AUTHOR=Lei Mingxing , Han Zhencan , Wang Shengjie , Guo Chunxue , Zhang Xianlong , Song Ya , Lin Feng , Huang Tianlong 

TITLE=Biological signatures and prediction of an immunosuppressive status—persistent critical illness—among orthopedic trauma patients using machine learning techniques

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.979877

DOI=10.3389/fimmu.2022.979877

ISSN=1664-3224

ABSTRACT=Background: Persistent critical illness (PerCI) is an immunosuppressive status. The underlying pathophysiology driving PerCI remains incompletely understood. The objectives of the study were to identify the biological signature of PerCI development, and to construct a reliable prediction model for patients who had suffered orthopaedic trauma.
Methods: This study enrolled 1257 patients from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Lymphocytes were tracked from ICU admission to more than 20 days following admission to examine the dynamic changes over time Over 40 possible variables were gathered for investigation. Four machine learning algorithms, including random forest, gradient boosting machine, decision tree, and support vector machine, and a logistic regression technique were utilized to train and optimize models using data from the training cohort. 
Results: 16.0% (201/1257) of all patients had PerCI in the MIMIC-III database. The means of lymphocytes (%) were consistently below the normal reference range across the time among PerCI patients (around 10.0%), whereas in patients without PerCI, the number of lymphocytes continued to increase and began to be in normal range on day 10 following ICU admission. Subgroup analysis demonstrated that patients with PerCI were in a more serious health condition at admission since those patients had worse nutritional status, more electrolyte imbalance and infection-related comorbidities, and more severe illness scores. Eight variables, including albumin, serum calcium, RDW, blood pH, heart rate, respiratory failure, pneumonia, and the Sepsis-related Organ Failure Assessment (SOFA) score, were significantly associated with PerCI, and these variables were all included in the modelling. In comparison to other algorithms, the random forest had the optimal prediction ability with the highest area under receiver operating characteristic (AUROC) (0.823, 95% CI: 0.757-0.889), highest Youden index (1.571), and lowest Brier score (0.107). The AUROC in the external validation cohort was also up to 0.800 (95% CI: 0.688-0.912). 
Conclusions: Patients with PerCI typically remain in an immunosuppressive status, but those without PerCI gradually regain normal immunity. The dynamic changes of lymphocytes can be a reliable biomarker for PerCI. This work developed a reliable model that may be helpful in improving early diagnosis and targeted intervention of PerCI.