Systemic inflammation that accompanies acute respiratory distress syndrome in COVID-19 [1] is associated with a high mortality rate, as high as 32.5% [2]. Treatment options for severe cases remain limited [3]. The high mortality rate, lack of effective therapies, and extremely high volume of cases have led to a clear need for reliable prognostic markers to indicate which patients are at the highest risk of death and thus require closer monitoring. One factor that is common to the majority of hospitalized COVID-19 patients is fever. The degree of temperature elevation might reflect the severity of inflammation. However, there are currently no published studies that have looked at body temperature (BT) as a potential prognostic marker. We sought to analyze how BT monitoring might inform mortality rate estimates in COVID-19-positive patients. We analyzed BT data in the de-identified database of COVID-19-suspected patients in Mount Sinai and its affiliated hospitals in the New York area as of May 3, 2020. A total of 9417 patients tested positive for the SARS-CoV-2 virus by RT-PCR detection. After excluding patients with missing temperature data (n = 1802), 7614 patients were included in the analysis (Table 1). Fifty percent had a BT > 37°C on the initial presentation and 78.5% of patients developed BT > 37°C during the course of the disease. The overall mortality was 16.9% with a median of 7 days to death from the initial presentation. As shown in Fig. 1a, higher BT at the initial presentation did not show a significant association to mortality. Importantly, patients presenting with BT ≤ 36°C had the highest mortality (26.5%, P = 0.003 relative to 36°C < BT ≤ 37°C), and this became even higher when the analysis was restricted to those with BT ≤ 35.5°C (44%), indicating low body temperature at the initial presentation is a marker of poor prognosis. Meanwhile, maximum BT during COVID-19 infection was significantly correlated with mortality rate (Fig. 1b).

BACKGROUND The enrollment of Black patients in cancer clinical trials continues to trend far below the true prevalence of disease in Black patients in the United States, limiting the generalizability of trial results. A potentially overlooked contributor to the underenrollment of Black patients may be the increasing enrollment of cancer trials in countries outside the United States. However, the impact of the globalization of cancer clinical trials on recruitment of racial minority patients has been understudied. METHODS In this study, race and accrual location data for all cancer drugs approved by the US Food and Drug Administration (FDA) between 2015 and 2018 were analyzed. A disparity score was calculated for each approval, a metric comparing Black enrollment in clinical trials with the estimated burden of disease in Black patients. RESULTS Of 49 global clinical trials supporting 35 FDA drug approvals with race data available, Black patients accounted for 2.5% of enrollment (range, 0%‐10%), with a median disparity score of 0.19 (range, 0.01‐0.98). In 21 clinical trials supporting 18 FDA drug approvals with both race and accrual location data available, 64% patients were enrolled outside the United States (range, 0%‐100%). Black patients accounted for 3.2% of enrollment (range, 0.2%‐10%), and the median disparity score was 0.23 (range, 0.01‐0.98). There was a significant inverse correlation between the proportion of trial patients enrolled outside the United States and the disparity score (Pearson correlation, –0.61; P = .007). CONCLUSIONS The globalization of cancer clinical trials is associated with a widening racial enrollment disparity gap in the United States. The impact of global trials on domestic clinical trial generalizability warrants further consideration from a regulatory and policy standpoint. LAY SUMMARY Black patients continue to be underrepresented in cancer clinical trials; this disparity has worsened in recent years perhaps because of the globalization of cancer clinical trials. In an analysis of demographic information from 21 cancer clinical trials leading to US Food and Drug Administration approvals between 2015 and 2018, clinical trials conducted primarily outside the United States were 2‐fold less likely to enroll Black participants than US clinical trials. Thus, the globalization of cancer clinical trials may have the unintended consequence of further exacerbating existing racial disparities in cancer clinical trial representation and ultimately the generalizability of trial results.

Identifying genomic alterations of cancer proteins has guided the development of targeted therapies, but proteomic analyses are required to validate and reveal new treatment opportunities. Herein, we develop a new algorithm, OPPTI, to discover overexpressed kinase proteins across 10 cancer types using global mass spectrometry proteomics data of 1,071 cases. OPPTI outperforms existing methods by leveraging multiple co-expressed markers to identify targets overexpressed in a subset of tumors. OPPTI-identified overexpression of ERBB2 and EGFR proteins correlates with genomic amplifications, while CDK4/6, PDK1, and MET protein overexpression frequently occur without corresponding DNA- and RNA-level alterations. Analyzing CRISPR screen data, we confirm expression-driven dependencies of multiple currently-druggable and new target kinases whose expressions are validated by immunochemistry. Identified kinases are further associated with up-regulated phosphorylation levels of corresponding signaling pathways. Collectively, our results reveal protein-level aberrations—sometimes not observed by genomics—represent cancer vulnerabilities that may be targeted in precision oncology.

Coronary microembolization is one of the main causes of the “no-reflow” phenomenon, which commonly occurs after reperfusion of an occluded coronary artery. Given its high incidence and the fact that it has been proven to be an independent predictor of cardiac morbidity and mortality, there is an imperative need to study its underlying mechanisms and pathophysiology. Large animal models are essential to perform translational studies. Currently there is no animal model that recapitulates a clinical scenario of thrombogenic microembolism with preceding myocardial ischemia. Therefore, the goal of this study was to develop and characterize a novel pig model of coronary microembolization using autologous thrombus injection (CMET). Twenty-three pigs underwent myocardial infarction through percutaneous balloon occlusion of the left anterior descending artery (LAD). Each animal was enrolled in one of two groups: (1) the CMET group, in which the LAD occlusion was followed by delivery of autologous clotted blood in the LAD (distal to the balloon occlusion) and reperfusion; (2) the ischemic reperfusion (I/R) group, in which the LAD ischemia was followed by reperfusion. Surviving animals underwent functional and morphological characterization at 1-week post-procedure. Three sham operated animals were used as a control. CMET resulted in impaired left ventricular function compared to I/R pigs at 1 week. Three-dimensional echocardiography demonstrated reduced ejection fraction in the CMET group (CMET vs. I/R: 35.6 ± 4.2% vs. 47.6 ± 2.4%, p = 0.028). Invasive hemodynamic measurements by Swan-Ganz and left ventricular pressure-volume catheters revealed that CMET impaired left ventricular contractility and diastolic function. This was confirmed by both load-dependent indices including cardiac output (CMET vs. I/R: 2.7 ± 0.2 l/min, vs. 4.0 ± 0.1 l/min, p = 0.002) and load independent indices including preload-recruitable stroke work (CMET vs. I/R: 25.8 ± 4.0 vs. 47.5 ± 6.5 mmHg, p = 0.05) and end-diastolic pressure-volume relationship (slope, 0.68 ± 0.07 vs. 0.40 ± 0.11 mmHg/ml, p = 0.01). Our unique closed-chest model of coronary microembolization using autologous thrombus injection resembles the clinical condition of thrombogenic coronary microembolization in I/R injury. This model offers opportunities to conduct translational studies for understanding and treating coronary microembolization in myocardial infarction.

<b><i>Background:</i></b> The Oncotype DX Breast Cancer Assay is a 21-gene assay used to predict the likelihood of distant recurrence and the benefit of chemotherapy in patients with node-negative, tamoxifen-treated breast cancer. Prior studies demonstrated 7–19% discordance, or a difference between the recurrence score (RS) and tumor grade (TG) in breast cancer patients. BRCA mutated tumors (BRCA+) have been shown to be associated with higher RS as compared to BRCA-negative patients (BRCA–). <b><i>Objectives:</i></b> We developed a large Oncotype RS database to determine if the BRCA mutation status is associated with discordance. <b><i>Methods:</i></b> We identified 723 patients (32 [4%] mutation-positive and 691 [96%] mutation-negative patients) with early-stage, hormone-positive breast cancer treated between 2006 and 2018, with tumor characteristics available for analysis. Discordance was defined as one- or two-step difference between RS (low, intermediate, high risk) and TG (well [WD], moderately [MD], and poorly [PD] differentiated). Mutation positive was defined as BRCA1 deleterious mutation, BRCA2 deleterious mutation, BRCA mutation of unknown type, BRCA variant of undetermined significance (VUS) or other mutation (classified as other VUS). Number (%) or median were used to describe patient characteristics between groups and were compared by the Kruskal-Wallis test at a significance level of 5%. <b><i>Results:</i></b> Among these patients, there were 32 (4% of total) who were identified as mutation-positive. Of those patients, 16% had a documented deleterious mutation in BRCA1, 22% in BRCA2, 6% had a BRCA mutation of unknown type (either 1 or 2), 25% were BRCA VUS, and 31% other VUS (most commonly CHEK2 and ATM). The median RS was 23.5 in patients with deleterious BRCA mutations (1, 2 or unknown) versus 16 in patients in the BRCA-negative database, which was statistically significant (<i>p</i> &#x3c; 0.01). One- and two-step discordance was present in 46 and 8%, respectively, of patients with deleterious BRCA mutations versus 53 and 11%, respectively, in the BRCA-negative database. <b><i>Conclusions:</i></b> Patients with deleterious BRCA mutations demonstrated no difference in rates of discordance as compared to BRCA-negative patients. We further demonstrated that patients with BRCA-positive tumors display higher RS than patients with BRCA-negative tumors.