To examine the rates of adverse surgical outcomes in patients undergoing cytoreductive nephrectomy (CN) compared to patients undergoing radical nephrectomy in the nonmetastatic setting using a large ...administrative database.
Patients in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) who underwent a radical nephrectomy between 2011 and 2016 were included. Patients were stratified by the preoperative variable of presence or absence of metastatic cancer. Perioperative outcomes were compared. A multivariable logistic regression analysis was performed to test the association between patients with metastatic cancer and perioperative morbidity and 30-day mortality.
There were 15,869 total patients included in this analysis of whom 1322 (8%) patients had metastatic cancer. Of the entire cohort, the majority of patients were over 60 years old (58%) and 9621 (61%) were male. Seventy-three of the patients were Caucasian. Patients with metastatic cancer had more minor (P< .01) and major (P< .01) complications, a higher rate of reoperation (P< .01), and a higher rate of unplanned readmissions (P< .01). Finally, the cohort with metastatic cancer had a higher rate of postoperative 30-day mortality (P< .01) than patients without metastatic cancer.
Patients undergoing a CN have significantly worse perioperative outcomes than patients undergoing a radical nephrectomy without evidence of metastases. Careful surgical risk stratification and appropriate patient counseling should be undertaken when selecting candidates for CN.
Chronic obstructive pulmonary disease (COPD) is a disease with marked metabolic disturbance. Previous studies have shown the association between single metabolites and lung function for COPD, but ...whether a combination of metabolites could predict phenotype is unknown. We developed metabolomic severity scores using plasma metabolomics from the Metabolon platform from two US cohorts of ever-smokers: the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) (
= 648; training/testing cohort; 72% non-Hispanic, white; average age 63 years) and the COPDGene Study (
= 1120; validation cohort; 92% non-Hispanic, white; average age 67 years). Separate adaptive LASSO (adaLASSO) models were used to model forced expiratory volume at one second (FEV
) and MESA-adjusted lung density using 762 metabolites common between studies. Metabolite coefficients selected by the adaLASSO procedure were used to create a metabolomic severity score (metSS) for each outcome. A total of 132 metabolites were selected to create a metSS for FEV
. The metSS-only models explained 64.8% and 31.7% of the variability in FEV
in the training and validation cohorts, respectively. For MESA-adjusted lung density, 129 metabolites were selected, and metSS-only models explained 59.0% of the variability in the training cohort and 17.4% in the validation cohort. Regression models including both clinical covariates and the metSS explained more variability than either the clinical covariate or metSS-only models (53.4% vs. 46.4% and 31.6%) in the validation dataset. The metabolomic pathways for arginine biosynthesis; aminoacyl-tRNA biosynthesis; and glycine, serine, and threonine pathway were enriched by adaLASSO metabolites for FEV
. This is the first demonstration of a respiratory metabolomic severity score, which shows how a metSS can add explanation of variance to clinical predictors of FEV
and MESA-adjusted lung density. The advantage of a comprehensive metSS is that it explains more disease than individual metabolites and can account for substantial collinearity among classes of metabolites. Future studies should be performed to determine whether metSSs are similar in younger, and more racially and ethnically diverse populations as well as whether a metabolomic severity score can predict disease development in individuals who do not yet have COPD.
► Zebrafish were used to evaluate the effect of drugs on embryofoetal development. ► Good sensitivity and rather poor specificity were obtained. ► Assay refinement with respect to endpoints and body ...burden threshold is required.
The zebrafish embryotoxicity/teratogenicity assay is described as a useful alternative screening model to evaluate the effect of drugs on embryofoetal development.
Fertilized eggs were exposed to different concentrations of 15 compounds with teratogenic (8) and non-teratogenic (7) potential until 96
h post-fertilization when 28 morphological endpoints and the level of compound uptake was assessed.
The majority of drugs testing positive in mammals was also positive in zebrafish (75% sensitivity), while a relative high number of false positives were noted (43% specificity). Compound uptake determination appears useful for clarifying classifications as teratogenic or potential overdose although assay sensitivity could be improved to 71% if the exposure threshold, previously suggested as ∼50
ng/larvae, is reconsidered.
The zebrafish assay shows some potential, though limited in its current form, as a screening tool for developmental toxicity within Janssen drug development. Further assay refinement with respect to endpoints and body burden threshold is required.
Background: Adverse respiratory effects in children with asthma are associated with exposures to nitrogen dioxide (NO 2 ). Levels indoors can be much higher than outdoors. Primary indoor sources of ...NO 2 are gas stoves, which are used for cooking by one-third of U.S. households. We investigated the effects of indoor NO 2 exposure on asthma severity among an ethnically and economically diverse sample of children, controlling for season and indoor allergen exposure. Methods: Children 5—10 years of age with active asthma (n = 1,342) were recruited through schools in urban and suburban Connecticut and Massachusetts (2006—2009) for a prospective, year-long study with seasonal measurements of NO 2 and asthma severity. Exposure to NO 2 was measured passively for four, month-long, periods with Palmes tubes. Asthma morbidity was concurrently measured by a severity score and frequency of wheeze, night symptoms, and use of rescue medication. We used adjusted, hierarchical ordered logistic regression models to examine associations between household NO 2 exposure and health outcomes. Results: Every 5-fold increase in NO 2 exposure above a threshold of 6 ppb was associated with a dose-dependent increase in risk of higher asthma severity score (odds ratio = 1.37 95% confidence interval = 1.01—1.89), wheeze (1.49 1.09—2.03), night symptoms (1.52 1.16—2.00), and rescue medication use (1.78 1.33—2.38). Conclusions: Asthmatic children exposed to NO 2 indoors, at levels well below the U.S. Environmental Protection Agency outdoor standard (53 ppb), are at risk for increased asthma morbidity. Risks are not confined to inner city children, but occur at NO 2 concentrations common in urban and suburban homes.
How should teachers spend their STEM-focused professional learning time? To answer this question, Heather Hill, Kathleen Lynch, Kathryn Gonzalez, and Cynthia Pollard analyzed a recent wave of ...rigorous new studies of STEM instructional improvement programs. They found that programs work best when focused on building knowledge teachers can use during instruction. This includes knowledge of the curriculum materials they will use, knowledge of content, and knowledge of how students learn that content. They argue that such learning opportunities improve teachers' professional knowledge and skill, potentially by supporting teachers in making more informed in-the-moment instructional decisions.
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