Editorial: Community series in translational insights into mechanisms and therapy of organ dysfunction in sepsis and trauma - volume III
Year: 2024
Type: editorial
Abstract: Translational research on trauma, sepsis, and multiple organ damage is continuously evolving,fostering advancements in the development of diagnostics and therapeutics, and improvingour understanding of the complex pathophysiological mechanisms underlying these life-threateningconditions. The contributors of this special issue explore the different aspects ofthe pathophysiology of trauma and critical illness. With different approaches, these studiesdescribe novel potential diagnostic markers, innovative therapeutic interventions, andelucidate the complex mechanisms underlying immune responses and organ damage inpatients with trauma, sepsis and/or multiple organ failure.Life-threatening organ dysfunction and failure in trauma and critically ill patients stem from adysregulated host response to infection and inflammation. Despite advancements inunderstanding the key signaling pathways involved, translating this knowledge into organprotectivetherapies remains challenging. Current treatments primarily rely on infectioncontrol, antibiotics, supportive care, and early goal-directed therapy.Trauma and sepsis-induced organ dysfunction are driven by excessive systemic inflammation,secondary to tissue damage and ischemia-reperfusion injury. The endothelial glycocalyx is acritical early site involved in triggering a pro-inflammatory response. Alterations in itsstructure lead to the release of degradation products and damage-associated molecularpatterns (DAMPs) that, along with pathogen-associated molecular patterns (PAMPs), amplifysystemic inflammation and, hence, contribute to organ dysfunction including acute kidneyinjury, respiratory failure, and cardiomyopathy.Three major fields of research have been covered by the authors. First, in terms of sepsisdiagnosis and treatment, Dennhardt et al. investigate the clinical significance of circulatingcell-free DNA (cfDNA) levels in sepsis patients as predictors of both mortality and sepsisassociatedacute kidney injury, suggesting elevated cfDNA levels as a potential enhancer ofrisk assessment in sepsis (1). Similarly, Qiang et al. explore the therapeutic potential ofprogesterone in sepsis, presenting promising results in septic mice and patients by inhibitingprocathepsin-L-mediated inflammation (2). Guggemos et al. investigate the impact of specificpolymorphisms of the ATP-sensitive P2X7 receptor on sepsis susceptibility and prognosis,revealing their potential role as genetic markers (3). Wakeley et al. examine the role ofHerpes virus entry mediator in neonatal sepsis response, highlighting its importance invascular and hemodynamic resilience (4), while Kasper et al. study the effects ofhemadsorption therapy on endothelial barrier dysfunction in sepsis in vitro, indicating itspotential transient clinical improvement (5).Second, with a focus on trauma, injury, and organ damage, Horner et al. explore the immunesuppressive role of DAMPs in sterile traumatic injury, proposing potential therapeuticstrategies to mitigate immune suppression in their review (6). Wolfschmitt et al. investigatethe impact of hyperoxemia on the metabolism of circulating immune cells during intensivecare, focusing on granulocytes in models of acute subdural hematoma and hemorrhagic shock(7). Groven et al. explore the association between circulating miRNA expression inextracellular vesicles (EVs) as biomarkers for specific injuries following multiple trauma andsurgical invasiveness (8). Meng et al. investigate how aging influences liver inflammation anddamage after trauma, highlighting dysregulated immune responses (9), while Zhou et al.examine the exacerbation of lung damage after trauma in aged mice, focusing on the role ofNF-κB and inflammasomes (10). Neu et al. explore the cardiovascular impairment in amurine model of hemolytic-uremic syndrome induced by Shiga toxin, a model whichreplicates the extrarenal manifestations observed in HUS patients (11). Fachet et al. propose afeature-based risk assessment system for predicting hyperinflammatory patterns andinfectious outcomes in polytrauma patients using predictive machine learning modeling (12).The third part of this article collection addresses therapeutic interventions and drugrepurposing. Verra et al. investigate the effects of baricitinib, a JAK1/JAK2 inhibitor, onsepsis-induced cardiac dysfunction and multiple-organ failure, suggesting its potential fortrauma-associated sepsis (13). Hof et al. study the effects of carbachol on gastric and oralmicrocirculation during hemorrhagic shock in dogs, highlighting its potential therapeutic usein improving tissue oxygenation (14). Yamaga et al. discuss potential therapeutic strategiestargeting DAMPs to alleviate radiation-induced injury, focusing on the mechanisms of DAMPrelease and their detrimental effects on the immune system (15). To advance ourunderstanding of critical illness, Li et al. identify key genes and pathways associated withDNA damage responses, inflammation, and cellular senescence in elderly patients with acuterespiratory distress syndrome, offering insights into potential diagnostic biomarkers andtherapeutic targets (16). Murao et al. utilize single-cell RNA sequencing to investigateimmune cell responses in sepsis, providing insights into distinct immune cell subsets and theirroles in inflammation and tissue repair, thus enhancing our understanding of thepathophysiology of sepsis (17). Wang et al. conducted the LiBOD study to assess thepotential of serum-derived EVs as biomarkers for decision-making in polytrauma cases,suggesting specific EVs as valuable biomarkers for assessing and monitoring the severity ofpolytrauma and associated organ damage (18).These studies collectively contribute to a better understanding of diagnostic markers,therapeutic interventions, immune responses, and the mechanisms underlying organ injuryand dysfunction in trauma, sepsis, and related conditions, offering potential avenues forimproving care and outcomes of patients with critical illness.As we review the research presented in this issue, it is clear how scientific researchsignificantly shapes the field of trauma and critical care medicine, addressing the issue ofimproving patient outcomes, moving towards precision medicine in intensive care.We conclude this special issue with deep gratitude to the researchers, clinicians, and patientswhose dedication has made this work possible. We hope the insights from these studies willbe interesting and educational to our readers and help developing this area of research on achallenging condition.
Source: Frontiers in Immunology
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,295
OpenAlex ID: W4400538479