Mapping host-related correlates of influenza vaccine-induced immune response: An umbrella review of the available systematic reviews and meta-analyses

Seasonal influenza is the leading infectious disease in terms of its health and socioeconomic impact. Annual immunization is the most efficient way to reduce this burden. Several correlates of influenza vaccine-induced protection are commonly used, owing to their ready availability and cheapness. Influenza vaccine-induced immunogenicity is a function of host-, virus-and vaccine-related factors. Host-related factors constitute the most heterogeneous group. The objective of this study was to analyze the available systematic evidence on the host factors able to modify influenza vaccine-induced immunogenicity. An umbrella review approach was undertaken. A total of 28 systematic reviews/meta-analyses were analyzed—these covered the following domains: intravenous drug use, psychological stress, acute and chronic physical exercise, genetic polymorphisms, use of pre-/pro-/symbiotics, previous Bacillus Calmette–Guérin vaccination, diabetes mellitus, vitamin D supplementation/deficiency, latent cytomegalovirus infection and various forms of immunosuppression. In order to present effect sizes on the same scale, all possible meta-analyses were re-performed and cumulative evidence synthesis ranking was carried out. The meta-analysis was conducted separately on each health condition category and virus (sub)type. A total of 97 pooled estimates were used in order to construct an evidence-based stakeholder-friendly map. The principal public health implications are discussed

Citizens' Attitudes, Knowledge, and Educational Needs in the Field of Omics Sciences: A Systematic Literature Review

Background: The huge development of omics sciences is changing the classical medical approach and making new technologies available. In this context, education of citizens is essential to allow appropriate decisions about their own health. Hence, we aimed to summarize existing literature regarding citizens' knowledge, attitudes, and educational needs on omics sciences. Methods: We performed a systematic literature review (SLR) using Pubmed, ISI Web of Science, and Embase databases. The eligibility criteria for inclusion in this review required that the studies investigated knowledge, attitudes, or educational needs regarding omics sciences among the general population. Results: We included 54 studies, published between 2006 and 2020. Most of the included studies (72%) investigated citizens' knowledge, half of them (56%) attitudes, and 20% educational needs in the field of omics sciences, while 52% investigated attitudes and perceptions about genetic and/or omics tests. Most studies (64%) reported a limited knowledge level among citizens, even though most (59%) reported participants understood the benefits of the use of omics sciences into medicine. As for omics tests, a controversial opinion toward their use into practice was reported among citizens. Most of the studies (82%) investigating citizens' educational needs highlighted a clear gap to be filled. Conclusions: Our SLR summarizes current knowledge on citizens' literacy, attitudes, and educational needs on omics science, underlining the need for strengthening public engagement on this topic. Further research is needed, however, to identify appropriate methods and models to achieve such an improvement

Immunogenicity measures of influenza vaccines: A study of 1164 registered clinical trials

Influenza carries an enormous burden each year. Annual influenza vaccination is the best means of reducing this burden. To be clinically effective, influenza vaccines must be immunogenic, and several immunological assays to test their immunogenicity have been developed. This study aimed to describe the patterns of use of the various immunological assays available to measure the influenza vaccine-induced adaptive immune response and to determine its correlates of protection. A total of 76.5% of the studies included in our analysis measured only the humoral immune response. Among these, the hemagglutination-inhibition assay was by far the most widely used. Other, less common, humoral immune response assays were: virus neutralization (21.7%), enzyme-linked immunosorbent (10.1%), single radial hemolysis (4.6%), and assays able to quantify anti-neuraminidase antibodies (1.7%). By contrast, cell-mediated immunity was quantified in only 23.5% of studies. Several variables were significantly associated with the use of single assays. Specifically, some influenza vaccine types (e.g., adjuvanted, live attenuated and cell culture-derived or recombinant), study phase and study sponsorship pattern were usually found to be statistically significant predictors. We discuss the principal findings and make some suggestions from the point of view of the various stakeholders

A Web Screening on Educational Initiatives to Increase Citizens’ Literacy on Genomics and Genetics

Introduction: Population awareness and empowerment in omics sciences represent a fundamental driver to increase the adoption of evidence-based approaches in personalized medicine. In this context, a pivotal role is played by citizens’ literacy, and educational initiatives carried out in this context are key assets to drive future effective interventions. With the present study, we summarized the educational initiatives conducted worldwide aimed at increasing citizens’ literacy in omics sciences. Materials and Methods: We conducted a web search of the educational initiatives aimed at improving citizens’ literacy in omics sciences undertaken worldwide, by using three search engines (Google, Bing, and Yahoo Search), in English and in Italian languages. Results: We identified five initiatives in Europe, 22 in non-European countries, and 13 in Italy. Overall, the majority (69%) were web-based initiatives, while 31% required in-person attendance. The online initiatives included web pages for reading, online lessons/courses, web portals, videos/short movies, animations, and apps for mobile devices. The residential initiatives, on the other hand, included exhibitions, seminars, courses, symposia, information stands in public places, guided visits to research laboratories, and interactive laboratories. All the initiatives were highly heterogeneous in terms of methodologies and the topics addressed. Discussion and Conclusion: Overall, we identified a variety of initiatives aimed at improving citizens’ literacy in omics sciences, with the largest majority carried out in the United States and being web-based. Our results showed heterogeneity among the initiatives as to the dealt topics and the adopted methods. Further research is needed, however, to quantitatively assess the effectiveness of educational initiatives to improve citizens’ literacy in omics sciences

[68Ga]Ga-DOTANOC Uptake at Pancreatic Head/Uncinate Process: Is It a Persistent Diagnostic Pitfall Over Time?

Simple Summary The purpose of the present study is to describe the frequency of non-malignant [68Ga]Ga-DOTANOC uncinate process (UP) uptake and to evaluate its variations over time. Among the first 6 months of enrolment of a monocentric prospective observational electronic archive, analyses of a large number of PET/CT scans (n = 268) of NEN pts (n = 172) demonstrated that: UP uptake is a frequent finding (observed in almost half of the cases, slightly higher than previously reported), mostly presenting with a diffuse pattern and, interestingly, characterized by variations over time in almost one third of the cases. The consciousness of this diagnostic pitfall is of utmost importance for accurate [68Ga]Ga-DOTANOC PET/CT reporting, since the pancreas represents one of the most frequent sites of NEN. Purpose: [68Ga]Ga-DOTA-peptide uptake in the pancreatic head/uncinate process (UP) is a frequent PET/CT finding. Although mostly physiologic, it can represent a pitfall in PET/CT reading, especially when focal. An increased frequency of UP uptake has been reported in patients (pts) affected by diabetes mellitus (DM). The aim of the study is to describe the frequency of [68Ga]Ga-DOTANOC UP uptake to evaluate its variations over time and its possible correlation with DM. Methods: In September 2017, a monocentric prospective observational electronic archive was initiated at our center to collect clinical and imaging data of pts undergoing [68Ga]Ga-DOTANOC PET/CT. Among the pts enrolled in the first 6 months (Sept 2017 to Feb 2018), those presenting [68Ga]Ga-DOTANOC PET/CT uptake at UP level were included. Pts with UP lesions already documented on CT/MRI or those that underwent surgical excision of UP before PET/CT were excluded from the analysis. [68Ga]Ga-DOTANOC UP uptake was classified as diffuse or focal and compared with the pattern observed in previous PET/CT scans performed at our center. An increased frequency of UP uptake was also correlated with the presence of DM. Results: In the first 6 months, 253 pts were enrolled in the archive and 172 out of them were included in the analysis. UP increased uptake was frequently observed (77/172, 44.8%) and was mostly diffuse (62/77). In 75/172 pts (43.6%), previous [68Ga]Ga-DOTANOC PET/CT scans were available (overall 268 scans; number of previous PET per pt range: 1-20) and were retrospectively reviewed. Despite the fact that, in most pts, the uptake pattern was stable over time (54/75 pts, 72%), it changed in approximately one third of cases (21/75, 28%). Among DM pts (29/172), only 10/29 (34.4%) presented increased UP uptake. Conclusions: UP [68Ga]Ga-DOTANOC uptake is a frequent non-malignant finding (slightly higher than previously reported), mostly presenting with a diffuse pattern. However, contrary to previous reports, our data show that the pattern of uptake may vary over time in approximately one third of the cases and it is not more frequently observed in pts with DM

Clinical and genetic characterization of patients with hypertrophic cardiomyopathy and right atrial enlargement

AIMS: Prevalence and clinical significance of right atrial enlargement (RAE) has been poorly characterized in hypertrophic cardiomyopathy. METHODS: One hundred and sixty consecutive patients with hypertrophic cardiomyopathy (35.5 ± 20 years; 64% men) were studied. They underwent clinical examination, standard ECG, M-mode, 2D and Doppler echocardiography, stress test and ECG Holter monitoring. Major adverse cardiac events were considered: cardiac death (sudden death, heart failure death); cardiac transplant; resuscitated cardiac arrest or appropriate implantable cardioverter defibrillator discharge. Genetic analysis of eight sarcomeric genes was performed using Sanger sequencing. RESULTS: RAE was observed in 22 patients (14%), associated with left atrial enlargement in all cases. Patients with RAE were likely to have restrictive mitral pattern (P < 0.001) and had higher New York Heart Association (P < 0.001), N-terminal prohormone of brain natriuretic peptide (P < 0.001), left atrial volume index (P < 0.001), lateral (P = 0.04) and septal (P = 0.002) E/e', systolic pulmonary artery pressure (P < 0.001) and lower ejection fraction (all P < 0.001). On cardiopulmonary exercise testing, peak VO2 was lower and VE/VCO2 higher in patients with RAE (P < 0.001). During a mean follow-up of 4 ± 2.1 years, 30 major adverse cardiac events in 24 patients (15%) were observed. Cox proportional hazards regression analysis identified RAE as an independent predictor of major adverse cardiac events (odds ratio = 2.6; confidence interval 1.5-4.6; P = 0.001). In patients with RAE who were genetically tested, there was a higher prevalence of sarcomeric gene mutations (68%), double mutations (16%) and troponin T mutations (21%). CONCLUSION: RAE is present in a small subset of patients with hypertrophic cardiomyopathy, and largely reflects increased pulmonary pressures because of severe diastolic and/or systolic left ventricular dysfunction. Patients with RAE had a higher prevalence of sarcomeric gene mutations, troponin T mutations and complex genotypes. In conclusion, RAE may serve as a very useful marker of disease progression and adverse outcome in patients with sarcomeric hypertrophic cardiomyopathy

Mapping host-related correlates of influenza vaccine-induced immune response: An umbrella review of the available systematic reviews and meta-analyses

Seasonal influenza is the leading infectious disease in terms of its health and socioeconomic impact. Annual immunization is the most efficient way to reduce this burden. Several correlates of influenza vaccine-induced protection are commonly used, owing to their ready availability and cheapness. Influenza vaccine-induced immunogenicity is a function of host-, virus-and vaccine-related factors. Host-related factors constitute the most heterogeneous group. The objective of this study was to analyze the available systematic evidence on the host factors able to modify influenza vaccine-induced immunogenicity. An umbrella review approach was undertaken. A total of 28 systematic reviews/meta-analyses were analyzed—these covered the following domains: intravenous drug use, psychological stress, acute and chronic physical exercise, genetic polymorphisms, use of pre-/pro-/symbiotics, previous Bacillus Calmette–Guérin vaccination, diabetes mellitus, vitamin D supplementation/deficiency, latent cytomegalovirus infection and various forms of immunosuppression. In order to present effect sizes on the same scale, all possible meta-analyses were re-performed and cumulative evidence synthesis ranking was carried out. The meta-analysis was conducted separately on each health condition category and virus (sub)type. A total of 97 pooled estimates were used in order to construct an evidence-based stakeholder-friendly map. The principal public health implications are discussed

HTA Training for Healthcare Professionals: International Overview of Initiatives Provided by HTA Agencies and Organizations

Background: Health Technology Assessment (HTA) is a multidisciplinary process that synthesizes, with a systematic, transparent, impartial and robust methodological approach, the main information on the medical, economic, ethical and social implications of the use and dissemination of a health technology. Its aim is to support decision-makers in identifying safe, effective, patient-centered and best-value health policies, in order to promote an equitable, efficient, and high-quality health system. Given the continued application of innovative technologies into clinical practice, healthcare professionals need to be able to adequately evaluate these technologies using evidence-based approaches such as HTA. Therefore, the implementation of training in HTA is crucial. The aim of this study was to investigate existing HTA training initiatives for healthcare professionals provided by international HTA agencies and organizations around the world. Methods: From March to November 2020, the websites of HTA agencies and organizations belonging to the European network for HTA (EUnetHTA) and to the International Network of Agencies for HTA (INAHTA), and the website of the HTA International (HTAi), were explored for identifying the HTA training initiatives directed to healthcare professionals. In addition, we screened the training initiatives proposed at European level by EUnetHTA as part of its Joint Actions and conducted in collaboration with its public-private partners. Specific keywords were searched in English and adapted to French, Portuguese, Spanish, Italian and German. Data extraction of the retrieved training initiatives was conducted from November 2020 to February 2021 and considered the following information: agency, country, website, coordinator, type of initiative, target, topic, main contents, and language. Results: Out of 124 agencies/organizations/EUnetHTA public-private partners screened, only 21 provided training initiatives for healthcare professionals. A total of 55 training initiatives were analyzed, 85.5% of which were delivered at the European level and 14.5% at the international level. The countries with a greater number of courses were: Austria, Argentina, Spain, Portugal, and the United Kingdom. Twenty-one training initiatives focused on HTA application and methodology while 34 on specific HTA domains, particularly on the economic one. The technologies covered were mainly drugs. Conclusions: Our study revealed a limited number of HTA training programs targeting healthcare professionals. HTA supports the decision-making processes concerning the use and application of health technologies with scientific evidence. Indeed, training of healthcare professionals in this field should be a key driver in implementing evidence-based healthcare choices and through rigorous methodological approaches such as HTA, in order to ensure proper health governance and value-based application of technological innovations in clinical practice. Therefore, capacity building of healthcare professionals in this area should be enhanced by using appropriate and effective training initiatives and educational strategies

Identification of Cdk8 and Cdkn2d as New Prame-Target Genes in 2C-like Embryonic Stem Cells

Embryonic stem cells (ESCs) present a characteristic pluripotency heterogeneity correspondent to specific metastates. We recently demonstrated that retinoic acid (RA) induces an increase in a specific 2C-like metastate marked by target genes specific to the two-cell embryo stage in preimplantation. Prame (Preferentially expressed antigen in melanoma) is one of the principal actors of the pluripotency stage with a specific role in RA responsiveness. Additionally, PRAME is overexpressed in a variety of cancers, but its molecular functions are poorly understood. To further investigate Prame’s downstream targets, we used a chromatin immunoprecipitation sequencing (ChIP-seq) assay in RA-enriched 2C-like metastates and identified two specific target genes, Cdk8 and Cdkn2d, bound by Prame. These two targets, involved in cancer dedifferentiation and pluripotency, have been further validated in RA-resistant ESCs. Here, we observed for the first time that Prame controls the Cdk8 and Cdkn2d genes in ESCs after RA treatment, shedding light on the regulatory network behind the establishment of naïve pluripotency