Assessment of perioperative risk of elderly patients in cardiac surgery is demanding. Most of the commonly used cardiac surgery risk scores over–or u

Ischemia/reperfusion injury (IRI), an inherent component of transplantation, affects organ quality and transplant outcomes. Although the complexity of the pathophysiology is recognized, detailed mechanisms remain unclear, and strategies preventing the consequences of IRI have been challenging. Of critical significance appears to be the link between IRI, the initiation of innate immune responses, and the (potential) augmentation of adaptive immunity. An improved understanding of those complex mechanisms and interactions may pave the way for more effective treatment strategies.

Assessment of perioperative risk of elderly patients in cardiac surgery is difficult, and most of the common risk scores show over- or underestimation. Two frailty scores, the comprehensive assessment of frailty (CAF) score and the Frailty predicts death One yeaR after CArdiac Surgery Test (FORECAST), were developed as additional tools to estimate the preoperative mortality risk, taking into consideration the frailty status of elderly patients. Four hundred and fifty patients who were referred for elective cardiac surgery were included. All the patients were assessed with the CAF test and the FORECAST. Thirty-day and 1-year mortality were evaluated by telephone interview. Univariate and bivariate logistic regression were performed to test the predictive power of the tests on mortality. Correlation of the scores with age was calculated with Spearman ranks. Three commensurate groups were built for each of the frailty scores and the outcome was compared between the groups. All analyses were performed for Society of Thoracic Surgeons (STS) and European System for Cardiac Operative Risk Evaluation (EuroSCORE) accordingly. A total of 227 male and 223 female patients were included. Thirty-day mortality was 6.1%, and 1-year mortality was 13.3%. Logistic regression showed that both scores are able to predict 30-day as well as 1-year mortality. Bivariate logistic regression showed that both frailty scores give relevant additional information to the STS and EuroSCORE for the prediction of 1-year mortality. The frailty scores were only weakly correlated with age in contrast to STS and EuroSCORE and therefore can be used as indicator of the biological age of patients besides the numerical age. Survival up to 1 year was relevantly reduced in the group of patients with the higher frailty scores. CAF and FORECAST are additional tools to evaluate elderly patients adequately before elective cardiac surgery, and showed an association with short- and mid-term mortality independently of age.

Demographic changes are associated with a steady increase of older patients with end-stage organ failure in need for transplantation. As a result, the majority of transplant recipients are currently older than 50 years, and organs from elderly donors are more frequently used. Nevertheless, the benefit of transplantation in older patients is well recognized, whereas the most frequent causes of death among older recipients are potentially linked to side effects of their immunosuppressants. Immunosenescence is a physiological part of aging linked to higher rates of diabetes, bacterial infections, and malignancies representing the major causes of death in older patients. These age-related changes impact older transplant candidates and may have significant implications for an age-adapted immunosuppression. For instance, immunosenescence is linked to lower rates of acute rejections in older recipients, whereas the engraftment of older organs has been associated with higher rejection rates. Moreover, new-onset diabetes mellitus after transplantation is more frequent in the elderly, potentially related to corticosteroids, calcineurin inhibitors, and mechanistic target of rapamycin inhibitors. This review presents current knowledge for an age-adapted immunosuppression based on both, experimental and clinical studies in and beyond transplantation. Recommendations of maintenance and induction therapy may help to improve graft function and to design future clinical trials in the elderly.

CD4(+) T cells are involved in the development of autoimmunity, including multiple sclerosis (MS). Here we show that nicotinamide adenine dinucleotide (NAD(+)) blocks experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by inducing immune homeostasis through CD4(+)IFNγ(+)IL-10(+) T cells and reverses disease progression by restoring tissue integrity via remyelination and neuroregeneration. We show that NAD(+) regulates CD4(+) T-cell differentiation through tryptophan hydroxylase-1 (Tph1), independently of well-established transcription factors. In the presence of NAD(+), the frequency of T-bet(-/-) CD4(+)IFNγ(+) T cells was twofold higher than wild-type CD4(+) T cells cultured in conventional T helper 1 polarizing conditions. Our findings unravel a new pathway orchestrating CD4(+) T-cell differentiation and demonstrate that NAD(+) may serve as a powerful therapeutic agent for the treatment of autoimmune and other diseases.