{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:30:44Z","timestamp":1761006644227,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T00:00:00Z","timestamp":1760832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation (NRF) grant from the Korean Government","doi-asserted-by":"publisher","award":["2020R1C1C1010362","RS-2023-00208807"],"award-info":[{"award-number":["2020R1C1C1010362","RS-2023-00208807"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015825","name":"Korea University Anam Hospital","doi-asserted-by":"publisher","award":["K2514031","K2401001"],"award-info":[{"award-number":["K2514031","K2401001"]}],"id":[{"id":"10.13039\/501100015825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation (NRF) grant from the Korean Government","doi-asserted-by":"publisher","award":["2020R1F1A1071620","RS-2023-00220894","RS-2025-00563782"],"award-info":[{"award-number":["2020R1F1A1071620","RS-2023-00220894","RS-2025-00563782"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Although tryptophanyl-tRNA synthetase (WRS) is a novel biomarker released during bacterial and viral infections, its prognostic value in sepsis has rarely been reported. This study aimed to evaluate the prognostic performance of WRS in patients with sepsis in the emergency department (ED). Methods: This prospective, observational study included 243 patients with sepsis. Blood samples were collected to measure full-length WRS levels. The prognostic value of WRS was evaluated using the area under the receiver operating characteristic curve, Kaplan\u2013Meier survival curve analysis, and the Cox proportional hazards model. Results: The WRS levels were higher in patients with septic shock than in those without shock (p = 0.018). WRS could predict 30-day mortality (area under the curve, 0.648; 95% confidence interval [CI], 0.569\u20130.726; sensitivity, 56.7%; specificity, 73.3%; cut-off value, 84.15 \u00b5g\/L; p &lt; 0.001). Patients with WRS levels of \u226584.15 \u00b5g\/L showed higher 30-day mortality than those with WRS levels of &lt;84.15 \u00b5g\/L. Among patients with WRS levels of \u226584.15 \u00b5g\/L, those with positive urine culture results had higher 30-day mortality than those with negative urine culture. Patients with renal Sequential Organ Failure Assessment (SOFA) score of \u22651 had higher 30-day mortality than those with renal SOFA score of 0. WRS was an independent risk factor of 30-day mortality (hazard ratio = 1.003; 95% CI, 1.001\u20131.005; p = 0.014). Conclusions: WRS effectively predicted clinical outcome in patients with sepsis and could be more useful in those with kidney dysfunction or urinary tract infection.<\/jats:p>","DOI":"10.3390\/diagnostics15202634","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:23:34Z","timestamp":1760952214000},"page":"2634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Value of Tryptophanyl-tRNA Synthetase in Sepsis Combined with Kidney Dysfunction or Urinary Tract Infection: A Prospective Observational Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3254-5754","authenticated-orcid":false,"given":"Uihwan","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Korea University Anam Hospital, Seoul 02841, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sijin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Korea University Anam Hospital, Seoul 02841, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0205-1269","authenticated-orcid":false,"given":"Kap Su","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Korea University Anam Hospital, Seoul 02841, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3769-9647","authenticated-orcid":false,"given":"Su Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Korea University Anam Hospital, Seoul 02841, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4492-0258","authenticated-orcid":false,"given":"Sungwoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Korea University Anam Hospital, Seoul 02841, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dae Won","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si 15355, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6217-7360","authenticated-orcid":false,"given":"Juhyun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Korea University Anam Hospital, Seoul 02841, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1056\/NEJMra1208623","article-title":"Severe sepsis and septic shock","volume":"369","author":"Angus","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/s13054-020-02950-2","article-title":"Mortality in sepsis and septic shock in Europe, North America and Australia between 2009 and 2019- results from a systematic review and meta-analysis","volume":"24","author":"Bauer","year":"2020","journal-title":"Crit. Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1097\/CCM.0b013e31827c09f8","article-title":"Benchmarking the incidence and mortality of severe sepsis in the United States","volume":"41","author":"Gaieski","year":"2013","journal-title":"Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1001\/jama.2017.0059","article-title":"Surviving Sepsis Guidelines: A Continuous Move Toward Better Care of Patients with Sepsis","volume":"317","author":"Dorman","year":"2017","journal-title":"Jama"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e1063","DOI":"10.1097\/CCM.0000000000005337","article-title":"Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021","volume":"49","author":"Evans","year":"2021","journal-title":"Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"i1585","DOI":"10.1136\/bmj.i1585","article-title":"Sepsis: Pathophysiology and clinical management","volume":"353","author":"Gotts","year":"2016","journal-title":"BMJ"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1001\/jama.2016.0288","article-title":"Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Seymour","year":"2016","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1001\/jama.2016.0289","article-title":"Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Phillips","year":"2016","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13049-019-0680-9","article-title":"The impact of the Sepsis-3 definition on ICU admission of patients with infection","volume":"27","author":"Klimpel","year":"2019","journal-title":"Scand. J. Trauma. Resusc. Emerg. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.jelectrocard.2017.08.013","article-title":"Early sepsis detection in critical care patients using multiscale blood pressure and heart rate dynamics","volume":"50","author":"Shashikumar","year":"2017","journal-title":"J. Electrocardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1097\/00003246-199811000-00016","article-title":"Use of the SOFA score to assess the incidence of organ dysfunction\/failure in intensive care units: Results of a multicenter, prospective study. Working group on \u201csepsis-related problems\u201d of the European Society of Intensive Care Medicine","volume":"26","author":"Vincent","year":"1998","journal-title":"Crit. Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1177\/0885066619871452","article-title":"Multiple Organ Dysfunction Syndrome","volume":"35","author":"Gourd","year":"2020","journal-title":"J. Intensive Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1055\/s-0031-1287868","article-title":"Organ failure in the intensive care unit","volume":"32","author":"Vincent","year":"2011","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1186\/s13054-019-2557-8","article-title":"Combined assessment of \u0394PCT and \u0394CRP could increase the ability to differentiate candidemia from bacteremia","volume":"23","author":"Wu","year":"2019","journal-title":"Crit. Care"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Song, J., Park, D.W., Moon, S., Cho, H.J., Park, J.H., Seok, H., and Choi, W.S. (2019). Diagnostic and prognostic value of interleukin-6, pentraxin 3, and procalcitonin levels among sepsis and septic shock patients: A prospective controlled study according to the Sepsis-3 definitions. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4618-7"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.cca.2013.09.019","article-title":"Presepsin (sCD14-ST) in emergency department: The need for adapted threshold values?","volume":"427","author":"Trabattoni","year":"2014","journal-title":"Clin. Chim. Acta"},{"key":"ref_18","first-page":"1395","article-title":"Role of presepsin for the evaluation of sepsis in the emergency department","volume":"52","author":"Pizzolato","year":"2014","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_19","first-page":"1","article-title":"Unique roles of tryptophanyl-tRNA synthetase in immune control and its therapeutic implications","volume":"51","author":"Jin","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ahn, Y.H., Oh, S.C., Zhou, S., and Kim, T.D. (2021). Tryptophanyl-tRNA Synthetase as a Potential Therapeutic Target. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094523"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12866","DOI":"10.1074\/jbc.RA119.009584","article-title":"Matrix metalloproteinases inactivate the proinflammatory functions of secreted moonlighting tryptophanyl-tRNA synthetase","volume":"294","author":"Jobin","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ahn, Y.H., Park, S., Choi, J.J., Park, B.K., Rhee, K.H., Kang, E., Ahn, S., Lee, C.H., Lee, J.S., and Inn, K.S. (2016). Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection. Nat. Microbiol., 2.","DOI":"10.1038\/nmicrobiol.2016.191"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1128\/IAI.02765-14","article-title":"Comparative proteomic analysis reveals activation of mucosal innate immune signaling pathways during cholera","volume":"83","author":"Ellis","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6669","DOI":"10.1073\/pnas.0401771101","article-title":"Genomic analysis of the host response to hepatitis B virus infection","volume":"101","author":"Wieland","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.ijid.2020.05.105","article-title":"Clinical value of full-length tryptophanyl-tRNA synthetase for sepsis detection in critically ill patients\u2014A retrospective clinical assessment","volume":"97","author":"Choi","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_26","unstructured":"(2013). World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA, 310."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/s00134-008-1367-2","article-title":"Acute kidney injury in septic shock: Clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy","volume":"35","author":"Bagshaw","year":"2009","journal-title":"Intensive Care Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1001\/jama.294.7.813","article-title":"Acute renal failure in critically ill patients: A multinational, multicenter study","volume":"294","author":"Uchino","year":"2005","journal-title":"JAMA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1093\/ndt\/gfad142","article-title":"Sepsis-associated acute kidney injury-treatment standard","volume":"39","author":"Zarbock","year":"2023","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1080\/14787210.2020.1700794","article-title":"Preventing sepsis development in complicated urinary tract infections","volume":"18","author":"Petrosillo","year":"2020","journal-title":"Expert. Rev. Anti Infect. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Balkrishna, A., Sinha, S., Kumar, A., Arya, V., Gautam, A.K., Valis, M., Kuca, K., Kumar, D., and Amarowicz, R. (2023). Sepsis-mediated renal dysfunction: Pathophysiology, biomarkers and role of phytoconstituents in its management. Biomed. Pharmacother., 165.","DOI":"10.1016\/j.biopha.2023.115183"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lee, S., Song, J., Park, D.W., Seok, H., Ahn, S., Kim, J., Park, J., Cho, H.J., and Moon, S. (2022). Diagnostic and prognostic value of presepsin and procalcitonin in non-infectious organ failure, sepsis, and septic shock: A prospective observational study according to the Sepsis-3 definitions. BMC Infect. Dis., 22.","DOI":"10.1186\/s12879-021-07012-8"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"117588","DOI":"10.1016\/j.cca.2023.117588","article-title":"Presepsin in the diagnosis of sepsis","volume":"550","author":"Paraskevas","year":"2023","journal-title":"Clin. Chim. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Miyoshi, M., Inoue, Y., Nishioka, M., Ikegame, A., Nakao, T., Kishi, S., Doi, T., and Nagai, K. (2019). Clinical evaluation of presepsin considering renal function. PLoS ONE, 14.","DOI":"10.1101\/604991"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Nagata, T., Yasuda, Y., Ando, M., Abe, T., Katsuno, T., Kato, S., Tsuboi, N., Matsuo, S., and Maruyama, S. (2015). Clinical impact of kidney function on presepsin levels. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129159"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1074\/mcp.M500279-MCP200","article-title":"A human protein atlas for normal and cancer tissues based on antibody proteomics","volume":"4","author":"Agaton","year":"2005","journal-title":"Mol. Cell. Proteom."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S1470-2045(18)30108-6","article-title":"Predictive test for chemotherapy response in resectable gastric cancer: A multi-cohort, retrospective analysis","volume":"19","author":"Cheong","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1158\/1055-9965.EPI-09-0456","article-title":"The prognostic significance of tryptophanyl-tRNA synthetase in colorectal cancer","volume":"18","author":"Ghanipour","year":"2009","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/his.13504","article-title":"Expression of PD-L1, indoleamine 2,3-dioxygenase and the immune microenvironment in gastric adenocarcinoma","volume":"73","author":"Patil","year":"2018","journal-title":"Histopathology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"21979","DOI":"10.18632\/oncotarget.4273","article-title":"Overexpressed tryptophanyl-tRNA synthetase, an angiostatic protein, enhances oral cancer cell invasiveness","volume":"6","author":"Lee","year":"2015","journal-title":"Oncotarget"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/nrm2956","article-title":"New functions of aminoacyl-tRNA synthetases beyond translation","volume":"11","author":"Guo","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1080\/15476286.2017.1377868","article-title":"An alternative conformation of human TrpRS suggests a role of zinc in activating non-enzymatic function","volume":"15","author":"Xu","year":"2018","journal-title":"RNA Biol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Nakamoto, T., Miyanokoshi, M., Tanaka, T., and Wakasugi, K. (2016). Identification of a residue crucial for the angiostatic activity of human mini tryptophanyl-tRNA synthetase by focusing on its molecular evolution. Sci. Rep., 6.","DOI":"10.1038\/srep24750"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.tibs.2005.11.002","article-title":"Inhibition of tumor angiogenesis by a natural fragment of a tRNA synthetase","volume":"31","author":"Tzima","year":"2006","journal-title":"Trends Biochem. Sci."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/20\/2634\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:38:25Z","timestamp":1760953105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/20\/2634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,19]]},"references-count":44,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["diagnostics15202634"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15202634","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,19]]}}}