Mind the GAHP: A novel protocol for improved vascular access in the hypotensive patient.

Background: Obtaining intravenous access in hypotensive patients is challenging and may critically delay resuscitation. The Graduated Vascular Access for Hypotensive Patient (GAHP) protocol leverages intraosseous fluid boluses to specifically dilate proximal veins. This study aims to evaluate the efficacy of GAHP in maximizing venous targets through early distal intraosseous access and a small fluid bolus.

OpTrust: An Effective Educational Bundle for Enhancing Faculty-resident Intraoperative Entrustment.

Objective: The purpose of this study was to measure the efficacy of a novel faculty and resident educational bundle focused on development of faculty-resident behaviors and entrustment in the operating room.

Summary Background Data: As surgical training environments are orienting to entrustable professional activities (EPAs), successful transitions to this model will require significant faculty and resident development. Identifying an effective educational initiative which prepares faculty and residents for optimizing assessment, teaching, learning, and interacting in this model is critical.

Management of a Persistent Cystic Duct Stump Leak Following Cholecystectomy With Percutaneous Transabdominal Cystic Duct Stump Embolization.

Cystic duct stump leak remains a difficult clinical problem despite advancements in endoscopic techniques. When these minimally invasive strategies fail, patients are often subject to high morbidity and mortality associated with open surgical exploration. We report the successful treatment of persistent biliary leak from the cystic duct stump following cholecystectomy using percutaneous transabdominal access of the cystic duct and coil embolization.

The 'Omics' of Epigenetic Modulation by Valproic Acid Treatment in Traumatic Brain Injury-What We Know and What the Future Holds.

Traumatic brain injury (TBI) is a heterogeneous injury that is a major cause of morbidity and mortality worldwide. Epigenetic modulation through the alteration of cellular acetylation by valproic acid (VPA) administration has shown promise as a novel pharmacological treatment for TBI. It improves clinical outcomes through multiple mechanisms, many of which are still poorly understood.

Greater faculty familiarity with residents improves intraoperative entrustment.

Background: Longitudinal contact between faculty and residents facilitates greater faculty entrustment. The purpose of this study is to assess the relationship between faculty familiarity with residents and faculty entrustment.

Materials And Methods: Researchers observed and rated entrustment behaviors using OpTrust, September 2015-June 2017 at Michigan Medicine.

Four-extremity amputation following disseminated intravascular coagulation and purpura fulminans.

Purpura fulminans (PF) is a rare but serious complication of septic shock in adults. The complex disease course makes it challenging to manage the condition. Here, we present the case of a healthy young woman who presented with sepsis and new-onset erythematous lesions 4 days after the vaginal delivery of a healthy baby.

Bridging the gap: The intersection of entrustability and perceived autonomy for surgical residents in the OR.

Background: Faculty entrustment decisions affect resident entrustability behaviors and surgical autonomy. The relationship between entrustability and autonomy is not well understood. This pilot study explores that relationship.

Impact of a resident's sex on intraoperative entrustment of surgery trainees.

Background: Optimizing intraoperative education is critical for development of autonomous residents. Faculty decisions concerning intraoperative entrustment determine the degree to which a resident gains intraoperative responsibility. Accordingly, residents exhibit entrustable behaviors that further faculty entrustment in the operating room.

Rapid valproic acid-induced modulation of the traumatic proteome in a porcine model of traumatic brain injury and hemorrhagic shock.

Background: Histone deacetylase inhibitors such as valproic acid (VPA) improve survival in lethal models of hemorrhagic shock and polytrauma. Although VPA is known to modulate transcription, its ability to reduce mortality within minutes of administration suggests involvement of a rapid, posttranslational mechanism. We hypothesized that VPA treatment would cause proteomic changes within minutes of treatment including quantitative and/or posttranslational differences in structural and/or effector proteins.

Alignment of Personality Is Associated With Increased Intraoperative Entrustment.

Objective: To determine the association between intraoperative entrustment and personality alignment.

Summary Background Data: For surgical residents, achieving operative autonomy has become increasingly difficult. The impact of faculty-resident operative interactions in accomplishing this goal is not well understood.

Transcriptomic changes following valproic acid treatment promote neurogenesis and minimize secondary brain injury.

Background: Early treatment with valproic acid (VPA) has demonstrated benefit in preclinical models of traumatic brain injury, including smaller brain lesion size, decreased edema, reduced neurologic disability, and faster recovery. Mechanisms underlying these favorable outcomes are not fully understood. We hypothesized that VPA treatment would upregulate genes involved in cell survival and proliferation and downregulate those associated with cell death and the inflammatory response.

Valproic acid induces prosurvival transcriptomic changes in swine subjected to traumatic injury and hemorrhagic shock.

Background: Valproic acid (VPA) is a histone deacetylase inhibitor that improves outcomes in large animal models of trauma. However, its protective mechanism of action is not completely understood. We sought to characterize the genetic changes induced by VPA treatment following traumatic injuries.

Evaluating the performance of the Minute Feedback System: A web-based feedback tool for medical students.

Background: Medical students often report dissatisfaction with the feedback they receive on their clerkships. This study evaluates the performance of the Minute Feedback System (MFS), a web-based tool designed to facilitate medical student acquisition of same day written feedback from surgery residents and faculty.

Methods: System-generated data, targeted surveys, and end of clerkship questionnaires were used to evaluate MFS performance over a one-year period.

Improving the feasibility and utility of OpTrust-A tool assessing intraoperative entrustment.

Background: Changes in the surgical training landscape have sparked an interest in developing new educational models anchored on entrustment assessment. We sought to optimize the validated OpTrust entrustment assessment tool by comparing ratings from short-course video reviews to previously validated intraoperative assessments.

Methods: Entrustment assessment scores for video-based and 1-h (short-course) observations were compared to previously validated intraoperative assessment scores.

Improvement of Blood-Brain Barrier Integrity in Traumatic Brain Injury and Hemorrhagic Shock Following Treatment With Valproic Acid and Fresh Frozen Plasma.

Objective: Combined traumatic brain injury and hemorrhagic shock are highly lethal. Following injuries, the integrity of the blood-brain barrier can be impaired, contributing to secondary brain insults. The status of the blood-brain barrier represents a potential factor impacting long-term neurologic outcomes in combined injuries.

Physiologically based pharmacokinetic modeling of disposition and drug-drug interactions for valproic acid and divalproex.

Valproic acid (VPA) is an older first-line antiepileptic drug with a complex pharmacokinetic (PK) profile, currently under investigation for several novel neurologic and non-neurologic indications. Our study objective was to design and validate a mechanistic model of VPA disposition in adults and children; and evaluate its predictive performance of drug-drug interactions (DDIs). This study expands upon existing physiologically based pharmacokinetic (PBPK) models for VPA by incorporating UGT enzyme kinetics and an advanced dissolution, absorption, and metabolism (ADAM) model for extended-release (ER) formulation.

Assessment of clinical feedback given to medical students via an electronic feedback system.

Background: The feedback medical students receive during clinical rotations, traditionally verbal and not formally captured, plays a critical role in student development. This study evaluates written daily feedback given to students through a novel web-based feedback system.

Methods: A Minute Feedback System was used to collect feedback given to medical students during their surgery clerkship from May 2015-April 2016.

The association of venous thromboembolism chemoprophylaxis timing on venous thromboembolism after major vascular surgery.

Objective: Venous thromboembolism (VTE) is reported to occur in up to 33% of patients undergoing major vascular surgery. Despite this high incidence, patients inconsistently receive timely VTE chemoprophylaxis. The true incidence of VTE among patients receiving delayed VTE chemoprophylaxis is unknown.

Valproic acid decreases brain lesion size and improves neurologic recovery in swine subjected to traumatic brain injury, hemorrhagic shock, and polytrauma.

Background: We have previously shown that treatment with valproic acid (VPA) decreases brain lesion size in swine models of traumatic brain injury (TBI) and controlled hemorrhage. To translate this treatment into clinical practice, validation of drug efficacy and evaluation of pharmacologic properties in clinically realistic models of injury are necessary. In this study, we evaluate neurologic outcomes and perform pharmacokinetic analysis of a single dose of VPA in swine subjected to TBI, hemorrhagic shock, and visceral hemorrhage.

Safety and Tolerability of Intravenous Valproic Acid in Healthy Subjects: A Phase I Dose-Escalation Trial.

Background: Valproic acid, a histone deacetylase inhibitor, has beneficial effects in the setting of cancer, neurologic diseases, and traumatic injuries. In animal models of traumatic injury, a single dose of valproic acid has been shown to reduce mortality. The purpose of this trial was to determine the maximum tolerated single dose of intravenous valproic acid in healthy humans.

Lung Protective Effects of Low-Volume Resuscitation and Pharmacologic Treatment of Swine Subjected to Polytrauma and Hemorrhagic Shock.

Hemorrhage is a common cause of death in the battlefield. Valproic acid (VPA) has been associated with improved outcomes in multiple models of trauma, when combined with isotonic fluid resuscitation. However, isotonic fluid administered in this setting is logistically impractical and may be associated with complications.

Valproic acid modulates platelet and coagulation function ex vivo.

: Trauma-induced coagulopathy is associated with adverse patient outcome. Animal models demonstrate that histone deacetylase inhibitors, such as valproic acid (VPA), improve survival following injury. While in-vivo data suggest that improved survival may in part be because of an attenuation of coagulopathy, it remains unknown whether this is a direct effect of the drug, or the establishment of an overall prosurvival phenotype.

Resuscitation with Lyophilized Plasma Is Safe and Improves Neurological Recovery in a Long-Term Survival Model of Swine Subjected to Traumatic Brain Injury, Hemorrhagic Shock, and Polytrauma.

We have shown previously that fresh frozen plasma (FFP) and lyophilized plasma (LP) decrease brain lesion size and improve neurological recovery in a swine model of traumatic brain injury (TBI) and hemorrhagic shock (HS). In this study, we examine whether these findings can be validated in a clinically relevant model of severe TBI, HS, and polytrauma. Female Yorkshire swine were subjected to TBI (controlled cortical impact), hemorrhage (40% volume), grade III liver and splenic injuries, rib fracture, and rectus abdominis crush.

Alterations in the human proteome following administration of valproic acid.

Background: High doses of the histone deacetylase inhibitor valproic acid (VPA, 150-400 mg/kg) improve outcomes in animal models of lethal insults. We are conducting a US Food and Drug Administration-approved Phase I, double-blind, placebo-controlled trial to evaluate the safety and tolerability of ascending doses of VPA in human volunteers. We hypothesized that VPA would induce significant changes in the proteome of healthy humans when given at doses lower than those used in prior animal studies.