Tuesday, April 7, 2009

Hot off the presses! May 01 Blood Rev

The May 01 issue of the Blood Rev is now up on Pubget (About Blood Rev): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

  • Ferritin for the clinician
    - Blood Rev 23(3):95-104 (2009)
    Ferritin, a major iron storage protein, is essential to iron homeostasis and is involved in a wide range of physiologic and pathologic processes. In clinical medicine, ferritin is predominantly utilized as a serum marker of total body iron stores. In cases of iron deficiency and overload, serum ferritin serves a critical role in both diagnosis and management. Elevated serum and tissue ferritin are linked to coronary artery disease, malignancy, and poor outcomes following stem cell transplantation. Ferritin is directly implicated in less common but potentially devastating human diseases including sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome. Additionally, recent research describes novel functions of ferritin independent of iron storage.
  • Splenomegaly: Investigation, diagnosis and management
    - Blood Rev 23(3):105-111 (2009)
    Splenomegaly is a feature of a broad range of diseases, and presents to clinicians in many fields. This review examines the aetiology of splenomegaly in the developed world, and describes a logical approach to the patient with splenomegaly. In some patients, extensive radiological and laboratory investigations will fail to yield a diagnosis: these cases of "isolated" splenomegaly are not uncommon and can be particularly challenging to manage. The risks of serious underlying disease must be balanced against the risks of invasive investigations such as splenic biopsy and diagnostic splenectomy. We discuss the options in isolated splenomegaly and their evidence base, and incorporate them into a management strategy to aid the clinician in cases of diagnostic difficulty.
  • Bloodstream infections in haematology: Risks and new challenges for prevention
    - Blood Rev 23(3):113-122 (2009)
    Bloodstream infections are an important cause of morbidity and mortality in the haematology population, and may contribute to delayed administration of chemotherapy, increased length of hospitalisation, and increased healthcare expenditure. For gram-positive, gram-negative, anaerobic and fungal infections, specific risk factors are recognised. Unique host and environmental factors contributing to pathogenesis are acknowledged in this population. Trends in spectrum and antimicrobial susceptibility of pathogens are examined, and potential contributing factors are discussed. These include the widespread use of empiric antimicrobial therapy, increasingly intensive chemotherapeutic regimens, frequent use of central venous catheters, and local infection control practices. In addition, the risks and benefits of prophylaxis, and spectrum of endemic flora are identified as relevant factors within individual centres. Finally, challenges are presented regarding prevention, early ! detection, surveillance and prophylaxis. To reduce the rate and impact of bloodstream infections multifaceted and customised strategies are required within individual haematology units.
  • Globalisation and blood safety
    - Blood Rev 23(3):123-128 (2009)
    Globalisation may be viewed as the growing interdependence of countries worldwide through the increasing volume and variety of cross-border transactions in goods and services, and also through the more rapid and widespread diffusion of technology. Globalisation is not just an economic phenomenon, although it is frequently described as such, but includes commerce, disease and travel, and immigration, and as such it affects blood safety and supply in various ways. The relatively short travel times offered by modern aviation can result in the rapid spread of blood-borne pathogens before measures to counteract transmission can be put in place; this would have happened with SARS if the basic life cycle of the SARS virus included an asymptomatic viraemia. This risk can be amplified by ecological factors which effect the spread of these pathogens once they are transferred to a naïve ecosystem, as happened with West Nile Virus (WNV) in North America. The rationalization and c! ontraction of the plasma products industry may be viewed as one aspect of globalisation imposed by the remorseless inevitability of the market; the effect of this development on the safety and supply of products has yet to be seen, but the oversight and assurance of a shrinking number of players will present particular challenges. Similarly, the monopolization of technology, through patent enforcement which puts access beyond the reach of developing countries, can have an effect on blood safety. The challenges presented to blood safety by globalisation are heightening the tensions between the traditional focus on the product safety – zero risk paradigm and the need to view the delivery of safe blood as an integrated process. As an illustration of this tension, donor deferral measures imposed by globalisation-induced risks such as vCJD and WNV have resulted in the loss of the safest and most committed portion of the blood donor population in many Western countries, leading! to an increased risk to safety and supply. It is only through! an appreciation of the basic needs of transfusion medicine, including the enunciation of appropriate principles to manage, rather than eliminate, risks, that the challenges imposed by globalisation may be overcome.
  • Does antithrombotic therapy improve survival in cancer patients?
    - Blood Rev 23(3):129-135 (2009)
    Venous thromboembolism (VTE) is a common complication of malignancy, and is associated with significant morbidity and mortality. Anticoagulant therapy, in the form of heparin and warfarin, plays an important role in the prevention of recurrent VTE. Recent studies have demonstrated that long-term therapy with low molecular weight heparin (LMWH) is more effective than warfarin in patients with cancer. In addition, accumulating clinical evidence suggests that LMWH significantly improves overall survival in cancer patients without VTE. Intriguingly, however, this improved survival cannot simply be explained by a reduction in fatal pulmonary embolism. Furthermore, the beneficial effects persist long after the LMWH has been discontinued, suggesting that LMWH can directly influence tumour cell biology. This hypothesis is entirely plausible, given the complex feedback mechanisms that exist between tumour cells, coagulation proteases, and vascular endothelial cells. Furthermore! , an accumulating body of in vitro experimental evidence suggests that both heparin and warfarin have direct antineoplastic effects. Further large randomized controlled trials will be required in order to validate these exciting preliminary data, and to define whether anticoagulant therapy may constitute a useful adjunctive therapy in the management of cancer patients without VTE.
  • Vaccines for lymphomas: Idiotype vaccines and beyond
    - Blood Rev 23(3):137-142 (2009)
    Therapeutic vaccines for lymphomas have been developed to induce active and long-lasting immune responses against lymphoma capable of eradicating the tumor. Most of these vaccines use the tumor B cell idiotype (the unique variable region of the surface immunoglobulin) as a tumor-specific antigen. The first human clinical trial for lymphoma vaccine was initiated 20 years ago. Along with several other phase I/II trials, it showed encouraging results which supported the initiation of three phase III trials. The results of these trials have recently been released (although not published yet) which failed to demonstrate a prolongation in progression-free survival following chemotherapy. Despite this disappointing result, a number of observations have accumulated over the years that suggest some clinical efficacy of lymphoma vaccines. Several strategies are being developed to improve these results that include optimization of antigen delivery and presentation as well as enha! ncement of anti-tumor T cell function. This review describes the clinical development of lymphoma vaccines and delineates advances, problems and prospects towards integration of this strategy in the therapeutic armamentarium for lymphoma.

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