BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR −4.8% [95% CI, −16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group. (Anesth Analg XXX;XXX:00-00) KEY POINTS• Question: Is it feasible to implement a bundle of supportive measures in high-risk patients undergoing cardiac surgery in a multinational setting? • Findings: In this multicenter randomized clinical trial, we found that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) bundle is feasible in a multinational setting and that these supportive measures significantly reduced the occurrence of moderate and severe acute kidney injury (AKI). • Meaning: The findings underpin the need for a definitive trial to evaluate whether the KDIGO bundle reduces the occurrence of AKI in high-risk patients after cardiac surgery.
BackgroundSimulation has become integral to the training of both undergraduate medical students and medical professionals. Due to the increasing degree of realism and range of features, the latest mannequins are referred to as high-fidelity simulators. Whether increased realism leads to a general improvement in trainees’ outcomes is currently controversial and there are few data on the effects of these simulators on participants’ personal confidence and self-assessment.MethodsOne-hundred-and-thirty-five fourth-year medical students were randomly allocated to participate in either a high- or a low-fidelity simulated Advanced Life Support training session. Theoretical knowledge and self-assessment pre- and post-tests were completed. Students’ performance in simulated scenarios was recorded and rated by experts.ResultsParticipants in both groups showed a significant improvement in theoretical knowledge in the post-test as compared to the pre-test, without significant intergroup differences. Performance, as assessed by video analysis, was comparable between groups, but, unexpectedly, the low-fidelity group had significantly better results in several sub-items. Irrespective of the findings, participants of the high-fidelity group considered themselves to be advantaged, solely based on their group allocation, compared with those in the low-fidelity group, at both pre- and post-self-assessments. Self-rated confidence regarding their individual performance was also significantly overrated.ConclusionThe use of high-fidelity simulation led to equal or even worse performance and growth in knowledge as compared to low-fidelity simulation, while also inducing undesirable effects such as overconfidence. Hence, in this study, it was not beneficial compared to low-fidelity, but rather proved to be an adverse learning tool.
Sodium chloride promotes vascular fibrosis, arterial hypertension, pro-inflammatory immune cell polarization and endothelial dysfunction, all of which might influence outcomes following stroke. But despite enormous translational relevance, the functional importance of sodium chloride in the pathophysiology of acute ischemic stroke is still unclear. In the current study, we show that high-salt diet leads to significantly worse functional outcomes, increased infarct volumes, and a loss of astrocytes and cortical neurons in acute ischemic stroke. While analyzing the underlying pathologic processes, we identified the migrasome as a novel, sodium chloride-driven pathomechanism in acute ischemic stroke. The migrasome was previously described in vitro as a migrating organelle, which incorporates and dispatches cytosol of surrounding cells and plays a role in intercellular signaling, whereas a pathophysiological meaning has not been elaborated. We here confirm previously reported characteristics of the migrasome in vivo. Immunohistochemistry, electron microscopy and proteomic analyses further demonstrate that the migrasome incorporates and dispatches cytosol of surrounding neurons following stroke. The clinical relevance of these findings is emphasized by neuropathological examinations, which detected migrasome formation in infarcted brain parenchyma of human stroke patients. In summary, we demonstrate that high-salt diet aggravates stroke outcomes, and we characterize the migrasome as a novel mechanism in acute stroke pathophysiology.
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