Normothermic regional perfusion in controlled DCD liver procurement: Outcomes of the Swedish national implementation protocol.

Liver transplantation using donors after controlled circulatory death (cDCD) is associated with poorer graft survival and increased incidence of non-anastomotic biliary strictures (NAS) compared to livers procured from brain dead donors (DBD). The use of Normothermic regional perfusion (NRP) during cDCD procurement may improve post-transplant outcome and reduce the incidence of NAS. In Sweden cDCD liver transplantation was introduced through a national pilot protocol with mandatory NRP. This study aims to evaluate the outcome of cDCD liver transplantation during the pilot period. Donor and recipient data were collected on all cDCD liver transplants during the pilot period between 2020 - December 2022. Outcome on NAS, patient- and graft survival, early allograft dysfunction, acute kidney injury, and comprehensive complication index was compared to a matched cohort of 28 patients transplanted with a DBD liver between 2018-2022. 18 patients were transplanted with a liver from a cDCD donor after using NRP. Mean functional warm ischemia time was 29±6 minutes. Mean lactate reduction during NRP was 8.7±2.4 mmol/L, end NRP perfusate ALT was 1.4±1 µkat/L. When comparing cDCD liver transplant recipients to DBD, no significant differences were observed in the incidence of NAS, patient and graft survival, comprehensive complication index, early allograft dysfunction, nor acute kidney injury. Study protocol MRCP in cDCD patients showed no signs of subclinical biliary strictures. Evaluation of the Swedish national pilot of cDCD liver transplantation with mandatory NRP shows comparable outcomes to a matched DBD cohort with 94.4 one-year patient and graft survival and no incidence of NAS within the first year.

Amaranthus caudatus extract inhibits the invasion of E. coli into uroepithelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Amaranthus caudatus is traditionally used to treat infections. Based on its traditional usage, we investigated the effect of A. caudatus on the bladder epithelial cells in the protection of E. coli infection. MATERIALS AND METHODS: The direct antimicrobial effects of A. caudatus on uropathogenic bacteria were investigated using minimum inhibitory concentration (MIC) assay. Bladder epithelial cell lines T24 and 5637 and uropathogenic E. coli strain #12 were used to investigate the effect of A. caudatus. Bacterial adhesion and invasion into bladder cells treated with A. caudatus was analyzed. Expression of uroplakin-1a (UPK1A), ß1 integrin (ITGB1), caveolin-1 (CAV1) and the antimicrobial peptides human ß defensin-2 (DEFB4A) and LL-37 (CAMP) was evaluated using RT-PCR. RESULTS: No direct antibacterial effect on E. coli or any of the tested uropathogenic strains was observed by A. caudatus. However, we demonstrated reduced mRNA expression of uroplakin-1a and caveolin-1, but not ß1 integrin after treatment of uroepithelial cells, mirrored by the decreased adhesion and invasion of E. coli. A. caudatus treatment did not induce increased gene expression of the antimicrobial peptides, LL-37 and human ß-defensin-2. CONCLUSIONS: Our results showed that A. caudatus has a protective role on bladder epithelial cells against uropathogenic E. coli infection by decreasing the bacterial adhesion and invasion, thereby preventing infection.

Lupinus mutabilis Edible Beans Protect against Bacterial Infection in Uroepithelial Cells.

Lupinus mutabilis is a South American herb with edible beans, known to reduce serum glucose levels in diabetic patients. Furthermore, L. mutabilis contains phytochemicals known to decrease bacterial load. Based on the increased urinary tract infections experienced among patients with diabetes, we investigated the effect of L. mutabilis on bladder epithelial cells in the protection of E. coli infection during normal and high glucose concentrations. We did not observe any direct antibacterial effect by L. mutabilis extract. Instead we observed an influence on the host cells, with indirect impact on bacteria and their possibility of causing infection. L. mutabilis extract decreased adhesion to bladder epithelial cells of uropathogenic bacteria, including drug-resistant strains. Moreover, uroplakin1a, involved in adhesion, was downregulated while the antimicrobial peptide RNase 7 was upregulated in L. mutabilis treated cells irrespectively of glucose concentration. This supports an early effect fighting bacteria. Additionally, L. mutabilis prevented bacterial biofilm formation, which is used by bacteria to evade the immune system and antibiotics. In summary, L. mutabilis protects against bacterial infection in uroepithelial cells by preventing adhesion through alteration of the cell surface, increasing antimicrobial peptide expression, and reducing biofilm formation. Together, this promotes bacterial clearance, suggesting that L. mutabilis as extract or as a dietary item can contribute to the prevention of urinary tract infections, which is of importance in an era of increasing antibiotic resistance.