{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T14:19:45Z","timestamp":1780928385296,"version":"3.54.1"},"reference-count":36,"publisher":"Pensoft Publishers","issue":"3","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FM"],"abstract":"<jats:p>\n                    <jats:bold>Introduction<\/jats:bold>\n                    : Restless legs syndrome (RLS) is a frequent yet underrecognized comorbidity in rheumatoid arthritis (RA), potentially driven by inflammation-mediated disturbances in iron metabolism.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Aim<\/jats:bold>\n                    : This study investigated the relationship between inflammatory markers and iron homeostasis in RA patients with and without RLS.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    : This monocentric cross-sectional study included 32 RA patients, 12 of whom had RLS and 20 who did not. RLS was diagnosed using ICSD-3 criteria, and severity was measured using IRLSSG scores. Clinical data, disease activity (DAS28-CRP), reported sleep parameters, and laboratory markers (IL-6, TNF-\u03b1, serum iron, ferritin, and hepcidin-25) were analyzed. Between-group comparisons and receiver operating characteristic (ROC) analyses were performed.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : The prevalence of RLS in our cohort was 37.5%. Compared to RA patients without RLS, those with RLS demonstrated significantly prolonged reported sleep latency (42.5 vs. 25.0 min,\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt;0.001, \u03b4=0.86); higher disease activity (DAS28-CRP 4.64 vs. 3.82,\n                    <jats:italic>p<\/jats:italic>\n                    =0.0029, \u03b4=0.64); elevated IL-6 (13.55 vs. 2.84 pg\/mL,\n                    <jats:italic>p<\/jats:italic>\n                    =0.0022, \u03b4=0.66); and hepcidin-25 levels (640 vs. 455 pg\/mL,\n                    <jats:italic>p<\/jats:italic>\n                    =0.0382, \u03b4=0.48) and lower serum iron (15.35 vs. 19.30 \u00b5mol\/L,\n                    <jats:italic>p<\/jats:italic>\n                    =0.0292, \u03b4=\u22120.47). Ferritin and TNF-\u03b1 did not differ significantly. ROC analysis showed strong discrimination for reported sleep latency (AUC 0.93), IL-6 (AUC 0.83), and DAS28-CRP (AUC 0.82).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions<\/jats:bold>\n                    : RA patients with RLS demonstrate a distinct biological profile characterized by heightened inflammatory activity and functional iron deficiency. The IL-6\u2013hepcidin\u2013iron axis emerges as a central mechanistic pathway linking systemic inflammation to RLS pathophysiology. These findings support the concept that the magnitude of inflammatory activation, rather than its mere presence, contributes to RLS development in RA and highlight potential targets for improved diagnostic and therapeutic strategies.\n                  <\/jats:p>","DOI":"10.3897\/folmed.68.e193784","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:26:49Z","timestamp":1780925209000},"source":"Crossref","is-referenced-by-count":0,"title":["Increased interleukin-6 and hepcidin-25 are associated with restless legs syndrome in rheumatoid arthritis patients"],"prefix":"10.3897","volume":"68","author":[{"given":"Krasimir","family":"Avramov","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Medical University of Plovdiv, Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snezhana","family":"Terziyska","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, MHAT \"Trimontium\", Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Yakov","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, MHAT \"Trimontium\", Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3220-6703","authenticated-orcid":true,"given":"Todor","family":"Georgiev","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Medical University of Plovdiv, Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneliya","family":"Draganova","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Medical University of Plovdiv, Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1314-7039","authenticated-orcid":true,"given":"Kiril","family":"Terziyski","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Medical University of Plovdiv, Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2258","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"193784_B1"},{"key":"193784_B2"},{"key":"193784_B3"},{"key":"193784_B4"},{"key":"193784_B5"},{"key":"193784_B6"},{"key":"193784_B7"},{"key":"193784_B8"},{"key":"193784_B9"},{"key":"193784_B10"},{"key":"193784_B11"},{"key":"193784_B12"},{"key":"193784_B13"},{"key":"193784_B14"},{"key":"193784_B15","unstructured":"Ta\u0144ski W, \u015awi\u0105toniowska-Lonc N, Tomasiewicz A, et al. The impact of sleep disorders on the daily activity and quality of life in rheumatoid arthritis patients\u2013a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci 2022; 26(9):3212\u201329."},{"key":"193784_B16"},{"key":"193784_B17"},{"key":"193784_B18"},{"key":"193784_B19"},{"key":"193784_B20"},{"key":"193784_B21"},{"key":"193784_B22"},{"key":"193784_B23"},{"key":"193784_B24"},{"key":"193784_B25"},{"key":"193784_B26"},{"key":"193784_B27"},{"key":"193784_B28","unstructured":"American Academy of Sleep Medicine. The AASM International Classification of Sleep Disorders \u2013 Third Edition, Text Revision (ICSD-3-TR). Published online June 2023."},{"key":"193784_B29"},{"key":"193784_B30"},{"key":"193784_B31"},{"key":"193784_B32"},{"key":"193784_B33"},{"key":"193784_B34"},{"key":"193784_B35"},{"key":"193784_B36"}],"container-title":["Folia Medica"],"original-title":[],"link":[{"URL":"https:\/\/foliamedica.bg\/article\/193784\/download\/pdf\/","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/foliamedica.bg\/article\/193784\/download\/xml\/","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/foliamedica.bg\/article_preview.php?id=193784&skip_redirect=1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:26:49Z","timestamp":1780925209000},"score":1,"resource":{"primary":{"URL":"https:\/\/foliamedica.bg\/article\/193784\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,6,8]]}},"URL":"https:\/\/doi.org\/10.3897\/folmed.68.e193784","relation":{},"ISSN":["1314-2143","0204-8043"],"issn-type":[{"value":"1314-2143","type":"electronic"},{"value":"0204-8043","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6,8]]},"article-number":"e193784"}}