CDKN2A-p16 Deletion and Activated KRAS Drive Barrett's-Like Gland Hyperplasia-Metaplasia and Synergize in the Development of Dysplasia Precancer Lesions.

Background & Aims: Barrett's esophagus is the precursor of esophageal dysplasia and esophageal adenocarcinoma. CDKN2A-p16 deletions were reported in 34%-74% of patients with Barrett's esophagus who progressed to dysplasia and esophageal adenocarcinoma, suggesting that p16 loss may drive neoplastic progression. KRAS activation frequently occurs in esophageal adenocarcinoma and precancer lesions.

Development of an Accessible and Scalable Quantitative Polymerase Chain Reaction Assay for Monkeypox Virus Detection.

During the 2022 monkeypox (MPX) outbreak, testing has been limited and results delayed, allowing ongoing transmission. Gold-standard quantitative polymerase chain reaction (qPCR) diagnostics are difficult to obtain. This research adapted the June 2022 CDC MPX qPCR assay for broad implementation.

Changes in SARS-CoV-2 viral load and mortality during the initial wave of the pandemic in New York City.

Public health interventions such as social distancing and mask wearing decrease the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they decrease the viral load of infected patients and whether changes in viral load impact mortality from coronavirus disease 2019 (COVID-19). We evaluated 6923 patients with COVID-19 at six New York City hospitals from March 15-May 14, 2020, corresponding with the implementation of public health interventions in March. We assessed changes in cycle threshold (CT) values from reverse transcription-polymerase chain reaction tests and in-hospital mortality and modeled the impact of viral load on mortality.

Machine Learning Highlights Downtrending of COVID-19 Patients with a Distinct Laboratory Profile.

Background: New York City (NYC) experienced an initial surge and gradual decline in the number of SARS-CoV-2-confirmed cases in 2020. A change in the pattern of laboratory test results in COVID-19 patients over this time has not been reported or correlated with patient outcome.

Methods: We performed a retrospective study of routine laboratory and SARS-CoV-2 RT-PCR test results from 5,785 patients evaluated in a NYC hospital emergency department from March to June employing machine learning analysis.

Pretest Symptom Duration and Cycle Threshold Values for Severe Acute Respiratory Syndrome Coronavirus 2 Reverse-Transcription Polymerase Chain Reaction Predict Coronavirus Disease 2019 Mortality.

Background: The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and patient symptom duration in both in- and outpatients, and the impact of these factors on patient outcomes, are currently unknown. Understanding these associations is important to clinicians caring for patients with coronavirus disease 2019 (COVID-19).

Methods: We conducted an observational study between March 10 and May 30, 2020 at a large quaternary academic medical center in New York City.

Blood component utilization in COVID-19 patients in New York City: Transfusions do not follow the curve.

Background: Blood suppliers and transfusion services have worked diligently to maintain an adequate blood supply during the COVID-19 pandemic. Our experience has shown that some COVID-19 inpatients require transfusion support; understanding this need is critical to blood product inventory management.

Study Design And Methods: Hospital-wide and COVID-19 specific inpatient blood product utilization data were collected retrospectively for our network's two tertiary academic medical centers over a 9-week period (March 1, 2020-May 2, 2020), when most inpatients had COVID-19.

SARS-CoV-2 Viral Load Predicts Mortality in Patients with and without Cancer Who Are Hospitalized with COVID-19.

Patients with cancer may be at increased risk of severe coronavirus disease 2019 (COVID-19), but the role of viral load on this risk is unknown. We measured SARS-CoV-2 viral load using cycle threshold (C) values from reverse-transcription polymerase chain reaction assays applied to nasopharyngeal swab specimens in 100 patients with cancer and 2,914 without cancer who were admitted to three New York City hospitals. Overall, the in-hospital mortality rate was 38.

Clinical Performance of SARS-CoV-2 Molecular Tests.

Molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the gold standard for diagnosis of coronavirus disease 2019 (COVID-19), but the clinical performance of these tests is still poorly understood, particularly with regard to disease course, patient-specific factors, and viral shedding. From 10 March to 1 May 2020, NewYork-Presbyterian laboratories performed 27,377 SARS-CoV-2 molecular assays from 22,338 patients. Repeat testing was performed for 3,432 patients, of which 2,413 had initial negative and 802 had initial positive results.

Racial Differences in the Association Between Luminal Master Regulator Gene Expression Levels and Breast Cancer Survival.

Purpose: Compared with their European American (EA) counterparts, African American (AA) women are more likely to die from breast cancer in the United States. This disparity is greatest in hormone receptor-positive subtypes. Here we uncover biological factors underlying this disparity by comparing functional expression and prognostic significance of master transcriptional regulators of luminal differentiation.

Using R and Bioconductor in Clinical Genomics and Transcriptomics.

Bioinformatics pipelines are essential in the analysis of genomic and transcriptomic data generated by next-generation sequencing (NGS). Recent guidelines emphasize the need for rigorous validation and assessment of robustness, reproducibility, and quality of NGS analytic pipelines intended for clinical use. Software tools written in the R statistical language and, in particular, the set of tools available in the Bioconductor repository are widely used in research bioinformatics; and these frameworks offer several advantages for use in clinical bioinformatics, including the breath of available tools, modular nature of software packages, ease of installation, enforcement of interoperability, version control, and short learning curve.

Downregulation of () follows the stepwise progression to gastric adenocarcinoma.

Gastric adenocarcinoma (GC) is a leading cause of cancer-related deaths worldwide. The transcription factor gene () is methylated and downregulated in human GC tissues. Using human GC samples, we determined which cells downregulate , when downregulation occurs, if downregulation correlates with clinical-pathologic characteristics, and whether plays a role in invasion and/or proliferation of cultured cells.

High-resolution genomic alterations in Barrett's metaplasia of patients who progress to esophageal dysplasia and adenocarcinoma.

The main risk factor for esophageal dysplasia and adenocarcinoma (DAC) is Barrett's esophagus (BE), characterized by intestinal metaplasia. The critical genomic mechanisms that lead to progression of nondysplastic BE to DAC remain poorly understood and require analyses of longitudinal patient cohorts and high-resolution assays. We tested BE tissues from 74 patients, including 42 nonprogressors from two separate groups of 21 patients each and 32 progressors (16 in a longitudinal cohort before DAC/preprogression-BE and 16 with temporally concurrent but spatially separate DAC/concurrent-BE).

When to re-order laboratory tests? Learning laboratory test shelf-life.

Most laboratory results are valid for only a certain time period (laboratory tests shelf-life), after which they are outdated and the test needs to be re-administered. Currently, laboratory test shelf-lives are not centrally available anywhere but the implicit knowledge of doctors. In this work we propose an automated method to learn laboratory test-specific shelf-life by identifying prevalent laboratory test order patterns in electronic health records.

High-definition CpG methylation of novel genes in gastric carcinogenesis identified by next-generation sequencing.

Gastric cancers are the most frequent gastric malignancy and usually arise in the sequence of Helicobacter pylori-associated chronic gastritis. CpG methylation is a central mechanism of epigenetic gene regulation affecting cancer-related genes, and occurs early in gastric carcinogenesis. DNA samples from non-metaplastic gastric mucosa with variable levels of gastritis (non-metaplastic mucosa), intestinal metaplasia, or gastric cancer were screened with methylation arrays for CpG methylation of cancer-related genes and 30 gene targets were further characterized by high-definition bisulfite next-generation sequencing.

Mutational analysis by next generation sequencing of gastric type dysplasia occurring in hyperplastic polyps of the stomach: Mutations in gastric hyperplastic polyps.

Unlabelled: Gastric hyperplastic polyps (GHP) are the most common type of polyps occurring in the stomach. Although GHP are broadly interpreted as benign lesions, they may progress to dysplasia and adenocarcinoma.

Objective: In this study, we aimed to identify genomic mutations that characterize and may drive malignant transformation in GHP by using next-generation sequencing.

Evaluation of Mutational Testing of Preneoplastic Barrett's Mucosa by Next-Generation Sequencing of Formalin-Fixed, Paraffin-Embedded Endoscopic Samples for Detection of Concurrent Dysplasia and Adenocarcinoma in Barrett's Esophagus.

Barrett's intestinal metaplasia (BIM) may harbor genomic mutations before the histologic appearance of dysplasia and cancer and requires frequent surveillance. We explored next-generation sequencing to detect mutations with the analytical sensitivity required to predict concurrent high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus by testing nonneoplastic BIM. Formalin-fixed, paraffin-embedded (FFPE) routine biopsy or endoscopic mucosal resection samples from 32 patients were tested: nonprogressors to HGD or EAC (BIM-NP) with BIM, who never had a diagnosis of dysplasia or EAC (N = 13); progressors to HGD or EAC (BIM-P) with BIM and a worse diagnosis of HGD or EAC (N = 15); and four BIM-negative samples.

Molecular and histologic considerations in the assessment of serrated polyps.

Unlabelled: CONTEXT : Colorectal cancer is a heterogeneous disease resulting from different molecular pathways of carcinogenesis. Recent data evaluating the histologic features and molecular basis of the serrated polyp-carcinoma pathway have significantly contributed to more comprehensive classifications of and treatment recommendations for these tumors.

Objective: To integrate the most recent molecular findings in the context of histologic classifications of serrated lesions and their implications in diagnostic pathology and colorectal cancer surveillance.

Temporal trends of hemoglobin A1c testing.

Objective: The study of utilization patterns can quantify potential overuse of laboratory tests and find new ways to reduce healthcare costs. We demonstrate the use of distributional analytics for comparing electronic health record (EHR) laboratory test orders across time to diagnose and quantify overutilization.

Materials And Methods: We looked at hemoglobin A1c (HbA1c) testing across 119,000 patients and 15 years of hospital records.

Identifying and mitigating biases in EHR laboratory tests.

Electronic health record (EHR) data show promise for deriving new ways of modeling human disease states. Although EHR researchers often use numerical values of laboratory tests as features in disease models, a great deal of information is contained in the context within which a laboratory test is taken. For example, the same numerical value of a creatinine test has different interpretation for a chronic kidney disease patient and a patient with acute kidney injury.

The ideal laboratory information system.

Context: Laboratory information systems (LIS) are critical components of the operation of clinical laboratories. However, the functionalities of LIS have lagged significantly behind the capacities of current hardware and software technologies, while the complexity of the information produced by clinical laboratories has been increasing over time and will soon undergo rapid expansion with the use of new, high-throughput and high-dimensionality laboratory tests. In the broadest sense, LIS are essential to manage the flow of information between health care providers, patients, and laboratories and should be designed to optimize not only laboratory operations but also personalized clinical care.

Variation in human erythrocyte membrane unsaturated Fatty acids: correlation with cardiovascular disease.

Context: Whether cell membrane fatty acid (FA) composition is a useful indicator of vascular disease is unclear.

Objective: To study variation of erythrocyte (RBC) membrane FA in samples from healthy volunteers, hospitalized patients, and cardiac troponin I-elevated patients with myocardial damage without a priori assumptions as to FA composition.

Design: We separated FAs extracted from RBCs by gas chromatography and identified them by mass spectrometry.

Cardiomyogenic differentiation potential of human adipose precursor cells.

DNA demethylation agent 5-azacytidine has been widely described in literature as an effective chemical stimulus used to promote cardiomyogenic differentiation in various cell types, ranging from embryonic stem cells, P19 cells, bone marrow-derived mesenchymal stem cells, and recently to adipose-derived stem cells. The purpose of this study was to examine the effects of 5-azacytidine on human adipose precursor cell differentiation along the cardiomyogenic lineage.

Value of CRP in coronary risk determination.

Initial studies showed that C-reactive protein (CRP) may have a role in the genesis of atherosclerotic lesions and as a novel biomarkers of patients at risk of developing coronary heart disease (CHD) events. Most of these studies had methodologic limitations, and recent data contradict these findings and suggest that inflammatory markers, such as CRP, have limited usefulness in the prediction of CHD events over and above conventional risk factors. Its low predictive value creates difficulty in interpreting the CRP data in an individual patient.