Elevated monocyte distribution width in trauma: An early cellular biomarker of organ dysfunction

Morales, A. Marcos; Barea‐Mendoza, Jesús Abelardo; García-Fuentes, C.; Felgueroso, Cecilia Cueto; López-Jiménez, Ana; Martín‐Loeches, Ignacio; Chico‐Fernández, Mario

doi:10.1016/j.injury.2021.11.026

Cited by 8 publications

(6 citation statements)

References 19 publications

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“…In-depth immune profiling of children with MIS-C also revealed increased markers of monocyte activation, such as increased CD64 expression [ 29 ], increased ICAM1 expression [ 29 ], and decreased CD16 expression [ 15 , 30 ]. Similar changes in monocytes, reflected in MDW above a threshold of 20, have been reported in sepsis and organ dysfunction in children [ 16 , 17 ] and adults [ 18 – 20 ], trauma [ 31 ], and viral infections like COVID-19 [ 32 , 33 ], and influenza [ 34 ]. Thus, monocyte anisocytosis should be used as a MIS-C screening test in concert with clinical findings as it is not a stand-alone diagnostic test.…”

Section: Discussionsupporting

confidence: 63%

Monocyte anisocytosis increases during multisystem inflammatory syndrome in children with cardiovascular complications

et al. 2022

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Background Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication that can develop weeks to months after an initial SARS-CoV-2 infection. A complex, time-consuming laboratory evaluation is currently required to distinguish MIS-C from other illnesses. New assays are urgently needed early in the evaluation process to expedite MIS-C workup and initiate treatment when appropriate. This study aimed to measure the performance of a monocyte anisocytosis index, obtained on routine complete blood count (CBC), to rapidly identify subjects with MIS-C at risk for cardiac complications. Methods We measured monocyte anisocytosis, quantified by monocyte distribution width (MDW), in blood samples collected from children who sought medical care in a single medical center from April 2020 to October 2020 (discovery cohort). After identifying an effective MDW threshold associated with MIS-C, we tested the utility of MDW as a tier 1 assay for MIS-C at multiple institutions from October 2020 to October 2021 (validation cohort). The main outcome was the early screening of MIS-C, with a focus on children with MIS-C who displayed cardiac complications. The screening accuracy of MDW was compared to tier 1 routine laboratory tests recommended for evaluating a child for MIS-C. Results We enrolled 765 children and collected 846 blood samples for analysis. In the discovery cohort, monocyte anisocytosis, quantified as an MDW threshold of 24.0, had 100% sensitivity (95% CI 78–100%) and 80% specificity (95% CI 69–88%) for identifying MIS-C. In the validation cohort, an initial MDW greater than 24.0 maintained a 100% sensitivity (95% CI 80–100%) and monocyte anisocytosis displayed a diagnostic accuracy greater that other clinically available hematologic parameters. Monocyte anisocytosis decreased with disease resolution to values equivalent to those of healthy controls. Conclusions Monocyte anisocytosis detected by CBC early in the clinical workup improves the identification of children with MIS-C with cardiac complications, thereby creating opportunities for improving current practice guidelines.

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Section: Discussionsupporting

confidence: 63%

Monocyte anisocytosis increases during multisystem inflammatory syndrome in children with cardiovascular complications

et al. 2022

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“…19 Avoiding antibiotic delays for those patients in whom antibiotics may be lifesaving, while constraining their use in those who cannot benefit, may require the application of biomarkers with the capability of specifically detecting the host response to infection, such as monocyte distribution width measurements or gene expression diagnostic assays. [35][36][37][38][39][40] Our study is strengthened by its inclusion of multiple centers and the cluster-randomized crossover design. We also demonstrate applicability in a real-world setting.…”

Section: Discussionmentioning

confidence: 99%

Trial of Antibiotic Restraint in Presumed Pneumonia: A Surgical Infection Society Multicenter Pilot

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Watson

et al. 2022

J Trauma Acute Care Surg

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“…The extremely up-regulated antigen processing and presentation will trigger an intense systemic inflammatory response and excessive release of pro-inflammatory mediators, inevitably leading to unfavorable clinical outcomes in trauma patients. Growing evidence has already confirmed that monocytes pathology contributes to unfavorable clinical outcomes for trauma patients ( 34 , 35 ). However, few studies reveal the underlying mechanisms behind this.…”

Section: Discussionmentioning

confidence: 98%

Activated autophagy of innate immune cells during the early stages of major trauma

et al. 2023

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BackgroundTrauma-induced immune dysfunction has been a major barrier to achieving reduced mortality, which is poorly understood. Autophagy is a crucial catabolic mechanism of immune cells during times of stress. Few studies have investigated the immune regulatory effects induced by autophagy after trauma. Here, we use single-cell transcriptomics analysis in a major trauma cohort to demonstrate the dominant role of autophagy in innate immune cells during the early stages of major trauma.MethodSingle-cell transcriptional profiling of peripheral blood mononuclear cells (PBMCs) was performed, which were sampled from three control participants and five major trauma patients within 6 hours of injury. In detail, after single-cell RNA-sequence data processing, cell type annotation and cluster marker identification were performed. A genetic toolbox with 604 autophagy-related genes was used to monitor the autophagy levels in immune cells. In addition, all transcriptome RNA sequencing data obtained from PBMCs in a cohort of 167 major trauma patients were downloaded from gene expression omnibus (GEO) datasets (GSE36809). Key deregulated biological processes and important autophagic hub genes involved in immune cells were identified by weighted gene co-expression network analysis and gene ontology enrichment analysis.ResultsA total of 20,445 differentially expressed genes were identified and five co-expression modules were constructed. Enrichment analysis indicated that activated autophagy is the most important biological process during the early stages of major trauma, and JMY (autophagy-related genes) were identified as hub genes. The single-cell transcriptional profiling of PBMCs demonstrated that all components of adaptive immune cells were significantly decreased, whereas components of innate immune cells (monocytes and neutrophils) were significantly increased in major trauma patients compared with control participants. Activated autophagy was detected in monocytes and neutrophils by monitoring the dynamic transcriptional signature of the autophagy-related genetic toolbox. Biological process analysis shows that antigen uptake, processing presentation, and major histocompatibility complex (MHC) class II protein complex assembly pathways were up-regulated in autophagy-positive monocytes, whereas antigen processing and presentation of endogenous antigen and type I interferon signaling pathways were up-regulated in autophagy-positive neutrophils during the early stages of major trauma.ConclusionOur study demonstrated that autophagy is a biological process crucial to the development of immune disorders in the early stages of major trauma. Furthermore, the results of our study generated a comprehensive single-cell immune landscape for major trauma patients, in which we determined that autophagy profoundly affects the main functions of innate immune cells and provides insight into the cellular basis of immune dysregulation after major trauma.

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Elevated monocyte distribution width in trauma: An early cellular biomarker of organ dysfunction

Cited by 8 publications

References 19 publications

Monocyte anisocytosis increases during multisystem inflammatory syndrome in children with cardiovascular complications

Monocyte anisocytosis increases during multisystem inflammatory syndrome in children with cardiovascular complications

Trial of Antibiotic Restraint in Presumed Pneumonia: A Surgical Infection Society Multicenter Pilot

Activated autophagy of innate immune cells during the early stages of major trauma

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