Neil G. Kumar

Bmi1 regulates mitochondrial function and the DNA damage response pathway

Mice deficient in the Polycomb repressor Bmi1 develop numerous abnormalities including a severe defect in stem cell self-renewal, alterations in thymocyte maturation and a shortened lifespan. Previous work has implicated de-repression of the Ink4a/Arf (also known as Cdkn2a) locus as mediating many of the aspects of the Bmi1-/- phenotype. Here we demonstrate that cells derived from Bmi1-/- mice also have impaired mitochondrial function, a marked increase in the intracellular levels of reactive oxygen species and subsequent engagement of the DNA damage response pathway. Furthermore, many of the deficiencies normally observed in Bmi1-/- mice improve after either pharmacological treatment with the antioxidant N-acetylcysteine or genetic disruption of the DNA damage response pathway by Chk2 (also known as Chek2) deletion. These results demonstrate that Bmi1 has an unexpected role in maintaining mitochondrial function and redox homeostasis and indicate that the Polycomb family of proteins can coordinately regulate cellular metabolism with stem and progenitor cell function.

Resident involvement is associated with worse outcomes after major lower extremity amputation

BACKGROUND Despite the recent major changes in vascular and general surgery training, there has been a paucity of literature examining the effect of these changes on training and surgical outcomes. Amputations represent a common cross-section in core competencies for general surgery and vascular surgery trainees. This study evaluates the effect of trainee participation on outcomes after above-knee and below-knee amputations. METHODS The American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) database (2005 to 2010) was queried using Current Procedural Terminology codes (American Medical Association, Chicago, Ill) for below-knee amputation (27880, 27882) and above knee-amputation (27590, 27592). Resident involvement was defined using the NSQIP variable and was narrowed to postgraduate year 1 to 5. Variables associated with resident involvement were identified, and mortality, morbidity, intraoperative transfusion, and operative time (75th percentile vs the bottom three quartiles) were evaluated as distinct categoric end points in logistic regression. Included in the model were variables with a P value <.1 on χ(2) or independent t-test, as appropriate. Significance was defined at P < .05. RESULTS Residents were involved in 6587 of 11,038 amputations (62%). After adjustment for preoperative and intraoperative factors on logistic regression, there was a significant increase in major morbidity (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.14-1.42; P < .001), intraoperative transfusion (OR, 1.78; 95% CI, 1.50-2.11; P < .001), and operative time (OR, 1.64 95% CI, 1.46-1.84; P < .001) in resident cases. CONCLUSIONS Resident involvement was associated with increased odds of major morbidity after amputation and also with increased operative time and risk for intraoperative transfusions.

Infusing an inter‐professional and inter‐university perspective into healthcare education

A national (USA) student‐led, case‐based CLinician/Administrator Relationship Improvement OrganizatioN (CLARION) competition focuses students in medical and related healthcare programs on the provision of healthcare that is safe, timely, equitable, patient‐centred, effective and efficient. Students work in four‐person, inter‐professional teams to research and analyse a designated case. They then present their findings and recommendations to a panel of independent judges. Students, with support from their faculty advisors, approach the case as they see fit. Following initial participation in this CLARION competition, an inter‐professional team of students from two universities and their advisory faculty developed a two‐semester, pre‐competition course as a model to facilitate transformation in healthcare education. The course is theoretical, empirical and practical. It has multiple levels of learning and is designed to mentor students, develop faculty, measure learning outcomes and stimulate administrators in higher education to think creatively about curriculum development across disciplines. This integrated and inter‐professional approach is pivotal in healthcare education to ensure students learn safe and evidence‐based clinical practice that meets the highest standards for quality care.

Lower extremity arteriovenous fistula with central venous stenosis iliocaval stenting to treat venous outflow obstruction

Maintenance of hemodialysis access for end-stage renal disease continues to be a major challenge for vascular surgeons, nephrologists, and primary care physicians. This case report highlights the complication and treatment of lower extremity central venous stenosis, allowing continued dialysis access for a patient with limited remaining fistula options. This stenosis resulted from the prolonged use of a lower extremity central venous catheter. This case highlights the importance of imaging the central veins in obstruction of lower extremity fistulas. Once detected, as in the upper extremity, this can be effectively treated using balloon dilation and stenting.

Fibrinolytic activity of endothelial cells from different venous beds

BACKGROUND Little is known about the molecular biology of endothelial cells from different venous vascular beds. As a result, our treatment of deep vein thrombosis and pulmonary artery embolism remain identical. As an initial step in understanding venous thromboembolic disease in the trauma and surgical patients, this study sought to investigate the balance between coagulation and fibrinolysis in the pulmonary and deep venous vascular beds and how trauma might influence this balance. MATERIALS AND METHODS Confluent human iliac vein endothelial cells (HIVECs) and human pulmonary artery endothelial cells (HPAECs), were cultured in the absence or presence of tumor necrosis factor (TNFα; 10 ng/mL) for 24 h. The expression of mediators of coagulation and fibrinolysis were determined by Western blot analysis, and plasminogen activator activity was determined by a fibrin clot degradation assay. RESULTS After TNFα stimulation, there was decreased expression of endothelial protein C receptor and thrombomodulin in both HIVECs and HPAECs. TNFα stimulation increased urokinase plasminogen activator expression in both HIVECs and HPAECs. There was an increase in the expression of tissue plasminogen activator and plasminogen activator inhibitor-1 in response to TNFα in HPAECs, but not in HIVECs. There was significantly greater clot degradation in the presence of both the conditioned media and cell extracts from HIVECs, when compared with HPAECs. CONCLUSIONS HPAECs and HIVECs react differently in terms of fibrinolytic potential when challenged with a cytokine associated with inflammation. These findings suggest that endothelial cells from distinct venous vascular beds may differentially regulate the fibrinolytic pathway.

Lower Extremity Vascular Trauma

Vascular trauma of the lower extremities is associated with high rates of morbidity and mortality and is especially challenging when it involves the junctional zone between the torso and the lower extremities. Lower extremity junctional injuries are those that occur to the distal iliac and proximal femoral vessels. In the absence of hard signs of injury, lower extremity junctional vascular trauma may be challenging to diagnose; and, in the presence of hard signs, they may be hard to control, expose, and repair. The successful management of lower extremity vascular injury is dependent on early diagnosis and control of hemorrhage, resuscitation of the patient, and prompt intervention to minimize associated ischemia. The most important factors in life- and limb-saving interventions relate to prompt control of hemorrhage and time to reperfusion in the setting of ischemia. The anatomic level of lower extremity vascular injury (iliac-femoral, femoral-popliteal, tibial), the severity of the mangled extremity, and the presence of associated injuries are also important factors influencing patient outcomes.

IP141. Surgical Management of a Recurrent Leiomyosarcoma of the Inferior Vena Cava Requiring Aortobifemoral Bypass

BMI, Body mass index; SD, standard deviation. Student t-test. Fig. A and B, Computed tomography demonstrates recurrent mass involving the right kidney, aorta, and inferior vena cava (IVC) graft. C, Angiogram reveals complete occlusion of the IVC by recurrent tumor. Author Disclosures: M. F. Amendola: Nothing to disclose; T. Connine: Nothing to disclose; S. Dukkipati: Nothing to disclose; L. G. Wolfe: Nothing to disclose.

Endovascular Treatments in the Field

The use of endovascular techniques to treat traumatic vascular injuries was first reported by Marin et al in 1993. In this report, seven vascular injuries to the superficial femoral artery or subclavian arteries were treated using transluminally placed covered stents. These grafts were successfully inserted percutaneously or through open arteriotomies that were remote from the site of vascular trauma. Endovascular treatment of these traumatic injuries resulted in decreased blood loss, reduced requirements for anesthesia, and limited need for extensive dissection in the traumatized field.

Inferior vena cava filters: Some evidence from the past and a look to the future

Venous thromboembolism is a national health concern. Up to 58% of patients suffering from major multisystem trauma will experience venous thromboembolism if no measures are taken to prevent it. Of those, 10% to 30% will be fatal. The appropriate use of lower extremity compression, anticoagulation, and the use of inferior vena cava (IVC) filters has helped reduce the overall morbidity and mortality from this disease. The development of lower-profile devices and the ability to retrieve IVC filters has led to a liberalization of their use. The majority of the filters used today have achieved U.S. Food and Drug Administration approval through the 510K mechanism (approval based on prior similar devices rather than safety studies of the proposed device), and therefore, no rigorous investigations have been performed on them. Initially seeming safe, a recent increase in reports of filter migration, vena cava perforation, and vena cava thrombosis has prompted the Food and Drug Administration to ask for more information on their patterns of use, safety, efficacy, and retrievability. This report details some of the available data on the subject of IVC filters and the discussion surrounding the topic of prophylactic IVC filters in trauma patients.