Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Severe AP is associated with significantly more retention of NIR 2-DG in the pancreas early during AP compared to controls.

<p><b>A:</b> Time course showing means of the Average radiant efficiency for the values obtained ±15 minutes for each time point within each group (i.e. control; Con, duct ligation; DL, and GTL) after normalizing to the 30 minute peak (100%) for that group. * depicts a significant (p<0.05) increase in the GTL vs. control and # depicts significance vs. DL on ANOVA at each time point. <b>B:</b> Time course showing Average radiant efficiency (ARE) normalized to controls. The initial mean AREs for each group prior to AP induction, were subtracted from those at each time point. The difference in the DL or GTL pancreatitis groups was divided by the corresponding difference in the control group, and this ratio is shown as fold change over control. Please note, that with the decline in the ARE values in controls over time (A), there is a significant increase in this ratio in the GTL group vs. DL group (#). There were 9–12 animals per group. <b>C:</b> Fluorescence images (upper panel) and gross appearance (lower panel) of the pancreas <i>ex vivo</i> in the control, DL and GTL groups. <b>D:</b> Bar graphs showing the quantification of the ARE for each group. “*” depicts a significant (p<0.05) increase in the GTL vs. control and “#” depicts significance vs. DL on ANOVA.</p

Severe AP is associated with a progressive increase in necrosis and mortality.

<p>A: time course of percentage of pancreatic parenchyma what was necrotic in the GTL (red) and DL (green) groups measured when electively sacrificed at 1, 3 hours and at euthanasia (≤ 8 hours). Values at 1 hour, 3 hours and at the time of euthanasia for each group were compared to each other and the controls by ANOVA. “*” depicts a significant (p<0.05) increase vs. control and “#” depicts significant differences in GTL vs. DL. Representative microscopic (5x, B) and gross (C) images are shown. D: Kaplan-Meyer curve showing % survival in the different study groups. There was 100% mortality in the GTL group by 8 hours, but none in the duct ligation group. There were 8–12 animals per group. Scale bars are 1mm in length.</p

The increase of AP parameters in the blood is similar in both mild and severe disease.

<p>Time course of the activities of amylase (A), Lipase (B), alanine amino transferase (ALT; C) and amount of bilirubin (D) measured in heparinized plasma samples after 1, 3 hours of AP induction, at euthanasia (≤ 8 hours), and as baseline control value without the procedure (0 hours). Values at 1 hour, 3 hours and at the time of euthanasia for each group (DL- green, GTL-red) were compared to each other and the controls by ANOVA. “*” depicts a significant (p<0.05) increase vs. control and “#” depicts significance in GTL vs. DL. There were 8–12 animals per group.</p

Parameters potentially affecting the NIR 2-DG signal measured in our system.

<p><b>A:</b> Images of a rat administered NIR 2-DG collected on the IVIS imaging system in the supine position over the first 10 minutes (first five images) and in the right lateral position (last image). Note the increase over the bladder but the lack of signal over the pancreas in the supine position. This pattern is reversed in the right lateral position. Fluorescent (B) and black and white(C) images of the duodenum, pancreas and spleen removed <i>en block</i> after 2 hours of NIR 2-DG administration in controls or pancreatitis in the DL and GTL groups. Please note an increased uptake in the duodenum (white outlines) especially in controls. <b>D:</b> Data from groups of 8–12 animals showing the time course of the increase in pancreatic edema (measured as % water content or pancreatic ATP concentrations (<b>E</b>) in the DL and GTL groups. The “*” depict <i>p</i><0.05 vs. corresponding controls “#” depicts significant differences in GTL vs. DL.</p