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Pathways leading to tissue and organ damage after trauma Tissue injury and haemorrhage can lead to systemic inflammatory response syndrome (SIRS), which, if persistent, may cause multiorgan failure. A loss of endothelial integrity can result from tissue hypoperfusion, and activation of coagulation and neuroendocrine pathways, thereby enabling humoral and cellular factors to damage tissues far from the site of the original injury. DAMPs: damage-associated molecular patterns; PICS: Persistent Inflammation/ Immunosuppression and Catabolism Syndrome.
Source publication
Improvements in the control of haemorrhage after trauma have resulted in the survival of many people who would otherwise have died from the initial loss of blood. However, the danger is not over once bleeding has been arrested and blood pressure restored. Two-thirds of patients who die following major trauma now do so as a result of causes other th...
Contexts in source publication
Context 1
... many survivors of massive haemorrhage now go on to develop multiorgan failure often accompanied by sepsis. 4 Multiorgan failure and sepsis are a result of the systemic response to severe injury, which compounds the original injury ( Figure 1). Patients who experience severe trauma are now able to survive because of advances in the control and correction of massive blood loss. ...
Context 2
... systemic response to severe injury involves interactions across the haemostatic, inflammatory, endocrine and neurological systems, aggravating initial damage caused by hypoperfusion (shock) and reperfusion ( Figure 1). Endothelium activated by exposure to inflammatory cytokines becomes more porous, allowing mediators of tissue damage to gain access to the intercellular space. ...
Citations
... Pro-inflammatory cytokines alter the levels of circulating acute phase proteins such as C-reactive protein (CRP), albumin, ferritin, transferrin, and fibrinogen. (8) However, the pathophysiology does not only stem from tissue damage, but is multifactorial in nature, ranging from anxiety, pain and coagulation disorders to hemodynamic alterations and hypoxia. Since the surgical stress response has several agents that favor inflammation, interventions should also be directed at its different components, as proposed by ERAS. ...
This scoping review aims to develop a descriptive summary of the included studies and identify possible gaps in the literature on the impact of the ERAS protocol on the inflammatory response from laparoscopic surgery. This review`s guiding question is: "Are there any studies analyzing the impact of the ERAS protocol on inflammatory markers from laparoscopic surgery? What evidence exists on the impact of ERAS on the immune system?"
... This process leads to a direct activation and release of many inflammatory mediators including oxygen-free radicals, arachidonic acid metabolites, cytokines, platelet-activating factor, nitric oxide, and endothelin [43]. Patients undergoing cardiac surgery with extracorporeal circuits also have a higher risk of infection, SIRS, and sepsis underlining the postoperative immunosuppressive phase [44]. As an example, a study conducted by Nguyen et al. indicated that higher preoperative neutrophil counts and low perioperative lymphocyte counts were associated with the occurrence of postoperative complications in patients undergoing cardiac surgery [45]. ...
Indoleamine 2,3-deoxygenase (IDO) plays an important role in the catabolism of the amino acid tryptophan. Tryptophan and its metabolites are key immune modulators. Increased IDO activity has been observed in various diseases and is associated with worse clinical outcomes. However , comprehensive research regarding its role in cardiac surgery remains limited. Therefore, we aimed to investigate perioperative changes in IDO activity and pathway metabolites, along with their impact on clinical outcomes in adult patients undergoing cardiac surgery. As an observational cohort study conducted at the Inselspital in Bern from January to December 2019, we retrospectively analyzed the data of prospectively collected biobank samples of patients undergoing cardiac surgery with the use of cardiopulmonary bypass. IDO pathway metabolite analysis was conducted by mass spectrometry. Perioperative dynamics were descriptively assessed and associated with pre-defined clinical outcome measures (30-day mortality, 1-year mortality, incidence of stroke and my-ocardial infarction, and length of hospital stay) through a multi-step exploratory regression analysis. A cohort of 192 adult patients undergoing cardiac surgery with the use of cardiopulmonary bypass were included (median age 67.0, IQR 60.0-73.0, 75.5% male). A significant perioperative decrease in the kynurenine/tryptophan (Kyn/Trp) ratio (−2.298, 95% CI −4.028 to −596, p = 0.009) and significant perioperative dynamics in the associated metabolites was observed. No association of perioperative changes in IDO activity and pathway metabolites with clinical outcomes was found. A significant decrease in the Kyn/Trp ratio among adult patients undergoing cardiac surgery indicates a perioperative downregulation of IDO, which stands in contrast to other pro-inflammatory conditions. Further studies are needed to investigate IDO in the setting of perioperative immuno-modulation, which is a key driver of postoperative complications in cardiac surgery patients.
... Elle se caractérise par une activation cellulaire immunitaire et endothéliale avec séquestration viscérale des PNNs notamment au niveau pulmonaire [60]. À l'instar du sepsis, les patients polytraumatisés sont susceptibles de développer des infections secondaires, en lien avec des dysfonctions immunitaires décrites au cours du sepsis [61]. ...
De nombreux états critiques, qu’ils soient d’origine infectieuse ou non, s’associent à une réponse inflammatoire aigue. L’immunité innée constitue la première ligne de défense contre l’agression, et caractérisée par sa mise en jeu rapide et non spécifique. Une activation excessive et dérégulée de l’immunité innée joue un rôle central dans la survenue des dysfonctions d’organes qui conduisent les patients en réanimation et participant à la survenue d’une morbi-mortalité précoce. Elle participe aussi à la survenue de dysfonctions immunitaires et facilitant la survenue d’infections secondaires et d’une morbi-mortalité plus tardive. Cette revue a pour but d’expliquer la physiopathologie de cette réponse immunitaire innée, les déterminants qui peuvent conduire à sa dérégulation. Ainsi, si l’immunomodulation est une piste prometteuse dans de nombreuses pathologies critiques, cette revue rappelle la complexité de trouver les meilleures cibles thérapeutiques, imposant de mieux appréhender l’hétérogénéité des réponses, selon le type d’agression, les caractéristiques de l’hôte et le timing de la prise en charge. Aussi, une meilleure compréhension des voies de régulation de cette réponse a permis de développer de nouveaux concepts comme l’immunothrombose, l’immunométabolisme et l’épigénétique, qui pourraient aboutir au développement de nouvelles thérapeutiques capables de restaurer l’homéostasie au cours des états d’agression aiguë. Ainsi, le réanimateur est plus que jamais, incité à s’intéresser à la réponse immunitaire innée.
... 5 Those afflicted with severe trauma often endure substantial tissue damage and profound blood loss, resulting in a considerable drain on medical resources. 6 Various factors can lead to severe trauma, ranging from natural disasters like earthquakes to unexpected conflicts and road traffic injuries. The impact of trauma is profound and cannot be overstated. ...
... 56 SIRS arises from the release of endogenous factors like damage-associated molecular patterns (DAMPs), distinct from the immune response to infection. 6 However, the body's defense weakens after acute trauma, increasing susceptibility to infection and sepsis, which can exacerbate multiple organ dysfunction syndrome (MODS) or even lead to death. 6,57 While the immune response aims to aid recovery, excessive or inappropriate activation can worsen outcomes. ...
... 6 However, the body's defense weakens after acute trauma, increasing susceptibility to infection and sepsis, which can exacerbate multiple organ dysfunction syndrome (MODS) or even lead to death. 6,57 While the immune response aims to aid recovery, excessive or inappropriate activation can worsen outcomes. 6,58 Researchers are increasingly recognizing the complexity and dynamics of the immune response after severe trauma. ...
Severe trauma is a critical aspect of medical practice, profoundly impacting patient care and outcomes. Over the past 20 years, advancements in trauma care concepts and the utilization of advanced technologies have led to substantial growth in severe trauma research, evidenced by a notable increase in research activity and subsequent publications. To understand the publication landscape in severe trauma, identify prevailing research trends, and highlight areas requiring further development for future insights, we conducted a bibliometric analysis. Our analysis indicates that there are 16,939 severe trauma‐related publications from the past 20 years, with a continuous increase in publication volume, particularly showing a rapid growth trend from 2018 to 2021. The United States leads in both volume and citation frequency. Moreover, we synthesized data on productive countries/regions and research institutions, showcasing extensive collaboration across diverse geographic locations and institutional affiliations. Substantial progress has been achieved in severe trauma research, particularly in clinical diagnosis, treatment, epidemiology, prevention, and pathogenesis. However, there is still a gap in adopting cutting‐edge interdisciplinary methodologies. This study provides a comprehensive overview of the current state of severe trauma research and suggests pathways for future advancement.
... With the development of tissue engineering techniques in recent years, the implantation of scaffolds or bone substitutes has become a new means of treating bone defects [4]. It is noteworthy that severe trauma could cause the body's stress response, which results in low immunity in the organism [5]. The surgical procedure of scaffold implantation is prone to bacterial infections, potentially leading to bone graft failure [6,7]. ...
Bacterial infection is a common complication in bone defect surgery, in which infection by clinically resistant bacteria has been a challenge for the medical community. Given this emerging problem, the discovery of novel natural-type inhibitors of drug-resistant bacteria has become imperative. Brucine, present in the traditional Chinese herb Strychnine semen, is reported to exert analgesic and anti-inflammatory effects. Brucine’s clinical application was limited because of its water solubility. We extracted high-purity BS by employing reflux extraction and crystallization, greatly improved its solubility, and evaluated its antimicrobial activity against E. coli and S. aureus. Importantly, we found that BS inhibited the drug-resistant strains significantly better than standard strains and achieved sterilization by disrupting the bacterial cell wall. Considering the safety concerns associated with the narrow therapeutic window of BS, a 3D BS-PLLA/PGA bone scaffold system was constructed with SLS technology and tested for its performance, bacteriostatic behaviors, and biocompatibility. The results have shown that the drug-loaded bone scaffolds had not only long-term, slow-controlled release with good cytocompatibility but also demonstrated significant antimicrobial activity in antimicrobial testing. The above results indicated that BS may be a potential drug candidate for the treatment of antibiotic-resistant bacterial infections and that scaffolds with enhanced antibacterial activity and mechanical properties may have potential applications in bone tissue engineering.
... Polytrauma patients undergo a systemic inflammatory response in the first 24 h after injury [95]. This systemic response has been shown to result in severe osseous clinical manifestations, such as delayed fracture healing and an increased risk of non-union [1,63]. ...
Bone healing occurs through three consecutive and interdependent phases. While the acute inflammatory response is vital to fracture healing, chronic and systemic inflammation negatively affect the healing process. The bone tissue relies heavily on the immune system for its normal physiology and turnover. The interactions are more pronounced in injury states, such as fractures and autoimmune disorders. Recently, the field of osteoimmunology, the study of the molecular interplay of the immune and skeletal systems, has gained much-needed attention to develop new therapeutic strategies to accelerate fracture healing and prevent the complications of fracture healing. This review provides an overview of the process of fracture healing and discusses the role of immune cells, their interplay with the released cytokines, and the current state of the art in the field of osteoimmunology.
... Chronic wounds exhibit a continuous inflammation with an overabundance of pro-inflammatory cytokines. 19 ASCs transplantation could effectively attenuate chronic inflammation and promote tissue repair. 20 Thus, we wondered that whether MS-mASCs transplantation alleviates highly inflammatory environment in chronic wounds. ...
Transplantation of adipose‐derived stem cells (ASCs) is a promising option in the field of chronic wounds treatment. However, the effectiveness of ASCs therapies has been hampered by highly inflammatory environment in chronic wound areas. These problems could be partially circumvented using efficient approaches that boost the survival and anti‐inflammatory capacity of transplanted ASCs. Here, by application of mechanical stretch (MS), we show that ASCs exhibits increased survival and immunoregulatory properties in vitro. MS triggers the secretion of macrophage colony stimulating factor (M‐CSF) from ASCs, a chemokine that is linked to anti‐inflammatory M2‐like macrophages polarization. When the MS‐ASCs were transplanted to chronic wounds, the wound area yields significantly faster closure rate and lower inflammatory mediators, largely due to macrophages polarization driven by transplanted MS‐ASCs. Thus, our work shows that mechanical stretch can be harnessed to enhance ASCs transplantation efficiency in chronic wounds treatment.
... Despite extensive basic science investigations into the mechanisms associated with the disordered acute inflammation, there has been essentially universal failure in the translation of that knowledge into effective therapeutics. While targeted manipulation of various cytokines/mediators, damage-associated molecular pattern molecules, oxygen and nitrogen free radicals, coagulation pathway intermediates, and vasoactive peptides and lipids have shown promise in pre-clinical studies, none of these have been found efficacious in Phase III clinical trials [2,3]. As such there is currently not a single drug approved by the U.S. Food and Drug Administration that specifically targets the underlying immune pathophysiology of sepsis [2,4]. ...
... • Test 1: Host Resilience = 0.1: Invasiveness = 1:Toxigenesis = 3: Initial Injury = 20. Notation Label (0. 1,1,3,20). Test 1 Parameters generated a Baseline Recovered Rate = 25%. This parameterization represents a group with higher health resilience (corresponding to better baseline health status), but exposed to a microbe that more rapidly kills infected cells. ...
On December 15, 2023, The National Academies of Sciences, Engineering and Medicine (NASEM) released a report entitled: “Foundational Research Gaps and Future Directions for Digital Twins.” The ostensible purpose of this report was to bring some structure to the burgeoning field of digital twins by providing a working definition and a series of research challenges that need to be addressed to allow this technology to fulfill its full potential. In the work presented herein we focus on five specific findings from the NASEM Report: 1) definition of a Digital Twin, 2) using “fit-for-purpose” guidance, 3) developing novel approaches to Verification, Validation and Uncertainty Quantification (VVUQ) of Digital Twins, 4) incorporating control as an explicit purpose for a Digital Twin and 5) using a Digital Twin to guide data collection and sensor development, and describe how these findings are addressed through the design specifications for a Critical Illness Digital Twin (CIDT) aimed at curing sepsis.
... 7 Nevertheless, an excessive inflammatory response can also lead to adverse consequences, such as pain, swelling, and further tissue damage. 8 Additionally, the inflammatory response can increase the risk of postoperative infection. Currently, the popularity of minimally invasive spine surgery for treating spine disorders is growing. ...
... Surgery is an invasive procedure for the human body, which can be reflected in changes in comprehensive inflammatory indicators. 8 We aimed to make a preliminary judgment about the degree of damage caused by open TLIF and BE-TLIF to the human body through perioperative systemic inflammatory markers. CRP, NLR, and PLR were significantly increased after operation in both groups (p < 0.05), while LMR was reduced considerably after surgery (p < 0.05). ...
Purpose
The purpose of this study is to preliminarily assess the change in perioperative systemic inflammatory markers and clinical outcomes between open TLIF and BE-TLIF procedures.
Patients and Methods
In total, 38 patients who underwent single-level lumbar fusion surgery (L4-5 or L5-S1) were retrospectively reviewed. 19 patients were treated by the BE-TLIF technique, while the other patients were managed using open TLIF. The perioperative serum C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR) of the two groups were compared to determine if there was a statistical difference. Meanwhile, clinical evaluations were conducted to assess various factors including operative duration, estimated blood loss (EBL), drainage catheter stay, length of hospitalization, visual analogue scale (VAS), and Oswestry disability index (ODI) scores.
Results
The perioperative analysis revealed that BE-TLIF cases experienced a longer operative duration than open TLIF cases (open TLIF: 138.63 ± 31.59 min, BE-TLIF: 204.58 ± 49.37 min, p < 0.001). Meanwhile, the EBL showed an increased trend in the BE-TLIF group (260.7 ± 211.9 mL) in comparison with the open TLIF group (200.9 ± 211.9 mL) (p =0.485). In terms of systemic inflammatory markers, the mean postoperative CRP, NLR, LMR, and PLR were lower in the BE-TLIF group than in the open TLIF group, although these differences were not statistically significant (p > 0.05). The VAS and ODI scores in both groups were significantly improved after surgery (p < 0.05).
Conclusion
There was no significant difference found between BE-TLIF and open TLIF in terms of systemic inflammatory markers, and clinical outcomes. Overall, BE-TLIF can be considered a viable choice for lumbar canal decompression and interbody fusion for less invasion. It is worth noting that BE-TLIF does have a longer operation time, indicating that there is still potential for further improvement in this technique.
... The clearance of pathogens and injured tissues and the activation and migration of neutrophils are crucial early phases of an inflammatory response [52]. Simultaneously, neutrophils release several inflammatory chemicals to initiate a cascade reaction [53]. In the low-expression group, the expression of TNF-β decreased, whereas the expression of the anti-inflammatory factors IL-4, IL-10, IL-11, and IL-13 increased dramatically (Fig. 9E). ...
Recent studies have found a link between deep vein thrombosis and inflammatory reactions. N6-methyladenosine (m6A), a crucial element in immunological regulation, is believed to contribute to the pathophysiology of venous thromboembolism (VTE). However, how the m6A-modified immune microenvironment is involved in VTE remains unclear. In the present study, we identified a relationship between VTE and the expression of several m6A regulatory elements by analyzing peripheral blood samples from 177 patients with VTE and 88 healthy controls from public GEO databases GSE19151 and GSE48000. We used machine learning to identify essential genes and constructed a diagnostic model for VTE using multivariate logistic regression. Unsupervised cluster analysis revealed a marked difference between m6A modification patterns in terms of immune cell infiltration, inflammatory reactivity, and autophagy. We identified two m6A-related autophagy genes (i.e., CHMP2B and SIRT1) and the crucial m6A regulator YTHDF3 using bioinformatics. We also examined two potential mechanisms through which YTHDF3 may affect VTE. m6A modification, immunity, and autophagy are closely linked in VTE, offering novel mechanistic and therapeutic insights.
