How is transfusion-associated graft-versus-host disease similar to,yet different from,organ transplantation-associated graft-versus-host disease?

Graft-versus-host disease (GVHD) is a rare, usually fatal complication following blood transfusion or organ transplantation, namely transfusion-associated GVHD (TA-GVHD) and organ transplantation-associated GVHD (OA-GVHD). The dominant mechanism of GVHD is exposure to viable donor lymphocytes that are not recognized as foreign by, but able to respond to, the recipient. The clinical features and relative risk factors of either TA-GVHD or OA-GVHD are yet to be fully understood. The current review article aims to discuss and summarize the similarities and differences between TA-GVHD and OA-GVHD to gain a deeper understanding of the pathogenesis.It is evident that the shared human leukocyte antigens (HLA) between donor and recipient and immunocompromised status of the recipient are the two main risk factors for the development of both TA-GVHD and OA-GVHD. In particular, the homozygous donor with donor-dominant one-way matching at the three loci HLA-A, -B, and -DR has a high risk of developing GVHD following liver transplantation, and such donors should be excluded to prevent it. However, the development of GVHD is thought to be related to a combination of several risk factors, and the contribution of each risk factor remains unknown. Further studies are warranted to determine the important contributing factors that lead to an accurate prediction of GVHD development.     

Can transfusion-associated graft-versus-host disease (TA-GvHD) be prevented with leukoreduction alone?

Transfusion-associated graft-versus-host disease (TA-GvHD) is a rare but devastating disease with a very high mortality rate. Because of the high mortality and lack of effective treatments, the current state of the art is aimed at preventing TA-GvHD and this can be accomplished via irradiation of all cellular blood products (red blood cells, granulocytes, and platelets). However, given that TA-GvHD is driven by contaminating white blood cells, and the fact that the international transfusion community has largely embraced leukoreduction, this raises the question as to whether the quantitative reduction of leukocytes via filtration can itself prevent TA-GvHD, thus allowing hospitals to skip irradiation steps? In this paper, we review the medical literature to determine how many leukocytes are needed to be removed to prevent TA-GvHD, while providing brief overviews of this entity itself and current irradiation strategies.     

How do I perform hematopoietic progenitor cell selection?

Graft‐versus‐host disease remains the most important source of morbidity and mortality associated with allogeneic stem cell transplantation. The implementation of hematopoietic progenitor cell (HPC) selection is employed by some stem cell processing facilities to mitigate this complication. Current cell selection methods include reducing the number of unwanted T cells (negative selection) and/or enriching CD34+ hematopoietic stem/progenitors (positive selection) using immunomagnetic beads subjected to magnetic fields within columns to separate out targeted cells. Unwanted side effects of cell selection as a result of T‐cell reduction are primary graft failure, increased infection rates, delayed immune reconstitution, possible disease relapse, and posttransplant lymphoproliferative disease. The Miltenyi CliniMACS cell isolation system is the only device currently approved for clinical use by the Food and Drug Administration. It uses magnetic microbeads conjugated with a high‐affinity anti‐CD34 monoclonal antibody capable of binding to HPCs in marrow, peripheral blood, or umbilical cord blood products. The system results in significantly improved CD34+ cell recoveries (50%‐100%) and consistent 3‐log CD3+ T‐cell reductions compared to previous generations of CD34+ cell selection procedures. In this article, the CliniMACS procedure is described in greater detail and the authors provide useful insight into modifications of the system. Successful implementation of cell selection procedures can have a significant positive clinical effect by greatly increasing the pool of donors for recipients requiring transplants. However, before a program implements cell selection techniques, it is important to consider the time and financial resources required to properly and safely perform these procedures.     

Dronedarone for atrial fibrillation: How does it compare with amiodarone?

Dronedarone (Multaq), an analogue of amiodarone (Cordarone), was designed to cause fewer adverse effects than the parent compound. Studies have indeed shown dronedarone to be safer than amiodarone, but less effective. Its official indication is to reduce the risk of hospitalization in patients with paroxysmal or persistent atrial fibrillation or atrial flutter and other cardiovascular risk factors, reflecting the parameters of its effectiveness in clinical trials.     

Nursing practice environment: How does one Australian hospital compare with magnet hospitals?

Magnet hospitals are recognized institutions of nursing excellence that provide an environment for the promotion of nursing and high-quality patient care. The Magnet Recognition Program, developed by the American Nurses Credentialing Centre, acknowledges health-care institutions that not only attract and retain nursing staff but also recognize nursing excellence in the delivery of quality patient care. Our study aimed to adapt the existing Practice Environment Scale to the Australian context and to pilot its use in measuring the nursing practice environment at a metropolitan hospital in Sydney, Australia. Nursing staff from four wards at a 400 bed major metropolitan acute general hospital in Sydney, Australia completed a self-administered questionnaire about their practice environment. Data were compared with the published norms from magnet and non-magnet hospitals in the USA, and means of two subscales were not significantly different from magnet hospital means. Hospitals could benefit from undertaking a similar practice environment baseline measure prior to applying for accreditation, thus enabling targeting of pre-identified service gaps and areas for improvement.     

Transfusion-associated graft-versus-host disease:Who is at Risk?

This issue marks the beginning of a new section in Transfusion Science entitled “Evolving Concepts in Transfusion Medicine.” This section is designed to feature critical discussions (2 pages or less) of evolving areas within transfusion medicine. It is meant to highlight new developments and areas of controversy within the broad scope of the medical, scientific, technical, epidemiologic, and public health aspects relating to the rationale for provision of blood component therapy. Recent and continued advances in our understanding of the biology of hematopoiesis, infectious diseases, and molecular genetics now provide the scientific basis for an evolution of our principles and practices within transfusion medicine. Ongoing technical advances, i.e. more effective leukodepletion methods and recombinant techniques, will make it possible to provide new components for transfusion. New sensitive and specific techniques for the detection of infectious disease, i.e. polymerase chain reaction technology, may have broad impact on the safety of transfusion. It is the goal of “Evolving Concepts in Transfusion Medicine” to relate these and other new research findings to their current and future impact on transfusion practice.     

How to compare adequacy of algorithms to control blood glucose in the intensive care unit?

Vogelzang et al. retrospectively assessed a derivative marker of blood glucose control over time in the intensive care unit (ICU), "the hyperglycemic index" (HGI), in relation to outcome. The HGI predicted mortality better than other indices of blood glucose control that do not take the duration of hyperglycemia into account. This provided further support to the concept of maintaining normoglycemia with insulin throughout intensive care in order to improve outcome. The HGI was also proposed as a tool to assess performance of glucose control algorithms. This, however, implies similar sampling frequency for the compared algorithms. Just as we prefer continuous, online display of blood pressure and/or cardiac output for optimal titration of inotropes and vasopressors, a continuous display of blood glucose levels is mandatory for optimal titration of insulin therapy in ICU. We anxiously await the development and validation of such devices.     

How does almotriptan compare with other triptans? A review of data from placebo-controlled clinical trials

Almotriptan, the new selective 5-HT1B/1D agonist, has a higher oral bioavailability than any other triptan, with more than two thirds of the administered dose absorbed within the first hour both inside and outside of a migraine attack. Gender or the presence of food in the stomach does not affect its pharmacokinetic profile, and the compound has no clinically relevant interactions with other drugs. Among the available triptans, response rates at 2 hours range from 50% to 80%, with 20% to 50% of patients pain-free. Almotriptan 12.5 mg provides similar efficacy, with significant advantage over placebo at 30 minutes and a reliable consistency (75% in two of three attacks). Headache typically recurs in 25% to 45% of patients with most triptans. The recurrence rate with almotriptan 12.5 mg, 18% to 27%, is among the lowest reported. The tolerability of almotriptan 12.5 mg is close to that of placebo with a low incidence of central nervous system side effects and chest symptoms. In conclusion, almotriptan's consistent pharmacokinetics and good efficacy, in combination with excellent tolerability, make it an attractive choice in the acute treatment of migraine attacks.