Low serum miR-19a expression as a novel poor prognostic indicator in multiple myeloma.

Multiple myeloma (MM) is the second most common hematologic malignancy characterized by the clonal expansion of plasma cells. Despite continuing advances, novel biomarkers are needed for diagnosis and prognosis of MM. In our study, we characterized the diagnostic and prognostic potential of circulating microRNAs (miRNAs) in MM. Serum miRNA levels were analyzed in 108 newly diagnosed symptomatic MM patients and 56 healthy donors (HDs). Our analysis identified 95 dysregulated miRNAs in newly diagnosed MM patients. Of the 95 dysregulated miRNAs, dysregulation of miR-19a, miR-92a, miR-214-3p, miR-135b-5p, miR-4254, miR-3658 and miR-33b was confirmed by quantitative reverse transcription PCR (RT-qPCR). Receiver operating characteristic analysis revealed that a combination of miR-19a and miR-4254 can distinguish MM from HD with a sensitivity of 91.7% and specificity of 90.5%. Decreased expression of miR-19a was positively correlated with international staging system advancement, del(13q14) and 1q21 amplification. Furthermore, downregulation of miR-19a resulted in significantly decreased progression-free survival (PFS) and overall survival (OS). Our analysis indicated that the poor prognostic correlation of miR-19a expression was independent of genetic abnormalities in MM. Multivariate analysis revealed that miR-19a was a significant predictor of shortened PFS and OS. Interestingly, although miR-19a levels portend a poor prognosis, patients with low miR-19a levels had an improved response to bortezomib compared to those with high miR-19a profile. Patients with downregulated miR-19a experienced a significantly extended survival upon bortezomib-based therapy. These data demonstrate that the expression patterns of serum microRNAs are altered in MM, and miR-19a levels are a valuable prognostic marker to identify high-risk MM.

Successful treatment of growing basilar artery dissecting aneurysm by pipeline flow diversion embolization device.

We describe a case of successful management of a growing basilar artery dissecting aneurysm by the Pipeline flow diversion embolization device (PED). A 48-year-old woman presented with severe headache, neck pain, and altered consciousness. Computed tomography showed subarachnoid hemorrhage located in basal cisterns, with a pontine infarct shown on magnetic resonance imaging. Digital subtraction angiography showed dissecting aneurysm of the trunk of the basilar artery, with growth over time on repeated imaging. Repeated imaging demonstrated growth in size of the aneurysm. The aneurysm was treated with PED with complete obliteration of the basilar artery aneurysm. Subsequent follow-up demonstrated good clinical recovery.

Prognostic relevance of circulating endothelial progenitor cells for severe traumatic brain injury.

OBJECTIVE: Traumatic brain injury (TBI) promotes the recruitment of endothelial progenitor cells (EPCs) into the injured tissue where EPCs play an important role in repairing injured vasculature. However, the repair mechanism and prognostic significance of EPCs after TBI remain poorly understood. METHODS: Blood samples were collected from 21 patients with severe TBI and 20 healthy subjects. EPCs were quantified by flow cytometry and serum VEGF and MMP-9 level measured by ELISA on days 1, 4, 7, 14 and 21 after TBI. RESULTS: EPCs in the patients decreased originally, then increased to the peak level at 7 days and was significantly correlated with GOS scores 6 months after TBI. VEGF and MMP-9 were significantly increased during the follow-up period after TBI. EPCs was also positively correlated with GCS score 1 day after TBI and with MMP-9 and VEGF 7 days and 14 days after TBI. CONCLUSION: The data demonstrate that TBI led to an increase of EPCs, VEGF and MMP-9, suggesting that increased VEGF and MMP-9 may mediate the recruitment of bone marrow-derived EPCs into the circulation. The association of EPCs with nerve functional recovery in patients provides evidence that EPCs may be a potential biomarker to monitor TBI angiogenesis and prognosis.

Dynamic changes of vascular endothelial growth factor and angiopoietin-1 in association with circulating endothelial progenitor cells after severe traumatic brain injury.

BACKGROUND: Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) can promote angiogenesis and vascular stability after brain injury. Circulating endothelial progenitor cells (EPCs) also play a crucial role in neovascularization and tissue repair after traumatic brain injury (TBI). We sought to compare the expression of VEGF and Ang-1 in serum and the circulating EPCs in patients after severe TBI with that of healthy control subjects. METHODS: We obtained peripheral blood and serum samples from 21 patients with severe TBI and 11 healthy control subjects. EPCs in blood samples from severe TBI patients and healthy controls were quantified by flow cytometry 1 day, 4 days, 7 days, 14 days, and 21 days after severe TBI. VEGF and Ang-1 were measured by enzyme linked immunosorbent assay at the same time points. RESULTS: Compared with control subjects, circulating EPCs in patients with severe TBI decreased 4 days (p < 0.05), but increased 7 days and 14 days (p < 0.05) after TBI. VEGF increased significantly during the follow-up period (p < 0.05). Ang-1 increased gradually and reached peak at 7 days and 14 days after TBI. The circulating EPCs were significantly correlated with VEGF and Ang-1 at 7 days and 14 days after severe TBI. CONCLUSIONS: Our results suggest that the increased VEGF and Ang-1 are closely related to increase in circulating EPCs in response to severe TBI, which may be needed for vascular repairs after severe TBI.