Clinical Research Directory

SIRAKI 02 Posthoc Analysis.

Our randomized controlled trial with 343 patients requiring non emergent cardiac surgery with a prolonged expected cardiopulmonary bypass (CPB) time (\>90 minutes) demonstrated that the use of an extracorporeal blood purification (EBP) device (oXiris) connected to the CPB circuit during all surgery was associated with a decrease in the incidence of CSA-AKI within the first 7 days from surgery (nearly 12% reduction). The study was conducted in two university centres of the Barcelona metropolitan area between 2016 and 2022, randomising 343 patients (1:1) to receive either an EBP device connected to the CPB circuit or a standard strategy with CPB alone. First of all the rate of acute kidney disease (AKD) and chronic kidney disease (CKD) in the sutdy population has not been reported and we will analyse if there were differences between groups as other studies have suggested with different interventions. Concerning the intervention safety, no differences were observed in terms of intraoperative blood products (red blood cells, plasma and platelets) requirements between both groups. In order to improve knowledge about the safety of the technique it is very important to ensure that antibiotics levels in plasma during the time the adsorption device is connected to CPB, are not being modified by the intervention. Antibiotic prophylaxis during cardiac surgery is one of the cornerstones and has proved to effectively reduce perioperative infection especially concerning valve replacement procedures. In this sense, our two centres use the same strategy with cephalosporins (Cefazolin in Germans Trias Hospital and Cefuroxime in Bellvitge Hospital) with an early administration at the operating room (OR) before connecting patient to CPB and a late dose after removing CPB (3 hours after the first dose). We know from previous reports that the use of antibiotics during CRRT with oXiris is safe and normally does not require dose adjustments although no reports have been made of its use connected to CPB and antibiotics dosing. Completing the safety issues, heparin and protamine doses during surgery have been registered in the patient's electronic history and should be checked and transferred to a database that allows to adequately analyse potential differences between groups. Other studies performed in cardiac surgery with adsorption devices have reported safety issues with platelets consumption and heparin requirements during surgery. In our protocol, heparin was administered prior to CPB initiation either based on the patient's weight or using hemostasis management system (HMS) plus technology in order to minimise overdosing. Heparin was administered during all CPB time in order to maintain activated clotting time (ACT) over 500 seconds and based on HMS plus technology. Protamine for heparin reversal at CPB withdrawal was administered using both methods too. Protamine administration can be associated with hypotensive episodes. In our study, the decrease in CSA-AKI within the first 7 days from surgery achieved with the use of EBP connected to the CPB was more significant in CKD, DM, Low LVEF, Hypertension and non-obese patients. Whether this effect can be partially explained by the mild cytokines concentration differences observed in IL-8 and TNF-a at T1 (after removing clamp from surgery) and T2 (at ICU admission) has still not been evaluated. This reduction of inflammatory response syndrome (SIRS) during CPB time that could be related with the use of adsorption devices, should be also translated into a decrease of catecholamines and probably insulin requirements during surgery. A noteworthy point to consider is that although the use of propofol has been extended in cardiac surgery, little is known about the potential antiinflammatory effect it may have in patients. It is important to identify those patients who received propofol to control this potential bias in terms of antiinflammatory effect. Besides this objective it is also very important to ensure that no adsorption of propofol took place with the use of EBP, as previous studies have reported higher requirements of sedation drugs with the use of CRRT or other devices with adsorption properties. Finally, nearly 25% of the patients in the EBP group received ultrafiltration with doses that vary from 200 mL up to 3000 mL. We know from previous trials that ultrafiltration is clearly related with the removal of middle weight molecules which is presumably beneficial for patients with SIRS but that in specific scenarios this effect could be even detrimental for some patients. Whether the ultrafiltration performed in our study may have an effect in antibiotics, heparin, protamine, catecholamines, insulin or even propofol should be elucidated in order to settle the idoneous modality in which EBP should be performed when connected to CPB during cardiac surgery. All these outcomes will be assessed controled by gender and age.

The Potential Protective Effect of Using Muscle Relaxants During Electroporation Ablation (PFA)

The study aims to improve the safety of the electroporation ablation (PFA) procedure by using muscle relaxants to reduce skeletal muscle damage during the procedure. It will also assess myocardial damage to improve the procedure's quality and speed up recovery after the procedure.

Intermittent ADVOS vs. Hemodialysis in Non-intensive Care Patients With Liver Dysfunction

In the planned randomized controlled prospective pilot study, we aim to evaluate ADVOS compared with conventional hemodialysis regarding the elimination of protein-bound toxins in patients with therapy-refractory hepatorenal syndrome. The study will be performed in a regular non-ICU ward with a large experience in the use of the ADVOS therapy.

Kidney Precision Medicine Project

Acute kidney injury (AKI) and chronic kidney disease (CKD) impose a significant global health burden. Yet, no effective therapies currently exist for AKI, and only a few are available for CKD. Despite significant effort from industry and academia, development of pharmacologic therapies for AKI and CKD has been hampered by: Non-predictive animal models The inability to identify and prioritize human targets The limited availability of human kidney biopsy tissue A poor understanding of AKI and CKD heterogeneity Historically, AKI and CKD have been described as single, uniform diseases. However, growing consensus suggests that different disease pathways lead to different subgroups of AKI and CKD (AKIs and CKDs). Access to human kidney biopsy tissue is a critical first step to define disease heterogeneity and determine the precise molecular pathways that will facilitate identification of specific drug targets and ultimately enable individualized care for people with AKI and CKD. A number of research centers across the United States are collaborating to bring state-of-the-art technologies together to: * Ethically obtain and evaluate kidney biopsies from participants with AKI or CKD * Define disease subgroups * Create a kidney tissue atlas * Identify critical cells, pathways, and targets for novel therapies The KPMP is made up of three distinct, but highly interactive, activity groups: * Recruitment Sites: The recruitment sites (RS) are responsible for recruiting participants with AKI or CKD into the longitudinal study and performing the kidney biopsy. * Tissue Interrogation Sites: The tissue interrogation sites (TIS) are responsible for developing and using innovative technologies to analyze the biopsy tissue. * Central Hub: The central hub is responsible for aggregating, analyzing, and visualizing the generated data and providing scientific, infrastructure, and administrative support for the KPMP consortium.

Non-invasive Evaluation of the Predictive Value of CEUS and SWE in ACLF, Renal Failure and Hepatorenal Syndrome

Evaluation of non-invasive prognostic parameters in patients developing ACLF and renal failure in patients receiving and not receiving transjugular intrahepatic portosystemic shunt (TIPS). Patients are cared according to the local standardized follow up program. Clinical and laboratory data from standard patient care are evaluated for potential prognostic value.