Longitudinal assessment of the inflammatory response: The next step in personalized medicine after severe trauma

Fraiture, E. J. de; Vrisekoop, Nienke; Leenen, Luke P. H.; Wessem, Karlijn J. P. van; Koenderman, Leo; Hietbrink, Falco

doi:10.3389/fmed.2022.983259

Cited by 3 publications

(1 citation statement)

References 73 publications

(105 reference statements)

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“…As it is now possible to measure the neutrophil functional phenotype at any time point after trauma, the longitudinal course of the inflammatory response and the impact of additional interventions can be followed. In the future, measuring the neutrophil compartment over time could possibly guide decision making regarding timing and extent of immune protective surgery and determine the administration of (preventive) antibiotics [22]. Second, our results showed that patients in Categories 0-2 had similarly low injury severity scores.…”

Section: Discussionmentioning

confidence: 71%

Visualization of the inflammatory response to injury by neutrophil phenotype categories

Fraiture

Bongers

Jukema

et al. 2022

Eur J Trauma Emerg Surg

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Purpose The risk of infectious complications after trauma is determined by the amount of injury-related tissue damage and the resulting inflammatory response. Recently, it became possible to measure the neutrophil phenotype in a point-of-care setting. The primary goal of this study was to investigate if immunophenotype categories based on visual recognition of neutrophil subsets are applicable to interpret the inflammatory response to trauma. The secondary goal was to correlate these immunophenotype categories with patient characteristics, injury severity and risk of complications. Methods A cohort study was conducted with patients presented at a level 1 trauma center with injuries of any severity, who routinely underwent neutrophil phenotyping. Data generated by automated point-of-care flow cytometry were prospectively gathered. Neutrophil phenotypes categories were defined by visual assessment of two-dimensional CD16/CD62L dot plots. All patients were categorized in one of the immunophenotype categories. Thereafter, the categories were validated by multidimensional analysis of neutrophil populations, using FlowSOM. All clinical parameters and endpoints were extracted from the trauma registry. Results The study population consisted of 380 patients. Seven distinct immunophenotype Categories (0–6) were defined, that consisted of different neutrophil populations as validated by FlowSOM. Injury severity scores and risk of infectious complications increased with ascending immunophenotype Categories 3–6. Injury severity was similarly low in Categories 0–2. Conclusion The distribution of neutrophil subsets that were described in phenotype categories is easily recognizable for clinicians at the bedside. Even more, multidimensional analysis demonstrated these categories to be distinct subsets of neutrophils. Identification of trauma patients at risk for infectious complications by monitoring the immunophenotype category is a further improvement of personalized and point-of-care decision-making in trauma care.

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Section: Discussionmentioning

confidence: 71%

Visualization of the inflammatory response to injury by neutrophil phenotype categories

Fraiture

Bongers

Jukema

et al. 2022

Eur J Trauma Emerg Surg

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Neuroma morphology: A macroscopic classification system

Raasveld,

Weigel,

Liu

et al. 2024

Muscle and Nerve

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Introduction/AimsNeuromas come in different shapes and sizes; yet the correlation between neuroma morphology and symptomatology is unknown. Therefore, we aim to investigate macroscopic traits of excised human neuromas and assess the validity of a morphological classification system and its potential clinical implications.MethodsEnd‐neuroma specimens were collected from prospectively enrolled patients undergoing symptomatic neuroma surgery. Protocolized images of the specimens were obtained intraoperatively. Pain data (Numeric rating scale, 0–10) were prospectively collected during preoperative interview, patient demographic and comorbidity factors were collected from chart review. A morphological classification is proposed, and the inter‐rater reliability (IRR) was assessed. Distribution of neuroma morphology with patient factors, was described.ResultsForty‐five terminal neuroma specimens from 27 patients were included. Residual limb patients comprised 93% of the population, of which 2 were upper (8.0%) and 23 (92.0%) were lower extremity residual limb patients. The proposed morphological classification, consisting of three groups (bulbous, fusiform, atypical), demonstrated a strong IRR (Cohen's kappa = 0.8). Atypical neuromas demonstrated higher preoperative pain, compared with bulbous and fusiform. Atypical morphology was more prevalent in patients with diabetes and peripheral vascular disease.DiscussionA validated morphological classification of neuroma is introduced. These findings may assist surgeons and researchers with better understanding of symptomatic neuroma development and their clinical implications. The potential relationship of neuroma morphology with the vascular and metabolic microenvironment requires further investigation.

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Limited impact of traumatic brain injury on the post-traumatic inflammatory cellular response

van Eerten,

de Fraiture,

Duebel

et al. 2024

Eur J Trauma Emerg Surg

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Purpose Trauma triggers a systemic inflammatory cellular response due to tissue damage, potentially leading to a secondary immune deficiency. Trauma severity is quantified by the Injury Severity Score (ISS). Severe Traumatic Brain Injury (TBI) is associated with high ISSs due to high lethality, despite limited tissue damage. Therefore, ISS might overestimate the post-traumatic inflammatory cellular response. This study investigated the effect of TBI on the occurrence of different systemic neutrophil phenotypes as alternative read-out for systemic inflammation. Methods A single-center retrospective cohort study was conducted at a level-1 trauma center. Patients aged ≥ 18 years, admitted between 01-03-2021–01-11-2022 and providing a diagnostic blood sample were included. Four groups were created: isolated TBI, isolated non-TBI, multitrauma TBI and multitrauma non-TBI. Primary outcome was occurrence of different neutrophil phenotypes determined by automated flow cytometry. Secondary outcome was infectious complications. Results In total, 404 patients were included. TBI and non-TBI patients demonstrated similar occurrences of different neutrophil phenotypes. However, isolated TBI patients had higher ISSs than their isolated non-TBI controls who suffered similar post-traumatic inflammatory cellular responses. Regardless of the type of injury, patients exhibiting higher systemic inflammation had a high infection risk. Conclusion When TBI is involved, ISS tends to be higher compared to similar patients in the absence of TBI. However, TBI patients did not demonstrate an increased inflammatory cellular response compared to non-TBI patients. Therefore, TBI does not add much to the inflammatory cellular response in trauma patients. The degree of the inflammatory response was related to the incidence of infectious complications.

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Longitudinal assessment of the inflammatory response: The next step in personalized medicine after severe trauma

Cited by 3 publications

References 73 publications

Visualization of the inflammatory response to injury by neutrophil phenotype categories

Visualization of the inflammatory response to injury by neutrophil phenotype categories

Neuroma morphology: A macroscopic classification system

Limited impact of traumatic brain injury on the post-traumatic inflammatory cellular response

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