Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial.

Purpose: This study aimed at determining whether intravenous artesunate is safe and effective in reducing multiple organ dysfunction syndrome in trauma patients with major hemorrhage.

Methods: TOP-ART, a randomized, blinded, placebo-controlled, phase IIa trial, was conducted at a London major trauma center in adult trauma patients who activated the major hemorrhage protocol. Participants received artesunate or placebo (2:1 randomization ratio) as an intravenous bolus dose (2.

CRLF3 plays a key role in the final stage of platelet genesis and is a potential therapeutic target for thrombocythemia.

The process of platelet production has so far been understood to be a 2-stage process: megakaryocyte maturation from hematopoietic stem cells followed by proplatelet formation, with each phase regulating the peripheral blood platelet count. Proplatelet formation releases into the bloodstream beads-on-a-string preplatelets, which undergo fission into mature platelets. For the first time, we show that preplatelet maturation is a third, tightly regulated, critical process akin to cytokinesis that regulates platelet count.

Transfer to the clinic: refining forward programming of hPSCs to megakaryocytes for platelet production in bioreactors.

The production of in vitro-derived platelets has great potential for transfusion medicine. Here, we build on our experience in the forward programming (FoP) of human pluripotent stem cells (hPSCs) to megakaryocytes (MKs) and address several aspects of the complex challenges to bring this technology to the bedside. We first identify clinical-grade hPSC lines that generate MKs efficiently.

Transcription Factor Levels after Forward Programming of Human Pluripotent Stem Cells with GATA1, FLI1, and TAL1 Determine Megakaryocyte versus Erythroid Cell Fate Decision.

The production of blood cells and their precursors from human pluripotent stem cells (hPSCs) in vitro has the potential to make a significant impact upon healthcare provision. We demonstrate that the forward programming of hPSCs through overexpression of GATA1, FLI1, and TAL1 leads to the production of a population of progenitors that can differentiate into megakaryocyte or erythroblasts. Using "rainbow" lentiviral vectors to quantify individual transgene expression in single cells, we demonstrate that the cell fate decision toward an erythroblast or megakaryocyte is dictated by the level of FLI1 expression and is independent of culture conditions.

Transfusion in adults: 10-year survival of red cell, plasma and platelet recipients following transfusion.

Objective: To determine the long-term survival of adult recipients (>16 years) transfused with red blood cells (RBC), platelets (PLT) and fresh frozen plasma (FFP) in England and Wales.

Study Design And Methods: The EASTR study (Epidemiology and Survival of Transfusion Recipients) was a national multi-centre epidemiological study with cross-sectional sampling from 29 representative hospitals in England supplied by NHS Blood and Transplant (NHSBT). Three separate groups of RBC (n = 9142), FFP (n = 4232) and PLT (3584) recipients were sampled over 1 year (1 October 2001-30 September 2002), with prospective survival monitoring for 10 years.

Transfusion in children: epidemiology and 10-year survival of transfusion recipients.

Objective: To describe the epidemiology of blood transfusion in children: including the incidence of transfusion, the diagnoses leading to transfusion, donor exposure (DE) and post-transfusion survival.

Study Design And Methods: The Epidemiology and Survival of Transfusion Recipients (EASTR) Study was a multi-centre epidemiological study with prospective survival monitoring. Cross-sectional sampling of adult and paediatric transfusion recipients in 29 hospitals was used to select three separate cohorts of red cell (RBC), platelet (PLT) and fresh frozen plasma (FFP) recipients between October 2001 and September 2002.

Head-to-head comparison of two transcription-mediated amplification assay versions for detection of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus Type 1 in blood donors.

Background: The second triplex transcription-mediated amplification (TMA) assay version (Ultrio Plus, Novartis Diagnostics) uses an additional reagent enhancing the disruption of hepatitis B virus (HBV) particles and release of DNA for the target capture probe. This study compares the performance of this new assay version with the previous one (Ultrio).

Study Design And Methods: For analytical sensitivity assessment the World Health Organization HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) international standards and various genotype dilution panels were used.

Hepatitis E virus infection in Ghanaian blood donors - the importance of immunoassay selection and confirmation.

Background And Objectives: Hepatitis E virus (HEV) infection is emerging as a potential new threat to blood safety after several cases of transfusion-transmission were reported from non-epidemic countries. On the basis of seroprevalence data, HEV is endemic in Ghana where poor sanitary conditions and regular flooding are prevalent. However, no data are available for HEV prevalence in blood donors.

HIV-1 subtypes D and F are prevalent in Guinea Conakry.

Background: Limited data is available upon the distribution of different HIV-1/2 genotypes in the blood donor population from Guinea Conakry.

Objectives: To investigate the prevalence of HIV-1/2 subtypes in asymptomatic blood donors in Guinea Conakry, in order to update knowledge of HIV-1/2 epidemiology within this country.

Study Design: Samples from 104 blood donors seropositive for HIV-1/2 were tested for HIV-1 by real-time RT-PCR.

Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence.

Objective: To investigate the molecular basis of occult hepatitis B virus (HBV) infection (OBI) in Asian blood donors.

Design: OBI donors from Hong Kong, Malaysia, Singapore, Taiwan and Thailand were tested for HBV serological markers, and strains were molecularly characterised.

Results: Among 138 confirmed OBI carriers (median age 47 years), HBV genotypes B and C were dominant (60% and 34%, respectively) in agreement with the genotype distribution in chronically infected donors in the region.

Characterization of hepatitis B virus in Turkish blood donors, and the prevalence of the SP1 splice variant.

Hepatitis B is a disease of the liver that can manifest acutely, or persist chronically as a result of infection with the hepatitis B virus (HBV). Turkey has a moderate endemicity level of HBV infection, and all data published to date has shown this to be of genotype D, predominantly of subgenotype D1. However the sequences of very few full genomes have been published.

Management of acquired coagulopathy in acute paediatrics.

Acquired coagulopathy is a relatively uncommon occurrence in acute paediatrics but when it occurs is usually associated with significant underlying pathology and often with critical illness. It can be caused by a number of disease processes but infection, blood loss, iatrogenic causes and liver dysfunction are among the commonest. The blood coagulation cascade is complex and intersects with many other physiological pathways.

Diversity of hepatitis B virus infecting Malaysian candidate blood donors is driven by viral and host factors.

Malaysia is a medium endemic country for hepatitis B virus (HBV) infection but little is known about HBV strains circulating in Malaysian blood donors. Viral load, HBsAg concentrations and nested PCR products from 84 HBV surface antigen (HBsAg) positive samples were analysed in detail. Median viral load was 3050 IU/mL and median HBsAg 1150 IU/mL.

Prevalence of persistent and latent viruses in untreated patients infected with HIV-1 from Ghana, West Africa.

Only limited epidemiological data, pertaining to the prevalence of common persistent viruses has been reported in Ghana. This study was conducted to determine the prevalence of persistent viruses in individuals with untreated HIV-1 infection and uninfected blood donors. Paired plasma and cellular samples from HIV-negative blood donors, asymptomatic HIV and symptomatic/AIDS cohorts were screened by multiplex PCR then qPCR for parvovirus B19 (B19V), hepatitis B virus (HBV), GB virus-C (GBV-C), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-8 (HHV-8) and varicella-zoster virus (VZV).

Transfusion-transmitted hepatitis B virus infection.

Hepatitis B virus (HBV) remains a major risk of transfusion-transmitted infection due to the pre-seroconversion window period (WP), infection with immunovariant viruses, and with occult carriage of HBV infection (OBI). Reduction of HBV residual risk depends upon developing more sensitive HBV surface antigen (HBsAg) tests, adopting anti-HBc screening when appropriate, and implementing HBV nucleic acid testing (NAT), either in minipools or more efficiently in individual samples. HBV NAT combines the ability to significantly reduce the window period and to detect occult HBV carriage substantiating decades of clinical observation that HBsAg-negative/anti-HBc-positive blood could transmit HBV.

Deletions and recombinations in the core region of hepatitis B virus genotype E strains from asymptomatic blood donors in Guinea, west Africa.

The prevalence of hepatitis B virus (HBV) surface antigen (HBsAg) chronic carriage in west Africa is the highest in the world, but its molecular epidemiology remains relatively poorly investigated. Plasma samples from random asymptomatic carriers of HBsAg in Conakry, Guinea, were studied and the complete genome sequences of 81 strains were obtained. Three additional samples from Kumasi, Ghana, were also included in the analysis.

Red blood cell transfusions in acute paediatrics.

Red blood cell (RBC) transfusions should usually be given only to restore or maintain oxygen delivery to vital organs and tissues. Medical history has clearly documented the importance of blood transfusion in saving lives threatened by acute haemorrhage or severe anaemia. The availability of blood products has facilitated many surgical and medical advances, allowing the support of patients who could not have previously survived invasive therapies.

A novel hepatitis B virus subgenotype, D7, in Tunisian blood donors.

Tunisia is a medium-level epidemic country for hepatitis B virus (HBV). This study characterizes, for the first time, full genome HBV strains from Tunisia. Viral load quantification and phylogenetic analyses of full genome or pre-S/S sequences were performed on 196 hepatitis B surface antigen (HBsAg)-positive plasma samples from Tunisian blood donors.

Deferred donor care in a regional hospital blood center in Ghana.

Background: In sub-Saharan Africa, the viral marker burden in blood donor populations ranges between 10 and 30 percent. Deferred donors constitute a rare population of asymptomatic human immunodeficiency virus (HIV)- and hepatitis B virus (HBV)-infected individuals with high likelihood of long survival if cared for. Deferred donor care provides an opportunity for a public health impact on highly pathogenic infections.

Differential reactivity of putative genotype 2 hepatitis C virus F protein between chronic and recovered infections.

To date, all studies regarding hepatitis C virus (HCV) F protein have been based on expression in vitro/in vivo of recombinant protein or monoclonal antibodies derived from genotype 1a or 1b sequences, but not from other genotypes. The objective of this study was to prepare a putative genotype 2 recombinant F protein and evaluate its reactivity in plasma from individuals with chronic HCV infection or who had recovered from infection. One genotype 2 strain was selected for F protein (F-2) and core expression in bacterial culture.

Characterization of occult hepatitis B virus from blood donors carrying genotype A2 or genotype D strains.

Background/aims: Nucleic acid testing (NAT) for hepatitis B virus (HBV) DNA in blood donations identified occult HBV infection (OBI) as a potential threat to blood safety.

Methods: A collaborative study was undertaken to explore the molecular basis of OBIs prevalent in Europe in relation to clinical and serological data.

Results: Ninety-one percent of 77 donor samples of European origin HBV DNA positive but HBV surface antigen (HBsAg) negative were confirmed.

Molecular characterization of occult hepatitis B virus in genotype E-infected subjects.

Occult hepatitis B virus (HBV) infection (OBI), defined as the presence of HBV DNA without detectable HBV surface antigen (HBsAg), is frequent in west Africa, where genotype E is prevalent. The prevalence of OBI in 804 blood donors and 1368 pregnant women was 1.7 and 1.

Maternofetal transmission of hepatitis B virus genotype E in Ghana, west Africa.

To determine whether maternofetal transmission of hepatitis B virus (HBV) is a common route of infection leading to chronic infection in west Africa, plasma samples, obtained at delivery from 1368 pregnant Ghanaian women and paired umbilical cord blood or newborn whole blood samples, were tested for HBV surface antigen (HBsAg) and DNA. A 16 % prevalence of HBV chronic carriers, defined as detectable HBsAg and/or HBV DNA, was found, >80 % contained less than 1 x 10(4) IU ml(-1) HBV DNA and 99 % were infected with genotype E strains. HBV maternofetal transmission was documented in 17 out of 204 (8.

Identification and genetic diversity of two human parvovirus B19 genotype 3 subtypes.

Three genotypes (1-3) of human parvovirus B19 have been identified. Analysis of 13 nearly full-length genotype 3 sequences from Ghana, Europe and Brazil identified two genetically distinct clusters. The classification of genotype 3 strains into two subtypes (B19/3a and B19/3b) is proposed.