Burnout: A Call to Action From the AUA Workforce Workgroup.

PURPOSE: We hypothesize burnout has failed to improve and certain demographics may be disproportionately affected. MATERIALS AND METHODS: The AUA Workforce Workgroup examined work from the annual AUA Census over the past several years. Particular to this study, relevant burnout-related data were examined from the past 5 years. RESULTS: In 2021, 36.7% of urologists reported burnout compared to 36.2% in 2016. Burnout in men decreased from 36.3% to 35.2%, but increased in women from 35.3% to 49.2%. When examined by age, the largest increases in burnout were seen in those <45 years old, increasing from 37.9% to 44.8%, followed by 45-54 years old, increasing from 43.4% to 44.6%. When asked about the effect of COVID-19 on burnout, 54% of urologists didn't feel COVID-19 impacted burnout. Beyond burnout, only 25.0% of men and 4.6% of women reported no conflict between work and personal responsibilities, while 25.7% of men and 44.7% of women resolved these conflicts in favor of work or were unable to resolve them. Of respondents, 22.5% of men and 37.1% of women were "dissatisfied" with work-life balance. Similarly, 33.6% of men reported their work schedule does not leave enough time for personal/family life, compared to 57.5% of women. CONCLUSIONS: Overall, urologists have higher burnout now when compared to 2016. The gender discrepancy has vastly widened with women experiencing burnout at an increased rate of 14% compared to 2016, while burnout in men decreased by 1%. Burnout has increased the most in those <45 years old. Further action is needed to substantiate the causes of burnout.

Investigation of urology intraoperative events leading to root cause analysis at national VA medical centers.

INTRODUCTION: Adverse events in urologic procedures are poorly studied. This study analyzes the Veterans Health Administration (VHA) Root Cause Analysis (RCA) data for patient safety adverse events during urologic procedures performed in a VHA operating room (OR). MATERIALS AND METHODS: The VHA National Center for Patient Safety RCA database was queried for fiscal years 2015-2019 using urologic terms including vasectomy, prostatectomy, nephrectomy, cystectomy, cystoscopy, lithotripsy, ureteroscopy, urethral, TURBT, etc. RCAs for events outside a VHA OR were excluded. Cases were categorized based on type of event. RESULTS: Sixty-eight RCAs were identified for 319,713 urologic procedures. The most common pattern identified was equipment or instrument issue, including broken scopes or smoking light cords, with 22 cases. Eighteen RCAs involved a sentinel event, including 12 retained surgical items (RSI) (surgical sponge, retained guidewire) and 6 wrong site surgeries (WSS) (incorrect laterality, wrong procedure) representing a serious safety event rate of 1 in 17,762 procedures. In addition, 8 RCAs pertained to medical or anesthesia events (incorrect dosing, postoperative myocardial infarction), 7 to pathology errors (missing or mislabeled specimen), 4 to incorrect patient information or consent, and 4 to surgical complications (hemorrhage, duodenal injury). In 2 cases there was inappropriate work up. One case caused a delay in treatment, one case had an incorrect count, and one case identified lack of credentialing. CONCLUSIONS: RCAs of patient safety adverse events occurring during urologic OR procedures highlight the need for targeted quality improvement projects to prevent WSS events, prevent RSI events, and maintain properly functioning equipment.

Operative duration and short term morbidity and mortality following radical cystectomy with urinary diversion.

INTRODUCTION: To elucidate the association between operative duration (OD) and postoperative complications, which has been poorly studied in radical cystectomy. We hypothesize an increase in morbidity in radical cystectomy cases which have a longer OD. MATERIALS AND METHODS: Data from the National Surgical Quality Improvement Program (NSQIP) between the years 2012 and 2018 were reviewed for radical cystectomy with ileal conduit urinary diversion or continent diversion. Total operative time was divided into deciles and stratified comparisons were made using univariable and multivariable analysis. RESULTS: A total of 11,128 patients were examined. OD by minutes was stratified into the following deciles: 90-201, 202-237, 238-269, 270-299, 300-330, 331-361, 362-397, 398-442, 443-508, > 508. Operative times were shorter for patients with advanced age (p < 0.001), male gender (p < 0.001), low body mass index (BMI) (p < 0.001), bleeding diathesis (p = 0.019), COPD (p = 0.004), and advanced ASA class (p < 0.001). Complications significantly associated with prolonged OD included surgical site infection, urinary tract infection, sepsis/septic shock, renal failure and venous thromboembolism. On multivariate analysis, factors predictive of perioperative morbidity included presence of bleeding disorder (OR 1.70, 95% confidence intervals (CI) 1.37-2.12, p < 0.001), ASA Class IV-V compared to I-II (OR 2.26, 95% CI 1.89-2.72, p < 0.001), and prolonged operative time (tenth decile OR 3.05, 95% CI 2.55-3.66, ninth decile OR 2.11 95% CI 1.77-2.50, third decile OR 1.31, 95% CI 1.11-1.56, second decile OR 1.02, 95% CI 0.86-1.21 compared to first decile, p < 0.001) Conclusion: OD is an independent predictor of post-operative morbidity in patients undergoing radical cystectomy, even when adjusting for patient specific factors. Those patients within the longest decile had over 3-fold increase in the risk of morbidity compared to those with shorter OD.

Incidental prostate cancer at holmium laser enucleation of prostate.

INTRODUCTION: The purpose of this study was to describe the current incidence, risk factors, and management of incidental diagnosis of prostate cancer (iPCa) among patients who underwent holmium laser enucleation of prostate (HoLEP) and have no history of prostate cancer. MATERIALS AND METHODS: We conducted a retrospective review of all patients who underwent HoLEP in our institution between 2013-2020. All patients were offered a PSA screening according to the latest guidelines. We gathered demographic data, perioperative information, and pathologic evaluation. For patients diagnosed with iPCa, we gathered work up, management, and oncologic outcome. We then conducted a univariate and multivariate analysis to find predictive factors for the diagnosis of incidental cancer. RESULTS: The cohort included 777 patients, among them 55 (7.1%) patients with iPCa. The median age of the entire cohort was 71 years, median PSA was 3.9 mg/dL, and median prostate volume of 96 mL. Of those with iPCa, 34 (61.8%) patients had grade-group (GG) 1. Larger prostate size was found to be protective against iPCa, with a 13% risk reduction for every increment of 10 mL in prostate size. For prostates smaller than 100 mL, iPCa rate was 12.6%. Older age and smaller prostate volume were found to predict GG2-and-above iPCa. CONCLUSIONS: iPCa at HoLEP is rare, with clinically significant cancer being even rarer. Smaller preoperative prostate was found to be a predictive factor for iPCa. Our results provide an insight into the current risk and predictive factors to iPCa and can be used to guide surgeons and patients in the preoperative recommendations and informed consent process.

Twitter and academic Urology in the United States and Canada: a comprehensive assessment of the Twitterverse in 2019.

OBJECTIVE: To provide the first comprehensive analysis of the Twitterverse amongst academic urologists and programmes in North America. METHODS: Using national accreditation and individual programme websites, all active urology residency programmes (USA and Canada) and academic Urology faculty at these programmes were identified. Demographic data for each programme American Urological Association [AUA] section, resident class size) and physician (title, fellowship training, Scopus Hirsch index [H-index] and citations) were documented. Twitter metrics (Twitter handle, date joined, # tweets, # followers, # following, likes) for programmes and physicians were catalogued (data capture: March-April 2019). Descriptive analyses and temporal trends in Twitter utilisation amongst programmes and physicians were assessed. Multivariable logistic regression was used to identify predictors of Twitter use. RESULTS: In all, 156 academic programmes (143 USA, 13 Canada) and 2214 academic faculty (2015 USA, 199 Canada) were identified. Twitter utilisation is currently 49.3% and 34.1% amongst programmes and physicians, respectively, and continues to increase. On multivariable analysis, programmes with 3-5 residents/year and programmes with a higher percentage of faculty Twitter engagement were more likely to have Twitter accounts. From a physician perspective, those with fellowship training, lower academic rank (Clinical Instructor, Assistant Professor, Associate Professor vs Professor) and higher H-indices were more likely to have individual Twitter accounts. CONCLUSION: There is a steady increase in Twitter engagement amongst Urology programmes and academic physicians. Faculty Twitter utilisation is an important driver of programme Twitter engagement. Twitter social media activity is strongly associated with academic productivity, and may in fact drive academic metrics. Within Urology, social media presence appears to be proportional to academic activity.

Industry payments to female pelvic medicine and reconstructive surgeons: an analysis of Sunshine Act open payments from 2014-2017.

INTRODUCTION AND HYPOTHESIS: We aim to examine the financial relationship between industry and female pelvic medicine and reconstructive surgeons (FPMRS) during the first four full calendar years since the implementation of the Sunshine Act. METHODS: All board-certified FPMRS specialists were identified using the American Board of Medical Specialties directory. Program directors (PDs) were identified using an Accreditation Council for Graduate Medical Education (ACGME) database. All identified physicians were categorized by gender, specialty, and American Urological Association (AUA) region. Payment data for each individual from 2014 to 2017 were accessed using the Centers for Medicare and Medicaid Services (CMS) Open Payments website. Statistical analyses were performed to elucidate payment trends. RESULTS: Of the 1,307 FPMRS physicians identified, 25.1% (n = 328) are urology-trained and 74.9% (n = 979) are obstetrics/gynecology (OB/GYN)-trained. Of all physicians analyzed, 6.8% had no reported payments over the 4-year period. 90.1%, 86.5%, 85.3%, and 84.4% received some sort of payment in 2014 to 2017 respectively. Median total payments for all physicians decreased yearly, whereas mean payments decreased from 2014 to 2015 before increasing in all subsequent years. Median general payments were higher for men versus women, urology-trained versus OB/GYN-trained, and PDs versus non-PDs in all years analyzed. The largest contributor to overall payments was the "others" compensation category, which includes gifts, royalties, honoraria, and non-continuing medical education speaking engagements. CONCLUSIONS: Since institution of the Sunshine Act, the percentage of physicians receiving payments has decreased each year. Additionally, there has been a decrease in median total payments and an increase in yearly research payments in all years analyzed.

How I Do It: Anticoagulation management for common urologic procedures.

Appropriate perioperative management of antithrombotic medications is critical; for every patient, the risk of bleeding must be balanced against individual risk of thrombosis. There has been a rapid influx of new antithrombotic therapies in the past 5 years, yet there is a lack of clear and concise guidelines on the management of anticoagulant and antiplatelet therapy during urologic surgery. Here we describe our approach to perioperative antithrombotic counseling, including the timing of stopping and restarting these medications. These practice guidelines have been developed in consultation with the Vascular Medicine service at our institution as well as after a review of current literature, and apply to common urologic procedures. Many cases are complex and require medical consultation or a multidisciplinary approach to management. We believe that by presenting our systematic method of antithrombotic management, including when to involve other discplines, we can increase knowledge and comfort amongst urologists in managing these medications in the perioperative period.

Next-generation DNA sequencing for infected genitourinary implants: How I do it.

Infection of artificial urinary sphincters or inflatable penile prostheses is one of the most devastating complications after prosthetic surgery and can have a significant impact on a quality of life. Patients undergoing revision surgery with or without device replacement may have increased risk for infection when compared to initial primary surgery. As such, surgeons may utilize traditional culture results to direct antimicrobial therapy for these patients. Unfortunately, culture results can be inconclusive in up to one-third of the time even in the setting of active device infection. Next-generation sequencing (NGS) of DNA is an emerging technology capable of sequencing entire bacterial genomes and has the potential to identify microbial composition in explanted devices. Herein, we describe our institutional experience on NGS utilization in patients with genitourinary prostheses. We also highlight our methods and techniques to inform readers on the potential practices that can enhance the utility and diagnostic yield of this new and upcoming technology.

Stress Urinary Incontinence post-Holmium Laser Enucleation of the Prostate: a Single-Surgeon Experience.

PURPOSE: To identify incidence and predictors of stress urinary incontinence (SUI) following Holmium laser enucleation of the prostate (HoLEP). MATERIALS AND METHODS: We performed a retrospective review of 589 HoLEP patients from 2012-2018. Patients were assessed at pre-operative and post-operative visits. Univariate and multivariate regression analyses were performed to identify predictors of SUI. RESULTS: 52/589 patients (8.8%) developed transient SUI, while 9/589 (1.5%) developed long-term SUI. tSUI resolved for 46 patients (88.5%) within the first six weeks and in 6 patients (11.5%) between 6 weeks to 3 months. Long-term SUI patients required intervention, achieving continence at 16.4 months on average, 44 men (70.9%) with incontinence were catheter dependent preoperatively. Mean prostatic volume was 148.7mL in tSUI patients, 111.6mL in long-term SUI, and 87.9mL in others (p < 0.0001). On univariate analysis, laser energy used (p < 0.0001), laser "on" time (p=0.0204), resected prostate weight (p < 0.0001), overall International Prostate Symptom Score (IPSS) (p=0.0005), and IPSS QOL (p=0.02) were associated with SUI. On multivariate analysis, resected prostate weight was predictive of any SUI and tSUI, with no risk factors identified for long-term SUI. CONCLUSION: Post-HoLEP SUI occurs in ~10% of patients, with 1.5% continuing beyond six months. Most patients with tSUI recover within the first six weeks. Prostate size >100g and catheter dependency are associated with increased risk tSUI. Larger prostate volume is an independent predictor of any SUI, and tSUI.

Knowledge Gaps in Urologic Care of Female Spinal Cord Injury Patients.

PURPOSE OF REVIEW: We highlight the substantial gaps in knowledge on urologic care of female spinal cord injury (SCI) patients. RECENT FINDINGS: Males account for approximately 80% of people living with SCI in developed nations. Although there is a robust body of literature in some aspects of urologic care of individuals with SCI, such as treatments for neurogenic detrusor overactivity, there are relatively few studies focusing specifically on females. There are also few studies focusing on other aspects of urologic care of women with SCI such as sexual dysfunction, pelvic organ prolapse, and bladder cancer. Established guidelines for bladder management exist, generally recommending intermittent catheterization, but the fact remains that a substantial number of women with SCI utilize indwelling catheters for bladder management. There remains a paucity of literature using patient-reported measures regarding both outcomes and experiences of urologic management in the SCI population. Bladder management is challenging for many women with SCI. There are few studies on other urologic concerns in women with SCI.

Holmium laser enucleation of the prostate (HoLEP): a review and update.

INTRODUCTION: Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) is one of the most common diseases affecting the aging man, with almost 80% of men greater than 70 affected. Historically, transurethral resection of the prostate (TURP) has been considered the historical gold standard in the treatment of LUTS due to BPH for many years, contemporary literature indicates that holmium laser enucleation of the prostate (HoLEP) has replaced TURP and open simple prostatectomy as the size independent surgical gold standard for BPH treatment. MATERIALS AND METHODS: In this review, we discuss the current techniques utilized, outcomes and safety, as well as the long term durability of results. Adverse events associated with the HoLEP procedure, both enucleation and morcellation, are covered as well. RESULTS: HoLEP has a robust body of literature supporting the technique, which demonstrates its ability to surpass other surgical BPH procedures, including TURP and open simple prostatectomy. Additionally, there is long term durability of both subjective and objective outcomes greater than 10 years associated with this procedure. One randomized trial showed specific postoperative outcome measures that were superior to TURP at 7 years of follow up, including Qmax (4.36 mL/s improvement), erectile function (2.39 points improvement on the IIEF erectile function section), and weight of prostate removed (15.7 grams greater), while other studies have shown greater reduction in postoperative PSA, lower detrusor pressure at Qmax, and more. CONCLUSIONS: Overall, HoLEP has proven to be an extremely durable and effective treatment for patients suffering from LUTS due to BPH. Both the Europeans and AUA guidelines on the surgical treatment of BPH recommend HoLEP as a size-independent treatment option for those men with moderate to severe symptoms. HoLEP is an excellent option for many patients who may not be good candidates for other procedures based on prostate size, age, or bleeding risk.

Aquablation of the prostate: a review and update.

INTRODUCTION: Invasive procedures, such as transurethral resection of the prostate (TURP), have long been the gold standard therapy for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). In recent years, newer treatment modalities have arisen, such as Aquablation, with similar efficacy and improved adverse event profiles, with particular emphasis on postoperative sexual function. MATERIALS AND METHODS: Aquablation is a new technology that utilizes machine-controlled water jets to ablate the soft tissue of the prostate as determined by the doctor. In this review, we will discuss the techniques currently being used to complete this procedure, the outcomes and safety, and finally, the long term data as well as the adverse events associated with Aquablation. RESULTS: Aquablation is rapidly effective in treating patients with LUTS due to BPH. Critically, in head to head comparison with TURP, Aquablation has equivalent objective results with much shorter resections times, and significantly less sexual side effects. Currently, the literature only reports results extending to 12 months post-procedure, and therefore long term durability of results beyond this time point remains unknown. CONCLUSIONS: Aquablation is a safe and effective option for treating LUTS secondary to BPH. Aquablation is a new surgical option that shows very promising short term results, in particular, due to its short resection time regardless of gland size and low rate of sexual side effects. This technology still requires further investigation to confirm durability and efficacy over time.

A retrospective comparison of diode to holmium for laser enucleation of the prostate.

INTRODUCTION: Holmium endoscopic laser enucleation of the prostate (HoLEP) is a well-established alternative to traditional transurethral resection and open prostatectomy for the treatment of benign prostatic hyperplasia (BPH). We investigate the 1470 nm diode laser for enucleation as an alternative to HoLEP. The safety, efficacy, and initial outcomes of diode enucleation of the prostate (DiLEP), when compared to HoLEP, were examined. MATERIALS AND METHODS: We reviewed records of 50 patients who underwent DiLEP between 2012 and 2015 and matched them with 50 HoLEP patients during the same time period. Objective evaluation of efficacy was determined by comparing preoperative post-void residual volume (PVR) and peak flow (Qmax) to postoperative values at 4-16 weeks and 1 year following surgery. Subjective evaluation was measured using the International Prostate Symptom Score (IPSS) before and after the operation. Safety was evaluated by the development of persistent Clavien-Dindo grade 1, or 2 or higher postoperative complications. Statistical analyses were conducted using chi-squared and paired Student's t-tests. RESULTS: Subjective and objective postoperative results showed no difference between DiLEP and HoLEP. Average PVR volume following DiLEP was 47.1 mL at 1 year. The mean increase in Qmax was 16.4 mL/s at 1 year. The IPSS improved by a mean of 12.7 points, and by 2.6 points on quality of life questioning at 1 year post operation. Compared to HoLEP patients there was no statistically significant difference. Safety assessments were the same across both procedures. CONCLUSIONS: Diode laser is safe and effective for use in patients with BPH, with no significant difference in outcomes compared to HoLEP.

Glutamate oxaloacetate transaminase enables anaplerotic refilling of TCA cycle intermediates in stroke-affected brain.

Ischemic stroke results in excessive release of glutamate, which contributes to neuronal cell death. Here, we test the hypothesis that otherwise neurotoxic glutamate can be productively metabolized by glutamate oxaloacetate transaminase (GOT) to maintain cellular energetics and protect the brain from ischemic stroke injury. The GOT-dependent metabolism of glutamate was studied in primary neural cells and in stroke-affected C57-BL6 mice using magnetic resonance spectroscopy and GC-MS. Extracellular Glu sustained cell viability under hypoglycemic conditions and increased GOT-mediated metabolism in vitro Correction of stroke-induced hypoxia using supplemental oxygen in vivo lowered Glu levels as measured by 1H magnetic resonance spectroscopy. GOT knockdown abrogated this effect and caused ATP loss in the stroke-affected brain. GOT overexpression increased anaplerotic refilling of tricarboxylic acid cycle intermediates in mouse brain during ischemic stroke. Furthermore, GOT overexpression not only reduced ischemic stroke lesion volume but also attenuated neurodegeneration and improved poststroke sensorimotor function. Taken together, our results support a new paradigm that GOT enables metabolism of otherwise neurotoxic extracellular Glu through a truncated tricarboxylic acid cycle under hypoglycemic conditions.-Rink, C., Gnyawali, S., Stewart, R., Teplitsky, S., Harris, H., Roy, S., Sen, C. K., Khanna, S. Glutamate oxaloacetate transaminase enables anaplerotic refilling of TCA cycle intermediates in stroke-affected brain.

Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle injury.

The efficacy and optimization of poststroke physical therapy paradigms is challenged in part by a lack of objective tools available to researchers for systematic preclinical testing. This work represents a maiden effort to develop a robot-assisted mechanical therapy (RAMT) device to objectively address the significance of mechanical physiotherapy on poststroke outcomes. Wistar rats were subjected to right hemisphere middle-cerebral artery occlusion and reperfusion. After 24 h, rats were split into control (RAMT-) or RAMT+ groups (30 min daily RAMT over the stroke-affected gastrocnemius) and were followed up to poststroke d 14. RAMT+ increased perfusion 1.5-fold in stroke-affected gastrocnemius as compared to RAMT- controls. Furthermore, RAMT+ rats demonstrated improved poststroke track width (11% wider), stride length (21% longer), and travel distance (61% greater), as objectively measured using software-automated testing platforms. Stroke injury acutely increased myostatin (3-fold) and lowered brain-derived neurotrophic factor (BDNF) expression (0.6-fold) in the stroke-affected gastrocnemius, as compared to the contralateral one. RAMT attenuated the stroke-induced increase in myostatin and increased BDNF expression in skeletal muscle. Additional RAMT-sensitive myokine targets in skeletal muscle (IL-1ra and IP-10/CXCL10) were identified from a cytokine array. Taken together, outcomes suggest stroke acutely influences signal transduction in hindlimb skeletal muscle. Regimens based on mechanical therapy have the clear potential to protect hindlimb function from such adverse influence.-Sen, C. K., Khanna, S., Harris, H., Stewart, R., Balch, M., Heigel, M., Teplitsky, S., Gnyawali, S., Rink, C. Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle injury.

Rectourethral fistula: a rare complication after HoLEP.

We report a rare complication of rectourethral fistula formation 6 weeks after a 70-year-old man underwent an uneventful HoLEP procedure. Cystourethrogram confirmed the diagnosis and the patient was managed conservatively with chronic indwelling catheter placement for 6 weeks. After this, his symptoms resolved completely and a repeat cystourethrogram showed marked resolution of the fistulous tract. The cause of the fistula formation is believed to be due to a delayed thermal or infectious reaction. Post-procedure follow up is necessary in all patients to monitor for complications that do not arise immediately after surgery.

Dorsal versus lateral plate fixation of finger proximal phalangeal fractures: a retrospective study.

INTRODUCTION: Unstable proximal phalanx fractures are relatively common injuries but consensus of standard treatment is lacking. Outcomes following plate fixation are highly variable, and it remains unclear which factors are predictive for poorer results. The purpose of this study was to compare dorsal and lateral plate fixation of finger proximal phalangeal fractures with regard to factors that influence the outcome. MATERIALS AND METHODS: A retrospective chart review of proximal phalanx fractures treated with dorsal and lateral plating over a 6-year study interval was performed. Demographic data and injury-specific factors were obtained from review of clinic and therapy notes of 42 patients. Fractures were classified based on the OTA classification using preoperative radiographs. Outcomes investigated included final range of motion (ROM) and total active motion (TAM) of all finger joints. Complications and revision surgeries were also analyzed. RESULTS: Fracture comminution, dorsal and a lateral plate position, occupational therapy, and demographic factors did not significantly influence the outcome, complication, and revision rate after plate fixation of finger proximal phalangeal fractures. CONCLUSIONS: Based on the results of this study, no differences in the outcome of finger proximal phalangeal fractures treated by both dorsal and lateral plate fixation were observed. LEVEL OF EVIDENCE: Therapeutic, retrospective comparative, level III.

Excessive α-tocopherol exacerbates microglial activation and brain injury caused by acute ischemic stroke.

The vitamin E family includes both tocopherols and tocotrienols, where α-tocopherol (αTOC) is the most bioavailable form. Clinical trials testing the therapeutic efficacy of high-dose αTOC against stroke have largely failed or reported negative outcomes when a "more is better" approach to supplementation (>400 IU/d) was used. This work addresses mechanisms by which supraphysiologic αTOC may contribute to stroke-induced brain injury. Ischemic stroke injury and the neuroinflammatory response were studied in tocopherol transfer protein-deficient mice maintained on a diet containing αTOC vitamin E at the equivalent human dose of 1680 IU/d. Ischemic stroke-induced brain injury was exacerbated in the presence of supraphysiologic brain αTOC levels. At 48 h after stroke, S100B and RAGE expression was increased in stroke-affected cortex of mice with elevated brain αTOC levels. Such increases were concomitant with aggravated microglial activation and neuroinflammatory signaling. A poststroke increase in markers of oxidative injury and neurodegeneration in the presence of elevated brain αTOC establish that at supraphysiologic levels, αTOC potentiates neuroinflammatory responses to acute ischemic stroke. Exacerbation of microglial activation by excessive αTOC likely depends on its unique cell signaling regulatory properties independent of antioxidant function. Against the background of clinical failure for high-dose αTOC, outcomes of this work identify risk for exacerbating stroke-induced brain injury as a result of supplementing diet with excessive levels of αTOC.