Immune activation, immune senescence and levels of Epstein Barr Virus in kidney transplant patients: Impact of mTOR inhibitors

Abstract Post-transplant lymphoproliferative disorders (PTLD) represent a severe complication in transplanted patients and Epstein-Barr Virus (EBV) is the main driver. Besides immunodepression, immune activation/chronic inflammation play an important role in both virus reactivation and expansion of EBV-positive B cells. The aim of this study was to assess the impact of immunosuppressive strategies on factors involved in the PTLD's pathogenesis. 124 kidney transplanted patients were enrolled in this study: 71 were treated with mycophenolic acid (MPA) and 53 treated with mTOR inhibitor (mTORi), both in combination with different doses of calcineurin inhibitor. At the time of the transplant (T0), profile of inflammation/immune activation and immune senescence didn't differ between the two groups, but after one year of treatment (T1) markers were significantly higher in MPA-treated patients; their immunosenescence process was supported by the greater erosion of telomeres despite their younger age. Percentages of activated B cells and levels of EBV-DNA significantly increased in MPA-treated patients, and at T1 were significantly higher in MPA- than in mTORi-treated patients. Overall, these findings indicate that mTOR inhibitors constrain the inflammation/immune activation and senescence status, thus reducing the expansion of EBV-infected B cells and the risk of virus-associated PTLD in kidney transplant recipients

First World Consensus Conference on pancreas transplantation: Part II - recommendations.

Funder: Fondazione Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/100007368Funder: Tuscany Region, Italy; Id: http://dx.doi.org/10.13039/501100009888Funder: Pisa University Hospital, Pisa, ItalyFunder: University of Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/501100007514The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246

A DISCRETE CHOICE EXPERIMENT (DCE) ON PATIENTS' TIME AND RISK PREFERENCES IN KIDNEY TRANSPLANTATION: PATIENTS' AGE AND WILLINGNESS TO WAIT (WTW) FOR BETTER ORGANS

Background: WTW from the perspective of the patients themselves is unknown. We run a DCE to elicit patients’ preferences, namely their risk attitude and time discounting. Method: From April 2015–February 2017, 211 candidates (mean age 50 yrs) on the waiting list for kidney transplant were interviewed. 16 pairs of alternatives were proposed: alternative differs along 4 attributes, waiting time, graft survival, infectious risk, neoplastic risk. Time attribute has 4 levels (6, 12, 36, 60 months), survival 3 levels (10, 15, 20 years) and both risks 2 levels (standard/increased). A mixture logit model was used to retrieve individual WTW and compare the entire distribution of preferences by different age groups. Results : Older patients are willing to wait much less than younger candidates for extra year of graft survival. After age of 37, the effect of age on WTW for graft survival becomes negative. WTW for an extra year of graft survival is lower for females compared to males by about 1 month. The result is robust to a number of different model specifications. For standard infectious risk, females are willing to wait 8 months more compared to males. Having completed high school education compared to elementary education lowers WTW to avoid standard infectious risk by 7 months. No statistically significant difference in term of risk attitude among different age levels can be detected. Older patients have more heterogeneous preferences in terms of risk attitude than younger patients: for them the benefit of reducing waiting time and the potential cost of receiving an organ with augmented risk, are larger compared to the younger patients and this induces heterogeneity. Conclusions: Our experiment suggests that pre-emptive transplantation with ECD to elderly patients maximizes the efficiency of allocation in terms of overall years of graft survival for transplanted organs and the patients’ welfare

Population transitions and temperature change in Minas Gerais, Brazil: a multidimensional approach

Climate change will exacerbate the vulnerability of places and people around the world in the next decades, especially in less developed regions. In this paper, we investigate future scenarios of population vulnerability to climate change for the next 30 years in 66 regions of the state of Minas Gerais, Brazil. Based upon the Alkire & Foster Index, we integrate simulated and projected dimensions of population vulnerability into a Multidimensional Index, showing how scenarios of temperature change would affect each region's relative vulnerability in the future. Results suggest that economic and health dimensions are the highest contributors to increases in temperature-related vulnerability, with the poorest and agribusiness regions being the most impacted in decades to come