Objective performance goals of safety and blood pressure efficacy for clinical trials of renal artery bare metal stents in hypertensive patients with atherosclerotic renal artery stenosis

Objective : To provide safety and performance goals for prospective single‐arm trials of bare metal renal artery stenting in patients with resistant hypertension associated with high grade atherosclerotic renal artery stenosis. Background : To date, there have been no US Pre‐Market Approval (PMA) bare metal renal stent device trials which have focused on improvement of blood pressure control as a primary effectiveness endpoint. Methods : Analysis of subject‐level data from three large industry sponsored pre‐market approval (PMA) trials was performed. Hypertensive patients (≥155 mmHg) with a ≥50% atherosclerotic renal artery stenosis were included. Thirty day and 9‐month systolic and diastolic blood pressure measurements, renal function and 9‐month duplex ultrasound assessment of renal artery patency were analyzed. Results : Initial data analysis of 600 patients from the 3 PMA trials identified 286 patients who met inclusion criteria. The mean baseline systolic blood pressure was 177.8 ± 19.3 mmHg with a mean 68.1% diameter renal artery stenosis. Nine months after successful stenting, the mean SBP was 156.7 ± 24.1 mmHg; the 9 month restenosis rate was 14.4%. Conclusion : Based on the statistical modeling of these data and a priori established performance criteria, the co‐primary endpoints of 9 month reduction in blood pressure and in‐stent restenosis are proposed. The reduction in blood pressure will be analyzed as a continuous variable and will be compared to this performance goal. © 2011 Wiley‐Liss, Inc.     

New antibiotic strategies in patients with cirrhosis and bacterial infection

Early diagnosis and adequate empirical antibiotic treatment of bacterial infections in advanced cirrhosis is essential to improve outcomes given the high risk of developing severe sepsis, multiple organ failure and death. β-lactams and quinolones are nowadays frequently ineffective in nosocomial and healthcare associated infections, due to the increasing prevalence of multidrug resistant (MDR) bacteria reported across different geographical areas. Recent antibiotic exposure also increases the risk of developing MDR bacterial infections. Initial antibiotic strategies should therefore be tailored according to the presence or absence of risk factors of MDR bacteria and to the severity of infection and should consider the local epidemiology. Empirical treatment in the population at high risk of MDR bacterial infections requires the use of broad-spectrum antibiotics (carbapenems or tigecycline) and of drugs active against specific resistant bacteria (glycopeptides, linezolid, daptomycin, amikacin, colistin). Early de-escalation policies are recommended to prevent the spread of MDR bacteria in cirrhosis.     

Some are more equal than others

The microbial communities found in the mammalian large intestine and rumen efficiently degrade many recalcitrant substrates that are resistant to the host’s digestive enzymes. These communities are known from molecular profiling to be highly diverse at the species and strain level, but it may be that only certain specialized organisms (“keystone species”) have the ability to initiate degradation of such substrates, thus releasing energy on which the rest of the community depends. We have recently reported that Ruminococcus bromii has a superior ability to degrade certain forms of particulate resistant starch (RS) when compared with other highly abundant species of amylolytic bacteria found in the human colon and have presented evidence that this bacterium provides an example of a keystone species within the microbial community with respect to RS fermentation. The concept of keystone species can be equally relevant to other activities, e.g., those involved in stabilizing the community.     

Preparation of Polyclonal Antibody against Human MxA Protein and Its Specificity to Diversified Myxovirus Resistant Protein A

Objective To study the human myxovirus resistant protein A （MxA）, a specifically induced peptide by interferon I, and to use its level as a diagnostic criterion for viral infections. Methods Anti-MxA antisera from immunized mice were prepared with the expressed MxA protein of pET32a-MxA in E. coli BL-21（DE3）. To confirm the antiserum activity and specificity, the expression product of BL21, wild type MxA pEGFP-CI-wMxA and site-directed mutant MxA pEGFP-Cl-mMxA（N589S） stably transfected 3T3 cells and induced A549 cells were detected by Western blot with the antisera using non-MxA transfected or non-IFN-[3 induced cells, intact A549, NIH 3T3 cells transfected with pEGFP-CI and pET32a （＋）-transformed BL-21 as controls. Results The antisera had specific positive immunoreactivity to the NIH3T3 cells transformed with pEGFP-CI-wMxA and pEGFP-CI-mMxA, INF-β induced A549 cells and BL21 proteins expressed with pET32a （＋）-MxA. The hybridization signals from IFN-β induced A549 cells depended on the IFN-β inducing concentrations. Meanwhile, immunohistochemical assay showed that NIH 3T3 cells with pEGFP-C 1-wMxA and pEGFP-C 1-mMxA had 〉 98% of positive cells at 1：50 dilution of the serum and A549 cells induced by 20 ng/mL IFN-[3 for 48 h showed 95% positive cells. pEGFP-Cl-transfected NIH 3T3 cells were all negative. Conclusion Anti-sera are highly specific to diversified MxAs. The antibody is detectable by Western blot, immunocytochemistry and immunofluorescence assay.     

c‐FOS expression in the visual system of tree shrews after monocular inactivation

Tree shrews possess an unusual segregation of ocular inputs to sublayers rather than columns in the primary visual cortex (V1). In this study, the lateral geniculate nucleus (LGN), superior colliculus (SC), pulvinar, and V1 were examined for changes in c‐FOS, an immediate‐early gene, expression after 1 or 24 hours of monocular inactivation with tetrodotoxin (TTX) in tree shrews. Monocular inactivation greatly reduced gene expression in LGN layers related to the blocked eye, whereas normally high to moderate levels were maintained in the layers that receive inputs from the intact eye. The SC and caudal pulvinar contralateral to the blocked eye had greatly (SC) or moderately (pulvinar) reduced gene expressions reflective of dependence on the contralateral eye. c‐FOS expression in V1 was greatly reduced contralateral to the blocked eye, with most of the expression that remained in upper layer 4a and lower 4b and lower layer 6 regions. In contrast, much of V1 contralateral to the active eye showed normal levels of c‐FOS expression, including the inner parts of sublayers 4a and 4b and layers 2, 3, and 6. In some cases, upper layer 4a and lower 4b showed a reduction of gene expression. Layers 5 and sublayer 3c had normally low levels of gene expression. The results reveal the functional dominance of the contralateral eye in activating the SC, pulvinar, and V1, and the results from V1 suggest that the sublaminar organization of layer 4 is more complex than previously realized. J. Comp. Neurol. 525:151–165, 2017. © 2016 Wiley Periodicals, Inc.     

耐多药结核分枝杆菌对二线抗结核药单药应用和交叉方案的耐药性研究

目的探讨耐多药结核分枝杆菌(MDR-TB)对二线抗结核药单药应用和交叉方案的耐药率,为临床治疗MDRTB感染提供指导。方法收集2012年6月至2014年3月保定市第三医院结核感染患者的痰标本,从中筛选获得225株MDR-TB菌株。通过药物敏感试验观察MDR-TB对卡那霉素(KAN)、氧氟沙星(OFX)、左氧氟沙星(LOFX)、莫西沙星(MFX)、阿米卡星(AMK)、卷曲霉素(CPM)、丙硫异烟胺(Pto)和对氨基水杨酸(PAS)的单药和交叉用药的耐药性。结果 225株MDR-TB菌株总耐药率为75.11%、全敏感率为24.89%,对二线抗结核药物单药耐药率依次为:OFX(28.44%)、MFX(25.78%)、KAN(17.78%)、LOFX(12.89%)、AMK(8.89%)、Pto(6.67%)、CPM(5.33%)、PAS(4.44%),对交叉耐药率依次为:AMK+OFX(5.33%)、AMK+PAS(4.00%)、CPM+PAS(3.56%)、OFX+CPM(3.56%)、MFX+CPM(3.56%)、LOFX+PAS(2.67%)、Pto+KAN(1.78%)。初治患者总耐药率低于复治患者(P<0.05),单药应用对KAN、MFX、Pto、LOFX的耐药率均低于复治患者(P<0.05),交叉方案对AMK+OFX、MFX+CPM、Pto+KAN、LOFX+PAS的耐药性均低于复治患者(P<0.05),差异均有统计学意义。结论 MDR-TB菌株对二线抗结核药物单药具有较高的耐药性,部分二线抗结核药物交叉用药方案也具有一定的耐药性,OFX、MFX可能已不适合于临床抗结核治疗。     

某基层医院特殊级抗菌药物临床会诊回顾分析

目的：评估基层医院特殊级抗菌药物临床使用管理的效果。方法收集医院特殊级抗菌药物会诊记录,对32例患者年龄、感染疾病分布、病原学、疗效、抗菌药物选择等进行分析。结果50岁以上占84.38%,下呼吸道感染占78.13%,呼吸科和重症监护室（ICU）占68.75%,平均使用疗程6.45 d,细菌学疗效清除率37.04%,临床疗效有效率68.75%,特殊级抗菌药物使用有效干预率34.38%。结论医生多关注临床疗效,对细菌学疗效重视不够。临床药师可利用专业特长,参与特殊级抗菌药物会诊,优化抗感染治疗方案,减少药品不良反应及细菌耐药性产生,促进特殊级抗菌药物的合理使用。     

Pre-conference workshop on drug resistant TB – NATCON 2020

Pre-conference workshop on Drug Resistant Tuberculosis was conducted under the banner of NATCON-2020 on 18th December 2020. The workshop covered various aspects of diagnosis including newer rapid genotypic methods, and gene sequencing. The workshop deliberated on the latest recommendations of the global and national guidelines about the management of DR-TB patients. Case scenarios focusing on the management of MDR TB and XDR TB patients were presented and the principles of making the regimen for DR-TB patients were discussed. Various aspects of shorter MDR TB regimen including bedaquiline containing shorter regimen and all oral longer regimen for DR-TB patients were also presented to the participants. The participants were also informed regarding what is in store in the near future at global and national level regarding the management of DR-TB patients.The participants included students, teaching faculty and the practicing physicians. The workshop informed the delegates on the latest recommendations of the global and national guidelines about the management of DR-TB. The detailed deliberations were very useful for the participants in their day-to-day clinical practice. The main highlights of the workshop have been mentioned below.