Purpose We investigated the effect of circulating factors and protein kinase Cβ (PKCβ) on blood-brain barrier permeability and edema during hyperglycemic stroke. Methods Male Wistar rats that were hyperglycemic by streptozotocin (50 mg/kg) for 5–6 days underwent middle cerebral artery occlusion (MCAO) for 2 hours with 2 hours of reperfusion. Blood-brain barrier permeability was measured in MCAs that were ischemic (MCAO) or nonischemic (CTL) and perfused with plasma (20% in buffer) from MCAO or CTL animals. A separate set of MCAO vessels was perfused with the PKCβ inhibitor CGP53353 (0.5 μmol/L) and permeability measured. Lastly, hyperglycemic rats were treated i.v. with CGP53353 (10 or 100 μg/kg or vehicle 15 minutes prior to reperfusion and edema formation measured by wet:dry weights (n=6/group). Results MCAO vessels had increased permeability compared to controls, regardless of the plasma perfusate. Permeability (water flux, μm3 × 108) of CTL vessel/CTL plasma (n=8), CTL vessel/MCAO plasma (n=7), MCAO vessel/CTL plasma (n=6) and MCAO vessel/MCAO plasma (n=6) was 0.98±0.11, 1.13±0.07, 1.36±0.02, and 1.34±0.06; p<0.01). Inhibition of PKCβ in MCAO vessels (n=6) reversed the increase in permeability (0.92±0.1; p<0.01). In vivo, hyperglycemia increased edema vs. normoglycemia after MCAO (water content = 78.84±0.11% vs. 81.38±0.21%; p<0.01). Inhibition of PKCβ with 10 or 100 μg/kg CGP53353 during reperfusion prevented the increased edema in hyperglycemic animals (water content = 79.54±0.56% and 79.99±0.43%; p<0.01 vs. vehicle). Conclusions These results suggest that the pronounced vasogenic edema that occurs during hyperglycemic stroke is mediated in large part by activation of PKCβ.

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We reviewed response to immune checkpoint inhibitors (ICI) of 207 patients with diagnoses of lung or head and neck cancer treated with chemotherapy/ICI combination therapy and ICI monotherapy between 2015 and 2020 at one of three clinical pavilions associated with the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine. Two of these pavilions (Harris Health System and the Michael E. DeBakey Veterans Affairs Medical Center) serve large minority populations and provide equal access to care regardless of means. 174 patients had a diagnosis of lung cancer (non-small cell or small cell) and 33 had a diagnosis of head and neck squamous cell carcinoma (HNSCC). 38% self-identified as Black, 45% as non-Hispanic White, and 18% as Hispanic. The objective response rate (ORR) was similar for lung cancer (35.057%) and HNSCC patients (30.3%) (p=0.894). The ORR for Hispanic and Black patients was lower compared to non-Hispanic White patients (H 27.0%, B 32.5%, W 38.7%; H vs. W p=0.209; B vs. W p=0.398). When considering only patients treated with ICI monotherapy, the ORR for Hispanic patients dropped further to 20.7% while the ORR of Black and non-Hispanic White patients remained about the same (B 29.3% and W 35.9%, H vs. W p=0.133; B vs. W p=0.419). Immune related adverse events were the lowest in the Hispanic population occurring in only 30% of patients compared to 40% of patients in the Black cohort and 50% of the non-Hispanic White cohorts.

Background: Acute Myeloid Leukemia (AML) outcomes are dependent on leukemia-specific factors, such as cytogenetics and patient-specific factors, such as age and performance status. Racial and socioeconomic disparities have become apparent with self-reported African American race associated with poor survival in AML pts &lt; 60 years (y) of age. We analyzed in-hospital death among AML-related hospitalizations and evaluated differences in sociodemographic characteristics, focusing on the effect of age and race. Methods: We conducted a retrospective cohort study using the Nationwide Inpatient Sample (HCUP-NIS), the largest all-payer database of hospital admissions in the United States, from January 1 st, 2009 through December 31 st, 2018. The study sample consisted of AML-associated hospitalizations of patients aged 18 years of age and older, identified on the basis of the presence of any ICD-9 and 10 codes indicative of AML We categorized patients' ages in groups of &lt;60 y and ≥ 60 y. Ethnicity was initially stratified by reported ethnicity (Hispanic, Non-Hispanic), and the Non-Hispanic group was subdivided into White, Black, or other. The primary payer for the hospitalization was classified. As a proxy for socioeconomic status, the HCUP-NIS provides zip-code-level estimates of median household income, grouped into quartiles based on the patient's residence. Hospital factors included census region, bed size, and hospital type. Patients' comorbidity status was captured using Elixhauser Comorbidity Index (0, 1-4, 5+). Outcome of interest was in-hospital death. Among different age groups and ethnic groups of patients with AML, we used survey logistic regression to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) that measured the independent associations between various patient hospitalization characteristics and inpatient death. We adopted a 5% type I error rate for the calculation of CIs, and used appropriate survey weighting to generate national prevalence estimates considering the complex sampling design of the NIS. Statistical analyses were performed using R (version 3∙6∙1) and RStudio (Version 1∙2∙5001). Results: Of 662,417 AML-related hospitalizations, 57.6% were in patients ≥60 y. Of AML-related hospitalizations in patients &lt;60 y, 61.6% were in NH-White patients, 11.2% were in NH Blacks, and 11.7% were in Hispanics. Of AML-related hospitalizations in patients ≥60 y, 74.6% were in NH-Whites, 7.3% in NH-Blacks and 5.4% in Hispanics. Analysis of in-hospital death among AML-related hospitalizations, stratified by race/ethnicity revealed increased in-hospital death among male NH-Black AML patients ≥ 60 y as compared to NH-Black females in the same age group (OR 1.24; CI 1.04-1.47) and an increased in-hospital death among Hispanic patients ≥ 60 years with comorbidities relative to their counterparts in the same age group without comorbidities (OR 17.8; CI 11.32-29.37 for Elixhauser Comorbidity Index 1-4 and OR 2.69; CI 1.09-5.26 for Elixhauser Comorbidity Index ≥5). Differences in income, primary payer, hospital region, size, location or teaching status were not associated with in-hospital death among AML patients stratified by race/ethnicity. See Table 1. Conclusions: We found a significant increase in in-hospital death among Hispanic patients ≥ 60 y with comorbidities relative to their counterparts in the same age group without comorbidities. Yet, comorbidities did not appear to have a statistically significant impact in mortality for patients of other race/ethnicity or those &lt;60 y. It is plausible that the relationship between comorbidities and re-hospitalizations might be impacting our data. Previous work not specific to acute myeloid leukemia has shown that higher comorbidity is associated with an increased risk of readmission. Since our data was based on AML-related hospitalizations rather than patients with AML, it is possible that we are dealing with a false negative error because of patients with comorbidities being readmitted more. The lack of cytogenetic data in NIS is another notable limitation to our work. Nonetheless, we have found striking differences in the outcomes of elderly Hispanic comorbid patients and further evaluations are needed for correlation and to identify areas of optimization in their care. Figure 1 Figure 1. Disclosures Mims: Incyte: Research Funding; AVEO: Research Funding; Pfizer: Research Funding; IDEC: Current holder of individual stocks in a privately-held company; Celgene: Research Funding; Biogen: Current holder of individual stocks in a privately-held company.