Veliparib in Combination with Carboplatin and Etoposide in Patients with Treatment-Naive Extensive-Stage Small Cell Lung Cancer:A Phase 2 Randomized Study

Purpose: This study investigated the efficacy and safety of oral PARP inhibitor veliparib, plus carboplatin and etoposide in patients with treatment-naive, extensive-stage small cell lung cancer (ED-SCLC). Patients and Methods: Patients were randomized 1:1:1 to veliparib [240 mg twice daily (BID) for 14 days] plus chemotherapy followed by veliparib maintenance (400 mg BID; veliparib throughout), veliparib plus chemotherapy followed by placebo (veliparib combination only), or placebo plus chemotherapy followed by placebo (control). Patients received 4-6 cycles of combination therapy, then maintenance until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) with veliparib throughout versus control. Results: Overall (N = 181), PFS was improved with veliparib throughout versus control [hazard ratio (HR), 0.67; 80% confidence interval (CI), 0.50-0.88; P = 0.059]; median PFS was 5.8 and 5.6 months, respectively. There was a trend toward improved PFS with veliparib throughout versus control in SLFN11-positive patients (HR, 0.6; 80% CI, 0.36-0.97). Median overall survival (OS) was 10.1 versus 12.4 months in the veliparib throughout and control arms, respectively (HR, 1.43; 80% CI, 1.09-1.88). Grade 3/4 adverse events were experienced by 82%, 88%, and 68% of patients in the veliparib throughout, veliparib combination-only and control arms, most commonly hematologic. Conclusions: Veliparib plus platinum chemotherapy followed by veliparib maintenance demonstrated improved PFS as first-line treatment for ED-SCLC with an acceptable safety profile, but there was no corresponding benefit in OS. Further investigation is warranted to define the role of biomarkers in this setting

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Plant chemicals and the sexual behavior of male tephritid fruit flies

Plant compounds affect insects in many different ways. In addition to being a food source, plants also contain secondary metabolites that may have positive and negative impacts on insects. The influence of these compounds on sexual behavior, in particular, has been the focus of many recent studies. Here, we review the existing literature on the effects of plant compounds on the sexual behavior of tephritid fruit fly males. We put special focus on polyphagous species whose males congregate in leks, where females exert strong mate selection. We first summarize the main findings related to plant compounds that increase male signaling behavior and attraction of females and consequently increase mating frequency, a phenomenon that has been recorded mainly for species of Anastrepha and Ceratitis. In other tephritid species, males are attracted to phenylpropanoids produced by plants (such as methyl eugenol or raspberry ketone) that, upon encounter, are consumed and sequestered by males. These compounds, or metabolic derivatives, which normally have negligible nutritional value, are included in the pheromone and also confer advantages in a sexual context: enhanced female attraction and improved male mating success. These phenomena have been reported for several Bactrocera species as well as for Zeugodacus cucurbitae. Because many tephritid species are serious pests, the effect of plant compounds on male behavior has been explored for potential incorporation into control strategies such as the sterile insect technique (SIT). We conclude noting several factors, such as age and nutrition during larval and adult stage, that modulate the effect of plant compounds on male mating behavior as well as some prominent gaps that preclude a thorough understanding of the plant-mediated enhancement of male sexual performance and hence limit our ability to effectively utilize phytochemicals in pest control strategies.Instituto de GenéticaFil: Segura, Diego Fernando. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética. Laboratorio de Genética de Insectos de Importancia Económica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Belliard, Silvina A. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética. Laboratorio de Genética de Insectos de Importancia Económica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vera, María Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; ArgentinaFil: Bachmann, Guillermo Enrique. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética. Laboratorio de Genética de Insectos de Importancia Económica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ruiz, María Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; ArgentinaFil: Jofre-Barud, Flavia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernández, Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Delta del Paraná; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lopez, M. Liza. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Shelly, Todd E. United States Department of Agriculture. Animal and Plant Health Inspection Service; Estados Unido

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

A Comparative Risk Assessment Of Burden Of Disease And Injury Attributable To 67 Risk Factors And Risk Factor Clusters In 21 Regions, 1990–2010: A Systematic Analysis For The Global Burden Of Disease Study 2010

Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake