Autologous transfusion: current trends and research issues. National Heart, Lung, and Blood Institute Autologous Transfusion Symposium Working Group

Dr. Toy concluded the meeting by summarizing the major controversial issues highlighted by the speakers. PABD PABD is, in principle, a safe and effective method for avoiding exposure to allogeneic blood in appropriate circumstances, and a substantial amount of clinical literature has been published to support its role. However, additional research is needed in the following areas: The optimal number of units that should be collected for specific surgical procedures to ensure maximum savings in use of allogenic blood and minimum wastage; The safety of PABD in patients, including a better understanding of which patients are at risk for complications, what the risks are, and what alternative collection strategies should be employed. Adequate control groups are needed in these studies; A definition of the transfusion trigger as it applies to autologous RBCs; An investigation of the role of rEPO in facilitating PABDs; The development of better collection logistics (e.g., double-unit collections) and storage protocols (e.g., improved additive solutions); and Additional studies of the costs associated with autologous blood collection and development of more cost-effective strategies. Acute normovolemic hemodilution Much of the published literature related to hemodilution describes the concept and specific protocols; in contrast, relatively little clinical research relating to the efficacy of this technique exists.(ABSTRACT TRUNCATED AT 250 WORDS)     

Restless legs syndrome: detection and management in primary care. National Heart, Lung, and Blood Institute Working Group on Restless Legs Syndrome

Restless legs syndrome (RLS) is a neurologic movement disorder that is often associated with a sleep complaint. Patients with RLS have an irresistible urge to move their legs, which is usually due to disagreeable sensations that are worse during periods of inactivity and often interfere with sleep. It is estimated that between 2 and 15 percent of the population may experience symptoms of RLS. Primary RLS likely has a genetic origin. Secondary causes of RLS include iron deficiency, neurologic lesions, pregnancy and uremia. RLS also may occur secondarily to the use of certain medications. The diagnosis of RLS is based primarily on the patient's history. A list of questions that may be used as a basis to assess the likelihood of RLS is included in this article. Pharmacologic treatment of RLS includes dopaminergic agents, opioids, benzodiazepines and anticonvulsants. The primary care physician plays a central role in the diagnosis and management of RLS.     

危重新生儿的血电解质紊乱分析

目的：探讨危重新生儿血电解质紊乱的类型及发生率、不同日龄电解质紊乱的发生比较，指导临床治疗．方法：患儿入室后立即取桡动脉血0．1mL，采用美国i-STAT便携式血气分析仪测定血电解质，以后根据病情再复查血电解质。结果：电解质紊乱898例共1418例次中，发生一种电解质紊乱1124例次（79．27％）、两种电解质紊乱267例次（18．83％）、三种电解质紊乱27例次（1．90％），且与日龄有关。结论：对危重新生儿监测血电解质变化，及时纠正电解质紊乱，有利于改善预后，降低危重新生儿的死亡率。     

Critical issues in gene therapy for neurologic disease

Gene therapy for the nervous system is a newly emerging field with special issues related to modes of delivery, potential toxicity, and realistic expectations for treatment of this vital and highly complex tissue. This review focuses on the potential for gene delivery to the brain, as well as possible risks and benefits of these procedures. This includes discussion of appropriate vectors, such as adeno-associated virus, lentivirus, gutless adenovirus, and herpes simplex virus hybrid amplicons, and cell vehicles, such as neuroprogenitor cells. Routes of delivery for focal and global diseases are enumerated, including use of migratory cells, facilitation of vascular delivery across the blood-brain barrier, cerebrospinal fluid delivery, and convection injection. Attention is given to examples of diseases falling into different etiologic types: metabolic deficiency states, including Canavan disease and lysosomal storage disorders; and degenerative conditions, including Parkinson's disease and other neurodegenerative conditions.     

Basic science focus on blood substitutes: a summary of the NHLBI Division of Blood Diseases and Resources Working Group Workshop, March 1, 2006

In March 2006, a workshop sponsored by the National Heart, Lung, and Blood Institute was convened to identify the role of basic science research in clarifying issues that are impeding progress in the development of hemoglobin-based oxygen carrying (HBOC) solutions. These discussions resulted in a consensus that, although HBOCs have shown clinical promise, various side effects have inhibited further development and regulatory approval, with cardiovascular events being of particular concern. As a consequence, workshop participants focused on formulating research recommendations to better understand and mitigate these side effects. In addition, several important corollary issues were identified, including better understanding of the impact of HBOC infusion on human physiology; the need for rapid, noninvasive methods for the measurement of tissue oxygenation in human patients to better inform transfusion decisions; further investigation of routes and consequences of hemoglobin metabolism; optimization of clinical protocols for HBOC use; and assessment of the impact of HBOC formulation excipients. Also discussed was the possibility and desirability of developing new HBOCs with improved characteristics, such as prolonged functional intravascular persistence, greater stability, and a decreased propensity to generate reactive oxygen species. One practical limitation in this area is the consistent availability of pure, well-characterized HBOC solutions for the research community. This communication summarizes the opinion of workshop participants on these issues and concludes with a list of specific recommended areas of research that could positively impact the development of blood substitutes.     

Familial clustering for features of the metabolic syndrome: the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study

OBJECTIVE: Metabolic syndrome-related traits (obesity, glucose intolerance/insulin resistance, dyslipidemia, and hypertension) have been shown to be genetically correlated. It is less clear, however, if the genetic correlation extends to novel risk factors associated with inflammation, impaired fibrinolytic activity, and hyperuricemia. We present a bivariate genetic analysis of MetS-related traits including both traditional and novel risk factors. RESEARCH DESIGN AND METHODS: Genetic correlations were estimated using a variance components procedure in 1,940 nondiabetic white individuals from 445 families in the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Twelve MetS-related traits, including BMI, waist circumference, blood pressure, white blood cell count, fasting serum triglycerides, HDL cholesterol, insulin, glucose, plasminogen activator inhibitor-1 antigen, uric acid, and C-reactive protein, were measured and adjusted for covariates, including lifestyle variables. RESULTS: Significant genetic correlations were detected among BMI, waist circumference, HDL cholesterol, triglycerides, insulin, and plasminogen activator inhibitor-1 antigen and between uric acid and all of the above variables except insulin. C-reactive protein and white blood cell count were genetically correlated with each other, and both showed significant genetic correlations with waist circumference and insulin. Fasting glucose was not significantly genetically correlated with any of the other traits. CONCLUSIONS: These results suggest that pleiotropic effects of genes or shared family environment contribute to the familial clustering of MetS-related traits.     

Principles of Blood Group Serology and Nomenclature: A Critical Review

The A-B-O group system of man is used as a model to explain the principles of blood group serology and nomenclature. A correct nomenclature must take into account three kinds of entities, genes, the gene products (agglutinogens or phenogroups), and the serological specificities (or blood factors). The tendency in the past to equate agglutinogen with blood factor has been a pitfall, which has given rise to fallacies and errors in studies on the human A-B-O groups and especially the Rh-Hr types. The requirements for a suitable terminology for the A-B-O groups are demonstrated, and it is pointed out that the same principles have universal applicability not only to other blood group systems in man, but also to studies on the blood groups of infra-human species, and antigens of soluble proteins, bacteria and viruses.     

The National Heart,Lung, and Blood Institute‐funded Production Assistance for Cellular Therapies (PACT) program: Eighteen years of cell therapy

The Production Assistance for Cellular Therapies (PACT) Program, is funded and supported by the US Department of Health and Human Services’ National Institutes of Health (NIH) National Heart Lung and Blood Institute (NHLBI) to advance development of somatic cell and genetically modified cell therapeutics in the areas of heart, lung, and blood diseases. The program began in 2003, continued under two competitive renewals, and ended June 2021. PACT has supported cell therapy product manufacturing, investigational new drug enabling preclinical studies, and translational services, and has provided regulatory assistance for candidate cell therapy products that may aid in the repair and regeneration of damaged/diseased cells, tissues, and organs. PACT currently supports the development of novel cell therapies through five cell processing facilities. These facilities offer manufacturing processes, analytical development, technology transfer, process scale‐up, and preclinical development expertise necessary to produce cell therapy products that are compliant with Good Laboratory Practices, current Good Manufacturing Practices, and current Good Tissue Practices regulations. The Emmes Company, LLC, serves as the Coordinating Center and assists with the management and coordination of PACT and its application submission and review process. This paper discusses the impact and accomplishments of the PACT program on the cell therapy field and its evolution over the duration of the program. It highlights the work that has been accomplished and provides a foundation to build future programs with similar goals to advance cellular therapeutics in a coordinated and centralized programmatic manner to support unmet medical needs within NHLBI purview.     

The Centers for Disease Control-National Heart, Lung and Blood Institute Lipid Standardization Program. An approach to accurate and precise lipid measurements

In collaboration with the National Heart, Lung, and Blood Institute, the CDC has supported programs for standardizing lipid measurements for more than 30 years. These programs were begun because comparable and accurate quantitative measurements were needed for epidemiologic studies of coronary heart disease. Since the first program was initiated, over 500 national and international laboratories have participated in the various CDC lipid standardization programs. The cornerstone of these standardization programs has been an accuracy base of lipid reference materials and methods developed by CDC. Specifically, CDC has developed human, serum-based reference materials for cholesterol, HDL, triglyceride, and apolipoproteins A-I and B and reference methods for total cholesterol, HDL, and triglyceride. The CDC reference method for cholesterol has been adopted as the national reference method for cholesterol by the National Reference System for the Clinical Laboratory Council of the National Committee for Clinical Laboratory Standards. The approved CDC reference method along with an approved NBS definitive method, an approved NBS certified Reference Material, and the CDC certified serum-based secondary reference materials make up the accuracy base for serum cholesterol measurements in the United States, and together they are recognized as the National Reference System for Cholesterol. The NCEP Laboratory Standardization Panel recommends that cholesterol measurements made by all clinical laboratories should be standardized so that cholesterol values are traceable to the National Reference System for Cholesterol. In support of the NCEP's efforts, CDC will establish a standardization program permitting the laboratory and manufacturing community to trace cholesterol measurements and the development of cholesterol diagnostic products back to the national reference system. The major emphasis of this standardization effort is to establish a network of reference method laboratories (1) to assign cholesterol values to all commercially prepared lots of calibrators and control materials and (2) to provide reference measurements on individual "fresh" human serum specimens to manufacturers and clinical laboratories. CDC is also working to (1) provide reference materials to manufacturers, (2) collaborate with NBS to maintain documentation of the national reference system accuracy base, (3) cooperate with proficiency testing organizations to assist in the accurate labeling of reference materials, and (4) provide training and education pertinent to cholesterol standardization.(ABSTRACT TRUNCATED AT 400 WORDS)     

A method for estimating hepatitis B virus incidence rates in volunteer blood donors. National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study

BACKGROUND: Calculations of the incidence of hepatitis B virus (HBV) infections in the blood donor setting that are based solely on data for seroconversion to hepatitis B surface antigen (HBsAg) will underestimate the incidence due to the transient nature of antigenemia. Estimates based on antibody to hepatitis B core antigen will overestimate the incidence due to false-positive results caused by the nonspecificity of the test. STUDY DESIGN AND METHODS: Serologic test results were obtained from multiple-time volunteer donors at five United States blood centers from January 1991 through December 1993. The observed HBsAg seroconversion rate was multiplied by an adjustment factor, derived from the weighted average probability of a positive HBsAg test for HBV-infected donors who become chronic carriers, for donors with a primary antibody response without detectable antigenemia, and for donors who develop transient antigenemia. RESULTS: Among 586,507 multiple-time donors giving 2,318,356 donations and observed for 822,426 person-years, the HBsAg incidence rate was 4.01 per 100,000 person-years. On the basis of prior reports of the duration of HBsAg positivity and the observed distribution of interdonation intervals among the study group, there was an estimated 53-percent chance that an HBV-infected donor with transient antigenemia would have a positive HBsAg test result. If 70 percent of newly HBV-infected adults have transient antigenemia, 25 percent have a primary antibody response without primary antigenemia, and 5 percent become chronic carriers, the overall chance of being detected by the HBsAg test was 42 percent, for an adjustment factor of 2.38. The total HBV incidence rate, therefore, was estimated to be 9.54 per 100,000 person-years. CONCLUSION: The crude HBV incidence rate observed from HBsAg test results will underestimate the true rate. The adjusted HBV incidence rate should be used in applications such as estimations of residual HBV risk to the blood supply and projections of the benefits of screening for HBV DNA.     

Funding Avenues for Research in Emergency Medicine at the National Institutes of Health and the National Heart, Lung, and Blood Institute

There are opportunities for research in EM at the NIH, which may be appropriate for a variety of Institutes, depending on the topic area. Most NIH-funded research is through investigator-initiated grant applications, and the PHS 398 application packet is a source of more information. RFAs and RFPs, which have set-aside funding, are released for specific topic areas when an Institute identifies an area requiring multiple studies or multicenter research. PAs, which do not have set-aside funding, announce areas of interest for an Institute. The NIH Guide to Grants and Contracts announces RFAs, RFPs, and PAs. It is important to become expert in a field of research to be successful in achieving research funding, whether investigator- or institute-initiated.     

血液病患者ABO血型抗原减弱及其输血对策

目的探讨血液病患者ABO血型抗原减弱与疾病的关系,以制定相应的输血措施。方法查阅1993-2005年所有ABO血型抗原减弱患者的病历,记录诊断及输血情况,随机选择同期血型抗原正常表达患者为对照组,比较两组患者的输血情况,并进行统计学处理。结果12年间共查出57例血型抗原减弱患者,其中AML41例、CML3例、MDS10例、MF3例。均予同型血输注,疗效与对照组相比差异无显著性。结论ABO血型抗原减弱在血液病患者中较常见,最多见于急、慢性非淋巴细胞白血病及骨髓增生异常综合征,随疾病缓解,减弱的血型抗原可恢复正常。输血时以输同型血为原则,不必输“O”型洗涤红细胞。     

2015 proceedings of the National Heart,Lung, and Blood Institute's State of the Science in Transfusion Medicine symposium

On March 25 and 26, 2015, the National Heart, Lung, and Blood Institute sponsored a meeting on the State of the Science in Transfusion Medicine on the National Institutes of Health (NIH) campus in Bethesda, Maryland, which was attended by a diverse group of 330 registrants. The meeting's goal was to identify important research questions that could be answered in the next 5 to 10 years and which would have the potential to transform the clinical practice of transfusion medicine. These questions could be addressed by basic, translational, and/or clinical research studies and were focused on four areas: the three “classical” transfusion products (i.e., red blood cells, platelets, and plasma) and blood donor issues. Before the meeting, four working groups, one for each area, prepared five major questions for discussion along with a list of five to 10 additional questions for consideration. At the meeting itself, all of these questions, and others, were discussed in keynote lectures, small‐group breakout sessions, and large‐group sessions with open discourse involving all meeting attendees. In addition to the final lists of questions, provided herein, the meeting attendees identified multiple overarching, cross‐cutting themes that addressed issues common to all four areas; the latter are also provided. It is anticipated that addressing these scientific priorities, with careful attention to the overarching themes, will inform funding priorities developed by the NIH and provide a solid research platform for transforming the future practice of transfusion medicine.