Interventional fetal balloon valvuloplasty for congenital heart disease—current shortcomings and possible perspectives

Fetal cardiac interventions are new and relatively unknown investigational options for modifying congenital heart disease in utero. Techniques for safer access to the fetus must be improved, and selection criteria for patients for whom these procedures are potentially beneficial must be developed. Currently, antenatal cardiac intervention attempts are being made to either prevent or reverse hydrops in fetuses with cardiac valve disease or outflow tract obstruction or to recruit hypoplastic ventricles. Most important are early detection and referral of these fetuses, thereby enabling timely procedures with improved outcomes. However, performing successful fetal cardiac interventions requires multidisciplinary collaboration between obstetricians, pediatric cardiologists, pediatric cardiac surgeons, and anesthesiologists, as each discipline provides specific skills for these critically ill babie

PATHFINDER-CHD: prospective registry on adults with congenital heart disease, abnormal ventricular function, and/or heart failure as a foundation for establishing rehabilitative, prehabilitative, preventive, and health-promoting measures: rationale, aims, design and methods

Background Adults with congenital heart defects (ACHD) globally constitute a notably medically underserved patient population. Despite therapeutic advancements, these individuals often confront substantial physical and psychosocial residua or sequelae, requiring specialized, integrative cardiological care throughout their lifespan. Heart failure (HF) is a critical challenge in this population, markedly impacting morbidity and mortality. Aims The primary aim of this study is to establish a comprehensive, prospective registry to enhance understanding and management of HF in ACHD. Named PATHFINDER-CHD, this registry aims to establish foundational data for treatment strategies as well as the development of rehabilitative, prehabilitative, preventive, and health-promoting interventions, ultimately aiming to mitigate the elevated morbidity and mortality rates associated with congenital heart defects (CHD). Methods This multicenter survey will be conducted across various German university facilities with expertise in ACHD. Data collection will encompass real-world treatment scenarios and clinical trajectories in ACHD with manifest HF or at risk for its development, including those undergoing medical or interventional cardiac therapies, cardiac surgery, inclusive of pacemaker or ICD implantation, resynchronization therapy, assist devices, and those on solid organ transplantation. Design The study adopts an observational, exploratory design, prospectively gathering data from participating centers, with a focus on patient management and outcomes. The study is non-confirmatory, aiming to accumulate a broad spectrum of data to inform future hypotheses and studies. Processes Regular follow-ups will be conducted, systematically collecting data during routine clinical visits or hospital admissions, encompassing alterations in therapy or CHD-related complications, with visit schedules tailored to individual clinical needs. Assessments Baseline assessments and regular follow-ups will entail comprehensive assessments of medical history, ongoing treatments, and outcomes, with a focus on HF symptoms, cardiac function, and overall health status. Discussion of the design The design of the PATHFINDER-CHD Registry is tailored to capture a wide range of data, prioritizing real-world HF management in ACHD. Its prospective nature facilitates longitudinal data acquisition, pivotal for comprehending for disease progression and treatment impacts. Conclusion The PATHFINDER-CHD Registry is poised to offer valuable insights into HF management in ACHD, bridging current knowledge gaps, enhancing patient care, and shaping future research endeavors in this domain.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546

Induction of neutralizing antibodies specific for the envelope proteins of the koala retrovirus by immunization with recombinant proteins or with DNA

Background: The koala retrovirus (KoRV) is the result of a transspecies transmission of a gammaretrovirus with fatal consequences for the new host. Like many retroviruses, KoRV induces lymphoma, leukemia and an immunodeficiency that is associated with opportunistic infections in the virus-infected animals. We recently reported the induction of neutralizing antibodies by immunization with the recombinant ectodomain of the transmembrane envelope protein p15E of KoRV. Since the neutralization titers of the p15E-specific sera were only moderate, we investigated the use of the surface envelope protein gp70 to induce neutralizing antibodies. Findings: We immunized rats and goats with the recombinant gp70 protein of the KoRV, an unglycosylated protein of 52kD (rgp70/p52) or with the corresponding DNA. In parallel we immunized with recombinant rp15E or with a combination of rp15E and rgp70/p52. In all cases binding and neutralizing antibodies were induced. The gp70-specific sera had titers of neutralizing antibodies that were 15-fold higher than the p15E-specific sera. Combining rp15E and rgp70/p52 did not significantly increase neutralizing titers compared to rgp70/p52 alone. High titers of neutralizing antibodies specific for gp70 were also induced by immunization with DNA. Since KoRV and PERV are closely related, we investigated cross-neutralization of the antisera. The antisera against p15E and gp70 of PERV and KoRV inhibited infection by both viruses. Conclusion: The envelope proteins of the KoRV may therefore form the basis of an effective preventive vaccine to protect uninfected koalas from infection and possibly an immunotherapeutic treatment for those already infected

Proposal for charging the sixth rupture fuel element experiment: GEH-10, 46, 47

The objective of the test discussed in this report is to verify further the corrosion rate of irradiated tubular fuel elements under conditions of high specific power and central core temperatures. The fuel will be the inner component of an NPR fuel element assembly. A proposal to charge two tubular fuel elements into the GEH-P7 Loop has been made. The upper fuel element of the two has been irradiated to 1660 MWD/T in a Hanford reactor. A hydraulic cylinder will be attached to the upper fuel element. The hydraulic cylinder will be used to move a chisel along the outer surface of the upper fuel element and shear off a cap which has been welded over a hole through the cladding. The lower fuel element of the two will be used to add heat to the loop so that the desired loop water temperatures can be maintained

Proposal for charging the fifth rupture fuel experiment: GEH-10, 34, 35

The objective of this irradiation is to further verify the corrosion rate of tubular-type fuel elements under conditions of high specific power and central core temperatures. This fuel will be the inner tube only of an NPR fuel assembly. As in previous tests, this inner tube rupture will be used to further substantiate the rupture detection instrumentation that is being used in the development of the NPR. Previously unirradiated fuel will be used in this test. The reactor is to operate at full power during the test. Permission is requested for charging two tubular elements The top element will have attached to it a hydraulic mechanism for opening a defect in the outer surface of the tube. The second or bottom element, will be used as a heater element to maintain loop temperature

In-reactor rupture testing of Zircaloy-2 clad seven-rod cluster fuel elements

Three tests have been run in the ETR in high temperature, high pressure, recirculating water. In one test, previously unirradiated fuel elements were used and in the other two the fuel was irradiated to 2400 MWD/T at HAPO prior to insertion in the ETR. Failure was initiated by shearing off a projection on the surface of one rod of a fuel element, thus opening a 25-mil hole through the cladding. The projection was sheared off by a hydraulically operated chisel controlled from outside the reactor. The first test was operated seven hours after the defect was opened with no failure. Failure is defined as having occurred when sufficient uranium oxide has formed to split open the cladding and release large amounts of fission products into the loop water. The second test was operated for fourteen hours after the defect was opened with again no failure. The third test was operated for only 33 minutes after the defect cap was sheared off before fission product activity in the loop water caused the test to be terminated

Proposal for charging the eighth fuel rupture experiment, GEH 10-57

The objective of this test is to prove a new method of intentional rupturing of fuel elements under conditions of high specific powers and central core temperatures. The fuel will be the inner component of an NPR fuel element assembly. Permission to change one tubular fuel element (GEH-10-57) into the GEH-P7 loop is requested. A hydraulic cylinder will be attached to the fuel basket assembly. The hydraulic cylinder will be used to move a cutter along the outer surface of the fuel element. The cutter is designed to machine through the Zircaloy cladding and expose the uranium core to the loop coolant

Proposal for charging the third rupture fuel element experiment, GEH 12--16, 17, 18

The objective of this irradiation is to verify the corrosion rate of a cluster-type fuel element under conditions of high specific power and central core temperatures. The test will also be used in the development of rupture detection instrumentation and decontamination procedures as a necessary part in the development of the NPR. In this test a fuel element irradiated to 3200 MWD/T will be ruptured, the rate of rupture product released will be determined and the gamma spectrum from fission products released into the coolant will be observed. Permission is requested for charging three 7-rod cluster fuel elements (one previously irradiated to 3200 MWD/T at the Hanford projects, the other two unirradiated) into the GEH-R33P7 loop of the ETR. The irradiated element will have attached to it a hydraulic mechanism for opening a defect in one of its fuel rods. The other two elements are to serve as heaters to enable the loop to operate at desired temperatures

In-reactor rupture testing of Zircaloy-2-clad, coextruded fuel elements in the Engineering Test Reactor. Final report

One of the problems involved in the design and operation of the Hanford N-Reactor is determining the manner and rate of fuel element failure once water has penetrated the cladding. Specifically, when the uranium core of a fuel element cones in contact with water at high temperatures and pressure, how fast is the reaction, how much damage will be done, and at what rate will the fuel material be released into the coolant stream? To provide data useful in the design of the reactor and for the initial stages of operation, considerable amount of testing has been done in out-of-reactor loops, in-reactor loops, and autoclaves. Of these tests, those which have provided the most direct data on the mode and rate of failure of a fuel element are the in-reactor rupture tests performed in the Engineering Test Reactor (ETR) at Idaho Falls, Idaho. An associated problem is the development and testing of instrumentation for detecting fuel element failures in the N-Reactor. If a failure could be detected and verified early enough, massive failure of the fuel element and the associated contamination of the reactor can be minimized. The in-reactor rupture test program was conducted to provide answers to these two problems. This report describes the rupture test program from the point of view of the first problem, the failure behavior of fuel elements