The impact of a pulmonary embolism response team on the efficiency of patient care in the emergency department.

The concept of a pulmonary embolism response team (PERT) is multidisciplinary, with the hope that it may positively impact patient care, hospital efficiency, and outcomes in the treatment of patients with intermediate and high risk pulmonary embolism (PE). Clinical characteristics of a baseline population of patients presenting with submassive and massive PE to URMC between 2014 and 2016 were examined (n = 159). We compared this baseline population before implementation of a PERT to a similar population of patients at 3-month periods, and then as a group at 18 months after PERT implementation (n = 146). Outcomes include management strategies and efficiency of the emergency department (ED) in diagnosing, treating, and dispositioning patients. Before PERT, patients with submassive and massive PE were managed fairly conservatively: heparin alone (85%), or additional advanced therapies (15%). Following PERT, submassive and massive PE were managed as follows: heparin alone (68%), or additional advanced therapies (32%). Efficiency of the ED in managing high risk PE significantly improved after PERT compared with before PERT; where triage to diagnosis time was reduced (384 vs. 212 min, 45% decrease, p = 0.0001), diagnosis to heparin time was reduced (182 vs. 76 min, 58% decrease, p = 0.0001), and the time from triage to disposition was reduced (392 vs. 290 min, 26% decrease, p < 0.0001). Our analysis showed that following PERT implementation, patients with intermediate and high risk acute PE received more aggressive and advanced treatment modalities and received significantly expedited care in the ED.

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.

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.

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.

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.

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.

Receptor tyrosine kinase EphB4 is a survival factor in breast cancer.

EphB4, a member of the largest family of receptor tyrosine kinases, is normally expressed on endothelial and neuronal cells. Although aberrant expression of EphB4 has been reported in several human tumors, including breast cancer, its functional significance is not understood. We report here that EphB4 is expressed in 7 of 12 (58%) human breast cancer specimens and 4 of 4 (100%) breast tumor cell lines examined. Overexpression of EphB4 in breast cancer cells was driven by gene amplification and by the erbB family of receptors via activation of Janus tyrosine kinase-signal transducers and activators of transcription and protein kinase B. The aberrantly expressed receptor was phosphorylated by its natural ligand, EphrinB2, and signaled via the protein kinase B pathway. Targeted knockdown of EphB4 expression by small interference RNA (and antisense oligodeoxynucleotides (ODNs)) led to dose-dependent reduction in cell survival, increased apoptosis, and sensitization to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Antisense ODN-mediated EphB4 knockdown resulted in reduced tumor growth in a murine tumor xenograft model. Antisense ODN-treated tumors were 72% smaller than control tumors at 6 weeks, with an 86% reduction in proliferating cells, 15-fold increase in apoptosis, and 44% reduction in tumor microvasculature. Our data indicate that biologically active EphB4 functions as a survival factor in breast cancer and is a novel target for therapy.