Practical guidelines for process validation and process control of white cell-reduced blood components: report of the Biomedical Excellence for Safer Transfusion (BEST) Working Party of the International Society of Blood Transfusion (ISBT)

Background: The increased use of white (WBC)-reduced blood components has prompted many institutions to develop quality assurance programs directed to such component preparation processes. For consistent preparation of WBC-reduced blood components that meet clinical needs as well as national standards, a program of process validation and control should be instituted. This involves controlling key factors that affect WBC reduction as well as periodic monitoring of the residual cellular content of components. Practical guidelines for the implementation of such a program are provided. Study Design and Methods: A program involving three phases of monitoring was developed by individuals belonging to an international working party of the International Society of Blood Transfusion. Results: The first phase, process validation, evaluates a minimum of 20 consecutive units (a minimum of 60 units when nonparametric measurements are used) to document the successful local implementation of a new or substantially modified process. Ongoing process control employing Levey-Jennings type control charts is used to demonstrate that the process remains stable over time. Process capability assessment and conformance with standards are evaluated once residual WBCs are counted in a sufficient number of units. This enables a facility to claim with a specified degree of confidence that a stated proportion of WBC-reduced units will meet national standards. Two approaches to determine the number of units that should be selected for counting are presented. The first approach considers units as either acceptable or not acceptable and assumes that the distribution of failed (or nonconforming) units approximates the Poisson distribution. The second approach takes into consideration the observed WBC content of the tested units, with the assumption that the residual WBC content in WBC-reduced components follows a lognormal distribution. A method to assess the lognormal distribution of residual WBCs is presented. Specific tables based on each of these approaches are provided to guide the reader in the design of a program that will verify conformance with any national standard at specific confidence levels. The approach can be generalized to other process control applications. Conclusion: Guidelines are presented for process validation, process control, and assessment of conformance in the production of WBC-reduced blood components. Policy makers retain the responsibility to establish, on the basis of the expected use of WBC- reduced components, requirements for the frequency of testing and for the proportion of prepared units that are expected with a stated degree of confidence to meet the standards. Facilities preparing WBC-reduced components can monitor key factors that influence the preparation of WBC-reduced blood, can periodically assess their conformance with the standards, and can intervene to correct adverse changes in the process. This approach can be used to ensure the consistent quality of WBC- reduced blood components.     

Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.     

A weak balance: the contribution of muscle weakness to postural instability and falls

Muscle strength is a potentially important factor contributing to postural control. In this article, we consider the influence of muscle weakness on postural instability and falling. We searched the literature for research evaluating muscle weakness as a risk factor for falls in community-dwelling elderly individuals, for evidence that strength training reduces falls, and for pathophysiological evidence from patients with neuromuscular disease that supports the link between muscle weakness and falls. In virtually all studies that included strength testing, muscle weakness was a consistent risk factor for falls in the elderly. Studies that evaluated the merits of muscle strength training often showed a reduction in fall rates, particularly when strength training was a component of a multifactorial intervention, although it was unclear whether strength training alone led to a fall reduction. Surprisingly few studies addressed the pathophysiological relationship between muscle strength and balance control. We conclude that muscle weakness is an important risk factor for falls that is potentially amenable to therapeutic intervention, and that future studies should further clarify the role of muscle weakness in balance control and the pathophysiology of falls.     

Use of educational games in the health professions: A mixed-methods study of educators' perspectives in the UK

Educational games have been shown to be effective in supporting learning, especially to reinforce knowledge, and students are generally positive about the use of games. The aim of this mixed-methods study that was conducted in the UK was to explore educators' views towards the use of educational games in the health sciences. The data were collected via semistructured interviews with 13 health educators and an online survey that was completed by 97 health educators. Three factors influence the use of classroom games: reflective practice, the impact of games on students, and the impact of logistical factors. Educators assess their own performance and the impact of the games on students when planning their use; however, large classes and the need for preparation time have a negative impact on educators' willingness to use games. Similar constraints might restrict the use of active learning strategies, such as simulation, that are crucial for enabling health professionals to develop competence. These issues require consideration when planning educational methods.     

The effect of gait approach velocity on the broken escalator phenomenon

Walking onto a stationary surface previously experienced as moving generates an after-effect commonly known as the “broken escalator” after-effect (AE). This AE represents an inappropriate expression of the locomotor adaptation necessary to step onto the moving platform (or escalator). It is characterised by two main biomechanical components, an increased gait approach velocity (GAV) and a forward trunk overshoot on gait termination. We investigated whether the trunk overshoot and other biomechanical measures are the direct inertial consequence of the increased GAV or whether these are the result of an independent adaptive mechanism. Forty-eight healthy young adults walked onto a movable sled. They performed 5 trials with the sled stationary at their preferred walking velocity (BEFORE trials), 5 with the sled moving (MOVING or adaptation trials), and 5 with the sled stationary again (AFTER trials). For the AFTER trials, subjects were divided into four groups. One group was instructed to walk slowly (“slower”), another with cueing at the BEFORE pace (“metronome”). The third group walked without cueing at the BEFORE pace (“normal”), and the fourth, fast (“faster”). We measured trunk pitch angle, trunk linear horizontal displacement, left shank pitch angular velocity and surface EMG from lower leg and trunk muscles. In the AFTER trials, an AE was observed in these biomechanical measures for all gait speeds, but these were not strongly dependent on GAV. An AE was present even when GAV was not different from that of BEFORE trials. Therefore, we conclude that, although contributary, the trunk overshoot is not the direct consequence of the increased GAV. Instead, it appears to be generated by anticipatory motor activity “just in case” the sled moves, herewith termed a “pre-emptive” postural adjustment.     

Mouse models in liver cancer research： A review of current literature

Primary liver cancer remains one of the most lethal malignancies worldwide. Due to differences in prevalence of etiological factors the incidence of primary liver cancer varies among the world, with a peak in East-Asia. As this disease is still lethal in most of the cases, research has to be done to improve our understanding of the disease, offering insights for possible treatment options. For this purpose, animal models are widely used, especially mouse models. In this review, we describe the different types of mouse models used in liver cancer research, with emphasis on genetically engineered mice used in this field. We focus on hepatocellular carcinoma （HCC）, as this is by far the most common type of primary liver cancer, accounting for 70%-85% of cases.     

In vitro killing of neuroblastoma cells by neutrophils derived from granulocyte colony-stimulating factor-treated cancer patients using an anti-disialoganglioside/anti-Fc gamma RI bispecific antibody

Neutrophils isolated from cancer patients treated with granulocyte colony-stimulating factor (G-CSF) express high levels of Fc gamma RI. They exhibited an efficient killing of GD2+ neuroblastoma cells in the presence of an antidisialoganglioside (GD2) mouse monoclonal antibody (MoAb; 7A4, IgG3 kappa). However, this cytotoxicity was totally blocked by human monomeric IgG. In contrast, a bispecific antibody (7A4 bis 22/MDX-260), prepared by chemically linking an F(ab') fragment of 7A4 with an F(ab') fragment of an anti-Fc gamma RI MoAb, 22, which binds outside the Fc binding domain, triggered antibody-dependent cell cytotoxicity, even when neutrophils were preincubated with human monomeric IgG. F(ab')2 22 MoAb abrogated the MDX-260 killing without affecting that of 7A4. The 3G8 MoAb, directed against the Fc gamma RIII binding site, did not inhibit the cytotoxicity induced by either antibody. Thus, these results indicate that G-CSF-activated neutrophils exert their cytotoxic effect against neuroblastoma cells through Fc gamma RI and not Fc gamma RIII, and that the saturation of the high affinity Fc gamma RI by monomeric IgG can be overcome by the use of bispecific antibodies binding epitopes outside the IgG Fc gamma RI binding site. A combined administration of such bispecific antibodies and G-CSF may be, therefore, an efficient therapeutic approach to trigger tumor lysis by cytotoxic neutrophils in vivo.     

抑制磷酸二酯酶5治疗心力衰竭的机制和临床意义

磷酸二酯酶5（PDE5）影响环磷酸鸟苷（cGMP）维持血管平滑肌紧张性的生理学效应,在阴茎海绵体的静脉系统和肺血管系统中尤为明显。     

推广规范化的胃癌淋巴结清扫术

胃癌外科治疗的历史始自Ｂｉｌｌｒｏｔｈ１８８１年在维也纳为胃癌患者成功施行世界上第１例胃切除,距今已近１２０ａ．本世纪初,胃癌是癌肿的头号杀手（ｔｈｅｌｅａｄｉｎｇｃａｎｃｅｒｋｉｌｌｅｒ）．最近几十年,全球的胃癌病死率有所下降,但我国农村幅员广阔,农村人口比例高,目前胃癌的病死率仍居各种肿瘤的首位．最近２０ａ～３０ａ,以日本为代表的胃癌的外科治疗已经获得长足的进步．我国胃癌的外科诊治水平也有明显的提高［１］,根治性切除率、早期胃癌比率以及５年生存率均有明显提高,手术死亡率及并发症发生率明显下降…     

Stimulation of eosinophil production in vitro by eosinophilopoietin and spleen-cell-derived eosinophil growth-stimulating factor

Eosinophilopoietin (EPP) was previously characterized by the ability to stimulate eosinophil production in vivo, but these studies could not ascertain whether EPP had a direct effect on the bone marrow or acted indirectly by causing release of eosinophilopoietic activity by other tissues. The present studies demonstrate that EPP stimulates eosinophil growth in liquid culture of mouse bone marrow in vitro. The timing of stimulation by EPP in vivo and in vitro were parallel, with maximal eosinophil growth after 48 hr. Moreover, EPP appears similar to, and possible identical with, the eosinophil growth-stimulating substance (EO-GSF) released by antigenic stimulation of immune nonadherent spleen cells. Both EPP and EO-GSF are of low molecular weight, both produce stimulation of eosinophil growth with identical kinetics, and both produced similar dose-response curves in the liquid culture system.