The novel biomarker t6A accurately identified septic patients at admission but failed to predict outcome

IF 8.8 1区 医学 Q1 CRITICAL CARE MEDICINE
Marcin F. Osuchowski, Barbara Adamik, Waldemar Gozdzik, Tomasz Skalec, Daniel Mascher, Heinz Redl, Johannes Zipperle, Gerhard Fritsch, Wolfgang Voelckel, Martin S. Winkler, Onnen Moerer, Helmut Schütz, Hermann Mascher
{"title":"The novel biomarker t6A accurately identified septic patients at admission but failed to predict outcome","authors":"Marcin F. Osuchowski, Barbara Adamik, Waldemar Gozdzik, Tomasz Skalec, Daniel Mascher, Heinz Redl, Johannes Zipperle, Gerhard Fritsch, Wolfgang Voelckel, Martin S. Winkler, Onnen Moerer, Helmut Schütz, Hermann Mascher","doi":"10.1186/s13054-025-05354-2","DOIUrl":null,"url":null,"abstract":"<p>Sepsis is a life-threatening condition caused by the body’s extreme response to infection [1]. Early diagnosis of sepsis is crucial for improving patient outcomes, yet current diagnostic methods including microbiological cultures are delayed and frequently inconclusive. This has driven the search for novel biomarkers and detection systems capable of recognizing sepsis more rapidly and accurately [2]. Procalcitonin (PCT) is the most widely used biomarker for sepsis detection but its use is limited as circulating PCT concentration is influenced by noninfectious inflammation (e.g. trauma, surgery).</p><p>Nucleoside modifications are a hallmark of the post-transcriptional processing of transfer ribonucleic acid (tRNA) that generate multiple structurally modified nucleosides [3]. One of such tRNA-modified nucleosides, N6-threonylcarbamoyladenosine (t<sup>6</sup>A), is critical for ensuring efficient protein synthesis in health and disease [4]. We discovered that circulating t<sup>6</sup>A possesses a diagnostic potential in sepsis. Consequently, we evaluated the diagnostic accuracy of t<sup>6</sup>A in differentiating bacterial sepsis and COVID-19 from two different non-septic patient cohorts: i) patients undergoing elective coronary artery bypass graft (CABG) surgery and ii) severe polytrauma patients. In all cohorts, t<sup>6</sup>A diagnostic accuracy was compared to PCT. Additionally, we tested t<sup>6</sup>A potential to predict death/survival in patients with sepsis.</p><p>This multicenter retrospective observational study analyzed plasma samples from four cohorts (Supplementary Table 1). The study included 81 patients with bacterial sepsis (cohort 1) and 49 patients with severe COVID-19 infection (cohort 2) diagnosed upon ICU/Emergency admission , 87 patients undergoing elective CABG surgery (cohort 3) and 64 severe (Injury Severity Score &gt; 15) polytrauma patients (cohort 4). Sepsis in cohort 1 was defined according to the Sepsis-3 criteria, and all patients received treatment aligned with the Surviving Sepsis Campaign guidelines. In COVID-19 patients, SARS-CoV-2 infection was confirmed by molecular test. The CABG and polytrauma groups were used as non-septic comparators to assess t<sup>6</sup>A’s diagnostic specificity and accuracy against patients with sepsis and those with COVID-19. We compared blood samples collected at admission for the sepsis and COVID-19 cohorts, to samples collected 24 h post-surgery (cohort 3) and trauma (cohort 4). Plasma t<sup>6</sup>A concentrations were measured using tandem mass spectrometry with stable isotope internal standardization. PCT was measured using standard Brahms PCT luminescence immunoassay. Statistical analyses of the receiver operating characteristic (ROC) curves were carried out with a total of 50,000 stratified bootstrap samples to estimate the 95% confidence interval (CI) of the area under the curve (AUC) of the ROC curve and its optimal threshold. The AUCs were compared via De Long’s two-sided test [5].</p><p>t<sup>6</sup>A demonstrated outstanding diagnostic accuracy for sepsis at the ICU/Emergency admission. In separately evaluated exploratory and validation CABG cohorts, t<sup>6</sup>A consistently showed greater accuracy (AUC &gt; 90%) compared to PCT (AUC 80–88%). t<sup>6</sup>A accuracy against the pooled CABG patients (cohort 3) achieved an AUC of 95% (vs. 88% for PCT, <i>p</i> &lt; 0.05) (Fig. 1A). Against the polytrauma group, which represented a more clinically relevant comparator, t<sup>6</sup>A again outperformed PCT; its AUC was 97% compared to 88% for PCT (<i>p</i> &lt; 0.05) (Fig. 1B). In the COVID-19 cohort, t<sup>6</sup>A also displayed excellent diagnostic performance when SARS-CoV-2-infected patients were compared to CABG (AUC 87%, Fig. 1C) and polytrauma (AUC 93%, Fig. 1D) patients. PCT measurement was not differentiating (AUC 50–52%, <i>p</i> &gt; 0.05). Notably, the optimal diagnostic threshold for t<sup>6</sup>A was nearly identical (3% deviation) against CABG (40.0 ng/mL) and polytrauma (38.8 ng/mL) comparators; it varied by 22% for PCT (2.04 and 1.6 ng/mL).</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 1</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13054-025-05354-2/MediaObjects/13054_2025_5354_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"666\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13054-025-05354-2/MediaObjects/13054_2025_5354_Fig1_HTML.png\" width=\"685\"/></picture><p>Diagnostic performance of t<sup>6</sup>A and PCT for detecting bacterial sepsis (<b>A</b>, <b>B</b>) and COVID-19 (<b>C</b>, <b>D</b>) at the ICU/Emergency admission. n: the first number in parentheses defines the number of sepsis or COVID-19 patients; the second number indicates the number of CABG or polytrauma patients. CI: 95% Confidence Intervals</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><p>Despite its strong diagnostic performance, t<sup>6</sup>A showed a limited utility for predicting sepsis outcomes. At the ICU/Emergency admission, t<sup>6</sup>A concentrations exhibited a considerable overlap between survivors and non-survivors and failed to show any protracted post-admission separation, resulting in an AUC of only 62%. PCT concentrations demonstrated a similar overlap dynamics and performed only modestly better, with an AUC of 72%, suggesting that while t<sup>6</sup>A is highly effective for identifying sepsis, it lacks prognostic value. This discrepancy highlights the biomarker’s primary utility in diagnosis rather than outcome prediction.</p><p>This is the first report regarding the potential utility of t<sup>6</sup>A as a diagnostic biomarker in patients with sepsis. We show t<sup>6</sup>A as a highly accurate and reliable biomarker for early sepsis diagnosis at the ICU/Emergency admission. t<sup>6</sup>A outperformed PCT in differentiating septic patients from non-septic controls including CABG and polytrauma cohorts. Insensitivity of t<sup>6</sup>A to sterile inflammation positions it as a promising diagnostic tool for clinical use. However, the lack of a commercially available assay for rapid t<sup>6</sup>A measurement limits its utility and this deficiency needs to be addressed. Further studies are required to evaluate t<sup>6</sup>A under different ICU conditions, including localized (non-sepsis) infections and extracorporeal therapies, to confirm its broader clinical applicability.</p><p>The patient datasets generated and/or analyzed during the current study are available from the corresponding author upon a reasonable request.</p><p>The patient datasets generated and/or analyzed during the current study are available from the corresponding author upon a reasonable request.</p><dl><dt style=\"min-width:50px;\"><dfn>\n<i>AUC</i> :</dfn></dt><dd>\n<p>Area under the curve</p>\n</dd><dt style=\"min-width:50px;\"><dfn>\n<i>CABG</i> :</dfn></dt><dd>\n<p>Coronary artery bypass graft surgery</p>\n</dd><dt style=\"min-width:50px;\"><dfn>\n<i>COVID-19</i> :</dfn></dt><dd>\n<p>Coronavirus disease 2019</p>\n</dd><dt style=\"min-width:50px;\"><dfn>\n<i>CI</i> :</dfn></dt><dd>\n<p>Confidence interval</p>\n</dd><dt style=\"min-width:50px;\"><dfn>\n<i>ICU</i> :</dfn></dt><dd>\n<p>Intensive care unit</p>\n</dd><dt style=\"min-width:50px;\"><dfn>\n<i>ISS</i> :</dfn></dt><dd>\n<p>Injury severity score</p>\n</dd><dt style=\"min-width:50px;\"><dfn>\n<i>PCT</i> :</dfn></dt><dd>\n<p>Procalcitonin</p>\n</dd><dt style=\"min-width:50px;\"><dfn>\n<i>ROC</i> :</dfn></dt><dd>\n<p>Receiver-operating characteristic</p>\n</dd><dt style=\"min-width:50px;\"><dfn>\n<i>t</i>\n<sup><i>6</i></sup>\n<i>A</i> :</dfn></dt><dd>\n<p><i>N</i><sup>6</sup>-Threonylcarbamoyladenosine</p>\n</dd><dt style=\"min-width:50px;\"><dfn>\n<i>tRNA</i> :</dfn></dt><dd>\n<p>Transfer ribonucleic acid</p>\n</dd></dl><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Vincent JL, Jones G, David S, et al. Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis. Crit Care. 2019;23(1):196.</p><p>PubMed PubMed Central Google Scholar </p></li><li data-counter=\"2.\"><p>Liu C, Song X, Liu J, et al. Consistency between metagenomic next-generation sequencing versus traditional microbiological tests for infective disease: systemic review and meta-analysis. Crit Care. 2025;29(1):55.</p><p>PubMed PubMed Central Google Scholar </p></li><li data-counter=\"3.\"><p>Boccaletto P, Machnicka MA, Purta E, et al. MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res. 2018;46(D1):D303–7.</p><p>CAS PubMed Google Scholar </p></li><li data-counter=\"4.\"><p>Chujo T, Tomizawa K. Human transfer RNA modopathies: diseases caused by aberrations in transfer RNA modifications. FEBS J. 2021;288(24):7096–122.</p><p>CAS PubMed PubMed Central Google Scholar </p></li><li data-counter=\"5.\"><p>DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837–45.</p><p>CAS PubMed Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><p>Not applicable.</p><p>Not applicable.</p><h3>Authors and Affiliations</h3><ol><li><p>Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation With AUVA, Donaueschingenstraße 13, 1200, Vienna, Austria</p><p>Marcin F. Osuchowski, Heinz Redl, Johannes Zipperle &amp; Gerhard Fritsch</p></li><li><p>Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Wroclaw, Poland</p><p>Barbara Adamik, Waldemar Gozdzik &amp; Tomasz Skalec</p></li><li><p>Pharm-Analyt Labor, Baden, Austria</p><p>Daniel Mascher &amp; Hermann Mascher</p></li><li><p>Department of Anesthesiology and Intensive Care Medicine, AUVA Trauma Center Salzburg, Salzburg, Austria</p><p>Gerhard Fritsch &amp; Wolfgang Voelckel</p></li><li><p>Department of Anesthesiology, University Medical Center Göttingen, Göttingen, Germany</p><p>Martin S. Winkler &amp; Onnen Moerer</p></li><li><p>BEBAC, Vienna, Austria</p><p>Helmut Schütz</p></li><li><p>Center for Medical Data Science of the Medical University of Vienna, Vienna, Austria</p><p>Helmut Schütz</p></li></ol><span>Authors</span><ol><li><span>Marcin F. Osuchowski</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Barbara Adamik</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Waldemar Gozdzik</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Tomasz Skalec</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Daniel Mascher</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Heinz Redl</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Johannes Zipperle</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Gerhard Fritsch</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Wolfgang Voelckel</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Martin S. Winkler</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Onnen Moerer</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Helmut Schütz</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Hermann Mascher</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li></ol><h3>Contributions</h3><p>MFO and HM conceived of the study and MFO wrote the text. MFO, BA, WG, WV and HM developed the study design. DM, HM, MFO, TS, JZ, OM and GF performed research analysis. HS, BA, JZ and MFO performed data analysis. All authors helped with data interpretation, editing of the manuscript, and read and approved the final text.</p><h3>Corresponding author</h3><p>Correspondence to Marcin F. Osuchowski.</p><h3>Ethics approval and consent to participate</h3>\n<p>The study including patients in the cohorts 1 (sepsis) and 3 (CABG) was approved by the Bioethical Committee of Wroclaw Medical University on November 29, 2018 (approval no. 710/2018). The study including patients in the cohort 3 (COVID-19) was approved by the Bioethical Committee of the University Medical Center Göttingen on June 27, 2018 (SeptImmun Study No. 24/4/19Ü). The study including patients in the cohort 4 (polytrauma) was approved by the Bioethical Committee of Allgemeine Unfallversicherungsanstalt on September 15, 2016 (PRIME study No. 09/2016). This research was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2008.</p>\n<h3>Consent for publication</h3>\n<p>Not applicable.</p>\n<h3>Competing interests</h3>\n<p>Prof. Mascher is a consultant at pharm-analyt Labor, Baden, Austria, and holds patent applications for the use of t<sup>6</sup>A to monitor sepsis conditions. The other authors report no competing interest.</p><h3>Publisher's Note</h3><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p><h3>Supplementary file 1.</h3><p><b>Open Access</b> This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.</p>\n<p>Reprints and permissions</p><img alt=\"Check for updates. 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novel biomarker t<sup>6</sup>A accurately identified septic patients at admission but failed to predict outcome. <i>Crit Care</i> <b>29</b>, 129 (2025). https://doi.org/10.1186/s13054-025-05354-2</p><p>Download citation<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><ul data-test=\"publication-history\"><li><p>Received<span>: </span><span><time datetime=\"2025-02-12\">12 February 2025</time></span></p></li><li><p>Accepted<span>: </span><span><time datetime=\"2025-03-04\">04 March 2025</time></span></p></li><li><p>Published<span>: </span><span><time datetime=\"2025-03-20\">20 March 2025</time></span></p></li><li><p>DOI</abbr><span>: </span><span>https://doi.org/10.1186/s13054-025-05354-2</span></p></li></ul><h3>Share this article</h3><p>Anyone you share the following link with will be able to read this content:</p><button data-track=\"click\" 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Abstract

Sepsis is a life-threatening condition caused by the body’s extreme response to infection [1]. Early diagnosis of sepsis is crucial for improving patient outcomes, yet current diagnostic methods including microbiological cultures are delayed and frequently inconclusive. This has driven the search for novel biomarkers and detection systems capable of recognizing sepsis more rapidly and accurately [2]. Procalcitonin (PCT) is the most widely used biomarker for sepsis detection but its use is limited as circulating PCT concentration is influenced by noninfectious inflammation (e.g. trauma, surgery).

Nucleoside modifications are a hallmark of the post-transcriptional processing of transfer ribonucleic acid (tRNA) that generate multiple structurally modified nucleosides [3]. One of such tRNA-modified nucleosides, N6-threonylcarbamoyladenosine (t6A), is critical for ensuring efficient protein synthesis in health and disease [4]. We discovered that circulating t6A possesses a diagnostic potential in sepsis. Consequently, we evaluated the diagnostic accuracy of t6A in differentiating bacterial sepsis and COVID-19 from two different non-septic patient cohorts: i) patients undergoing elective coronary artery bypass graft (CABG) surgery and ii) severe polytrauma patients. In all cohorts, t6A diagnostic accuracy was compared to PCT. Additionally, we tested t6A potential to predict death/survival in patients with sepsis.

This multicenter retrospective observational study analyzed plasma samples from four cohorts (Supplementary Table 1). The study included 81 patients with bacterial sepsis (cohort 1) and 49 patients with severe COVID-19 infection (cohort 2) diagnosed upon ICU/Emergency admission , 87 patients undergoing elective CABG surgery (cohort 3) and 64 severe (Injury Severity Score > 15) polytrauma patients (cohort 4). Sepsis in cohort 1 was defined according to the Sepsis-3 criteria, and all patients received treatment aligned with the Surviving Sepsis Campaign guidelines. In COVID-19 patients, SARS-CoV-2 infection was confirmed by molecular test. The CABG and polytrauma groups were used as non-septic comparators to assess t6A’s diagnostic specificity and accuracy against patients with sepsis and those with COVID-19. We compared blood samples collected at admission for the sepsis and COVID-19 cohorts, to samples collected 24 h post-surgery (cohort 3) and trauma (cohort 4). Plasma t6A concentrations were measured using tandem mass spectrometry with stable isotope internal standardization. PCT was measured using standard Brahms PCT luminescence immunoassay. Statistical analyses of the receiver operating characteristic (ROC) curves were carried out with a total of 50,000 stratified bootstrap samples to estimate the 95% confidence interval (CI) of the area under the curve (AUC) of the ROC curve and its optimal threshold. The AUCs were compared via De Long’s two-sided test [5].

t6A demonstrated outstanding diagnostic accuracy for sepsis at the ICU/Emergency admission. In separately evaluated exploratory and validation CABG cohorts, t6A consistently showed greater accuracy (AUC > 90%) compared to PCT (AUC 80–88%). t6A accuracy against the pooled CABG patients (cohort 3) achieved an AUC of 95% (vs. 88% for PCT, p < 0.05) (Fig. 1A). Against the polytrauma group, which represented a more clinically relevant comparator, t6A again outperformed PCT; its AUC was 97% compared to 88% for PCT (p < 0.05) (Fig. 1B). In the COVID-19 cohort, t6A also displayed excellent diagnostic performance when SARS-CoV-2-infected patients were compared to CABG (AUC 87%, Fig. 1C) and polytrauma (AUC 93%, Fig. 1D) patients. PCT measurement was not differentiating (AUC 50–52%, p > 0.05). Notably, the optimal diagnostic threshold for t6A was nearly identical (3% deviation) against CABG (40.0 ng/mL) and polytrauma (38.8 ng/mL) comparators; it varied by 22% for PCT (2.04 and 1.6 ng/mL).

Fig. 1
Abstract Image

Diagnostic performance of t6A and PCT for detecting bacterial sepsis (A, B) and COVID-19 (C, D) at the ICU/Emergency admission. n: the first number in parentheses defines the number of sepsis or COVID-19 patients; the second number indicates the number of CABG or polytrauma patients. CI: 95% Confidence Intervals

Full size image

Despite its strong diagnostic performance, t6A showed a limited utility for predicting sepsis outcomes. At the ICU/Emergency admission, t6A concentrations exhibited a considerable overlap between survivors and non-survivors and failed to show any protracted post-admission separation, resulting in an AUC of only 62%. PCT concentrations demonstrated a similar overlap dynamics and performed only modestly better, with an AUC of 72%, suggesting that while t6A is highly effective for identifying sepsis, it lacks prognostic value. This discrepancy highlights the biomarker’s primary utility in diagnosis rather than outcome prediction.

This is the first report regarding the potential utility of t6A as a diagnostic biomarker in patients with sepsis. We show t6A as a highly accurate and reliable biomarker for early sepsis diagnosis at the ICU/Emergency admission. t6A outperformed PCT in differentiating septic patients from non-septic controls including CABG and polytrauma cohorts. Insensitivity of t6A to sterile inflammation positions it as a promising diagnostic tool for clinical use. However, the lack of a commercially available assay for rapid t6A measurement limits its utility and this deficiency needs to be addressed. Further studies are required to evaluate t6A under different ICU conditions, including localized (non-sepsis) infections and extracorporeal therapies, to confirm its broader clinical applicability.

The patient datasets generated and/or analyzed during the current study are available from the corresponding author upon a reasonable request.

The patient datasets generated and/or analyzed during the current study are available from the corresponding author upon a reasonable request.

AUC :

Area under the curve

CABG :

Coronary artery bypass graft surgery

COVID-19 :

Coronavirus disease 2019

CI :

Confidence interval

ICU :

Intensive care unit

ISS :

Injury severity score

PCT :

Procalcitonin

ROC :

Receiver-operating characteristic

t 6 A :

N6-Threonylcarbamoyladenosine

tRNA :

Transfer ribonucleic acid

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Authors and Affiliations

  1. Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation With AUVA, Donaueschingenstraße 13, 1200, Vienna, Austria

    Marcin F. Osuchowski, Heinz Redl, Johannes Zipperle & Gerhard Fritsch

  2. Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Wroclaw, Poland

    Barbara Adamik, Waldemar Gozdzik & Tomasz Skalec

  3. Pharm-Analyt Labor, Baden, Austria

    Daniel Mascher & Hermann Mascher

  4. Department of Anesthesiology and Intensive Care Medicine, AUVA Trauma Center Salzburg, Salzburg, Austria

    Gerhard Fritsch & Wolfgang Voelckel

  5. Department of Anesthesiology, University Medical Center Göttingen, Göttingen, Germany

    Martin S. Winkler & Onnen Moerer

  6. BEBAC, Vienna, Austria

    Helmut Schütz

  7. Center for Medical Data Science of the Medical University of Vienna, Vienna, Austria

    Helmut Schütz

Authors
  1. Marcin F. OsuchowskiView author publications

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Contributions

MFO and HM conceived of the study and MFO wrote the text. MFO, BA, WG, WV and HM developed the study design. DM, HM, MFO, TS, JZ, OM and GF performed research analysis. HS, BA, JZ and MFO performed data analysis. All authors helped with data interpretation, editing of the manuscript, and read and approved the final text.

Corresponding author

Correspondence to Marcin F. Osuchowski.

Ethics approval and consent to participate

The study including patients in the cohorts 1 (sepsis) and 3 (CABG) was approved by the Bioethical Committee of Wroclaw Medical University on November 29, 2018 (approval no. 710/2018). The study including patients in the cohort 3 (COVID-19) was approved by the Bioethical Committee of the University Medical Center Göttingen on June 27, 2018 (SeptImmun Study No. 24/4/19Ü). The study including patients in the cohort 4 (polytrauma) was approved by the Bioethical Committee of Allgemeine Unfallversicherungsanstalt on September 15, 2016 (PRIME study No. 09/2016). This research was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2008.

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Not applicable.

Competing interests

Prof. Mascher is a consultant at pharm-analyt Labor, Baden, Austria, and holds patent applications for the use of t6A to monitor sepsis conditions. The other authors report no competing interest.

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Osuchowski, M.F., Adamik, B., Gozdzik, W. et al. The novel biomarker t6A accurately identified septic patients at admission but failed to predict outcome. Crit Care 29, 129 (2025). https://doi.org/10.1186/s13054-025-05354-2

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来源期刊
Critical Care
Critical Care 医学-危重病医学
CiteScore
20.60
自引率
3.30%
发文量
348
审稿时长
1.5 months
期刊介绍: Critical Care is an esteemed international medical journal that undergoes a rigorous peer-review process to maintain its high quality standards. Its primary objective is to enhance the healthcare services offered to critically ill patients. To achieve this, the journal focuses on gathering, exchanging, disseminating, and endorsing evidence-based information that is highly relevant to intensivists. By doing so, Critical Care seeks to provide a thorough and inclusive examination of the intensive care field.
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