RESUMO
BACKGROUND: The increase of healthcare digitalization comes along with potential information security risks. Thus, the EU H2020 KONFIDO project aimed to provide a toolkit supporting secure cross-border health data exchange. METHODS: KONFIDO focused on the so-called "User Goals", while also identifying barriers and facilitators regarding eHealth acceptance. Key user scenarios were elaborated both in terms of threat analysis and legal challenges. Moreover, KONFIDO developed a toolkit aiming to enhance the security of OpenNCP, the reference implementation framework. RESULTS: The main project outcomes are highlighted and the "Lessons Learned," the technical challenges and the EU context are detailed. CONCLUSIONS: The main "Lessons Learned" are summarized and a set of recommendations is provided, presenting the position of the KONFIDO consortium toward a robust EU-wide health data exchange infrastructure. To this end, the lack of infrastructure and technical capacity is highlighted, legal and policy challenges are identified and the need to focus on usability and semantic interoperability is emphasized. Regarding technical issues, an emphasis on transparent and standards-based development processes is recommended, especially for landmark software projects. Finally, promoting mentality change and knowledge dissemination is also identified as key step toward the development of secure cross-border health data exchange services.
Assuntos
Telemedicina , Atenção à Saúde , HumanosRESUMO
To further our understanding about antigen involvement in mantle cell lymphoma (MCL), we analyzed the expression levels of activation-induced cytidine deaminase (AID), a key player in B-cell responses to antigen triggering, in 133 MCL cases; assessed the functionality of AID by evaluating in vivo class switch recombination in 52 MCL cases; and sought for indications of ongoing antigen interactions by exploring intraclonal diversification within 14 MCL cases. The AID full-length transcript and the most frequent splice variants (AID-ΔE4a, AID-ΔE) were detected in 128 (96.2%), 96 (72.2%), and 130 cases (97.7%), respectively. Higher AID full-length transcript levels were significantly associated (P < 0.001) with lack of somatic hypermutation within the clonotypic immunoglobulin heavy variable (IGHV) genes. Median AID transcript levels were higher in lymph node material compared to cases in which peripheral blood was analyzed, implying that clonal behavior is influenced by the microenvironment. Switched tumor-derived IGHV-IGHD-IGHJ transcripts were identified in 5 of 52 cases (9.6%), all of which displayed somatic hypermutation and AID-mRNA expression. Finally, although most cases exhibited low levels of intraclonal diversification, analysis of the mutational activity revealed a precise targeting of somatic hypermutation indicative of an active, ongoing interaction with antigen(s). Collectively, these findings strongly allude to antigen involvement in the natural history of MCL, further challenging the notion of antigen naivety.