Pediatric ventricular assist devices

The domain of pediatric ventricular assist device (VAD) has recently gained considerable attention. Despite the fact that, historically, the practice of pediatric mechanical circulatory support (MCS) has lagged behind that of adult patients, this gap between the two groups is narrowing. Currently, the Berlin EXCOR VAD is the only pediatric-specific durable VAD approved by the U.S Food and Drug Administration (FDA). The prospective Berlin Heart trial demonstrated a successful outcome, either bridge to transplantation (BTT), or in rare instances, bridge to recovery, in approximately 90% of children. Also noted during the trial was, however, a high incidence of adverse events such as embolic stroke, bleeding and infection. This has incentivized some pediatric centers to utilize adult implantable continuous-flow devices, for instance the HeartMate II and HeartWare HVAD, in children. As a result of this paradigm shift, the outlook of pediatric VAD support has dramatically changed: Treatment options previously unavailable to children, including outpatient management and even destination therapy, have now been becoming a reality. The sustained demand for continued device miniaturization and technological refinements is anticipated to extend the range of options available to children—HeartMate 3 and HeartWare MVAD are two examples of next generation VADs with potential pediatric application, both of which are presently undergoing clinical trials. A pediatric-specific continuous-flow device is also on the horizon: the redesigned Infant Jarvik VAD (Jarvik 2015) is undergoing pre-clinical testing, with a randomized clinical trial anticipated to follow thereafter. The era of pediatric VADs has begun. In this article, we discuss several important aspects of contemporary VAD therapy, with a particular focus on challenges unique to the pediatric population.     

沙利度胺联合VAD方案治疗多发性骨髓瘤的疗效

目的:探讨沙利度胺联合VAD方案治疗多发性骨髓瘤(multiple myeloma,MM)的疗效及不良反应。方法:选取2011年1月—2012年12月住院治疗的38例MM患者,将其随机分为对照组和观察组。对照组(VAD组)16例,采用长春新碱+阿霉素+地塞米松治疗;观察组(TVAD组)22例,在对照组治疗方法的基础上加用沙利度胺。比较两组的疗效及不良反应。结果:TVAD组总有效率(77.2%)明显高于VAD组(50.0%),差异有统计学意义(P0.05)。TVAD组治疗后较治疗前血清β2-微球蛋白(β2-microglobulin,β2-MG)、C-反应蛋白(C-reactive protein,CRP)、红细胞沉降率(erythrocyte sedimentation rate,ESR)、浆细胞比例的下降及血红蛋白(haemoglobin,Hb)的升高幅度均大于VAD组,差异有统计学意义(均P0.05)。TVAD组不良反应发生率高于VAD组,不良反应经对症处理后均消失,不影响治疗。结论:沙利度胺联合VAD方案治疗MM疗效显著、给药方便、患者耐受性好。     

Persistent hepatitis C virus (HCV) infection impairs HCV‐specific cytotoxic T cell reactivity through Mcl‐1/Bim imbalance due to CD127 down‐regulation

Summary. In persistent hepatitis C virus (HCV) infection, HCV‐specific cytotoxic T lymphocyte (CTL) reactivity is impaired and this affects HCV control. Interleukin‐7 receptor (CD127) expression on these cells could regulate CTL reactivity through Mcl‐1/Bim balance modulation. Bim is a pro‐apoptotic molecule blocked by the action of Mcl‐1. Mcl‐1/Bim expression and T cell reactivity on HCV‐specific CTLs were compared according to CD127 phenotype. Peripheral blood lymphocytes (PBL) from HLA‐A2⁺ HCV⁺ patients were obtained. HCV‐specific CTLs were visualized by staining PBL with anti‐CD8 and HLA‐A2/peptide pentameric complexes (pentamer). Mcl‐1/Bim/CD127 phenotype of HCV‐specific CTLs was tested by staining detectable CD8⁺/pentamer⁺ cells with anti‐Mcl‐1/Bim/CD127 antibodies. HCV‐specific CTL proliferation ability after specific in vitro challenge was tested in the presence and absence of pancaspase inhibitor z‐VAD‐fmk. All stained cells were analysed by flow cytometry. CD127^low‐expressing HCV‐specific CTLs associated with high HCV viraemia, while CD127^high correlated with undetectable viral loads (P < 0.001). Directly ex vivo, pentamer⁺ cell frequency was similar according to CD127 expression level. Nevertheless, CD127^low pentamer⁺ cell proliferation after specific in vitro challenge was impaired (P < 0.05), although this was corrected by z‐VAD‐fmk treatment (P < 0.05). Mcl‐1 expression was low directly ex vivo (P < 0.01), and Bim was up‐regulated after antigen encounter (P < 0.05) of CD127^low pentamer⁺ cells. The ex vivo difference between Mcl‐1 and Bim expression on pentamer⁺ cells correlated positively with CD127 expression level (P < 0.001) and with pentamer⁺ cell reactivity (P < 0.05). In summary, a low ex vivo Mcl‐1 expression and Bim up‐regulation after antigen encounter are involved in CD127^low HCV‐specific CTL hyporeactivity during chronic infection, but it can be overcome by apoptosis blockade.     

Serum Retinol and Xerophthalmia Among a Prison Population in Papua New Guinea

Purpose: To estimate the prevalence of vitamin A deficiency (VAD) and one of its clinical manifestations, xerophthalmia, and examine the predictive value of nyctalopia and ocular signs for serum retinol concentrations among a prison population in Papua New Guinea.

Methods: A cross-sectional study of 148 prisoners and 9 guards; all males aged ≥18 years. Interview-based questionnaire; ocular examination; serum retinol concentration determination.

Results: Two guards had marginal (retinol <1.05–≥0.70?µmol/L) VAD. For prisoners: mean retinol was 0.84?±?0.49?µmol/L; 43.9% (95% CI 35.9, 52.2) had VAD (retinol <0.70?µmol/L); 9.6% (95% CI 5.1, 17.0) self-reported nyctalopia prior to, and 36.1% (95% CI 27.7, 45.5) after incarceration; 10.9% (95% CI 6.7, 17.0) exhibited at least one sign of xerophthalmia (2 had fundus changes; all 4 with more than conjunctival xerosis alone had severe [<0.35 µmol/L] retinol deficiency). Prisoners with ocular signs were more likely than those without to have VAD (OR 10.4; 95% CI 2.5, 70.3; P?<?0.001) and severe retinol deficiency (OR 19.1; 95% CI 5.5, 77.2; P?<?0.001). Positive (PPV) and Negative (NPV) Predictive Values: of nyctalopia for any (PPV 62.9%; NPV 32.8%) and severe (PPV 25.7%; NPV 85.9%) retinol deficiency; of ocular signs for any (PPV 93.3%; NPV 38.2%) and severe (PPV 73.1%; NPV 87.8%) retinol deficiency, and VAD (PPV 86.5%, NPV 38.2%).

Conclusions: VAD and xerophthalmia were present in this prison population. There may be VAD in the wider community. The former needs remedy and the latter deserves investigation. Self-reported nyctalopia was not a useful indicator of retinol deficiency. Absence of ocular signs was unhelpful for ruling out VAD.     

The effect of surface roughness on activation of the coagulation system and platelet adhesion in rotary blood pumps

Abstract:  The surface roughness of left ventricular assist devices (LVADs) is important for the biocompatibility of blood pumps. However, little is known about the effect of surface roughness on the antithrombogenicity of the device. The present study investigated the effect of surface roughness on the activation of the coagulation system and platelet adhesion in an impeller-type blood pump. Three identical Baylor Gyro 710 centrifugal blood pumps (Baylor College of Medicine, Houston, TX, USA) were manufactured with impeller surface roughness of 0.05, 0.2, and 0.4 µm, respectively, as determined by a stylus profilometer and by scanning electron microscopy. Whole blood was anticoagulated (1-IU heparin/mL, ACT 250 s) and circulated for 60 min in an artificial circulatory system, simulating LVAD perfusion (5-L/min flow against 100 mm Hg). Enzyme-linked immunosorbent assays were developed to quantify fibrinogen- and von Willebrand factor (vWf) adsorption as well as platelet adhesion directly on the impellers of the pumps. Levels of prothrombin fragment F1.2 and thrombin–antithrombin (TAT) complex were measured in order to quantify activation of coagulation. Compared with the 0.05-µm surface, platelet adhesion was 40 and 76% higher on the 0.2- and 0.4-µm surface, respectively ( P  < 0.01). The evaluation of adsorbed fibrinogen and vWf showed significant higher protein antigen levels on the rougher surfaces ( P  < 0.01). Furthermore, nonpulsatile perfusion activated the coagulation system. By contrast, the surface roughness had no significant influence on plasma prothrombin F1.2 fragment- and TAT concentrations. Antithrombogenicity was significantly reduced in pumps with inferior metal-finishing quality.     

Surgical treatment of advanced heart failure: alternatives to heart transplantation and mechanical circulatory assist devices

Although orthotopic heart transplantation is the gold standard for definitive surgical treatment of end-stage heart failure, other operative therapies exist for dealing with severe systolic left ventricular dysfunction. The choice of surgical intervention depends on the etiology and functional characteristics of the patient's ventricular dysfunction. In patients with ischemic cardiomyopathy, surgical revascularization improves survival. Patients with mitral regurgitation experience significant functional improvement from mitral valve repair and replacement. In patients with aortic valve dysfunction, aortic valve replacement results in improved survival and functional status. Although surgical ventricular reconstruction is controversial, significant data exist suggesting that it is an effective therapy in a subset of patients with left ventricular dysfunction. Finally, passive restraint devices are effective at halting further ventricular dilation. Although cardiac surgery in patients with severe ventricular dysfunction can be complicated by significant morbidity and mortality, experienced centers have demonstrated acceptable outcomes in carefully selected patients.