Modulation of the inflammatory response by increasing fetal wound size or interleukin-10 overexpression determines wound phenotype and scar formation.

Wound size impacts the threshold between scarless regeneration and reparative healing in the fetus with increased inflammation showed in fetal scar formation. We hypothesized that increased fetal wound size increases pro-inflammatory and fibrotic genes with resultant inflammation and fibroplasia and that transition to scar formation could be reversed by overexpression of interleukin-10 (IL-10). To test this hypothesis, 2-mm and 8-mm dermal wounds were created in mid-gestation fetal sheep. A subset of 8-mm wounds were injected with a lentiviral vector containing the IL-10 transgene (n = 4) or vehicle (n = 4). Wounds were harvested at 3 or 30 days for histology, immunohistochemistry, analysis of gene expression by microarray, and validation with real-time polymerase chain reaction. In contrast to the scarless 2-mm wounds, 8-mm wounds showed scar formation with a differential gene expression profile, increased inflammatory cytokines, decreased CD45+ cells, and subsequent inflammation. Lentiviral-mediated overexpression of the IL-10 gene resulted in conversion to a regenerative phenotype with decreased inflammatory cytokines and regeneration of dermal architecture. In conclusion, increased fetal wounds size leads to a unique gene expression profile that promotes inflammation and leads to scar formation and furthermore, these results show the significance of attenuated inflammation and IL-10 in the transition from fibroplasia to fetal regenerative healing.

Medical student education in the Department of Surgery at the University of Mississippi Medical Center in the 21st Century.

The approach of the Department of Surgery at the University of Mississippi to the education of medical students is considerably different from that of earlier eras. An overview of the current strategies for medical student education adopted by the Department in recent years and the philosophies behind them is presented.

Lentiviral-mediated over-expression of hyaluronan synthase-1 (HAS-1) decreases the cellular inflammatory response and results in regenerative wound repair.

Fetal wounds have been found to have increased levels of high-molecular-weight hyaluronan (HMW-HA) compared with those of adults. The primary enzyme responsible for producing HMW-HA is hyaluronic acid synthase-1 (HAS-1). We hypothesized that over-expression of HAS-1 in adult dermal wounds would decrease inflammation and promote regenerative healing. To test this hypothesis, the flanks of adult C57Bl/6 mice were treated with a lentiviral construct containing either HAS-1-GFP or GFP transgenes. After 48 h, a 4-mm excisional wound was made at the site of treatment. Wounds were harvested at days 3, 7, or 28 after wounding. Wound phenotype was assessed by histology to examine tissue architecture and immunohistochemistry for CD45. At 7 and 28 days, lenti-HAS-1-treated wounds demonstrated the restoration of the normal dermal elements and organized collagen fiber orientation. In contrast, the lenti-GFP-treated wounds lacked normal dermal architecture and demonstrated a disorganized collagen scar. At 3 and 7 days, wounds treated with lenti-HAS-1 exhibited a significant decrease in the number of inflammatory cells when compared with wounds treated with lenti-GFP. Thus, HAS-1 over-expression promotes dermal regeneration, in part by decreasing the inflammatory response and by recapitulation of fetal extracellular matrix HMW-HA content.

Contained Giant Abdominal Aortic Aneurysm Rupture Secondary to Type I and III Endoleaks Requiring Open Repair With Endograft Explantation.

Endovascular aneurysm repair (EVAR) is a minimally invasive treatment for abdominal aortic aneurysms (AAAs). Common complications include endoleaks, which are continued blood flow into the aneurysm sac external to the graft. Type I endoleaks occur proximally or distally, resulting from inadequate seals between the graft and artery. Type III endoleaks stem from defects between components in modular grafts or fabric tears. Re-intervention is indicated for type I and III endoleaks due to pressurization of the aneurysm sac resulting in a high risk of rupture. A 68 year-old man presented with an infrarenal AAA and underwent EVAR. He developed a late type I endoleak requiring reintervention with a stent graft cuff, and later presented with a recurrent type I endoleak and type IIIb endoleak. The AAA increased in size to 18 cm with contained rupture, requiring emergent endograft explantation and repair with a bifurcated Dacron graft. His postoperative course was uncomplicated.

Inferior Vena Cava Filter Occlusion Causing Phlegmasia Alba Dolens.

Phlegmasia alba dolens is a rare sequela of acute extensive venothrombus of the iliofemoral segments. Rarely, phlegmasia alba dolens can also result from clotted inferior vena cava filter. A 39-year-old with protein S deficiency, and prior inferior vena cava filter placement after remote trauma presented to the emergency department with progressive bilateral lower extremity pain and swelling. Venous duplex revealed extensive bilateral deep vein thromboses from the external iliac veins to popliteal veins, as well as thrombophlebitis of the left great saphenous vein. Venography confirmed patency of the suprarenal vena cava with abrupt occlusion of the infrarenal segment at the level of the inferior vena cava filter. The filter was removed followed by endovascular thrombectomy and adjunctive venoplasty. The patient progressed well and discharged on therapeutic anticoagulation. This case illustrates that a staged endovascular approach may be utilized for acute on chronic caval thrombosis and filter removal.

Saddle Pulmonary Embolus and Simultaneous Common Carotid and Subclavian Artery Emboli.

A patent foramen ovale (PFO) is present in 27-35% of the population. Right to left cardiac shunts predispose patients to arterial emboli in the presence of venous thromboembolisms. Paradoxical embolus should be suspected in patients with deep venous thrombosis (DVT) and arterial emboli. A 45-year-old man with hypercoagulability and history of DVT presented with a week-long history of chest pain, shortness of breath, and left arm numbness. Imaging showed a saddle pulmonary embolus (PE) and emboli involving the aortic arch, left common carotid, and left subclavian artery. The patient proceeded with an endovascular thrombectomy of the pulmonary artery, followed by open thrombectomy. Echocardiogram confirmed a right to left intra-cardiac shunt consistent with a PFO. Paradoxical emboli are rare manifestations of venous thromboemboli in patients with right to left intra-cardiac shunts. Patients should be evaluated for these to help prevent further manifestations.

Impaired biomechanical properties of diabetic skin implications in pathogenesis of diabetic wound complications.

Diabetic skin is known to have deficient wound healing properties, but little is known of its intrinsic biomechanical properties. We hypothesize that diabetic skin possesses inferior biomechanical properties at baseline, rendering it more prone to injury. Skin from diabetic and nondiabetic mice and humans underwent biomechanical testing. Real-time PCR was performed for genes integral to collagen synthesis and degradation. MMP-2 and MMP-9, and TIMP-1 protein levels were assessed by ELISA and zymography. Collagen I and III content was assessed using Western blot analysis. At baseline, both murine and human diabetic skin was biomechanically inferior compared to nondiabetic skin, with decreased maximum stress and decreased modulus (P < 0.001 and < 0.05, respectively). Surprisingly, the expression of genes involved in collagen synthesis were significantly up-regulated, and genes involved in collagen degradation were significantly down-regulated in murine diabetic skin (P < 0.01). In addition, MMP-2 and MMP-9/TIMP-1 protein ratios were significantly lower in murine diabetic skin (P < 0.05). Collagen I levels and I:III ratios were lower in diabetic skin (P < 0.05). These findings suggest that the predisposition of diabetics to wounds may be the result of impaired tissue integrity at baseline, and are due, in part, to a defect in the regulation of collagen protein synthesis at the post-transcriptional level.

Ectopic liver masquerading as a floating intracaval mass.

Ectopic liver is defined as liver parenchyma situated outside the liver proper with no connection to native hepatic tissue. This rare developmental anomaly is most commonly described as an attachment to the gallbladder with an incidence <0.3%, but it has been reported in other locations within the abdomen and thorax.(2-4) Most cases are found incidentally in asymptomatic patients, but ectopic liver has been known to cause visceral or vascular obstruction.(4,5) Herein we present a unique case of ectopic liver attached by a thin stalk seemingly floating in the suprahepatic inferior vena cava.

Emergency procedures on the descending thoracic aorta in the endovascular era.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR), initially developed for the treatment of degenerative aneurysms of the descending thoracic aorta, has been applied to the entire spectrum of descending thoracic aortic pathology in both the elective and emergent settings. This single center study evaluates the effectiveness of TEVAR for the treatment of acute surgical emergencies involving the descending thoracic aorta, including traumatic aortic disruption (TAD), ruptured descending thoracic aneurysm (RDTA), and acute complicated Type B dissection (cTBD). METHODS: A retrospective review of the medical records of all patients undergoing emergent TEVAR at the University of Mississippi Medical Center between August 2007 and November 2010 was undertaken. Patients were studied for 30-day survival, complications, type of device used for the repair, and technical aspects of the procedure. RESULTS: A total of 44 patients (59% male) with an average age of 49 years (range, 16-87 years) underwent emergent TEVAR during the study period. The technical success rate was 100%, with no patient requiring emergent open surgery for conditions involving the descending thoracic aorta at our institution during the study period. The majority (73%) of the repairs were accomplished using commercially available thoracic stent grafts. Abdominal endograft proximal extension cuffs were used in 12 (38%) of the 32 patients undergoing repair of TAD. Twenty-one patients (48%) required coverage of the left subclavian artery, two (10%) of whom subsequently required subclavian artery revascularization. Procedure-related complications included two strokes, one spinal cord ischemia, one unintentional coverage of the left carotid artery, one episode of acute renal failure, and three access site injuries. One patient undergoing repair of TAD had collapse of the stent graft in the early postoperative period. He was successfully treated by placement of an additional stent graft. Seven patients (16%) died within 30 days of surgery. Three of the deaths occurred in patients who had successfully undergone repair of a TAD and died of associated injuries. CONCLUSIONS: Emergent TEVAR has become the treatment of choice for acute surgical emergencies involving the descending thoracic aorta. Short-term morbidity and mortality compare favorably with historic results for emergent open surgical procedures on the descending thoracic aorta. Survival is highest in patients undergoing repair of TAD. Using current endograft technology, nearly all emergent conditions of the descending thoracic aorta can be successfully treated with TEVAR.

Inhibition of stromal cell-derived factor-1α further impairs diabetic wound healing.

OBJECTIVE: Impaired diabetic wound healing is associated with abnormal stromal cell-derived factor (SDF)-1α production, decreased angiogenesis, and chronic inflammation. Lentiviral-mediated overexpression of SDF-1α can correct the impairments in angiogenesis and healing in diabetic wounds. We hypothesized that SDF-1α is a critical component of the normal wound-healing response and that inhibition of SDF-1α would further delay the wound-healing process. METHODS: dB/Db diabetic mice and Db/+ nondiabetic mice were wounded with an 8-mm punch biopsy and the wounds treated with a lentiviral vector containing either the green fluorescent protein (GFP) or SDF-1α inhibitor transgene. The inhibitor transgene is a mutant form of SDF-1α that binds, but does not activate, the CXCR4 receptor. Computerized planimetry was used to measure wound size daily. Wounds were analyzed at 3 and 7 days by histology and for production of inflammatory markers using real-time polymerase chain reaction. The effect of the SDF-1α inhibitor on cellular migration was also assessed. RESULTS: Inhibition of SDF-1α resulted in a significant decrease in the rate of diabetic wound healing, (3.8 vs 6.5 cm(2)/day in GFP-treated wounds; P = .04), and also impaired the early phase of nondiabetic wound healing. SDF-1α inhibition resulted in fewer small-caliber vessels, less granulation tissue formation, and increased proinflammatory gene expression of interleukin-6 and macrophage inflammatory protein-2 in the diabetic wounds. CONCLUSIONS: The relative level of SDF-1α in the wound plays a key role in the wound-healing response. Alterations in the wound level of SDF-1α, as seen in diabetes or by SDF-1α inhibition, impair healing by decreasing cellular migration and angiogenesis, leading to increased production of inflammatory cytokines and inflammation. Inhibition of SDF-1α further impairs diabetic wound healing.

Factors in fellowship selection: effect of services and fellows.

PURPOSE: General Surgery residents are increasingly pursuing fellowships. We examine whether perceived subspecialty content, dedicated services, and fellows impact fellowship choices. METHODS: Specialty content was assessed through a survey linking 228 operations to 9 content areas. The presence of dedicated services and fellows and the post-residency activities of graduates 1997-2006 were collected from 2 program directors. RESULTS: A total of 75% of residents (26 University of Mississippi, UM; 22 Vanderbilt University, VU) completed surveys. Five dedicated services and 2 fellowships at UM and VU were identical; VU had an additional 4 services and 3 fellowships. UM and VU residents similarly associated 184 operations (81%) with General Surgery. Agreement was not linked to services or fellows. A total of 44% of UM graduates and 68% of VU graduates pursued fellowships. The top choice at UM was Plastic/Hand (14%, versus 6% VU) and Oncology/Endocrine at VU (19%, versus 2% UM). Differences in specialties selected could not be linked consistently to dedicated services or fellows. CONCLUSION: Dedicated services and fellows appear to have little impact on fellowship specialty selection by chief residents. There may be a generic effect of dedicated services favoring fellowship versus no fellowship. Differential faculty mentoring skills may influence specific fellowship choices.

Endovascular repair of a chronic aortocaval fistula using a thoracic aortic endoprosthesis.

Penetrating abdominal trauma with injury to the aorta and vena cava usually requires emergent intervention and is frequently lethal. Formation of a chronic aortocaval fistula (ACF) is an uncommon late complication of these injuries. We report a case of an ACF presenting 17 years after a gunshot wound to the abdomen, with progressive congestive heart failure as the presenting symptom. The ACF was successfully treated with an endoprosthesis designed for the thoracic aorta.

The role of the Vascular Surgery Board in surgical education.

The American Board of Surgery (ABS) has more than 80 years of both direct and indirect involvement in US surgical education, with its primary role being certification of graduates of Accreditation Council for Graduate Medical Education-approved surgical training programs. The ABS's impact on education has been at multiple levels, including the development of the content and administration of qualifying and certifying examinations; original education research based on the Board's unique data sets; and surgical training and education-related initiatives in partnership with multiple regulatory bodies and surgical societies. Within these efforts, by incremental steps, the specialty of vascular surgery attained recognition as a primary specialty of the ABS, and the Vascular Surgery Board of the ABS was established 20 years ago, in 1998. The 2 decades that followed have witnessed significant transformations in the evaluation and treatment of vascular disease, the paradigms for training vascular and endovascular surgeons, and the Vascular Surgery Board has partnered with stakeholder organizations to continually ensure quality education for the evolving vascular surgical workforce. Looking forward, while surgical education remains outside of its primary mission, the ABS and Vascular Surgery Board will continue as key stakeholders and leaders in the complex network of professional societies and training institutions that will guide the evolution of vascular surgery training.

Brachial artery injuries in a rural catchment trauma center: are the upper and lower extremity the same?

BACKGROUND: The predictors of amputation for patients with lower extremity vascular trauma are well described in the literature, but the predictors of amputation in the upper extremity are not so well defined. We hypothesize that the predictors of amputation in the lower extremity are much different when compared with the upper extremity. METHODS: Retrospective chart review of all brachial artery traumatic injuries presenting to a rural-state university trauma center. RESULTS: In a 6-year period, 41 patients presented with brachial artery injuries. Operative management was performed in 38 (93%) patients which included 23 reversed saphenous vein grafts, 13 primary repairs, and 2 synthetic grafts. There were four deaths (9.8%) and four (9.8%) amputations. Comparing the amputation and limb salvage groups, the Injury Severity Score (ISS) was 32 versus 12, whereas the Mangled Extremity Severity Score (MESS) was 7 versus 4.3. Five patients had a MESS score greater than 7; four of whom had an amputation or died. Amputation was performed in only 4 of 23 patients with neurologic deficits. Limb salvage was successful in 24 of 28 patients without a palpable pulse on arrival. CONCLUSIONS: Predictors of amputation in brachial artery injuries differ from lower extremity vascular injuries. Delayed presentation greater than 6 hours, MESS, open fracture, nerve deficits, and diminished capillary refill were not predictive of amputation for patients with brachial artery injuries. These data suggest that the vast majority of upper extremity injuries should have attempted salvage regardless of the severity scoring systems.

Barriers to endovascular aortic aneurysm repair: past experience and implications for future device development.

Despite improvements in endovascular aortic aneurysm repair (EVAR) devices and techniques, significant anatomic constraints still preclude successful EVAR in a large number of patients. The authors sought to identify the current barriers to EVAR and examine their evolution over time. Patients were evaluated for potential endovascular repair by computed tomography angiography (CTA) with or without supplemental conventional arteriograms. The patient population was separated into 2 groups (A and B) based on early and late time periods in the experience with EVAR, corresponding to the availability of various devices. Group A (early) consisted of the Guidant Ancure, Medtronic Talent, and AneuRx devices and comprised patients presenting between April 1997 through June 2000. Group B (late) consisted of the Medtronic AneuRx, Cook Zenith, Edwards Lifepath, Gore Excluder, and Endologix PowerLink devices and comprised patients presenting between July 2000 and December 2003. Patient demographics and anatomic reasons for rejection were recorded in a database for statistical analysis. In total, 547 patients were evaluated (463 men, 84 women). Of these, 346 patients (63%; 312 men, 34 women) were deemed suitable candidates for EVAR and 201 (37%; 151 men, 50 women) were rejected. There was no significant difference in the overall rate of rejection in the early vs the late time period (34% A, 41% B, p = 0.08), but the number of exclusion criteria per patient decreased over time; patients rejected for EVAR had an overall average of 1.6 exclusion criteria (Group A, 1.9; Group B, 1.2). The reasons for rejection did significantly change over time. Specifically, rejection on the basis of inadequate arterial access, presence of extensive iliac artery aneurysms, or an inadequate proximal neck decreased. A disproportionate number of women were excluded throughout the study: Group A, 56% of women compared to 30% of men (p = 0.0003); Group B, 63% of women compared to 36% of men (p = 0.0022). Women were more likely than men to have inadequate arterial access routes. In addition, patients with high operative risk were also more likely to be excluded from EVAR, a finding that persisted over time. Anatomic constraints continue to pose significant challenges to aortic endografting. Progress has been made in that technological advances have conquered some of the previous anatomic challenges, chiefly those of arterial access and treatment of concomitant iliac aneurysm disease. However, the overall rate of rejection for EVAR remains the same. The chief anatomic barriers continue to be the difficult aortic neck and management of branched vascular segments.