Management of Seat Belt-type Blunt Abdominal Aortic Trauma and Associated Injuries in Pediatric Patients.

BACKGROUND: "Seat belt-type" pediatric abdominal aortic trauma is uncommon but potentially lethal. During high speed motor vehicle collisions (MVCs), seat or lap belt restraints may concentrate forces in a band-like pattern across the abdomen, resulting in the triad of hollow viscus perforation, spine fracture, and aortoiliac injury. We report 4 cases of pediatric seat belt-type aortic trauma and review management strategies for the aortic disruption and the associated constellation of injuries. METHODS: -approved, retrospective review of all pediatric patients requiring surgical intervention for seat belt-type constellation of abdominal aortic/iliac and associated injuries over a 5-year period. Blunt thoracic aortic injuries were excluded. RESULTS: We identified 4 patients, ranging from 2 to 17 years of age, who required surgical correction of seat belt-type aortoiliac trauma and associated injuries: 3 abdominal aortas and 1 left common iliac artery. The majority (3/4 patients) were hemodynamically unstable at emergency room presentation, and all underwent computed tomography angiography of the chest/abdomen/pelvis during initial resuscitation. Injuries of the suprarenal and proximal infrarenal aorta were accompanied by unilateral renal artery avulsion requiring nephrectomy. Presumed or proven spinal instability mandated supine positioning and midline laparotomy, with medial visceral rotation utilized for proximal injuries. Aortoiliac injuries requiring repair were accompanied by significant distal intraluminal prolapse of dissected intima, with varying degrees of obstruction. Conduit selection was dictated by the presence of enteric contamination and the rapid availability of an autologous conduit. The sole neurologic deficit was irreparable at presentation. CONCLUSIONS: Seat belt aortoiliac injuries in pediatric patients require prompt multidisciplinary evaluation. Evidence of contained aortoiliac transection, major branch vessel avulsion, and bowel perforation mandates immediate exploration, which generally precedes spinal interventions. Lesser degrees of aortoiliac injuries have been managed with surveillance, but long-term follow-up is needed to fully validate this approach.

The natural history of splanchnic artery aneurysms and outcomes after operative intervention.

OBJECTIVE: Splanchnic artery aneurysms (SAAs) are uncommon, and standards for surveillance and intervention are lacking. The goal of this study was to review our 20-year experience with managing SAAs. METHODS: The Research Patient Data Registry at the Massachusetts General Hospital was queried, and all patients with SAAs identified by axial imaging from 1994 to 2014 were included. Aneurysms were stratified into two cohorts: those that underwent early intervention (<6 months after lesion discovery) and those that received surveillance. Primary study end points included aneurysm growth or rupture during surveillance and patient 30-day morbidity or mortality after aneurysm repair. RESULTS: There were 264 SAAs identified in 250 patients. In 166 patients, 176 SAAs (66.6%) were placed into the surveillance cohort; 38 SAAs (21.6%) did not have subsequent axial imaging and were considered lost to follow-up. Mean aneurysm size in the surveillance cohort at first imaging study was 16.28 mm (8-41 mm), and mean surveillance time was 36.1 months (2-155 months); 126 SAAs (91.3%) remained stable in size over time, and 8 SAAs (5.8%) required intervention for aneurysm growth after a mean of 24 months. There were no ruptures in the surveillance cohort. There were 88 SAAs (33.3%) repaired early. Mean size of SAAs that were repaired early was 31.1 mm (10-140 mm). For intact SAAs, 30-day morbidity and mortality rates after repair were 13% and 3%, respectively. In the early repair cohort, 13 SAAs (14.7%) were ruptured at presentation. The 30-day morbidity and mortality rates after rupture were 54% and 8%, respectively. Five ruptured SAAs (38%) were anatomically located in the pancreaticoduodenal arcade. On univariate analysis, pancreaticoduodenal aneurysms were strongly associated with rupture (P = .0002). CONCLUSIONS: Small SAAs (≤25 mm) are not prone to significant expansion and do not require frequent surveillance imaging. Imaging every 3 years for small SAAs is adequate. Aneurysms of the pancreaticoduodenal arcade and gastroduodenal aneurysms are more likely to rupture and therefore warrant a more aggressive interventional approach.

Increased 18F-FDG uptake is predictive of rupture in a novel rat abdominal aortic aneurysm rupture model.

OBJECTIVE: To determine whether F-fluorodeoxyglucose (F-FDG) micro-positron emission tomography (micro-PET) can predict abdominal aortic aneurysm (AAA) rupture. BACKGROUND: An infrarenal AAA model is needed to study inflammatory mechanisms that drive rupture. F-FDG PET can detect vascular inflammation in animal models and patients. METHODS: After exposing Sprague-Dawley rats to intra-aortic porcine pancreatic elastase (PPE) (12 U/mL), AAA rupture was induced by daily, subcutaneous, ß-aminopropionitrile (BAPN, 300 mg/kg, N = 24) administration. Negative control AAA animals (N = 15) underwent daily saline subcutaneous injection after PPE exposure. BAPN-exposed animals that did not rupture served as positive controls [nonruptured AAA (NRAAA) 14d, N = 9]. Rupture was witnessed using radiotelemetry. Maximum standard uptakes for F-FDG micro-PET studies were determined. Aortic wall PAI-1, uPA, and tPA concentrations were determined by western blot analyses. Interleukin (IL)-1ß, IL-6, IL-10, and MIP-2 were determined by Bio-Plex bead array. Neutrophil and macrophage populations per high-power field were quantified. Matrix metalloproteinase (MMP) activities were determined by zymography. RESULTS: When comparing ruptured AAA (RAAA) to NRAAA 14d animals, increased focal F-FDG uptakes were detected at subsequent sites of rupture (P = 0.03). PAI-1 expression was significantly less in RAAA tissue (P = 0.01), with comparable uPA and decreased tPA levels (P = 0.02). IL-1ß (P = 0.04), IL-6 (P = 0.001), IL-10 (P = 0.04), and MIP-2 (P = 0.02) expression, neutrophil (P = 0.02) and macrophage presence (P = 0.002), and MMP9 (P < 0.0001) activity were increased in RAAA tissue. CONCLUSIONS: With this AAA rupture model, increased prerupture F-FDG uptake on micro-PET imaging was associated with increased inflammation in the ruptured AAA wall. F-FDG PET imaging may be used to monitor inflammatory changes before AAA rupture.

Ketosis prevents abdominal aortic aneurysm rupture through C-C chemokine receptor type 2 downregulation and enhanced extracellular matrix balance.

Abdominal aortic aneurysms (AAAs) are prevalent with aging, and AAA rupture is associated with increased mortality. There is currently no effective medical therapy to prevent AAA rupture. The monocyte chemoattractant protein (MCP-1)/C-C chemokine receptor type 2 (CCR2) axis critically regulates AAA inflammation, matrix-metalloproteinase (MMP) production, and extracellular matrix (ECM) stability. We therefore hypothesized that a diet intervention that can modulate CCR2 axis may therapeutically impact AAA risk of rupture. Since ketone bodies (KBs) can trigger repair mechanisms in response to inflammation, we evaluated whether systemic ketosis in vivo could reduce CCR2 and AAA progression. Male Sprague-Dawley rats underwent surgical AAA formation using porcine pancreatic elastase and received daily ß-aminopropionitrile to promote AAA rupture. Rats with AAAs received either a standard diet, ketogenic diet (KD), or exogenous KBs (EKB). Rats receiving KD and EKB reached a state of ketosis and had significant reduction in AAA expansion and incidence of rupture. Ketosis also led to significantly reduced aortic CCR2 content, improved MMP balance, and reduced ECM degradation. Consistent with these findings, we also observed that Ccr2-/- mice have significantly reduced AAA expansion and rupture. In summary, this study demonstrates that CCR2 is essential for AAA expansion, and that its modulation with ketosis can reduce AAA pathology. This provides an impetus for future clinical studies that will evaluate the impact of ketosis on human AAA disease.

Ketosis Prevents Abdominal Aortic Aneurysm Rupture Through CCR2 Downregulation and Enhanced MMP Balance.

Abdominal aortic aneurysms (AAAs) are common in aging populations, and AAA rupture is associated with high morbidity and mortality. There is currently no effective medical preventative therapy for AAAs to avoid rupture. It is known that the monocyte chemoattractant protein (MCP-1) / C-C chemokine receptor type 2 (CCR2) axis critically regulates AAA tissue inflammation, matrix-metalloproteinase (MMP) production, and in turn extracellular matrix (ECM) stability. However, therapeutic modulation of the CCR2 axis for AAA disease has so far not been accomplished. Since ketone bodies (KBs) are known to trigger repair mechanisms in response to vascular tissue inflammation, we evaluated whether systemic in vivo ketosis can impact CCR2 signaling, and therefore impact AAA expansion and rupture. To evaluate this, male Sprague-Dawley rats underwent surgical AAA formation using porcine pancreatic elastase (PPE), and received daily ß-aminopropionitrile (BAPN) to promote AAA rupture. Animals with formed AAAs received either a standard diet (SD), ketogenic diet (KD), or exogenous KB supplements (EKB). Animals that received KD and EKB reached a state of ketosis, and had significantly reduced AAA expansion and incidence of rupture. Ketosis also led to significantly reduced CCR2, inflammatory cytokine content, and infiltrating macrophages in AAA tissue. Additionally, animals in ketosis had improved balance in aortic wall matrix-metalloproteinase (MMP), reduced extracellular matrix (ECM) degradation, and higher aortic media Collagen content. This study demonstrates that ketosis plays an important therapeutic role in AAA pathobiology, and provides the impetus for future studies investigating the role of ketosis as a preventative strategy for individuals with AAAs.

Chemokine Receptor 2 Is A Theranostic Biomarker for Abdominal Aortic Aneurysms.

Abdominal aortic aneurysm (AAA) is a degenerative vascular disease impacting aging populations with a high mortality upon rupture. There are no effective medical therapies to prevent AAA expansion and rupture. We previously demonstrated the role of the monocyte chemoattractant protein-1 (MCP-1) / C-C chemokine receptor type 2 (CCR2) axis in rodent AAA pathogenesis via positron emission tomography/computed tomography (PET/CT) using CCR2 targeted radiotracer 64 Cu-DOTA-ECL1i. We have since translated this radiotracer into patients with AAA. CCR2 PET showed intense radiotracer uptake along the AAA wall in patients while little signal was observed in healthy volunteers. AAA tissues collected from individuals scanned with 64 Cu-DOTA-ECL1i and underwent open-repair later demonstrated more abundant CCR2+ cells compared to non-diseased aortas. We then used a CCR2 inhibitor (CCR2i) as targeted therapy in our established male and female rat AAA rupture models. We observed that CCR2i completely prevented AAA rupture in male rats and significantly decreased rupture rate in female AAA rats. PET/CT revealed substantial reduction of 64 Cu-DOTA-ECL1i uptake following CCR2i treatment in both rat models. Characterization of AAA tissues demonstrated decreased expression of CCR2+ cells and improved histopathological features. Taken together, our results indicate the potential of CCR2 as a theranostic biomarker for AAA management.

CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction.

BACKGROUND: The monocyte chemoattractant protein-1/CCR2 (chemokine receptor 2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. We assessed the expression of CCR2 in a rodent model and human tissues, using a targeted positron emission tomography radiotracer (64Cu-DOTA-ECL1i). METHODS: AAAs were generated in Sprague-Dawley rats by exposing the infrarenal, intraluminal aorta to PPE (porcine pancreatic elastase) under pressure to induce aneurysmal degeneration. Heat-inactivated PPE was used to generate a sham operative control. Rat AAA rupture was stimulated by the administration of ß-aminopropionitrile, a lysyl oxidase inhibitor. Biodistribution was performed in wild-type rats at 1 hour post tail vein injection of 64Cu-DOTA-ECL1i. Dynamic positron emission tomography/computed tomography imaging was performed in rats to determine the in vivo distribution of radiotracer. RESULTS: Biodistribution showed fast renal clearance. The localization of radiotracer uptake in AAA was verified with high-resolution computed tomography. At day 7 post-AAA induction, the radiotracer uptake (standardized uptake value [SUV]=0.91±0.25) was approximately twice that of sham-controls (SUV=0.47±0.10; P<0.01). At 14 days post-AAA induction, radiotracer uptake by either group did not significantly change (AAA SUV=0.86±0.17 and sham-control SUV=0.46±0.10), independent of variations in aortic diameter. Competitive CCR2 receptor blocking significantly decreased AAA uptake (SUV=0.42±0.09). Tracer uptake in AAAs that subsequently ruptured (SUV=1.31±0.14; P<0.005) demonstrated uptake nearly twice that of nonruptured AAAs (SUV=0.73±0.11). Histopathologic characterization of rat and human AAA tissues obtained from surgery revealed increased expression of CCR2 that was co-localized with CD68+ macrophages. Ex vivo autoradiography demonstrated specific binding of 64Cu-DOTA-ECL1i to CCR2 in both rat and human aortic tissues. CONCLUSIONS: CCR2 positron emission tomography is a promising new biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture prediction.

Utility of (18) F-FDG and (11)C-PBR28 microPET for the assessment of rat aortic aneurysm inflammation.

BACKGROUND: The utility of (18) F-FDG and (11)C-PBR28 to identify aortic wall inflammation associated with abdominal aortic aneurysm (AAA) development was assessed. METHODS: Utilizing the porcine pancreatic elastase (PPE) perfusion model, abdominal aortas of male Sprague-Dawley rats were infused with active PPE (APPE, AAA; N = 24) or heat-inactivated PPE (IPPE, controls; N = 16). Aortic diameter increases were monitored by ultrasound (US). Three, 7, and 14 days after induction, APPE and IPPE rats were imaged using (18) F-FDG microPET (approximately 37 MBq IV) and compared with (18) F-FDG autoradiography (approximately 185 MBq IV) performed at day 14. A subset of APPE (N = 5) and IPPE (N = 6) animals were imaged with both (11)C-PBR28 (approximately 19 MBq IV) and subsequent (18) F-FDG (approximately 37 MBq IV) microPET on the same day 14 days post PPE exposure. In addition, autoradiography of the retroperitoneal torso was performed after (11)C-PBR28 (approximately 1,480 MBq IV) or (18) F-FDG (approximately 185 MBq IV) administration at 14 days post PPE exposure. Aortic wall-to-muscle ratios (AMRs) were determined for microPET and autoradiography. CD68 and translocator protein (TSPO) immunohistochemistry (IHC), as well as TSPO gene expression assays, were performed for validation. RESULTS: Mean 3 (p = 0.009), 7 (p < 0.0001) and 14 (p < 0.0001) days aortic diameter increases were significantly greater for APPE AAAs compared to IPPE controls. No significant differences in (18) F-FDG AMR were determined at days 3 and 7 post PPE exposure; however, at day 14, the mean (18) F-FDG AMR was significantly elevated in APPE AAAs compared to IPPE controls on both microPET (p = 0.0002) and autoradiography (p = 0.02). Similarly, mean (11)C-PBR28 AMR was significantly increased at day 14 in APPE AAAs compared to IPPE controls on both microPET (p = 0.04) and autoradiography (p = 0.02). For APPE AAAs, inhomogeneously increased (18) F-FDG and (11)C-PBR28 uptake was noted preferentially at the anterolateral aspect of the AAA. Compared to controls, APPE AAAs demonstrated significantly increased macrophage cell counts by CD68 IHC (p = 0.001) as well as increased TSPO staining (p = 0.004). Mean TSPO gene expression for APPE AAAs was also significantly elevated compared to IPPE controls (p = 0.0002). CONCLUSION: Rat AAA wall inflammation can be visualized using (18) F-FDG and (11)C-PBR28 microPET revealing regional differences of radiotracer uptake on microPET and autoradiography. These results support further investigation of (18) F-FDG and (11)C-PBR28 in the noninvasive assessment of human AAA development.

Imaging of carrageenan-induced local inflammation and adjuvant-induced systemic arthritis with [(11)C]PBR28 PET.

INTRODUCTION: [(11)C] PBR28 binding to translocator protein (TSPO) was evaluated for imaging of acute and chronic inflammation using two established rat models. METHODS: Acute inflammation was induced by local carrageenan injection into the paw of Fisher 344 rats (model A). T-cell mediated adjuvant arthritis was induced by heat-inactivated Mycobacterium butyricum injection in Lewis rats (model B). Micro-PET scan was performed after injection of approximately 35 MBq [(11)C]PBR28. In model A, volumes of interest (VOIs) were defined in the paw of Fisher 344 rats (n=6) with contralateral sham treatment as control. For model B, VOIs were defined in the tail, sacroiliac joints, hips, knees and thigh muscles of M. butyricum treated animals (n=8) and compared with sham-treated controls (n=4). The peak (11)C-PBR28 SUV (SUVpeak) and area under the curve (AUCSUV) of 60-minute time-activity data were calculated. Immunohistochemistry for CD68, a macrophage stain, was performed from paw tissues. In addition, the [(11)C]PBR28 cell uptake was measured in lipopolysaccharide (LPS)-stimulated and non-stimulated macrophage cultures. RESULTS: LPS-stimulated macrophages displayed dose-dependent increased [(11)C]PBR28 uptake, which was blocked by non-labeled PBR28. In both models, radiotracer uptake of treated lesions increased rapidly within minutes and displayed overall accumulative kinetics. The SUVpeak and AUCSUV of carrageenan-treated paws was significantly increased compared to controls. Also, the [(11)C]PBR28 uptake ratio of carrageenan-treated vs. sham-treated paw correlated significantly with CD68 staining ratios of the same animals. In adjuvant arthritis, significantly increased [(11)C]PBR28 SUVpeak and AUCSUV values were identified at the tail, knees, and sacroiliac joints, while no significant differences were identified in the lumbar spine and hips. CONCLUSIONS: Based on our initial data, [(11)C]PBR28 PET appears to have potential for imaging of various inflammatory processes involving macrophage activation.

Carotid artery stenting: identification of risk factors for poor outcomes.

OBJECTIVES: Age greater than 80 has been identified as a risk factor for complications, including stroke and death, in patients undergoing carotid artery angioplasty and stenting (CAS). This study evaluates other potential predictors of perioperative complications in patients undergoing CAS. METHODS: All cerebrovascular endovascular procedures performed by the vascular surgery division at our university hospital between July 2003 and December 2005 were retrospectively examined. During the course of 212 admissions, 198 patients underwent 215 procedures. Patient age, comorbidities, and admission status were analyzed as independent (predictor) variables. Complication rate, discharge disposition, and length of hospital stay were considered dependent (outcome) variables. Logistic regression and Fisher exact test or Student t test were performed, as appropriate. RESULTS: Complications included major and minor stroke, myocardial infarction, femoral artery pseudoaneurysm, and death. The rates of perioperative major and minor stroke were 0.5% and 2.8%, respectively. Chronic renal insufficiency was a predictor of perioperative complications, including stroke: patients with serum creatinine greater than 1.3 mg/dL had a 37% complication rate and a 11.1% stroke rate, while those with normal renal function had a 13% complication rate (P = .003) and a 0.6% stroke rate (P =.001). Similar association was seen between creatinine clearance and both stroke and complications. Obesity was a risk factor for complications, but not stroke: obese patients had a complication rate of 28%, while others had a 16% complication rate (P = .024). Emergency admission predicted both extended hospital stay (P < .001) and requirement for further inpatient care in a rehabilitation or nursing facility (P = .007). There was no significant difference in complication rate or stroke rate between octogenarians and others. CONCLUSION: This experience demonstrates that chronic renal insufficiency, obesity, and emergent clinical setting are risk factors for patients undergoing CAS.

Influence of body temperature on the BOLD effect in murine SCC tumors.

Changes in the blood oxygen level dependent (BOLD) enhancements in tumors (squamous cell carcinoma, (SCCVII)) implanted in mice maintained at core temperatures of 30 degrees C or 37 degrees C were measured using MRI and compared to tumor oxygen levels obtained using an oxygen-sensitive Eppendorf electrode. Tumors were implanted in a hindleg of the mice intramuscularly. Tumor-bearing mice were imaged by BOLD MRI, while first breathing air and then carbogen (95% O2, 5% CO2) for 15-min intervals at a core temperature of 30 degrees C. After an equilibration period, the identical regimen was conducted with the same animal maintained at 37 degrees C. This procedure was repeated with additional mice starting at 37 degrees C followed by imaging at 30 degrees C. Likewise, oxygen electrode measurements of the tumor were determined at core temperatures of 30 degrees C and 37 degrees C. The Eppendorf measurements showed that tumors in animals maintained at 30 degrees C were significantly more hypoxic than at 37 degrees C. MRI studies demonstrated stronger BOLD enhancement at 30 degrees C than at 37 degrees C, suggesting significant changes in hypoxia and/or blood flow in tumors at these temperatures. The findings of the study stress the importance of maintaining normal core temperature when assessing tumor oxygen status using functional imaging modalities or oxygen-sensitive electrodes.