Strategies to accelerate immune recovery after allogeneic hematopoietic stem cell transplantation

The interplay existing between immune reconstitution and patient outcome has been extensively demonstrated in allogeneic hematopoietic stem cell transplantation. One of the leading causes of infection-related mortality is the slow recovery of T-cell immunity due to the conditioning regimen and/or age-related thymus damage, poor naïve T-cell output, and restricted T-cell receptor (TCR) repertoires. With the aim of improving posttransplantation immune reconstitution, several immunotherapy approaches have been explored. Donor leukocyte infusions are widely used to accelerate immune recovery, but they carry the risk of provoking graft-versus-host disease. This review will focus on sophisticated strategies of thymus function-recovery, adoptive infusion of donor-derived, allodepleted T cells, T-cell lines/clones specific for life-threatening pathogens, regulatory T cells, and of T cells transduced with suicide genes.     

Recipient and donor cells in the graft-versus-solid tumor effect: It takes two to tango

Allogeneic hematopoietic stem cell transplantation (alloHSCT) produces –similar to the long-established graft-versus-leukemia effect– graft-versus-solid-tumor effects. Clinical trials reported response rates of up to 53%, occurring mostly but not invariably in association with full donor chimerism and/or graft-versus-host disease. Although donor-derived T cells are considered the principal effectors of anti-tumor immunity after alloHSCT or donor leukocyte infusion (DLI), growing evidence indicate that recipient-derived immune cells may also contribute. Whereas the role of recipient-derived antigen-presenting cells in eliciting graft-versus-host reactions and priming donor T cells following DLI is well known, resulting inflammatory responses may also break tolerance of recipient effector cells towards the tumor. Additionally, mouse studies indicated that post-transplant recipient leukocyte infusion produces anti-leukemia and anti-solid-tumor effects that were exclusively mediated by recipient-type effector cells, without graft-versus-host disease. Here, we review current preclinical and clinical evidence on graft-versus-solid-tumor effects and growing evidence on the effector role of recipient-derived immune cells in the anti-tumor effect of alloHSCT.     

Metabolomic method to detect a metabolite corona on amino-functionalized polystyrene nanoparticles

Abstract

Protein coronas on nanoparticles (NPs) affect their physicochemical properties, cellular uptake, and toxicity, and have been described extensively. To date, studies of the occurrence of small molecule (metabolite) coronas are limited. We sought to determine whether a metabolite corona forms on NPs, using high-sensitivity metabolomics combined with a model system for freshwater ecotoxicology (Daphnia magna feeding on Chlorella vulgaris). Using amino-functionalized polystyrene NPs (NH₂-pNPs), we showed the impact of this material on Daphnia feeding to provide a rationale for the detailed molecular investigations. We then employed a targeted LC-MS/MS approach for sodium dodecyl sulfate (SDS) as an analog to signaling molecules known to occur in our freshwater model system and optimized a corona extraction method for this representative metabolite. Next, we performed an untargeted discovery-based metabolomics study – using high-sensitivity nanoelectrospray direct infusion mass spectrometry (DIMS) – to enable an unbiased assessment of the metabolite corona of NH₂-pNPs in the freshwater model system. Our results demonstrate that SDS was successfully recovered from NH₂-pNPs, confirming that the extraction protocol was fit-for-purpose. Untargeted DIMS metabolomics reproducibly detected 100?s of small molecule peaks extracted from NH₂-pNPs exposed to conditioned media from the D. magna–C. vulgaris model system. Attempts to annotate these extracted metabolites, including by using van Krevelen and Kendrick Mass Defect plots, indicate a diverse range of metabolites that were not clustered into any particular class. Overall we demonstrate the existence of an ecologically relevant metabolite corona on the surface of NPs through application of a high-sensitivity, untargeted mass spectrometry metabolomics workflow.     

Continuous Deep Intravenous Infusion in Rat Embryotoxicity Studies: The Effects of Infusion Volume and two Different Infusion Fluids on Pregnancy

Intravenous infusion over long periods is an increasingly common method of administration for novel medicinal agents. This investigation was undertaken to evaluate the suitability of a new catheter implantation technique in the rat and to determine the effects of two different infusion fluids and volumes on litter parameters. Female Sprague-Dawley rats were anesthetized on day 1 of gestation and an indwelling catheter was implanted into the posterior vena cava by introduction into the femoral vein. A swivel joint in the roof of the cage allowed unrestricted movement of the animal. One group of rats was not treated further. Other groups were maintained on continuous infusion with physiological saline or isotonic glucose (dextrose) solution at various rates until day 15 of gestation (the test article would normally be dissolved in the infusion fluid starting from day 6 of gestation). Anesthesia and catheter implantation without infusion caused a slight transient reduction in maternal weight gain by comparison with historical data from untreated rats. This parameter then showed a clear inverse relationship to infusion volume in the infused groups. An infusion rate of 0.25 mL/h (i.e., 24 mL/kg day^?1) did not adversely affect gestation. Infusion of 1.0 mL/h of saline caused an increase in early resorption incidence and retarded fetal development. The same volume of isotonic glucose solution caused only a minor increase in resorptions with no effects on surviving fetuses.     

The Evidence Base for Diabetes Technology: Appropriate and Inappropriate Meta-Analysis

When we are interested in making decisions about best use, comparative therapeutic efficacy, or cost-effectiveness of diabetes technologies such as insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] or continuous glucose monitoring, meta-analysis for the purpose of literature summary is inappropriate and may be misleading. Instead, “decision-making meta-analysis” is more appropriate and should involve either preselection of trials based on intended use [e.g., elevated baseline hemoglobin A1c or hypoglycemia rate for trials of multiple daily injections (MDI) versus CSII] or metaregression of summary effect sizes in different trials against potential effect-modifying covariates such as baseline risk, or models of the covariates that determine effect size using individual patient data. Appropriate meta-analysis should also only include trials that are of sufficient duration to accurately measure outcomes such as severe hypoglycemia, and they should not use obsolete technology that is of proven inferiority to current technology. The use of appropriate decision-making meta-analysis is illustrated by the change in the rate ratio for severe hypoglycemia in randomized controlled trials of MDI versus CSII in type 1 diabetes from 1.56 (95% confidence interval 0.96–2.55; p = .074) for literature-summary meta-analysis to 2.0 (1.08–3.69; p = .027) for decision-making meta-analysis of all patients and 3.91 (1.35–11.36; p = .01) for trials in children.     

分合式（Y型）输液器在优质护理服务中的效果体会

目的探讨分合式输液器在优质护理服务中的应用。方法选择2012年6～12月在胸外科静脉输液的患者，对照组（n=520）使用普通输液器；试验组（n=542）使用分合式输液器，采取单盲方法，收集每日更换液体的次数、输液器异常情况次数、患者的满意度，进行统计学分析。结果更换液体的次数、异常情况次数及患者的满意度，两组差异有统计学意义（P〈0．05）。结论使用分合式输液器，可以有效减少护士耗费在静脉治疗上的时间，提高工作效率，减轻患者及家属的恐慌，增加患者的满意度，便于优质护理工作的开展和完善。     

门诊输液护理差错原因分析与防范对策

目的 分析门诊输液护理差错发生的原因,并提出防范对策.方法 回顾性分析2011年5月～2014年5月本院门诊输液室发生26例护理差错的资料.结果 护理差错类型包括医嘱转抄错误、注射错误及液体外渗等,护理差错主要发生在白班,工作年限5年内护士护理差错的发生率高于其他工作年限的护士（P＜0.05）.结论 未严格执行“三查七对”是发生差错的重要原因.科学管理、完善各项规章制度是预防门诊输液护理差错的主要对策.