Kirstyn Brownson

Disturbed shear stress reduces Klf2 expression in arterial-venous fistulae in vivo

Laminar shear stress (SS) induces an antiproliferative and anti‐inflammatory endothelial phenotype and increases Klf2 expression. We altered the diameter of an arteriovenous fistula (AVF) in the mouse model to determine whether increased fistula diameter produces disturbed SS in vivo and if acutely increased disturbed SS results in decreased Klf2 expression. The mouse aortocaval fistula model was performed with 22, 25, or 28 gauge needles to puncture the aorta and the inferior vena cava. Duplex ultrasound was used to examine the AVF and its arterial inflow and venous outflow, and SS was calculated. Arterial samples were examined with western blot, immunohistochemistry, and immunofluorescence analysis for proteins and qPCR for RNA. Mice with larger diameter fistulae had diminished survival but increased AVF patency. Increased SS magnitudes and range of frequencies were directly proportional to the needle diameter in the arterial limb proximal to the fistula but not in the venous limb distal to the fistula, with 22‐gauge needles producing the most disturbed SS in vivo. Klf2 mRNA and protein expression was diminished in the artery proximal to the fistula in proportion to increasing SS. Increased fistula diameter produces increased SS magnitude and frequency, consistent with disturbed SS in vivo. Disturbed SS is associated with decreased mRNA and protein expression of Klf2. Disturbed SS and reduced Klf2 expression near the fistula are potential therapeutic targets to improve AVF maturation.

Systemic Inflammatory Disease and Its Association With Type II Endoleak and Late Interventions After Endovascular Aneurysm Repair

IMPORTANCE Abdominal aortic aneurysms are associated with chronic inflammation within the aortic wall, and previous studies have suggested that chronic inflammation may be a consequence of a dysregulated and persistent autoimmune response. Persistent aortic remodeling after aneurysm repair could place the patient at risk for endoleak or sac rupture. OBJECTIVE To determine whether patients with systemic inflammatory disease and large aneurysms have persistent aortic remodeling after endovascular aneurysm repair (EVAR). DESIGN, SETTING, AND PARTICIPANTS The records of all patients who underwent EVAR between July 2002 and June 2011 at the Veterans Affairs Connecticut Healthcare System were included in this retrospective review. Patients were considered to have a systemic inflammatory disease when confirmed by a referring specialist. Post-EVAR surveillance was performed by yearly imaging. INTERVENTION Endovascular aneurysm repair. MAIN OUTCOMES AND MEASURES Significant endoleak, defined as endoleak and sac diameter increase of 0.5 cm or greater. RESULTS A total of 51 of 79 patients (65%) had a systemic inflammatory disease. These patients had similar comorbid conditions compared with patients without inflammation but significantly greater numbers of major postoperative complications after EVAR (23.5% vs 3.6%; P = .02) and overall postoperative complications after EVAR (27.5% vs 7.1%; P = .03). Patients with a history of systemic inflammatory disease developed more endoleaks (45.1% vs 17.9%; P = .02) and late sac expansion (51.0% vs 21.4%; P = .01) and required more interventions (21.6% vs 3.6%; P = .03) during long-term follow-up. Systemic inflammatory disease was significantly associated with significant endoleak (odds ratio, 5.18; 95% CI, 1.56-17.16; P = .007). CONCLUSIONS AND RELEVANCE Patients with systemic inflammatory disease are at high risk for postoperative complications, type II endoleak, sac expansion, and additional interventions after EVAR. Additional strategies for improving the efficacy of EVAR in these patients may be warranted.

Management of isolated calf vein thrombosis in cancer patients

The treatment of isolated calf vein thrombosis remains widely debated. This study highlights the characteristics of isolated calf vein thrombosis in cancer patients and compares to isolated calf vein thrombosis in patients without history of cancer. Between July 2013 and April 2014, a retrospective chart review of consecutive patients with isolated calf vein thrombosis was performed recording patient risk factors, ultrasound characteristics of the thrombus, treatment modalities, long-term recurrence of venous-thromboembolism, incidence of bleeding, and mortality. Of 131 patients with isolated calf vein thrombosis, 53 (40.1%) had history of cancer. Isolated calf vein thrombosis occurred at an older age in cancer patients (66.7 vs 58.5 years, p = 0.004). The anatomical characteristics of isolated calf vein thrombosis on ultrasound were comparable in both groups. Isolated calf vein thrombosis in cancer patients was less likely to be treated with anticoagulation (60.4% vs 80.8%, p = 0.018). However, a trend towards higher incidence of bleeding after initiation of anticoagulation for isolated calf vein thrombosis in cancer patients (11.3% vs 6.4%, p = 0.351) was noted. Mortality in cancer patients was higher (37.7% vs 9.00%, p < 0.001) but was unrelated to isolated calf vein thrombosis or its treatment. In conclusion, the risks of bleeding seem to exceed the benefits of anticoagulation in approximately 50% of cancer patients with isolated calf vein thrombosis. The management of isolated calf vein thrombosis does not seem to impact the survival of cancer patients.

Embryological Basis for Vascular Anomalies

Abnormal embryonic development of the vascular system causes a variety of vascular anomalies. Vasculogenesis is genetically determined with a specific sequence of formation, selective regression, and remodeling that must occur in the correct sequence to produce the typical mature vascular system. Investigation into the genes and signaling pathways that guide this complex process are crucial to understanding how vascular anomalies develop and may ultimately provide clues for therapeutic intervention or treatment of these conditions.