Kidney transplantation remains the gold standard treatment for patients suffering from end-stage kidney disease. To meet the constantly growing organ demands grafts donated after circulatory death (DCD) or retrieved from extended criteria donors (ECD) are increasingly utilized. Not surprisingly, usage of those organs is challenging due to their susceptibility to ischemia-reperfusion injury, high immunogenicity, and demanding immune regulation after implantation. Lately, a lot of effort has been put into improvement of kidney preservation strategies. After demonstrating a definite advantage over static cold storage in reduction of delayed graft function rates in randomized-controlled clinical trials, hypothermic machine perfusion has already found its place in clinical practice of kidney transplantation. Nevertheless, an active investigation of perfusion variables, such as temperature (normothermic or subnormothermic), oxygen supply and perfusate composition, is already bringing evidence that ex-vivo machine perfusion has a potential not only to maintain kidney viability, but also serve as a platform for organ conditioning, targeted treatment and even improve its quality. Many different therapies, including pharmacological agents, gene therapy, mesenchymal stromal cells, or nanoparticles (NPs), have been successfully delivered directly to the kidney during ex-vivo machine perfusion in experimental models, making a big step toward achievement of two main goals in transplant surgery: minimization of graft ischemia-reperfusion injury and reduction of immunogenicity (or even reaching tolerance). In this comprehensive review current state of evidence regarding ex-vivo kidney machine perfusion and its capacity in kidney graft treatment is presented. Moreover, challenges in application of these novel techniques in clinical practice are discussed.

Background: Hypoxia-induced genes are potential targets in cancer therapy. Responses to hypoxia have been extensively studied in vitro, however, they may differ in vivo due to the specific tumor microenvironment. In this study gene expression profiles were obtained from fresh human lung cancer tissue fragments cultured ex vivo under different oxygen concentrations in order to study responses to hypoxia in a model that mimics human lung cancer in vivo. Methods: Non-small cell lung cancer (NSCLC) fragments from altogether 70 patients were maintained ex vivo in normoxia or hypoxia in short-term culture. Viability, apoptosis rates and tissue hypoxia were assessed. Gene expression profiles were studied using Affymetrix GeneChip 1.0 ST microarrays. Results: Apoptosis rates were comparable in normoxia and hypoxia despite different oxygenation levels, suggesting adaptation of tumor cells to hypoxia. Gene expression profiles in hypoxic compared to normoxic fragments largely overlapped with published hypoxia-signatures. While most of these genes were up-regulated by hypoxia also in NSCLC cell lines, membrane metallo-endopeptidase (MME, neprilysin, CD10) expression was not increased in hypoxia in NSCLC cell lines, but in carcinoma-associated fibroblasts isolated from non-small cell lung cancers. High MME expression was significantly associated with poor overall survival in 342 NSCLC patients in a meta-analysis of published microarray datasets. Conclusions: The novel ex vivo model allowed for the first time to analyze hypoxia-regulated gene expression in preserved human lung cancer tissue. Gene expression profiles in human hypoxic lung cancer tissue overlapped with hypoxia-signatures from cancer cell lines, however, the elastase MME was identified as a novel hypoxia-induced gene in lung cancer. Due to the lack of hypoxia effects on MME expression in NSCLC cell lines in contrast to carcinoma-associated fibroblasts, a direct up-regulation of stroma fibroblast MME expression under hypoxia might contribute to enhanced aggressiveness of hypoxic cancers.

Probiotics have been used in trials to therapeutically modulate the gut microbiome and have shown beneficial effects in cirrhosis. However, their effect on the microbiome of cirrhosis patients is not fully understood yet. Here, we tested the effects of a multispecies probiotic on microbiome composition in compensated cirrhosis. The gut microbiome composition of 58 patients with compensated cirrhosis from a randomized controlled trial who received a daily dose of multispecies probiotics or placebo for six months was analysed by 16S rRNA gene sequencing. Microbiome composition of patients who received probiotics was enriched with probiotic strains and the abundance of Faecalibacterium prausnitzii, Syntrophococcus sucromutans, Bacteroides vulgatus, Alistipes shahii and a Prevotella species was increased in the probiotic group compared to the placebo group. Patients who had microbiome changes in response to probiotic treatment also showed a significant increase in neopterin and a significant decrease in faecal zonulin levels after intervention, which was not observed in placebo-treated patients or patients with unchanged microbiome compositions. In conclusion, multispecies probiotics may enrich the microbiome of compensated cirrhotic patients with probiotic bacteria during a six-month intervention and beneficially change the residential microbiome and gut barrier function.

As organ shortage is increasing, the acceptance of marginal donors increases, which might result in poor organ function and patient survival. Mostly, organ damage is caused during brain death (BD), cold ischemic time (CIT) or after reperfusion due to oxidative stress or the induction of apoptosis. The aim of this study was to study a panel of genes involved in oxidative stress and apoptosis and compare these findings with immunohistochemistry from a BD and living donation (LD) pig model and after cold ischemia time (CIT).

Colorectal cancer (CRC) is the second most commonly diagnosed cancer in females (incidence 16.4/10,000) and the third in males (incidence 23.4/10,000) worldwide. Surgery, chemotherapy (CTx), radiation therapy (RTx), or a combined treatment of those are the current treatment modalities for primary CRC. Chemotherapeutic drug-induced gastrointestinal (GIT) toxicity mainly presents as mucositis and diarrhea. Preclinical studies revealed that probiotic supplementation helps prevent CTx-induced side effects by reducing oxidative stress and proinflammatory cytokine production and promoting crypt cell proliferation. Moreover, probiotics showed significant results in preventing the loss of body weight (BW) and reducing diarrhea. However, further clinical studies are needed to elucidate the exact doses and most promising combination of strains to reduce or prevent chemotherapy-induced side effects. The aim of this review is to overview currently available literature on the impact of probiotics on CTx-induced side effects in animal studies concerning CRC treatment and discuss the potential mechanisms based on experimental studies’ outcomes.

Background: A survey on the knowledge and attitudes towards the Austrian organ donation legislation (an opt-out solution) of selected groups of the Austrian population taking into account factors such as age, gender, level of education, affiliation to healthcare professions and health related studies was conducted. Methods: An online survey among 3 target groups (ICU nurses, health science students and non health science students) was performed and results were compared to the answers from transplantation patients to a paper questionnaire. A total of 8415 persons were asked to participate in the survey and 2025 (24%) persons correctly completed the questionnaire. 1945 online responses (ICU nurses n = 185; students of health sciences n = 1277; students of non-health science related courses n = 483) were analysed and data were compared to 80 manually filled-in responses from patients from a previous study. Results: 84% of participants state that they know the Austrian organ donation legislation; this percentage varies significantly (p < 0.05) within the target groups and is influenced by demographic variables of the participants. 74% think that the law is good and 79% do not favour a change. Opinions and attitudes towards the legal situation are positively influenced by the affiliation to healthcare professions and health-related fields of study. Interviewed persons who were aware of the legislation before the survey had a more positive attitude towards the existing legislation (77% versus 74%, p < 0.05). Conclusions: The information level on Austrian organ donation legislation is high. ICU nurses and those who did not know the law before were most critical towards the existing legislation. Therefore education to increase knowledge in the general population and goal-oriented efforts to increase awareness in the target groups should be emphasized.