{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T17:16:57Z","timestamp":1783099017440,"version":"3.54.6"},"reference-count":35,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Universiti Malaya Specialist Centre C.A.R.E. Fund Research Grant","award":["UMG004C-2025"],"award-info":[{"award-number":["UMG004C-2025"]}]},{"name":"Universiti Malaya Bantuan Khas Penyelidikan - Early Career Research Grant","award":["BKP031-2025-ECRG"],"award-info":[{"award-number":["BKP031-2025-ECRG"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["The International Journal of Lower Extremity Wounds"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Clinical guidelines conventionally define nutritional adequacy using a 35\u2005g\/L serum albumin threshold. However, its biological sufficiency for driving diabetic foot ulcer (DFU) regeneration remains unvalidated. This investigation utilized a structural modeling framework to interrogate the non-linear relationship between albumin and DFU repair and to identify the precise physiological threshold required for active healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective, dual-center cohort study of 733 DFU patients utilized a 20-week observation window anchored to baseline enrollment (Time Zero, T0). To isolate the independent metabolic effect of albumin from systemic inflammatory confounding, we implemented a doubly robust framework integrating generalized propensity score (GPS) weighting with restricted cubic spline (RCS) modeling. The primary endpoint was Percentage Area Reduction (PAR) at 20 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Baseline albumin was identified as a significant independent driver of wound reduction (\u03b2\u2009=\u20093.25; 95% CI: 0.76-5.73; P\u2009=\u20090.01) and a protective factor against major amputation (OR\u2009=\u20090.89; 95% CI: 0.79-0.99; P\u2009=\u20090.037). RCS analysis revealed a highly significant non-linear trajectory (P for non-linearity &lt; 0.001) with a biological inflection point at 37.9\u2005g\/L. No significant regenerative progress occurred within the 31.4\u201337.9\u2005g\/L stagnation plateau. Sensitivity analysis confirmed the conventional 35\u2005g\/L cutoff failed to differentiate healing outcomes (P\u2009=\u20090.869), resulting in 45.8% of normoalbuminemic patients being misclassified within a state of regenerative arrest. The calculated E-value of 3.40 confirms profound robustness against unmeasured confounding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The conventional 35\u2005g\/L albumin threshold is clinically inadequate to sustain the metabolic demands of DFU repair. To breach the identified stagnation plateau and transition the wound bed toward active regeneration, clinicians should prioritize a new physiological target of 37.9\u2005g\/L (clinically operationalized as\u2009\u2265\u200938\u2005g\/L). This necessitates a strategic shift toward metabolic intensification in limb salvage protocols.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15347346261465333","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T19:27:35Z","timestamp":1782847655000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Intensification in Limb Salvage: A Doubly Robust Dual-Center Study Establishing 37.9\u2005g\/L as the Physiological Requirement for Diabetic Foot Ulcer Regeneration"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6729-0230","authenticated-orcid":false,"given":"Terry Hao-Yu","family":"Qin","sequence":"first","affiliation":[{"name":"National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Universiti Malaya"},{"name":"Department of Orthopaedic Surgery, Foot &amp; Ankle Unit and Traumatology, Faculty of Medicine, National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Universiti Malaya, Kuala Lumpur, Malaysia"},{"name":"University Malaya Medical Centre (UMMC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atiqah","family":"Aziz","sequence":"additional","affiliation":[{"name":"National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Universiti Malaya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Wen","family":"Ling","sequence":"additional","affiliation":[{"name":"University Malaya Medical Centre (UMMC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Haseeb","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Foot &amp; Ankle Unit and Traumatology, Faculty of Medicine, National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Universiti Malaya, Kuala Lumpur, Malaysia"},{"name":"University Malaya Medical Centre (UMMC)"},{"name":"University Malaya Specialist Centre (UMSC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Mahirah","family":"Zulkifli","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Foot &amp; Ankle Unit and Traumatology, Faculty of Medicine, National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Universiti Malaya, Kuala Lumpur, Malaysia"},{"name":"University Malaya Medical Centre (UMMC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tunku","family":"Kamarul","sequence":"additional","affiliation":[{"name":"National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Universiti Malaya"},{"name":"University Malaya Medical Centre (UMMC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Ling","family":"Tan","sequence":"additional","affiliation":[{"name":"National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Universiti Malaya"},{"name":"Department of Orthopaedic Surgery, Foot &amp; 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