Molecular convergence in ex vivo models of Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by erythroid hypoplasia, usually without perturbation of other hematopoietic lineages. Approximately 65% of DBA patients with autosomal dominant inheritance have heterozygous mutations or deletions in ribosomal protein (RP) genes while <1% of patients with X-linked inheritance have been identified with mutations in the transcription factor GATA1 Erythroid cells from patients with DBA have not been well characterized, and the mechanisms underlying the erythroid specific effects of either RP or GATA1 associated DBA remain unclear. We have developed an ex vivo culture system to expand peripheral blood CD34+ progenitor cells from patients with DBA and differentiate them into erythroid cells. Cells from patients with RP or GATA1 mutations showed decreased proliferation and delayed erythroid differentiation in comparison with controls. RNA transcript analyses of erythroid cells from controls and patients with RP or GATA1 mutations showed distinctive differences, with upregulation of heme biosynthesis genes prominently in RP-mediated DBA and failure to upregulate components of the translational apparatus in GATA1-mediated DBA. Our data show that dysregulation of translation is a common feature of DBA caused by both RP and GATA1 mutations. This trial was registered at www.clinicaltrials.gov as #NCT00106015.

Endovascular reconstruction of vertebral artery occlusion prior to basilar thrombectomy in a series of six patients presenting with acute symptomatic basilar thrombosis.

INTRODUCTION AND PURPOSE: Symptomatic acute basilar thrombosis is associated with a high mortality rate. Aggressive endovascular management has led to survival rates of 35-50%. We report the largest series of endovascular reconstruction of occluded dominant vertebral arteries prior to basilar thrombectomy. MATERIALS AND METHODS: A prospective database since August 2010 of all neuroendovascular interventions was mined for patients undergoing basilar artery thrombolysis from which a group with vertebral artery reconstruction was selected. Patient charts were retrospectively reviewed for relevant clinical, technical, and outcome data. RESULTS: From August 2010 to September 2012, six patients were identified who underwent vertebral reconstruction prior to basilar thrombectomy. Patients ranged in age from 42 to 57 years (mean 51 years). Mean time from symptoms until recanalization was approximately 6 h. Angiographic Thrombolysis in Cerebral Infarction IIB reconstitution of the basilar trunk was achieved in all cases. There were no technical complications. Two patients had care withdrawn secondary to massive completed brainstem infarction and poor neurological status post intervention. Three patients are now independent at 12, 14, and 31 months, respectively. One patient, after a follow-up of only 8 months, has achieved a modified Rankin Scale score of 3. CONCLUSIONS: Complete vertebral occlusion below a basilar thrombus can be recanalized prior to thrombectomy. In this case series, 100% of the acutely occluded vertebral arteries could be opened using either anterograde or retrograde access. However, basilar thrombosis continues to be a devastating illness, with one-third of the patients in this series dying of progressive infarction despite angiographic patency of the large conduit vessels with technical complications.