Predicting the Safety and Effectiveness of Inferior Vena Cava Filters (PRESERVE): Outcomes at 12 months.

OBJECTIVE: To determine the safety and effectiveness of vena cava filters (VCFs). METHODS: A total of 1429 participants (62.7 ± 14.7 years old; 762 [53.3% male]) consented to enroll in this prospective, nonrandomized study at 54 sites in the United States between October 10, 2015, and March 31, 2019. They were evaluated at baseline and at 3, 6, 12, 18, and 24 months following VCF implantation. Participants whose VCFs were removed were followed for 1 month after retrieval. Follow-up was performed at 3, 12, and 24 months. Predetermined composite primary safety (freedom from perioperative serious adverse events [AEs] and from clinically significant perforation, VCF embolization, caval thrombotic occlusion, and/or new deep vein thrombosis [DVT] within 12-months) and effectiveness (composite comprising procedural and technical success and freedom from new symptomatic pulmonary embolism [PE] confirmed by imaging at 12-months in situ or 1 month postretrieval) end points were assessed. RESULTS: VCFs were implanted in 1421 patients. Of these, 1019 (71.7%) had current DVT and/or PE. Anticoagulation therapy was contraindicated or had failed in 1159 (81.6%). One hundred twenty-six (8.9%) VCFs were prophylactic. Mean and median follow-up for the entire population and for those whose VCFs were not removed was 243.5 ± 243.3 days and 138 days and 332.6 ± 290 days and 235 days, respectively. VCFs were removed from 632 (44.5%) patients at a mean of 101.5 ± 72.2 days and median 86.3 days following implantation. The primary safety end point and primary effectiveness end point were both achieved. Procedural AEs were uncommon and usually minor, but one patient died during attempted VCF removal. Excluding strut perforation greater than 5 mm, which was demonstrated on 31 of 201 (15.4%) patients' computed tomography scans available to the core laboratory, and of which only 3 (0.2%) were deemed clinically significant by the site investigators, VCF-related AEs were rare (7 of 1421, 0.5%). Postfilter, venous thromboembolic events (none fatal) occurred in 93 patients (6.5%), including DVT (80 events in 74 patients [5.2%]), PE (23 events in 23 patients [1.6%]), and/or caval thrombotic occlusions (15 events in 15 patients [1.1%]). No PE occurred in patients following prophylactic placement. CONCLUSIONS: Implantation of VCFs in patients with venous thromboembolism was associated with few AEs and with a low incidence of clinically significant PEs.

Extracellular glutamate and IDH1R132H inhibitor promote glioma growth by boosting redox potential.

PURPOSE: Somatic mutations of the isocitrate dehydrogenase 1 (IDH1) gene, mostly substituting Arg132 with histidine, are associated with better patient survival, but glioma recurrence and progression are nearly inevitable, resulting in disproportionate morbidity and mortality. Our previous studies demonstrated that in contrast to hemizygous IDH1R132H (loss of wild-type allele), heterozygous IDH1R132H is intrinsically glioma suppressive but its suppression of three-dimensional (3D) growth is negated by extracellular glutamate and reducing equivalent. This study sought to understand the importance of 3D culture in IDH1R132H biology and the underlying mechanism of the glutamate effect. METHODS: RNA sequencing data of IDH1R132H-heterozygous and IDH1R132H-hemizygous glioma cells cultured under two-dimensional (2D) and 3D conditions were subjected to unsupervised hierarchal clustering and gene set enrichment analysis. IDH1R132H-heterozygous and IDH1R132H-hemizygous tumor growth were compared in subcutaneous and intracranial transplantations. Short-hairpin RNA against glutamate dehydrogenase 2 gene (GLUD2) expression was employed to determine the effects of glutamate and the mutant IDH1 inhibitor AGI-5198 on redox potential in IDH1R132H-heterozygous cells. RESULTS: In contrast to IDH1R132H-heterozygous cells, 3D-cultured but not 2D-cultured IDH1R132H-hemizygous cells were clustered with more malignant gliomas, possessed the glioblastoma mesenchymal signature, and exhibited aggressive tumor growth. Although both extracellular glutamate and AGI-5198 stimulated redox potential for 3D growth of IDH1R132H-heterozygous cells, GLUD2 expression was required for glutamate, but not AGI-5198, stimulation. CONCLUSION: 3D culture is more relevant to IDH1R132H glioma biology. The importance of redox homeostasis in IDH1R132H glioma suggests that metabolic pathway(s) can be explored for therapeutic targeting, whereas IDH1R132H inhibitors may have counterproductive consequences in patient treatment.

Society of Interventional Radiology Clinical Practice Guideline for Inferior Vena Cava Filters in the Treatment of Patients with Venous Thromboembolic Disease: Developed in collaboration with the American College of Cardiology, American College of Chest Physicians, American College of Surgeons Committee on Trauma, American Heart Association, Society for Vascular Surgery, and Society for Vascular Medicine.

PURPOSE: To provide evidence-based recommendations on the use of inferior vena cava (IVC) filters in the treatment of patients with or at substantial risk of venous thromboembolic disease. MATERIALS AND METHODS: A multidisciplinary expert panel developed key questions to address in the guideline, and a systematic review of the literature was conducted. Evidence was graded based on a standard methodology, which was used to inform the development of recommendations. RESULTS: The systematic review identified a total of 34 studies that provided the evidence base for the guideline. The expert panel agreed on 18 recommendations. CONCLUSIONS: Although the evidence on the use of IVC filters in patients with or at risk of venous thromboembolic disease varies in strength and quality, the panel provides recommendations for the use of IVC filters in a variety of clinical scenarios. Additional research is needed to optimize care for this patient population.

Differential expression of Hedgehog/Notch and transforming growth factor-ß in human abdominal aortic aneurysms.

OBJECTIVE: The molecular mechanisms leading to the development of abdominal aortic aneurysms (AAAs) remain poorly understood. The aim of this study was to determine the expression of Sonic Hedgehog (SHh), transforming growth factor ß (TGF-ß), and Notch signaling components in human aneurysmal and nonaneurysmal aorta in vivo. METHODS: Paired tissue samples were obtained from aneurysmal and nonaneurysmal (control) segments of the aortic wall of eight patients with suitable anatomy undergoing open repair of infrarenal AAAs. Protein and messenger RNA (mRNA) expression levels were determined by Western blot and quantitative real-time polymerase chain reaction analysis. RESULTS: Aneurysm development resulted in a significant reduction in vascular smooth muscle (vSMC) differentiation genes α-actin and SMC22α at both mRNA and protein levels. In parallel experiments, an 80.0% ± 15% reduction in SHh protein expression was observed in aneurysmal tissue compared with control. SHh and Ptc-1 mRNA levels were also significantly decreased, by 82.0% ± 10% and 75.0% ± 5%, respectively, in aneurysmal tissue compared with nonaneurysmal control tissue. Similarly, there was a 50.0% ± 9% and 60.0% ± 4% reduction in Notch receptor 1 intracellular domain and Hrt-2 protein expression, respectively, in addition to significant reductions in Notch 1, Notch ligand Delta like 4, and Hrt-2 mRNA expression in aneurysmal tissue compared with nonaneurysmal tissue. There was no change in Hrt-1 expression observed in aneurysmal tissue compared with control. In parallel experiments, we found a 2.2 ± 0.2-fold and a 5.6 ± 2.2-fold increase in TGF-ß mRNA and protein expression, respectively, in aneurysmal tissue compared with nonaneurysmal tissue. In vitro, Hedgehog signaling inhibition with cyclopamine in human aortic SMCs resulted in decreased Hedgehog/Notch signaling component and vSMC differentiation gene expression. Moreover, cyclopamine significantly increased TGF-ß1 mRNA expression by 2.6 ± 0.9-fold. CONCLUSIONS: These results suggest that SHh/Notch and TGF-ß signaling are differentially regulated in aneurysmal tissue compared with nonaneurysmal tissue. Changes in these signaling pathways and the resulting changes in vSMC content may play a causative role in the development of AAAs.

Contemporary results of carotid endarterectomy in "normal-risk" patients from the Society for Vascular Surgery Vascular Registry.

OBJECTIVE: Acceptable complication rates after carotid endarterectomy (CEA) are drawn from decades-old data. The recent Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated improved stroke and mortality outcomes after CEA compared with carotid artery stenting, with 30-day periprocedural CEA stroke rates of 3.2% and 1.4% for symptomatic (SX) and asymptomatic (ASX) patients, respectively. It is unclear whether these target rates can be attained in "normal-risk" (NR) patients experienced outside of the trial. This study was done to determine the contemporary results of CEA from a broader selection of NR patients. METHODS: The Society for Vascular Surgery (SVS) Vascular Registry was examined to determine in-hospital and 30-day event rates for NR, SX, and ASX patients undergoing CEA. NR was defined as patients without anatomic or physiologic risk factors as defined by SVS Carotid Practice Guidelines. Raw data and risk-adjusted rates of death, stroke, and myocardial infarction (MI) were compared between the ASX and SX cohorts. RESULTS: There were 3977 patients (1456 SX, 2521 ASX) available for comparison. The SX group consisted of more men (61.7% vs 57.0%; P = .0045) but reflected a lower proportion of white patients (91.3% vs 94.4%; P = .0002), with lower prevalence of coronary artery disease (P < .0001), prior MI (P < .0001), peripheral vascular disease (P = .0017), and hypertension (P = .029), although New York Heart Association grade >3 congestive heart failure was equally present in both groups (P = .30). Baseline stenosis >80% on duplex imaging was less prevalent among SX patients (54.2% vs 67.8%; P < .0001). Perioperative stroke rates were higher for SX patients in the hospital (2.8% vs 0.8%; P < .0001) and at 30 days (3.4% vs 1.0%; P < .0001), which contributed to the higher composite death, stroke, and MI rates in the hospital (3.6% vs 1.8; P = .0003) and at 30 days (4.5% vs 2.2%; P < .0001) observed in SX patients. After risk adjustment, the rate of stroke/death was greater among SX patients in the hospital (odds ratio, 2.05; 95% confidence interval, 1.18-3.58) although not at 30 days (odds ratio, 1.36; 95% confidence interval, 0.85-2.17). No in-hospital or 30-day differences were observed for death or MI by symptom status. CONCLUSIONS: The SVS Vascular Registry results for CEA in NR patients are similar by symptom status to those reported for CREST and may serve as a benchmark for comparing results of alternative therapies for treatment of carotid stenosis in NR patients outside of monitored clinical trials. The contemporary perioperative risk of stroke after CEA in NR patients continues to be higher for SX than for ASX patients.

OKN-007 decreases tumor necrosis and tumor cell proliferation and increases apoptosis in a preclinical F98 rat glioma model.

BACKGROUND: Glioblastoma is a malignant World Health Organization (WHO) grade IV glioma with a poor prognosis in humans. New therapeutics are desperately required. The nitrone OKN-007 (2,4-disulfophenyl-PBN) has demonstrated effective anti-glioma properties in several rodent models and is currently being used as a clinical investigational drug for recurrent gliomas. We assessed the regional effects of OKN-007 in the tumor necrotic core and non-necrotic tumor parenchyma. METHODS: An F98 rat glioma model was evaluated using proton magnetic resonance spectroscopy ((1) H-MRS), diffusion-weighted imaging (DWI), morphological T2-weighted imaging (T2W) at 7 Tesla (30 cm-bore MRI), as well as immunohistochemistry and microarray assessments, at maximum tumor volumes (15-23 days following cell implantation in untreated (UT) tumors, and 18-35 days in OKN-007-treated tumors). RESULTS: (1) H-MRS data indicates that Lip0.9/Cho, Lip0.9/Cr, Lip1.3/Cho, and Lip1.3/Cr ratios are significantly decreased (all P < 0.05) in the OKN-007-treated group compared with UT F98 gliomas. The Cho/Cr ratio is also significantly decreased in the OKN-007-treated group compared with UT gliomas. In addition, the OKN-007-treated group demonstrates significantly lower ADC values in the necrotic tumor core and the nonnecrotic tumor parenchyma (both P < 0.05) compared with the UT group. There was also an increase in apoptosis following OKN-007 treatment (P < 0.01) compared with UT. CONCLUSION: OKN-007 reduces both necrosis and tumor cell proliferation, as well as seems to mediate multiple effects in different tumor regions (tumor necrotic core and nonnecrotic tumor parenchyma) in F98 gliomas, indicating the efficacy of OKN-007 as an anti-cancer agent and its potential clinical use.

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.

Correlation of intravascular ultrasound and computed tomography scan measurements for placement of intravascular ultrasound-guided inferior vena cava filters.

OBJECTIVE: The single puncture intravascular ultrasound (IVUS)-guided bedside placement of inferior vena cava (IVC) filters has been shown to be an effective technique. The major disadvantage of this procedure is a steep learning curve that can lead to an increased risk of filter malposition. In an effort to increase the safety and efficacy of IVUS-guided bedside IVC filter placement, we proposed that preoperative planning could reduce the incidence of IVUS-guided filter malpositions. As a first step, we examined the correlation between preoperative abdominal computed tomography (CT) scan measurements and intraprocedural IVUS derived measurements of vena cava anatomy and its surrounding structures. As a second step, we attempted to determine the safety of this protocol by assessing the incidence of malposition. METHODS: A retrospective review of prospectively collected data was performed on all patients receiving bedside IVUS-guided filters from July 1, 2010 to August 31, 2011. Measurements of the IVC length from the atrial-IVC junction to the midportion of the crossing right renal artery, the lowest renal vein, and iliac vein confluence were obtained prior to IVC filter placement by both CT-based measurement, as well as intraprocedural IVUS pullback lengths. Regression analysis (significant for P < .05) was used to determine the correlation between these imaging modalities. RESULTS: Forty-six patients had adequate CT scans available to perform the analysis and were candidates for bedside IVUS-guided IVC filter placement. All IVUS-guided filters were placed using a single puncture technique with the Cook Celect Filter. This study found there was a close correlation between IVUS and CT derived measurements of the right atrium to right renal artery distance, lowest renal vein distance, and iliac confluence distance. In addition, we found that the IVUS distances from the atrial-IVC junction to the right renal artery and lowest renal vein were statistically similar. Nine patients had 10 vascular anatomic variations, all identified by both IVUS and CT. There were no complications or malpositions of IVC filters using this protocol. CONCLUSIONS: These data suggest that IVUS pullback measurements from the right atrium used in combination with preprocedure CT derived measurements of the distance from the right atrium to the lowest renal vein and iliac vein confluence provide an accurate roadmap for the placement of bedside IVC filters under IVUS guidance. We provide a method for organizing this information in a preplanning document to aid this procedure. We suggest this easily employed technique be more fully utilized to help decrease the incidence of malpositioned filters using single puncture IVUS guidance.

Preoperative symptom type influences the 30-day perioperative outcomes of carotid endarterectomy and carotid stenting in the Society for Vascular Surgery Vascular Registry.

OBJECTIVE: The objective of this study was to determine the effect of presenting symptom types on 30-day periprocedural outcomes of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in contemporary vascular practice. METHODS: Retrospective review was undertaken of the Society for Vascular Surgery Vascular Registry database subjects who underwent CEA or CAS from 2004 to 2011. Patients were grouped by discrete 12-month preprocedural ipsilateral symptom type: stroke, transient ischemic attack (TIA), transient monocular blindness (TMB), or asymptomatic (ASX). Risk-adjusted odds ratios (ORs) were used to compare the likelihood of the 30-day outcomes of death, stroke, and myocardial infarction (MI) and the composite outcomes of death + stroke and death + stroke + MI. RESULTS: Symptom type significantly influences risk-adjusted 30-day outcomes for carotid intervention. Presentation with stroke predicted the poorest outcomes (death + stroke + MI composite: OR, 1.3; 95% confidence interval [CI], 0.83-2.03 vs TIA; OR, 2.56; 95% CI, 1.18-5.57 vs TMB; OR, 2.12; 95% CI, 1.46-3.08 vs ASX), followed by TIA (death + stroke + MI composite: OR, 1.97; 95% CI, 0.91-4.25 vs TMB; OR, 1.63; 95% CI, 1.14-2.33 vs ASX). For both CAS and CEA patients, presentation with stroke or TIA predicted a higher risk of periprocedural stroke than in ASX patients. Presentation with stroke predicted higher 30-day risk of death with CAS but not with CEA. MI rates were not affected by presenting symptom type. The 30-day outcomes for the TMB and ASX patient groups were equivalent in both treatment arms. CONCLUSIONS: Presenting symptom type significantly affects the 30-day outcomes of both CAS and CEA in contemporary vascular surgical practice. Presentation with stroke and TIA predicts higher rates of periprocedural complications, whereas TMB presentation predicts a periprocedural risk profile similar to that of ASX disease.

Predictive multivariate regression to increase the specificity of carotid duplex ultrasound for high-grade stenosis in asymptomatic patients.

BACKGROUND: Carotid duplex ultrasound (CDUS) is commonly used to screen for carotid artery stenosis. Specificities of CDUS criteria however are lower than sensitivities, potentially resulting in false-positive examinations with subsequent unnecessary imaging or surgery. Our objective was to establish a multivariate logistic regression to increase the specificity of CDUS for high-grade (≥70%) stenosis. METHODS: A retrospective review collected CDUS velocities and radiographic measurements from patients who underwent both CDUS and computed tomography angiography (CTA). After stratification with standard CDUS criteria, a logistic regression was created using peak systolic velocity (PSV), end diastolic velocity (EDV), and PSV ratio (PSV of internal carotid artery [ICA]/PSV of common carotid artery [CCA]) as predictor variables. A receiver operating characteristic curve was generated to test the model's predictive ability. A cutoff probability for unequivocal high-grade stenosis was chosen based on optimal specificity. The regression model was applied to patients with equivocal high-grade stenosis. Probabilities for detection of high-grade stenosis were calculated. Descriptive statistics were generated to quantify the accuracy of the model. RESULTS: A total of 244 vessels were included. Standardized velocity criteria for ≥70% stenosis yielded a sensitivity of 90.6% (95% confidence interval [CI], 82.3-95.6%), specificity of 63.5% (95% CI, 55.4-70.5%), positive predictive value (PPV) of 57.0% (95% CI, 48.8-65.5%), and negative predictive value (NPV) of 92.7% (95% CI, 85.8-96.5%). Regression analysis produced a model for predicting the probability of high-grade stenosis defined as probability = logit(-1) (-4.97 + [0.00938 × PSV] + [0.0135 × EDV] + [0.103 × PSV ICA/CCA ratio]). A cutoff probability of 0.65 for high-grade stenosis yielded a sensitivity of 54.7% (95% CI, 43.9-65.0%), specificity of 94.3% (95% CI, 89.3-97.2%), PPV of 83.9% (95% CI, 71.6-91.9%), and NPV of 79.3% (95% CI, 72.8-84.5%). A cutoff PSV of 400 cm/sec was chosen for unequivocal stenosis of ≥70%. A total of 94 patients were found to meet criteria for high-grade stenosis (PSV ≥ 230 cm/sec) but fall short of criteria for unequivocal high-grade stenosis (PSV < 400 cm/sec). Application of the regression model resulted in identification of 15 patients with probability ≥0.65 for high-grade stenosis and 79 patients with probability <0.65. This resulted in a 16% potential reduction in CTA scans. CONCLUSIONS: Our regression model provides increased specificity of CDUS for high-grade stenosis in patients who have met initial highly sensitive screening criteria. Application of this model may limit the need for additional imaging and increase the threshold for operative intervention in asymptomatic patients with equivocal high-grade carotid stenosis.

CT angiography-derived duplex ultrasound velocity criteria in patients with carotid artery stenosis.

BACKGROUND: Validation of carotid duplex ultrasound velocity criteria (CDUS VC) to grade the severity of extracranial carotid artery stenosis has traditionally been based on conventional angiography measurements. In the last decade, computed tomographic angiography (CTA) has largely replaced conventional arch and carotid arteriography (CA) for diagnostic purposes. Given the low number of CA being performed, it is impractical to expect noninvasive vascular laboratories to be validated using this modality. CDUS VC have not been developed with the use of CTA-derived measurements. The objective was to determine optimal CDUS VC from CTA-derived measurements with the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method for 50% and 80% stenosis. METHODS: A retrospective review of all patients who underwent CDUS and CTA from 2000 to 2009 was performed. Vessel diameters were measured on CTA, and corresponding CDUS velocities were recorded. Percent stenosis was calculated using the NASCET method. Receiver operating characteristic (ROC) curves were generated for internal carotid artery (ICA) peak systolic velocity (PSV), ICA end diastolic velocity (EDV), and ICA PSV to common carotid artery PSV ratio (PSVR) for 50% and 80% stenosis. Velocity cut points were determined with equal weighting of sensitivity and specificity. RESULTS: A total of 575 vessels were analyzed to create the ROC curves. A 50% stenosis analysis yielded ideal cut points for PSV, EDV, and PSVR of 130 cm/sec, 42 cm/sec, and 1.75. An 80% stenosis analysis yielded ideal cut points for PSV, EDV, and PSVR of 297 cm/sec, 84 cm/sec, and 3.06. CONCLUSIONS: CTA-derived CDUS VC appeared to be reliable in defining 50% and 80% stenosis in patients with carotid artery stenosis. Although CDUS VC defined in this study were different from many of the previously published VC for the same percent stenosis, there were many similarities to those reported by the Society of Radiologists in Ultrasound consensus conference. We feel that CTA should be the gold standard imaging technique for validating CDUS VC.

Imaging-Guided Metabolic Radiosensitization of Pediatric Rhabdoid Tumors.

Tumor hypoxia leads to increased resistance to radiation therapy (RT), resulting in markedly worse clinical outcomes in the treatment and management of pediatric malignant rhabdoid tumors (MRT). To alleviate hypoxia in MRT, we repurposed an FDA approved, mitochondrial oxidative phosphorylation (OXPHOS) inhibitor, Atovaquone (AVO), to inhibit oxygen consumption and thereby enhance the sensitivity of tumor cells to low dose RT in MRT by hypoxia alleviation. Additionally, to better understand the tumor response induced by AVO and optimize the combination with RT, we employed an emerging, noninvasive imaging modality, known as multispectral optoacoustic tomography (MSOT), to monitor and evaluate real-time dynamic changes in tumor hypoxia and vascular perfusion. Oxygen-Enhanced (OE)-MSOT could measure the change of tumor oxygenation in the MRT xenograft models after AVO and RT treatments, indicating its potential as a response biomarker. OE-MSOT showed that treating MRT mouse models with AVO resulted in a transient increase in oxygen saturation (ΔsO 2 ) in tumors when the mice were subjected to oxygen challenge, while RT or saline treated groups produced no change. In AVO+RT combination groups, the tumors showed an increase in ΔsO 2 after AVO administration followed by a significant decrease after RT, that correlated with a strong anti-tumor response, demarcated by complete regression of tumors, with no relapse on long-term monitoring. These observations were histologically validated. In MRT models of acquired AVO resistance, combination therapy failed to alleviate tumoral hypoxia and elicit any therapeutic benefit. Together, our data highlights the utility of repurposing anti-malarial AVO as an anticancer adjuvant for enabling low dose RT for pediatric patients.

Early management of pediatric vascular injuries through humanitarian surgical care during U.S. military operations.

BACKGROUND: The objective of this report is to describe our experience of pediatric vascular injuries in a U.S. military combat support hospital in Baghdad, Iraq. A retrospective study was designed using Joint Theater Trauma Registry (JTTR) records in order to evaluate the pediatric (age <18 years) population presenting with vascular trauma to a combat hospital in Baghdad, Iraq between April 2006 and August 2008. Demographic data comprised casualty, age, gender, and mechanism of injury. Physiologic data included presenting vital signs (rectal temperature, blood pressure, and heart rate), arterial pH, base deficit, hemoglobin (g/dL), and international normalized ratio. RESULTS: Twenty-five children, median age 14 years (range, 5-17 years), median weight 48 kg (range, 15-80 kg) sustained 18 (72%) blast and 7 (28%) gunshot wounds. The mean Injury Severity Score was 25 ± 16.2. The median operative time for the vascular repairs was 189 minutes (range, 41-505 minutes). Patients were tachycardic (mean ± standard deviation, 136 ± 29 bpm), hypotensive (109/63 ± 29/19 mm Hg), and acidemic (pH 7.26 ± 0.07; BD -5.57 ± 5.1 mEq/L) on arrival to the emergency department and were physiologically improved upon admission to the intensive care unit 3 hours later. Repair techniques were ligation (14; 39%), saphenous graft (11; 31%), lateral suture (7; 19%), end anastomosis (2; 5%), patch (1; 3%), and thrombectomy (1; 3%). Twenty-four hour mean transfusion requirements included crystalloid 102 mL/kg (range, 19-253), transfused blood 47 mL/kg (range, 0-119), fresh frozen plasma 14 mL/kg (range, 0-68), and apheresis platelets (1.2 ± 3.68 units). Over a follow-up of 22 ± 5.5 days, the amputation-free survival was 80%. CONCLUSIONS: This is the largest reported wartime series to demonstrate in children that damage control resuscitation despite high injury severity permits simultaneous limb salvage.

Prediction of postdischarge venous thromboembolism using a risk assessment model.

OBJECTIVE: The risk of postdischarge venous thromboembolism (VTE) (either deep vein or pulmonary embolism) is increasingly recognized yet the prescription of postdischarge thromboprophylaxis is inconsistent. There is a paucity of information to aid clinicians in identifying surgical patients who are at increased risk for postdischarge VTE. This study aimed to determine the incidence and risk factors associated with symptomatic postdischarge VTE and develop a risk score to identify patients who may benefit from extended duration thromboprophylaxis. METHODS: This was a retrospective study. All nonorthopedic cases in which the patient was discharged alive without inpatient VTE were selected from the 2005-2009 National Surgical Quality Improvement Program database. A multivariate logistic regression was used to create a risk score for postdischarge VTE prediction. The dataset was split into two-thirds for risk score development and validated in the remaining one-third. RESULTS: The overall incidence of early postdischarge VTE for 2005-2009 National Surgical Quality Improvement Program was 0.3%. The risk score stratified patients into low, moderate, and high risk for postdischarge VTE with the incidence based on the risk score ranging from 0.07% to 2.2%. The risk score had good predictive ability with c-statistic = 0.72 for model development and c-statistic = 0.71 in the validation dataset. Factors associated with postdischarge VTE on multivariate analysis included race, increasing age, steroid use, body mass index ≥30, malignancy, higher American Society of Anesthesiologists class, increasing operative time, length of postsurgical stay, and major postoperative complication. CONCLUSIONS: This novel postdischarge VTE prediction score utilizes patient, operative, and early outcome factors to accurately identify patients at increased risk of a postdischarge thromboembolic event. The development of a patient- specific postdischarge VTE risk profile may help address the challenge of determining postdischarge prophylaxis requirements.

Cross-sectional area for the calculation of carotid artery stenosis on computed tomographic angiography.

OBJECTIVE: The use of cross-sectional area (CSA) measurements obtained from computed tomographic angiography (CTA) for the calculation of carotid artery stenosis has been suggested but not yet validated in a large population. The objective of this study was to determine whether CTA-derived CSA measurements were able to predict carotid stenosis with a level of confidence similar to CTA-derived diameter measurements, using Strandness criteria applied to carotid duplex ultrasound (CDUS) as a surrogate for true stenosis. METHODS: A retrospective review was conducted to identify patients who underwent both CDUS and CTA between 2000 and 2009. Percent stenosis was calculated using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) formula with diameter measurements and again with CSA measurements. A nonparametric correlation coefficient was calculated to detect correlation between the two groups. Two-dimensional receiver-operating characteristic curves with corresponding area under the curve (AUC) statistics were generated for >50% stenosis and >80% stenosis. Three-dimensional receiver-operating characteristic plots with corresponding volume under the surface (VUS) statistics were generated to measure the comparative accuracy of diameter-based and CSA-based stenosis for <50%, 50%-79%, and >80% stenosis. RESULTS: A total of 575 vessels in 313 patients were included in the study. Spearman's correlation coefficient between diameter and CSA-derived stenosis was ρ = 0.938 (95% confidence interval [CI], 0.927-0.947; P < .0001). For diameter-derived stenosis, AUC was 0.905 (95% CI, 0.878-0.932; P < .0001) for >50% stenosis and 0.950 (95% CI, 0.928-0.972; P < .0001) for 80%-99% stenosis. For CSA-derived percent stenosis, the AUC was 0.908 (95% CI, 0.882-0.935; P < .0001) for >50% stenosis and 0.935 (95% CI, 0.908-0.961; P < .0001) for 80%-99%. The nonparametric estimate for VUS in the diameter-based stenosis group was 0.761, whereas in the CSA-based group, the VUS was 0.735. The difference between VUS was 0.026 (95% CI, -0.022 and 0.077; P = .318). CONCLUSIONS: These data support the use of CTA as an accurate method of calculating carotid artery stenosis based on agreement with Strandness criteria applied to CDUS velocities. When additional imaging beyond CDUS is necessary, we report no significant difference between diameter and CSA measurements obtained from CTA for preoperative evaluation of carotid disease.

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.

Predicting the Safety and Effectiveness of Inferior Vena Cava Filters (PRESERVE): Outcomes at 12 months.

OBJECTIVE: To determine the safety and effectiveness of vena cava filters (VCFs). METHODS: A total of 1429 participants (62.7 ± 14.7 years old; 762 [53.3% male]) consented to enroll in this prospective, nonrandomized study at 54 sites in the United States between October 10, 2015, and March 31, 2019. They were evaluated at baseline and at 3, 6, 12, 18, and 24 months following VCF implantation. Participants whose VCFs were removed were followed for 1 month after retrieval. Follow-up was performed at 3, 12, and 24 months. Predetermined composite primary safety (freedom from perioperative serious adverse events [AEs] and from clinically significant perforation, VCF embolization, caval thrombotic occlusion, and/or new deep vein thrombosis [DVT] within 12-months) and effectiveness (composite comprising procedural and technical success and freedom from new symptomatic pulmonary embolism [PE] confirmed by imaging at 12-months in situ or 1 month postretrieval) end points were assessed. RESULTS: VCFs were implanted in 1421 patients. Of these, 1019 (71.7%) had current DVT and/or PE. Anticoagulation therapy was contraindicated or had failed in 1159 (81.6%). One hundred twenty-six (8.9%) VCFs were prophylactic. Mean and median follow-up for the entire population and for those whose VCFs were not removed was 243.5 ± 243.3 days and 138 days and 332.6 ± 290 days and 235 days, respectively. VCFs were removed from 632 (44.5%) patients at a mean of 101.5 ± 72.2 days and median 86.3 days following implantation. The primary safety end point and primary effectiveness end point were both achieved. Procedural AEs were uncommon and usually minor, but one patient died during attempted VCF removal. Excluding strut perforation greater than 5 mm, which was demonstrated on 31 of 201 (15.4%) patients' computed tomography scans available to the core laboratory, and of which only 3 (0.2%) were deemed clinically significant by the site investigators, VCF-related AEs were rare (7 of 1421, 0.5%). Postfilter, venous thromboembolic events (none fatal) occurred in 93 patients (6.5%), including DVT (80 events in 74 patients [5.2%]), PE (23 events in 23 patients [1.6%]), and/or caval thrombotic occlusions (15 events in 15 patients [1.1%]). No PE occurred in patients following prophylactic placement. CONCLUSIONS: Implantation of VCFs in patients with venous thromboembolism was associated with few AEs and with a low incidence of clinically significant PEs.

Early thrombus removal strategies for acute deep venous thrombosis: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum.

BACKGROUND: The anticoagulant treatment of acute deep venous thrombosis (DVT) has been historically directed toward the prevention of recurrent venous thromboembolism. However, such treatment imperfectly protects against late manifestations of the postthrombotic syndrome. By restoring venous patency and preserving valvular function, early thrombus removal strategies can potentially decrease postthrombotic morbidity. OBJECTIVE: A committee of experts in venous disease was charged by the Society for Vascular Surgery and the American Venous Forum to develop evidence-based practice guidelines for early thrombus removal strategies, including catheter-directed pharmacologic thrombolysis, pharmacomechanical thrombolysis, and surgical thrombectomy. METHODS: Evidence-based recommendations are based on a systematic review and meta-analysis of the relevant literature, supplemented when necessary by less rigorous data. Recommendations are made according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, incorporating the strength of the recommendation (strong: 1; weak: 2) and an evaluation of the level of the evidence (A to C). RESULTS: On the basis of the best evidence currently available, we recommend against routine use of the term "proximal venous thrombosis" in favor of more precise characterization of thrombi as involving the iliofemoral or femoropopliteal venous segments (Grade 1A). We further suggest the use of early thrombus removal strategies in ambulatory patients with good functional capacity and a first episode of iliofemoral DVT of <14 days in duration (Grade 2C) and strongly recommend their use in patients with limb-threatening ischemia due to iliofemoral venous outflow obstruction (Grade 1A). We suggest pharmacomechanical strategies over catheter-directed pharmacologic thrombolysis alone if resources are available and that surgical thrombectomy be considered if thrombolytic therapy is contraindicated (Grade 2C). CONCLUSIONS: Most data regarding early thrombus removal strategies are of low quality but do suggest patient-important benefits with respect to reducing postthrombotic morbidity. We anticipate revision of these guidelines as additional evidence becomes available.

R-flurbiprofen, a novel nonsteroidal anti-inflammatory drug, decreases cell proliferation and induces apoptosis in pituitary adenoma cells in vitro.

R-flurbiprofen, a nonsteroidal anti-inflammatory drug derivative, has been shown to inhibit colonic adenoma formation in mice. We investigated the effects of R-flurbiprofen on cell proliferation and apoptosis in pituitary adenoma cell lines. GH4C1 rat pituitary cell line cultures and low-passage human primary pituitary cell cultures were treated with varying concentrations of R-flurbiprofen (0.1-1.0 mM). R-flurbiprofen inhibited cell proliferation in a dose-dependent fashion. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay and chromatin condensation/dead cell apoptosis assay demonstrated induction of apoptosis at higher concentrations of R-flurbiprofen. R-flurbiprofen decreases cell proliferation and induces apoptosis in pituitary adenoma cells in vitro. This may be a potential therapy in the management of pituitary adenoma.

Recruiting strategies for potential 0+5 vascular residency applicants.

BACKGROUND: The 0+5 integrated vascular residency training pathway was established in 2006 to allow for trainee-focused training culminating in vascular surgery certification only. An early concern was whether enough medical students could be recruited directly into a vascular internship without the exposure that a general surgery residency provides. We hypothesized that programs that send a large percentage of their general surgical graduates to vascular fellowships have models that can be adapted to medical student recruitment. METHODS: Opinions and practices were sought from program directors through survey and from trainees taking the Vascular Surgery In-Training Examination. RESULTS: Eight programs were identified that sent 20% or more of their residents to vascular fellowships over the past 5 years (projecting a mean of 1.6 residents entering vascular fellowships in 2011). Almost all such programs have a formal mentoring system in place that match mentors to residents by interest, and almost all send residents to academic meetings before their senior year. Seventy-five percent of such programs have formal vascular lecture exposure to the first and second year medical student classes, offer clinical shadowing experiences, and have time on the vascular service during the MS3 clerkship; 83% offer a third- or fourth-year elective in vascular surgery. Vascular Surgery In-Training Examination responses were collected from 156 fellows and 13 "0+5" residents. Although fellows had initially been attracted to vascular surgery by the technical aspects of the field learned during residency (43%), the most important factor initially attracting medical students was an interested mentor (46%). However, the most important factor for both residents and students in making a final decision was the technical aspects of the field (66% and 63%, respectively). CONCLUSIONS: Although residents are automatically exposed to the field during residency, students can only be exposed to vascular surgery if a conscious effort is made by interested educators. Programs that send a high proportion of students and residents into vascular surgery tend to have planned exposure at the MS1 and MS2 levels, formal clinical rotations in place at the MS3 and MS4 levels, and pay personal attention to those who display interest. A guide is presented to help specifically plan these steps. Successful recruiting of students into a 0+5 integrated training program requires specific planning and action.