Citations

Stent-grafts are ideally terminated within the common iliac artery (CIA). However, CIA ectasia may require hypogastric artery occlusion, with stent-graft extension to the external iliac artery. Alternatively, the diameter of the distal stent-graft may be increased, or flared, to allow exclusion of the abdominal aortic aneurysm. This report details the authors’ experience with this technique. Forty-one patients received bifurcated stent-grafts (BSG): 20 received an AneuRx device, and 21 received a Zenith device. CIA ectasia (diameter 15–25 mm) was treated with a distal flare of 2–4 mm greater than the CIA diameter. Patients were followed up with computed tomography scan at 1, 6, and 12 months. Statistical analysis was performed using ANOVA within groups and unpaired two-tailed t test between groups. A p value of <0.05 was considered significant. Eight of 20 patients (40%) (11 CIA) received an AneuRx device and 13/21 (62%) (17 CIA) received a Zenith device, with a distal flare. Values are (n) mean (mm) ± SE. There were no deaths, endoleaks, migrations, or conversions to open repair. Follow-up mean was 24.7 and 20.6 (range 15–28) months for AneuRx and Zenith groups, respectively. In comparing initial and 12-month CIA diameters, AneuRx grafts 20 ±0.8 vs 21.5 ±1.0 were not significantly different, p= 0.2, nor was the same comparison for Zenith, 17 ±0.5 vs 19.1 ±0.4, significant, p= 0.57. At a mean follow-up of 12 months, distal flare of iliac limbs with either AneuRx or Zenith devices affords a seal for CIA ectasia and/or aneurysms complicating EVAR.

Abstract Background: The American Heart Association (AHA) case definition for acute myocardial infarction (AMI) requires an “adequate set” of biomarkers: 2 measurements of the same marker at least 6 h apart. A sensitive troponin assay might detect significant changes in concentration earlier. We determined AMI prevalence, using protocols with shorter intervals between measurements, with and without incorporating the time from onset of symptoms. Methods: The AHA case definition was used to retrospectively assign a diagnosis in 258 patients presenting to the emergency department with symptoms of cardiac ischemia. AMI was diagnosed if either specimen in an adequate set had a cardiac troponin I (cTnI) above the 99th percentile (AccuTnI® &gt;0.04 μg/L; Beckman Coulter) with a ≥20% change in concentration between specimens. We assessed positivity for AMI after progressively decreasing the time interval between specimens in specimen sets. In addition, for each patient, 2 additional specimen pairs were selected: pairs collected at least 1 h apart with 1 specimen being either ≥3 h after onset or ≥6 h after onset. Results: When we used the AHA definition, the AMI prevalence was 35.7%. Prevalence was not significantly diminished when the interval between specimens was ≥5, ≥4, or ≥3 h (36.4%, 34.5%, and 33.7%, respectively) compared with the AHA ≥6 h interval. When the time from onset of symptoms was included in the specimen selection algorithm, a 1-h interval was sufficient provided that at least one specimen was collected ≥6 h after onset (prevalence, 34.1%; P = 0.48 vs AHA definition). Conclusion: A sensitive cTnI assay in specimen sets with time intervals ≥3 h, or having one specimen ≥6 h after onset, gave an AMI prevalence equivalent to the AHA definition.

AbstractMetastatic renal cell carcinoma (RCC) is an aggressive disease refractory to most existing therapeutic modalities. Identifying new markers for disease progression and drug targets for RCC will benefit this unmet medical need. We report a subset of clear cell and papillary cell RCC aberrantly expressing the lymphocyte activation marker CD70, a member of the tumor necrosis factor superfamily. Importantly, CD70 expression was found to be maintained at the metastatic sites of RCC. Anti-CD70 antibody-drug conjugates (ADC) consisting of auristatin phenylalanine phenylenediamine (AFP) or monomethyl auristatin phenylalanine (MMAF), two novel derivatives of the anti-tubulin agent auristatin, mediated potent antigen-dependent cytotoxicity in CD70-expressing RCC cells. Cytotoxic activity of these anti-CD70 ADCs was associated with their internalization and subcellular trafficking through the endosomal-lysosomal pathway, disruption of cellular microtubule network, and G2-M phase cell cycle arrest. The efficiency of drug delivery using anti-CD70 as vehicle was illustrated by the much enhanced cytotoxicity of antibody-conjugated MMAF compared with free MMAF. Hence, ADCs targeted to CD70 can selectively recognize RCC, internalize, and reach the appropriate subcellular compartment(s) for drug release and tumor cell killing. In vitro cytotoxicity of these ADCs was confirmed in xenograft models using RCC cell lines. Our findings provide evidence that CD70 is an attractive target for antibody-based therapeutics against metastatic RCC and suggest that anti-CD70 ADCs can provide a new treatment approach for advanced RCC patients who currently have no chemotherapeutic options. (Cancer Res 2006; 66(4): 2328-37)