Georgetown University Research Articles

Medical educators’ perceptions of race in clinical practice

BackgroundWhile several medical societies endorse race as a social construct, it is still often used as a biological trait in medical education. How medical educators employ race while teaching is likely impacted by their beliefs as to what race represents and its relevance in clinical care. Understanding these beliefs is necessary to guide medical education curriculum reform.MethodsThis was a qualitative survey study, conducted in June 2020, of Georgetown University Medical Center faculty. As part of the survey, faculty were asked to rate, on a 5-point Likert scale, the extent to which they perceived race as a biological trait and its importance in clinical care. Self-identified clinical or preclinical faculty (N = 147) who believed that race had any importance were asked to provide an example illustrating its significance. Free-text responses were coded using content analysis with an inductive approach and contextualized by faculty’s perspectives on the biological significance of race.ResultsThere were 130 (88%) responses categorized into two major themes: race is important for (1) screening, diagnosing, and treating diseases and (2) contextualizing patients’ experiences and health behaviors. Compared to faculty who perceived race as biological, those who viewed race as strictly social were more likely to report using race to understand or acknowledge patients’ exposure to racism. However, even among these faculty, explanations that suggested biological differences between racial groups were prevalent.ConclusionsMedical educators use race primarily to understand diseases and frequently described biological differences between racial groups. Efforts to reframe race as sociopolitical may require education that examines race through a global lens, accounting for the genetic and cultural variability that occurs within racial groups; greater awareness of the association between structural racism and health inequities; movement away from identity-based risk stratification; and incorporation of tools that appraise race-based medical literature.

Georgetown and Slavery, from Plantation to Campus

Abstract: In 1838, the Maryland Province Jesuits sold the nearly three hundred people they enslaved on their plantations to Louisiana. Part of the proceeds of that sale went to pay down the debts amassed by Georgetown University. This is how most people understand the historical ties between Georgetown and slavery. This article situates Georgetown’s relationship to the institution in a more sustained context. It emphasizes slavery’s role in the daily life of campus, examines the lives of the enslaved there, and illuminates the university’s deeper relationship to both the Maryland plantations and regional Catholic slaveholding networks. Further, it considers how these connections influenced intellectual thought on campus. The article extends scholarship on slavery and higher education to not only focus on the institution’s foundational complicities, but also emphasizes the demands of the enslaved and their descendants in our contemporary moment.

Expanded Indications for Nipple-Sparing Mastectomy and Immediate Breast Reconstruction in Patients Older Than 60 Years.

Although nipple-sparing mastectomy (NSM) and immediate breast reconstruction (IBR) have long been praised for excellent cosmetic results and the resultant psychosocial benefits, the feasibility and safety of these procedures in patients older than 60 years have yet to be demonstrated in a large population. Patients undergoing NSM with or without IBR at the MedStar Georgetown University Hospital between 1998 and 2017 were included. Patient demographics, surgical intervention, and complication and recurrence events were retrieved from electronic medical records. Primary outcomes were recurrence and complication rates by age groups older and younger than 60 years. There were 673 breasts from 397 patients; 58 (8.6%) older than 60 years and 615 (91.4%) younger than 60 years with mean follow-up of 5.43 (0.12) years. The mean age for those older than 60 was 63.9 (3.3) years, whereas that for those younger than 60 was 43.1 (7.9) years (P < 0.001). The older than 60 group had significantly higher prevalence of diabetes, rates of therapeutic (vs prophylactic) and unilateral (vs bilateral) NSM, and mastectomy weight. However, there were no significant differences by age group in complication rates or increased risk of locoregional or distant recurrence with age. Based on similar complication profiles in both age groups, we demonstrate safety and feasibility of both NSM and IBR in the aging population. Despite increased age and comorbidity status, appropriately selected older women were able to achieve similar outcomes to younger women undergoing NSM with or without IBR.

Supportive Care of Hematopoietic Stem Cell Donors.

Supportive care needs for hematopoietic stem cell recipients have been studied. Less is known about the care needs of stem cell donors. Care challenges arise at donor selection, preparation for the donation, the donation procedure and the immediate and long-term after-care. Care needs were analyzed for 1,831 consecutive bone marrow and peripheral stem cell donors at MedStar Georgetown University Hospital between January 2018 and August 2023 in support of a review of the current literature. During the selection, related donors may experience psychological pressures affecting their motivation, while donation centers may be willing to accept co-morbidities in these donors which might preclude donation in unrelated peers. For bone marrow donations, it is important to select donors not only according to optimal genetic matching criteria but also according to suitable donor/recipient weight ratios, to facilitate sufficient stem cell yields. During the donation preparation phase, side effects and complications related to stem cell stimulation must be anticipated and managed for peripheral cell donors, while the pros and cons of autologous blood donation should be evaluated carefully for bone marrow donors. The stem cell donation procedure itself carries potential side effects and complications as well. Peripheral cell donors may require a central line and may encounter hypocalcemia, thrombocytopenia, and anemia. Bone marrow donors face risks associated with anesthesia, blood loss and pain. Post-procedure care focusses on pain management, blood cell recovery and the psychological support necessary to regain a high quality-of-life existence. Hematopoietic stem donors are giving part of themselves to save another's life. They deserve comprehensive supportive care to accompany them throughout the donation process.

(290) Impact of Neoadjuvant Relugolix on Patient-Reported Sexual Function and Bother

Abstract Introduction Relugolix is an oral GnRH receptor antagonist used in combination with radiation therapy in the treatment of unfavorable prostate cancer. It has been shown to achieve rapid and profound testosterone suppression (total testosterone &amp;lt;20 ng/dL) without the need for bothersome injections. Such low testosterone levels may impact sexual functioning and perceptions. Objective Given the potential benefits of Relugolix over other androgen deprivation therapies (ADTs), this prospective study sought to assess neoadjuvant Relugolix-induced sexual dysfunction prior to the initiation of stereotactic body radiation therapy (SBRT). Methods Prospective, patient-reported data was collected from a male cohort diagnosed with localized prostate cancer and subsequently treated with neoadjuvant Relugolix and SBRT. Relugolix was initiated at least 2 months prior to SBRT. Sexual function and bother were assessed via the sexual domain of the validated Expanded Prostate Index Composite (EPIC-26) survey which includes five function questions (erections and orgasm) and one overall bother question. Individual scores ranged from 0-100 with higher scores reflecting improved function/less bother. EPIC-26 was collected for each patient at pre-Relugolix baseline and one hour prior to SBRT initiation. Individual items were evaluated for statistical significance (paired t-test, p &amp;lt; 0.05) and clinical significance by minimally important difference (MID, +/- 0.5 SD from baseline score). Results Between July 2021 and January 2023, 49 patients with localized prostate cancer were treated with neoadjuvant Relugolix (4-6 months) and SBRT (36.25-40 Gy in 5 fractions) at Georgetown University Hospital per institutional protocol IRB 12-1775. The median age was 73 years. 27% of patients were black and 26.1% were obese (BMI ≥30 kg/m2). Patients initiated Relugolix at a median of 3.6 months prior to SBRT. 82% of patients had intermediate risk disease. All individual EPIC sexual function scores declined in a similar manner following neoadjuvant Relugolix therapy. These declines were both statistically and clinically significant. There was no statistically or clinically significant change in the EPIC sexual overall bother score. Conclusions In concordance with known side effects of ADT, neoadjuvant Relugolix was associated with a significant decline in self-reported sexual function. However, patients indicated only a minimal and non-significant increase in bother. Relugolix was well-tolerated as patients on Relugolix did not subjectively find their sexual dysfunction troublesome. Future investigations should compare outcomes while on Relugolix directly to GnRH agonist-induced sexual dysfunction. Disclosure No.

Unlocking integration opportunities: How Dahlgren Memorial Library implemented the circulation of room keys for the Georgetown University School of Medicine rooms

Dahlgren Memorial Library, the Graduate Health and Life Sciences Research Library at Georgetown University implemented the circulation of room keys in 2007. The rooms were outside of the library and managed by Georgetown University School of Medicine’s Office of Financial Affairs who were integral in the implementation of the keys and the management of the rooms. This article will discuss the policies and procedures for circulating the room keys, downfalls and benefits, and future plans.

Christopher J. King, PhD, FACHE, Dean of the School of Health, Georgetown University.

Christopher J. King, PhD, FACHE, Dean of the School of Health, Georgetown University.

Visual Intelligence Education as a Tool for Enhancing Medical Students' Self-Perception of Communication Skills.

Visual arts-based exposure and training are effective tools to enhance medical education. The visual arts can increase emotional intelligence and critical thinking skills. This study, conducted at Georgetown University School of Medicine (GUSoM) and the National Gallery of Art (NGA) in Washington, DC, was designed to measure the effect of a visual arts elective course on medical students' self-perception of their communication skills. This 6-week course involved lessons at the NGA and GUSoM for16 second-year medical students. The intervention students were age and gender-matched to14 second-year medical student control participants who took different elective courses. Prior to and following the intervention, the participants completed the Communication Skills Attitude Scale (CSAS). Statistical analysis was performed with either the 2-sided t-test or 2-sided Wilcoxon rank-sum test. There were no statistically significant differences in the presurvey scores between the groups. However, there were 6 CSAS questions in the postsurveys that had statistically significant differences between the 2 groups. Within each group, there were also numerous statistically significant differences between their presurvey and postsurvey responses, with positive changes occurring in the intervention group (IG) and primarily negative changes occurring in the control group (CG). The NGA course improved the self-perception of communication skills, with students reporting stronger views on the importance of communication skills in teamwork and patient rapport. The CG, on the other hand, did not have as many improved perceptions of communication skills and had stronger opinions regarding not needing the ability to communicate well to be a good physician. This study indicates that medical student communication skills can benefit from exposure to visual arts activities and experiences. Future physicians must become effective communicators, and this study paves the way for research investigating the relationship between visual arts education and the development of a physician's communication skills.

THE HASHTAG SYLLABUS AS CLASS ASSIGNMENT: FROM CRITICAL INFORMATION LITERACY TO CULTURAL CRITIQUE

In the immediate aftermath of the 2014 murder of 18-year Michael Brown in Missouri, hashtags like #ferguson, #justiceformikebrown, and #handsupdontshoot begin trending on Twitter. At the same time, Marcia Chatelain, Georgetown University Professor of History and American Studies, began crowdsourcing materials for educators trying to address what happened in their classrooms using the hashtag #fergusonsyllabus. What resulted was a list of highly interdisciplinary and multimedia sources including scholarly texts, news stories, songs, poems, films, public addresses, and children’s books. Chatelain’s call spoke both to the present crisis, the murder of a Black teenager by police, and to the historical and cultural context in which this shooting happened. The efforts of Chatelain and the community that came together around this hashtag expanded our understanding of information production and curation and the function of a syllabus beyond the college classroom. In introducing our undergraduate classes to the idea of the hashtag syllabus, we attempt to engage our students in practices of information literacy with the hope of providing them tools to look critically at the inequities that permeate academic and non-academic spaces. Here, we explore the ways in which this format operates in interdisciplinary social science programs and the ways in which it supports unique learning objectives in both introductory and upper-level courses. In doing so, we hope to engage in pedagogical praxis that connects our fields and our students with questions of social justice and to do so in a way that prepares them for meaningful civic engagement.

The eco-ethical contribution of Menico Torchio – a forgotten pioneer of European Bioethics

BackgroundIn 1926, Fritz Jahr described bio-ethics (German: bio-ethik) as “the assumption of moral obligations not only towards humans, but towards all forms of life.” Jahr summarized his philosophy by declaring, “Respect every living being on principle as an end in itself and treat it, if possible, as such!.” Bioethics was thus originally an ethical system concerned with the “problems of interference with other living beings… and generally everything related to the balance of the ecosystem” according to the 1978 Encyclopedia of Bioethics. This definition was predicated on the work of Fritz Jahr, Menico Torchio, and Van Rensselaer Potter.MethodsIn order to proceed with depthful analysis of the origin and major bioethical flare up, we will use critical analysis of existing literature, followed by a study trip to relevant bioethical localities (collecting photo and other documentations regarding Menico Torchio).ResultsWhile Jahr and Potter are typically given intellectual credit for developing the field of bioethics, the eco-ethical contributions of Menico Torchio have been forgotten.This article will first trace the origins of “bioethics” – now commonly bifurcated into “biomedical ethics” and “environmental bioethics.” The former was developed by Tom Beauchamp from the Philosophy Department and James Childress of the Religious Studies department at Georgetown University and is based on principlism, with a narrow focus on medical settings. The latter addresses the environmental impact of the medical industry and climate change health hazards. Second, we will present a panorama of Torchio’s significant intellectual contribution to bioethics. Menico Torchio’s concept of bioethics synthesized work of both Jahr and Potter, advocating “the need to expand our ethical obligations and embrace the most developed groups of animals, not only physically but also psychologically.” Third, we will reflect on the lasting legacy of “bioethics” on biomedical and environmental bioethics today. Thematic elements such as interconnectedness of planetary health and human health, dedication to living in harmony with nature, and emphasis on systems and symbiosis remain unchanged from the legacy of Tochio onward.ConclusionOur conclusion will underscore the necessity of understanding the connections between planetary, environmental, and human health.

Cell Phone Use in American Civics and History Classrooms

The use of digital devices in K-12 classrooms has become increasingly contested with their ubiquity. This study examines policies governing cell phone use in elementary and secondary school civics, social studies, American government, and history classes in the United States. Cell phone policies implemented by teachers differ vastly across and even within schools. Data from an original national survey of civics and history teachers conducted by the Civic Education Research Lab at Georgetown University were used to examine cell phone policies nationwide. While there was near universal agreement among teachers about the importance of digital tools for learning, the propriety of using cell phones for instruction was hotly contested. Grade level and school characteristics, such as school size, Title I status, and one-to-one school programs, were better predictors of cell phone policies than teacher characteristics. Teachers with more years of experience were the most likely to institute strict cell phone policies. These findings indicate that there is no one-size-fits-all policy for cell phones and provide insights for teachers and schools for adapting workable strategies given the school context.

Closing the patient-provider gap along the surgical journey one click at a time: results of a phase I pilot trial of a patient navigation tool

BackgroundPatients diagnosed with complex hepato-pancreaticobiliary (HPB) conditions experience a challenging journey through the healthcare system. Patient navigation is commonly offered to patients and their caregivers throughout this process. Here, we report on the development and phase I testing of a prototype web-based dual (patient and provider) navigation application ‘PatientNav.’MethodsEvidence-based recommendations were determined through a needs assessment. The PatientNav app was designed to be a highly customizable tool based on the needs of the patients, the care team, and the characteristics of the institution. Our phase I pilot trial targeted adult patients who reported the capacity to use a mobile app or desktop website presenting to our HPB transplant clinic at MedStar Georgetown University Hospital/Lombardi Comprehensive Cancer Center over two months. Usability, functionality, and reliability testing were conducted by applying multiple strategies, including biometric data analysis, task completion, questionnaires, and interviews.ResultsOut of 22 patients, 18 (81.8%) completed the in-app survey whose responses were included in the analysis. The usability rate of PatientNav among patient app users was 95.4%. Among patient app users who completed the in-app survey questionnaire, 66.6% reported that the content in the PatientNav app was relevant. In terms of the app's reliability, none of the patient app users reported technical issues with accessing PatientNav throughout the study period. To further elucidate the characteristics of individuals who exhibited high usage of the PatientNav assigned task functions, we divided our cohort based on the median number of tasks used (N = 75 total tasks). The univariable comparison showed that high function users were older, with a median (IQR) age of 61.5 (57.8, 71.3) compared to 52.2 (34.5, 65.7) years among low function users. No differences were observed based on gender, racial distribution, living condition, or occupation. However, 41.7% of low function users had Medicare/Medicaid insurance, whereas all high function users had private or combined insurance.ConclusionOur phase I pilot study showed that PatientNav is a feasible, usable, and functional technological tool that enables patients with complex HPB diagnoses and their care team to interface in real-time using patient-reported outcome measures (PROMs). PatientNav is a reliable tool that can be used by clinical and support staff to help navigate patients through surgery and aftercare and by patients to assist in navigation and self-management.Trial registrationThe trial was registered at ClinicalTrials.gov; Registration number: NCT04892927; date of registration: 5/19/2021.

Abstract PR019: Evaluating the role of ambient air pollution in racial disparities of colorectal cancer incidence and survival in metropolitan Detroit

Abstract Colorectal cancer (CRC) is the third most diagnosed cancer in the United States and the third leading cause of cancer-related deaths. Moreover, Non-Hispanic Black (NHB) individuals have the highest rates of CRC incidence and mortality in the United States. We have become increasingly aware of the potential impact of social determinants of health (SDOH) on colorectal physiology and carcinogenesis. Other than individual and neighborhood level socioeconomic status (SES), neighborhood quality can also affect an individual’s risk of exposure to harmful environmental contaminants including ambient air pollution. Moreover, as NHB individuals are more likely to live in areas of lower area-level SES they experience these effects even further. We sought to understand whether higher exposure rates to fine particulate matter (PM2.5) played a role in racial differences in CRC incidence and survival in metropolitan Detroit. To do this, we obtained data from the Environmental Protection Agency (EPA) Environmental Justice Mapping and Screening Tool through the Georgetown University Environmental Impact Data Collective (EIDC) and patient data from the Metropolitan Detroit Cancer Surveillance System (MDCSS) registry. Incidence rates were calculated using population data from the American Community Survey. Associations between PM2.5 exposure and CRC incidence were estimated using Poisson modeling. Data were obtained for NHB (n=3778) and Non-Hispanic White (NHW) (n=9727) individuals diagnosed with invasive CRC between 2010 and 2019 in Wayne, Oakland, and Macomb counties, including their geocoded census tract at diagnosis as well as demographic and clinical features. Vital status was reported as months from the date of diagnosis to either death or last contact. PM2.5 metrics were converted to the national percentile of PM2.5 in the air utilizing the Bayesian space-time downscaling fusion model for derived estimates of air quality at the census tract level. Survival was assessed using Cox Proportional Hazards modeling. We found that an increase in the PM2.5 percentile increased the risk for CRC overall for NHB and NHW patients (Relative Risk [RR] = 1.80, 95% Confidence Interval [CI] = 1.55 - 2.08, p-value &amp;lt;0.0001). This association was even stronger among NHB patients (RR = 7.94, 95% CI = 5.45 - 11.52, p-value &amp;lt; 0.0001), but was not statistically significant among NHW patients (RR = 1.12, 95% CI = 0.95 – 1.32, p-value = 0.16). PM2.5 exposure was not associated with survival overall or stratified by race. We conclude that ambient air pollution, particularly PM2.5, increases the risk of CRC cancer and disproportionately affects NHB patients but may not play a role in mortality risk. These results highlight the importance of environmental justice research in biomedical research and the need for a better understanding of the etiology of CRC within and among differing genetic ancestries and races by evaluating the genetic and epigenetic differences in patient tumor samples. Citation Format: Natalie G. Snider, Theresa Hastert, Ed Peters, Elena M. Stoffel, Laura Rozek, Ann Schwartz, Kristen Purrington. Evaluating the role of ambient air pollution in racial disparities of colorectal cancer incidence and survival in metropolitan Detroit [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr PR019.

Real-World Validation of the European Leukemia Network 2022 Risk Stratification in Acute Myelogenous Leukemia

Background: The 2017 European LeukemiaNet (ELN 2017) guidelines have become foundational for the risk stratification, prognostication, and treatment of acute myelogenous leukemia (AML). The updated 2022 European LeukemiaNet (ELN 2022) guidelines include additional cytogenetic abnormalities and genetic mutations for risk group assignment. It remains unknown how these updated guidelines compare for risk stratification and prognosis. Methods: We studied (N=287) adults with newly diagnosed AML from MedStar Georgetown University, MedStar Washington Hospital Center, and Baylor University Medical Center from 2012 to June 2023. Patients were stratified as favorable (fav), intermediate (int), or adverse (adv) risk according to ELN 2017 and ELN 2022 criteria. Overall survival (OS) was compared by age, race, and sex. Statistical analysis performed with SAS. Results: Median age was 65+16 years with a predominance of males (N=168, 59%). African-Americans (AA) composed 15% (N=44) of the cohort. Myelodysplastic-related mutations were present in 33 patients (15%), whereas the prevalence of epigenetic mutations was 25% (N=55). By ELN 2017 criteria, 19 (7%) patients were characterized as fav, 64 (23%) as int, and 198 (70%) as adv risk. Using ELN 2022 criteria, 18 (6%) patients were categorized as fav, 52 (19%) as int, and 211 (75%) as adv risk. Kaplan-Meier (KM) curves revealed a median overall survival of 200 days (d), 400 d, and 1532 d in the adv, int, and fav risk groups, respectively (log-rank p&amp;lt;0.001) by ELN 2017 criteria. Median OS was 379 d, 527 d, and 1552 d for the adv, int, and fav groups, respectively (log-rank p&amp;lt;0.001) in the ELN 2022 cohort. Stratifying by age &amp;lt;60 years, median OS was 390 d in the adv group and 832 d in the int group (log-rank p=.021)by ELN 2017 criteria,as compared to 350 d in the adv group and 757 d in the int group (log-rank p=.0012) by ELN 2022 criteria.Among those &amp;gt;60 years of age, median OS was 244 d and 349 d in the adv and int groups, respectively by ELN 2017 criteria (Anova p&amp;lt;0.25). In the ELN 2022 cohort, median OS among those &amp;gt;60 years of age was 284 d for the adv group and 209 days in the int group (Anova p&amp;lt;0.62). Among females, median OS in the adv group was 224 d and 342 d in the int group by ELN 2017 criteria (Anova p=0.4). In the ELN 2022 cohort, median OS among females was 214 d in the adv group and 421 d in the int group (Anova p=.13). Median OS among male patients in the ELN 2017 cohort was 324 d for those of adv risk and 623 d for those of int risk (Anova p&amp;lt;0.004). In the ELN 2022 cohort, median OS in males was 352 d and 563 d in the adv and int groups, respectively (Anova p&amp;lt;0.07) . In the ELN 2017 cohort, median OS was 259 d in AA patients as compared to 719 d in non-AA patients; this was not statistically significant (Anova p=0.16). Comparatively, in the ELN 2022 cohort, median OS for the AA patients was 153 d as compared to 212 d for the non-AA patient population (Anova p=0.86) .Conclusions: In this real-world dataset, the updated ELN 2022 guidelines reproduce differential survival for proposed favorable, intermediate, and adverse risk categories. When considering time to endpoint survival [Kaplan Meier curves] in our study, ELN 2022 seems to lack the ability to clearly discriminate among the adverse and intermediate risk subgroups. It is possible that patients seen in academic institutions not participating in FLT3 directed therapy trials retained inferior survival whereas similar patients fared better through early enrollment in trials using molecular targeted therapy. Finally, neither ELN 2017 nor ELN 2022 discriminate survival in AA populations for either adverse or intermediate subgroups. Efforts should be directed to develop novel risk stratification schemas to better encapsulate this vulnerable population.

Fluoroquinolone-Resistant Enterobacteriaceae Prevalence for Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation (aHSCT) in the Treatment of Multiple Myeloma (MM)

Background: Fluoroquinolones (FQL) are commonly used in antimicrobial prophylaxis in immunocompromised cancer patients (pts) during prolonged neutropenia. A possibly high and increasing proportion of pts harboring FQL-resistant Enterobacteriaceae (FRE) challenges the assumption that prophylaxis with FQLs is still of benefit in preventing sepsis. Previous studies reported that colonization of FRE in allogeneic transplant patients may be an infection risk factor (cf. Satlin et al. Clin Infect Dis 202;73:1257-65). This prospective study aims to determine the prevalence of FRE in defined pt populations in two metropolitan areas treated with dose-intense melphalan with autologous peripheral blood stem cell (PBSC) transplantation, and to determine the possible clinical effects of FRE in the host microbiome on transplant outcomes. Methods: Pts eligible for this prospective, ongoing study have a diagnosis of MM and are undergoing autologous PBSC transplantation after conditioning with dose-intense melphalan 200 mg/m 2 at Hackensack University Medical Center (HUMC) and MedStar Georgetown University Hospital (MGUH). Peri-rectal swabs are scheduled before chemotherapy mobilization of PBSC given with FQL prophylaxis, before transplant admission with initiation of antimicrobial prophylaxis, at time of hospital discharge, and 3 months after aHSCT. Prophylaxis is discontinued with fever or hospital discharge. Blood cultures are obtained at time of fever (&amp;gt;38 °C) with adjustments in antibiotics per standard of care. A central catheter is placed for venous access in all patients throughout their transplant course. Pts are discharged after achieving neutrophil (ANC) engraftment and control of conditioning regimen toxicities. Bacterial cultures from perirectal swabs (fresh or frozen for shipping) were purified on CHROMagar™ Orientation Plates and grown in the presence of ≥5 ug/ml ciprofloxacin to select for quinolone-resistant organisms. Results: To date, 39 pts are evaluable (Table 1). PBSC were mobilized using filgrastim/plerixafor (G-Moz) or cyclophosphamide/etoposide/dexamethasone (CDE) followed by filgrastim with levofloxacin prophylaxis. The quantity of CD34+ cells infused is in Table 1. All pts achieved ANC engraftment at a median of 10.8 days (range 9-14) and were hospitalized for a median of 13 days (range 11-24). 37/39 pts collected swabs before transplant admission (and swabs were obtained at discharge for the other 2 pts). 13/37 (35%) admission swabs demonstrated FRE colonization (Table 2). 6/33 swabs at time of discharge were positive for FRE including for 4 pts negative for FRE on transplant admission with a total of 17/39 pts (44%) showing FRE colonization at some point during the transplant admission. Samples collected at 3 months after transplantation for 24 pts reaching that timepoint showed FRE colonization for 4 pts including 2 pts not previously testing positive at time of transplantation. 27/107 samples tested positive for FRE and 21/39 pts (54%) had at least one FRE positive culture. Seven pts (20%) developed neutropenic fever but no pt experienced a blood-stream infection (BSI). One pt developed Clostridium difficile colitis during the period of neutropenia. One pt tested positive for MRSA colonization at admission but did not develop fever or BSI. One pt was readmitted after initial hospital discharge for evaluation of fever without a source of infection determined. Ten pts (5 FRE colonized during transplant course) were given prednisone for persistent diarrhea attributed to engraftment syndrome (cf: Spitzer TR. Bone Marrow Transplant 2001;27:893-8) commencing at a median of 10 (range, 8-13) days after aHSCT and not associated with CDE mobilization or detection of FRE. Nineteen other patients, 8 of whom tested positive for FRE, did not receive corticosteroids for management of regimen-related toxicities (an additional 7 pts received preplanned corticosteroids starting at day +8). No center effect is yet evident. Conclusions: FRE are detected in a high proportion of pts undergoing aHSCT in the treatment of MM. However, FQL prophylaxis is not associated with FRE BSI in this ongoing study. FRE colonization is not predictive of delayed engraftment or prolonged hospitalization, and does not appear predictive of non-infectious diarrhea.

Timing of Thrombosis with Myeloproliferative Neoplasm Diagnosis Among Veterans and Civilians

Rates of Arterial (AT) and Venous Thrombosis (VT) are increased in Veterans with Myeloproliferative Neoplasms (Vet-MPN), including Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PMF), compared to matched controls (J Clin Oncology 2023 41:16_suppl, 7011). The timing of first AT or VT episode in Vet-MPNs remains undefined when compared to Civilians with MPN (Civ-MPN). These findings could elucidate optimal timing for risk mitigation strategies to prevent thrombotic complications and should help to determine duration of thrombotic risk and need for systemic anticoagulation prophylaxis. The Veterans Affairs Informatics and Computing Infrastructure (VINCI) database was queried from January 1, 2006 to January 26, 2023 to identify Vet-MPNs, AT, and VT through ICD-9 and -10 codes. This process yielded 2,752 Vet-MPN and 583,803 Veterans without MPN from Illinois, the state most representative of the US population. These cohorts were compared to data derived from a retrospective chart review of Civ-MPN cared for between January 1, 2019 to December 31, 2022, at MedStar Georgetown University Hospital and MedStar Washington Hospital Center. Service-Connected Exposures (SCE) to potential carcinogens among Veterans were verified through their duration and location of service. We subdivided time to first AT and VT from MPN diagnosis as follows: more than 3 months prior to MPN diagnosis, within 3 months of diagnosis, 3 months to 1 year post diagnosis, 1 to 5 years, and more than 5 years after MPN diagnosis. Mean data from various cohorts were analyzed utilizing Fisher's exact test. Vet-MPN experienced a statistically higher incidence of AT compared to Civ-MPN (p=.0019) and Civ-MPN experienced a statistically higher incidence of AT compared to Veterans without MPN (p=0.02) which served as a control. In contrast, there was a higher incidence of VT among both Vet- and Civ-MPN cohorts compared to Veterans without MPN (p&amp;lt;.0001) (Table 1). The mean ages at MPN diagnosis and onset of first AT were similar (≥63 years) in both Civ- and Vet-MPN. In contrast, the mean age of MPN diagnosis and age of first VT were considerably earlier for Civ-MPN (51 years) versus both Vet-MPN with VT and Veterans without MPN with VT (≥67 years). There was a higher prevalence of hypertension, hyperlipidemia, diabetes, heart failure, and smoking among Veterans with or without MPN compared to Civ-MPN with either AT or VT (Table 1). A trend toward statistical significance was observed for the presence of hypertension and hyperlipidemia (p=0.049 and p=0.02, respectively) in Vet-MPN compared to Civ-MPN, while Veterans without MPN had a statistically higher prevalence of hyperlipidemia (p=0.02) and heart failure (p=0.001) in AT. Notably, a trend toward statistical significance in VT was observed for the presence of diabetes among all Veterans with or without MPN compared to Civ-MPN (p=0.01 and p=0.007, respectively). There was a biphasic distribution in time to onset of first AT and VT in all Vet- and Civ-MPN cohorts (Figure 1). There was a higher cumulative incidence of first AT and VT in Vet-MPN at more than 3 months prior to MPN diagnosis compared to Civ-MPN with AT and VT (Figure 1). On the other hand, the Civ-MPN cohort had a late surge of first VT more than 5 years after MPN diagnosis compared to the other MPN cohorts. A biphasic distribution in time to onset of first AT and VT was also observed among the Vet-MPN cohort when stratified by SCEs from World War II, the Korean War, the Vietnam War, and the Gulf War. The vast majority of both AT and VT in Vet-MPN from all SCE examined experienced onset of thrombotic events more than 3 months prior to MPN diagnosis. Most VT in Gulf War Vet-MPN occurred within 3 months of MPN diagnosis. In conclusion, the predominant risk for developing thrombotic complications in MPN, particularly in Vet-MPN, occurs in a biphasic pattern, beginning more than 3 months prior to MPN diagnosis and becoming apparent again at more than 5 years after MPN diagnosis. These findings suggest that the MPNs convey an enduring hypercoagulability potential throughout the natural history of the disease. There appears to be an accelerated onset of thrombotic complications earlier in the course of disease in Vet-MPN, perhaps reflecting their SCE with toxic carcinogens. More work is necessary to determine epigenetic influences on MPN natural history.

Investigating Metabolic and Immunologic Consequences of Nucleotide Substitutions in Acute Myeloid Leukemia

Background Stressors, conventionally defined as cell extrinsic factors with the ability to promote clonal evolution, have been implicated as modulators of cancer development and progression. Smoking has previously been linked to unique single-base substitutions (SBSs), which may facilitate the development and progression of acute myeloid leukemia (AML). Similar to smoking in lung cancer, we previously reported unique C&amp;gt;A single-base substitutions (SBSs) in AML. SBS4 mutational signature (COSMIC database) is characterized by C&amp;gt;A transversions and may induce “immunogenicity”. Interestingly, C&amp;gt;A associates with G&amp;gt;A in elderly AML with previous smoking history (Patel, ASH, 2022). In recent years, high body mass index (BMI) has been associated with risk for clonal hematopoiesis (CH). However, a SBS correlation with metabolic parameters (i.e. lipid studies and BMI) remains uncharacterized. In this study, we aimed to: (1) confirm the association of smoking with C&amp;gt;A and G&amp;gt;A SBSs in an expanded cohort of leukemia patients and (2) to investigate metabolic and immunologic factors associated with these SBSs among patients with leukemia. Methods After IRB approval, we conducted a retrospective analysis of AML patients (pt) from Baylor and MedStar Georgetown University Hospital (MGUH). Genetic data using next generation sequencing (NGS), as well as demographic and clinical information was obtained. For patients from MGUH, FASTA nucleotide sequences were obtained by subjecting mutations to transcript expression and cDNA alignment in the NCBI gene database. MHC I binding neopeptides were identified by mapping FASTA nucleotide sequences and HLA class I alleles in the Net MHC pan 4.1 database. SBSs with neopeptides that exhibited binding were grouped for further analysis of associations. Descriptive statistics were obtained using SAS software. Results Our expanded database included 85 pt with AML that had NGS performed at diagnosis. This increased the number of SBSs in our database from 148 to 213. Median age was 64.8 years (y) (range, 22-89). 42/85 patients (49.4%) had a positive smoking exposure. 41/213 (19.2%) of SBSs were C&amp;gt;T, 14/213 (6.6%) were C&amp;gt;A, 12/213 (5.6%) were G&amp;gt;C, 68/213 (31.9%) were G&amp;gt;A, 12/213 (5.6%) were A&amp;gt;C, 8/213 (3.8%) were A&amp;gt;T, 25/213 (11.7%) were G&amp;gt;T, 13/213 (6.1%) were A&amp;gt;G, 4/213 (1.9%) were T&amp;gt;A, 6/213 (2.8%) were T&amp;gt;C, 8/213 (3.8%) were C&amp;gt;G, and 2/213 (0.9%). 4/80 (5%) of G&amp;gt;A transitions were in pts age &amp;lt;40y, 18/80 (22%) age 40-59 y, and 58/80 (73%) &amp;gt;60y ( Fig 1A). Smoking significantly increased association with C&amp;gt;A transversion rate from 2.44% to 12.94% ( p=0.003). C&amp;gt;A combined with G&amp;gt;A showed an increased smoking rate of 50.59% vs 29.27%( p=0.002). When compared with patients without a smoking exposure, patients with C&amp;gt;A or G&amp;gt;A mutations and a smoking exposure had significantly higher total cholesterol of 165.2mg/dL compared to 125.8mg/dL ( p=0.02) and LDL of 101.8mg/dL compared to 74.5mg/dL ( p=0.04). Interestingly, higher frequency of G&amp;gt;T, (previously recognized to be associated with oxidative damage) was observed among AML patients aged 40-59 exhibiting higher body mass index (BMI) ( Fig 1B). Given dominance of G&amp;gt;A expression in older AML pt, we investigated MHC class I neopeptide immunogenicity initiated by G&amp;gt;A mutations as a suggestion of functional interference. Among pathogenic G&amp;gt;A variants demonstrating TCR-reactivity, 1/18 (5.6%) vs 7/21 (33.3%) neopeptides were observed in AML pt less than 60 y vs older than 60 y ( p = 0.03). Discussion Our data confirm the association of smoking exposure with C&amp;gt;A and G&amp;gt;A mutagenicity. Subsequent analysis demonstrated a significant association with increased TC and LDL levels, indicating an altered lipidome may affect the acquisition of these mutations in AML patients with smoking exposure. We have also seen that G&amp;gt;A is enriched in older AML patients. In this pt subgroup, our data suggests that neopeptides derived from G&amp;gt;A SBS retain immunogenic potential. While this has been previously associated with aging, other etiologic associations have yet to be established. Additionally, younger obese AML pt exhibit increased susceptibility for G&amp;gt;T mutagenesis possibly as result of oxidative stress. Continued work is needed to elucidate the spectrum of stressors associated with mutational signatures in AML and their underlying mechanisms, as this will have important biologic implications for preventative and therapeutic interventions.

The Human Leukemia Immunopeptidome Is Driven By Pathogenic Molecular Variant Biotypes

Background Historically, acute myelogenous leukemia (AML) has been characterized as having a low somatic mutational burden and is predicted to have low neoantigen levels compared to solid tumors. However, recent data has shown that AML is an immunogenic malignancy and oncogenic driver mutations promote immune escape through immunoediting. Downregulation of human leukocyte antigen (HLA) class II HLA-DRB1, HLA-DQB1, HLA-DPA1 and HLA-DPB1 gene expression on leukemia cells has previously been associated with immune escape in AML following allogeneic hematopoietic stem cell transplantation (allo-HCT). While allo-HCT and cellular therapies are well-known potentially curative treatment options in AML, the human leukemia immunopeptidome has still not been well characterized. Here, we sought to uncover the human leukemia immunopeptidome by detecting differential major histocompatibility complex (MHC) class I neopeptide expression using molecular biotype subgroups. Methods We conducted retrospective analysis on 31 patients with hematopoietic malignancies including AML, chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), MDS, chronic myelogenous leukemia (CML) and other hematopoietic malignancies (i.e. NK cell leukemia) at MedStar Georgetown University Hospital. Mutations were identified using next generation sequencing and separated into the following annotated molecular biotypes based on the mechanism of pathogenesis: Group 0 (G0) DNA repair, G1 splicing, G2 transcription factor, G3 kinase activation, G4 epigenetic modification, G5 chromatin remodeling, G6 cohesin, G7 tumor suppressor (i.e. p53), G8 telomere maintenance, G9 histone modification, G10 nucleotransport (i.e. NPM1) and G11 cell cycle regulation. FASTA nucleotide sequences were obtained by subjecting mutations to transcript expression and cDNA alignment in the National Center for Biotechnology Information (NCBI) gene database. MHC class I binding neopeptides were identified by mapping patient FASTA nucleotide sequences and HLA class I alleles in the Net MHC pan 4.1 database. Neopeptides were grouped by % Rank and categorized as weak binding (WB) if &amp;gt; 0.5 and strong binding (SB) if ≤0.5. Descriptive and inferential statistics were performed using SAS. Results Thirty-one patients were evaluated including 17 AML (54.8%), 5 MDS (16.1%), 3 CMML (9.7%), 2 MDS/MPN (6.5%), 1 CML (3.2%) and 3 hematopoietic malignancies (9.7%). The median age was 65 years (range 28 -89); 43.8% were female and 43.3% were African American (AA). 144mutations were identified; thus far, 82 mutations have been subjected to FASTA NP_ protein extraction. The G3 biotype had the highest frequency of neopeptide bindings (n=59) followed by G2 (n=50) and G4 biotypes (n=42) ( Fig.1). Among patients with MDS, smokers were more likely to exhibit neopeptide binding compared to non-smokers (p=0.032). Patients with neopeptide binding had a longer median overall survival (mOS) compared to patients without neopeptide binding (mOS = 566 vs 114 days, p=0.0174) (Fig 2). Data exploration allowed isolation of a 54-year-old Asian male with Li-Fraumeni syndrome and p53 mutated AML who demonstrated high affinity neopeptide binding to HLA-B*39:01 with %Rank 0.08. Additionally, a 34 -year-old AA female with FLT3 mutated AML showed very high affinity neopeptide binding to HLA-A*29:02 with %Rank 0.007 as well as evidence of somatic HLA-A*03:01 deletion. Conclusions Pathogenic molecular variant biotypes constitute a novel immune signature, the human leukemia immunopeptidome. Smoking increased the likelihood of MHC class I neopeptide binding among patients with MDS. The presence of neopeptide binding predicted improved mOS in patients with myeloid malignancies. Further investigation of the human leukemia immunopeptidome may provide additional prognostic significance above that of standard molecular and cytogenetic risk stratification.

Countering Islamophobia through Sports: Qatar's Initiatives during the 2022 FIFA World Cup

This paper examines how Qatar used the 2022 FIFA World Cup as a platform to address global Islamophobia. Taking place in the context of a conference on Islamophobia at Georgetown University in Qatar, the study analyzes the role Western media played in reinforcing negative stereotypes and biases against Muslims before and during the event. It highlights Qatar's wide-ranging efforts to educate the public, influence policy, and promote open discussions on how to counteract these prejudices. Special attention is given to the significant role of sports celebrities, particularly football star Mo Salah, in reducing anti-Muslim sentiment. Empirical data support the idea that Salah's public Muslim identity contributed to a decline in hate crimes and negative social media chatter. Additionally, the study explores the possible positive impact, known as the "Qatar effect," that hosting the World Cup could have on reducing negative attitudes towards Muslims. This is similar to how Mo Salah's presence and influence have positively affected public opinion, known as the "Salah effect." The paper also discusses how Qatar infused cultural elements, like Quranic verses and Bedouin traditions, into the event to foster a broader understanding and appreciation of its heritage. It further addresses ethical and human rights concerns such as the conditions of migrant workers and civil liberties, emphasizing the inconsistency in how the world reacts to these issues in different contexts. Overall, this research offers a comprehensive look at how the 2022 FIFA World Cup served as a stage for Qatar to influence global perspectives on Islamophobia while shedding light on the social and political complexities tied to hosting a world-renowned event.

The Secret Life of Junior Pathologists: Challenges and Future Directions.

Transition from pathology trainee to independent pathologist is stressful. No study has examined junior pathologists' challenges and concerns during this transition. To identify challenges and concerns of junior pathologists. Junior pathologists were defined as those who had been practicing independently for up to 5 years after completion of residency/fellowship. An institutional review board-approved electronic survey was created and distributed to recent pathology graduates of MD Anderson Cancer Center (Houston, Texas) and MedStar Georgetown University Hospital (Washington, District of Columbia). The survey was open from October 13, 2022, to January 31, 2023. The survey included 16 multiple-choice and free-text questions. Responses were received from 39 junior pathologists. Participants working in academic settings indicated independence, work-life balance, and professional identity formation as challenges; those in nonacademic settings indicated pathology reporting, efficiency, and administration as challenges. Areas where participants wished they received more guidance differed by practice setting: participants in academic settings more often chose effective time management and importance of turnaround time (35% [7 of 20] versus 0% [0 of 14], P = .03) and tumor board conference presentation skills (25% [5 of 20] versus 0% [0 of 14], P = .06), while those in nonacademic settings more often chose Current Procedural Terminology (CPT) coding, billing, and cost-effective patient care (79% [11 of 14] versus (35% [7 of 20]; P = .02). More female than male participants indicated that they wished they had received more guidance in leadership and soft skills (79% [11 of 14] versus 28% [5 of 18]; P = .01). This study identified challenges experienced by junior pathologists. Collective efforts from training programs, experienced pathologists, and professional organizations can explore ways to improve the transition experience.