Citations

Background: The use of breast magnetic resonance imaging (MRI) for screening high-risk patients is well established. However, the role of MRI as a diagnostic problem-solving tool is less well studied. With the increasing availability of MRI, its use for problem solving has increased. This small retrospective study examines the use and utility of breast MRI in evaluating palpable breast masses with negative diagnostic mammogram and ultrasound studies. Methods: We reviewed our breast MRI database, selecting breast MRI studies performed to assess palpable abnormalities with negative mammogram and ultrasound findings. Evidence of cancer was determined by biopsy. Results: Seventy-seven studies were included, comprising 1.3% of all breast MRI studies performed at our institution during the study period (2005–2011). Twenty-two patients underwent biopsy, and 55 were followed clinically without biopsy. Approximately half (27 of 55) of the patients without biopsy were lost to follow-up after negative MRI, and the rest had no evidence of cancer on imaging or clinical examination at 1 year. Of the 22 patients who underwent biopsy, 2 were diagnosed with cancer, both with positive MRI studies. Sensitivity of MRI when compared to tissue diagnosis was 100%, and specificity was 70%. Positive and negative predictive values were 25% and 100%, respectively. Conclusions: When used for evaluation of a palpable breast mass with negative traditional imaging, breast MRI likely offers low yield of cancer diagnosis and low specificity. Negative MRI results may cause a low compliance rate for recommended follow-up. Because a biopsy is indicated for persistent palpable masses, the addition of diagnostic MRI only adds another step, with associated costs and burdens.

Revascularization improves blood pressure but not renal function in most patients with atherosclerotic renal artery stenosis (ARAS), possibly related to injury incurred during renal reperfusion. Bendavia, a novel tetrapeptide that inhibits mitochondrial permeability transition pore opening, reduces apoptosis, oxidative stress, and ischemia-reperfusion injury in experimental models. However, its potential for improving renal response to revascularization of chronic ARAS is unknown. We hypothesized that adjunct Bendavia would improve renal structure and function after percutaneous transluminal renal angioplasty (PTRA). Pigs were treated after 6 weeks of ARAS or control with PTRA+stenting (or sham), adjunct continuous 4-hour infusion of Bendavia (0.05 mg/kg IV) or vehicle (n=7 each) during PTRA. Single-kidney renal blood flow and glomerular filtration rate were studied 4 weeks later and renal mitochondrial biogenesis, microvascular architecture, and injurious pathways evaluated ex vivo. Monocyte chemoattractant protein-1 levels rose after PTRA, suggesting inflammatory injury. Bendavia did not immediately affect inflammatory cytokine levels, yet 4 weeks later, stenotic kidney renal blood flow and glomerular filtration rate both improved (44.00 ± 0.21% and 36.40 ± 10.21%, respectively) in ARAS+PTRA+Bendavia compared with ARAS+PTRA+vehicle. Renal mitochondrial biogenesis was restored after PTRA+Bendavia, and microvascular rarefaction, apoptosis, oxidative stress, tubular injury, and fibrosis decreased. Infusion of Bendavia during PTRA preserved mitochondrial biogenesis, renal hemodynamics, and function, and attenuated tissue injury in swine ARAS. Thus, functional mitochondrial injury during renal reperfusion may sustain renal inflammatory injury and limit kidney recovery after PTRA. Potent antiapoptotic and antioxidant effects provide Bendavia a novel therapeutic potential for improving kidney outcomes after PTRA in experimental ARAS.

ObjectiveOur aim was to identify patient and procedure characteristics that correlate with increased likelihood of bleeding during and after endoscopic mucosal resection (EMR), and thus anticipate the need for preventative therapy.MethodsThis was a retrospective, observational, descriptive study using a prospective EMR database, performed in a tertiary‐care center. A total of 935 EMR of various locations within the gastrointestinal tract were collected. The main outcome measurement was early bleeding (occurring during the procedure) and delayed bleeding (occurring after the completion of the procedure and up to 30 days after).ResultsEarly bleeding occurred in 5.3% (50/935) of the procedures. In multivariate logistic regression analysis, esophageal EMR (OR 2.5, 95% CI 1.2–5, P = 0.0009) and increase in lesion size (OR 1.24, 95% CI 1.1–1.5, P = 0.003) were both associated with higher odds of early bleeding in EMR when controlling for age, gender and non‐steroidal anti‐inflammatory drugs (NSAIDs)/clopidogrel use. Delayed bleeding occurred after 3.1% (n = 29) of the procedures. Of these, 86.2% (25/29) required hospital admission and endoscopic intervention to confirm and/or treat bleeding site. In multivariate logistic regression analysis, increased lesion size (OR 1.3, 95% CI 1.1–1.5, P = 0.004) was associated with higher incidence of delayed bleeding post‐EMR.ConclusionsIn experienced hands bleeding during and after EMR appears to be uncommon. Larger lesions are at increased risk of early and delayed bleeding.

Abstract Background: Non-Hodgkin lymphoma (NHL) is a malignancy of lymphocytes, and there is growing evidence for a role of germline genetic variation in immune genes in NHL etiology. Methods: To identify susceptibility immune genes, we conducted a 2-stage analysis of single-nucleotide polymorphisms (SNP) from 1,253 genes using the Immune and Inflammation Panel. In Stage 1, we genotyped 7,670 SNPs in 425 NHL cases and 465 controls, and in Stage 2 we genotyped the top 768 SNPs on an additional 584 cases and 768 controls. The association of individual SNPs with NHL risk from a log-additive model was assessed using the OR and 95% confidence intervals (CI). Results: In the pooled analysis, only the TAP2 coding SNP rs241447 (minor allele frequency = 0.26; Thr655Ala) at 6p21.3 (OR = 1.34, 95% CI 1.17–1.53) achieved statistical significance after accounting for multiple testing (P = 3.1 × 10−5). The TAP2 SNP was strongly associated with follicular lymphoma (FL, OR = 1.82, 95%CI 1.46–2.26; p = 6.9 × 10−8), and was independent of other known loci (rs10484561 and rs2647012) from this region. The TAP2 SNP was also associated with diffuse large B-cell lymphoma (DLBCL, OR = 1.38, 95% CI 1.08–1.77; P = 0.011), but not chronic lymphocytic leukemia (OR = 1.08; 95% CI 0.88–1.32). Higher TAP2 expression was associated with the risk allele in both FL and DLBCL tumors. Conclusion: Genetic variation in TAP2 was associated with NHL risk overall, and FL risk in particular, and this was independent of other established loci from 6p21.3. Impact: Genetic variation in antigen presentation of HLA class I molecules may play a role in lymphomagenesis. Cancer Epidemiol Biomarkers Prev; 21(10); 1799–806. ©2012 AACR.

Objective— Endothelial cell (EC) inflammatory status is critical to many vascular diseases. Emerging data demonstrate that mutations of Krüppel-like factor-11 (KLF11), a gene coding maturity-onset diabetes mellitus of the young type 7 ( MODY7 ), contribute to the development of neonatal diabetes mellitus. However, the function of KLF11 in the cardiovascular system still remains to be uncovered. In this study, we aimed to investigate the role of KLF11 in vascular endothelial inflammation. Methods and Results— KLF11 is highly expressed in vascular ECs and induced by proinflammatory stimuli. Adenovirus-mediated KLF11 overexpression inhibits expression of tumor necrosis factors-α–induced adhesion molecules. Moreover, small interfering RNA–mediated KLF11 knockdown augments the proinflammatory status in ECs. KLF11 inhibits promoter activity of adhesion molecules induced by tumor necrosis factor-α and nuclear factor-κB p65 overexpression. Mechanistically, KLF11 potently inhibits nuclear factor-κB signaling pathway via physical interaction with p65. Furthermore, KLF11 knockdown results in increased binding of p65 to vascular cell adhesion molecule-1 and E-selectin promoters. At the whole organism level, KLF11 −/− mice exhibit a significant increase in leukocyte recruitment to ECs after lipopolysaccharide administration. Conclusion— Taken together, our data demonstrate for the first time that KLF11 is a suppressor of EC inflammatory activation, suggesting that KLF11 constitutes a novel potential molecular target for inhibition of vascular inflammatory diseases.