How to implement of patient blood management pillar 1: An Italian expert opinion based on a "bundles" approach.

Worldwide iron anemia is a common disorder with a significant economic burden on health-care systems. Red blood cell transfusion is the mainstay to correct anemia in surgical settings, but it is also an overused procedure and recent data support its possible role in worsening patient outcomes. Patient Blood Management (PBM) is a multidisciplinary approach to optimize hemostasis, manage anemia, minimize iatrogenic blood loss, and improve tolerance to anemia. The present paper aims to provide a "bundles" approach, based on several preoperative anemia management measures, to implement PBM Pillar 1 in clinical practice

Endovesical instillation of platelet rich fibrin for treatment of interstitial cystitis: case report of two patients

Interstitial cystitis, also called painful bladder syndrome, is a chronic condition causing bladder pain and sometimes pelvic pain. The exact cause of interstitial cystitis is not known. Often, signs and symptoms are hard to elucidate and no single treatment works for everyone. We report two cases of patients affected by interstitial cystitis treated with endovesical instillation of platelets rich fibrin (PRF). PRF is an autologous component that promotes angiogenesis, tissue growth and repair. This report presents the safety and the efficacy of PRF instillations in controlling clinical symptoms and restoring quality of life

Risk of Thromboembolism in patients with idiopathic autoimmune hemolytic disease and antiphospholipid antibodies: results from a prospective, case-control study

During a period of 4 years, 21 consecutive patients with newly diagnosed idiopathic autoimmune hemolytic disease (IAHD) and 42 healthy, sex- and age-matched subjects, were tested for the presence of antiphospholipid antibodies (APA). At diagnosis, APA were detected in 10/21 (47.6%) patients and in 2/42 (4.76%) controls (p 0.01). No thromboembolic events were registered during the follow-up period

Mitral valve replacement in a patient with severe thrombophilic status and direct antiglobulin test positivity: case report.

The case is reported of a patient with a symptomatic thrombophilic status and a positivity for both direct and indirect antiglobulin tests who underwent mitral valve replacement. Because of the antiglobulin test positivity, the patient was enrolled in a preoperative autologous blood donation program in order to avoid exposure to allogenic blood. The operation was successful, and the postoperative course uneventful; the patient was discharged on postoperative day 6 and prescribed oral anticoagulation. This case suggests that a safe valve replacement can be carried out even in the presence of a symptomatic thrombophilic preoperative status

Evidence that ITGB3 promoter variants increase serotonin blood levels by regulating platelet serotonin transporter trafficking

Elevated serotonin (5-HT) blood levels, the first biomarker identified in autism research, has been consistently found in 20-30% of patients with Autism Spectrum Disorder (ASD). Hyperserotonemia is mainly due to greater 5-HT uptake into platelets, mediated by the 5-HT transporter (SERT) located at the platelet plasma membrane. The protein complex involved in platelet SERT trafficking and externalization includes integrin β3, the beta subunit of the platelet membrane adhesive GP IIb/IIIa. Integrin β3 is encoded by the ITGB3 gene, previously identified as a QTL for 5-HT blood levels in ASD at SNP rs2317385. The present study aims to identify the functional ITGB3 gene variants contributing to hyperserotonemia. ITGB3 gene sequencing in 20 individuals selected on the basis of rs2317385 genotypes defined four haplotypes encompassing six SNPs located in the ITGB3 gene promoter region, all in linkage disequilibrium with rs2317385. Luciferase assays in two hematopoietic cell lines, K-562 and HEL 92.1.7, demonstrate that ITGB3 gene promoter activity is enhanced by the presence of the C allele at rs55827077 specifically during differentiation into megakaryocytes (P<0.01), with modulatory effects by flanking SNPs. This same allele is strongly associated with (a) higher 5-HT blood levels in 176 autistic individuals (P<0.001), (b) greater platelet integrin β3 protein expression (P<0.05), and (c) enhanced SERT trafficking from the cytosol toward the platelet plasma membrane (P=4,05 x 10-11). Our results support rs55827077 as the functional ITGB3 gene promoter variant contributing to elevated 5-HT blood levels in ASD and define a mechanistic chain of events linking ITGB3 to hyperserotonemia

The GLO1 C332 (Ala111) allele confers autism vulnerability: family-based genetic association and functional correlates

Glyoxalase I (GLO1) is a homodimeric Zn(2+)-dependent isomerase involved in the detoxification of methylglyoxal and in limiting the formation of advanced glycation end-products (AGE). We previously found the rs4746 A332 (Glu111) allele of the GLO1 gene, which encodes for glyoxalase I, associated with "unaffected sibling" status in families with one or more children affected by Autism Spectrum Disorder (ASD). To identify and characterize this protective allele, we sequenced GLO1 exons and exon-intron junctions, detecting two additional SNPs (rs1049346, rs1130534) in linkage disequilibrium with rs4746. A family-based association study involving 385 simplex and 20 multiplex Italian families yielded a significant association with autism driven only by the rs4746 C332 (Ala111) allele itself (P < 0.05 and P < 0.001 under additive and dominant/recessive models, respectively). Glyoxalase enzymatic activity was significantly reduced both in leukocytes and in post-mortem temporocortical tissue (N = 38 and 13, respectively) of typically developing C332 allele carriers (P < 0.05 and <0.01), with no difference in Glo1 protein levels. Conversely, AGE amounts were significantly higher in the same C332 post-mortem brains (P = 0.001), with a strong negative correlation between glyoxalase activity and AGE levels (τ = -0.588, P < 0.01). Instead, 19 autistic brains show a dysregulation of the glyoxalase-AGE axis (τ = -0.209, P = 0.260), with significant blunting of glyoxalase activity and AGE amounts compared to controls (P < 0.05), and loss of rs4746 genotype effects. In summary, the GLO1 C332 (Ala111) allele confers autism vulnerability by reducing brain glyoxalase activity and enhancing AGE formation, but years after an autism diagnosis the glyoxalase-AGE axis appears profoundly disrupted, with loss of C332 allelic effects

Refining of vegetable oils and fats; formation pathway and mitigation of 3-MCPDe and Glycidyl esters

Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFNΔ4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-ΔG/ΔG), 35% (CC-TT/TT) and 29.2% (CT-TT/ΔG) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFNλ4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-ΔG/ΔG (83%) population with respect to CC-TT/TT (21%) and CT-TT/ΔG (40%) patients. Our data suggest a negative role of TT-ΔG/ΔG genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation

A standardized flow cytometry network study for the assessment of circulating endothelial cell physiological ranges

Circulating endothelial cells (CEC) represent a restricted peripheral blood (PB) cell subpopulation with high potential diagnostic value in many endothelium-involving diseases. However, whereas the interest in CEC studies has grown, the standardization level of their detection has not. Here, we undertook the task to align CEC phenotypes and counts, by standardizing a novel flow cytometry approach, within a network of six laboratories. CEC were identified as alive/nucleated/CD45negative/CD34bright/CD146positive events and enumerated in 269 healthy PB samples. Standardization was demonstrated by the achievement of low inter-laboratory Coefficients of Variation (CVL), calculated on the basis of Median Fluorescence Intensity values of the most stable antigens that allowed CEC identification and count (CVL of CD34bright on CEC ~ 30%; CVL of CD45 on Lymphocytes ~ 20%). By aggregating data acquired from all sites, CEC numbers in the healthy population were captured (medianfemale = 9.31 CEC/mL; medianmale = 11.55 CEC/mL). CEC count biological variability and method specificity were finally assessed. Results, obtained on a large population of donors, demonstrate that the established procedure might be adopted as standardized method for CEC analysis in clinical and in research settings, providing a CEC physiological baseline range, useful as starting point for their clinical monitoring in endothelial dysfunctions

Kaplan Meier plot of CMV reactivation according to the type of conditioning chemotherapy regimen (BEAM vs. FEAM vs. MEL).

<p>Kaplan Meier plot of CMV reactivation according to the type of conditioning chemotherapy regimen (BEAM vs. FEAM vs. MEL).</p