General vaccination willingness and current vaccination status in relation to clinical and psychological variables in patients with multiple sclerosis

BackgroundInfections can have a significant impact on morbidity and mortality in multiple sclerosis (MS) patients. Therefore, vaccinations are of immense importance. If vaccination willingness is to be increased, possible influencing factors should be identified. The aim of the present study was to investigate the status of active immunisation in MS patients in association with sociodemographic, clinical-neurological, psychopathological and personality variables using the NEO-Five Factor Inventory, the Temperament and Character Inventory-Revised and the Hospital Anxiety and Depression Scale.MethodFour hundred and four MS patients from two German neurological hospitals were examined for their vaccination attitudes, in detail, the general willingness to vaccinate and the current vaccination status of mumps, measles and rubella (MMR) as well as tetanus and influenza. We also looked at the current level of disability in relation to the current vaccination status, as well as possible associated personality and psychopathological variables.ResultsPatients with a complete MMR vaccination status were significantly younger and those with a complete influenza vaccination status were significantly older than those with related incomplete vaccination status. Tetanus vaccination status completeness did not differ depending on age and did not show substantial association with personality scores. However, influenza vaccination completeness was associated with differences in personality and psychopathological variables; extraversion, openness, novelty seeking, harm avoidance and anxiety. A reported general vaccination willingness was significantly correlated with the current completeness of tetanus and influenza vaccinations. Novelty seeking, persistence, extraversion, agreeableness, conscientiousness and neuroticism were found associated with an increased vaccination willingness. Anxiety and depression were not related to general vaccination willingness.ConclusionsNo specific personality trait could be defined on its own in relation to general vaccination willingness or complete vaccination status. Younger patients should be made more aware of influenza vaccination. Reasons for rather low vaccination rates need to be further investigated.     

Hepatitis B and circadian rhythm of the liver

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.     

Management of immune-related adverse events resulting from immune checkpoint blockade

Introduction: Immune checkpoint inhibitors (ICI) are now a standard of care in the treatment of many cancers leading to durable responses in patients with metastatic disease. These agents are generally well tolerated but may lead to the occurrence of immune-related adverse events (irAEs). As any organ may be affected, clinicians should be aware of the broad range of clinical manifestations and symptoms and keep in mind that toxicities may occur late, at any point along a patient’s treatment course. Although the most common irAEs are rarely severe, some of them may be associated with great morbidity and even become life-threatening. The rate of occurrence, type and severity of irAEs may vary with the type of ICI; thus, grade 3 and 4 irAEs are reported in more than 55% of patients treated with the combination of ipilimumab 3 mg/kg and nivolumab 1 mg/kg.

Area covered: This review presents the management of irAEs resulting from checkpoint blockade, with a focus on rare irAEs.

Expert commentary: With the development of immuno-oncology and the expanding role of ICI, physicians have learnt to diagnose and treat most of the irAEs that can occur. This review provides an overview of current guidelines, previously published studies and our multidisciplinary team based practices.     

Does frequent residential mobility in early years affect the uptake and timeliness of routine immunisations? An anonymised cohort study

BackgroundThere are conflicting findings regarding the impact of residential mobility on immunisation status. Our aim was to determine whether there was any association between residential mobility and take up of immunisations and whether they were delayed in administration.MethodsWe carried out a cohort analysis of children born in Wales, UK. Uptake and time of immunisation were collected electronically. We defined frequent movers as those who had moved: 2 or more times in the period prior to the final scheduled on-time date (4 months) for 5 in 1 vaccinations; and 3 or more times in the period prior to the final scheduled on-time date (12 months) for MMR, pneumococcal and meningitis C vaccinations. We defined immunisations due at 2–4 months delayed if they had not been given by age 1; and those due at 12–13 months as delayed if they had not been given by age 2.ResultsUptake rates of routine immunisations and whether they were given within the specified timeframe were high for both groups. There was no increased risk (odds ratios (95% confidence intervals) between frequent movers compared to non-movers for the uptake of: primary MMR 1.08 (0.88–1.32); booster Meningitis C 1.65 (0.93–2.92); booster pneumococcal 1.60 (0.59–4.31); primary 5 in 1 1.28 (0.92–1.78); and timeliness: primary MMR 0.92 (0.79–1.07); booster Meningitis C 1.26 (0.77–2.07); booster pneumococcal 1.69 (0.23–12.14); and primary 5 in 1 1.04 (0.88–1.23).DiscussionFindings suggest that children who move home frequently are not adversely affected in terms of the uptake of immunisations and whether they were given within a specified timeframe. Both were high and may reflect proactive behaviour in the primary healthcare setting to meet Government coverage rates for immunisation.     

Papillary thyroid carcinoma with a high tumor mutation burden has a poor prognosis

BackgroundTumor mutation burden (TMB) as a prognostic marker for immunotherapy has shown prognostic value in many cancers. However, there is no systematic investigation on TMB in papillary thyroid carcinoma (PTC).MethodsBased on the somatic mutation data of 487 PTC patients from The Cancer Genome Atlas (TCGA), TMB was calculated, and we classified the samples into high-TMB (H-TMB) and low-TMB (L-TMB) groups. Bioinformatics methods were used to explore the characteristics and potential mechanism of TMB in PTC.ResultsHigh TMB predicts shorter progression-free survival (PFS) (P < 0.001). TMB was positively correlated with age, stage, tumor size, metastasis, the male sex and tall cell PTC. Compared to the L-TMB group, the H-TMB group presented with lower immune cell infiltration, a higher proportion of tumor-promoting immune cells (M0 macrophages, activated dendritic cells and monocytes) and a lower proportion of antitumor immune cells (M1 macrophages, CD8⁺ T cells and B cells). Additionally, the characteristics displayed by different TMB groups were not driven by critical driver mutations such as BRAF and RAS.ConclusionsPTC patients with high TMB have a worse prognosis. By stratifying PTC patients according to their TMB, advanced PTC patients who are candidates for immunotherapy could be selected.     

中医健康状态辨识模式的研究现状与展望

健康状态的辨识是把握健康的前提。当前学界已存在专家辨识模式、标准辨识模式、数字辨识模式、智能辨识模式以及微观辨识模式等。联合多种辨识方法,构建健康状态辨识体系,形成常态与动态结合、主观与客观结合、人机互参的中医健康状态个体化辨识方法是研究的趋势所在。文章对未来的研究方向进行展望,探讨了多元辨识模式、远程辨识模式、终身辨识模式、自动辨识模式的思路方法,以期促进全民健康事业,助力"健康中国"战略。     

Interferon-induced Transmembrane Protein 3 Prevents Acute Influenza Pathogenesis in Mice

Objective Interferon-induced transmembrane protein 3(IFITM3) is an important member of the IFITM family. However, the molecular mechanisms underlying its antiviral action have not been completely elucidated. Recent studies on IFITM3, particularly those focused on innate antiviral defense mechanisms, have shown that IFITM3 affects the body's adaptive immune response. The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo.Methods We performed proteomics, flow cytometry, and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer(NK) cell numbers, their activation, and their immune function in the lungs of Ifitm3-/-and wild-type mice.Results Ifitm3-/-mice developed more severe inflammation and apoptotic responses compared to wild-type mice. Moreover, the NK cell activation was higher in the lungs of Ifitm3-/-mice during acute influenza infection.Conclusions Based on our results, we speculate that the NK cells are more readily activated in the absence of IFITM3, increasing mortality in Ifitm3-/-mice.     

罗伊氏乳杆菌对轮状病毒感染肠炎患儿免疫功能与肠道菌群及临床疗效的影响

目的探究罗伊氏乳杆菌DSM 17938在治疗轮状病毒感染肠炎患儿中的疗效及对免疫功能、肠道菌群的影响。方法收集于2018年2月-2019年2月在阳光融和医院进行诊治的轮状病毒感染肠炎患儿126例,随机分为试验组(63例)和对照组(63例)。对照组给予常规补液治疗及蒙脱石散和枯草杆菌二联活菌口服治疗,试验组采用常规补液治疗及蒙脱石散和罗伊氏乳杆菌DSM 17938辅助治疗。观察两组患儿的腹泻改善情况,并分析对免疫功能(IgG、IgA、CD4^+/CD8^+水平)及肠道菌群失调的影响。结果在治疗72 h后,试验组患儿的治疗总有效率为92.06%,高于对照组的74.60%(P=0.009);且治疗后两组患儿的IgG、IgA、CD4^+/CD8^+水平均较治疗前有升高(P<0.05),且试验组水平高于对照组(P<0.05)。对患儿肠道菌群进行分析,在治疗1周后,试验组患儿肠道菌群失调程度低于对照组,且试验组的肠道菌群正常比例高于对照组(P<0.05)。结论罗伊氏乳杆菌DSM 17938对于辅助治疗轮状病毒感染肠炎患儿具有良好的疗效,能够提高患儿免疫力,改善肠道菌群失调,减轻患儿腹泻症状,具有一定的临床应用价值。