Faculty Bibliography

The therapeutic benefit of recently developed mutant KRAS (KRAS∗) inhibitors remains limited by the rapid onset of resistance. Here, we aim to delineate mechanisms underlying acquired resistance and identify actionable targets for overcoming this clinical challenge. Previously, we identified syndecan-1 (SDC1) as a key effector for pancreatic cancer progression whose surface expression is driven by KRAS∗. By leveraging both pancreatic and colorectal cancer models, we show that surface SDC1 expression initially diminishes upon KRAS∗ inhibition but recovers in tumor cells that bypass KRAS∗ dependency. Mechanistically, we reveal that YAP1 activation drives the recovery of SDC1 surface localization to enhance macropinocytosis-mediated nutrient salvaging and activation of multiple receptor tyrosine kinases for tumor maintenance, promoting resistance to KRAS∗-targeted therapy. Overall, our study provides a strong rationale for targeting the YAP-SDC1 axis to overcome resistance to KRAS∗ inhibition, thereby revealing promising therapeutic opportunities for improving the clinical outcome of patients with KRAS∗-mutated cancers.

Although the severity of pathology in incoming college students has increased over the last decade, hospitalized students remain an under-researched group at risk for attrition, trauma, suicide, and disconnection with their universities. The present study sought to explore the experiences of hospitalization for college students at a large, public, Southwestern university through a lens of student retention theory, Self-Determination Theory (SDT), and institutional betrayal. Qualitative interviews were conducted with ten current or recently graduated students, hospitalized between Fall 2017 and Spring 2021, about their experiences with psychological services prior to hospitalization, the hospitalization process, the hospitalization itself, and post discharge. Interview participants had complex and nuanced experiences with hospitalization. Themes included neutral experiences with psychological services pre-hospitalization, trust/distrust, powerlessness, interpersonal connections, uncertainty, negative perceptions of the university, academic supports, and shifts in perspective. Future clinical and research implications are discussed.

BACKGROUND:Neoadjuvant chemotherapy has been used to downstage locally advanced ER+/HER2- breast cancer with low response rates. The optimal neoadjuvant regimen for this population is unknown. PATIENTS AND METHODS/METHODS:Between 2017 and 2022, 192 patients (ages 28-78) with stage II/III ER+/Her2- breast cancer at our institution were evaluated. Patients were divided into 4 groups based on the neoadjuvant chemotherapy regimen used (AC-T, TC, TAC, or other). The responses were categorized as complete (ypT0/is ypN0), partial, no response, or progressive disease. RESULTS:The choice of neoadjuvant chemotherapy was not predictive of pCR (P = .3864), even among those with more advanced nodal disease. No significant difference was noted in OS or IDFS at 24 or 48 months between the AC-T and TC groups. In the AC-T group (n = 130), 9 patients had a CR (6.98%), while no patients in TC group had a CR. Those who were premenopausal were more likely to achieve pCR compared to those postmenopausal. Race significantly impacted IDFS. CONCLUSIONS:In this single center study, we found no differences in IDFS or OS when comparing neoadjuvant TC to AC-T. The AC-T regimen group had a higher pCR rate of 6.98% compared to 0% in TC regimen group. Further exploration is needed to understand why non-white populations have inferior IDFS.

INTRODUCTION/BACKGROUND:The discharge process is a crucial component of the emergency department (ED) encounter, with poor discharge quality often leading to negative patient outcomes. While numerous interventions have been implemented to improve this process, a comprehensive review of these interventions has not been conducted. This study provides a scoping, summative review of adult ED discharge interventions to date, evaluating the literature for potential best practices and future directions. METHODS:We conducted a scoping review of published literature on MEDLINE ALL (Ovid), Embase (Ovid), the Cochrane Central Register of Controlled Trials (Wiley), and CINAHL (EBSCOhost) on February 7, 2023, for articles reporting on ED-based discharge interventions. We excluded the following: studies involving pediatric patient populations; discharge from non-ED settings; in-ED risk screening and/or case management as the primary intervention; interventions occurring mostly after the ED encounter (even if initiated at time of discharge); and studies not written in English. RESULTS:The initial electronic database search yielded 3,842 unique titles and abstracts. After applying inclusion/exclusion criteria at various screening stages, we included 100 papers and abstracts in the final review. These studies, published between 2003 - 2023, predominantly originated from the US (66%). Using narrative synthesis, we summarized ED discharge intervention themes to form seven concept subgroups by consensus: mode of discharge; additional resource provision; addition of a discharge coordinator; follow-up assistance; pharmaceutical intervention; patient-centered education; and clinician/discharger-centered education. Effective strategies included enhanced discharge discussions and education by dedicated personnel, structured discharge checklists, and delivery of instructions at an appropriate reading level. However, because few studies have examined long-term patient-centered outcomes, such as ED return visits, hospitalizations, and mortality, cost-benefit analysis for interventions is lacking. Furthermore, the experiences of vulnerable populations who have limited-English proficiency are under-represented in current attempts to innovate ED discharge. CONCLUSION/CONCLUSIONS:We found that interventions aimed at improving patient comprehension of discharge instructions were the most frequently studied and had the greatest impact on patient outcomes. This review highlights promising directions for patient-centered innovation; it also underscores the need for more research to optimize the adult ED discharge process and warrants a call to action.

OBJECTIVES/OBJECTIVE:To compare the effectiveness of tabletop exercises (TTX) and high-fidelity in-person simulations (IPS) in improving knowledge, confidence, and perceived preparedness in disaster medicine among emergency medicine residents. METHODS:< 0.01. RESULTS:= 0.079). CONCLUSIONS:TTX is an effective modality for disaster medicine education, with outcomes comparable to IPS. While TTX may better align with knowledge-based assessments, IPS remains essential for practicing real-time decision-making under stress. Combining these 2 modalities may provide both the knowledge base and psychological duress required for robust disaster scenario training.

PURPOSE/OBJECTIVE:Residency programs are increasingly interested in or required to assess residents using Accreditation Council for Graduate Medical Education (ACGME) milestones and specialty-defined entrustable professional activities (EPAs). The authors aimed to develop a model to predict individual residents' milestone levels based on their assigned EPA entrustment-supervision levels. METHOD/METHODS:During 3 academic years from 2021 to 2024, the authors conducted a multisite prospective cohort study at 48 U.S. pediatric residency programs. Programs collected entrustment-supervision levels for the 17 general pediatrics EPAs and milestone levels for the 22 ACGME pediatric milestones for every resident biannually. EPA and milestone ratings were assigned by clinical competency committees. The first 4 of 6 biannual data reporting cycles were used to fit multilevel structural equation models and produce equations to generate, for each resident, predicted milestone levels based on EPA entrustment-supervision levels. They developed 2 models: one using 17 EPAs and one using 12 EPAs. RESULTS:Data used for modeling represented 4,328 residents, with 164,886 total entrustment-supervision levels across the general pediatrics EPAs and 243,949 total milestone levels across the pediatric milestones. The fit of the round 1 to 4 model to the round 1 to 4 data (internal prediction) was excellent for both models, with comparative fit indexes of 0.982 (17 EPAs) and 0.981 (12 EPAs). The ability of the round 1 to 4 model to predict milestones for reporting cycles 5 and 6 (external prediction) was similar to the internal predictions, with correlation coefficients of 0.68 (17 EPAs) and 0.69 (12 EPAs) for round 5 and 0.72 (17 EPAs) and 0.68 (12 EPAs) for round 6. CONCLUSIONS:This study demonstrates a strong ability to predict milestone levels based on EPA entrustment-supervision levels in a manner that enables meaningful use of EPAs and milestones in assessment efforts at residency programs.

PURPOSE:Genitourinary syndrome of menopause (GSM) describes the symptoms and physical changes that result from declining estrogen and androgen concentrations in the genitourinary tract during the menopausal transition. There has not been a consensus reached about the number or type of symptoms needed to diagnose GSM, and the associated urinary symptoms are also linked with other common urologic conditions such as overactive bladder. This guideline provides information to clinicians regarding identification, diagnosis, counseling, and treatment for patients with GSM to optimize symptom control and quality of life while minimizing adverse events. MATERIALS AND METHODS:The systematic review utilized in the creation of this guideline is based on research conducted by the Minnesota Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality and funded by the Patient Centered Outcomes Research Institute. The Evidence-based Practice Center extracted and synthesized effectiveness and/or harms outcomes from 68 publications. An additional 66 publications evaluating 46 non-hormonal interventions, were described in an evidence map. RESULTS:Clinicians diagnose GSM based on symptoms, with or without related physical findings, and after ruling out other etiologies or co-occurring pathologies. There is a large body of evidence examining the use of hormonal and non-hormonal treatment options to manage the symptoms of GSM; however, the local low-dose vaginal estrogen has the most robust evidence base. CONCLUSIONS:The strategies defined in this document were derived from evidence-based and consensus-based processes. Given that there is insufficient information to recommend one hormonal therapy over another, this guideline is not meant to support a stepwise progression through different hormonal approaches. The clinician should make treatment decisions in the context of shared decision-making considering patient goals and preferences, using the evidence of efficacy and adverse events of each possible intervention as a guide.

PURPOSE:Genitourinary syndrome of menopause (GSM) describes the symptoms and physical changes that result from declining estrogen and androgen concentrations in the genitourinary tract during the menopausal transition. This guideline provides information to clinicians regarding identification, diagnosis, counseling, and treatment for patients with GSM to optimize symptom control and quality of life while minimizing adverse events. METHODS:The systematic review used in the creation of this guideline is based on research conducted by the Minnesota Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality and funded by the Patient Centered Outcomes Research Institute. The EPC synthesized effectiveness and/or harms outcomes from 68 publications. An additional 66 articles evaluating 46 nonhormonal interventions were described in an evidence map. RESULTS:Clinicians diagnose GSM based on symptoms, with or without related physical findings, and after ruling out other etiologies or co-occurring pathologies. There is a large body of evidence examining the use of hormonal and nonhormonal treatment options to manage the symptoms of GSM; however, the local low-dose vaginal estrogen has the most robust evidence base. CONCLUSION:The strategies defined in this document were derived from evidence-based and consensus-based processes. Given that there is insufficient information to recommend one hormonal therapy over another, this guideline is not meant to support a stepwise progression through different hormonal approaches. The clinician should make treatment decisions in the context of shared decision-making, considering patient goals and preferences, using the evidence of efficacy and adverse events of each possible intervention as a guide.

AIM/UNASSIGNED:To better understand the real-world impact that wearable technologies with vibration feedback are having on the treatment of body focused repetitive behaviours (BFRBs). MATERIALS AND METHODS/UNASSIGNED:A manual content analysis was performed on 173 Amazon, Google Play, and Apple reviews, collected from September 2016 to September 2023, on 3 wearable technologies designed to treat BFRBs: 1. Habit Aware Keen (versions 1 and 2), 2. Slightly Robot, and 3. Face Touch Aware. RESULTS/UNASSIGNED:96 % of all clinical commentary was positive. The most frequent endorsements were 1. symptomatic improvement, 2. increased awareness of BFRBs throughout the day, and 3. rapid symptom reduction. 8 % of clinical commentary reported complete remission of BFRBs. CONCLUSION/UNASSIGNED:Our findings suggest that wearable technologies are being favourably adopted by the public to treat BFRBs. This treatment approach offers a unique advantage over traditional behaviour modification therapies, which have been limited by lack of trained therapists and cost.