Faculty Bibliography

BACKGROUND/UNASSIGNED:In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting. OBJECTIVES/UNASSIGNED:The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial. DESIGN/UNASSIGNED:RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared with CP alone in patients with primary advanced or recurrent EC. METHODS/UNASSIGNED:Patients were randomized 1:1 to dostarlimab 500 mg, or placebo, plus CP every 3 weeks for 6 cycles, followed by dostarlimab 1000 mg, or placebo, every 6 weeks for up to 3 years. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events, version 4.03. RESULTS/UNASSIGNED:The safety population included 487 patients who received ⩾1 dose of treatment (241 dostarlimab plus CP; 246 placebo plus CP). Treatment-emergent AEs were experienced by 100% of patients in both arms. TRAEs occurred in 97.9% of the dostarlimab arm and 98.8% of the placebo arm.The most common TRAEs occurred at similar rates between arms and were mostly low grade. IrAEs occurred in 58.5% of patients in the dostarlimab arm and 37.0% of patients in the placebo arm. Dostarlimab- or placebo-related irAEs were reported in 40.7% of patients in the dostarlimab arm and 16.3% of the placebo arm. CONCLUSION/UNASSIGNED:The safety profile of dostarlimab plus CP was generally consistent with that of the individual components. Dostarlimab plus CP has a favorable benefit-risk profile and is a new standard of care for patients with primary advanced or recurrent EC. TRIAL REGISTRATION/UNASSIGNED:NCT03981796.

Highly effective antiobesity and diabetes medications such as glucagon-like peptide 1 (GLP-1) agonists and glucose-dependent insulinotropic polypeptide/GLP-1 (dual) receptor agonists (RAs) have ushered in a new era of treatment of these highly prevalent, morbid conditions that have increased across the globe. However, the rapidly escalating use of GLP-1/dual RA medications is poised to overwhelm an already overburdened health care provider workforce and health care delivery system, stifling its potentially dramatic benefits. Relying on existing systems and resources to address the oncoming rise in GLP-1/dual RA use will be insufficient. Generative artificial intelligence (GenAI) has the potential to offset the clinical and administrative demands associated with the management of patients on these medication types. Early adoption of GenAI to facilitate the management of these GLP-1/dual RAs has the potential to improve health outcomes while decreasing its concomitant workload. Research and development efforts are urgently needed to develop GenAI obesity medication management tools, as well as to ensure their accessibility and use by encouraging their integration into health care delivery systems.

In medical education, pathology has traditionally been concentrated in only the preclinical years, often without sufficient emphasis on its practical application in clinical practice. Correspondingly, medical students' interest in pathology as a career has been low. To address this issue and foster a deeper understanding of pathology's clinical relevance and encourage appropriate utilization, we introduced a required exposure to pathology in the surgery clerkship featuring clinicopathological case review in a small group setting. Unlike other approaches, we wanted to create a program that concentrates on pathology cases directly linked to patients whom students cared for during their clerkship rotation, emphasizing the relevance of pathology diagnosis. Feedback has been overwhelmingly positive from participating students, who report an increased awareness of pathology's importance in patient management and of the significance of interdisciplinary collaboration between pathologists and clinicians. A notable feature of this program is its relatively low time and personnel requirements, which facilitate inclusion in the busy clerkship and acceptance in the Department of Pathology. Challenges, such as timely case selection and administrative co-ordination, are being addressed to optimize the program's implementation. In the future, we are considering expanding this model to other clerkships. By rekindling interest in pathology through practical engagement and highlighting its real-world relevance, this approach offers a promising strategy to counteract recruitment challenges in this crucial medical field.

BACKGROUND/UNASSIGNED:Spontaneous coronary artery dissection (SCAD) is a disease entity that often occurs in young, healthy women and can cause life-threatening ventricular arrhythmias and sudden cardiac arrest. However, the characteristics and outcomes of SCAD with cardiac arrest are not well characterized. METHODS/UNASSIGNED:This study investigated the baseline characteristics of SCAD patients with cardiac arrest using the National Inpatient Sample (NIS) database between 2016 and 2020. In addition, we also sought to determine the potential impact that implantable cardioverter defibrillator (ICD) therapy had on morbidity and mortality in SCAD patients presenting with cardiac arrest. RESULTS/UNASSIGNED:Our findings showed that the SCAD with cardiac arrest population had significantly higher comorbidities, including cardiac arrhythmias, congestive heart failure, pulmonary circulation disorders, liver diseases, solid tumors, coagulopathy, fluid disorders, chronic kidney disease (CKD), anemia secondary to deficiency, psychosis, neurological disorders, carotid artery disease, atrial fibrillation, ventricular arrhythmias (ventricular tachycardia (VT), ventricular fibrillation (VF)), and acute myocardial infarction (AMI), compared to the SCAD without cardiac arrest population. Likewise, for SCAD patients who did not have an ICD in place, we found increasing age, fluid and electrolyte disorders, uncomplicated diabetes, neurological disorders, peripheral vascular disease, pulmonary circulatory disorders, cardiac arrhythmias, and congestive heart failure to be associated with greater mortality. CONCLUSIONS/UNASSIGNED:SCAD patients with certain comorbidities (e.g., pulmonary diseases, liver diseases, cancers, coagulopathy, and CKD) who presented with AMI or congestive heart failure should be monitored closely for ventricular arrhythmias as they have a higher chance of progressing to cardiac arrest. ICD therapy can be considered for these patients, but data on the success of this treatment option are limited, and more research needs to be performed to determine whether the benefits of this outweigh the risks.

We argue that generalist radiology artificial intelligence (GRAI) challenges current healthcare reimbursement frameworks. Unlike narrow AI tools, GRAI's multi-task capabilities render existing pathways inadequate. This perspective examines key questions surrounding GRAI reimbursement, including issues of coding, valuation, and coverage policies. We aim to catalyze dialogue among stakeholders about how reimbursement might evolve to accommodate GRAI, potentially influencing AI reimbursement strategies in radiology and beyond.

Tau interacts with multiple heterogeneous nuclear ribonucleoproteins (hnRNPs)-a family of RNA binding proteins that regulate multiple known cellular functions, including mRNA splicing, mRNA transport, and translation regulation. We have previously demonstrated particularly significant interactions between phosphorylated tau and three hnRNPs (hnRNP A1, hnRNP A2B1, and hnRNP K). Although multiple hnRNPs have been previously implicated in tauopathies, knowledge of whether these hnRNPs colocalize with tau aggregates or show cellular mislocalization in disease is limited. Here, we performed a neuropathological study examining the colocalization between hnRNP A1, hnRNP A2B1, hnRNP K, and phosphorylated tau in two brain regions (hippocampus and frontal cortex) in six disease groups (Alzheimer's disease, mild cognitive impairment, progressive supranuclear palsy, corticobasal degeneration, Pick's disease, and controls). Contrary to expectations, hnRNP A1, hnRNP A2B1, and hnRNP K did not colocalize with AT8-immunoreactive phosphorylated tau pathology in any of the tauopathies examined. However, we did observe significant cellular mislocalization of hnRNP A1, hnRNP A2B1 and hnRNP K in tauopathies, with unique patterns of mislocalization observed for each hnRNP. These data point to broad dysregulation of hnRNP A1, A2B1 and K across tauopathies with implications for disease processes and RNA regulation.

The 2022 American Society of Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) updated the indications for Metabolic and Bariatric Surgery (MBS), replacing the previous guidelines established by the NIH over 30 years ago. The evidence supporting these updated guidelines has been strengthened to assist metabolic and bariatric surgeons, nutritionists, and other members of multidisciplinary teams, as well as patients. This study aims to assess the level of evidence and the strength of recommendations compared to the previously published criteria.