functions in a Lef1-dependent transcriptional network required for expression of the stress response inhibitor in the zebrafish hypothalamus.

The vertebrate hypothalamus regulates physiological and behavioral responses to environmental stimuli through the function of evolutionarily-conserved neuronal subpopulations. Our previous work found that mutation of zebrafish , which encodes a transcriptional mediator of the Wnt signaling pathway, leads to the loss of hypothalamic neurons and behavioral phenotypes that are both associated with stress-related human mood disorders However, the specific Lef1 target genes that link neurogenesis to behavior remain unknown. One candidate is , which encodes a transcription factor with known roles in hypothalamic development.

A transgene targeted to the zebrafish nkx2.4b locus drives specific green fluorescent protein expression and disrupts thyroid development.

Background: With the goal of labeling and manipulating the zebrafish hypothalamus, we sought to target a green fluorescent protein (gfp) transgene to the expression domains of nkx2.4b, a gene expressed during hypothalamic and thyroid development. We combined transcription activator-like effector nucleases (TALENs)-mediated mutagenesis with a targeting construct to enable insertion of a gfp transgene into the endogenous nkx2.

Effect of red blood cell storage duration on major postoperative complications in cardiac surgery: A randomized trial.

Background: Although observational studies suggest an association between transfusion of older red blood cell (RBC) units and increased postoperative risk, randomized trials have not supported this. The objective of this randomized trial was to test the effect of RBC storage age on outcomes after cardiac surgery.

Methods: From July 2007 to May 2016, 3835 adults undergoing coronary artery bypass grafting, cardiac valve procedures, or ascending aorta repair, either alone or in combination, were randomized to transfusion of RBCs stored for ≤14 days (younger units) or for ≥20 days (older units) intraoperatively and throughout the postoperative hospitalization.

Effect of bone marrow CD34+cells and T-cell subsets on clinical outcomes after myeloablative allogeneic hematopoietic cell transplantation.

Donor-derived T-cells mediate graft-versus-leukemia effect, immune reconstitution, and graft-versus-host-disease (GvHD) after allogeneic hematopoietic cell transplantation (HCT). We examined the association of donor cell subsets with outcomes in recipients of myeloablative allogeneic HCT using bone marrow (BM, N = 359) grafts from 2002 to 2014 with related or unrelated donors. Analysis considered pre-infusion graft total nucleated cell (TNC), CD34+ CD3+, CD4+, CD8+ doses.

Real Age: Red Blood Cell Aging During Storage.

Background: During cold storage, some red blood cell (RBC) units age more rapidly than others. Yet, the Food and Drug Administration has set a uniform storage limit of 42 days. Objectives of this review are to present evidence for an RBC storage lesion and suggest that functional measures of stored RBC quality-which we call real age-may be more appropriate than calendar age.

Red blood cell storage and in-hospital mortality: a secondary analysis of the INFORM randomised controlled trial.

Background: No randomised trials have addressed whether exposure to red blood cells (RBCs) stored longer than 35 days is associated with harm in patients. We aimed to assess the risk of in-hospital mortality associated with transfusing blood stored longer than 35 days.

Methods: We did a secondary analysis of the INforming Fresh versus Old Red cell Management (INFORM) trial, a pragmatic, multicentre, randomised controlled trial of patients (≥18 years) admitted to one of six hospitals in Australia, Canada, Israel, and the USA and expected to need RBC transfusions.

Astrocyte-enriched feeder layers from cryopreserved cells support differentiation of spontaneously active networks of human iPSC-derived neurons.

Background: Human induced pluripotent stem cell (hiPSC)-derived neuronal cultures are a useful tool for studying the mechanisms of neurological disorders and developing novel therapeutics. While plating hiPSC-derived neuronal progenitors onto glial feeder layers prepared from rodent cortex has been reported to promote functional differentiation of neuronal networks, this has not been examined in detail.

New Method: Here we describe a method of using cryopreserved cells from primary cultures for generation of mouse astrocyte-enriched, neuron-free feeder layers that grow from 10% to 100% confluence in 1 week.

Effect of Short-Term vs. Long-Term Blood Storage on Mortality after Transfusion.

Background: Randomized, controlled trials have suggested that the transfusion of blood after prolonged storage does not increase the risk of adverse outcomes among patients, although most of these trials were restricted to high-risk populations and were not powered to detect small but clinically important differences in mortality. We sought to find out whether the duration of blood storage would have an effect on mortality after transfusion in a general population of hospitalized patients.

Methods: In this pragmatic, randomized, controlled trial conducted at six hospitals in four countries, we randomly assigned patients who required a red-cell transfusion to receive blood that had been stored for the shortest duration (short-term storage group) or the longest duration (long-term storage group) in a 1:2 ratio.

Cold Antibodies in Cardiovascular Surgery: Is Preoperative Screening Necessary?

Objectives: Cold antibodies (CAs) are rarely significant for transfusion, but they can cause complications under the hypothermic conditions of cardiovascular surgery. The purpose of this study was to determine the incidence of such complications.

Methods: Patients with CAs who underwent cardiovascular surgery were identified, and their records were reviewed for intraoperative complications attributable to CAs.

Rationale and Design of the Informing Fresh versus Old Red Cell Management (INFORM) Trial: An International Pragmatic Randomized Trial.

Although red blood cell transfusion is a potentially lifesaving intervention in severely anemic and acutely bleeding patients, some observational studies have suggested that prolonged red cell storage before transfusion is associated with harm. INFORM is a large, pragmatic, randomized controlled trial comparing the effect of the shorter storage with longer storage red blood cell transfusions on inhospital mortality in hospitalized patients who require a blood transfusion. The trial is being conducted in centers in Australia, Canada, Israel, and the United States and is expected to enroll 31497 patients.

Cocaine-induced microangiopathic hemolytic anemia mimicking idiopathic thrombotic thrombocytopenic purpura: a case report and review of the literature.

Our understanding of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura (TTP) has increased, but remains incomplete, particularly with respect to cases of suspected TTP that are either unresponsive to therapeutic plasma exchange (TPE) or have normal ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) activity. A 53-year-old woman presented with severe anemia (hemoglobin 1.8 g/dL) and clinical and laboratory findings consistent with TTP in conjunction with acute cocaine use.

How do we use molecular red blood cell antigen typing to supplement pretransfusion testing?

The molecular basis of many blood group antigens is known, and it provides a means for predicting the red blood cell phenotype. Molecular typing methods are useful when serologic typing cannot be performed, due to sample or reagent limitations. We discuss the implementation of a commercial molecular typing assay at our Transfusion Service, the indications for testing, and the advantages and drawbacks of the assay.

Red blood cell storage: how long is too long?

Red blood cells (RBCs) undergo biochemical and structural changes during storage, commonly referred to as the "storage lesion." Evidence suggests that the longer the RBC product is stored, the less effective is the transfused blood. Many studies linking morbidity to transfusion have not considered duration of RBC storage as a variable that may modulate the effect.

Erythrocyte storage duration is not associated with increased mortality in noncardiac surgical patients: a retrospective analysis of 6,994 patients.

Background: More than 5 million patients receive erythrocyte transfusions in the United States every year. Previous studies linked the storage duration of allogeneic erythrocytes to the risk of severe postoperative complications, especially after cardiac or trauma surgery. Limited data are available for noncardiac surgical patients.

An evolution in blood management: past, present, and future.

Blood management is a concept that adopts a principle of improving patient outcome by integrating all available techniques to ensure safety, availability, and appropriate allocation of blood products. This constitutes a model of multidisciplinary care where the changes in culture are system directed on the basis of evidence-based medicine. There are about 14% US hospitals where any kind of blood management program exists, although the idea remains the same but the programs vary in their execution, implementation, and ultimately providing the value to patients.

Transfusion increases the risk for vasoplegia after cardiac operations.

Background: Perioperative vasoplegia is associated with increased morbidity. Red blood cell (RBC) transfusion increases plasma concentrations of inflammatory mediators, possibly contributing to the development of vasoplegia. We investigated the prevalence of mild and profound postoperative vasoplegia, identified factors associated with its development, and examined the role of RBC and component transfusion on the occurrence of postoperative vasoplegia.

Predicting hematopoietic stem cell mobilization failure in patients with multiple myeloma: a simple method using day 1 CD34+ cell yield.

Early and reliable prediction of the likelihood of achieving adequate stem cell collection for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) would improve collection efficiency, prevent unnecessary aphereses, and permit appropriate treatment alterations. No previous study has reported a threshold CD34+ cell collection quantity on Day 1 or 2 of leukapheresis that could predict successful stem cell collection. We performed a retrospective analysis of all MM patients undergoing first attempt of stem cell collection at our institution from 2001 through 2008.

Safety of the blood supply in a rural area of China.

Objective: To determine the sensitivity and specificity of tests for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV), and syphilis conducted by laboratories of 3 blood collection organizations in a rural area of China.

Methods: From October to December 2003, 1068 samples were collected from blood donors presenting to the 3 collection centers. All samples were tested twice using 2 different test kits for HBsAg, HCV, and syphilis.

Toward extended phenotype matching: a new operational paradigm for the transfusion service.

Background: Conventional pretransfusion testing uses hemagglutination to ensure donor-recipient compatibility for ABO/D status and recipient alloantibodies. While screening large numbers of donor units for multiple antigens by hemagglutination is impractical, novel methods of DNA analysis permit the rapid determination of an extended human erythrocyte antigen (xHEA) phenotype. A prospective observational study was conducted at four hospital transfusion services to test an alternative paradigm of identifying xHEA-typed units for patients in three cohorts by utilizing DNA analysis and a novel inventory management model.

Transfusion and pulmonary morbidity after cardiac surgery.

Background: True lung injury is among the leading causes of transfusion-related mortality. Pulmonary morbidity after cardiac surgery has been related to damaging effects of cardiopulmonary bypass and transfusion, but is confounded by cardiac-related events that may not reflect true lung injury. Thus, cardiac surgery poses unique challenges to criteria-specific diagnosis of transfusion-related acute lung injury (TRALI).

Platelet transfusion in cardiac surgery does not confer increased risk for adverse morbid outcomes.

Background: Platelet transfusion has been reported to confer increased morbidity after cardiac surgery but prior studies were limited by confounding variables including red blood cell (RBC) transfusions. Our objective was to examine the impact of platelet transfusion on outcomes in cardiac surgery controlling perioperative risk factors.

Methods: A total of 32,298 patients underwent on-pump isolated coronary artery bypass grafting (CABG), an isolated valve, or a combined CABG and valve procedure between January 1, 1993 and January 1, 2006.

Duration of red-cell storage and complications after cardiac surgery.

Background: Stored red cells undergo progressive structural and functional changes over time. We tested the hypothesis that serious complications and mortality after cardiac surgery are increased when transfused red cells are stored for more than 2 weeks.

Methods: We examined data from patients given red-cell transfusions during coronary-artery bypass grafting, heart-valve surgery, or both between June 30, 1998, and January 30, 2006.

Retrospective targeted HCV lookback using centralized contracted notification service.

Background: Mandated HCV 2.0 lookback significantly challenged the human and financial resources available to the six Los Angeles County Department of Health Services (DHS) hospital blood banks. To comply with FDA requirements, DHS developed a centralized process that utilized the services of a contract vendor for performing HCV lookback.