Real-World Impact of Comprehensive Genomic Profiling on Biomarker Detection, Receipt of Therapy, and Clinical Outcomes in Advanced Non-Small Cell Lung Cancer.

Purpose: Therapeutic decision making for patients with advanced non-small cell lung cancer (aNSCLC) includes a growing number of options for genomic, biomarker-guided, targeted therapies. We compared actionable biomarker detection, targeted therapy receipt, and real-world overall survival (rwOS) in patients with aNSCLC tested with comprehensive genomic profiling (CGP) versus small panel testing (SP) in real-world community health systems.

Methods: Patients older than 18 years diagnosed with aNSCLC between January 1, 2015, and December 31, 2020, who received biomarker testing were followed until death or study end (September 30, 2021), and categorized by most comprehensive testing during follow-up: SP (≤52 genes) or CGP (>52 genes).

Cardiovascular Mortality and Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-term Update of NRG/RTOG 9202.

Background: Androgen deprivation therapy (ADT) has been associated with coronary heart disease and myocardial infarction (MI) in prostate cancer patients, but controversy persists regarding its effects on cardiovascular mortality (CVM).

Objective: We assessed the long-term relationship between ADT and CVM in a prostate cancer randomized trial (NRG Oncology/Radiation Therapy Oncology Group 9202).

Design, Setting, And Participants: From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-T4, prostate-specific antigen <150 ng/ml) received radiotherapy with 4 mo (short-term [STADT]) versus 28 mo (longer-term [LTADT]) of ADT.

Arsenic metabolism, diabetes prevalence, and insulin resistance among Mexican Americans: A mendelian randomization approach.

Background: Differences in arsenic metabolism capacity may influence risk for type 2 diabetes, but the mechanistic drivers are unclear. We evaluated the associations between arsenic metabolism with overall diabetes prevalence and with static and dynamic measures of insulin resistance among Mexican Americans living in Starr County, Texas.

Methods: We utilized data from cross-sectional studies conducted in Starr County, Texas, from 2010-2014.

Relationships Between Urinary Metals and Diabetes Traits Among Mexican Americans in Starr County, Texas, USA.

Hispanics/Latinos have higher rates of type 2 diabetes (T2D), and the origins of these disparities are poorly understood. Environmental endocrine-disrupting chemicals (EDCs), including some metals and metalloids, are implicated as diabetes risk factors. Data indicate that Hispanics/Latinos may be disproportionately exposed to EDCs, yet they remain understudied with respect to environmental exposures and diabetes.

Associations between age of menarche and genetic variation in women of African descent: genome-wide association study and polygenic score analysis.

Introduction: Many diseases of adulthood are associated with a woman's age at menarche. Genetic variation affects age at menarche, but it remains unclear whether in women of African ancestry the timing of menarche is regulated by genetic variants that were identified in predominantly European and East Asian populations.

Methods: We explored the genetic architecture of age at menarche in 3145 women of African ancestry who live in the USA, Barbados and Nigeria.

Cross-Sectional Analysis of Baseline Visual Parameters in Subjects Recruited Into the RESCUE and REVERSE ND4-LHON Gene Therapy Studies.

Objective: This report presents a cross-sectional analysis of the baseline characteristics of subjects with Leber hereditary optic neuropathy enrolled in the gene therapy trials RESCUE and REVERSE, to illustrate the evolution of visual parameters over the first year after vision loss.

Methods: RESCUE and REVERSE were 2 phase III clinical trials designed to assess the efficacy of rAAV2/2-ND4 gene therapy in ND4-LHON subjects. At enrollment, subjects had vision loss for ≤6 months in RESCUE, and between 6 and 12 months in REVERSE.

Mendelian randomization analysis of arsenic metabolism and pulmonary function within the Hispanic Community Health Study/Study of Latinos.

Arsenic exposure has been linked to poor pulmonary function, and inefficient arsenic metabolizers may be at increased risk. Dietary rice has recently been identified as a possible substantial route of exposure to arsenic, and it remains unknown whether it can provide a sufficient level of exposure to affect pulmonary function in inefficient metabolizers. Within 12,609 participants of HCHS/SOL, asthma diagnoses and spirometry-based measures of pulmonary function were assessed, and rice consumption was inferred from grain intake via a food frequency questionnaire.

Exposure to metal mixtures in relation to blood pressure among children 5-7 years old: An observational study in Bangladesh.

Unlabelled: Hypertension in later life, a significant risk factor for cardiovascular disease, has been linked to elevated blood pressure in early life. Exposure to metals may influence childhood blood pressure; however, previous research is limited and has mainly focused on evaluating the toxicity of single metal exposures. This study evaluates the associations between exposure to metal mixtures and blood pressure among Bangladeshi children age 5-7 years.

Mismatch in Supply and Demand for Neuro-Ophthalmic Care.

Background: Previous research suggests the number of neuro-ophthalmologists in the United States may be below a level that provides sufficient access to neuro-ophthalmic care in much of the United States. However, national estimates of the amount of clinical time spent on neuro-ophthalmology are lacking.

Methods: The North American Neuro-Ophthalmology Society administered a survey on professional time allocation to its active members.

Machine Learning Models of Arsenic in Private Wells Throughout the Conterminous United States As a Tool for Exposure Assessment in Human Health Studies.

Arsenic from geologic sources is widespread in groundwater within the United States (U.S.).

Coronavirus disease 2019 (COVID-19) mortality and neighborhood characteristics in Chicago.

Purpose: To describe coronavirus disease 2019 (COVID-19) mortality in Chicago during the spring of 2020 and identify at the census-tract level neighborhood characteristics that were associated with higher COVID-19 mortality rates.

Methods: Using Poisson regression and regularized linear regression (elastic net), we evaluated the association between neighborhood characteristics and COVID-19 mortality rates in Chicago through July 22 (2514 deaths across 795 populated census tracts).

Results: Black residents (31% of the population) accounted for 42% of COVID-19 deaths.

Gravidity, parity, blood pressure and mortality among women in Bangladesh from the HEALS cohort.

Objectives: Despite a hypothesised connection of reproductive history with hypertension and mortality, the nature of this association is poorly characterised. We evaluated the association of parity and gravidity with blood pressure, hypertension and all-cause mortality.

Design: Prospective cohort study.

Association between prenatal arsenic exposure, birth outcomes, and pregnancy complications: An observational study within the National Children's Study cohort.

Background: Chronic arsenic exposure has been associated with pregnancy complications and reduced fetal growth in populations where total arsenic exposure exceeds 50 μg/L. However, the potential effect on pregnancy outcomes remains unclear at lower levels of arsenic exposure, such as those most commonly observed in the United States.

Objectives: We evaluated the associations between arsenic exposure during pregnancy with fetal growth and risk of pregnancy complications using data from mother-infant pairs participating in the National Children's Study.

Change in visual acuity and retinal structures following Repository Corticotropin Injection (RCI) therapy in patients with acute demyelinating optic neuritis: Improvement in low contrast visual acuity in both affected and contralateral eyes in a single-armed open-label study.

Background: Current treatments after an episode of optic neuritis have limited success protecting the retinal nerves and restoring visual function.

Objective: To assess the effectiveness of Repository Corticotropin Injection (RCI) after the onset of optic neuritis.

Methods: Twenty-four adults were treated with RCI within 2 weeks of symptom onset.

Mendelian randomization of inorganic arsenic metabolism as a risk factor for hypertension- and diabetes-related traits among adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort.

Background: Hypertension and diabetes have been associated with inefficient arsenic metabolism, primarily through studies undertaken in populations exposed through drinking water. Recently, rice has been recognized as a source of arsenic exposure, but it remains unclear whether populations with high rice consumption but no known water exposure are at risk for the health problems associated with inefficient arsenic metabolism.

Methods: The relationships between arsenic metabolism efficiency (% inorganic arsenic, % monomethylarsenate and % dimethylarsinate in urine) and three hypertension- and seven diabetes-related traits were estimated among 12 609 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Changes in blood pressure associated with lead, manganese, and selenium in a Bangladeshi cohort.

Background: Heavy metal contamination is widespread in Bangladesh. Previous studies have observed lead increases blood pressure over time. However, the role of other metal contaminants and essential micronutrients, which could also adversely affect blood pressure or act as protective factors, is understudied.

Germline Variation and Breast Cancer Incidence: A Gene-Based Association Study and Whole-Genome Prediction of Early-Onset Breast Cancer.

Although germline genetics influences breast cancer incidence, published research only explains approximately half of the expected association. Moreover, the accuracy of prediction models remains low. For women who develop breast cancer early, the genetic architecture is less established.

Investigating the Effect of Reirradiation or Systemic Therapy in Patients With Glioblastoma After Tumor Progression: A Secondary Analysis of NRG Oncology/Radiation Therapy Oncology Group Trial 0525.

Purpose: To determine the impact on overall survival with different salvage therapies, including no treatment, reirradiation, systemic therapy, or radiation and systemic therapy, in participants of a phase 3 clinical trial evaluating dose-dense versus standard-dose temozolomide for patients with newly diagnosed glioblastoma.

Methods And Materials: This analysis of patients from Trial RTOG 0525 investigated the effect of reirradiation or systemic treatment after tumor progression. Survival from first progression was compared between patients receiving no therapy, systemic therapy alone, radiation alone, and both modalities.

Limited influence of germline genetic variation on all-cause mortality in women with early onset breast cancer: evidence from gene-based tests, single-marker regression, and whole-genome prediction.

Purpose: Women diagnosed with breast cancer have heterogeneous survival outcomes that cannot be fully explained by known prognostic factors, and germline variation is a plausible but unconfirmed risk factor.

Methods: We used three approaches to test the hypothesis that germline variation drives some differences in survival: mortality loci identification, tumor aggressiveness loci identification, and whole-genome prediction. The 2954 study participants were women diagnosed with breast cancer before age 50, with a median follow-up of 15 years who were genotyped on an exome array.

Retinal Ganglion Cell and Inner Plexiform Layer Loss Correlate with Visual Acuity Loss in LHON: A Longitudinal, Segmentation OCT Analysis.

Purpose: Describe changes in the retina as vision loss progresses in Leber's Hereditary Optic Neuropathy (LHON) using spectral-domain optical coherence tomography (SD-OCT) autosegmentation, and determine if relationship exists between retinal changes and vision loss.

Methods: From patient records we identified nine LHON patients who underwent periodic neuro-ophthalmologic examinations and high-resolution SD-OCT as part of their care. We describe the impact of LHON progression on each retinal layer, and the relationship between these structural changes and visual acuity using generalized estimating equations and nonparametric tests.

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.

Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and mounting evidence indicates that toxicant exposures can profoundly impact on CVD risk. Epidemiologic studies have suggested that arsenic (As) exposure is positively related to increases in blood pressure (BP), a primary CVD risk factor. However, evidence of whether genetic susceptibility can modify the association between As and BP is lacking.