Faculty Bibliography

BACKGROUND:The existence of sociodemographic disparities in pancreatic cancer has been well-studied but how these disparities have changed over time is unclear. The purpose of this study was to longitudinally assess patient management in the context of sociodemographic factors to identify persisting disparities in pancreatic cancer care. METHODS:Using the National Cancer Database, patients diagnosed with pancreatic ductal adenocarcinoma from 2010 to 2017 were identified. The primary outcomes were surgical resection and/or receipt of chemotherapy. Outcome measures included changes in associations between sociodemographic factors (i.e., sex, age, race, comorbidity index, SES, and insurance type) and treatment-related factors (i.e., clinical stage at diagnosis, surgical resection, and receipt of chemotherapy). For each year, associations were assessed via univariate and multivariate analyses. RESULTS:Of 75,801 studied patients, the majority were female (51%), White (83%), and had government insurance (65%). Older age (range of OR 2010-2017 [range-OR]:0.19-0.29), Black race (range-OR: 0.61-0.78), lower SES (range-OR: 0.52-0.94), and uninsured status (range-OR: 0.46-0.71) were associated with lower odds of surgical resection (all p < 0.005), with minimal fluctuations over the study period. Older age (range-OR: 0.11-0.84), lower SES (range-OR: 0.41-0.63), and uninsured status (range-OR: 0.38-0.61) were associated with largely stable lower odds of receiving chemotherapy (all p < 0.005). CONCLUSIONS:Throughout the study period, age, SES, and insurance type were associated with stable lower odds for both surgery and chemotherapy. Black patients exhibited stable lower odds of resection underscoring the continued importance of mitigating racial disparities in surgery. Investigation of mechanisms driving sociodemographic disparities are needed to promote equitable care.

Mitral annular calcifications have been known to increase complexity during mitral valve replacement (MVR). Standard procedure requires decalcification followed by reconstruction of the mitral annulus prior to placing the prosthesis. While this is the ideal technique, it is not feasible in every patient due to the associated risks. The mere attempt at valve replacement without proper annular decalcification has been associated with a high incidence of periprosthetic leak which complicates the postoperative course and has been associated with increased morbidity and mortality. With the advances in transcatheter therapy, postoperative periprosthetic regurgitation can be managed with devices and primary transcatheter valve implantation could be alternative to standard valve replacement; however, these alternate strategies are not without its own limitations and drawbacks. In the current report, we present a novel strategy to be used in a select group of patients with severe but non-circumferential annular calcifications to prevent/minimize periprosthetic regurgitation during MVR. This involves placing a patch over the posteriorly located calcium bar, thus minimizing tension on the posterior suture line and contain any periprosthetic regurgitation if to develop. This modification has been performed in a total of nine cases with acceptable early results.

BACKGROUND:Binimetinib and selumetinib are two mitogen-activated protein kinase kinase (MEK) inhibitors used to treat low-grade gliomas and plexiform neurofibromas. Cutaneous toxicities are commonly associated with MEK inhibitors; however, limited studies have examined cutaneous effects in a pediatric population or whether toxicities vary between MEK inhibitors. METHODS:We conducted an IRB-approved, single-center, retrospective review of pediatric neuro-oncology patients on binimetinib or selumetinib who presented to NYU from April 2016 through July 2022. RESULTS:Forty-six children met inclusion criteria (23 females, 23 males) with a mean age of 11.7 years. Thirty-three were treated with binimetinib and 13 with selumetinib. Dermatologic adverse events were encountered in 97.8% of the cohort, and the most common were acneiform eruption (63.0%), paronychia (58.7%), and xerosis (54.3%). Children 12 years and older were more likely to have acneiform eruption (p < 0.001) and seborrheic dermatitis (p < 0.001), while children under 12 were more likely to have xerosis (p = 0.037). The incidence of cutaneous adverse events was significantly different between MEK inhibitors for folliculitis and hair pigment dilution (39.4% binimetinib, 0% selumetinib, p = 0.009). Significantly, more patients required MEK inhibitor dose reduction/hold on binimetinib (87.9%) than selumetinib (46.2%) (p = 0.006). Severity of cutaneous disease was not associated with tumor response. CONCLUSIONS:Our study confirms dermatologic adverse events are common in children on MEK inhibitors. Age appears to be associated with increased likelihood of certain cutaneous reactions. Overall, the selumetinib patients in our cohort presented with less severe adverse events and decreased risk of MEK inhibitor dose reduction/hold. Our results will aid clinicians in providing appropriate counseling, treatments, and improved preventive care.

INTRODUCTION/UNASSIGNED:Addressing systemic bias in medical school assessment is an urgent task for medical education. This paper outlines recommendations on topic areas for further research on systemic bias, developed from a workshop discussion at the 2023 annual meeting of the Society of Directors of Research in Medical Education. MATERIALS AND METHODS/UNASSIGNED:During the workshop, directors engaged in small-group discussions on guidelines to address bias in assessment practices following a proposed categorization of 'Do's,' 'Don'ts,' and 'Don't knows' and listed their insights using anonymous sticky notes, which were shared and discussed with the larger group of participants. The authors performed a content analysis of the notes through deductive and inductive coding. We reviewed and discussed our analysis to reach consensus. RESULTS/UNASSIGNED:The workshop included 31 participants from 28 institutions across the US and Canada, generating 51 unique notes. Participants identified 23 research areas in need of further study. The inductive analysis of proposed research areas revealed four main topics: 1) The role of interventions, including pre-medical academic interventions, medical-education interventions, assessment approaches, and wellness interventions; 2) Professional development, including the definition and assessment of professionalism and professional identity formation; 3) Context, including patient care and systemic influences; and 4) Research approaches. DISCUSSION/UNASSIGNED:While limited to data from a single workshop, the results offered perspectives about areas for further research shared by a group of directors of medical education research units from diverse backgrounds. The workshop produced valuable insights into the need for more evidence-based interventions that promote more equitable assessment practices grounded in real-world situations and that attenuate the effects of bias.

INTRODUCTION/UNASSIGNED:Over the past decade, the growth of accelerated three-year MD (3YMD) programs has flourished. In 2015, with support from the Josiah Macy Jr. Foundation, the Consortium of Medical Pathway Programs (CAMPP) started with eight North American medical schools. The objective of this paper is to evaluate the current state of the 3YMD programs. MATERIAL AND METHODS/UNASSIGNED:Since 2015, the CAMPP has tracked new and prospective 3YMD programs. An electronic survey collecting curricular and programmatic information about the programs was disseminated to all members of the CAMPP in August 2023. The survey included elements related to year of initiation, number of graduates, and curricular elements. RESULTS/UNASSIGNED:Of the schools with known established three-year MD programs, 29 of 32 programs responded (response rate 90%). There is growth of Accelerated Medical Pathway Programs over time with almost 20% of United States Allopathic Medical Schools having or developing an accelerated program. There have been 817 graduates from these programs from 2013-2023. Most schools include an opportunity for a 'directed pathway' experience for students. A directed pathway is where a student completes the MD degree in three-years and then has a direct placement into an affiliated residency program, provided they meet the goals and objectives of the curriculum. Most of the schools report a mission to reduce medical student debt and build a workforce for a specialty, for a population of patients, or geographical distribution. CONCLUSIONS/UNASSIGNED:Accelerated three-year medical pathway programs have grown significantly over the last decade, consistent with an overall effort to redesign medical curricula, reduce debt and contribute to the workforce.

The United States faces a shortage of primary care physicians. To address this, there have been pioneering efforts to develop accelerated pathways with a primary care focused curriculum for undergraduate medical education. The New York University Grossman Long Island School of Medicine (NYU GLISOM) was conceptualized as the first standalone, accelerated, tuition-free program in the US in over 100 years, with mission-centered curriculum on primary care and health system leadership. The aim of this article is to map the process for the development of a three-year integrated curriculum, describe the pedagogical approach that guided the design of the longitudinal courses, share the student and faculty's perspective about the curriculum, and describe the early outcomes of the first two graduate classes. A major key driver for curricular design is integrating longitudinal courses of Clinical Ambulatory Practice Experience (CAPE), Health Systems Science (HSS), and Learning Community - Social Sciences, Humanities, Ethics and Professionalism (LC-SHEP) over three years and active learning through Problem Based Learning (PBL). We have successfully operationalized an accelerated, standalone, integrated medical school curriculum mission-centered on primary care and health system leadership. Our outcomes reveal a higher percentage (76% N =45) of NYU GLISOM students entering primary care compared to national benchmarks. The integration of the longitudinal courses of HSS, LC-SHEP, and CAPE is a key pillar to reinforce the tenants of primary care and health system leadership. Focused interview of graduates from the pioneer cohort consistently stated that the longitudinal courses prepared them well for residency in primary care and as a health systems' change agent. Despite the challenges of an accelerated program, NYU GLISOM successfully integrated the longitudinal courses with optimal performance and achievement of educational program objectives. Our experience can serve as a model for innovation and design of an accelerated three-year primary care curriculum.

Metabolites can double as a signaling modality that initiates physiological adaptations. Metabolism, a chemical language encoding biological information, has been recognized as a powerful principle directing inflammatory responses. Cytosolic pH is a regulator of inflammatory response in macrophages. Here, we found that L-malate exerts anti-inflammatory effect via BiP-IRF2BP2 signaling, which is a sensor of cytosolic pH in macrophages. First, L-malate, a TCA intermediate upregulated in pro-inflammatory macrophages, was identified as a potent anti-inflammatory metabolite through initial screening. Subsequent screening with DARTS and MS led to the isolation of L-malate-BiP binding. Further screening through protein‒protein interaction microarrays identified a L-malate-restrained coupling of BiP with IRF2BP2, a known anti-inflammatory protein. Interestingly, pH reduction, which promotes carboxyl protonation of L-malate, facilitates L-malate and carboxylate analogues such as succinate to bind BiP, and disrupt BiP-IRF2BP2 interaction in a carboxyl-dependent manner. Both L-malate and acidification inhibit BiP-IRF2BP2 interaction, and protect IRF2BP2 from BiP-driven degradation in macrophages. Furthermore, both in vitro and in vivo, BiP-IRF2BP2 signal is required for effects of both L-malate and pH on inflammatory responses. These findings reveal a previously unrecognized, proton/carboxylate dual sensing pathway wherein pH and L-malate regulate inflammatory responses, indicating the role of certain carboxylate metabolites as adaptors in the proton biosensing by interactions between macromolecules.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and a major global health concern. In the United States (US), individuals of Black or African American racial identity experience disproportionately higher rates of TBI and suffer from worse post-injury outcomes. Contemporary research agendas have largely overlooked or excluded Black populations, resulting in the continued marginalization of Black patient populations in TBI studies, thereby limiting the generalizability of ongoing research to patients in the US and around the world. This review aims to highlight what is currently known, and identify knowledge gaps, in research on molecular biomarkers associated with TBI in Black populations. A PubMed literature search was conducted to identify studies that investigate molecular biomarkers associated with TBI outcomes that include participants of Black racial identity and those of African ancestry. Studies identified for this review investigate biomarkers associated with TBI outcomes through a lens that specifically examines race, ethnicity, or ancestry. Most studies focused on blood- or cerebrospinal fluid-derived protein biomarkers. Studies identified statistical variation in S100ß, ubiquitin C-terminal hydrolase-L1, amyloid-ß, and tau across participant race, either at baseline or following TBI. Additionally, several studies identified genetic polymorphisms associated with TBI outcomes related to apolipoprotein E, ANKK1, and COMT polymorphism and TBI outcome and identified allele frequency variation across population ancestry. The role of race and ancestry on biomarkers associated with TBI outcome remains indeterminate and subsequent work is still required to understand the implications for patients with TBI.

Circadian rhythms are intrinsic, 24 h cycles that regulate key physiological, mental, and behavioral processes, including sleep-wake cycles, hormone secretion, and metabolism. These rhythms are controlled by the brain's suprachiasmatic nucleus, which synchronizes with environmental signals, such as light and temperature, and consequently maintains alignment with the day-night cycle. Molecular feedback loops, driven by core circadian "clock genes", such as Clock, Bmal1, Per, and Cry, are essential for rhythmic gene expression; disruptions in these feedback loops are associated with various health issues. Dysregulated lipid metabolism in the brain has been implicated in the pathogenesis of neurological disorders by contributing to oxidative stress, neuroinflammation, and synaptic dysfunction, as observed in conditions such as Alzheimer's and Parkinson's diseases. Disruptions in circadian gene expression have been shown to perturb lipid regulatory mechanisms in the brain, thereby triggering neuroinflammatory responses and oxidative damage. This review synthesizes current insights into the interconnections between circadian rhythms and lipid metabolism, with a focus on their roles in neurological health and disease. It further examines how the desynchronization of circadian genes affects lipid metabolism and explores the potential mechanisms through which disrupted circadian signaling might contribute to the pathophysiology of neurodegenerative disorders.

PURPOSE/OBJECTIVE:Financial toxicity (FT) is increasingly recognized as a major issue in cancer care. We evaluated the prevalence and risk factors for FT in patients with pancreatic ductal adenocarcinoma (PDAC) and FT associations with treatment adherence and quality of life (QOL). METHODS:A screening questionnaire based on the Comprehensive Score for Financial Toxicity (COST) was implemented at our National Cancer Institute-designated comprehensive cancer center. Respondents with pathologic diagnosis of PDAC who completed >50% of prompts between June 2022 and June 2023 were analyzed. COST ≤16 was categorized as FT. Associations between FT and demographic and clinical factors were assessed using logistic regression, and QOL was assessed using linear regression. RESULTS:= .049). Patients experiencing FT reported worse QOL, with a median score of 5 (IQR, 4-7) versus 8 (IQR, 6-9) without FT. This relationship persisted after adjusting for demographic and clinical factors; the effect size of FT (β = -1.5; 95% CI, -1.1 to -1.9) was nearly double that of poor performance status (β = -.8; 95% CI, -1.3 to -0.4). CONCLUSION/CONCLUSIONS:FT affected nearly one in four patients with PDAC at a high-volume cancer center and was associated with worse QOL and medication nonadherence. Universal screening and interventions to reduce FT are warranted. Clinical trials investigating QOL as an end point must account for potential confounding due to FT.