Jeffrey D. Crawford

Vasculogenic Cytokines in Wound Healing

Chronic wounds represent a growing healthcare burden that particularly afflicts aged, diabetic, vasculopathic, and obese patients. Studies have shown that nonhealing wounds are characterized by dysregulated cytokine networks that impair blood vessel formation. Two distinct forms of neovascularization have been described: vasculogenesis (driven by bone-marrow-derived circulating endothelial progenitor cells) and angiogenesis (local endothelial cell sprouting from existing vasculature). Researchers have traditionally focused on angiogenesis but defects in vasculogenesis are increasingly recognized to impact diseases including wound healing. A more comprehensive understanding of vasculogenic cytokine networks may facilitate the development of novel strategies to treat recalcitrant wounds. Further, the clinical success of endothelial progenitor cell-based therapies will depend not only on the delivery of the cells themselves but also on the appropriate cytokine milieu to promote tissue regeneration. This paper will highlight major cytokines involved in vasculogenesis within the context of cutaneous wound healing.

A modern series of acute aortic occlusion.

OBJECTIVE Acute aortic occlusion (AAO) is a rare condition associated with substantial morbidity and mortality. The most recent large series was published over 15 years ago and included patients from the 1980s. Previous studies reported up to 50% of AAOs are caused by embolization, with a mortality rate approaching 50%. We reviewed our recent experience with AAOs to identify current etiologies and outcomes in a contemporary series of patients with AAOs. METHODS Current Procedural Terminology codes and data from a prospectively maintained vascular surgical database were used to identify patients with acute occlusion of the native aorta between 2005 and July 2013. AAOs secondary to trauma, dissection, or graft occlusion were excluded. RESULTS We identified 29 patients with AAOs treated at our institution. Twenty-three patients were transferred from referring hospitals with a mean transfer time of 3.9 hours (range, 0.5-7.5 hours). Twenty-two presented with occlusion below the renal arteries and seven with occlusion extending above the renal arteries. Resting motor/sensory lower extremity deficits were noted in 17 patients. Eight patients presented with complete paraplegia. Etiology was felt to be aortoiliac thrombosis in 22 cases, embolic occlusion in 2, and indeterminate in 5. Surgical revascularization was performed in 26 cases (extra-anatomic bypass in 18, thromboembolectomy in 5, and aortobifemoral bypass in 3 patients. Three patients had no intervention. Acute renal failure developed in 15 patients and rhabomyolysis in 10 patients. Fasciotomy was performed in 19 extremities. Nine extremities were amputated in six patients. Overall mortality was 34% with a 30-day mortality of 24% and a postprocedure mortality of 15%. CONCLUSIONS AAO is an infrequent but devastating event. The dominant etiology of AAOs is now thrombotic occlusion. Despite advances in vascular surgery and critical care over the past 2 decades, associated morbidity and mortality remain substantial with high rates of limb loss, acute renal failure, rhabdomyolysis, and death. Mortality may be improved with expeditious extra-anatomic bypass.

The Natural History of Indeterminate Blunt Cerebrovascular Injury

IMPORTANCE The Denver criteria grade blunt cerebrovascular injuries (BCVIs) but fail to capture many patients with indeterminate findings on initial imaging. OBJECTIVE To evaluate outcomes and clinical significance of indeterminate BCVIs (iBCVIs). DESIGN, SETTING, AND PARTICIPANTS A retrospective review of all patients treated for BCVIs at our institution from January 1, 2007, through July 31, 2014, was completed. Patients were divided into 2 groups: those with true BCVIs as defined by the Denver criteria and those with iBCVIs, which was any initial imaging suggestive of a cerebrovascular arterial injury not classifiable by the Denver criteria. MAIN OUTCOMES AND MEASURES Primary outcomes were rate of resolution of iBCVIs, freedom from cerebrovascular accident (CVA) or transient ischemic attack (TIA), and 30-day mortality. RESULTS We identified 100 patients with 138 BCVIs: 79 with true BCVIs and 59 with iBCVIs. With serial imaging, 23 iBCVIs (39.0%) resolved and 21 (35.6%) remained indeterminate, whereas 15 (25.4%) progressed to true BCVI. The rate of CVA or TIA in the iBCVI group was 5.1% compared with 15.2% in the true BCVI group (P = .06). Of the 15 total CVAs or TIAs, 11 (73.3%) resulted from carotid injury and 4 (26.7%) from vertebral artery occlusion (P = .03). By Kaplan-Meier analysis, there was no difference in freedom from CVA or TIA for the 2 groups (P = .07). Median clinical follow-up was 91 days. Overall and 30-day mortality for the entire series were 17.4% and 15.2%, respectively. There was no difference in long-term or 30-day mortality between true BCVI and iBCVI groups. CONCLUSIONS AND RELEVANCE Detection of iBCVI has become a common clinical conundrum with improved and routine imaging. Indeterminate BCVI is not completely benign, with 25.4% demonstrating anatomical progression to true BCVI and 5.1% developing cerebrovascular symptoms. We therefore recommend serial imaging and antiplatelet therapy for iBCVI.

Routine completion axillary lymph node dissection for positive sentinel nodes in patients undergoing mastectomy is not associated with improved local control.

BACKGROUND The current practice of completion axillary lymph node dissection (ALND) for patients with a positive sentinel lymph node (SLN) is being questioned. This led us to examine the outcomes of patients with positive SLNs undergoing mastectomy who underwent ALND compared with those who did not. METHODS A retrospective review of cancer registry data identified 561 women with stages 1 to 3 breast cancer with positive SLNs who underwent mastectomy between 2000 and 2010. Four hundred twenty-six women underwent formal ALND and 135 were managed expectantly. Recurrence-free survival was defined as no locoregional or distant metastases. RESULTS Mean time to recurrence was 29.9 months. Mean follow-up for patients without recurrence was 40.3 months. Survival curves showed no significant difference in recurrence-free survival between the 2 groups (P = .23). CONCLUSIONS In our experience, there is no significant difference in recurrence-free survival in patients with positive SLNs undergoing mastectomy when completion ALND was not performed, suggesting that a closer look at the indications for ALND in early breast cancer be further explored.

Intraluminal thrombus is associated with early rupture of abdominal aortic aneurysm

Background: The implications of intraluminal thrombus (ILT) in abdominal aortic aneurysm (AAA) are currently unclear. Previous studies have demonstrated that ILT provides a biomechanical advantage by decreasing wall stress, whereas other studies have associated ILT with aortic wall weakening. It is further unclear why some aneurysms rupture at much smaller diameters than others. In this study, we sought to explore the association between ILT and risk of AAA rupture, particularly in small aneurysms. Methods: Patients were retrospectively identified and categorized by maximum aneurysm diameter and rupture status: small (<60 mm) or large (≥60 mm) and ruptured (rAAA) or nonruptured (non‐rAAA). Three‐dimensional AAA anatomy was digitally reconstructed from computed tomography angiograms for each patient. Finite element analysis was then performed to calculate peak wall stress (PWS) and mean wall stress (MWS) using the patients systolic blood pressure. AAA geometric properties, including normalized ILT thickness (mean ILT thickness/maximum diameter) and % volume (100 × ILT volume/total AAA volume), were also quantified. Results: Patients with small rAAAs had PWS of 123 ± 51 kPa, which was significantly lower than that of patients with large rAAAs (242 ± 130 kPa; P = .04), small non‐rAAAs (204 ± 60 kPa; P < .01), and large non‐rAAAs (270 ± 106 kPa; P < .01). Patients with small rAAAs also had lower MWS (44 ± 14 kPa vs 82 ± 20 kPa; P < .02) compared with patients with large non‐rAAAs. ILT % volume and normalized ILT thickness were greater in small rAAAs (68% ± 11%; 0.16 ± 0.04 mm) compared with small non‐rAAAs (53% ± 16% [P = .02]; 0.11 ± 0.04 mm [P < .01]) and large non‐rAAAs (57% ± 12% [P = .02]; 0.12 ± 0.03 mm [P < .01]). Increased ILT % volume was associated with both decreased MWS and decreased PWS. Conclusions: This study found that although increased ILT is associated with lower MWS and PWS, it is also associated with aneurysm rupture at smaller diameters and lower stress. Therefore, the protective biomechanical advantage that ILT provides by lowering wall stress seems to be outweighed by weakening of the AAA wall, particularly in patients with small rAAAs. This study suggests that high ILT burden may be a surrogate marker of decreased aortic wall strength and a characteristic of high‐risk small aneurysms.

Management of catheter-associated upper extremity deep venous thrombosis

Central venous catheters or peripherally inserted central catheters are major risk factors for upper extremity deep venous thrombosis (UEDVT). The body and quality of literature evaluating catheter-associated (CA) UEDVT have increased, yet strong evidence on screening, diagnosis, prevention, and optimal treatment is limited. We herein review the current evidence of CA UEDVT that can be applied clinically. Principally, we review the anatomy and definition of CA UEDVT, identification of risk factors, utility of duplex ultrasound as the preferred diagnostic modality, preventive strategies, and an algorithm for management of CA UEDVT.

Genetics, Pregnancy, and Aortic Degeneration

We present a case of familial thoracic aortic aneurysm and dissection (FTAAD) in a pregnant female. FTAAD is an inherited, nonsyndromic aortopathy resulting from several genetic mutations critical to aortic wall integrity have been identified. One such mutation is the myosin heavy chain gene (MYH11) which is responsible for 1-2% of all FTAAD cases. This mutation results in aortic medial degeneration, loss of elastin, and reticulin fiber fragmentation predisposing to TAAD. Aortic disease is more aggressive during pregnancy as a result of increased wall stress from hyperdynamic cardiovascular changes and estrogen-induced aortic media degeneration. Our patient was a 29-year-old G2P1 woman at 26 weeks gestation presenting with abdominal and back pain. Work-up revealed a 6.4-cm ascending aortic aneurysm with a type A dissection extending into all arch vessels, aortic coarctation at the isthmus, and a separate focal type B aortic dissection with visceral involvement. Surgical management included concomitant cesarean section with delivery of a live premature infant, tubal ligation, ascending aortic replacement with reconstruction of the arch vessels, and aortic valve resuspension. The type B dissection was managed medically without complication. This is the first reported case of aortic dissection in a patient with FTAAD/MYH11 mutation and pregnancy. This case highlights that FTAAD and pregnancy cause aortic degeneration via distinct mechanisms and that hyperdynamics of pregnancy increase aortic wall stress. Management of pregnancy associated with aortopathy requires early transfer to a tertiary center, careful investigation to identify familial aortopathy, fetal monitoring, and a multidisciplinary team approach.

Characterization of tibial velocities by duplex ultrasound in severe peripheral arterial disease and controls.

BACKGROUND The relationship between tibiopopliteal velocities and peripheral arterial disease (PAD) severity is not well understood. We sought to characterize tibiopopliteal velocities in severe PAD and non-PAD control patients. METHODS Patients with an arterial duplex ultrasound (DUS) examination with PAD evaluated during a 5-year period were retrospectively compared with non-PAD controls. Control DUS examinations were collected sequentially during a 6-month period, retrospectively. PAD patients included those with lifestyle-limiting intermittent claudication warranting revascularization and patients with critical limb ischemia, defined as ischemic rest pain, gangrene, or a nonhealing ischemic ulcer. For each, tibial and popliteal artery peak systolic velocity (PSV) was measured at the proximal, mid, and distal segment of each artery, and a mean PSV for each artery was calculated. Mean PSV, ankle-brachial indices, peak ankle velocity (PAV), average ankle velocity (AAV), mean tibial velocity (MTV), and ankle-profunda index (API) were compared between the two groups using independent t-tests. PAV is the maximum PSV of the distal peroneal, posterior tibial (PT), or anterior tibial (AT) artery; AAV is the average PSV of the distal peroneal, PT, and AT arteries; MTV is calculated by first averaging the proximal, mid, and distal PSV for each tibial artery and then averaging the three means together; API is the AAV divided by proximal PSV of the profunda. RESULTS DUS was available in 103 patients with PAD (68 patients with critical limb ischemia and 35 patients with intermittent claudication) and 68 controls. Mean ankle-brachial index in the PAD group was 0.64 ± 0.25 compared with 1.08 ± 0.09 in controls (P = .006). Mean PSVs were significantly lower in PAD patients than in controls at the popliteal (64.6 ± 42.2 vs 76.2 ± 29.6; P = .037), peroneal (34.3 ± 26.4 vs 53.8 ± 23.3; P < .001), AT (43.7 ± 31.4 vs 65.4 ± 25.0; P < .001), and PT (43.4 ± 42.3 vs 74.1 ± 30.6; P < .001) and higher at the profunda (131.5 ± 88.0 vs 96.2 ± 44.8; P = .001). Tibial parameters including PAV (52.6 ± 45.0 vs 86.9 ± 35.7; P < .001), AAV (37.4 ± 26.4 vs 64.5 ± 21.7; P < .001), MTV (41.7 ± 30.4 vs 65.4 ± 21.7; P < .001), and API (0.43 ± 0.45 vs 0.75 ± 0.30; P < .001) were significantly lower in the PAD group than in controls. Nonoverlapping 95% confidence interval reference ranges were established for severe PAD and non-PAD controls. CONCLUSIONS This study aims to characterize lower extremity arterial PSVs and ankle parameters in severe PAD and non-PAD controls. These early criteria establish reference ranges to guide vascular laboratory interpretation and clinical decision-making.

Outcomes of unilateral graft limb excision for infected aortobifemoral graft limb

OBJECTIVE Aortobifemoral graft (ABFG) infections presenting with apparent single-limb involvement can be managed with unilateral graft limb excision or complete graft removal. This study aimed to identify outcomes of unilateral graft limb excision for infected ABFGs and factors predictive of subsequent contralateral or main body graft limb infection. METHODS A retrospective review of patients treated with unilateral graft limb excision for infection of an isolated limb of an ABFG from 2001 to July 2014 was performed. Endovascular and aortic tube graft infections were excluded. Outcomes were freedom from contralateral graft limb excision, overall survival, and factors predicting subsequent contralateral limb or main body infection. RESULTS Fifteen patients underwent unilateral graft limb excision and revascularization for treatment of an infected ABFG isolated to one graft limb. Indications for the original ABFG were aortoiliac occlusive disease in 11 patients and aortoiliac aneurysm in 4 patients. All patients presented with clinical evidence consistent with unilateral graft limb infection and clinical findings confirmed radiographically. Unilateral graft explantation was performed for isolated infrainguinal graft limb infection with no retroperitoneal infection on exploration or if patients were too ill to tolerate total graft explantation despite infection in the retroperitoneum. Seven patients, all of whom underwent initial operation for aortoiliac occlusive disease, developed contralateral limb infection at a median follow-up of 23.2 months after unilateral excision. The remaining eight patients remained free of contralateral graft limb infection at median follow-up of 38.8 months. Patient demographics were similar between the two groups. Factors predictive of contralateral graft limb infection included an ABFG placed for aortoiliac occlusive disease (P = .03) and culture evidence of infection above the inguinal ligament (P = .07; positive predictive value of 71%). Median duration of targeted antibiotic therapy was 42 days, and neither duration of antibiotics nor cultured microorganism predicted recurrent graft infection. Overall mortality was 40% and was similar between patients who developed contralateral or main body graft infection and those who did not. There was no limb loss, and overall median follow-up was 44.7 months. CONCLUSIONS Isolated unilateral infection of an ABFG limb can be managed with single graft limb excision, provided the infection is isolated to the infrainguinal graft segment. Factors predicting subsequent contralateral or main body graft infection include ABFGs originally placed for aortoiliac occlusive disease and culture-positive graft infection above the inguinal ligament.

A Comparison of Breast-Specific Gamma Imaging of Invasive Lobular Carcinomas and Ductal Carcinomas

A Comparison of Breast-Specific Gamma Imaging of Invasive Lobular Carcinomas and Ductal Carcinomas The practice of preoperatively evaluating the breast tissue of patients with newly diagnosed breast cancer has evolved, with increased use of advanced imaging. The evaluation of breast tissue using functional breast-specific gamma imaging (BSGI) has proven to be a valuable method of imaging as an adjunct to mammography and ultrasonography for early detection of breast cancer.1 The use of BSGI specifically in imaging invasive lobular carcinomas (ILCs), which are known to be difficult to detect, has not been well characterized.2,3 We reviewed our experience with BSGI as an adjunct imaging method used specifically for detecting ILCs.