp":1742773507000},"page":"e096330","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Role of inflammation and haemostasis on aetiology and prognosis in young patients with ischaemic stroke: study protocol of the Observational Dutch Young Symptomatic StrokE study\u2014EXTended (ODYSSEY-nEXT) \u2013 a multicentre prospective cohort study"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct05853796","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4766-3322","authenticated-orcid":false,"given":"Janneke P","family":"Spiegelenberg","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esm\u00e9e","family":"Verburgt","sequence":"additional","affiliation":[{"name":"Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heleen","family":"den Hertog","sequence":"additional","affiliation":[{"name":"Department of Neurology, Isala Hospital, Zwolle, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karlijn F","family":"de Laat","sequence":"additional","affiliation":[{"name":"Department of Neurology, Haga Hospital, Den Haag, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank G","family":"van Rooij","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Centre Leeuwarden, Leeuwarden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inge W M","family":"van Uden","sequence":"additional","affiliation":[{"name":"Department of Neurology, Catharina Hospital, Eindhoven, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renate M","family":"Arntz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medisch Spectrum Twente, Enschede, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ido R","family":"van den Wijngaard","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Centre Haaglanden, Den Haag, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9500-9793","authenticated-orcid":false,"given":"Roy P C","family":"Kessels","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands"},{"name":"Department of Psychiatry, Vincent Van Gogh Instituut, Venray, The Netherlands"},{"name":"Department of Medical Psychology and Radboudumc Alzheimer Center, Radboud University Medical Center, Nijmegen, The 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