Ex Vivo Costimulatory Blockade to Generate Regulatory T Cells From Patients Awaiting Kidney Transplantation

Short‐term outcomes of kidney transplantation have improved dramatically, but chronic rejection and regimen‐related toxicity continue to compromise overall patient outcomes. Development of regulatory T cells (Tregs) as a means to decrease alloresponsiveness and limit the need for pharmacologic immunosuppression is an active area of preclinical and clinical investigation. Nevertheless, the immunomodulatory effects of end‐stage renal disease on the efficacy of various strategies to generate and expand recipient Tregs for kidney transplantation are incompletely characterized. In this study, we show that Tregs can be successfully generated from either freshly isolated or previously cryopreserved uremic recipient (responder) and healthy donor (stimulator) peripheral blood mononuclear cells using the strategy of ex vivo costimulatory blockade with belatacept during mixed lymphocyte culture. Moreover, these Tregs maintain a CD3⁺CD4⁺CD25⁺CD127^lo surface phenotype, high levels of intracellular FOXP3 and significant demethylation of the FOXP3 Treg‐specific demethylation region on allorestimulation with donor stimulator cells. These data support evaluation of this simple, brief Treg production strategy in clinical trials of mismatched kidney transplantation.     

Incentivizing Authorization for Deceased Organ Donation With Organ Allocation Priority: The First 5 Years

The allocation system of donor organs for transplantation may affect their scarcity. In 2008, Israel's Parliament passed the Organ Transplantation Law, which grants priority on waiting lists for transplants to candidates who are first‐degree relatives of deceased organ donors or who previously registered as organ donors themselves. Several public campaigns have advertised the existence of the law since November 2010. We evaluated the effect of the law using all deceased donation requests made in Israel during the period 1998–2015. We use logistic regression to compare the authorization rates of the donors’ next of kin in the periods before (1998–2010) and after (2011–2015) the public was made aware of the law. The authorization rate for donation in the period after awareness was substantially higher (55.1% vs. 45.0%, odds ratio [OR] 1.43, p = 0.0003) and reached an all‐time high rate of 60.2% in 2015. This increase was mainly due to an increase in the authorization rate of next of kin of unregistered donors (51.1% vs. 42.2%). We also found that the likelihood of next‐of‐kin authorization for donation was approximately twice as high when the deceased relative was a registered donor rather than unregistered (89.4% vs. 44.6%, OR 14.27, p < 0.0001). We concluded that the priority law is associated with an increased authorization rate for organ donation.     

A Smartphone App for Increasing Live Organ Donation

The incidence of live donor transplantation has declined over the past decade, and waitlisted candidates report substantial barriers to identifying a live donor. Since asking someone to donate feels awkward and unfamiliar, candidates are hesitant to ask directly and may be more comfortable with a passive approach. In collaboration with Facebook leadership (Facebook Inc., Menlo Park, CA), we developed a mobile application—an app—that enables waitlisted candidates to create a Facebook post about their experience with organ failure and their need for a live donor. We conducted a single‐center prospective cohort study of 54 adult kidney‐only and liver‐only waitlisted candidates using the Facebook app. Cox proportional hazards models were used to describe donor referral on behalf of candidates using the app compared with matched controls. The majority of candidates who used the app reported it to be “good” or “excellent” with regard to the installation process (82.9%), readability (88.6%), simplicity (70.6%), clarity (87.5%) and the information provided (85.3%). Compared with controls, candidates using the Facebook app were _2.436.61_17.98 times more likely to have a donor come forward on their behalf (p < 0.001). The Facebook app is an easy‐to‐use instrument that enables waitlisted candidates to passively communicate with their social network about their need for a live donor.     

艾司洛尔对腹腔镜胆囊切除术血流动力学及内分泌的影响

目的:探讨艾司洛尔对腹腔镜手术患者手术期间血流动力学及内分泌的影响。方法:30例全麻下腹腔镜手术患者被随机分为对照组(A组,n=15)和艾司洛尔组(B组,n=15),B组于诱导时经静脉推注艾司洛尔0.5mg/kg,气腹前给予艾司洛尔0.5mg/kg,然后以50μg/kg.m in-1速度持续输注。记录A组与B组患者气腹前(T1)、气腹10m in(T2)、20m in(T3)及放气后10m in(T4)、拔管后(T5)的心率(heart rate,HR)、收缩压(systolic b lood pressure,SBP)、舒张压(d iastolic b lood pressure,DBP)、平均动脉压(m ean arterial pressure,MAP)的改变,同时测定T1~T5血中儿茶酚胺和多巴胺的浓度。结果:A组气腹期间相应时点的SBP、DBP、MAP比T1明显升高(P<0.01);T3时A组儿茶酚胺、多巴胺比T1明显增高(P<0.01),B组上述指标相应时点与T1相比无明显改变。结论:艾司洛尔能很好地稳定气腹引起的血流动力学及内分泌的变化,维持内环境稳定,同时可减少吸入异氟醚最低肺泡有效浓度,缩短拔管时间。     

每搏输出量变异度监测不同潮气量通气时全麻患者血容量变化的准确性

目的 评价每搏输出量变异度(SVV)监测不同潮气量通气时全麻患者血容量变化的准确性.方法 择期行胃肠手术的全麻患者50例,年龄31～59岁,ASAⅠ或Ⅱ级,随机分为2组:常规潮气量组(C组,n=20)和小潮气量组(L组,n=30).C组潮气量(VT)8 ml/kg,呼吸频率(RR)12次/min,呼气末正压力0,吸入氧浓度80%,氧流量2 L/min,行间歇正压通气;L组VT 6 ml/kg,RR16次/min,余同c组.气管插管后10 min,两组均以0.3 ml·kg-1·min-1的速率静脉输注6%羟乙基淀粉130/0.4氯化钠注射液7 ml/kg,输注后开始手术.于输注前(T1)和输注后10 min(T2)时记录MAP、HR、CVP、体循环血管阻力(SVR)、SVV和每搏指数(SI),并计算其变化率.绘制各项血液动力学指标监测血容量变化的ROC曲线.结果 ROC曲线结果 分析显示:以SI变化率≥25%为监测血容量变化的标准时,SVV的诊断周值为9.5%,C组SVV>9.5%监测血容量变化的灵敏度为100%,特异度为57.1%;L组SVV>9.5%监测血容量变化的灵敏度为91.3%,特异度为71.4%.ROC曲线下面积显示:两组SVV监测血容量变化的准确性高于MAP、HR、CVP、SVR.结论 在常规潮气量(8 ml/kg)和小潮气量(6 ml/kg)/机械通气时,SVV均可准确地监测全麻患者血容量变化.     

吸入不同浓度氧化亚氮对全麻患者双腔喉罩囊内压的影响

目的 评价吸入不同浓度氧化亚氮对全麻患者双腔喉罩囊内压的影响.方法 择期全麻患者48例,ASAⅠ或Ⅱ级,年龄25～64岁,随机分为4组(n=12):C组、N1组、N2组及N3组.根据患者身高和体重选择合适型号的双腔喉罩.依次静脉注射异丙酚、瑞芬太尼、利多卡因及维库溴铵行麻醉诱导,喉罩置入成功后,套囊内注入空气,调节囊内压使其达加cm H2O(基础值),连接麻醉机行机械通气,C组、N1组、N2组及N3组分别吸入100%O2、65%O2+35%N2O、50%O2+50%N2O及35%O2+65%N2O,于吸入15、30、45、60、75、90 min时(T1-6)测定喉罩囊内压.结果 与C组比较,N1-3组T1-6时囊内压升高;与N1组比较,N2,3组T1-6时囊内压升高;与N2组比较,N3组,T1-6时囊内压升高(P<0.05).与T0时比较,C组T2-6时囊内压降低,N1组T2-6时囊内压升高,N2,3组T1-6时囊内压升高(P<0.05).N1-3组囊内压与吸入时间呈正相关(相关系数分别为0.968、0.987、0.973,P<0.05).结论 吸入N2O可使喉罩囊内压升高,呈浓度及时间依赖性.     

全麻苏醒期患儿躁动风险预测模型的建立与验证

目的 建立与验证全麻苏醒期患儿躁动风险列线图预测模型,为识别躁动高风险患儿提供评估工具。方法 收集全麻手术的1～6岁患儿651例,随机分为建模组(n=459)和验证组(n=192),利用多因素logistic回归分析确定建模组全麻苏醒期患儿躁动的危险因素,构建列线图预测模型,分别使用建模组和验证组数据集对模型进行验证。结果 苏醒期发生躁动160例(建模组113例,验证组47例),躁动发生率24.58%。多因素logistic回归显示,年龄、手术科室、身体约束、麻醉方式、镇痛治疗、留置尿管是全麻苏醒期患儿躁动的影响因素(均P<0.05)。基于6个危险因素构建列线图预测模型,模型验证的校正曲线显示模型准确度良好,建模组ROC曲线下面积为0.767,验证组为0.827。结论 全麻苏醒期患儿躁动风险列线图预测模型具有良好的准确度和区分度,可为临床筛查术后躁动高危患儿提供评估工具。