Comparing genomic and epigenomic features across species using the WashU Comparative Epigenome Browser.

Genome browsers have become an intuitive and critical tool to visualize and analyze genomic features and data. Conventional genome browsers display data/annotations on a single reference genome/assembly; there are also genomic alignment viewer/browsers that help users visualize alignment, mismatch, and rearrangement between syntenic regions. However, there is a growing need for a comparative epigenome browser that can display genomic and epigenomic data sets across different species and enable users to compare them between syntenic regions. Here, we present the WashU Comparative Epigenome Browser. It allows users to load functional genomic data sets/annotations mapped to different genomes and display them over syntenic regions simultaneously. The browser also displays genetic differences between the genomes from single-nucleotide variants (SNVs) to structural variants (SVs) to visualize the association between epigenomic differences and genetic differences. Instead of anchoring all data sets to the reference genome coordinates, it creates independent coordinates of different genome assemblies to faithfully present features and data mapped to different genomes. It uses a simple, intuitive genome-align track to illustrate the syntenic relationship between different species. It extends the widely used WashU Epigenome Browser infrastructure and can be expanded to support multiple species. This new browser function will greatly facilitate comparative genomic/epigenomic research, as well as support the recent growing needs to directly compare and benchmark the T2T CHM13 assembly and other human genome assemblies.

Summix: A method for detecting and adjusting for population structure in genetic summary data.

Publicly available genetic summary data have high utility in research and the clinic, including prioritizing putative causal variants, polygenic scoring, and leveraging common controls. However, summarizing individual-level data can mask population structure, resulting in confounding, reduced power, and incorrect prioritization of putative causal variants. This limits the utility of publicly available data, especially for understudied or admixed populations where additional research and resources are most needed. Although several methods exist to estimate ancestry in individual-level data, methods to estimate ancestry proportions in summary data are lacking. Here, we present Summix, a method to efficiently deconvolute ancestry and provide ancestry-adjusted allele frequencies (AFs) from summary data. Using continental reference ancestry, African (AFR), non-Finnish European (EUR), East Asian (EAS), Indigenous American (IAM), South Asian (SAS), we obtain accurate and precise estimates (within 0.1%) for all simulation scenarios. We apply Summix to gnomAD v.2.1 exome and genome groups and subgroups, finding heterogeneous continental ancestry for several groups, including African/African American (∼84% AFR, ∼14% EUR) and American/Latinx (∼4% AFR, ∼5% EAS, ∼43% EUR, ∼46% IAM). Compared to the unadjusted gnomAD AFs, Summix's ancestry-adjusted AFs more closely match respective African and Latinx reference samples. Even on modern, dense panels of summary statistics, Summix yields results in seconds, allowing for estimation of confidence intervals via block bootstrap. Given an accompanying R package, Summix increases the utility and equity of public genetic resources, empowering novel research opportunities.

An Op-Ed Writing Curriculum for Medical Students to Engage in Advocacy Through Public Writing.

BACKGROUND: Op-ed writing can be a powerful and accessible advocacy tool for physicians, but training is lacking in undergraduate medical education. AIM: To train and engage first-year medical students in op-ed writing. SETTING: Midwestern research-intensive medical school. PARTICIPANTS: All students in a required first-year health policy course in 2021 and 2022. PROGRAM DESCRIPTION: For their health policy course's final assignment, students could opt to write an op-ed on a healthcare issue of their choice. All students received written instruction on op-ed writing. Additionally, they could access a seminar, coaching and editing by peers and faculty, and publication guidance. PROGRAM EVALUATION: Of 179 students over 2 years, 105 chose to write op-eds. Fifty-one attended the seminar, 35 attended peer coaching sessions, 33 accessed structured peer editing, and 23 received faculty assistance. Thirty-eight students submitted a total of 42 op-eds for publication. Twenty-two pieces were published in major outlets and 17 in the university's health policy review. Of the 22 in major outlets, 21 received editing from either peers or faculty. DISCUSSION: An op-ed writing curriculum can be integrated into an existing medical school health policy course, resulting in a high level of engagement and in published op-eds by medical students.

Technique and Outcomes of Concomitant Aortic and Caval Resection and Reconstruction for Retroperitoneal Tumors.

BACKGROUND: Major vascular involvement is often considered a contraindication to resection of malignant tumors, but in highly selected patients, it can be performed safely, with results that are highly dependent upon the tumor biology. Resection of both the aorta and inferior vena cava (IVC) is a rare undertaking, requiring both favorable tumor biology and a patient fit for a substantial surgical insult; nevertheless, it provides the possibility of a cure. METHODS: Patients requiring resection and reconstruction of both the aorta and IVC from 2009 through 2019 at 2 university medical centers were included. Patient characteristics, operative technique, and outcomes were retrospectively collected. RESULTS: We identified 9 patients, all with infrarenal reconstruction or repair of the aorta and IVC. All cases were performed with systemic heparinization and required simultaneous aortic and caval cross-clamping for tumor resection. No temporary venous or arterial bypass was used. Since arterial reperfusion with the IVC clamped was poorly tolerated in 1 patient, venous reconstruction was typically completed first. Primary repair was performed in 1 patient, while 8 required replacements. In 2 patients, aortic homograft was used for replacement of both the aortoiliac and iliocaval segments in contaminated surgical fields. In the remaining 6, Dacron was used for arterial replacement; either Dacron (n = 2) or polytetrafluoroethylene (n = 4) were used for venous replacement. Patients were discharged after a median stay of 8 days (range: 5-16). At median follow-up of 17 months (range 3-79 months), 2 patients with paraganglioma and 1 patient with Leydig cell carcinoma had cancer recurrences. Venous reconstructions occluded in 3 patients (38%), although symptoms were minimal. One patient presented acutely with a thrombosed iliac artery limb and bilateral common iliac artery anastomotic stenoses, treated successfully with thrombolysis and stenting. CONCLUSIONS: Patients with tumor involving both the aorta and IVC can be successfully treated with resection and reconstruction. En bloc tumor resection, restoration of venous return before arterial reconstruction, and most importantly, careful patient selection, all contribute to positive outcomes in this otherwise incurable population.

WashU Epigenome Browser update 2022.

WashU Epigenome Browser (https://epigenomegateway.wustl.edu/browser/) is a web-based genomic data exploration tool that provides visualization, integration, and analysis of epigenomic datasets. The newly renovated user interface and functions have enabled researchers to engage with the browser and genomic data more efficiently and effectively since 2018. Here, we introduce a new integrated panel design in the browser that allows users to interact with 1D (genomic features), 2D (such as Hi-C), 3D (genome structure), and 4D (time series) data in a single web page. The browser can display three-dimensional chromatin structures with the 3D viewer module. The 4D tracks, called 'Dynamic' tracks, animatedly display time-series data, allowing for a more striking visual impact to identify the gene or genomic region candidates as a function of time. Genomic data, such as annotation features, numerical values, and chromatin interaction data can all be viewed in the dynamic track mode. Imaging data from microscopy experiments can also be displayed in the browser. In addition to software development, we continue to service and expand the data hubs we host for large consortia including 4DN, Roadmap Epigenomics, TaRGET and ENCODE, among others. Our growing user/developer community developed additional track types as plugins, such as qBed and dynseq tracks, which extend the utility of the browser. The browser serves as a foundation for additional genomics platforms including the WashU Virus Genome Browser (for COVID-19 research) and the Comparative Genome Browser. The WashU Epigenome Browser can also be accessed freely through Amazon Web Services at https://epigenomegateway.org/.

aPKC is a key polarity determinant in coordinating the function of three distinct cell polarities during collective migration.

Apical-basal polarity is a hallmark of epithelia and needs to be remodeled when epithelial cells undergo morphogenetic cell movements. Here, we analyze border cells in the Drosophila ovary to address how apical-basal polarity is remodeled and turned into front-back and inside-outside as well as apical-basal polarities, during collective migration. We find that the Crumbs (Crb) complex is required for the generation of the three distinct but interconnected cell polarities of border cells. Specifically, the Crb complex, together with the Par complex and the endocytic recycling machinery, ensures the strict distribution of two distinct populations of aPKC at the inside apical junction and near the outside lateral membrane. Interestingly, aPKC distributed near the outside lateral membrane interacts with Sif and promotes Rac-induced protrusions, whereas alteration of the aPKC distribution pattern changes the pattern of protrusion formation, leading to disruption of all three polarities. Therefore, we demonstrate that aPKC, spatially controlled by the Crb complex, is a key polarity molecule coordinating the generation of three distinct but interconnected cell polarities during collective migration.

Iatrogenic Arteriovenous Fistula Formation after Endovenous Laser Treatment Resulting in High-output Cardiac Failure: A Case Report and Review of the Literature.

Formation of a clinically significant iatrogenic arteriovenous fistula after endovenous laser treatment of the great saphenous vein is an extremely rare complication. Because of the infrequency of reported cases, there is no clear consensus on how to best manage this complication. We present a unique case of an iatrogenic high-output superficial femoral artery-common femoral vein fistula resulting in right heart failure and a distal deep vein thrombosis. Deployment of a covered arterial stent graft resulted in resolution of the arteriovenous fistula and high-output cardiac state. Clinically significant arteriovenous fistulas resulting from inadvertent vessel injury during endovenous laser treatment appear to be amenable to percutaneous endovascular interventions. During these challenging endovascular cases, intravascular ultrasonography can be used to help delineate the morphology of the fistula tract and obtain vessel measurements to ensure accurate endoprosthesis sizing and placement.

Federated Quantum Machine Learning.

Distributed training across several quantum computers could significantly improve the training time and if we could share the learned model, not the data, it could potentially improve the data privacy as the training would happen where the data is located. One of the potential schemes to achieve this property is the federated learning (FL), which consists of several clients or local nodes learning on their own data and a central node to aggregate the models collected from those local nodes. However, to the best of our knowledge, no work has been done in quantum machine learning (QML) in federation setting yet. In this work, we present the federated training on hybrid quantum-classical machine learning models although our framework could be generalized to pure quantum machine learning model. Specifically, we consider the quantum neural network (QNN) coupled with classical pre-trained convolutional model. Our distributed federated learning scheme demonstrated almost the same level of trained model accuracies and yet significantly faster distributed training. It demonstrates a promising future research direction for scaling and privacy aspects.

Utilization of Carbon Dioxide Angiography and Percutaneous Balloon Angioplasty for Treatment of Transplant Renal Artery Stenosis.

BACKGROUND: Transplant renal artery stenosis (TRAS) may lead to graft dysfunction and failure. Progressive deterioration of renal allograft function may be exacerbated by contrast-induced nephrotoxicity during iodine contrast administration for renovascular imaging of allografts. We present our institutional experience of endovascular management for TRAS using CO2 digital subtraction angiography (CO2-DSA) and balloon angioplasty to manage failing renal transplants. METHODS: Four patients with renal allografts from March 2017-May 2018 were referred for graft dysfunction and pending renal transplant failure. Indications for referral included refractory hypertension, decreasing renal functioning, and elevated renovascular systolic velocities. RESULTS: Median age of the four patients was 41.5 years (22-60 years). There were two male and female patients. Chronic hypertension and type 2 diabetes mellitus were the most common comorbidities. An average total of 75 mL of CO2 was used, supplemented with 17.4 mL of iodinated contrast. All patients had improvements in renal function following intervention with a mean decrease in systolic and diastolic blood pressure of 25.8% and 21.4%, respectively. We also observed a mean decrease of BUN by 13.6% and creatinine by 37.4%. Additionally, eGFR increased by 37.7%. All allografts survived after surgery, and only one patient required repeat angioplasty for recurrence. CONCLUSIONS: CO2-DSA with balloon angioplasty can be successfully utilized to salvage deteriorating kidney allograft function in patients with TRAS.

Engineering Artificial MicroRNAs for Multiplex Gene Silencing and Simplified Transgenic Screen.

Artificial microRNA (amiRNA) technology offers reversible and flexible gene inactivation and complements genome-editing technologies. However, obtaining transgenic plants with maximal gene silencing remains a major technical challenge in current amiRNA applications. Here, we incorporated an empirically determined feature of effective amiRNAs to the amiRNA design and in silico generated a database containing 533,429 gene-specific amiRNAs for silencing 27,136 genes in Arabidopsis (Arabidopsis thaliana), with a genome coverage of 98.87%. In both single-gene and multiple-gene silencing, we observed an overall improvement in performance by amiRNAs designed using our strategy in Arabidopsis protoplasts and transgenic plants. In addition, the endogenous tRNA-processing system was used to generate multiple amiRNAs from tRNA-pre-amiRNA tandem repeats for multiplex gene silencing. An intronic amiRNA-producing fluorescent reporter was explored as a visual screening strategy for transgenic Arabidopsis and rice (Oryza sativa) plants with maximal whole-plant or cell type-specific gene silencing. These improvements enable the amiRNA technology to be a functional gene knockout tool for basic and applied plant research.

Locoregional Anesthesia Offers Improved Outcomes after Endovascular Repair of Ruptured Abdominal Aortic Aneurysms.

BACKGROUND: General anesthesia (GA) and locoregional anesthesia (LA) are two anesthetic options for endovascular repair of ruptured abdominal aortic aneurysms (REVAR). Studies on elective endovascular repair of nonruptured aneurysms have indicated that in select patients, LA may provide improved outcomes compared with GA. We aimed to examine the 30-day outcomes in patients undergoing REVAR using GA and LA in a contemporary nationwide cohort of patients presenting with ruptured abdominal aortic aneurysms. METHODS: Patients who underwent REVAR using GA and LA from January 2011 through December 2015, inclusively, were studied in the American College of Surgeons' National Surgical Quality Improvement Program (ACS NSQIP)-targeted EVAR database. Univariate and multivariate analyses were used to compare preoperative demographics, operation-specific variables, and 30-day postoperative outcomes between the two groups. RESULTS: Six-hundred ninety patients were identified to have undergone REVAR from 2011 to 2015, of which 12.5% (86) were performed under LA. For the entire cohort, the mean age was 74.3 years, and 80% were male. Mean aneurysm size was 7.6 cm and did not differ between the two anesthetic groups. Major comorbidities were similar between both groups, except a slightly higher rate of congestive heart failure in the LA group (7.0% vs. 2.5%, P = 0.02). Proximal or distal aneurysm extent also did not differ between the two groups. There was a significantly higher rate of bilateral percutaneous access in the LA group (59.3% vs. 25.2%, P < 0.01). REVAR under LA had shorter mean operative time (132 vs. 166 min, P < 0.01) and lower rate of concomitant lower extremity revascularization (2.3% vs. 10.6%, P < 0.01). There were no differences in need for perioperative transfusion or any other adjunctive procedures. Ultimately, 30-day mortality was significantly lower in the LA group (16.3% vs. 25.2%, P < 0.01). This difference was more pronounced in the subgroup of patients with hemodynamic instability (15.4% vs. 39.4%, P < 0.01). The LA group also demonstrated significantly shorter intensive care unit (ICU) length of stay (3.0 vs. 5.0 days, P = 0.01) and low rates of postoperative pneumonia (3.5% vs. 10.9%, P = 0.03). After adjustment for demographics, comorbid conditions, hypotensive status, and aneurysm characteristics, there was a two-fold higher mortality in patients undergoing REVAR using GA versus LA, with a four-fold increase in the hemodynamically unstable cohort. CONCLUSIONS: The ACS NSQIP-targeted EVAR database shows that LA is used in only 12.5% of patients undergoing REVAR in this nationwide cohort. This rate does not change when examining the subset of patients who are hemodynamically unstable. Other benefits include shorter ICU lengths of stay and lower rates of pneumonia. These data suggest that LA should be considered in patients undergoing REVAR, regardless of hemodynamic instability.

Decreased National Rate of below the Knee Amputation in Patients with Popliteal Artery Injury.

BACKGROUND: Popliteal arterial injury (PAI) is the second most common infrainguinal arterial injury after femoral artery injury with an incidence < 0.2%. A 2003 analysis of the National Trauma Data Bank (NTDB) reported a below the knee amputation (BKA) rate of 7.1% in patients with PAI as well as higher risk in those with an associated fracture or nerve injury. Given advances in vascular surgical techniques, improved multidisciplinary care, and expeditious diagnosis with computed tomography angiography, we hypothesized that the national rate of BKA in patients with PAI has decreased and sought to identify risk factors for BKA in patients with PAI. METHODS: A retrospective analysis of the NTDB was performed from 2007 to 2015. Patients ≥15 years of age with PAI were included and grouped by mechanism of injury (blunt versus penetrating). Interfacility transfers were excluded. The primary outcome of interest was BKA. Univariable and multivariable analyses were performed to identify predictors of BKA in patients with PAI. RESULTS: From 4,385,698 patients, 5,143 were identified with PAI (<0.2%) with most involved in a blunt mechanism (56.8%). The overall limb loss rate was 5.1% (decreased from 7.1% in 2003, P = 0.0037). After adjusting for covariates, a blunt mechanism (odds ratio [OR] = 3.53, confidence intervals [CI] = 2.49-5.01, P < 0.001) and open proximal tibia/fibula fracture or dislocation (OR = 2.71, CI = 2.08-3.54, P < 0.001) were independent risk factors for BKA in patients with PAI. A combined popliteal vein injury (PVI) did not increase the risk for BKA (P = 0.64). CONCLUSIONS: The national rate of limb loss in trauma patients with PAI has decreased from 7.1 to 5.1%. A blunt mechanism of injury as well as proximal open tibia/fibula fracture or dislocation continue to be the independent risk factors for BKA. Confirming a previous report, we found a combined PVI not to be associated with higher risk for BKA. Future prospective research to determine other possible contributing factors such as intraoperative hemodynamics and utilization of vascular shunt and fasciotomy appears warranted.

Perioperative risk factors for hospital readmission after elective endovascular aortic aneurysm repair.

BACKGROUND: Elective endovascular aneurysm repair (EVAR) is generally well tolerated. However, the incidence of hospital readmission after EVAR and the risk factors and reasons for it are not well studied. This study sought to determine the incidence, to characterize the indications, and to identify perioperative patient-centered risk factors for hospital readmission within 30 days after elective EVAR. METHODS: All patients who underwent EVAR electively in 2012 to 2013 were identified from the American College of Surgeons National Surgical Quality Improvement Program Targeted Vascular database (n = 3886). Preoperative demographics, operation-specific variables, and postoperative outcomes were compared between those who were readmitted within 30 days of the index operation and those who were not. Multivariate logistic regression was then used to determine independent predictors of hospital readmission. RESULTS: The unadjusted 30-day readmission rate after EVAR was 8.2%. Of all readmissions, 55% were for reasons related to the procedure. Median time to readmission was 12 days. Significant preoperative risk factors associated with readmission were female sex, preoperative steroid use, congestive heart failure, and dialysis dependence (P < .05). Multiple postoperative medical complications were independently predictive of readmission, including myocardial infarction and deep venous thrombosis (P < .05). Surgical complications that were independently predictive of readmission were surgical site infection (odds ratio, 10.24; 95% confidence interval, 5.31-19.75; P < .01) and need for unplanned reoperation (odds ratio, 17.50; 95% confidence interval, 10.43-29.37; P < .01). Readmitted patients ultimately had significantly higher rates of 30-day mortality (3.5% vs 0.3%; P < .01). CONCLUSIONS: Hospital readmissions remain a costly problem after vascular surgery and are associated with 30-day mortality after elective EVAR. Whereas female sex and certain irreversible medical comorbidities are nonmodifiable, focusing on medical optimization and identifying those perioperative variables that can affect the need for post-EVAR interventions will be an important step in decreasing hospital readmission.

Transcriptome analyses reveal SR45 to be a neutral splicing regulator and a suppressor of innate immunity in Arabidopsis thaliana.

BACKGROUND: Regulation of pre-mRNA splicing diversifies protein products and affects many biological processes. Arabidopsis thaliana Serine/Arginine-rich 45 (SR45), regulates pre-mRNA splicing by interacting with other regulatory proteins and spliceosomal subunits. Although SR45 has orthologs in diverse eukaryotes, including human RNPS1, the sr45-1 null mutant is viable. Narrow flower petals and reduced seed formation suggest that SR45 regulates genes involved in diverse processes, including reproduction. To understand how SR45 is involved in the regulation of reproductive processes, we studied mRNA from the wild-type and sr45-1 inflorescences using RNA-seq, and identified SR45-bound RNAs by immunoprecipitation. RESULTS: Using a variety of bioinformatics tools, we identified a total of 358 SR45 differentially regulated (SDR) genes, 542 SR45-dependent alternative splicing (SAS) events, and 1812 SR45-associated RNAs (SARs). There is little overlap between SDR genes and SAS genes, and neither set of genes is enriched for flower or seed development. However, transcripts from reproductive process genes are significantly overrepresented in SARs. In exploring the fate of SARs, we found that a total of 81 SARs are subject to alternative splicing, while 14 of them are known Nonsense-Mediated Decay (NMD) targets. Motifs related to GGNGG are enriched both in SARs and near different types of SAS events, suggesting that SR45 recognizes this motif directly. Genes involved in plant defense are significantly over-represented among genes whose expression is suppressed by SR45, and sr45-1 plants do indeed show enhanced immunity. CONCLUSION: We find that SR45 is a suppressor of innate immunity. We find that a single motif (GGNGG) is highly enriched in both RNAs bound by SR45 and in sequences near SR45- dependent alternative splicing events in inflorescence tissue. We find that the alternative splicing events regulated by SR45 are enriched for this motif whether the effect of SR45 is activation or repression of the particular event. Thus, our data suggests that SR45 acts to control splice site choice in a way that defies simple categorization as an activator or repressor of splicing.

Comparison of percutaneous versus open femoral cutdown access for endovascular repair of ruptured abdominal aortic aneurysms.

OBJECTIVE: Ruptured endovascular aortic aneurysm repair (REVAR) is being increasingly used to treat ruptured abdominal aortic aneurysms (rAAAs). However, the comparison between totally percutaneous (pREVAR) vs femoral cutdown (cREVAR) access for REVAR has not been studied. We used a national surgical database to evaluate the 30-day outcomes in patients undergoing pREVAR vs cREVAR. METHODS: Patients who underwent EVAR for rAAA between 2011 and 2014, inclusively, were studied in the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) targeted vascular database. Univariate and multivariate analyses were used to compare preoperative demographics, operation-specific variables, and postoperative outcomes between those who had pREVAR and cREVAR. RESULTS: We identified 502 patients who underwent REVAR, of which 129 had pREVAR (25.7%) and 373 cREVAR (74.3%). Between 2011 and 2014, the use of totally percutaneous access for repair increased from 14% to 32%. Of all patients undergoing REVAR, 24% had bilateral percutaneous access, 2% had attempted percutaneous access converted to cutdown, 64% had bilateral femoral cutdowns, and 10% had single femoral cutdown. Univariate analysis showed there were no significant differences in age, gender, body mass index, AAA size, or other high-risk physiologic comorbidities between the two groups. There was also no difference in rates of preoperative hemodynamic instability (48.1% vs 45.0%; P = .55) or need for perioperative transfusion (67.4% vs 67.8%; P = .94). There was a higher incidence of use of regional anesthesia for pREVAR compared with cREVAR (20.9% vs 7.8%; P < .01). The incidence of postoperative wound complications was similar between both groups (4.8% vs 5.4%; P = .79), whereas hospital length of stay was shorter in the pREVAR group (mean difference, 1.3 days). Overall 30-day mortality was higher in the pREVAR group (28.7% vs 20.1%; P = .04), and operative time was longer (mean difference, 6.3 minutes). However, when pREVARs done in 2011 to 2012 were compared with those done in 2013 to 2014, 30-day mortality decreased from 38.2% to 25.3% and operative time decreased by 25 minutes (188 to 163 minutes). Multivariate analysis showed there were no significant differences in mortality, wound complications, hospital length of stay, or operative time between pREVAR and cREVAR. CONCLUSIONS: The ACS NSQIP targeted vascular database shows that there has been increased adoption of pREVAR in recent years, with improved mortality and operative time over the 4-year study period. At this point, pREVAR has not yet been shown to be superior to cREVAR for rAAA, but these outcome improvements are encouraging and likely attributable to increased operator experience.

Outcomes of open and endovascular lower extremity revascularization in active smokers with advanced peripheral arterial disease.

OBJECTIVE: Concern over perioperative and long-term durability of lower extremity revascularizations among active smokers is a frequent deterrent for vascular surgeons to perform elective lower extremity revascularization. In this study, we examined perioperative outcomes of lower extremity endovascular (LEE) revascularization and open lower extremity bypass (LEB) in active smokers with intermittent claudication (IC) and critical limb ischemia (CLI). METHODS: Active smokers undergoing LEE or LEB from 2011 to 2014 were identified in the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) targeted vascular data set. Patient demographics, comorbidities, anatomic features, and perioperative outcomes were compared between LEE and LEB procedures. Subgroup analysis was performed for patients undergoing revascularization for IC and CLI independently. RESULTS: From 2011 to 2014, 4706 lower extremity revascularizations were performed in active smokers (37% of all revascularizations). In this group, 1497 were LEE (55.6% for CLI, 13.4% for below-knee pathology) and 3209 were LEB (68.9% CLI, 34.7% below-knee). Patients undergoing LEE had higher rates of female gender, hypertension, end-stage renal disease, and diabetes (all P ≤ .02). LEE patients also had a higher frequency of prior percutaneous interventions (22.7% vs 17.2%; P < .01) and preoperative antiplatelet therapy (82.3% vs 78.7%; P = .02). On risk-adjusted multivariate analysis, LEE patients had higher need for reintervention on the treated arterial segment than LEB (5.1% vs 5.2%; odds ratio [OR], 1.52; 95% confidence interval [CI], 1.08-2.13; P = .02) but had lower wound complications (3.1% vs 13.2%; OR, 0.32; 95% CI, 0.23-0.45; P < .01) and no statistically significant difference in 30-day mortality (0.6% vs 0.9%), myocardial infarction or stroke (1.1% vs 2.6%), or major amputation (3.2% vs 2.1%) in the overall cohort of active smokers. In the IC subgroup, myocardial infarction or stroke was significantly higher in the LEB group (1.9% vs 0.6%; OR, 1.83; 95% CI, 1.17-1.97; P = .03), although no difference was found in the CLI subgroup (2.8% vs 1.4%; OR, 0.75; 95% CI, 0.37-1.52; P = .42,). Also in IC group, there was a trend for lower major amputation rates ≤30 days in the LEE group, whereas in the CLI group, LEE had a trend toward higher risk of early amputation compared with LEB. CONCLUSIONS: In active smokers, LEB for IC and CLI requires fewer reinterventions but is associated with a higher rate of postoperative wound complications compared with LEE revascularization. However, the risk for limb amputation is higher in actively smoking patients when treated by LEE compared with LEB for CLI. Importantly, cardiovascular complications are significantly higher in actively smoking patients with IC undergoing LEB compared with LEE. This additional cardiovascular risk should be carefully weighed when proposing LEB for actively smoking patients with nonlimb-threatening IC.

Endovascular Management of Concomitant Thoracic and Abdominal Aortic Ruptures Resulting from Brucellosis Aortitis.

BACKGROUND: Acute aortic symptomatology is an unusual manifestation of Brucella melitensis infection. We present a rare case of acute multifocal thoracic and abdominal aortic ruptures arising from Brucellosis aortitis managed exclusively with endovascular surgery. METHODS: A 71-year-old Hispanic male with a history of atrial fibrillation and prior stroke on chronic anticoagulation presented with shortness of breath and malaise. In addition, he had been treated approximately 1 year previously in Mexico for B. melitensis bacteremia after eating fresh unpasteurized cheese. Computed tomography (CT) angiography demonstrated an acute rupture of the descending thoracic aorta just proximal to the celiac trunk and synchronous rupture at the abdominal aortic bifurctation. RESULTS: The patient was taken emergently to the hybrid operating room, where synchronous supraceliac thoracic aorta and abdominal aortoiliac stent grafts were deployed under local anesthesia. Completion angiography demonstrated total exclusion of the thoracic and abdominal extravasation with no evidence of endoleak. Twenty hours postoperatively, the patient became acutely obtunded and hypotensive. Repeat CT angiography demonstrated contrast extravasation at the level of the excluded aortic bifurcation. Emergent angiography confirmed a type II endoleak with free extraluminal rupture. Multiple coils were placed at the level of the aortic bifurcation between the left limb of the stent graft and the aortic wall to tamponade the endoleak. No further extravasation was noted on final aortography. Postoperatively, blood cultures confirmed the diagnosis of B. melitensis. The patient was treated with systemic doxycycline, gentamicin, and rifampin. Resolution of the acute event occurred without additional sequelae and he was discharged from the hospital to a rehabilitation facility. CONCLUSIONS: Concomitant multifocal aortic ruptures arising from Brucellosis aortic infection is a very rare event. In this case, the patient was successfully treated with thoracic and abdominal endovascular stent-graft exclusion, coiling, and long-term targeted antibiotics.

Physiologic Cryoamputation in Managing Critically Ill Patients with Septic, Advanced Acute Limb Ischemia.

BACKGROUND: Certain critically ill patients with advanced acute limb ischemia with a nonviable extremity may be unsuitable for transport to the operating room to undergo definitive amputation. In these unstable patients, rapid regional cryotherapy allows for prompt infectious source control and correction of hemodynamic and metabolic abnormalities, thereby lessening the risk associated with definitive surgical amputation. We describe our refined technique for lower extremity physiologic cryoamputation and review our institutional experience. METHODS: After adequate analgesia is administered to the patient, a heating pad is secured circumferentially at the proximal amputation margin and the affected extremity is placed in a customized Styrofoam cooler. A circumferential seal is secured at the proximal chill zone without use of a tourniquet and dry ice is placed into the cooler to surround the entire affected leg. Delayed definitive lower extremity amputation is later performed when hemodynamic and metabolic derangements are corrected. RESULTS: We reviewed 5 patients who underwent lower extremity cryoamputation with this technique identified at our institution between 2005 and 2015. Age ranged from 31 to 79 years old. All presented with severe foot infection and septic shock requiring vasopressor support. All 5 patients stabilized hemodynamically following the initial cryoamputation and later underwent definitive lower extremity amputation, with a median time of 3 days following initial cryoamputation. CONCLUSIONS: Lower extremity physiologic cryoamputation is an effective, immediate bedside procedure that can provide local source control and the opportunity for correction of metabolic derangements in initially unstable patients to lessen the risk for definitive major lower extremity amputation. Refinement of the cryoamputation technique, as described in this report, allows for a predictable and reproducible physiologic amputation.

Influence of gender and use of regional anesthesia on carotid endarterectomy outcomes.

OBJECTIVE: Carotid endarterectomy (CEA) is the most commonly performed surgical procedure to reduce the risk of stroke. The operation may be performed under general anesthesia (GA) or regional anesthesia (RA). We used a national database to determine how postoperative outcomes were influenced by gender and type of anesthesia used. METHODS: All patients who underwent CEA between 2005 and 2011 were identified from the American College of Surgeons National Surgical Quality Improvement Program database (N = 41,442). Incidence of stroke and myocardial infarction (MI) within 30 days as well as other postoperative complications, operative time, and hospital length of stay were examined in groups separated by gender and anesthesia type. Multivariable logistic regression with effect modification was used to determine significant risk-adjusted differences between genders and type of anesthesia to assess outcomes after CEA. RESULTS: The male-to-female ratio among CEA cases performed was approximately 3:2. Most cases were performed under GA (85% male patients, 86% female patients). Adjusted multivariable analysis showed no statistical difference in rates of MI and stroke based on gender or type of anesthesia used. There were, however, higher 30-day postoperative local complications and MI (both P < .05) in those who had GA vs RA regardless of gender before adjustment. Total operative time was decreased (mean difference, -8.15 minutes; 95% confidence interval, -10.09 to -6.21; P < .001) and length of stay was increased (mean difference, 0.34 day; 95% confidence interval, 0.14-0.54; P < .02) in women, with statistical significance, whether RA or GA was used. CONCLUSIONS: On adjusted multivariate analysis, there is no statistically significant difference in postoperative incidence of MI or stroke between men and women undergoing CEA. Use of RA vs GA did not affect this finding. Furthermore, there was no correlation between gender and the type of anesthesia chosen. Women, however, experienced decreased operative times and increased length of stay regardless of anesthesia type.

Risk factors and outcomes of postoperative ischemic colitis in contemporary open and endovascular abdominal aortic aneurysm repair.

OBJECTIVE: Postoperative ischemic colitis (IC) can be a serious complication following infrarenal abdominal aortic aneurysm (AAA) repair. We sought to identify risk factors and outcomes in patients developing IC after open AAA repair and endovascular aneurysm repair (EVAR). METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used to examine clinical data of patients undergoing AAA repair from 2011 to 2012 who developed postoperative IC. Multivariate regression analysis was performed to identify risk factors and outcomes. RESULTS: We evaluated a cohort of 3486 patients who underwent AAA repair (11.6% open repair and 88.4% EVAR). The incidence of postoperative IC was 2.2% (5.2% for open repair and 1.8% for EVAR). Surgical treatment was needed in 49.3% of patients who developed IC. The mortality of patients with IC was higher than that of patients without IC (adjusted odds ratio [AOR], 4.23; 95% confidence interval [CI], 2.26-7.92; P < .01). The need for surgical treatment (AOR, 7.77; 95% CI, 2.08-28.98; P < .01) and age (AOR, 1.11; 95% CI, 1.01-1.22; P = .01) were mortality predictors of IC patients. Predictive factors of IC included need for intraoperative or postoperative transfusion (AOR, 6; 95% CI, 3.08-11.72; P < .01), rupture of the aneurysm before surgery (AOR, 4.07; 95% CI, 1.78-9.31; P < .01), renal failure requiring dialysis (AOR, 3.86; 95% CI, 1.18-12.62; P = .02), proximal extension of the aneurysm (AOR, 2.19; 95% CI, 1.04-4.59; P = .03), diabetes (AOR, 1.87; 95% CI, 1.01-3.46; P = .04), and female gender (AOR, 1.75; 95% CI, 1.01-3.02; P = .04). Although open AAA repair had three times higher rate of postoperative IC compared with endovascular repair, in multivariate analysis we did not find any statistically significant difference between open repair and EVAR in the development of IC (5.2% vs 1.8%; AOR, 1.25; 95% CI, 0.70-2.25; P = .43). CONCLUSIONS: Postoperative IC has a rate of 2.2% after AAA repair. However, it is associated with 38.7% mortality rate. Rupture of the aneurysm before surgery, need for transfusion, proximal extension of the aneurysm, renal failure requiring dialysis, diabetes, and female gender were significant predictors of postoperative IC. AAA patients who develop IC have four times higher mortality compared with those without IC. Surgical treatment is needed in nearly 50% of IC patients and is a predictor of higher mortality.