Marvin E. Morris

Thoracic Mural Thrombi: A Case Series and Literature Review

Thoracic mural thrombi (TMT) are rare but an important source of distal emboli. Treatment options are dynamic, ranging from open, endovascular to conservative therapies. We report two cases of TMT, one successfully treated with thoracic aortic endoluminal stent placement for visceral and peripheral embolization, the second treated conservatively for digital embolization secondary to TMT in the innominate artery.

The Use of the Amplatzer Plug to Treat Dysphagia Lusoria Caused by an Aberrant Right Subclavian Artery

Emerging technology with endovascular techniques has expanded our armamentarium to treat the aberrant right subclavian artery. We describe a hybrid technique using an Amplatzer plug in combination with a carotid subclavian bypass to treat a patient with dysphagia lusoria.

Systemically Delivered Adipose Stromal Vascular Fraction Cells Disseminate to Peripheral Artery Walls and Reduce Vasomotor Tone Through a CD11b+ Cell-Dependent Mechanism

Vasoactivity, an important aspect of tissue healing, is often compromised in disease and tissue injury. Dysfunction in the smaller vasoactive arteries is most impactful, given the role of these vessels in controlling downstream tissue perfusion. The adipose stromal vascular fraction (SVF) is a mix of homeostatic cells shown to promote tissue healing. Our objective was to test the hypothesis that autologous SVF cells therapeutically modulate peripheral artery vasoactivity in syngeneic mouse models of small artery function. Analysis of vasoactivity of saphenous arteries isolated from normal mice 1 week after intravenous injection of freshly isolated SVF cells revealed that pressure‐dependent artery vasomotor tone was decreased by the SVF cell isolate, but not one depleted of CD11b+ cells. Scavenging hydrogen peroxide in the vessel wall abrogated the artery relaxation promoted by the SVF cell isolate. Consistent with a CD11b+ cell being the relevant cell type, SVF‐derived F4/80‐positive macrophages were present within the adventitia of the artery wall coincident with vasorelaxation. In a model of artery inflammation mimicking a common disease condition inducing vasoactive dysfunction, the SVF cells potentiated relaxation of saphenous arteries without structurally remodeling the artery via a CD11b+ cell‐dependent manner. Our findings demonstrate that freshly isolated, adipose SVF cells promote vasomotor relaxation in vasoactive arteries via a hydrogen peroxide‐dependent mechanism that required CD11b+ cells (most likely macrophages). Given the significant impact of small artery dysfunction in disease, we predict that the intravenous delivery of this therapeutic cell preparation would significantly improve tissue perfusion, particularly in diseases with diffuse vascular involvement.

Restoration of Physiologically Responsive Low-Density Lipoprotein Receptor-Mediated Endocytosis in Genetically Deficient Induced Pluripotent Stem Cells.

Acquiring sufficient amounts of high-quality cells remains an impediment to cell-based therapies. Induced pluripotent stem cells (iPSC) may be an unparalleled source, but autologous iPSC likely retain deficiencies requiring correction. We present a strategy for restoring physiological function in genetically deficient iPSC utilizing the low-density lipoprotein receptor (LDLR) deficiency Familial Hypercholesterolemia (FH) as our model. FH fibroblasts were reprogrammed into iPSC using synthetic modified mRNA. FH-iPSC exhibited pluripotency and differentiated toward a hepatic lineage. To restore LDLR endocytosis, FH-iPSC were transfected with a 31 kb plasmid (pEHZ-LDLR-LDLR) containing a wild-type LDLR (FH-iPSC-LDLR) controlled by 10 kb of upstream genomic DNA as well as Epstein-Barr sequences (EBNA1 and oriP) for episomal retention and replication. After six months of selective culture, pEHZ-LDLR-LDLR was recovered from FH-iPSC-LDLR and transfected into Ldlr-deficient CHO-a7 cells, which then exhibited feedback-controlled LDLR-mediated endocytosis. To quantify endocytosis, FH-iPSC ± LDLR were differentiated into mesenchymal cells (MC), pretreated with excess free sterols, Lovastatin, or ethanol (control), and exposed to DiI-LDL. FH-MC-LDLR demonstrated a physiological response, with virtually no DiI-LDL internalization with excess sterols and an ~2-fold increase in DiI-LDL internalization by Lovastatin compared to FH-MC. These findings demonstrate the feasibility of functionalizing genetically deficient iPSC using episomal plasmids to deliver physiologically responsive transgenes.

Meningococcal sepsis and purpura fulminans: the surgical perspective

Meningococcal sepsis and purpura fulminans is a rare but highly lethal disease process that requires a multidisciplinary team of experts to optimise morbidity and mortality outcomes due to the breadth of complications of the disease. The surgical perspective involves the critical care management which utilises all currently available measured outcomes of critical care management as well as experimental therapies. Limb loss is common, and is reflective of the high incidence of compartment syndrome compounded by the significant soft tissue loss secondary to purpura and limb ischaemia, presumptively due to digital microemboli. A multidisciplinary approach involving current standards in critical care and early surgical evaluation are important in improving patient outcomes and limb salvage.

Varying Presentations in Patients With Symptomatic Type IV Vascular Ehlers-Danlos Syndrome

Ehlers-Danlos syndrome (EDS) represents a group of inheritable connective tissue disorders. Patients with type IV or vascular EDS, autosomal dominant pattern of inheritance, may present with aneurysm formation or arterial dissection. Due to vessel fragility, operative therapy for such disorders has been reserved for compelling indications in which benefit clearly warrants risk, yet assessment of risk is largely clinical with operative decisions guided by factors such as response to previous operations and age at onset of index vascular complications. We present 2 patients with differences in their clinical presentations and outcomes and review the literature with emphasis on operative decision making.

Concentration-Dependent Vascularization of Adipose Stromal Vascular Fraction Cells.

Adipose-derived stromal vascular fraction (SVF) cells have been shown to self-associate to form vascular structures under both in vitro and in vivo conditions. The angiogenic (new vessels from existing vessels) and vasculogenic (new vessels through self-assembly) potential of the SVF cell population may provide a cell source for directly treating (i.e., point of care without further cell isolation) ischemic tissues. However the correct dosage of adipose SVF cells required to achieve a functional vasculature has not been established. Accordingly, in vitro and in vivo dose response assays were performed evaluating the SVF cell vasculogenic potential. Serial dilutions of freshly isolated rat adipose SVF cells were plated on growth factor reduced Matrigel and vasculogenesis, assessed as cellular tube-like network assembly, was quantified after 3 days of culture. This in vitro vasculogenesis assay indicated that rat SVF cells reached maximum network length at a concentration of 2.5 × 105 cells/ml and network maintained at the higher concentrations tested. The same concentrations of rat and human SVF cells were used to evaluate vasculogenesis in vivo. SVF cells were incorporated into collagen gels and subcutaneously implanted into Rag1 immunodeficient mice. The 3D confocal images of harvested constructs were evaluated to quantify dose dependency of SVF cell vasculogenesis potential. Rat- and human-derived SVF cells yielded a maximum vasculogenic potential at 1 × 106 and 4 × 106 cells/ml, respectively. No adverse reactions (e.g., toxicity, necrosis, tumor formation) were observed at any concentration tested. In conclusion, the vasculogenic potential of adipose-derived SVF cell populations is dose dependent.

Ruptured hypogastric artery aneurysms: a contemporary review.

The ruptured hypogastric artery aneurysm (RHAA) is a rare clinical entity with an evolving and dynamic therapeutic armamentarium. The anatomical location and varied clinical presentation can pose a challenge for successful repair. Recently, endovascular and hybrid operative repairs have significantly improved the historically high-operative mortality rate. We present an illustrative case and contemporary review of the literature with respect to RHAA.

Infection of an Aortic Stent Graft with Suprarenal Fixation

We report a case of an elderly man admitted with abdominal pain and fever, 5 months after endovascular aortic aneurysm repair of a suspected inflammatory abdominal aortic aneurysm. He underwent successful explantation of an infected stent graft with suprarenal fixation following extra-anatomic revascularization. After a prolonged hospitalization, he was discharged on antibiotics and at follow-up has returned to baseline activity level. Although explantation of an infected prosthesis following endovascular aortic aneurysm repair has been previously reported, our case prompted a review of the literature to evaluate mode of presentation, putative factors, and management decisions associated with reduced morbidity and mortality.

Obstructive jaundice secondary to multiple hepatic artery aneurysms in a 14-year-old boy with neurofibromatosis type 1.

Neurofibromatosis type 1 is the most common inherited disorder of the nervous system, affecting approximately 1 in 3,000 people. A small but significant subset of these patients develop vasculopathies. We present the first reported case of neurofibromatosis type 1 presenting with obstructive jaundice secondary to multiple hepatic artery aneurysms. Therapy included staged coil embolization of the hepatic artery aneurysms and resection of a large retroperitoneal neurofibroma.