Georgetown University Research Articles

Predictions from Regina LaBelle on drug policy under Trump

Regina LaBelle, director of the Center on Addiction and Public Policy at the O'Neill Institute for National and Global Health Law at Georgetown University Law Center, released her predictions on what steps the Trump administration could take. Her report came out November 7, the day after the election. Here is a summary.

Design and implementation of a project management training program to develop workforce ready skills and career readiness in STEM PhD students and postdoctoral trainees

A growing number of STEM doctorates pursue careers across the broader biomedical workforce, including industry, policy, and healthcare. Graduate and postdoctoral trainees need training to develop professional skills that prepare them for diverse workforce options. Through engagement with faculty and trainees, we determined that formal management skills are underdeveloped in trainees, particularly around managing projects in a way that is translatable to broader industries. At Georgetown University Medical Center, we adapted Kern's six-steps of curriculum design to develop the Academy for Transferable Management Skills (ATMS) program to help graduate and postdoctoral trainees develop linear experience in utilizing project management tools in their academic research contexts. ATMS includes a self-paced online CANVAS course with learning objectives and content modules that map to the project management cycle from initiation to closure, developed in consultation with PhD-level industry experts. From 2021–2024, 25 trainees have completed the ATMS program, including the capstone project and posttest evaluation. Trainees also complete brief quizzes after each module as a formative assessment of learning. The pre-test evaluation (n = 92) revealed a baseline of project management “pain points” regularly encountered by trainees (risk management, project charters, work breakdown structures, and managing project scope). Posttest data (n = 25) reveal a significant increase (p < 0.0001) in project management self-efficacy measures across the aforementioned pain point scales. Notably, 100% of trainees indicated that they may/would refer the program to colleagues. ATMS offers trainees the flexibility to pick frameworks that apply to their projects with trainees planning to use project schedules (84%), Work Break Down Structures (80%), lessons learned reports (68%), and communication plans (68%) in their work. This integrated experiential learning approach equips trainees to develop and execute their projects according to industry-informed project management principles, which allows them to perform their current research more efficiently and to utilize project management frameworks in a way that is directly transferable to broad careers.

Outcomes with initiation of inpatient immunotherapy.

7 Background: Immune checkpoint inhibitors (ICIs) have transformed cancer care; however, studies establishing their benefit have been primarily conducted in robust patients (pts) with good performance status. Administration of ICI to hospitalized pts remains a subject of debate. While there is often a desire to reverse clinical course in patients who are acutely ill, previous studies show minimal benefit from anticancer therapy near the end of life with the potential for toxicity. While ICI are generally better tolerated than traditional cancer therapies, the median time to response ranges from 2-6 months and pts with a poor PS may not derive benefit. ICIs also bring significant financial burdens to pts and healthcare systems. The role of ICIs in the inpatient setting remains unclear. Methods: This study retrospectively examined pts who received PD-(L)1 inhibitors while IP between 2016 and 2023 at MedStar Georgetown University Hospital. Data were collected manually from institutional EMR. Descriptive statistics were used to depict the pt population and show their outcomes. The Kaplan-Meier method estimated survival probabilities from treatment initiation to follow-up or death, with 95% confidence intervals (α = 0.05). The Log rank non-parametric test compared survival distributions among ICIs. Results: Of the 38 pts who initiated ICI as an inpatient, 16 were male (42.1%) and 22 were female (57.9%). The median age was 60 years (31–88 years). Gastrointestinal malignancies were most common indication (31.6%), followed by thoracic/head and neck (21.1%) and hematologic (18.4%) cancers. Among the cohort, 26.3% received nivolumab, 68.4% received pembrolizumab, and 5.3% received a combination of nivolumab and ipilimumab. PD-L1 status was unknown for the majority (79.0%) of pts at time of ICI; 15.8 % were known to be PD-L1 high. Only 14 of 35 (40.0%) patients went on to receive any additional immunotherapy after discharge. The median days to death after discharge was 16 days (0-376 days), with a mean of 36.4 days. The median overall survival was 137 days from IP treatment initiation. The survival probability at 91 days was 65.5% (95% CI: 45.4-79.7) and 31.0% (95% CI: 15.6-47.9) at 182 days. No significant differences were observed between the survival distributions by ICI type (p=0.966) or primary malignancy (p=0.488). Conclusions: Our findings underscore the complexities of initiating inpatient ICI treatment and question its appropriateness. Delaying ICI to outpatient settings may enhance pt tolerance, optimize outcomes, and potentially mitigate unnecessary costs. This approach may allow thorough consideration of performance status outside the hospital, possibly improving treatment effectiveness while reducing futile acute care costs.

The Albert Nekimken Turkish Theater Collection: Censorship, Contentious Politics, and the Cold War Stage

Turkish political theater of the 1960s-1970s was a genre that galvanized both its intellectual proponents and drew the ire of state authorities. Deeply marked by the work of Bertolt Brecht produced some half a century earlier, the stage became an important setting where the broader violence between far-left groups, far-right groups, and the government was recast in literary form. During his doctoral research on the influence of German Marxism on Turkish political theater, former U.S. Peace Corps volunteer Albert Nekimken collected plays, works of theatrical criticism, periodicals, short stories, novels, and rare recordings of performances, among other materials. The Albert Nekimken Turkish Theater Collection, primarily composed of Nekimken’s research materials, began to grow as playwrights, intellectuals, and others contributed interviews or gifted materials to the young scholar in the mid-to-late 1970s. These works were acquired by Nekimken at a time of rampant political censorship and ntellectual persecution–exemplified by the fact that many of the publications and performances in the collection were banned or subject to great censorship by the Turkish government. Among the works in the collection are those by well-known writers such as Orhan Asena, Engin Cezzar, Güngör Dilmen, Muhsin Ertuğrul, Nâzım Hikmet, Orhan Kemal, Aziz Nesin, and Haldun Taner. This newly described and processed collection held in the Booth Family Center for Special Collections at Georgetown University offers new directions to students and scholars of political theater, the history of Modern Turkey, Turkish-German literary exchanges, and intellectual histories of the Cold War. The collection also gives educators hoping to bring primary sources into the classroom new pedagogical tools to explore histories of censorship, erasure, and contentious politics.

The Evolving Stethoscope: Insights Derived from Studying Phonocardiography in Trainees.

Phonocardiography (PCG) is used as an adjunct to teach cardiac auscultation and is now a function of PCG-capable stethoscopes (PCS). To evaluate the efficacy of PCG and PCS, the authors investigated the impact of providing PCG data and PCSs on how frequently murmurs, rubs, and gallops (MRGs) were correctly identified by third-year medical students. Following their internal medicine rotation, third-year medical students from the Georgetown University School of Medicine completed a standardized auscultation assessment. Sound files of 10 different MRGs with a corresponding clinical vignette and physical exam location were provided with and without PCG (with interchangeable question stems) as 10 paired questions (20 total questions). Some (32) students also received a PCS to use during their rotation. Discrimination/difficulty indexes, comparative chi-squared, and McNemar test p-values were calculated. The addition of phonocardiograms to audio data was associated with more frequent identification of mitral stenosis, S4, and cardiac friction rub, but less frequent identification of ventricular septal defect, S3, and tricuspid regurgitation. Students with a PCS had a higher frequency of identifying a cardiac friction rub. PCG may improve the identification of low-frequency, usually diastolic, heart sounds but appears to worsen or have little effect on the identification of higher-frequency, often systolic, heart sounds. As digital and phonocardiography-capable stethoscopes become more prevalent, insights regarding their strengths and weaknesses may be incorporated into medical school curricula, bedside rounds (to enhance teaching and diagnosis), and telemedicine/tele-auscultation efforts.

Parabolic Regularity of Spectral Functions

This paper is devoted to the study of the second-order variational analysis of spectral functions. It is well-known that spectral functions can be expressed as a composite function of symmetric functions and eigenvalue functions. We establish several second-order properties of spectral functions when their associated symmetric functions enjoy these properties. Our main attention is given to characterize parabolic regularity for this class of functions. It was observed recently that parabolic regularity can play a central rule in ensuring the validity of important second-order variational properties, such as twice epi-differentiability. We demonstrates that for convex spectral functions, their parabolic regularity amounts to that of their symmetric functions. As an important consequence, we calculate the second subderivative of convex spectral functions, which allows us to establish second-order optimality conditions for a class of matrix optimization problems. Funding: The research of A. Mohammadi is funded by a postdoctoral fellowship from Georgetown University. E. Sarabi is partially supported by the U.S. National Science Foundation [Grant DMS 2108546].

Visual Learning Equity Initiative Enhances Preclinical Dermatologic Image Representation: A Cross-Sectional Study.

Despite growing diversity in the United States population, studies show that medical education lacks representation of conditions in darker skin tones. Given that medical conditions present differently in different skin tones, limited exposure to images of darker tones in medical training may contribute to incorrect or delayed diagnoses, perpetuating health inequities. This study examines the preclinical curriculum at the Georgetown University School of Medicine (GUSOM) to report on its image representation with respect to skin tone and to assess the impact of a student-driven initiative in achieving visual learning equity (VLE). Of 1050 preclinical images, 58.2% depicted conditions in light/white skin tones, 31.3% in medium/brown, and 10.5% in dark/black. The microbiology and pathology courses had the highest percentages of dark/black and medium/brown images. Infectious disease images made up 36.3% of all images with 54.6% light/white, 31.5% medium/brown, and 13.9% dark/black. Overall, the first images representing conditions were 63.5% light/white, 30.0% medium/brown, and 6.6% dark/black. When dark/black images were presented first, 64.3% were of infectious diseases, compared to 35.1% for medium/brown and only 28.4% for white/light first images that were infectious diseases. A significant increase in images of conditions in darker skin tones was observed in the IRD course 2022 compared to the IRD course 2020 (P<.001). Our study highlights an underrepresentation of darker skin tones compared to lighter skin tones in the GUSOM preclinical curriculum. A student-led initiative significantly increased the representation of darker skin tones in dermatologic images, demonstrating the potential impact of such efforts in achieving VLE in medical education.J Drugs Dermatol. 2024;23(7):519-524.  doi:10.36849/JDD.7992.

Indolent CD4+ CAR T-Cell Lymphoma after Cilta-cel CAR T-Cell Therapy

SummaryIndolent CD4+ cytotoxic chimeric antigen receptor (CAR) T-cell lymphoma involving the small intestine was diagnosed in a patient who had previously received ciltacabtagene autoleucel (cilta-cel) CAR T-cell therapy for treatment of myeloma. Targeted messenger RNA sequencing revealed the presence of CAR gene product in tumor cells. Whole-genome sequencing of samples of tumor and peripheral blood identified a single lentiviral insertion site within the second intron of the SSU72 gene. In addition, numerous genetic alterations that may have contributed to malignant transformation were identified in the tumor sample. (Funded by MedStar Georgetown University Hospital.)

Governance Ethics: Bibliometric VOSviewer Analysis and Future Research Opportunities

This study aimed to conduct a bibliometric analysis to map Scopus-indexed scientific publications on Governance Ethics. The Publishing or Perish software collected Research data using the “governance ethic” keyword. This data was then processed using a VOS viewer to analyze and visualize the number of publications, researchers, keywords, and future research opportunities. The results revealed 499 scientific articles on governance and ethics, with the highest number published in 2021, totaling 42 articles. The earliest publication dates to 1982 by T. Purcell from Georgetown University, Washington, D.C., United States. The most prolific journal of publications is the Journal of Business Ethics, published by Springer Netherlands. Among researchers, Sison and Alejo Jose G. from Spain emerged as the most productive, with 8 publications and an H-index of 17. Sison is affiliated with the University of De Navarra, Pamplona, Spain. 926 authors were filtered down to 93, forming 10 networks and 2 clusters. Regarding keywords, 843 were filtered down to 138, with the most common being ethics, governance, business ethics, research ethics, and corporate social responsibility. The theoretical implication of this study lies in its utilization of bibliometric analysis for mapping governance ethics in Scopus-indexed scientific publications.

Patients with hepatocellular carcinoma (HCC) who require multiple transarterial chemoembolization (TACE) treatments in quick succession and prediction of outcome.

e16208 Background: TACE has been one of the standard treatments for intermediate-stage HCC patients for over 20 years. The outcome of patients from TACE treatment is variable as the result of the differences in tumor burden, liver function, and comorbidities. Given the advancement made in systemic therapies for advanced-stage HCC, and emerging data on the combination of TACE and immunotherapy, there is an unmet need to identify patients with intermediate-stage HCC who may benefit from early introduction of systemic therapy. The purpose of the study is to identify clinical factors that predict poorer outcomes in patients who receive TACE treatment. Methods: This retrospective analysis is a single-institutional study involving patients from MedStar Georgetown University Hospital. The investigation includes 167 individuals diagnosed with HCC who underwent TACE from 2007 to 2021. The data compiled for analysis encompassed patient demographics, clinical features, risk factors, and treatment outcomes. The log-rank test is used to test whether there is a difference between the survival times of different groups. Results: 167 HCC patients, with 105 in intermediate/advanced BCLC stages B and C were included. The cohort, with a median age of 62, comprised 128 males and 43 females. Cirrhosis was seen in 83% of patients mostly due to viral etiology. Hepatitis C (58%) and hepatitis B (13%) were common, with 4% having both. The remaining 24% had cirrhosis from metabolic-associated fatty liver disease (MAFLD). The median overall survival (OS) durations for patients in BCLC-A (n = 62), BCLC-B (n = 64), and BCLC-C (n = 41) stages who underwent TACE as a component of their comprehensive treatment strategy were 67.9, 29.7, and 30.6 months, respectively (P = 0.035). In 64 subjects with BCLC stage B disease, patients who received 3 or more TACE treatments had higher OS (43.6 months) than those with two or fewer treatments (25.4 months, P = 0.042). Among the patients who had 2 or fewer TACE treatments, 6 patients had liver decompensation and discontinued treatment and 21 patients developed cancer progression and went on to receive systemic therapy. The median time to progression from the last TACE treatment was 5 months. Interestingly, among the patients who received 3 or more TACE treatments, 10 patients who had 3 or more TACE treatments within 6 months from the 1st TACE treatment had an mOS of 25.8 months while 25 patients who had 3 or more TACE treatments over a time span more than 6 months had a mOS of 49.4 months (P = 0.0186). Conclusions: Rapid disease progression in 6 months from the start of TACE treatment was predictive of aggressive tumor biology, and these patients may benefit from the early introduction to systemic therapy. Molecular biomarkers used to predict aggressive tumor biology are an unmet need for selecting patients to receive the combination of TACE and systemic therapy.

Cross-cultural differences in diet and quality of life between Taiwanese and American women during breast cancer treatment.

e23187 Background: Limited research has examined the role of different food types (vegetables, fruits, meat, fat, and whole grains) on quality of life (QoL) among cancer patients undergoing active treatment. This study aimed to examine what different food intakes are associated with QoL among American and Taiwanese women who are newly diagnosed with breast cancer (BC). Methods: This ongoing observational study enrolled 77 American (Black, Latina, and non-Hispanic White) adult women from MedStar Georgetown University Hospital and 79 Taiwanese women from National Taiwan University Hospital. They were diagnosed with stage 0-III primary BC within six months prior to enrollment, were undergoing surgery, chemotherapy, and radiation, with no other cancers. Patient-reported overall health and QoL were assessed using the two global health items from the EORTC-QLQ30. Three random 24-hour diet recalls (two weekdays and one weekend) were administered using the NIH-developed ASA24 program. Linear regression was conducted to examine the associations between food categories and QoL outcome, adjusting for nationality, age, cancer stage, treatment type, body mass index, physical activities, financial problems, and appetite loss. Results: American and Taiwanese patients displayed differing food intake during BC treatment. Taiwanese patients consumed less starchy vegetables and total fat (both p < .01) than American patients, on average. Multivariate results indicated that QoL was positively associated with higher total vegetable intake (excluding starchy vegetables and legumes; β = 5.38, 95% CI: 0.22, 1.20), controlling for other food types and covariates. Starchy vegetables and legumes showed non-significant negative effects on QoL. QoL was positively associated with total fat intake (β = 0.11, 95% CI: 0.02, 0.21). Total meat, fruit, and whole grain intakes were not significantly associated with QoL. Conclusions: The associations between food intakes and QoL were not affected by nationality, regardless of food type. Non-starchy vegetables and adequate total fat intakes may support BC patients undergoing treatments. More research is needed to verify the identified associations and explore how cancer treatment affects the digestion of certain food types and their potential impact on QoL. This study provides cross-cultural insights into potential nutritional influence on QoL among patients undergoing cancer treatment.

Developing behavioral intervention to support molecular testing of patients with biliary tract cancer.

TPS1641 Background: Biliary tract cancer (BTC) represents 7% of gastrointestinal malignancies in the United States, with an incidence of 0.5 to 2.0 cases per 100,000 individuals. Standard care involves systemic chemotherapy, predominantly gemcitabine and cisplatin. Recent advancements in immunotherapy, as evidenced by the TOPAZ-1 trial and KN966, support the use of durvalumab, and pembrolizumab as treatment options. Genetic tumor testing identifies up to 40% of BTC patients with targetable mutations, leading to recent FDA approvals for FGFR2 inhibitors - pemigatinib, infigratinib, futibatinib, and IDH1 inhibitor ivosidenib. The emerging data on inhibitors targeting the BRAF mutation, together with HER2 amplification, underscore the importance of understanding the tumor's molecular profile. Navigating this evolving treatment landscape emphasizes an unmet need for patients to comprehend the pivotal significance of tumor molecular profiling in formulating effective and personalized treatment plans. Identifying knowledge gaps among BTC patients concerning tumor genetic testing and precision medicine, along with strategies to address these gaps, holds promise for improving the management and the outcome of patients with BTC. Methods: This is a behavioral intervention study where participants will undergo two in-person survey interviews before and after an educational intervention. The initial survey aims to establish baseline knowledge about the BTC diagnosis and treatment and ascertain preferences for various educational interventions. Patients’ knowledge gap will be determined by comparing their responses to the initial survey and medical history documented by their treating physicians. They will then be provided with a 10-minute educational video. Participants will have the flexibility to access the video multiple times. Within 6 weeks from enrollment, they will have a post-education survey to determine the effectiveness of the education intervention. Following completion of baseline surveys, collaboration with key stakeholders including medical oncology and community perspectives will be initiated to identify knowledge gaps and inform the design of an educational intervention. The study enrollment will be targeted at BTC patients receiving systemic therapy at Georgetown University Hospital, Fox Chase Cancer Center, and Hackensack Meridian Health. Ten participants are enrolled and have completed the first survey and intervention. This study is currently enrolling participants: GUIRB: STUDY00007119.

A case of confusion: context matters when using reference images on exams

Instructors utilize reference figures from textbooks, journals, and other sources on quizzes and exams to illustrate concepts that would otherwise be diffcult to convey using written text. Examples within biomedical teaching include anatomical images and graphs that students are expected to analyze or interpret. However, the use of a figure may cause confusion and lead students to select an incorrect answer. As such, instructors must evaluate the use of figures to ensure that they enhance students’ ability to correctly answer the question rather than hinder it. This report shows an example where the inclusion of a reference figure led to the majority of students incorrectly answering a question.Over 6 semesters in a master’s level graduate neuroscience course between 2019 and 2021, the same question was used with and without a reference figure in a variety of contexts to determine the factors that contributed to students overwhelmingly selecting an incorrect answer. In the question, students were asked to identify neuroarchitectural adaptations in the somatosensory cortex following amputation. To determine the correct answer, students needed to integrate knowledge of the discriminative touch sensory pathways with knowledge of cortical plasticity.In semesters where the figure was presented without specific teaching interventions, 57% of students selected an incorrect answer that utilized the proximity of cortical sites but was not supported by the signaling pathways. In these semesters, only 39% of students correctly answered. In semesters where the figure was not used, 94% of students correctly answered the question while only 6% of students selected the most common incorrect answer when the figure was present.Teaching interventions were introduced during two semesters in an attempt to “teach the question.” Students were asked to read primary literature on the topic, additional examples and cases were introduced, and in one semester, a similar practice question using was given to the students. Students were then presented with the question containing the image. 56% of students selected the most common incorrect answer while only 42% of students correctly answered the question.While no formal survey of the students was conducted, anecdotal evidence from student offce hours, directed inquiries, and casual conversations indicate that students generally felt that use of the figure, when present, was critical to answering the question and many reported that using the figure led them to prioritize their knowledge of cortical plastic adaptations over that of the signaling pathways.These results demonstrate the importance of carefully utilizing reference images on questions for quizzes and exams. The visual cues of the image can be powerful stimuli for students when analyzing the information and can sometimes lead to incorrect answers on the assessment. This work was supported by internal funding from the Georgetown University Graduate School of Biomedical Sciences and Georgetown University Medical Center’s Center for Innovation and Leadership in Education (CENTILE). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Designing and Developing a Medical-Legal Partnership to Address Cancer Patients' Health-Harming Legal Needs

Summary: The Georgetown University's Cancer Legal Assistance and Well-being Project launched in 2020 as a medical-legal partnership that works with health care providers at a Washington, D.C. safety-net hospital to treat the health-harming legal needs of historically and intentionally marginalized patients with cancer.

Stereotactic Body Radiation Therapy for Clinically Localized Prostate Cancer in Men With Hip Prostheses: A Cautionary Note.

Stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for prostate cancer. SBRT requires high accuracy to reduce treatment margins. Metal hip prostheses create artifacts that distort pelvic imaging and potentially decrease the accuracy of target/organ at risk (OAR) identification and radiation dose calculations. Data on the safety and efficacy of SBRT after hip replacement is limited. This single-institution study sought to evaluate the safety and local control following SBRT for prostate cancer in men with hip replacements. 23 patients treated with localized prostate cancer and a history of pre-treatment hip replacement, treated with SBRT from 2007 to 2017 at MedStar Georgetown University Hospital were included in this retrospective analysis. Treatment was administered with the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) at doses of 35 Gy or 36.25 Gy in 5 fractions. The targets and OARs were identified and contoured by a single experienced Radiation Oncologist (SPC).The adequacy of the CT and T2W MRI images for treatment planning was assessed with a three-point scale (good, adequate, or suboptimal).During treatment planning, care was taken to avoid treatment beams that directly traversed the hip prosthesis. Toxicities were recorded and scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Local recurrence was confirmed by magnetic resonance imaging and/or prostate biopsy. The median follow-up was seven years. The patients were elderly (median age = 71 years) with a high rate of comorbidities (Charlson Comorbidity Index > 2 in 25%). Four patients had bilateral hip replacements. The majority of patients were low to intermediate risk per the D'Amico classification. Around 13% received upfront ADT. In total, 13 patients were treated with 35 Gy, and 10 were treated with 36.25 Gy.The rates of late > Grade 3 GU toxicity and> Grade 2 GI toxicity were 8.6% and 4.3%, respectively. There were no Grade 4 or 5 toxicities.Six patients (26%) developed a local recurrence at a median time of 7.5 years. Of these six patients, four had unilateral hip replacements and two had bilateral.Three underwent salvage cryotherapy and three received salvage ADT. In the general population, high-grade toxicities and local recurrences are uncommon following prostate SBRT.However, in this cohort of patients with prior hip replacements, prostate SBRT had higher than expected rates of late toxicity and local recurrence. In the opinion of the authors, such patients should be counseled regarding an elevated risk of late toxicity and local recurrence with prostate SBRT. With its ultrasound guidance, brachytherapy would have the advantage of circumventing the need for MRI/CT-based imaging and thus may represent a preferable radiation alternative in this patient population. If these patients are treated with SBRT, they should be monitored closely for local recurrence so early salvage can be performed. We hopethat recent advances in metal artifact reduction techniques and dose-calculation algorithms will improve future outcomes.

Vertical contour calcanectomy: A case series in rural Northeastern Pennsylvania

Diabetes is an epidemic in the United States contributing to poor outcomes related to ulceration and lower leg amputations. Physicians from a number of specialties are continuing to seek opportunities to improve patient outcomes and maintain independence. Podiatric surgeons have an affinity for limb salvage in the face of acute or chronic ulcer complications of the lower extremity. In particular, heel ulcerations increase the risk of proximal amputation due to locality and the propensity for heel osteomyelitis. Partial calcanectomy (PC) had been a viable option prior to below knee amputation, but recent literature by Elmarsafi et al. shows an increasing number of positive outcomes with a new procedure called the vertical contour calcanectomy (VCC). This has prompted researchers from Georgetown University to develop and publish this technique since 2019. The purpose of this article was to validate the versality and reproducibility of limb salvage with use of the VCC in the rural region of Northeast Pennsylvania in the management of complicated infections of the heel.

American Catholics and the Quest for Equality in the Civil War Era

In American Catholics and the Quest for Equality in the Civil War Era, Robert Emmett Curran argues that nineteenth-century America did not offer equal opportunities for Blacks, Native Americans, Jews, Catholics, and women. Curran, a professor emeritus of history at Georgetown University, focuses on Catholics’ pursuit of equality from 1846 to 1877, showcasing their transformation from “internal aliens” to full-fledged citizens, which did not prevent them from seeking to deprive others, especially African Americans, of the same.

Deter, Disrupt, or Deceive: Assessing Cyber Conflict as an Intelligence Contest, Robert Chesney and Max Smeets, Eds. Georgetown University Press, 2023

Deter, Disrupt, or Deceive: Assessing Cyber Conflict as an Intelligence Contest, Robert Chesney and Max Smeets, Eds. Georgetown University Press, 2023

Abstract 1074: Plasma EV profiling facilitates low abundance biomarker discovery in pancreatic cancer

Abstract The lack of reliable biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) results in poor prognosis due to advanced disease at diagnosis. Biopsies for pancreatic cancer are known to be particularly difficult to perform because of the location of the pancreas and low volume of primary tumors that metastasize aggressively. Currently, there is no blood test or other screening modality in use, for stratification of individuals with higher-than-average risk (5-8-fold) of developing PDAC in their lifetime. Given this existing void in the US and worldwide, an FDA-compliant, minimally invasive, quantitative biomarker test for the early detection of PDAC would be critical for screening subpopulations with, a) inherent genetic or familial predisposition; history of chronic pancreatitis; c) precursor lesions of pancreas; and d) older patients (>50 years) with new onset diabetes or sudden weight loss. Extracellular vesicles (EVs) are shed by normal and cancer cells and carry a rich molecular cargo that can be leveraged for biomarker discovery. Whereas molecular profiling of bio-fluids poses intrinsic limitations for detection of low abundant, disease-specific biomarkers due to matrix effects; EVs, on the other hand, offer promise as a robust and minimally invasive biomarker resource. Mass spectrometry data were developed in our laboratory, based on multi-omics (proteomics, lipidomics and metabolomics) analyses of plasma EVs derived from patients diagnosed with early-stage PC (N=60), pancreatitis (N=39), precursor lesions of pancreas (N=45) as well as normal controls (N=50). These clinically annotated samples were made available by the Georgetown University Medical Center (GUMC) repository. Feature selection using a training-validation design allowed the development of a multiplexed biomarker panel comprising of 12-analytes (5-lipids, 2-metabolites and 5-proteins) that can robustly stratify early-stage PC from normal controls with high accuracy (AUC>95%). Availability of a FDA compliant, multi-analyte-based classification algorithm that can stratify patients with precursor lesions of the pancreas that are at potential risk of progression to PC with > 90% specificity and sensitivity is a critical clinical need. Refinement of panel to improve positive predictive value as well as identification of markers predictive of progression of precursor lesions to malignant transformation is ongoing. Citation Format: Shivani Bansal, Shu Wang, Yaoxiang Li, Sunil Bansal, Jill Smith, John B. Tyburski, Keith Unger, Amrita Cheema. Plasma EV profiling facilitates low abundance biomarker discovery in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1074.

Bothersome Hot Flashes Following Neoadjuvant Androgen Deprivation Therapy and Stereotactic Body Radiotherapy for Localized Prostate Cancer.

Androgen deprivation therapy (ADT) improves local cancer control in unfavorable localized prostate cancer treated with radiotherapy. ADT is known to cause hormonally related symptoms that resolve with testosterone recovery. Hot flashes are particularly burdensome. This study sought to evaluate the timeline of hot flashes following short-course ADT and stereotactic body radiotherapy (SBRT) as well as its relationship with testosterone recovery. Institutional IRB approval was obtained for this retrospective review of prospectively collected data (IRB#: 2009-510). ADT was initiated three months prior to the start of SBRT. Hot flashes were self-reported via question 13a of the Expanded Prostate Index Composite (EPIC)-26 prior to ADT initiation, the first day of robotic SBRT, and at each follow-up (one, three, six, nine, 12, 18, 24, and 36 months). The responses were grouped into three relevant categories (no problem, very small-small problem, and moderate-big problem). Scores were transformed to a 0-100 scale with higher scores reflecting less bother. Testosterone levels were measured at each follow-up. From 2007 to 2010, 122 localized prostate cancer patients (nine low-, 64 intermediate-, and 49 high-risk according to the D'Amico classification) at a median age of 72 years (range 54.5-88.3) were treated with short course ADT (three to six months) and SBRT (35-36.25 Gy) at Georgetown University Hospital. Thirty-two percent were Black and 27% were obese. Seventy-seven percent of patients received three months of ADT. At baseline, 2% of men experienced hot flashes that were a "moderate to big problem" and that proportion peaked at the start of SBRT (45%) before returning to baseline (2%) nine months post-SBRT with a cumulative incidence of 52.4%. The median baseline EPIC-26 hot flash score of 94 declined to 50 at the start of SBRT but this returned to baseline (92) by six months post SBRT. These changes were both statistically and clinically significant (MID = 9.5083, p<0.01). Testosterone recovery (> 230 ng/dL) occurred in approximately 70% of patients by 12 months post SBRT. Resolution of hot flashes correlated with testosterone recovery. Bothersome hot flashes occur in greater than 50% of men treated with neoadjuvant ADT. Resolution of hot flashes occurs in the majority of patients within one year after treatment. Reassurance of the temporary nature of hot flashes may assist in reducing patient anxiety. Measuring testosterone levels at follow-up visits may allow for anticipatory counseling that may limit the associated bother.