Faculty Bibliography

Atherosclerosis is a chronic disease characterized by the formation of calcified, arterial plaques. Microcalcifications (5 μm to 100 μm), mainly composed of hydroxyapatite (HA, Ca₅(PO₄)₃(OH)), develop in the fibrous caps of atherosclerotic plaques and can trigger plaque rupture due to the loss of compliance and elasticity. Ultimately, plaque rupture can cause arterial occlusion and embolization and result in ischemic events such as strokes and myocardial infarctions. Unfortunately, current imaging technologies used to detect calcifications are limited by low signal-to-noise ratio or use invasive procedures that pose risk of arterial dissection. To mitigate these drawbacks, in our study, we developed a novel, fluorescently-labeled peptide amphiphile micelle (PAM) that uses a 12 amino acid HA-binding peptide (HABP) [SVSVGMKPSPRP] to target and detect atherosclerotic calcification (HA PAM). Our results show HA PAMs can successfully target HA microcrystals with a strong binding affinity (K_D = 6.26 ± 1.2 μM) in vitro. In addition, HA PAMs detected HA mineralization (HA PAM vs. non-targeting micelle, p≤ 0.001; HA PAM vs. scrambled HABP PAM, p≤ 0.01) formed by calcifying mouse aortic vascular smooth muscle cells (MOVAS). Moreover, HA PAMs successfully detected calcifications in atherosclerotic mouse models as well as in patient-derived arteries. Our studies show that HA PAMs show promise as calcium-targeting nanoparticles for the detection of calcifications in atherosclerosis.

We report a case of a frozen elephant trunk arch repair, where the stent graft was unintentionally placed into the false lumen. Postoperative imaging demonstrated an enlarged false lumen with no thoracic aorta fenestrations that could be traversed to place another thoracic endovascular aortic repair endograft into the true lumen. An atraumatic radiofrequency wire (PowerWire, Baylis Medical, Montreal, Quebec, Canada) was used to create a new septal fenestration, enabling thoracic endovascular aortic repair endograft extension into the thoracic true lumen. This novel use of a radiofrequency wire can enable safe and controlled endovascular septal fenestration even in chronic dissections to redirect flow into the true lumen.

OBJECTIVE:The incidence of morbidity and mortality for iliac vascular injuries in the literature are likely overestimated owing to associated injuries. Data for isolated iliac vascular injuries are very limited. No large studies have reported the incidence of morbidity for repair versus ligation of isolated iliac vein injuries. METHODS:Patients in the National Trauma Data Bank (NTDB; 2007-2012) with at least one iliac vascular injury were analyzed. Isolated iliac vessels were defined as cases with Abbreviated Injury Scale severity score of greater than 3 for extraabdominal injuries and an Organ Injury Scale grade of greater than 3 for intraabdominal injuries. RESULTS:Overall, 6262 iliac vascular injuries (2809 penetrating, 3453 blunt) were identified in 271,076 patients with abdominal trauma (2.3%). There were 3379 patients (1841 penetrating, 1538 blunt) with isolated iliac vascular injuries (1.2%) and 557 patients (514 penetrating, 43 blunt) with combined iliac artery and vein injuries (0.2%). The 30-day mortality rate was 16.5% for isolated iliac vein injury, 19.3% for isolated iliac artery injury, and 48.7% for combined isolated iliac artery and vein injury. The 30-day mortality rate was 23.4% for isolated iliac vascular injuries compared with 39.0% for nonisolated iliac vascular injuries (P < .001). Patients with isolated iliac vein injuries had morbidity rates of deep venous thrombosis (repair, 14.6%; ligation, 14.1%; P = .875), pulmonary embolism (repair, 1.8%; ligation, 0.5%; P = .38), fasciotomy (repair, 9.3%; ligation, 14.6%; P = .094), amputation (repair, 1.8%; ligation, 2.6%; P = .738), acute kidney injury (repair, 5.8%; ligation, 4.7%; P = .627). Multivariate logistic regression demonstrated that ligation of isolated iliac vein injuries had an odds ratio of 2.2 for mortality compared with repair (95% confidence interval, 1.08-4.66). CONCLUSIONS:Isolated iliac vascular injuries are associated with a high incidence of mortality, especially for combined venous and arterial injury, but mortality is significantly lower than in patients with nonisolated iliac vascular injuries. In patients with isolated iliac vein injuries, mortality was higher in patients who underwent ligation compared with repair; however, the rates of deep venous thrombosis, pulmonary embolism, fasciotomy, amputation, and acute kidney injury were not different between the treatment groups. These data lend credence to the assessment that repair of iliac vein injuries is preferable to ligation whenever feasible.

Vasospasm immediately after lower extremity arterial bypass may represent an uncommon cause of early graft failure. We report a successful case of catheter-directed, intra-arterial continuous vasodilator infusion to salvage a bypass graft threatened by severe, refractory vasospasm after incomplete response to nicardipine, verapamil, and nitroglycerin boluses. A continuous nitroglycerin infusion was administered for 24 hours, by which time the vasospasm resolved. At 12 months postoperatively, the graft remained patent with normal results of vascular laboratory studies. This report demonstrates that in cases of refractory vasospasm after peripheral bypass, continuous vasodilator infusion can be an effective treatment to prevent early graft failure.

PURPOSE:It remains unknown whether critically ill trauma patients can be successfully managed by advanced practitioners (APs). The purpose of this study was to examine the impact of night coverage by APs in a high-volume trauma intensive care unit (ICU) on patient outcomes and care processes. MATERIALS AND METHODS:During the study period, our ICU was staffed by APs during the night shift (7 pm-7 am) from Sunday to Wednesday and by resident physicians (RPs) from Thursday to Saturday. On-call trauma fellows and attending surgeons in house supervised both APs and RPs. Patient outcomes and care processes by APs was compared with those admitted by RPs. RESULTS:A total of 289 patients were identified between July 2013 and February 2014. Median lactate clearance rate within 24 hours of admission was similar between study groups (10.0% vs 9.1%; P = .39). Advanced practitioners and RPs transfused patients requiring massive transfusion with a similar blood product ratio (packed red blood cell:fresh frozen plasma) (2.1:1 vs 1.7:1; P = .32). In a multiple logistic regression analysis, AP coverage was not associated with any clinical outcome differences. CONCLUSIONS:Our data suggest that, with adequate supervision, a high-volume trauma ICU can be safely staffed by APs overnight.

BACKGROUND:It remains unclear whether the timing of neurosurgical intervention impacts the outcome of patients with isolated severe traumatic brain injury (TBI). We hypothesized that a shorter time between emergency department (ED) admission to neurosurgical intervention would be associated with a significantly higher rate of patient survival. METHODS:Our institutional trauma registry was queried for patients (2003-2013) who required an emergent neurosurgical intervention (craniotomy, craniectomy) for TBI within 300 minutes after the ED admission. We included patients with altered mental status upon presentation in the ED (Glasgow Coma Scale [GCS] score < 9). Patients with associated severe injuries (Abbreviated Injury Scale [AIS] score ≥ 2) in other body regions were excluded. In-hospital mortality of patients who underwent surgery in less than 200 minutes (early group) was compared with those who underwent surgery in 200 minutes or longer (late group) using univariate and multivariate analyses. RESULTS:A total of 161 patients were identified during the study time frame. Head computed tomographic scan demonstrated subdural hematoma in 85.8%, subarachnoid hemorrhage in 55.5%, and equal numbers of epidural hematoma and intraparenchymal hemorrhage in 22.6%. Median time between ED admission and neurosurgical intervention was 133 minutes. In univariate analysis, a significantly lower in-hospital mortality rate was identified in the early group (34.5% vs. 59.1%, p = 0.03). After adjusting for clinically important covariates in a logistic regression model, early neurosurgical intervention was significantly associated with a higher odds of patient survival (odds ratio, 7.41; 95% confidence interval, 1.66-32.98; p = 0.009). CONCLUSION/CONCLUSIONS:Our data suggest that the survival rate of isolated severe TBI patients who required an emergent neurosurgical intervention could be time dependent. These patients might benefit from expedited process (computed tomographic scan, neurosurgical consultation, etc.) to shorten the time to surgical intervention. LEVEL OF EVIDENCE/METHODS:Prognostic study, level IV.

We have studied incorporation of [14C]doxorubicin within protease-sensitive casein microspheres both by 14C-activity, measuring total drug, and HPLC, measuring free drug only. It was found that total drug content (27.7 micrograms mg-1) exceeded free drug content (3.2 micrograms mg-1) suggesting that the major portion of doxorubicin was incorporated via a covalent linkage to matrix protein. In-vivo drug disposition and activity studies suggested that this fraction of doxorubicin was the major species within tumour tissue (total vs free: 5 min, 14.3 micrograms g-1 vs 0.7 micrograms g-1; 24 h, 11.7 micrograms g-1 vs 1.1 micrograms g-1; 48 h, 11.2 micrograms g-1 vs 1.2 micrograms g-1; 72 h, 10.0 micrograms g-1 vs 0.8 micrograms g-1), did not exhibit a 'burst' effect, was slowly cleared (30% loss over 3 days), and was equiactive (growth delay = 12 days) compared with drug in solution (growth delay = 10 days). This work clearly implicates in-vivo microsphere matrix biodegradation in drug release and subsequent disposition and activity.