Prathima Nandivada

Prevalence and Impact of the Subclavian Steal Syndrome

Objective:To determine the prevalence and impact of subclavian steal syndrome (SSS) in patients undergoing assessment of the carotid arteries. Summary Background Data:Vertebral artery flow reversal is often found among patients undergoing imaging of the extracranial vessels; however, there are no large studies evaluating the prevalence and natural history of SSS in stratified patients. Methods:Patients presenting for duplex ultrasound of the carotid arteries underwent 2 sets of bilateral arm pressure measurements. Patients with a pressure differential (PD) >20 mm Hg were examined in detail for vascular obstruction ipsilateral to the affected arm. When appropriate, computer tomographic angiography (CTA), magnetic resonance angiography, and angiography were performed. Signs and symptoms related to SSS and the types of interventions performed were recorded. Results:In a period of 6 years, 7881 carotid duplex scans were performed, with a PD >20 mm Hg in 514 (6.5%) patients and a left arm preponderance (82%). SSS was complete in 61%, partial in 23%, and absent in 16%. Symptoms were present in 38 patients with 32 experiencing symptoms of the posterior circulation, 4 of arm ischemia, and 2 of cardiac ischemia. Symptoms occurred more frequently as the arm PD increased. Of the 38 symptomatic patients, only 7 underwent an intervention (2 with subclavian-carotid bypass and 5 with percutaneous transluminal angioplasty stenting of the subclavian). Conclusions:SSS is a frequent finding in patients undergoing carotid duplex scanning. Patients are commonly asymptomatic and rarely require an intervention. A significantly elevated arm PD (>40–50 mm Hg) is more commonly associated with symptoms, complete steal, and the need for intervention.

Laser-induced endothelial cell activation supports fibrin formation

Laser-induced vessel wall injury leads to rapid thrombus formation in an animal thrombosis model. The target of laser injury is the endothelium. We monitored calcium mobilization to assess activation of the laser-targeted cells. Infusion of Fluo-4 AM, a calcium-sensitive fluorochrome, into the mouse circulation resulted in dye uptake in the endothelium and circulating hematopoietic cells. Laser injury in mice treated with eptifibatide to inhibit platelet accumulation resulted in rapid calcium mobilization within the endothelium. Calcium mobilization correlated with the secretion of lysosomal-associated membrane protein 1, a marker of endothelium activation. In the absence of eptifibatide, endothelium activation preceded platelet accumulation. Laser activation of human umbilical vein endothelial cells loaded with Fluo-4 resulted in a rapid increase in calcium mobilization associated cell fluorescence similar to that induced by adenosine diphosphate (10 μM) or thrombin (1 U/mL). Laser activation of human umbilical vein endothelial cells in the presence of corn trypsin inhibitor treated human plasma devoid of platelets and cell microparticles led to fibrin formation that was inhibited by an inhibitory monoclonal anti-tissue factor antibody. Thus laser injury leads to rapid endothelial cell activation. The laser activated endothelial cells can support formation of tenase and prothrombinase and may be a source of activated tissue factor as well.

Prosthetic graft infections involving the femoral artery

BACKGROUND Prosthetic graft infection is a major complication of peripheral vascular surgery. We investigated the experience of a single institution over 10 years with bypass grafts involving the femoral artery to determine the incidence and risk factors for prosthetic graft infection. METHODS A retrospective cohort single-institution review of prosthetic bypass grafts involving the femoral artery from 2001 to 2010 evaluated patient demographics, body mass index, comorbidities, indications, location of bypass, type of prosthetic material, case urgency, and previous ipsilateral bypass or percutaneous interventions and evaluated the incidence of graft infections, amputations, and mortality. RESULTS There were 496 prosthetic grafts identified with a graft infection rate of 3.8% (n = 19) at a mean follow-up of 27 months. Multivariable analysis showed that redo bypass (hazard ratio [HR], 5.8; 95% confidence interval [CI], 2.2-15.0), active infection at the time of bypass (HR, 5.2; 95% CI, 1.9-14.2), female gender (HR, 4.5; 95% CI, 1.6-12.7), and diabetes mellitus (HR, 4.6; 95% CI, 1.5-14.3) were significant predictors of graft infection. Graft infection was predictive of major lower extremity amputation (HR, 9.8; 95% CI, 3.5-27.1), as was preoperative tissue loss (HR, 4.7; 95% CI, 1.8-11.9). Graft infection did not predict long-term mortality; however, chronic renal insufficiency (HR, 2.3; 95% CI, 1.6-3.4), tissue loss (HR, 1.4; 95% CI, 1.0-1.9), and active infection (HR, 2.3; 95% CI, 1.6-3.4) did. Infected grafts were removed 79% of the time. Staphylococcus epidermidis (37%) and methicillin-sensitive Staphylococcus aureus (26%) were the most common pathogens isolated. CONCLUSIONS Redo bypass, female gender, diabetes, and active infection at the time of bypass are associated with a higher risk for prosthetic graft infection and major extremity amputation but do not confer an increased risk of mortality. Autologous vein for lower extremity bypass and endovascular interventions should be considered when feasible in high-risk patients.

Treatment of Parenteral Nutrition-Associated Liver Disease: The Role of Lipid Emulsions

Parenteral nutrition is a life-saving therapy for infants with intestinal failure. However, long-term parenteral nutrition carries the risk of progressive liver disease. Substantial data has implicated components of parenteral soybean oil in the pathogenesis of parenteral nutrition-associated liver disease (PNALD). Elevated serum concentrations of phytosterols, an abundance of omega-6 polyunsaturated fatty acids, and a relative paucity of α-tocopherol have been associated with the risk of cholestasis and hepatic injury observed in PNALD. Currently available treatment strategies include the reduction of the dose of administered parenteral soybean oil and/or the replacement of parenteral soybean oil with alternative parenteral lipid emulsions. The purpose of this review is to provide an overview of the pathogenetic mechanisms associated with the development of PNALD and the data evaluating currently available treatment strategies.

The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy.

OBJECTIVE To determine the natural history of cirrhosis from parenteral nutrition-associated liver disease (PNALD) after resolution of cholestasis with fish oil (FO) therapy. BACKGROUND Historically, cirrhosis from PNALD resulted in end-stage liver disease, often requiring transplantation for survival. With FO therapy, most children now experience resolution of cholestasis and rarely progress to end-stage liver disease. However, outcomes for cirrhosis after resolution of cholestasis are unknown and patients continue to be considered for liver/multivisceral transplantation. METHODS Prospectively collected data were reviewed for children with cirrhosis because of PNALD who had resolution of cholestasis after treatment with FO from 2004 to 2012. Outcomes evaluated included need for liver/multivisceral transplantation, mortality, and the clinical progression of liver disease. RESULTS Fifty-one patients with cirrhosis from PNALD were identified, with 76% demonstrating resolution of cholestasis after FO therapy. The mean direct bilirubin decreased from 6.4 ± 4 mg/dL to 0.2 ± 0.1 mg/dL (P < 0.001) 12 months after resolution of cholestasis, with a mean time to resolution of 74 days. None of the patients required transplantation or died from end-stage liver disease. Pediatric End-Stage Liver Disease scores decreased from 16 ± 4.6 to -1.2 ± 4.6, 12 months after resolution of cholestasis (P < 0.001). In children who remained PN-dependent, the Pediatric End-Stage Liver Disease score remained normal throughout the follow-up period. CONCLUSIONS Cirrhosis from PNALD may be stable rather than progressive once cholestasis resolves with FO therapy. Furthermore, these patients may not require transplantation and show no clinical evidence of liver disease progression, even when persistently PN-dependent.

Lipid emulsions in the treatment and prevention of parenteral nutrition-associated liver disease in infants and children.

Long-term parenteral nutrition (PN) carries the risk of progressive liver disease in infants with intestinal failure. Although PN-associated liver disease (PNALD) is multifactorial in etiology, components of soybean oil lipid emulsions have been implicated in the diseases pathogenesis. Historically, infants with PNALD who were unable to wean from PN to full enteral feeding developed cirrhosis and end-stage liver disease, which require liver transplantation to survive. Over the past 2 decades, novel strategies for the management of parenteral lipids have improved morbidity and mortality from PNALD in infants with intestinal failure. Current strategies for the treatment of PNALD include restricting the dose of parenteral soybean oil lipid emulsion and/or replacing the soybean oil with a parenteral fish-oil lipid emulsion or emulsions of mixed-lipid sources. The purpose of this report is to review published data that evaluate these strategies in parenteral lipid management for the treatment and prevention of PNALD.

Mechanisms for the effects of fish oil lipid emulsions in the management of parenteral nutrition-associated liver disease

Parenteral nutrition (PN) can be life saving for infants unable to adequately absorb enteral nutrients due to intestinal failure from inadequate bowel length or function. However, long-term PN carries significant morbidity and mortality, with 30 to 60% of patients developing progressive liver dysfunction. The etiology of PN-associated liver disease (PNALD) is poorly understood, however the involvement of lipid emulsions in its pathogenesis has been clearly established, with new emphasis emerging on the role of omega-6 polyunsaturated fatty acids and omega-3 polyunsaturated fatty acids. Recent studies evaluating the use of parenteral fish oil lipid emulsions instead of soybean oil lipid emulsions have demonstrated marked improvements in cholestasis, morbidity, and mortality in patients with PNALD treated with fish oil. This review provides an overview of the role of lipid emulsions in the pathogenesis of PNALD and the proposed mechanisms by which parenteral fish oil lipid emulsions may be exerting their beneficial effects.

Fish oil-based lipid emulsion in the treatment of parenteral nutrition-associated liver disease.

Purpose of review Parenteral nutrition-associated liver disease (PNALD) is a major cause of morbidity and mortality in the parenteral nutrition-dependent population. Here, we review the most recent literature involving a fish oil-based lipid emulsion (FOLE) and its effects on PNALD. Recent findings Vegetable oil-based lipid emulsions (VBLEs) contribute to PNALD. This may be due to parenteral phytosterols and/or the presence of pro-inflammatory mediators. Whereas a small reduction in the dose of VBLE does not appear to prevent PNALD, a significant reduction in the dose may reverse PNALD; however, it carries the risk of essential fatty acid deficiency. Furthermore, the impact of extreme lipid restriction on subsequent neurodevelopment is unknown. Combination lipid emulsions containing fish oil are associated with decreased bilirubin levels, though no studies compare these emulsions with the outcomes with FOLE alone. The utility of FOLE in the reversal of PNALD has been demonstrated and its administration does not lead to essential fatty acid deficiency. Furthermore, there is evidence that FOLE may prevent PNALD. Conclusion FOLE appears to be an efficacious treatment to reverse PNALD. However, more studies are necessary to determine if FOLE might also be beneficial in the prevention of PNALD. Future studies should additionally focus on the preterm infant population, as they represent a major population requiring parenteral nutrition support for survival.

Intravenous Lipid Emulsions in Parenteral Nutrition.

Fat is an important macronutrient in the human diet. For patients with intestinal failure who are unable to absorb nutrients via the enteral route, intravenous lipid emulsions play a critical role in providing an energy-dense source of calories and supplying the essential fatty acids that cannot be endogenously synthesized. Over the last 50 y, lipid emulsions have been an important component of parenteral nutrition (PN), and over the last 10-15 y many new lipid emulsions have been manufactured with the goal of improving safety and efficacy profiles and achieving physiologically optimal formulations. The purpose of this review is to provide a background on the components of lipid emulsions, their role in PN, and to discuss the lipid emulsions available for intravenous use. Finally, the role of parenteral fat emulsions in the pathogenesis and management of PN-associated liver disease in PN-dependent pediatric patients is reviewed.

The impact of endovascular procedures on fellowship training in lower extremity revascularization

OBJECTIVE The introduction of endovascular aneurysm repair has resulted in a decline in open abdominal aortic aneurysm repairs performed by vascular residents. The purpose of this study was to evaluate if a similar trend has occurred with open lower extremity revascularization procedures, with increased endovascular procedures producing a decrease in the number of open lower extremity revascularizations. Furthermore, this study evaluates the effect of endovascular procedure volume on the frequency of subtypes of open lower extremity procedures performed. METHODS The total number of vascular procedures, lower extremity bypasses, and endovascular interventions from 2000 to 2010 were analyzed from case logs of vascular residents as reported by the Accreditation Council for Graduate Medical Education. RESULTS The average number of cases performed by vascular residents has increased by 150% from 463.9 in 2000 to 1168 in 2009, due to the increased number of endovascular procedures. The average number of endovascular revascularizations has increased by 317% from 40.5 performed in 2000 to 168.9 in 2009. Femoral-popliteal bypasses have increased in frequency by 27% whereas the number of infrapopliteal bypass has remained unchanged. The largest difference is seen in femoral endarterectomies with a 234% increase from 3.2 per resident in 2001 to 10.7 per resident in 2010. Comparison of the proportion of femoral-popliteal and tibioperoneal interventions performed by angioplasty or bypass after 2007 revealed that endovascular interventions comprise 50% of procedures in the femoral-popliteal distribution, whereas 65% of infrapopliteal interventions are still performed using open techniques. CONCLUSIONS The number of procedures performed during vascular residency has dramatically increased over the last decade secondary to the increased number of endovascular procedures. The average vascular surgery residents open operative experience has been stable over the last 10 years, despite the increasing endovascular case volume. Residents perform femoral endarterectomy with increasing frequency, perhaps representing an increasing volume of hybrid procedures. Gaps in information available for evaluating resident training remain a significant obstacle. Moving forward, revision of the current reporting system to a format that more accurately reflects resident experience would be beneficial.