Faculty Bibliography

In the United States, it is estimated that 0.3% of Americans aged 65 and older, or almost 172,000 individuals, identify as transgender. Aging comes with a unique set of challenges and experiences for this population, including health care disparities, mental health concerns, and social isolation. It is crucial for clinicians to use a patient-centered and trauma-informed care approach to address their specific needs and provide evidence-based quality health care, including preventive screenings, mental health support, and advocating for legal protections.

PURPOSE/OBJECTIVE:Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. METHODS:We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan-Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). RESULTS:442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96-155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good-excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. CONCLUSIONS:Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.

OBJECTIVES/OBJECTIVE:Physicians with training in anesthesiology, emergency medicine, internal medicine, neurology, and surgery may gain board certification in critical care medicine upon completion of fellowship training. These clinicians often only spend a portion of their work effort in the ICU. Other work efforts that benefit an ICU infrastructure, but do not provide billing opportunities, include education, research, and administrative duties. For employed or contracted physicians, there is no singular definition of what constitutes an intensive care full-time equivalent (FTE). Nevertheless, hospitals often consider FTEs in assessing hiring needs, salary, and eligibility for benefits. DATA SOURCES/METHODS:Review of existing literature, expert opinion. STUDY SELECTION/METHODS:Not applicable. DATA EXTRACTION/METHODS:Not applicable. DATA SYNTHESIS/RESULTS:Not applicable. CONCLUSIONS:Understanding how an FTE is calculated, and the fraction of an FTE to be assigned to a particular cost center, is therefore important for intensivists of different specialties, as many employment models assign salary and benefits to a base specialty department and not necessarily the ICU.

BACKGROUND:Recent studies suggest the transplantation of Hepatitis C (HCV) hearts from viremic donors is associated with comparable 1 year survival to nonviremic donors. Though HCV viremia is a known risk factor for accelerated atherosclerosis, data on cardiac allograft vasculopathy (CAV) outcomes are limited. We compared the incidence of CAV in heart transplant recipients from HCV viremic donors (nucleic acid amplification test positive; NAT+) compared to non-HCV infected donors (NAT-). METHODS:We retrospectively reviewed annual coronary angiograms with intravascular ultrasound from April 2017 to August 2020 at two large cardiac transplant centers. CAV was graded according to ISHLT guidelines. Maximal intimal thickness (MIT) ≥ 0.5 mm was considered significant for subclinical disease. RESULTS:Among 270 heart transplant recipients (mean age 54; 77% male), 62 patients were transplanted from NAT+ donors. CAV ≥ grade 1 was present in 8.8% of the NAT+ versus 16.8% of the NAT- group at 1 year, 20% versus 28.8% at 2 years, and 33.3% versus 41.5% at 3 years. After adjusting for donor age, donor smoking history, recipient BMI, recipient, hypertension, and recipient diabetes, NAT+ status did not confer increased risk of CAV (HR.80; 95% CI.45-1.40, p = 0.43) or subclinical IVUS disease (HR.87; 95% CI.58-1.30, p = 0.49). Additionally, there was no difference in the presence of rapidly progressive lesions on IVUS. CONCLUSION/CONCLUSIONS:Our data show that NAT+ donors conferred no increased risk for early CAV or subclinical IVUS disease following transplantation in a cohort of heart transplant patients who were treated for HCV, suggesting the short-term safety of this strategy to maximize the pool of available donor hearts.

Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3⁺ T-cells to engage and lyse CD19⁺ target cells. Here we demonstrate that subcutaneous (SC) blinatumomab can provide high efficacy and greater convenience of administration. In the expansion phase of a multi-institutional phase 1b trial (ClinicalTrials.gov, NCT04521231), heavily pretreated adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) received SC blinatumomab at two doses: (1) 250 μg once daily (QD) for week 1 and 500 μg three times weekly (TIW) thereafter (250 μg/500 μg) or (2) 500 μg QD for week 1 and 1000 μg TIW thereafter (500 μg/1000 μg). The primary endpoint was complete remission/complete remission with partial hematologic recovery (CR/CRh) within two cycles. At the data cutoff of September 15, 2023, 29 patients were treated: 14 at the 250 μg/500 μg dose and 13 at 500 μg/1000 μg dose. Data from two ineligible patients were excluded. At the end of two cycles, 12 of 14 patients (85.7%) from the 250 μg/500 μg dose achieved CR/CRh of which nine patients (75.0%) were negative for measurable residual disease (MRD; <10^-4 leukemic blasts). At the 500 μg/1000 μg dose, 12 of 13 patients (92.3%) achieved CR/CRh; all 12 patients (100.0%) were MRD-negative. No treatment-related grade 4 cytokine release syndrome (CRS) or neurologic events (NEs) were reported. SC injections were well tolerated and all treatment-related grade 3 CRS and NEs responded to standard-of-care management, interruption, or discontinuation. Treatment with SC blinatumomab resulted in high efficacy, with high MRD-negativity rates and acceptable safety profile in heavily pretreated adults with R/R B-ALL.

Improving the outcome of high-risk myeloma (HRMM) is a key therapeutic aim for the next decade. To achieve this aim, it is necessary to understand in detail the genetic drivers underlying this clinical behavior and to target its biology therapeutically. Advances have already been made, with a focus on consensus guidance and the application of novel immunotherapeutic approaches. Cases of HRMM are likely to have impaired prognosis even with novel strategies. However, if disease eradication and minimal disease states are achieved, then cure may be possible.

INTRODUCTION/BACKGROUND:The mainstay of acute pulmonary embolism (PE) treatment is anticoagulation. Timely anticoagulation correlates with decreased PE-associated mortality, but the ability to achieve a therapeutic activated partial thromboplastin time (aPTT) with unfractionated heparin (UFH) remains limited. Although some institutions have switched to a more accurate and reproducible test to assess for heparin's effectiveness, the anti-factor Xa (antiXa) assay, data correlating a timely therapeutic antiXa to PE-associated clinical outcomes remains scarce. We evaluated time to a therapeutic antiXa using intravenous heparin after PE response team (PERT) activation and assessed clinical outcomes including bleeding and recurrent thromboembolic events. METHODS:This was a retrospective cohort study at NYU Langone Health. All adult patients ≥18 years with a confirmed PE started on IV UFH with >2 antiXa levels were included. Patients were excluded if they received thrombolysis or alternative anticoagulation. The primary endpoint was the time to a therapeutic antiXa level of 0.3-0.7 units/mL. Secondary outcomes included recurrent thromboembolism, bleeding and PE-associated mortality within 3 months. RESULTS:A total of 330 patients with a PERT consult were identified with 192 patients included. The majority of PEs were classified as sub massive (64.6%) with 87% of patients receiving a bolus of 80 units/kg of UFH prior to starting an infusion at 18 units/kg/hour. The median time to the first therapeutic antiXa was 9.13 hours with 93% of the cohort sustaining therapeutic anticoagulation at 48 hours. Recurrent thromboembolism, bleeding and mortality occurred in 1%, 5% and 6.2%, respectively. Upon univariate analysis, a first antiXa <0.3 units/ml was associated with an increased risk of mortality [27.78% (5/18) vs 8.05% (14/174), p = 0.021]. CONCLUSION/CONCLUSIONS:We observed a low incidence of recurrent thromboembolism or PE-associated mortality utilizing an antiXa titrated UFH protocol. The use of an antiXa based heparin assay to guide heparin dosing and monitoring allows for timely and sustained therapeutic anticoagulation for treatment of PE.

Loss-of-function mutations in KEAP1 frequently occur in lung cancer and are associated with poor prognosis and resistance to standard of care treatment, highlighting the need for the development of targeted therapies. We previously showed that KEAP1 mutant tumors consume glutamine to support the metabolic rewiring associated with NRF2-dependent antioxidant production. Here, using preclinical patient-derived xenograft models and antigenic orthotopic lung cancer models, we show that the glutamine antagonist prodrug DRP-104 impairs the growth of KEAP1 mutant tumors. We find that DRP-104 suppresses KEAP1 mutant tumors by inhibiting glutamine-dependent nucleotide synthesis and promoting antitumor T cell responses. Using multimodal single-cell sequencing and ex vivo functional assays, we demonstrate that DRP-104 reverses T cell exhaustion, decreases T_regs, and enhances the function of CD4 and CD8 T cells, culminating in an improved response to anti-PD1 therapy. Our preclinical findings provide compelling evidence that DRP-104, currently in clinical trials, offers a promising therapeutic approach for treating patients with KEAP1 mutant lung cancer.