Twelve-hour normothermic liver perfusion in a rat model: characterization of the changes in the ex-situ bio-molecular phenotype and metabolism.

The partial understanding of the biological events that occur during normothermic machine perfusion (NMP) and particularly during prolonged perfusion might hinder its deployment in clinical transplantation. The aim of our study was to implement a rat model of prolonged NMP to characterize the bio-molecular phenotype and metabolism of the perfused organs. Livers (n = 5/group) were procured and underwent 4 h (NMP4h) or 12 h (NMP12h) NMP, respectively, using a perfusion fluid supplemented with an acellular oxygen carrier. Organs that were not exposed to any procedure served as controls (Native). All perfused organs met clinically derived viability criteria at the end of NMP. Factors related to stress-response and survival were increased after prolonged perfusion. No signs of oxidative damage were detected in both NMP groups. Evaluation of metabolite profiles showed preserved mitochondrial function, activation of Cori cycle, induction of lipolysis, acetogenesis and ketogenesis in livers exposed to 12 h-NMP. Increased concentrations of metabolites involved in glycogen synthesis, glucuronidation, bile acid conjugation, and antioxidant response were likewise observed. In conclusion, our NMP12h model was able to sustain liver viability and function, thereby deeply changing cell homeostasis to maintain a newly developed equilibrium. Our findings provide valuable information for the implementation of optimized protocols for prolonged NMP.

IMPACT OF A SARS-COV-2 INFECTION IN PATIENTS WITH CELIAC DISEASE

ObjectiveThe SARS-CoV-2 pandemic has spread across the world causing a dramatic number of infections and deaths. No data are available about the effects of an infection in patients affected by celiac disease (CD) in terms of the development of related symptoms and antibodies. We aimed to investigate the impact of the SARS-CoV-2 pandemic in celiac patients. DesignDuring a lockdown, the celiac patients living in the Milan area were contacted and interviewed about the development of COVID-19 symptoms as well as adherence to an anti-virus lifestyle and a gluten-free diet (GFD). They were also given a stress questionnaire to fill in. The development of anti-SARS-CoV-2 IgG and IgA (anti-RBD and N proteins) and the expression of the duodenal ACE2 receptor were investigated. When available, duodenal histology, anti-tissue transglutaminase IgA (tTGA), presence of immunologic comorbidities and adherence to the GFD were analysed as possible risk factors. Results362 celiac patients have been interviewed and 42 (11%) presented with COVID-19 symptoms. The presence of symptoms was not influenced by tTGA positivity, presence of duodenal atrophy or adherence to GFD. 37% of the symptomatic patients presented anti-SARS-CoV-2 immunoglobulins (Ig). Globally, 18% of celiac patients showed anti-SARS-CoV-2 Ig vs 25% of the non-celiac control (p=0.18). The values of anti-RBD IgG/IgA and anti-N IgG did not differ from the non-celiac controls. Celiac patients had a significant lower level of anti-N IgA. The ACE2 receptor was detected in the non-atrophic duodenal mucosa of celiac patients; atrophy was associated with a lower expression of the ACE2 receptor. ConclusionCD patients have an anti-SARS-CoV-2 Ig positiveness and profile similar to non-celiac controls, except for anti-N IgA. The main celiac parameters and adherence to the GFD do not influence the development of a different Ig profile. What is already known about this subject?The SARS-CoV-2 pandemic has spread across the world causing infections and deaths. little is known about the possible relationship between autoimmune comorbidities and SARS-CoV-2 infection and COVID-19, and nothing it known about celiac disease. What are the new findings?In a large cohort of celiac patients living in a high SARS-CoV-2 incidence area in Northern Italy, no difference was observed evidenced in terms of the development of anti-SARS-CoV-2 Ig and their IgG and IgA profile compared with the normal population How might it impact clinical practice in the foreseeable future?The absence of a relationship between celiac disease and SARS-CoV-2/COVID-19 has a relevant impact on health policy to control the pandemic by supporting an optimal resource location.