promising role of extracellular vesicles as biomarkers of acute graft vs host disease

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Applying Data Warehousing to a Phase III Clinical Trial From the Fondazione Italiana Linfomi Ensures Superior Data Quality and Improved Assessment of Clinical Outcomes

Data collection in clinical trials is becoming complex, with a huge number of variables that need to be recorded, verified, and analyzed to effectively measure clinical outcomes. In this study, we used data warehouse (DW) concepts to achieve this goal. A DW was developed to accommodate data from a large clinical trial, including all the characteristics collected. We present the results related to baseline variables with the following objectives: developing a data quality (DQ) control strategy and improving outcome analysis according to the clinical trial primary end points

Comparative external validation of the PRECISE-DAPT and PARIS risk scores in 4424 acute coronary syndrome patients treated with prasugrel or ticagrelor

Background: The PRECISE-DAPT and PARIS risk scores (RSs) were recently developed to help clinicians at individualizing the optimal dual antiplatelet therapy duration (DAPT) after percutaneous coronary intervention (PCI). Nevertheless, external validation of these RSs it has not yet been performed in ACS (acute coronary syndrome) patients treated with prasugrel or ticagrelor in a real- world scenario. Methods: 4424 ACS patients who underwent PCI and survived to hospital discharge, from January 2012 to December 2016 at 12 European centers, were included. PRECISE-DAPT and PARIS bleeding RS, as well as PARIS ischemic RS, were computed, and their performance at predicting major bleeding (MB; BARC type 3 or 5) and ischemic events (MI and stent thrombosis) during follow up was compared. Results: After a median follow-up of 14 (interquartile range 12–20.9) months, 83 (1.88%) patients developed MB and 133 (3.0%) suffered an ischemic episode. PRECISE-DAPT performed better than PARIS bleeding RS (c-statistic = 0.653 vs. 0.593; p =.01 for comparison) in predicting MB. The RSs performance for MB prediction remained consistent in STEMI patients (c-statistic = 0.632 vs 0.575) or in those treated with prasugrel (c-statistic = 0.623 vs 0.586). PARIS ischemic RS exhibited superior discrimination in predicting ischemic complications compared to PRECISE-DAPT (c-statistic = 0.604 vs 0.568 p =.05 for comparison). Conclusion: Our data provide support to the use of PRECISE-DAPT in MB risk stratification for patients receiving DAPT in form of aspirin and prasugrel or ticagrelor whereas the PARIS ischemic RS has potential to complement the risk prediction with respect to ischemic events

A simple, effective and inexpensive method to highlight antigen-antibody reaction based on liquid-semisolid phase

Identification of the immunological antigen-antibody reaction performed either in liquid phase or in agarose have several limits: antigen excess, low sensitivity, low speed reaction. A new method is described for the antigen-antibody reaction, easy, simple to perform and inexpensive. It is based on a reaction where the specific antibody is mixed with a semi-solid gel on a transparent surface and the antigen to be identified is inoculated into the gel. In this method, an immune precipitate can be shown in just few minutes, obtaining a good sensitivity compared with manual methods such as the Ouchterlony technique and other similar methods. By using albumin, IgG, RBP, transferrin, alpha-2-macroglobulin as antigen, the immune precipitate is formed within 10 min at 2–8 microgram/ml and, after 30 min, at 1–4 microgram/ml may be detected. The display of the immune precipitate is favored by oblique observation on a black background with a perpendicular light illuminating the gel from the bottom upwards. This method also allows a good control of antigen excess, a problem that is instead found in immunoturbidimetric reactions. The method here described has also been tested in serum and urine, and then it can be advantageously used as qualitative or semi-quantitative immunological test in research or diagnostic. Moreover, it could be particularly useful in low resources geographical areas, where an immunoassay that requires the use of dedicated equipment is not economically sustainable. The authors have waived the patent rights to allow the free development of new tests based on this method

Promising Role of Extracellular Vesicles as Biomarkers of Acute Graft-vs.-Host Disease

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Counting circulating endothelial cells in allo-HSCT: an ad hoc designed polychromatic flowcytometry-based panel versus the CellSearch System

Abstract Physio-pathologic interrelationships between endothelial layer and graft-versus-host disease (GVHD) have been described leading to assess the entity “endothelial GVHD” as the early step for clinical manifestations of acute GVHD. The availability of the CellSearch system has allowed us to monitor Circulating Endothelial Cells (CEC) changes in allogeneic hematopoietic stem cell transplantation (allo-HSCT) as useful tool to help clinicians in GVHD diagnostic definition. We have compared CEC counts generated by an ad hoc designed polychromatic-flowcytometry (PFC) Lyotube with those of the CellSearch system. CEC were counted in parallel at 5 timepoints in 50 patients with malignant hematologic disorders undergoing allo-HSCT (ClinicalTrials.gov, NCT02064972). Spearman rank correlation showed significant association between CEC values at all time points (p = 0.0001). The limits of agreement was demonstrated by Bland Altman plot analysis, showing bias not significant at T1, T3, T4, while at T2 and T5 resulted not estimable. Moreover, Passing Bablok regression analysis showed not significant differences between BD Lyotube and CellSearch system. We show that CEC counts, generated with either the CellSearch system or the PFC-based panel, have a superimposable kinetic in allo-HSCT patients and that both counting procedures hold the potential to enter clinical routine as a suitable tool to assist clinicians in GVHD diagnosis