Bone Anchor Fixation in the Repair of Blunt Traumatic Abdominal Wall Hernias: A Western Trauma Association Multicenter Study.

BACKGROUND: Blunt traumatic abdominal wall hernias (TAWHs) are rare but require a variety of operative techniques to repair including bone anchor fixation (BAF) when tissue tears off bony structures. This study aimed to provide a descriptive analysis of BAF technique for blunt TAWH repair. Bone anchor fixation and no BAF repairs were compared, hypothesizing increased hernia recurrence with BAF repair. METHODS: A secondary analysis of the WTA blunt TAWH multicenter study was performed including all patients who underwent repair of their TAWH. Patients with BAF were compared to those with no BAF with bivariate analyses. RESULTS: 176 patients underwent repair of their TAWH with 41 (23.3%) undergoing BAF. 26 (63.4%) patients had tissue fixed to bone, with 7 of those reinforced with mesh. The remaining 15 (36.6%) patients had bridging mesh anchored to bone. The BAF group had a similar age, sex, body mass index, and injury severity score compared to the no BAF group. The time to repair (1 vs 1 days, P = .158), rate of hernia recurrence (9.8% vs 12.7%, P = .786), and surgical site infection (SSI) (12.5% vs 15.6%, P = .823) were all similar between cohorts. CONCLUSIONS: This largest series to date found nearly one-quarter of TAWH repairs required BAF. Bone anchor fixation repairs had a similar rate of hernia recurrence and SSI compared to no BAF repairs, suggesting this is a reasonable option for repair of TAWH. However, future prospective studies are needed to compare specific BAF techniques and evaluate long-term outcomes including patient-centered outcomes such as pain and quality of life.

A western trauma association multicenter comparison of mesh versus non-mesh repair of blunt traumatic abdominal wall hernias.

BACKGROUND: Blunt traumatic abdominal wall hernias (TAWH) occur in <1 % of trauma patients. Optimal repair techniques, such as mesh reinforcement, have not been studied in detail. We hypothesize that mesh use will be associated with increased surgical site infections (SSI) and not improve hernia recurrence. MATERIALS AND METHODS: A secondary analysis of the Western Trauma Association blunt TAWH multicenter study was performed. Patients who underwent TAWH repair during initial hospitalization (1/2012-12/2018) were included. Mesh repair patients were compared to primary repair patients (non-mesh). A logistic regression was conducted to assess risk factors for SSI. RESULTS: 157 patients underwent TAWH repair during index hospitalization with 51 (32.5 %) having mesh repair: 24 (45.3 %) synthetic and 29 (54.7 %) biologic. Mesh patients were more commonly smokers (43.1 % vs. 22.9 %, p = 0.016) and had a larger defect size (10 vs. 6 cm, p = 0.003). Mesh patients had a higher rate of SSI (25.5 % vs. 9.5 %, p = 0.016) compared to non-mesh patients, but a similar rate of recurrence (13.7 % vs. 10.5%, p = 0.742), hospital length of stay (LOS), and mortality. Mesh use (OR 3.66) and higher ISS (OR 1.06) were significant risk factors for SSI in a multivariable model. CONCLUSION: Mesh was used more frequently in flank TAWH and those with a larger defect size. Mesh use was associated with a higher incidence and risk of SSI but did not reduce the risk of hernia recurrence. When repairing TAWH mesh should be employed judiciously, and prospective randomized studies are needed to identify clear indications for mesh use in TAWH.

"You've Got Gratitude!"- A Multispecialty and Multi-institution Program Encouraging Expressions of Gratitude.

OBJECTIVE: Efforts to improve physician well-being have focused on gratitude, which predicts health and happiness. Despite reported benefits, expressions of gratitude in healthcare can seem infrequent. Here, we describe Gratitude-Grams, an intervention to cultivate expressions of gratitude throughout a department. METHODS/APPROACH: Piloted in our Department of Surgery and adopted by others, Gratitude-Grams employs a web-based platform (Qualtrics). Program feedback was solicited during teaching conferences using an anonymous department survey. RESULTS: Gratitude-Grams streamlines and encourages expressions of gratitude while minimizing maintenance, cost, and time. The platform has been highly utilized and well-received in our Department of Surgery. CONCLUSION: Expressing and receiving gratitude has been shown to be critical for well-being. Gratitude-Grams is a highly utilized, simple, and attainable system to support expressions of gratitude and is ready for rapid implementation.

The Demands of Surgery Residency: More Than Just Duty Hours?

INTRODUCTION: Efforts to improve surgical resident well-being could be accelerated with an improved understanding of resident job demands and resources. In this study, we sought to obtain a clearer picture of surgery resident job demands by assessing how residents distribute their time both inside and outside of the hospital. Furthermore, we aimed to elucidate residents' perceptions about current duty hour regulations. METHODS: A cross-sectional survey was sent to 1098 surgical residents at 27 US programs. Responses regarding work hours, demographics, well-being (utilizing the physician well-being index), and perceptions of duty hours in relation to education and rest, were collected. Data were evaluated using descriptive statistics and content analysis. RESULTS: A total of 163 residents (14.8% response rate) were included in the study. Residents reported a median total patient care hours per week of 78.0 h. Trainees spent 12.5 h on other professional activities. Greater than 40% of residents were "at risk" for depression and suicide based on physician well-being index scores. Four major themes associated with education and rest were identified: 1) duty hour definitions and reporting mechanisms do not completely reflect the amount of work residents perform, 2) quality patient care and educational opportunities do not fit neatly within the duty hour framework, 3) resident perceptions of duty hours are impacted the educational environment, and 4) long work hours and lack of adequate rest negatively affect well-being. CONCLUSIONS: The breadth and depth of trainee job demands are not accurately captured by current duty hour reporting mechanisms, and residents do not believe that their current work hours allow for adequate rest or even completion of other clinical or academic tasks outside of the hospital. Many residents are unwell. Duty hour policies and resident well-being may be improved with a more holistic accounting of resident job demands and greater attention to the resources that residents have to offset those demands.

Prolonging the zone 1 aortic occlusion time to 4 hours using a partial resuscitative endovascular balloon in a swine model.

BACKGROUND: The clinical usage of the resuscitative endovascular balloon occlusion of the aorta (REBOA) is limited by distal ischemia resulting from complete aortic occlusion. We hypothesized that animals would physiologically tolerate the prolonged partial occlusion using the novel partially occluding REBOA (pREBOA) with survivable downstream injuries. METHODS: This study used the pREBOA-PRO catheter in a previously established swine model. Female Yorkshire swine (n = 10) underwent a volume-controlled hemorrhage (40% estimated blood). After 1 hour of shock (mean arterial pressure, 28-32 mm Hg), animals were randomized to partial occlusion for either 2 hours or 4 hours. The pREBOA was inflated in zone 1 to achieve partial occlusion defined as a distal systolic blood pressure (SBP) of 20 ± 2 mm Hg. The balloon was deflated at the end of the occlusion period, and animals were resuscitated for 2 hours. Tissues were examined for gross and histologic injury. The primary endpoint was histologic organ injury, and secondary end points were hemodynamic variables and degree of distal organ ischemia. RESULTS: All animals survived to the endpoint. Both groups had similar proximal and distal SBP at baseline, with a divergence of pressures ranging from 55 mm Hg to 90 mm Hg on inflation. The lactate levels increased throughout the occlusion and decreased approximately 40% during the observation period. More animals required norepinephrine and fluid in the 4-hour group compared with the 2-hour group. There was no gross small bowel ischemia noted in the 2-hour animals. The 4-hour group had surgically resectable patchy short segment ischemia. Neither group showed nonsurvivable organ ischemia on pathology or laboratory values. CONCLUSION: This is the first study showing that the zone 1 aorta can be occluded for over 4 hours using a new pREBOA device without need for balloon titration. In conclusion, simple changes in balloon design offer reliable partial aortic occlusion, with potentially survivable and surgically manageable downstream injuries.

Risk factors for recurrence in blunt traumatic abdominal wall hernias: A secondary analysis of a Western Trauma association multicenter study.

BACKGROUND: Few studies have investigated risk factors for recurrence of blunt traumatic abdominal wall hernias (TAWH). METHODS: Twenty trauma centers identified repaired TAWH from January 2012 to December 2018. Logistic regression was used to investigate risk factors for recurrence. RESULTS: TAWH were repaired in 175 patients with 21 (12.0%) known recurrences. No difference was found in location, defect size, or median time to repair between the recurrence and non-recurrence groups. Mesh use was not protective of recurrence. Female sex, injury severity score (ISS), emergency laparotomy (EL), and bowel resection were associated with hernia recurrence. Bowel resection remained significant in a multivariable model. CONCLUSION: Female sex, ISS, EL, and bowel resection were identified as risk factors for hernia recurrence. Mesh use and time to repair were not associated with recurrence. Surgeons should be mindful of these risk factors but could attempt acute repair in the setting of appropriate physiologic parameters.

"The Story I Will Never Forget": Critical Incident Narratives in Surgical Residency.

OBJECTIVE: We sought to better understand what defines a critical incident experience for the surgical trainee. SUMMARY BACKGROUND DATA: Critical incidents are formative moments stamped indelibly on one's memory that shape professional identity. The critical incident technique-using participants' narratives to identify patterns and learn from their perceptions-has been explored in some healthcare settings, but there has been no inquiry within surgery. METHODS: Surgical residents at 5 residency programs (1 community, 1 university-affiliated, 3 university) were surveyed using an online questionnaire from November to December 2020. Convenience sampling was used to identify the study population. Participants were invited to write about formative, impactful experiences in training. Interpretive description was the qualitative methodology used to locate information, analyze, and record patterns in the data. Individual responses were categorized and assessed for overlying themes. RESULTS: Overall, 28 narratives were collected from surgery residents in 3 specialties (general surgery, plastic surgery, and urology), with postgraduate year representation of post-graduate years 1 to 6. Respondents were 40% female. Nineteen of the narratives reported a negative experience. Four themes were identified from responses: 1) growth through personal self-reflection, 2) difficult interpersonal interactions, 3) positive team dynamics as a psychological safety net, and 4) supportive program cultures that promote learning. CONCLUSIONS: Critical incident narratives among surgical residents indicate that unforgettable and formative experiences-both positive and negative- occur in 4 domains: within the individual, within a relationship, among a team, and within a program. Further exploring these domains in surgical training will inform optimal educational programming to support trainee development and wellbeing.

Assessment of Determinants of Value in Carotid Endarterectomy.

BACKGROUND: Over 150,000 carotid endarterectomies (CEA) are performed annually worldwide, accounting for $900 million in the United States alone. How cost/spending and quality are related is not well understood but remain essential components in maximizing value. We sought to identify determinants of variability in hospital 90-day episode value for CEA. METHODS: Medicare and private-payer admissions for CEA from January 2, 2014 to August 28, 2020 were linked to retrospective clinical registry data for hospitals in Michigan performing vascular surgery. Hospital-specific, risk-adjusted, 30-day composite complications (defined as reoperation, new neurologic deficit, myocardial infarction, additional procedure including CEA or carotid artery stenting, readmission, or mortality) and 30-day risk-adjusted, price-standardized total episode payments were used to categorize hospitals into low or high value by defining the intersection between complications and spending. RESULTS: A total of 6,595 patients across 39 hospitals were identified across both datasets. Patients at low-value hospitals had a higher rate of 30-day composite complications (17.9% vs. 10.1%, P < 0.001) driven by a significantly higher rate of reoperation (3.0% vs. 1.4%, P = 0.016), readmission (10.7% vs. 6.2%, P = 0.012), new neurologic deficit (4.6% vs. 2.3%, P = 0.017), and mortality (1.6% vs. 0.6%, P < 0.049). Mean total episode payments were $19,635 at low-value hospitals compared to $15,709 at high-value hospitals driven by index hospitalization ($10,800 vs. $9,587, P = 0.002), professional ($3,421 vs. $2,827, P < 0.001), readmission ($3,011 vs. $1,826, P < 0.001), and post-acute care payments ($2,335 vs. $1,486, P < 0.001). Findings were similar when only including patients who did not suffer a complication. CONCLUSIONS: There is tremendous variation in both quality and payments across hospitals included for CEA. Importantly, costs were higher at low-value hospitals independent of postoperative complication. There appears to be little to no relationship between total episode spending and surgical quality, suggesting that improvements in value may be possible by decreasing total episode cost without affecting surgical outcomes.

"Why would you want to do that?"Surgical Interns Reflect on Discouragement From Entering Surgical Fields.

INTRODUCTION: Decreasing numbers of medical students are choosing to pursue surgical careers. This study highlights individual experiences of surgical interns receiving discouragement from pursuing surgery as a career. METHODS: We interviewed 24 incoming surgical interns from 7 institutions and 7 surgical subspecialties about their experiences with discouragement from surgery. RESULTS: All surgical interns discussed experiencing discouragement from pursuing surgery as a career. Family, friends, the general public, and medical professionals, including surgeons, served as sources of discouragement. Reasons for discouragement fell into 3 main themes: The Surgeon and Surgical Culture, The Sacrifices, and The Sexism. Despite its pervasiveness, participants reconciled the discouragement received. DISCUSSION: Discouragement from surgery is pervasive and centered around surgeon stereotypes and perceptions of surgical culture, significant personal sacrifices required, and traditional gender-related expectations. These results highlight the importance of individual surgeons' comments on student experience and can be used to improve the perception of surgery amongst prospective interns.

How We Do It: An Innovative General Surgery Mentoring Program.

OBJECTIVE: The taxing nature of surgery residency is well-documented in the literature, with residents demonstrating high rates of burnout, depression, suicidal thoughts, sexual harassment, and racial discrimination. Mentoring has been shown to improve camaraderie, address challenges of underrepresentation in medicine, and be associated with lower burnout. However, existing formal mentoring programs tend to be career-focused and hierarchal without opportunity to discuss important sociocultural issues. An innovative approach is needed to address these cultural and anthropological issues in surgery residencies while creating camaraderie and learning alternative perspectives across different levels of training. We sought to describe the framework we used to fill these needs by creating and implementing a novel mentoring program. DESIGN: A vertical, near-peer mentoring system of 7 groups was created consisting of the following members: 1 to 2 medical students, a PGY-1 general surgery resident, a PGY-4 research resident, and a faculty member. Meetings occur every 3 to 4 months in a casual setting with the first half of the meeting dedicated to intentional reflection and the second half focused on an evidence-based discussion regarding a specific topic in the context of surgery (i.e., burnout, discrimination, allyship, and finding purpose). SETTING: Program implementation took place at the University of Michigan in Ann Arbor, MI. PARTICIPANTS: Medical students, general surgery residents, and general surgery faculty were recruited. CONCLUSIONS: We have successfully launched the pilot year of a cross-spectrum formal mentoring program in general surgery. This program emphasizes camaraderie throughout training while providing opportunities for evidence-based discussion regarding sociocultural topics. We have included increased opportunities for community inclusivity and mentoring while allowing trainees and faculty members to discuss sensitive topics in a supportive environment. We plan to continue developing the program with robust evaluation and to expand the program to other surgical specialties and to other institutions.

Reliability of hospital-level mortality in abdominal aortic aneurysm repair.

OBJECTIVE: The relationship between volume and surgical outcomes has been shown for a variety of surgical procedures. The effects in abdominal aortic aneurysm repair have continued to be debated. Reliability adjustment has been used as a method to remove statistical noise from hospital-level outcomes. However, its impact on aortic aneurysm repair is not well understood. METHODS: We used prospectively collected data from the Vascular Quality Initiative to identify all patients who had undergone abdominal aortic aneurysm repair from 2003 to 2019. We first calculated the hospital-level risk-adjusted 30-day mortality rates. We subsequently used hierarchical logistic regression modeling to adjust for measurement reliability using empirical Bayes techniques. The effect of volume on risk- and reliability-adjusted mortality rates was then assessed using linear regression. RESULTS: Between 2003 and 2019, 67,073 abdominal aortic aneurysms were repaired, of which 11,601 (17.3%) were repaired with an open approach. The median annual volume was 7.4 (interquartile range, 3.0-13.3) for open repairs and 35.4 (interquartile range, 18.8-59.8) for endovascular repairs. Of the 223 hospitals that had performed open repairs during the study period, only 11 (4.9%) had performed ≥15 open repairs annually, and the risk-adjusted mortality rates varied from 0% to 75% across all centers. After reliability adjustment, the variability of the risk-adjusted mortality rates had decreased significantly to 1.3% to 8.2%. The endovascular repair risk-adjusted mortality rate variability had decreased from 0% to 14.3% to 0.3% to 2.8% after reliability adjustment. A decreasing trend in mortality was found with increasing an annual case volume for open repair with each additional annual case associated with a 0.012% decrease in mortality (P = .05); however, the relationship was not significant for endovascular repair (P = .793). CONCLUSIONS: We found that most hospitals do not perform a sufficient number of annual cases to generate a reliable center-specific mortality rate for open aneurysm repair. Center-specific mortality rates for low-volume centers should be viewed with caution, because a substantial proportion of the variation for these outcomes will be statistical noise rather than true center-level differences in the quality of care.

Hardship and Humanity: A Closer Qualitative Look at Surgical Training and Its Effects on Trainees From the Perspectives of Loved Ones.

OBJECTIVE: The aim of this study was to obtain novel perspectives regarding the effects that surgical training has on the well-being of trainees. SUMMARY BACKGROUND DATA: Improving trainee well-being is a national concern given high rates of burnout, depression, and suicide among physicians. Supporters of surgical trainees may offer new perspectives regarding the effects of surgical training and point to strategies to optimize trainee wellness. METHODS: This qualitative study employs semi-structured interviews of 32 support persons of trainees at a single tertiary care center with multiple surgical training programs. Interviews focused on perspectives related to supporting a surgical trainee. Interview transcripts underwent qualitative analysis with semantic and conceptual coding. Themes related to effects of training on trainee wellness are reported. RESULTS: Four themes were identified: Who Can Endure the Most Hardship?-trainee attributes and programmatic factors contribute to trainees feeling the need to constantly endure the most hardship; Consequences of Hardship-constantly enduring hardships has significant negative effects on wellness; Trainees are Humans-trainees are people with basic human needs, especially the need for worth; Research Time as Refuge-dedicated research time is treated as an oasis away from clinical hardships. CONCLUSIONS: Perspectives from support persons can offer valuable insight into the wellness needs of surgical trainees. According to support persons, surgical training profoundly negatively impacts trainee wellness. Unlike during clinical training, dedicated research time is a period during which wellness can be prioritized. Programs should provide greater attention to mitigating the negative ramifications of surgical training and promoting wellness in a longitudinal fashion throughout training.

Resident Perceptions of Faculty Behaviors Promoting Learner Operative Skills and Autonomy.

OBJECTIVE: To better understand the resident perceived faculty factors associated with the promotion of resident operative skill and autonomy DESIGN: Qualitative retrospective analysis utilizing anonymous open-ended comments from residents on department of surgery faculty teaching evaluations and cross references them to observed faculty entrustment scores SETTING: Single tertiary midwestern allopathic academic medical center using data obtained between January 2016-August 2019 PARTICIPANTS: Forty-six resident and fourteen faculty surgeons from general, plastic, thoracic, and vascular surgery sections. RESULTS: Themes of personal traits, the working environment created, and teaching techniques employed were identified across resident promoting attendings and resident limiting attendings. Promoting attendings employed preoperative goal setting, increased operative autonomy, and postoperative feedback while creating environments conducive to learning by promoting teamwork and collaboration. Alternatively, limiting attendings used more ineffective teaching techniques including micromanaging, lack of delegation, and treating residents as observers. Additionally, trainees described these operating room environments as stressful and strained. CONCLUSIONS: Qualitative analysis of resident teaching evaluations of attending surgeons highlights the importance of relationships between learner and teacher, the learning environment, and teaching techniques. Continuous professional development programs centered on entrustment and promoting behaviors have the potential to disseminate strategies to enhance educator skills among surgeons.

Management of blunt traumatic abdominal wall hernias: A Western Trauma Association multicenter study.

BACKGROUND: Blunt traumatic abdominal wall hernias (TAWH) occur in approximately 15,000 patients per year. Limited data are available to guide the timing of surgical intervention or the feasibility of nonoperative management. METHODS: A retrospective study of patients presenting with blunt TAWH from January 2012 through December 2018 was conducted. Patient demographic, surgical, and outcomes data were collected from 20 institutions through the Western Trauma Association Multicenter Trials Committee. RESULTS: Two hundred and eighty-one patients with TAWH were identified. One hundred and seventy-six (62.6%) patients underwent operative hernia repair, and 105 (37.4%) patients underwent nonoperative management. Of those undergoing surgical intervention, 157 (89.3%) were repaired during the index hospitalization, and 19 (10.7%) underwent delayed repair. Bowel injury was identified in 95 (33.8%) patients with the majority occurring with rectus and flank hernias (82.1%) as compared with lumbar hernias (15.8%). Overall hernia recurrence rate was 12.0% (n = 21). Nonoperative patients had a higher Injury Severity Score (24.4 vs. 19.4, p = 0.010), head Abbreviated Injury Scale score (1.1 vs. 0.6, p = 0.006), and mortality rate (11.4% vs. 4.0%, p = 0.031). Patients who underwent late repair had lower rates of primary fascial repair (46.4% vs. 77.1%, p = 0.012) and higher rates of mesh use (78.9% vs. 32.5%, p < 0.001). Recurrence rate was not statistically different between the late and early repair groups (15.8% vs. 11.5%, p = 0.869). CONCLUSION: This report is the largest series and first multicenter study to investigate TAWHs. Bowel injury was identified in over 30% of TAWH cases indicating a significant need for immediate laparotomy. In other cases, operative management may be deferred in specific patients with other life-threatening injuries, or in stable patients with concern for bowel injury. Hernia recurrence was not different between the late and early repair groups. LEVEL OF EVIDENCE: Therapeutic/care management, Level IV.

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.

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).