Obesity Predisposes Anthracycline-Treated Survivors of Childhood and Adolescent Cancers to Subclinical Cardiac Dysfunction.

Anthracyclines are effective chemotherapeutics used in approximately 60% of pediatric cancer cases but have a well-documented risk of cardiotoxicity. Existing cardiotoxicity risk calculators do not include cardiovascular risk factors present at the time of diagnosis. The goal of this study is to leverage the advanced sensitivity of strain echocardiography to identify pre-existing risk factors for early subclinical cardiac dysfunction among anthracycline-exposed pediatric patients. We identified 115 pediatric patients with cancer who were treated with an anthracycline between 2013 and 2019. Peak longitudinal left ventricular strain was retroactively calculated on 495 surveillance echocardiograms via the TOMTEC AutoSTRAIN software. Cox proportional hazards models were employed to identify risk factors for abnormal longitudinal strain (> - 16%) following anthracycline treatment. High anthracycline dose (≥ 250 mg/m2 doxorubicin equivalents) and obesity at the time of diagnosis (BMI > 95th percentile-for-age) were both significant predictors of abnormal strain with hazard ratios of 2.79, 95% CI (1.07-7.25), and 3.85, 95% CI (1.42-10.48), respectively. Among pediatric cancer survivors, patients who are obese at the time of diagnosis are at an increased risk of sub-clinical cardiac dysfunction following anthracycline exposure. Future studies should explore the incidence of symptomatic cardiomyopathy 10-15 years post-treatment among patients with early subclinical cardiac dysfunction.

WellNest: A Medical Student-Run Housing Support Program.

PROBLEM: Being unhoused and facing housing insecurity contribute to poor health outcomes. Medical school curricula may include social determinants of health (SDOH) topics. However, experiential learning opportunities allow students to better contextualize how SDOH impact patients. The WellNest Housing Support Program (WellNest) was conceived and developed by Duke University medical students to learn from and support community members with a history of housing insecurity. APPROACH: Under the supervision of community organizations providing housing assistance services, WellNest was created in April 2020. Medical student-volunteers (MSVs) call clients, who are referred to WellNest by the community organizations, to plan move-ins. Local experts provide trainings on topics relevant to health care for individuals experiencing loss of housing. MSVs source and move furniture and clients' belongings into the new homes. Following move-in, MSVs are paired with clients to provide longitudinal tenancy support for at least 1 year. Student-volunteers contemplate their experiences and learning takeaways through debriefing sessions and an optional online survey. OUTCOMES: From fall 2021 to spring 2023, 83 student-volunteers from across the university participated in WellNest. Student-volunteers were generally medical students (37, 45%), and 16 MSVs served on the leadership team. WellNest facilitated 29 move-ins, and 26 clients requested to be paired with MSVs for longitudinal tenancy support. Following participation in WellNest, student-volunteers reported increased comfort, awareness, knowledge, and motivation related to caring for, discussing, and advocating for individuals experiencing housing insecurity. NEXT STEPS: As students from other programs are also interested in WellNest, there is potential for interprofessional education. Student-volunteers will be encouraged to participate in additional opportunities for reflection and advocacy activities. The impact of WellNest on clients will be explored through a questionnaire and narrative interviews. Long-term financial support was secured from community donations and partnering community organizations.

Development of a curricular thread to foster medical students' critical reflection and promote action on climate change, health, and equity.

INTRODUCTION: Due to the health consequences arising from climate change, medical students will inevitably interact with affected patients during their training and careers. Accordingly, medical schools must incorporate education on the impacts of climate change on health and equity into their curricula. We created a curricular thread called "Climate Change, Health, and Equity" in the first-year preclinical medical program to teach foundational concepts and foster self-reflection and critical consciousness. METHODS: The authors developed a continuum of practice including administrators, educators and faculty members, students, and community partners to plan and design curricular activities. First-year medical students at Duke University School of Medicine participated in seven mandatory foundational lectures and two experiential learning opportunities in the local community. Following completion of activities, students wrote a critical reflection essay and completed a self-directed learning exercise. Essays were evaluated using the REFLECT rubric to assess if students achieved critical reflection and for thematic analysis by Bloom's Taxonomy. RESULTS: All students (118) submitted essays. A random sample of 30 (25%) essays underwent analysis. Evaluation by the REFLECT rubric underscored that all students were reflecting or critically reflecting on thread content. Thematic analysis highlighted that all students (30/30, 100%) were adept at identifying new areas of medical knowledge and connecting concepts to individual experiences, institutional practices, and public health and policy. Most students (27/30; 90%) used emotionally laden words, expressing negative feelings like frustration and fear but also positive sentiments of solidarity and hope regarding climate change and effects on health. Many students (24/30; 80%) expressed actionable items at every level including continuing self-directed learning and conversing with patients, minimizing healthcare waste, and advocating for climate-friendly policies. CONCLUSION: After participating in the curricular thread, most medical students reflected on cognitive, affective, and actionable aspects relating to climate change, health, and equity.

Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection.

Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals. Among uninfected children and adolescents, young age was associated with upregulation of innate and adaptive immune pathways within the URT, suggesting that young children are primed to mount robust mucosal immune responses to exogeneous respiratory pathogens. SARS-CoV-2 infection was associated with broad induction of innate and adaptive immune responses within the URT of children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents were dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways was observed only in adults. Systemic symptoms among SARS-CoV-2-infected subjects were associated with blunted innate and adaptive immune responses in the URT and upregulation of many of these same pathways within peripheral blood. Finally, within individuals, robust URT immune responses were correlated with decreased peripheral immune activation, suggesting that effective immune responses in the URT may promote local viral control and limit systemic immune activation and symptoms. These findings demonstrate that there are differences in immune responses to SARS-CoV-2 across the lifespan, including between young children and adolescents, and suggest that these varied host responses contribute to observed differences in the clinical presentation of SARS-CoV-2 infection by age. One Sentence Summary: Age is associated with distinct upper respiratory and peripheral blood transcriptional responses among children and adults with SARS-CoV-2 infection.