{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:40:55Z","timestamp":1792622455268,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:00:00Z","timestamp":1792195200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006389","name":"Universit\u00e9 de Gen\u00e8ve","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006389","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["esskajournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J. exp. orthop."],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Cyclops syndrome is a clinically relevant complication of anterior cruciate ligament (ACL) reconstruction characterized by the formation of a fibrotic nodule (cyclops lesion) that causes extension loss and often requires a revision surgery. Biological mechanisms underlying lesion formation remain poorly understood. The purpose of this study is to characterize the tissue architecture, cellular composition, inflammatory profile and single\u2010cell cytokine secretion patterns of patient\u2010derived biopsies to gain mechanistic insight into disease pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This prospective observational comparative study included three patient groups: patients undergoing revision surgery for cyclops syndrome (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910), patients undergoing primary ACL reconstruction with subsequent successful recovery (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) and patients undergoing revision surgery for ACL graft re\u2010rupture (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092). Tissue biopsies and synovial fluid samples were collected intraoperatively and used for histological, cellular and cytokine analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Histological analyses demonstrated that cyclops lesions exhibited disorganized collagen architecture, neovascularization and infiltration of immune cells. Flow cytometry identified activated FAP\n                      <jats:sup>+<\/jats:sup>\n                      CD54\n                      <jats:sup>+<\/jats:sup>\n                      fibroblasts as the predominant cell population (~80%), accompanied by CD206\n                      <jats:sup>+<\/jats:sup>\n                      pro\u2010fibrotic macrophages. Synovial fluid from cyclops patients contained significantly elevated IL\u20106 and TNF\u2010\u03b1 concentrations, whereas IL\u20101\u03b2 levels did not differ among the groups. Looking at the cells, single\u2010cell cytokine secretion profiles revealed detectable IL\u20106 secretion in up to 11% of cells, while IL\u20101\u03b2, TNF\u2010\u03b1 and TGF\u2010\u03b2 secretion were not detected, indicating that at least the source of TNF\u2010\u03b1 has to be found elsewhere.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our preliminary data from a small patient cohort show that cyclops syndrome may be observed as an active fibro\u2010inflammatory process rather than a purely mechanical post\u2010operative complication. Patient\u2010derived samples revealed persistent inflammatory activity characterized by immune cell infiltration, elevated levels of pro\u2010inflammatory mediators, and sustained activation of fibroblasts. The absence of detectable TGF\u2010\u03b2 secretion despite established fibrosis suggests that lesion persistence may be maintained through alternative fibrotic pathways (non\u2010TGF\u2010\u03b2\/non\u2010canonical pathways), which requires further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>N\/A.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jeo2.70953","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T13:25:50Z","timestamp":1792243550000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Patients with cyclops syndrome exhibit elevated synovial fluid interleukin\u20106 (IL\u20106) and tumor necrosis factor alpha (TNF\u2010\u03b1) levels and disorganized collagen remodelling within the lesion: A histological and molecular study"],"prefix":"10.1002","volume":"13","author":[{"given":"Luca","family":"Morici","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Sciences of Western Switzerland University of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe M.","family":"Tscholl","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Trauma Surgery University Hospital of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline. 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