Analysis of Presentation and Outcomes in Acute Limb Ischemia Patients During COVID-19 State of Emergency.

BACKGROUND: During the COVID-19 pandemic, cardiovascular patients were found to be presenting to hospitals with myocardial infarctions and cerebrovascular accidents at progressed disease states. We noticed a parallel in acute limb ischemia (ALI) patients presenting during Massachusetts' COVID-19 State of Emergency declaration. We question whether patients developed a hesitancy to seek medical attention at hospitals due to fear of COVID-19. Our objective was to compare acuity of ALI, interventions, and limb survival in patients presenting before, during, and after a state of emergency. METHODS: Four timeframes were set to compare patients presenting peri-2020 COVID-19 State of Emergency and patients presenting during a pre-pandemic era at a tertiary, academic institution. A reference period from 2019, Pre-State of Emergency period, State of Emergency period, and Post-State of Emergency period were designated. Patient characteristics, interventions, and outcomes data were collected. Unpaired t-test, ANOVA, and Chi-square statistical analyses were used. RESULTS: A total of 95 patients presenting with ALI were identified. Compared to Reference group, state of emergency group had more patients presenting with Rutherford Class III, 12.9% vs 35%, and less patient presenting with Class I, 45.1% vs 0%, P = .02. State of emergency group had more delayed presentations with ≥6 hours after symptom onset, 45% vs 85%, P = .01. Above-knee amputations were performed in 20% of patients during state of emergency and 31.6% for Post-State of Emergency, vs 6.5% in the Reference group; P = .03. There was no difference in intensive care unit admission, length of stay, or mortality between patients from different groups. CONCLUSION: During a state of emergency, ALI patients were noted to present later from symptom onset, have greater disease severity, and more likely to undergo amputations. We suspect delay in presentation and limb lost to be attributed to reluctance to seek immediate medical attention.

The Progression of Billowing of Endologix AFX2® Abdominal Aortic Aneurysm Device as a Precursor for the Rupture of an Abdominal Aortic Aneurysm.

Despite recent publications indicating billowing (aneurysmal degeneration of the outer fabric material manifesting as a bulging sac of contained contrast due to weakening of the fabric material between the metal struts) as a benign finding, we present a unique case of billowing that resulted in aneurysmal rupture with the AFX2® stent graft (Endologix, Inc., Irvine, CA). AFX2® consists of an inner metallic endoskeleton with multiple metallic struts covered by a polytetrafluoroethylene graft fabric. It allows the flow of blood or contrast beyond the border of the metallic endoskeleton without evidence of endoleak or rupture secondary to the outer cover being anchored to the endoskeleton with polypropylene sutures only at the proximal and distal ends. Our report raises the concern that although billowing may be a relatively common manifestation with Endologix stent grafts, clinicians have to be diligent as the phenomenon may progress to abdominal aortic aneurysm rupture.

Exertional Abdominal Pain as a Rare Presenting Manifestation of Chronic Mesenteric Ischemia from a Single Mesenteric Vessel Stenosis.

We present an atypical manifestation of chronic mesenteric ischemia in a patient with progressively worsening exertional abdominal pain. Imaging modalities revealed significant isolated stenosis of superior mesenteric artery (SMA). Successful angioplasty and stenting of SMA relieved patient's symptoms, thereby confirming the diagnosis of chronic mesenteric ischemia. Exertional abdominal pain may be a unique manifestation of this disease, but when it presents, clinicians should have acute clinical awareness of this diagnosis.

Eversion Femoral Endarterectomy for Iliofemoral Occlusive Disease: A Description of Technique and Series of Cases.

BACKGROUND: Eversion endarterectomy (EE) is a well-described technique for the treatment of extracranial cerebrovascular disease. Longitudinal arteriotomy and closure with patch angioplasty is the standard for infrainguinal arterial occlusive disease in the iliofemoral segment. A potential drawback of this technique is the introduction of exogenous material into the field. We herein describe a technique of transverse femoral arteriotomy with primary closure for treatment of chronic limb ischemia involving the iliofemoral system. METHODS: We retrospectively evaluated all patients who underwent EE at our institution for chronic limb ischemia. Eleven patients were identified who underwent EE by a single surgeon (M.N.) at our institution from 2013 to 2014. Indications for operation included life-limiting claudication, rest pain, and tissue loss. In each case, the external iliac artery (EIA), common femoral artery (CFA), or superficial femoral artery (SFA) was divided with eversion of the proximal and distal segments and endarterectomy. Reconstruction was achieved with primary end-to-end closure. Preoperative demographics were evaluated, as well as preoperative and postoperative ankle-brachial indices and Trans-Atlantic Inter-Society Consensus (TASC) II lesion classification when available. In addition, all adjunctive procedures performed both at the time of index operation and subsequently were recorded. Clinical improvement was gauged using the recommended scale for gauging change in clinical status according to Rutherford. RESULTS: Follow-up ranged from 6 weeks to 16 months. There were no amputations, deaths, or surgical site infections. Two patients required concomitant patch angioplasty in the treated segment at the index operation. There was symptom improvement in 9 of 11 patients, with 2 requiring reintervention due to poor outflow. CONCLUSIONS: In patients with arterial occlusive disease of the iliofemoral segment, EE either alone or in association with endovascular stenting or open bypass appears to be a safe and effective technique. It may obviate the need for patch closure. In our initial case series, there were no amputations, deaths, or surgical site infections. Symptoms improved in 9 of 11 patients with only 2 requiring reintervention due to recurrent symptoms during the follow-up period.

Point-of-Care Adipose-Derived Stromal Vascular Fraction Cell Isolation and Expanded Polytetrafluoroethylene Graft Sodding.

Adipose-derived stromal vascular fraction (SVF) cell populations are being evaluated for numerous clinical applications. The current study evaluated a point-of-care technology, the Tissue Genesis "TGI 1000" Cell Isolation System™, to perform an automated isolation of adipose-derived SVF cells to be used in the fabrication of a tissue-engineered vascular graft in the operating room. A total of seven patients were enrolled in this study and received femoral to tibial expanded polytetrafluoroethylene bypass grafts to treat peripheral arterial disease. Lipoaspiration of fat was performed on five patients, and the fat sample was processed immediately in the automated system in the operating room. The mean processing time, from the point of fat delivery into the instrument to removal of the SVF-containing syringe, was 70 min. The SVF cell population was evaluated for cell yield, cell viability, endotoxin levels, and microbial contamination. Samples of the SVF preparation were further subjected to microbiologic evaluation both microscopically before implantation of the graft and through a microbiologic screening using aerobic and anaerobic culture conditions. Mean cell yield was 1E5 cells per cc of fat, and endotoxin levels were below the FDA recognized standards. All SVF preparations were released for graft preparation, and the intimal surface of 90-cm-long grafts was pressure sodded with cells at a concentration of 2E5 cells/cm2. The sodded grafts (n = 5) and control grafts (n = 2) were immediately implanted and graft patency assessed for 1 year. One year patency was 60% for sodded grafts and 50% for control grafts. Automated preparation of autologous adipose-derived SVF cells for immediate use to create cellular linings on vascular grafts is feasible and safe.

Blunt traumatic celiac artery avulsion managed with celiac artery ligation and open aorto-celiac bypass.

Traumatic celiac artery injuries are rare and highly lethal with reported mortality rates of 38-62%. The vast majority are caused by penetrating trauma with only 11 reported cases due to blunt trauma (Graham et al., 1978; Asensio et al., 2000, 2002). Only 3 of these cases were complete celiac artery avulsions. Management options described depend upon the type of injury and have included medical therapy with anti-platelet agents or anti-coagulants, endovascular stenting, and open ligation. We report a case of a survivor of complete celiac artery avulsion from blunt trauma managed by open bypass.

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.

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.

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 × 10(5) 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 × 10(6) and 4 × 10(6) 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.

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.

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.

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.

Uterine trauma with fetal loss associated with chronic perforation of the inferior vena cava by an infrarenal vena cava filter.

Gestational complications in pregnant women have been considered a theoretical sequelae of vena cava filters (VCFs) positioned in the infrarenal segment of the inferior vena cava. We describe a 32-year-old woman who became pregnant with the known existence of an asymptomatic but chronically perforated, permanent infrarenal VCF. At 24 weeks gestation, uterine trauma leading to massive intraperitoneal hemorrhage and fetal loss occurred. Our case documents that gestational risk, heretofore theoretical, is real and calls for heightened awareness of the need for appropriate VCF management in women of childbearing age and consideration for preconception evaluation of the filter-bearing inferior vena cava in women considering pregnancy in whom VCFs have been previously implanted.

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.

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.