Background Skin disorders in neonates can be regarded as determining concepts for prognosis and genetic counseling. Few studies have so far been conducted on determining and recording the relative frequency of skin disorders. The present study was therefore conducted to investigate skin manifestations and their relationship with other variables in the neonates hospitalized in the neonatal intensive care unit (NICU). Methods The present cross-sectional study was conducted on 403 neonates, hospitalized in the NICU of Rasoul Akram Hospital in 2014 and selected using convenience sampling. The data collected from
Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders.
Vascular anomalies can cause significant morbidity and mortality. Advances in diagnosis will be improved if noninvasive biomarkers can be identified, as obtaining a tissue biopsy can worsen the disease and precipitate complications. The goal of this study was to identify biomarkers for vascular anomaly patients to aid diagnosis and potentially give insights into pathogenesis. Blood was collected at baseline and then 6 and 12 months after treatment with the mTOR inhibitor sirolimus. Patients groups included generalized lymphatic anomaly (GLA), kaposiform lymphangiomatosis (KLA) and kaposiform hemangioendothelioma (KHE) with or without the Kasabach-Merritt phenomenon (KMP) coagulopathy. Serum was obtained from healthy controls selected to match the age and sex of the patients (21 days-28.5 years; 42% males; 58% females). Angiogenic and lymphangiogenic factors (VEGF-A, C, D, Ang-1 and Ang-2) were measured in serum using ELISA. In lymphatic anomaly patients, baseline levels of VEGF-A and VEGF-D were not different compared to controls. Angiopoietin-2 (Ang-2) levels were near controls levels in GLA patients but 10-fold greater in KLA patients and 14-fold greater in KHE patients when the KMP coagulopathy was present but not when it was absent. VEGF-C and angiopoietin-1 (Ang-1) levels were lower in KHE patients with KMP. Our analyses suggest that Ang-2 and Ang-1 can be used as biomarkers to help identify KLA and KHE patients with KMP coagulopathy with high sensitivity and specificity. After 12 months of sirolimus treatment, Ang-2 levels were lower in KLA and KHE with KMP patients compared to baseline levels and with most patients showing a clinical response. Hence, serum Ang-2 and Ang-1 levels may help in the diagnosis of patients with lymphatic anomalies and are concordant to sirolimus response.
Summary
Angiosarcoma/lymphangiosarcoma is a rare malignancy with poor prognosis. We generated a mouse model with inducible endothelial cell-specific deletion of Tsc1 to examine mTORC1 signaling in lymphangiosarcoma. Tsc1 loss increased retinal angiogenesis in neonates, and led to endothelial proliferative lesions from vascular malformations to vascular tumors in adult mice. Sustained mTORC1 signaling was required for lymphangiosarcoma development and maintenance. Increased VEGF expression in tumor cells was seen, and blocking autocrine VEGF signaling abolished vascular tumor development and growth. We also found significant correlations between mTORC1 activation and VEGF, HIF1α, and c-Myc expression in human angiosarcoma samples. These studies demonstrated critical mechanisms of aberrant mTORC1 activation in lymphangiosarcoma, and validate the mice as a valuable model for further study.
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