Gaussian Surface Curvature Mapping Indicating High Risk Type B Thoracic Aortic Dissections.

BACKGROUND: Identifying fragile aortas that are more likely to lead to adverse clinical outcomes would provide surgeons with a better sense of how to balance the risks of surgical versus medical management in patients with type B dissections. We examine the progression of a type B dissection into a type A dissection in a patient and analyze changes in the Gaussian surface curvature distribution, as well as the response of the stress distribution at the lesser curve in response to pressurization. We hypothesize that examining the Gaussian curvature will provide us with a link between aortic surface geometry and the stress distribution, which is crucial to understanding the process driving aortic dissection. METHODS: Computed tomography scans of a patient before and after the type A dissection are obtained. These are segmented in Simpleware ScanIP. Centerline curvatures are calculated on segmented models in ScanIP. Models are then pressurized in the finite element analysis software Abaqus. The Gaussian curvature is calculated by exporting segmentations into the computational program Matlab and applying a modified previously published algorithm. RESULTS: The centerlines generated in ScanIP fail to capture the change in the acuity of the lesser curve before and after the type A dissection. Instead, Gaussian curvature analysis shows that the curvature distribution before the type A dissection is much wider compared with the distribution after the type A dissection. In addition, analyzing the stress distribution in response to pressurization reveals that before the type A dissection there is a large divergence in the principal stress vectors at the lesser curve but this transitions to a more uniform hoop stress after the type A dissection. CONCLUSIONS: Our analysis demonstrates that Gaussian surface curvature analysis captures changes in aortic geometry that are otherwise silent in centerline curvature analysis. Here, we show that as the aorta develops a type A dissection it is able to more smoothly handle the hoop stress at the lesser curve compared with the stress focusing seen in the before type A geometry. We propose that the geometric focusing before type A creates a higher energy stress state, which is relaxed on retrograde dissection. Thus, Gaussian curvature analysis may provide a window to capture underlying geometric instability in type B dissections.

Intravascular ultrasound-guided transcaval approach for thoracic endovascular aneurysm repair.

Thoracic endovascular aortic repair will typically require adequate caliber iliofemoral arteries for device deployment. We describe the case of a patient with extensive iliofemoral disease, which necessitated transcaval delivery of an aortic graft to repair a distal aortic arch aneurysm. Our case report highlights the novel use of intravascular ultrasound to localize an optimal site for creation of an aortocaval connection and the subsequent use of a ventricular septal defect occluder to close the connection after successful stent deployment.

Enhancing chemotherapy response through augmented synthetic lethality by co-targeting nucleotide excision repair and cell-cycle checkpoints.

In response to DNA damage, a synthetic lethal relationship exists between the cell cycle checkpoint kinase MK2 and the tumor suppressor p53. Here, we describe the concept of augmented synthetic lethality (ASL): depletion of a third gene product enhances a pre-existing synthetic lethal combination. We show that loss of the DNA repair protein XPA markedly augments the synthetic lethality between MK2 and p53, enhancing anti-tumor responses alone and in combination with cisplatin chemotherapy. Delivery of siRNA-peptide nanoplexes co-targeting MK2 and XPA to pre-existing p53-deficient tumors in a highly aggressive, immunocompetent mouse model of lung adenocarcinoma improves long-term survival and cisplatin response beyond those of the synthetic lethal p53 mutant/MK2 combination alone. These findings establish a mechanism for co-targeting DNA damage-induced cell cycle checkpoints in combination with repair of cisplatin-DNA lesions in vivo using RNAi nanocarriers, and motivate further exploration of ASL as a generalized strategy to improve cancer treatment.