bims-heshmo 2021-04-25 papers

Issue of 2021–04–25
seven papers selected by
Andreia Luís, Ludwig Boltzmann Institute

BMC Emerg Med. 2021 Apr 20. 21(1): 52

Endothelial glycocalyx degradation is associated with early organ impairment in polytrauma patients.

Feng Qi, Hao Zhou, Peng Gu, Zhi-He Tang, Bao-Feng Zhu, Jian-Rong Chen, Jin-Song Zhang, Feng Li.

BACKGROUND: Endothelial glycocalyx (EG) abnormal degradation were widely found in critical illness. However, data of EG degradation in multiple traumas is limited. We performed a study to assess the EG degradation and the correlation between the degradation and organ functions in polytrauma patients.
METHODS: A prospective observational study was conducted to enroll health participants (control group) and polytrauma patients (trauma group) at a University affiliated hospital between Feb 2020 and Oct 2020. Syndecan1 (SDC1) and heparin sulfate (HS) were detected in serum sample of both groups. In trauma group, injury severity scores (ISS) and sequential organ failure assessments (SOFA) were calculated. Occurrences of acute kidney injury (AKI), trauma-induced coagulopathy (TIC) within 48 h and 28-day all-cause mortality in trauma group were recorded. Serum SDC1 and HS levels were compared between two groups. Correlations between SDC1/HS and the indicators of organ systems in the trauma group were analyzed. ROC analyses were performed to assess the predictive value of SDC1 and HS for AKI, TIC within 48 h, and 28-day mortality in trauma group.
RESULTS: There were 45 polytrauma patients and 15 healthy participants were collected, totally. SDC1 and HS were significantly higher in trauma group than in control group (69.39 [54.18-130.80] vs. 24.15 [13.89-32.36], 38.92 [30.47-67.96] vs. 15.55 [11.89-23.24], P < 0.001, respectively). Trauma group was divided into high degradation group and low degradation group according to SDC1 median. High degradation group had more severe ISS, SOFA scores, worse organ functions (respiratory, kidney, coagulation and metabolic system), and higher incidence of hypothermia, acidosis and shock. The area under the receiver operator characteristic curves (AUC) of SDC1 to predict AKI, TIC occurrence within 48 h and 28-day mortality were 0.838 (95%CI: 0.720-0.957), 0.700 (95%CI: 0.514-0.885) and 0.764 (95%CI: 0.543-0.984), respectively.
CONCLUSIONS: EG degradation was elevated significantly in polytrauma patients, and the degradation was correlated with impaired respiratory, kidney, coagulation and metabolic systems in early stage. Serum SDC1 is a valuable predictive indicator of early onset of AKI, TIC, and 28-day mortality in polytrauma patients.

Keywords: Acute kidney injury; Glycocalyx; Heparan sulfate; Risk factor; Syndecan-1; Trauma; Trauma induced coagulopathy

DOI: https://doi.org/10.1186/s12873-021-00446-y

Front Med (Lausanne). 2021 ;8 645589

Alterations of Phagocytic Activity and Capacity in Granulocytes and Monocytes Depend on the Pathogen Strain in Porcine Polytrauma.

Jan Tilmann Vollrath, Felix Klingebiel, Felix Marius Bläsius, Johannes Greven, Eftychios Bolierakis, Andrea Janicova, Ildiko Rita Dunay, Frank Hildebrand, Ingo Marzi, Borna Relja.

Background: Polytraumatized patients undergo a strong immunological stress upon insult. Phagocytes (granulocytes and monocytes) play a substantial role in immunological defense against bacteria, fungi and yeast, and in the clearance of cellular debris after tissue injury. We have reported a reduced monocytes phagocytic activity early after porcine polytrauma before. However, it is unknown if both phagocyte types undergo those functional alterations, and if there is a pathogen-specific phagocytic behavior. We characterized the phagocytic activity and capacity of granulocytes and monocytes after polytrauma. Methods: Eight pigs (Sus scrofa) underwent polytrauma consisting of lung contusion, liver laceration, tibial fracture and hemorrhagic shock with fluid resuscitation and fracture fixation with external fixator. Intensive care treatment including mechanical ventilation for 72 h followed. Phagocytic activity and capacity were investigated using an in vitro ex vivo whole blood stimulation phagocytosis assays before trauma, after surgery, 24, 48, and 72 h after trauma. Blood samples were stimulated with Phorbol-12-myristate-13-acetate and incubated with FITC-labeled E. coli, S. aureus or S. cerevisiae for phagocytosis assessment by flow cytometry. Results: Early polytrauma-induced significant increase of granulocytes and monocytes declined to baseline values within 24 h. Percentage of E. coli-phagocytizing granulocytes significantly decreased after polytrauma and during further intensive care treatment, while their capacity significantly increased. Interestingly, both granulocytic phagocytic activity and capacity of S. aureus significantly decreased after trauma, although a recovery was observed after 24 h and yet was followed by another decrease. The percentage of S. cerevisiae-phagocytizing granulocytes significantly increased after 24 h, while their impaired capacity after surgery and 72 h later was detected. Monocytic E. coli-phagocytizing percentage did not change, while their capacity increased after 24-72 h. After a significant decrease in S. aureus-phagocytizing monocytes after surgery, a significant increase after 24 and 48 h was observed without capacity alterations. No significant changes in S. cerevisiae-phagocytizing monocytes occurred, but their capacity dropped 48 and 72 h. Conclusion: Phagocytic activity and capacity of granulocytes and monocytes follow a different pattern and significantly change within 72 h after polytrauma. Both phagocytic activity and capacity show significantly different alterations depending on the pathogen strain, thus potentially indicating at certain and possibly more relevant infection causes after polytrauma.

Keywords: infection; inflammation; pathogen; phagocytes; trauma

DOI: https://doi.org/10.3389/fmed.2021.645589

Injury. 2021 Mar 26. pii: S0020-1383(21)00268-0. [Epub ahead of print]

Hemorrhage and saline resuscitation are associated with epigenetic and proteomic reprogramming in the rat lung.

Alexander Bonde, Trine G Eskesen, Jacob Steinmetz, Erwin M Schoof, Lene H D Blicher, Lars S Rasmussen, Martin Sillesen.

BACKGROUND: Epigenetic changes have been described in trauma patients in the form of histone acetylation events, but whether DNA-methylation occurs remains unknown. We hypothesized that the combination of hemorrhage and saline resuscitation would alter DNA-methylation and associated proteomic profiles in the rat lung.
METHODS: Ten rats were subjected to a pressure-controlled hemorrhage and resuscitation model consisting of hemorrhage to a mean arterial pressure (MAP) of 35mmHg for 90 minutes, followed by saline resuscitation to a MAP >70mmHg for 90 minutes (n=5) or sham (only anesthesia and cannulation). Lungs were harvested and subjected to reduced genome wide DNA-methylation analysis through bisulphite sequencing as well as proteomics analysis. Data was analyzed for differentially methylated regions and associated alterations in proteomic networks through a weighted correlation network analysis (WCNA). Pathway analysis was used to establish biological relevance of findings.
RESULTS: Hemorrhage and saline resuscitation were associated with differential methylation of 353 sites across the genome compared to the sham group. Of these, 30 were localized to gene promoter regions, 31 to exon regions and 87 to intron regions. Network analysis identified an association between hemorrhage/resuscitation and DNA-methylation events located to genes involved in areas of endothelial and immune response signaling. The associated proteomic response was characterized by activations of mRNA processing as well as endothelial Nitric Oxide Synthase (eNOS) metabolism.
CONCLUSION: We demonstrated an association between DNA-methylation and hemorrhage/saline resuscitation. These results suggest a potential role of DNA-methylation in the host response to injury.

Keywords: Epigenetics; Hemorrhage; Resuscitation; Trauma

DOI: https://doi.org/10.1016/j.injury.2021.03.050

Shock. 2021 Apr 13.

Myeloid-Derived Suppressor Cells (MDSCs) and The Immunoinflammatory Response To Injury (Mini Review).

Shannon R Sayyadioskoie, Martin G Schwacha.

ABSTRACT: Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of immature myeloid cells hallmarked by their potent immunosuppressive function in a vast array of pathologic conditions. MDSCs have recently been shown to exhibit marked expansion in acute inflammatory states including traumatic injury, burn, and sepsis. Although MDSCs have been well characterized in cancer, there are significant gaps in our knowledge of their functionality in trauma and sepsis, and their clinical significance remains unclear. It is suggested that MDSCs serve an important role in quelling profound inflammatory responses in the acute setting; however, MDSC accumulation may also predispose patients to developing persistent immune dysregulation with increased risk for nosocomial infections, sepsis and multiorgan failure (MOF). Whether MDSCs may serve as the target for novel therapeutics or an important biomarker in trauma and sepsis is yet to be determined. In this review, we will discuss the current understanding of MDSCs within the context of specific traumatic injury types and sepsis. In order to improve delineation of their functional role, we propose a systemic approach to MDSC analysis including phenotypic standardization, longitudinal analysis and expansion of clinical research.

DOI: https://doi.org/10.1097/SHK.0000000000001795

Semin Intervent Radiol. 2021 Mar;38(1): 96-104

Hepatic Trauma Interventions.

Akshita S Pillai, Girish Kumar, Anil K Pillai.

The liver is the second most commonly involved solid organ (after spleen) to be injured in blunt abdominal trauma, but liver injury is the most common cause of death in such trauma. In patients with significant blunt abdominal injury, the liver is involved approximately 35 to 45% of the time. Its large size also makes it a vulnerable organ, commonly injured in penetrating trauma. Other than its position and size, the liver is surrounded by fragile parenchyma and its location under the diaphragm makes it vulnerable to shear forces during deceleration injuries. The liver is also a vascular organ made of large, thin-walled vessels with high blood flow. In severe hepatic trauma, hemorrhage is a common complication and uncontrolled bleeding is usually fatal. In fact, in patients with severe abdominal trauma, liver injury is the primary cause of death. This article reviews the clinical presentation of patients with liver injury, the grading system for such injuries that is most frequently used, and management of the patient with liver trauma.

Keywords: bleeding; embolization; hepatic injury; interventional radiology; liver; trauma

DOI: https://doi.org/10.1055/s-0041-1724014

Semin Thromb Hemost. 2021 Apr 20.

Tranexamic Acid Treatment for Trauma Victims.

Ian Roberts, Amy Brenner, Haleema Shakur-Still.

Worldwide, traumatic injury is responsible for over 5 million deaths per year, the majority due to exsanguination and head injury. The antifibrinolytic drug tranexamic acid is the only drug proven to reduce deaths after traumatic injury. Several large randomized controlled trials have provided high-quality evidence of its effectiveness and safety in trauma patients. Early tranexamic acid reduces deaths on the day of the injury in polytrauma patients and patients with isolated traumatic brain injury by around 20%. Treatment is time critical; for patients to benefit, tranexamic acid must be given as soon as possible after injury. Intramuscular administration is well tolerated and rapidly absorbed, with the potential to reduce time to treatment. Because the proportional reduction in bleeding death with tranexamic acid does not vary by baseline risk, a wide range of trauma patients stands to benefit. There are far more low-risk trauma patients than high-risk patients, with a substantial proportion of bleeding deaths in the low-risk group. As such, treatment should not be limited to patients with severe traumatic hemorrhage. We must give paramedics and physicians the confidence to treat a far wider range of trauma patients while emphasizing the importance of early treatment.

DOI: https://doi.org/10.1055/s-0041-1725097

Circ Res. 2021 Apr 21.

Perivascular Macrophages Regulate Blood Flow Following Tissue Damage.

Evelina Vågesjö, Kristel Parv, David Ahl, Cédric Seignez, Carmen Herrera Hidalgo, Antoine Giraud, Catarina Amoêdo-Leite, Olle Korsgren, Håkan Wallén, Greta Juusola, Harri H Hakovirta, Helene Rundqvist, Magnus Essand, Lena Holm, Randall Johnson, Charlotte Thålin, Petra Korpisalo, Gustaf Christoffersson, Mia Phillipson.

Rationale: Ischemic injuries remain a leading cause of mortality and morbidity worldwide, and restoration of functional blood perfusion is vital to limit tissue damage and support healing. Objective: To reveal a novel role of macrophages in reestablishment of functional tissue perfusion following ischemic injury that can be targeted to improve tissue restoration. Methods and Results: Using intravital microscopy of ischemic hind limb muscle in mice, and confocal microscopy of human tissues from amputated legs, we found that macrophages accumulated perivascularly in ischemic muscles, where they expressed high levels of iNOS. Genetic depletion of iNOS specifically in macrophages (Cx3cr1-CreERT2;Nos2fl/fl or LysM-Cre;Nos2fl/fl) did not affect vascular architecture but highly compromised blood flow regulation in ischemic but not healthy muscle, which resulted in aggravated ischemic damage. Thus, the ability to upregulate blood flow was shifted from eNOS (endothelial)-dependence in healthy muscles to completely rely on macrophage-derived iNOS during ischemia. Macrophages in ischemic muscles expressed high levels of CXCR4 and CCR2, and local overexpression by DNA plasmids encoding the corresponding chemokines CXCL12 or CCL2 increased macrophage numbers, while CXCL12 but not CCL2 induced their perivascular positioning. As a result, CXCL12-overexpression increased the number of perfused blood vessels in the ischemic muscles, improved functional muscle perfusion in a macrophage-iNOS-dependent manner, and ultimately restored limb function. Conclusions: This study establishes a new function for macrophages during tissue repair, as they regulate blood flow through the release of iNOS-produced NO. Further, we demonstrate that macrophages can be therapeutically targeted to improve blood flow regulation and functional recovery of ischemic tissues.

Keywords: immunotherapy

DOI: https://doi.org/10.1161/CIRCRESAHA.120.318380