The geometric evolution of aortic dissections: Predicting surgical success using fluctuations in integrated Gaussian curvature.

Clinical imaging modalities are a mainstay of modern disease management, but the full utilization of imaging-based data remains elusive. Aortic disease is defined by anatomic scalars quantifying aortic size, even though aortic disease progression initiates complex shape changes. We present an imaging-based geometric descriptor, inspired by fundamental ideas from topology and soft-matter physics that captures dynamic shape evolution. The aorta is reduced to a two-dimensional mathematical surface in space whose geometry is fully characterized by the local principal curvatures. Disease causes deviation from the smooth bent cylindrical shape of normal aortas, leading to a family of highly heterogeneous surfaces of varying shapes and sizes. To deconvolute changes in shape from size, the shape is characterized using integrated Gaussian curvature or total curvature. The fluctuation in total curvature (δK) across aortic surfaces captures heterogeneous morphologic evolution by characterizing local shape changes. We discover that aortic morphology evolves with a power-law defined behavior with rapidly increasing δK forming the hallmark of aortic disease. Divergent δK is seen for highly diseased aortas indicative of impending topologic catastrophe or aortic rupture. We also show that aortic size (surface area or enclosed aortic volume) scales as a generalized cylinder for all shapes. Classification accuracy for predicting aortic disease state (normal, diseased with successful surgery, and diseased with failed surgical outcomes) is 92.8±1.7%. The analysis of δK can be applied on any three-dimensional geometric structure and thus may be extended to other clinical problems of characterizing disease through captured anatomic changes.

Antibiotic use in acute mesenteric ischemia: a review of the evidence and call to action.

Acute mesenteric ischemia (AMI) is a life-threatening condition with a high mortality rate. The standard practice after making the diagnosis includes aggressive resuscitation, anticoagulation, followed by revascularization and resection of necrotic bowel. The role of empiric antibiotics in the management of AMI is not well defined in the literature. This review article aims to examine our current understanding on this matter, based on bench research and clinical studies. It is demonstrated in animal study model that the ischemia/reperfusion (I/R) injury damages intestinal epithelium, and subsequently lead to barrier dysfunction, a condition that can support bacterial translocation through a complex interplay between the intestinal epithelium, the intestinal immune system and the intestine's endogenous bacterial population. Based on this mechanism, it is possible that the use of antibiotics may help mitigate the consequences of I/R injury, which is examined in few animal studies. In clinical practice, many guidelines support the use of prophylactic antibiotics, based on a meta-analysis of randomized control trials (RCTs) demonstrating the benefit of antibiotics in multi-organ dysfunction syndrome. However, there is no direct reference to AMI in this meta-analysis. Most clinical studies that focus on AMI and mentions the use of antibiotics are retrospective and single institution, and very few comments on the role of antibiotics in their discussions. We conclude that there is limited evidence in literature to support the use of prophylactic antibiotic in AMI to improve outcome. More clinical studies with high level of evidence and basic science research are needed to improve our understanding on this topic and ultimately help build a better clinical pathway for patients with AMI.

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.

Computational analysis of endovascular aortic repair proximal seal zone preservation with endoanchors: A case study in cylindrical neck anatomy.

BACKGROUND: Endovascular aortic repair is the common approach for abdominal aortic aneurysms, but endoleaks remain a significant problem with long-term success. Endoanchors have been found to reduce the incidence of type 1A endoleaks and can treat intraoperative type 1a endoleaks. However, little is known about the optimal number and position of endoanchors to achieve the best outcome. METHODS: Using image segmentation and a computational model derived from a reconstructed native patient abdominal aortic aneurysm geometry, the stability of the proximal seal zone was examined through finite element analysis in Abaqus (Dassault Systèmes, Providence, RI). The biomechanical parameter of contact area was compared for varying numbers (0, 2, 4, 8) and positions (proximal, medial, distal) of endoanchors under different adhesion strengths and physiologic pressure conditions. RESULTS: In every simulation, an increase in adhesion strength is associated with maintenance of proximal seal. For biologically plausible adhesion strengths, under conditions of normal blood pressure (120 mm Hg), the addition of any number of endoanchors increases the stability of the endograft-wall interface at the proximal seal zone by approximately 10% compared with no endoanchors. At hypertensive pressures (200 mm Hg), endoanchors increase the stability of the interface by 20% to 60% compared with no endoanchors. The positioning of endoanchors within the proximal seal zone has a greater effect at hypertensive pressures, with proximal positioning increasing stability by 15% compared with medial and distal positioning and 30% compared with no endoanchors. CONCLUSIONS: Endoanchors improve fixation within the proximal seal zone particularly under conditions of high peak systolic pressure. Seal zone stabilization provides a mechanism through which endoanchor addition may translate into lower rates of type 1a endoleaks for patients.

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.

Plasmin thrombelastography rapidly identifies trauma patients at risk for massive transfusion, mortality, and hyperfibrinolysis: A diagnostic tool to resolve an international debate on tranexamic acid?

BACKGROUND: Trauma patients with hyperfibrinolysis and depletion of fibrinolytic inhibitors (DFIs) measured by thrombelastography (TEG) gain clot strength with TXA, but TEG results take nearly an hour. We aimed to develop an assay, plasmin TEG (P-TEG), to more expeditiously stratify risk for massive transfusion (MT), mortality, and hyperfibrinolysis. METHODS: Trauma patients (N = 148) were assessed using TEG assays without exogenous additives (rapid/native), with exogenous plasmin (P-TEG) or tissue plasminogen activator (tPA TEG). The plasmin dose used does not effect healthy-control clot lysis 30 minutes after maximum amplitude (LY30) but causes shortened reaction time (R time) relative to native TEG (P-TEG R time < native TEG R time considered P-TEG negative). If P-TEG R time is greater than or equal to native TEG R time, the patient was considered P-TEG positive. Each assay's ability to predict MT, mortality, and (risk for) hyperfibrinolysis was determined. χ and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. Results were reported as median ± interquartile range or n (%). RESULTS: Plasmin TEG provided results faster than all other assays (4.7 ± 2.5-9.1 minutes), approximately 11-fold faster than rapid-TEG (rTEG) LY30 (54.2 ± 51.1-58.1 minutes; p < 0.001). Plasmin TEG-positive patients had greater than fourfold higher MT rate (30% vs. 7%; p = 0.0015) with an area under the receiver operating characteristic curve of 0.686 (p = 0.028), greater than fourfold higher 24-hour mortality (33.3% vs. 7.8%; p = 0.0177), greater than twofold higher 30-day mortality (35% vs. 16.4%; p = 0.0483), higher rates of DFI (55% vs. 18%; p < 0.001), and a trend toward elevated D-dimer (19.9 vs. 3.3 µg/mL; p = 0.14). Plasmin TEG was associated with hyperfibrinolysis on rTEG LY30 at the 7.6% threshold (p = 0.04) but not the 3% threshold (p = 0.40). Plasmin TEG performed best in relation to DFI, with a positive predictive value of 58% and negative predictive value of 81%. When combined with tPA TEG time to maximum amplitude, P-TEG outperformed rTEG LY30 for predicting MT (area under the receiver operating characteristic curve, 0.811 vs. 0.708). CONCLUSION: Within 5 minutes, P-TEG can stratify patients at highest risk for MT, mortality, and risk for hyperfibrinolysis. In composite with tPA TEG time to maximum amplitude, P-TEG outperforms rTEG LY30 for predicting MT and does so four times faster (12.7 vs. 54.1 minutes). The rapid results of P-TEG may be useful for those who practice selective TXA administration to maximize TXA's time-dependent efficacy. LEVEL OF EVIDENCE: Diagnostic test, level V.

Modern Management of Bleeding, Clotting, and Coagulopathy in Trauma Patients: What Is the Role of Viscoelastic Assays?

PURPOSE OF REVIEW: The purpose of this review is to briefly outline the current state of hemorrhage control and resuscitation in trauma patients with a specific focus on the role viscoelastic assays have in this complex management, to include indications for use across all phases of care in the injured patient. RECENT FINDINGS: Viscoelastic assay use to guide blood-product resuscitation in bleeding trauma patients can reduce mortality by up to 50%. Viscoelastic assays also reduce total blood products transfused, reduce ICU length of stay, and reduce costs. There are a large number of observational and retrospective studies evaluating viscoelastic assay use in the initial trauma resuscitation, but only one randomized control trial. There is a paucity of data evaluating use of viscoelastic assays in the operating room, post-operatively, and during ICU management in trauma patients, rendering their use in these settings extrapolative/speculative based on theory and data from other surgical disciplines and settings. SUMMARY: Both hypocoagulable and hypercoagulable states exist in trauma patients, and better indicate what therapy may be most appropriate. Further study is needed, particularly in the operating room and post-operative/ICU settings in trauma patients.

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.