Risk assessment in liver transplantation : the impact of donor organ quality on surgical and renal outcomes

Liver transplantation is the only life-saving treatment for patients with end-stage liver disease, but there has always been a disbalance between the number of patients on the waiting list and the availability of donor livers. The worsening organ shortage has led to an increased use of marginal grafts, including donation after circulatory death (DCD) grafts. The aim of this thesis was to analyse the impact of graft quality on the outcomes of patients undergoing liver transplantation, with a focus on surgical and renal outcomes. In Part I of this thesis we present the additional morbidity for recipients of DCD grafts with the novel Comprehensive Complication Index , identify prolonged hypoxia during DCD donation as the driving force of hepatic ischemia/reperfusion injury and present the new UK DCD Risk Score as a tool to assist the transplant surgeon in choosing the best DCD graft and recipient combination. This prediction model can also be used to assess which graft will require additional therapy before implantation, e.g. machine perfusion. The results presented in Part II of this thesis highlight the impact of DCD grafts and other marginal grafts on postoperative acute kidney injury (AKI). Duration of warm ischemia time and severe hypotension after reperfusion of the new liver are correlated with an increased risk to AKI. By combining donor, recipient and surgical risk factors, we developed a new model to predict the risk for postoperative AKI. This AKI Prediction Score can be helpful to assess if a recipient will benefit from renal-sparing immunosuppression. Additional analysis of long-term kidney function after liver transplantation showed that the use of marginal grafts is not directly associated with chronic kidney disease. However, severe AKI (requiring RRT) should be avoided at all costs, as those recipients have an increased risk for long-term renal impairment

Binocular Onset Rivalry at the Time of Saccades and Stimulus Jumps

Recent studies suggest that binocular rivalry at stimulus onset, so called onset rivalry, differs from rivalry during sustained viewing. These observations raise the interesting question whether there is a relation between onset rivalry and rivalry in the presence of eye movements. We therefore studied binocular rivalry when stimuli jumped from one visual hemifield to the other, either through a saccade or through a passive stimulus displacement, and we compared rivalry after such displacements with onset and sustained rivalry. We presented opponent motion, orthogonal gratings and face/house stimuli through a stereoscope. For all three stimulus types we found that subjects showed a strong preference for stimuli in one eye or one hemifield (Experiment 1), and that these subject-specific biases did not persist during sustained viewing (Experiment 2). These results confirm and extend previous findings obtained with gratings. The results from the main experiment (Experiment 3) showed that after a passive stimulus jump, switching probability was low when the preferred eye was dominant before a stimulus jump, but when the non-preferred eye was dominant beforehand, switching probability was comparatively high. The results thus showed that dominance after a stimulus jump was tightly related to eye dominance at stimulus onset. In the saccade condition, however, these subject-specific biases were systematically reduced, indicating that the influence of saccades can be understood from a systematic attenuation of the subjects' onset rivalry biases. Taken together, our findings demonstrate a relation between onset rivalry and rivalry after retinal shifts and involvement of extra-retinal signals in binocular rivalry

The Hip Fracture Surgery in Elderly Patients (HIPELD) study: protocol for a randomized, multicenter controlled trial evaluating the effect of xenon on postoperative delirium in older patients undergoing hip fracture surgery

BackgroundStrategies to protect the brain from postoperative delirium (POD) after hip fracture are urgently needed. The development of delirium often is associated with the loss of independence, poor functional recovery, and increased morbidity, as well as increases in length of hospital stay, discharges to nursing facilities, and healthcare costs. We hypothesize that xenon may reduce the burden of POD, (i) by avoiding the need to provide anesthesia with a drug that targets the γ-amino-butyric acid (GABA)A receptor and (ii) through beneficial anesthetic and organ-protective effects.Methods and designAn international, multicenter, phase 2, prospective, randomized, blinded, parallel group and controlled trial to evaluate the incidence of POD, diagnosed with the Confusion Assessment Method (CAM), in older patients undergoing hip fracture surgery under general anesthesia with xenon or sevoflurane, for a period of 4 days post surgery (primary outcome) is planned. Secondary objectives are to compare the incidence of POD between xenon and sevoflurane, to evaluate the incidence of POD from day 5 post surgery until discharge from hospital, to determine the time to first POD diagnosis, to evaluate the duration of POD, to evaluate the evolution of the physiological status of the patients in the postoperative period, to evaluate the recovery parameters, to collect preliminary data to evaluate the economical impact of POD in the postoperative period and to collect safety data. Patients are eligible if they are older aged (≥ 75 years) and assigned to a planned hip fracture surgery within 48 h after the hip fracture. Furthermore, patients need to be willing and able to complete the requirements of this study including the signature of the written informed consent. A total of 256 randomized patients in the 10 participating centers will be recruited, that is, 128 randomized patients in each of the 2 study groups (receiving either xenon or sevoflurane).Trial registrationEudraCT Identifier: 2009-017153-35; ClinicalTrials.gov Identifier: NCT0119927