Elliot L. Chaikof

The care of patients with an abdominal aortic aneurysm: The Society for Vascular Surgery practice guidelines

The Clinical Practice Council of the Society for Vascular Surgery charged a writing committee with the task of updating practice guidelines, initally published in 2003, for surgeons and physicians who are involved in the preoperative, operative, and postoperative care of patients with abdominal aortic aneurysms (AAA). This document provides recommendations for evaluating the patient, including risk of aneurysm rupture and associated medical co-morbidities, guidelines for selecting surgical or endovascular intervention, intraoperative strategies, perioperative care, long-term follow-up, and treatment of late complications. Decision making related to the care of patients with AAA is complex. Aneurysms present with varying risks of

Engineered collagen–PEO nanofibers and fabrics

Type I collagen-PEO fibers and non-woven fiber networks were produced by the electrospinning of a weak acid solution of purified collagen at ambient temperature and pressure. As determined by high-resolution SEM and TEM, fiber morphology was influenced by solution viscosity, conductivity, and flow rate. Uniform fibers with a diameter range of 100-150 nm were produced from a 2-wt% solution of collagen-PEO at a flow rate of 100 μl min-1. Ultimate tensile strength and elastic modulus of the resulting non-woven fabrics was dependent upon the chosen weight ratio of the collagen-PEO blend. 1H NMR dipolar magnetization transfer analysis suggested that the superior mechanical properties, observed for collagen-PEO blends of weight ratio 1 : 1, were due to the maximization of intermolecular interactions between the PEO and collagen components. The process outlined herein provides a convenient, non-toxic, non-denaturing approach for the generation collagen-containing nanofibers and non-woven fabrics that have potential application in wound healing, tissue engineering, and as hemostatic agents.

2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Incorporated Into the ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery

It is essential that the medical profession play a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced and tested in the detection, management, or prevention of disease states. Rigorous and expert analysis of the available data documenting

A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy.

BACKGROUND Clinically relevant postoperative pancreatic fistulas (CR-POPF) are serious inherent risks of pancreatic resection. Preoperative CR-POPF risk assessment is currently inadequate and rarely disqualifies patients who need resection. The best evaluation of risk occurs intraoperatively, and should guide fistula prevention and response measures thereafter. We sought to develop a risk prediction tool for CR-POPF that features intraoperative assessment and reveals associated clinical and economic significance. STUDY DESIGN Based on International Study Group of Pancreatic Fistula classification, recognized risk factors for CR-POPF (small duct, soft pancreas, high-risk pathology, excessive blood loss) were evaluated during pancreaticoduodenectomy. An optimal risk score range model, selected from 3 different constructs, was first derived (n = 233) and then validated prospectively (n = 212). Clinical and economic outcomes were evaluated across 4 ranges of scores (negligible risk, 0 points; low risk, 1 to 2; intermediate risk, 3 to 6; high risk, 7 to 10). RESULTS Clinically relevant postoperative pancreatic fistulas occurred in 13% of patients. The incidence was greatest with excessive blood loss. Duct size <5 mm was associated with increased fistula rates that rose with even smaller ducts. These factors, together with soft pancreatic parenchyma and certain disease pathologies, afforded a highly predictive 10-point Fistula Risk Score. Risk scores strongly correlated with fistula development (p < 0.001). Notably, patients with scores of 0 points never developed a CR-POPF, while fistulas occurred in all patients with scores of 9 or 10. Other clinical and economic outcomes segregated by risk profile across the 4 risk strata. CONCLUSIONS A simple 10-point Fistula Risk Score derived during pancreaticoduodenectomy accurately predicts subsequent CR-POPF. It can be readily learned and broadly deployed. This prediction tool can help surgeons anticipate, identify, and manage this ominous complication from the outset.

Reporting standards for thoracic endovascular aortic repair (TEVAR).

Reporting standards for studies involving endovascular repair of infrarenal abdominal aortic aneurysms were introduced by the Society for Vascular Surgery in 1997 and revised in 2002. Although the 2002 standards addressed endovascular aortic aneurysm repair in a more general sense, they did not focus on thoracic endografts. With the development of endovascular grafts to treat thoracic aortic pathology, there is a need for reporting standards specific to this procedure. Many of concepts and definitions of success are extrapolated from the prior publications regarding standards for endovascular abdominal aortic aneurysm repair (EVAR). Nonetheless, thoracic endovascular aortic repair (TEVAR) incorporates some unique aspects, ranging from specific anatomic issues to the differing etiologies of diseases affecting the thoracic aorta, such as dissection, traumatic injury, penetrating ulcer, and pseudoaneurysm. The framework for TEVAR reporting will be addressed in this article. The reporting standards for aortic dissection are particularly complex and will be addressed in more detail in a separate publication.

Self-Assembly of Thermally Responsive Amphiphilic Diblock Copolypeptides into Spherical Micellar Nanoparticles†

As structure–property relationships for protein self-assembly have been elucidated, advances in chemistry and structural biology have facilitated the development of biologically inspired polypeptides through chemical and biosynthetic schemes that have afforded novel protein-based films, fibers, micelles, and gels. In a number of instances, reversible protein self-assembly has been driven by welldefined conformational changes of peptide units induced in response to an external stimulus. Indeed, designed molecular assembly of stimuli-responsive peptides has emerged as a “bottom-up” approach for creating complex, but ordered, hierarchical structures from simple amino acid building blocks. As illustrated by the design of diand triblock polypeptides, microand nanoscale features can be tuned by control of the amino acid sequence, molecular weight, and secondary structure of the peptide. In particular, amphiphilic block copolypeptides can self-assemble into a variety of diverse structures, including rods, cylinders, spheres, and vesicles. Although diblock copolymers consisting of chemically and conformationally distinctive individual polypeptide blocks have been produced by chemical and biosynthetic schemes, to date, relatively few recombinant amphiphilic diblock polypeptides have been synthesized. Given the capacity to incorporate targeting ligands, cell membrane fusion sequences, receptor activating peptides, fluorescent or chelating groups, as well as the ability to tailor pharmacokinetics, biodistribution, and peptide stability, significant opportunities exist for micelles or vesicles produced from recombinant protein block copolymers. Elastin-mimetic polypeptides based on the pentameric repeat sequence (Val-Pro-Gly-Xaa-Gly) undergo thermal and pH-responsive self-assembly in aqueous solution. Spontaneous phase separation of the polypeptide coincides with a conformational rearrangement of local secondary structure above a unique transition temperature (Tt) determined by the chemical identity of the fourth amino acid (Xaa) in the pentapeptide repeat. Recent studies have demonstrated the potential of engineered materials derived from elastin in a broad range of biomedical and biotechnological applications and, in particular, drug delivery. 8] Characteristically, elastin-mimetic blocks that contain hydrophobic amino acids in the fourth amino acid position, such as tyrosine, display a conformational transition from random coil to repetitive type II b turns at temperatures well below 37 8C, whereas blocks that contain a charged amino acid in this position, such as glutamic acid, persist as a random coil throughout the physiologic temperature range. Thus, we postulated that amphiphilic diblock copolymers bearing glutamic acid and tyrosine residues in Nand C-terminal blocks, respectively, would promote micelle formation by temperature-induced self-assembly with a core–shell structure. Moreover, we speculated that at a sufficiently high density of glutamic acid units, charge repulsion would limit the association of the hydrophilic blocks andminimize micelle aggregation. Micelles stabilized by self-assembly alone are typically unstable in a complex environment containing naturally occurring amphiphiles, such as plasma proteins, glycolipids, and lipopeptides. Therefore, by positioning cysteine residues between blocks, we hypothesized that highmolecular-weight protein aggregation or uncontrolled micelle–micelle association would be avoided by nanoparticle stabilization through disulfide cross-linking. These studies represent the first report of thermally responsive and crosslink stabilized protein micelles produced through the tailored design of recombinant amphiphilic diblock copolymers. Two amphiphilic diblock polypeptides (ADP1 and ADP2) were synthesized and self-assembled into micellar structures with consecutive cysteine residues incorporated at the core– shell interface (Scheme 1). Expression of the diblock synthetic genes in E. coli expression strain, BL21(DE3), afforded recombinant protein polymers in high yield after immobilized-metal-affinity chromatography (IMAC) purification from the cell lysate. Mass spectrometry confirmed a correspondence between the observed and expected masses of the respective diblocks with consistent sequence composition by amino acid analysis. The presence of cysteine residues within the polypeptide chain was characterized by the use of a thiolreactive fluorescent dye (see the Supporting Information). Differential scanning calorimetry (DSC) demonstrated an endothermic transition at around 10 8C for both diblock copolymers, which conforms to the established relationship between the position of the transition temperature and the mole fraction of tyrosine in elastin-mimetic protein poly[*] Dr. W. Kim, Dr. E. L. Chaikof Emory University Departments of Biomedical Engineering and Surgery Georgia Institute of Technology, School of Chemical Engineering 101 Woodruff Circle, Rm 5105, Atlanta, GA 30322 (USA) Fax: (+1)404-727-3667 E-mail: echaiko@emory.edu

Delayed rupture of aortic aneurysms following endovascular stent grafting

BACKGROUND Deployment of transfemoral, endovascular stent grafts for treatment of abdominal aortic aneurysms is appealing for several reasons: avoidance of abdominal incision, lack of aortic cross-clamping, potential for regional anesthesia, and shortened hospital stay. Concerns remain, however, regarding the ability of these devices to completely exclude the aneurysm and prevent aneurysm rupture and the long-term integrity of the device. The availability of endografts and the likely development of percutaneous devices have also raised the delicate issue of personnel training for patient selection, endograft implantation, and postoperative follow-up. PATIENTS AND METHODS The cases of 2 patients are reported in which Dacron endovascular grafts, anchored proximally and distally by Palmaz stents, were deployed for treatment of infrarenal abdominal aortic aneurysms. RESULTS In a patient with and absent distal cuff, choosing this procedure represented a clear error in patient selection. The endograft failed to reach the aortic bifurcation and the aneurysm ruptured, with the death of the patient 4 months postimplantation. In a patient with anatomy suitable for endograft placement, a perigraft leak persisted at the distal anastomosis following device placement. The aneurysm ruptured 14 days postprocedure. Although the patient survived emergent aneurysm repair, he developed acute renal failure. CONCLUSION Careful preoperative assessment of aortic anatomy is crucial in selection of patients for transfemoral endovascular graft placement. Lack of a distal cuff of at least 1 cm precludes tube graft implantation. Patients with a perigraft leak are not protected by the endograft from aneurysm rupture. Vascular surgeons must be involved in the preoperative evaluation of these patients and are the only specialty group who can provide the prerequisite care in evaluation and management of postoperative complications.

Biomaterials for vascular tissue engineering.

Cardiovascular disease is the leading cause of mortality in the USA. The limited availability of healthy autologous vessels for bypass grafting procedures has led to the fabrication of prosthetic vascular conduits. While synthetic polymers have been extensively studied as substitutes in vascular engineering, they fall short of meeting the biological challenges at the blood-material interface. Various tissue engineering strategies have emerged to address these flaws and increase long-term patency of vascular grafts. Vascular cell seeding of scaffolds and the design of bioactive polymers for in situ arterial regeneration have yielded promising results. This article describes the advances made in biomaterials design to generate suitable materials that not only match the mechanical properties of native vasculature, but also promote cell growth, facilitate extracellular matrix production and inhibit thrombogenicity.

Pathogen-Sensing Plasmacytoid Dendritic Cells Stimulate Cytotoxic T-Cell Function in the Atherosclerotic Plaque Through Interferon-α

Background— Unstable atherosclerotic plaque is characterized by an infiltrate of inflammatory cells. Both macrophages and T cells have been implicated in mediating the tissue injury leading to plaque rupture; however, signals regulating their activation remain unidentified. Infectious episodes have been suspected to render plaques vulnerable to rupture. We therefore explored whether plasmacytoid dendritic cells (pDCs) that specialize in sensing bacterial and viral products can regulate effector functions of plaque-residing T cells and thus connect host infection and plaque instability. Methods and Results— pDCs were identified in 53% of carotid atheromas (n=30) in which they localized to the shoulder region and produced the potent immunoregulatory cytokine interferon (INF)-&agr;. IFN-&agr; transcript concentrations in atheroma tissues correlated strongly with plaque instability (P<0.0001). Plaque-residing pDCs responded to pathogen-derived motifs, CpG-containing oligodeoxynucleotides binding to toll-like receptor 9, with enhanced IFN-&agr; transcription (P=0.03) and secretion (P=0.007). IFN-&agr; emerged as a potent regulator of T-cell function, even in the absence of antigen recognition. Specifically, IFN-&agr; induced a 10-fold increase of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) on the surface of CD4 T cells (P<0.0001) and enabled them to effectively kill vascular smooth muscle cells (P=0.0003). Conclusions— pDCs in atherosclerotic plaque sense microbial motifs and amplify cytolytic T-cell functions, thus providing a link between host-infectious episodes and acute immune-mediated complications of atherosclerosis.

Layer-by-Layer Assembly of a Conformal Nanothin PEG Coating for Intraportal Islet Transplantation

Encapsulation of cells and tissue offers a rational approach for attenuating deleterious host responses toward transplanted cells, but a need exists to develop cell encapsulation strategies that minimize transplant volume. In this report, we describe the formation of nanothin, PEG-rich conformal coatings on individual pancreatic islets via layer-by-layer self-assembly of poly( l-lysine)- g-poly(ethylene glycol)(biotin) (PPB) and streptavidin (SA). Through control of grafting ratio, PPB could be rendered nontoxic and facilitated growth of PPB/SA multilayer thin films that conformed to the heterogeneous islet surface. (PPB/SA) 8 multilayer films could be assembled without loss of islet viability or function, and coated islets performed comparably to untreated controls in vivo in a murine model of allogenic intraportal islet transplantation.