Female gender increases risk of stroke and readmission after carotid endarterectomy and carotid artery stenting.

OBJECTIVE: Carotid endarterectomy (CEA) has historically demonstrated a higher rate of perioperative adverse events for female patients. However, recent evidence suggests similar outcomes for CEA between genders. In contrast, fewer studies have examined gender in carotid artery stenting (CAS). Using contemporary data from the American College of Surgeons National Surgical Quality Improvement Program database, we aim to determine if gender impacts differences in postoperative complications in patients who undergo CEA or CAS. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2005 to 2017 using Current Procedural Terminology and International Classification of Diseases codes for retrospective review. Patients with carotid intervention (CEA or CAS) were stratified into asymptomatic vs symptomatic cohorts to determine the effect of gender on 30-day postoperative outcomes. Symptomatic patients were defined as those with perioperative transient cerebral ischemic attack or stenosis of carotid artery with cerebral infarction. Descriptive statistics were calculated. Risk-adjusted odds of 30-day postoperative outcomes were calculated using multivariate regression analysis with fixed effects for age, race, and comorbidities. RESULTS: There were 106,568 patients with CEA or CAS (104,412 CEA and 2156 CAS). The average age was 70.9 years, and female patients accounted for 39.9% of the population. For asymptomatic patients that underwent CEA or CAS, female gender was associated with significantly higher rates of cerebrovascular accident (CVA)/stroke (13%; P = .005), readmission (10%; P = .004), bleeding complication (32%; P = .001), and urinary tract infection (54%; P = .001), as well as less infection (26%; P = .001). In the symptomatic cohort, female gender was associated with significantly higher rates of CVA/stroke (32%; P = .034), bleeding complication (203%; P = .001), and urinary tract infection (70%; P = .011), whereas female gender was associated with a lower rate of pneumonia (39%; P = .039). Subset analysis found that, compared with male patients, female patients <75 years old have an increased rate of CVA/stroke (21%; P = .001) and readmission (15%; P < .001), whereas female patients ≥75 years old did not. In asymptomatic and symptomatic patients that underwent CEA, female gender was associated with significantly higher rates of CVA/stroke (13%; P = .006 and 31%; P = .044, respectively), but this finding was not present in patients undergoing CAS. CONCLUSIONS: In patients undergoing carotid intervention, female gender was associated with significantly increased rates of postoperative CVA/stroke in the asymptomatic and symptomatic cohorts as well as readmission in the asymptomatic cohort. Female gender was associated with higher rates of CVA/stroke following CEA, but not CAS. We recommend that randomized control trials ensure adequate representation of female patients to better understand gender-based disparities in carotid intervention.

Carotid Body Tumor Resection: Just as Safe without Preoperative Embolization.

BACKGROUND: Carotid body tumors (CBTs) are rare entities for which surgical resection remains the gold standard. Given their hypervascularity, preoperative embolization is often used; however, controversy exists over whether a benefit is associated. Proponents of embolization argue it minimizes blood loss and complications. Critics argue cost and stroke outweigh benefits. This study aimed to investigate the impact of embolization on outcomes after CBT resection. METHODS: Patients undergoing CBT resection were identified using the Healthcare Cost and Utilization Project State Inpatient Database for 5 states during the years 2006-2013. Patients were divided into 2 groups: carotid body tumor resection alone (CBTR) and carotid body embolization prior to tumor resection (CBETR). Descriptive statistics were calculated using arithmetic means with standard deviations for continuous and proportions for categorical variables. Patients were propensity score matched on the basis of sex, age, race, insurance, and comorbidity before analysis. Risk-adjusted odds of mortality, stroke, nerve injury, blood loss, and length of stay (LOS) were calculated using mixed-effects regression models with fixed effects for age, race, sex, and comorbidities. RESULTS: A total of 547 patients were identified. Of these, 472 underwent CBTR and 75 underwent CBETR. Mean age was 54.7 ± 16 years. Mean number of days between embolization and resection was 0.65 ± 0.72, (range 0-3) days. When compared to CBTR, there were no significant differences in mortality for CBETR (1.35 vs. 0% P = 0.316), cranial nerve injury (2.7 vs. 0% P = 0.48), and blood loss (2.7 vs. 6.8% P = 0.245). After risk adjustment, CBETR increased the odds of prolonged LOS (OR: 5.3; CI 2.1-13.3). CONCLUSIONS: CBT resection is a relatively rare procedure. The utility of preoperative tumor embolization has been questioned. This study demonstrates no benefit of preoperative tumor embolization.

The Use of the Agatston Calcium Score in Predicting Carotid Plaque Vulnerability.

BACKGROUND: The use of the Agatston calcium scoring method has been described extensively in the coronary circulation, but to date, it has not been investigated in the extracranial carotid domain. We sought to evaluate this calcium scoring method in its ability to predict carotid plaque vulnerability. METHODS: We retrospectively reviewed all computed tomography angiogram studies of the carotid arteries performed between March 2012 and March 2017 at a single institution. We identified 68 consecutive patients with 99 internal carotid arteries who met criteria for review. Total calcium was quantified by the Agatston scoring method using the OsiriX software. Stenosis severity was determined using North American Symptomatic Carotid Endarterectomy Trial criteria. The relation between Agatston score and degree of stenosis was evaluated using the Spearman's Rho coefficient (R). RESULTS: Of 99 internal carotid arteries, 71 were asymptomatic and 28 were symptomatic. Baseline characteristics were comparable, with no significant difference in patient characteristics. There were significant differences in mean Agatston scores for asymptomatic versus symptomatic arteries (121.95 ± 70.27 vs. 34.83 ± 47.77, P = 0.0098, 50%-69% stenosis; 151.07 ± 88.30 vs. 71.59 ± 77.27, P = 0.0006, 70%-99% stenosis). In both asymptomatic and symptomatic groups, Agatston calcium score increased as severity of stenosis increased. Higher Agatston score is protective against symptoms ipsilateral to the carotid lesion. CONCLUSIONS: Agatston calcium score may predict carotid plaque vulnerability, with higher scores associated with lower likelihood of developing symptoms ipsilateral to the carotid lesion. This score may be useful in predicting clinical behavior of carotid plaques.

Through-knee amputation is a feasible alternative to above-knee amputation.

OBJECTIVE: Through-knee amputation (TKA) is a rare amputation performed in <2% of all major lower extremity amputations in the United States. Despite biomechanical benefits and improved rehabilitation compared with above-knee amputation (AKA), TKA has largely been abandoned by vascular surgeons because of concerns for poor wound healing. The purpose of this study was to evaluate surgical outcomes of TKA. METHODS: The American College of Surgeons National Surgical Quality Improvement Program between 2005 and 2012 was queried using Current Procedural Terminology codes indicating AKA and TKA. Baseline characteristics were reviewed, and logistic regression analysis was performed to identify predictors of 30-day mortality. Propensity score matching was used to balance comorbidities between AKA and TKA. Operative variables and postoperative complications were compared between the groups. RESULTS: A total of 7469 AKA and 251 TKA patients were identified among 15,932 major lower extremity amputations. Baseline characteristics were examined. White race, chronic obstructive pulmonary disease, dyspnea, emergent operation, steroid use, myocardial infarction, congestive heart failure, high American Society of Anesthesiologists score, old age, preoperative sepsis or septic shock, and dialysis dependency were associated with increased 30-day mortality. Independent lifestyle and smoking (within 1 year) were protective against early death. Baseline comorbidities were not statistically significant after 1:1 propensity score matching. Operative outcomes were similar in both groups (AKA vs TKA). Wound infection (7.2% vs 11.2%; P = .16), dehiscence rate (1.2% vs 0.8%; P = 1.0), and 30-day mortality (9.6% vs 11.2%; P = .66) were comparable. Other outcome parameters, including cardiopulmonary and genitourinary complications, were similar except for a higher likelihood of return to the operating room in the TKA group (27.9% vs 12.4%; P < .01). Postoperative mortality was not associated with TKA (P = .77) or reoperation (P = .42), but it was associated with the patients' physiologic conditions (dyspnea, sepsis, emergent operation, high American Society of Anesthesiologists score, and dependent lifestyle). Predictors of reoperation were contaminated wound (hazard ratio [HR], 2.19; confidence interval [CI], 1.17-3.23; P = .015), sepsis or septic shock (HR, 2.63; CI, 1.37-5.05; P = .004), chronic obstructive pulmonary disease (HR, 2.81; CI, 1.23-6.42; P = .014), and wound infection (HR, 4.91; CI, 2.06-11.70; P < .001). Presence of peripheral vascular disease was not associated with post-TKA reoperation (P = .073). CONCLUSIONS: TKA demonstrated similar postoperative morbidity and mortality compared with AKA. Wound infection and risk of dehiscence were equivalent. TKA did demonstrate a higher rate of reoperation; however, neither TKA nor reoperation predicted postoperative mortality. Patients in stable physiologic condition without active infection can safely undergo elective TKA to maximize rehabilitation potential.

Epidemiology, treatment, and outcomes of acute limb ischemia in the pediatric population.

OBJECTIVE: Acute limb ischemia (ALI) in a pediatric patient is a rare condition but may result in lifelong disability. A paucity of evidence exists to derive treatment guidelines; some surgeons advocate conservative management over invasive measures. The purpose of this study was to evaluate the role of surgical revascularization in the pediatric population and outcomes of conservative vs surgical management. METHODS: The Healthcare Cost and Utilization Project State Inpatient Database (California, Iowa, and New York) between 2007 and 2013 was queried using International Classification of Diseases, Ninth Revision codes. Patients were stratified into two cohorts: conservative management and surgical management. Each group was further subdivided into three age groups: infant (<24 months), child (<12 years), and adolescent (<18 years). Outcome variables included mortality, amputation status, length of hospital stay, and hospital charge. RESULTS: A total of 1576 pediatric patients with ALI were identified among 6,122,535 pediatric admissions (26 per 100,000 admissions). Average age was 9.9 ± 7.1 years. There were 263 patients who underwent surgical revascularization. The conservative management group was younger (5.8 ± 6.2 vs 9.2 ± 6.1 years; P < .01). Otherwise, baseline characteristics were similar between the two groups. Overall, the amputation rate was low (<2%; n = 28), especially in the upper extremities (<0.2%). Outcomes of conservative management and surgical revascularization were similar for mortality (5.0% vs 3.4%; P = .34), amputation (1.9% vs 1.1%; P = .46), length of hospital stay (15.4 vs 12.9 days; P = .07), and hospital charge ($281,794 vs $288,507; P = .28). In subgroup analysis, infants had less concomitant orthopedic injury than other age groups. Children demonstrated a higher likelihood of associated upper extremity injury and operative revascularization (P < .01) than infants or adolescents. In infants, mortality was higher and surgical intervention was associated with longer hospital stay (29.5 ± 34.4 days vs 45.6 ± 31.6 days; P = .02) and larger health care expenditure ($467,885 ± $638,653 vs $1,099,343 ± $695,872; P < .01). CONCLUSIONS: Pediatric ALI is a rare entity and is associated with low amputation and mortality rates. Among the pediatric age cohorts, infants with ALI are at higher risk of in-hospital mortality than older age groups are. Surgical intervention is not associated with improved limb salvage or mortality. Nonoperative management may be considered an initial treatment modality, but further research is needed to elucidate which important subset of pediatric patients benefit from open or endovascular operative intervention.

Malignancy Does not Affect Outcomes of Pharmacomechanical Thrombolysis in Acute Symptomatic Iliofemoral Deep Vein Thrombosis.

BACKGROUND: Cancer patients demonstrate increased risk for venous thromboembolism (VTE), VTE recurrence, and anticoagulation-associated bleeding. Pharmacomechanical thrombolysis (PMT) aand thrombectomy improves venous patency, venous valve function, and quality of life in patients with acute iliofemoral deep vein thrombosis (DVT). It remains unknown whether pharmacomechanical thrombolysis can be used safely in patients with active cancer. We hypothesized that perioperative and short-term outcomes of pharmacomechanical iliofemoral DVT thrombolysis would not differ between patients with cancer and those without cancer. METHODS: A retrospective chart review of consecutive patients with symptomatic iliofemoral DVT undergoing PMT by AngioJet Power Pulse spray and thrombectomy at a single tertiary care university institution between December 2013 and December 2016 was performed. Outcomes between patients with cancer and without cancer were compared. RESULTS: We identified 22 limbs in 18 consecutive patients: 6 patients (7 limbs) with cancer and 12 patients (15 limbs) without cancer. Between these groups, the mean age was 60.5 ± 4.3 vs. 53.8 ± 26.8 years, respectively (P = 0.5593), and females comprised 66.7% vs. 25.0%, respectively (P = 0.0878). No significant difference in inferior vena cava (IVC) involvement between the groups (57.1% vs. 53.3%, P = 0.8676) was noted. Grade II (50-94% lysis) and III (95% complete lysis) thrombus lysis with restoration of venous patency was achieved in both the groups. Overnight catheter-directed thrombolysis (CDT) was rarely used. Notably, stenting was more frequently employed in cancer patients than in those without cancer (57.1% vs. 13.3%, P = 0.0316). The mean duration of follow-up was 3.42 ± 4.41 months for the cancer group and 4.50 ± 2.43 months for the noncancer group (P = 0.5060). Overall outcomes were excellent as no patient in both the groups experienced recurrent DVT, major bleeding, or postthrombotic syndrome. There was no mortality associated with the endovascular thrombolysis procedures. CONCLUSIONS: The results of our study suggest that the presence of malignancy does not affect short-term outcomes of endovascular thrombolytic therapy in symptomatic DVT. Further follow-up is needed to evaluate long-term outcomes.

Carotid Body Tumor Resection: Just as Safe without Preoperative Embolization.

BACKGROUND: Carotid body tumors (CBTs) are rare entities for which surgical resection remains the gold standard. Given their hypervascularity, preoperative embolization is often used; however, controversy exists over whether a benefit is associated. Proponents of embolization argue that it minimizes blood loss and complications. Critics argue that cost and stroke outweigh benefits. This study aimed to investigate the impact of embolization on outcomes following CBT resection. METHODS: Patients undergoing CBT resection were identified using the Healthcare Cost and Utilization Project State Inpatient Database for 5 states between 2006 and 2013. Patients were divided into 2 groups: carotid body tumor resection alone (CBTR) and carotid body tumor resection with preoperative arterial embolization (CBETR). Descriptive statistics were calculated using arithmetic means with standard deviations for continuous variables and proportions for categorical variables. Patients were propensity score matched on the basis of sex, age, race, insurance, and comorbidity prior to analysis. Risk-adjusted odds of mortality, stroke, nerve injury, blood loss, and length of stay (LOS) were calculated using mixed-effects regression models with fixed effects for age, race, sex, and comorbidities. RESULTS: A total of 547 patients were identified. Of these, 472 patients underwent CBTR and 75 underwent CBETR. Mean age was 54.7 ± 16 years. Mean number of days between embolization and resection was 0.65 ± 0.72 days (range 0-3). When compared with CBTR, there were no significant differences in mortality for CBETR (1.35% vs. 0%, P = 0.316), cranial nerve injury (2.7% vs. 0%, P = 0.48), and blood loss (2.7% vs. 6.8%, P = 0.245). Following risk adjustment, CBETR increased the odds of prolonged LOS (odds ratio 5.3, 95% confidence interval 2.1-13.3). CONCLUSIONS: CBT resection is a relatively rare procedure. The utility of preoperative tumor embolization has been questioned. This study demonstrates no benefit of preoperative tumor embolization.

Iliac Stent Migration during Thoracic Endovascular Aortic Aneurysm Repair Resulting in Functional Coarctation.

Iliac arterial disease, unfavorable anatomy, and prior stenting all pose challenges to access in endovascular abdominal aortic repair (EVAR) and thoracic aortic repair (TEVAR). Iliac access injury during T/EVAR may lead to rupture, dissection, thrombosis, or distal ischemia. Some have advocated iliac stent prior to T/EVAR in patients with suboptimal iliac access. The rate of complication and iliac stent migration during subsequent T/EVAR is undocumented. This case report describes a unique instance of self-expanding iliac stent migration during TEVAR which pinched the thoracic aortic endograft causing functional aortic coarctation.

Giant Spontaneous Greater Saphenous Vein Aneurysm.

Venous aneurysm, a rare venous anomaly, poses increased risk of distal thromboembolic event. Superficial venous aneurysm, such as greater saphenous vein aneurysm, is an uncommon subset with nonspecific symptoms and often a delay in diagnosis. Symptomatic patients or patients with a thromboembolic event may benefit from surgical intervention with low morbidity. This case report describes an isolated spontaneous greater saphenous vein aneurysm which was successfully ligated and resected for symptomatic relief and prevention of distal thromboembolism.

Outcomes of endovascular abdominal aortic aneurysm repair in high-risk patients.

OBJECTIVE: Although the endovascular aneurysm repair trial 2 (EVAR-2) demonstrated no benefit of EVAR in high-risk (HR) patients, EVAR is still performed widely in this patient cohort. This study compares the midterm outcomes after EVAR in HR patients with those in normal-risk (NR) patients. In turn, these data are compared with the EVAR-2 data. METHODS: A retrospective review from January 2006 to December 2013 identified 247 patients (75 HR [30.4%], 172 NR [69.6%]) who underwent elective EVAR for infrarenal aortic aneurysm in an academic tertiary institution and its affiliated Veterans Administration hospital. The same HR criteria used in the EVAR-2 trial were employed. Overall survival, graft-related complications, and reintervention rates were estimated by the Kaplan-Meier method. HR group outcomes were compared with the EVAR-2 data. RESULTS: HR patients had a larger abdominal aortic aneurysm size and had a higher prevalence of cardiac disease (P < .01), chronic obstructive pulmonary disease (P = .02), renal insufficiency (P < .01), and cancer (P < .01). Use of aspirin (63% HR vs 66% NR; P = .6), statin (83% HR vs 72% NR; P = .2), and beta-blockers (71% HR vs 60% NR; P = .2) was similar; in the EVAR-2 trial, the corresponding use of these medications was 58%, 42%, and not available, respectively. Perioperative mortality (0% HR vs 1.2% NR; P = 1.0) and early complication rates (4% HR vs 6% NR; P = .8) were similar. In contrast, perioperative mortality in the EVAR-2 trial was 9%. At a mean follow-up of 3 years, the incidence rates of delayed secondary interventions for aneurysm- or graft-related complications were 7% for HR patients and 10% for NR patients (P = .5). The 1-, 2-, and 4-year survival rates in HR patients (85%, 77%, 65%) were lower than those in NR patients (97%, 97%, 93%; P < .001), but this was more favorable compared with a 36% 4-year survival in the EVAR-2 trial. No difference was seen in long-term reintervention-free survival in HR and NR patients (P = .8). Backward stepwise logistic regression analysis identified five prognostic indicators for post-EVAR death: age, chronic kidney disease stages 4 and 5, congestive heart failure, home oxygen use, and current cancer therapy. CONCLUSIONS: EVAR can be performed in patients unfit for open surgical repair with excellent early survival and long-term durability. These outcomes in the HR group compare more favorably to the EVAR-2 trial data. However, not all HR patients for open surgical repair derive the benefit from EVAR. The decision to proceed with EVAR in HR patients should be individualized, depending on the number and severity of risk factors.

Spontaneous ruptured dissection of the right common iliac artery in a patient with classic Ehlers-Danlos syndrome phenotype.

Unlike vascular Ehlers-Danlos syndrome (EDS), classic EDS is rarely associated with vascular manifestation. We report the case of a 39-year-old man who presented with acute abdominal pain. At the time of presentation, the patient was in hypovolemic shock, and computed tomography angiogram demonstrated common iliac artery dissection with rupture. He underwent an attempted endovascular repair that was converted to an open repair of a ruptured right common iliac artery dissection. Subsequent genetic testing revealed a substitution of arginine for cysteine in type I collagen, COL1A1 exon 14 c.934C>T mutation, consistent with a rare variant of classic EDS.

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.

A review of arterial thoracic outlet syndrome.

Arterial thoracic outlet syndrome (TOS) is a condition in which anatomic abnormalities in the thoracic outlet cause compression of the subclavian or, less commonly, axillary artery. Patients are usually younger and typically have an anatomic abnormality causing the compression. The condition usually goes undiagnosed until patients present with signs of acute or chronic hand or arm ischemia. Workup of this condition includes a thorough history and physical examination; chest x-ray to identify potential anatomic abnormalities; and arterial imaging, such as computed tomographic angiography or duplex to identify arterial abnormalities. Patients will usually require operative intervention, given their symptomatic presentation. Intervention should always include decompression of the thoracic outlet with at least a first-rib resection and any other structures causing external compression. If the artery is identified to have intimal damage, mural thrombus, or is aneurysmal, then arterial reconstruction is warranted. Stenting should be avoided due to external compression. In patients with symptoms of embolization, a combination of embolectomy, lytic catheter placement, and/or therapeutic anticoagulation should be done. Typically, patients have excellent outcomes, with resolution of symptoms and high patency of the bypass graft, although patients with distal embolization may require finger amputation.

Iliac artery-enteric fistulas following failed pancreatic transplant.

Arterial-enteric fistulas occur from a multitude of causes, especially following surgical manipulation of vasculature. The development of an iliac artery-enteric fistula (IEF) occurs rarely in patients with failed pancreatic transplants. IEFs warrant urgent intervention due to the high mortality from hemorrhagic and septic shock. The diagnosis can be delayed by a lack of suspicion, the low sensitivity of diagnostic tests, and the nonspecific signs of fistulas on computed tomography. The management of IEFs is adapted from guidelines for arterial-enteric fistulas of other causes, with little consensus on ideal vascular reconstruction and postoperative antimicrobial management. The outcomes are limited to the short-term results from case reports and case series. We report two cases of IEFs in patients with a history of simultaneous pancreatic kidney transplant. Our patients underwent successful resolution of gastrointestinal bleeding and sepsis, with definitive management of fistula resection and interposition iliac artery bypass. The index of suspicion for IEFs should be high, and they should be considered as a source of anemia or gastrointestinal bleeding of an unknown source in patients with failed pancreatic transplant. Definitive management should be pursued in patients who can tolerate fistula resection, allograft explant, and arterial reconstruction.

Period frequency of iliofemoral venous occlusive disease by Doppler ultrasound and corresponding treatment in a tertiary care facility.

BACKGROUND: Patients with iliofemoral deep venous thrombosis (DVT) are at highest risk for the postthrombotic morbidity including all aspects of the postthrombotic syndrome. Invasive therapies such as catheter-directed thrombolysis (CDT) and/or mechanical thrombectomy with or without angioplasty and stenting and in some cases open operative thrombectomy improves venous patency, venous valve function, and quality of life in patients with acute iliofemoral DVT. What is the current frequency of acute iliofemoral DVT and how aggressively is it being treated? We hypothesize that the 10-year period frequency of iliofemoral DVT among acute DVT cases is greater than previously reported. Further, we hypothesize that thrombus removal to treat acute iliofemoral DVT is little utilized in current practice. METHODS: Indiana University (IU) vascular laboratory records from January 1, 1998 to December 31, 2008 were searched by CPT code for venous Doppler ultrasound study (n=7240). A random sample based on the IU medical record number of lower extremity Doppler studies was then selected (n=1020) for retrospective chart review. Corresponding clinical information was gathered from the patients' electronic medical record. RESULTS: Acute DVT occurred in 6.8%, and chronic DVT in 8.8% of patients studied (25.7% inpatient, 61.7% female; median age, 56.0 years [range, 4-91 years, 1.1% less than 16 years]). History of previous DVT (33.3%) and cancer (30.4%) were the most common risk factors in patients with acute DVT. Iliofemoral DVT defined as having an iliac or common femoral vein component was identified in 49.3% of acute DVT and in 36.0% of chronic DVT. CDT was utilized in 14.3% and mechanical thrombectomy in 4.8% of acute iliofemoral DVT, and was never used with distal DVT. Warfarin anticoagulation+unfractionated heparin or low-molecular-weight heparin overlap was the most common treatment for acute iliofemoral DVT (100.0%). In 2008, the referral base of our laboratory increased significantly. Acute DVT occurred significantly less often during the 1-year period 2008 (5.3%) than the 10-year period 1998-2007 (7.6%), but iliofemoral+common femoral DVT as a component of acute DVT did not differ significantly. CONCLUSIONS: Iliofemoral DVT may be more frequent than previously reported and represents a significant portion of acute DVT. Current recommendations of acute thrombus removal for the treatment of iliofemoral DVT is underutilized suggesting that perhaps greater education of clinicians and patients regarding invasive therapy for iliofemoral DVT is required.

Mechanisms of sex differences in TNFR2-mediated cardioprotection.

BACKGROUND: TNFR1/TNFR2 signaling may mediate different cellular and molecular responses (injury versus protection) and the balance may be affected by sex hormones. Previous studies have shown that females have improved myocardial functional recovery, TNFR1 signaling resistance, and increased SOCS3 expression after acute ischemia/reperfusion when compared with males. However, it is unknown whether the TNFR2 pathway protects the myocardium from ischemia/reperfusion injury, and if so, whether sex differences exist in TNFR2-mediated cardioprotection. Therefore, we hypothesized that (1) TNFR2 mediates myocardial protection from ischemia/reperfusion through STAT3, SOCS3, and vascular endothelial growth factor in both sexes; and (2) TNFR2 elicits greater protective signaling in females compared with males. METHODS AND RESULTS: Isolated male and female mouse hearts from TNFR2 knockout, TNFR1/2 knockout, and wild-type (C57BL/6J or B6129SF2/J; n=5 to 6/group) were subjected to 20 minutes ischemia followed by 60 minutes reperfusion. TNFR2 deficiency decreased postischemic myocardial recovery in both sexes but had a greater effect on females. The deleterious effects of TNFR2 ablation were associated with a decrease in mRNA and protein levels of SOCS3, STAT3, and vascular endothelial growth factor as well as an increase in myocardial interleukin-1-beta production in female hearts. However, a significant increase in JNK activation and interleukin-1-beta protein levels was noted in male TNFR2KO hearts after ischemia/reperfusion. Additionally, TNFR1/2 knockout decreased myocardial function in female hearts but not males. This observation was associated with a decrease in mRNA levels of SOCS3, STAT3, and vascular endothelial growth factor and an increase in myocardial p38 mitogen-activated protein kinase activation in females. CONCLUSIONS: Sex differences in the mechanisms of TNFR2-mediated cardioprotection occur by increasing STAT3, SOCS3, and vascular endothelial growth factor in females and by decreasing JNK in males.

Estradiol-treated mesenchymal stem cells improve myocardial recovery after ischemia.

BACKGROUND: Stem cell therapy is a promising treatment modality for injured cardiac tissue. A novel mechanism for this cardioprotection may include paracrine actions. Our lab has recently shown that gender differences exist in mesenchymal stem cell (MSC) paracrine function. Estrogen is implicated in the cardioprotection found in females. It remains unknown whether 17beta-estradiol (E2) affects MSC paracrine function and whether E2-treated MSCs may better protect injured cardiac tissue. We hypothesize that E2-exposed MSCs infused into hearts prior to ischemia may demonstrate increased vascular endothelial growth factor (VEGF) production and greater protection of myocardial function compared to untreated MSCs. MATERIALS AND METHODS: Untreated and E2-treated MSCs were isolated, cultured, and plated and supernatants were harvested for VEGF assay (enzyme-linked immunosorbent assay). Adult male Sprague-Dawley rat hearts (n = 13) were isolated and perfused via Langendorff model and subjected to 15 min equilibration, 25 min warm global ischemia, and 40 min reperfusion. Hearts were randomly assigned to perfusate vehicle, untreated male MSC, or E2-treated male MSC. Transcoronary delivery of 1 million MSCs was performed immediately prior to ischemia in experimental hearts. RESULTS: E2-treated MSCs provoked significantly more VEGF production than untreated MSCs (933.2 +/- 64.9 versus 595.8 +/- 10.7 pg/mL). Postischemic recovery of left ventricular developed pressure was significantly greater in hearts infused with E2-treated MSCs (66.9 +/- 3.3%) than untreated MSCs (48.7 +/- 3.7%) and vehicle (28.9 +/- 4.6%) at end reperfusion. There was also greater recovery of the end diastolic pressure with E2-treated MSCs than untreated MSCs and vehicle. CONCLUSIONS: Preischemic infusion of MSCs protects myocardial function and viability. E2-treated MSCs may enhance this paracrine protection, which suggests that ex vivo modification of MSCs may improve therapeutic outcome.

Are neonatal stem cells as effective as adult stem cells in providing ischemic protection?

BACKGROUND: Bone marrow stem cells (BMSCs) may be a novel treatment modality for organ ischemia, possibly through beneficial paracrine mechanisms. However, stem cells from older hosts exhibit decreased function during stress. We therefore hypothesized that (1) BMSCs derived from neonatal hosts would provide protection to ischemic myocardium, and (2) neonatal stem cells would enhance postischemic myocardial recovery above that seen with adult stem cell therapy. MATERIALS AND METHODS: Female adult Sprague Dawley rat hearts were subjected to an ischemia/reperfusion protocol via Langendorff isolated heart preparation (15 min equilibration, 25 min ischemia, and 60 min reperfusion). BMSCs were harvested from adult and neonatal mice and cultured through several passages under normal conditions (37 degrees C, 5% CO(2)/air). Immediately prior to ischemia, 1 million adult or neonatal BMSCs were infused into the coronary circulation. Cardiac functional parameters were continuously recorded. RESULTS: Pretreatment with adult BMSCs significantly increased postischemic myocardial recovery as noted by improved left ventricular developed pressure, end diastolic pressure, contractility, and rate of relaxation. Neonatal stem cells, however, did not cause any noticeable improvement in myocardial functional parameters following ischemia. CONCLUSION: Neonatal and adult BMSCs are distinctly different in the degree of beneficial tissue protection that they can provide. The data herein suggests that a critical age exists as to when stem cells become fully activated to provide their beneficial protective properties. Defining the genes that initiate these protective properties may allow for genetic amplification of beneficial signals, and the generation of "super stem cells" that provide maximum protection to ischemic tissues.

Contemporary Management of Acute Mesenteric Ischemia in the Endovascular Era.

OBJECTIVE:: Acute mesenteric ischemia is a rare disease entity associated with high morbidity and mortality. Disparate etiologies and nonspecific symptoms make the diagnosis challenging and often result in delayed diagnosis and intervention. Open laparotomy with mesenteric revascularization and resection of necrotic bowel has been considered the gold standard of care. With recent advances in percutaneous catheter-directed techniques, multiple retrospective studies have demonstrated the outcomes of endovascular therapy. Herein, we review the etiology, presentation, and diagnosis of acute mesenteric ischemia with contemporary outcomes associated with both open and endovascular treatments. METHODS:: The PubMed electronic database was queried in the English language using the search words mesenteric, acute ischemia, embolism, thromboembolism, thrombosis, revascularization, and endovascular in various combinations. Abstracts of the relevant titles were examined to confirm their relevance and the full articles then extracted. References from extracted articles were checked for any additional relevant articles. This systematic review encompassed literature for the past 5 years (between 2011 and 2016). RESULTS:: Early diagnosis and intervention improves acute mesenteric ischemia outcomes. Early restoration of mesenteric flow minimizes morbidity and mortality. In comparison to open laparotomy with mesenteric revascularization and resection of necrotic bowel, several retrospective studies using administrative data and single-center chart reviews demonstrate noninferior outcomes of an endovascular first approach in acute arterial mesenteric occlusion. CONCLUSIONS:: For acute mesenteric arterial occlusive disease, both endovascular and open revascularization techniques are viable options. Although there is lack of level 1 evidence, single-center retrospective studies and administrative database studies demonstrated that an endovascular first approach may have improved outcomes in the immediate postoperative period. However, selection and other bias in these studies necessitate the need for definitive randomized prospective studies between endovascular and open mesenteric intervention. In contrast, mesenteric venous thrombosis may be treated with systemic anticoagulation without surgical revascularization. Catheter-directed thrombectomy and thrombolysis can be considered at the discretion of the clinician.