Endothelial Microvesicles Circulating in Peripheral and Coronary Circulation Are Associated With Central Blood Pressure in Coronary Artery Disease.

Background: Endothelial microvesicles (EMVs) have emerged as markers of endothelial injury. However, little is known about their levels in the coronary circulation of acute coronary syndrome (ACS) and stable coronary artery disease (CAD). We hypothesized that ACS patients exhibit a more pronounced increase of EMVs both in the peripheral and coronary circulation when compared with CAD.

Autologous Hematopoietic Cell Transplantation in Multiple Sclerosis: Changing Paradigms in the Era of Novel Agents.

Autologous hematopoietic stem cell transplantation (AHSCT) is established as a standard of care for diseases ranging from hematological malignancies to other neoplastic pathologies and severe immunological deficiencies. In April 1995, our group performed the first AHSCT in progressive multiple sclerosis (MS). Since then, a plethora of studies have been published with encouraging but controversial results.

Early Prediction of Cardiovascular Risk after Hematopoietic Cell Transplantation: Are We There Yet?

Cardiovascular (CV) events have emerged as a major cause of morbidity and mortality among hematopoietic cell transplantation (HCT) survivors. Accumulating evidence supports the presence of increased CV risk in HCT recipients. Most studies have focused mainly on traditional CV risk factors, such as the metabolic syndrome and hypertension.

Inhibition of EZH2 and immune signaling exerts synergistic antitumor effects in chronic lymphocytic leukemia.

Microenvironmental stimuli affect EZH2 expression and function in CLL. Combined B-cell signaling and EZH2 inhibition showed synergistic effects on primary CLL cells.

EZH2 upregulates the PI3K/AKT pathway through IGF1R and MYC in clinically aggressive chronic lymphocytic leukaemia.

EZH2 is overexpressed in poor-prognostic chronic lymphocytic leukaemia (CLL) cases, acting as an oncogene; however, thus far, the EZH2 target genes in CLL have not been disclosed. In this study, using ChIP-sequencing, we identified EZH2 and H3K27me3 target genes in two prognostic subgroups of CLL with distinct prognosis and outcome, i.e.

Isolated Extramedullary Relapse as a Poor Predictor of Survival after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia.

Limited and conflicting data exist on outcomes of patients with extramedullary relapses (EMRs) after allogeneic hematopoietic cell transplantation (allo-HCT) for acute leukemias. We retrospectively reviewed charts of consecutive allo-HCT recipients who underwent transplantation in our center with the indication of acute leukemia (July 1990 to July 2018). Incidences of isolated EMR (iEMR) and bone marrow relapse (BMR) were calculated using cumulative incidence (CI) analysis, with each and treatment-related mortality considered a competing risk.

Neurological adverse events post allogeneic hematopoietic cell transplantation: major determinants of morbidity and mortality.

Background: Despite advances in the field, diagnosis and management of the wide spectrum of neurological events post allogeneic hematopoietic cell transplantation (alloHCT) remain challenging. Therefore, we investigated their incidence, diagnosis, management and long-term prognosis in alloHCT recipients.

Methods: We retrospectively recorded data from consecutive alloHCT recipients with or without neurological complications in our center.

Hypertension in hematologic malignancies and hematopoietic cell transplantation: An emerging issue with the introduction of novel treatments.

Blood pressure levels are directly associated with cardiovascular and cerebrovascular morbidity and mortality, rendering arterial hypertension a major public health problem affecting almost 1 billion people worldwide. Several models have been used for cardiovascular risk prediction based on traditional cardiovascular risk factors. Among them, hypertension represents a factor that may be triggered by distinct pathogenetic mechanisms in specific disease populations.

Complement in Thrombotic Microangiopathies: Unraveling Ariadne's Thread Into the Labyrinth of Complement Therapeutics.

Thrombotic microangiopathies (TMAs) are a heterogeneous group of syndromes presenting with a distinct clinical triad: microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. We currently recognize two major entities with distinct pathophysiology: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Beyond them, differential diagnosis also includes TMAs associated with underlying conditions, such as drugs, malignancy, infections, scleroderma-associated renal crisis, systemic lupus erythematosus (SLE), malignant hypertension, transplantation, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), and disseminated intravascular coagulation (DIC).

Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1.

Minimal residual disease (MRD) is a powerful prognostic factor in acute lymphoblastic leukemia (ALL) and is used for patient stratification and treatment decisions, but its precise role in Philadelphia chromosome positive ALL is less clear. This uncertainty results largely from methodological differences relating to the use of real-time quantitative PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD analysis. We here describe the first results by the EURO-MRD consortium on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in Ph + ALL, designed to overcome the lack of standardisation of laboratory procedures and data interpretation.

Uncovering the clinical impact of kallikrein-related peptidase 5 (KLK5) mRNA expression in the colorectal adenoma-carcinoma sequence.

Background Kallikrein-related peptidases (KLKs) are a subgroup of serine proteases located on chromosome 19q13.3. Most KLKs have been extensively studied as potential biomarkers for several carcinomas and other diseases.

Successful Outcome of Hyperhemolysis in Sickle Cell Disease following Multiple Lines of Treatment: The Role of Complement Inhibition.

Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication in patients with sickle cell disease, characterized by difficulties in diagnosis and management. Certain reports have suggested successful salvage treatment with the terminal complement inhibitor, eculizumab. We here report evidence of complement activation and successful complement inhibition with one dose of eculizumab in an adult sickle cell disease patient presenting DHTR with hyperhemolysis.

Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact.

Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL.

Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations.

The B cell receptor immunoglobulin (Ig) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n = 488), i.e.

Integrated epigenomic and transcriptomic analysis reveals TP63 as a novel player in clinically aggressive chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) stereotyped subsets #6 and #8 include cases expressing unmutated B cell receptor immunoglobulin (BcR IG) (U-CLL). Subset #6 (IGHV1-69/IGKV3-20) is less aggressive compared to subset #8 (IGHV4-39/IGKV1(D)-39) which has the highest risk for Richter's transformation among all CLL. The underlying reasons for this divergent clinical behavior are not fully elucidated.

Aspergillus galactomannan detection: Trichoderma as a cause of positive results.

Aspergillus galactomannan immunoassay is a main diagnostic and monitoring tool in medical mycology. However, the specificity of the method can be skewered by the presence of several other fungi. Trying to diagnose a possible fungal infection of the lower respiratory tract in a haematology patient, it appeared that the fungus Trichoderma longibrachiatum is an additional probable cause of positive galactomannan results.

Early life stress and trauma: developmental neuroendocrine aspects of prolonged stress system dysregulation.

Experience of early life stress (ELS) and trauma is highly prevalent in the general population and has a high public health impact, as it can trigger a health-related risk cascade and lead to impaired homeostatic balance and elevated cacostatic load even decades later. The prolonged neuropsychobiological impact of ELS can, thus, be conceptualized as a common developmental risk factor for disease associated with increased physical and mental morbidity in later life. ELS during critical periods of brain development with elevated neuroplasticity could exert a programming effect on particular neuronal networks related to the stress response and lead to enduring neuroendocrine alterations, i.

Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to-first-treatment and a treatment probability at five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively.

Disruption of the BCL11A Erythroid Enhancer Reactivates Fetal Hemoglobin in Erythroid Cells of Patients with β-Thalassemia Major.

In the present report, we carried out clinical-scale editing in adult mobilized CD34+ hematopoietic stem and progenitor cells (HSPCs) using zinc-finger nuclease-mediated disruption of BCL11a to upregulate the expression of γ-globin (fetal hemoglobin). In these cells, disruption of the erythroid-specific enhancer of the BCL11A gene increased endogenous γ-globin expression to levels that reached or exceeded those observed following knockout of the BCL11A coding region without negatively affecting survival or long-term proliferation of edited HSPCs and other lineages. In addition, BCL11A enhancer modification in mobilized CD34+ cells from patients with β-thalassemia major resulted in a readily detectable γ-globin increase with a preferential increase in G-gamma, leading to an improved phenotype and, likely, a survival advantage for maturing erythroid cells after editing.

Transplant-associated thrombotic microangiopathy: Incidence, prognostic factors, morbidity, and mortality in allogeneic hematopoietic cell transplantation.

Renewed interest has emerged in transplant-associated thrombotic microangiopathy (TA-TMA) with novel prognostic, diagnostic, and treatment algorithms. We aimed to investigate the incidence, prognostic factors, morbidity, and mortality of TA-TMA in allogeneic hematopoietic cell transplantation (HCT) recipients. We enrolled consecutive HCT recipients (1990-2017).

Long-term outcomes of total body irradiation plus cyclophosphamide versus busulfan plus cyclophosphamide as conditioning regimen for acute lymphoblastic leukemia: a comparative study.

The role of total body irradiation (TBI) in allogeneic hematopoietic stem cell transplantation (HCT) for adult acute lymphoblastic leukemia (ALL) remains controversial. Therefore, we investigated long-term treatment outcomes of transplanted ALL patients aiming to identify prognostic factors and the impact of conditioning. We enrolled consecutive ALL patients transplanted from 1990 to 2016, following TBI- or busulfan (Bu)-based conditioning regimen.