{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:54:06Z","timestamp":1791140046231,"version":"4.1.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"crossref","award":["2024YFA0918404"],"award-info":[{"award-number":["2024YFA0918404"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82003560"],"award-info":[{"award-number":["82003560"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Research and Development Project of Shandong Province","award":["2024TSGC0151"],"award-info":[{"award-number":["2024TSGC0151"]}]},{"name":"the National Natural Science Foundation of Shandong","award":["ZR2020MH340"],"award-info":[{"award-number":["ZR2020MH340"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    This study aimed to investigate the associations between age, red blood cell distribution width (RDW), and short-term mortality in patients with traumatic brain injury (TBI), with a particular focus on the role of RDW in mediating the impact of age on mortality. We conducted a retrospective cohort analysis of 1,203 ICU-admitted TBI patients from the MIMIC-IV database (v3.1). Cox proportional hazards regression, restricted cubic splines (RCS), and mediation analysis were employed to evaluate the relationships between age, RDW, and mortality outcomes. Both advanced age (adjusted hazard ratio [HR] = 1.022 for 28-day mortality; HR\n                    <jats:sub>adj<\/jats:sub>\n                    \u2009=\u20091.031 for in-hospital mortality) and RDW (HR\n                    <jats:sub>adj<\/jats:sub>\n                    \u2009=\u20091.085 for 28-day mortality; HR\n                    <jats:sub>adj<\/jats:sub>\n                    \u2009=\u20091.094 for in-hospital mortality) were found to predict mortality (all\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05) independently. RDW demonstrated a dose\u2013response relationship with mortality: the highest quartile (Q4) exhibited a 2.061-fold increased risk of 28-day mortality (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.010) and a 2.086-fold increased risk of in-hospital mortality (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.022) compared to the lowest quartile (Q1). RCS analysis revealed significant nonlinear associations between age and 28-day mortality (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05) and between RDW and in-hospital mortality (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). The mediation analysis demonstrated that RDW played a partial mediating role in age-related mortality, accounting for 4.40% of the total effect on 28-day mortality and 4.62% on in-hospital mortality (both\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). Deep learning survival models (e.g., Deepsurv: C-index: 0.759; IBS: 0.113; AUC (95% CI): 0.824 (0.735\u20130.900)) that incorporate age, RDW, and other clinical variables achieved robust predictive performance. Age and RDW are independent predictors of short-term mortality in TBI. RDW partially mediates the effect of age on TBI prognosis and shows potential as a practical biomarker for clinical risk stratification.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0339879","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T18:28:31Z","timestamp":1767378511000},"page":"e0339879","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Prognostic value of red blood cell distribution width in traumatic brain injury: A mediation and deep learning analysis"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0869-4381","authenticated-orcid":true,"given":"Shuting","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifu","family":"Bo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Di","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manli","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzhen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3806-1613","authenticated-orcid":true,"given":"Yujia","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,2]]},"reference":[{"issue":"8","key":"pone.0339879.ref001","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/S1474-4422(08)70164-9","article-title":"Moderate and severe traumatic brain injury in adults","volume":"7","author":"AIR Maas","year":"2008","journal-title":"Lancet Neurol"},{"issue":"4","key":"pone.0339879.ref002","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.3171\/2017.10.JNS17352","article-title":"Estimating the global incidence of traumatic brain injury","volume":"130","author":"MC Dewan","year":"2018","journal-title":"J Neurosurg"},{"key":"pone.0339879.ref003","doi-asserted-by":"crossref","first-page":"1556147","DOI":"10.3389\/fpubh.2025.1556147","article-title":"Global, regional, and national burdens of traumatic brain injury from 1990 to 2021","volume":"13","author":"J Yan","year":"2025","journal-title":"Front Public Health"},{"issue":"1","key":"pone.0339879.ref004","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/bja\/aem131","article-title":"Pathophysiology of traumatic brain injury","volume":"99","author":"C Werner","year":"2007","journal-title":"Br J Anaesth"},{"issue":"1","key":"pone.0339879.ref005","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.nurt.2009.10.016","article-title":"Involvement of pro- and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury","volume":"7","author":"JM Ziebell","year":"2010","journal-title":"Neurotherapeutics"},{"issue":"7","key":"pone.0339879.ref006","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/nrneurol.2010.74","article-title":"Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury","volume":"6","author":"D Shlosberg","year":"2010","journal-title":"Nat Rev Neurol"},{"key":"pone.0339879.ref007","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.mcn.2015.03.001","article-title":"Epidemiology of mild traumatic brain injury and neurodegenerative disease","volume":"66","author":"RC Gardner","year":"2015","journal-title":"Mol Cell Neurosci"},{"issue":"4","key":"pone.0339879.ref008","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrneurol.2013.22","article-title":"Changing patterns in the epidemiology of traumatic brain injury","volume":"9","author":"B Roozenbeek","year":"2013","journal-title":"Nat Rev Neurol"},{"issue":"2","key":"pone.0339879.ref009","first-page":"212","article-title":"The 2002 Tanner-Vandeput-Boswick Burn Prize Awarded","volume":"53","author":"Na","journal-title":"The Journal of Trauma: Injury, Infection, and Critical Care"},{"issue":"7641","key":"pone.0339879.ref010","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1136\/bmj.39461.643438.25","article-title":"Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients","volume":"336","author":"MRC CRASH Trial Collaborators","year":"2008","journal-title":"BMJ"},{"issue":"8","key":"pone.0339879.ref011","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.0050165","article-title":"Predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics","volume":"5","author":"EW Steyerberg","year":"2008","journal-title":"PLoS Med"},{"issue":"1","key":"pone.0339879.ref012","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jacc.2007.02.067","article-title":"Red cell distribution width as a novel prognostic marker in heart failure: data from the CHARM Program and the Duke Databank","volume":"50","author":"GM Felker","year":"2007","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"pone.0339879.ref013","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.ajem.2012.10.017","article-title":"Red cell distribution width is a prognostic factor in severe sepsis and septic shock","volume":"31","author":"YH Jo","year":"2013","journal-title":"Am J Emerg Med"},{"key":"pone.0339879.ref014","first-page":"1942078","article-title":"Relation between Red Cell Distribution Width and Mortality in Critically Ill Patients with Acute Respiratory Distress Syndrome","volume":"2019","author":"B Wang","year":"2019","journal-title":"Biomed Res Int"},{"issue":"1","key":"pone.0339879.ref015","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s41747-021-00243-z","article-title":"Effects of red blood cells with reduced deformability on cerebral blood flow and vascular water transport: measurements in rats using time-resolved pulsed arterial spin labelling at 9.4\u2009T","volume":"5","author":"A Bibic","year":"2021","journal-title":"Eur Radiol Exp"},{"issue":"3","key":"pone.0339879.ref016","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s13760-020-01409-z","article-title":"Red blood cell distribution width as mortality biomarker in patients with traumatic brain injury","volume":"121","author":"L Lorente","year":"2021","journal-title":"Acta Neurol Belg"},{"issue":"10","key":"pone.0339879.ref017","first-page":"19172","article-title":"Red blood cell distribution width as a prognostic biomarker for mortality in traumatic brain injury","volume":"8","author":"B Zhang","year":"2015","journal-title":"Int J Clin Exp Med"},{"issue":"1","key":"pone.0339879.ref018","doi-asserted-by":"crossref","first-page":"9","DOI":"10.14740\/jocmr3173w","article-title":"Does Red Cell Distribution Width Predict Outcome in Traumatic Brain Injury: Comparison to Corticosteroid Randomization After Significant Head Injury","volume":"10","author":"F Sadaka","year":"2018","journal-title":"J Clin Med Res"},{"issue":"4","key":"pone.0339879.ref019","doi-asserted-by":"crossref","first-page":"666","DOI":"10.3171\/jns.2003.99.4.0666","article-title":"Patient age and outcome following severe traumatic brain injury: an analysis of 5600 patients","volume":"99","author":"CWPM Hukkelhoven","year":"2003","journal-title":"J Neurosurg"},{"issue":"5","key":"pone.0339879.ref020","first-page":"907","article-title":"Isolated traumatic brain injury: age is an independent predictor of mortality and early outcome","volume":"52","author":"AC Mosenthal","year":"2002","journal-title":"J Trauma"},{"issue":"8","key":"pone.0339879.ref021","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000213506","article-title":"Neuroimaging Correlates of Traumatic Brain Injury in an Older Community-Dwelling Population: The Atherosclerosis Risk in Communities Study","volume":"104","author":"AE Walter","year":"2025","journal-title":"Neurology"},{"issue":"2","key":"pone.0339879.ref022","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.mcna.2019.11.001","article-title":"Traumatic Brain Injury: An Overview of Epidemiology, Pathophysiology, and Medical Management","volume":"104","author":"A Capizzi","year":"2020","journal-title":"Med Clin North Am"},{"issue":"6","key":"pone.0339879.ref023","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1227\/neu.0000000000001911","article-title":"Machine Learning for Predicting Discharge Disposition After Traumatic Brain Injury","volume":"90","author":"N Satyadev","year":"2022","journal-title":"Neurosurgery"},{"issue":"6","key":"pone.0339879.ref024","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0268962","article-title":"Deep learning for behaviour classification in a preclinical brain injury model","volume":"17","author":"L Teoh","year":"2022","journal-title":"PLoS One"},{"issue":"19","key":"pone.0339879.ref025","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.3390\/cancers15194757","article-title":"A Study on Survival Analysis Methods Using Neural Network to Prevent Cancers","volume":"15","author":"C-Y Bae","year":"2023","journal-title":"Cancers (Basel)"},{"issue":"2","key":"pone.0339879.ref026","doi-asserted-by":"crossref","DOI":"10.1097\/00005373-200208000-00004","article-title":"Traumatic brain injury in the elderly: increased mortality and worse functional outcome at discharge despite lower injury severity","volume":"53","author":"M Susman","year":"2002","journal-title":"J Trauma"},{"issue":"4","key":"pone.0339879.ref027","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrneurol.2013.22","article-title":"Changing patterns in the epidemiology of traumatic brain injury","volume":"9","author":"B Roozenbeek","year":"2013","journal-title":"Nat Rev Neurol"},{"issue":"10","key":"pone.0339879.ref028","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1111\/j.1532-5415.2006.00894.x","article-title":"Traumatic brain injury in older adults: epidemiology, outcomes, and future implications","volume":"54","author":"HJ Thompson","year":"2006","journal-title":"J Am Geriatr Soc"},{"key":"pone.0339879.ref029","doi-asserted-by":"crossref","first-page":"804139","DOI":"10.3389\/fneur.2021.804139","article-title":"Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats","volume":"12","author":"TRF Green","year":"2022","journal-title":"Front Neurol"},{"issue":"12","key":"pone.0339879.ref030","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.3390\/ijms19123753","article-title":"Traumatic Brain Injury in Aged Mice Induces Chronic Microglia Activation, Synapse Loss, and Complement-Dependent Memory Deficits","volume":"19","author":"K Krukowski","year":"2018","journal-title":"Int J Mol Sci"},{"issue":"2","key":"pone.0339879.ref031","doi-asserted-by":"crossref","DOI":"10.1093\/braincomms\/fcac036","article-title":"Ageing is associated with maladaptive immune response and worse outcome after traumatic brain injury","volume":"4","author":"F Moro","year":"2022","journal-title":"Brain Commun"},{"issue":"3","key":"pone.0339879.ref032","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.jointm.2023.02.005","article-title":"Red blood cell distribution width improves the prediction of 28-day mortality for patients with sepsis-induced acute kidney injury: A retrospective analysis from MIMIC-IV database using propensity score matching","volume":"3","author":"H Lai","year":"2023","journal-title":"J Intensive Med"},{"issue":"6","key":"pone.0339879.ref033","first-page":"730","article-title":"Red cell distribution width is associated with hospital mortality in unselected critically ill patients","volume":"5","author":"Z Zhang","year":"2013","journal-title":"J Thorac Dis"},{"issue":"1","key":"pone.0339879.ref034","doi-asserted-by":"crossref","first-page":"14027","DOI":"10.1038\/s41598-023-39836-6","article-title":"Association between red blood cell distribution width and the prognosis of brain death in patients with a Glasgow Coma Scale\u2009<\u20096","volume":"13","author":"M Latifi","year":"2023","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0339879.ref035","doi-asserted-by":"crossref","first-page":"278","DOI":"10.4103\/2229-5151.147518","article-title":"Broadening of the red blood cell distribution width is associated with increased severity of illness in patients with sepsis","volume":"4","author":"NA Mahmood","year":"2014","journal-title":"Int J Crit Illn Inj Sci"},{"issue":"5","key":"pone.0339879.ref036","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1001\/archinternmed.2009.11","article-title":"Red blood cell distribution width and the risk of death in middle-aged and older adults","volume":"169","author":"KV Patel","year":"2009","journal-title":"Arch Intern Med"},{"key":"pone.0339879.ref037","doi-asserted-by":"crossref","first-page":"413","DOI":"10.2147\/JBM.S367660","article-title":"Red Blood Cell Distribution Width as Novel Biomarker in Cardiovascular Diseases: A Literature Review","volume":"13","author":"M Arkew","year":"2022","journal-title":"J Blood Med"},{"issue":"3","key":"pone.0339879.ref038","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/gerona\/glp163","article-title":"Red cell distribution width and mortality in older adults: a meta-analysis","volume":"65","author":"KV Patel","year":"2010","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"5","key":"pone.0339879.ref039","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1007\/s12603-015-0470-7","article-title":"Change in Red Blood Cell Distribution width During the Last Years of Life in Geriatric Patients","volume":"19","author":"N Mart\u00ednez-Velilla","year":"2015","journal-title":"J Nutr Health Aging"},{"key":"pone.0339879.ref040","doi-asserted-by":"crossref","DOI":"10.1093\/geroni\/igz038.388","article-title":"Age-related differences in immuno-hematologic profiles and their association with all-cause mortality","volume":"3","author":"JE Dalton","year":"2019","journal-title":"Innovation in Aging"},{"issue":"12","key":"pone.0339879.ref041","first-page":"2015","article-title":"Effect of age and gender on reference intervals of red blood cell distribution width (RDW) and mean red cell volume (MCV)","volume":"53","author":"JJML Hoffmann","year":"2015","journal-title":"Clin Chem Lab Med"},{"key":"pone.0339879.ref042","doi-asserted-by":"crossref","DOI":"10.1093\/geroni\/igz038.388","article-title":"Age-related differences in immuno-hematologic profiles and their association with all-cause mortality","volume":"3","author":"JE Dalton","year":"2019","journal-title":"Innovation in Aging"},{"issue":"1","key":"pone.0339879.ref043","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1186\/s12967-024-05544-6","article-title":"Development and validation of novel interpretable survival prediction models based on drug exposures for severe heart failure during vulnerable period","volume":"22","author":"Y Guo","year":"2024","journal-title":"J Transl Med"},{"issue":"4","key":"pone.0339879.ref044","doi-asserted-by":"crossref","first-page":"5497","DOI":"10.1007\/s11357-024-01438-z","article-title":"Artificial intelligence improves risk prediction in cardiovascular disease","volume":"47","author":"AB Teshale","year":"2025","journal-title":"Geroscience"},{"issue":"9442","key":"pone.0339879.ref045","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/S0140-6736(04)17188-2","article-title":"Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial","volume":"364","author":"I Roberts","year":"2004","journal-title":"Lancet"},{"issue":"8","key":"pone.0339879.ref046","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.0050165","article-title":"Predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics","volume":"5","author":"EW Steyerberg","year":"2008","journal-title":"PLoS Med"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0339879","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T18:28:38Z","timestamp":1767378518000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0339879"}},"subtitle":[],"editor":[{"given":"Aleksandra","family":"Klisic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,2]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0339879","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,2]]}}}