Introduction: Translational science has gained prominence in medicine, but there is still much work to be done before scientific results are used optimally and incorporated into everyday health practice. As the main focus is still on generating new scientific data with financial resources primarily available for that purpose, other activities that are necessary in the transition from research to community benefit are considered less needy. The European Statistical Office of the European Commission has recently reported that 1.7 million people under 75 years of age died in Europe in 2016, with around 1.2 million of those deaths being avoidable through effective primary prevention and public health intervention. Therefore, Academia Europaea, one of the five Pan-European networks that form SAPEA (Science Advice for Policy by European Academies), a key element of the European Commission’s Scientific Advice Mechanism (SAM), has launched a project to develop a model to facilitate and accelerate the utilisation of scientific knowledge for public and community benefit. Methods: During the process, leaders in the field, including prominent basic and clinical researchers, editors-in-chief of high-impact journals publishing translational research articles, translational medicine (TM) centre leaders, media representatives, academics and university leaders, developed the TM cycle, a new model that we believe could significantly advance the development of TM. Results: This model focuses equally on the acquisition of new scientific results healthcare, understandable and digestible summation of results, and their communication to all participants. We have also renewed the definition in TM, identified challenges and recommended solutions. Conclusion: The authors, including senior officers of Academia Europaea, produced this document to serve as a basis for revising thinking on TM with the end result of enabling more efficient and cost-effective healthcare.

Antagonists of the transient receptor potential vanilloid-1 (TRPV1) channel alter body temperature (Tb) in laboratory animals and humans: most cause hyperthermia; some produce hypothermia; and yet others have no effect. TRPV1 can be activated by capsaicin (CAP), protons (low pH), and heat. First-generation (polymodal) TRPV1 antagonists potently block all three TRPV1 activation modes. Second-generation (mode-selective) TRPV1 antagonists potently block channel activation by CAP, but exert different effects (e.g., potentiation, no effect, or low-potency inhibition) in the proton mode, heat mode, or both. Based on our earlier studies in rats, only one mode of TRPV1 activation - by protons - is involved in thermoregulatory responses to TRPV1 antagonists. In rats, compounds that potently block, potentiate, or have no effect on proton activation cause hyperthermia, hypothermia, or no effect on Tb, respectively. A Tb response occurs when a TRPV1 antagonist blocks (in case of hyperthermia) or potentiates (hypothermia) the tonic TRPV1 activation by protons somewhere in the trunk, perhaps in muscles, and - via the acido-antithermogenic and acido-antivasoconstrictor reflexes - modulates thermogenesis and skin vasoconstriction. In this work, we used a mathematical model to analyze Tb data from human clinical trials of TRPV1 antagonists. The analysis suggests that, in humans, the hyperthermic effect depends on the antagonist's potency to block TRPV1 activation not only by protons, but also by heat, while the CAP activation mode is uninvolved. Whereas in rats TRPV1 drives thermoeffectors by mediating pH signals from the trunk, but not Tb signals, our analysis suggests that TRPV1 mediates both pH and thermal signals driving thermoregulation in humans. Hence, in humans (but not in rats), TRPV1 is likely to serve as a thermosensor of the thermoregulation system. We also conducted a meta-analysis of Tb data from human trials and found that polymodal TRPV1 antagonists (ABT-102, AZD1386, and V116517) increase Tb, whereas the mode-selective blocker NEO6860 does not. Several strategies of harnessing the thermoregulatory effects of TRPV1 antagonists in humans are discussed.

Unwarranted administration of antibiotics in acute pancreatitis presents a global challenge. The clinical reasoning behind the misuse is poorly understood. Our aim was to investigate current clinical practices and develop recommendations that guide clinicians in prescribing antibiotic treatment in acute pancreatitis. Four methods were used. 1) Systematic data collection was performed to summarize current evidence; 2) a retrospective questionnaire was developed to understand the current global clinical practice; 3) five years of prospectively collected data were analysed to identify the clinical parameters used by medical teams in the decision making process, and finally; 4) the UpToDate Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was applied to provide evidence based recommendations for healthcare professionals. The systematic literature search revealed no consensus on the start of AB therapy in patients with no bacterial culture test. Retrospective data collection on 9728 patients from 22 countries indicated a wide range (31-82%) of antibiotic use frequency in AP. Analysis of 56 variables from 962 patients showed that clinicians initiate antibiotic therapy based on increased WBC and/or elevated CRP, lipase and amylase levels. The above mentioned four laboratory parameters showed no association with infection in the early phase of acute pancreatitis. Instead, procalcitonin levels proved to be a better biomarker of early infection. Patients with suspected infection because of fever had no benefit from antibiotic therapy. The authors formulated four consensus statements to urge reduction of unjustified antibiotic treatment in acute pancreatitis and to use procalcitonin rather than WBC or CRP as biomarkers to guide decision-making.

Herbal products, especially Hypericum perforatum extracts, have been widely used as first-line treatments for mild to moderate depression. Recently, several randomized, controlled clinical trials have been conducted to evaluate the efficacy of another plant, saffron (Crocus sativus), in mild to moderate depression. We have carried out a literature review of currently available published randomized, controlled clinical trials to give an up-to-date evaluation of the efficacy of saffron in mild to moderate depression, compared to placebo or routinely used antidepressants. The meta-analysis is reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines using the PICO (patients, intervention, comparison, outcome) format and was conducted using the statistical programs Comprehensive Meta-analysis and RevMan. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for relevant studies. Only placebo or active controlled, randomized clinical studies involving patients suffering from mild to moderate depression and using pharmacological doses of saffron per os were included. Hedgesʼ g was used to calculate effect sizes. Risk of bias was assessed using the Cochrane Collaboration tool, and heterogeneity was tested by both performing the Cochranʼs Q test and calculating Higginsʼ I² indicator. Eleven randomized trials were included in the qualitative analysis, and nine were pooled for statistical analysis. According to the present meta-analysis, saffron has a significant effect on the severity of depression. Available data from randomized, controlled clinical trials support that saffron is significantly more effective than placebo (g = 0.891; 95% CI: 0.369 – 1.412, p = 0.001), and non-inferior to tested antidepressant drugs (g = − 0.246; 95% CI: − 0.495 – 0.004, p = 0.053).

Background: The role of artificial and bioartificial liver support systems in acute-on-chronic liver failure (ACLF) is still controversial. We aimed to perform the first network meta-analysis comparing and ranking different liver support systems and standard medical therapy (SMT) in patients with ACLF. Methods: The study protocol was registered with PROSPERO (CRD42020155850). A systematic search was conducted in five databases. We conducted a Bayesian network meta-analysis of randomized controlled trials assessing the effect of artificial or bioartificial liver support systems on survival in patients with ACLF. Ranking was performed by calculating the surface under cumulative ranking (SUCRA) curve values. The RoB2 tool and a modified GRADE approach were used for the assessment of the risk of bias and quality of evidence (QE). Results: In the quantitative synthesis 16 trials were included, using MARS®, Prometheus®, ELAD®, plasma exchange (PE) and BioLogic-DT®. Overall (OS) and transplant-free (TFS) survival were assessed at 1 and 3 months. PE significantly improved 3-month OS compared to SMT (RR 0.74, CrI: 0.6–0.94) and ranked first on the cumulative ranking curves for both OS outcomes (SUCRA: 86% at 3 months; 77% at 1 month) and 3-month TFS (SUCRA: 87%) and second after ELAD for 1-month TFS (SUCRA: 76%). Other comparisons did not reach statistical significance. QE was moderate for PE concerning 1-month OS and both TFS outcomes. Other results were of very low certainty. Conclusion: PE seems to be the best currently available liver support therapy in ACLF regarding 3-month OS. Based on the low QE, randomized trials are needed to confirm our findings for already existing options and to introduce new devices.

Patients with inflammatory bowel disease (IBD) are at risk of sarcopenia, which is associated with poor clinical outcomes. We conducted this study to assess whether sarcopenia predicts the need for surgery and postoperative complications in patients with IBD. We performed a systematic search of four electronic databases, last updated in March, 2019. Data from studies comparing rates of surgery and postoperative complications in sarcopenic IBD patients versus non-sarcopenic IBD patients were pooled with the random-effects models. We calculated the odds ratios (OR) with a 95% confidence interval (CI). Ten studies with a collective total of 885 IBD patients were included in our meta-analysis. Although the analysis of raw data did not reveal significant differences between the two groups with respect to the rate of surgery and postoperative complications (OR = 1.826; 95% CI 0.913–3.654; p = 0.089 and OR = 3.265; 95% CI 0.575–18.557; p = 0.182, respectively), the analysis of adjusted data identified sarcopenia as an independent predictor for both of the undesirable outcomes (OR = 2.655; 95% CI 1.121–6.336; p = 0.027 and OR = 6.097; 95% CI 1.756–21.175; p = 0.004, respectively). Thus, early detection of sarcopenia in patients with IBD is important to prevent undesirable outcomes.