Tau Burden is Best Captured by Magnitude and Extent: Tau-MaX as a Measure of Global Tau.

Tau exhibits change in both spatial extent and density of pathology along the Alzheimer's disease (AD) spectrum with each aspect contributing to the overall burden of pathological tau. Nevertheless, studies using Tau PET have measured either magnitude using standardized uptake value ratios (SUVRs) or extent using number of Tau+ regions. We hypothesized that combining these two dimensions into a single measure of Magnitude and eXtent, Tau-MaX, would provide improved quantification of global tau burden as well as allowing for a region-agnostic measure of global tau burden that does not require a pre-specified region of interest (ROI) or meta-ROI.

Analytical Validation and Performance Evaluation of Amplicon-Based Next-Generation Sequencing Assays for Detecting and Other Gene Amplifications in Solid Tumors.

Background: Targeted next-generation sequencing (NGS) panels are increasingly being utilized to identify actionable gene amplifications (copy number > 4) among solid tumors.

Methods: This study validated the analytical performance of two amplicon-based NGS assays, the Oncomine Comprehensive Panel (OCAv3) and the Oncomine Focus Assay (OFA), for detecting gene amplification in formalin-fixed paraffin-embedded (FFPE) tumors of varying cellularity. OCAv3 was assessed for amplification detection in 756 FFPE samples comprising various tumor types.

Advances in Vulvar Cancer Biology and Management.

Purpose: Vulvar squamous cell carcinoma (VSCC), a rare gynecologic malignancy, has been rising in incidence. Molecular classification on the basis of human papilloma virus (HPV) and tumor protein 53 (p53) status has identified three clinically distinct subtypes, but we still treat all VSCCs the same. Here, we review molecular classification of VSCC, outline treatment landscape, and highlight potential for targeted therapies in advanced VSCC.

Implementation of HER2 Testing in Endometrial Cancer, a Summary of Real-World Initial Experience in a Large Tertiary Cancer Center.

HER2-targeted therapies have transformed the management of advanced or recurrent serous endometrial cancer (EC), leading to an increased clinical demand for HER2 testing. Despite its adoption in select academic centers, the global extent of such tumor testing is unclear. In this study, we report on the initial two-year experience of HER2 testing at a major academic center with a reference gynecologic oncology service and biomarker reference laboratory.

Fit-for-Purpose Ki-67 Immunohistochemistry Assays for Breast Cancer.

New therapies are being developed for breast cancer, and in this process, some "old" biomarkers are reutilized and given a new purpose. It is not always recognized that by changing a biomarker's intended use, a new biomarker assay is created. The Ki-67 biomarker is typically assessed by immunohistochemistry (IHC) to provide a proliferative index in breast cancer.

Paradigm Shifts in Vascular Surgery: Analysis of the Top 100 Innovative and Disruptive Academic Publications.

Background: Disruption score (DS) is a novel bibliometric created to identify research that shifts paradigms, which may be overlooked by citation count (CC). We analyzed the most disruptive, compared to the most cited, literature in vascular surgery, and hypothesized that DS and CC would not correlate.

Methods: A PubMed search identified vascular surgery publications from 1954 to 2014.

Human Epidermal Growth Factor Receptor 2-Low Breast Cancer Brain Metastases: An Opportunity for Targeted Systemic Therapies in a High-Need Patient Population.

Purpose: Trastuzumab deruxtecan is a new treatment option for patients with advanced human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC). Although HER2-low status has been characterized in early and advanced BC, it has yet to be fully characterized in brain metastases (BrM).

Methods: Patients who underwent surgery for BC BrM at Sunnybrook Health Sciences Centre and for whom HER2 status was available on resected BrM were studied.

Overcoming Barriers: Sex Disparity in Surgeon Ergonomics.

Background: Musculoskeletal discomfort is widely experienced by surgeons across multiple surgical specialties. Developing technologies and new minimally invasive techniques add further complexity and ergonomic stressors. These stressors differentially affect male and female surgeons, but little is known about the role these sex disparities play in surgical ergonomic stress.

Benchmarking differential abundance methods for finding condition-specific prototypical cells in multi-sample single-cell datasets.

Background: To analyze the large volume of data generated by single-cell technologies and to identify cellular correlates of particular clinical or experimental outcomes, differential abundance analyses are often applied. These algorithms identify subgroups of cells whose abundances change significantly in response to disease progression, or to an experimental perturbation. Despite the effectiveness of differential abundance analyses in identifying critical cell-states, there is currently no systematic benchmarking study to compare their applicability, usefulness, and accuracy in practice across single-cell modalities.

Methylation Testing as an Integral Component of Universal Endometrial Cancer Screening-A Critical Appraisal.

MLH1/PMS2 loss due to promoter hypermethylation (-PHM) is the most common cause of mismatch repair (MMR) deficiency in endometrial cancer (EC). This study aimed to determine the proportion of -deficient EC with PHM, assess the impact of the reflex -PHM testing strategy, and evaluate the associated costs within the publicly funded Canadian healthcare system. In a cohort of 2504 EC samples, 534 (21.

Budget impact analysis of molecular subtype profiling in endometrial cancer.

Objective: This study evaluated the costs associated with four approaches to classifying endometrial cancer (EC), including histomorphological, histomorphological with ancillary immunohistochemical assays, histomolecular and selective molecular classification.

Methods: Direct costs were determined per EC sample from the hospital's perspective. A budget impact analysis and sensitivity analysis were conducted to estimate the mean, minimum and maximum costs per sample and annual institutional costs in adjusted 2022 Canadian dollars.

Nitro-benzylideneoxymorphone, a bifunctional mu and delta opioid receptor ligand with high mu opioid receptor efficacy.

There is a major societal need for analgesics with less tolerance, dependence, and abuse liability. Preclinical rodent studies suggest that bifunctional ligands with both mu (MOPr) and delta (DOPr) opioid peptide receptor activity may produce analgesia with reduced tolerance and other side effects. This study explores the structure-activity relationships (SAR) of our previously reported MOPr/DOPr lead, benzylideneoxymorphone (BOM) with C7-methylene-substituted analogs.

Epidemiology, repair technique, and predictors of stroke and mortality in penetrating carotid artery injuries.

Objective: Penetrating carotid artery injuries (PCAI) are significantly morbid and deadly, often presenting in extremis with associated injuries and central nervous system deficit. Repair may be challenging with arterial reconstruction vs ligation role poorly defined. This study evaluated contemporary outcomes and management of PCAI.

Effective early antiretroviral therapy in perinatal-HIV infection reduces subsequent plasma inflammatory profile.

Background: The long-term immunologic effects of antiretroviral therapy (ART) in children with perinatally-acquired HIV (PHIV) have not been fully elucidated. Here, we investigated how the timing of ART initiation affects the long-term immune profile of children living with PHIV by measuring immunomodulatory plasma cytokines, chemokines, and adenosine deaminases (ADAs).

Methods: 40 PHIV participants initiated ART during infancy.

International Multi-Institutional Experience with Presentation and Management of Aortic Arch Laterality in Aberrant Subclavian Artery and Kommerell's Diverticulum.

Background: Aberrant subclavian artery (ASA) with or without Kommerell's diverticulum (KD) is a rare anatomic aortic arch anomaly that can cause dysphagia and/or life-threatening rupture. The objective of this study is to compare outcomes of ASA/KD repair in patients with a left versus right aortic arch.

Methods: Using the Vascular Low Frequency Disease Consortium methodology, a retrospective review was performed of patients ≥18 years old with surgical treatment of ASA/KD from 2000 to 2020 at 20 institutions.

Ki67 in Breast Cancer Assay: An Ad Hoc Testing Recommendation from the Canadian Association of Pathologists Task Force.

Ki67, a marker of cellular proliferation, is commonly assessed in surgical pathology laboratories. In breast cancer, Ki67 is an established prognostic factor with higher levels associated with worse long-term survival. However, Ki67 IHC is considered of limited clinical use in breast cancer management largely due to issues related to standardization and reproducibility of scoring across laboratories.

Benchmarking differential abundance methods for finding condition-specific prototypical cells in multi-sample single-cell datasets.

Modern single-cell data analysis relies on statistical testing (e.g. differential expression testing) to identify genes or proteins that are up-or down-regulated in relation to cell-types or clinical outcomes.

The Impact of the Pathologist in Multidisciplinary Cancer Conferences on Patient Care : Evidence From the Literature.

Objectives: Multidisciplinary cancer conferences (MCCs) are important tools in the treatment of patients with complex health issues, helping clinicians achieve optimal outcomes in oncological practice. To explore the role of pathologists at MCCs, we conducted a review of prior research on this topic.

Methods: We conducted a scoping review by searching MEDLINE, EMBASE, and the Cochrane Library for English-language qualitative, quantitative, or multiple/mixed methods studies on the role and impact of pathologists on MCCs.

Cystic neutrophilic granulomatous mastitis: sensitivity and specificity of 16s rRNA and Sanger sequencing for spp.

Aims: Cystic neutrophilic granulomatous mastitis (CNGM) is a subtype of granulomatous mastitis (GM) associated with spp infection. We aimed to analyse the prevalence of Corynebacteria in CNGM and non-CNGM cases.

Methods: Breast specimens diagnosed as granulomatous inflammation between 2010 and 2020 were reviewed to identify a CNGM cohort and a non-CNGM cohort.

Contemporary outcomes after treatment of aberrant subclavian artery and Kommerell's diverticulum.

Objective: Aberrant subclavian artery (ASA) and Kommerell's diverticulum (KD) are rare vascular anomalies that may be associated with lifestyle-limiting and life-threatening complications. The aim of this study is to report contemporary outcomes after invasive treatment of ASA/KD using a large international dataset.

Methods: Patients who underwent treatment for ASA/KD (2000-2020) were identified through the Vascular Low Frequency Disease Consortium, a multi-institutional collaboration to investigate uncommon vascular disorders.

The annoying flaws of gerontological research.

Gerontological research has accelerated dramatically in the last few decades. However, despite increased public interest, federal funding, an army of researchers, and many notable discoveries and high-impact publications, the goal of achieving even a modest extension of human lifespan seems to be as far away as ever or, at best, remains within the realm of lifestyle and diet optimization efforts. Humanity has already benefited from a lifespan revolution in the first half of the 20th Century, which was brought about by improved sanitation and hygiene, clean water, and our successful war on infectious diseases.

Gynecologic pathology services in low- and middle-income countries.

Objective: The International Gynecologic Cancer Society (IGCS) offers multidisciplinary conferences to underserved communities. Mentor pathologists have become an integral part of these tumor boards, as pathology services in low-to-middle-income countries are often inadequate and disjointed. The IGCS Pathology Working Group conducted a survey to assess barriers to quality pathology services in low-to-middle-income countries and identified potential solutions.