Outcomes of Sarcoma Resections Requiring Vascular Surgical Assistance: A Single-Center Experience.

Objective: To describe the types of intervention and determine patency and survival after arterial and venous reconstruction after surgical excision of sarcomas. Methods: Between November 2001 and July 2015, 42 patients with sarcomas and vascular involvement underwent surgical oncologic resection followed by arterial or venous reconstruction or preservation of the native vascular bundle. Univariate, multivariate, and Kaplan-Meier survival analyses were performed on abstracted data, which included demographics, risk factors, oncologic and vascular treatment modalities, postoperative complications, graft patency, and survival outcomes. Results: A total of 42 sarcomas required vascular assistance for oncologic removal. The majority of sarcomas were malignant fibrous histiocytoma (23.8%), and the most common anatomic location was the retroperitoneum (48%). A total of 12 revascularizations procedures were performed, including 5 arterial, 3 venous, and 2 concomitant arterial and venous. In 32 cases, a vascular surgeon was needed for vessel ligation, repair, or mobilization. The overall 2- and 5-year survival was 77.7% and 26.2%, respectively, with no significant survival difference between patients who underwent revascularization compared to those without revascularization. There was a 100% patency rate in all cases at last follow-up, regardless of the type of vascular reconstruction (median 18 months, range 1-29 months). On multivariate analysis, chronic obstructive pulmonary disease (COPD; P = .002) and positive surgical margins (P = .003) were associated with decreased survival. Most cases were performed in the last 5 years of the study (n = 27, 64.3%). Conclusions: Vascular reconstruction is feasible after surgical oncologic resection of sarcomas with good mid-term patency and limb preservation. Factors independently associated with mortality included COPD and positive surgical margins.

Impact of Body Mass Index on Outcomes after Mesenteric Revascularization for Chronic Mesenteric Ischemia.

BACKGROUND: Historically, patients with chronic mesenteric ischemia (CMI) are underweight with a low body mass index (BMI). However, with the recent obesity epidemic many of these patients now are overweight with a high BMI. We evaluated the impact of BMI on outcomes after mesenteric revascularization for CMI. METHODS: A retrospective chart review of patients undergoing open or endovascular mesenteric revascularization for CMI between January 2000 and June 2015 was performed. Demographics, comorbidities, BMI, Society for Vascular Surgery-combined comorbidity score, treatment modality, postoperative complications, reintervention, and all-cause mortality were analyzed. The primary end point for the study was all-cause mortality at 5 years. Patients were stratified using the World Health Organization BMI criteria. Univariate, Kaplan-Meier survival, and multivariate analyses were performed. RESULTS: In the study period, 104 unique patients underwent mesenteric revascularization for CMI, for 77 of whom BMI information was available. Of these 77, 30 patients were treated by endovascular revascularization, and 47 patients were treated by open revascularization. Overall, 27 (35.1%) were overweight or obese with a BMI ≥25. Median follow-up time was 41 months. High BMI patients were less likely to have weight loss at the time of surgery (P = 0.004). Stratified by BMI <25 versus BMI ≥25, 5-year survival for patients treated by open revascularization was 90% versus 50% (P = 0.02); survival for patients treated by endovascular revascularization was 27% vs. 53% (P = 0.37). Multivariate survival analysis identified active smoking, hypertensive chronic kidney disease, open repair with the use of venous conduit instead of prosthetic conduit (P < 0.001), and history of peripheral arterial disease (PAD) (P = 0.002), as independent predictors of increased all-cause mortality. CONCLUSIONS: BMI needs to be considered in assessing and counseling patients on outcomes of mesenteric revascularization for CMI, as a BMI over 25 is associated with poorer long-term survival after open revascularization. Smoking, hypertensive chronic kidney disease, PAD, and open repair with the use of venous conduit are independent predictors of long-term mortality after mesenteric revascularization independent of BMI.

Why Temporary Filters Are Not Removed: Clinical Predictors in 1,000 Consecutive Cases.

BACKGROUND: Compared to permanent inferior vena cava (IVC) filters, higher complication rates occur with long-term use of temporary IVC filters. We aimed to identify patient clinical factors at the time of placement that could predict failure to remove a temporary IVC filter. METHODS: A retrospective review was performed of both vascular surgery and interventional radiology prospective databases between December 2008 and December 2013. We analyzed a total number of 1,024 consecutive, temporary IVC filters stratified by whether retrieval was attempted or made permanent. Univariate, multivariate, and prediction modeling analyses with internal validation were performed on abstracted data, which included risk factors, treatment modalities, and indications for IVC filter placement. RESULTS: Of 1,024 temporary IVC filters, removal was attempted in 60% and no attempt at removal (kept permanent) in 40%. Of the 619 with attempted removal, the overall successful retrieval rate was 95%. The majority of filters were not attempted to be removed because of persistent filter indications (360 cases). Risk factors associated with IVC filter permanence included male sex, older age, history, or indication of venous thromboembolism (VTE) with inability to anticoagulate, malignancy, and neurologic condition. Risk factors most predictive of permanence in the multivariate model were malignancy (odds ratio [OR]: 3.0, P < 0.001) or neurologic disorder (OR: 2.69, P = 0.0005). Validation revealed our model had a sensitivity of 60.4% and specificity of 69.9%. CONCLUSIONS: Our study shows that patients who are more likely to have a temporary IVC filter kept permanent are more likely to be older males with a history of malignancy, neurologic condition, or VTE. These factors are also predictive of permanence and can be used in our predictive model to provide insight into the significant preoperative risk factors that should play into the decision-making process.

Surveillance, anticoagulation, or filter in calf vein thrombosis.

OBJECTIVE: This study compared the efficacy and complication rates of inferior vena cava (IVC) filters for calf vein thrombosis (CVT) vs conservative treatment with or without anticoagulation. METHODS: Vascular laboratory studies of patients who had an isolated CVT (anterior and posterior tibialis, peroneal, soleal, and gastrocnemius veins) from April 2009 to January 2014 were retrospectively analyzed from a single institution. Of 647 patients with isolated CVT, 285 (44%) received an IVC filter, and 362 (56%) received medical treatment alone (38.9% surveillance, 11.6% prophylactic anticoagulation, and 49.4% therapeutic anticoagulation). Univariate, multivariate, propensity matching, and Kaplan-Meier analyses were performed on abstracted data, which included, but was not limited to, risk factors, treatment modalities, venous thromboembolism (VTE) complications (defined as propagation of deep vein thrombosis [DVT] or pulmonary embolism [PE]), bleeding complications, and IVC filter-related complications (ie, filter tilting >15°, perforation >3 mm, fracture, migration >10 mm). RESULTS: The overall incidence of PE in was 2.5% in the IVC filter group and 3.3% in the medical group (P = .27). The overall incidence of VTE complications (propagation of DVT, PE) was 35% for the surveillance group without anticoagulation, 30% in patients treated with prophylactic anticoagulation, and 10% in patients treated with therapeutic anticoagulation (P = .0003). Only a minority of patients underwent duplex ultrasound imaging after filter insertion. In the IVC filter group, the most common reasons that contraindicated anticoagulation were bleeding (35%) or recent surgery (27%). The number of IVC filter-related complications in the IVC filter group was 29 (10%). Because the IVC filter group was older (mean age, 65 vs 61 years, P = .004) and more likely to have a history of thromboembolic events (56% vs 16%, P < .0001), and malignancy (49% vs 28%, P < .0001), propensity analyses were performed yielding a homogenous cohort. The overall complication and thromboembolic rates did not differ for muscular (soleal, gastrocnemius) vs tibial DVTs (anterior, posterior, peroneal veins). CONCLUSIONS: The use of anticoagulation in patients with CVT significantly decreases the rates of VTE complications. The use of IVC filters in this study was associated with a 10% complication rate and did not significantly reduce the incidence of PE. Nevertheless, given the overall low rates of PE and the higher risk of VTE in patients who receive filters, the decision to insert a filter in patients with calf CVT should be individualized.

Determining If Sex Bias Exists in Human Surgical Clinical Research.

Importance: Sex is a variable that is poorly controlled for in clinical research. Objectives: To determine if sex bias exists in human surgical clinical research, to determine if data are reported and analyzed using sex as an independent variable, and to identify specialties in which the greatest and least sex biases exist. Design, Setting, and Participants: For this bibliometric analysis, data were abstracted from 1303 original peer-reviewed articles published from January 1, 2011, through December 31, 2012, in 5 surgery journals. Main Outcomes and Measures: Study type, location, number and sex of participants, degree of sex matching of included participants, and inclusion of sex-based reporting, statistical analysis, and discussion of data. Results: Of 2347 articles reviewed, 1668 (71.1%) included human participants. After excluding 365 articles, 1303 remained: 17 (1.3%) included males only, 41 (3.1%) included females only, 1020 (78.3%) included males and females, and 225 (17.3%) did not document the sex of the participants. Although female participants represent more than 50% (n = 57 688 606) of the total number (115 377 213) included, considerable variability existed with the number of male (46 111 818), female (58 805 665), and unspecified (10 459 730) participants included among the journals, between US domestic and international studies, and between single vs multicenter studies. For articles included in the study, 38.1% (497 of 1303) reported these data by sex, 33.2% (432 of 1303) analyzed these data by sex, and 22.9% (299 of 1303) included a discussion of sex-based results. Sex matching of the included participants in the research overall was poor, with 45.2% (589 of 1303) of the studies matching the inclusion of both sexes by 50%. During analysis of the different surgical specialties, a wide variation in sex-based inclusion, matching, and data reporting existed, with colorectal surgery having the best matching of male and female participants and cardiac surgery having the worst. Conclusions and Relevance: Sex bias exists in human surgical clinical research. Few studies included men and women equally, less than one-third performed data analysis by sex, and there was wide variation in inclusion and matching of the sexes among the specialties and the journals reviewed. Because clinical research is the foundation for evidence-based medicine, it is imperative that this disparity be addressed so that therapies benefit both sexes.

Inadvertent Arterial Placement of Central Venous Catheters: Diagnostic and Therapeutic Strategies.

BACKGROUND: Central venous catheterization (CVC) is among the most ubiquitous medical procedures. Inadvertent arterial placement of the catheter presents a challenging dilemma to the interventionalist. Treatment options include: removal and manual compression, off-label use of percutaneous closure devices and/or stent grafts, and open surgical removal. Potential sequelae include bleeding, thrombosis, stroke, limb ischemia, neurologic deficit, and death. Our aim is to evaluate the use of open and endovascular techniques for the management of iatrogenic carotid, subclavian, and brachiocephalic arterial injuries related to inadvertent arterial CVC placement. METHODS: Retrospective chart review revealed 13 patients with iatrogenic arterial injuries related to inadvertent arterial CVC placement over a 5-year period at Northwestern Memorial Hospital using Current Procedural Terminology codes and interventional radiology and vascular databases. Presenting features, radiographic diagnosis, therapeutic maneuvers, and outcomes were reviewed. RESULTS: Endovascular therapy was instituted in 10 cases with 3 requiring an adjunctive open procedure. In the endovascular therapy group, stent grafts were used in 5 patients and 4 patients were managed with percutaneous closure devices. In 1 patient, multiple embolization procedures were performed in an attempt to close a large innominate artery arteriovenous fistula (AVFs) that ultimately required sternotomy and surgical ligation for complete closure. Primary open repair was carried out in 3 patients. Two patients developed embolic stroke before therapy and removal, with 1 death reported at 36-month follow-up. Overall success rate with a single intervention was 100% (4 of 4) with closure devices, 80% (4 of 5) covered stents, 0% (0 of 1) with embolization, and 100% (3 of 3) with open intervention. Overall complication rate was 7% (1 of 13) requiring further open, invasive intervention. CONCLUSIONS: Management of carotid, subclavian, and brachiocephalic arterial injuries from attempted jugular or subclavian venous cannulation can be challenging. The risk of embolic phenomenon associated with arterial catheterization, and the noncompressible anatomic location at the base of the neck frequently prevent simple removal. We use a strategy of immediate computed tomography or magnetic resonance to facilitate the most appropriate therapy. Endovascular treatment with covered stent grants, percutaneous closure devices, and embolization offer good results when selected appropriately based on imaging evaluation. However, more complex cases with associated pseudoaneurysms and/or AVFs with larger catheters may require definitive open repair.

Sex bias exists in basic science and translational surgical research.

BACKGROUND: Although the Revitalization Act was passed in 1993 to increase enrollment of women in clinical trials, there has been little focus on sex disparity in basic and translational research. We hypothesize that sex bias exists in surgical biomedical research. METHODS: Manuscripts from Annals of Surgery, American Journal of Surgery, JAMA Surgery, Journal of Surgical Research, and Surgery from 2011 to 2012 were reviewed. Data abstracted included study type, sex of the animal or cell studied, location, and presence of sex-based reporting of data. RESULTS: Of 2,347 articles reviewed, 618 included animals and/or cells. For animal research, 22% of the publications did not specify the sex of the animals. Of the reports that did specify the sex, 80% of publications included only males, 17% only females, and 3% both sexes. A greater disparity existed in the number of animals studied: 16,152 (84%) male and 3,173 (16%) female (P < .0001). For cell research, 76% of the publications did not specify the sex. Of the papers that did specify the sex, 71% of publications included only males, 21% only females, and 7% both sexes. Only 7 (1%) studies reported sex-based results. For publications on female-prevalent diseases, 44% did not report the sex studied. Of those reports that specified the sex, only 12% studied female animals. More international than national (ie, United States) publications studied only males (85% vs 71%, P = .004), whereas more national publications did not specify the sex (47% vs 20%, P < .0001). A subanalysis of a single journal showed that across three decades, the number of male-only studies and usage of male animals has become more disparate over time. CONCLUSION: Sex bias, be it overt, inadvertent, situational, financial, or ignorant, exists in surgical biomedical research. Because biomedical research serves as the foundation for subsequent clinical research and medical decision-making, it is imperative that this disparity be addressed because conclusions derived from such studies may be specific to only one sex.

Bridge to transplant experience: factors influencing survival to and after cardiac transplant.

OBJECTIVE: Balancing longer duration of mechanical circulatory support while awaiting functional recovery against the increased risk of adverse events with each day on support is difficult. Therefore, we investigated the complex interplay of duration of mechanical circulatory support and patient and device factors affecting survival on support, as well as survival after transplantation. METHODS: From December 21, 1991, to July 1, 2006, mechanical circulatory support was used in 375 patients as a bridge to transplantation, with 262 surviving to transplant. Implantable pulsatile devices were used in 321 patients, continuous flow was used in 11 patients, a total artificial heart was used in 5 patients, external pulsatile devices were used in 34 patients, and extracorporeal membrane oxygenation was used in 68 patients. Two time-related models were developed: (1) a competing-risks multivariable model of death on mechanical circulatory support, with modulated renewal for each sequential support mode; and (2) a model of death after transplant in which patient factors and duration of mechanical circulatory support were investigated as risk factors. RESULTS: Survival after initiating mechanical circulatory support, irrespective of transplantation, was 86% at 30 days, 55% at 5 years, and 41% at 10 years; survival was 94%, 74%, and 58% at the same time intervals, respectively, after transplantation in those surviving the procedure. Risk factors for death included longer, but not shorter, duration of mechanical circulatory support, use of multiple devices, global sensitization, and poor renal function. CONCLUSION: Initiating mechanical circulatory support early with a single definitive device may improve survival to and after cardiac transplantation. Early transplant, which avoids infection, sensitization, and neurologic complications, may improve bridge and transplant survival.

Decision support in surgical management of ischemic cardiomyopathy.

OBJECTIVES: The surgical approach to ischemic cardiomyopathy maximizing survival remains a dilemma, with decisions complicated by secondary mitral regurgitation, ventricular remodeling, and heart failure. As a component of decision support, we sought to develop prediction models for comparing survival after coronary artery bypass grafting alone, coronary artery bypass grafting plus mitral valve anuloplasty, coronary artery bypass grafting plus surgical ventricular restoration, and listing for cardiac transplantation. METHODS: From 1997 to 2007, 1468 patients with ischemic cardiomyopathy (ejection fraction <30%) underwent coronary artery bypass grafting alone (n = 386), coronary artery bypass grafting plus mitral valve anuloplasty (n = 212), coronary artery bypass grafting plus surgical ventricular restoration (n = 360), or listing for cardiac transplantation (n = 510). Mean follow-up was 3.8 +/- 2.8 years, with 5577 patient-years of data available for analysis. Risk factors were identified for early and late mortality by using 80% training and 20% validation sets. Outcomes were calculated for each applicable strategy to identify which maximized predicted 5-year survival. Models were programmed as a strategic decision-support tool. RESULTS: One-, 5-, and 9-year survival were as follows, respectively: coronary artery bypass grafting, 92%, 72%, and 53%; coronary artery bypass grafting plus mitral valve anuloplasty, 88%, 57%, and 34%; coronary artery bypass grafting plus surgical ventricular restoration, 94%, 76%, and 55%; and listing for cardiac transplantation, 79%, 66%, and 54%. Risk factors included older age, higher New York Heart Association class, lower ejection fraction, longer interval from myocardial infarction to operation, and numerous comorbidities. Predicted and observed survivals in validation groups were similar (P > .1). Patient-specific simultaneous solutions of applicable models revealed therapy potentially providing maximum survival benefit. Coronary artery bypass grafting alone and listing for cardiac transplantation often maximized 5-year survival; only 15% of patients undergoing coronary artery bypass grafting plus mitral valve anuloplasty were predicted to fare best with this therapy. CONCLUSION: Validated prediction models can aid surgeons in recommending personalized treatment plans that maximize short- and long-term survival for ischemic cardiomyopathy.

Frontal dopaminergic abnormality in Tourette syndrome: a postmortem analysis.

Frontal-subcortical abnormalities have been implicated in the pathophysiology of Tourette syndrome (TS). The goal of this study was to more extensively evaluate a possible underlying neurochemical abnormality in frontal cortex. Postmortem brain tissue from frontal and occipital regions (Brodmann's areas 4, 6, 9, 10, 11, 12, and 17) from three TS patients and three age-and sex-matched controls were analyzed by semiquantitative immunoblotting. Relative densities were measured for a variety of neurochemical markers including dopamine (D1, D2), serotonin (5HT-1A), and alpha-adrenergic (alpha-2A) receptors, the dopamine transporter (DAT), a monoamine terminal marker (vesicular monoamine transporter type 2, VMAT-2), and vesicular docking and release proteins (VAMP-2, synaptotagmin, SNAP-25, syntaxin, synaptophysin). Data from each TS sample, corrected for actin content, was expressed as a percentage value of its control. Results identified consistent increases of DAT and D2 receptor density in five of six frontal regions in all three TS subjects. D1 and alpha-2A receptor density were increased in a few frontal regions. These results support the hypothesis of a dopaminergic dysfunction in the frontal lobe and a likely role in the pathophysiology of TS.

Dopaminergic polymorphisms in Tourette syndrome: association with the DAT gene (SLC6A3).

Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by involuntary motor and phonic tics. The pattern of inheritance and associated genetic abnormality has yet to be fully characterized. A dopaminergic abnormality in this disorder is supported by response to specific therapies, nuclear imaging, and postmortem studies. In this protocol, dopaminergic polymorphisms were examined for associations with TS and attention-deficit hyperactivity disorder (ADHD). Polymorphisms investigated included the dopamine transporter (DAT1 DdeI and DAT1 VNTR), dopamine receptor (D4 Upstream Repeat and D4 VNTR), dopamine converting enzyme (dopamine beta-hydroxylase), and the acid phosphatase locus 1 (ACP1) gene. DNA was obtained from 266 TS individuals +/- ADHD and 236 controls that were ethnicity-matched. A significant association, using a genotype-based association analysis, was identified for the TS-total and TS-only versus control groups for the DAT1 DdeI polymorphism (AG vs. AA, P = 0.004 and P = 0.01, respectively). Population structure, estimated by the genotyping of 27 informative SNP markers, identified 3 subgroups. A statistical re-evaluation of the DAT1 DdeI polymorphism following population stratification confirmed the association for the TS-total and TS-only groups, but the degree of significance was reduced (P = 0.017 and P = 0.016, respectively). This study has identified a significant association between the presence of TS and a DAT polymorphism. Since abnormalities of the dopamine transporter have been hypothesized in the pathophysiology of TS, it is possible that this could be a functional allele associated with clinical expression.

Norepinephrine transporter polymorphisms in Tourette syndrome with and without attention deficit hyperactivity disorder: no evidence for significant association.

Noradrenergic abnormalities have been proposed in the pathophysiology of Tourette syndrome and attention-deficit hyperactivity disorder. Patients with Tourette syndrome with (n=115) and without (n=110) attention-deficit hyperactivity disorder were evaluated for association with two single nucleotide polymorphisms of the norepinephrine transporter gene (SLC6A2); a T-182C single nucleotide polymorphism located in the 5' flanking promoter region and a silent mutation (G1287A) occurring in exon 9. A polymerase chain reaction restriction enzyme assay was developed for the T-182C single nucleotide polymorphism based on a prior sequencing methodology. In this case-control study, no association was identified between either polymorphism and Tourette syndrome or attention-deficit hyperactivity disorder. In a small subset, these NET polymorphisms did not predict therapeutic response to the noradrenergic transporter inhibitor atomoxetine. Further research with additional NET polymorphisms and larger sample sizes are indicated in the pursuit of biomarkers for therapeutic responders.

Antibrain antibodies in children with autism and their unaffected siblings.

Serum autoantibodies to human brain, identified by ELISA and Western immunoblotting, were evaluated in 29 children with autism spectrum disorder (22 with autistic disorder), 9 non-autistic siblings and 13 controls. More autistic subjects than controls had bands at 100 kDa in caudate, putamen and prefrontal cortex (p<0.01) as well as larger peak heights of bands at 73 kDa in the cerebellum and cingulate gyrus. Both autistic disorder subjects and their matched non-autistic siblings had denser bands (peak height and/or area under the curve) at 73 kDa in the cerebellum and cingulate gyrus than did controls (p<0.01). Results suggest that children with autistic disorder and their siblings exhibit differences compared to controls in autoimmune reactivity to specific epitopes located in distinct brain regions.