Anterior fundoplication at the time of congenital diaphragmatic hernia repair

The loss of normal anatomic barriers in neonates with congenital diaphragmatic hernia (CDH) can predispose children to gastroesophageal reflux (GER). In an attempt to improve post-operative feeding, we have added a modified anterior fundoplication to restore natural gastric and esophageal positioning. The institutional review board of both participating centers approved this study. Between 1997 and 2008, 13 neonates with high-risk anatomy underwent repair of CDH combined with an anterior fundoplication (Boix-Ochoa). The anatomic indications for concomitant fundoplication were absence of an intra-abdominal esophagus, an obtuse angle of His, and a small, vertically oriented stomach. Ten patients survived to discharge and eight were on full oral nourishment. One required partial gastrostomy feedings for an improving oral aversion and quickly progressed to full oral feedings. One patient with chromosomal anomalies and swallowing dysfunction remained on long-term bolus gastrostomy feedings. Two with progressive symptoms of GER and failure to thrive required conversion to a 360° wrap after 18 months of medical management. This was performed in conjunction with a planned, staged muscle flap reconstruction in one patient. There were no complications related to the fundoplication. Anatomic predictors of severe GER can be efficiently countered at the time of CDH repair. A modified fundoplication should be considered in the operative management of high-risk infants

Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein in Pregnant Women Are Associated with Higher Birth Weight in a Multicenter Study

A vaccine to eliminate malaria would need a multi-stage and multi-species composition to achieve robust protection, but the lack of knowledge about antigen targets and mechanisms of protection precludes the development of fully efficacious malaria vaccines, especially for Plasmodium vivax (Pv). Pregnant women constitute a risk population who would greatly benefit from a vaccine preventing the adverse events of Plasmodium infection during gestation. We hypothesized that functional immune responses against putative targets of naturally acquired immunity to malaria and vaccine candidates will be associated with protection against malaria infection and/or poor outcomes during pregnancy. We measured (i) IgG responses to a large panel of Pv and Plasmodium falciparum (Pf) antigens, (ii) the capacity of anti-Pv ligand Duffy binding protein (PvDBP) antibodies to inhibit binding to Duffy antigen, and (iii) cellular immune responses to two Pv antigens, in a subset of 1,056 pregnant women from Brazil, Colombia, Guatemala, India, and Papua New Guinea (PNG). There were significant intraspecies and interspecies correlations for most antibody responses (e.g., PfMSP119 versus PfAMA1, Spearman's rho = 0.81). Women from PNG and Colombia had the highest levels of IgG overall. Submicroscopic infections seemed sufficient to boost antibody responses in Guatemala but not antigen-specific cellular responses in PNG. Brazil had the highest percentage of Duffy binding inhibition (p-values versus Colombia: 0.040; Guatemala: 0.047; India: 0.003, and PNG: 0.153) despite having low anti-PvDBP IgG levels. Almost all antibodies had a positive association with present infection, and coinfection with the other species increased this association. Anti-PvDBP, anti-PfMSP1, and anti-PfAMA1 IgG levels at recruitment were positively associated with infection at delivery (p-values: 0.010, 0.003, and 0.023, respectively), suggesting that they are markers of malaria exposure. Peripheral blood mononuclear cells from Pv-infected women presented fewer CD8+IFN-γ+ T cells and secreted more G-CSF and IL-4 independently of the stimulus used in vitro. Functional anti-PvDBP levels at recruitment had a positive association with birth weight (difference per doubling antibody levels: 45 g, p-value: 0.046). Thus, naturally acquired binding-inhibitory antibodies to PvDBP might confer protection against poor outcomes of Pv malaria in pregnancy