Prediction of postoperative cardiac events in multiple surgical cohorts using a multimodal and integrative decision support system.

Postoperative patients are at risk of life-threatening complications such as hemodynamic decompensation or arrhythmia. Automated detection of patients with such risks via a real-time clinical decision support system may provide opportunities for early and timely interventions that can significantly improve patient outcomes. We utilize multimodal features derived from digital signal processing techniques and tensor formation, as well as the electronic health record (EHR), to create machine learning models that predict the occurrence of several life-threatening complications up to 4 hours prior to the event. In order to ensure that our models are generalizable across different surgical cohorts, we trained the models on a cardiac surgery cohort and tested them on vascular and non-cardiac acute surgery cohorts. The best performing models achieved an area under the receiver operating characteristic curve (AUROC) of 0.94 on training and 0.94 and 0.82, respectively, on testing for the 0.5-hour interval. The AUROCs only slightly dropped to 0.93, 0.92, and 0.77, respectively, for the 4-hour interval. This study serves as a proof-of-concept that EHR data and physiologic waveform data can be combined to enable the early detection of postoperative deterioration events.

Adapting to the Times: Combining Microlearning Videos and Twitter to Teach Surgical Technique.

OBJECTIVE: Surgical videos are commonly utilized by trainees to prepare for surgical cases. However, currently available videos tend to be of excessive length, variable quality, and exist behind paywalls or in other exclusive formats. Our objective was to create a series of videos that would address these shortcomings, and further allow for dynamic engagement between learners and experts. DESIGN: Our group created surgical videos using principles of microlearning, an educational strategy which deconstructs content into small units and uses social media platforms where learners and educators may actively engage. We published a library of short (<3 min) videos covering various steps of abdominal transplantation operations on a YouTube channel. We leveraged Twitter to disseminate the content and engage with experts and learners from around the world. SETTING: Multi-institutional. RESULTS: Over the period from July 2020 to January 2021, 24 microlearning videos were created, stored on a YouTube channel, and posted to Twitter weekly using a newly created account. During that time period, the videos, averaging 124 seconds in length, were viewed 4393 times and watched for a total of 127 hours. The account gained 611 followers in 37 countries and 37 US states with 312,400 impressions (defined as tweet views). Twitter users who engaged with our microlearning content (favorite, retweet, or reply) included faculty (27%), residents (21%), fellows (8%), and medical students (11%). CONCLUSIONS: Broad participation with the educational material and discussion on Twitter demonstrated the potential for the microlearning technique to provide educational benefit for learners internationally. The spread of the tweets shows an opportunity to augment traditional surgical education, and the willingness of faculty to discuss alternative techniques with their peers. Our group will continue to develop a library of microlearning videos for surgical operations and engage with other institutions for collaboration and expansion.

Prehospital end-tidal carbon dioxide is predictive of death and massive transfusion in injured patients: An Eastern Association for Surgery of Trauma multicenter trial.

BACKGROUND: Prehospital identification of the injured patient likely to require emergent care remains a challenge. End-tidal carbon dioxide (ETCO2) has been used in the prehospital setting to monitor respiratory physiology and confirmation of endotracheal tube placement. Low levels of ETCO2 have been demonstrated to correlate with injury severity and mortality in a number of in-hospital studies. We hypothesized that prehospital ETCO2 values would be predictive of mortality and need for massive transfusion (MT) in intubated patients. METHODS: This was a retrospective multicenter trial with 24 participating centers. Prehospital, emergency department, and hospital values were collected. Receiver operating characteristic curves were created and compared. Massive transfusion defined as >10 U of blood in 6 hours or death in 6 hours with at least 1 U of blood transfused. RESULTS: A total of 1,324 patients were enrolled. ETCO2 (area under the receiver operating characteristic curve [AUROC], 0.67; confidence interval [CI], 0.63-0.71) was better in predicting mortality than shock index (SI) (AUROC, 0.55; CI, 0.50-0.60) and systolic blood pressure (SBP) (AUROC, 0.58; CI, 0.53-0.62) (p < 0.0005). Prehospital lowest ETCO2 (AUROC, 0.69; CI, 0.64-0.75), SBP (AUROC, 0.75; CI, 0.70-0.81), and SI (AUROC, 0.74; CI, 0.68-0.79) were all predictive of MT. Analysis of patients with normotension demonstrated lowest prehospital ETCO2 (AUROC, 0.66; CI, 0.61-0.71), which was more predictive of mortality than SBP (AUROC, 0.52; CI, 0.47-0.58) or SI (AUROC, 0.56; CI, 0.50-0.62) (p < 0.001). Lowest prehospital ETCO2 (AUROC, 0.75; CI, 0.65-0.84), SBP (AUROC, 0.63; CI, 0.54-0.74), and SI (AUROC, 0.64; CI, 0.54-0.75) were predictive of MT in normotensive patients. ETCO2 cutoff for MT was 26 mm Hg. The positive predictive value was 16.1%, and negative predictive value was high at 98.1%. CONCLUSION: Prehospital ETCO2 is predictive of mortality and MT. ETCO2 outperformed traditional measures such as SBP and SI in the prediction of mortality. ETCO2 may outperform traditional measures in predicting need for transfusion in occult shock. LEVEL OF EVIDENCE: Diagnostic test, level III.

Population-based Trends in Obesity and Kidney Transplantation Among Patients With End-stage Kidney Disease.

Obesity is a barrier to transplant, reducing access and leading to worse outcomes versus nonobese adults. Most transplant centers in the United States maintain body mass index (BMI) cutoffs to listing for kidney transplantation of 35 to 40 kg/m2. There is little contemporary data on the prevalence of obesity among patients with end-stage kidney disease (ESKD) despite its impact on clinical outcomes and healthcare expenditures. METHODS: We utilized data from the US Renal Data System from 2008 to 2016 to identify a prevalent cohort of 1 079 410 patients with ESKD. Linear regression determined trends in the proportion of patients within each category of BMI. We also evaluated geographic variation in rates of obesity and transplantation across the United States. RESULTS: Among the 1 079 410 ESKD patients, the largest cohort of patients were those with obesity (n = 423 270; 39.2%). There were 309 707 (28.7%) patients with an overweight BMI and 274 683 (25.4%) with a normal BMI. The proportion of patients with obesity increased significantly from 36.8% in 2008 to 40.2% in 2016 (trend 0.28; 95% confidence interval, 0.05-0.51). There was significant geographic variation by state with rates of obesity ranging from 32.3% to 45.4% and state transplant rates among those obese patients ranging from 22.5% to 46.8%. There is a weak correlation between states with increased rates of obese ESKD patients and states with an increased obesity transplant rate as indicated with r = 0.40 (P = 0.003). CONCLUSIONS: Beneficiaries with obesity are now the largest and fastest growing demographic among patients with ESKD in the United States.

A single dose of valproic acid improves neurologic recovery and decreases brain lesion size in swine subjected to an isolated traumatic brain injury.

BACKGROUND: We lack specific treatments for traumatic brain injury (TBI), which remains the leading cause of trauma-related morbidity and mortality. Treatment with valproic acid (VPA) improves outcomes in models of severe TBI with concurrent hemorrhage. However, it is unknown if VPA will have similar benefits after isolated nonlethal TBI, which is the more common clinical scenario. The goal of this study was to evaluate the effect of VPA treatment in a preclinical isolated TBI swine model on neurologic outcomes and brain lesion size and to perform detailed pharmacokinetic analyses for a future clinical trial. METHODS: Yorkshire swine (n = 10; 5/cohort) were subjected to TBI (8-mm controlled cortical impact). An hour later, we randomized them to receive VPA (150 mg/kg) or saline placebo (control). Neuroseverity scores were assessed daily (0 [normal] to 36 [comatose]), brain lesion size was measured on postinjury 3, and serial blood samples were collected for pharmacokinetic studies. RESULTS: Physiologic parameters and laboratory values were similar in both groups. Valproic acid-treated animals demonstrated significantly better neuroseverity scores on postinjury 1 (control, 9.2 ± 4.4; VPA, 0 ± 0; p = 0.001). Valproic acid-treated animals had significantly smaller brain lesion sizes (mean volume in microliter: control, 3,130 ± 2,166; VPA, 764 ± 208; p = 0.02). Pharmacokinetic data confirmed adequate plasma and tissue levels of VPA. CONCLUSION: In this clinically relevant model of isolated TBI, a single dose of VPA attenuates neurological impairment and decreases brain lesion size.

Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma.

INTRODUCTION: Trauma is the leading cause of death among young people. These patients have a high incidence of kidney injury, which independently increases the risk of mortality. As valproic acid (VPA) treatment has been shown to improve survival in animal models of lethal trauma, we hypothesized that it would also attenuate the degree of acute kidney injury. METHODS: We analyzed data from two separate experiments where swine were subjected to lethal insults.  Model 1: hemorrhage (50% blood volume hemorrhage followed by 72-h damage control resuscitation). Model 2: polytrauma (traumatic brain injury, 40% blood volume hemorrhage, femur fracture, rectus crush and grade V liver laceration). Animals were resuscitated with normal saline (NS) +/- VPA 150 mg/kg after a 1-h shock phase in both models (n = 5-6/group). Serum samples were analyzed for creatinine (Cr) using colorimetry on a Liasys 330 chemistry analyzer. Proteomic analysis was performed on kidney tissue sampled at the time of necropsy. RESULTS: VPA treatment significantly (P < 0.05) improved survival in both models. (Model 1: 80% vs 20%; Model 2: 83% vs. 17%). Model 1 (Hemorrhage alone): Cr increased from a baseline of 1.2 to 3.0 in NS control animals (P < 0.0001) 8 h after hemorrhage, whereas it rose only to 2.1 in VPA treated animals (P = 0.004). Model 2 (Polytrauma): Cr levels increased from baseline of 1.3 to 2.5 mg/dL (P = 0.01) in NS control animals 4 h after injury but rose to only 1.8 in VPA treated animals (P = 0.02). Proteomic analysis of kidney tissue identified metabolic pathways were most affected by VPA treatment. CONCLUSIONS: A single dose of VPA (150 mg/kg) offers significant protection against acute kidney injury in swine models of polytrauma and hemorrhagic shock.

Assessment of the Cytoprotective Effects of High-Dose Valproic Acid Compared to a Clinically Used Lower Dose.

OBJECTIVE: Valproic acid (VPA) treatment improves survival in animal models of injuries on doses higher than those allowed by Food and Drug Administration (FDA). We investigated the proteomic alterations induced by a single high-dose (140mg/kg) of VPA (VPA140) compared to the FDA-approved dose of 30mg/kg (VPA30) in healthy humans. We also describe the proteomic and transcriptomic changes induced by VPA140 in an injured patient. We hypothesized that VPA140 would induce cytoprotective changes in the study participants. METHODS: Serum samples were obtained from healthy subjects randomized to two groups; VPA140 and VPA30 at 3 timepoints: 0h(baseline), 2h, and 24h following infusion(n = 3/group). Samples were also obtained from an injured patient that received VPA140 at 0h, 6h and 24h following infusion. Proteomic analyses were performed using liquid chromatography-mass spectrometry (LC-MS/MS), and transcriptomic analysis was performed using RNA-sequencing. Differentially expressed (DE) proteins and genes were identified for functional annotation and pathway analysis using iPathwayGuide and gene set enrichment analysis (GSEA), respectively. RESULTS: For healthy individuals, a dose comparison was performed between VPA140 and VPA30 groups at 2 and 24 h. Functional annotation showed that top biological processes in VPA140 versus VPA30 analysis at 2 h included regulation of fatty acid (P = 0.002) and ATP biosynthesis (P = 0.007), response to hypoxia (P = 0.017), cell polarity regulation (P = 0.031), and sequestration of calcium ions (P = 0.031). Top processes at 24 h in VPA140 versus VPA30 analysis included amino acid metabolism (P = 0.023), collagen catabolism (P = 0.023), and regulation of protein breakdown (P = 0.023). In the injured patient, annotation of the DE proteins in the serum showed that top biological processes at 2 h included neutrophil chemotaxis (P = 0.002), regulation of cellular response to heat (P = 0.008), regulation of oxidative stress (P = 0.008) and regulation of apoptotic signaling pathway (P = 0.008). Top biological processes in the injured patient at 24 h included autophagy (P = 0.01), glycolysis (P = 0.01), regulation of apoptosis (P = 0.01) and neuron apoptotic processes (P = 0.02). CONCLUSIONS: VPA140 induces cytoprotective changes in human proteome not observed in VPA30. These changes may be responsible for its protective effects in response to injuries.

Validation of intraosseous delivery of valproic acid in a swine model of polytrauma.

BACKGROUND: Intraosseous (IO) drug delivery may be necessary in emergency situations when intravenous access is unattainable. Valproic acid (VPA) is a histone deacetylase inhibitor that has previously been shown to improve survival in preclinical models of lethal polytrauma. In this study, we sought to compare serum levels of intravenously and IO-delivered VPA, and to analyze the effect of IO-delivered VPA. METHODS: Swine were subjected to 40% blood volume hemorrhage, brain injury, femur fracture, rectus crush injury and liver laceration. After 1 hour of shock, animals were randomized (n=3/group) to receive normal saline resuscitation (control), normal saline+intravenous VPA 150 mg/kg (intravenous group) or normal saline +IO VPA 150 mg/kg (IO group). Serum levels of VPA were assessed between groups, and proteomics analyses were performed on IO and control groups on heart, lung and liver samples. RESULTS: Intravenous and IO serum VPA levels were similar at 1, 3, 5 and 7 hours after starting the infusion (p>0.05). IO-delivered VPA induced significant proteomics changes in the heart, lung and liver, which were most pronounced in the lung. Biologic processes affected included inflammation, metabolism and transcriptional & translational machinery. The control group had 0% survival, and the intravenous and IO group both had 100% survival to the end of the experiment (p<0.05). DISCUSSION: IO-delivered VPA is noninferior to intravenous administration and is a viable option in emergent situations when intravenous access is unattainable. LEVEL OF EVIDENCE: Not applicable (animal study).

Assessment of Potentially Preventable Hospital Readmissions After Major Surgery and Association With Public vs Private Health Insurance and Comorbidities.

Importance: Rehospitalization after major surgery is common and represents a significant cost to the health care system. Little is known regarding the causes of these readmissions and the degree to which they may be preventable. Objective: To evaluate the degree to which readmissions after major surgery are potentially preventable. Design, Setting, and Participants: This retrospective cohort study used a weighted sample of 1 937 354 patients from the 2017 National Readmissions Database to evaluate all adult inpatient hospitalizations for 1 of 7 common major surgical procedures. Statistical analysis was performed from January 14 to November 30, 2020. Main Outcomes and Measures: The study calculated 90-day readmission rates as well as rates of readmissions that were considered potentially preventable. Potentially preventable readmissions (PPRs) were defined as those with a primary diagnosis code for superficial surgical site infection, acute kidney injury, aspiration pneumonitis, or any of the Agency for Healthcare Research and Quality-defined ambulatory care sensitive conditions. Multivariable logistic regression was used to identify factors associated with PPRs. Results: A total weighted sample of 1 937 354 patients (1 048 046 women [54.1%]; mean age, 66.1 years [95% CI, 66.0-66.3 years]) underwent surgical procedures; 164 755 (8.5%) experienced a readmission within 90 days. Potentially preventable readmissions accounted for 29 321 (17.8%) of all 90-day readmissions, for an estimated total cost to the US health care system of approximately $296 million. The most common reasons for PPRs were congestive heart failure exacerbation (34.6%), pneumonia (12.0%), and acute kidney injury (22.5%). In a multivariable model of adults aged 18 to 64 years, patients with public health insurance (Medicare or Medicaid) had more than twice the odds of PPR compared with those with private insurance (adjusted odds ratio, 2.09; 95% CI, 1.94-2.25). Among patients aged 65 years or older, patients with private insured had 18% lower odds of PPR compared with patients with Medicare as the primary payer (adjusted odds ratio, 0.82; 95% CI, 0.74-0.90). Conclusions and Relevance: This study suggests that nearly 1 in 5 readmissions after surgery are potentially preventable and account for nearly $300 million in costs. In addition to better inpatient care, improved access to ambulatory care may represent an opportunity to reduce costly readmissions among surgical patients.

Brain proteomic changes by histone deacetylase inhibition after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality. There are currently no cytoprotective treatments for TBI. There is growing evidence that the histone deacetylase inhibitor valproic acid (VPA) may be beneficial in the treatment of TBI associated with hemorrhagic shock and in isolation. We sought to further evaluate the mechanistic underpinnings of this demonstrated efficacy via proteomic analysis of injured brain tissue. METHODS: Swine were subjected to TBI via controlled cortical impact, randomized to treatment with VPA or control and observed for 6 hours. The brains of the pigs were then sectioned, and tissue was prepared and analyzed for proteomic data, including gene ontology (GO), gene-set enrichment analysis and enrichment mapping, and network mapping. RESULTS: Proteomic analysis demonstrated differential expression of hundreds of proteins in injured brain tissue after treatment with VPA. GO analysis and network analyses revealed groups of proteins and processes that are known to modulate injury response after TBI and impact cell fate. Processes affected included protein targeting and transport, cation and G-protein signaling, metabolic response, neurotransmitter response and immune function. DISCUSSION: This proteomic analysis provides initial mechanistic insight into the observed rescue of injured brain tissue after VPA administration in isolated TBI. LEVEL OF EVIDENCE: Not applicable (animal study).

Development of a large animal model of lethal polytrauma and intra-abdominal sepsis with bacteremia.

BACKGROUND: Trauma and sepsis are individually two of the leading causes of death worldwide. When combined, the mortality is greater than 50%. Thus, it is imperative to have a reproducible and reliable animal model to study the effects of polytrauma and sepsis and test novel treatment options. Porcine models are more translatable to humans than rodent models due to the similarities in anatomy and physiological response. We embarked on a study to develop a reproducible model of lethal polytrauma and intra-abdominal sepsis, which was lethal, though potentially salvageable with treatment. METHODS: Our laboratory has a well-established porcine model that was used as the foundation. Animals were subjected to a rectus crush injury, long bone fracture, liver and spleen laceration, traumatic brain injury and hemorrhage that was used as a foundation. We tested various colon injuries to create intra-abdominal sepsis. All animals underwent injuries followed by a period of shock, then subsequent resuscitation. RESULTS: All animals had blood culture-proven sepsis. Attempts at long-term survival of animals after injury were ceased because of poor appetite and energy. We shifted to an 8-hour endpoint. The polytrauma injury pattern remained constant and the colon injury pattern changed with the intention of creating a model that was ultimately lethal but potentially salvageable with a therapeutic drug. An uncontrolled cecal injury (n=4) group resulted in very early deaths. A controlled cecal injury (CCI; n=4) group had prolonged time prior to mortality with one surviving to the endpoint. The sigmoid injury (n=5) produced a similar survival curve to CCI but no animals surviving to the endpoint. CONCLUSION: We have described a porcine model of polytrauma and sepsis that is reproducible and may be used to investigate novel treatments for trauma and sepsis. LEVEL OF EVIDENCE: Not applicable. Animal study.

How I Do It: Pilot Study of Video-Based Feedback as an Educational Tool for Medical Students' Presentations on Morning Rounds.

OBJECTIVE: Morning rounds are a bedrock learning opportunity during clinical rotations in medical school. Specific feedback is critical for students to improve presentation skills and build confidence, however, current feedback mechanisms are fragmented and nonstandard. We aimed to assess whether video-based coaching of morning rounds could improve student feedback and self-awareness without increasing anxiety during patient presentations. DESIGN: Medical students during core clinical clerkships were filmed presenting on morning rounds during their surgery clerkship. A designated faculty coach reviewed the video prior to an in-person coaching session. Students reviewed the video with faculty and were coached on content, presentation style, and presence. A short survey assessed students' pre- and postcoaching confidence, skill, and the utility of the coaching session. SETTING: University of Michigan Health System, Department of Surgery, Division of General Surgery, Ann Arbor, Michigan PARTICIPANTS: Eight medical student volunteers during their core clinical clerkships at University of Michigan Medical School during the surgery clerkship. RESULTS: Comparison of pre- and post self-assessments showed that students underestimated their knowledge of basic and clinical science and overestimated their clinical assessment skills and ability to appropriately address the core components of a presentation. Most students (75%) did not think that the filming process altered their performance and only 25% of students felt increased anxiety due to filming. All students agreed that the feedback session was useful and helped them understand how to improve their oral presentations. CONCLUSION: This pilot demonstrates the feasibility and value of video-based coaching as an educational tool for medical students on clerkships. A larger sample size is needed to further evaluate the effectiveness of video-based coaching in establishing baseline clinical abilities and identifying potential areas for improvement.

A novel partial resuscitative endovascular balloon aortic occlusion device that can be deployed in zone 1 for more than 2 hours with minimal provider titration.

BACKGROUND: Hemorrhage is a leading cause of mortality in trauma. Resuscitative endovascular balloon occlusion of the aorta (REBOA) can control hemorrhage, but distal ischemia, subsequent reperfusion injury, and the need for frequent balloon titration remain problems. Improved device design can allow for partial REBOA (pREBOA) that may provide hemorrhage control while also perfusing distally without need for significant provider titration. METHODS: Female Yorkshire swine (N = 10) were subjected to 40% hemorrhagic shock for 1 hour (mean arterial pressure [MAP], 28-32 mm Hg). Animals were then randomized to either complete aortic occlusion (ER-REBOA) or partial occlusion (novel pREBOA-PRO) without frequent provider titration or distal MAP targets. Detection of a trace distal waveform determined partial occlusion in the pREBOA-PRO arm. After 2 hours of zone 1 occlusion, the hemorrhaged whole blood was returned. After 50% autotransfusion, the balloon was deflated over a 10-minute period. Following transfusion, the animals were survived for 2 hours while receiving resuscitation based on objective targets: lactated Ringer's fluid boluses (goal central venous pressure, ≥ 6 mm Hg), a norepinephrine infusion (goal MAP, 55-60 mm Hg), and acid-base correction (goal pH, >7.2). Hemodynamic variables, arterial lactate, lactate dehydrogenase, aspartate aminotransferase, and creatinine levels were measured. RESULTS: All animals survived throughout the experiment, with similar increase in proximal MAPs in both groups. Animals that underwent partial occlusion had slightly higher distal MAPs. At the end of the experiment, the partial occlusion group had lower end levels of serum lactate (p = 0.006), lactate dehydrogenase (p = 0.0004) and aspartate aminotransferase (p = 0.004). Animals that underwent partial occlusion required less norepinephrine (p = 0.002), less bicarbonate administration (p = 0.006), and less fluid resuscitation (p = 0.042). CONCLUSION: Improved design for pREBOA can decrease the degree of distal ischemia and reperfusion injury compared with complete aortic occlusion, while providing a similar increase in proximal MAPs. This can allow pREBOA zone-1 deployment for longer periods without the need for significant balloon titration.

Surgery Provider Perceptions on Telehealth Visits During the COVID-19 Pandemic: Room for Improvement.

BACKGROUND: COVID-19 has mandated rapid adoption of telehealth for surgical care. However, many surgical providers may be unfamiliar with telehealth. This study evaluates the perspectives of surgical providers practicing telehealth care during COVID-19 to help identify targets for surgical telehealth optimization. MATERIALS AND METHODS: At a single tertiary care center with telehealth capabilities, all department of surgery providers (attending surgeons, residents, fellows, and advanced practice providers) were emailed a voluntary survey focused on telehealth during the pandemic. Descriptive statistics and Mann-Whitney U analyses were performed as appropriate on responses. Text responses were thematically coded to identify key concepts. RESULTS: The completion rate was 41.3% (145/351). Providers reported increased telehealth usage relative to the pandemic (P < 0.001). Of respondents, 80% (116/145) had no formal telehealth training. Providers estimated that new patient video visits required less time than traditional visits (P = 0.001). Satisfaction was high for several aspects of video visits. Comparatively lower satisfaction scores were reported for the ability to perform physical exams (sensitive and nonsensitive) and to break bad news. The largest barriers to effective video visits were limited physical exams (55.6%; 45/81) and lack of provider or patient internet access/equipment/connection (34.6%; 28/81). Other barriers included ineffective communication and difficulty with fostering rapport. Concerns regarding video-to-telephone visit conversion were loss of physical exam/visual cues (34.3%; 24/70), less personal interactions (18.6%; 13/70), and reduced efficiency (18.6%; 13/70). CONCLUSIONS: Telehealth remains a new experience for surgical providers despite its expansion. Optimization strategies should target technology barriers and include specialized virtual exam and communication training.

Facilitators and barriers to allyship in academic surgery: A qualitative study.

BACKGROUND: Academic health centers have promoted initiatives to improve diversity, equity and inclusion in medicine. Despite this emphasis, there has been limited discussion on practical strategies for navigating bias within academic surgery. This study analyzes experiences of confronting bias within the department of surgery at the University of Michigan. MATERIALS AND METHODS: We conducted telephone interviews (n = 15) from January 2019 to January 2020 with surgeon volunteers at one academic institution. Two investigators conducted interviews following a semi-structured guide based on personal experiences with bias between healthcare workers with diverse identities. Interviews were conducted concurrently with thematic coding, coded independently by two investigators, and discussed until consensus was reached. Analysis proceeded following the inductive and comparative approach of interpretive description. RESULTS: The most common incidents of bias were based on gender and race. They occurred along numerous relationship axes, including physician-patient and resident-faculty. A critical factor in bias response was unambiguously recognizing bias. Responding to bias consists of timing and nature of the response, defined as when the subject responded relative to the incident and the actions done in response to the incident respectively. Barriers to bias response were fear of retribution and extensive energy required to respond. Institutional culture was important, specifically in representation and support from peers and administration. CONCLUSIONS: This study probes deeper into equity and inclusivity in the academic field of surgery, offering insight into common barriers to confronting bias. Overall, these findings offer a basic framework for allies to identify bias and to partner with colleagues to address biases in a supportive manner.

Administration of valproic acid in clinically approved dose improves neurologic recovery and decreases brain lesion size in swine subjected to hemorrhagic shock and traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) and hemorrhage remain the leading causes of death after trauma. We have previously shown that a dose of valproic acid (VPA) at (150 mg/kg) can decrease brain lesion size and hasten neurologic recovery. The current Food and Drug Administration-approved dose of VPA is 60 mg/kg. We evaluate neurologic outcomes and brain lesion size of a single dose of VPA at a level currently within Food and Drug Administration-approved dose in swine subjected to TBI and hemorrhagic shock. METHODS: Swine (n = 5/group) were subjected to TBI and 40% blood volume hemorrhage. Animals remained in shock for 2 hours before randomization to normal saline (NS) resuscitation alone (control), NS-VPA 150 mg/kg (VPA 150), or NS-VPA 50 mg/kg (VPA 50). Neurologic severity scores (range, 0-32) were assessed daily for 14 days, and brain lesion size was measured via magnetic resonance imaging on postinjury day (PID) 3. RESULTS: Shock severity and laboratory values were similar in all groups. Valproic acid-treated animals demonstrated significantly less neurologic impairment on PID 1 and returned to baseline faster (PID 1 mean neurologic severity score, control = 22 ± 3 vs. VPA 150 mg/kg = 8 ± 7 or VPA 50 mg/kg = 6 ± 6; p = 0.02 and 0.003). Valproic acid-treated animals had significantly smaller brain lesion sizes (mean volume in mm3, control = 1,268.0 ± 241.2 vs. VPA 150 mg/kg = 620.4 ± 328.0 or VPA 50 mg/kg = 438.6 ± 234.8; p = 0.007 and 0.001). CONCLUSION: In swine subjected to TBI and hemorrhagic shock, VPA treatment, in a dose that is approved for clinical use, decreases brain lesion size and reduces neurologic impairment compared with resuscitation alone.

Fostering Passion and Skills in Surgical Research Across the Medical Education Continuum: The Transplant Research, Education, and Engagement Group.

OBJECTIVE: We describe a multilevel, collaborative research group for trainees and faculty engaging in transplant surgery research within one institution. DESIGN: Transplant Research, Education, and Engagement (TREE) was designed to develop trainees' research skills and foster enthusiasm in transplant surgery along the educational continuum. Our research model intentionally empowers junior researchers, including undergraduates and medical students, to assume active roles on a range of research projects and contribute new ideas within a welcoming research and learning environment. SETTING: Section of Transplant Surgery, Department of Surgery, Michigan Medicine, Ann Arbor, Michigan. PARTICIPANTS: Undergraduate premedical students, first through fourth year medical students, general surgery residents, transplant surgery fellows, and transplant surgery faculty. RESULTS: TREE was founded in September 2019 and has grown to include over 30 active members who meet weekly and collaborate virtually on a range of research projects, many of which are led by students. Trainees can assume both mentee and mentor roles and build their research, presentation and writing skills while collaborating academically. CONCLUSIONS: Our model has increased trainees' engagement in transplant research projects and fosters early enthusiasm for the field. This model can be feasibly replicated at other institutions and within other subspecialties.

Valproic acid treatment rescues injured tissues after traumatic brain injury.

BACKGROUND: No agents that are specifically neuroprotective are currently approved to emergently treat patients with traumatic brain injury (TBI). The histone deacetylase inhibitor, high-dose valproic acid (VPA) has been shown to have cytoprotective potential in models of combined TBI and hemorrhagic shock, but it has not been tested in an isolated TBI model. We hypothesized that VPA, administered after isolated TBI, will penetrate the injured brain, attenuate the lesion size, and activate prosurvival pathways. METHODS: Yorkshire swine were subjected to severe TBI by cortical impact. One hour later, animals were randomized to VPA treatment (150 mg/kg delivered intravenously for 1 hour; n = 4) or control (saline vehicle; n = 4) groups. Seven hours after injury, animals were sacrificed, and brain lesion size was measured. Mass spectrometry imaging was used to visualize and quantitate brain tissue distribution of VPA. Sequential serum samples were assayed for key biomarkers and subjected to proteomic and pathway analysis. RESULTS: Brain lesion size was 50% smaller (p = 0.01) in the VPA-treated animals (3,837 ± 948 mm) compared with the controls (1,900 ± 614 mm). Endothelial regions had eightfold higher VPA concentrations than perivascular regions by mass spectrometry imaging, and it readily penetrated the injured brain tissues. Serum glial fibrillary acid protein was significantly lower in the VPA-treated compared with the control animals (p < 0.05). More than 500 proteins were differentially expressed in the brain, and pathway analysis revealed that VPA affected critical modulators of TBI response including calcium signaling pathways, mitochondria metabolism, and biosynthetic machinery. CONCLUSION: Valproic acid penetrates injured brain tissues and exerts neuroprotective and prosurvival effects that resulted in a significant reduction in brain lesion size after isolated TBI. Levels of serum biomarkers reflect these changes, which could be useful for monitoring the response of TBI patients during clinical studies.