{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:01:40Z","timestamp":1789970500818,"version":"4.0.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study aimed to comprehensively evaluate the association of twelve inflammation-related biomarkers with amputation level (major vs. minor) in diabetic foot ulcer (DFU) patients undergoing amputation, with particular focus on identifying the strongest associated factor and exploring differences between above-knee amputation (AKA) and below-knee amputation (BKA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively enrolled DFU patients who underwent amputation between January 2020 and June 2025. Twelve indices were calculated: SIRI, SII, AISI, NAR, MAR, RAR, HALP, PNI, ALI, CALLY, IBI, and CLR. LASSO regression and multivariate logistic regression were used for variable selection. AUC comparisons and Bootstrap internal validation assessed model performance. Subgroup analysis compared AKA vs. BKA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 538 patients were included (271 major, 267 minor). In univariate analysis, higher levels of NAR, MAR, RAR, SIRI, SII, AISI, IBI, and CLR were associated with major amputation, whereas lower levels of HALP, PNI, ALI, and CALLY were associated with major amputation. RAR exhibited the highest odds ratio (OR\u00a0=\u00a03.25, 95% CI: 2.54-4.16, p &amp;lt; 0.001) for major versus minor amputation. LASSO regression selected eight indices; multivariate analysis confirmed RAR, HALP, PNI, and ALI as independently associated with amputation level. The combined model incorporating RAR, HALP, PNI, and ALI demonstrated superior predictive performance compared to RAR alone (AUC: 0.816 vs. 0.773, p = 0.001). Bootstrap validation confirmed the stability of the combined model (optimism-corrected AUC: 0.811; optimism: 0.005). In the exploratory subgroup analysis, AKA patients had significantly higher RAR levels and lower PNI and ALI levels compared to BKA patients (all p &amp;lt; 0.05); however, only RAR remained significantly associated with AKA after multivariable adjustment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The combined model may provide modest incremental predictive value over RAR alone, but the clinical gain is limited. RAR alone remains a practical and sufficient tool for risk stratification, particularly in resource-limited settings. However, these findings are retrospective, and external validation is warranted before clinical application.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1925839","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:36:12Z","timestamp":1789968972000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of novel inflammatory biomarkers with major amputation level in diabetic foot ulcer patients undergoing amputation: a retrospective comparative study"],"prefix":"10.3389","volume":"17","author":[{"given":"Hua","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Shanghai Sixth People\u2019s Hospital, JiaoTong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Shanghai Sixth People\u2019s Hospital, JiaoTong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiezhi","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Shanghai Sixth People\u2019s Hospital, JiaoTong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra1615439","article-title":"Diabetic foot ulcers and their recurrence","volume":"376","author":"Armstrong","year":"2017","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.jfas.2016.01.012","article-title":"Mortality after nontraumatic major amputation among patients with diabetes and peripheral vascular disease: a systematic review","volume":"55","author":"Thorud","year":"2016","journal-title":"J Foot Ankle Surg"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/js9.0000000000004179","article-title":"Development and evaluation of thirteen inflammation-related markers for erectile dysfunction in U.S. adults","volume":"112","author":"Wu","year":"2025","journal-title":"Int J Surg (London England)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2025.0074","article-title":"Renal foot in diabetes: implications for wound healing and solutions","volume":"15","author":"Rastogi","year":"2025","journal-title":"Adv Wound Care (New Rochelle)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtv.2024.09.007","article-title":"Systematic review and meta-analysis of the diagnostic accuracy of inflammatory markers for infected diabetic foot ulcer","volume":"33","author":"Chen","year":"2024","journal-title":"J Tissue Viability"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/js9.0000000000002996","article-title":"Extensive study on the associations of 12 composite inflammatory indices with colorectal cancer risk and mortality: a cross-sectional analysis of NHANES 2001-2020","volume":"111","author":"Zhou","year":"2025","journal-title":"Int J Surg (London England)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1654831","article-title":"Association of inflammation and nutrition-based indicators and diabetic foot ulcers: a cross-sectional study and a retrospective study","volume":"16","author":"Chen","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1155\/mi\/7709529","article-title":"Association between three systemic inflammatory biomarkers and diabetic foot ulcer: a cross-sectional study and a clinical retrospective study","volume":"2026","author":"Chen","year":"2026","journal-title":"Mediators Inflammation"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1602361","article-title":"Nutritional-inflammatory status and diabetic retinopathy: exploring the association between advanced lung cancer inflammation index and retinal complications in diabetes","volume":"12","author":"Peng","year":"2025","journal-title":"Front Nutr"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1177\/00368504251387822","article-title":"CALLY index and hypertension in diabetes: a composite inflammation-nutrition-immunity marker","volume":"108","author":"Peng","year":"2025","journal-title":"Sci Prog"},{"key":"B11","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s12902-025-01911-6","article-title":"Association of the inflammatory burden index with the risk of pre-diabetes and diabetes mellitus: a cross-sectional study","volume":"25","author":"Yu","year":"2025","journal-title":"BMC Endocr Disord"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"Jama"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13051076","article-title":"Diabetic foot ulcers: pathophysiology, immune dysregulation, and emerging therapeutic strategies","volume":"13","author":"Dawi","year":"2025","journal-title":"Biomedicines"},{"key":"B14","doi-asserted-by":"publisher","first-page":"43","DOI":"10.5005\/jp\/books\/11137_18","article-title":"Nutritional status in a group of patients with wounds due to diabetic foot disease and chronic venous insufficiency","volume":"14","author":"Sk\u00f3rka","year":"2024","journal-title":"J Clin Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.17733","article-title":"Relationship between neutrophil\/albumin ratio and early mortality after major lower extremity amputation","volume":"13","author":"G\u00fcnay","year":"2021","journal-title":"Cureus"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2147\/ijgm.s322441","article-title":"The red blood cell distribution width-albumin ratio: a promising predictor of mortality in stroke patients","volume":"14","author":"Zhao","year":"2021","journal-title":"Int J Gen Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5629","article-title":"Prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study","volume":"6","author":"Chen","year":"2015","journal-title":"Oncotarget"},{"key":"B18","article-title":"Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients","volume":"85","author":"Onodera","year":"1984","journal-title":"Nihon Geka Gakkai Zasshi"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-13-158","article-title":"Advance lung cancer inflammation index (ALI) at diagnosis is a prognostic marker in patients with metastatic non-small cell lung cancer (NSCLC): a retrospective review","volume":"13","author":"Jafri","year":"2013","journal-title":"BMC Cancer"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30057","article-title":"A novel systemic inflammation response index (SIRI) for predicting the survival of patients with pancreatic cancer after chemotherapy","volume":"122","author":"Qi","year":"2016","journal-title":"Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-14-0442","article-title":"Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma","volume":"20","author":"Hu","year":"2014","journal-title":"Clin Cancer Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/ans.14557","article-title":"Inflammatory cell indexes as preoperative predictors of hospital stay in open elective thoracic surgery","volume":"88","author":"Paliogiannis","year":"2018","journal-title":"Anz J Surg"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.hpb.2021.06.414","article-title":"Superiority of CRP-albumin-lymphocyte index (CALLY index) as a non-invasive prognostic biomarker after hepatectomy for hepatocellular carcinoma","volume":"24","author":"Iida","year":"2022","journal-title":"HPB Off J Int Hepato Pancreato Biliary Assoc"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnesp.2022.09.366","article-title":"Inflammatory burden as a prognostic biomarker for cancer","volume":"41","author":"Xie","year":"2022","journal-title":"Clin Nutr (Edinburgh Scotland)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-020-08301-3","article-title":"Prognostic value of the C-reactive protein\/lymphocyte ratio in pancreatic cancer","volume":"27","author":"Fan","year":"2020","journal-title":"Ann Surg Oncol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s12933-022-01534-4","article-title":"Impact of red cell distribution width and red cell distribution width\/albumin ratio on all-cause mortality in patients with type 2 diabetes and foot ulcers: a retrospective cohort study","volume":"21","author":"Hong","year":"2022","journal-title":"Cardiovasc Diabetol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/jpen.1451","article-title":"Hypoalbuminemia: pathogenesis and clinical significance","volume":"43","author":"Soeters","year":"2019","journal-title":"JPEN J Parenteral Enteral Nutr"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1177\/15347346241273156","article-title":"Association between red cell distribution width\/albumin ratio and diabetic lower extremity ulcers (DLEU) among US outpatients in the NHANES: a retrospective cross-sectional study","volume":"25","author":"Huang","year":"2026","journal-title":"Int J Low Extrem Wounds"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2026.1875176","article-title":"Inflammation and nutrition-derived indicators for predicting amputation risk in patients with type 2 diabetic foot ulcers","volume":"13","author":"He","year":"2026","journal-title":"Front Nutr"},{"key":"B30","doi-asserted-by":"publisher","first-page":"15347346251355578","DOI":"10.1177\/15347346251355578","article-title":"Association between hemoglobin, albumin, lymphocyte, and platelet score and diabetic foot ulcer: a cross-sectional study","author":"Li","year":"2025","journal-title":"Int J Low Extrem Wounds"},{"key":"B31","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1007\/s00423-025-03884-5","article-title":"Prognostic role of HALP score, CRP\/albumin ratio and CALLY index in diabetic foot ulcer-related major amputations","volume":"410","author":"Keskink\u0131l\u0131\u00e7 Ya\u011f\u0131z","year":"2025","journal-title":"Langenbeck's Arch Surg"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1925839\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:36:13Z","timestamp":1789968973000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1925839\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":31,"alternative-id":["10.3389\/fendo.2026.1925839"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1925839","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]},"article-number":"1925839"}}