{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T04:34:08Z","timestamp":1793594048330,"version":"4.5.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Alcohol consumption is a significant risk factor for adverse outcomes in trauma patients. Despite this, effective predictive biomarkers for postoperative complications remain elusive. This study aims to identify potential immune system biomarkers associated with postoperative complications in trauma patients with a history of chronic alcohol consumption.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective cohort study was conducted on trauma patients admitted to a level 1 Trauma Center. Chronic alcohol consumption and drinking habits were assessed using the Alcohol Use Disorders Identification Test (AUDIT-C) questionnaire. Specifically, 26% of patients reported no alcohol consumption, 44% reported moderate alcohol consumption, and 30% were identified as having risky alcohol consumption. Acute systemic alcohol levels at the time of injury were not measured or considered in this study, as the focus was on chronic consumption patterns. Routine blood screening data were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Except for CRP, blood values were comparable between patients with risky alcohol consumption and controls. However, CRP\u2019s ability to predict complications in patients with risky alcohol consumption remained limited (ROC-AUC = 0.6288). In order to identify other predictive markers, patients were matched based on relevant covariates in further analyses. Cytokine Array screening identified CD28, B7-1, Eotaxin-3, TIMP-1, and IL-13 as potential markers to predict complications. Verification with ELISA, however, showed that potential differences could only be detected in the control group. The discrepancies observed between cytokine array and ELISA results can be best explained by methodological differences, particularly since the serum samples were pooled for initial target screening. Additionally, variations in assay sensitivity, dynamic range, and calibration protocols contribute to these discrepancies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings suggest that chronic alcohol consumption alters cytokine responses, posing challenges for identifying reliable immune biomarkers for postoperative complications. Future studies should explore alternative approaches for biomarker validation and consider individualized assessment strategies for trauma patients with alcohol consumption history.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1492288","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T05:18:05Z","timestamp":1744607885000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of alcohol consumption on outcomes and potential of immune biomarkers for postoperative complications in trauma patients"],"prefix":"10.3389","volume":"16","author":[{"given":"Mohammad Majd","family":"Hammour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelda","family":"Anuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Breinbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina H.","family":"Aspera-Werz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanqiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Histing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Ehnert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas K.","family":"N\u00fcssler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"D\u00f6bele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2020.0160","article-title":"Global and regional impacts of alcohol use on public health: Emphasis on alcohol policies","volume":"26","author":"Park","year":"2020","journal-title":"Clin Mol Hepatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.3390\/ijerph19031515","article-title":"Alcohol consumption, bone mineral density, and risk of osteoporotic fractures: A dose\u2013response meta-analysis","volume":"19","author":"Godos","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B3","volume-title":"Alcohol atlas Germany 2022","author":"Schaller","year":"2022"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agad013","article-title":"Alcoholic beverage preference in Germany: an age-period-cohort analysis of trends 1995-2018","volume":"58","author":"Wilms","year":"2023","journal-title":"Alcohol Alcohol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2","DOI":"10.17886\/RKI-GBE-2016-029","article-title":"Alcohol consumption of adults in Germany: Harmful drinking quantities, consequences and measures","volume":"1","author":"Lange","year":"2016","journal-title":"J Health Monit"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.3390\/nu13082777","article-title":"Alcohol and the risk of injury","volume":"13","author":"Chikritzhs","year":"2021","journal-title":"Nutrients"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00068-010-0038-5","article-title":"Alcohol exposure and outcomes in trauma patients","volume":"37","author":"Hadjizacharia","year":"2011","journal-title":"Eur J Trauma Emerg Surg"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/34.6.830","article-title":"Consequences of alcohol consumption on host defence","volume":"34","author":"Szabo","year":"1999","journal-title":"Alcohol Alcoholism"},{"key":"B9","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s13167-017-0081-y","article-title":"Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine","volume":"8","author":"Avishai","year":"2017","journal-title":"EPMA J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s15006-019-1157-5","article-title":"Komorbidit\u00e4ten gef\u00e4hrden die Wundheilung","volume":"161","author":"Lampert","year":"2019","journal-title":"MMW - Fortschr der Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"17891","DOI":"10.1038\/s41598-020-74753-y","article-title":"Alcohol use in severely injured trauma patients","volume":"10","author":"Riuttanen","year":"2020","journal-title":"Sci Rep"},{"key":"B12","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s00268-017-4106-4","article-title":"Association of elevated pre-operative hemoglobin A1c and post-operative complications in non-diabetic patients: A systematic review","volume":"42","author":"Karimian","year":"2018","journal-title":"World J Surg"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000001029","article-title":"Prognostic significance of the hemoglobin A1c level in non-diabetic patients undergoing percutaneous coronary intervention: a meta-analysis","volume":"133","author":"Li","year":"2020","journal-title":"Chin Med J (Engl)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s00423-023-03186-8","article-title":"Role of specific nutritional biomarkers in predicting post-operative complications among patients undergoing elective abdominal surgery","volume":"408","author":"Raghuraman","year":"2023","journal-title":"Langenbecks Arch Surg"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1159\/000078350","article-title":"Different C-reactive protein kinetics in post-operative hip-fractured geriatric patients with and without complications","volume":"50","author":"Beloosesky","year":"2004","journal-title":"Gerontology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12871-019-0693-y","article-title":"Pre-operative biomarkers and imaging tests as predictors of post-operative delirium in non-cardiac surgical patients: a systematic review","volume":"19","author":"Ayob","year":"2019","journal-title":"BMC Anesthesiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.17179\/excli2024-7306","article-title":"Smoking increases risk of complication after musculoskeletal surgery: analysis of single immune parameter to predict complication risk","volume":"23","author":"T\u00fcmen","year":"2024","journal-title":"EXCLI J"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-008-0594-0","article-title":"Effectiveness of the AUDIT-C as a screening test for alcohol misuse in three race\/ethnic groups","volume":"23","author":"Frank","year":"2008","journal-title":"J Gen Intern Med"},{"key":"B19","article-title":"Alcohol use disorder","author":"Nehring","year":"2025","journal-title":"StatPearls"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/1753-6405.13017","article-title":"The effect of alcohol consumption on clinical outcomes in regional patients with chronic disease: a retrospective chart audit","volume":"44","author":"Mudd","year":"2020","journal-title":"Aust New Z J Public Health"},{"key":"B21","article-title":"Substanzkonsum und substanzbezogene St\u00f6rungen in Deutschland im Jahr 2012","volume-title":"Sucht","author":"Pabst","year":"2013"},{"key":"B22","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s12875-019-1006-8","article-title":"Are German family practitioners and psychiatrists sufficiently trained to diagnose and treat patients with alcohol problems","volume":"20","author":"Hoffmann","year":"2019","journal-title":"BMC Family Pract"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e204687","DOI":"10.1001\/jamanetworkopen.2020.4687","article-title":"Associations between medical conditions and alcohol consumption levels in an adult primary care population","volume":"3","author":"Sterling","year":"2020","journal-title":"JAMA Network Open"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e3182988d59","article-title":"Preoperative alcohol consumption and postoperative complications: a systematic review and meta-analysis","volume":"258","author":"Eliasen","year":"2013","journal-title":"Ann Surg"},{"key":"B25","doi-asserted-by":"publisher","first-page":"Cd008343","DOI":"10.1002\/14651858.CD008343.pub3","article-title":"Perioperative alcohol cessation intervention for postoperative complications","volume":"11","author":"Egholm","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0000000000000706","article-title":"Gaps in alcohol screening and intervention practices in surgical healthcare: A qualitative study","volume":"15","author":"Fernandez","year":"2021","journal-title":"J Addict Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.3390\/jcm9072081","article-title":"The inflammatory response to alcohol consumption and its role in the pathology of alcohol hangover","volume":"9","author":"van de Loo","year":"2020","journal-title":"J Clin Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.24875\/RIC.23000116","article-title":"Alcohol: immunomodulatory effects and cancer","volume":"75","author":"Molina","year":"2023","journal-title":"Rev investigaci\u00f3n cl\u00ednica"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2147\/JMDH.S104807","article-title":"Information bias in health research: definition, pitfalls, and adjustment methods","volume":"9","author":"Althubaiti","year":"2016","journal-title":"J Multidiscip Healthc"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.addbeh.2009.11.001","article-title":"Social desirability biases in self-reported alcohol consumption and harms","volume":"35","author":"Davis","year":"2010","journal-title":"Addict Behav"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1186\/1471-2458-14-1297","article-title":"Drinking pattern is more strongly associated with under-reporting of alcohol consumption than socio-demographic factors: evidence from a mixed-methods study","volume":"14","author":"Boniface","year":"2014","journal-title":"BMC Public Health"},{"key":"B32","doi-asserted-by":"publisher","first-page":"345702","DOI":"10.1155\/2013\/345702","article-title":"Impact of the body mass on complications and outcome in multiple trauma patients: what does the weight weigh","volume":"2013","author":"Andruszkow","year":"2013","journal-title":"Mediators Inflammation"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0280345","article-title":"Epidemiology, injury pattern and outcome of older trauma patients: A 15-year study of level-I trauma centers","volume":"18","author":"Benhamed","year":"2023","journal-title":"PLoS One"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400025200","article-title":"C-reactive protein*","volume":"279","author":"Black","year":"2004","journal-title":"J Biol Chem"},{"key":"B35","article-title":"C-reactive protein levels determine the severity of soft-tissue injuries","volume":"25","author":"Pritchett","year":"1996","journal-title":"Am J Orthop (Belle Mead NJ)"},{"key":"B36","doi-asserted-by":"publisher","first-page":"13444","DOI":"10.1038\/s41598-024-63875-2","article-title":"Associations of lifestyle characteristics with circulating immune markers in the general population based on NHANES 1999 to 2014","volume":"14","author":"Guo","year":"2024","journal-title":"Sci Rep"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0132995","article-title":"Predictive value of C-reactive protein for major complications after major abdominal surgery: A systematic review and pooled-analysis","volume":"10","author":"Straatman","year":"2015","journal-title":"PLoS One"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S187249","article-title":"Perioperative C-reactive protein is associated with pain outcomes after major laparoscopic abdominal surgery: a retrospective analysis","volume":"12","author":"Choi","year":"2019","journal-title":"J Pain Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.22270","article-title":"C-reactive protein is a diagnostic tool for postoperative infection in orthopaedics","volume":"14","author":"Shetty","year":"2022","journal-title":"Cureus"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/anae.v78.11","article-title":"Postoperative systemic inflammation after major abdominal surgery: patient-centred outcomes","volume":"78","author":"Bain","year":"2023","journal-title":"Anaesthesia"},{"key":"B41","first-page":"153","article-title":"Alcohol and the immune system","volume":"37","author":"Sarkar","year":"2015","journal-title":"Alcohol research: Curr Rev"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i11.1304","article-title":"Alcohol, inflammation, and gut-liver-brain interactions in tissue damage and disease development","volume":"16","author":"Wang","year":"2010","journal-title":"World J Gastroenterol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2014.47741","article-title":"The immune response to surgery and infection","volume":"39","author":"D\u0105browska","year":"2014","journal-title":"Cent Eur J Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7150\/ijms.21433","article-title":"Innate immunity recovers earlier than acquired immunity during severe postoperative immunosuppression","volume":"15","author":"Lachmann","year":"2018","journal-title":"Int J Med Sci"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s00540-019-02651-3","article-title":"Post-surgical immune suppression: another target to improve postoperative outcomes","volume":"33","author":"Uchida","year":"2019","journal-title":"J Anesth"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.04.020","article-title":"CD28 costimulation: from mechanism to therapy","volume":"44","author":"Esensten","year":"2016","journal-title":"Immunity"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0000000000000883","article-title":"Measuring the human immune response to surgery: multiomics for the prediction of postoperative outcomes","volume":"27","author":"Verdonk","year":"2021","journal-title":"Curr Opin Crit Care"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.6.809","article-title":"Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1)","volume":"194","author":"Lee","year":"2001","journal-title":"J Exp Med"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.11.045","article-title":"Eotaxin-2 and eotaxin-3 expression is associated with persistent eosinophilic bronchial inflammation in patients with asthma after allergen challenge","volume":"115","author":"Ravensberg","year":"2005","journal-title":"J Allergy Clin Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.bbamcr.2010.01.003","article-title":"The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity","volume":"1803","author":"Brew","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"B51","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1007\/s00204-013-1191-5","article-title":"Chronic CCl4 intoxication causes liver and bone damage similar to the human pathology of hepatic osteodystrophy: a mouse model to analyse the liver-bone axis","volume":"88","author":"Nussler","year":"2014","journal-title":"Arch Toxicol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v13.i11.1667","article-title":"Effects of immune cells on mesenchymal stem cells during fracture healing","volume":"13","author":"Ehnert","year":"2021","journal-title":"World J Stem Cells"},{"key":"B53","first-page":"5","article-title":"Exploring alcohol\u2019s effects on liver function","volume":"21","author":"Maher","year":"1997","journal-title":"Alcohol Health Res World"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2006.00084.x","article-title":"Cytokines and alcohol","volume":"30","author":"Crews","year":"2006","journal-title":"Alcohol Clin Exp Res"},{"key":"B55","article-title":"Alcoholic liver disease: pathogenesis and current management","volume":"38","author":"Osna","year":"2017","journal-title":"Alcohol Res"},{"key":"B56","doi-asserted-by":"publisher","first-page":"10358","DOI":"10.1038\/s41598-018-28563-y","article-title":"Fatty liver is associated with blood pathways of inflammatory response, immune system activation and prothrombotic state in Young Finns Study","volume":"8","author":"Taipale","year":"2018","journal-title":"Sci Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1492288\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T05:18:08Z","timestamp":1744607888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1492288\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,14]]},"references-count":56,"alternative-id":["10.3389\/fimmu.2025.1492288"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1492288","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,14]]},"article-number":"1492288"}}