Transplantation of autoimmune regulator-encoding bone marrow cells delays the onset of experimental autoimmune encephalomyelitis.

The autoimmune regulator (AIRE) promotes "promiscuous" expression of tissue-restricted antigens (TRA) in thymic medullary epithelial cells to facilitate thymic deletion of autoreactive T-cells. Here, we show that AIRE-deficient mice showed an earlier development of myelin oligonucleotide glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). To determine the outcome of ectopic Aire expression, we used a retroviral transduction system to over-express Aire in vitro, in cell lines and in bone marrow (BM). In the cell lines that included those of thymic medullary and dendritic cell origin, ectopically expressed Aire variably promoted expression of TRA including Mog and Ins2 (proII) autoantigens associated, respectively, with the autoimmune diseases multiple sclerosis and type 1 diabetes. BM chimeras generated from BM transduced with a retrovirus encoding Aire displayed elevated levels of Mog and Ins2 expression in thymus and spleen. Following induction of EAE with MOG(35-55), transplanted mice displayed significant delay in the onset of EAE compared with control mice. To our knowledge, this is the first example showing that in vivo ectopic expression of AIRE can modulate TRA expression and alter autoimmune disease development.

Association between frailty, cerebral oxygenation and adverse post-operative outcomes in elderly patients undergoing non-cardiac surgery: An observational pilot study.

BACKGROUND AND AIMS: Although both frailty and low cerebral oxygen saturation increase the risk of post-operative complications, their relationship is yet to be investigated. The purpose of this observational study was to investigate the association between frailty, intraoperative cerebral oxygen saturation and post-operative complications in elderly patients undergoing non-cardiac surgery. METHODS: After approval from the Institutional Review Board, 25 elderly patients (>65 years) undergoing non-cardiac major surgery were included in this study. Pre-operatively, all included patients were assessed for frailty and classified into frail and non-frail groups. All patients had routine intraoperative monitors, and a cerebral oximeter applied during anaesthesia. The 'intraoperative' anaesthesiologist and the post-operative study investigator were blinded to cerebral oximeter readings throughout the study. The incidence of significant intraoperative cerebral oxygen desaturation, adverse post-operative outcomes and length of hospital stay were compared. Statistical significance was defined as a value of P < 0.05. RESULTS: We found that the frail group had more intraoperative cerebral desaturation (odds ratio [OR] [95% confidence interval [CI]]: 1.75 [1.11-2.75]) and longer median (interquartile range) length of hospital stay compared to the non-frail group (13.5 days [8.75-27.5] and 8 days [6-11], respectively). Furthermore, in patients with a low-baseline cerebral oxygen saturation (<55%), intraoperative cerebral desaturation (OR [95% CI]: 2.10 [1.00-4.42]), adverse post-operative outcomes (OR [95% CI]: 1.80 [1.00-3.23]) and median (interquartile range) length of hospital stay (15 days [9-31.5] vs. 9 days [6.25-13.75], P = 0.04) were significantly higher compared to subjects with higher baseline (≥55%) cerebral oxygen saturation. CONCLUSIONS: Frail patients have more intraoperative cerebral desaturation and longer lengths of hospital stay compared to non-frail patients.