Efficacious and Clinically Relevant Conditioned Medium of Human Adipose-derived Stem Cells for Therapeutic Angiogenesis

Using stem cell–conditioned medium (CM) might be a viable alternative to stem cell transplantation, which is often hampered by low grafting efficiency and potential tumorigenesis, but the concentrations of angiogenic growth factors in CM are too low for therapeutic use and some components of the medium are not for human use. We used three-dimensional (3D) spheroid culture of human adipose-derived stem cells (ADSCs) with clinically relevant medium composed of amino acids, vitamins, glucose, and human serum to produce clinically relevant CM containing angiogenic and/or antiapoptotic factors such as vascular endothelial cell growth factor, fibroblast growth factor 2, hepatocyte growth factor, and chemokine (C-X-C motif) ligand 12. The concentrations of these factors were 23- to 27-fold higher than that in CM produced by conventional monolayer culture. Compared with injection of either monolayer culture CM or human ADSC, injection of spheroid culture CM to an ischemic region in mice significantly enhanced endothelial cell growth, CD34⁺/PTPRC⁻ (endothelial progenitor) cell mobilization from bone marrow, and bone marrow cell homing to the ischemic region, resulting in improved blood vessel density, limb salvage, and blood perfusion in a mouse hindlimb ischemia model. The stem cell CM developed in this study will likely be an effective alternative to conventional stem cell transplantation therapy.     

Analysis and Optimization of a Regional Blood Bank Distribution Process: II. Derivation and Use of a Method for Evaluating Hospital Management Procedures

The practice of allowing participating hospitals in a regional blood bank system to return unneeded blood units to the central bank for redistribution (recycling) makes it difficult to account for each hospital's role in the production of outdates. The usual blood management efficiency criterion of measuring the rate of outdating occurring at a particular hospital has limited meaning when there is recycling because some hospitals avoid high outdate rates by "dumping" their old units on the central bank, while other hospitals have high outdate rates, because they receive disproportionately large numbers of old blood units which have been returned by other hospitals. By using data from a one-year period at Milwaukee Blood Center, a new blood management efficiency criterion, effective outdate rate, is derived with the use of basic Markovian principles. This is the rate at which a hospital contributes to outdates anywhere in the regional system. The rate for each hospital may be compared to evaluate the relative performance of that hospital. The rate is also converted to a "cost of transfusion" to give a direct "dollar" method for informing hospital blood bank managers of their performance.     

Clinical applications of hematopoietic growth factors.

OBJECTIVE: To explore the history and current clinical uses of hematopoietic growth factors. DATA SOURCES: Recent professional literature and texts dealing with recombinant DNA technology, the development of hematopoietic growth factors, and their use in various disease states. STUDY SELECTION: Not specified. DATA EXTRACTION: Not specified. DATA SYNTHESIS: Hematopoietic growth factors are glycoproteins that regulate the differentiation and proliferation of hematopoietic precursor cells, and, in some cases, the function of mature blood cells. Several have been molecularly characterized and produced in quantity via recombinant DNA technology. Medically, hematopoietic growth factors can be used to replenish hematopoietic lineages by raising cell counts to normal levels; to augment host defenses against infection; to stimulate the immune system against malignancy; and to increase production of effector cells with cytotoxic activities. CONCLUSION: In the past eight years, the hematopoietic growth factors have been used in a variety of clinical settings. They have proven to be effective in stimulating marrow proliferation, increasing circulating blood cell counts, and stimulating various host defense mechanisms. Others are in earlier stages of clinical studies, and their full therapeutic potential remains to be evaluated. New therapies are expected to emerge at a rapid pace.     

A Narrative Review on Hospital-Acquired Anemia: Keeping Blood where It Belongs

Hospital-acquired anemia (HAA) is a prevalent condition that is independently associated with worse clinical outcomes including prolongation of hospital stay and increased morbidity and mortality. While multifactorial in general, iatrogenic blood loss has been long recognized as one of the key contributing factors to development and worsening of HAA during hospital stay. Patients can be losing over 50 mL of blood per day to diagnostic blood draws. Strategies such as elimination of unnecessary laboratory tests that are not likely to alter the course of management, use of pediatric-size or small-volume tubes for blood collection to reduce phlebotomy volumes and avoid blood wastage, use of closed blood sampling devices, and substituting invasive tests with point-of-care testing alone or bundled together have generally been shown to be effective in reducing the volume of iatrogenic blood loss, hemoglobin decline, and blood transfusions, with no negative impact on the availability of test results for the clinical team. These strategies are important components of Patient Blood Management programs and their adoption can lead to improved clinical outcomes for patients.     

The National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Studies (Retrovirus Epidemiology Donor Study and Retrovirus Epidemiology Donor Study-II): Twenty Years of Research to Advance Blood Product Safety and Availability

The Retrovirus Epidemiology Donor Study (REDS), conducted from 1989 to 2001, and the REDS-II, conducted from 2004 to 2012, were National Heart, Lung, and Blood Institute-funded, multicenter programs focused on improving blood safety and availability in the United States. The REDS-II also included international study sites in Brazil and China. The 3 major research domains of REDS/REDS-II have been infectious disease risk evaluation, blood donation availability, and blood donor characterization. Both programs have made significant contributions to transfusion medicine research methodology by the use of mathematical modeling, large-scale donor surveys, innovative methods of repository sample storage, and establishing an infrastructure that responded to potential emerging blood safety threats such as xenotropic murine leukemia virus-related virus. Blood safety studies have included protocols evaluating epidemiologic and/or laboratory aspects of human immunodeficiency virus, human T-lymphotropic virus 1/2, hepatitis C virus, hepatitis B virus, West Nile virus, cytomegalovirus, human herpesvirus 8, parvovirus B19, malaria, Creutzfeldt-Jakob disease, influenza, and Trypanosoma cruzi infections. Other analyses have characterized blood donor demographics, motivations to donate, factors influencing donor return, behavioral risk factors, donors' perception of the blood donation screening process, and aspects of donor deferral. In REDS-II, 2 large-scale blood donor protocols examined iron deficiency in donors and the prevalence of leukocyte antibodies. This review describes the major study results from over 150 peer-reviewed articles published by these 2 REDS programs. In 2011, a new 7-year program, the Recipient Epidemiology and Donor Evaluation Study-III, was launched. The Recipient Epidemiology and Donor Evaluation Study-III expands beyond donor-based research to include studies of blood transfusion recipients in the hospital setting and adds a third country, South Africa, to the international program.     

Development of secreted proteins as biotherapeutic agents

As one of the most important classes of proteins, secreted factors account for about one-tenth of the human genome, 3000 - 4000 in total, including factors of signalling pathways, blood coagulation and immune defence, as well as digestive enzymes and components of the extracellular matrix. Secreted proteins are a rich source of new therapeutics and drug targets, and are currently the focus of major drug discovery programmes throughout the industry. Many of the most important novel drugs developed in biotechnology have resulted from the application of secreted proteins as therapeutics. Secreted proteins often circulate throughout the body and, therefore, have access to most organs and tissues. Because of that, many of the factors are themselves therapeutic agents. This paper gives an overview on the features and functions of human secreted proteins and peptides, as well as strategies by which to discover additional therapeutic proteins from the human 'secretome'. Furthermore, a variety of examples are provided for the therapeutic use of recombinant secreted proteins as 'biologicals', including features and applications of recombinant antibodies, erythropoietin, insulin, interferon, plasminogen activators, growth hormone and colony-stimulating factors.     

Overview on diagnosis, treatment and therapeutic angiogenesis for arteriosclerosis obliterans

Arteriosclerosis of the extremities is a disease of the blood vessels characterized by hardening and/or narrowing of the arteries that supply the legs and feet. This causes a decrease in blood flow that can injure nerves and other tissues. Therapeutic angiogenesis using angiogenic growth factor is expected to be a new treatment for patients with critical limb ischemia. The first human clinical trial treating peripheral vascular disease was started in 1994 using vascular endothelial growth factor. To date, other potent angiogenic growth factors, such as hepatocyte growth factor(HGF), have been also estimated in clinical trials for peripheral arterial disease. Several results from phase 1 or 2 trials using HGF gene were encouraging. Phase 3 trials are now ongoing and their results are expected.     

Determination of the bacteriocidal activity of the blood serum and lymph

A microbiologic method for measurements of the blood serum and lymph bactericidal activity with the use of the test system with Bac. subtilis spore suspension and agar dosed for the nutrient and growth substances is suggested for clinical practice. These activities have been measured in patients with mammary carcinomas during surgical treatment; the levels of nonspecific antibacterial defense factors of the body have proved to be sufficiently high.     

The impact of a 10-year audit cycle on blood usage in a district general hospital

As clinical governance moves from concept to practice, it is emerging as a realistic strategy to promote and improve quality within the National Health Service, as well as satisfying the demand for external accountability. In the context of blood transfusion, the area of responsibility encompasses product liability, as well as efficient use of blood as a resource and transfusion as an appropriate clinical response. Clinical governance may be a modern catch phrase, but the principles it enshrines have long been established within blood transfusion, and in other aspects of haematology. Here, an audit cycle comprising four audits over a 10-year period to monitor the use of cross-matched blood in a large district general hospital is described. Initially, blood use was considered by hospital site, and by the surgical procedure for which it was requested. Later, the scope of the audit was expanded to consider usage by individual consultant. A standard of efficient use of cross-matched blood was taken to be a cross-match to transfusion ratio of < 1.5. The information was reviewed by the hospital transfusion committee, who have a key role in co-ordinating and assessing the practice of transfusion within a hospital. In this hospital, audit has been one of the main tools for improving practice, in particular by enabling the implementation and continuous revision of a maximum blood order schedule. Further, as the process of audit has developed, problem areas have been highlighted, and strategies to improve usage have been brought in with encouraging results. The audit is now being expanded again to include a greater focus on usage of cross-matched blood in the nonsurgical setting.     

Building better hospital transfusion committees for Ontario

Hospital transfusion committees can be instrumental in ensuring appropriate blood utilization and that best practice standards are followed. In Ontario, Canada, the provincial Ministry of Health and Long-Term Care Blood Programs Coordinating Office has implemented several initiatives to support these multi-disciplinary hospital committees to fulfill their mandate. The primary goal is to improve patient safety and the secondary goal is to reinforce the importance of appropriate use of blood components and blood products. Recognizing the challenges in developing a fully functional hospital transfusion committee, several initiatives have been launched to provide educational resources and tools to achieve a successful outcome. The number of hospital transfusion committees in Ontario has increased over the past 5 years. Attendance at the annual educational forum for transfusion committees continues to be high. The majority of hospitals are using the resources and tools being provided. More work is needed to achieve the success of this strategy.     

Topical treatment of ocular surface defects: comparison of the epitheliotrophic capacity of fresh frozen plasma and serum on corneal epithelial cells in an in vitro cell culture model

Accelerated healing of ocular surface disorders was reported using serum for topical application. It is supposed that growth factors, fibronectin and vitamins in serum support the proliferation of corneal epithelial cells. The use of fresh frozen plasma (FFP) instead of serum is theoretically attractive, as it is more easily available from blood banks. In this study, serum and FFP were investigated for composition of epitheliotrophic factors and effect on corneal epithelial cells. Whole blood was taken from five donors. Serum and FFP were prepared, and the concentrations of epithelial growth factor (EGF), Platelet-derived growth factor (PDGF), transforming growth factor-beta1, fibronectin and vitamin A were determined. Immortalized human corneal epithelial cells were used to investigate growth, migration and differentiation in response to both blood products. Significant differences were found regarding the mediator composition of serum and FFP. Serum rather than FFP was significantly superior in stimulating cell growth, migration and differentiation. The epitheliotrophic capacity of blood products depends upon the composition of growth factors and vitamins. Blood clotting strongly influences the growth factor pattern. The superior epitheliotrophic capacity of serum might be due to the higher concentration of proliferation mediators such as EGF and PDGF and its higher content of vitamin A.     

西藏自治区人民医院2014~2018年临床用血情况分析

目的了解西藏自治区人民医院(简称自治区医院)临床用血情况,为进一步提高科学合理用血水平提供依据。方法使用成电医星HIS系统收集自治区医院各科室2014~2018年临床用血数据,包括全血及成分血用量、成分血及用血总量;临床用血ABO血型分布;出院人数、手术台次、手术用血;内科与外科临床用血量情况;临床用血的民族分布情况;临床不同种类疾病用量等,做回顾性调查分析。结果 2014~2018自治区医院临床用血总量21 654.5 U,由3 930.5 U上升至4 949 U,年均增长率5.93%;成分血输注率从47.18%提升至99.02%;临床用血总量的血型分布占比依次B型36.4%、O型36.2%、A型20.4%和AB型7.0%;人均用血量年均增长率1.6%,手术台次平均用血量年均增长率-1.9%;内科与外科临床用血科室的历年用血总量比例66.2%,33.8%,重症监护疾病类、血液病类、妇科产科病占本院临床用血总量前3位,占52.4%;藏族、汉族和其他临床用血总量比例分别为:97.52%,2.59%,0.35%。结论自治区医院用血总量逐年上升,开展成分输血比例逐年上升,但临床科学、合理用血仍有待加强。     

Reducing red cell transfusion by audit, education and a new guideline in a large teaching hospital

Safety concerns combined with the greatly increased costs and difficulties of maintaining the blood supply are major considerations for transfusion services. Previous local surveys demonstrated that hospital blood use at our hospital could be improved. Excessive cross-matching, unnecessary transfusion and high return rates of unused blood were commonplace. Transfusion practice was audited over a 3-month period. An education package with guidelines for transfusion was delivered to all clinician groups within the hospital, over the following 9 months. The audit was repeated exactly 1 year later at the same time period. During the second audit, inpatient hospital numbers increased by 1.02% (from n = 7262 to n = 7336) but no differences in length of stay, cardiovascular morbidity or mortality were demonstrated. Twenty percent (n = 254, 2002; n = 316, 2001) fewer patients received blood, and the number of red cell packs used reduced by 19% (from n = 1093 to n = 880). Total number of patients transfused reduced from 4.4% to 3.5% which, as an absolute difference, is a reduction of 0.9% (CI 0.3-1.5, P = 0.006). The audit, guideline and education package had a major impact on red cell use within the hospital with no adverse effects. Blood use can be improved by the implementation of a suitable education package and guideline. If it is possible to replicate the results of this education programme nationwide, the effect on blood use, with subsequent savings and enhanced patient safety could be significant.     

影响临床胎儿生长受限的多因素分析及预防措施

目的分析影响临床胎儿前3个月生长受限的因素及相应的预防措施。方法选择2013年1月—2014年12月本院56例住院分娩FGR孕妇为研究对象(FGR组),同时选择同期56例正常足月妊娠的孕妇为对照组,对孕妇一般资料进行问卷调查,并测量孕妇的身高和体质量,计算体质量指数,测量血压,检测血细胞比容和血红素水平。记录头三个月胎儿的生长。同时,对孕早期因素对顶臀长度的影响进行多变量分析,评估早期胎儿生长受限对出生胎儿的不良影响。结果 FGR组和对照组的孕妇在年龄、血细胞比容、血红素水平、文化水平、吸烟、饮酒、叶酸补充、初次分娩、舒张压等单因素方面差异均具有统计学意义(P0.05);FGR组和对照组胎儿在前3个月股骨长度、出生头围、出生身长、出生体质量、出生孕龄等方面差异均具有统计学意义(P0.05)。产妇的年龄、血细胞比容、血红素水平、吸烟(≥10支/d)、叶酸补充等因素对胎儿顶臀长度的影响差异显著(P0.05)。早期胎儿顶臀长度的生长受限会增加胎儿早产、出生体质量轻、胎龄小等风险。结论产妇高龄、文化程度低、高血细胞比容、血红素水平、吸烟、饮酒、叶酸补充不足、高舒张压均是胎儿生长受限发生的高危因素,孕早期胎儿的生长受限对出生胎儿会产生不利的影响。因此,在孕期应针对以上高危因素积极采取及时、有效、综合的防治措施。     

Human tissue oversight in hospitals: an AABB survey

BACKGROUND: Reports of human tissue allograft–transmitted infections have underscored the need for better accounting of allografts in health-care facilities. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) implemented new storage and issuance tissue standards for hospital oversight as of July 1, 2005. This study sought to survey hospital tissue responsibilities.
STUDY DESIGN AND METHODS: The AABB Tissue Task Force conducted a Web-based survey distributed to all 904 hospital institutional members in January 2005. The survey asked about tissue type used, breadth of responsibility, hospital department involvement, and views on AABB involvement. Data from 402 of 904 (45%) respondents were tabulated and analyzed.
RESULTS: Among the 402 respondents, 325 (81%) used allogeneic and/or autologous human tissue. The most frequently used tissues were musculoskeletal (n = 240, 74%) and skin (n = 169, 52%) allografts. The department of surgery (e.g., operating room; n = 245, 76%) most often had responsibility for tissue use, followed by the blood bank (i.e., transfusion service; n = 164, 51%); surgery most frequently had responsibility for all tissue types except peripheral blood progenitor cells. Only 32 of 402 (8%) respondents had plans for increased oversight in the next 12 months; 129 of 178 (72%) thought there was a role for AABB in developing guidance on hospital tissue responsibilities.
CONCLUSIONS: In this survey, most AABB member hospital respondents indicated facility use of allogeneic and/or autologous tissues. Although tissue allograft responsibility by surgery was extensive, hospital blood banks also had significant involvement. Few blood banks, however, plan increased oversight in the near future. Given JCAHO standards, blood banks have an opportunity to assist their hospital in planning for assigned tissue responsibilities and oversight to ensure patient safety.     

The role of hospital transfusion committees in blood product conservation

Transfusion committees have been created in different countries to oversee all aspects of blood product transfusion within individual institutions. A fundamental role of hospital transfusion committees is to ensure appropriate blood product use by developing local policies, educating clinicians, and auditing blood use. Unfortunately, this task is hampered by the lack of universally accepted criteria for blood product transfusion. Several examples of specific interventions directed toward improving blood use have been described in the literature. Despite some limitations of these reports, largely because of shortfalls in study design, such interventions appear to be generally effective, but there is not enough evidence to recommend a specific course of action to ensure appropriate blood use. Notwithstanding such problems, a functional hospital transfusion committee can have a major impact on local rates of inappropriate transfusion.     

An examination of hospital satisfaction with blood suppliers

BACKGROUND: The purpose of this study was to identify factors that predict overall hospital satisfaction with blood suppliers. STUDY DESIGN AND METHODS: The data for this study came from a 2001 satisfaction survey of hospital blood bank managers conducted by the National Blood Data Resource Center. A total of 1325 blood-utilizing hospitals were included in the final study database. The measurement of hospital satisfaction with its blood supplier encompasses the five composites of the SERVQUAL model. The five composites are 1) tangibles, 2) reliability, 3) responsiveness, 4) assurance, and 5) empathy. Linear regression was performed with overall hospital satisfaction as the dependent variable and the five composites of the SERVQUAL model and control variables as predictors of overall hospital satisfaction with blood suppliers. RESULTS: Significant predictors of hospital satisfaction with blood suppliers are satisfaction with medical and clinical support provided by the blood center, satisfaction with the routine delivery schedule, and price (service fee) of red cells. CONCLUSION: Prior studies have demonstrated the importance of customer satisfaction to organizations. As organizations, blood centers can benefit from improved satisfaction from their hospital customers. Blood center strategies that focus on improving these three predictors of overall hospital satisfaction with primary blood suppliers will be the most likely to improve and/or maintain hospital customer satisfaction with primary blood suppliers.     

Dendritic cells stimulate primary human cytolytic lymphocyte responses in the absence of CD4+ helper T cells

Cytotoxic lymphocytes are typically generated from unfractionated suspensions of human lymphocytes by stimulating with heterogeneous APCs and exogeneous growth factors. We have found that human blood dendritic cells can directly stimulate allogeneic human CD8+ T cells to proliferate and express antigen-specific cytotoxic activity. These primary responses, which are accompanied by the release of T cell growth factor(s), are induced in the absence of CD4+ helper T cells and are not inhibited by anti-CD4 mAb. Both antigen-specific CTL as well as nonspecific NK cells can be elicited by dendritic cells. The NK cell response can be depleted at the precursor level by panning with an anti-CD11b mAb, which removes a CD11b+/CD28-, CD16+ subset from the starting CD4- responders. Allogeneic blood monocytes are neither stimulatory nor inhibitory of these primary CD4- MLRs, even though monocytes present alloantigen in such a way as to be recognized as specific targets for CTL that have been sensitized by dendritic cells. The number of CD8+ cells that are blast transformed and express an activated phenotype (i.e., HLA DR/DQ+, CD25/IL-2R+, CD45R-) reaches 30-40% of the culture at day 4-5, the peak of the helper-independent response. We conclude that antigen-presentation by dendritic cells is sufficient in itself to prime cytolytic precursors. We speculate that using dendritic cell stimulators and CD4- responders in MLRs may be more efficient than standard tissue typing approaches for the detection of subtle, but important class I MHC-restricted histoincompatibilities in human transplantation.