Andrew A. Hill

Effect of a chimeric antibody to tumor necrosis factor-alpha on cytokine and physiologic responses in patients with severe sepsis-a randomized, clinical trial

OBJECTIVES Tumor necrosis factor (TNF)-alpha appears central to the pathogenesis of severe sepsis, but aspects of the cytokine cascade and the link to physiologic responses are poorly defined. We hypothesized that a monoclonal antibody to TNF-alpha given early in the course of severe sepsis would modify the pattern of systemic cytokine release and, as a consequence, resuscitation fluid requirements, net proteolysis, and hypermetabolism would be reduced. DESIGN Randomized, double-blind, placebo-controlled trial. SETTING Critical Care Unit and University Department of Surgery in a single tertiary care center. PATIENTS Fifty-six patients (from 92 eligible patients) with severe sepsis. Twenty-eight patients were randomized to treatment, and were comparable with the placebo group for age, gender, race, Acute Physiology and Chronic Health Evaluation II score, and site and type of infection. INTERVENTIONS A 300-mg single dose of cA2 (a chimeric neutralizing antibody to TNF-alpha) was given intravenously within 12 hrs of the onset of severe sepsis. Standard surgical and intensive care therapy was otherwise delivered. MEASUREMENTS AND MAIN RESULTS Plasma concentrations of TNF-alpha, interleukin (IL)-1beta IL-6, IL-8, IL-10, soluble 75-kilodalton TNF-alpha receptor (sTNFR-75), and IL-1beta receptor antagonist (IL-1ra) were measured by sandwich enzyme-linked immunosorbent assay before cA2 infusion, 8 hrs later, and then daily for a minimum of 4 days. Sequential changes in total body protein, body water spaces, and resting energy expenditure over 21 days were measured, as soon as patients achieved hemodynamic stability, by in vivo neutron activation analysis, tritium and bromide dilution, and indirect calorimetry, respectively. Twenty-one patients died, ten having received cA2. Suppression of measurable TNF-alpha was observed at 8 hrs with subsequent rebound by 24 hrs after cA2 treatment. The concentrations of other cytokines were high, were not reduced by intervention, and decreased logarithmically over 5 days. Both groups reached hemodynamic stability at similar times (57.5 +/- 11.8 hrs in controls vs. 58.6 +/- 9.2 hrs in the cA2 group) and following similar volumes of infused fluids (29.1 +/- 3.4 L vs. 28.9 +/- 4.4 L). No differences in net proteolysis, resolution of body water expansion, or alteration in resting energy expenditure were demonstrated. CONCLUSION A single dose of cA2 did not alter the overall pattern of cytokine activation or the profound derangements in physiologic function that accompany severe sepsis.

Initial clinical experience with a sac-anchoring endoprosthesis for aortic aneurysm repair

OBJECTIVE All current aortic endografts depend on proximal and distal fixation to prevent migration. However, migration and rupture can occur, particularly in patients with aortic necks that are short or angulated, or both. We present our initial clinical experience with a new sac-anchoring endoprosthesis designed to anchor and seal the device within the aneurysm sac. METHODS The initial worldwide experience using a new endoprosthesis for the treatment of aortic aneurysms (Nellix Endovascular, Palo Alto, Calif) was reviewed. The endoprosthesis consists of dual balloon-expandable endoframes surrounded by polymer-filled endobags designed to obliterate the aneurysm sac and maintain endograft position. Clinical results and follow-up contrast computed tomography (CT) scans at 30 days and 6 and 12 months were reviewed. RESULTS The endograft was successfully deployed in 21 patients with infrarenal aortic aneurysms measuring 5.7 ± 0.7 cm (range, 4.3-7.4 cm). Two patients with common iliac aneurysms were treated with sac-anchoring extenders that maintained patency of the internal iliac artery. Infusion of 71 ± 37 mL of polymer (range, 19-158 mL) into the aortic endobags resulted in complete aneurysm exclusion in all patients. Mean implant time was 76 ± 35 minutes, with 33 ± 17 minutes of fluoroscopy time and 180 ± 81 mL of contrast; estimated blood loss was 174 ± 116 mL. One patient died during the postoperative period (30-day mortality, 4.8%), and one died at 10 months from non-device-related causes. During a mean follow-up of 8.7 ± 3.1 months and a median of 6.3 months, there were no late aneurysm- or device-related adverse events and no secondary procedures. CT imaging studies at 6 months and 1 year revealed no increase in aneurysm size, no device migration, and no new endoleaks. One patient had a limited proximal type I endoleak at 30 days that resolved at 60 days and remained sealed. One patient has an ongoing distal type I endoleak near the iliac bifurcation, with no change in aneurysm size at 12 months. CONCLUSION Initial clinical experience with this novel intrasac anchoring prosthesis is promising, with successful aneurysm exclusion and good short-term results. This new device platform has the potential to address the anatomic restrictions and limitations of current endografts. Further studies with a longer follow-up time are needed.

A sequence variant associated with sortilin-1 (SORT1) on 1p13.3 is independently associated with abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is a common human disease with a high estimated heritability (0.7); however, only a small number of associated genetic loci have been reported to date. In contrast, over 100 loci have now been reproducibly associated with either blood lipid profile and/or coronary artery disease (CAD) (both risk factors for AAA) in large-scale meta-analyses. This study employed a staged design to investigate whether the loci for these two phenotypes are also associated with AAA. Validated CAD and dyslipidaemia loci underwent screening using the Otago AAA genome-wide association data set. Putative associations underwent staged secondary validation in 10 additional cohorts. A novel association between the SORT1 (1p13.3) locus and AAA was identified. The rs599839 G allele, which has been previously associated with both dyslipidaemia and CAD, reached genome-wide significance in 11 combined independent cohorts (meta-analysis with 7048 AAA cases and 75 976 controls: G allele OR 0.81, 95% CI 0.76-0.85, P = 7.2 × 10(-14)). Modelling for confounding interactions of concurrent dyslipidaemia, heart disease and other risk factors suggested that this marker is an independent predictor of AAA susceptibility. In conclusion, a genetic marker associated with cardiovascular risk factors, and in particular concurrent vascular disease, appeared to independently contribute to susceptibility for AAA. Given the potential genetic overlap between risk factor and disease phenotypes, the use of well-characterized case-control cohorts allowing for modelling of cardiovascular disease risk confounders will be an important component in the future discovery of genetic markers for conditions such as AAA.

Massive nitrogen loss in critical surgical illness: effect on cardiac mass and function.

OBJECTIVE The authors measured cardiac mass and function to determine whether these changed in patients who were critically ill who were losing large amounts of nitrogen from the body. SUMMARY BACKGROUND DATA The large losses of body nitrogen that occur in patients with protein-energy malnutrition are associated with a loss of cardiac mass and function. It is not known if this also occurs in patients who were critically ill who are losing massive amounts of nitrogen. METHODS Once hemodynamically stable, 13 patients who were critically ill underwent sequential measurements of left ventricular mass (LVM) and function, total body nitrogen (TBN), total body potassium, body weight, fat-free mass, and limb muscle mass. RESULTS Over a 21-day study period, there was no change in LVM or function despite falls of 14% and 21% in TBN and total body potassium, respectively, a 21% fall in limb muscle mass, and a deterioration in skeletal muscle function by approximately 40%. CONCLUSIONS In patients who were critically ill, cardiac mass does not decrease and function does not deteriorate after hemodynamic stability has been achieved despite massive losses of protein from the body.

Endoluminal repair of a thoracic arch aneurysm using a scallop-edged stent-graft.

Purpose: To report a new technique of endoluminal thoracic aortic arch aneurysm repair using a scalloped stent-graft. Case Report: A 79-year-old man presented with a 7.5-cm thoracic aneurysm involving the inner curve of the aortic arch. Endoluminal repair was performed with a scalloped stent-graft that allowed perfusion of the brachiocephalic (innominate) artery. Preliminary extra-anatomical left common carotid and subclavian artery bypass grafting had been performed to allow coverage of the origins of these vessels. Conclusions: The use of fenestrated endoluminal grafts in the aortic arch can be achieved safely and may increase the treatment options for the high-risk patient.

Imaging After Nellix Endovascular Aneurysm Sealing: A Consensus Document

Endovascular aneurysm sealing (EVAS) using the Nellix system is a new and different method of abdominal aortic aneurysm repair. Normal postoperative imaging has unique appearances that change with time; complications also have different and specific appearances. This consensus document on the imaging findings after Nellix EVAS is based on the collective experience of the sites involved in the Nellix EVAS Global Forward Registry and the US Investigational Device Exemption Trial. The normal findings on computed tomography (CT), duplex ultrasound, magnetic resonance imaging, and plain radiography are described. With time, endobag appearances change on CT due to contrast migration to the margins of the hydrogel polymer within the endobag. Air within the endobag also has unique appearances that change over time. Among the complications after Nellix EVAS, type I endoleak usually presents as a curvilinear area of flow between the endobag and aortic wall, while type II endoleak is typically small and usually occurs where an aortic branch artery lies adjacent to an irregular aortic blood lumen that is not completely filled by the endobag. Procedural aortic injury is an uncommon but important complication that occurs as a result of overfilling of the endobags during Nellix EVAS. The optimum imaging surveillance algorithm after Nellix EVAS has yet to be defined but is largely CT-based, especially in the first year postprocedure. However, duplex ultrasound also appears to be a sensitive modality in identifying normal appearances and complications.

Predictive factors for limb occlusions after endovascular aneurysm repair

OBJECTIVE Greater flexibility and smaller sizes for introducer sheaths in the newest stent grafts increase the feasibility of endovascular aneurysm repair but raise concerns about long-term limb patency. The aim of the study was to determine the incidence of and predictive factors for limb occlusion after use of the Endurant stent graft (Medtronic Inc, Minneapolis, Minn) for abdominal aortic aneurysm. METHODS The Endurant Stent Graft Natural Selection Global Postmarket Registry (ENGAGE) prospectively included 1143 patients treated with bifurcated devices who were observed for up to 2 years. Limb occlusions were evidenced by computed tomography, angiography, or ultrasound. To predict stent graft limb occlusion, a two-step model-building technique was applied. We first identified predictors from a total of 47 covariates obtained at baseline and in the periprocedural period. Subsequently, we reduced the set of potential predictors to key factors that are clinically meaningful. To handle large numbers of covariates, we used the Classification And Regression Tree (CART) method. RESULTS Forty-two stent graft limbs occluded in 39 patients (3.4% of the patients). At 2 years, the rate of freedom from stent graft limb occlusion calculated by Kaplan-Meier plot was 97.9% (standard error [SE], 0.33%). Of the 42 occlusions, 13 (31%) were observed within 30 days and 30 (71%) within 6 months. The strongest independent predictors were distal landing zone on the external iliac artery, external iliac artery diameter ≤10 mm, and kinking. High-risk vs low-risk patients were identified according to a decision tree based on the strongest predictors. Freedom from stent graft limb occlusion was 96.1% (SE, 0.64%) in high-risk patients vs 99.6% (SE, 0.19%) in low-risk patients. CONCLUSIONS After Endurant stent grafting, the incidence of limb occlusion was low. Classifying patients as high risk vs low risk according to the algorithm used in this study may help define specific strategies to prevent limb occlusion and improve the overall results of endovascular aneurysm repair using the latest generation of stent grafts.

Antegrade Superficial Femoral Artery versus Common Femoral Artery Punctures for Infrainguinal Occlusive Disease

PURPOSE To compare the outcomes of planned superficial femoral artery (SFA) and common femoral artery (CFA) antegrade punctures in patients undergoing endovascular interventions for infrainguinal occlusive arterial disease in a single center. MATERIALS AND METHODS Between August 2010 and July 2011, consecutive patients who underwent antegrade puncture of CFA or SFA for infrainguinal occlusive disease were studied. Data including sheath size, rate of closure device usage, and complications relating to the arterial puncture were classified according to Society of Interventional Radiology (SIR) classification and analyzed retrospectively. RESULTS There were 199 antegrade arterial punctures, of which 28 (14%) were planned SFA punctures, performed in 184 patients. All patients had ultrasound-guided puncture. The sheath size ranged from 4 F to 8 F. In 2 of 28 (7%) SFA punctures, a closure device was deployed compared with 43 of 171 (25%) CFA punctures. Six bleeding complications were noted in the CFA puncture group (6 of 171 [3.5%]), of which 2 required urgent operations (repair of a pseudoaneurysm and evacuation of retroperitoneal hematoma). In comparison, only one minor groin hematoma was noted in the SFA puncture group; this did not require any further treatment. No thromboembolic complications were associated with SFA puncture. CONCLUSIONS Planned antegrade SFA puncture under ultrasound guidance can be performed safely in selected cases with no added morbidity. Interventionalists should have a low threshold for considering antegrade SFA puncture as a first-line access site, especially in patients with a hostile groin.

Use of an implantable needle guide to access difficult or impossible to cannulate arteriovenous fistulae using the buttonhole technique

Purpose The aim of this work was to assess the safety and efficacy of the VWING Vascular Needle Guide to assist in cannulation of difficult or impossible to access fistulae using the buttonhole cannulation technique. Methods VWING devices were surgically implanted into patients with difficult to access fistulae. A nondevice site and a device site were used to access the fistula and perform dialysis over a six month period. The device site utilized the buttonhole cannulation technique. The performance of each access site was recorded. Results VWING devices were implanted in nine patients. A total of 387 cannulations took place over 1367 study days. The device site was successfully used 94% of the time compared to 77% for the nondevice site. Cannulation success was comparable between the device and nondevice sites. Ease of insertion, pain during insertion and complication rates were also comparable. No interventions were required at the device site to maintain access compared with four interventions for the nondevice access site. Conclusions The VWING performed as intended by facilitating required repeated access to the vascular system and access for hemodialysis treatment. The study has demonstrated that the VWING is a potential solution for access to difficult to cannulate fistulae.

A Technique for Controlled Partial Closure of a Transjugular Intrahepatic Portosystemic Shunt Tract in a Patient with Hepatic Encephalopathy

A novel endovascular technique to reduce flow through a transjugular intrahepatic portosystemic shunt (TIPS) is described in a patient with severe hepatic encephalopathy. This technique allows controlled and potentially adjustable partial closure of the TIPS without thromboembolic risk. The patient experienced a dramatic clinical improvement after the procedure.