Cangrelor versus crushed ticagrelor in patients with acute myocardial infarction and cardiogenic shock: rationale and design of the randomised, double-blind DAPT-SHOCK-AMI trial.

Cardiogenic shock (CS) is a devastating and fatal complication of acute myocardial infarction (AMI). CS can affect the pharmacokinetics and pharmacodynamics of medications. The unique properties of cangrelor make it the optimal P2Y12 inhibitor for CS-AMI, in terms of both efficacy and safety.

Milking Temperament and Its Association with Test-Day Milk Yield in Bulgarian Murrah Buffaloes.

The goal of this research was to evaluate milking temperament and its relationship with test-day milk (TDMY0) yield in Bulgarian Murrah buffaloes. This study involved 90 buffalo cows reared under a tie-stall production system which were milked twice a day with a milking pipeline. The behavioral responses of the buffaloes were reported during preparation for milking and during actual milking.

Validation of a single tube 3-colour immature red blood cell screening assay for the detection and enumeration of small, medium and large paroxysmal nocturnal haemoglobinuria clones by flow cytometry.

Introduction: The reliable diagnosis of paroxysmal nocturnal haemoglobinuria (PNH) by flow cytometry is based on mandatory analysis of the erythroid, neutrophilic and monocytic lineages. In this study, we have evaluated the performance characteristics of a recently published immature red blood cell (iRBC) assay as a potential screening test for PNH by flow cytometry.

Methods: Intra- and inter-assay imprecision were determined in five replicates of small, medium and large PNH iRBC clones.

Influence of Heat Stress and Physiological Indicators Related to It on Health Lipid Indices in Milk of Holstein-Friesian Cows.

The aim of the survey was to study the effect of heat stress (HS) on health lipid indices in milk of Holstein-Friesian cows. The study was conducted in a cattle farm with Holstein-Friesian cows in the region of Karnobat (Southeastern Bulgaria) in 2018. Cows were housed in semi-open free stall dairy barn, fed year-round ad libitum with a total mixed ration.

WT1 Gene Expression in Peripheral Blood Before and After Allogeneic Stem Cell Transplantation is a Clinically Relevant Prognostic Marker in AML - A Single-center 14-year Experience.

Background: This work summarizes our experience with WT1 monitoring before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Patients And Methods: The expression of WT1 gene was measured by real-time polymerase chain reaction in peripheral blood according to the European Leukemia Net recommendations. Between May 2005 and August 2019, we analyzed 147 consecutive patients with acute myeloid leukemia with high WT1 expression at diagnosis, transplanted in first (CR1) or second (CR2) complete remission.

CD71 improves delineation of PNH type III, PNH type II, and normal immature RBCS in patients with paroxysmal nocturnal hemoglobinuria.

Background: The diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) relies on flow cytometric demonstration of loss of glycosyl-phosphatidyl inositol (GPI)-anchored proteins from red blood cells (RBC) and white blood cells (WBC). High-sensitivity multiparameter assays have been developed to detect loss of GPI-linked structures on PNH neutrophils and monocytes. High-sensitivity assays to detect PNH phenotypes in RBCs have also been developed that rely on the loss of GPI-linked CD59 on CD235a-gated mature RBCs.

Immunophenotyping of Paroxysmal Nocturnal Hemoglobinuria (PNH).

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare but often debilitating disease which may lead to death in up to 35% of patients within 5 years if unrecognized and untreated. Detection of PNH and assessment of PNH clone size in RBC and WBC lineages by flow cytometric analysis has increased in importance due to the availability of novel therapies. These therapies typically block the hemolysis of red blood cells and thus significantly lower the morbidities and mortality associated with this disease.

Sensitive and accurate identification of PNH clones based on ICCS/ESCCA PNH Consensus Guidelines-A summary.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disorder resulting from the somatic mutation of the X-linked phosphatidyl-inositol glycan complementation Class A (PIG-A) gene. Depending on the severity of the mutation in the PIG-A gene, there is a partial or absolute inability to make glycosylphosphatidyl-inositol (GPI)-anchored proteins including complement-defense structures such as CD55 and CD59 on RBCs and WBCs. Flow cytometric detection of PNH clones has become the gold standard and has played an increasingly important role in the diagnosis, monitoring, and clinical management of patients with PNH.

High-sensitivity 5-, 6-, and 7-color PNH WBC assays for both Canto II and Navios platforms.

Background: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder characterized by an inability to make Glyco-Phosphatidyl-Inositol (GPI)-linked cell surface structures. Fluorescent proaerolysin (FLAER-Alexa488) is increasingly used to detect GPI-deficient WBCs by flow cytometry. However, FLAER is not available in all countries and is expensive to obtain in others.

ICCS/ESCCA consensus guidelines to detect GPI-deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and related disorders part 2 - reagent selection and assay optimization for high-sensitivity testing.

Since publication in 2010 of the International Clinical Cytometry Society (ICCS) Consensus Guidelines for detection of Paroxysmal nocturnal hemoglobinuria (PNH) by flow cytometery, a great deal of work has been performed to develop, optimize, and validate a number of high-sensitivity assays to detect PNH phenotypes in both red blood cells (RBCs) and white blood cells (WBCs, neutrophils, and monocytes). This section (Part 2) of the updated ICCS PNH Consensus Guidelines will focus on specific instrument setup for these PNH assays, the identification and proper testing of appropriate antibody conjugates and combinations therof, and basic assay design. © 2017 International Clinical Cytometry Society.

ICCS/ESCCA consensus guidelines to detect GPI-deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and related disorders part 3 - data analysis, reporting and case studies.

Over the past several years, a diverse group of physicians and other laboratory scientists have developed various recommendations and guidelines regarding best practices for PNH testing. This manuscript is based on these previous recommendations as well as various other relevant publications of experts in the area of PNH testing. The goal is to provide flow cytometry laboratories with an updated consensus approach to analysis and reporting of PNH results and to address the most common analytical challenges for accurate reporting of this rare disease.

Performance Characteristics of a Non-Fluorescent Aerolysin-Based Paroxysmal Nocturnal Hemoglobinuria (PNH) Assay for Simultaneous Evaluation of PNH Neutrophils and PNH Monocytes by Flow Cytometry, Following Published PNH Guidelines.

Background: CD157 has been recently reported as a useful glycosylphosphatidylinositol (GPI)-linked marker for the detection of paroxysmal nocturnal hemoglobinuria (PNH) clones in patients with suspected paroxysmal nocturnal hemoglobinuria by flow cytometry as it targets both neutrophils and monocytes. The aim of this study is to test the feasibility of a non-fluorescent aerolysin (FLAER) approach and propose an alternative for laboratories, where FLAER is not available.

Methods: We validated a non-FLAER-based single-tube, 6-color assay targeting the GPI-linked structures CD157, CD24, and CD14.

Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.

Bone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML) harboring the T315I mutation and compound or polyclonal mutations. However, in some individual cases, these treatment scenarios cannot be applied. We used an alternative treatment strategy with interferon-α (IFN-α) given solo, sequentially or together with TKI in a group of 6 cases of high risk CML patients, assuming that the TKI-independent mechanism of action may lead to mutant clone repression.

A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study.

In chronic lymphocytic leukemia (CLL) the level of minimal residual disease (MRD) after therapy is an independent predictor of outcome. Given the increasing number of new agents being explored for CLL therapy, using MRD as a surrogate could greatly reduce the time necessary to assess their efficacy. In this European Research Initiative on CLL (ERIC) project we have identified and validated a flow-cytometric approach to reliably quantitate CLL cells to the level of 0.

FY*A silencing by the GATA-motif variant FY*A(-69C) in a Caucasian family.

Background: The c.1-67C variant polymorphism in a GATA motif of the FY promoter is known to result in erythroid-specific FY silencing, that is, in Fy(a-) and Fy(b-) phenotypes. A Caucasian donor presented with the very rare Fy(a-b-) phenotype and was further investigated.

Early MRD response as a prognostic factor in adult patients with acute lymphoblastic leukemia.

Objective: To evaluate the prognostic power of minimal residual disease (MRD) monitored by polymerase chain reaction at defined time points during early treatment in adult patients with acute lymphoblastic leukemia (ALL).

Methods: Seventy-one patients were treated according to the GMALL 07/2003 protocol and evaluated for MRD in bone marrow by specific clonal rearrangements of Ig/TCR in BCR-ABL negative ALL or fusion gene transcript in BCR-ABL positive ALL.

Results: Three-year overall survival (OS) was 94% in patients with BCR-ABL negative ALL reaching complete molecular response (CMR) after the first course of chemotherapy (vs.

Clinical relevance of CD157 for rapid and cost-effective simultaneous evaluation of PNH granulocytes and monocytes by flow cytometry.

Introduction: CD157 has been reported as a potentially useful marker for paroxysmal nocturnal hemoglobinuria (PNH) testing by flow cytometry (FCM).

Methods: We determined the performance characteristics of a CD157-based five-color assay and compared results from patient analysis with results obtained with a previously validated CD14/CD24-based six-color protocol.

Results: Coefficient of variation (CV) for intra-/interassay precision analysis of granulocytes ranged from 0.

Rosiglitazone influences the expression of leukocyte adhesion molecules and CD14 receptor in type 2 diabetes mellitus patients.

Diabetes mellitus is associated with increased inflammatory response, which may contribute to atherosclerosis progression. Experimental results demonstrated anti-inflammatory activity of glitazones; their effect on leukocyte adhesion molecules has not been studied to date. We therefore studied the effect of rosiglitazone treatment on leukocyte surface expression of adhesion molecules in patients with type 2 diabetes mellitus and compared our results with findings in healthy subjects.

Evaluation and comparison of different approaches for the detection of PNH clones by flow cytometry following the ICCS guidelines.

Background: Comparison between consensual approaches for the detection of paroxysmal nocturnal hemoglobinuria (PNH) clones by flow cytometry (FCM) following the international clinical cytometry society (ICCS) guidelines has not been widely reported.

Methods: We determined the performance characteristics of 4, 5, and 6-color protocols for white blood cell (WBC) and one and two-color protocols for red blood cell (RBC) evaluation for different PNH target clones and compared results from PNH patient analysis.

Results: Coefficient of variation (CV) for precision/reproducibility analysis ranged from 0.

Cell death induced on cell cultures and nude mouse skin by non-thermal, nanosecond-pulsed generated plasma.

Non-thermal plasmas are gaseous mixtures of molecules, radicals, and excited species with a small proportion of ions and energetic electrons. Non-thermal plasmas can be generated with any high electro-magnetic field. We studied here the pathological effects, and in particular cell death, induced by nanosecond-pulsed high voltage generated plasmas homogeneously applied on cell cultures and nude mouse skin.

Performance characteristics of consensus approaches for small and minor paroxysmal nocturnal hemoglobinuria clone determination by flow cytometry.

Background: Evaluation of paroxysmal nocturnal hemoglobinuria (PNH) clones by flow cytometry (FCM) is not standardized and is associated with consistent inter-laboratory variability.

Methods: In order to rule out the influence of particular approach in generating final results, we analyzed the performance characteristics of individual consensus strategies for small to intermediate (1%-20%) and minor (<1%) PNH clones within the white blood cell (WBC) and red blood cell (RBC) compartments with sensitivity up to 0.1%.

Intra- and interlaboratory variability of paroxysmal nocturnal hemoglobinuria testing by flow cytometry following the 2012 Practical Guidelines for high-sensitivity paroxysmal nocturnal hemoglobinuria testing.

Background: Sutherland et al. recently published the Practical Guidelines for high-sensitivity detection of paroxysmal nocturnal hemoglobinuria (PNH) clones by flow cytometry (FCM), containing concise protocols for PNH testing.

Methods: Using this approach, we studied the intra- and interlaboratory variability observed in a multicenter study in which fresh blood samples containing three clinically relevant PNH clone sizes within the granulocytic, monocytic, and red blood cell (RBC) populations were shipped to each participating center.

Novel human multiple myeloma cell line UHKT-893.

Unlabelled: We established and characterized a new IL-6 dependent multiple myeloma (MM) cell line UHKT-893 from the bone marrow of a relapsed 57-year-old woman.

Results: Using nephelometry, cells with plasma cell phenotype and morphology were found to secrete IgG and free kappa (κ)-light chain of immunoglobulin. κ-Light chain was also recognized intracellularly by flow cytometry and by mass spectrometry.

The effect of simvastatin and fenofibrate on the expression of leukocyte adhesion molecules and lipopolysaccharide receptor CD14 in type 2 diabetes mellitus.

Background: Mixed hyperlipidemia is often associated with type 2 diabetes mellitus and contributes to atherosclerosis progression in diabetes patients. Leukocyte activation plays an important role in atherogenesis. Both statins and fibrates are used in the treatment of mixed dyslipidemia, but their specific effect on leukocyte function remains to be elucidated.