Upfront use of eculizumab to treat early acute antibody-mediated rejection after kidney allotransplantation and relevance for xenotransplantation

Acute antibody-mediated rejection (AMR) early after transplant remains a challenge, both in allotransplantation and in xenotransplantation. We report the case of an early and severe acute AMR episode in a kidney transplant recipient that was successfully treated with upfront eculizumab. A 58-year-old woman had been on dialysis since 2014. She underwent a first kidney transplant in 2018 with primary non-function and received several blood transfusions. Postoperatively, she developed anti-HLA antibodies. One year later, she received a second allograft from a deceased donor. At day 0, there was only one preformed low-level donor-specific antibody (DSA) anti-DQ7. After initial excellent allograft function, serum creatinine increased on days 7-9, and this was associated with oligo-anuria. On day 7, there was an increase in her DSA anti-DQ7 and 4 de novo DSA had developed at high MFI values. Allograft biopsy showed severe active AMR with diffuse C4d deposits in peritubular capillaries. The early acute AMR episode was treated with upfront eculizumab administration (2 doses) with efficient CH50 blockade (< 10% CH50). Rituximab was also administered on day 12, and intravenous immunoglobulin (IVIG) was given over the following days. There was an excellent clinical response to eculizumab administration. Eculizumab administration rapidly reversed the acute AMR episode without the need for plasmapheresis. Rituximab and IVIG were also used as B-cell immunomodulators to decrease DSA. Blocking efficiently the terminal complement pathway may become a useful strategy to treat acute AMR in sensitized recipients of allografts, and possibly in recipients of discordant xenografts.     

Quadritherapy vs standard tritherapy immunosuppressant regimen after heart transplantation: A propensity score–matched cohort analysis

After heart transplant, adding everolimus (EVL) to standard immunosuppressive regimen mostly relies on converting calcineurin inhibitors (CNIs) into EVL. The aim of this study was to describe the effects of combining low‐dose EVL and CNIs in maintenance immunosuppression regimen (quadritherapy) and compare it with standard tritherapy associating standard‐dose CNIs, mycophenolate mofetil, and corticosteroids. In the 3‐year registry cohort of heart transplanted patients, those who received quadritherapy were compared with those who received tritherapy. EVL was added after 3 months posttransplant. Three analyses were performed to control for confounders: propensity score matching, multivariable survival, and inverse probability score weighting analyses. Among 213 patients who were included (75 with quadritherapy), propensity score matching selected 64 unique pairs of patients with similar characteristics. In the matched cohort (n = 128), quadritherapy was associated with fewer deaths (3 [4.7%] vs 17 [21.9%], P = .007) and biopsy‐proven acute rejections (15 [23.4%] vs 31 [48.4%], P = .002). These results were confirmed in the overall cohort (n = 213), after multivariable and inverse probability score weighting analyses. Renal function and donor‐specific HLA‐antibodies remained similar in both groups. Low‐dose combination quadritherapy was associated with fewer deaths and rejections, compared with standard immunosuppression tritherapy.     

Decision-making,cognition, and aphasia: developing a foundation for future discussions and inquiry

Background: Making a decision is a cognitive task that requires the use of cognitive functions such as attention, memory, language, and executive function. Researchers have found people with cognitive deficits perform worse than healthy controls on experimental measures of decision-making. Researchers have also shown that persons with aphasia (PWA) may have deficits in the cognitive functions implicated in rational decision-making.

Aims: In this paper, we will discuss the cognitive processes associated with decision-making by examining decision-making abilities in populations with cognitive deficits. Then we will discuss cognitive functions within the dual-process theory of decision-making, and describe the way(s) in which these processes may be impaired in PWA. We will also present a theoretical model of cognitive processes involved in decision-making and discuss the potential clinical implications of cognitive impairments on decision-making in PWA.

Main contribution: This paper provides a theoretical foundation to support future discussions and investigations of decision-making in PWA.

Conclusions: Making a rational decision may be more challenging for PWA, given the possibility of concomitant cognitive impairments. Future research is needed to validate or refute the theoretical synthesis presented in this paper. This could be accomplished through a variety of qualitative, quantitative, and mixed-methods research studies.