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OBJECTIVE The receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) signaling pathway (RANKL/RANK/OPG signaling) is implicated in the osteolysis associated with diabetic Charcot neuroarthropathy (CN); however, the links with medial arterial calcification (MAC) seen in people with CN are unclear. This study aimed to investigate the role of RANKL/OPG in MAC in patients with CN. RESEARCH DESIGN AND METHODS Enzyme-linked immunosorbent assay and Bio-plex multiarray technology were used to quantify a range of cytokines, including RANKL and OPG in sera from 10 patients with diabetes, 12 patients with CN, and 5 healthy volunteers. Human tibial artery segments were immunohistochemically stained with Alizarin red and human RANKL antibody. Human vascular smooth muscle cells (VSMCs) were also explanted from arterial segments for in vitro studies. RESULTS We demonstrate colocalization and upregulation of RANKL expression in areas displaying MAC. Systemic levels of RANKL, OPG, and inflammatory cytokines (interleukin-8, granulocyte colony–stimulating factor) were elevated in those with CN compared with diabetic patients and healthy control subjects. Human VSMCs cultured in CN serum showed accelerated osteoblastic differentiation (alkaline phosphatase activity) and mineralization (alizarin red staining) compared with cells treated with diabetic or control serum (P < 0.05). Coincubation with OPG, the decoy receptor for RANKL, attenuated osteogenic differentiation of VSMCs and was independent of a high calcium-phosphate milieu. The accelerated mineralization induced by RANKL and CN serum correlated with nuclear translocation of nuclear factor-κB, a process abrogated by OPG. CONCLUSIONS Our data provide direct evidence that RANKL/RANK/OPG signaling is modulated in patients with CN and plays a role in vascular calcification. This study highlights this pathway as a potential target for intervention.

Extending the proximal landing zone to facilitate endovascular repair of aortic aneurysms with short proximal necks using the chimney, top-fenestration, or snorkel technique has been previously reported. In addition, extending the distal landing zone using the periscope technique has also been recently described. In this study, we used an extended chimney technique, the “telescoping technique,” to successfully treat a ruptured Crawford type III thoracoabdominal aortic aneurysm in a patient with pre-existing renal failure and an occluded superior mesenteric artery.

6098 Background: CareFirst BlueCross BlueShield (CFBCBS) insurance network partnered with Cardinal Health Specialty Solutions (CHSS) to develop a cancer care pathway for network physicians in 2008. The program included a recommendation for molecular diagnostic testing with the Oncotype DX assay for pts with early-stage estrogen receptor-positive breast cancer. Based on NCCN guidelines, the pathway suggested adjuvant chemotherapy for all pts with Oncotype DX Recurrence Scores (RS) in the high-risk category. We aimed to determine the RS risk distribution among pts who received Oncotype DX testing and assess the patterns of care that followed. Methods: Using data from CFBCBS, CHSS proprietary claims software, and Genomic Health, we retrospectively identified a cohort of women with breast cancer who were treated on the CFBCBS clinical care pathways program from 8/2008 to 6/2011 and received Oncotype DX testing. We determined the number of pts with a RS value in the low- (RS

569 Background: Cardinal Health Specialty Solutions (CHSS) partners with payers to manage clinical care pathways in oncology and rheumatology. Observations from one such pathway with CareFirst BlueCross BlueShield revealed that pts with estrogen receptor-positive ESBC who underwent Oncotype DX testing and were found to have high-risk Recurrence Scores (RS) received less chemotherapy than expected. To better understand physician behavior as it relates to Oncotype DX testing, CHSS examined patterns of Oncotype DX use in a large private practice oncology group with a robust electronic medical record (EMR), Georgia Cancer Specialists (GCS). We aimed to determine the RS risk distribution among pts who received Oncotype DX testing and assess the patterns of care that followed. Methods: Using GCS EMR data from 2009 to 2011, the number of pts who were eligible to undergo Oncotype DX testing was compared to the number of pts who underwent testing. Pts were considered eligible for testing if they had node-negative, estrogen receptor-positive, HER2-negative ESBC. We determined the number of pts with a RS value in the low- (RS

571 Background: Cardinal Health Specialty Solutions (CHSS) partners with payers to manage clinical care pathways in oncology and rheumatology. Observations from one such pathway with CareFirst BlueCross Blue Shield revealed lower than expected use of CT in patients (pts) with estrogen receptor-positive early-stage breast cancer (ESBC) at high-risk for recurrence by ODX RS. To better understand physician behavior, CHSS examined patterns of care in a large private practice oncology group with a robust EMR, Georgia Cancer Specialists (GCS). Pt characteristics and physician-prescribing patterns were analyzed to determine variables that most impacted the physician’s decision to treat high-risk pts with CT. Methods: Using the GCS EMR from 2009 to 2011, we retrospectively identified pts with ESBC (stage I-II, node-negative, estrogen receptor-positive, HER2-negative) who underwent ODX testing. We determined the number of pts with a RS value in the low- (RS 66 y. CT use in high-risk pts was 82% and 86% in pts with tumor sizes 60% of the time. There were no significant differences in patterns of CT use. Conclusions: The less than expected use of CT in high-risk patients appears to be related to physician preference and pt age. Tumor size and grade did not appear to influence choice of therapy.

e11002 Background: Cardinal Health Specialty Solutions (CHSS) partners with payers to manage clinical care pathways in oncology and rheumatology. Observations from one such pathway with CareFirst BlueCross Blue Shield revealed that in patients with estrogen receptor-positive early-stage breast cancer (ESBC), there was an underuse of Oncotype DX testing. To better understand physician behavior as it relates to Oncotype DX testing, CHSS examined patterns of Oncotype DX use in a large private practice oncology group with a robust electronic medical record (EMR), Georgia Cancer Specialists (GCS). We aimed to determine the variables that most impacted the use of Oncotype DX testing. Methods: Using the GCS EMR from 2009 to 2011, we retrospectively identified patients diagnosed with ESBC who were eligible for Oncotype DX testing (stage I-II, node-negative, estrogen receptor-positive, HER2-negative). The use of Oncotype DX testing was analyzed by patient age, tumor size, tumor grade, and physician prescribing patterns. Results: Of the 1908 patients identified with ESBC, 788 were eligible for Oncotype DX testing and 288 (37%) underwent testing. In an analysis by age, Oncotype DX was utilized in 34% of patients ≤ 45 years, 49% in patients 46-55 years, 37% in patients 56-65 years, 34% in patients 66-75 years, and 13% in patients > 75 years old. Oncotype DX use was 37% and 36% in patients with tumor sizes 60% of the time. There were no significant differences in patterns of chemotherapy use. Conclusions: Based on this analysis, eligible patients with ESBC between 46-55 years of age, with small and intermediate sized tumors (

Repeated ischemic insults at one hour intervals result in more severe neuronal damage than a single similar duration insult. The mechanism for the more severe damage with repetitive ischemia is not fully understood. We hypothesized that the prolonged reperfusion periods between the relatively short ischemic insults may result in a pronounced generation of oxygen free radicals (OFRs). In this study, we tested the protective effects of superoxide dismutase (SOD) and catalase (alone or in combination), and U78517F in a gerbil model of repetitive ischemia. Three episodes (two min each) of bilateral carotid occlusion were used at one hour intervals to produce repetitive ischemia. Superoxide dismutase and catalase were infused via osmotic pumps into the lateral ventricles. Two doses of U78517F were given three times per animal, one half hour prior to each occlusion. Neuronal damage was assessed 7 days later in several brain regions using the silver staining technique. The Mann-Whitney U test was used for statistical comparison. Superoxide dismutase showed significant protection in the hippocampus (CA4), striatum, thalamus and the medial geniculate nucleus (MGN). Catalase showed significant protection in the striatum, hippocampus, thalamus, and MGN and the substantia nigra reticulata. Combination of the two resulted in additional protection in the cerebral cortex. Compared to the controls, there was little protection with a dose of 3 mg/kg of U78517F. There was significant protection with a dose of 10 mg/kg in the hippocampus (CA4), striatum, thalamus, medial geniculate nucleus and the substantia nigra reticulata. The significant protection noted with SOD, catalase or U78517F with repeated ischemia supports, the hypothesis that OFRs may play a role in neuronal damage in repeated cerebral ischemia.

Le prolongement de la zone proximale d'atterrissage pour faciliter la reparation endovasculaire des anevrysmes de l'aorte avec des collets proximaux courts en utilisant la cheminee, la fenestration, ou la technique de prise d'air a ete precedemment rapportee. En outre, l'elargissement de la zone distale d'atterrissage en utilisant la technique du periscope a egalement a ete recemment decrit. Dans cette etude, nous avons employe une technique prolongee de la cheminee, « technique de telescopage » pour traiter avec succes un anevrysme rompu de l'aorte thoracoabdominal type III de Crawford chez un patient en insuffisance renale et avec une artere mesenterique superieure occluse.

Load-deformation data were used to determine the strength of healing abdominal incisions in dogs at 7, 14, and 21 days after wounding. The breaking energy of paramedian incisions closed by suturing the internal and external leaves of the sheath of the rectus abdominis muscle vs. incisions closed by suturing the external leaf only was similar in the 12 dogs studied. Closure of abdominal incisions by suturing only the external leaf of the rectus sheath provided wound strength comparable to the traditional method.