Evolving management for critical pulmonary stenosis in neonates and young infants

Over the years, management of critical pulmonary stenosis in young infants has evolved from surgical reconstruction of the right ventricular outflow tract and closed pulmonary valvotomy to transcatheter balloon valvoplasty. Our study aimed at evaluating how the changing policy for management had affected the immediate and long term outcomes of babies with this cardiac lesion. Interventions were made in 34 infants at a median age of 8.5 days (2-90 days). Reconstruction of the right ventricular outflow tract reconstruction was performed in 10 patients, closed pulmonary valvotomy in 13, and balloon valvoplasty in 11. Initial procedure-related mortality was 50%, 15% and 0% respectively. Multivariate analysis revealed transannular patching of the right ventricular outflow tract, and male sex, to be significant factors for death. For the 27 survivors, the ratio of right ventricular to systemic systolic pressure decreased from 1.6 ± 0.3 to 0.3 ± 0.2 after reconstruction of the outflow tract, 1.8 ± 0.5 to 0.8 ± 0.4 after closed valvotomy, and 1.8 ± 0.6 to 0.9 ± 0.3 after balloon valvoplasty. The decrease was significantly greater after patch reconstruction (p=0.025) that required no further reinterventions. The overall rate of reintervention for the survivors was 37% (10/27). The freedom from reintervention after closed valvotomy was 82%, 64% and 51% at 1, 5 and 10 years respectively. The figure remained at 78% at both 1 and 5 years (p=0.66) after balloon valvoplasty. The higher reintervention rate for closed valvotomy corresponded to the significantly greater residual gradient across the pulmonary valve noted on follow-up (p=0.01). Reinterventions included balloon dilation (n=6), reconstruction of the outflow tract (n=4), and 1 each of ligation of an arterial duct and systemic-pulmonary arterial shunting. The risk factor for reintervention was a hypoplastic right ventricle. In conclusion, transcatheter balloon valvoplasty appears to be the optimum initial approach in view of its low mortality, efficacy at relieving the obstruction, and low rate of reintervention. © Greenwich Medical Media Ltd.published_or_final_versio

Systematic phylogenetic analysis of influenza A virus reveals many novel mosaic genome segments

Recombination plays an important role in shaping the genetic diversity of a number of DNA and RNA viruses. Although some recent studies have reported bioinformatic evidence of mosaic sequences in a variety of influenza A viruses, it remains controversial as to whether these represent bona fide natural recombination events or laboratory artifacts. Importantly, mosaic genome structures can create significant topological incongruence during phylogenetic analyses, which can mislead additional phylogeny-based molecular evolutionary analyses such as molecular clock dating, the detection of selection pressures and phylogeographic inference. As a result, there is a strong need for systematic screenings for mosaic structures within the influenza virus genome database. We used a combination of sequence-based and phylogeny-based methods to identify 388 mosaic influenza genomic segments, of which 332 are previously unreported and are significantly supported by phylogenetic methods. It is impossible, however, to ascertain whether these represent natural recombinants. To facilitate the future identification of recombinants, reference sets of non-recombinant sequences were selected for use in an automatic screening protocol for detecting mosaic sequences. Tests using real and simulated mosaic sequences indicate that our screening protocol is both sensitive (average >90%) and accurate (average >77%) enough to identify a range of different mosaic patterns. The relatively high prevalence of mosaic influenza virus sequences implies that efficient systematic screens, such as that proposed here, should be performed routinely to detect natural recombinant strains, potential laboratory artifacts, and sequencing contaminants either prior to sequences being deposited in GenBank or before they are used for phylogenetic analyses. © 2013 Elsevier B.V