R. Murray et al.: J Extra Corpor Technol 2025, 57, 96 – 104 103
Discovery of biomarkers able to differentiate true infection in the pediatric MCS population is imperative not only to identify and treat true infection more rapidly but also to decrease exposure to antimicrobials in patients who do not need them. Unnecessary use of antimicrobials could result in the development of resistant organisms, making treatment of future infections more challenging. Thus, identifying more reliable biomarkers of infection for patients supported with MCS has the potential to not only improve outcomes but also decrease unnecessary antimicrobial use.
This study is limited in that it is a small pilot study with built in restrictions on sample size and thus power. The sample size is limited as this is a retrospective use of a prospectively collected blood bank with limitations on how many patients developed an infection during their MCS course. The retrospective nature of our study does introduce a selection bias that we were not able to mitigate. A further limitation of our study is that while we utilized each patient as their own uninfected control, we did not have a matched control group who never developed an infection. The absence of this form of control group may lead to unmeasured confounding and other forms of bias. The sum of these limitations require that we clearly state that a larger, more strongly powered study is required before the conclusions and associations between novel biomarkers and infection we have found in our study can or should be utilized clinically.
While false positives, colonization or contamination are possible we believe that our approach of using clinically obtained cultures coupled with the fact that all patients included in our study received antimicrobial therapy as determined by their clinical team, gave us the most accurate definition of infection for this retrospective cohort study, but it is not without some limitations.
The emerging biomarkers sTREM-1 and Presepsin may not be affected by MCS initiation but have significantly higher values than reported in other patient populations. Within our patient population Presepsin and Procalcitonin may have utility in identifying infection but with a decrease rather than the expected increase in their values. These findings highlight the importance of biomarker studies specifically performed in the MCS patient population, and the potential lack of translatability of biomarkers in other patient populations to the MCS patient population.
Acknowledgements
Authors would like to thank the Hall Lab for CRP sample analysis and the ECMO / VAD team at Nationwide Children’ s Hospital for assistance in obtaining pre MCS Samples.
Funding
Funding for this project provided by the Nationwide Children’ s Hospital Intramural Funding Program and the Nationwide Children’ s Hospital Heart Center Clinical / Translational funding program.
Conflicts of interest
Authors declare no conflicts of interest. Dr. Andrew Yates has served as a consultant for Alexion Pharmaceuticals on topics unrelated to the manuscript.
Data availability statement
All available data is incorporated into the manuscript and the included Supplementary materials.
Author contribution statement
All authors were involved in the conceptualization of, drafting of, the critical revision of and final approval of this article. Authors Murray, Bi, Alexander, Frazier and Yates were involved in securing funding for this article. Authors Murray, Bi, Seabrook, Frazier and Yates were involved in data collection. Authors Murray, Alexander, Haque and Yates were involved in data analysis and interpretation.
Ethics approval
Nationwide Children’ s Hospital Institutional Review Board approval with a waiver of informed consent was obtained prior to the initiation of research( IRB number: STUDY00002511).
Supplementary materials
The supplementary materials of this article are available at https:// ject. edpsciences. org / 10.1051 / ject / 2025008 / olm. Supplemental Figure 1: Kinetics of biomarkers while on mechanical circulatory support. Supplemental Figure 2: Kinetics of biomarkers while cannulated by mode of support. Supplemental Figure 3: Biomarker response to infection. Supplemental Table 1: Pre and post MCS cannulation biomarker kinetics with missing values identified. Supplemental Table 2: Pre cannulation levels of biomarkers based on mode of mechanical circulatory support with missing values identified. Supplemental Table 3: Biomarker values while on mechanical circulatory support with missing values identified. Supplemental Table 4: Biomarker values while cannulated by mode of support with missing values identified. Supplemental Table 5: Pre cannulation levels of biomarkers based on mode of mechanical circulatory support. Supplemental Table 6: Biomarker values while cannulated by mode of support.
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