Hemodynamic Changes in an Actively Rupturing Abdominal Aortic Aneurysm.

Computational fluid dynamics were used to assess hemodynamic changes in an actively rupturing abdominal aortic aneurysm (AAA) over a 9-day period. Active migration of contrast from the lumen into the thickest region of intraluminal thrombus (ILT) was demonstrated until it ultimately breached the adventitial layer. Four days after symptom onset, there was a discrete disruption of adventitial calcium with bleb formation at the site of future rupture. Rupture occurred in a region of low wall shear stress and was associated with a marked increase in AAA diameter from 6.6 to 8.4 cm. The cross-sectional area of the flow lumen increased across all time points from 6.28 to 12.08 cm2. The increase in luminal area preceded the increase in AAA diameter and was characterized by an overall deceleration in recirculation flow velocity with a coinciding increase in flow velocity penetrating the ILT. We show that there are significant hemodynamic and structural changes in the AAA flow lumen in advance of any appreciable increase in aortic diameter or rupture. The significant increase in AAA diameter with rupture suggests that AAA may actually rupture at smaller sizes than those measured on day of rupture. These findings have implications for algorithms the predict AAA rupture risk.

A Canadian multicenter experience describing outcomes after endovascular abdominal aortic aneurysm repair stent graft explantation.

BACKGROUND: Most studies describing the outcomes after endovascular abdominal aortic aneurysm repair (EVAR) explantation have been from single, high-volume, centers. We performed a multicenter cross-Canadian study of outcomes after EVAR stent graft explantation. Our objectives were to describe the outcomes after late open conversion and EVAR graft explantation at various Canadian centers and the techniques and outcomes stratified by the indication for explant. METHODS: The Canadian Vascular Surgery Research Group performed a retrospective multicenter study of all cases of EVAR graft explantation at participating centers from 2003 to 2018. Data were collected using a standardized, secure, online platform (RedCap [Research Electronic Data Capture]). Univariate statistical analysis was used to compare the techniques and outcomes stratified the indication for graft explantation. RESULTS: Patient data from 111 EVAR explants collected from 13 participating centers were analyzed. The mean age at explantation was 74 years, the average aneurysm size was 7.5 cm, and 28% had had at least one instructions for use violation at EVAR. The average time between EVAR and explantation was 42.5 months. The most common indication for explantation was endoleak (n = 66; type Ia, 46; type Ib, 2; type II, 9; type III, 2; type V, 7), followed by infection in 20 patients; rupture in 18 patients (due to type Ia endoleak in 10 patients, type Ib in 1, type II in 1, type III in 2, and type V in 1), and graft thrombosis in 7 patients. The overall 30-day mortality was 11%, and 45% of the patients had experienced at least one major perioperative complication. Mortality was significantly greater for patients with rupture (33.3%) and those with infection (15%) compared with patients undergoing elective explantation for endoleak (4.5%; P = .003). The average center volume during the previous 15 years was 8 cases with a wide range (2-19 cases). A trend was seen toward greater mortality for patients treated at centers with fewer than eight cases compared with those with eight or more cases (19% vs 9%). However, the difference did not reach statistical significance (P = .23). Overall, 41% of patients had undergone at least one attempt at endovascular salvage before explantation, with the highest proportion among patients who had undergone EVAR explantation for endoleak (51%). Only 22% of patients with rupture had undergone an attempt at endovascular salvage before explantation. CONCLUSIONS: The performance of EVAR graft explantation has increasing in Canada. Patients who had undergone elective explantation for endoleak had lower mortality than those treated for either infection or rupture. Thus, patients with an indication for explanation should be offered surgery before symptoms or rupture has occurred. A trend was seen toward greater mortality for patients treated at centers with lower volumes.

Thromboangiitis Obliterans (Buerger's Disease) in an Adolescent Male.

Arterial occlusive disease of the limb is very rare in children. Buerger's disease (BD) is a nonatherosclerotic, segmental inflammatory arteritis affecting the small and medium-sized vessels of the extremities. We report BD in a 16-year-old male presenting with arterial insufficiency of left foot and history of smoking cigarettes and cannabis for 2 years. BD was diagnosed based on history of smoking in combination with clinical, laboratory, and radiologic findings. Pediatric hemato-oncologists should consider BD in the differential diagnosis in adolescents who smoke cigarettes and/or cannabis and present with vascular insufficiency of the hands and/or feet.

A simple method for sphingolipid analysis of tissues embedded in optimal cutting temperature compound.

MS-assisted lipidomic tissue analysis is a valuable tool to assess sphingolipid metabolism dysfunction in disease. These analyses can reveal potential pharmacological targets or direct mechanistic studies to better understand the molecular underpinnings and influence of sphingolipid metabolism alterations on disease etiology. But procuring sufficient human tissues for adequately powered studies can be challenging. Therefore, biorepositories, which hold large collections of cryopreserved human tissues, are an ideal retrospective source of specimens. However, this resource has been vastly underutilized by lipid biologists, as the components of OCT compound used in cryopreservation are incompatible with MS analyses. Here, we report results indicating that OCT compound also interferes with protein quantification assays, and that the presence of OCT compound impacts the quantification of extracted sphingolipids by LC-ESI-MS/MS. We developed and validated a simple and inexpensive method that removes OCT compound from OCT compound-embedded tissues. Our results indicate that removal of OCT compound from cryopreserved tissues does not significantly affect the accuracy of sphingolipid measurements with LC-ESI-MS/MS. We used the validated method to analyze sphingolipid alterations in tumors compared with normal adjacent uninvolved lung tissues from individuals with lung cancer and to determine the long-term stability of sphingolipids in OCT compound-cryopreserved normal lung tissues. We show that lung cancer tumors have significantly altered sphingolipid profiles and that sphingolipids are stable for up to 16 years in OCT compound-cryopreserved normal lung tissues. This validated sphingolipidomic OCT compound-removal protocol should be a valuable addition to the lipid biologist's toolbox.

Low wall shear stress predominates at sites of abdominal aortic aneurysm rupture.

OBJECTIVE: Aortic diameter as the primary criterion in the decision to repair abdominal aortic aneurysms (AAAs) has drawbacks as some rupture below size thresholds, whereas others reach extreme size without rupture. Predictions of static aortic wall stress have also failed to reliably predict rupture potential. The objective of this study was to computationally assess blood flow characteristics at the site of infrarenal AAA rupture. On the basis of the finite element literature correlating rupture location with high static local wall stress, we hypothesized that a computational fluid dynamics approach would also demonstrate rupture at regions of high pressure and wall shear stress (WSS). METHODS: Three-dimensional AAA geometry was generated from computed tomography angiography images of seven ruptured AAAs. Aortic blood flow velocity, pressure, and WSS were computationally determined. Flow characteristics at the site of rupture were determined and compared across all cases. RESULTS: AAA size at the time of rupture was 8.3 ± 0.9 cm. Only three of the seven AAAs ruptured at the site of maximal diameter. Blood flow velocity in the aneurysmal aorta showed dominant flow channels with zones of recirculation, where low WSS predominated. Regardless of aneurysm size or configuration, rupture occurred in or near these flow recirculation zones in all cases. WSS was significantly lower and thrombus deposition was more abundant at the site of rupture. CONCLUSIONS: This computational study was the first to assess blood flow characteristics at the site of infrarenal AAA rupture in realistic aortic geometries. In contradiction to our initial hypothesis, rupture occurred not at sites of high pressure and WSS but rather at regions of predicted flow recirculation, where low WSS and thrombus deposition predominated. These findings raise the possibility that this flow pattern may lead to thrombus deposition, which may elaborate adventitial degeneration and eventual AAA rupture.

A randomized controlled trial on the effects of goal-directed therapy on the inflammatory response open abdominal aortic aneurysm repair.

INTRODUCTION: Goal-directed therapy (GDT) has been shown in numerous studies to decrease perioperative morbidity and mortality. The mechanism of benefit of GDT, however, has not been clearly elucidated. Targeted resuscitation of the vascular endothelium with GDT might alter the postoperative inflammatory response and be responsible for the decreased complications with this therapy. METHODS: This trial was registered at ClinicalTrials.gov as NCT01681251. Forty patients undergoing elective open repair of their abdominal aortic aneurysm, 18 years of age and older, were randomized to an interventional arm with GDT targeting stroke volume variation with an arterial pulse contour cardiac output monitor, or control, where fluid therapy was administered at the discretion of the attending anesthesiologist. We measured levels of several inflammatory cytokines (C-reactive protein, Pentraxin 3, suppressor of tumorgenicity--2, interleukin-1 receptor antagonist, and tumor necrosis factor receptor-III) preoperatively and at several postoperative time points to determine if there was a difference in inflammatory response. We also assessed each group for a composite of postoperative complications. RESULTS: Twenty patients were randomized to GDT and twenty were randomized to control. Length of stay was not different between groups. Intervention patients received less crystalloid and more colloid. At the end of the study, intervention patients had a higher cardiac index (3.4 ± 0.5 vs. 2.5 ± 0.7 l/minute per m(2), p < 0.01) and stroke volume index (50.1 ± 7.4 vs. 38.1 ± 9.8 ml/m(2), p < 0.01) than controls. There were significantly fewer complications in the intervention than control group (28 vs. 12, p = 0.02). The length of hospital and ICU stay did not differ between groups. There was no difference in the levels of inflammatory cytokines between groups. CONCLUSIONS: Despite being associated with fewer complications and improved hemodynamics, there was no difference in the inflammatory response of patients treated with GDT. This suggests that the clinical benefit of GDT occurs in spite of a similar inflammatory burden. Further work needs to be performed to delineate the mechanism of benefit of GDT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01681251 . Registered 18 May 2011.

Lipidomic Profiling Reveals Biological Differences between Tumors of Self-Identified African Americans and Non-Hispanic Whites with Cancer.

In the US, the incidence and mortality of many cancers are disproportionately higher in African Americans (AA). Yet, AA remain poorly represented in molecular studies investigating the roles that biological factors might play in the development, progression, and outcomes of many cancers. Given that sphingolipids, key components of mammalian cellular membranes, have well-established roles in the etiology of cancer progression, malignancy, and responses to therapy, we conducted a robust mass spectrometry analysis of sphingolipids in normal adjacent uninvolved tissues and tumors of self-identified AA and non-Hispanic White (NHW) males with cancers of the lung, colon, liver, and head and neck and of self-identified AA and NHW females with endometrial cancer. In these cancers, AA have worse outcomes than NHW. The goal of our study was to identify biological candidates to be evaluated in future preclinical studies targeting race-specific alterations in the cancers of AA. We have identified that various sphingolipids are altered in race-specific patterns, but more importantly, the ratios of 24- to 16-carbon fatty acyl chain-length ceramides and glucosylceramides are higher in the tumors of AA. As there is evidence that ceramides with 24-carbon fatty acid chain length promote cellular survival and proliferation, whereas 16-carbon chain length promote apoptosis, these results provide important support for future studies tailored to evaluate the potential roles these differences may play in the outcomes of AA with cancer.

Establishing a core outcome set for blunt cerebrovascular injury: an EAST modified Delphi method consensus study.

Objectives: Our understanding of blunt cerebrovascular injury (BCVI) has changed significantly in recent decades, resulting in a heterogeneous description of diagnosis, treatment, and outcomes in the literature which is not suitable for data pooling. Therefore, we endeavored to develop a core outcome set (COS) to help guide future BCVI research and overcome the challenge of heterogeneous outcomes reporting. Methods: After a review of landmark BCVI publications, content experts were invited to participate in a modified Delphi study. For round 1, participants submitted a list of proposed core outcomes. In subsequent rounds, panelists used a 9-point Likert scale to score the proposed outcomes for importance. Core outcomes consensus was defined as >70% of scores receiving 7 to 9 and <15% of scores receiving 1 to 3. Feedback and aggregate data were shared between rounds, and four rounds of deliberation were performed to re-evaluate the variables not achieving predefined consensus criteria. Results: From an initial panel of 15 experts, 12 (80%) completed all rounds. A total of 22 items were considered, with 9 items achieving consensus for inclusion as core outcomes: incidence of postadmission symptom onset, overall stroke incidence, stroke incidence stratified by type and by treatment category, stroke incidence prior to treatment initiation, time to stroke, overall mortality, bleeding complications, and injury progression on radiographic follow-up. The panel further identified four non-outcome items of high importance for reporting: time to BCVI diagnosis, use of standardized screening tool, duration of treatment, and type of therapy used. Conclusion: Through a well-accepted iterative survey consensus process, content experts have defined a COS to guide future research on BCVI. This COS will be a valuable tool for researchers seeking to perform new BCVI research and will allow future projects to generate data suitable for pooled statistical analysis with enhanced statistical power. Level of evidence: Level IV.

Surgical resection and graft replacement for primary inferior vena cava leiomyosarcoma: A multicenter experience.

OBJECTIVE: Primary leiomyosarcoma of the inferior vena cava (IVC) is best managed with surgical resection when technically feasible. However, consensus is lacking regarding the best choice of conduit and reconstruction technique. The aim of the present multicenter study was to perform a comprehensive assessment through the VLFDC (Vascular Low Frequency Disease Consortium) to determine the most effective method for caval reconstruction after resection of primary leiomyosarcoma of the IVC. METHODS: A multicenter, standardized database review of patients who had undergone surgical resection and reconstruction of the IVC for primary leiomyosarcoma from 2007 to 2017 was performed. The demographics, periprocedural details, and postoperative outcomes were analyzed. RESULTS: A total of 92 patients (60 women and 32 men), with a mean age of 60.1 years (range, 30-88 years) were treated. Metastatic disease was present in 22%. The tumor location was below the renal veins in 49 (53%), between the renal and hepatic veins in 52 (57%), and above the hepatic veins in 13 patients (14%). The conduits used for reconstruction included ringed polytetrafluoroethylene (PTFE; n = 80), nonringed PTFE (n = 1), Dacron (n = 1), autogenous vein (n = 1), bovine pericardium (n = 4), and cryopreserved tissue (n = 5). Complete R0 resection was accomplished in 73 patients (79%). In-hospital mortality was 2%, with a median length of stay of 8 days. The primary patency of PTFE reconstructed IVCs was 97% and 92% at 1 and 5 years, respectively, compared with 73% at 1 and 5 years for the non-PTFE reconstructed IVCs. The overall 1-, 3-, and 5-year survival for the entire cohort were 94%, 86%, and 65%, respectively CONCLUSIONS: The findings from our multi-institutional study have demonstrated that complete en bloc resection of IVC leiomyosarcoma with vascular surgical reconstruction in selected patients results in low perioperative mortality and is associated with excellent long-term patency. A ringed PTFE graft was the most commonly used conduit for caval reconstruction, yielding excellent long-term primary patency.

Intraluminal thrombus: Innocent bystander or factor in abdominal aortic aneurysm pathogenesis?

BACKGROUND: Abdominal aortic aneurysms (AAAs) represent a complex multifactorial hemodynamic, thrombotic, and inflammatory process that can ultimately result in aortic rupture and death. Despite improved screening and surgical management of AAAs, the mortality rates have remained high after rupture, and little progress has occurred in the development of nonoperative treatments. Intraluminal thrombus (ILT) is present in most AAAs and might be involved in AAA pathogenesis. The present review examined the latest clinical and experimental evidence for possible involvement of the ILT in AAA growth and rupture. METHODS: A literature review was performed after a search of the PubMed database from 2012 to June 2020 using the terms "abdominal aortic aneurysm" and "intraluminal thrombus." RESULTS: The structure, composition, and hemodynamics of ILT formation and propagation were reviewed in relation to the hemostatic and proteolytic factors favoring ILT deposition. The potential effects of the ILT on AAA wall degeneration and rupture, including a review of the current controversies regarding the position, thickness, and composition of ILT, are presented. Although initially potentially protective against increased wall stress, increasing evidence has shown that an increased volume and greater age of the ILT have direct detrimental effects on aortic wall integrity, which might predispose to an increased rupture risk. CONCLUSIONS: ILT does not appear to be an innocent bystander in AAA pathophysiology. However, its exact role remains elusive and controversial. Despite computational evidence of a possible protective role of the ILT in reducing wall stress, increasing evidence has shown that the ILT promotes AAA wall degeneration in humans and in animal models. Further research, with large animal models and with more chronic ILT is crucial for a better understanding of the role of the ILT in AAAs and for the potential development of targeted therapies to slow or halt AAA progression.

Preparation of Human Tissues Embedded in Optimal Cutting Temperature Compound for Mass Spectrometry Analysis.

Sphingolipids are cellular components that have well-established roles in human metabolism and disease. Mass spectrometry can be used to determine whether sphingolipids are altered in a disease and investigate whether sphingolipids can be targeted clinically. However, properly powered prospective studies that acquire tissues directly from the surgical suite can be time consuming, and technically, logistically, and administratively challenging. In contrast, retrospective studies can take advantage of cryopreserved human specimens already available, usually in large numbers, at tissue biorepositories. Other advantages of procuring tissues from biorepositories include access to information associated with the tissue specimens including histology, pathology, and in some instances clinicopathological variables, all of which can be used to examine correlations with lipidomics data. However, technical limitations related to the incompatibility of optimal cutting temperature compound (OCT) used in the cryopreservation and mass spectrometry is a technical barrier for the analysis of lipids. However, we have previously shown that OCT can be easily removed from human biorepository specimens through cycles of washes and centrifugation without altering their sphingolipid content. We have also previously established that sphingolipids in human tissues cryopreserved in OCT are stable for up to 16 years. In this report, we outline the steps and workflow to analyze sphingolipids in human tissue specimens that are embedded in OCT, including washing tissues, weighing tissues for data normalization, the extraction of lipids, preparation of samples for analysis by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), mass spectrometry data integration, data normalization, and data analysis.

Increased matrix metalloproteinase 9 activity correlates with flow-mediated intraluminal thrombus deposition and wall degeneration in human abdominal aortic aneurysm.

OBJECTIVE: We have previously demonstrated that human abdominal aortic aneurysm (AAA) rupture occurs in zones of low wall shear stress where flow recirculation and intraluminal thrombus (ILT) deposition are increased. Matrix metalloproteinase-9 (MMP-9) is involved in the pathogenesis of AAA via its lytic effect on collagen and elastin. We hypothesize that flow-mediated ILT deposition promotes increased local inflammatory and MMP-9 activity that leads to AAA wall degeneration. The purpose of this study was to examine the correlation between predicted pulsatile flow dynamics and regional differences in MMP-9, elastin, collagen, and ILT deposition in human AAA. METHODS: Full-thickness aortic tissue samples were collected from 24 patients undergoing open AAA repair. Control infrarenal aortic tissue was obtained from 6 patients undergoing aortobifemoral bypass. Full-thickness aortic tissue and ILT were assessed for MMP-9 levels using a cytokine array assay. Histologic and immunohistochemical assessment of inflammation, collagen and elastin content, and MMP-9 levels were also measured. Three-dimensional AAA geometry was generated from computed tomography angiogram (CTA) images using Mimics software and computational fluid dynamics was used to predict pulsatile aortic blood flow. RESULTS: The majority of AAA showed eccentric ILT deposition which was correlated with predicted recirculation blood flow (R2 = -0.17; P < .05). The regions of high ILT were associated with significant increases in inflammation and loss of elastin and collagen compared with regions of low ILT, or with control tissue. MMP-9 was significantly higher in areas of high ILT deposition compared with areas devoid of ILT. Tissue MMP-9 was correlated with the thickness of ILT deposition (R2 = 0.46; P < .05), and was also present in high levels in thick compared with thin ILT. CONCLUSIONS: We have shown a correlation between flow-mediated ILT deposition with increased tissue levels of MMP-9 activity, increased inflammatory infiltrate, and decreased elastin and collagen content in stereotactically sampled human AAA, suggesting that ILT deposition is associated with local increases in proteolytic activity that may preferentially weaken and promote rupture at selected regions.

The Relationship Between Pulsatile Flow Impingement and Intraluminal Thrombus Deposition in Abdominal Aortic Aneurysms.

Direct numerical simulations were performed on four patient-specific abdominal aortic aneurysm (AAA) geometries and the resulting pulsatile blood flow dynamics were compared to aneurysm shape and correlated with intraluminal thrombus (ILT) deposition. For three of the cases, turbulent vortex structures impinged/sheared along the anterior wall and along the posterior wall a zone of recirculating blood formed. Within the impingement region the AAA wall was devoid of ILT and remote to this region there was an accumulation of ILT. The high wall shear stress (WSS) caused by the impact of vortexes is thought to prevent the attachment of ILT. WSS from impingement is comparable to peak-systolic WSS in a normal-sized aorta and therefore may not damage the wall. Expansion occurred to a greater extent in the direction of jet impingement and the wall-normal force from the continuous impact of vortexes may contribute to expansion. It was shown that the impingement region has low oscillatory shear index (OSI) and recirculation zones can have either low or high OSI. No correlation could be identified between OSI and ILT deposition since different flow dynamics can have similar OSI values.

Improving the success rate of gluteal intramuscular injections.

OBJECTIVES: This study aimed to improve the success rate of gluteal intramuscular (IM) injection. METHODS: The outcomes of 328 intended gluteal IM injections in 115 patients receiving depot octreotide were evaluated using computed tomography performed in routine clinical practice. Patient-, nursing-, and technique-dependent factors were correlated with successful delivery of medication. Techniques associated with successful injection were taught to center nurses. RESULTS: At baseline, 52% of injections were successfully delivered (66% men, 36% women; P = 0.001). Factors associated with successful delivery included nurses' frequency of injections (P = 0.008), landmarks use to select injection site (P < 0.001), quick needle insertion (P < 0.001), and use of nonsyringe hand to compress injection site (P < 0.001). Patient-related factors included male sex (P < 0.001), lower body mass index (P < 0.001), and lower skin-to-muscle depth at injection site (P < 0.001). Techniques associated with successful injections were then taught to center nurses. After instruction, the success rate increased from 52% to 75% (P = 0.001). Importantly, improvements were observed in both men (66%-75%; P = 0.43) and women (38%-75%; P < 0.001). Successful injection was associated with better control of flushing among those with carcinoid syndrome (P = 0.005). CONCLUSIONS: Intended gluteal IM injections often are given into the subcutaneous space. Education in techniques associated with successful injections improves IM delivery rates.