Citations

Mayo Clinic annually trains over 1000 predoctoral students and postdoctoral research fellows in medicine and biomedical sciences. However, training opportunities are limited for those interested in teaching and mentoring methodologies. Therefore, Mayo Clinic predoctoral students sought to provide trainee‐led learning opportunities for fellow trainees. A survey was sent to all Mayo Clinic predoctoral and postdoctoral trainees to determine preferences for pedagogy education formats. In response to survey results, the Twin Talk Series was developed. A Twin Talk is a set of one‐hour talks comprised of a Take‐in session and one or more Try‐out session(s). At the Take‐in session, a content expert discusses a pedagogical technique, and at the following Try‐out session(s), trainee volunteers practice the technique among themselves. Eight Twin Talks have been organized to date on several teaching techniques and pedagogical development topics. The impact of each Twin Talk, including understanding, format, and interest level, was evaluated through survey tools. Survey results suggested trainees favored in‐person pedagogy expert presenters during the Take‐in session over video conferences. Furthermore, modeling of the teaching technique by the expert presenter during the Take‐in session was well‐received. However, participation in the follow‐up Try‐out practice session was limited. Overall, the Twin Talk Series is a promising method for trainee‐led, peer‐to‐peer pedagogy education, particularly at institutions with limited access to pedagogical resources. The Twin Talk Series will continue to be refined to increase trainee participation, particularly in the follow‐up Try‐out sessions, and to provide relevant opportunities for trainees to practice teaching. Support or Funding Information Mayo Foundation of Medical Education and Research This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Abstract Lineage-ambiguous leukemias are high-risk malignancies of poorly understood genetic basis. Here, we describe a distinct subgroup of acute leukemia with expression of myeloid, T lymphoid, and stem cell markers driven by aberrant allele-specific deregulation of BCL11B, a master transcription factor responsible for thymic T-lineage commitment and specification. Mechanistically, this deregulation was driven by chromosomal rearrangements that juxtapose BCL11B to superenhancers active in hematopoietic progenitors, or focal amplifications that generate a superenhancer from a noncoding element distal to BCL11B. Chromatin conformation analyses demonstrated long-range interactions of rearranged enhancers with the expressed BCL11B allele and association of BCL11B with activated hematopoietic progenitor cell cis-regulatory elements, suggesting BCL11B is aberrantly co-opted into a gene regulatory network that drives transformation by maintaining a progenitor state. These data support a role for ectopic BCL11B expression in primitive hematopoietic cells mediated by enhancer hijacking as an oncogenic driver of human lineage-ambiguous leukemia. Significance: Lineage-ambiguous leukemias pose significant diagnostic and therapeutic challenges due to a poorly understood molecular and cellular basis. We identify oncogenic deregulation of BCL11B driven by diverse structural alterations, including de novo superenhancer generation, as the driving feature of a subset of lineage-ambiguous leukemias that transcend current diagnostic boundaries. This article is highlighted in the In This Issue feature, p. 2659

e16266 Background: Pancreatic cancer is one of the deadliest malignancies, with a 5 year OS of around 3%. Up to 3% of unselected patients (pts) with (PDAC) have the BRCA 1/2 mutation, while up to 15% possess HRD (ARID1A, ATM, BAP1, BARD1, BRIP1, CHEK1/2, FANCA, PALB2, RAD50, RAD51). PARP inhibitors, like olaparib, demonstrate clinical benefit in metastatic PDAC with BRCA mutations (mBRCA) and may have a role in those with HRD. The objective of this study is to determine the role of PARP inhibition in PDAC with HRD. Methods: This was a retrospective chart review of metastatic PDAC pts with germline (g) or somatic (s) mBRCA or HRD who received olaparib. An analysis of PFS and OS was performed for PDAC pts with mBRCA vs. HRD. Results: Forty-six pts with metastatic pancreatic cancer were identified to have mBRCA (n = 13) or HRD (n = 23) and received olaparib in our database. Median age was 73 years for mBRCA and 66 years for HRD. Five pts received olaparib as maintenance therapy after disease control with platinum: 2 mBRCA and 3 HRD pts. Six pts with mBRCA and 7 pts with HRD were platinum naïve prior to olaparib. Zero pts with mBRCA and 3 pts with HRD received olaparib after disease progression on platinum. The median (med)PFS for mBRCA vs. HRD was 6.1 months vs. 2.8 months (HR 0.5, 95% CI: 0.2-1.1, p = 0.07). The medOS for mBRCA vs. HRD was 7.7 vs. 5.3 months (HR 0.7, 95% CI: 0.2-1.9, p = 0.4). Of those with mBRCA who received olaparib, prior cisplatin exposure (n = 8) vs. cisplatin naïve (n = 5) led to medPFS of 6.1 vs. 7.8 months (HR 1.8, 95% CI 0.5-6.7, p = 0.3) and medOS of 6.8 months vs. 9.5 months (HR 1.5, 95% 0.3-6.4, p = 0.6). Six pts with HRD including gCHEK2 c.407T > C, gCHEK2 c.1461+1 G > A, gPALB2 gain (exon 11), sFANCI p.N1252S, sATM p.V2716A, sARID1A Q944fs*14 were noted to have disease control of at least 3 months on olaparib. Only one of these pts received olaparib as maintenance therapy after platinum. The medPFS was 6.1 months and medOS was not reached. One pt with HRD (sFANCI N1252S) had progressive disease on platinum prior to olaparib, but had stable disease > 5 months with olaparib. Conclusions: Our study suggests olaparib may have anticancer activity in PDAC with certain HRD. In addition, olaparib may have a role outside maintenance therapy in PDAC with mBRCA. Prospective studies are needed to confirm these findings.

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.

Objective The aim of the study was to determine the prevalence of second victim experience (SVE) among obstetrics and gynecology (OBGYN) clinical and nonclinical healthcare workers and compare healthcare workers who did and did not identify as a second victim (SV) in the last year. Methods The validated Second Victim Experience and Support Tool and additional questions designed to explore SVE topics specific to OBGYN healthcare workers were administered to a multidisciplinary group. Results Of 571 individuals sent a survey link, 205 completed the survey: 117 worked in obstetrics (OB), 73 in gynecology (GYN), and 15 in both areas. Overall, 44.8% of respondents identified as an SV sometime during their career, 18.8% within the last 12 months. Among nonclinical staff respondents, 26.7% identified as an SV during their career and 13.3% in the last 12 months. Respondents who identified as an SV in the last 12 months reported experiencing significantly more psychological and physical distress, a greater degree to which colleague and institutional support were perceived as inadequate, decreased professional self-efficacy, and increased turnover intentions. The most common events identified as likely triggers for SVE were fetal or neonatal loss (72.7%) and maternal death (68.2%) in OB and patient accusations or complaints (69.3%) in GYN. Conclusions Among survey respondents, there was a high prevalence of SVs in OBGYN staff, distributed equally between OB and GYN. Nonclinical healthcare workers also identified as SVs. The OBGYN departments should consider using the Second Victim Experience and Support Tool to screen for potential SV among their healthcare workers to provide additional support after events.

AbstractSex chromosome aneuploidies (SCAs) occur in 1 in every 400 births. SCAs are highly variable and have uncertain prognoses, complicating the delivery of prenatal cell‐free DNA (cfDNA) results or diagnosis following amniocentesis or chorionic villus sampling. Using a mixed‐methods approach, we explored the experiences of parents receiving a prenatal diagnosis of a fetus with SCA. Responses to open‐ended questions were qualitatively analyzed. Of the 323 parents who completed the survey, 122 received a prenatal diagnosis and answered at least one open‐ended question. Most parents did not recall being informed that cfDNA screening or amniocentesis could reveal the presence of a SCA prior to testing and described feeling unprepared for a positive result. Variation was found between parents who were delivered a diagnosis by a genetic professional versus other clinical specialties. Many parents expressed that the diagnosis was delivered in a way that emphasized the negative attributes of the SCA and that they were provided limited support materials. Parents who received a prenatal diagnosis of a SCA expressed a desire for more supportive delivery of prenatal diagnosis that focuses on parental education and nuanced discussion of potential phenotypes. Genetic counselors should be aware of the range of parental experiences when receiving a SCA diagnosis from non‐genetic providers. Prenatal SCA diagnoses are predicted to increase as prenatal cfDNA screening becomes more widely used. Collaborations for greater provider education and comprehensive materials on SCAs are essential to facilitate the delivery of SCA diagnoses and improve parent understanding and support.

AbstractObjectiveCareer paths leading to department chair positions are elusive. Women represent only 11% of academic emergency department (ED) chairs. It is unclear whether the pathway to chair is different for men and women; the characteristics, achievements, and qualifications among those who become ED chairs is unknown.MethodsThis study is a cross‐sectional analysis of curriculum vitae (CV) of current ED chairs in departments with Accreditation Council for Graduate Medical Education (ACGME)‐accredited residency programs. Former women chairs were included due to paucity of current women chairs. Statistics were calculated using bivariate and multivariate analysis.ResultsOf 163 eligible chairs, 88 CV (54%) were obtained, including six former women chairs. A majority (86.4%) self‐identified as White/Caucasian, 21.5% were women, 46% were chief residents, 28.4% completed additional postgraduate degrees, and 21.8% were fellowship trained. At time of chair appointment, 58% were professor rank, 53.5% held ED operations roles, and 32% served as vice chair. Women were more likely to be in educational (53% vs. 22%) versus operational (26% vs. 61%, p = 0.02) roles. Women obtained more advanced degrees (47% vs. 25%, p = 0.02), were awarded more nonfederal grants (median = 7 vs. 3, p = 0.04), and achieved more national committee leadership (median = 4 vs. 1, p = 0.02). There were no gender differences in fellowship training, awards, leadership training programs, publications, federal grants, or national/international lectures after adjusting for years in practice.ConclusionWhile the majority of chairs held prior leadership roles in ED operations, only one in five women chairs did, suggesting gender differences in the path to chair attainment. These differences in paths may contribute to persistent gender disparities in ED chairs and may be influenced by career path choices, implicit bias, and structural barriers.

Background and ObjectivesABO blood group may affect risk of SARS‐CoV‐2 infection and/or severity of COVID‐19. We sought to determine whether IgG, IgA and neutralizing antibody (nAb) to SARS‐CoV‐2 vary by ABO blood group.Materials and MethodsAmong eligible convalescent plasma donors, ABO blood group was determined via agglutination of reagent A1 and B cells, IgA and IgG were quantified using the Euroimmun anti‐SARS‐CoV‐2 ELISA, and nAb titres were quantified using a microneutralization assay. Differences in titre distribution were examined by ABO blood group using non‐parametric Kruskal–Wallis tests. Adjusted prevalence ratios (aPR) of high nAb titre (≥1:160) were estimated by blood group using multivariable modified Poisson regression models that adjusted for age, sex, hospitalization status and time since SARS‐CoV‐2 diagnosis.ResultsOf the 202 potential donors, 65 (32%) were blood group A, 39 (19%) were group B, 13 (6%) were group AB, and 85 (42%) were group O. Distribution of nAb titres significantly differed by ABO blood group, whereas there were no significant differences in anti‐spike IgA or anti‐spike IgG titres by ABO blood group. There were significantly more individuals with high nAb titre (≥1:160) among those with blood group B, compared with group O (aPR = 1·9 [95%CI = 1·1–3·3], P = 0·029). Fewer individuals had a high nAb titre among those with blood group A, compared with group B (aPR = 0·6 [95%CI = 0·4‐1·0], P = 0·053).ConclusionEligible CCP donors with blood group B may have relatively higher neutralizing antibody titres. Additional studies evaluating ABO blood groups and antibody titres that incorporate COVID‐19 severity are needed.

415 Background: Immune checkpoint inhibitors (ICI) have been approved in solid tumors with dMMR. However, only limited data are available for PDAC with dMMR given the rarity of dMMR in PDAC. We evaluated efficacy of ICIs in PDAC with dMMR. Methods: Retrospective clinical and pathologic data were collected for patients (pts) with pancreatic adenocarcinoma from May 2017 to June 2020 at Moffitt cancer center. Results: We identified 10 pts with dMMR PDAC. The median age was 64.5 years (range: 42-86) and 4 pts were male. 4 pts had resectable disease, 3 had locally advanced and 3 had metastatic disease at initial diagnosis. MSH6 deficiency (def) was found in 2 cases, PMS2 def in 2, MLH/PMS2 def in 5, and MSH2/MSH6 in 1. 7 pts were treated with ICIs. 3 pts had locally advanced and 4 had metastatic disease when they started ICIs. 5 received Pembrolizumab (pem), 1 received ipilimumab/ nivolumab (ipi/nivo), and 1 received pem then ipi/nivo after progressive disease (PD) on pem. The median number of prior lines of chemotherapy was 1 (range 0-2). 6 pts were evaluable, and 1 had rapid disease progression after 1 dose of pem. Among 6 evaluable pts, 3 had an objective response (1: complete response and 2: partial response), and 2 had stable disease (SD). Median progression-free survival was 8.2 mo, and median overall survival was not reached with median follow-up (FU) of 6.8 mo. The median duration of response was not reached with a median FU of 22.6 mo. The pt with CR remained disease-free for up to 22 months. The pt whose treatment was switched to ipi/nivo after PD on pem achieved SD > 4mo on ipi/nivo. While on immunotherapy, one patient with ipi/nivo developed immunotherapy associated rash requiring systemic steroids, and another on pem developed hypothyroidism requiring levothyroxine. Conclusions: This series suggest ICIs can provide durable clinical efficacy in pts with dMMR PDAC.