{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:27:11Z","timestamp":1785421631872,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,16]]},"group-title":"Orthopedics","reference-count":140,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["UH3AG05692"],"award-info":[{"award-number":["UH3AG05692"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30AG072958"],"award-info":[{"award-number":["P30AG072958"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30AG028716"],"award-info":[{"award-number":["P30AG028716"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K76AG074943"],"award-info":[{"award-number":["K76AG074943"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Chronic postsurgical pain (CPSP) prevalence after total knee arthroplasty (TKA) is &gt;20%. Circulating immune biomarkers are associated with musculoskeletal pain but poorly understood as CPSP predictors. This prospective, longitudinal study of 203 patients undergoing TKA tested presurgical plasma biomarkers associated with 6-month CPSP, using approaches from geriatrics biomarker research: expected recovery differential (ERD; resilience outcome) and penalized, machine-learning regularization modeling (elastic net and LASSO regression). Forty-nine presurgical candidate biomarkers were considered. CPSP was operationalized using ERDs built around PROMIS pain intensity and pain interference, which quantified the difference between observed and expected recovery after accounting for demographic, comorbidity, reserve, and perioperative factors. Plasma\/ERDs from \u223c130 patients revealed 13 biomarkers with the highest selection stability criteria, and either positive or negative (+\/\u2013) associations with ERDs. Interleukin (IL) \u22125 (\u2013) and Lipopolysaccharide-Binding Protein (LBP; +) were associated with both ERDs. Unique associations with pain intensity ERD included Cytomegalovirus-Specific IgG Negative (CMV IgG\u2013; \u2013), Macrophage Inflammatory Protein-1 Beta (MIP-1\u03b2; \u2013), IL-12p70 (\u2013), Cluster of Differentiation 30 (sCD30; \u2013), Interferon alpha 2a (IFN\u03b12a; +), and Leukemia Inhibitory Factor (LIF; +). Unique associations with pain interference ERD included Lipopolysaccharide (LPS; \u2013), Activin A (\u2013), IL-8 (\u2013), Serum Amyloid A (SAA; \u2013), and IL-7 (+). Protein-protein interaction and topological analyses suggest a centralized subnetwork with higher-than-expected connectivity involving IL-5, IL-7, IL-8, MIP-1\u03b2, and IFN\u03b1-2a, among others. This study proposes rigorous yet feasible approaches to expedite pain biomarker research and introduces presurgical biomarkers to consider in future TKA-CPSP biosignature derivation.<\/jats:p>\n                <jats:sec>\n                  <jats:title>SUMMARY<\/jats:title>\n                  <jats:p>Methodological approaches used in geriatric biomarker studies were applied to identify 13 pre-surgical plasma biomarkers associated with chronic postsurgical pain outcomes following total knee arthroplasty.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.15.26355689","type":"posted-content","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:30:30Z","timestamp":1781667030000},"source":"Crossref","is-referenced-by-count":0,"title":["Presurgical immune biomarkers associated with pain intensity and pain interference recovery after total knee arthroplasty: findings from the PRIME-KNEE 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NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet L","family":"Huebner","sequence":"additional","affiliation":[{"name":"Center for the Study of Aging and Human Development, Duke University School of Medicine, Durham, NC"},{"name":"Duke Molecular Physiology Institute, Duke University, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa C.","family":"Ashner","sequence":"additional","affiliation":[{"name":"Center for the Study of Aging and Human Development, Duke University School of Medicine, Durham, NC"},{"name":"Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Bareja","sequence":"additional","affiliation":[{"name":"Center for the Study of Aging and Human Development, Duke University School of Medicine, Durham, NC"},{"name":"Duke Molecular Physiology Institute, Duke University, Durham, 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