Citations

Background— Whether mechanical dyssynchrony indices predict reverse remodeling (RR) or clinical response to cardiac resynchronization therapy (CRT) remains controversial. This prospective study evaluated whether echocardiographic dyssynchrony indices predict RR or clinical response after CRT. Methods and Results— Of 184 patients with heart failure with anticipated CRT who were prospectively enrolled, 131 with wide QRS and left ventricular ejection fraction <35% had 6-month follow-up after CRT implantation. Fourteen dyssynchrony indices (feasibility) by M-mode (94%), tissue velocity (96%), tissue Doppler strain (92%), 2D speckle strain (65% to 86%), 3D echocardiography (79%), and timing intervals (98%) were evaluated. RR (end-systolic volume reduction ≥15%) occurred in 55% and more frequently in patients without (71%) than in patients with (42%) ischemic cardiomyopathy ( P =0.002). Overall, only M-mode, tissue Doppler strain, and total isovolumic time had a receiver operating characteristic area under the curve (AUC) greater than the line of no information, but none of these were strongly predictive of RR (AUC, 0.63 to 0.71). In nonischemic cardiomyopathy, no dyssynchrony index predicted RR. In ischemic cardiomyopathy, M-mode (AUC, 0.67), tissue Doppler strain (AUC, 0.79), and isovolumic time (AUC, 0.76) -derived indices predicted RR ( P <0.05 for all), although the incremental value was modest. No indices predicted clinical response assessed by Minnesota Living with Heart Failure Questionnaire, 6-minute walk distance, and peak oxygen consumption. Conclusions— These findings are consistent with the Predictors of Response to CRT study and do not support use of these dyssynchrony indices to guide use of CRT.

Background— Contrast-induced nephropathy (CIN) is associated with significant morbidity and mortality. The objective of our meta-analysis was to assess the efficacy of iodixanol compared with low-osmolar contrast media (LOCM) for prevention of CIN. Methods and Results— We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and internet sources of cardiology trial results for individual and relevant reviews of randomized, controlled trials, for the terms contrast media, contrast nephropathy, renal failure, iodixanol, Visipaque, and low-osmolar contrast media. All studies reported an incidence rate of CIN for each study group; there was no restriction on the definition of CIN. There were no restrictions on journal type or patient population. Overall, 36 trials were identified for analysis of aggregated summary data on 7166 patients; 3672 patients received iodixanol and 3494 patients received LOCM. Overall, iodixanol showed no statistically significant reduction in CIN incidence below that observed with heterogeneous comparator agents ( P =0.11). Analysis of patient subgroups revealed that there was a significant benefit of iodixanol when compared with iohexol alone (odds ratio, 0.25; 95% confidence interval, 0.11 to 0.55; P <0.001) but not when compared with LOCM other than iohexol or with other ionic dimers or among patients receiving intra-arterial contrast injections or among patients undergoing coronary angiography with or without percutaneous intervention. Conclusions— Analysis of aggregated summary data from multiple randomized, controlled trials of iodixanol against diverse LOCMs for heterogeneous procedures and definitions of CIN show an iodixanol-associated reduction that is suggestive but statistically nonsignificant.

Abstract Reflux-induced injury promotes esophageal adenocarcinoma, one of the most rapidly increasing, highly lethal cancers in Western countries. Here, we investigate the efficacy of a combinatorial chemoprevention strategy for esophageal adenocarcinoma and characterize the underlying molecular mechanisms. Specifically, our approach involves the use of ursodeoxycholic acid (Urso) due to its ability to decrease injury-inducing bile salts in combination with Aspirin to mitigate the consequences of injury. We find that Urso-Aspirin combination reduces the risk of adenocarcinoma in vivo in animals with reflux, decreases the proliferation of esophageal adenocarcinoma cells, and downregulates a key cell cycle regulator, CDK2. Mechanistically, using cell growth, luciferase reporter, expression, and chromatin immunoprecipitation assays, we identify GLI1, a Hedgehog-regulated transcription factor, as a novel target of Urso-Aspirin combination. We show that GLI1 is upregulated during esophageal carcinogenesis, and GLI1 can bind to the CDK2 promoter and activate its expression. Although the Urso-Aspirin combination downregulates GLI1, the GLI1 overexpression not only abrogates the effect of this combination on proliferation but it also restores CDK-2 expression. These findings support that the chemopreventive effect of the Urso-Aspirin combination occurs, at least in part, through a novel GLI1-CDK2–dependent mechanism. To further understand the regulation of CDK2 by GLI1, both pharmacologic and RNAi-mediated approaches show that GLI1 is a transcriptional activator of CDK2, and this regulation occurs independent of Smoothened, the central transducer of the Hedgehog canonical pathway. Collectively, these results identify a novel GLI1-to-CDK2 pathway in esophageal carcinogenesis, which is a bona fide target for effective combinatorial chemoprevention with Urso and Aspirin. Cancer Res; 70(17); 6787–96. ©2010 AACR.

Mechanical ventricular assistance has become a reliable tool for the support of children and infants with heart failure. The devices have shown efficacy both as a bridge to transplantation and as a bridge to recovery. The potential complications that may occur with long-term support have not been fully described. This article reports the occurrence of a large pseudoaneurysm associated with the ascending aorta following explantation of the EXCOR Pediatric ventricular assist device. A management strategy for this potentially lethal complication is described.

Irreparable mitral pathology may lead to early mitral valve replacement (MVR) in children. Often, a small mechanical prosthesis (<23 mm) is required, raising concerns about annular growth in patients who may eventually require subsequent mitral valve re-replacement (MVRR). The aim of this study was to evaluate interval mitral annular growth in this cohort. Between January 1972 and December 2006, 164 children underwent MVR with a mechanical prosthesis; 110 of these children (median age, 4 years; range, 7 days to 14 years) received a small mechanical prosthesis (<23 mm). The most common diagnoses were congenital mitral stenosis (10%), regurgitation (46%), and left atrioventricular valve dysfunction after previous atrioventricular septal defect repair (44%). The cohort was analyzed for age, body surface area (BSA), prosthesis size, and Z score at the time of MVR and MVRR. At the time of MVR, 78 patients had a BSA of 0.77 ± 0.06 m2, had an annular size of 24 ± 0.62 mm ( Z score, 2.91 ± 0.23), and ultimately did not require MVRR. Another cohort, who eventually did require MVRR (n = 24), had an initial BSA at the time of MVR of 0.62 ± 0.05 m2 ( P = NS vs MVR only) and an annular size of 20 ± 0.49 mm ( Z score, 1.85 ± 0.22) ( P = .008 vs MVR only). In the interval between MVR and MVRR (7.8 ± 1.1 years), BSA increased to 1.12 ± 0.07 m2, and annulus size increased to 24 ± 0.47 mm ( Z score, 1.80 ± 0.28). These data suggest growth of the mitral annulus following MVR with a small mechanical prosthesis, as evidenced by an unchanged Z score in the setting of normal interval increase in BSA. Additionally, there was a statistically significant difference in initial Z scores between the cohorts requiring MVRR and those who have not needed re-replacement, suggesting that the feasibility of placement of a slightly larger prosthesis may be associated with a decreased need for MVRR.

Purpose We determined whether the association between breast density and breast cancer risk and cancer severity differs according to menopausal status and postmenopausal hormone therapy (HT) use. Methods We collected data on 587,369 women who underwent 1,349,027 screening mammography examinations; 14,090 women were diagnosed with breast cancer. We calculated 5-year breast cancer risk from a survival model for subgroups of women classified by their Breast Imaging Reporting and Data System (BIRADS) breast density, age, menopausal status, and current HT use, assuming a body mass index of 25 kg/m 2 . Odds of advanced (ie, IIb, III, IV) versus early (ie, I, IIa) stage invasive cancer was calculated according to BIRADS density. Results Breast cancer risk was low among women with low density (BIRADS-1): women age 55 to 59 years, 5-year risk was 0.8% (95% CI, 0.6 to 0.9%) for non-HT users and 0.9% (95% CI, 0.7% to 1.1%) for estrogen and estrogen plus progestin users. Breast cancer risk was high among women with very high density (BIRADS-4), particularly estrogen plus progestin users: women age 55 to 59 years, 5-year risk was 2.4% (95% CI, 2.0% to 2.8%) for non-HT users, 3.0% (95% CI, 2.6% to 3.5%) for estrogen users, and 4.2% (95% CI, 3.7% to 4.6%) for estrogen plus progestin users. Advanced-stage breast cancer risk was increased 1.7-fold for postmenopausal HT users who had very high density (BIRADS-4) compared to those with average density (BIRADS-2). Conclusion Postmenopausal women with high breast density are at increased risk of breast cancer and should be aware of the added risk of taking HT, especially estrogen plus progestin.

The current study sought to provide practical information for the clinical use of child and parent reports of child anxiety symptoms by investigating agreement between parent, child, and clinician as well as the predictive value of this information. Examining 88 anxious children and their parents, the study compared agreement by correlating parent and child responses on the Spence Children’s Anxiety Scale (SCAS); comparing parent and child responses to clinician data operationalized through continuous and dichotomous variables from the Anxiety Disorder Interview Schedule for Children; and examining the relative clinical utility of parent and child reports on the SCAS in terms of positive and negative predictive value. Results indicated that parent and child agreement on the SCAS was moderate to high for most anxiety disorder symptoms and that both were generally consistent with clinician impressions. Moreover, both child and parent provided unique information to the diagnostic process.