A quality improvement initiative standardizing premedication for blood product transfusions.

For children with cancer, blood product transfusions are crucial, but can be complicated by transfusion reactions. To prevent these complications, premedication is often given, although not always evidence-based. Herein, we describe a significant decrease in the use of premedication (72%-28%) at our institution after the implementation of standardized guidelines, without an increase in transfusion reactions (3.

Evaluation of peripheral blood mononuclear cell collection by leukapheresis.

Background: Adoptive immunotherapy using engineered lymphocytes has shown promising results in treating cancers even in patients who have failed other treatments. As the first essential step, the number of peripheral mononuclear cell (MNC) collection procedures is rapidly increasing. In this retrospective study, we reviewed the collection results to determine factors that affect MNC collection.

Designing Trials of Disease Modifying Agents for Early and Preclinical Alzheimer's Disease Intervention: What Evidence is Meaningful to Patients, Providers, and Payers?

Background: Drug development for disease modifying agents in Alzheimer's disease (AD) is focused increasingly on targeting underlying pathology in very early stages of AD or in cognitively normal patients at elevated risk of developing dementia due to Alzheimer's. Very early interventional studies of this type have many uncertainties, including whether they can provide the clinical results that payers, providers, and patients will wish to see for decisions. This paper describes an initiative to create greater transparency for researchers to anticipate these decision needs.

Injustice perceptions about pain: parent-child discordance is associated with worse functional outcomes.

Pain is experienced within and influenced by social environments. For children with chronic pain, the child-parent relationship and parental beliefs about pain are particularly important and may influence pain outcomes. Pain-related injustice perceptions have recently been identified as an important cognitive-emotional factor for children with pain.

Elimination of micropollutants by activated carbon produced from fibers taken from wastewater screenings using hydrothermal carbonization.

Activated Carbon (AC) can be used to reduce organic micropollutants (OMPs) in wastewater treatment plants (WWTPs). While producing ACs conventionally still damages the environment, this can be reduced by using renewable raw material from waste streams und producing AC locally. In this study, fibers (toilet paper) were separated out of wastewater by screening WWTP influents in full scale and then used as a no-cost, carbon-rich and heavy metal-poor raw material to produce ACs.

Large-scale identification of clinical and genetic predictors of motor progression in patients with newly diagnosed Parkinson's disease: a longitudinal cohort study and validation.

Background: Better understanding and prediction of progression of Parkinson's disease could improve disease management and clinical trial design. We aimed to use longitudinal clinical, molecular, and genetic data to develop predictive models, compare potential biomarkers, and identify novel predictors for motor progression in Parkinson's disease. We also sought to assess the use of these models in the design of treatment trials in Parkinson's disease.

A Bayesian mathematical model of motor and cognitive outcomes in Parkinson's disease.

Background: There are few established predictors of the clinical course of PD. Prognostic markers would be useful for clinical care and research.

Objective: To identify predictors of long-term motor and cognitive outcomes and rate of progression in PD.

Amyloid-β concentration and structure influences the transport and immunomodulatory effects of IVIG.

Intravenous immunoglobulin (IVIG) contains anti-amyloid-β antibodies as well as antibodies providing immunomodulatory effects that may modify chronic inflammation in Alzheimer's disease. Answers to important questions about IVIG transport into the central nervous system and assessments of any impact amyloid-β has on this transport can be provided by in vitro models of the blood-brain barrier. In this study, amyloid-β[1-42] was pre-aggregated into fibrillar or oligomeric structures, and various concentrations were incubated in the brain side of the blood-brain barrier model, followed by IVIG administration in the blood side at the therapeutically relevant concentrations of 5 and 20 mg/mL.

Membrane configuration optimization for a murine in vitro blood-brain barrier model.

A powerful experimental tool used to study the dynamic functions of the blood-brain barrier (BBB) is an in vitro cellular based system utilizing cell culture inserts in multi-well plates. Currently, usage of divergent model configurations without explanation of selected variable set points renders data comparisons difficult and limits widespread understanding. This work presents for the first time in literature a comprehensive screening study to optimize membrane configuration, with aims to unveil influential membrane effects on the ability of cerebral endothelial cells to form a tight monolayer.

Optimization of endothelial cell growth in a murine in vitro blood-brain barrier model.

In vitro cell culture models of the blood-brain barrier (BBB) are important tools used to study cellular physiology and brain disease therapeutics. Although the number of model configurations is expanding across neuroscience laboratories, it is not clear that any have been effectively optimized. A sequential screening study to identify optimal primary mouse endothelial cell parameter set points, grown alone and in combination with common model enhancements, including co-culturing with primary mouse or rat astrocytes and addition of biochemical agents in the media, was performed.

Genomics in mammalian cell culture bioprocessing.

Explicitly identifying the genome of a host organism including sequencing, mapping, and annotating its genetic code has become a priority in the field of biotechnology with aims at improving the efficiency and understanding of cell culture bioprocessing. Recombinant protein therapeutics, primarily produced in mammalian cells, constitute a $108 billion global market. The most common mammalian cell line used in biologic production processes is the Chinese hamster ovary (CHO) cell line, and although great improvements have been made in titer production over the past 25 years, the underlying molecular and physiological factors are not well understood.

Predicting the risk of perioperative transfusion for patients undergoing elective hepatectomy.

Objective: To develop 2 instruments that predict the probability of perioperative red blood cell transfusion in patients undergoing elective liver resection for primary and secondary tumors.

Summary Background Data: Hepatic resection is the most effective treatment for several benign and malign conditions, but may be accompanied by substantial blood loss and the need for perioperative transfusions. While blood conservation strategies such as autologous blood donation, acute normovolemic hemodilution, or cell saver systems are available, they are economically efficient only if directed toward patients with a high risk of transfusion.

A prospective randomized trial of acute normovolemic hemodilution compared to standard intraoperative management in patients undergoing major hepatic resection.

Background: Hepatic resection is the most effective treatment for many malignant and benign conditions affecting the liver and biliary tree. Despite improvements, major partial hepatectomy can be associated with considerable blood loss and transfusion requirements. Transfusion of allogeneic blood products, although potentially life-saving, is associated with many potential complications.

Autologous versus allogeneic transfusions: no difference in perioperative outcome after partial hepatectomy. Autologous transfusion on hepatectomy outcome.

Blood transfusion is often necessary in patients undergoing liver resection. Because of the risks associated with allogeneic blood products, preoperative autologous blood donation has been advocated, but its benefit with respect to perioperative outcome remains unclear. This study compares perioperative outcome in patients transfused only with autologous blood to a matched cohort receiving only allogeneic blood.

Transfusion policy: when to stop the use of extremely rare blood for an allogeneic hematopoietic progenitor cell transplant recipient with a history of red cell alloimmunization.

Background: Decisions for when to select, and when to discontinue, antigen-negative blood in hematopoietic progenitor cell transplantation (HPCT) recipients with red blood cell (RBC) antibodies can be confusing. In HPCT performed for sickle cell anemia patients who require extremely rare antigen-negative blood, the balance of caution and practicality is further complicated.

Case Reports: Four sickle cell anemia patients with current or historic RBC antibodies underwent allogeneic HPC transplantation.

Influence of transfusions on perioperative and long-term outcome in patients following hepatic resection for colorectal metastases.

Objective: To determine if transfusion affected perioperative and long-term outcome in patients undergoing liver resection for metastatic colorectal cancer.

Summary Background Data: Blood transfusion produces host immunosuppression and has been postulated to result in adverse outcome for patients undergoing surgical resection of malignancies.

Methods: Blood transfusion records and clinical outcomes for 1,351 patients undergoing liver resection at a tertiary cancer referral center were analyzed.

N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age.

Background: The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy (as in N6 protocol [Kushner et al.: J Clin Oncol 12:2607-2613, 1994] but with lower dosing of vincristine) for induction, surgical resection and 2100 cGy hyperfractionated radiotherapy for local control, and for consolidation, targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m2).

Procedure: The chemotherapy consists of: cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2, for courses 1, 2, 4, and 6; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3, for courses 3, 5, and 7.

Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction.

Background: We have previously demonstrated that maintenance of a low central venous pressure (LCVP) combined with extrahepatic control of venous outflow reduced the overall blood loss during major hepatic resections. This study examined the overall outcomes and, in particular, renal morbidity associated with a large series of consecutive major liver resections performed with this approach. In addition, the rationale for the anesthetic management to maintain LCVP was carefully reviewed.

Effects of prior therapy on the in vitro proliferative potential of stem cell factor plus filgrastim-mobilized CD34-positive progenitor cells.

The quantity of hematopoietic progenitors in an apheresis collection is defined by the number of CD34(+) cells or granulocyte macrophage colony-forming units present. These parameters are believed to give roughly equivalent information on graft quality. We here report that the in vitro proliferative potential of r-metHuSCF (stem cell factor) plus filgrastim (granulocyte colony-stimulating factor; r-metHuG-CSF) mobilized peripheral blood (PB) CD34(+) cells obtained from previously heavily treated non-Hodgkin's lymphoma patients inversely correlates with extent of prior therapy.

Use of preoperative autologous blood donation in liver resections for colorectal metastases.

Background: Transfusion of allogeneic blood is associated with risks of human immunodeficiency virus and hepatitis transmission, transfusion reactions, and other potential immunologic and infectious complications. To determine if predonation of autologous blood impacts upon transfusion practice and clinical outcome following liver resection, clinical records of 379 consecutive patients undergoing hepatic resection for metastases of colorectal cancer were identified from the prospective hepatobiliary database and reviewed.

Methods: Of the 379 hepatic resections performed for colorectal metastases between January 1991 and January 1996, 240 (63%) were hepatic lobectomy or trisegmentectomy.

Phase II study of "dose-dense" high-dose chemotherapy treatment with peripheral-blood progenitor-cell support as primary treatment for patients with advanced ovarian cancer.

Purpose: We performed a pilot phase II study to evaluate the potential for delivery of rapidly sequenced high-dose chemotherapy treatments rescued with autologous peripheral-blood progenitor cells (PBP) in patients with previously untreated, advanced ovarian cancer.

Patients And Methods: A single cycle of mobilization was used, primed with cyclophosphamide (CPA)/paclitaxel (Txl) and filgrastim (granulocyte colony-stimulating factor [G-CSF]), followed by three cycles of high-dose carboplatin (CBDCA)/Txl and one cycle of high-dose melphalan (MEL), each rescued by PBP. We then analyzed the outcome for a total of 56 consecutive patients treated with high-dose chemotherapy as part of this program.

Factors affecting mobilization of peripheral blood progenitor cells in patients with lymphoma.

The objective of this study was to identify factors associated with poor mobilization of peripheral blood progenitor cells (PBPCs) or delayed platelet engraftment after high-dose therapy and autologous stem cell transplantation in patients with lymphoma. Fifty-eight patients with Hodgkin's disease or non-Hodgkin's lymphoma underwent PBPC transplantation as the "best available therapy" at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1993 and 1995. PBPCs were mobilized with either granulocyte colony-stimulating factor (G-CSF) alone (n = 19) or G-CSF following combination chemotherapy (n = 39).

Removal of ABO-incompatible red cells from lymphocytapheresis and granulocytapheresis components before transfusion.

Background: The collection of allogeneic lymphocytapheresis and granulocytapheresis components containing significant volumes of ABO-incompatible red cells is sometimes necessary.

Study Design And Methods: Twenty-nine ABO-incompatible lymphocytapheresis components collected for transfusion to three patients and 11 ABO-incompatible granulocytapheresis components collected for transfusion to five patients were depleted of red cells by gravity sedimentation aided by the addition of hetastarch solution. The efficacy of red cell depletion and white cell retention and the complications of transfusion were analyzed.