Faculty Bibliography

Purpose/Objective(s): The LGBTQ community is an understudied and medically underserved population who experience increased cancer risk and worse cancer outcomes. Negative provider interactions, including discrimination and lack of knowledge regarding LGBTQ-specific health issues are cited by patients as barriers to care, including in radiation oncology (RO). Notably, little is known regarding LGBTQ knowledge and attitudes among RO residents (ROR) or LGBTQ-specific training in RO residency training programs. Thus, we sought to assess the extent of current LGBTQ-specific training in U.S. RO residency programs. Materials/Methods: Two published surveys of LGBTQ-education in residency were adapted to RO. The first assessed LGBTQ education from the perspective of program directors (PD) and associate PDs (APD), while the second survey was to RORs. The surveys were sent to all ACGME-accredited U.S. RO residency PD, APD, and program coordinators (PC), with the ROR survey being disseminated by the respective PCs. Each survey consisted of subsections of attitudes and knowledge in the care of LGBTQ patients, RO program characteristics, program inclusion of LGBTQ-specific education, and individual demographics.
Result(s): There were 69 responses (29 PD, APD and 40 ROR). The majority of respondents (PD, APD/ROR) identified as white (79%/58%), non-Hispanic (76%/72%), male (55%/55%), and heterosexual (86%/78%). The majority of PD, APDs did not receive LGBTQ education in medical school (60%) or residency training (96%), while the majority of residents (68%) did receive LGBTQ training in medical school; yet, both groups felt this training was insufficient to care for LGBTQ patients during residency (76%/68%). Overall, respondents felt comfortable treating LGB (90%/85%) and T (79%/62.5%) patients. However, the majority did not feel confident in their knowledge for LGB (52%/62.5%) or T (79%/85%) health needs. The majority of respondents' programs have never had a didactic session on LGBTQ health (78%/80%) resulting in 61%/61% of respondents feeling their program inadequately prepares residents to work confidently with LGBTQ patients. However, the majority felt their program is receptive to incorporating LGBTQ health content into their curriculum (75%/75%) and expressed a personal interest in such education (97%/80%). Additional data will be available by time of conference.
Conclusion(s): We found an increase of LGTBQ education in medical schools between PD, APD and ROR, suggestive of a recent improvement in LGBTQ content; yet most residency programs still lacked any LGBTQ-specific education. While the majority felt comfortable treating LGBTQ patients, they simultaneously lacked confidence in knowledge regarding LGBTQ health needs; yet, possessed desire for additional education and belief that such trainings should require. Conclusion is that residencies need to do a better job incorporating LGBTQ health content into their curricula, which is supported by interest from ROR and program leadership.
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INTRODUCTION/BACKGROUND:Coronavirus 2019 (COVID-19) illness continues to affect national and global hospital systems, with a particularly high burden to intensive care unit (ICU) beds and resources. It is critical to identify patients who initially do not require ICU resources but subsequently rapidly deteriorate. We investigated patient populations during COVID-19 at times of full or near-full (surge) and non-full (non-surge) hospital capacity to determine the effect on those who may need a higher level of care or deteriorate quickly, defined as requiring a transfer to ICU within 24 hours of admission to a non-ICU level of care, and to provide further knowledge on this high-risk group of patients. METHODS:This was a retrospective cohort study of a single health system comprising four emergency departments and three tertiary hospitals in New York, NY, across two different time periods (during surge and non-surge inpatient volume times during the COVID-19 pandemic). We queried the electronic health record for all patients admitted to a non-ICU setting with unexpected ICU transfer (UIT) within 24 hours of admission. We then made a comparison between adult patients with confirmed coronavirus 2019 and without during surge and non-surge time periods. RESULTS:During the surge period, there was a total of 86 UITs in a one-month period. Of those, 60 were COVID-19 positive patients who had a mortality rate of 63.3%, and 26 were COVID-19 negative with a 30.8 % mortality rate. During the non-surge period, there was a total of 112 UITs; of those, 24 were COVID-19 positive with a 37.5% mortality rate, and 90 were COVID-19 negative with a 11.1% mortality rate. CONCLUSION/CONCLUSIONS:During the surge, the mortality rate for both COVID-19 positive and COVID-19 negative patients experiencing an unexpected ICU transfer was significantly higher.

Standardisation of hashtags for urologic diseases in the Urology Tag Ontology (UTO) project has facilitated more efficient filtering of social media content. Hashtags must be recognisable and easy to understand. The UTO list should be expanded to include hashtags for urologic procedures and the hashtags could be used on social media platforms other than Twitter to reach a wider audience.

BACKGROUND:Feeding problems are common in early childhood, and some evidence suggests that feeding problems may be associated with psychopathology. Few prospective studies have explored whether toddler feeding problems predict later psychopathology. METHODS:Mothers of 1,136 children from the Upstate KIDS cohort study provided data when children were 2.5 and 8 years of age. Food refusal (picky eating) and mechanical/distress feeding problems and developmental delays were assessed at 2.5 years. Child eating behaviors (enjoyment of food, food fussiness, and emotional under and overeating) and child psychopathology (attention-deficit/hyperactivity (ADHD), oppositional-defiant (OD), conduct disorder (CD), and anxiety/depression) symptoms were assessed at 8 years. RESULTS:Mechanical/distress feeding problems at age 2.5, but not food refusal problems, were associated with ADHD, problematic behavior (OD/CD), and anxiety/depression symptoms at 8 years in models adjusting for eating behaviors at 8 years and child and family covariates. Associations with mechanical/distress feeding problems were larger for ADHD and problematic behavior than anxiety/depression symptoms, though all were modest. Model estimates were similar for boys and girls. CONCLUSIONS:Much of the research on feeding problems focuses on picky eating. This study suggests that early mechanical and mealtime distress problems may serve as better predictors of later psychopathology than food refusal. Parents and pediatricians could monitor children with mechanical/distress feeding problems for signs of developing psychopathology.

Background Solid tumors comprise >90% of cancers. Nonsmall cell lung cancer (NSCLC), metastatic colorectal cancer (CRC), and pancreatic cancer are the leading causes of cancerrelated mortality (5-year overall survival: 26%, 15%, and 11%, respectively).1 Chimeric antigen receptor (CAR) T-cell therapy has demonstrated clinical efficacy in hematologic malignancies.2,3 However, translating engineered T-cell therapies to solid tumors has proven to be challenging due to a lack of tumor-specific targets that can discriminate cancer cells from normal cells. Previous studies using carcinoembryonic antigen (CEA) T-cell receptors and mesothelin (MSLN) CARs resulted in dose-limiting on-target, off-tumor toxicities.4,5 To create a therapeutic safety window, Tmod CAR T-cell therapy utilizes dual-signaling receptors to create a robust logic gate capable of killing tumor cells, while leaving healthy cells intact.6,7 The 2 receptors in Tmod CAR T-cell therapy comprise an activator that recognizes an antigen on the surface of tumor cells that may also be present on normal cells, such as CEA and MSLN, and a blocker that recognizes a second surface antigen from an allele lost only in tumor cells (figure 1).8,9 Human leukocyte antigen (HLA) loss of heterozygosity (LOH) offers a definitive tumor versus normal discriminator target for CAR T-cell therapy.10 The frequency of HLA LOH among advanced NSCLC, CRC, and pancreatic cancers in the Tempus real-world dataset is 16.3% with a range of 15.6%- 23.1%.11 LOH can be reliably detected using the Tempus xTOnco next-generation sequencing (NGS) assay.12,13 Different activator/blocker combinations can be engineered with the Tmod platform technology and may be applied to T cells and natural killer cells in autologous and allogeneic settings. BASECAMP-1 is a currently enrolling observational study with key objectives: 1) To identify patients with somatic HLA LOH eligible for Tmod CAR T-cell therapy, and 2) Subsequent apheresis and manufacturing feasibility for the future EVEREST CEA or MSLN Tmod CAR T-cell studies. Methods BASECAMP-1 (NCT04981119) patient eligibility has 2 parts (figure 2): 1) Patients will be initially screened to identify germline HLA-A*02 heterozygosity by central NGS. If HLA-A*02 heterozygosity is confirmed, primary archival tumor tissue will be analyzed for somatic mutations by xTOnco NGS testing; 2) If the tumor demonstrates HLAA* 02:01 LOH and the patient is eligible after screening, the patient will undergo apheresis. Banked T cells will be available for the autologous EVEREST Tmod CAR T-cell therapy interventional study to reduce waiting time at relapse. (Figure Presented)

BACKGROUND:The diagnosis of multiple sclerosis (MS) requires demyelinating events that are disseminated in time and space. Peripapillary retinal nerve fiber layer (pRNFL) thickness as measured by optical coherence tomography (OCT) distinguishes eyes with a prior history of acute optic neuritis (ON) and may provide evidence to support a demyelinating attack. OBJECTIVE:To investigate whether a deep learning (DL)-based network can distinguish between eyes with prior ON and healthy control (HC) eyes using peripapillary ring scans. METHODS:We included 1033 OCT scans from 415 healthy eyes (213 HC subjects) and 510 peripapillary ring scans from 164 eyes with prior acute ON (140 patients with MS). Data were split into 70% training, 15% validation, and 15% test data. We included 102 OCT scans from 80 healthy eyes (40 HC) and 61 scans from 40 ON eyes (31 MS patients) from an independent second center. Receiver operating characteristic curve analyses with area under the curve (AUC) were used to investigate performance. RESULTS:We used a dilated residual convolutional neural network for the classification. The final network had an accuracy of 0.85 and an AUC of 0.86, whereas pRNFL only had an AUC of 0.77 in recognizing ON eyes. Using data from a second center, the network achieved an accuracy of 0.77 and an AUC of 0.90 compared to pRNFL, which had an AUC of 0.84. INTERPRETATION:DL-based disease classification of prior ON is feasible and has the potential to outperform thickness-based classification of eyes with and without history of prior ON.

Chronic kidney disease (CKD) is defined by a low glomerular filtration rate or high albuminuria, and affects 15-20% of adults globally. CKD increases the risk of various adverse outcomes, but cardiovascular disease (CVD) is of particular relevance because it is the leading cause of death in this clinical population. CKD is associated with several CVD outcomes, including coronary heart disease, stroke, peripheral artery disease, arrhythmias, heart failure and venous thrombosis. Notably, CKD is particularly strongly associated with severe CVD outcomes such as CVD mortality, heart failure and lower extremity amputations. This broad impact of CKD on the cardiovascular system probably reflects the involvement of several pathophysiological mechanisms that link CKD to CVD development - shared risk factors (for example, diabetes and hypertension), changes in bone mineral metabolism, anaemia, volume overload, inflammation and the presence of uraemic toxins. Understanding the status of CKD is crucial for appropriate CVD risk prediction in CKD populations. However, major clinical guidelines are not consistent in their incorporation of CKD measures for CVD risk prediction. Mitigating CVD risk in patients with CKD effectively requires multidisciplinary care that involves nephrologists, cardiologists and other health professionals, as well as further work to address current research and implementation gaps.

BACKGROUND:Melamine, melamine derivatives, and aromatic amines are nitrogen-containing compounds with known toxicity and widespread commercial uses. Nevertheless, biomonitoring of these chemicals is lacking, particularly during pregnancy, a period of increased susceptibility to adverse health effects. OBJECTIVES/OBJECTIVE:We aimed to measure melamine, melamine derivatives, and aromatic amine exposure in pregnant women across the United States (U.S.) and evaluate associations with participant and urine sample collection characteristics. METHODS:We measured 43 analytes, representing 45 chemicals (i.e., melamine, three melamine derivatives, and 41 aromatic amines), in urine from pregnant women in nine diverse ECHO cohorts during 2008-2020 (N = 171). To assess relations with participant and urine sample collection characteristics, we used generalized estimating equations to estimate prevalence ratios (PRs) for analytes dichotomized at the detection limit, % differences (%Δ) for continuous analytes, and 95% confidence intervals. Multivariable models included age, race/ethnicity, marital status, urinary cotinine, and year of sample collection. RESULTS:Twelve chemicals were detected in >60% of samples, with near ubiquitous detection of cyanuric acid, melamine, aniline, 4,4'-methylenedianiline, and a composite of o-toluidine and m-toluidine (99-100%). In multivariable adjusted models, most chemicals were associated with higher exposures among Hispanic and non-Hispanic Black participants. For example, concentrations of 3,4-dichloroaniline were higher among Hispanic (%Δ: +149, 95% CI: +17, +431) and non-Hispanic Black (%Δ: +136, 95% CI: +35, +311) women compared with non-Hispanic White women. We observed similar results for ammelide, o-/m-toluidine, 4,4'-methylenedianiline, and 4-chloroaniline. Most chemicals were positively associated with urinary cotinine, with strongest associations observed for o-/m-toluidine (%Δ: +23; 95% CI: +16, +31) and 3,4-dichloroaniline (%Δ: +25; 95% CI: +17, +33). Some chemicals exhibited annual trends (e.g., %Δ in melamine per year: -11; 95% CI: -19, -1) or time of day, seasonal, and geographic variability. DISCUSSION/CONCLUSIONS:Exposure to melamine, cyanuric acid, and some aromatic amines was ubiquitous in this first investigation of these analytes in pregnant women. Future research should expand biomonitoring, identify sources of exposure disparities by race/ethnicity, and evaluate potential adverse health effects.

Investigations into the causal underpinnings of disease processes can be aided by the incorporation of genetic information. Genetic studies require populations varied in both ancestry and prevalent disease in order to optimize discovery and ensure generalizability of findings to the global population. Here, we report the genetic determinants of the serum proteome in 466 African Americans with chronic kidney disease attributed to hypertension from the richly phenotyped African American Study of Kidney Disease and Hypertension (AASK) study. Using the largest aptamer-based protein profiling platform to date (6,790 proteins or protein complexes), we identified 969 genetic associations with 900 unique proteins; including 52 novel cis (local) associations and 379 novel trans (distant) associations. The genetic effects of previously published cis-protein quantitative trait loci (pQTLs) were found to be highly reproducible, and we found evidence that our novel genetic signals colocalize with gene expression and disease processes. Many trans- pQTLs were found to reflect associations mediated by the circulating cis protein, and the common trans-pQTLs are enriched for processes involving extracellular vesicles, highlighting a plausible mechanism for distal regulation of the levels of secreted proteins. Thus, our study generates a valuable resource of genetic associations linking variants to protein levels and disease in an understudied patient population to inform future studies of drug targets and physiology.

PURPOSE/OBJECTIVE:We investigated the relationship between measures of self-reported health and well-being and concurrent and prospective healthcare utilization and costs to assess the added value of these self-reported measures in understanding utilization and cost. METHODS:Kaiser Permanente members (N = 6752) completed a 9-item survey measuring life evaluation, financial situation, social support, meaning and purpose, physical health, and mental health. Responses were linked to medical record information during the period 12 months before and after the survey. RESULTS:Correlations between health and well-being measures and healthcare utilization and cost variables were generally weak, with stronger correlations for future life evaluation and selected health measures (ρ = .20-.33, ps < .001). Better overall life evaluation had a significant but weak association with lower total cost and hospital days in the following year after controlling for age, sex, and race/ethnicity (p < .001). Full multivariate models, adjusting for age, sex, race/ethnicity, prior utilization, and relative risk models, showed weak associations between health and well-being measures and following year total healthcare cost and utilization, though the associations were relatively stronger for the health variables than the well-being variables. CONCLUSION/CONCLUSIONS:Overall, the health and well-being variables added little to no predictive utility for future utilization and cost beyond prior utilization and cost and the inclusion of predictive models based on clinical information. Perceptions of well-being may be associated with factors beyond healthcare utilization. When information about prior use is unavailable, self-reported health items have some predictive utility.