Citations

Secondary, radiation-induced neoplasms represent a significant long-term risk after radiation treatment, and radiation-induced sarcomas (RAS) have an especially poor prognosis. These have rarely been reported after irradiation for pituitary adenomas.

We present a case of an intramedullary melanotic schwannoma (IMS) of the thoracic spinal cord. To our knowledge, this is the seventh reported case of an IMS of the central nervous system. Schwannomas are benign nerve sheath tumors of neural crest origin composed entirely of well differentiated Schwann cells that typically occur in peripheral nerves. Both the intramedullary location and the melanotic component of the reported lesion make it exceedingly rare. We will present our case, theories as to the origin of these tumors, clues in radiographic identification, and current clinical follow-up recommendations.

Abstract The importance of inflammation pathways to the development of many human cancers prompted us to examine the associations between single-nucleotide polymorphisms (SNP) in inflammation-related genes and risk of ovarian cancer. In a multisite case–control study, we genotyped SNPs in a large panel of inflammatory genes in 930 epithelial ovarian cancer cases and 1,037 controls using a custom array and analyzed by logistic regression. SNPs with P < 0.10 were evaluated among 3,143 cases and 2,102 controls from the Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI) post-GWAS collaboration. Combined analysis revealed association with SNPs rs17561 and rs4848300 in the interleukin gene IL1A which varied by histologic subtype (Pheterogeneity = 0.03). For example, IL1A rs17561, which correlates with numerous inflammatory phenotypes, was associated with decreased risk of clear cell, mucinous, and endometrioid subtype, but not with the most common serous subtype. Genotype at rs1864414 in the arachidonate 5-lipoxygenase ALOX5 was also associated with decreased risk. Thus, inherited variation in IL1A and ALOX5 seems to affect ovarian cancer risk which, for IL1A, is limited to rarer subtypes. Given the importance of inflammation in tumorigenesis and growing evidence of subtype-specific features in ovarian cancer, functional investigations will be important to help clarify the importance of inherited variation related to inflammation in ovarian carcinogenesis. Cancer Res; 72(5); 1064–9. ©2012 AACR.

Abstract We are in the midst of a rapidly evolving era of technology-assisted medicine. The field of telemedicine provides the opportunity for highly individualized medical management in a way that has never been possible before. Evolving medical technologies using cardiac implantable devices (CIEDs) with capabilities for remote monitoring permit evaluation of multiple parameters of cardiovascular physiology and risk, including cardiac rhythm, device function, blood pressure values, the presence of myocardial ischaemia, and the degree of compensation of congestive heart failure. Cardiac risk, device status, and response to therapies can now be assessed with these electronic systems of detection and reporting. This document reflects the extensive experience from investigators and innovators around the world who are shaping the evolution of this rapidly expanding field, focusing in particular on implantable pacemakers (IPGs), implantable cardioverter-defibrillators (ICDs), devices for cardiac resynchronization therapy (CRT) (both, with and without defibrillation properties), loop recorders, and haemodynamic monitoring devices. This document covers the basic methodologies, guidelines for their use, experience with existing applications, and the legal and reimbursement aspects associated with their use. To adequately cover this important emerging topic, the International Society for Holter and Noninvasive Electrocardiology (ISHNE) and the European Heart Rhythm Association (EHRA) combined their expertise in this field. We hope that the development of this field can contribute to improve care of our cardiovascular patients.

Abstract BACKGROUND Aberrantly methylated genes represent important markers for cancer diagnosis. We describe a multiplex detection approach to efficiently quantify these markers for clinical applications such as colorectal cancer screening. METHODS Quantitative allele-specific real-time target and signal amplification (QuARTS) combines a polymerase-based target amplification with an invasive cleavage-based signal amplification. The fluorescence signal is detected in a fashion similar to real-time PCR. We measured the dynamic range and analytical sensitivity of multiplex QuARTS reactions with titrated plasmid DNA. We used the QuARTS technology to quantify methylated BMP3, NDRG4, VIM, and TFPI2 genes on 91 DNA samples extracted from colorectal tissues, including 37 cancers, 25 adenomas, and 29 healthy epithelia. The assays were designed in triplex format that incorporated ACTB as a reference gene. Percent methylation was calculated by dividing methylated strands over ACTB strands and multiplying by 100. RESULTS The QuARTS method linearly detected methylated or unmethylated VIM gene down to 10 copies. No cross-reactivity was observed when methylated assays were used to amplify 105 copies of unmethylated gene and vice versa. The multiplex assay detected methylated genes spiked in unmethylated genes at a 0.01% ratio and vice versa. At a diagnostic specificity cutoff of 95%, methylated BMP3, NDRG4, VIM, and TFPI2 detected 84%, 92%, 86%, and 92% of colorectal cancers and 68%, 76%, 76%, and 88% of adenomas, respectively. CONCLUSIONS The QuARTS technology provides a promising approach for quantifying methylated markers. The markers assayed highly discriminated colorectal neoplasia from healthy epithelia.

Abstract Ischemic stroke (IS) is among the leading causes of death in Western countries. There is a significant genetic component to IS susceptibility, especially among young adults. To date, research to identify genetic loci predisposing to stroke has met only with limited success. We performed a genome-wide association (GWA) analysis of early-onset IS to identify potential stroke susceptibility loci. The GWA analysis was conducted by genotyping 1 million SNPs in a biracial population of 889 IS cases and 927 controls, ages 15–49 years. Genotypes were imputed using the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic regression models adjusting for age, recruitment stages, and population structure were used to determine the association of IS with individual SNPs. Although no single SNP reached genome-wide significance (P < 5 × 10−8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P = 1.2 × 10−7) and rs1986743 (in ARL6IP6; P = 2.7 × 10−7), strongly associated with early-onset stroke. These data suggest that a novel locus on human chromosome 2q23.3 may be associated with IS susceptibility among young adults.

OBJECTIVE: Long-QT syndrome (LQTS) is both underdiagnosed and overdiagnosed. Many patients are incorrectly diagnosed as having LQTS after presenting to an emergency department (ED) with presyncope/syncope and demonstrating “borderline” QT-interval prolongation (QTc ≥ 440 milliseconds) in a sentinel ED-obtained electrocardiogram (ECG). We sought to evaluate the distribution and clinical significance of QT intervals in the ED. METHODS: We retrospectively reviewed data for all patients 22 years of age or younger (N = 626; 369 females; age, mean ± SD: 17 ± 5 years) who had ECGs obtained in our ED between July 1, 2007, and June 30, 2008. A total of 223 patients were excluded because of known structural heart disease, arrhythmias, electrolyte abnormalities, or exposure to QT-interval–prolonging medications. RESULTS: The average QTc was 428 ± 28 milliseconds (range: 344–566 milliseconds), and approximately one-third of patients had QTc values of ≥440 milliseconds (females: 41%; males: 21%). Overall, 104 patients presented with presyncope/syncope, of whom 14 (13%) had follow-up ECGs. On follow-up, these patients demonstrated significant decreases in QTc values of 33 ± 43 milliseconds (P < .04). Only 8 (31%) of 26 patients with presyncope/syncope with borderline QT values had follow-up ECGs performed, in 5 of which the QTc values were decreased significantly. No patients ultimately received LQTS diagnoses. CONCLUSIONS: In the ED setting, approximately one-third of pediatric patients exhibited QTc values of ≥440 milliseconds and had significant normalization of QTc values in follow-up evaluations. First-time ECGs obtained after a syncopal episode must be interpreted with caution, particularly in the context of so-called borderline QT intervals.