Virtual Resection: A New Tool for Preparing for Nephron-Sparing Surgery in Wilms Tumor Patients

Nephron-sparing surgery (NSS) in Wilms tumor (WT) patients is a surgically challenging procedure used in highly selective cases only. Virtual resections can be used for preoperative planning of NSS to estimate the remnant renal volume (RRV) and to virtually mimic radical tumor resection. In this single-center evaluation study, virtual resection for NSS planning and the user experience were evaluated. Virtual resection was performed in nine WT patient cases by two pediatric surgeons and one pediatric urologist. Pre- and postoperative MRI scans were used for 3D visualization. The virtual RRV was acquired after performing virtual resection and a questionnaire was used to assess the ease of use. The actual RRV was derived from the postoperative 3D visualization and compared with the derived virtual RRV. Virtual resection resulted in virtual RRVs that matched nearly perfectly with the actual RRVs. According to the questionnaire, virtual resection appeared to be straightforward and was not considered to be difficult. This study demonstrated the potential of virtual resection as a new planning tool to estimate the RRV after NSS in WT patients. Future research should further evaluate the clinical relevance of virtual resection by relating it to surgical outcome

Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators

Impact of renin-angiotensin system inhibitors on mortality and major cardiovascular endpoints in hypertension: A number-needed-to-treat analysis

Objective: To assess the effectiveness of renin-angiotensin aldosterone system (RAAS) inhibitors to prevent all-cause and cardiovascular death, myocardial infarction and stroke in hypertensive patients considering the number needed to treat (NNT). Methods: Data from a meta-analysis of 18 prospective, randomized, controlled morbidity-mortality trials (68 343 RAAS inhibitor; 84 543 control) were used to calculate NNTs for the prevention of all-cause and cardiovascular mortality, myocardial infarction, and stroke. Results: Angiotensin-converting enzyme (ACE) inhibitors were used in 7 trials and angiotensin receptor blockers (ARBs) in 11 trials. Mean follow-up was 4.3 years. The annual incidence rate of all-cause mortality was 0.0233 in patients randomized to RAAS inhibitors versus 0.0252 in controls (hazard ratio 0.95, 95% confidence interval 0.91 to 0.99). The corresponding median NNT to prevent one death was 113 (2.5-97.5th percentile, 85 to 168) in favor of RAAS inhibitors, which was driven by ACE inhibitors (NNT 67, 2.5-97.5th percentile, 53 to 92) rather than ARBs (NNT 335, 2.5-97.5th percentile, -4341 to 5076). Results for cardiovascular mortality (NNT 116 for ACE inhibitors and 409 for ARBs, respectively) and myocardial infarction (NNT 80 and 338, respectively) also appeared to be driven by ACE inhibitors. We found a lower NNT for stroke in favor of ARB (NNT 337 and 131, respectively) although this difference was statistically non-significant. Conclusion: Among hypertensive patients, ACE inhibitors but not ARBs, substantially reduce all-cause and cardiovascular mortality and myocardial infarction. (C) 2014 Published by Elsevier Ireland Ltd

Methylation Markers for CCNA1 and C13ORF18 Are Strongly Associated with High-Grade Cervical Intraepithelial Neoplasia and Cervical Cancer in Cervical Scrapings

Purpose: Recently, we reported 13 possible cervical cancer-specific methylated biomarkers identified by pharmacologic unmasking microarray in combination with large-genome computational screening. The aim of the present study was to perform an in-depth analysis of the methylation patterns of these 13 candidate genes in cervical neoplasia and to determine their diagnostic relevance. Experimental Design and Results: Five of the 13 gene promoters (C13ORF18, CCNA1, TFPI2, C1ORF166, and NPTX1) were found to be more frequently methylated in frozen cervical cancer compared with normal cervix specimens. Quantitative methylation analysis for these five markers revealed that both CCNA1 and WORM were methylated in 68 of 97 cervical scrapings from cervical cancer patients and in only 5 and 3 scrapings, respectively, from 103 healthy controls W <0.0005). In cervical scrapings from patients referred with an abnormal Pap smear, CCNA1 and C13ORF18 were methylated in 2 of 43 and 0 of 43 CIN 0 (no cervical intraepithelial neoplasia) and in 1 of 41 and 0 of 41 CIN I, respectively. Furthermore, 8 of 43 CIN II, 22 of 43 CIN III, and 3 of 3 microinvasive cancer patients were positive for both markers. Although sensitivity for CIN II or higher (for both markers 37%) was low, specificity (96% and 100%, respectively) and positive predictive value (92% and 100%, respectively) were high. Conclusion: Methylation of CCNA1 and C13ORF18 in cervical scrapings is strongly associated with CIN II or higher-grade lesions. Therefore, these markers might be used for direct referral to gynecologists for patients with a methylation-positive scraping. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3000-7

Role of Linker Functionality in Polymers Exhibiting Main‐Chain Thermally Activated Delayed Fluorescence

Excellent performance has been reported for organic light-emitting diodes (OLEDs) based on small molecule emitters that exhibit thermally activated delayed fluorescence. However, the necessary vacuum processing makes the fabrication of large-area devices based on these emitters cumbersome and expensive. Here, the authors present high performance OLEDs, based on novel, TADF polymers that can be readily processed from a solution. These polymers are based on the acridine-benzophenone donor–acceptor motif as main-chain TADF chromophores, linked by various conjugated and non-conjugated spacer moieties. The authors’ extensive spectroscopic and electronic analysis shows that in particular in case of alkyl spacers, the properties and performance of the monomeric TADF chromophores are virtually left unaffected by the polymerization. They present efficient solution-processed OLEDs based on these TADF polymers, diluted in oligostyrene as a host. The devices based on the alkyl spacer-based TADF polymers exhibit external quantum efficiencies (EQEs) ≈12%, without any outcoupling-enhancing measures. What's more, the EQE of these devices does not drop substantially upon diluting the polymer down to only ten weight percent of active material. In contrast, the EQE of devices based on the monomeric chromophore show significant losses upon dilution due to loss of charge percolation

Impact of Selection Bias on Estimation of Subsequent Event Risk

Background - Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection of subjects who both experience and survive the primary indexing event. Currently, the magnitude of any selection bias, particularly for subsequent time-to-event analysis in genetic association studies, is unknown. Methods and Results - We used empirically inspired simulation studies to explore the impact of selection bias on the marginal hazard ratio for risk of subsequent events among those with established coronary heart disease. The extent of selection bias was determined by the magnitudes of genetic and nongenetic effects on the indexing (first) coronary heart disease event. Unless the genetic hazard ratio was unrealistically large (>1.6 per allele) and assuming the sum of all nongenetic hazard ratios was <10, bias was usually <10% (downward toward the null). Despite the low bias, the probability that a confidence interval included the true effect decreased (undercoverage) with increasing sample size because of increasing precision. Importantly, false-positive rates were not affected by selection bias. Conclusions - In most empirical settings, selection bias is expected to have a limited impact on genetic effect estimates of subsequent event risk. Nevertheless, because of undercoverage increasing with sample size, most confidence intervals will be over precise (not wide enough). When there is no effect modification by history of coronary heart disease, the false-positive rates of association tests will be close to nominal