Signal analysis biomarkers, in an intra-operative setting, may be complementary tools to guide and tailor the resection in drug-resistant focal epilepsy patients. Effective assessment of biomarker performances are needed to evaluate their clinical usefulness and translation. We defined a realistic ground-truth scenario and compared the effectiveness of different biomarkers alone and combined to localize epileptogenic tissue during surgery. We investigated the performances of univariate, bivariate and multivariate signal biomarkers applied to 1 min inter-ictal intra-operative electrocorticography to discriminate between epileptogenic and non-epileptogenic locations in 47 drug-resistant people with epilepsy (temporal and extra-temporal) who had been seizure-free one year after the operation. The best result using a single biomarker was obtained using the phase-amplitude coupling measure for which the epileptogenic tissue was localized in 17 out of 47 patients. Combining the whole set of biomarkers provided an improvement of the performances: 27 out of 47 patients. Repeating the analysis only on the temporal-lobe resections we detected the epileptogenic tissue in 29 out of 30 combining all the biomarkers. We suggest that the assessment of biomarker performances on a ground-truth scenario is required to have a proper estimate on how biomarkers translate into clinical use. phase-amplitude coupling seems the best performing single biomarker and combining biomarkers improves localization of epileptogenic tissue. Performance achieved is not adequate as a tool in the operation theater yet, but it can improve the understanding of pathophysiological process. Epilepsy is a disorder which affects the life of around 50 millions of people worldwide 1. One third of epileptic patients are drug-resistant 2,3. Epilepsy surgery provides a potential cure for these patients. The success of surgery is linked to the mapping of the epileptogenic zone (EZ), the minimum cortical area that needs to be resected to achieve seizure freedom 4. Visual analysis of intra-operative electro-corticography (ioECoG) has been used during surgery to assess and adjust the boundaries of the proposed resection area. Typically, inter-ictal epileptiform activity (i.e. spikes) is the main factor to delineate the resection 5. The complete removal of spikes has been correlated with a good post-surgical seizure outcome 6-11 , but good outcomes are also seen in cases where not all spikes are removed, and bad outcomes in cases where no spikes were seen 12-14. Ictiform spike patterns are a more specific marker than sporadic spikes 11. Recently, it was found that high frequency oscillations (HFOs; above 80 Hz) may be more specific predictors of outcome, especially when still present after the resection 15-17. However, there is still

Background and Aims The COVID-19 pandemic has serious impact on health and economics worldwide. Despite the recent advent of SARS-Cov-2 vaccines, treatment options are needed, yet pharmacologic interventions remain limited. Several extracorporeal treatments are currently explored concerning their potential to improve the clinical course and outcome of critically ill patients with COVID-19. The Seraph® 100 Microbind® Affinity adsorber (Exthera Medical, CA, USA) has recently been introduced for the elimination of several pathogens from the blood and an emergency authorization in patients with COVID-19 was granted by the FDA. Bacteria, viruses (including the SARS-CoV-2 spike glycoprotein), fungi and toxins have been shown to bind to the immobilized heparin on the ultra-high molecular weight polyethylene beads of the device in a similar way to the interaction with heparan sulfate on the cell-surface and are thereby removed from the bloodstream. Here we report the interim analysis of the COVID-19 patients treated with the Seraph® 100 Microbind® Affinity filter (COSA) registry. The goal of the registry is to gather data regarding the safety and efficacy of the Seraph® 100 in the treatment of COVID-19 patients. Method Participating sites were advised to insert patient data of COVID-19 patients, treated with the Seraph® 100, during their hospital stay into the COSA registry (ClinicalTrials.gov Identifier: NCT04361500). A total of 66 items were asked in a web-based platform. Results Until January 2021, 33 patients with 39 treatment sessions form six different hospitals were reported to the register (seven female, median age 61 years, Table 1). The patients were treated between March and December 2020. Eleven patients with a hospital admission between March and August and 22 between September and December 2020. The Seraph® 100 treatment was initiated 9 days after symptom onset, without any difference between survivors and non-survivors. Overall, a mortality of 27% was reported. Serious comorbidities (as preadmission immunosuppressive therapy, lung fibrosis or CKD5T) were reported in all of the non-survivors. Invasive ventilation was needed in 67% of these patients when Seraph treatment was initiated. A non-significant trend towards higher Ferritin levels in non-survivors (2000 (1963 – 8326) vs. 989 (644 – 2000), p=0.09) was reported. All treatments were well tolerated, three clotting events were reported. Conclusion Viral SARS-CoV-2 RNA is frequently (up to 78%) seen in the blood of critically ill COVID-19 patients and correlates with the severity of the disease. The Seraph® 100 can bind to viral spike protein, proinflammatory cytokines may be reduced by the device and hemodynamic stabilization has been reported during the Seraph®100 treatment of COVID-19 patients. Platelets can be hyperactivated in association with SARS-CoV-2 proteins and thus presumably trigger the hypercoagulation and thrombosis. In this context, the removal of SARS-CoV-2 proteins to prevent hyperactivated platelets appears to be a sensible approach. All reported deaths were associated with serious preexisting comorbidities, immunosuppression, dialysis dependent renal failure, or a combination of these factors. Hence, Seraph® 100 treatment may be most beneficial in COVID-19 courses of patients without multi organ failure. More clinical data is needed to describe possible benefits of the Seraph®100 in the treatment of COVID-19 patients.

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