Long-Term Risk of Infective Endocarditis After Transcatheter Aortic Valve Replacement

Background

Patients undergoing surgical aortic valve replacement (SAVR) are considered at high risk of infective endocarditis (IE). However, data on the risk of IE following transcatheter aortic valve replacement (TAVR) are sparse and limited by the lack of long-term follow-up as well as a direct comparison with patients undergoing SAVR.

Two weeks of postsurgical therapy may be enough for high-risk cases of endocarditis caused by Streptococcus viridans or Streptococcus bovis

The duration of antimicrobial therapy after surgery for infective endocarditis (IE) is controversial. A short course of postsurgical therapy is currently accepted only for patients with negative valve culture. We performed a retrospective (1994–2008) analysis of patients who underwent surgery for IE in our hospital and had a high risk of complications (one of more of the following: <2 weeks of antibiotic treatment before surgery; embolism; perivalvular extension; and positive valve culture) to compare outcomes of patients who received short-course antimicrobial therapy (SAT) (median 15 days) or long-course antimicrobial therapy (LAT) (median 32 days), irrespective of the results of valve culture. Our endpoints included length of hospital stay, renal and hepatic failure, relapse, re-infection, and mortality rates 1 year after surgery. During the study period, 140 patients underwent surgery for IE (valve replacement, 87.9%). Of these, 133 fulfilled the high-risk group criteria and 92 completed the antimicrobial schedule. Comparison of patients receiving SAT (37) and LAT (55) showed that the SAT group had a shorter length of hospital stay (29 vs. 40 days, p 0.01), and a trend towards lower frequency of renal failure (5.4% vs. 18.2%, p 0.11) and hepatic failure (5.4% vs. 9.1%, p 0.69), whereas mortality (5.4% vs. 3.6%, p 1), relapse (0% vs. 1.8%, p 1) and re-infection (5.4% vs. 3.6%, p 1) rates were similar between both groups. Multivariate analysis showed that IE caused by Streptococcus viridans or Streptococcus bovis was independently associated with SAT. Postsurgical SAT is safe, especially when IE is caused by Streptococcus viridans or Streptococcus bovis, even in patients at high risk of complications.     

Variable Significance of Brain MRI Findings in Infective Endocarditis and Its Effect on Surgical Decisions

ObjectiveTo determine how brain magnetic resonance imaging (MRI) findings impact clinical outcomes in patients with infective endocarditis (IE) and to propose a management algorithm for patients with neurologic symptoms who are candidates for valve surgery (VS).Patients and MethodsData from our center were retrospectively reviewed for patients hospitalized with IE between January 1, 2007, and December 31, 2014. Outcomes were postoperative intracerebral hemorrhage (ICH), 6-month mortality, and functional outcome at last follow-up as described by the modified Rankin Scale (mRS) score. Good outcome was defined as an mRS score of 2 or less.ResultsA total of 361 patients with IE were identified, including 127 patients (35%) who had MRI. One hundred twenty-six of 361 patients (35%) had neurologic symptoms, which prompted MRI in 79 of 127 patients (62%); 74 of 79 (94%) had acute or subacute MRI abnormalities. One patient with subarachnoid and multifocal ICH on MRI developed postoperative ICH. Patients with VS despite MRI abnormalities had lower 6-month mortality (odds ratio [OR], 0.17; 95% CI, 0.06-0.48; P<.001) and better functional outcome (OR, 4.43; 95% CI, 1.51-13.00; P=.005). Irrespective of VS, lobar or posterior fossa ICH on MRI was associated with 6-month mortality (OR, 3.58; 95% CI, 1.22-10.50; P=.02) and territorial ischemic stroke was inversely associated with good mRS (OR, 0.29; 95% CI, 0.13-0.66; P=.002). In neurologically asymptomatic patients who had VS, MRI findings did not impact 6-month mortality or functional outcomes.ConclusionMagnetic resonance imaging detects a large number of abnormalities in patients with IE. Preoperative lobar hematoma and large territorial stroke determine outcome irrespective of VS. When indicated, VS increases the odds of a good outcome despite MRI abnormalities.     

The virus-induced HSPs regulate the apoptosis of operatus APCs that results in autoimmunity,not in homeostasis

The viruses are salient in the roles of environmental factors that trigger autoimmunity. The virus realizes its effects by the power of its induction of heat shock proteins (HSPs) as well as by the viral IE-axis-mediated conversion of organ epithelial cells into virgin de novo professional antigen-presenting cells (APCs). The HSP is the accomplished operator in homeostasis by the logic of it being the regulator of apoptosis. That HSP which regulates and controls different points in the pathways of apoptosis is rationally propitious as both HSP and apoptosis are highly conserved in multicellular organisms. By virtue of its regulation of apoptosis, the HSP is also involved in human autoimmunity and this involvement is tripartite: (i) adornment of viral IE-axis-generated virgin de novo professional APCs with HSP-induced co-stimulatory molecules which transform these otherwise epithelial cells to achieve the status of fledged competent antigen-presenters, the operatus APCs, which are liable to apoptosis that becomes the initiator of organ damages that can culminate in the autoimmune syndrome(s); apoptosis is a routine fate that befalls all APCs following their antigen presentation; (ii) molecular mimicry mechanism: epitopes on the HSP may be mistaken for viral peptides and be presented by operatus APCs to autoreactive TCRs resulting in the apoptosis of the operatus APCs; and (iii) regulation of MHC class II-DR-mediated apoptosis of operatus APCs which can ultimately consequent in organ-specific autoimmune syndromes. We should remember, however, that Nature's intended purpose for the apoptosis of the professional APCs is benevolence: as a principal regulator of homeostasis. It is only from the apoptosis of our postulated operatus APCs that the apoptotic consequence can be deleterious, an autoimmune syndrome(s). The transformation of virgin de novo professional APCs to operatus APCs mirrors the maturation of DCs, through their acquisition of HSP-induced co-stimulatory molecules; and what happens to mature DCs as antigen-presenters that ends in homeostasis is replicated by what happens to operatus APCs that ends instead in autoimmune syndromes (Fig. 1).     

HCMV IE1和pp65在人神经胶质瘤U251细胞中的时序表达

目的:研究人神经胶质瘤U251细胞对人巨细病毒(human cytomegalovirus, HCMV)的容许性,并探讨病毒蛋白IE1及pp65的时序表达特点.方法:HCMV感染U251细胞,以透射电镜观察U251细胞的形态学改变,以PCR方法检测HCMV核酸,于不同的时间点分别用抗蛋白IE1及蛋白pp65单克隆抗体进行免疫细胞化学染色,检测IE1及pp65的表达水平.结果:受染的U251细胞出现了明显的形态学改变,并用PCR方法检测到了HCMV核酸.免疫细胞化学染色表明,蛋白IE1在感染后30min～2h无表达,4h开始表达,14h达高峰,随后下降;蛋白pp65在感染后1 h为入侵型pp65,4～96h一直呈低水平表达,至120h表达急剧升高.结论:U251细胞是HCMV的容许细胞,HCMV在其中的表达具有时序性,但是其时序表达较在人成纤维细胞中延迟.     

Use of an N-terminal half truncated IE1 as an antagonist of IE1, an essential regulatory protein in baculovirus

An immediate-early gene product of baculovirus, IE1, is essential for viral gene expression and for viral DNA replication. It has been demonstrated for Autographa californica nuclear polyhedrosis virus (AcNPV) that the C-terminal region of IE1 is required for dimerization. And the acidic N-terminal region of IE1 has been identified as the activation domain. We constructed an N-terminal 267 amino acid (a.a.) truncated mutant of Bombyx mori nuclear polyhedrosis virus (BmNPV) IE1, which was defective as a transactivator of a viral early gene (p35) promoter. We then examined possible IE1 antagonistic functions of this defective IE1, IE1TN, in BmNPV-infected cells. A transient expression experiment demonstrated that IE1TN strongly repressed the activation of the hr5-dependent p35 promoter derived from BmNPV infection. In addition, DpnI assay elucidated an inhibitory effect of IE1TN on the hr5-dependent replication of plasmid in BmN cells induced by NPV infection. A marked reduction in the production of virus was observed when the BmN cells were infected with BmNPV after transfection with IE1TN-expression plasmids. These results suggested that IE1TN could act as an IE1 antagonist in silkworm cells infected with BmNPV. We then analyzed the ability of IE1TN to inhibit the multiplication of BmNPV using transgenic silkworms. The BmNPV-resistance of the transgenic silkworms was very weak, suggesting insufficient expression of the transgene product, IE1TN.     

用IE—HPLC、PAGE分析合成的硫代寡核苷酸相关物质“n—1”、“n—2”和“n—3”

目的:分析合成的n=20-mer硫代寡核苷酸中相关物质“n-1”、“ n-2”和“ n-3”杂质失败序列。方法:离子交换高效液相色谱(IE-HPLC)法和聚丙烯酰胺凝胶电泳法(PAGE)。色谱柱为Gen-Pak~(TM)FAX离子交换柱(4.6 mm×100mm),流动相A为62.5mmol·L~(-1)三羟甲基氨基甲烷盐酸(Tris·Cl),pH 8.15,流动相B为62.5mmol·L~(-1) Tris·Cl,pH 8.15,2.5 mol·L~(-1) LiCl,流动相C为100％乙腈;梯度洗脱条件为B:30％→50％ 30 min,C:恒为20％;流速为0.75mL·min~(-1);检测波长为260nm。PAGE分析采用20％变性聚丙烯酰胺凝胶,恒定功率25W进行电泳。结果:IE-HPLC分离纯化出3种相关物质,通过PAGE印证了它们是由于合成偶联不完全而产生的n-1、n-2和n-3的杂质失败序列。结论:所用离子交换高效液相色谱法能将合成的硫代寡核苷酸中相关物质“n-1”、“n-2”和“n-3”杂质失败序列与全序列n一一分离出来,对硫代寡核苷酸的纯化和分析具有重要的参考价值。     

Heavy metal levels in patients with ineffective erythropoiesis

Objectives

Iron is taken into enterocytes at the duodenum via apical divalent metal-ion transporter 1 protein. Besides iron, divalent metal-ion transporter 1 also transports other divalent metals. We aimed to investigate blood heavy metal levels in patients with ineffective erythropoiesis.

Immune evasion proteins gpUS2 and gpUS11 of human cytomegalovirus incompletely protect infected cells from CD8 T cell recognition

Human cytomegalovirus (HCMV) encodes four glycoproteins, termed gpUS2, gpUS3, gpUS6 and gpUS11 that interfere with MHC class I biosynthesis and antigen presentation. Despite gpUS2-11 expression, however, HCMV infection is efficiently controlled by cytolytic CD8 T lymphocytes (CTL). To address the role of gpUS2 and gpUS11 in antigen presentation during viral infection, HCMV mutants were generated that expressed either gpUS2 or gpUS11 alone without coexpression of the three other proteins. Fibroblasts infected with these viruses showed reduced HLA-A2 and HLA-B7 surface expression. Surprisingly, however, CTL directed against the tegument protein pp65 and the regulatory IE1 protein still recognized and lysed mutant virus infected fibroblasts. Yet, suppression of IE1 derived peptide presentation by gpUS2 or gpUS11 was far more pronounced. The results show that gpUS2 and gpUS11 alone only incompletely protect HCMV infected fibroblasts from CTL recognition and underline the importance of studying infected cells to elucidate HCMV immune evasion.