Neighborhood effect and obesity in adult survivors of pediatric cancer: A report from the St. Jude lifetime cohort study

Survivors of childhood cancer are at risk for obesity, a condition potentially modifiable if dietary intake and physical activity are optimized. These health behaviors are likely influenced by neighborhood of residence, a determinant of access to healthy, affordable food and safe and easy exercise opportunities. We examined associations between neighborhood level factors and obesity among survivors in the St. Jude Lifetime cohort and community comparison group members. Persons with residential addresses available for geocoding were eligible for analysis (n = 2,265, mean age 32.5 [SD 9.1] years, 46% female, 85% white). Survivors completed questionnaires regarding individual behaviors; percent body fat was assessed via dual X-ray absorptiometry (obesity: ≥25% males; ≥35% females); neighborhood effect was characterized using census tract of residence (e.g., neighborhood socioeconomic status [SES], rurality). Structural equation modeling was used to determine associations between neighborhood effect, physical activity, diet, smoking, treatment exposures and obesity. Obese survivors (n = 1,420, 62.7%) were more likely to live in neighborhoods with lower SES (RR: 1.23, 95% CI: 1.10–1.38) and rural areas (RR: 1.22, 95% CI: 1.07–1.39) compared to survivors with normal percent body fat. Resource-poor neighborhoods (standardized effect: 0.06, p < 0.001) and cranial radiation (0.16, p < 0.001) had direct effects on percent body fat. Associations between neighborhood of residence and percent body fat were increased (0.01, p = 0.04) among individuals with a poor diet. Neighborhoods where survivors reside as an adult is associated with obesity. Interventions targeting survivors should incorporate strategies that address environmental influences on obesity.     

Testicular cancer incidence predictions in Europe 2010–2035: A rising burden despite population ageing

Testicular cancer is the most common cancer among young men of European ancestry, with about one-third of all cases occurring in Europe. With the historically increasing trends in some high-incidence populations reported to have stabilised in recent years, we aimed to assess recent trends and predict the future testicular cancer incidence burden across Europe. We extracted testicular cancer (ICD-10 C62) incidence data from Cancer Incidence in Five Continents Volumes VII–XI and complemented this with data published by registries from 28 European countries. We predicted cancer incidence rates and the number of incident cases in Europe in the year 2035 using the NORDPRED age-period-cohort model. Testicular cancer incidence rates will increase in 21 out of 28 countries over the period 2010–2035, with trends attenuating in the high-incidence populations of Denmark, Norway, Switzerland and Austria. Although population ageing would be expected to reduce the number of cases, this demographic effect is outweighed by increasing risk, leading to an overall increase in the number of cases by 2035 in Europe, and by region (21, 13 and 32% in Northern, Western and Eastern Europe, respectively). Declines are however predicted in Italy and Spain, amounting to 12% less cases in 2035 in Southern Europe overall. In conclusion, the burden of testicular cancer incidence in Europe will continue to increase, particularly in historically lower-risk countries. The largest increase in the number of testicular cancer patients is predicted in Eastern Europe, where survival is lower, reinforcing the need to ensure the provision of effective treatment across Europe.     

Super selective intra-arterial cerebral infusion of modern chemotherapeutics after blood–brain barrier disruption: where are we now,and where we are going

Journal of Neuro-Oncology - Intra-arterial (IA) delivery of therapeutic agents across the blood-brain barrier (BBB) is an evolving strategy which enables the distribution of high concentration...     

A multi-institutional analysis of clinical outcomes and patterns of care of 1p/19q codeleted oligodendrogliomas treated with adjuvant or salvage radiation therapy

Journal of Neuro-Oncology - Practice patterns vary for adjuvant treatment of 1p/19q-codeleted oligodendroglioma patients. This study evaluates the outcomes of adjuvant (aRT) versus salvage...     

Correction to: Serum microRNA is a biomarker for post-operative monitoring in glioma

Journal of Neuro-Oncology - We performed a systematic review and meta-analysis of clinical outcomes for patients with acromegaly treated with stereotactic radiosurgery (SRS). Primary outcomes were...     

Prediagnostic blood levels of organochlorines and risk of non-Hodgkin lymphoma in three prospective cohorts in China and Singapore

Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case–control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE), the primary DDT metabolite, and β-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher β-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0–3.2; p_trend = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1–3.9; p_trend = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p′-DDE. Our findings provide support for an association between β-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p′-DDE do not support an association.     

From the Cover: Complex history of the amphibian-killing chytrid fungus revealed with genome resequencing data

Understanding the evolutionary history of microbial pathogens is critical for mitigating the impacts of emerging infectious diseases on economically and ecologically important host species. We used a genome resequencing approach to resolve the evolutionary history of an important microbial pathogen, the chytrid Batrachochytrium dendrobatidis (Bd), which has been implicated in amphibian declines worldwide. We sequenced the genomes of 29 isolates of Bd from around the world, with an emphasis on North, Central, and South America because of the devastating effect that Bd has had on amphibian populations in the New World. We found a substantial amount of evolutionary complexity in Bd with deep phylogenetic diversity that predates observed global amphibian declines. By investigating the entire genome, we found that even the most recently evolved Bd clade (termed the global panzootic lineage) contained more genetic variation than previously reported. We also found dramatic differences among isolates and among genomic regions in chromosomal copy number and patterns of heterozygosity, suggesting complex and heterogeneous genome dynamics. Finally, we report evidence for selection acting on the Bd genome, supporting the hypothesis that protease genes are important in evolutionary transitions in this group. Bd is considered an emerging pathogen because of its recent effects on amphibians, but our data indicate that it has a complex evolutionary history that predates recent disease outbreaks. Therefore, it is important to consider the contemporary effects of Bd in a broader evolutionary context and identify specific mechanisms that may have led to shifts in virulence in this system.Emerging infectious diseases (EIDs) pose significant challenges for human health, agricultural crops, and economically and ecologically important populations in nature (1–4). The incidence of EIDs has been steadily rising over the last several decades (5, 6), and EIDs are of particular concern in an increasingly globalized world. For example, the majority of human EIDs is zoonoses that originate in wildlife (5) and subsequently, create a significant burden for global economies and public health (7, 8). Therefore, scientific efforts to understand and respond to EIDs are critical in diverse fields from biomedicine to conservation biology.Although EIDs result from a complex interplay of factors, many studies focus primarily on the emergence of novel microbial pathogens. There are, in fact, high-profile examples of EIDs caused by the rapid appearance of novel, hypervirulent, or host-switching strains (9–11), but EIDs are not always caused by rapid or recent evolution of the pathogen itself. Virulence itself is an emergent property of microbe–host–environment interactions (12). Thus, EIDs can result from shifts in any factor—or combination of factors—in the microbe–host–environment epidemiological triangle (13). Characterizing the evolutionary history of emerging pathogens is, thus, critical, allowing us to determine whether observed EIDs result from rapid, recent shifts in organisms with pathogenic potential.Chytridiomycosis is an EID responsible for declines in amphibian species around the world. The chytrid fungus Batrachochytrium dendrobatidis (Bd) was discovered and linked to amphibian declines in 1998 (14, 15). Chytridiomycosis is caused by Bd and kills amphibians by disrupting the integrity of their skin, a physiologically important organ that is involved in gas exchange, electrolyte balance, hydration, and protection from other pathogens (16, 17). Bd infects hundreds of species of amphibians, is found on all continents where amphibians occur, and is responsible for declines and extirpations in a diversity of amphibian hosts (18).Soon after Bd was discovered, researchers proposed two competing hypotheses for the emergence of chytridiomycosis. The emerging pathogen hypothesis posited that a novel disease agent caused chytridiomycosis, and the endemic pathogen hypothesis proposed that an environmental shift disrupted a previously benign microbe–host interaction (19). Over the years, spatiotemporal and genetic data have supported the emerging pathogen hypothesis (reviewed in refs. 20 and 21). Spatiotemporal data provided clear evidence that Bd arrived and spread through geographic regions where it was not present historically (22–24). Early genetic studies also found very little genetic differentiation in Bd with no geographic signal, consistent with a recent, rapid spread of a novel disease agent (25–27). Recently, genetic and genomic data have been used to describe a geographically widespread Bd lineage [termed the global panzootic lineage (GPL)] (28) and several putatively endemic Bd lineages (28–30). However, different studies have used different methods and focused sampling in different parts of the world, precluding integration across studies to determine the evolutionary history leading to the emergence of Bd as a global threat to amphibians.Here, we present whole-genome sequencing from a global panel of Bd isolates to show that Bd has a historically deeper and more complex evolutionary history than previously appreciated. We sequenced Bd genomes from around the world and also, a non-Bd chytrid outgroup that does not attack amphibians [Homolaphlyctis polyrhiza (Hp)] (31). Our focus was primarily on the evolutionary dynamics of Bd in the Americas, because many of the most devastating outbreaks have occurred in the New World. We address outstanding questions about the origins, genetic diversity, and genome structure of Bd that can be resolved using whole-genome data. We also integrate our genomic data with those data from a previous study with complementary geographic sampling (28). Our results reveal that the evolutionary history of Bd is complex, with multiple divergent lineages, heterogeneous patterns of genomic evolution, and no simple link between a single evolutionary event and observed amphibian declines.     

Naproxen-induced liver injury

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the- counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractable pruritus that...