Resuscitation with epinephrine worsens cerebral capillary no-reflow after experimental pediatric cardiac arrest: An multiphoton microscopy evaluation.

Epinephrine is the principal resuscitation therapy for pediatric cardiac arrest (CA). Clinical data suggest that although epinephrine increases the rate of resuscitation, it fails to improve neurological outcome, possibly secondary to reductions in microvascular flow. We characterized the effect of epinephrine vs.

Presenting predictors and temporal trends of treatment-related outcomes in diabetic ketoacidosis.

Objective: This study examines temporal trends in treatment-related outcomes surrounding a diabetic ketoacidosis (DKA) performance improvement intervention consisting of mandated intensive care unit admission and implementation of a standardized management pathway, and identifies physical and biochemical characteristics associated with outcomes in this population.

Methods: A retrospective cohort of 1225 children with DKA were identified in the electronic health record by international classification of diseases codes and a minimum pH less than 7.3 during hospitalization at a quaternary children's hospital between April, 2009 and May, 2016.

Cerebral microcirculatory alterations and the no-reflow phenomenon in vivo after experimental pediatric cardiac arrest.

Decreased cerebral blood flow (CBF) after cardiac arrest (CA) contributes to secondary ischemic injury in infants and children. We previously reported cortical hypoperfusion with tissue hypoxia early in a pediatric rat model of asphyxial CA. In order to identify specific alterations as potential therapeutic targets to improve cortical hypoperfusion post-CA, we characterize the CBF alterations at the cortical microvascular level in vivo using multiphoton microscopy.

The pharmacogenomics of severe traumatic brain injury.

Pharmacotherapy for traumatic brain injury (TBI) is focused on resuscitation, prevention of secondary injury, rehabilitation and recovery. Pharmacogenomics may play a role in TBI for predicting therapies for sedation, analgesia, seizure prevention, intracranial pressure-directed therapy and neurobehavioral/psychiatric symptoms. Research into genetic predictors of outcomes and susceptibility to complications may also help clinicians to tailor therapeutics for high-risk individuals.

The Oral and Maxillofacial Surgery Anesthesia Team Model.

Oral and maxillofacial surgeons have been providing safe anesthesia to their patients using the anesthesia team model; this has allowed access to care for patients that have significant anxiety. The AAOMS strives to maintain the excellent safety record of the anesthesia team model by creating simulation programs in anesthesia, regularly updating the office anesthesia evaluation program, convening anesthesia safety conferences and strengthening the standards in our training programs. Through these efforts, our delivery of anesthesia to our patients will remain safe and effective.

Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases.

Unlabelled: The recent clinical availability of the PARP inhibitor olaparib (Lynparza) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, we have selected indications, where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, to provide first-line options for therapeutic repurposing. These indications are as follows: acute ischaemic stroke; traumatic brain injury; septic shock; acute pancreatitis; and severe asthma and severe acute lung injury.

International Survey of Critically Ill Children With Acute Neurologic Insults: The Prevalence of Acute Critical Neurological Disease in Children: A Global Epidemiological Assessment Study.

Objective: The international scope of critical neurologic insults in children is unknown. Our objective was to assess the prevalence and outcomes of children admitted to PICUs with acute neurologic insults.

Design: Prospective study.

The far-reaching scope of neuroinflammation after traumatic brain injury.

The 'silent epidemic' of traumatic brain injury (TBI) has been placed in the spotlight as a result of clinical investigations and popular press coverage of athletes and veterans with single or repetitive head injuries. Neuroinflammation can cause acute secondary injury after TBI, and has been linked to chronic neurodegenerative diseases; however, anti-inflammatory agents have failed to improve TBI outcomes in clinical trials. In this Review, we therefore propose a new framework of targeted immunomodulation after TBI for future exploration.

Polynitroxylated Pegylated Hemoglobin-A Novel, Small Volume Therapeutic for Traumatic Brain Injury Resuscitation: Comparison to Whole Blood and Dose Response Evaluation.

Resuscitation with polynitroxylated pegylated hemoglobin (PNPH), a pegylated bovine hemoglobin decorated with nitroxides, eliminated the need for fluid administration, reduced intracranial pressure (ICP) and brain edema, and produced neuroprotection in vitro and in vivo versus Lactated Ringer's solution (LR) in experimental traumatic brain injury (TBI) plus hemorrhagic shock (HS). We hypothesized that resuscitation with PNPH would improve acute physiology versus whole blood after TBI+HS and would be safe and effective across a wide dosage range. Anesthetized mice underwent controlled cortical impact and severe HS to mean arterial pressure (MAP) of 25-27 mm Hg for 35 min, then were resuscitated with PNPH, autologous whole blood, or LR.

Enduring disturbances in regional cerebral blood flow and brain oxygenation at 24 h after asphyxial cardiac arrest in developing rats.

Background: Disturbances in cerebral blood flow (CBF) and brain oxygenation (PbO) are present early after pediatric cardiac arrest (CA). CBF-targeted therapies improved neurological outcome in our CA model. To assess the therapeutic window for CBF- and PbO-targeted therapies, we propose to determine if CBF and PbO disturbances persist at 24 h after experimental pediatric CA.

Mechanistic characterization of nitrite-mediated neuroprotection after experimental cardiac arrest.

Nitrite acts as an ischemic reservoir of nitric oxide (NO) and a potent S-nitrosating agent which reduced histologic brain injury after rat asphyxial cardiac arrest (ACA). The mechanism(s) of nitrite-mediated neuroprotection remain to be defined. We hypothesized that nitrite-mediated brain mitochondrial S-nitrosation accounts for neuroprotection by reducing reperfusion reactive oxygen species (ROS) generation.

Probenecid and N-Acetylcysteine Prevent Loss of Intracellular Glutathione and Inhibit Neuronal Death after Mechanical Stretch Injury In Vitro.

Probenecid and N-acetylcysteine (NAC) can preserve intracellular levels of the vital antioxidant glutathione (GSH) via two distinct biochemical pathways. Probenecid inhibits transporter-mediated GSH efflux and NAC serves as a cysteine donor for GSH synthesis. We hypothesized that probenecid and NAC alone would maintain intracellular GSH concentrations and inhibit neuronal death after traumatic stretch injury, and that the drugs in combination would produce additive effects.

ABCC8 Single Nucleotide Polymorphisms are Associated with Cerebral Edema in Severe TBI.

Objective: Cerebral edema (CE) in traumatic brain injury (TBI) is the consequence of multiple underlying mechanisms and is associated with unfavorable outcomes. Genetic variability in these pathways likely explains some of the clinical heterogeneity observed in edema development. A role for sulfonylurea receptor-1 (Sur1) in CE is supported.

Combined Neurotrauma Models: Experimental Models Combining Traumatic Brain Injury and Secondary Insults.

Patients with severe traumatic brain injury (TBI) frequently present with concomitant injuries that may cause secondary brain injury and impact outcomes. Animal models have been developed that combine contemporary models of TBI with a secondary neurologic insult such as hypoxia, shock, long bone fracture, and radiation exposure. Combined injury models may be particularly useful when modeling treatment strategies and in efforts to map basic research to a heterogeneous patient population.

Probenecid, an organic anion transporter 1 and 3 inhibitor, increases plasma and brain exposure of N-acetylcysteine.

1. N-acetylcysteine (NAC) is being investigated as an antioxidant for several conditions including traumatic brain injury, but the mechanism by which it crosses membrane barriers is unknown. We have attempted to understand how the transporter inhibitor, probenecid, affects NAC pharmacokinetics and to evaluate the interaction of NAC with transporters.

Intracranial Hypertension and Cerebral Hypoperfusion in Children With Severe Traumatic Brain Injury: Thresholds and Burden in Accidental and Abusive Insults.

Objectives: The evidence to guide therapy in pediatric traumatic brain injury is lacking, including insight into the intracranial pressure/cerebral perfusion pressure thresholds in abusive head trauma. We examined intracranial pressure/cerebral perfusion pressure thresholds and indices of intracranial pressure and cerebral perfusion pressure burden in relationship with outcome in severe traumatic brain injury and in accidental and abusive head trauma cohorts.

Design: A prospective observational study.

Exploratory study of serum ubiquitin carboxyl-terminal esterase L1 and glial fibrillary acidic protein for outcome prognostication after pediatric cardiac arrest.

Introduction: Brain injury is the leading cause of morbidity and death following pediatric cardiac arrest. Serum biomarkers of brain injury may assist in outcome prognostication. The objectives of this study were to evaluate the properties of serum ubiquitin carboxyl-terminal esterase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) to classify outcome in pediatric cardiac arrest.

Plasma Mitochondrial DNA--a Novel DAMP in Pediatric Sepsis.

Mitochondrial DNA (mtDNA) is a novel danger-associated molecular pattern that on its release into the extracellular milieu acts via toll-like receptor-9, a pattern recognition receptor of the immune system. We hypothesized that plasma mtDNA concentrations will be elevated in septic children, and these elevations are associated with an increase in the severity of illness. In a separate set of in vitro experiments, we test the hypothesis that exposing peripheral blood mononuclear cells (PBMC) to mtDNA activates the immune response and induces tumor necrosis factor (TNF) release.

Effectiveness of Pharmacological Therapies for Intracranial Hypertension in Children With Severe Traumatic Brain Injury--Results From an Automated Data Collection System Time-Synched to Drug Administration.

Objectives: To describe acute cerebral hemodynamic effects of medications commonly used to treat intracranial hypertension in children with traumatic brain injury. Currently, data supporting the efficacy of these medications are insufficient.

Design: In this prospective observational study, intracranial hypertension (intracranial pressure ≥ 20 mm Hg for > 5 min) was treated by clinical protocol.

Applications of Cone-Beam Computed Tomography in Oral and Maxillofacial Surgery: An Overview of Published Indications and Clinical Usage in United States Academic Centers and Oral and Maxillofacial Surgery Practices.

Purpose: The American Association of Oral and Maxillofacial Surgeons appointed a task force to study the indications, safety, and clinical practice patterns of cone-beam computed tomography (CBCT) in oral and maxillofacial surgery (OMS). The charge was to review the published applications of CBCT in OMS, identify the current position of academic thought leaders in the field, and research the adoption and usage of the technology at the clinical practitioner level.

Materials And Methods: This study reviewed the CBCT world literature and summarized published indications for the modality.