A multicenter study to evaluate the analytical precision by pathologists using the Aperio GT 450 DX.

Background: Digital pathology systems (DPS) are emerging as capable technologies for clinical practice. Studies have analyzed pathologists' diagnostic concordance by comparing reviews of whole slide images (WSIs) to glass slides (e.g.

Understanding the financial aspects of digital pathology: A dynamic customizable return on investment calculator for informed decision-making.

Background: The adoption of digital pathology has transformed the field of pathology, however, the economic impact and cost analysis of implementing digital pathology solutions remain a critical consideration for institutions to justify. Digital pathology implementation requires a thorough evaluation of associated costs and should identify and optimize resource allocation to facilitate informed decision-making. A dynamic cost calculator to estimate the financial implications of deploying digital pathology systems was needed to estimate the financial effects on transitioning to a digital workflow.

Establishing guidelines for sentinel lymph node ultrastaging in endometrial cancer.

Background: Many sentinel lymph node (SLN) ultrastaging protocols for endometrial cancer exist, but there is no consensus method.

Objective: This study aims to develop guidelines for size criteria in SLN evaluation for endometrial cancer, to determine whether a single cytokeratin AE1:AE3 immunohistochemical slide provides sufficient data for diagnosis, and to compare cost efficiency between current and limited ultrastaging protocols at a large tertiary care institution.

Methods: Our current SLN ultrastaging protocol consists of cutting two adjacent paraffin block sections at two levels (L1 and L2), 50 μm apart, with two slides at each level stained with hematoxylin and eosin and cytokeratin AE1:AE3 immunohistochemistry.

Digital pathology operations at a tertiary cancer center: Infrastructure requirements and operational cost.

Whole slide imaging is revolutionizing the field of pathology and is currently being used for clinical, educational, and research initiatives by an increasing number of institutions. Pathology departments have distinct needs for digital pathology systems, yet the cost of digital workflows is cited as a major barrier for widespread adoption by many organizations. Memorial Sloan Kettering Cancer Center (MSK) is an early adopter of whole slide imaging with incremental investments in resources that started more than 15 years ago.

Quality Management System in Clinical Digital Pathology Operations at a Tertiary Cancer Center.

Digital pathology workflows can improve pathology operations by allowing reliable and fast retrieval of digital images, digitally reviewing pathology slides, enabling remote work and telepathology, use of computer-aided tools, and sharing of digital images for research and educational purposes. The need for quality systems is a prerequisite for successful clinical-grade digital pathology adoption and patient safety. In this article, we describe the development of a structured digital pathology laboratory quality management system (QMS) for clinical digital pathology operations at Memorial Sloan Kettering Cancer Center (MSK).

Digital pathology systems enabling quality patient care.

Pathology laboratories are undergoing digital transformations, adopting innovative technologies to enhance patient care. Digital pathology systems impact clinical, education, and research use cases where pathologists use digital technologies to perform tasks in lieu of using glass slides and a microscope. Pathology professional societies have established clinical validation guidelines, and the US Food and Drug Administration have also authorized digital pathology systems for primary diagnosis, including image analysis and machine learning systems.

Digital Pathology Operations at an NYC Tertiary Cancer Center During the First 4 Months of COVID-19 Pandemic Response.

Implementation of an infrastructure to support digital pathology began in 2006 at Memorial Sloan Kettering Cancer Center. The public health emergency and COVID-19 pandemic regulations in New York City required a novel workflow to sustain existing operations. While regulatory enforcement discretions offered faculty workspace flexibility, a substantial portion of laboratory and digital pathology workflows require on-site presence of staff.

Efficient Visualization of Whole Slide Images in Web-based Viewers for Digital Pathology.

Context.—: Wide adoption of digital pathology requires efficient visualization and navigation in Web-based digital slide viewers, which is poorly defined.

Objective.

Integrating digital pathology into clinical practice.

The field of anatomic pathology has been evolving in the last few decades and the advancements have been largely fostered by innovative technology. Immunohistochemistry enabled a paradigm shift in discovery and diagnostic evaluation, followed by booming genomic advancements which allowed for submicroscopic pathologic characterization, and now the field of digital pathology coupled with machine learning and big data acquisition is paving the way to revolutionize the pathology medical domain. Whole slide imaging (WSI) is a disruptive technology where glass slides are digitized to produce on-screen whole slide images.

Integrated digital pathology at scale: A solution for clinical diagnostics and cancer research at a large academic medical center.

Objective: Broad adoption of digital pathology (DP) is still lacking, and examples for DP connecting diagnostic, research, and educational use cases are missing. We blueprint a holistic DP solution at a large academic medical center ubiquitously integrated into clinical workflows; researchapplications including molecular, genetic, and tissue databases; and educational processes.

Materials And Methods: We built a vendor-agnostic, integrated viewer for reviewing, annotating, sharing, and quality assurance of digital slides in a clinical or research context.

Dissecting the Business Case for Adoption and Implementation of Digital Pathology: A White Paper from the Digital Pathology Association.

We believe the switch to a digital pathology (DP) workflow is imminent and it is essential to understand the economic implications of conversion. Many aspects of the adoption of DP will be disruptive and have a direct financial impact, both in short term costs, such as investment in equipment and personnel, and long term revenue potential, such as improved productivity and novel tests. The focus of this whitepaper is to educate pathologists, laboratorians and other stakeholders about the business and monetary considerations of converting to a digital pathology workflow.

(Re) Defining the High-Power Field for Digital Pathology.

Background: The microscope high-power field (HPF) is the cornerstone for histopathology diagnostic evaluation such as the quantification of mitotic figures, lymphocytes, and tumor grading. With traditional light microscopy, HPFs are typically evaluated by quantifying histologic events in 10 fields of view at × 400 magnification. In the era of digital pathology, new variables are introduced that may affect HPF evaluation.

Validation of a digital pathology system including remote review during the COVID-19 pandemic.

Remote digital pathology allows healthcare systems to maintain pathology operations during public health emergencies. Existing Clinical Laboratory Improvement Amendments regulations require pathologists to electronically verify patient reports from a certified facility. During the 2019 pandemic of COVID-19 disease, caused by the SAR-CoV-2 virus, this requirement potentially exposes pathologists, their colleagues, and household members to the risk of becoming infected.

Clinical Laboratory Employees' Attitudes Toward Artificial Intelligence.

Objective: The objective of this study was to determine the attitudes of laboratory personnel toward the application of artificial intelligence (AI) in the laboratory.

Methods: We surveyed laboratory employees who covered a range of work roles, work environments, and educational levels.

Results: The survey response rate was 42%.

Detection of Intestinal Protozoa in Trichrome-Stained Stool Specimens by Use of a Deep Convolutional Neural Network.

Intestinal protozoa are responsible for relatively few infections in the developed world, but the testing volume is disproportionately high. Manual light microscopy of stool remains the gold standard but can be insensitive, time-consuming, and difficult to maintain competency. Artificial intelligence and digital slide scanning show promise for revolutionizing the clinical parasitology laboratory by augmenting the detection of parasites and slide interpretation using a convolutional neural network (CNN) model.

The effect of valinomycin in fibroblasts from patients with fatty acid oxidation disorders.

Disorders of the carnitine cycle and of the beta oxidation spiral impair the ability to obtain energy from fats at time of fasting and stress. This can result in hypoketotic hypoglycemia, cardiomyopathy, cardiac arrhythmia and other chronic medical problems. The in vitro study of fibroblasts from patients with these conditions is impaired by their limited oxidative capacity.

Genotype-phenotype correlation in primary carnitine deficiency.

Primary carnitine deficiency is caused by defective OCTN2 carnitine transporters encoded by the SLC22A5 gene. Lack of carnitine impairs fatty acid oxidation resulting in hypoketotic hypoglycemia, hepatic encephalopathy, skeletal and cardiac myopathy. Recently, asymptomatic mothers with primary carnitine deficiency were identified by low carnitine levels in their infant by newborn screening.

Disorders of creatine transport and metabolism.

Creatine is a nitrogen containing compound that serves as an energy shuttle between the mitochondrial sites of ATP production and the cytosol where ATP is utilized. There are two known disorders of creatine synthesis (both transmitted as autosomal recessive traits: arginine: glycine amidinotransferase (AGAT) deficiency; OMIM 602360; and guanidinoacetate methyltransferase (GAMT) deficiency (OMIM 601240)) and one disorder of creatine transport (X-linked recessive SLC6A8 creatine transporter deficiency (OMIM 300036)). All these disorders are characterized by brain creatine deficiency, detectable by magnetic resonance spectroscopy.

Glycosylation of the OCTN2 carnitine transporter: study of natural mutations identified in patients with primary carnitine deficiency.

Primary carnitine deficiency is caused by impaired activity of the Na(+)-dependent OCTN2 carnitine/organic cation transporter. Carnitine is essential for entry of long-chain fatty acids into mitochondria and its deficiency impairs fatty acid oxidation. Most missense mutations identified in patients with primary carnitine deficiency affect putative transmembrane or intracellular domains of the transporter.

Creatine transporter deficiency in two half-brothers.

X-linked cerebral creatine deficiency is caused by the deficiency of the creatine transporter encoded by the SLC6A8 gene. Here, we report two half-brothers with this condition and characterize creatine transport in human fibroblasts. The propositus presented at 6 months of age with delays in development and slow progress since then with no regression.

HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system.

HIV-1 Vpr is a viral accessory protein that activates ATR through the induction of DNA replication stress. ATR activation results in cell cycle arrest in G2 and induction of apoptosis. In the present study, we investigate the role of the ubiquitin/proteasome system (UPS) in the above activity of Vpr.

HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT.

The HIV-1 accessory protein viral protein R (Vpr) causes G2 arrest and apoptosis in infected cells. We previously identified the DNA damage-signaling protein ATR as the cellular factor that mediates Vpr-induced G2 arrest and apoptosis. Here, we examine the mechanism of induction of apoptosis by Vpr and how it relates to induction of G2 arrest.