Citations

BACKGROUND:Annually, millions of children are exposed to anesthetic agents that cause apoptotic neurodegeneration in immature animals. To explore the possible significance of these findings in children, we investigated the association between exposure to anesthesia and subsequent (1) learning disabilities (LDs), (2) receipt of an individualized education program for an emotional/behavior disorder (IEP-EBD), and (3) scores of group-administered achievement tests.METHODS:This was a matched cohort study in which children (N = 8548) born between January 1, 1976, and December 31, 1982, in Rochester, Minnesota, were the source of cases and controls. Those exposed to anesthesia (n = 350) before the age of 2 were matched to unexposed controls (n = 700) on the basis of known risk factors for LDs. Multivariable analysis adjusted for the burden of illness, and outcomes including LDs, receipt of an IEP-EBD, and the results of group-administered tests of cognition and achievement were outcomes.RESULTS:Exposure to multiple, but not single, anesthetic/surgery significantly increased the risk of developing LDs (hazard ratio: 2.12 [95% confidence interval: 1.26–3.54]), even when accounting for health status. A similar pattern was observed for decrements in group-administered tests of achievement and cognition. However, exposure did not affect the rate of children receiving an individualized education program.CONCLUSIONS:Repeated exposure to anesthesia and surgery before the age of 2 was a significant independent risk factor for the later development of LDs but not the need for educational interventions related to emotion/behavior. We cannot exclude the possibility that multiple exposures to anesthesia/surgery at an early age may adversely affect human neurodevelopment with lasting consequence.

Abstract Purpose: Oncolytic viruses are self-amplifying anticancer agents that make use of the natural ability of viruses to kill cells. Adenovirus serotype 5 (Ad5) has been extensively tested against solid cancers, but less so against B-cell cancers because these cells do not generally express the coxsackie and adenoviral receptor (CAR). To determine whether other adenoviruses might have better potency, we “mined” the adenovirus virome of 55 serotypes for viruses that could kill B-cell cancers. Experimental Design: Fifteen adenoviruses selected to represent Ad species B, C, D, E, and F were tested in vitro against cell lines and primary patient B-cell cancers for their ability to infect, replicate in, and kill these cells. Select viruses were also tested against B-cell cancer xenografts in immunodeficient mice. Results: Species D adenoviruses mediated most robust killing against a range of B-cell cancer cell lines, against primary patient marginal zone lymphoma cells, and against primary patient CD138+ myeloma cells in vitro. When injected into xenografts in vivo, single treatment with select species D viruses Ad26 and Ad45 delayed lymphoma growth. Conclusions: Relatively unstudied species D adenoviruses have a unique ability to infect and replicate in B-cell cancers as compared with other adenovirus species. These data suggest these viruses have unique biology in B cells and support translation of novel species D adenoviruses as oncolytics against B-cell cancers. Clin Cancer Res; 17(21); 6712–22. ©2011 AACR.

OBJECTIVE: We determined the incidence of written-language disorder (WLD) among children with and without attention-deficit/hyperactivity disorder (ADHD) in a population-based birth cohort. METHODS: Subjects included a birth cohort of all children born in 1976–1982 who remained in Rochester, Minnesota, after 5 years of age (N = 5718). Information from medical, school, and private tutorial records was abstracted. Cumulative incidences of WLD with or without reading disability (RD), identified with any of 3 formulas, among children with and without ADHD and hazard ratios (HRs) were calculated. RESULTS: For both genders, the cumulative incidence of WLD by 19 years of age was significantly higher for children with ADHD than for children without ADHD (boys: 64.5% vs 16.5%; girls: 57.0% vs 9.4%). The magnitude of association between ADHD and WLD with RD was significantly higher for girls than for boys (adjusted HR: girls: 9.8; boys: 4.2; P < .001). However, this was not true for WLD without RD (adjusted HR: girls: 7.4; boys: 6.6; P = .64). CONCLUSIONS: ADHD is strongly associated with an increased risk of WLD (with or without RD) for both boys and girls. Girls with ADHD are at higher risk of having WLD with RD compared with boys with ADHD, whereas boys and girls are at the same risk of having WLD without RD.

Abstract Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. Cancer Res; 71(19); 6240–9. ©2011 AACR.

Background— Prior studies demonstrate a direct relationship between treatment delays to primary percutaneous intervention and mortality in patients with ST-segment elevation myocardial infarction (STEMI). This analysis compared the relationship of symptom onset-to-balloon time and door-to-balloon time on mortality in patients with STEMI. Methods and Results— We analyzed different treatment delays (symptom onset-to-balloon time, door-to-balloon time) and mortality in 5745 STEMI patients. Baseline characteristics, flow grade, 90-day mortality, and clinical outcomes were compared in patients stratified by treatment delay. Multivariable logistic regression modeling was performed to assess the independent and relative effect of each treatment delay on 90-day mortality. Female sex, increased age, and worse thrombolysis in myocardial infarction flow grade were significantly associated with longer symptom onset-to-balloon times and door-to-balloon times. Longer symptom onset-to-balloon time was significantly associated with worse 90-day mortality (3.7%, 4.2%, and 6.5% for time delays <3 hours, 3 to 5 hours, and >5 hours, respectively, P <0.0001). Similarly, longer door-to-balloon times were significantly associated with worse 90-day mortality (3.2%, 4.0%, 4.6%, and 5.3% for delays <60 minutes, 60 to 90 minutes, 90 to 120 minutes, and ≥120 minutes respectively, P <0.0001). In a multivariate model of 90-day mortality, door-to-balloon time (χ 2 6.0, P <0.014), and symptom onset-to-hospital arrival (χ 2 9.8, P <0.007) remained independent determinants. Conclusions— Both symptom onset-to-balloon time and hospital door-to-balloon time are strongly associated with 90-day mortality following STEMI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00091637.

OBJECTIVE: To determine the incidence of reading disability (RD) among children with and without research-identified attention-deficit/hyperactivity disorder (ADHD), separately according to gender, in a population-based birth cohort. METHOD: Subjects included all children born in 1976–1982 remaining in Rochester, Minnesota, after 5 years of age (n = 5718). Information from medical, school, and private tutorial records was abstracted. Cumulative incidence of RD, by any of 3 RD formulas, in children with and without ADHD and corresponding hazard ratios (HRs) were calculated separately according to gender. RESULTS: Cumulative incidence of RD by the age of 19 years was significantly higher in children with ADHD (51% in boys, 46.7% in girls) compared with those without ADHD (14.5% in boys, 7.7% in girls). Among children with ADHD, the risk for RD was similar in boys versus girls (HR: 1.0). However, among children without ADHD, boys were 2.0 times more likely than girls to meet RD criteria. Among girls, the HR for the risk for RD associated with ADHD (versus those without ADHD) was 8.1 (95% confidence interval: 5.7–11.5), which was significantly higher than the corresponding HR among boys (3.9 [95% confidence interval: 3.2–4.9]). CONCLUSIONS: The risk for RD is significantly greater among children with ADHD compared with those without ADHD. Among children with ADHD, the risk for RD is the same for boys and girls. However, among children without ADHD, boys are more at risk for RD than girls. Among girls, the magnitude of increased risk for RD associated with ADHD is nearly twice that among boys, because girls without ADHD are less likely to have RD than boys without ADHD.