{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:24:44Z","timestamp":1786944284044,"version":"build-2736575974"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"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. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute brain injury (ABI) requires early, interpretable risk stratification to support ICU risk assessment. We evaluated whether longitudinal albumin-to\u2013red cell distribution width ratio (ARR) trajectories provide time-dependent prognostic information and support prediction with multicenter validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this multicenter, retrospective cohort study (NSICU, MIMIC-IV, eICU), latent class growth modeling identified ARR trajectories. Nonproportional hazards were addressed with time-stratified Cox models (0\u20137, 7\u201314, &amp;gt;14\u202fdays) and restricted mean survival time (RMST) at 7, 14, and 28\u202fdays. Multiple machine-learning classifiers were benchmarked to develop an interpretable prediction model with internal and external validation. Performance assessment included discrimination, calibration, decision-curve analysis, and SHAP-based interpretability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 8,270 ICU patients (NSICU n\u202f=\u202f5,093; MIMIC-IV n\u202f=\u202f744; eICU n\u202f=\u202f2,433), four ARR trajectories were identified. Relative to Gradual Decline, recovery-type trajectories were associated with lower early mortality risk (0\u20137\u202fdays: HRs 0.29 and 0.14; 7\u201314\u202fdays: HRs 0.43 and 0.50), whereas the Sustained High-Risk trajectory showed excess hazard primarily beyond 14\u202fdays (HR 1.42). These time-dependent patterns were broadly supported by RMST and sensitivity analyses. The final ExtraTrees model achieved AUROC 0.869 and Brier score 0.066 on the internal hold-out set; external validation yielded AUROC 0.731, PR AUC 0.429, and Brier score 0.161, indicating attenuated but informative external performance with modest decision-curve benefit. A web-based research calculator provides individualized risk estimates and SHAP explanations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Standardized ARR trajectories provide dynamic, phase-specific prognostic information in ABI and complement static assessments. When integrated into an interpretable machine-learning model, these trajectories may support adjunctive risk estimation as patient status evolves. Prospective evaluation and site-level recalibration are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1855636","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:37:06Z","timestamp":1786941426000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic albumin-to\u2013RDW trajectories for time-dependent risk stratification in acute brain injury"],"prefix":"10.3389","volume":"13","author":[{"given":"Juan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]},{"name":"Department of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"Neurosurgical Institute, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Man","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]},{"name":"Department of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"Neurosurgical Institute, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"Neurosurgical Institute, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Juan","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Medical Big Data, Nanjing Drum Tower Hospital, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Lian","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]},{"name":"Department of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"Neurosurgical Institute, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Hua","family":"Hang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]},{"name":"Department of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"Neurosurgical Institute, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Lai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]},{"name":"Department of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"Neurosurgical Institute, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e282","DOI":"10.1161\/STR.0000000000000407","article-title":"2022 guideline for the Management of Patients with Spontaneous Intracerebral Hemorrhage: a guideline from the American Heart Association\/American Stroke Association","volume":"53","author":"Greenberg","year":"2022","journal-title":"Stroke"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e199","DOI":"10.1161\/STR.0000000000000464","article-title":"2024 AHA\/ASA performance and quality measures for spontaneous intracerebral hemorrhage: a report from the American Heart Association\/American Stroke Association","volume":"55","author":"Ruff","year":"2024","journal-title":"Stroke"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1001\/jamasurg.2015.1678","article-title":"Compliance with evidence-based guidelines and Interhospital variation in mortality for patients with severe traumatic brain injury","volume":"150","author":"Dawes","year":"2015","journal-title":"JAMA Surg"},{"key":"ref4","first-page":"425","article-title":"Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients","volume-title":"BMJ","author":"Perel","year":"2008"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ijsu.2019.04.005","article-title":"Diagnostic accuracy of hematological parameters in acute mesenteric ischemia-a systematic review","volume":"66","author":"Khan","year":"2019","journal-title":"Int J Surg"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e2413213","DOI":"10.1001\/jamanetworkopen.2024.13213","article-title":"Ratio of red blood cell distribution width to albumin level and risk of mortality","volume":"7","author":"Hao","year":"2024","journal-title":"JAMA Netw Open"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.ijsu.2013.06.003","article-title":"The introduction of an acute physiological support service for surgical patients is an effective error reduction strategy","volume":"11","author":"Clarke","year":"2013","journal-title":"Int J Surg"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"7350","DOI":"10.1097\/JS9.0000000000002864","article-title":"Troponin I\/albumin (TBI) index: a new tool for the prediction of mortality in hospitalized patients with traumatic brain injury","volume":"111","author":"Wang","year":"2025","journal-title":"Int J Surg"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e078378","DOI":"10.1136\/bmj-2023-078378","article-title":"TRIPOD+AI statement: updated guidance for reporting clinical prediction models that use regression or machine learning methods","volume":"385","author":"Collins","year":"2024","journal-title":"BMJ"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"51","DOI":"10.7326\/M18-1376","article-title":"PROBAST: a tool to assess the risk of bias and applicability of prediction model studies","volume":"170","author":"Wolff","year":"2019","journal-title":"Ann Intern Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1146\/annurev-clinpsy-081122-012416","article-title":"Recent advances in group-based trajectory modeling for clinical research","volume":"20","author":"Nagin","year":"2024","journal-title":"Annu Rev Clin Psychol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1161\/STROKEAHA.123.044248","article-title":"Albumin levels and risk of early cardiovascular complications after ischemic stroke: a propensity-matched analysis of a global federated health network","volume":"55","author":"Bucci","year":"2024","journal-title":"Stroke"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.3390\/nu16101486","article-title":"Serum albumin and post-stroke outcomes: analysis of UK regional registry data, systematic review, and Meta-analysis","volume":"16","author":"Thuemmler","year":"2024","journal-title":"Nutrients"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1136\/svn-2020-000676","article-title":"Low serum albumin levels predict poor outcome in patients with acute ischaemic stroke or transient ischaemic attack","volume":"6","author":"Zhou","year":"2021","journal-title":"Stroke Vasc Neurol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1161\/STROKEAHA.121.034366","article-title":"Prevalence and prognostic significance of malnutrition risk in patients with acute ischemic stroke: results from the third China National Stroke Registry","volume":"53","author":"Zhang","year":"2022","journal-title":"Stroke"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1007\/s12028-020-01103-1","article-title":"Red cell distribution width is associated with 30-day mortality in patients with spontaneous intracerebral hemorrhage","volume":"34","author":"Pinho","year":"2021","journal-title":"Neurocrit Care"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"tkab050","DOI":"10.1093\/burnst\/tkab050","article-title":"Red cell distribution width\/albumin ratio and 90-day mortality after burn surgery","volume":"10","author":"Seo","year":"2022","journal-title":"Burns Trauma"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1617199","DOI":"10.3389\/fnut.2025.1617199","article-title":"Association between red cell distribution width to albumin ratio and clinical outcomes in elderly patients with sepsis: a cohort study","volume":"12","author":"An","year":"2025","journal-title":"Front Nutr"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"2472866","DOI":"10.1080\/07853890.2025.2472866","article-title":"C-reactive protein to albumin ratio and Glasgow coma scale score as the predictors for weaning outcomes in traumatic brain injury","volume":"57","author":"Zeng","year":"2025","journal-title":"Ann Med"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.3390\/nu16183176","article-title":"The combination effect of the red blood cell distribution width and prognostic nutrition index on the prognosis in patients undergoing PCI","volume":"16","author":"Huo","year":"2024","journal-title":"Nutrients"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.4103\/0366-6999.205858","article-title":"Dynamic change of red cell distribution width levels in prediction of hospital mortality in Chinese elderly patients with septic shock","volume":"130","author":"Ju","year":"2017","journal-title":"Chin Med J"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e13106","DOI":"10.1111\/bpa.13106","article-title":"Inflammatory and oxidative stress markers in intracerebral hemorrhage: relevance as prognostic markers for quantification of the edema volume","volume":"33","author":"Rendevski","year":"2023","journal-title":"Brain Pathol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"107577","DOI":"10.1016\/j.compbiomed.2023.107577","article-title":"An interpretable ensemble learning model facilitates early risk stratification of ischemic stroke in intensive care unit: development and external validation of ICU-ISPM","volume":"166","author":"Hu","year":"2023","journal-title":"Comput Biol Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"2718","DOI":"10.1161\/STROKEAHA.113.002033","article-title":"Validation of the DRAGON score in 12 stroke centers in anterior and posterior circulation","volume":"44","author":"Strbian","year":"2013","journal-title":"Stroke"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1161\/01.str.32.4.891","article-title":"The ICH score: a simple, reliable grading scale for intracerebral hemorrhage","volume":"32","author":"Hemphill","year":"2001","journal-title":"Stroke"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1161\/STROKEAHA.116.012802","article-title":"External validation of the ASTRAL and DRAGON scores for prediction of functional outcome in stroke","volume":"47","author":"Cooray","year":"2016","journal-title":"Stroke"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"109634","DOI":"10.1016\/j.compbiomed.2024.109634","article-title":"AI-based models to predict decompensation on traumatic brain injury patients","volume":"186","author":"Ribeiro","year":"2025","journal-title":"Comput Biol Med"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"3967","DOI":"10.1109\/JBHI.2021.3085881","article-title":"Prediction of life-threatening intracranial hypertension during the acute phase of traumatic brain injury using machine learning","volume":"25","author":"Lee","year":"2021","journal-title":"IEEE J Biomed Health Inform"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ejim.2022.05.004","article-title":"Low serum albumin: a neglected predictor in patients with cardiovascular disease","volume":"102","author":"Manolis","year":"2022","journal-title":"Eur J Intern Med"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1056\/NEJMoa067514","article-title":"Saline or albumin for fluid resuscitation in patients with traumatic brain injury","volume":"357","author":"Myburgh","year":"2007","journal-title":"N Engl J Med"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3109\/10408363.2014.992064","article-title":"Red blood cell distribution width: a simple parameter with multiple clinical applications","volume":"52","author":"Salvagno","year":"2015","journal-title":"Crit Rev Clin Lab Sci"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1182\/blood.2021013472","article-title":"The role of iron in chronic inflammatory diseases: from mechanisms to treatment options in anemia of inflammation","volume":"140","author":"Marques","year":"2022","journal-title":"Blood"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41590-018-0064-8","article-title":"Innate immune responses to trauma","volume":"19","author":"Huber-Lang","year":"2018","journal-title":"Nat Immunol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/nm.2399","article-title":"The immunology of stroke: from mechanisms to translation","volume":"17","author":"Iadecola","year":"2011","journal-title":"Nat Med"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1001\/jamaneurol.2022.1991","article-title":"One-year outcome trajectories and factors associated with functional recovery among survivors of intracerebral and intraventricular hemorrhage with initial severe disability","volume":"79","author":"Shah","year":"2022","journal-title":"JAMA Neurol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1186\/s13054-025-05458-9","article-title":"Cerebral perfusion pressure targets after traumatic brain injury: a reappraisal","volume":"29","author":"Bogli","year":"2025","journal-title":"Crit Care"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1016\/j.clnu.2023.07.011","article-title":"ESPEN practical and partially revised guideline: clinical nutrition in the intensive care unit","volume":"42","author":"Singer","year":"2023","journal-title":"Clin Nutr"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1855636\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:37:08Z","timestamp":1786941428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1855636\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":37,"alternative-id":["10.3389\/fnut.2026.1855636"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1855636","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"article-number":"1855636"}}