Unusual presentation of distal ICA aneurysm in relation to dental abscess.

Mycotic extracranial carotid artery aneurysms are a rare vascular phenomenon with a number of implicated pathogens, most commonly Staphylococcus aureus and Salmonella. Presentation of a mycotic extracranial carotid artery aneurysm after dental abscess or procedure is similarly not frequently described in the literature. We present a unique case of a large, distal mycotic internal carotid artery aneurysm, which developed secondary to Haemophilus parainfluenzae infection and dental abscess.

Use of Direct Oral Anticoagulant and Associated Bleeding and Thrombotic Complication after Lower Extremity Bypass.

BACKGROUND: Therapeutic anticoagulation with either a vitamin K antagonist (VKA) or direct anticoagulant (DOAC) is often newly prescribed to patients undergoing lower extremity bypass (LEB) to aid in graft patency when risk factors for thrombosis are present or to treat postoperative venous thromboembolism or atrial fibrillation. There is a gap in knowledge as to how DOAC usage impacts postoperative outcomes compared with the standard-of-care VKAs. STUDY DESIGN: To determine temporal trends in DOAC prescription after infrainguinal LEB, impact on length of stay (LOS), and associated bleeding and thrombotic complications, patients undergoing elective LEB were identified from the Vascular Quality Initiative between January 2013 and May 2019. Postoperative bleeding, LOS, and graft occlusion for patients receiving VKA compared with DOAC were evaluated. RESULTS: A total of 24,459 LEBs were performed during the study period. Among 2,656 patients newly prescribed an anticoagulant, 78.0% (n = 2,072) received VKA and 22.0% (n = 584) received a DOAC, with DOAC use increasing throughout the study period. There was no significant difference in postoperative bleeding (VKA 2.3%, DOAC 1.7%, p = 0.413) or graft occlusion (VKA 1.2%, DOAC 1.4%, p = 0.762) between the anticoagulant classes. LOS was shorter in the DOAC group than in the VKA group (5.7 vs 6.8 days; p < 0.001). CONCLUSIONS: This analysis demonstrates that DOAC use is increasing with time in Vascular Quality Initiative centers. DOACs are a safe and comparable alternative to VKAs in the postoperative setting with similar rates of bleeding complications and early graft patency and are associated with a reduced postoperative LOS.

Endoscopic and fluoroscopic-guided closure of the eustachian tube using a biliary cytology brush and liquid embolic agent for a persistent CSF leak after schwannoma resection.

Vestibular schwannoma is a known cause of progressive sensorineural hearing loss. Treatment options include observation, radiation therapy and surgical resection. Cerebrospinal fluid (CSF) fistula is a known postsurgical complication that can lead to CSF otorrhoea, rhinorrhoea or CSF leakage from the surgical wound. We present a case report of a patient who underwent vestibular schwannoma resection and postoperatively developed CSF rhinorrhoea, which was refractory to multiple attempts at surgical repair. This was successfully treated under endoscopic and fluoroscopic guidance using a biliary cytology brush to disrupt the surface of the eustachian tube followed by injection of n-Butyl cyanoacrylate.

Intranodal lymphangiography and interstitial lymphatic embolization to treat chyluria caused by a lymphatic malformation in a pediatric patient.

Chyluria is characterized by chyle in the urinary tract and often presents as milky-white urine. We present a case of chyluria from a lymphatic malformation in a 13-year-old boy diagnosed using dynamic intranodal contrast-enhanced magnetic resonance (MR) lymphangiography. This report demonstrates the utility of intranodal lymphangiography and interstitial lymphatic embolization to treat a pediatric patient presenting with persistent chyluria. Glue migration into the urinary collecting system is a potential complication of this procedure that can be mitigated by adjusting the n-butyl cyanoacrylate dilution with Lipiodol.

Hemodynamic regulation of perivalvular endothelial gene expression prevents deep venous thrombosis.

Deep venous thrombosis (DVT) and secondary pulmonary embolism cause approximately 100,000 deaths per year in the United States. Physical immobility is the most significant risk factor for DVT, but a molecular and cellular basis for this link has not been defined. We found that the endothelial cells surrounding the venous valve, where DVTs originate, express high levels of FOXC2 and PROX1, transcription factors known to be activated by oscillatory shear stress. The perivalvular venous endothelial cells exhibited a powerful antithrombotic phenotype characterized by low levels of the prothrombotic proteins vWF, P-selectin, and ICAM1 and high levels of the antithrombotic proteins thrombomodulin (THBD), endothelial protein C receptor (EPCR), and tissue factor pathway inhibitor (TFPI). The perivalvular antithrombotic phenotype was lost following genetic deletion of FOXC2 or femoral artery ligation to reduce venous flow in mice, and at the site of origin of human DVT associated with fatal pulmonary embolism. Oscillatory blood flow was detected at perivalvular sites in human veins following muscular activity, but not in the immobile state or after activation of an intermittent compression device designed to prevent DVT. These findings support a mechanism of DVT pathogenesis in which loss of muscular activity results in loss of oscillatory shear-dependent transcriptional and antithrombotic phenotypes in perivalvular venous endothelial cells, and suggest that prevention of DVT and pulmonary embolism may be improved by mechanical devices specifically designed to restore perivalvular oscillatory flow.

Hemodynamic Forces Sculpt Developing Heart Valves through a KLF2-WNT9B Paracrine Signaling Axis.

Hemodynamic forces play an essential epigenetic role in heart valve development, but how they do so is not known. Here, we show that the shear-responsive transcription factor KLF2 is required in endocardial cells to regulate the mesenchymal cell responses that remodel cardiac cushions to mature valves. Endocardial Klf2 deficiency results in defective valve formation associated with loss of Wnt9b expression and reduced canonical WNT signaling in neighboring mesenchymal cells, a phenotype reproduced by endocardial-specific loss of Wnt9b. Studies in zebrafish embryos reveal that wnt9b expression is similarly restricted to the endocardial cells overlying the developing heart valves and is dependent upon both hemodynamic shear forces and klf2a expression. These studies identify KLF2-WNT9B signaling as a conserved molecular mechanism by which fluid forces sensed by endothelial cells direct the complex cellular process of heart valve development and suggest that congenital valve defects may arise due to subtle defects in this mechanotransduction pathway.

Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling.

Cerebral cavernous malformations (CCMs) are common inherited and sporadic vascular malformations that cause strokes and seizures in younger individuals. CCMs arise from endothelial cell loss of KRIT1, CCM2 or PDCD10, non-homologous proteins that form an adaptor complex. How disruption of the CCM complex results in disease remains controversial, with numerous signalling pathways (including Rho, SMAD and Wnt/ß-catenin) and processes such as endothelial-mesenchymal transition (EndMT) proposed to have causal roles. CCM2 binds to MEKK3 (refs 7, 8, 9, 10, 11), and we have recently shown that CCM complex regulation of MEKK3 is essential during vertebrate heart development. Here we investigate this mechanism in CCM disease pathogenesis. Using a neonatal mouse model of CCM disease, we show that expression of the MEKK3 target genes Klf2 and Klf4, as well as Rho and ADAMTS protease activity, are increased in the endothelial cells of early CCM lesions. By contrast, we find no evidence of EndMT or increased SMAD or Wnt signalling during early CCM formation. Endothelial-specific loss of Map3k3 (also known as Mekk3), Klf2 or Klf4 markedly prevents lesion formation, reverses the increase in Rho activity, and rescues lethality. Consistent with these findings in mice, we show that endothelial expression of KLF2 and KLF4 is increased in human familial and sporadic CCM lesions, and that a disease-causing human CCM2 mutation abrogates the MEKK3 interaction without affecting CCM complex formation. These studies identify gain of MEKK3 signalling and KLF2/4 function as causal mechanisms for CCM pathogenesis that may be targeted to develop new CCM therapeutics.