Building a Physician-Scientist Pathway for Underrepresented Medical Students Through a Summer Research Experience.

PROBLEM: There is a need to increase the number of physician-scientists from underrepresented in medicine (URiM) groups. To engage URiM medical students, a committee of pediatric departmental leaders at the Children's Hospital of Philadelphia created the Summer Underrepresented in Medicine Medical Student Research program. This 8-week, onsite research and clinical experience takes place during the summer between students' first and second years of medical school. APPROACH: Applications were solicited between 2019-2023 through nationwide outreach to medical school deans and members of URiM student organizations. Accepted students were assigned a mentor to lead their research and clinical exposure. A curriculum highlighting aspects of academic medicine was developed. Students received a $3,000-$5,500 stipend for in-person participation. In 2020 and 2021, adjustments were made (e.g., virtual programming) to avoid interruptions during the COVID-19 pandemic. OUTCOMES: In the 2019-2023 application cycles, 298 students applied. Of 128 students who participated, 78 (61%) completed a postprogram survey. Students' survey feedback was positive. They indicated the program met expectations (mean rating = 1.3; scale: 1 = strongly agree to 5 = strongly disagree). Students reported they learned valuable information/skills (mean = 1.3) and that participation was worth time spent away from other responsibilities (mean = 1.3). The 2019 cohort (n = 12) achieved a 100% residency match rate. In addition, 4 (33%) of these students reported they are obtaining additional degrees or are performing research. After the program, many mentors continued to include students in their research projects. NEXT STEPS: Next steps include incorporating a standardized, scored rubric for selecting applicants; adding 3 lead mentors, an executive committee, and a faculty advisory board; establishing earlier pathway programming (e.g., at elementary and middle school levels); continuing to track/support alumni throughout their careers; and pursuing federal funding to expand the program.

Breast cancer-related lymphedema rates after modern axillary treatments: How accurate are our estimates?

BACKGROUND: Clinical trials have demonstrated methods to minimize the risk of breast cancer-related lymphedema while preserving regional control. We sought to determine the percent lifetime-risk of breast cancer-related lymphedema that surgeons and radiation oncologists discuss with patients before axillary interventions. METHODS: A nationwide survey of surgeons and radiation oncologists was performed from July to August 2020. Participants were asked to identify what number they discuss with patients when estimating the percent lifetime-risk of breast cancer-related lymphedema after different axillary interventions. RESULTS: Six hundred and eighty surgeons and 324 radiation oncologists responded (14% response rate). While the estimated rate after sentinel lymph node biopsy was clinically similar between surgeons and radiation oncologists, statistically surgeons quoted a higher percent lifetime-risk (5.7% vs 5.0%, P = .03). Surgeons estimated significantly higher rates of breast cancer-related lymphedema compared with radiation oncologists (P < .001) for axillary lymph node dissection (21.8% vs 17.5%), sentinel lymph node biopsy with regional nodal irradiation (14.1% vs 11.2%), and axillary lymph node dissection with regional nodal irradiation (34.8% vs 26.2%). CONCLUSION: There is variability in the estimated rates of breast cancer-related lymphedema providers discuss with patients. These findings highlight the need for physician education on the current evidence of percent lifetime-risk of breast cancer-related lymphedema to provide patients with accurate estimates before axillary interventions.

A National Survey of Breast Surgeons and Radiation Oncologists on Contemporary Axillary Management in Mastectomy Patients.

BACKGROUND: Management of axillary lymph nodes in breast cancer has undergone significant change over the past decade through landmark clinical trials. This study aimed to assess national practice patterns in axillary management in patients undergoing upfront mastectomy and examines what guides provider recommendations. METHODS: A national case-based survey study was performed of surgeons and radiation oncologists from July to August 2020. Surgeons were identified through the American Society of Breast Surgeons (ASBrS) after review and approval by the ASBrS Research Committee, and radiation oncologists were identified through an institutional database. Both descriptive and comparative statistical analyses were performed. RESULTS: Overall, 994 providers responded-680 surgeons and 314 radiation oncologists. Surgeons were older and in practice longer (p < 0.05) and treated a higher percentage of breast patients (81% vs. 40%, p < 0.001). Most surgeons were hospital-employed (43%), whereas most radiation oncologists were in private practice (40%; p < 0.001). Fifty-two percent of surgeons routinely send sentinel lymph nodes (SLNs) for frozen section (52%) during mastectomy, of which 78% proceed directly to axillary lymph node dissection (ALND) if positive. There was significant variability in treatment recommendations between the two groups among the hypothetical cases (p < 0.001). In the setting of low disease burden in the SLNs, > 30% of surgeons recommended ALND, while radiation oncologists recommend axillary radiotherapy over axillary clearance (p < 0.001). CONCLUSION: There is significant heterogeneity in the management of the axilla in mastectomy patients with pathologically positive SLNs, both between and among surgeons and radiation oncologists. Efforts should be made to assist both groups in identifying de-escalation opportunities to ensure that mastectomy patients with positive SLNs are treated appropriately.

Role of thrombomodulin expression on hematopoietic stem cells.

BACKGROUND: Activation of protease-activated receptor 1 (PAR1) by either thrombin or activated protein C (aPC) differentially regulate the quiescence and bone marrow (BM) retention of hematopoietic stem cells (HSC). Murine HSC co-express THBD, PAR1, and endothelial protein C receptor (EPCR), suggesting that HSC sustain quiescence in a quasi-cell autonomous manner due to the binding of thrombin present in the microenvironment to THBD, activation of EPCR-bound protein C by the thrombin-THBD-complex, and subsequent activation of PAR1 by the aPC-EPCR complex. OBJECTIVE: To determine the role of THBD expression on HSC for sustaining stem cell quiescence and BM retention under homeostatic conditions. METHODS: Hematopoietic stem cell function was analyzed in mice with constitutive or temporally controlled complete THBD-deficiency by flow cytometry, functional assays, and single cell RNA profiling. RESULTS: THBD was expressed in mouse, but not human, HSC, progenitors, and immature B cells. Expression in vascular endothelium was conserved in humans' BM. Mice with constitutive THBD deficiency had a normal peripheral blood profile, altered BM morphology, reduced numbers of progenitors and immature B cells, pronounced extramedullary hematopoiesis, increased HSC frequency, and marginally altered transcriptionally defined HSC stemness. Transplantation experiments indicated near normal engraftment and repopulating ability of THBD-deficient HSC. Transgenic aPC supplementation normalized BM histopathology and HSC abundance, and partially restored transcriptional stemness, but had no effect on B cell progenitors and extramedullary hematopoiesis. Temporally controlled THBD gene ablation in adult mice did not cause the above abnormalities. CONCLUSION: THBD expression on HSPC has minor effects on homeostatic hematopoiesis in mice, and is not conserved in humans.

The Adult Murine Intestine is Dependent on Constitutive Laminin-γ1 Synthesis.

Laminin-γ1 is required for early embryonic development; however, the need for laminin-γ1 synthesis in adulthood is unknown. A global and inducible mouse model of laminin-γ1 deficiency was generated to address this question. Genetic ablation of the Lamc1 gene in adult mice was rapidly lethal. Despite global Lamc1 gene deletion in tamoxifen-induced mutant mice, there was minimal change in total cardiac, pulmonary, hepatic or renal laminin protein. In contrast, laminin-γ1 was significantly depleted in the small intestines, which showed crypt hyperplasia and dissociation of villous epithelium from adjacent mesenchyme. We conclude that the physiologic requirement for laminin-γ1 synthesis in adult mice is dependent on a tissue-specific basal rate of laminin-γ1 turnover that results in rapid depletion of laminin-γ1 in the intestine.