Transcarotid arterial revascularization is feasible and safe with concomitant inferior vena cava occlusion.

Transcarotid artery revascularization (TCAR) has risen as a promising minimally invasive intervention for high-risk patients with favorable anatomy. TCAR's noninferiority to carotid endarterectomy regarding stroke is reliant on its flow reversal technology and lack of aortic arch manipulation. We present the case of a 79-year-old man with a chronically occluded inferior vena cava who safely underwent staged bilateral TCAR for bilateral high-grade carotid artery stenosis. Although chronic inferior vena cava occlusion alters flow mechanics, we suspect that any pressure gradient facilitating retrograde flow from the carotid artery to the femoral vein provides neuroprotective benefits.

Preoperative risk score for mortality within 3 years of visceral segment fenestrated endovascular aortic repair.

OBJECTIVE: The purpose of this study was to create a risk score for the event of mortality within 3 years of complex fenestrated visceral segment endovascular aortic repair utilizing variables existing at the time of preoperative presentation. METHODS: After exclusions, 1916 patients were identified in the Vascular Quality Initiative who were included in the analysis. The first step in development of the risk score was univariable analysis for the primary outcome of mortality within 3 years of surgery. χ2 analysis was performed for categorical variables, and comparison of means with independent Student t-test was performed for ordinal variables. Variables that achieved a univariable P value less than 0.1 were then placed into Cox regression multivariable time dependent analysis for the development of mortality within 3 years. Variables that achieved a multivariable significance of less than 0.1 were utilized for the risk score, with point weighting based on the beta-coefficient. Variables with a beta coefficient of 0.25 to 0.49 were assigned 1 point, 0.5 to 0.74 2 points, 0.75 to 0.99 3 points, and 1.0 to 1.25 4 points. A cumulative score for each patient was then summed, the percentage of patients at each score experiencing mortality within 3 weeks was then calculated, and a comparison of score outcomes was conducted with binary logistic regression. Area under the curve analysis was performed. RESULTS: The primary outcome of mortality within 3 years of surgery occurred in 12.8% of patients (245/1916). The mean age for the study population was 73.35 years (standard deviation [SD], 8.26 years). The mean maximal abdominal aortic aneurysm (AAA) diameter was 60.43 mm (SD, 10.52 mm). The mean number of visceral vessels stented was 3.3 (SD, 0.76). Variables present at the time of surgery that were included in the risk score were: hemodialysis (3 points); age >87, chronic obstructive pulmonary disease, hypertension, AAA diameter >77 mm (all 2 points); and body mass index <20 kg/m2, female sex, congestive heart failure, active smoking, chronic renal insufficiency, age 80 to 87 years, and AAA diameter 67 to 77 mm (all 1 point). BMI >30 kg/m2 (mean, 34.46 kg/m2) and age <67 years were protective (-1 point). Testing the model resulted in an area under the curve of 0.706. Hosmer and Lemeshow goodness of fit test for logistic regression utilizing the 15 different risk score total groups revealed a model predictive accuracy of 87.3%. Significant escalations in 3-year mortality were noted to occur at scores of 6 and greater. Mean AAA diameter was significantly larger for patients who had higher risk scores (P < .001). CONCLUSIONS: A novel risk score for mortality within 3 years of fenestrated visceral segment aortic endograft has been developed that has excellent accuracy in predicting which patients will survive and derive the strongest benefit from intervention. This facilitates risk-benefit analysis and counseling of patients and families with realistic long-term expectations. This potentially enhances patient-centered decision-making.

Carotid Endarterectomy With Simultaneous Proximal Common Carotid Endovascular Intervention is Beneficial for Symptomatic Stenosis and Likely Confers No Advantage for Asymptomatic Lesions.

INTRODUCTION: Carotid bifurcation stenosis may co-exist simultaneously with more proximal common carotid artery (CCA) atherosclerotic plaquing, primarily at the vessel origin in the aortic arch. This scenario is relatively infrequent and its' management does not have quality randomized data to support medical vs surgical treatment. It is logical to treat any high grade common carotid lesions proximal to a carotid bifurcation endarterectomy (CEA) site both to prevent perioperative emboli or thrombosis as well as future embolization. Prior long-term investigations of the combined treatment paradigm have been low volume analysis. Further, prior studies focus on perioperative outcomes with respect to stroke prevention. The only prior VQI study investigating mid-term outcomes following simultaneous CEA with proximal CCA endovascular therapy provided data on less than 10 patients beyond 1.5 years. The long-term follow-up (LFTU) component initiative within VQI has been emphasized in recent years, now allowing for much more robust LTFU analysis. METHODS: Four cohorts were created for perioperative outcome analysis and Kaplan Meier freedom from event analysis: CEA in isolation for asymptomatic disease; CEA in isolation for symptomatic patients; CEA with proximal CCA endovascular intervention for asymptomatic; and, CEA with proximal CCA intervention for symptomatic patients. Binary logistic multivariable regression was performed for perioperative neurological event and 90-day mortality risk determination and Cox multivariable regression analysis was performed for long term freedom from cumulative ischemic neurological event and long-term mortality analysis. Symptomatology and type of surgery (CEA with or without CCA intervention) were individual variables in the multivariable analysis. Neurological ischemic event in this study encompassed transient ischemic attack (TIA) and stroke combined. RESULTS: We noted a statistically significant (P < .001) escalation in rates of perioperative neurological event, myocardial infarction (MI), carotid re-exploration, 90 day mortality and combined neurological event and 90 day mortality moving from: A) asymptomatic CEA in isolation to B) symptomatic CEA in isolation to C) asymptomatic CEA combined with proximal CCA intervention to D) symptomatic CEA in combination with proximal CCA intervention. The positivity rate for the combined outcome of perioperative ischemic neurological event and 90 day mortality was 2.2% amongst asymptomatic CEA in isolation, 4.1% amongst symptomatic CEA in isolation, 4.4% amongst asymptomatic CEA in combination with proximal CCA intervention; and 8.8% in patients with symptomatic lesions undergoing combined CEA with proximal CCA intervention. On multivariable analysis patients undergoing CEA with proximal CCA endovascular intervention experienced greater risk for perioperative neurological ischemic event (aOR 2.03, 1.43-2.90, P < .001), combined perioperative neurological ischemic event and 90 day mortality (aOR 2.13, 1.62-2.80, P < .001), long term mortality (HR 1.62, 1.12-2.29, P < .001), and cumulative neurological ischemic event in long term follow up (HR 1.62, 1.12-2.29, P = .007). Amongst 4395 cumulative ischemic neurological events in all study patients, 34% were TIA. CONCLUSIONS: Carotid bifurcation endarterectomy in combination with proximal endovascular common carotid artery intervention caries an over two fold higher perioperative risk of neurologic ischemic event and 90 day mortality relative to CEA in isolation for asymptomatic and symptomatic cohorts respectively. After surgery, freedom from cerebral ischemia and mortality for patients undergoing dual intervention is closely aligned with patients undergoing CEA in isolation. Despite high adverse perioperative event rates for the combined CEA and CCA treatment, there is likely long term stroke reduction and mortality benefit to this approach in symptomatic patients based on the event free rates seen herein after initial hospital discharge. The benefit of treating asymptomatic tandem ICA and CCA lesions remains vague but the 4.4% perioperative neurologic event and death rate suggests that these patients would be better managed with medical therapy.

Carotid Endarterectomy for Asymptomatic Stenosis Based on Duplex Ultrasound Alone Achieves Equivalent Perioperative and Long-Term Outcomes Relative to Advanced Imaging Based Endarterectomy.

BACKGROUND: The purpose of this study is to compare both perioperative as well as long-term outcomes of patients undergoing carotid endarterectomy (CEA) for asymptomatic carotid bifurcation stenosis based on duplex ultrasound in isolation relative to a combination of duplex and more advanced imaging. METHODS: All CEA in the VQI between January 2003 and May 2022 were queried. We identified 171,816 CEAs in the database. Exclusions were symptomatic carotid lesion (57,742), lack of imaging documentation (908), lack of advanced imaging status (1,816), simultaneous additional arterial intervention in the carotid, coronary, or peripheral arterial system (n = 4,118), and anatomic high-risk status for CEA (n = 4,071). Included patients were then placed into 1 of 2 cohorts: patients undergoing CEA based on duplex imaging alone (n = 33,437) and those undergoing CEA based on advanced imaging (CTA, MRA, or invasive angiography) with or without duplex (n = 69,715). We performed multivariable analysis for the following outcomes utilizing CEA based on duplex in isolation as 1 of the variables: perioperative neurological ischemic event utilizing binary logistic regression; combined 90-day mortality and neurological ischemic event utilizing binary logistic regression; neurological event in long-term follow-up with date of surgery serving as time zero; time dependent Cox regression analysis; mortality in long-term follow-up utilizing time-dependent Cox regression. RESULTS: Carotid endarterectomy based on duplex alone and CEA based on advanced imaging had essentially equivalent rates of 90-day mortality (0.9% vs. 1.0%, P = 0.108); combined perioperative neurological event and 90-day mortality (2.0% vs. 2.2%, P = 0.042); and, return to the operating room (1.6% vs. 1.7%, P = 0.154). On multivariable analysis CEA based on advanced imaging was noted to have a slightly higher absolute rate of perioperative neurological event without achieving multivariable significance (1.3% vs. 1.2%, adjusted odds ratio 1.11 (0.98-1.25), P = 0.092. CEA based on advanced imaging had a higher rate of neurological event after index hospital admission relative to duplex in isolation (hazard ratio (HR) 1.44 (1.31-1.60), P < 0.001). However, the absolute percentage difference was just 0.5% (1.6% vs. 2.1%). CEA based on duplex alone was associated with a slightly increased risk of mortality in LTFU (HR 1.16 (1.11-1.21), P < 0.001). At 5 years the absolute risk of mortality was less than 1% different between the cohorts. CONCLUSIONS: Performing CEA for asymptomatic bifurcation stenosis based on duplex ultrasound alone is a safe practice which achieves clinically equivalent perioperative and long-term freedom from cerebral ischemia and mortality relative to CEA based on advanced imaging. This has potential implications for health care cost saving as well as avoidance of radiation and iodinated contrast.

Investigation of center-specific saphenous vein utilization rates in femoral popliteal artery bypass and associated impact of conduit on outcomes.

OBJECTIVE: The purpose of this study is to investigate variation in great saphenous vein (GSV) use among the various centers participating in the Vascular Quality Initiative infrainguinal bypass modules. Further, differences in outcomes in femoral-popliteal artery bypass with single segment GSV conduit vs prosthetic conduit will be documented. Center GSV use rate impact on outcomes will be investigated. METHODS: Primary exclusions were patients undergoing redo bypass, urgent or emergent bypass, and those in whom prosthetic graft was used while having undergone prior coronary artery bypass grafting. The distribution of GSV use across the 260 centers participating in Vascular Quality Initiative infrainguinal bypass module was placed into histogram and variance in mean GSV use evaluated with analysis of variance analysis. Centers that used GSV in >50% of bypasses were categorized as high use centers and centers that used the GSV in <30% of cases were categorized as low use centers. Baseline differences in patient characteristics and comorbidities in those undergoing bypass with GSV vs prosthetic conduit were analyzed with χ2 testing and the Student t test, as were those undergoing treatment in high vs low use centers. Multivariable time-dependent Cox regression analyses were then performed for the primary outcomes of major amputation ipsilateral to the operative side and mortality in long-term follow-up. High vs low use center was a dichotomous variable in these regressions. Secondary outcomes of freedom from graft infection and freedom from loss of primary patency were performed with Kaplan-Meier analysis. RESULTS: Among centers with >50 patients meeting inclusion criteria for this study, GSV use ranged from 15% to 93% (analysis of variance P < .001). When considering all centers irrespective of number of patients, the range was 0% to 100%. On Kaplan-Meier analysis, GSV conduit use was associated with improved freedom from loss of primary or primary assisted patency, improved freedom from major amputation after index hospitalization, improved freedom from graft infection after the index hospitalization, and improved freedom from mortality in long-term follow-up (log-rank P < .001 for all four outcomes). Both low use center (hazard ratio, 1.35; P < .001) and prosthetic graft use (hazard ratio, 1.24; P < .001) achieved multivariable significance as risks for mortality in long-term follow-up. Other variables with a multivariable mortality association are presented in the manuscript. Low use center and prosthetic bypass were significant univariable but not multivariable risks for major amputation after index hospitalization. CONCLUSIONS: There is remarkably wide variation in GSV use for femoral popliteal artery bypass among various medical centers. GSV use is associated with enhanced long-term survival as well as freedom from loss of bypass patency and graft infection. The data herein indicate institutional patterns of prosthetic conduit choice, which has the potential to be altered to enhance outcomes.

Objective assessment of physician work in infrainguinal arterial bypass surgery.

OBJECTIVE: The purpose of this study is obtain robust objective data from the Vascular Quality Initiative on physician work in infrainguinal artery bypass surgery. Operative time, patient comorbidities, anatomical complexity, consequences of adverse outcomes, and postoperative length of stay all factor into procedure relative value unit assignment and physician reimbursement. METHODS: Baseline demographics and comorbidities were identified among 74,920 infrainguinal bypass surgeries in Vascular Quality Initiative between 2003 and 2022. Investigation into areas of progressive complexity over time was conducted. Bypasses were divided into 10 cohorts based on inflow and target arteries and conduit type. Mean operative times, lengths of stay, major morbidity rates, and 90-day mortality rates were identified across the various bypasses. Comparison of relative value unit per minute service time during the acute inpatient hospital admission was performed between the most 4 common bypasses and 14 commonly performed highly invasive major surgeries across several subdisciplines. RESULTS: Patients undergoing infrainguinal arterial bypass have an advanced combination of medical complexities highlighted by diabetes mellitus in 40%, hypertension in 88%, body mass index >30 in 30%, coronary artery disease that has clinically manifested in 31%, renal insufficiency in 19%, chronic obstructive pulmonary disease in 27%, and prior lower extremity arterial intervention (endovascular and open combined) in >50%. The need for concomitant endarterectomy at the proximal anastomosis site of infrainguinal bypasses has increased over time (P < .001). The indication for bypass being limb-threatening ischemia as defined by ischemic rest pain, pedal tissue loss, or acute ischemia has also increased over time (P < .001), indicating more advanced extent of arterial occlusion in patients undergoing infrainguinal bypass. Finally, there has been a significant (P < .001) progression in the percentage of patients who have undergone a prior ipsilateral lower extremity endovascular intervention at the time of their bypass (increasing from 9.9% in 2003-2010 to 31.9% in the 2018-2022 eras). Among the 18 procedures investigated, the 4 most commonly performed infrainguinal bypasses were included in the analysis. These ranked 14th, 16th, 17th and 18th as the most poorly compensated per minute service time during the acute operative inpatient stay. CONCLUSIONS: Infrainguinal arterial bypass surgery has an objectively undervalued physician work relative value unit compared with other highly invasive major surgeries across several subdisciplines. There are elements of progressive complexity in infrainguinal bypass patients over the past 20 years among a patient cohort with a very high comorbidity rate, indicating escalating intensity for infrainguinal bypass.

Temporal Trends and Contemporary Regional Variation in Management of Patients Undergoing Carotid Endarterectomy.

INTRODUCTION: The purpose of this study is to investigate regional variation and temporal trends in seven quality metrics amongst CEA patients: discharge on antiplatelet after CEA; discharge on statin after CEA; protamine administration during CEA; patch placement at conventional CEA site; continued statin usage at the time of most recent follow-up; continued antiplatelet usage at the time of most recent follow-up; and smoking cessation at the time of long term follow up. METHODS: There are 19 de-identified regions within the VQI database in the United States. Patients were placed into one of three temporal eras based on the time of their CEA: 2003-2008; 2009-2015; and 2016-2022. We first investigated temporal trends across the seven quality metrics for all regions combined on a national basis. The percentage of patients in each time era with the presence/absence of each metric was identified. Chi-squared testing was performed to confirm statistical significance of the differences across eras. Next, analysis was performed within each region and within each time metric. We separated out the 2016-2022 patients within each region to serve as the status of each metric application in the most modern era. We then compared the frequency of metric non-adherence in each region utilizing Chi-squared testing. RESULTS: There was statistically significant improvement in achievement of all seven metrics between the initial 2003-2008 era and the modern 2016-2022 era. The most marked change in practice pattern was noted for lack of protamine usage at surgery (decreased from 48.7% to 25.9%), discharge home postoperatively without statin (decreased from 50.6% to 15.3%), and lack of statin usage confirmed at time of most recent long term follow up (decreased from 24% to 8.9%). Significant regional variation exists across all metrics (P < .01 for all). Lack of patch placement at the time of conventional endarterectomy ranges from 1.9% to 17.8% across regions in the modern era. Lack of protamine utilization ranges from 10.8% to 49.7%. Lack of antiplatelet and statin at the time of discharge varies from 5.5% to 8.2% and 4.8% to 14.4% respectively. Adherence to the various measures at the time of most recent follow up are more tightly aligned across regions with ranges of: 5.3% to 7.5% for lack of antiplatelet usage; 6.6% to 11.7% lack of statin utilization; and 13.3 to 15.4% for persistent smoking. CONCLUSIONS: Prior studies and societal initiatives on CEA documenting the beneficial effects of patch angioplasty, protamine use at surgery, smoking cessation, antiplatelet utilization and statin compliance have positively impacted adherence to these measures over time. In the modern 2016-2022 era the widest regional variation is noted in patch placement, protamine utilization and discharge medications allowing individual geographic areas to identify areas for potential improvement via internal VQI administrative feedback.

Investigation of Combined Carotid Endarterectomy and Coronary Artery Bypass Graft Surgery Outcomes and Adverse Event Risk Factors in the Vascular Quality Initiative.

OBJECTIVE: The purpose of this study was to investigate outcomes of simultaneous CEA and CABG utilizing the Vascular Quality Initiative (VQI). Additionally, we seek to investigate risks for both perioperative and long-term mortality and adverse neurological outcomes. METHODS: All carotid endarterectomies in the VQI between January 2003 and May 2022 were queried. We identified 171,816 CEA in the database. We extracted 2 cohorts from these CEA. The first group was patients who underwent simultaneous carotid endarterectomy (CEA) and coronary artery bypass (CABG) (N = 3137). The second group encompassed patients who underwent CABG or percutaneous coronary artery angioplasty/stent within 5 years of ultimately undergoing CEA (N = 27,387). We investigated the following outcomes in a multivariable fashion: 1. Risks for mortality in long term follow-up for both cohorts combined; 2. Risks for ischemic event in the cerebral hemisphere ipsilateral to the CEA site after index hospital admission in follow up for both cohorts combined. Tertiary outcomes are also investigated in the manuscript. RESULTS: On multivariable analysis, patients undergoing simultaneous combined CEA and CABG had equivalent long-term survival to patients who underwent coronary revascularization within 5 years of ultimately undergoing CEA. Five-year survival is noted to be 84.5% vs 86% with a Cox regression non-significant P-value (.203). Significant multivariable risks for reduced long term survival (P < .03 for all) included: advancing age (HR 2.48/year); smoking history (HR 1.26); Diabetes (HR 1.33); history of CHF (HR 1.66); history of COPD (HR 1.54); baseline renal insufficiency at the time of surgery (HR 1.30); anemia (HR1.64); lack of preoperative aspirin (HR 1.12); and lack of preoperative statin (HR 1.32); lack of patch placement at CEA site (HR 1.16); perioperative MI (HR 2.04); perioperative CHF (1.66); perioperative dysrhythmia (HR 1.36); cerebral reperfusion injury (HR 2.23); perioperative ischemic neurological event (HR 2.48); and lack of statin at discharge (HR 2.04). Amongst patients with documented neurological status in follow up, combined CEA and CABG had over 99% freedom from ischemic cerebral event ipsilateral to the CEA site after discharge. CONCLUSIONS: Combined CEA and CABG provides excellent long-term mortality prevention in patients with co-existing severe coronary and carotid atherosclerosis. Simultaneous CEA and CABG provides equivalent stroke prevention and long-term survival to both a cohort of patients undergoing coronary revascularization within 5 years of CEA and patients undergoing isolated CEA or CABG in the literature. The two most impactful modifiable risk factors towards long-term stroke and mortality prevention for patients undergoing simultaneous CEA-CABG are patch placement at CEA site and adherence to statin medication therapy.

The Impact of Perioperative Morbidities, Lack of Discharge Aspirin, and Lack of Discharge Statin on Long Term Survival Following EVAR.

OBJECTIVE: Adverse perioperative events and discharge medications both have the potential to impact survival following endovascular abdominal aortic aneurysm repair (EVAR). We hypothesize that variables such as blood loss, reoperation in the same hospital admission, and lack of discharge statin/aspirin have significant effect on long term survival following EVAR. Similarly, other perioperative morbidities, are hypothesized to affect long term mortality. Quantifying the mortality effect of perioperative events and treatment emphasizes to physicians the critical nature of preoperative optimization, case planning, operative execution and postoperative patient management. METHODS: All EVAR in the Vascular Quality Initiative between 2003 and 2021 were queried. Exclusions were: ruptured/symptomatic aneurysm; concomitant renal artery or supra-renal intervention at the time of EVAR; conversion to open aneurysm repair at the time of initial operation; and undocumented mortality status at the 5 year mark postoperatively. 18,710 patients met inclusion criteria. Multivariable Cox regression time dependent analysis was performed to investigate the strength of mortality association of the exposure variables. Standard demographic variables and pre-existing major co-morbidities were included in the regression analysis to account for disproportionate, deleterious co-variables amongst those experiencing the various morbidities. Kaplan-Meier survival analysis was performed to provide survival curves for the key variables. RESULTS: Mean follow up was 5.99 years and 5-year survival for included patients was 69.2%. Cox regression revealed increased long term mortality to be associated with the following perioperative events: reoperation during the index hospital admission (HR 1.21, P = .034), perioperative leg ischemia (HR 1.34, P = .014), perioperative acute renal insufficiency (HR 1.24, P = .013), perioperative myocardial infarction (HR 1.87, P < .001), perioperative intestinal ischemia (HR 2.13, P < .001), perioperative respiratory failure (HR 2.15, P < .001), lack of discharge aspirin (HR 1.26, P < .001), and lack of discharge statin (HR 1.26, P < .001). The following pre-existing co-morbidities correlated with increased long term mortality (P < .001 for all) : body mass index under 20 kg/m2, hypertension, diabetes, coronary artery disease, reported history congestive heart failure, chronic obstructive pulmonary disease, peripheral artery disease, advancing age, baseline renal insufficiency and left ventricular ejection fraction less than 50%. Females were more likely to have EBL >300 mL, reoperation, perioperative MI, limb ischemia and acute renal insufficiency than males (P < .01 for all). Female sex trended but was not associated with increased long term mortality risk (HR 1.06, 95% CI .995-1.14, P = .072). CONCLUSIONS: Survival after EVAR is improved with optimal operative planning to facilitate evading the need for reoperation and ensuring patients without contra-indication are discharged with aspirin and statin medications. Females and patients with pre-existing co-morbidity are at particularly higher risk for perioperative limb ischemia, renal insufficiency, intestinal ischemia and myocardial ischemia necessitating appropriate preparation and preventative measures.

Unusual presentation of colon cancer as rectal prolapse in middle-aged male.

Rectal prolapse is typically a benign idiopathic condition. Rarely, rectal prolapse can be due to or associated with colorectal carcinoma. Here we present a middle-aged gentleman with no previous medical or surgical history, who presented with rectal prolapse secondary to sigmoid adenocarcinoma.

Investigation of Renal Decline and New Onset Dialysis Following Endovascular Aneurysm Repair in the Vascular Quality Initiative.

INTRODUCTION: The purpose of this study is to identify variables significantly associated with renal function decline after elective endovascular infra-renal abdominal aortic aneurysm repair and to identify the rate and risks of subsequent progression to dialysis. Specifically, we investigate the long-term impact of supra-renal fixation, female gender, and physiologically stressful perioperative events on renal function following endovascular aneurysm repair (EVAR). METHODS: Review of all EVAR cases in the Vascular Quality Initiative between 2003 and 2021 was conducted to investigate variable associations with three primary outcomes: postoperative acute renal insufficiency (ARI); greater than 30% decline in glomerular filtration rate (GFR) in patients beyond 1 year of follow up; and new onset dialysis requirement at any point in follow up. Binary logistic regression analysis was performed for the events of acute renal insufficiency and new onset dialysis requirement. Cox proportional hazard regression was performed regarding long term GFR decline. RESULTS: Postoperative ARI occurred in 3.4% (1692/49 772) of patients. Significant (P < .05) association with postoperative ARI was noted for: age (OR 1.014/year, 95% CI 1.008-1.021); female gender (OR 1.44, 95% CI 1.27-1.67); hypertension (OR 1.22, 95% CI 1.04-1.44); chronic obstructive pulmonary disease (OR 1.34, 95% CI 1.20-1.50); anemia (OR 4.24, 95% CI 3.71-4.84); reoperation at index admission (OR 7.86, 95% CI 6.47-9.54); baseline renal insufficiency (OR 2.29, 95% CI 2.03-2.56); larger aneurysm diameter; increased blood loss; and higher volumes of intra-operative crystalloid. Risk factors (P < .05) correlating with a decline of 30% in GFR at any time beyond 1 year were: female gender (HR 1.43, 95% CI 1.24-1.65); body mass index (BMI) less than 20 (HR 1.34, 95% CI 1.03-1.74); hypertension (HR 1.38, 95% CI 1.15-1.64); diabetes (HR 1.34, 95% CI 1.17-1.53); COPD (HR 1.21, 95% CI 1.07-1.37); anemia (HR 1.92, 95% CI 1.52-2.42); baseline renal insufficiency (HR 1.31, 95% CI 1.15-1.49); absence of discharge ace-inhibitor (HR 1.27, 95% CI 1.13-1.42); long term re-intervention (HR 2.43, 95% CI 1.84-3.21) and larger AAA diameter. Patients who experienced long term GRF decline had a significantly higher long-term morality. New onset dialysis following EVAR occurred in .47% (234/49 772) of those meeting inclusion criteria. Higher rate (P < .05) of new onset dialysis was associated with age (OR 1.03/year, 95% CI 1.02-1.05); diabetes (OR 1.376, 95% CI 1.005-1.885); baseline renal insufficiency (OR 6.32, 95% CI4.59-8.72); Reoperation at index admission (OR 2.41, 95% CI 1.03-5.67); postoperative ARI (OR 23.29, 95% CI 16.99-31.91); absence of beta blocker (OR 1.67, 95% CI 1.12-2.49); long term graft encroachment on renal arteries (OR 4.91, 95% CI 1.49-16.14). CONCLUSIONS: New onset dialysis following EVAR is a rare event. Perioperative variables influencing renal function following EVAR include blood loss, arterial injury, and reoperation. Supra-renal fixation is not associated with postoperative acute renal insufficiency or new onset dialysis in long term follow up. Renal protective measures are recommended for patients with baseline renal insufficiency undergoing EVAR as acute renal insufficiency following EVAR portends a 20-fold increased risk of new onset dialysis in long term follow up.

A rare case of angioinvasive aspergillosis aortic graft infection causing peripheral thromboembolism.

Angioinvasive aspergillosis is a fungal infection that rarely involves vascular grafts. This case illustrates a patient with a history of aortic arch Dacron graft reconstruction presenting with acute bilateral lower extremity ischemia. The patient underwent emergent open thromboembolectomy. The intraluminal contents had an atypical appearance for thromboembolism, and histologic examination was consistent with aspergillosis. Cardiac computed tomography and transesophageal echocardiography showed an aortic arch graft vegetation. Aortic graft excision and reconstruction were performed for control of the fungal source. Investigation into the etiology of thromboembolism should include consideration for septic emboli in patients with indwelling vascular grafts. When suspected, graft excision should be considered for definitive management.

Modifiable risk factors for occurrence of ipsilateral ischemic events after carotid endarterectomy beyond perioperative period.

OBJECTIVE: The purpose of this study was to quantify the effects of several modifiable variables on the occurrence of stroke after the initial perioperative period for patients who had undergone carotid endarterectomy (CEA). METHODS: The primary outcome for the present study was the development of an ischemic stroke or transient ischemic attack (TIA) in the cerebral hemisphere ipsilateral to CEA after the initial hospitalization. All CEAs in the VQI between January 2003 and May 2022 were queried. We identified 171,816 CEAs in the database. The exclusion criteria for the study were the lack of follow-up data for >30 days, concomitant coronary artery bypass surgery, concomitant proximal or distal carotid intervention at CEA, other arterial interventions at CEA, and stroke or TIA during the initial hospital admission, leaving 126,290 patients for analysis. We used the χ2 test for statistical analysis of the outcome of ipsilateral ischemic stroke or TIA after the initial CEA hospital admission to determine the relevant variables. Age was evaluated as an ordinal variable using the Student t test. Variables with P ≤ .05 on univariable analysis were included in the multivariable Cox regression time-to-event analysis for the primary outcome. Kaplan-Meier curves were constructed of the most significant variables on Cox regression as a visual aid. RESULTS: The following variables achieved significance on Cox regression for an association with development of ipsilateral hemispheric ischemic events after the index CEA hospital admission: lack of patch placement at CEA site (hazard ratio [HR], 18.24; P < .0001), lack of antiplatelet therapy at long-term follow-up (LTFU; HR, 9.75; P < .0001), lack of statin therapy at LTFU (HR, 3.18; P < .001), lack of statin therapy at hospital discharge (HR, 1.25; P = .015), anticoagulation at LTFU (HR, 1.53; P < .001), development of >70% recurrent stenosis (HR, 2.15; P < .001), and shunt use at surgery (HR, 1.20; P = .007). Patients with patch placement at surgery and patients with confirmed antiplatelet therapy at LTFU had had 99.8% and 99.6% freedom from an ischemic event ipsilateral to the side of the CEA at LTFU, respectively. This finding is in contrast to the 5.7% and 4.7% positivity for ischemic events for those without patch placement at surgery and those not receiving antiplatelet therapy at LTFU, respectively (P < .0001 for both). CONCLUSIONS: Performance of patch angioplasty arterial closure was remarkably protective against ipsilateral cerebral ischemic events at LTFU after CEA. Discharging and maintaining patients with antiplatelet and statin medication after CEA significantly reduces the incidence of future ipsilateral ischemic events. Thus, a significant opportunity exists for enhanced outcomes with improved implementation of these measures.

The Effect of Smoking Status on Perioperative Morbidity and Mortality after Open and Endovascular Abdominal Aortic Aneurysm Repair.

BACKGROUND: This study quantifies the extent to which active tobacco smoking is deleterious toward outcomes following open and endovascular abdominal aortic aneurysm (AAA) repair. METHODS: Open and endovascular AAA repairs between January 2003 and June 2020 in the Vascular Quality Initiative were queried. Rupture, symptomatic status, and lack of 90 day follow-up were exclusions. Patients were then placed into 1 of 6 groups: open AAA with active smoking (n = 3,788), open AAA with prior smoking (n = 4,614), open AAA never smokers (817), endovascular AAA active smokers (n = 14,173), endovascular AAA former smokers (n = 25,831), and endovascular AAA never smokers (n = 6,064). Comparison of baseline characteristics, comorbidities, and adverse outcomes across each of the 6 cohorts was performed with open AAA in active smokers serving as the reference. Subanalysis investigating open AAA repair in active smokers relative to open AAA in patients confirmed in Vascular Quality Initiative to have quit smoking between 30 and 90 days before surgery was performed. Smoking cessation for a minimum of 30 days before surgery was required to fall into the former smoker category. RESULTS: In comparing open AAA in active smokers to open AAA in former and never smokers, the active smokers experienced significantly higher rates of pneumonia (P < 0.001). Combined additive morbidity and mortality was highest (54%) in active smokers (P < 0.001) relative to all cohorts other than open AAA former smokers (P = 0.21). Smoking status did not impact morbidity or mortality incidence across individuals undergoing endovascular aneurysm repair. Binary logistic regression for all AAA patients (open and endovascular combined) revealed those with any history of smoking to be more likely to experience 90 day mortality (adjusted odds ratio [OR] 2.5 [2.2-2.9], P < 0.001) relative to never smokers. Active smokers were similarly more likely to experience 90 day mortality than prior/never smokers combined (OR 1.23 [1.07-1.38], P < 0.001). Mortality within 90 days was significantly more likely (P < 0.001) with aging, female gender, larger aneurysms, preoperative history of congestive heart failure, chronic obstructive pulmonary disease, chronic renal insufficiency, peripheral artery disease, and body mass index less than 20 and more than 35 mg/kg2. Diabetes and coronary artery disease were also associated with 90 day mortality (P = 0.045 and 0.049, respectively). Quitting smoking between 30 and 90 days before open repair reduced combined additive morbidity and mortality relative to active smokers (OR 1.34, P = 0.038). CONCLUSIONS: Smoking cessation 30 days before open AAA repair reduces perioperative morbidity and mortality. Smoking status does not impact morbidity and mortality in patients undergoing endovascular AAA repair. When combining all patients (open and endovascular), higher rates of 90 day mortality are associated with any history of smoking, aging, female gender, and advanced pre-existing comorbidities on a multivariable analysis.

Variation in Hospital Cost and 1-Year Episodes of Care after Diaphragmatic Hernia Repair.

BACKGROUND: Diaphragmatic hernia repair is a common operation performed at all types of hospitals. The variation in costs and repeat episodes of care after this operation is not known. STUDY DESIGN: The Healthcare Cost and Utilization Project State Inpatient and State Ambulatory Surgery and Services Databases for Florida were queried to identify patients undergoing diaphragmatic hernia repair between 2011 and 2018 and the associated inpatient and outpatient encounters within 12 months postoperatively. Hospitals were ranked by cost and grouped into quintiles. All costs and charges were reliability and case-mix adjusted with the use of hierarchical multivariable regression. RESULTS: In total, 8,848 patients underwent diaphragmatic hernia operations at 158 hospitals. The most expensive hospital quintile had lower surgical volume, location in rural settings, and fewer than 100 beds. There was a wide variation in costs after diaphragmatic hernia repair. On unadjusted comparison, index costs were $23,041 more expensive in hospitals in the highest quintile than in the lowest quintile. Cost differences were persistent even after case-mix and reliability adjustment. The variation in adjusted aggregate charges for associated outpatient and inpatient encounters in the first year after the index operation was considerably lower than that of the index hospitalization. CONCLUSION: There is nearly a 2-fold variation in the cost of a diaphragmatic hernia repair across hospitals. Most of the variation occurs during the index surgical encounter and not for repeat encounters during the first postoperative year. As bundled payment models mature, hospitals and payers will need to target this variation to ensure cost-efficiency.

Chronic Kidney Disease as Risk Factor for Enlarged Perivascular Spaces in Patients With Stroke and Relation to Racial Group.

BACKGROUND AND PURPOSE: Enlarged perivascular spaces (EPVS) are considered subclinical markers of small vessel disease, associated with increased risk of stroke and dementia. Increasing evidence links chronic kidney disease (CKD) to small vessel disease. We explored the relationship between CKD and EPVS burden and the influence of racial group in this relation. METHODS: Consecutive patients with stroke who underwent brain magnetic resonance imaging were included (n=894). Racial group was categorized as White, Black, or other (other racial groups). CKD was defined by glomerular filtration rate <60 mL/minute per 1.73 m2 for >3 months. EPVS were rated following a standardized method, dichotomized for analyses (mild [<20] versus severe [≥20]), and stratified by brain region (basal ganglia and centrum semiovale). RESULTS: In multivariable-adjusted analysis, the association of CKD with severe EPVS varied across racial groups. Comparing patients with and without CKD within racial groups, we found that Whites with CKD had higher odds of severe centrum semiovale EPVS (odds ratio [OR], 2.41 [95% CI, 0.98-5.88]). Among patients with CKD, Black patients had higher odds of severe EPVS in the basal ganglia and centrum semiovale compared with Whites (OR, 1.93 [95% CI, 1.18-3.16] and OR, 1.90 [95% CI, 1.16-3.11], respectively) and other racial groups (OR, 2.03 [95% CI, 1.23-3.36] and OR, 2.02 [95% CI, 1.22-3.34], respectively). CONCLUSIONS: CKD was more prevalent in our sample of patients with stroke with severe EPVS in the centrum semiovale. The relation differed when stratified by racial group and brain topography. Further studies are needed to confirm that CKD may relate differently to subclinical measures of small vessel disease according to race.

Generation of Vascular Networks from Adipocytes In Vitro.

Multipotent cells derived from white mature adipocytes, referred to as dedifferentiated fat (DFAT) cells have the capacity differentiate into endothelial cells. The objective of this study was to modify the isolation method for DFAT cells in order to optimize the endothelial lineage potential. The adipocytes were preincubated for 24 hours, washed, and then incubated for 5 days to allow the generated DFAT cells to remain in proximity to the adipocytes while the cells aggregated into cell clusters. The DFAT cells rapidly differentiated into adipocytes after which endothelial-like cells (ECs) emerged and formed tube-like structure closely associated with the newly differentiated adipocytes. The lipid-filled cells then gradually disappeared whereas the network of tube structure expanded over the course of 3 weeks. ECs accounted for 35-45% of the cells derived from the DFAT cells, as assessed by qPCR, immunofluorescence and fluorescence-activated cell sorting. The DFAT cell-derived ECs could also be further enriched by magnetic sorting, thereby serving as a mouse cell line for further research.

Vertical suppression of the EGFR pathway prevents onset of resistance in colorectal cancers.

Molecular targeted drugs are clinically effective anti-cancer therapies. However, tumours treated with single agents usually develop resistance. Here we use colorectal cancer (CRC) as a model to study how the acquisition of resistance to EGFR-targeted therapies can be restrained. Pathway-oriented genetic screens reveal that CRC cells escape from EGFR blockade by downstream activation of RAS-MEK signalling. Following treatment of CRC cells with anti-EGFR, anti-MEK or the combination of the two drugs, we find that EGFR blockade alone triggers acquired resistance in weeks, while combinatorial treatment does not induce resistance. In patient-derived xenografts, EGFR-MEK combination prevents the development of resistance. We employ mathematical modelling to provide a quantitative understanding of the dynamics of response and resistance to these single and combination therapies. Mechanistically, we find that the EGFR-MEK Combo blockade triggers Bcl-2 and Mcl-1 downregulation and initiates apoptosis. These results provide the rationale for clinical trials aimed at preventing rather than intercepting resistance.

Systematic identification of signaling pathways with potential to confer anticancer drug resistance.

Cancer cells can activate diverse signaling pathways to evade the cytotoxic action of drugs. We created and screened a library of barcoded pathway-activating mutant complementary DNAs to identify those that enhanced the survival of cancer cells in the presence of 13 clinically relevant, targeted therapies. We found that activation of the RAS-MAPK (mitogen-activated protein kinase), Notch1, PI3K (phosphoinositide 3-kinase)-mTOR (mechanistic target of rapamycin), and ER (estrogen receptor) signaling pathways often conferred resistance to this selection of drugs. Activation of the Notch1 pathway promoted acquired resistance to tamoxifen (an ER-targeted therapy) in serially passaged breast cancer xenografts in mice, and treating mice with a γ-secretase inhibitor to inhibit Notch signaling restored tamoxifen sensitivity. Markers of Notch1 activity in tumor tissue correlated with resistance to tamoxifen in breast cancer patients. Similarly, activation of Notch1 signaling promoted acquired resistance to MAPK inhibitors in BRAF(V600E) melanoma cells in culture, and the abundance of Notch1 pathway markers was increased in tumors from a subset of melanoma patients. Thus, Notch1 signaling may be a therapeutic target in some drug-resistant breast cancers and melanomas. Additionally, multiple resistance pathways were activated in melanoma cell lines with intrinsic resistance to MAPK inhibitors, and simultaneous inhibition of these pathways synergistically induced drug sensitivity. These data illustrate the potential for systematic identification of the signaling pathways controlling drug resistance that could inform clinical strategies and drug development for multiple types of cancer. This approach may also be used to advance clinical options in other disease contexts.