{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:49:35Z","timestamp":1792799375123,"version":"4.5.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the dynamic prognostic value of multicategory biomarkers in burn sepsis and identify patient phenotypes based on their longitudinal trajectories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective cohort study included 712 adult patients with burn sepsis (Sepsis\u22123) admitted to a regional burn ICU (2022\u20132025). Seventeen biomarkers covering nutrition (albumin, ALB; prealbumin, PA; transferrin, TRF; nitrogen balance), immunity (immunoglobulins A\/G\/M; CD3\n                      <jats:sup>+<\/jats:sup>\n                      \/CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      ratio; natural killer, NK cells), and inflammation (interleukin\u22126, IL\u22126; C\u2212reactive protein, CRP; procalcitonin, PCT; platelet count, lactate) were measured at five time points (days 1, 3, 7, 14, and 21). We compared survivor\/non-survivor trajectories using linear mixed-effects models, assessed baseline biomarker associations with 21\u2212day mortality via Cox regression, and evaluated predictive performance with Harrell\u2019s C-index. Growth mixture modeling (GMM) identified phenotypes from integrated ALB, IL\u22126, and immunoglobulin G (IgG) trajectories.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The 21\u2212day mortality was 17.9% (81 deaths). Survivor and non-survivor trajectories differed significantly for multiple biomarkers (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). Growth mixture modeling identified two distinct patient phenotypes: a high-risk phenotype (\n                      <jats:italic>n<\/jats:italic>\n                      = 267, mortality 15.7%) characterized by persistently lower ALB and IgG and sustained IL\u22126 elevation over 21 days and a low-risk phenotype (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0445, mortality 8.8%) with favorable biomarker trajectories (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.005). Univariable analysis associated several baseline markers with mortality (e.g.,\u00a0ALB: HR = 0.97,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.013; IL\u22126: HR\u00a0=\u00a01.004,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.004). However, no biomarker retained independent significance in multivariable analysis, likely due to multicollinearity among nutritional markers [variance inflation factor (VIF) up to 8.4]. Harrell\u2019s C-indices for baseline ALB, PA, and IgG were modest (0.604, 0.583, and 0.585, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Longitudinal multicategory biomarker trajectories predict 21\u2212day survival in burn sepsis. Trajectory-based phenotyping identifies patient subgroups with markedly different outcomes, offering superior prognostic stratification over static measurements. The integrated phenotype, reflecting the dynamic interplay of catabolism, immune paralysis, and inflammation, emerges as a robust prognostic marker, supporting personalized management approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1710916","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T05:24:48Z","timestamp":1776317088000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Dynamic biomarker profiling and phenotyping in burn sepsis: a retrospective cohort study using growth mixture modeling"],"prefix":"10.3389","volume":"16","author":[{"given":"Pei","family":"Xu","sequence":"first","affiliation":[{"name":"Burn Department, Ningbo No. 2 Hospital, Wenzhou Medical University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Lou","sequence":"additional","affiliation":[{"name":"Burn Department, Ningbo No. 2 Hospital, Wenzhou Medical University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Kong","sequence":"additional","affiliation":[{"name":"Ningbo College of Health Sciences","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiliang","family":"Li","sequence":"additional","affiliation":[{"name":"Burn Department, Ningbo No. 2 Hospital, Wenzhou Medical University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Xiang","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine, University of Bonn","place":["Bonn, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Health Science Center, Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyong","family":"Cui","sequence":"additional","affiliation":[{"name":"Burn Department, Ningbo No. 2 Hospital, Wenzhou Medical University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neng","family":"Huang","sequence":"additional","affiliation":[{"name":"Burn Department, Ningbo No. 2 Hospital, Wenzhou Medical University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sida","family":"Xu","sequence":"additional","affiliation":[{"name":"Burn Department, Ningbo No. 2 Hospital, Wenzhou Medical University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Le","sequence":"additional","affiliation":[{"name":"Burn Department, Ningbo No. 2 Hospital, Wenzhou Medical University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youfen","family":"Fan","sequence":"additional","affiliation":[{"name":"Burn Department, Ningbo No. 2 Hospital, Wenzhou Medical University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoying","family":"Jin","sequence":"additional","affiliation":[{"name":"Burn Department, Ningbo No. 2 Hospital, Wenzhou Medical University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.jinf.2014.12.010","article-title":"Transcriptomic correlates of organ failure extent in sepsis","volume":"70","author":"Almansa","year":"2015","journal-title":"J. Infection"},{"key":"B2","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.burns.2008.01.014","article-title":"Comparison of WBC, ESR, CRP and PCT serum levels in septic and non-septic burn cases","volume":"34","author":"Barati","year":"2008","journal-title":"Burns: J. Int. Soc. For. Burn Injuries"},{"key":"B3","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s12871-018-0585-6","article-title":"Procalcitonin kinetics after burn injury and burn surgery in septic and non-septic patients - a retrospective observational study","volume":"18","author":"Cabral","year":"2018","journal-title":"BMC Anesthesiology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002352","article-title":"Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: a prospective cohort study","volume":"14","author":"Cabrera","year":"2017","journal-title":"PloS Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0140-6736(18)30696-2","article-title":"Sepsis and septic shock","volume":"392","author":"Cecconi","year":"2018","journal-title":"Lancet (London England)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/S2213-2600(16)00046-1","article-title":"Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study","volume":"4","author":"Davenport","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/BCR.0000000000000419","article-title":"Scald burn injuries caused by showers among the adult population in the southwest region","volume":"38","author":"Emam","year":"2017","journal-title":"J. Burn Care Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jcrc.2018.06.012","article-title":"Six subphenotypes in septic shock: latent class analysis of the PROWESS Shock study","volume":"47","author":"G\u00e5rdlund","year":"2018","journal-title":"J. Crit. Care"},{"key":"B9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1164\/rccm.201201-0037OC","article-title":"Combination biomarkers to diagnose sepsis in the critically ill patient","volume":"186","author":"Gibot","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/S2213-2600(17)30045-0","article-title":"Enhanced understanding of the host-pathogen interaction in sepsis: new opportunities for omic approaches","volume":"5","author":"Goh","year":"2017","journal-title":"Lancet Respir. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1016\/j.jpedsurg.2020.01.051","article-title":"Non-neurologic organ dysfunction plays a major role in predicting outcomes in pediatric traumatic brain injury","volume":"55","author":"Hanna","year":"2020","journal-title":"J. Pediatr. Surg."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1056\/NEJMoa1212722","article-title":"A randomized trial of glutamine and antioxidants in critically ill patients","volume":"368","author":"Heyland","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"16045","DOI":"10.1038\/nrdp.2016.45","article-title":"Sepsis and septic shock","volume":"2","author":"Hotchkiss","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/cc8232","article-title":"Association between regulatory T cell activity and sepsis and outcome of severely burned patients: a prospective, observational study","volume":"14","author":"Huang","year":"2010","journal-title":"Crit. Care (London England)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/s41598-018-36743-z","article-title":"The Pediatric Sepsis Biomarker Risk Model (PERSEVERE) biomarkers predict clinical deterioration and mortality in immunocompromised children evaluated for infection","volume":"9","author":"Jacobs","year":"2019","journal-title":"Sci. Rep."},{"key":"B16","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41572-020-0145-5","article-title":"Burn injury","volume":"6","author":"Jeschke","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B17","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1007\/s00134-015-3764-7","article-title":"Phenotypic clusters within sepsis-associated multiple organ dysfunction syndrome","volume":"41","author":"Knox","year":"2015","journal-title":"Intensive Care Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.burns.2019.11.006","article-title":"Doxepin cream is not effective in reducing itch in burn scar patients: a multicenter triple-blind randomized clinical crossover trial","volume":"46","author":"Kwa","year":"2020","journal-title":"Burns: J. Int. Soc. For. Burn Injuries"},{"key":"B19","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.burns.2006.07.001","article-title":"Inflammatory markers in patients with severe burn injury. What is the best indicator of sepsis","volume":"33","author":"Lavrentieva","year":"2007","journal-title":"Burns: J. Int. Soc. For. Burn Injuries"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1038\/s41591-019-0673-2","article-title":"Undulating changes in human plasma proteome profiles across the lifespan","volume":"25","author":"Lehallier","year":"2019","journal-title":"Nat. Med."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175130","article-title":"Validation of two multiplex platforms to quantify circulating markers of inflammation and endothelial injury in severe infection","volume":"12","author":"Leligdowicz","year":"2017","journal-title":"PloS One"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000020161","article-title":"Research \"recover from illness defense complex\" helper T cell immune mechanisms based on the \"Fuxie\" theory clearing away heat evil thoroughly nourishing kidney treatment of recurrent blood-heat syndrome psoriasis","volume":"99","author":"Li","year":"2020","journal-title":"Medicine"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1186\/s40064-016-3591-5","article-title":"Biomarkers for diagnosis of sepsis in patients with systemic inflammatory response syndrome: a systematic review and meta-analysis","volume":"5","author":"Liu","year":"2016","journal-title":"SpringerPlus"},{"key":"B24","first-page":"116","article-title":"Procalcitonin: a diagnostic and prognostic biomarker of sepsis in burned patients","volume":"28","author":"Mokline","year":"2015","journal-title":"Ann. Burns Fire Disasters"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1097\/BCR.0000000000000355","article-title":"Burns: pathophysiology of systemic complications and current management","volume":"38","author":"Nielson","year":"2017","journal-title":"J. Burn Care Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.ebiom.2014.10.003","article-title":"An endotoxin tolerance signature predicts sepsis and organ dysfunction at initial clinical presentation","volume":"1","author":"Pena","year":"2014","journal-title":"EBioMedicine"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1186\/cc8872","article-title":"Sepsis biomarkers: a review","volume":"14","author":"Pierrakos","year":"2010","journal-title":"Crit. Care (London England)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000002732","article-title":"Sepsis reduces bone strength before morphologic changes are identifiable","volume":"45","author":"Puthucheary","year":"2017","journal-title":"Crit. Care Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.1097\/CCM.0000000000001244","article-title":"Dire straits for biomarkers of neurosurgery-associated meningitis","volume":"43","author":"Puttgen","year":"2015","journal-title":"Crit. Care Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.burns.2014.08.019","article-title":"Serum procalcitonin as a diagnostic biomarker for sepsis in burned patients: a meta-analysis","volume":"41","author":"Ren","year":"2015","journal-title":"Burns: J. Int. Soc. For. Burn Injuries"},{"key":"B31","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet (London England)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/S2213-2600(17)30294-1","article-title":"Classification of patients with sepsis according to blood genomic endotype: a prospective cohort study","volume":"5","author":"Scicluna","year":"2017","journal-title":"Lancet Respir. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.burns.2013.11.018","article-title":"Procalcitonin in the burn unit and the diagnosis of infection","volume":"40","author":"Seoane","year":"2014","journal-title":"Burns: J. Int. Soc. For. Burn Injuries"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1001\/jama.2019.5791","article-title":"Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis","volume":"321","author":"Seymour","year":"2019","journal-title":"JAMA"},{"key":"B35","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/s13054-019-2398-5","article-title":"Sepsis: personalization v protocolization","volume":"23","author":"Singer","year":"2019","journal-title":"Crit. Care (London England)"},{"key":"B36","doi-asserted-by":"publisher","first-page":"801","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":"B37","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.jcrc.2018.06.010","article-title":"Non-invasive ventilation in low- and low-middle income countries: insights for real-world analysis","volume":"47","author":"Singha","year":"2018","journal-title":"J. Crit. Care"},{"key":"B38","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1089\/sur.2017.288","article-title":"Status and challenges of predicting and diagnosing sepsis in burn patients","volume":"19","author":"Stanojcic","year":"2018","journal-title":"Surg. Infections"},{"key":"B39","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1097\/CCM.0000000000003084","article-title":"Unsupervised analysis of transcriptomics in bacterial sepsis across multiple datasets reveals three robust clusters","volume":"46","author":"Sweeney","year":"2018","journal-title":"Crit. Care Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/s41467-018-03078-2","article-title":"A community approach to mortality prediction in sepsis via gene expression analysis","volume":"9","author":"Sweeney","year":"2018","journal-title":"Nat. Commun."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2026.157107","article-title":"Inflammatory imbalance in ambulance patients is associated with sepsis and septic shock","volume":"199","author":"Tuerxun","year":"2026","journal-title":"Cytokine"},{"key":"B42","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nri.2017.36","article-title":"The immunopathology of sepsis and potential therapeutic targets","volume":"17","author":"van der Poll","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1001\/jama.2016.2691","article-title":"Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis","volume":"315","author":"van Vught","year":"2016","journal-title":"JAMA"},{"key":"B44","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nrneph.2017.165","article-title":"Advances in the understanding and treatment of sepsis-induced immunosuppression","volume":"14","author":"Venet","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1186\/cc8170","article-title":"The leading causes of death after burn injury in a single pediatric burn center","volume":"13","author":"Williams","year":"2009","journal-title":"Crit. Care (London England)"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax9000","article-title":"Prospective clinical testing and experimental validation of the Pediatric Sepsis Biomarker Risk Model","volume":"11","author":"Wong","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"B47","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s13613-017-0316-z","article-title":"Comparison of diagnostic accuracy in sepsis between presepsin, procalcitonin, and C-reactive protein: a systematic review and meta-analysis","volume":"7","author":"Wu","year":"2017","journal-title":"Ann. Intensive Care"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2581","DOI":"10.1084\/jem.20111354","article-title":"A genomic storm in critically injured humans","volume":"208","author":"Xiao","year":"2011","journal-title":"J. Exp. Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.clinthera.2024.07.006","article-title":"Longitudinal vasoactive inotrope score trajectories and their prognostic significance in critically ill sepsis patients: a retrospective cohort analysis","volume":"46","author":"Xiao","year":"2024","journal-title":"Clin. Ther."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000046699","article-title":"Association of serum calcium levels within the first hour of ER admission with 28-day mortality in sepsis: a retrospective ICU analysis","volume":"104","author":"Xu","year":"2025","journal-title":"Medicine"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1710916\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T05:24:49Z","timestamp":1776317089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1710916\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":50,"alternative-id":["10.3389\/fcimb.2026.1710916"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1710916","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"article-number":"1710916"}}