Monitoring performance in laparoscopic gastric bypass surgery using risk-adjusted cumulative sum at 2 high-volume centers.

BACKGROUND: Traditional surgical outcomes are measured retrospectively and intermittently, limiting opportunities for early intervention. OBJECTIVES: The objective of this study was to use risk-adjusted cumulative sum (RA-CUSUM) to track perioperative surgical outcomes for laparoscopic gastric bypass. We hypothesized that RA-CUSUM could identify performance variations between surgeons. SETTING: Two mid-Atlantic quaternary care academic centers. METHODS: Patient-level data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) were abstracted for laparoscopic gastric bypasses performed by 3 surgeons at 2 high-volume centers from 2014 to 2021. Estimated probabilities of serious complications, reoperation, and readmission were derived from the MBSAQIP risk calculator. RA-CUSUM curves were generated to signal observed-to-expected odds ratios (ORs) of 1.5 (poor performance) and .5 (superior performance). Control limits were set based on a false positive rate of 5% (α = .05). RESULTS: We included 1192 patients: Surgeon A = 767, Surgeon B = 188, and Surgeon C = 237. Overall rates of serious complications, 30-day reoperations, and 30-day readmissions were 3.9%, 2.5%, and 5.2% respectively, with expected rates of 4.7%, 2.2%, and 5.8%. RA-CUSUM signaled lower-than-expected (OR < .5) rates of readmission and serious complication in Surgeon A, and higher-than-expected (OR > 1.5) readmission rate in Surgeon C. Surgeon A further demonstrated an early period of higher-than-expected (OR > 1.5) reoperation rate before April 2015, followed by superior performance thereafter (OR < .5). Surgeon B's performance generally reflected expected standards throughout the study period. CONCLUSIONS: RA-CUSUM adjusts for clinical risk factors and identifies performance outliers in real-time. This approach to analyzing surgical outcomes is applicable to quality improvement, root-cause analysis, and surgeon incentivization.

Assessing Content of Accredited Colon and Rectal Surgery Fellowship Websites: Is there Adequate Information for Applicants?

Electronic information is a vital resource used by fellowship applicants. This study aimed to assess the completeness of colon and rectal surgery (CRS) fellowship program online information. Program information on the Association of Program Directors for Colon and Rectal Surgery (APDCRS) website as well as each institutional website was evaluated based on templated criteria. Sixty-eight accredited fellowship programs were identified. Six (9%) programs had complete profiles on the APDCRS platform, with an average of 3.5 details completed per program. Sixty-two (91%) websites were easily accessible. None of these contained all 28 criteria assessed and 47 (69%) contained less than half of assessed content. The most common data point was fellowship program description (96%), while board pass rate (1%) was the least common. Most CRS fellowship websites were grossly incomplete. Electronically available information is vital to fellowship applicants, and programs should try to provide easily accessible information about their program.

Keep it SIMPL: Improved Feedback After Implementation of an App-Based Feedback Tool.

BACKGROUND: Data defining the utility of the system for improving and measuring procedural learning (SIMPL) in surgical education is limited. The aim of this pilot study is to describe the impact of SIMPL on resident and faculty perspectives regarding operative feedback. METHODS: Residents and faculty were surveyed prior to and 6 months after SIMPL implementation. Associations were analyzed using χ2 for categorical and Student's t-test for continuous variables. Statistical significance was defined as P-value < .05. RESULTS: The proportion of residents receiving intraoperative feedback at least once/day increased significantly (35% to 73%, P = .025); there was a trend toward increased postoperative feedback (15% to 33%, P = .201). Faculty reported an increase in intraoperative (55% to 91%, P = .041) and postoperative feedback (21% to 64%, P = .020). Satisfaction with intraoperative feedback improved from a score of 3.50 ± 1.05 to 3.93 ± .62, although not statistically significant (P = .181). Satisfaction with postoperative feedback improved significantly from 2.85 ± .93 to 3.50 ± .65 (P = .032). The proportion of faculty who felt they were providing effective feedback increased (53% to 91%, P = .032). The proportion of residents who perceived that feedback enhanced their surgical skill increased as well (65% to 93%, P = .048). DISCUSSION: Despite a modest increase in frequency of postoperative feedback, perceived quality of feedback improved substantially after implementation of SIMPL. Introduction of SIMPL also increased the amount of feedback provided by faculty intraoperatively. SIMPL, via direct and indirect effects, has a positive impact on the resident operative learning environment. Further work is necessary to examine the influence this may have on resident operative skill and patient outcomes.

Insurance Coverage of Pediatric Bariatric Surgery: a Cross-Sectional Analysis of the USA.

PURPOSE: Pediatric bariatric surgery is increasingly recognized as a safe and effective option for the management of obesity and obesity-related conditions. However, insurance coverage is a key barrier to accessing these procedures. Criteria are variable and often not evidence-based. In an effort to characterize common patterns in insurance coverage, we report coverage criteria for adolescents relative to adults. MATERIALS AND METHODS: We surveyed medical policies of the 50 highest market share health insurance providers in the USA. Private insurer coverage criteria included age, Tanner staging, skeletal maturity, body mass index, procedures covered, medical weight management requirements, co-morbidities, and multidisciplinary team criteria. These were then compared to the American Society for Metabolic and Bariatric Surgery (ASMBS) guidelines. RESULTS: Two thirds (n = 33, 66%) of companies provided inclusion criteria for adolescents. All policies covered RYGB (n = 33), most covered sleeve gastrectomy (n = 32, 97.0%). Obstructive sleep apnea (OSA) (n = 32, 97%), hypertension (HTN) (n = 27, 81.8%), and gastroesophageal reflux disease (GERD) (n = 11, 33.3%) were the three most commonly cited co-morbidities used as inclusion criteria. Tanner staging or skeletal maturity were most commonly used (n = 10, 30.3%). Similarly, twenty (60.6%) insurers required medical weight management programs. Multi-disciplinary teams were required by 81.8% of adolescent policies (n = 27) as described by the ASMBS. Seventeen (51.5%) policies defined providers for these teams, and 10 (30.3%) provided other defined criteria. CONCLUSION: Contrary to ASMBS guidelines, companies commonly require Tanner staging and/or skeletal maturity criteria as well as participation in medical weight management programs. Also, multi-disciplinary team are frequently required but not well defined.

Ten Year Trends in Minimally Invasive Surgery Fellowship.

BACKGROUND: Minimally Invasive Surgery (MIS) is one of the more recently established surgical fellowships, with many candidates applying due to a perception of inadequate exposure to advanced MIS during residency. The desire for advanced training should be reflected in increased competitiveness for fellowship positions. The aim of this study is to determine the desirability of MIS fellowships over time through review of national application data. METHODS: We reviewed the fellowship match statistics obtained from The Fellowship Council, the organizing body behind the MIS fellowship match. Data from January 1, 2008 - December 31, 2019 were included. We compared match rates to other specialties using the National Resident Matching Program, a nonprofit organization established for US residency and some fellowship programs. RESULTS: In the period of 2008 to 2019, the number of certified MIS fellowship programs increased from 124 to 141. While this program expansion was associated with a 19% increase in available positions, the number of applications increased 36%. As a result, the number of positions filled increased from 83% to 97%, but the match rate among US applicants fell from 82% to 71% during this interval. In comparison, the match rates for pediatric surgery, surgical oncology, vascular surgery, and surgical critical care fellowships remained largely unchanged, most recently 50%, 56%, 99%, and 100% respectively. CONCLUSION: Over the last decade, US residents have shown an increased interest in pursuing MIS fellowship positions. As a consequence, the match process for MIS fellowships is becoming increasingly competitive.

Love at First Click: Surgery Residency Websites in the Virtual Era.

INTRODUCTION: Frequently, a residency program's website is the first interaction students interested in surgery have with the program. In the setting of virtual interviews for residency in 2020, the online availability of program information is of heightened importance. We sought to assess how academic versus community-based general surgery residency programs compared with respect to certain details on their websites. METHODS: A total of n = 268 surgery residency programs were investigated. Our database of website characteristics included: direct link to residency website from the American Council on Graduate Medical Education (ACGME) program page, resident research requirement, listing of residents' publications, availability of residents' demographic information, program alumni information, board pass rates, attrition rate, detail of educational/academic activities, residents' evaluation methods, diversity, and mentorship. Inter-group analyses between academic and community-based programs were performed using Pearson's Chi-squared test. RESULTS: Academic and community-based general surgery residency program websites were compared based on twelve (12) different parameters. Statistically significant differences were observed for eight of these comparisons: direct website access from ACGME (p = 0.007), research highlighted (p < 0.001), resident research requirement (p = 0.002), resident demographic information available (p=0.004), alumni information (p = 0.005), resident evaluation methods (p = 0.016), diversity (p < 0.001), and mentorship (p = 0.012). Across these domains, academic programs had more information available on their websites than the community programs did. The program websites did not differ significantly based on the frequency of mentioning resident publications, board pass rate, attrition rate, or resident education. CONCLUSION: Many general surgery programs are lacking detailed information on their websites. The amount of website information available on general surgery residency programs differs when comparing academic and community-based programs.

USMLE Step 1 Is Pass/Fail - Should the ABSITE Follow Suit?

The United States Medical Licensing Examination (USMLE) Step 1 was recently made pass/fail. This decision was controversial largely because of the reliance on USMLE Step 1 scores in resident selection. However, these scores do not correlate with resident ability. In this manuscript, we consider if the American Board of Surgery In-Training Examination (ABSITE) should be pass/fail as well. The ABSITE has been used for "high-stakes" purposes, such as preliminary resident advancement and prospective fellow evaluation, for which it was not intended. Moreover, similar to the USMLE Step 1 exam, ABSITE scores have demonstrated no correlation with clinical ability. A pass/fail ABSITE would return the exam to its original purpose and minimize an over-reliance on scores. Moving forward, new objective measures will need to be developed to assess surgical trainees in a more holistic manner.

Understanding the Well-Being of General Surgery Residents.

BACKGROUND: In 2017, the Accreditation Council for Graduate Medical Education program guidelines changed to include a section that requires programs to optimize resident and faculty member well-being. There is still a poor understanding of general surgery resident wellness, and there are few well-established wellness programs. METHODS: We created a novel 50-question anonymous survey to assess burnout, depression, and wellness that was distributed to the general surgery residents as part of a pilot study. Univariate analysis was performed to assess wellness and wellness changes. Bivariate analysis was performed to determine the association between wellness variables and gender, age, and postgraduate year (PGY) level. RESULTS: Thirty-five of 55 residents participated in the survey. Over half of the residents (54%) reported gaining weight during residency. Nearly 70% reported working while having an ongoing family issue, and 77% worked at least once while ill. Fourteen residents (40%) reported that their wellness worsened over the previous academic year, while 7 (20%) reported that it remained the same, and 11 (31%) reported that it improved. These changes varied significantly by the PGY level (P < .01). Age (younger vs older than 30) and sex were found to be effective measure modifiers of the association between wellness change and PGY level. DISCUSSION: The overall wellness of the general surgery residents at our institution varies greatly. Poor wellness may lead to inferior patient care, burnout and depression, and negative resident morale. Residency programs need to implement programming to address wellness deficiencies.

Bariatric surgery outcomes: is age just a number?

INTRODUCTION: Obesity and its associated comorbidities represent a pervasive problem in the United States across all age groups. There are conflicting data regarding the effectiveness and postoperative recovery of bariatric surgery in elderly patients. The aim of this study was to compare outcomes of bariatric surgery across age groups. MATERIALS AND METHODS: After obtaining institutional review board approval, patients with morbid obesity who underwent non-revisional laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (LSG) at our institution between 2011 and 2015 were included in this retrospective study. Patients were subdivided into five age groups: < 30, 30-39, 40-49, 50-59, and ≥ 60 years. Patient baseline demographics and comorbidities were collected. Postoperative outcomes including reinterventions/reoperations, 30-day-readmissions, 90-day-mortality, comorbidities' resolution, and change in BMI (ΔBMI) up to 4 years were recorded and compared. The groups were compared with ANOVA and chi-square tests and multivariable analyses. RESULTS: LRYGB was performed in 74.7% of the 1026 study patients. Patients ≥ 60 years old demonstrated lower preoperative BMI than patients < 50 years (p < 0.001). Patients 50-59 years old had increased length of stay compared to 30-39 (p = 0.003) and a higher prevalence of all comorbidities was found in older patients (p < 0.001). There was no significant difference in 30-day-readmissions; 90-day-mortality; reoperations; and reinterventions among the study groups. The ΔBMI was higher in younger patients and comorbidity resolution was more likely in younger patients with the exception of obstructive sleep apnea. CONCLUSION: Bariatric surgery can be accomplished safely across all age groups with satisfiable postoperative weight loss. However, older age had higher hospital stay and convalescence and lower comorbidity resolution compared to younger patients. Thus, bariatric surgery should be offered earlier in life to allow the patients to reap its benefits.

The Rise of Minimally Invasive Surgery: 16 Year Analysis of the Progressive Replacement of Open Surgery with Laparoscopy.

OBJECTIVE: The expansion of Minimally Invasive Surgery (MIS) has been exponential since the introduction of laparoscopic surgery in the late 1980s. This shift in operative technique has led many to believe that surgery residents are not developing the skills needed to adequately perform open operations. METHODS: We performed a retrospective review of the Accreditation Council for Graduating Medical Education national operative case log database of general surgery residents from January 2003 to December 2019. We compared the open vs. laparoscopic case numbers for six different operations, including cholecystectomy, appendectomy, inguinal hernia repair, colectomy, gastrectomy, and Nissen fundoplication. The Cochran-Armitage test was used to assess the linear trend in the procedures performed. RESULTS: Total average residency case volumes for the procedures studied have increased from 270 to 368 (36%) over the 16-year period with MIS steadily representing a greater proportion of these cases. From 2003 to 2018, MIS representation increased in all studied procedures: cholecystectomy (88% to 94%, p = 0.048), inguinal hernia repair (20% to 47%, p ≤ 0.001), appendectomy (38% to 93%, p ≤ 0.001), colectomy (8% to 43%, p ≤ 0.001), gastrectomy (43% to 84%, p = 0.048), and Nissen (71% to 91%, p = 0.21). CONCLUSION: While the overall operative volume has increased nationally for surgical residents, the representation of open cases has steadily declined since the advent of MIS. The experience needed in open surgery during resident training is still to be determined and may be necessary now that laparoscopy is progressively replacing open operations.

Laparoscopic sigmoid colectomy and splenectomy for diverticulitis and splenic sarcoidosis.

Splenectomy together with colectomy is most commonly performed as a result of iatrogenic injury and not as an additional elective procedure. A 50-year-old African American female presented with recurrent episodes of diverticulitis. She had mediastinal, and porta hepatis lymphadenopathy and subcutaneous nodules, but multiple biopsies were unable to establish the diagnosis. On computed tomography scan, innumerable hypodense splenic lesions were noted. The patient underwent combined laparoscopic sigmoid colectomy and splenectomy. First, the severely inflamed sigmoid colon was mobilised followed by descending colon and splenic flexure. The spleen, which showed multiple granulomas, was dissected out and the hilum secured with a stapler. The rectum was now stapled, the Pfannenstiel incision was reopened, the spleen was removed in a retrieval bag and the colon was pulled out. The colorectal anastomosis was created with an end-to-end anastomotic (circular) stapler. Pathology demonstrated multiple non-caseating granulomas indicative for sarcoidosis and acute/chronic diverticulitis. The patient developed a superficial surgical site infection but no other complications. Prednisone and methotrexate were started and her sarcoidosis improved. She was well at her 2 years of follow-up. Only few patients have an indication for elective splenectomy together with segmental colectomy. The procedure can be safely performed using a laparoscopic approach.

Multilevel Quality Improvement Teams: An Alternative Approach for Surgical Academic Training Programs to Meet ACGME Core Competency Milestones.

BACKGROUND: Quality improvement (QI) activities are an integral part of residency training. We started the process to implement team-based, multilevel QI project streams within our academic surgical residency by studying resident perceptions. OBJECTIVE: Our residency carried out 6 QI projects in line with the American Council for Graduate Medical Education competencies. A resident survey was completed in 2016 to measure resident perceptions of an individual versus team-based QI project approach. METHODS: This was a descriptive study looking at resident's preference for team projects and ongoing projects within the training program. We started in 2014 utilizing Wait's Team Action Projects in surgery paradigm to conduct 6 QI projects. After initiation of projects, we allotted 2 full years to pass prior to assessing resident perceptions via a 12-item survey. RESULTS: Notably, this was a descriptive study aiming to capture resident perceptions on team-based QI and the foundational elements necessary to create and sustain such projects by integrating into our curriculum from the intern year. In 2016, 40 residents completed surveys (72.7% response rate), all (100%) opined that they preferred team-based approaches over individual ones, and 75% were on board to move forward with only a team-based approach in the future. CONCLUSIONS: This was a pivotal start to adopting a team-based QI project strategy in the future and laid a solid foundation to build upon. We found residents in our program desire to work within teams early on to develop effective solutions to clinical problems. Residents perceived that the team-based model resulted in an improved resident experience with the QI process and improved patient care. We hope to publish a series of articles updating our progress as we move forward in this endeavor.

Pilot Study of Delayed ICOS/ICOS-L Blockade With αCD40 to Modulate Pathogenic Alloimmunity in a Primate Cardiac Allograft Model.

BACKGROUND: Inducible costimulator (ICOS) is rapidly upregulated with T-cell stimulation and may represent an escape pathway for T-cell costimulation in the setting of CD40/CD154 costimulation blockade. Induction treatment exhibited no efficacy in a primate renal allograft model, but rodent transplant models suggest that the addition of delayed ICOS/ICOS-L blockade may prolong allograft survival and prevent chronic rejection. Here, we ask whether ICOS-Ig treatment, timed to anticipate ICOS upregulation, prolongs NHP cardiac allograft survival or attenuates pathogenic alloimmunity. METHODS: Cynomolgus monkey heterotopic cardiac allograft recipients were treated with αCD40 (2C10R4, d0-90) either alone or with the addition of delayed ICOS-Ig (d63-110). RESULTS: Median allograft survival was similar between ICOS-Ig + αCD40 (120 days, 120-125 days) and αCD40 (124 days, 89-178 days) treated animals, and delayed ICOS-Ig treatment did not prevent allograft rejection in animals with complete CD40 receptor coverage. Although CD4+ TEM cells were decreased in peripheral blood (115 ± 24) and mLNs (49 ± 1.9%) during ICOS-Ig treatment compared with monotherapy (214 ± 27%, P = 0.01; 72 ± 9.9%, P = 0.01, respectively), acute and chronic rejection scores and kinetics of alloAb elaboration were similar between groups. CONCLUSIONS: Delayed ICOS-Ig treatment with the reagent tested is probably ineffective in modulating pathogenic primate alloimmunity in this model.

Comparative Evaluation of αCD40 (2C10R4) and αCD154 (5C8H1 and IDEC-131) in a Nonhuman Primate Cardiac Allotransplant Model.

BACKGROUND: Specific blockade of T cell costimulation pathway is a promising immunomodulatory approach being developed to replace our current clinical immunosuppression therapies. The goal of this study is to compare results associated with 3 monoclonal antibodies directed against the CD40/CD154 T cell costimulation pathway. METHODS: Cynomolgus monkey heterotopic cardiac allograft recipients were treated with either IDEC-131 (humanized αCD154, n = 9), 5C8H1 (mouse-human chimeric αCD154, n = 5), or 2C10R4 (mouse-rhesus chimeric αCD40, n = 6) monotherapy using a consistent, comparable dosing regimen for 3 months after transplant. RESULTS: Relative to the previously reported IDEC-131-treated allografts, median survival time (35 ± 31 days) was significantly prolonged in both 5C8H1-treated (142 ± 26, P < 0.002) and 2C10R4-treated (124 ± 37, P < 0.020) allografts. IDEC-131-treated grafts had higher cardiac allograft vasculopathy severity scores during treatment relative to either 5C8H1 (P = 0.008) or 2C10R4 (P = 0.0002). Both 5C8H1 (5 of 5 animals, P = 0.02) and 2C10R4 (6/6, P = 0.007), but not IDEC-131 (2/9), completely attenuated IgM antidonor alloantibody (alloAb) production during treatment; 5C8H1 (5/5) more consistently attenuated IgG alloAb production compared to 2C10R4 (4/6) and IDEC-131 (0/9). All evaluable explanted grafts experienced antibody-mediated rejection. Only 2C10R4-treated animals exhibited a modest, transient drop in CD20 lymphocytes from baseline at day 14 after transplant (-457 ± 152 cells/µL) compared with 5C8H1-treated animals (16 ± 25, P = 0.037), and the resurgent B cells were primarily of a naive phenotype. CONCLUSIONS: In this model, CD154/CD40 axis blockade using IDEC-131 is an inferior immunomodulatory treatment than 5C8H1 or 2C10R4, which have similar efficacy to prolong graft survival and to delay cardiac allograft vasculopathy development and antidonor alloAb production during treatment.

Transgenic expression of human leukocyte antigen-E attenuates GalKO.hCD46 porcine lung xenograft injury.

BACKGROUND: Lung xenografts remain susceptible to loss of vascular barrier function within hours in spite of significant incremental advances based on genetic engineering to remove the Gal 1,3-αGal antigen (GalTKO) and express human membrane cofactor protein (hCD46). Natural killer cells rapidly disappear from the blood during perfusion of GalTKO.hCD46 porcine lungs with human blood and presumably are sequestered within the lung vasculature. Here we asked whether porcine expression of the human NK cell inhibitory ligand HLA-E and ß2 microglobulin inhibits GalTKO.hCD46 pig cell injury or prolongs lung function in two preclinical perfusion models. METHODS: Lungs from pigs modified to express GalTKO.hCD46 (n=37) and GalTKO.hCD46.HLA-E (n=5) were harvested and perfused with human blood until failure or elective termination at 4 hours. Airway pressures and pulmonary artery hemodynamics were recorded in real time. Blood samples were also collected throughout the experiment for analysis. Porcine aortic endothelial cells (PAECs) from each genotype were cultured in monolayers in microfluidic channels and used in fluorescent cytotoxicity assays using human NK cells. RESULTS: HLA-E expression on GalTKO.hCD46 PAECs was associated with significantly decreased antibody-dependent and antibody-independent NK-mediated cytotoxicity under in vitro conditions simulating physiologic shear stress. Relative to GalTKO.hCD46 pig lungs perfused with human blood on an ex vivo platform, additional expression of HLA-E increased median lung survival (>4 hours, vs 162 minutes, P=.012), and was associated with attenuated rise in pulmonary vascular resistance, and decreased platelet activation and histamine elaboration. As expected, HLA-E expression was not associated with a significant difference in NK cell adhesion to endothelial cells in vitro, or NK cell and neutrophil sequestration during organ perfusion. CONCLUSIONS: We conclude human NK cell activation contributes significantly to GalTKO.hCD46 pig endothelial injury and lung inflammation and show that expression of HLA-E is associated with physiologically meaningful protection of GalTKO.hCD46 cells and organs exposed to human blood.

Current status of pig lung xenotransplantation.

Human organ transplantation has improved duration and quality of life for many people, but its full potential is critically limited by short supply of available organs. One solution is xenotransplantation, although this comes with its own set of challenges. Lungs in particular are highly sensitive to injury, during the transplantation process generally, and to multiple immune rejection mechanisms. Using pig lung donors, our lab has been working on lung transplants into baboons as a surrogate for a human recipient. Several ex vivo human blood perfusion models have also proven useful. The combination of these experiments allows us to test large animal models as well as whole organ or isolated endothelial reactions to perfusion with human blood. We have found that a multi-modality therapeutic approach to prevent various pathogenic cascades - such as antibody-driven complement activation, other immune pathway activation, thrombosis, and tissue ischemia-reperfusion injury - has met with progressively greater success to protect the xeno lung from injury. Pig gene knockout and human gene transfer has been perhaps the greatest contributor. This review will discuss mechanisms of xeno lung injury, relevant experimental models, as well as recent results and future targets for research.

Natural vitamin E α-tocotrienol protects against ischemic stroke by induction of multidrug resistance-associated protein 1.

BACKGROUND AND PURPOSE: α-Tocotrienol (TCT) represents the most potent neuroprotective form of natural vitamin E that is Generally Recognized As Safe certified by the U.S. Food and Drug Administration. This work addresses a novel molecular mechanism by which α-TCT may be protective against stroke in vivo. Elevation of intracellular oxidized glutathione (GSSG) triggers neural cell death. Multidrug resistance-associated protein 1 (MRP1), a key mediator of intracellular oxidized glutathione efflux from neural cells, may therefore possess neuroprotective functions. METHODS: Stroke-dependent brain tissue damage was studied in MRP1-deficient mice and α-TCT-supplemented mice. RESULTS: Elevated MRP1 expression was observed in glutamate-challenged primary cortical neuronal cells and in stroke-affected brain tissue. MRP1-deficient mice displayed larger stroke-induced lesions, recognizing a protective role of MRP1. In vitro, protection against glutamate-induced neurotoxicity by α-TCT was attenuated under conditions of MRP1 knockdown; this suggests the role of MRP1 in α-TCT-dependent neuroprotection. In vivo studies demonstrated that oral supplementation of α-TCT protected against murine stroke. MRP1 expression was elevated in the stroke-affected cortical tissue of α-TCT-supplemented mice. Efforts to elucidate the underlying mechanism identified MRP1 as a target of microRNA (miR)-199a-5p. In α-TCT-supplemented mice, miR-199a-5p was downregulated in stroke-affected brain tissue. CONCLUSIONS: This work recognizes MRP1 as a protective factor against stroke. Furthermore, findings of this study add a new dimension to the current understanding of the molecular bases of α-TCT neuroprotection in 2 ways: by identifying MRP1 as a α-TCT-sensitive target and by unveiling the general prospect that oral α-TCT may regulate miR expression in stroke-affected brain tissue.