{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:53:00Z","timestamp":1785775980354,"version":"3.56.0"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["No. 2023YFC2410804"],"award-info":[{"award-number":["No. 2023YFC2410804"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["No. 23Y11908200"],"award-info":[{"award-number":["No. 23Y11908200"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Preoperative identification of infectious nonunion remains challenging, particularly in patients without overt clinical signs of infection. Conventional inflammatory markers alone often provide insufficient diagnostic accuracy, creating uncertainty in surgical planning. This study aimed to develop and internally evaluate a predictive model combining novel and conventional biomarkers for preoperative diagnosis of infectious nonunion in long bone fractures. We hypothesized that integrating procalcitonin (PCT) with classical inflammatory markers would enhance diagnostic accuracy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analyzed 276 patients treated for femoral or tibial nonunion after internal fixation (2018\u20132023). Patients were randomly divided into a model\u2010development cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009221) and a hold\u2010out test cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200955). A multivariable logistic regression model was built using serum levels of PCT, interleukin\u20106 (IL\u20106), C\u2010reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Model performance was assessed by AUC, calibration plots, and decision curve analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the model\u2010development cohort, 110 patients had infectious nonunion and 111 had aseptic nonunion. Infected cases had significantly higher biomarker levels (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Among single markers, ESR had the best performance (AUC ~0.79), followed by PCT (~0.71), IL\u20106 (~0.62), and CRP (~0.61). The best multivariable model included PCT, CRP, and ESR, achieving an AUC of ~0.85 (95% CI ~0.80\u20130.90). Bootstrapping confirmed minimal overfitting (corrected AUC ~0.84). In the hold\u2010out test cohort, this model maintained strong performance (AUC ~0.85, 95% CI ~0.72\u20130.96), with ~75% sensitivity and 85% specificity\u2014superior to any single biomarker. Calibration plots showed good agreement, and decision analysis demonstrated higher clinical benefit than using individual markers or treating all patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The PCT\u2009+\u2009CRP\u2009+\u2009ESR model reliably distinguishes infectious from aseptic nonunion, outperforming traditional markers alone. It offers a practical, accurate preoperative tool for infection screening, supporting more informed surgical decision\u2010making. In clinical use, interpretation should be based on the predicted probability generated by the combined model rather than isolated elevation of individual biomarkers. Further prospective and external validation is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/os.70365","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:02:10Z","timestamp":1782208930000},"page":"1601-1612","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and Internal Evaluation of a Biomarker\u2010Based Model for Preoperative Diagnosis of Infectious Nonunion"],"prefix":"10.1111","volume":"18","author":[{"given":"Heng","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Orthopedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University  Shanghai China"},{"name":"Department of Orthopedics Shanghai Eighth People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University  Shanghai China"},{"name":"Department of Orthopedics Shanghai Zhujiajiao People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1530\/EOR-24-0032"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000152868.29134.92"},{"issue":"6","key":"e_1_2_12_4_1","first-page":"814","article-title":"Management of Infected Nonunion of the Long Bones by a Multidisciplinary Team","volume":"97","author":"Bose D.","year":"2015","journal-title":"Bone & Joint Journal"},{"issue":"15","key":"e_1_2_12_5_1","first-page":"1409","article-title":"Preoperative Diagnosis of Infection in Patients With Nonunions","volume":"95","author":"Stucken C.","year":"2013","journal-title":"Journal of Bone and Joint Surgery. 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