Search

Background: Congenital aortic coarctation (CoA) associated with aortic rupture is a rare but extremely lethal condition. In pregnant patients, the condition becomes very risky.Case Presentation: We presented a case of a pregnant (20 weeks gestation) patient with CoA associated with ruptured aortic pseudoaneurysm who was successfully rescued using a novel hybrid strategy.Conclusions: This hybrid approach may be a life-saving bridging intervention in patients with CoA associated with devastating complications, such as ruptured aneurysms, especially with extremely narrowed access. [ABSTRACT FROM AUTHOR]

Background: Endovascular aneurysm repair has revolutionized the therapeutic strategy for abdominal aortic aneurysm. However, hostile proximal aneurysmal neck and tortuosity of access vessels remain challenges in selecting optimal stent-grafts in abdominal aortic aneurysms with difficult anatomy.Case Presentation: A 65-year-old woman complained of intermittent abdominal pain for one week. Computed tomography angiogram demonstrated a tortuous infrarenal abdominal aortic aneurysm with a tapered neck and a 136° of infrarenal angulation. Aneurysmal dilatation and severe calcification of bilateral iliac arteries and tortuous aortoiliac access were also showed. Endovascular approach using Endurant stent-graft was attempted at an outside hospital, but failed because of the significant tortuosity of the abdominal aorta and iliac arteries. Since the patient refused to have open aneurysm repair, he was transferred to our hospital for further evaluation and possible EVAR with a different approach. EVAR was performed successfully using Gore Excluder stent-grafts (W.L. Gore & Associates, Flagstaff, AZ, USA). During the procedure, cannulation of the contralateral limb was unable to be achieved because of the tortuous aortoiliac course. Therefore, a snare was inserted from right radial artery, through the contralateral gate, to grasp the wire from left femoral artery. Two iliac stent-grafts were sequentially deployed with the lower end distal to the opening of the left internal iliac artery. Angiography confirmed complete sealing of the aneurysm with patency of bilateral renal arteries and external iliac arteries. The postoperative courses were uneventful and follow-up computed tomography angiogram at 6 months demonstrated patent bilateral femoral and renal arteries without endoleaks or stent migration.Conclusion: Although endovascular repair of aortic aneurysm with hostile neck and tortuous access is rather challenging, choosing flexible stent-grafts and suitable techniques is able to achieve an encouraging outcome. [ABSTRACT FROM AUTHOR]

Background: Most cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Acute skin damage from cancer radiotherapy diminishes patients' quality of life, yet effective biological interventions for this damage are lacking. Protecting microvascular endothelial cells from irradiation-induced perturbations is emerging as a targeted damage-reduction strategy. Since Angiopoetin-1 signaling through the Tie2 receptor on endothelial cells opposes microvascular perturbations in other disease contexts, we used a preclinical Angiopoietin-1 mimic called Vasculotide to investigate its effect on skin radiation toxicity using a preclinical model.Methods: Athymic mice were treated intraperitoneally with saline or Vasculotide and their flank skin was irradiated with a single large dose of ionizing radiation. Acute cutaneous damage and wound healing were evaluated by clinical skin grading, histology and immunostaining. Diffuse reflectance optical spectroscopy, myeloperoxidase-dependent bioluminescence imaging of neutrophils and a serum cytokine array were used to assess inflammation. Microvascular endothelial cell response to radiation was tested with in vitro clonogenic and Matrigel tubule formation assays. Tumour xenograft growth delay experiments were also performed. Appreciable differences between treatment groups were assessed mainly using parametric and non-parametric statistical tests comparing areas under curves, followed by post-hoc comparisons.Results: In vivo, different schedules of Vasculotide treatment reduced the size of the irradiation-induced wound. Although skin damage scores remained similar on individual days, Vasculotide administered post irradiation resulted in less skin damage overall. Vasculotide alleviated irradiation-induced inflammation in the form of reduced levels of oxygenated hemoglobin, myeloperoxidase bioluminescence and chemokine MIP-2. Surprisingly, Vasculotide-treated animals also had higher microvascular endothelial cell density in wound granulation tissue. In vitro, Vasculotide enhanced the survival and function of irradiated endothelial cells.Conclusions: Vasculotide administration reduces acute skin radiation damage in mice, and may do so by affecting several biological processes. This radiation protection approach may have clinical impact for cancer radiotherapy patients by reducing the severity of their acute skin radiation damage. [ABSTRACT FROM AUTHOR]

Background: The HOX11/TLX1 (hereafter referred to as HOX11) homeobox gene was originally identified at a t(10;14)(q24;q11) translocation breakpoint, a chromosomal abnormality observed in 5-7% of T cell acute lymphoblastic leukemias (T-ALLs). We previously reported a predisposition to aberrant spindle assembly checkpoint arrest and heightened incidences of chromosome missegregation in HOX11-overexpressing B lymphocytes following exposure to spindle poisons. The purpose of the current study was to evaluate cell cycle specific expression of HOX11., Results: Cell cycle specific expression studies revealed a phosphorylated form of HOX11 detectable only in the mitotic fraction of cells after treatment with inhibitors to arrest cells at different stages of the cell cycle. Mutational analyses revealed phosphorylation on threonine-247 (Thr247), a conserved amino acid that defines the HOX11 gene family and is integral for the association with DNA binding elements. The effect of HOX11 phosphorylation on its ability to modulate expression of the downstream target, cyclin B1, was tested. A HOX11 mutant in which Thr247 was substituted with glutamic acid (HOX11 T247E), thereby mimicking a constitutively phosphorylated HOX11 isoform, was unable to bind the cyclin B1 promoter or enhance levels of the cyclin B1 protein. Expression of the wildtype HOX11 was associated with accelerated progression through the G2/M phase of the cell cycle, impaired synchronization in prometaphase and reduced apoptosis whereas expression of the HOX11 T247E mutant restored cell cycle kinetics, the spindle checkpoint and apoptosis., Conclusions: Our results demonstrate that the transcriptional activity of HOX11 is regulated by phosphorylation of Thr247 in a cell cycle-specific manner and that this phosphorylation modulates the expression of the target gene, cyclin B1. Since it is likely that Thr247 phosphorylation regulates DNA binding activity to multiple HOX11 target sequences, it is conceivable that phosphorylation functions to regulate the expression of HOX11 target genes involved in the control of the mitotic spindle checkpoint.