Heterogeneity of mammary lesions represent molecular differences

BACKGROUND: Human breast cancer is a heterogeneous disease, histopathologically, molecularly and phenotypically. The molecular basis of this heterogeneity is not well understood. We have used a mouse model of DCIS that consists of unique lines of mammary intraepithelial neoplasia (MIN) outgrowths, the premalignant lesion in the mouse that progress to invasive carcinoma, to understand the molecular changes that are characteristic to certain phenotypes. Each MIN-O line has distinguishable morphologies, metastatic potentials and estrogen dependencies. METHODS: We utilized oligonucleotide expression arrays and high resolution array comparative genomic hybridization (aCGH) to investigate whole genome expression patterns and whole genome aberrations in both the MIN-O and tumor from four different MIN-O lines that each have different phenotypes. From the whole genome analysis at 35 kb resolution, we found that chromosome 1, 2, 10, and 11 were frequently associated with whole chromosome gains in the MIN-Os. In particular, two MIN-O lines had the majority of the chromosome gains. Although we did not find any whole chromosome loss, we identified 3 recurring chromosome losses (2F1-2, 3E4, 17E2) and two chromosome copy number gains on chromosome 11. These interstitial deletions and duplications were verified with a custom made array designed to interrogate the specific regions at approximately 550 bp resolution. RESULTS: We demonstrated that expression and genomic changes are present in the early premalignant lesions and that these molecular profiles can be correlated to phenotype (metastasis and estrogen responsiveness). We also identified expression changes associated with genomic instability. Progression to invasive carcinoma was associated with few additional changes in gene expression and genomic organization. Therefore, in the MIN-O mice, early premalignant lesions have the major molecular and genetic changes required and these changes have important phenotypic significance. In contrast, the changes that occur in the transition to invasive carcinoma are subtle, with few consistent changes and no association with phenotype. CONCLUSION: We propose that the early lesions carry the important genetic changes that reflect the major phenotypic information, while additional genetic changes that accumulate in the invasive carcinoma are less associated with the overall phenotype

Crop pests and predators exhibit inconsistent responses to surrounding landscape composition

The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win–win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies

Society for Vascular Surgery Vascular Registry evaluation of stent cell design on carotid artery stenting outcomes

ObjectiveThe Society for Vascular Surgery (SVS) Vascular Registry (VR) collects data on outcomes of carotid endarterectomy and carotid artery stenting (CAS). The purpose of this study was to evaluate the impact of open vs closed cell stent design on the in-hospital and 30-day outcome of CAS.MethodsThe VR collects provider-reported data on patients using a Web-based database. Data were analyzed both in-hospital and at 30 days postprocedure. The primary outcome is combined death/stroke/myocardial infarction (MI).ResultsAs of October 14, 2009, there were 4337 CAS with discharge data and 2397 with 30-day data. Open cell stents (OPEN) were used in 3451 patients (79.6%), and closed cell stents (CLOSED) were used in 866 patients (20.4%). Baseline demographics showed no differences in age, gender, race, and ethnicity. However, the OPEN group had more patients with atherosclerosis (74.5% vs 67.4%; P = .0003) as the etiology of carotid artery disease. The OPEN group also had a higher prevalence of preprocedural stroke (25.8% vs 21.4%; P = .0079), chronic obstructive pulmonary disease (COPD; 21.0% vs 17.6%; P = .0277), cardiac arrhythmia (14.7% vs 11.4%; P = .0108), valvular heart disease (7.4% vs 3.7%; P < .0001), peripheral vascular disease (PVD; 40.0% vs 35.3%; P = .0109), and smoking history (59.0% vs 54.1%; P = .0085). There are no statistically significant differences in the in-hospital or 30-day outcomes between the OPEN and CLOSED patients. Further subgroup analyses demonstrated symptomatic patients had a higher event rate than the asymptomatic cohort in both the OPEN and CLOSED groups. Among symptomatic patients, the OPEN patients had a lower (0.43% vs 1.41%; P = .0349) rate of in-hospital mortality with no difference in stroke or transient ischemic attack (TIA). There were no differences in 30-day event rates. In asymptomatic patients, there were also no statistically significant differences between the OPEN and CLOSED groups. After risk adjustment, there remained no statistically significant differences between groups of the primary endpoint (death/stroke/MI) during in-hospital or 30 days.ConclusionIn-hospital and 30-day outcomes after CAS were not significantly influenced by stent cell design. Symptomatic patients had higher adverse event rates compared to the asymptomatic cohort. As there is no current evidence of differential outcome between the use of open and closed cell stents, physicians should continue to use approved stent platforms based on criteria other than stent cell design

Aggressive Renal Angiomyolipoma of the Lipomatous Variant With Inferior Vena Cava Thrombus: A Case Report and Review of the Literature

Two variants of renal angiomyolipoma (AML)—classic and epithelioid—have been described. Although the epithelioid variant has been reported to demonstrate an aggressive clinical behavior, classic AML is usually benign. Herein, we report a case of a 42-year-old asymptomatic woman with a lipomatous variant of renal AML associated with an inferior vena cava thrombus managed with radical nephrectomy and caval thrombectomy

Infections of Prosthetic Grafts and Patches Used for Infrainguinal Arterial Reconstructions.

BACKGROUND: Prosthetic grafts are often used as alternative conduits in patients with peripheral vascular disease who do not have an adequate autologous vein for bypass. Prosthetic grafts, unfortunately, carry an increased risk of infection and are associated with increased morbidity and mortality. The goal of this study was to identify potential risk factors and subsequent outcomes associated with lower extremity prosthetic graft infections. METHODS: Two hundred seventy-two lower extremity prosthetic bypasses and patches were performed at an academic medical center between 2014 and 2016. A retrospective review of patients\u27 demographics, comorbidities, indication for surgery, type of procedures performed, and procedural characteristics was conducted. Outcomes, including limb loss and mortality, were analyzed. RESULTS: Forty-three (15.8%) patients with graft infections were identified during a median follow-up of 668 days (interquartile range [IQR] = 588). The median time to graft infection was 43 days (IQR = 85) with Staphylococcus being the most common bacteria cultured. Infections were associated with a 30.2% rate of limb loss and a 34.9% rate of mortality. The risk of infection was 2.4 times greater among those with a history of redo surgery (95% confidence interval [CI] of the hazard ratio [HR]: 1.3, 4.3) and 2.1 times greater in women (95% CI: 1.1, 3.8), by multivariable statistics. A 1 g/dL increase in albumin level was associated with a 33.5% decrease in hazard of infection (HR: 0.67, 95% CI: 0.46, 0.96) in the multivariable model. The estimated cumulative incidence of infection for female patients with hypertension and mean albumin of 3.36 undergoing redo surgery was 19.4% at 30 days after surgery (95% CI: 10.6, 35.6) and 39.9% at 1 year (95% CI: 26.8, 59.3). CONCLUSIONS: Female gender, redo surgery, and malnutrition are associated with increased risk of prosthetic graft infections leading to a high rate of limb loss and mortality. Endovascular interventions and bypasses with vein conduits should be considered in these patients

Transradial access for balloon-assisted maturation of arteriovenous fistulas

Balloon-assisted maturation (BAM) of arteriovenous fistulas has conventionally been performed via direct fistula access. The transradial approach has not been well described for BAM, although its use has been reported throughout the cardiology literature. The purpose of the present study was to assess the outcomes of transradial access for its use with BAM. A retrospective review of 205 patients with transradial access for BAM was performed. One sheath was inserted into the radial artery distal to the anastomosis. We have described the procedural details, complications, and outcomes. The procedure was considered technically successful if transradial access had been established and the AVF had been ballooned with at least one balloon without major complications. The procedure was considered clinically successful if no further interventions had been required for AVF maturation. The average time for BAM via transradial access was 35 ± 20 minutes, with 31 ± 17 mL of contrast used. No access-related perioperative complications, including access site hematoma, symptomatic radial artery occlusion, or fistula thrombosis, had occurred. The technical success rate was 100%, and the rate of clinical success was 78%, with 45 patients requiring additional procedures to achieve maturation. Transradial access is an efficient alternative to trans-fistula access for BAM. It is technically easier and allows for better visualization of the anastomosis