Angiotensin-Converting Enzyme Inhibitor Washout Period Prior to Angiotensin Receptor/Neprilysin Inhibitor Initiation in the Inpatient Setting.

Background: The 2022 AHA-ACC HFSA Guideline for Management of Heart Failure recommend initiating an angiotensin receptor/neprilysin inhibitor (ARNI) in patients with heart failure with reduced ejection fraction (HFrEF) who can tolerate an angiotensin-converting enzyme inhibitor (ACEi). The manufacturer recommends initiating a 36-hour washout period when switching from ACEi to ARNI due to an increased risk of adverse effects, including angioedema. This study investigated the adherence to the washout period when transitioning from ACEi to ARNI at a community hospital.

Acute Kidney Injury Incidence, Stage, and Recovery in Patients with COVID-19.

Purpose: To determine the incidence, mortality, stage, and recovery of acute kidney injury (AKI) in COVID-19 patients and further analyze the effect of patient demographics and comorbidities on AKI incidence.

Study Design: Our study looked at 1545 charts of patients over 18 years old who presented to BronxCare Hospital in NY with a positive SARS-CoV-2 PCR test. Using the KDIGO criteria, any patient presenting with a creatinine of 1.

Spontaneous Tissue Expander Migration in an Irradiated Field: A Case Report.

A 59-year-old woman with a history of bilateral breast cancer, bilateral mastectomy, and bilateral latissimus dorsi flap reconstruction with tissue expanders, before expansion, developed spontaneous unilateral tissue expander migration on the side that had been irradiated. During the operation to return the migrated tissue expander to the chest, the expander was found at the back with a seroma. The chest pocket had collapsed, and a subcutaneous tunnel inferior to the flap inset was encountered, indicating the path of migration.

Integrated genomic profiling expands clinical options for patients with cancer.

Genomic analysis of paired tumor-normal samples and clinical data can be used to match patients to cancer therapies or clinical trials. We analyzed 500 patient samples across diverse tumor types using the Tempus xT platform by DNA-seq, RNA-seq and immunological biomarkers. The use of a tumor and germline dataset led to substantial improvements in mutation identification and a reduction in false-positive rates.

Clinical validation of the tempus xT next-generation targeted oncology sequencing assay.

We developed and clinically validated a hybrid capture next generation sequencing assay to detect somatic alterations and microsatellite instability in solid tumors and hematologic malignancies. This targeted oncology assay utilizes tumor-normal matched samples for highly accurate somatic alteration calling and whole transcriptome RNA sequencing for unbiased identification of gene fusion events. The assay was validated with a combination of clinical specimens and cell lines, and recorded a sensitivity of 99.

Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control.

To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts ( = 3,246) and seven African American cohorts ( = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes.

A genome-wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes.

Purpose: Diabetic retinopathy is the most common eye complication in patients with diabetes. The purpose of this study is to identify genetic factors contributing to severe diabetic retinopathy.

Methods: A genome-wide association approach was applied.

Clinical validation of the Tempus xO assay.

We have developed a clinically validated NGS assay that includes tumor, germline and RNA sequencing. We apply this assay to clinical specimens and cell lines, and we demonstrate a clinical sensitivity of 98.4% and positive predictive value of 100% for the clinically actionable variants measured by the assay.

Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics.

Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression to compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy and general robustness to misspecified reference sets. We apply this framework to 44 GTEx tissues and 100+ phenotypes from GWAS and meta-analysis studies, creating a growing public catalog of associations that seeks to capture the effects of gene expression variation on human phenotypes.

A novel MERTK mutation causing retinitis pigmentosa.

Purpose: Retinitis pigmentosa (RP) is a genetically heterogeneous inherited retinal dystrophy. To date, over 80 genes have been implicated in RP. However, the disease demonstrates significant locus and allelic heterogeneity not entirely captured by current testing platforms.

Survey of the Heritability and Sparse Architecture of Gene Expression Traits across Human Tissues.

Understanding the genetic architecture of gene expression traits is key to elucidating the underlying mechanisms of complex traits. Here, for the first time, we perform a systematic survey of the heritability and the distribution of effect sizes across all representative tissues in the human body. We find that local h2 can be relatively well characterized with 59% of expressed genes showing significant h2 (FDR < 0.

A gene-based association method for mapping traits using reference transcriptome data.

Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype.

Novel Associations between Common Breast Cancer Susceptibility Variants and Risk-Predicting Mammographic Density Measures.

Mammographic density measures adjusted for age and body mass index (BMI) are heritable predictors of breast cancer risk, but few mammographic density-associated genetic variants have been identified. Using data for 10,727 women from two international consortia, we estimated associations between 77 common breast cancer susceptibility variants and absolute dense area, percent dense area and absolute nondense area adjusted for study, age, and BMI using mixed linear modeling. We found strong support for established associations between rs10995190 (in the region of ZNF365), rs2046210 (ESR1), and rs3817198 (LSP1) and adjusted absolute and percent dense areas (all P < 10(-5)).

Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk.

Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (P<5 × 10(-8)) loci for dense area (AREG, ESR1, ZNF365, LSP1/TNNT3, IGF1, TMEM184B and SGSM3/MKL1), non-dense area (8p11.

A method to prioritize quantitative traits and individuals for sequencing in family-based studies.

Owing to recent advances in DNA sequencing, it is now technically feasible to evaluate the contribution of rare variation to complex traits and diseases. However, it is still cost prohibitive to sequence the whole genome (or exome) of all individuals in each study. For quantitative traits, one strategy to reduce cost is to sequence individuals in the tails of the trait distribution.

Cerebellar cortical atrophy in experimental autoimmune encephalomyelitis.

Brain atrophy measured by MRI is an important correlate with clinical disability and disease duration in multiple sclerosis (MS). Unfortunately, neuropathologic mechanisms which lead to this grey matter atrophy remain unknown. The objective of this study was to determine whether brain atrophy occurs in the mouse model, experimental autoimmune encephalomyelitis (EAE).