Detection of glycocalyx degradation in real time: A conceptual model of thromboelastography.

Background: The endothelial glycocalyx is a critical component of the vascular barrier; its disruption after shock states may contribute to coagulopathy in a variety of conditions. Measurement of glycocalyx components in plasma have been used to index glycocalyx degradation but are not available as a point of care test. Heparanoids, such as heparan sulfate, may affect coagulation which may be detected by either thromboelastography or activated clotting time.

Effect of albumin solutions on endothelial oxidant injury: A microfluidic study.

Background: Studies have suggested a beneficial effect of early plasma-based resuscitation in patients following trauma-hemorrhagic shock. The underlying mechanism(s) are unknown but may be owing to protective effects of plasma components on the endothelium and its glycocalyx layer. Albumin, the major protein in plasma, influences vascular integrity and has antioxidant properties in vivo.

Effect of tranexamic acid on endothelial von Willebrand factor/ADAMTS-13 response to in vitro shock conditions.

Background: Traumatic/hemorrhagic shock, sepsis and other inflammatory processes lead to endothelial activation and a loss of the endothelial glycocalyx. von Willebrand factor (vWF) is an acute phase reactant that is released from endothelial cells and megakaryocytes. Stimulated but not basal vWF leads to significant formation of ultralarge multimers (ultralarge vWF [ULvWF]) and risk for thrombotic complications.

The effect of tranexamic acid dosing regimen on trauma/hemorrhagic shock-related glycocalyx degradation and endothelial barrier permeability: An in vitro model.

Background: Improved outcomes with early tranexamic acid (TXA) following trauma hemorrhagic shock (T/HS) may be related to its antifibrinolytic, as well as anti-inflammatory properties. Previous in vitro studies have shown that early TXA administration protects against T/HS endothelial barrier dysfunction and associated glycocalyx degradation. An intact endothelial glycocalyx may protect against subsequent neutrophil mediated tissue injury.

Plasma components to protect the endothelial barrier after shock: A role for sphingosine 1-phosphate.

Background: Hemorrhagic shock leads to endothelial glycocalyx shedding, endothelial cellular inflammation, and increased vascular permeability. Early plasma administration improves survival in severely injured patients; this may be due in part to its ability to ameliorate this trauma-induced endotheliopathy. The protective effect of early plasma administration may be due to its sphingosine 1-phosphate content.

A biomimetic shock model on the effect of endothelial aging on vascular barrier properties.

Background: Aging is characterized by a decline in cellular function, which has an adverse effect on the biologic response to injury. Both aging and trauma/hemorrhagic shock (T/HS) increase oxidative stress which impairs the vascular endothelium (EC) and glycocalyx (EG). The additive effect of aging on EC and EG damage following T/HS are unknown.

The effect of perturbations of the glycocalyx on microvascular perfusion in the obese trauma population: an in vitro study.

Objectives: Patients with morbid obesity have impaired responses to resuscitation following severe injury, which may contribute to adverse outcomes. Obesity is associated with microvascular dysfunction and metabolic changes associated with altered hemorheological profiles. These include decreased red blood cell (RBC) deformity associated with increased aggregation and adhesion.

The protective role of estrogen on endothelial and glycocalyx barriers after shock conditions: A microfluidic study.

Background: Sexual dimorphism has been demonstrated after major trauma and hemorrhage shock with protective effects related to female sex or estrogen. Traumatic endotheliopathy is an important component of trauma-induced coagulopathy. Components of endothelial barrier dysfunction include degradation of the endothelial glycocalyx and endothelial cellular injury.

Obesity and impaired barrier function after shock: A biomimetic in vitro model using microfluidics.

Background: Impaired microvascular perfusion in the obese patient has been linked to chronic adverse health consequences. The impact on acute illnesses including trauma, sepsis, and hemorrhagic shock (HS) is uncertain. Studies have shown that endothelial glycocalyx and vascular endothelial derangements are causally linked to perfusion abnormalities.

Clostridioides difficile in COVID-19 Patients, Detroit, Michigan, USA, March-April 2020.

We describe 9 patients at a medical center in Detroit, Michigan, USA, with severe acute respiratory syndrome coronavirus 2 and Clostridioides difficile. Both infections can manifest as digestive symptoms and merit screening when assessing patients with diarrhea during the coronavirus disease pandemic. These co-infections also highlight the continued importance of antimicrobial stewardship.

Protective effects of plasma products on the endothelial-glycocalyx barrier following trauma-hemorrhagic shock: Is sphingosine-1 phosphate responsible?

Background: Plasma is an important component of resuscitation after trauma and hemorrhagic shock (T/HS). The specific plasma proteins and the impact of storage conditions are uncertain. Utilizing a microfluidic device system, we studied the effect of various types of plasma on the endothelial barrier function following T/HS.

Rapid Detection of Clostridium difficile Toxins in Stool by Raman Spectroscopy.

Background: Clinical practice guidelines define Clostridium difficile infections (CDI) as diarrhea (≥3 unformed stools in 24 h) with either a positive C difficile stool test or detection of pseudomembranous colitis. Diagnostic modalities such as toxigenic culture and nucleic acid amplification testing can identify the presence of toxigenic C difficile in stools. But these tests are confounded by the presence of asymptomatic colonization of toxigenic C difficile and lead to overdiagnosis of CDI.

Red blood cell storage and adhesion to vascular endothelium under normal or stress conditions: An in vitro microfluidic study.

Background: Observational studies have identified an association between duration of red blood cell (RBC) storage and adverse outcomes in trauma. Hemorrhagic shock (HS) leads to impaired tissue perfusion which is associated with endothelial cell glycocalyx (eGC) shedding. Adhesion of stored RBC to the vascular endothelium has been shown to lead to impaired perfusion in the microcirculation and contribute to organ failure and poor outcome.

Acute hyperglycemia increases sepsis related glycocalyx degradation and endothelial cellular injury: A microfluidic study.

Background: Hyperglycemia promotes vascular inflammation; however its effect on endothelial dysfunction in sepsis is unknown. Microfluidic devices (MFD) may closely mimic the in vivo endothelial cell microenvironment. We hypothesized that stress glucose concentrations would increase sepsis related endothelial injury/activation.

Rapid Detection of Clostridium difficile Toxins in Serum by Raman Spectroscopy.

Background: Clostridium difficile infection (CDI) is due to the effects of toxins, toxin A and toxin B on the host. Severe CDI is associated with systemic signs of infection. Animal models of CDI demonstrate a strong correlation between systemic toxemia and the occurrence of severe disease.

Acute hyperglycemia exacerbates trauma-induced endothelial and glycocalyx injury: An in vitro model.

Background: Early hyperglycemia is associated with higher mortality in trauma and predicts multiple organ failure. Endothelial cell (EC) injury and glycocalyx (GC) degradation occur following traumatic shock and are key factors in the development of trauma-induced coagulopathy and result in impaired microvascular perfusion and accompanying organ failure. Acute hyperglycemia has been shown to result in the loss of the GC layer, EC inflammation, and activation of coagulation in vivo.

Excess sodium is deleterious on endothelial and glycocalyx barrier function: A microfluidic study.

Background: Hypernatremia is a common problem affecting critically ill patients, whether due to underlying pathology or the subsequent result of hypertonic fluid resuscitation. Numerous studies have been published, suggesting that hypernatremia may adversely affect the vascular endothelial glycocalyx. Our study aimed to evaluate if high sodium concentration would impair the endothelial and glycocalyx barrier function and if stress conditions that simulate the shock microenvironment would exacerbate any observed adverse effects of hypernatremia.

Microfluidics: A high-throughput system for the assessment of the endotheliopathy of trauma and the effect of timing of plasma administration on ameliorating shock-associated endothelial dysfunction.

Background: Early resuscitation after trauma-hemorrhagic shock with plasma rather than crystalloid may ameliorate systemic endothelial cell (EC) injury and dysfunction (endotheliopathy of trauma). We postulated that endothelial-lined microfluidic networks would be a useful platform to study the EC activation/injury under flow conditions to mimic trauma-hemorrhagic shock. We then used the microfluidic system to further characterize the protective effects and optimal timing of plasma infusion on the development of "endotheliopathy of trauma" in our model.

The temporal response and mechanism of action of tranexamic acid in endothelial glycocalyx degradation.

Background: The endothelial glycocalyx (GCX) plays an important role in vascular barrier function. Damage to the GCX occurs due to a variety of causes including hypoxia, ischemia-reperfusion, stress-related sympathoadrenal activation, and inflammation. Tranexamic acid (TXA) may prevent GCX degradation.

Disparate effects of catecholamines under stress conditions on endothelial glycocalyx injury: An in vitro model.

Background: Geriatric trauma patients have high circulating norepinephrine (NE) levels but attenuated release of epinephrine (Epi) in response to increasing severity of injury. We hypothesized that NE and Epi have different effects on the endothelial and glycocalyx components of the vascular barrier following shock.

Methods: Human umbilical vein endothelial cells (HUVEC) were treated with varying concentrations of NE or Epi and exposed to simulated shock conditions (HR).

Early tranexamic acid administration ameliorates the endotheliopathy of trauma and shock in an in vitro model.

Background: Systemic vascular endothelial injury is a consequence of trauma (T)/hemorrhagic shock (HS) which results in disturbances of coagulation, inflammation, and endothelial barrier integrity. The effect of T/HS on the endothelium (endotheliopathy of trauma [EoT]) is of intense research interest and may lead to EoT-directed therapies. Administration of tranexamic acid (TXA) in trauma patients is associated with a survival benefit and fewer complications if given early after injury.

Tranexamic acid and the gut barrier: Protection by inhibition of trypsin uptake and activation of downstream intestinal proteases.

Objective: Intraluminal pancreatic trypsin and other digestive enzymes injure the gut barrier following trauma-hemorrhagic shock (T/HS). Intestinal proteases (sheddases) exert important effects on normal gut function but may cause barrier disruption due to exaggerated production following T/HS. We hypothesized that the protective mechanism of TXA on the gut barrier following T/HS includes inhibition of these "downstream" proteases.

INFIX/EXFIX: Massive Open Pelvic Injuries and Review of the Literature.

Introduction. Open pelvic fractures make up 2-5% of all pelvic ring injuries. Their mortality has been reported to be as high as 50%.