Collagen-related biomarkers in severe sepsis: a big stretch?

Biomedical scientists are aggressively investigating biomarkers of disease and injury. The rationale for identifying biomarkers during pathological states, such as severe sepsis, is to improve clinical prognostication and stratify therapeutic interventions for optimal recovery. An added benefit of biomarker studies is knowledge genesis on pathophysiological mechanisms, critical information that provides a basis for hypothesis-driven research. Unfortunately, biomarkers rarely alter our clinical approach in severe sepsis as they are often non-specific, lack adequate sensitivity and/or are difficult to measure and interpret accurately. Given the complexity and heterogeneity of severe sepsis, and the unique genetically derived susceptibilities of individuals, it is highly unlikely that one or even a handful of biomarkers will provide adequate biomedical information for clinical guidance. Thus, biomarkers will ultimately alter clinical decision making only once a panel of promising biomarkers is identified, maximizing sensitivity and specificity, and then adequately scrutinized with quantitative scoring methods over large populations of patients

Endothelial Glycocalyx Degradation in Critical Illness and Injury

The endothelial glycocalyx is a gel-like layer on the luminal side of blood vessels that is composed of glycosaminoglycans and the proteins that tether them to the plasma membrane. Interest in its properties and function has grown, particularly in the last decade, as its importance to endothelial barrier function has come to light. Endothelial glycocalyx studies have revealed that many critical illnesses result in its degradation or removal, contributing to endothelial dysfunction and barrier break-down. Loss of the endothelial glycocalyx facilitates the direct access of immune cells and deleterious agents (e.g., proteases and reactive oxygen species) to the endothelium, that can then further endothelial cell injury and dysfunction leading to complications such as edema, and thrombosis. Here, we briefly describe the endothelial glycocalyx and the primary components thought to be directly responsible for its degradation. We review recent literature relevant to glycocalyx damage in several critical illnesses (sepsis, COVID-19, trauma and diabetes) that share inflammation as a common denominator with actions by several common agents (hyaluronidases, proteases, reactive oxygen species, etc.). Finally, we briefly cover strategies and therapies that show promise in protecting or helping to rebuild the endothelial glycocalyx such as steroids, protease inhibitors, anticoagulants and resuscitation strategies

Endothelial Glycocalyx Degradation in Critical Illness and Injury

The endothelial glycocalyx is a gel-like layer on the luminal side of blood vessels that is composed of glycosaminoglycans and the proteins that tether them to the plasma membrane. Interest in its properties and function has grown, particularly in the last decade, as its importance to endothelial barrier function has come to light. Endothelial glycocalyx studies have revealed that many critical illnesses result in its degradation or removal, contributing to endothelial dysfunction and barrier break-down. Loss of the endothelial glycocalyx facilitates the direct access of immune cells and deleterious agents (e.g., proteases and reactive oxygen species) to the endothelium, that can then further endothelial cell injury and dysfunction leading to complications such as edema, and thrombosis. Here, we briefly describe the endothelial glycocalyx and the primary components thought to be directly responsible for its degradation. We review recent literature relevant to glycocalyx damage in several critical illnesses (sepsis, COVID-19, trauma and diabetes) that share inflammation as a common denominator with actions by several common agents (hyaluronidases, proteases, reactive oxygen species, etc.). Finally, we briefly cover strategies and therapies that show promise in protecting or helping to rebuild the endothelial glycocalyx such as steroids, protease inhibitors, anticoagulants and resuscitation strategies

Diabetic ketoacidosis-associated stroke in children and youth

Diabetic ketoacidosis (DKA) is a state of severe insulin deficiency, either absolute or relative, resulting in hyperglycemia and ketonemia. Although possibly underappreciated, up to 10 of cases of intracerebral complications associated with an episode of DKA, and/or its treatment, in children and youth are due to hemorrhage or ischemic brain infarction. Systemic inflammation is present in DKA, with resultant vascular endothelial perturbation that may result in coagulopathy and increased hemorrhagic risk. Thrombotic risk during DKA is elevated by abnormalities in coagulation factors, platelet activation, blood volume and flow, and vascular reactivity. DKA-associated cerebral edema may also predispose to ischemic injury and hemorrhage, though cases of stroke without concomitant cerebral edema have been identified. We review the current literature regarding the pathogenesis of stroke during an episode of DKA in children and youth. Copyright © 2011 Jennifer Ruth Foster et al

Diabetic Ketoacidosis-Associated Stroke in Children and Youth

Diabetic ketoacidosis (DKA) is a state of severe insulin deficiency, either absolute or relative, resulting in hyperglycemia and ketonemia. Although possibly underappreciated, up to 10% of cases of intracerebral complications associated with an episode of DKA, and/or its treatment, in children and youth are due to hemorrhage or ischemic brain infarction. Systemic inflammation is present in DKA, with resultant vascular endothelial perturbation that may result in coagulopathy and increased hemorrhagic risk. Thrombotic risk during DKA is elevated by abnormalities in coagulation factors, platelet activation, blood volume and flow, and vascular reactivity. DKA-associated cerebral edema may also predispose to ischemic injury and hemorrhage, though cases of stroke without concomitant cerebral edema have been identified. We review the current literature regarding the pathogenesis of stroke during an episode of DKA in children and youth

An epidemiologic profile of pediatric concussions: Identifying urban and rural differences

BACKGROUND: The objective of this study was to describe the epidemiology of concussions presenting to the emergency department (ED). METHODS: A retrospective cohort of concussions for pediatric (age G 18 years) patients treated in the ED of a regional pediatric Level 1 trauma center from 2006 to 2011 was examined. Descriptive and geographic analyses were completed, with comparisons by age groups and residence (urban/rural). RESULTS: There were a total of 2,112 treated pediatric concussions. Two thirds of the concussions occurred in males (67%), with a median age of 13 years (interquartile range [IQR], 6). Nearly half of the pediatric concussions were sports related (48%); 36% of these concussions were from hockey. Significant differences were found in the distribution of the mechanism of injury across age groups (p G 0.001). Falls were most prevalent among young children, and sports concussions, for children 10 years and older. Two fifths of concussions occurred during winter months. Discharge disposition significantly differed by age ( p G 0.001), with home discharge increasing with age up to 14 years. There were a total of 387 rural (19%) and 1,687 urban (81%) concussed patients, for a mean ED concussion visit rate of 2.2 per 1,000 and 3.5 per 1,000, respectively. Rural patients were older (14 [IQR, 6] vs. 13 [IQR, 6], p = 0.019] and sustained 2.5 times more concussions from a motor vehicle crash compared with urban youth patients ( p G 0.001). CONCLUSION: Males in early adolescence are at highest risk for concussion, particularly from sport-related activities. Urban and rural children have differences in their etiology and severity of concussions. Concussions are predictable, and their prevention should be targeted based on epidemiologic and environmental data

Cardiac failure following inadvertent administration of high-dose epinephrine subcutaneously

Our aim is to report the consequences of epinephrine toxicity leading to cardiac failure in a child and the successful management with dopamine and milrinone. A previously healthy 13-year-old girl undergoing a left tympanomastoidectomy was inadvertently administered 10 mL of 1:1000 epinephrine subcutaneously (0.175 mg/kg) on the left post auricular region in lieu of lidocaine. She developed sudden supraventricular tachycardia, hypertension and flash pulmonary edema. She was initially treated with propofol, nitrogycerin and increased peak end-expiratory pressure. Within 4 h, she remained tachycardic, but was hypotensive with an increased central venous pressure. Electrocardiogram and echocardiogram investigations showed ST changes indicative of myocardial ischemia and globally reduced function, respectively. Dopamine infusion was administered, together with milrinone, resulting in a gradual improvement of cardiac function within 3 days. She was transitioned to enalapril and discharged home. This case highlights the clinical features of high dose epinephrine toxicity secondary to iatrogenic subcutaneous overdose followed by hypotension and pulmonary edema as a possible late effect of epinephrine and the successful management of secondary cardiac failure with administration of dopamine, milrinone and enalapril. © 2012 - IOS Press and the authors