Waardenburg Syndrome and Left Persistent Superior Vena Cava

Waardenburg syndrome (WS) is a rare genetic disorder secondary to neural crest cell developmental abnormalities. It is predominantly described as an auditory-pigmentary syndrome with diverse patient presentation, typically involving congenital sensorineural hearing loss and pigmentation abnormalities of the skin, hair, and iris. Other developmental abnormalities that may be associated with this syndrome are Hirschsprung\u27s disease and a myriad of cardiovascular congenital defects. We present a case of a young girl with WS who found to have a persistent left superior vena cava (PLSVC) draining into the coronary sinus. The prevalence of PLSVC is increased in patients with chromosomal and genetic abnormalities. However, we are the first to report its presence in association with WS while discussing the challenges that may arise during central venous catheter placement in patients with PLSVC

Breast Cancer Screening in Patients With Newly Diagnosed Lung and Colorectal Cancer: A Population-Based Study of Utilization

Purpose—To assess breast cancer screening utilization in Medicare beneficiaries with colorectal and lung cancer versus cancer-free controls. Methods—Female fee-for-service Medicare beneficiaries who were ≥ 67 years old and diagnosed with lung or colorectal cancer between 2000 and 2011 and who reported to a Surveillance, Epidemiology, and End Results (SEER) registry (case group) were followed for 2 years after their diagnoses, unless death, a diagnosis of breast cancer, or the end of 2013 came first. A similar number of cancer-free controls were individually matched to cases by age, race, registry region, and follow-up time. Screening utilization was defined as the percentage of women with ≥1 screening mammogram during follow-up. Results—Overall, 104,164 cases (48% colorectal, 52% lung; 30% advanced cancer) and 104,164 controls were included. Among women with lung or colorectal cancer, 22% underwent ≥ 1 screening mammogram versus 26% of controls (odds ratio [OR] 0.80; 95% confidence interval [CI] 0.78–0.82). Stratified by cancer type, 28% of colorectal cancer cases versus 29% of controls (OR 0.98; 95% CI 0.95–1.01) and 17% of lung cancer cases versus 23% of controls (OR 0.63; 95% CI 0.60–0.65) received ≥ 1 mammogram. When stratified by stage, 8% with advanced cancer versus 18% of controls (OR 0.33; 95% CI 0.31–0.35) and 30% with early-stage cancer versus 30% of controls (OR 1; 95% CI 0.97–1.02) underwent ≥ 1 mammogram. Conclusion—Screening mammography utilization rates are similar between Medicare beneficiaries with early-stage cancer versus controls. Although the majority of patients with advanced-stage cancer appropriately do not pursue screening mammography, a small number (8%) continue with screening

July 2004 Report of Progress

Progress of each ALS-NSCORT project given by each project lead. 10 pages

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

February 2005 Report of Progress

Progress of each ALS-NSCORT project given by each project lead. 8 pages

May 2004 Report of Progress

Progress of each ALS-NSCORT project given by each project lead. 11 pages

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

Purpose We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. Methods We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. Results These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. Conclusion These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis

Image Gently: A campaign to promote radiation protection for children worldwide

With the goal of raising awareness and developing stakeholder educational tools for the appropriate imaging of children, the Image Gently campaign was launched in 2007. This campaign is a product of a multidisciplinary alliance with international representation which now numbers nearly 100 medical and dental professional societies and organisations, and includes regulatory organisations. The alliance focuses on increasing awareness and developing education materials that support the protection of children worldwide from unnecessary radiation in medicine. The alliance members work with agencies and regulatory bodies to improve standards and measures that are specific to children. The campaign has produced open source modules for all stakeholders regarding CT, fluoroscopy, nuclear medicine, interventional radiology, digital radiography and dental imaging. The philosophy of the Image Gently steering committee is to collaborate, to share information freely, to keep messaging simple and to commit to lifelong learning. Many healthcare practitioners may not understand how to decrease children’s radiation exposure; the goal of Image Gently is to increase all stakeholders’ understanding of both the benefits and the risks and to encourage radiation reduction strategies. This article summarises the rationale and goals of the global campaign to date