Inflammatory cells in the ascending aortic aneurysm in patients with type 2 diabetes versus patients with hypertension

Aortic aneurysms occur relatively frequently in the ascending thoracic aorta, but are rarely seen in patients with type 2 diabetes. Our aim was to evaluate inflammatory cell infiltration in the ascending aortic aneurysm wall in patients with diabetes without arterial hypertension (DM2 group, N=6) versus hypertensive non-diabetic patients (AH group, N=34). For histologic analysis, the sections were stained with hematoxylin-eosin and Movat pentachrome. The immunohistochemical staining was used to analyze the infiltration of pro-inflammatory (CD68) and anti-inflammatory macrophages (CD163), T helper (CD4) and T killer cells (CD8), and B (CD79a) and plasma cells (CD138) in all three layers of aneurysms of both groups. The statistical significance of the differences between groups was evaluated by ANOVA and the Welch test. In comparison to the AH group, the DM2 group developed less severe infiltration of pro-inflammatory macrophages (P=0.004) and B cells (P=0.025) in the tunica intima, and tunica media (P=0.049, P=0.007, respectively), and fewer plasma cells in the tunica media (P=0.024) and tunica adventitia (P=0.017). We found no significant differences in the number of T helper, T killer cells, and anti-inflammatory macrophages and in the amount of collagen and elastic fibers, ground substance, and smooth muscle cells in all three layers of the vessel wall. Except in tunica adventitia of DM2 group, there were more collagen fibers overall (P=0.025). Thus, we conclude that the histological structure of the aneurysm in diabetics without hypertension is almost the same as in hypertensive patients without diabetes. Diabetics had significantly less inflammatory infiltration in all three layers of the vessel wall, and more collagen fibers in tunica adventitia.

Comparison of survivor scores for differentiation therapy of cancer to those for checkpoint inhibition: Half full or half empty

Differentiation therapy is directed to the self-renewing cancer stem cells, as well as their progeny transit amplifying cells, to force them to mature to terminal differentiation. Differentiation therapy is effective in treatment of neuroblastomas and myeloid leukemias. Checkpoint inhibition therapy removes blocks to cancer reactive T-killer cells and allows them to react to malignant cells and limit the growth of cancer. The percentage of patients with a given cancer that responds to either therapy is less than hoped for, and the duration of response is variable. Multiplying the response rate (percentage of patients responding to therapy) by the duration of response may be used to derive a survival score for patients treated with differentiation therapy or checkpoint inhibition. By this criterion, differentiation therapy gives better survival scores than checkpoint inhibition. Yet, checkpoint inhibition is considered a great success, mostly because it may be applied to many different types of cancer, and differentiation therapy is considered relatively ineffective because it is limited to a few specific cancers. On the other hand, the cost of checkpoint inhibition treatment is 10–20 times more per patient than that of differentiation therapy. Hopefully, future combined treatments and advances in both approaches will increase the effectiveness of these cancer treatments.

The Utility of Detection Populations of T-Lymphocytes, T-Killer Cells and Natural Killer Cells by CD2 Expression In White Blood Cell Differential Using Flow Cytometry

Abstract 4879 Introduction. The differential leukocyte count using Cytodiff™ reagent from Beckman Coulter (BEC) allows to detect a wide spectrum of normal and pathological cells in peripheral blood and is useful as a screening test. The CytoDiff™ tube is a 5-color/6-marker panel that provides an extended cytometric differential for whole blood specimens and comprises of: CD36-FITC, (CD2+CD294)-PE, CD19-ECD, CD16-PC5, and CD45-PC7. This provides clinicians with a diagnostic tool to determine appropriate therapies for a variety of blood-related diseases rapidly. CytoDiff™ allows to detect T&NK lymphocytes in the mutual gate using the gating strategy. The aim of this study was to analyze the CD2 expression on T-lymphocytes, T killer cells and natural killer cells in order to separate T&NK lymphocytes, as it was published by Catovsky (Catovsky et al., 1996) and to investigate if CytoDiff™ reagent can be useful to differentiate these types of lymphocytes. Materials and methods. 18 normal peripheral blood (PB) samples in K2EDTA were enrolled into this study. Each sample was stained with the CytoDiff™ reagent and with the reference mixture of monoclonals to detect T-killer, NK-cells and T-Lymphocytes (CD3-FITC, CD(16+56)-PE, CD45-ECD, CD2-PC7, all BEC). The PB was lyzed using VersaLyse (BEC) to prevent selective loss of cells and to conserve light scatter characteristics. PB leukocytes were analyzed according to their immunofluorescence reactivity. At least 20,000 CD45+ events per tube were acquired on FC500 Cytomics flow cytometer (BEC) and analyzed using CXP software (BEC). In the reference tube we identified three populations using the CD45brightSSlow lymphocyte gate in the CD3-FITC/CD(16+56)-PE plot: CD3+CD(16+56)- T lymphocytes, CD3+CD(16+56)+ T killer cells and CD3-CD(16+56)+ natural killer cells. Each population after detecting was applied to CD2/SS plot and X-mean value of CD2 population was calculated. For the CytoDiff tube we analyzed the expression of CD2 and CD16 on the different sub-populations of the T&NK lymphocytes, The X-mean values of CD2 expression and percentages of sub-populations of T&NK lymphocytes in the reference tube and in the CytoDiff™ tube were calculated. For statistic analysis we used Statistica 6.0. The study was approved by The Pavlov State Medical University's Institutional Review Board. Results. The data, obtained with reference tube, shows that the populations of T-lymphocytes, T killer cells and natural killer cells are different by X-mean of CD2 expression (p<0.001). The natural killer cells have the lower intensity the CD2 antigen compared with CD3+CD(16+56)- T lymphocytes (p<0.001), while the highest CD2 expression was found in the CD3+CD(16+56)+ T killer cells (p<0.001). According to Mann-Whithey test the percentages and X-mean value of CD2 of the described populations are not different in the reference and in the CytoDiff™ tubes. Conclusion. These findings show that different populations of T&NK cells can be differentiated by CD2 expression and flow cytometric WBC differential can provide more wide possibilities for screening of pathology, especially in cases of viral infection and T-cell leukemia. Disclosures: Sukhacheva: Beckman Coulter: Employment. Simon-Lopez: Beckman Coulter: Employment.