Predictive preventive personalized medicine Liver cancer is the fifth most common form of cancer worldwide [1], with an incidence rate almost equals the mortality rate and ranks 3 rd among causes of cancer related death [2]. The coexistence of two life threatening conditions, cancer and liver cirrhosis makes the staging challenging. However, there are some staging systems, e.g. the Barcelona staging system for Hepatocellular carcinoma (HCC) [3], that suggest treatment options and management. Whereas diagnosis in early stages gives hope for a curative outcome, the treatment regime for around 80 % [2] of the patients classified as severe stages only gears towards palliation [4]. An intra-arterial radiation approach, radioembolisation (RE) is ubiquitously applied as one of palliative approaches. Although, in general RE shows promising results in intermediate and advanced stage HCC [5], individual treatment outcomes are currently unpredictable. Corresponding stratification criteria are still unclear. We hypothesised that individual radioresistance/radiosensitivity may play a crucial role in treatment response towards RE strongly influencing individual outcomes. Further, HCC represents a highly heterogeneous group of patients which requires patient stratification according to clear criteria for treatment algorithms to be applied individually. Multilevel diagnostic approach (MLDA) is considered helpful to set-up optimal predictive and prognostic biomarker panel for individualised application of radioembolisation. Besides comprehensive medical imaging, our MLDA includes non-invasive multi-omics and sub-cellular imaging. Individual patient profiles are expected to give a clue to targeting shifted molecular pathways, individual RE susceptibility, treatment response. Hence, a dysregulation of the detoxification pathway (SOD2/Catalase) might indicate possible adverse effects of RE, and highly increased systemic activities of matrix metalloproteinases indicate an enhanced tumour aggressiveness and provide insights into molecular mechanisms/targets. Consequently, an optimal set-up of predictive and prognostic biomarker panels may lead to the changed treatment paradigm from untargeted "treat and wait" to the cost-effective predictive, preventive and personalised approach, improving the life quality and life expectancy of HCC patients. Keywords: Market access, Value, Strategy, Companion diagnostics, Cost-effectiveness, Reimbursement, Health technology assessment, Economic models, Predictive preventive personalized medicine Achieving and sustaining seamless "drug -companion diagnostic" market access requires a sound strategy throughout a product life cycle, which enables timely creation, substantiation and communication of value to key stakeholders [1, 2]. The study aims at understanding the root-cause of market access inefficiencies of companies by gazing at the "Rx-CDx" co-development process through the prism of "value", and developing a perfect co-development scenario based on the literature review and discussions with the ...

The current market of probiotic supplements is significantly growing although the quality and effectiveness of the commonly sold products are variable. Parameters such as the composition of each individual microbiota, strain specificity, production procedures, or storage can influence the potential positive outcome of probiotic supplements on consumers. The aim of this study was to determine changes of selected markers within the microbiota after 3 months treatment by the personalized probiotic supplement. Stool samples of 48 volunteers were analyzed by 16s ribsosomal RNA sequencing. The composition (selection of species, number of species used, and number of colony-forming units) of the probiotic mixture was designed based on the gut microbiota analysis and it was prepared for each patient separately. After 3 months of probiotic supplementation, a control sample was analyzed. Data confirmed a statistically significant increase in abundance of genera Lactobacillus and Bifidobacterium and phylum Actinobacteria. The overall number of species was also increased thus increasing the overall diversity of the microbiota, which is considered a marker of healthy gut microbiota.

The gut microbiota is being recognized as a factor with a significant influence on host physiology, health maintenance, and disease prevention. Distinct alterations of the gut microbiota are correlated with several chronic diseases. Currently, gut microbiota can be modulated by diet, probiotics, prebiotics, postbiotics, pharmabiotics, and fecal microbiota transplantation. An effective strategy in gut microbiota modulation is needed for the prevention and supportive treatment of chronic diseases. New and more effective approaches toward gut microbiota modulation are emerging, namely personalization and targeted modulation. The composition of novel products and treatments based on the individual gut microbiome, metabolome, strain specificity, and clinical data analysis can reveal and address specific changes to the diversity, composition, and function of gut microbiota. These analyses enable the development of personalized and targeted gut microbiota modulation, by the application of beneficial microorganisms, their consortia, their metabolites, and their effective combination.