Faculty Bibliography

BACKGROUND:Evading immune surveillance is a hallmark for the development of multiple cancer types. Whether immune evasion contributes to the pathogenesis of high-grade prostate cancer (HGPCa) remains an area of active inquiry. METHODS:Through single-cell RNA sequencing and multicolor flow cytometry of freshly isolated prostatectomy specimens and matched peripheral blood, we aimed to characterize the tumor immune microenvironment (TME) of localized prostate cancer (PCa), including HGPCa and low-grade prostate cancer (LGPCa). RESULTS: TILs. The PCa TME was infiltrated by macrophages but these did not clearly cluster by M1 and M2 markers. CONCLUSIONS:T cell exhaustion in localized PCa, a finding enriched in HGPCa relative to LGPCa. These studies suggest a possible link between the clinical-pathologic risk of PCa and the associated TME. Our results have implications for our understanding of the immunologic mechanisms of PCa pathogenesis and the implementation of immunotherapy for localized PCa.

In data collection for predictive modeling, under-representation of certain groups, based on gender, race/ethnicity, or age, may yield less-accurate predictions for these groups. Recently, this issue of fairness in predictions has attracted significant attention, as data-driven models are increasingly utilized to perform crucial decision-making tasks. Existing methods to achieve fairness in the machine learning literature typically build a single prediction model in a manner that encourages fair prediction performance for all groups. These approaches have two major limitations: i) fairness is often achieved by compromising accuracy for some groups; ii) the underlying relationship between dependent and independent variables may not be the same across groups. We propose a Joint Fairness Model (JFM) approach for logistic regression models for binary outcomes that estimates group-specific classifiers using a joint modeling objective function that incorporates fairness criteria for prediction. We introduce an Accelerated Smoothing Proximal Gradient Algorithm to solve the convex objective function, and present the key asymptotic properties of the JFM estimates. Through simulations, we demonstrate the efficacy of the JFM in achieving good prediction performance and across-group parity, in comparison with the single fairness model, group-separate model, and group-ignorant model, especially when the minority group's sample size is small. Finally, we demonstrate the utility of the JFM method in a real-world example to obtain fair risk predictions for under-represented older patients diagnosed with coronavirus disease 2019 (COVID-19). This article is protected by copyright. All rights reserved.

Despite recent advances in algorithmic fairness, methodologies for achieving fairness with generalized linear models (GLMs) have yet to be explored in general, despite GLMs being widely used in practice. In this paper we introduce two fairness criteria for GLMs based on equalizing expected outcomes or log-likelihoods. We prove that for GLMs both criteria can be achieved via a convex penalty term based solely on the linear components of the GLM, thus permitting efficient optimization. We also derive theoretical properties for the resulting fair GLM estimator. To empirically demonstrate the efficacy of the proposed fair GLM, we compare it with other wellknown fair prediction methods on an extensive set of benchmark datasets for binary classification and regression. In addition, we demonstrate that the fair GLM can generate fair predictions for a range of response variables, other than binary and continuous outcomes.

BACKGROUND/UNASSIGNED:There has been a call by both patients and health professionals for the integration of palliative care with nephrology care, yet there is little evidence describing the effect of this approach. The objective of this paper is to report the feasibility and acceptability of a pilot randomized controlled trial testing the efficacy of integrated palliative and nephrology care. METHODS/UNASSIGNED:English speaking patients with CKD stage 5 were randomized to monthly palliative care visits for 3 months in addition to their usual care, as compared with usual nephrology care. Feasibility of recruitment, retention, completion of intervention processes, and feedback on participation was measured. Other outcomes included differences in symptom burden change, measured by the Integrated Palliative Outcome Scale-Renal, and change in quality of life, measured by the Kidney Disease Quality of Life questionnaire and completion of advance care planning documents. RESULTS/UNASSIGNED:Of the 67 patients approached, 45 (67%) provided informed consent. Of these, 27 patients completed the study (60%), and 14 (74%) of those in the intervention group completed all visits. We found small improvements in overall symptom burden (-2.92 versus 1.57) and physical symptom burden scores (-1.92 versus 1.79) in the intervention group. We did not see improvements in the quality-of-life scores, with the exception of the physical component score. The intervention group completed more advance care planning documents than controls (five health care proxy forms completed versus one, nine Medical Orders for Life Sustaining Treatment forms versus none). CONCLUSIONS/UNASSIGNED:We found that pilot testing through a randomized controlled trial of an ambulatory integrated palliative and nephrology care clinical program was feasible and acceptable to participants. This intervention has the potential to improve the disease experience for those with nondialysis CKD and should be tested in other CKD populations with longer follow-up. CLINICAL TRIALS REGISTRY NAME AND REGISTRATION NUMBER/UNASSIGNED:Pilot Randomized-controlled Trial of Integrated Palliative and Nephrology Care Versus Usual Nephrology Care, NCT04520984.

Importance/UNASSIGNED:Older adults vary widely in age at diagnosis and duration of type 2 diabetes, but treatment often ignores this heterogeneity. Objectives/UNASSIGNED:To investigate the associations of diabetes vs no diabetes, age at diagnosis, and diabetes duration with negative health outcomes in people 50 years and older. Design, Setting, and Participants/UNASSIGNED:This cohort study included participants in the 1995 through 2018 waves of the Health and Retirement Study (HRS), a population-based, biennial longitudinal health interview survey of older adults in the US. The study sample included adults 50 years or older (n = 36 060) without diabetes at entry. Data were analyzed from June 1, 2021, to July 31, 2022. Exposures/UNASSIGNED:The presence of diabetes, specifically the age at diabetes diagnosis, was the main exposure of the study. Age at diagnosis was defined as the age when the respondent first reported diabetes. Adults who developed diabetes were classified into 3 age-at-diagnosis groups: 50 to 59 years, 60 to 69 years, and 70 years and older. Main Outcomes and Measures/UNASSIGNED:For each diabetes age-at-diagnosis group, a propensity score-matched control group of respondents who never developed diabetes was constructed. The association of diabetes with the incidence of key outcomes-including heart disease, stroke, disability, cognitive impairment, and all-cause mortality-was estimated and the association of diabetes vs no diabetes among the age-at-diagnosis case and matched control groups was compared. Results/UNASSIGNED:A total of 7739 HRS respondents developed diabetes and were included in the analysis (4267 women [55.1%]; mean [SD] age at diagnosis, 67.4 [9.9] years). The age-at-diagnosis groups included 1866 respondents at 50 to 59 years, 2834 at 60 to 69 years, and 3039 at 70 years or older; 28 321 HRS respondents never developed diabetes. Age at diagnosis of 50 to 59 years was significantly associated with incident heart disease (hazard ratio [HR], 1.66 [95% CI, 1.40-1.96]), stroke (HR, 1.64 [95% CI, 1.30-2.07]), disability (HR, 2.08 [95% CI, 1.59-2.72]), cognitive impairment (HR, 1.30 [95% CI, 1.05-1.61]), and mortality (HR, 1.49 [95% CI, 1.29-1.71]) compared with matched controls, even when accounting for diabetes duration. These associations significantly decreased with advancing age at diagnosis. Respondents with diabetes diagnosed at 70 years or older only showed a significant association with the outcome of elevated mortality (HR, 1.08 [95% CI, 1.01-1.17]). Conclusions and Relevance/UNASSIGNED:The findings of this cohort study suggest that age at diabetes diagnosis was differentially associated with outcomes and that younger age groups were at elevated risk of heart disease, stroke, disability, cognitive impairment, and all-cause mortality. These findings reinforce the clinical heterogeneity of diabetes and highlight the importance of improving diabetes management in adults with earlier diagnosis.

PURPOSE:Adjuvant immunotherapy produces durable benefit for patients with resected melanoma, but many develop recurrence and/or immune-related adverse events (irAE). We investigated whether baseline serum autoantibody (autoAb) signatures predicted recurrence and severe toxicity in patients treated with adjuvant nivolumab, ipilimumab, or ipilimumab plus nivolumab. EXPERIMENTAL DESIGN:This study included 950 patients: 565 from CheckMate 238 (408 ipilimumab versus 157 nivolumab) and 385 from CheckMate 915 (190 nivolumab versus 195 ipilimumab plus nivolumab). Serum autoAbs were profiled using the HuProt Human Proteome Microarray v4.0 (CDI Laboratories, Mayaguez, PR). Analysis of baseline differentially expressed autoAbs was followed by recurrence and severe toxicity signature building for each regimen, testing of the signatures, and additional independent validation for nivolumab using patients from CheckMate 915. RESULTS:In the nivolumab independent validation cohort, high recurrence score predicted significantly worse recurrence-free survival [RFS; adjusted HR (aHR), 3.60; 95% confidence interval (CI), 1.98-6.55], and outperformed a model composed of clinical variables including PD-L1 expression (P < 0.001). Severe toxicity score was a significant predictor of severe irAEs (aHR, 13.53; 95% CI, 2.59-86.65). In the ipilimumab test cohort, high recurrence score was associated with significantly worse RFS (aHR, 3.21; 95% CI, 1.38-7.45) and severe toxicity score significantly predicted severe irAEs (aHR, 11.04; 95% CI, 3.84-37.25). In the ipilimumab plus nivolumab test cohort, high autoAb recurrence score was associated with significantly worse RFS (aHR, 6.45; 95% CI, 1.48-28.02), and high severe toxicity score was significantly associated with severe irAEs (aHR, 23.44; 95% CI, 4.10-212.50). CONCLUSIONS:Baseline serum autoAb signatures predicted recurrence and severe toxicity in patients treated with adjuvant immunotherapy. Prospective testing of the signatures that include datasets with longer follow-up and rare but more severe toxicities will help determine their generalizability and potential clinical utility. See related commentary by Hassel and Luke, p. 3914.

BACKGROUND:Recent data suggest that patients with stage III melanoma are at high risk for developing central nervous system (CNS) metastases. Because a subset of patients with stage II melanoma experiences worse survival outcomes than some patients with stage III disease, the authors investigated the risk of CNS metastasis in stage II melanoma to inform surveillance guidelines for this population. METHODS:test, the cumulative incidence, and Cox multivariable regression analyses were performed to evaluate the association between baseline characteristics and the development of CNS metastases. RESULTS:Patients with stage III melanoma had a higher rate of developing brain metastases than those with stage II melanoma (100 of 468 patients [21.4%] vs. 82 of 586 patients [14.0%], respectively; p = .002). However, patients who had stage IIC melanoma had a significantly higher rate of isolated first recurrences in the CNS compared with those who had stage III disease (12.1% vs. 3.6%; p = .002). The risk of ever developing brain metastases was similarly elevated for patients who had stage IIC disease (hazard ratio [HR], 3.16; 95% CI, 1.77-5.66), stage IIIB disease (HR, 2.83; 95% CI, 1.63-4.91), and stage IIIC disease (HR, 2.93; 95% CI, 1.81-4.74), and the risk was highest in patients who had stage IIID disease (HR, 8.59; 95% CI: 4.11-17.97). CONCLUSIONS:Patients with stage IIC melanoma are at elevated risk for first recurrence in the CNS. Surveillance strategies that incorporate serial neuroimaging should be considered for these individuals until more accurate predictive markers can be identified.

Outcomes: 1. Understand the historical use of palliative care for patients with acute kidney injury (AKI) 2. Describe the use of palliative care for patients with AKI and COVID-19 during the surge at our institution 3. Describe the associations of palliative care with subsequent health care utilization such as hospice use, ICU time, and mechanical ventilation Original Research Background: Acute kidney injury (AKI) is a common morbidity seen in patients with COVID-19 and is associated with high mortality. Palliative care is valuable for these patients yet is historically underused in AKI. Research Objectives: To describe the use of palliative care and subsequent health care utilization by COVID-19 patients with AKI.
Method(s): A retrospective analysis of NYU's electronic health data of COVID-19 hospitalizations between March 2, 2020 and August 25, 2020. AKI was defined by the AKI Network creatinine criteria. Regression models examined characteristics associated with a receiving palliative care and discharge to hospice versus death in the hospital.
Result(s): Patientswith COVID-19 and AKI were more likely than those without AKI to receive palliative care (42% vs 7%, p < 0.001); however, consults came significantly later (10 days from admission vs 5 days, p < 0.001). 66% of patients initiated on renal replacement therapy (RRT) received palliative care versus 37% (p < 0.001) of those with AKI not on RRT, also later in timing (12 days from admission vs 9 days, p = 0.002). Patients with AKI had a significantly longer stay, more ICU admissions, use of mechanical ventilation, discharges to hospice (6% vs 3%), and changes in code status (34% vs 7%, p < 0.001) than those without AKI. Among those who received palliative care, AKI both without RRT (adjusted odds ratio [aOR] 0.51, 95% confidence interval [CI] 0.27-0.95) and with RRT (aOR 0.18, 95% CI 0.04-0.67) was associated with a lower likelihood of discharge to hospice versus hospital death compared to those without AKI.
Conclusion(s): Palliative care was used more for patients with AKI and COVID-19 than historically reported, yet this consultation came later in the hospital course and did not avoid invasive interventions despite high mortality. Implications for Research, Policy, or Practice: These data can lead to further exploration of earlier timing of palliative care consultation in AKI.
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BACKGROUND:Morbidity and death due to coronavirus disease 2019 (COVID-19) experienced by older adults in nursing homes have been well described, but COVID-19's impact on community-living older adults is less studied. Similarly, the previous ambulatory care experience of such patients has rarely been considered in studies of COVID-19 risks and outcomes. METHODS:To investigate the relationship of advanced age (65+), on risk factors associated with COVID-19 outcomes in community-living elders, we identified an electronic health records cohort of older patients aged 65+ with laboratory-confirmed COVID-19 with and without an ambulatory care visit in the past 24 months (n = 47,219) in the New York City (NYC) academic medical institutions and the NYC public hospital system from January 2020 to February 2021. The main outcomes are COVID-19 hospitalization; severe outcomes/Intensive care unit (ICU), intubation, dialysis, stroke, in-hospital death), and in-hospital death. The exposures include demographic characteristics, and those with ambulatory records, comorbidities, frailty, and laboratory results. RESULTS:The 31,770 patients with an ambulatory history had a median age of 74 years; were 47.4% male, 24.3% non-Hispanic white, 23.3% non-Hispanic black, and 18.4% Hispanic. With increasing age, the odds ratios and attributable fractions of sex, race-ethnicity, comorbidities, and biomarkers decreased except for dementia and frailty (Hospital Frailty Risk Score). Patients without ambulatory care histories, compared to those with, had significantly higher adjusted rates of COVID-19 hospitalization and severe outcomes, with strongest effect in the oldest group. CONCLUSIONS:In this cohort of community-dwelling older adults, we provided evidence of age-specific risk factors for COVID-19 hospitalization and severe outcomes. Future research should explore the impact of frailty and dementia in severe COVID-19 outcomes in community-living older adults, and the role of engagement in ambulatory care in mitigating severe disease.