Anomalous venoatrial connections – CT and MRI assessment

Abnormal venous atrial (VA) connections present a congenital heart disease (CHD) challenge for pediatric cardiologists. Fully anatomical evaluation is very difficult in prenatal and perinatal follow-up, but it has a profound impact on surgical correction and outcome. The echocardiogram is first-line imaging and represents the gold standard tool for simple abnormal VA connection. CT and MRI are mandatory for more complex heart disease and “nightmare cases”. 3D post-processing of volumetric CT and MRI acquisition helps to clarify anatomical relationships and allows for the creation of 3D printing models that can become crucial in customizing surgical strategy. Our article describes a ten-year (2013–2022) tertiary referral CHD center of abnormal AV connections investigated with CT and MRI, illustrating most of these complex diseases with the help of volume rendering (VR) or multiplanar reconstructions (MPR). The nightmarish cases will also be addressed due to the complex cardiovascular arrangement that requires a challenging surgical solution for correction along with the post-surgical complications.</p

Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein

Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2´ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice expressing human ACE2 against infection when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants

Implantation of a Berlin Heart as single ventricle by-pass on Fontan circulation in univentricular heart failure

The clinical management of ventricular failure after the Fontan operation presents a formidable challenge to surgeons. We report our experience with successful implantation of a Berlin Heart EXCOR ventricular assist device as a bridge to transplantation in a child with Fontan circulation

Bidirectional Glenn and antegrade pulmonary blood flow: temporary or definitive palliation?

BACKGROUND: We sought to investigate the role of the bidirectional Glenn with antegrade pulmonary blood flow in the surgical history of children with univentricular hearts. METHODS: A series of 246 patients, from three joint institutions, having univentricular heart with restricted but not critical pulmonary blood flow received a bidirectional cavopulmonary shunt with additional forward pulmonary blood flow. All patients have been studied according to their progression, or not, to Fontan operation. Two hundred and eight (84.5%) patients underwent bidirectional cavopulmonary anastomosis as primary palliation. Twenty patients (8.1%) with previous pulmonary artery banding were also enrolled in the study. Patients who had received additional pulmonary blood flow through a previous systemic to pulmonary artery shunt for the critical pulmonary blood flow were excluded. RESULTS: No in-hospital death occurred. Follow-up was complete at 100%. Mean follow-up was 4.2 +/- 2.8 years (range, 6 months to 7 years). During the observational period 73 (29.7%) patients, considered optimal candidates, underwent Fontan completion for increasing cyanosis and (or) hematocrit and (or) fatigue with exertion. Three patients expired after total cavopulmonary connection (3 of 73; 4.1% mortality rate). The remaining 173 (70.3%) patients are alive with initial palliation. All patients were still well palliated with an arterial oxygen saturation at rest about 90%. CONCLUSIONS: According to our experience and results, bidirectional Glenn with antegrade pulmonary blood flow may be an excellent temporary palliation prior to a Fontan operation, which can be performed at the onset of symptoms. Bidirectional Glenn may also be the best possible palliation for a suboptimal candidate for Fontan

Adequate vs. deep response to UDCA in PBC: To what extent and under what conditions is normal ALP level associated with complication-free survival gain?

BACKGROUND AND AIMS: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (xULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. APPROACH AND RESULTS: We performed a retrospective cohort study of 1,047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation or death was assessed using adjusted restricted mean survival time analysis. The overall incidence rate of events was 17.0 (95%CI 13.7 - 21.1) per 1,000 out of 4,763.2 patient-years. On the whole population, normal serum ALP values (but not normal GGT, ALT, or AST; or total bilirubin < 0.6 xULN) were associated with an overall absolute complication-free survival gain at 10 years of 7.6 months (95%CI 2.7 - 12.6, p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95%CI 45.7 - 59.9, p < 0.001) when these two conditions were met. CONCLUSIONS: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 xULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients