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.

Magnesium lithospermate B acts against dextran sodiumsulfate-induced ulcerative colitis by inhibiting activation of the NRLP3/ASC/Caspase-1 pathway

This study aimed to observe the therapeutic effects of magnesium lithospermate B on acute and chronic colitis induced by dextran sodiumsulfate (DSS) and the role of inflammasome complex (NOD-like receptor protein, NLRP; apoptosis-associated speck-like protein containing, ASC; caspase-1). Establishment of acute and chronic colitis models were by using 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (240 mg/kg body weight) was given by subcutaneous injection. Samples were collected for biomarker assay, histological examination, immunohistochemical evaluation and western blot. There was obvious increase in TNF-α level and NLPR3, ASC, and caspase-1 expressions in acute and chronic colitis groups compared with the normal control. Significant decrease of the tumor necrosis factor-α level and the expressions of NLPR3, ASC, and caspase-1 were observed after treatment with magnesium lithospermate B. This study showed that magnesium lithospermate B could be used to treat acute and chronic colitis by inhibiting the activation of the NLRP3/ASC/Caspase-1 pathway.     

Supplemental one-carbon metabolism related B vitamins and lung cancer risk in the Women's Health Initiative

We and others have reported associations between B vitamins principally involved in one-carbon metabolism and increased lung cancer risk; however, results for women have been inconsistent. Here we report on the association of supplemental vitamins B₆, folic acid and B₁₂ intake and lung cancer risk using data from the Women's Health Initiative (WHI) study of postmenopausal women. Between 1993 and 1998, 161,808 women were recruited to participate in the WHI at 40 clinical centers in the US. After exclusions, 159,232 women were available for analysis and followed prospectively for an average of 18.3 years. Among them, 3,836 incident lung cancer cases were diagnosed. At baseline, supplemental B vitamins from multivitamins, vitamin mixtures and individual supplements were assessed. Adjusted Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between supplemental B vitamin intake and lung cancer risk. Relative to no intake, women who took ≥50 mg/day of vitamin B₆ had 16% (HR 0.84, 95% CI: 0.71–0.99) reduced lung cancer risk. Associations did not differ significantly by smoking status or lung cancer histology. Intakes of folic acid and vitamin B₁₂ were not associated with risk. There is a need for replication of our findings from other large, prospective studies with similar high-quality measurement of supplement intakes before any recommendations can be made at present on B₆ supplementation for lung cancer prevention in women.     

Status of vaccine research and development of vaccines for herpes simplex virus

Herpes simplex virus type-1 (HSV-1) and -2 (HSV-2) are highly prevalent global pathogens which commonly cause recurrent oral and genital ulcerations. Less common but more serious complications include meningitis, encephalitis, neonatal infection, and keratitis. HSV-2 infection is a significant driver of the HIV epidemic, increasing the risk of HIV acquisition 3 fold. As current control strategies for genital HSV-2 infection, including antiviral therapy and condom use, are only partially effective, vaccines will be required to reduce infection. Both preventive and therapeutic vaccines for HSV-2 are being pursued and are in various stages of development. We will provide an overview of efforts to develop HSV-2 vaccines, including a discussion of the clinical need for an HSV vaccine, and status of research and development with an emphasis on recent insights from trials of vaccine candidates in clinical testing. In addition, we will touch upon aspects of HSV vaccine development relevant to low and middle income countries.     

Arachidonic acid-stimulated platelet tests: Identification of patients less sensitive to aspirin treatment

Serum thromboxane-B2 (TxB2), together with arachidonic acid (AA)-induced platelet aggregation, are, at the moment, the most used tests to identify patients displaying high on-aspirin treatment platelet reactivity (HAPR). Both tests are specific for aspirin action on cyclooxygenase-1. While the correlation between serum TxB2 assay and clinical outcome is established, data are conflicting with regard to aspirin treatment and a possible association with AA-stimulated platelet markers and clinical outcome. To understand such discrepancy, we performed a retrospective study to compare both assays. We collected data from 132 patients receiving a daily dose of aspirin (100?mg/day) and data from 48 patients receiving aspirin on alternate days. All Patients who received a daily dose of aspirin were studied for AA-induced platelet aggregation together with serum TxB2 levels and AA-induced TxB2 formation was also studied in 71 patients out of entire population. Consistent with recommendations in the literature, we defined HAPR by setting a cut-off point at 3.1?ng/ml for serum levels of thromboxane B2 and 20% for AA-induced platelet aggregation. According to this cut-off point, we divided our overall population into two groups: (1) TxB2?<?3.1?ng/ml and (2) TxB2?>?3.1?ng/ml. We found low agreement between such tests to identify patients displaying HAPR. Our results show that AA-induced platelet aggregation >20% identify a smaller number of HAPR patients in comparison with TxB2. A good correlation between serum TxB2 and arachidonic acid-induced TxB2 production was found (r?=?0.76619).     

Rotavirus,vaccine failure or diagnostic error?

Immunochromatography (ICG) is highly used in clinical settings for rotavirus (RV) diagnosis. The specificity of the tests differs by brand type and is not 100%, therefore its use when the prevalence of the disease is low (i.e. in vaccinated children) may result in a proportion of false positive diagnoses.In some areas, vaccine effectiveness studies or surveillance is done using ICG. Our objective was to estimate the validity of ICG test in vaccinated children, and estimate the number of false positive results in the Valencian Region of Spain, where all RV infections are diagnosed using ICG and are not confirmed by PCR.Population based registries were used to identify all results from the RV antigen tests performed between January 2008 and June 2012 in children under 37 months. Hospitalization and vaccination status of the patients were obtained by linking different databases through a unique identification number. The Positive Predictive Value of the ICG test depending on the vaccination status of the child, hospitalization and the rotavirus season was estimated by a Bayesian model of latent classes.Of the 48,833 tests with valid results, 9429 were done in vaccinated children, and of those 3963 (42%) during the rotavirus season. The prevalence of positive results in vaccinated varied from 2.9 to 21.4% of the tests depending on the hospitalization and seasonality. The estimated PPV also varied from 27.1 to 84.6% when stratified by these two parameters. Globally it is calculated that approximately 267 out of the 520 (51.3%) positives in vaccinated children were false positive tests.The large percentage of false positives, due to an excessive number of tests in vaccinated and out of the RV season, if interpreted as vaccine failures, can cause a loss of confidence in the vaccine and lower the estimates of vaccine effectiveness.     

细胞因子白细胞介素-4对认知功能改善的研究进展

白细胞介素4(IL-4)是T辅助2(Th2)介导的免疫反应的基本免疫调节细胞因子,IL-4具有复杂的信号系统和多效的功能,但在脑组织中,诸多研究发现IL-4可在炎症中保护认知功能。该文总结了关于IL-4保护认知功能的证据及机制,以及在阿尔茨海默病、缺血性脑血管病以及手术后认知功能障碍中IL-4保护认知功能的途径及证据。     

Dynamic Indicators That Impact the Outcomes of Thoracic Endovascular Aortic Repair in Complicated Type B Aortic Dissection

PurposeTo investigate dynamic variables obtained from retrospective computed tomography angiography for ability to predict thoracic endovascular aortic repair (TEVAR) outcomes in patients with complicated type B aortic dissection (cTBAD).Materials and MethodsSeventy-nine patients with cTBAD who received TEVAR from March 2009 to June 2018 were retrospectively enrolled. Relative true lumen area (r-TLA) was computed at the level of tracheal bifurcation every 5% of all R-R intervals. Parameters that reflect the state of intimal motion were evaluated, including difference between maximum and minimum r-TLA (D-TLA) and true lumen collapse. The endpoints comprised early (≤ 30 days) and late (> 30 days) outcomes after intervention.ResultsOverall early mortality rate was 13.9% (11/79), and early adverse events rate was 24.1% (19/79). Patients who received TEVAR within 2 days of symptom onset demonstrated the worst outcomes. A longer time of r-TLA < 25% in 1 cardiac cycle (P = .049) and larger D-TLA (P < .001) were correlated to an increased early death. In addition, D-TLA was an independent predictor of early mortality. Area under the curve of D-TLA was 0.849 (95% confidence interval 0.730–0.967) for predicting early mortality and 0.742 (95% CI 0.611–0.873) for predicting early adverse events. Survival and event-free survival rates during follow-up were decreased in the D-TLA > 21.5% group compared with the D-TLA ≤ 21.5% group (all P < .001).ConclusionsLarger D-TLA is correlated with worse postoperative outcomes and might be a crucial parameter for future risk stratification in patients with cTBAD.     

创伤后重型急性弥漫性脑肿胀临床治疗策略

目的 探讨重型创伤后急性弥漫性脑肿胀（PADBS）患者保守治疗与手术治疗的疗效。方法 分析 2016年1月—2019年12月该院神经外科收治的44例重型PADBS患者，根据治疗方式分为手术组和保守治疗组，统计入院时格拉斯哥昏迷量表（GCS）评分、头颅CT检查情况、伤后6个月格拉斯哥预后量表（GOS）评分等资料。结果 两组患者入院时年龄、性别及GCS评分比较，差异无统计学意义（P>0.05）。两组患者伤后6个月时GOS评分比较，差异无统计学意义（P>0.05），但两组住院时间比较，差异有统计学意义（P<0.05），手术组长于保守治疗组。结论 重型PADBS在无瞳孔变化及GCS评分下降的情况下，可密切观察病情下选择保守治疗。