Periventricular Leukomalacia Following Bowel Resection for Necrotizing Enterocolitis in a Premature Neonate.

Necrotizing enterocolitis (NEC) and periventricular leukomalacia (PVL) are relatively common conditions in premature infants with low birth weight (VLBW). However, in the current literature, there are limited case reports of patients with concomitant NEC and PVL. We report a case of a premature female born at a gestational age of 25 weeks and five days who developed cystic intracranial lesions after emergent bowel resection due to NEC. Transcranial ultrasound and magnetic resonance imaging confirmed the presence of cystic PVL in the right middle cerebral artery distribution. Several observational studies note the association between spontaneous intestinal perforation, surgical NEC, and the presence of cystic PVL. When infants are unresponsive to medical management for NEC, exploratory laparotomy with resection of the necrotic or perforated intestine is indicated. However, infants treated surgically have poorer neurodevelopmental outcomes than those with medical therapy. Pathogenesis of neurodevelopmental impairment in preterm infants undergoing surgery involves dysfunctional cerebrovascular autoregulation (CAR), which is associated with harmful changes in cerebral perfusion that lead to neuronal injury. Ill preterm infants, such as those with NEC, cannot regulate cerebral perfusion appropriately, and impaired CAR may be present in more than half the preterm infants during laparotomy. Impaired CAR leads to poor cerebral perfusion that potentiates neuronal injury, such as PVL. This case also brings awareness to the need for adherence to screening practices for white matter injury in critical NICU patients through cost-effective transcranial ultrasound.

Intra-tracheal administration of a naked plasmid expressing stromal derived factor-1 improves lung structure in rodents with experimental bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification and disordered angiogenesis. Stromal derived factor-1 (SDF-1) is a chemokine which modulates cell migration, proliferation, and angiogenesis. Here we tested the hypothesis that intra-tracheal (IT) administration of a naked plasmid DNA expressing SDF-1 would attenuate neonatal hyperoxia-induced lung injury in an experimental model of BPD, by promoting angiogenesis. DESIGN/METHODS: Newborn Sprague-Dawley rat pups (n = 18-20/group) exposed to room air (RA) or hyperoxia (85% O2) from postnatal day (P) 1 to 14 were randomly assigned to receive IT a naked plasmid expressing SDF-1, JVS-100 (Juventas Therapeutics, Cleveland, Ohio) or placebo (PL) on P3. Lung alveolarization, angiogenesis, inflammation, vascular remodeling and pulmonary hypertension (PH) were assessed on P14. PH was determined by measuring right ventricular systolic pressure (RVSP) and the weight ratio of the right to left ventricle + septum (RV/LV + S). Capillary tube formation in SDF-1 treated hyperoxia-exposed human pulmonary microvascular endothelial cells (HPMEC) was determined by matrigel assay. Data is expressed as mean ± SD and analyzed by two-way ANOVA. RESULTS: Exposure of neonatal pups to 14 days of hyperoxia decreased lung SDF-1 gene expression. Moreover, whilst hyperoxia exposure inhibited capillary tube formation in HPMEC, SDF-1 treatment increased tube length and branching in HPMEC. PL-treated hyperoxia-exposed pups had decreased alveolarization and lung vascular density. This was accompanied by an increase in RVSP, RV/LV + S, pulmonary vascular remodeling and inflammation. In contrast, IT JVS-100 improved lung structure, reduced inflammation, PH and vascular remodeling. CONCLUSIONS: Intratracheal administration of a naked plasmid expressing SDF-1 improves alveolar and vascular structure in an experimental model of BPD. These findings suggest that therapies which modulate lung SDF-1 expression may have beneficial effects in preterm infants with BPD.

TNFα-stimulated protein 6 (TSG-6) reduces lung inflammation in an experimental model of bronchopulmonary dysplasia.

BACKGROUND: Inflammation is a key factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Tumor necrosis factor-stimulated protein 6 (TSG-6) is a glycoprotein that modulates inflammation. Here we tested the hypothesis that intra-tracheal (IT) administration of an adenovirus overexpressing TSG-6 (AdTSG-6) would decrease inflammation and restore lung structure in experimental BPD. METHODS: Newborn Sprague-Dawley rats exposed to normoxia (RA) or hyperoxia (85% O2) from postnatal day (P) 1-P14 were randomly assigned to receive IT AdTSG-6 or placebo (PL) on P3. The effect of IT AdTSG-6 on lung inflammation, alveolarization, angiogenesis, apoptosis, pulmonary vascular remodeling, and pulmonary hypertension were evaluated on P14. Data were analyzed by two-way ANOVA. RESULTS: TSG-6 mRNA was significantly increased in pups who received IT AdTSG-6. Compared to RA, hyperoxia PL-treated pups had increased NF-kß activation and lung inflammation. In contrast, IT AdTSG-6 hyperoxia-treated pups had decreased lung phosphorylated NF-kß expression and markers of inflammation. This was accompanied by an improvement in alveolarization, angiogenesis, pulmonary vascular remodeling, and pulmonary hypertension. CONCLUSIONS: IT AdTSG-6 decreases lung inflammation and improves lung structure in neonatal rats with experimental BPD. These findings suggest that therapies that increase lung TSG-6 expression may have beneficial effects in preterm infants with BPD.

A Rare Presentation of Isolated Congenital Splenic Hemangioma With Kasabach-Merritt Syndrome.

INTRODUCTION: Splenic hemangiomas (SHs) are the most common benign neoplasms of the spleen. However, they are rare in the newborn period. We present an extremely rare case of congenital SH complicated by Kasabach-Merritt syndrome. CASE PRESENTATION: A 2.93 kg male infant was delivered at term with a prenatal diagnosis of a left infrarenal mass diagnosed by ultrasound at 35 weeks of gestation. Magnetic resonance imaging demonstrated a well-defined splenic mass with multiple flow voids and scattered areas of high intensity suggestive of hemorrhage. He developed anemia, thrombocytopenia, and coagulopathy which required transfusion with packed red cells, platelets, cryoprecipitate, and fresh frozen plasma. Excision biopsy of the spleen led to resolution of anemia, thrombocytopenia, and coagulopathy. The diagnosis of SH was confirmed by histopathology. At 2 months outpatient follow-up, the patient was growing well without any evidence of tumor recurrence. CONCLUSIONS: Congenital SH is a rare entity that can be fatal if the potential complication of Kasabach-Merritt syndrome is not anticipated, evaluated, and promptly treated. Our patient had a favorable outcome with early surgical excision of the SH.