Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study-protocol for a phase 3, randomized, controlled trial.

Background: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates.

Convalescent Plasma for Preventing Critical Illness in COVID-19: a Phase 2 Trial and Immune Profile.

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring frequent adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28-day mortality or alter levels of specific antibody responses before and after CIP infusion.

Mouse background genetics in biomedical research: The devil's in the details.

Background: Genetically modified mice are used widely to explore mechanisms in most biomedical fields-including transfusion. Concluding that a gene modification is responsible for a phenotypic change assumes no other differences between the gene-modified and wild-type mice besides the targetted gene.

Study Design And Methods: To test the hypothesis that the N-terminus of Band3, which regulates metabolism, affects RBC storage biology, RBCs from mice with a modified N-terminus of Band3 were stored under simulated blood bank conditions.

Convalescent plasma for preventing critical illness in COVID-19: A phase 2 trial and immune profile.

Rationale: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring rapid adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting.

Objectives: We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28 day mortality.

Differences in Steap3 expression are a mechanism of genetic variation of RBC storage and oxidative damage in mice.

Red blood cells (RBCs) are the most numerous cell type in the body and serve a vital purpose of delivering oxygen to essentially all tissues. In addition to the central role of RBCs in health and disease, RBC storage is a requirement for the >90 million units of RBC transfusions given to millions of recipients each year, worldwide. It is well known that there is genetic donor-to-donor variability in how human RBCs store, rendering blood a nonstandardized therapeutic with a wide range of biological properties from unit to unit, by the time it is transfused.

International assessment of massive transfusion protocol contents and indications for activation.

Background: Massive transfusion protocols (MTPs) provide blood products rapidly and in fixed amounts. MTPs are commonly used in trauma but may also be used in other clinical settings, although evidence to support fixed-ratio resuscitation in nontraumatic hemorrhage is lacking. The goals of this study were to describe the types and contents of available MTPs and the clinical indications for MTP activation.

"SHOUT" to improve the quality of care delivered to patients with acute kidney injury at Great Western Hospital.

Acute kidney injury (AKI) affects up to 20% of all patients admitted to hospital, and is associated with a higher risk of adverse clinical outcomes, increased healthcare costs, as well as long term risks of chronic kidney disease and end stage renal failure. The aim of this project was to improve the quality of care for patients with AKI admitted to the acute medical unit (AMU) at the Great Western Hospital (GWH). We assessed awareness and self reported confidence among physicians in our Trust, in addition to basic aspects of care relevant to AKI on our AMU.

Rapid ADAMTS13 availability impacts treatment for microangiopathic hemolytic anemia and thrombocytopenia.

Thrombotic thrombocytopenic purpura (TTP) can present with a spectrum of clinical manifestations. When TTP is in a patient's clinical differential diagnosis, therapeutic plasma exchange (TPE) should be initiated emergently. Enzyme activity level of A Disintegrin And Metalloproteinase with a Thrombospondin type 1 motif, member 13 (ADAMTS13) in conjunction with the evolving clinical picture can guide further therapy, including duration and frequency of TPE and choice of fluid replacement.

Coincidental loss of DOCK8 function in NLRP10-deficient and C3H/HeJ mice results in defective dendritic cell migration.

Dendritic cells (DCs) are the primary leukocytes responsible for priming T cells. To find and activate naïve T cells, DCs must migrate to lymph nodes, yet the cellular programs responsible for this key step remain unclear. DC migration to lymph nodes and the subsequent T-cell response are disrupted in a mouse we recently described lacking the NOD-like receptor NLRP10 (NLR family, pyrin domain containing 10); however, the mechanism by which this pattern recognition receptor governs DC migration remained unknown.

Appropriate development of the liver Treg compartment is modulated by the microbiota and requires TGF-β and MyD88.

Neither the early postnatal development of the liver Treg compartment nor the factors that regulate its development has been characterized. We compared the early developmental patterns of Treg cell accumulation in murine liver, thymus, and spleen. A FoxP3(EGFP) reporter mouse was employed to identify Treg cells.

The microbiota regulates susceptibility to Fas-mediated acute hepatic injury.

Whereas a significant role for intestinal microbiota in affecting the pathogenesis and progression of chronic hepatic diseases is well documented, the contribution of the intestinal flora to acute liver injury has not been extensively addressed. Elucidating the influence of the intestinal microbiota on acute liver inflammation would be important for better understanding the transition from acute injury to chronic liver disease. Using the Concanavalin A (ConA)-induced liver injury model in laboratory mice, we show that the severity of acute hepatic damage varies greatly among genetically identical mice raised in different environments and harboring distinct microbiota.

1 + 1 = 3: Development and validation of a SNP-based algorithm to identify genetic contributions from three distinct inbred mouse strains.

State-of-the-art, genome-wide assessment of mouse genetic background uses single nucleotide polymorphism (SNP) PCR. As SNP analysis can use multiplex testing, it is amenable to high-throughput analysis and is the preferred method for shared resource facilities that offer genetic background assessment of mouse genomes. However, a typical individual SNP query yields only two alleles (A vs.

Liver inflammation in a mouse model of Th1 hepatitis despite the absence of invariant NKT cells or the Th1 chemokine receptors CXCR3 and CCR5.

The specific mechanisms that mediate CD4(+) T-cell-mediated liver injury have not been fully elucidated. CD4(+) invariant natural killer T (iNKT) cells are required for liver damage in some mouse models of hepatitis, while the chemokine receptors CXCR3 and CCR5 are considered dominant Th1 chemokine receptors involved in Th1 trafficking in inflammatory conditions. BALB/c-Tgfb1(-/-) mice spontaneously develop Th1 hepatitis.

MDSC in autoimmunity.

Myeloid derived suppressor cells (MDSC) were first described nearly two decades ago. Until recently, however, descriptions of MDSC populations were found almost exclusively in animal models of cancer or in cancer patients. Over the last few years, an increasing number of reports have been published describing populations of myeloid cells with MDSC-like properties in murine models of autoimmune disease.

Dueling models in head and neck tumor formation.

The two leading models that have been used to explain tumor progression in head and neck squamous cell carcinoma (HNSCC) are the stochastic clonal evolution model, in which many tumor cells are individually capable of recapitulating the entire tumor mass, and the cancer stem hierarchy model, in which only rare totipotential tumor stem cells can recapitulate the tumor. In this issue, Cameron et al use cell surface marker and clonal cell analyses in combination with a xenotransplant approach to provide data that support the stochastic clonal evolution model in HNSCC. This interpretation is subject, however, to limitations inherent in the experimental approach employed.

Type 1 T helper cells induce the accumulation of myeloid-derived suppressor cells in the inflamed Tgfb1 knockout mouse liver.

Unlabelled: Immune-mediated liver injury in hepatitis is due to activated T cells producing interferon-γ (IFN-γ). It is important to identify negative feedback immune mechanisms that can regulate T cell activity. In this study, we demonstrate that liver inflammation mediated by type 1 T helper (Th1) cells can induce the accumulation of myeloid-derived suppressor cells (MDSCs), pleiomorphic cells capable of modulating T cell-mediated immunity, that heretofore have been studied almost exclusively in the context of tumor-associated inflammation.

Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma.

Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC-driven immunomodulation is mediated by the suppression of proinflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2-dominant environment.

The role of Ifng in alterations in liver gene expression in a mouse model of fulminant autoimmune hepatitis.

Background/aims: BALB/c mice with a homozygous deficiency in the Tgfb1 gene are a model of fulminant autoimmune hepatitis (AIH), spontaneously and rapidly developing Th1-mediated IFN-gamma-dependent necroinflammatory liver disease. We sought to understand the molecular basis for fulminant Th1 liver disease and the specific role of the Ifng gene.

Methods: Global gene expression in livers from BALB/c Tgfb1(-/-) mice with and without an intact Ifng gene was assessed by microarray analysis.

End-organ damage in a mouse model of fulminant liver inflammation requires CD4+ T cell production of IFN-gamma but is independent of Fas.

Fulminant inflammation in the liver is often accompanied by the accumulation of IFN-gamma-producing T cells. The BALB/c-Tgfb1(-/-) mouse exhibits extensive, spontaneously developing necroinflammation in the liver, accompanied by the accumulation of IFN-gamma-producing CD4(+) and CD8(+) T cells. Liver damage depends on the presence of an intact Ifng gene.

The effects of additive solution pH and metabolic rejuvenation on anaerobic storage of red cells.

Background: Red cell (RBC) storage can be extended to 9 weeks under anaerobic or alkaline conditions. Simultaneous use of these approaches has not provided additive benefit. Our objective was to determine whether anaerobic storage with acidified additive solution (AS) coupled with metabolic rejuvenation might further improve the benefits of anaerobic storage.