Edelã©ny, Hungary

ABTECT - Maintenance

All eligible subjects who have completed either one of the induction studies above mentioned, will be given the opportunity to take part in the present ABX464-107 study which consists of 2 treatment phases. This study consists of a 44-week maintenance treatment phase (Part 1 and Part 2), followed by a 4-year Long Term Extension (LTE) treatment phase and a 28-days follow-up period consisting in the End of Study (EOS) visit. The maintenance phase is a 44-week double blind, placebo-controlled, phase. Subjects who are clinical responders after 8 weeks induction will be randomized to Part 1, and those who are non-clinical responders will be randomized to Part 2. At the end of the 44-week maintenance phase, subjects will continue their allocated treatment until the maintenance phase is unblinded. Once the study is unblinded, all subjects receiving obefazimod will continue their allocated treatment. Subjects receiving placebo will be allocated to obefazimod 25 mg or can terminate the study.

Intracoronary ECG ST-segment Shift Remission Time During Reactive Coronary Hyperemia

Cardiovascular disease is the major cause of death globally, accounting for 17.9 million deaths per year in 2019. Aside from the acute coronary syndrome, where percutaneous coronary intervention (PCI) has been shown to improve outcome, the number of patients with chronic coronary syndrome (CCS) is also increasing. PCI of hemodynamically relevant stenotic lesions causing myocardial ischemia is the standard treatment in these patients. Effective revascularization, as recommended by the European Society of Cardiology (ESC) guidelines, requires to differentiate between hemodynamically relevant and non-significant stenotic coronary lesions. Currently, coronary stenosis assessment is performed by structural visual angiographic assessment or by coronary pressure measurements up- and downstream of the lesion. The latter is recommended by the ESC and is based on its prognostic value derived from large randomized clinical trials. Given temporary paralysis of the coronary microcirculation by a hyperemia-inducing substance such as adenosine (ADO), pressure is, in theory, directly related to coronary flow. Therefore, the pressure drop during hyperemia across a coronary stenosis, i.e., fractional flow reserve (FFR) provides an estimate of its restrictive effect on flow. However, this method depends on expensive pressure sensor angioplasty guidewires, and on hyperemia-inducing substances, such as ADO. Hence, pharmacologic limitations such as atrioventricular conduction defects and asthma and other potential adverse events (e.g. arrhythmias) aside from costs are major drawbacks of pressure-derived FFR. In order to avoid potential drug-induced side effects and achieve maximal hyperemia, the study group performs reactive hyperemia FFR measurements induced by a proximal, 1-minute coronary artery balloon occlusion. This method has been documented non-inferior in its ability to detect relevant coronary stenosis compared to adenosine-induced FFR. The present project aims at validating a novel, potentially more harmless, faster and less costly diagnostic approach for measuring hemodynamic coronary stenosis severity. The commonly obtained surface lead electrocardiogram (ECG) is limited in detecting short-lasting or minor myocardial ischemia. In comparison, intracoronary ECG (icECG) is more time- and space-sensitive in detecting myocardial ischemia, the latter being due to its close vicinity to the myocardial region of interest. It can be easily obtained by attaching an alligator clamp to a coronary guidewire. Based on the sensitivity of the icECG, several clinical trials have assessed the value of icECG to guide PCI, and rated it useful to predict post-procedural myocardial injury. The investigators research group performed a trial to determine the diagnostic accuracy of icECG ST-segment shift during pharmacologic inotropic stress in assessing functional coronary lesion severity versus structural stenosis severity as obtained by quantitative coronary angiography in % diameter narrowing (%S by QCA), and versus other functional hemodynamic indices (FFR, instantaneous wave-free ratio (iFR)). IcECG ST-segment shift showed a significant correlation with all established parameters. Evaluation of icECG required the development of a specific software algorithm, which robustly determines quantitative icECG ST-segment shift in every single heartbeat. The validation analysis of the algorithm took place in an offline setting and demonstrated an excellent correlation as compared to the results of ECG experts (r2 = 0.932; p<0.001). The development of this fully autonomous icECG analyzing algorithm was set up on an existing ECG software, denoted as "EsoLive", developed at the Institute for Medical Engineering and Medical Informatics, University of Applied Sciences and Arts Northwestern Switzerland. In short, the algorithm starts with a baseline wander extraction method related to Kalman filtering, then sets the initial points for an "edge", i.e., J-point, before, it processes in a similar way the isoelectric line level. Quantitative time as well as voltage measurements of those two points allow the calculation of the icECG ST-segment shift for each single QRS complex. This study evaluates a new diagnostic approach based on icECG ST-segment shift remission time, denoted as τ-icECG (τ=tau, i.e., the remission half-time fitted by an exponential function to the disappearing ST-segment shift), to be used for PCI guidance.

Evaluation and Further Development of an Artificial Intelligence-based Algorithm for Clinical Decision Support

Amivantamab, Lazertinib and Bevacizumab in Patients With EGFR-mutant Advanced Non-small Cell Lung Cancer With Progression on Previous Third-generation EGFR-TKI

Impact of Personalised Cardiac Anaesthesia and Cerebral Autoregulation on Neurological Outcomes in Patients Undergoing Cardiac Surgery

Adverse neurological events include perioperative neurocognitive disorders and stroke and remain one of the major risks after cardiac surgery. A lack of a comprehensive knowledge of their causes and neuroprotective strategies has hindered the development of strategies to effectively reduce these complications. Against this background, this research project will take three approaches. First, non-invasive, personalised cerebral autoregulation-oriented blood pressure monitoring aims to reduce complications by uncovering blood pressure targets tailored to individual characteristics. In parallel, establishing biological associations between adverse neurological outcomes, brain injury biomarkers and genetic studies are complementary strategies that make a move to a proactive patient-tailored paradigm, ultimately understanding the mechanisms and improving patient outcomes, patient safety and quality of life. Therefore, this international, multicentre prospective cohort study will assess whether perioperative duration and magnitude of MAP outside of an individual's CA limits using NIRS and TCD are associated with adverse neurological events. It is to investigate whether patients with a higher burden of cerebral haemodynamic insults, defined by the duration and magnitude spent outside of an individual's CA limits based on NIRS and/or TCD, have an increased incidence of postoperative delirium (POD), stroke or cognitive decline. Biological associations between adverse neurological outcomes, the role of brain injury serum biomarkers will be explored. Genetic studies will be conducted on participants who give written informed consent for these further investigations.

MiECC Versus Conventional Cardiopulmonary Bypass in Cardiac Surgery (MiECS)

Despite a fall in mortality rates over the past decade, patients having cardiac surgery continue to experience serious postoperative complications. The risk of serious and relatively common surgical complications is often a consequence of stopping the heart during the operation, using the heart and lung machine (conventional cardiopulmonary bypass; cCPB), and restarting and reperfusing the heart at the end of the operation. Although several strategies have been developed to reduce such complications, they still occur and can be life threatening; they also increase the length of time a patient spends in the hospital. Miniaturised heart lung machines (minimally invasive extracorporeal circulation; MiECC) have been developed with the aim of reducing the number of postoperative complications arising from using cCPB. Because of the variety of miniaturised systems that have been evaluated, the different types of patients and outcomes investigated, and the poor quality of previous studies, the effectiveness of MiECC in reducing postoperative complications has not been established and most hospitals continue to use cCPB. Our primary hypothesis is that, compared to cCPB, using a MiECC system during cardiac surgery reduces the proportion of patients having one of several serious postoperative complications (death, myocardial infarction, stroke, acute kidney injury, reintubation, tracheostomy, mechanical ventilation for more than 48 hours, or reoperation) up to 30 days after surgery. In addition, the investigators hypothesise that MiECC reduces the amount of blood products transfused, time to discharge from the cardiac intensive care unit and hospital and the health care resources used during the hospital stay. Study investigators propose to carry out a large, multicentre randomised controlled trial in 10 to 15 cardiac surgery centres worldwide. Patients will be eligible if they are having coronary artery bypass surgery, aortic valve replace or both using a heart lung machine without circulatory arrest. Centres may recruit patients having all, or a subset of, operation types. It is expected that 20 % to 23% of patients will experience one or more of the serious complications (the primary outcome). In order to be able confidently to detect a 30% relative reduction in the risk of this outcome, the investigators plan to recruit 1,300 participants across all sites.

Virtual Reality Games in Pediatric Surgery