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Early medical education courses provide opportunities for promoting leadership in future physicians. Our research sought to integrate explicit activities of teamwork and leadership into the first‐year gross anatomy course and assess student leaders through self reflection and team evaluation. Fifty first‐year medical students were assigned to three‐ or four‐member dissection teams with group leaders designated on a rotating basis. Teamwork was emphasized through daily group quizzes, oral patient presentations relating clinical diagnoses to anatomy, and extensive embryology presentations. Group leaders were responsible for leading the dissections after attending daily orientation sessions on the teaching cadaver. Team and self evaluations of group leaders were gathered with weekly electronic surveys. Preliminary results suggest that team leaders rate themselves lower than their teammates do with respect to altruism, accountability and responsibility. One explanation for this discrepancy is decreased self‐awareness of student leaders regarding their own performance. Further research may demonstrate whether increased communication between leaders and team members can improve leaders' awareness of their capabilities. Research support came from the Mayo Clinic Department of Anatomy. Grant Funding Source N/A

Recent curricular redesign at Mayo Medical School integrated radiology into first‐year gross and developmental anatomy. The resulting six‐week (120 contact hours) Human Structure block teaches gross anatomy through dissection, radiologic imaging, and correlation with embryology. To further promote holistic physician‐development, refinement of the Human Structure course has been driven by the six core competencies of the Accreditation Council for Graduate Medical Education (ACGME): patient care, medical knowledge, practice‐based learning, interpersonal skills, professionalism, and systems‐based practice. We report here more than 20 educational interventions built into the Human Structure block that may serve as a model for incorporating the ACGME core competencies into early medical education. The block emphasizes clinically oriented anatomy, invites self‐ and peer‐evaluation, provides daily formative feedback through an audience response system, and employs team‐based learning. The course curriculum includes didactic briefing sessions and roles for students as teachers, leaders, and collaborators. Third‐year medical students serve as teaching assistants, enhancing their own knowledge of anatomy, bettering their skills as medical educators, and facilitating group communication and critiques. This work was supported by the Mayo Clinic Department of Anatomy. Grant Funding Source None

PURPOSE This study assessed the joint association of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC in the general population. METHODS A total of 26,798 non-Hispanic white BC cases and 26,127 controls from predominately population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium were evaluated for PVs in BRCA1, BRCA2, ATM, CHEK2, PALB2, BARD1, BRIP1, CDH1, and NF1. PRS based on 105 common variants were created using effect estimates from BC genome-wide association studies; the performance of an overall BC PRS and estrogen receptor–specific PRS were evaluated. The odds of BC based on the PVs and PRS were estimated using penalized logistic regression. The results were combined with age-specific incidence rates to estimate 5-year and lifetime absolute risks of BC across percentiles of PRS by PV status and first-degree family history of BC. RESULTS The estimated lifetime risks of BC among general-population noncarriers, based on 10th and 90th percentiles of PRS, were 9.1%-23.9% and 6.7%-18.2% for women with or without first-degree relatives with BC, respectively. Taking PRS into account, more than 95% of BRCA1, BRCA2, and PALB2 carriers had > 20% lifetime risks of BC, whereas, respectively, 52.5% and 69.7% of ATM and CHEK2 carriers without first-degree relatives with BC, and 78.8% and 89.9% of those with a first-degree relative with BC had > 20% risk. CONCLUSION PRS facilitates personalization of BC risk among carriers of PVs in predisposition genes. Incorporating PRS into BC risk estimation may help identify > 30% of CHEK2 and nearly half of ATM carriers below the 20% lifetime risk threshold, suggesting the addition of PRS may prevent overscreening and enable more personalized risk management approaches.

12003 Background: AIMSS are common and frequently lead to early discontinuation of adjuvant AI therapy. Single nucleotide polymorphisms (SNPs) in candidate genes have been associated with AIMSS and AI discontinuation. The primary objective of E1Z11 was to validate previously identified associations between 10 specific SNPs in candidate genes and AI discontinuation due to AIMSS in a community-based, racially diverse cohort. Methods: Postmenopausal women with hormone receptor-positive stage I-III breast cancer enrolled onto a prospective multi-site cohort study, the majority through the NCI Community Oncology Research Program (NCORP). Participants received anastrozole 1 mg oral daily, and completed patient-reported outcomes (PROs) at baseline, 3, 6, 9, and 12 months. AIMSS was defined as >20% increase in Stanford Health Assessment Questionnaire (HAQ) score over baseline occurring within 1 year of AI therapy. We projected 40% would develop AIMSS and 25% would discontinue AI treatment within 1 year, informing a planned enrollment of 1000 women with a fixed number per strata (600 Caucasian, 200 African-American [AA] & 200 Asian) to provide 80% power to detect an effect size of 1.5-4. SNPs include ESR1 (rs2234693, rs2347868, rs9340835), CYP19A1 (rs1062033, rs4646), TCL1A (rs11849538, rs2369049, rs7158782, rs7159713), and HTR2A (rs2296972). Hardy-Weinberg equilibrium (HWE) was evaluated within each racial subset. SNP genotypes were coded as additive effects on the log odds ratio by coding as 0, 1 or 2 for the count of the minor allele. A Cochran-Armitage trend test was used with a 1-sided alpha of 0.0025 (Bonferroni correction for 10 tests). Results: We enrolled 999 evaluable women (616 Caucasian, 184 AA, 199 Asian). Genotyping was successful in 974 (98%). AIMSS developed in 43%, and AI therapy was discontinued in 12% within 1 year. While more AA and Asians developed AIMSS compared to Caucasians (48% vs 38%, p=0.017; 50% vs 38%, p=0.004), AI discontinuation rates were similar across racial groups. HWE was satisfied for all SNPs at the 5% alpha level, except for TCL1A/rs11849538 (p=0.002) in the AA cohort. None of the 10 SNPs were significantly associated with AI discontinuation or development of AIMSS in the overall population, or in any of the 3 cohorts. Conclusions: Although AIMSS were more common in AA and Asians, AI discontinuation rates were similar in the 3 cohorts. We were unable to prospectively validate 10 SNPs in 4 genes previously associated with AI discontinuation due to AIMSS. Future analyses will include other predictors of AIMSS, PROs, and additional genetic markers for the entire cohort and by race. Support: NCI UG1CA189828, UG1CA233196, UG1CA233277, UG1CA233320, UG1CA233178, UG1CA233160, UG1CA232760, UG1CA233341, UG1CA233329, U10CA180821, UG1CA189821, UG1CA189830, U10CA180888, UG1CA189859, UG1CA189863, UG1CA189971. Clinical trial information: NCT01824836.

Abstract Intracranial atherosclerotic disease (ICAD) is a common cause of stroke. Antiplatelet therapy is the mainstay for symptomatic ICAD treatment. Endovascular management with submaximal angioplasty and/or intracranial stenting is reserved for patients with repeated ischemic events despite optimal medical therapy. We demonstrate intracranial angioplasty and stenting technique, technique indications, and sizing of stent and target vessel diameter. Stenting and angioplasty have been described in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis and Wingspan Stent System Post Market Surveillance trials. 1,2 Submaximal angioplasty has also been described. 3 This patient, who had been on dual antiplatelet therapy for several months, initially presented with occlusion of the left middle cerebral artery M2 inferior division and underwent mechanical thrombectomy with successful reperfusion. Postoperatively, the patient's symptoms did not improve. Medical management was optimized with heparin infusion. However, repeat stroke study demonstrated M2 inferior division reocclusion. A decision was made to proceed with intracranial angioplasty and stenting. P2Y12 levels were therapeutic. Under moderate conscious sedation, submaximal angioplasty of up to 80% of the normal M2 caliber was attempted. However, we observed persistent high-grade stenosis of the M2 inferior division. The major risk of crossing the lesion for angioplasty is vessel perforation. To safely perform this maneuver, we used a J-configured Synchro-2 microwire (Stryker). Because of the patient's recent thrombectomy, we also had prior tactile feedback about how much resistance was encountered while crossing the occlusion. We then deployed a balloon-mounted intracranial stent for optimal radial force across the stenotic area to restore perfusion. Postoperative computed tomography perfusion showed resolution of the previously noticed perfusion deficit. The patient gave informed consent for the procedures and video recording. Institutional review board approval was deemed unnecessary. Video. ©University at Buffalo Neurosurgery, September 2020. With permission.

The optimal training of the highly specialized congenital heart surgeon is a long and complex process, which is a significant challenge in most parts of the world. The World Society for Pediatric and Congenital Heart Surgery (WSPCHS) has established the Global Council on Education for Congenital Heart Surgery as a nonprofit organization with the goal of assessing current training and certification and ultimately establishing standardized criteria for the training, evaluation, and certification of congenital heart surgeons around the world. The Global Council and the WSPCHS have reviewed the present status of training and certification for congenital cardiac surgery around the world. There is currently lack of consensus and standardized criteria for training in congenital heart surgery, with significant disparity between continents and countries. This represents significant obstacles to international job mobility of competent congenital heart surgeons and to the efforts to improve the quality of care for patients with Congenital Heart Disease worldwide. The purpose of this article is to summarize and document the present state of training and certification in congenital heart surgery around the world.

Purpose: To investigate the association of body mass index (BMI) with Fuchs endothelial corneal dystrophy (FECD) severity and TCF4 CTG18.1 expansion. Methods: A total of 343 patients with FECD were enrolled from the Mayo Clinic. FECD severity was graded by slit-lamp biomicroscopy. BMI values were obtained from the electronic medical records. DNA extracted from leukocytes was analyzed for CTG18.1 expansion length, with ≥40 repeats considered expanded. Wilcoxon signed-rank tests were used to compare FECD grade and CTG18.1 expansion length in patients by BMI (<25, ≥25 to <30, and ≥30 kg/m2). FECD grade was regressed on age, sex, BMI, and CTG18.1 expansion and, separately, BMI on CTG18.1 expansion. Models were investigated for effect modification by age and sex with an interaction term of P < 0.05 considered statistically significant. Results: When examining the association between BMI and FECD, there was a significant interaction between BMI and sex (P for interaction = 0.004). When controlling for age and CTG18.1 expansion, a positive association was observed between BMI and FECD grade in women, but not in men. In addition, BMI was not associated with CTG18.1 expansion when controlling for age and sex. Conclusions: BMI was positively associated with FECD severity among women but not men. There was no significant association between BMI and CTG18.1 expansion. These findings suggest that increased BMI is potentially a modifiable risk factor for FECD disease progression among women.

Abstract Glioblastoma (GBM) is a common deadly malignant brain cancer of the central nervous system, with a median survival of 12–15 months. Scientific advancements are lacking in developing effective therapies for both primary GBM, as well as secondary GBMs, that typically originate as malignant transformation of lower-grade isocitrate dehydrogenase (IDH) 1-mutant tumors. The unique metabolomic profile of IDH1-mutant tumors presents opportunities to develop biomarker signatures of therapeutic efficacy. Microdialysis is an extracellular fluid sampling collection technique utilizing a perfused semipermeable catheter to permit diffusion of molecules between brain interstitium and the perfusate. We hypothesized that microdialysis may identify a metabolomics-based biomarker response to therapy in IDH1-mutant tumors. To test this hypothesis, orthotopic xenografts were generated from patient-derived xenografts (PDX) harboring mutant IDH-1 (R132H). Perfusates were collected from intra-cranial tumors in athymic nude mice sampled at baseline and 72h post treatment with temozolomide (TMZ), an oral alkylating agent used to treat IDH1-mutant gliomas, compared with vehicle treatment. Perfusates were analyzed via untargeted metabolomic profiling using liquid chromatography-mass spectrometry. Tumor specific metabolites such as (D)-2 hydroxyglutarate, were detected in microdialysate from IDH-1 mutant tumor bearing mice compared to non-tumor bearing mice. We also found high levels of metabolites such as 5-methylthioadenosine, and dimethylarginine and wide range of amino acids in microdialysate from IDH-1 mutant tumor bearing mice. TMZ treatment induced changes to metabolites in creatine and histidine metabolism. Our results indicate that microdialysis is a feasible technology to identify metabolomics-based biomarkers in IDH1-mutant gliomas and their response to therapy. We suggest that in vivo intratumoral microdialysis over several days could yield metabolic pharmacodynamic biomarkers of value to therapeutic translation for IDH-mutant gliomas.

Objectives: STAT Mortality Categories (developed 2009) stratify congenital heart surgery procedures into groups of increasing mortality risk to characterize case mix of congenital heart surgery providers. This update of the STAT Mortality Score and Categories is empirically based for all procedures and reflects contemporary outcomes. Methods: Cardiovascular surgical operations in the Society of Thoracic Surgeons Congenital Heart Surgery Database (January 1, 2010 – June 30, 2017) were analyzed. In this STAT 2020 Update of the STAT Mortality Score and Categories, the risk associated with a specific combination of procedures was estimated under the assumption that risk is determined by the highest risk individual component procedure. Operations composed of multiple component procedures were eligible for unique STAT Scores when the statistically estimated mortality risk differed from that of the highest risk component procedure. Bayesian modeling accounted for small denominators. Risk estimates were rescaled to STAT 2020 Scores between 0.1 and 5.0. STAT 2020 Category assignment was designed to minimize within-category variation and maximize between-category variation. Results: Among 161,351 operations at 110 centers (19,090 distinct procedure combinations), 235 types of single or multiple component operations received unique STAT 2020 Scores. Assignment to Categories resulted in the following distribution: STAT 2020 Category 1 includes 59 procedure codes with model-based estimated mortality 0.2% to 1.3%; Category 2 includes 73 procedure codes with mortality estimates 1.4% to 2.9%; Category 3 includes 46 procedure codes with mortality estimates 3.0% to 6.8%; Category 4 includes 37 procedure codes with mortality estimates 6.9% to 13.0%; and Category 5 includes 17 procedure codes with mortality estimates 13.5% to 38.7%. The number of procedure codes with empirically derived Scores has grown by 58% (235 in STAT 2020 vs 148 in STAT 2009). Of the 148 procedure codes with empirically derived Scores in 2009, approximately one-half have changed STAT Category relative to 2009 metrics. The New STAT 2020 Scores and Categories demonstrated good discrimination for predicting mortality in an independent validation sample (July 1, 2017-June 30, 2019; sample size 46,933 operations at 108 centers) with C-statistic = 0.791 for STAT 2020 Score and 0.779 for STAT 2020 Category. Conclusions: The updated STAT metrics reflect contemporary practice and outcomes. New empirically based STAT 2020 Scores and Category designations are assigned to a larger set of procedure codes, while accounting for risk associated with multiple component operations. Updating STAT metrics based on contemporary outcomes facilitates accurate assessment of case mix.