Transfusion medicine in the era of proteomics

Blood components (BCs) are highly complex mixtures of plasma proteins and cells. At present, BC and blood derivatives (BDs) quality control is mainly focused on standardized quantitative assessment, providing relatively limited information about products. Unfortunately, during the production, inactivation, and storage processes there is the risk of changes in their integrity, especially at the protein level, which could cause negative effects on transfusion. It is therefore a major challenge to identify significant alterations of these products, and, in this context, proteomics can play a potentially relevant role in transfusion medicine (TM) to assess the protein composition of blood-derived therapeutics, particularly for identifying modified proteins. It can provide comprehensive information about changes occurring during processing and storage of BCs and BDs and can be applied to assess or improve them, therefore potentially enabling a global assessment of processing, inactivation and storage methods, as well as of possible contaminants and neoantigens that may influence the immunogenic capacity of blood-derived therapeutics. Thus, proteomics could become a relevant part of quality-control process to verify the identity, purity, safety, and potency of various blood therapeutics. A more detailed understanding of the proteins found in blood and blood products, and the identification of their interactions, may also yield important information for the design of new small molecule therapeutics and also for future improvements in TM.

Proteomics, together with genomics in the near future, will presumably have an impact on disease diagnosis and prognosis as well as on further advances in the production, pathogen inactivation and storage processes of blood-based therapeutics.     

Transfusion medicine and safety

Advances in safety of blood transfusion in clinical practice principally relate to preventing transfusion-transmitted infections (TTI). Epidemiological studies of TTI have resulted in the development, standardization, and implementation of an expanding array of immunoassays employed worldwide in routine screening of blood donated by voluntary blood donors. Exclusion of infected blood and their donors has remarkably reduced the risk of transmitting HBV, HCV, HIV-1/2, and HTLV-I/II infections. Nucleic acid tests (NAT) using enzymatic amplification of viral gene sequences have augmented the risk reduction in “window period” infections that are undetectable by the serological tests. Improved viral safety of transfusion therapy has led us to recognize the risk of bacterial contamination, especially in platelet concentrates stored optimally at room temperature. Besides the current effort devoted to microbial risk reduction, pathogen inactivation technologies promise reduction of the residual risk of known and emerging infectious agents. The clinical effectiveness of the foregoing measures, international harmonization/standardization of practices and procedures, and continued hemovigilance portend safest possible safety in the clinical practice of blood transfusion.     

Disability and genetics in the era of genomic medicine

Genomic medicine offers a growing number of methods to diagnose, cure or prevent disability. Although many disabled people welcome these advances, others have reservations about the impact of genetic knowledge on disabled people's lives, arguing that genetic science might exacerbate the deep ambivalence that society as a whole has towards physical difference and anomaly. It is also possible, however, that being able to specify the genetic bases of disability, and distinguish them from other causative factors, will contribute to a fuller understanding of disability and a better response to disabled people.     

Growth hormone therapy in Canada: end of one era and beginning of another.

This paper reviews the difficulties in diagnosing a true deficiency of growth hormone (GH), the long-term results of therapy, the Canadian experience in treating GH deficiency, including the contributions made by the Medical Research Council''s Therapeutic Trial of Human Growth Hormone, and the occurrence of Creutzfeldt-Jakob disease in recipients of GH therapy. It also speculates on potential alternatives to treatment with GH derived from human pituitaries.     

Multiple endocrine neoplasias in the era of translational medicine.

Medicine is an ever changing art, continuously adjusting to the shifting principles of philosophy and constant discoveries of science; it was beautifully said by Hippocrates: "... medicine does not do the same thing at this moment and the next..." Unabated dissemination of information is the only way that patients are assured that physicians will continue to practice medicine that reflects contemporary science. In the field of Multiple Endocrine Neoplasias (MENs), this is at least in part accomplished by biennially held International Workshops. The articles led by this editorial are the second and last installment of a collection of state-of-the-art presentations given in the course of the ninth such workshop that was held in Bethesda, MD, June 19-22, 2004. In addition to serving as an introduction to the articles that were written by some of the leaders in the field, the text of the editorial review that follows also supports the notion that MENs are poised to lead translational research in endocrinology: these disorders have benefited remarkably from the discoveries of the human genome project and are at a unique position to take advantage of new modalities in basic and clinical science.     

Stereotactic radiation therapy in the era of precision medicine for cancer

Unlike conventional radiation therapy, stereotactic radiation therapy(SRT) is an emerging tumor-ablative radiation technology with a high-dose delivery to targets while dramatically sparing adjacent normal tissues. The strengths of SRT involve noninvasive and short-course treatment, high rates of tumor local control with a low risk of side effects. Although the scientific concepts of radiobiology fail to be totally understood currently, SRT has shown its potential and advantages against various tumors, especially for those adjacent to less tolerable normal organs(spinal cord, optic nerve, bowels, etc.). Nowadays, the clinical efficacy of SRT has been widely confirmed in certain patients, especially for those medically inoperable, unwilling to undergo surgery, medicine ineffective with tumor progression. Moreover, SRT could be properly used as palliative treatment aiming at relieving local symptoms and pain, and eventually achieving a potential survival benefit of several months. However, the weaknesses of SRT relate to inevitable radiation-induced toxicities as well as the inaccessibility of prophylactic irradiation. In general, one flaw cannot obscure the splendor of the jade. The emergence and development of SRT has opened the new era of precision radiation therapy, and SRT will probably step gloriously onto the remarkable stage for precision medicine.     

Proton beam therapy for cancer in the era of precision medicine

Precision radiotherapy, which accurately delivers the dose on a tumor and confers little or no irradiation to the surrounding normal tissue and organs, results in maximum tumor control and decreases the toxicity to the utmost extent. Proton beam therapy (PBT) provides superior dose distributions and has a dosimetric advantage over photon beam therapy. Initially, the clinical practice and study of proton beam therapy focused on ocular tumor, skull base, paraspinal tumors (chondrosarcoma and chordoma), and unresectable sarcomas, which responded poorly when treated with photon radiotherapy. Then, it is widely regarded as an ideal mode for reirradiation and pediatrics due to reducing unwanted side effects by lessening the dose to normal tissue. During the past decade, the application of PBT has been rapidly increasing worldwide and gradually expanding for the treatment of various malignancies. However, to date, the role of PBT in clinical settings is still controversial, and there are considerable challenges in its application. We systematically review the latest advances of PBT and the challenges for patient treatment in the era of precision medicine.     

Management of non-small cell lung cancer in the era of personalized medicine

Despite major advances in the molecular definition of the disease, screening and therapy, non-small cell lung cancer (NSCLC) is still characterized by a disappointing overall survival, depending on subtype and tumor stage. To address this challenge, in the last years the therapeutic algorithm of NSCLC has become much more complex and articulated, with different kinds of drugs, including chemotherapy, targeted-based agents, angiogenesis inhibitors and immunotherapy, and multiple lines of treatments, for patients with squamous and non-squamous hystology, EGFR mutation and ALK rearrangement. This short viewpoint describes the emerging strategies for the management of NSCLC, indicating how a personalized approach, characterized by a specific multidisciplinary involvement, implies a process that starts with early detection and includes surgery and systemic therapy.     

Residency training in internal medicine: program design in an era of constraint.

Directors of postgraduate internal medicine programs face many problems in program design, particularly when numbers of house staff continue to decrease. This paper examines the training requirements of a resident in internal medicine and proposes a curriculum based on set rotations in the three key areas of training--subspecialty services, critical care and the clinical teaching unit. The distribution of time in these three areas and the balance of exposure to inpatients and outpatients are discussed in detail. This program design ensures exposure to all the key elements of internal medicine in 3 years and should prevent significant gaps in knowledge at the time of certification. The implications for "service" in major teaching hospitals is discussed. Hospital departments and administrators must confront the prospect of hospital units without house staff. Most important, program directors must resist sacrificing the pedagogic essentials of a training program for service requirements.