Transcriptomic Changes Within Human Bone Marrow After Severe Trauma
Conclusions: A unique transcriptomic response within the bone marrow was identified following severe trauma compared to elective hip replacement. These transcriptomic differences were related to the innate immune response as well as known inhibitors of erythropoiesis. Although confined to just one time point, this differential transcriptional response may be linked to refractory anemia and inflammation after injury. (Source: Shock)
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research

Sepsis-Induced Myopathy and Gut Microbiome Dysbiosis: Mechanistic Links and Therapeutic Targets
Sepsis is currently defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The skeletal muscle system is among the host organ systems compromised by sepsis. The resulting neuromuscular dysfunction and impaired regenerative capacity defines sepsis-induced myopathy and manifests as atrophy, loss of strength, and hindered regeneration after injury. These outcomes delay recovery from critical illness and confer increased vulnerability to morbidity and mortality. The mechanisms underlying sepsis-induced myopathy, including the potential contribution of peripheral organs, remain larg...
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Review Articles Source Type: research

Selective Prehospital Advanced Resuscitative Care – Developing a Strategy to Prevent Prehospital Deaths From Noncompressible Torso Hemorrhage
Hemorrhage, and particularly noncompressible torso hemorrhage remains a leading cause of potentially preventable prehospital death from trauma in the United States and globally. A subset of severely injured patients either die in the field or develop irreversible hemorrhagic shock before they can receive hospital definitive care, resulting in poor outcomes. The focus of this opinion paper is to delineate (a)the need for existing trauma systems to adapt so that potentially life-saving advanced resuscitation and truncal hemorrhage control interventions can be delivered closer to the point-of-injury in select patients, and...
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Review Articles Source Type: research

Pathomechanisms Underlying Hypoxemia in Two COVID-19-Associated Acute Respiratory Distress Syndrome Phenotypes: Insights From Thrombosis and Hemostasis
Conclusions: Right-to-left shunts and high VA/Q ratios caused by lung microvascular thrombosis contribute to hypoxemia in type H and L ARDS, respectively. D-dimer monitoring-based anticoagulation therapy may prevent the progression to and/or worsening of ARDS in COVID-19 patients. (Source: Shock)
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Review Articles Source Type: research

Response to A Letter to the Editor: In Septic ICU Patients, Presepsin is A Predictor of AKI, ARDS, and DIC—Renal Replacement Therapy Initiation only has A Minor Impact on The Results of The Present Study
No abstract available (Source: Shock)
Source: Shock - November 26, 2021 Category: Emergency Medicine Tags: Letters to the Editor Source Type: research

In Septic ICU Patients, Presepsin is Predictor of AKI, ARDS, and DIC: Beware of Some Potential Confounding Factors!
No abstract available (Source: Shock)
Source: Shock - November 26, 2021 Category: Emergency Medicine Tags: Letters to the Editor Source Type: research

An Ovine Model of Hemorrhagic Shock and Resuscitation, to Assess Recovery of Tissue Oxygen Delivery and Oxygen Debt, and Inform Patient Blood Management
Background: Aggressive fluid or blood component transfusion for severe hemorrhagic shock may restore macrocirculatory parameters, but not always improve microcirculatory perfusion and tissue oxygen delivery. We established an ovine model of hemorrhagic shock to systematically assess tissue oxygen delivery and repayment of oxygen debt; appropriate outcomes to guide Patient Blood Management. Methods: Female Dorset-cross sheep were anesthetized, intubated, and subjected to comprehensive macrohemodynamic, regional tissue oxygen saturation (StO2), sublingual capillary imaging, and arterial lactate monitoring confirme...
Source: Shock - November 26, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

LBP Protects Hepatocyte Mitochondrial Function Via the PPAR-CYP4A2 Signaling Pathway in a Rat Sepsis Model
Conclusion: LBP protects hepatic mitochondria against LPS-induced damage via the LBP-PPARα-CYP4a2 signaling pathway. (Source: Shock)
Source: Shock - November 26, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

α7 Nicotinic Acetylcholine Receptor Agonists Regulate Inflammation and Growth Hormone Resistance in Sepsis
We examined the effects of selective afferent vagotomy (SAV) and α7nAChR activation on sepsis-induced mortality, hepatic and systemic inflammation, the GH/IGF system and hepatic GH resistance using Sprague Dawley (SD) rats, C57BL/6 wild type (WT) mice, and α7nAChR knockout (KO) mice. Capsaicin was used to perform SAV and GTS-21 (α7nAChR agonist) was used to activate the α7nAChR. Sepsis-induced mortality, hepatic NF-κB activation, and plasma cytokine levels were increased in SAV rats and reduced in GTS-21-treated mice. The effects of sepsis on the GH/IGF-I system plasma IGF-I, IGF binding protein-1 (IGFBP-1), hepatic I...
Source: Shock - November 26, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Modulation of the Permeability-Inducing Factor Angiopoietin-2 Through Bifonazole in Systemic Inflammation
Background: Vascular barrier breakdown in sepsis represents a key component of the maladaptive host response to infection and the release of endothelial Angiopoietin-2 (Angpt-2) is a mechanistic driver of endothelial hyperpermeability. Angpt-2 is associated with morbidity and mortality but a targeted therapeutic approach is not available. We screened for U.S. Food and Drug Administration (FDA) approved drugs that might have off-target effects decreasing Angpt-2 and therefore, ameliorating capillary leakage. Methods: Endothelial cells were isolated from human umbilical veins (HUVECs) and used for in vitro studies...
Source: Shock - November 26, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Memantine Alleviates Acute Lung Injury Via Inhibiting Macrophage Pyroptosis
In this study, we demonstrate that memantine, a N-methyl-D-aspartic acid receptor (NMDAR) antagonist, through suppressing Ca2+ influx and subsequent ASC oligomerization inhibits macrophage Nlrp3 inflammasome activation and pyroptosis, therefore, alleviates ALI in septic mice. This finding explores a novel application of memantine, an FDA already approved medication, in the treatment of ALI, which is currently lacking effective therapy. (Source: Shock)
Source: Shock - November 26, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

The Role of Alpha-1-Acid Glycoprotein in the Diagnosis and Treatment of Crush Syndrome-Induced Acute Kidney Injury
Conclusion: Our findings demonstrated that the severity of crush injury is causally related to extrusion pressure and increase in blood serum markers. Our identification of the biomarker and treatment candidate, α1-AGP, suggests its implication in predicting the severity of CS and its use as a mediator of CS-induced AKI, respectively. (Source: Shock)
Source: Shock - November 26, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Secretory Leukocyte Proteinase Inhibitor Protects Acute Kidney Injury Through Immune and Non-Immune Pathways
Acute kidney injury (AKI) is characterized by rapid loss of excretory function and is the clinical manifestation of several disorders affecting the kidney. The aim of the present study was to investigate the mechanism of action of Secretory Leukocyte Proteinase Inhibitor (SLPI) that protects the kidneys form AKI. In vivo and in vitro experiments were performed to assess the effect of SLPI on kidney injury. Animal models of kidney injury was generated by 40 min obstruction of kidney artery and vein (ischemia-reperfusion injury model) or daily administration of 60 mg/kg/day of gentamicine for 5 day (gentamicin-associat...
Source: Shock - November 26, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Irisin Protects Against LPS-Stressed Cardiac Damage Through Inhibiting Inflammation, Apoptosis, and Pyroptosis
Septic cardiac dysfunction remains a clinical problem due to its high morbidity and mortality. Uncontrolled cell death and excessive inflammatory response are closely related to sepsis-induced cardiac dysfunction. Irisin has been found to play cardioprotective roles in sepsis. However, there is enough uncertainty in the mechanism of irisin-mediated cardioprotection. We hypothesized that irisin may ameliorate myocardial dysfunction via reducing cardiac apoptosis, pyroptosis, and inflammation during LPS-induced sepsis. Mice were subjected to LPS with or without irisin treatment. After stimuli of LPS, the function of myocardi...
Source: Shock - November 26, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Single-Cell Transcriptomics Reveals Compartment-Specific Differences in Immune Responses and Contributions for Complement Factor 3 in Hemorrhagic Shock Plus Tissue Trauma
Hemorrhagic shock with tissue trauma (HS/T) leads to the activation of a system-wide immune-inflammatory response that involves all organs and body compartments. Recent advances in single-cell analysis permit the simultaneous assessment of transcriptomic patterns in a large number of cells making it feasible to survey the landscape of immune cell responses across numerous anatomic sites. Here, we used single-cell RNA sequencing of leukocytes from the blood, liver, and spleen to identify the major shifts in gene expression by cell type and compartment in a mouse HS/T model. At 6 h, dramatic changes in gene expression were...
Source: Shock - November 26, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research