左卡尼汀联合重组人促红素注射液治疗规律透析慢性肾功能衰竭合并贫血患者的临床效果

目的探究左卡尼汀联合重组人促红素注射液治疗规律透析慢性肾功能衰竭合并贫血患者的临床效果。方法选择2017年1月至2020年1月收治的100例规律透析慢性肾功能衰竭合并贫血患者,以计算机随机化法将其分为对照组和试验组,每组50例。对照组给予重组人促红素注射液治疗,试验组给予左卡尼汀与重组人促红素注射液联合治疗。比较两组患者的治疗效果。结果试验组的治疗总有效率为96.00%,高于对照组的80.00%(P<0.05);治疗后,两组患者的MCHC、MCH、MCV、SF、Hb、RBC水平均高于治疗前,且试验组高于对照组(P<0.05);两组患者的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论规律透析慢性肾功能衰竭合并贫血患者接受左卡尼汀与重组人促红素注射液联合治疗,可获得较好的效果,改善贫血相关生化指标水平,且不良反应发生率低,安全有效。     

Interrelationships between Cellular Density,Mosaic Patterning,and Dendritic Coverage of VGluT3 Amacrine Cells

Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.     

Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

Idarucizumab for Intravenous Thrombolysis and Endovascular Thrombectomy in Acute Stroke: A Case Report

BackgroundNon–vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran, are widely used to prevent ischemic stroke in patients with nonvalvular atrial fibrillation. Nonetheless, stroke occurs in 1–2% of patients, and the use of NOACs may increase the bleeding risk for patients who are receiving acute treatment of intravenous thrombolysis (IVT) or endovascular thrombectomy (EVT). Idarucizumab, a monoclonal antibody developed to bind dabigatran, has been proven safe and effective for patients with uncontrolled bleeding or for patients planning to receive emergent procedures. It is now accepted that patients taking dabigatran with recurrent stroke may benefit from IVT after idarucizumab. However, there are limited data regarding idarucizumab use in patients planning to have EVT.Case ReportWe present the case of a male patient taking dabigatran who had a stroke and who was treated with idarucizumab followed by combined IVT and EVT. The patient had immediate recanalization of the occluded vessel and near total recovery of function after 3 months.Why Should an Emergency Physician be Aware of This?Our case report supports the evidence that patients presenting with acute ischemic stroke (AIS) despite being under dabigatran therapy should be evaluated for reversal by idarucizumab which can contribute to the eligibility for IVT as well as EVT. It has also been proved to provide better outcomes for patients with AIS. The availabilities of specific reversal agents for NOACs will probably alter the current management of patients with AIS.     

Evaluation of the efficacy and safety of home treatment with the recombinant human C1-inhibitor in hereditary angioedema resulting from C1-inhibitor deficiency

ObjectiveConestat alpha, a C1-inhibitor produced by recombinant technology (rhC1-INH) is an acute treatment for edematous attacks occurring in hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE). Our study evaluated the efficacy and safety of rhC1-INH administered during HAE attacks, and for short-term prophylaxis (STP).Materials & methodOur prospective study analyzed the course of 544 HAE attacks experienced by the 21 C1-INH-HAE patients treated, as well as the outcome of 97 instances of STP implemented with rhC1-INH. Using a purpose-designed questionnaire, the patients recorded relevant, treatment-related information.ResultsTime to the administration of rhC1-INH was 90.0 min (median) after the onset of HAE attacks. The symptoms started to improve as early as 60 min after the injection of rhC1-INH, and the attack resolved 730.0 min after treatment. The interval between the onset of the HAE attack and the administration of rhC1-INH correlated with time until the onset of improvement (R = 0.2053 p < 0.0001), and with time to the complete resolution of symptoms (R = 0.2805, p < 0.0001). Nine patients received STP with rhC1-INH in 97 instances. STP successfully prevented the HAE attack within 72 h of the event on 93/97 occasions. No local and serious systemic adverse events/effects were observed.ConclusionsTreatment with rhC1-INH is effective and safe both for acute management, and for STP. Following the onset of an HAE attack, early administration of rhC1-INH may reduce time to the improvement and to the complete resolution of symptoms. Repeated administration of rhC1-INH does not impair its efficacy.     

Adjuvant Systems for vaccines: 13 years of post-licensure experience in diverse populations have progressed the way adjuvanted vaccine safety is investigated and understood

Adjuvant Systems (AS) are combinations of immune stimulants that enhance the immune response to vaccine antigens. The first vaccine containing an AS (AS04) was licensed in 2005. As of 2018, several vaccines containing AS04, AS03 or AS01 have been licensed or approved by regulatory authorities in some countries, and included in vaccination programs. These vaccines target diverse viral and parasitic diseases (hepatitis B, human papillomavirus, malaria, herpes zoster, and (pre)pandemic influenza), and were developed for widely different target populations (e.g. individuals with renal impairment, girls and young women, infants and children living in Africa, adults 50 years of age and older, and the general population). Clearly, the safety profile of one vaccine in one target population cannot be extrapolated to another vaccine or to another target population, even for vaccines containing the same adjuvant. Therefore, the assessment of adjuvant safety poses specific challenges. In this review we provide a historical perspective on how AS were developed from the angle of the challenges encountered on safety evaluation during clinical development and after licensure, and illustrate how these challenges have been met to date. Methods to evaluate safety of adjuvants have evolved based on the availability of new technologies allowing a better understanding of their mode of action, and new ways of collecting and assessing safety information. Since 2005, safety experience with AS has accumulated with their use in diverse vaccines and in markedly different populations, in national immunization programs, and in a pandemic setting. Thirteen years of experience using antigens combined with AS attest to their acceptable safety profile. Methods developed to assess the safety of vaccines containing AS have progressed the way we understand and investigate vaccine safety, and have helped set new standards that will guide and support new candidate vaccine development, particularly those using new adjuvants.Focus on the patientWhat is the context? Adjuvants are immunostimulants used to modulate and enhance the immune response induced by vaccination. Since the 1990s, adjuvantation has moved toward combining several immunostimulants in the form of Adjuvant System(s) (AS), rather than relying on a single immunostimulant. AS have enabled the development of new vaccines targeting diseases and/or populations with special challenges that were previously not feasible using classical vaccine technology.What is new? In the last 13 years, several AS-containing vaccines have been studied targeting different diseases and populations. Over this period, overall vaccine safety has been monitored and real-life safety profiles have been assessed following routine use in the general population in many countries. Moreover, new methods for safety assessment, such as a better determination of the mode of action, have been implemented in order to help understand the safety characteristics of AS-containing vaccines.What is the impact? New standards and safety experience accumulated over the last decade can guide and help support the safety assessment of new candidate vaccines during development.     

Protection of White Leghorn chickens by recombinant fowlpox vector vaccine with an updated H5 insert against Mexican H5N2 avian influenza viruses

Despite decades of vaccination, surveillance, and biosecurity measures, H5N2 low pathogenicity avian influenza (LPAI) virus infections continue in Mexico and neighboring countries. One explanation for tenacity of H5N2 LPAI in Mexico is the antigenic divergence of circulating field viruses compared to licensed vaccines due to antigenic drift. Our phylogenetic analysis indicates that the H5N2 LPAI viruses circulating in Mexico and neighboring countries since 1994 have undergone antigenic drift away from vaccine seed strains. Here we evaluated the efficacy of a new recombinant fowlpox virus vector containing an updated H5 insert (rFPV-H5/2016), more relevant to the current strains circulating in Mexico. We tested the vaccine efficacy against a closely related subcluster 4 Mexican H5N2 LPAI (2010 H5/LP) virus and the historic H5N2 HPAI (1995 H5/HP) virus in White Leghorn chickens. The rFPV-H5/2016 vaccine provided hemagglutinin inhibition (HI) titers pre-challenge against viral antigens from both challenge viruses in almost 100% of the immunized birds, with no differences in number of birds seroconverting or HI titers among all tested doses (1.5, 2.0, and 3.1 log₁₀ mean tissue culture infectious doses/bird). The vaccine conferred 100% clinical protection and a significant decrease in oral and cloacal virus shedding from 1995 H5/HP virus challenged birds when compared to the sham controls at all tested doses. Virus shedding titers from vaccinated 2010 H5/LP virus challenged birds significantly decreased compared to sham birds especially at earlier time points. Our results confirm the efficacy of the new rFPV-H5/2016 against antigenic drift of LPAI virus in Mexico and suggest that this vaccine would be a good candidate, likely as a primer in a prime-boost vaccination program.