Racial and Neighborhood-Level Disparities in COVID-19 Incidence among Patients on Hemodialysis in New York City.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected socially disadvantaged populations. Whether disparities in COVID-19 incidence related to race/ethnicity and socioeconomic factors exist in the hemodialysis population is unknown. METHODS: Our study involved patients receiving in-center hemodialysis in New York City. We used a validated index of neighborhood social vulnerability, the Social Vulnerability Index (SVI), which comprises 15 census tract-level indicators organized into four themes: socioeconomic status, household composition and disability, minority status and language, and housing type and transportation. We examined the association of race/ethnicity and the SVI with symptomatic COVID-19 between March 1, 2020 and August 3, 2020. COVID-19 cases were ascertained using PCR testing. We performed multivariable logistic regression to adjust for demographics, individual-level social factors, dialysis-related medical history, and dialysis facility factors. RESULTS: Of the 1378 patients on hemodialysis in the study, 247 (17.9%) developed symptomatic COVID-19. In adjusted analyses, non-Hispanic Black and Hispanic patients had significantly increased odds of COVID-19 compared with non-Hispanic White patients. Census tract-level overall SVI, modeled continuously or in quintiles, was not associated with COVID-19 in unadjusted or adjusted analyses. Among non-Hispanic White patients, the socioeconomic status SVI theme, the minority status and language SVI theme, and housing crowding were significantly associated with COVID-19 in unadjusted analyses. CONCLUSIONS: Among patients on hemodialysis in New York City, there were substantial racial/ethnic disparities in COVID-19 incidence not explained by neighborhood-level social vulnerability. Neighborhood-level socioeconomic status, minority status and language, and housing crowding were positively associated with acquiring COVID-19 among non-Hispanic Whites. Our findings suggest that socially vulnerable patients on dialysis face disparate COVID-19-related exposures, requiring targeted risk-mitigation strategies.

A comparison of coronary CTA and stress testing using high-efficiency SPECT MPI for the evaluation of chest pain in the emergency department.

BACKGROUND: Recent studies have compared CTA to stress testing and MPI using older Na-I SPECT cameras and traditional rest-stress protocols, but are limited by often using optimized CTA protocols but suboptimal MPI methodology. We compared CTA to stress testing with modern SPECT MPI using high-efficiency CZT cameras and stress-first protocols in an ED population. METHODS: In a retrospective, non-randomized study, all patients who underwent CTA or stress testing (ETT or Tc-99m sestamibi SPECT MPI) as part of their ED assessment in 2010-2011 driven by ED attending preference and equipment availability were evaluated for their disposition from the ED (admission vs discharge, length of time to disposition), subsequent visits to the ED and diagnostic testing (within 3 months), and radiation exposure. CTA was performed using a 64-slice scanner (GE Lightspeed VCT) and MPI was performed using a CZT SPECT camera (GE Discovery 530c). Data were obtained from prospectively acquired electronic medical records and effective doses were calculated from published conversion factors. A propensity-matched analysis was also used to compare outcomes in the two groups. RESULTS: A total of 1,458 patients underwent testing in the ED with 192 CTAs and 1,266 stress tests (327 ETTs and 939 MPIs). The CTA patients were a lower-risk cohort based on age, risk factors, and known heart disease. A statistically similar proportion of patients was discharged directly from the ED in the stress testing group (82% vs 73%, P = .27), but their time to disposition was longer (11.0 ± 5 vs 20.5 ± 7 hours, P < .0001). There was no significant difference in cardiac return visits to the ED (5.7% CTA vs 4.3% stress testing, P = .50), but more patients had follow-up studies in the CTA cohort compared to stress testing (14% vs 7%, P = .001). The mean effective dose of 12.6 ± 8.6 mSv for the CTA group was higher (P < .0001) than 5.0 ± 4.1 mSv for the stress testing group (ETT and MPI). A propensity score-matched cohort showed similar results to the entire cohort. CONCLUSIONS: Stress testing with ETT, high-efficiency SPECT MPI, and stress-only protocols had a significantly lower patient radiation dose and less follow-up diagnostic testing than CTA with similar cardiac return visits. CTA had a shorter time to disposition, but there was a trend toward more revascularization than with stress testing.

A new approach for quantitative phosphoproteomic dissection of signaling pathways applied to T cell receptor activation.

Reversible protein phosphorylation plays a pivotal role in the regulation of cellular signaling pathways. Current approaches in phosphoproteomics focus on analysis of the global phosphoproteome in a single cellular state or of receptor stimulation time course experiments, often with a restricted number of time points. Although these studies have provided some insights into newly discovered phosphorylation sites that may be involved in pathways, they alone do not provide enough information to make precise predictions of the placement of individual phosphorylation events within a signaling pathway. Protein disruption and site-directed mutagenesis are essential to clearly define the precise biological roles of the hundreds of newly discovered phosphorylation sites uncovered in modern proteomics experiments. We have combined genetic analysis with quantitative proteomic methods and recently developed visual analysis tools to dissect the tyrosine phosphoproteome of isogenic Zap-70 tyrosine kinase null and reconstituted Jurkat T cells. In our approach, label-free quantitation using normalization to copurified phosphopeptide standards is applied to assemble high density temporal data within a single cell type, either Zap-70 null or reconstituted cells, providing a list of candidate phosphorylation sites that change in abundance after T cell stimulation. Stable isotopic labeling of amino acids in cell culture (SILAC) ratios are then used to compare Zap-70 null and reconstituted cells across a time course of receptor stimulation, providing direct information about the placement of newly observed phosphorylation sites relative to Zap-70. These methods are adaptable to any cell culture signaling system in which isogenic wild type and mutant cells have been or can be derived using any available phosphopeptide enrichment strategy.