Faculty Bibliography

BACKGROUND:Moral distress, which occurs when the ethically correct action cannot be taken because of internal or external constraints, is associated with depression, burnout, and the desire to leave the healthcare profession among healthcare workers. This study compares internal medicine (IM) residents’ experiences of moral distress while caring for patients with COVID-19 in the year prior to and during the first year of the COVID-19 pandemic. METHODS:This is a mixed methods prospective observational cohort study that enrolled IM residents on a rolling basis beginning December 2018. Moral distress was evaluated via the validated Moral Distress Score-Revised (MDS-R) and Measure of Moral Distress for Healthcare Professionals (MDD-HP) and open-ended questions every 4-months via online surveys and through five resident focus groups. The moral distress scores (MDS) before and during the COVID-19 pandemic were compared using paired t-tests. Transcripts and free text were independently coded by investigators and analyzed by major themes and sub-themes. RESULTS: < .05). Qualitive findings included the exacerbation of existing moral distress and the emergence of new drivers of moral distress, including personal protective equipment, visitor policies, lack of moral framework, and tension between protecting one’s own health and caring for others. CONCLUSIONS:The results of this preliminary analysis suggest that the COVID-19 pandemic exacerbated pre-existing experiences of moral distress and brought to light new and different morally distressing situations for trainees. This analysis of the impact of the pandemic is valuable not only for identifying leverage points for intervention, but also for informing future crisis preparedness and cultivating moral resilience in trainees and the healthcare workforce. SUPPLEMENTARY INFORMATION:The online version contains supplementary material available at 10.1186/s12910-025-01274-6.

Non-small cell lung cancer (NSCLC) patients with loss of the tumor suppressor gene STK11 are resistant to immune checkpoint therapies like anti-PD-1. Here, we conducted an in vivo CRISPR screen that identified HDAC1 as a target to reverse anti-PD-1 resistance driven by loss of STK11 and developed TNG260, a potent small-molecule inhibitor of the CoREST complex with selectivity exceeding previously generated inhibitors in this class in preclinical studies. Treatment with TNG260 led to increased expression of immunomodulatory genes in STK11-deficient cancer cells. When combined with anti-PD-1, TNG260 induced immune-mediated stasis and/or regression in STK11-deficient syngeneic tumor models and autochthonous NSCLC models. In the tumors of patients with STK11-deficient cancers on a clinical trial (NCT05887492), treatment with a combination of TNG260 and pembrolizumab increased intratumoral histone acetylation, PD-L1 tumor proportion scores, and T cell infiltration into the tumor microenvironment. This study illustrates a promising treatment strategy for addressing immune evasion in STK11-mutant NSCLC patients.

Artificial intelligence (AI) applications for radiology workflow have the potential to improve patient and health-system-level outcomes through more efficient and accurate diagnosis and clinical decision making. For a variety of time-intensive steps, numerous types of applications are now available with variable reported measures and degrees of success. The tools we highlight aim to accelerate imaging acquisition, reduce cognitive and manual burden on radiologists and others involved in the care pathway, improve diagnostic accuracy, and shorten the time to clinical action based on imaging results. Most existing studies have focused on intermediate outcomes, such as task duration or time to the next step in care. In this article, we present an examination of AI applications across the medical imaging exam workflow, review examples of real-world evidence on these tools, and summarize the relevant performance metrics by application type. Beyond the more immediately acquired measures, to demonstrate benefit to patient health and economic outcomes, a more integrated assessment is necessary, and in an iterative fashion. To evolve beyond early workflow gains, interoperable tools must be tied to measurable downstream impacts, such as reduced disease severity, lower mortality, and shorter hospital stays, while we acknowledge that current empirical evaluations are limited.

PURPOSE/OBJECTIVE:Financial toxicity can negatively affect treatment adherence, quality of life, and survival in patients with cancer. Although screening for financial toxicity is increasingly implemented across oncology practices and cancer centers, less is known about challenges in delivering timely interventions after a positive screen. We evaluated outcomes and barriers in a systematic financial toxicity screening and referral program at a large comprehensive cancer center. METHODS:From March 2023 to December 2024, patients in breast, gynecologic, GI, and thoracic oncology clinics at Memorial Sloan Kettering Cancer Center completed an electronic survey assessing health-related social risks and the 12-item Comprehensive Score for Financial Toxicity (COST). A positive screen was defined as COST <16, unmet essential need, or new loan/borrowing for treatment. Patients screening positive and requesting assistance were referred to Patient Financial Services (PFS) for follow-up. Outcomes included proportions with documented outreach, receipt of any intervention, intervention types, and barriers. RESULTS:A total of 83,978 patients were eligible; of whom 50,949 (61%) completed screening. Of 9,724 positive screens, 8,004 (82%) requested follow-up, and 6,987 referrals were placed. PFS attempted follow-up in 3,383 patients (of the 6,987 = 48%), with documented interventions in 1,510 of 3,383 (45%). Counseling on financial resources (983/3,383 = 29%) was most common, followed by insurance-related counseling (402/3,383 = 12%) and formal program referrals (823/3,383 = 24%). Among patients referred to assistance programs, this was most often to the institutional Financial Assistance Program (438/796 = 55%) or social work (318/796 = 40%). The most frequent barrier was the inability to contact patients (1,464/3,383 = 43%). CONCLUSION/CONCLUSIONS:Routine financial toxicity screening was implemented at scale and connected many patients to meaningful financial support. However, 81% of those who screened positive did not receive an intervention, underscoring the need for expanded infrastructure and policy reforms to address financial toxicity in cancer care.

BACKGROUND:Patients with heart failure (HF) often have difficulty obtaining life-saving medications due to coverage barriers, such as prior authorizations and high out-of-pocket costs. To promote better coverage for high value therapies and inform policymakers about cost effectiveness, the American Heart Association/American College of Cardiology/Heart Failure Society of America added Value Statements to HF guidelines. We assessed whether these guidelines influenced Medicare drug coverage policies for 2 life-saving, costly HF medications: angiotensin receptor neprilysin inhibitors (ARNI-guideline "high value") and sodium glucose cotransporter-2 inhibitors (SGLT2i-guideline "intermediate value"). METHODS:We performed an observational study using Medicare prescription drug plan formulary files from April 2020 to April 2023 to separately assess for changes in coverage barriers to ARNI and SGLT2i after Value Statement publication (April 2022), and subsequent Medicare plan online update (October 2022). The primary outcome was the percentage of plans each month with any barrier to drug coverage (prior authorizations, tier ≥3 out-of-pocket cost-sharing, step therapy, or no coverage). Analyses used interrupted time series and difference-in-differences approaches. Difference-in-differences analyses used direct oral anticoagulants as a control due to their comparable cost and use as ARNI and SGLT2i, but without a Value Statement. RESULTS:Among 7396 Medicare drug plans, monthly rates of any coverage barrier ranged from 94.3% to 97.4% for ARNI and 93.2% to 96.6% for SGLT2i. Most barriers were due to tier ≥3 out-of-pocket cost-sharing requirements (ARNI: 94.3%-95.8%; SGLT2i: 93.2%-95.6%). Coverage barriers remained stable in April 2022 and declined slightly in October 2022. In difference-in-differences analyses, the presence of a Value Statement was associated with a ~1 percentage point decline in coverage barriers for both ARNI (difference-in-differences estimate, -1.07% [95% CI, -1.44% to -0.70%]) and SGLT2i (-1.32% [95% CI, -1.63% to -1.00%]). CONCLUSIONS:Coverage barriers to ARNI and SGLT2i were common and changed only slightly after publication of Value Statements in HF guidelines. There is a critical need for robust strategies to improve access to life-saving HF medications.

BACKGROUND:Delayed diagnosis of venous thromboembolism (VTE) is prevalent among hospitalized patients, yet case identification is challenging and feedback limited. OBJECTIVE:To develop a large language model (LLM)-based electronic-trigger to identify VTE diagnostic delays. METHODS:All admissions to internal medicine (IM) residents at NYU Langone Health between January 2022 and December 2023 (n = 20,843) were included. Using an open-source LLM, prompts were validated to detect (1) residents considering VTE in admission notes and (2) VTE confirmation in five types of imaging reports (n = 100 for each prompt validation set). The validated prompts were applied to determine discordance between admission note differential omitting VTE and imaging report confirming VTE. Two hospitalists reviewed discordant cases using a validated tool to identify diagnostic delays. Hospitalizations were labeled as diagnostic delays, in-hospital complication, or false-positive. Based on in-hospital complication and false-positive patterns, exclusion criteria were implemented. Positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS:The LLM prompts correctly classified admission notes and VTE imaging studies with high accuracy (range 98%-100%, n = 699 VTE cases identified). Of the 137 diagnostic delays the LLM-based electronic-trigger identified, 31 were true-positives, 60 in-hospital complications, and 46 false-positives. 4.4% of all VTE hospitalizations had a diagnostic delay. With the exclusion criteria, the PPV was 48% (95% confidence interval [CI], 35%-62%) and NPV was 95% (95% CI, 87%-98%). CONCLUSIONS:We developed the first LLM-based electronic-trigger to identify VTE diagnostic delays, with higher performance than existing non-LLM electronic-triggers. LLM-based approaches can facilitate diagnostic performance feedback and are scalable to other conditions and institutions.

BACKGROUND:Cardiovascular disease is the most common cause of morbidity and mortality in kidney transplant recipients. Screening for coronary disease is frequently required prior to kidney transplantation, but coronary intervention has not been shown to be beneficial except in complex coronary artery disease. The likelihood of finding significant coronary artery disease and the benefits of routine pre-transplant screening are uncertain. METHODS:We performed a systematic review and meta-analysis. Medline & Embase were searched to identify manuscripts published between 1998 and 2024 reporting the results of pre-transplant screening. The primary endpoints were the frequency of detecting significant coronary lesions for which there are AHA class 1 indications for revascularization: a) >50% left main stenosis; or b) multi-vessel disease with ejection fraction < 35% during pre-kidney transplant screening. Secondary endpoints included frequency of detecting multivessel disease, proximal left anterior descending artery (LAD) disease, and number of patients who underwent invasive coronary angiography. Meta-regression was used to explore outcome heterogeneity according to the presence of hypertension, diabetes, and age. RESULTS:We identified 1273 studies out of which 44 met eligibility criteria. The mean prevalence of class 1 indications was 2%, although the heterogeneity was high with estimates ranging from 0% to 17%. Estimated prevalence of proximal LAD disease was 2% and left main stenosis was 1%, whereas 10% of patients had multi-vessel coronary artery disease, and 35% were referred for invasive angiography. There was no evidence of significant heterogeneity according to sex of the population or prevalence of diabetes or hypertension. CONCLUSIONS:Identification of class I indications for revascularization during pre-transplant coronary screening was rare.

The scarcity of transplantable organs represents a worldwide public health crisis, and as a result, thousands of people with end-stage kidney disease (ESKD) die waiting for a transplant each year. Xenotransplantation involves transplanting organs from an animal source into humans, offering a potential solution to this significant unmet need. Indeed, if there is a limitless supply of organs, many more patients who do not meet the current criteria for transplant eligibility could also be considered candidates. While there are examples of attempts to transplant animal tissues or organs into humans dating back over 300 years, none were successful due to cross-species immunologic incompatibility. Even so, significant advances in genetic engineering and the emergence of novel immunosuppressive agents have spurred impressive improvements in xenograft survival in preclinical studies involving nonhuman primates. Furthermore, recent reports of genetically modified pig kidney and heart xenotransplants in human decedents and living recipients on a compassionate use basis have provided impetus to advancing the field towards first-in-human trials. However, studies in nonhuman primates and humans thus far have described adaptive as well as innate immune-mediated xenograft injury. Understanding the mechanistic aspects of these responses at the cellular and molecular levels is critical to the development of targeted genetic modifications and innovative therapeutic strategies aimed at preventing rejection and inducing tolerance. Moreover, the physiological components of the bidirectional communication between the human host and pig xenograft must also be understood and manipulated. Here, we review the breakthroughs in renal xenotransplantation in the past few decades and highlight the immunologic hurdles that have yet to be overcome.