Chelny, Russian Federation

Comparison of Esketamine/Propofol and Methohexital Anesthesia for ECT

VIATORR Device Registry

1. Registry Procedures 1.1. Informed Consent Process All patients must provide informed consent prior to any registry related procedures. The original signed informed consent form will be retained in the subject records. A copy of the informed consent document will be given to the subject. 1.1.1. Vulnerable Populations No vulnerable populations are included in this registry. 1.1.2. Emergent Cases Emergent cases, in which prior informed consent of the subject is not possible because of the subject's medical condition, can be enrolled in this registry by signing the inform consent before discharge. 1.2. Enrollment The patient is considered enrolled when informed consent is obtained. 1.3. Screening All patients who sign an informed consent will be considered entered into the screening phase of the registry. The following evaluations will be conducted: - Informed consent - Inclusion / exclusion criteria - Demographics - Medical history including o Primary: variceal bleeding (gastric or esophageal), ascites (per EASL (European Association for the Study of the Liver) guidelines), other o Secondary: variceal bleeding, ascites (per EASL guidelines), hepatic hydrothorax, gastropathy, hepatorenal syndrome, other - Physical examination - Child-Pugh Score, MELD (Model for end-stage liver disease), MELD-Na (Model for end-stage liver disease including sodium level), Clif C AD (Acute Decompensation) Score. - Portal Hypertension details covering prior 12 months before ICF (Inform Consent Form) signature - HE (Hepatic Encephalopathy) Assessment - Medication - Alcohol intake - Pregnancy test - EQ-5D-5L (Health Questionnaire - 5 dimensions) Questionnaire - CLDQ (Chronic Liver Disease Questionnaire) Questionnaire 1.4. Screen Failure If the subject signed an informed consent and then is considered a screen failure prior to procedure, the Subject Identification (ID) will be entered into the Electronic Database Capture (EDC) system and the Inclusion / Exclusion Criteria Case Report Form (CRF) will be completed to reflect criteria not met. Additionally, the Completion / Discontinuation form has to be completed to capture when the subject is no longer enrolled in the registry. 1.5. Procedure The GORE® VIATORR® TIPS Endoprosthesis with Controlled Expansion procedure will be performed according to standard practice of the enrolling institution and the IFU (Instructions for Use). No planned surgical concomitant procedures should be performed during the TIPS procedure. If any unplanned surgical concomitant procedures are required during the TIPS procedure the reason should be documented and entered into the Electronic Data Capture (EDC) system. The following details will be collected on the TIPS placement: • Access vein, starting vein and portal vein entry location - TIPS set used - Pre- and post-dilation details - Additional procedures performed - PSG (Portosystemic Gradient) measurements - Completion imaging (per site standard) - Adverse Events (as occurred) Any implanted GORE® VIATORR® TIPS Endoprosthesis with Controlled Expansion will be recorded on the subject's Procedure and Device Accountability electronic Case Report Forms (eCRFs). If a GORE® VIATORR® TIPS Endoprosthesis with Controlled Expansion was introduced into the vasculature and not implanted as part of the registry procedure (e.g., no shunt implant), the subject is considered an unsuccessful implant. The subject's Procedure, AE (Adverse Event), Device Accountability, and Device Deficiency eCRFs will be completed (as applicable), as well as a 30-day safety follow-up, where only AEs will be collected. After this 30-day safety follow-up, the Completion/Discontinuation form must be completed for patients with an unsuccessful GORE® VIATORR® TIPS Endoprosthesis with Controlled Expansion. Any procedural complications arising after enrollment of an eligible subject (signed ICF) will be treated per investigator's best medical judgment and recorded in the EDC system as an AE. 1.6. HE Assessment Hepatic encephalopathy diagnosis detail should include covert and overt classification, history of recurrent HE prior to TIPS, HE diagnosis at time of TIPS, or HE at any time following TIPS procedure. Detail will be also collected on the HE medication therapy. 1.7. Concomitant Medication Medication detail collected should include albumin, antibiotics, antivirals, alcohol dependence medication, antiplatelets/antithrombotics, chelating agents, corticosteroids, blood coagulation, diuretics, somatostatins, Proton Pump Inhibitors, laxatives, and beta-blockers. 1.8. Imaging Images might be requested from sites for safety follow-up reasons. 1.9. Repeat Interventions Repeat interventions performed on the original pathology or directly on the GORE® VIATORR® TIPS Endoprosthesis with Controlled Expansion following the initial treatment will be recorded in the EDC system. The underlying cause for repeat interventions should be recorded as an AE along with the treatment as specified. The following details will be collected on the TIPS revision: - Access vein, starting vein and portal vein entry location - TIPS set used - Pre- and post-dilation details - Additional procedures performed - PSG measurements - Completion imaging (per site standard) - Adverse Events (as occurred) If the GORE® VIATORR® TIPS Endoprosthesis with Controlled Expansion is completely removed as part of the reintervention, then the subject is discontinued from the registry and should be followed as per the treating physician's standard of care. 1.10. Follow Up The follow-up visits should be completed within an acceptable time frame and in accordance with the protocol-defined visit windows. Subjects will continue to be followed by the site's standard of care after completion of the registry. 1.10.1. Discharge or Day 7 Visit The first visit after the procedure will be performed at discharge or day 7 post-surgery, whatever comes first. The following data will be collected during this visit: • Portal Hypertension - update on any new or existing portal hypertension symptoms and treatments since last visit • HE Assessment - Medication - TIPS imaging per site standard - Adverse Events 1.10.2. FU (Follow-Up) Visit at 1, 3, 6, 12, 24 and 36 Months During the Follow-Up period, visits will be conducted per visit windows as listed above in Table 5. The following data will be collected during the follow-up visits: • Physical examination • Child-Pugh Score, MELD, MELD-Na, Clif C AD Score • Portal Hypertension - update on any new or existing portal hypertension symptoms and treatments since last visit • HE Assessment • Medication • EQ-5D-5L Questionnaire • CLDQ Questionnaire • TIPS imaging per site standard - Adverse Events (as occurred) 1.11. Subject Questionnaires Two health-related quality of life instruments will be used, EQ-5D-5L as a general instrument and CLDQ as disease-specific instrument (Chronic Liver Disease Questionnaire). 1.12. Subject Withdrawal from the Registry A subject may withdraw from the registry at any time and should notify the investigator in this event. The investigator may also withdraw the subject from the registry at any time based on his / her medical judgment. If such withdrawal is due to problems related to the registry device safety or performance, the investigator shall ask for the subject's permission to follow his / her status / condition outside the clinical investigation. 1.13. Subject Lost to Follow Up A subject will be considered lost to follow up and withdrawn from the registry once they have missed two consecutive follow-up visits and three documented attempts have been made by the investigator or designee to contact the subject or next of kin. One of the three documented attempts must include a certified letter. The subject's end date will be the last date of contact made with the subject. 1.14. Subject Registry Completion A subject has completed the registry once the 36-month follow-up visit has been performed. Any subject that does not complete these requirements due to voluntary withdrawal, physician withdrawal, death, or any other reason will be considered a withdrawal. Subjects who miss two consecutive visits and three documented attempts will be considered lost to follow up. Subjects will not be provided with any medical care by the sponsor after registry completion or withdrawal. Subjects with a liver transplant or abandonment of the implanted device will exit the registry at that timepoint and no further follow-up information will be collected from these subjects.

HEM ISMART-D: Trametinib + Dexamethasone + Chemotherapy in Children with Relapsed or Refractory Hematological Malignancies

HEM-iSMART is a master protocol with sub-protocols. The overarching objective is that introducing targeted therapy using a biomarker driven approach for treatment stratification may improve the outcome of children with R/R acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) It is characterized by a shared framework that allows for the investigation of multiple IMPs and generate pivotal safety and efficacy evidence within the sub-protocols to establish and define the benefits and risks of new treatments for children with R/R leukemia. Sub-Protocol D within HEM-iSMART, is a phase I/II, multicenter, international, open-label clinical trial designed to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of trametinib in combination with dexamethasone, cyclophosphamide and cytarabine in children, adolescents and young with R/R ALL and LBL. Patients with actionable alterations in the RAS-RAF-MAPK pathway will be eligible for sub-protocol D including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del.

Coagulation in Cirrhosis

Patients with cirrhosis commonly have deranged coagulation parameters, in particular thrombocytopenia and/or an increased INR. However, these laboratory findings do not necessarily correlate with an increased tendency of bleeding. In fact, the reduced synthesis of both pro- and anticoagulant factors often equates to a new equilibrium in the coagulation system. Nevertheless, out of fear of bleeding, liver cirrhosis patients with deviated laboratory coagulation parameters are often aggressively treated with coagulation products (such as platelet concentrates and prothrombin complex concentrate (PCC)) before minor interventions and punctures. Since these products can also have procoagulant side effects, we will investigate whether patients with liver cirrhosis without a history of bleeding or clinical bleeding signs benefit from a restrictive substitution regime. The study will be carried out monocentrically at the General Hospital of Vienna, and will include 400 patients divided into two groups (liberal vs. restrictive substitution of thrombocytes and/or PCC) over an est. period of 4 years.

A Study to Evaluate XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in subjects diagnosed with generalized epilepsy and experiencing probable or possible PGTCS (with or without other subtypes of generalized seizures), and taking 1 to 3 anti-seizure medications (ASMs). Eligible subjects will be randomly assigned 1:1 to XEN1101 or placebo: subjects aged ≥ 18 years will receive XEN1101 25 mg or placebo, and subjects aged ≥12 years and <18 years will receive either XEN1101 15 mg, 25 mg, or placebo. Randomization will be stratified based on region, age group, and background use of CYP3A4-inducer ASMs. Eligible subjects will have up to 9.5 weeks durations to assess the baseline frequency of seizures, followed by a double-blind treatment period (DBP) where subjects will receive 12 weeks of blinded treatment. During the DBP, subjects will be instructed to orally take XEN1101 or placebo once daily with an evening meal. Subjects who complete the 12-week DBP will have the opportunity to enroll in a separate open-label-extension (OLE) study for continued treatment with XEN1101. Subjects who do not enroll in the OLE will enter an 8 week post-treatment follow-up period.

Retinal Neurovascular Coupling in Patients Previously Infected With COVID-19

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is affecting almost all countries in the world and because of its worldwide spread has been declared as pandemic in March 2020. While respiratory symptoms are the main manifestation of acute infection, there is also increasing evidence that neurological and vascular symptoms occur, and it is unknown whether residuals remain after patients have recovered. A recent report shows that changes in the human retina are even present one month after onset of symptoms. The eye, as an extension of the brain, offers the advantage that blood vessels as well as neural tissue can be visualized non-invasively in-vivo. Neurovascular coupling is the ability of neural tissue to adapt its blood flow to its metabolic demands, a phenomenon that does not only occur in the brain, but also in the retina. In the retina, neurovascular coupling can be studied by stimulating the retina with flicker light and measuring the response of the vessels. Retinal neurovascular coupling has been found to be impaired in diseases of the central nervous system (CNS) as well as in diseases associated with endothelial dysfunction. Since COVID-19 comes with CNS manifestations as well as endothelial dysfunction, we speculate that retinal neurovascular coupling might be impaired in patients even after they have recovered from COVID-19 infection. In the current study, retinal neurovascular coupling will be measured in patients who have recovered from COVID-19 infection with and without long COVID-19 and in healthy age- and sex-matched controls with no history of COVID-19 infection. In addition, retinal oxygen saturation, vessel diameters, vessel density as well as retinal and optic nerve head blood flow will be measured. To assess structural changes, measurement of central retinal thickness as well as retinal nerve fiber layer thickness will be performed.