Multiplexed Dilute-and-Shoot Liquid Chromatography-Multiple-Reaction Monitoring Mass Spectrometry Clinical Assay for Metanephrines and Catecholamines in Human Urine.

Quantifying urinary catecholamines and metanephrines is essential for the clinical screening and diagnosis of neuroendocrine tumours. HPLC with electrochemical detection (HPLC-ECD) is commonly used for this type of analysis but requires extensive sample cleanup. Simple and rapid dilute-and-shoot LC-multiple-reaction monitoring (MRM)-MS assays have been developed for quantitating these analytes in urine but have not yet been validated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines.

The Real-World Clinical Outcomes of Heavily Pretreated HER2+ and HER2-Low Metastatic Breast Cancer Patients Treated with Trastuzumab Deruxtecan at a Single Centre.

Background: Trastuzumab deruxtecan (TDXd) is an antibody-drug conjugate that has demonstrated impressive activity in randomized controlled clinical trials in the context of patients with HER2-amplified and HER2-low metastatic breast cancer. We aimed to review the activity and adverse event profile of TDXd in heavily pretreated breast cancer patients in real practice.

Methods: We describe a single-center retrospective case series of metastatic breast cancer patients who were treated with TDXd.

Characterization of 53 Multiplexed Targeted Proteomics Assays for Verification Studies in Cancer Cell Lines.

The National Cancer Institute's Clinical Proteomics Tumor Analysis Consortium (CPTAC) was established to address the need for improved design, standardization, and validation of proteomics assays to enable better translation of biomarkers from the analytical lab to the clinic. Here, we applied CPTAC guidelines to characterize quantitative mass spectrometry (MS) assays in a new multiple reaction monitoring (MRM) proteomics panel. The panel of 50 proteins was developed in response to a previous study that identified a proteomic profile of altered translational control associated with response to a new cancer drug.

Molecular Mutations and Clinical Behavior in Bethesda III and IV Thyroid Nodules: A Comparative Study.

Thyroid cancer is the most common endocrine malignancy, and accurate diagnosis is crucial for effective management. Fine needle aspiration cytology, guided by the Bethesda System for Reporting Thyroid Cytopathology, categorizes thyroid nodules into six categories, with Bethesda III and IV representing indeterminate diagnoses that pose significant challenges for clinical decision-making. Understanding the molecular profiles of these categories may enhance diagnostic accuracy and guide treatment strategies.

Disentangling the effect of sex from brain size on brain organization and cognitive functioning.

Neuroanatomical sex differences estimated in neuroimaging studies are confounded by total intracranial volume (TIV) as a major biological factor. Employing a matching approach widely used for causal modeling, we disentangled the effect of TIV from sex to study sex-differentiated brain aging trajectories, their relation to functional networks and cytoarchitectonic classes, brain allometry, and cognition. Using data from the UK Biobank, we created subsamples that removed, maintained, or exaggerated the TIV differences in the original sample.

The Emerging Role of Multimodality Imaging in the Diagnosis and Management of Post Pericardiotomy Syndrome.

Purpose Of Review: This review aims to evaluate current diagnostic and therapeutic strategies for postpericardiotomy syndrome (PPS), with a focus on the evolving role of multimodality imaging, including echocardiography, cardiac computed tomography (CCT), and cardiac magnetic resonance imaging (CMR). The review also explores the potential benefits of advanced imaging in improving the accuracy and management of PPS.

Recent Findings: PPS, a common complication following cardiac surgery, presents with pleuritic chest pain, fever, and pericardial or pleural effusion.

The Role of Stereotactic Body Radiotherapy in Oligometastatic Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is a major cause of mortality in Canada, with many patients presenting with metastatic disease. The oligometastatic state (OM-NSCLC) may be amenable to cure using aggressive local consolidative therapies. Stereotactic body radiotherapy (SBRT), which entails the utilization of a high dose of radiation in one or few fractions, has many benefits in this setting, including its applicability in varied patient populations to ablate lesions in varied anatomical locations.

Obstetric outcomes in women with vulvodynia and vaginismus: a systematic review.

Purpose: Vulvodynia and vaginismus are pain disorders associated with adverse pregnancy outcomes. The few published studies addressing this topic were limited in terms of the different outcomes studied; hence, the purpose of our study was to perform the first systematic review examining maternal, neonatal and obstetric outcomes in patients with vulvodynia and/or vaginismus (VV).

Methods: We conducted a systematic review searching PubMed, EMBASE, Cochrane Library and SCOPUS until November 2023 for observational studies reporting maternal and/or neonatal outcomes of VV in pregnancy.

An adaptive enrichment design using Bayesian model averaging for selection and threshold-identification of predictive variables.

Precision medicine is transforming healthcare by offering tailored treatments that enhance patient outcomes and reduce costs. As our understanding of complex diseases improves, clinical trials increasingly aim to detect subgroups of patients with enhanced treatment effects. Biomarker-driven adaptive enrichment designs, which initially enroll a broad population and later restrict to treatment-sensitive patients, are gaining popularity.

Spectral characterization and comparison of EBT3, EBT4, and EBT-XD radiochromic films.

This study analyzed the spectral response of EBT3, EBT4, and EBT-XD radiochromic films using absorption spectroscopy. The primary focus was on characterizing the evolution of spectral signatures across a range of absorbed doses, thereby elucidating the unique dose-dependent response profiles of each film type. Ten samples of each film type were subjected to open field irradiation within their designated dose ranges (1-20 Gy for EBT3 and EBT4, 1-50 Gy for EBT-XD).

Reproducible protein quantitation of 270 human proteins at increased depth using nanoparticle-based fractionation and multiple reaction monitoring mass spectrometry with stable isotope-labelled internal standards.

Here we show that when using a mix of 274 light synthetic peptide standards (NAT) as surrogates for 270 human plasma proteins, as well as stable isotope-labelled standards (SIS) as normalizers (both from MRM Proteomics Inc.) for targeted quantitative analysis by liquid chromatography multiple reaction monitoring mass spectrometry (LC/MRM-MS), the Seer Proteograph™ platform allowed for the enrichment and absolute quantitation of up to an additional 62 targets (median) compared to two standard proteomic workflows without enrichment, representing an increase of 44%. The nanoparticle-based fractionation workflow resulted in improved reproducibility compared to a traditional proteomic workflow with no fractionation (median 8.

Strategies to reduce 28-day mortality in adult patients with bacteremia in the emergency department.

Background: Bacteremia, a common emergency department presentation, has a high burden of mortality, cost and morbidity. We aimed to identify areas for potential improvement in emergency department bacteremia management.

Methods: This retrospective cohort study included adults with bacteremia in an emergency department in 2019 and 2022.

A comprehensive experience-based framework of actionable priorities to enhance Canada's health and social care system: discussions with older persons, clinicians, managers, and decision-makers using nominal group technique.

Background: Existing frameworks of older persons' experiences in health and social care systems are usually based on single stakeholder perspectives and focused on limited aspects that are independent from one another. This study aimed to describe such experiences from the perspective of diverse stakeholders and develop a comprehensive experience-based framework for actionable priorities to enhance Canada's health and social care system.

Methods: We adapted a nominal group technique with a qualitative approach.

SARS-CoV-2 Assembly: Gaining Infectivity and Beyond.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was responsible for causing the COVID-19 pandemic. Intensive research has illuminated the complex biology of SARS-CoV-2 and its continuous evolution during and after the COVID-19 pandemic. While much attention has been paid to the structure and functions of the viral spike protein and the entry step of viral infection, partly because these are targets for neutralizing antibodies and COVID-19 vaccines, the later stages of SARS-CoV-2 replication, including the assembly and egress of viral progenies, remain poorly characterized.

Sex-Related Differences in Immunotherapy Outcomes of Patients with Advanced Non-Small Cell Lung Cancer.

Background: Immunotherapy with ICIs has revolutionized the treatment for NSCLC. The impact of sex on treatment outcomes remains unclear. The aim of this study was to evaluate sex-related differences in immunotherapy outcomes in a real-world population of NSCLC patients.

Guidance for Canadian Breast Cancer Practice: National Consensus Recommendations for Clinical Staging of Patients Newly Diagnosed with Breast Cancer.

The accurate staging of breast cancer is fundamental for guiding treatment decisions and predicting patient outcomes. However, there can be considerable variation in routine clinical practice based on individual interpretation of guidelines and depending on the healthcare provider initially involved in working up patients newly diagnosed with breast cancer, ranging from primary care providers, triage nurses, surgeons, and/or oncologists. The optimal approach for clinical staging, particularly in asymptomatic patients presenting with intermediate-risk disease, remains a topic of dialogue among clinicians.

Guidance for Canadian Breast Cancer Practice: National Consensus Recommendations for the Systemic Treatment of Patients with HER2+ Breast Cancer in Both the Early and Metastatic Setting.

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is an aggressive subtype of breast cancer associated with a poor prognosis when sub-optimally treated. Recent advances include new and effective targeted therapies that have significantly improved outcomes for patients. Despite these advances, there are significant gaps across Canada, underscoring the need for evidence-based consensus guidance to inform treatment decisions.

Founder pathogenic variants in colorectal neoplasia susceptibility genes in Ashkenazi Jews undergoing colonoscopy.

Background: Colorectal neoplasia is one of the most common tumors affecting Western populations.

Methods: In this study we used a custom amplicon sequencing platform and an in-house bioinformatic pipeline to study constitutional DNA from two different case series of Ashkenazi Jews undergoing colonoscopy (n = 765). The first series all had pathologically confirmed colorectal adenomas and/or carcinoma.

3D-Q-FISH/Telomere/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma.

The bi- or multinucleated Reed-Sternberg cell (RS) is the diagnostic cornerstone of Epstein-Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC)-derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS.

Engagement of people with lived experience in studies published in high-impact psychiatry journals: meta-research review.

Background: We evaluated studies published in high-impact psychiatry journals to assess (1) the proportion that reported in articles whether they engaged people with lived experience; (2) the proportion that likely engaged people with lived experience; and, if engagement occurred, (3) stages of research (planning, conduct, interpretation, dissemination); and (4) engagement level (consult, involve, partner).

Methods: We searched PubMed on December 14, 2022, for articles in psychiatry journals with impact factor ≥ 10 and reviewed articles in reverse chronological order until 141 were included, based on pre-study precision estimation. We contacted authors to obtain information on engagement.

Master regulators of neurogenesis: the dynamic roles of Ephrin receptors across diverse cellular niches.

The ephrin receptors (EphRs) are the largest family of receptor tyrosine kinases (RTKs) that are abundantly expressed in the developing brain and play important roles at different stages of neurogenesis ranging from neural stem cell (NSC) fate specification to neural migration, morphogenesis, and circuit assembly. Defects in EphR signalling have been associated with several pathologies including neurodevelopmental disorders (NDDs), intellectual disability (ID), and neurodegenerative diseases (NDs). Here, we review our current understanding of the complex and dynamic role of EphRs in the brain and discuss how deregulation of these receptors contributes to disease, highlighting their potential as valuable druggable targets.

Mechanisms of Metal-Induced Hepatic Inflammation.

Purpose Of Review: Worldwide, there is an increasing prevalence of hepatic diseases. The most common diseases include alcoholic-associated liver disease (ALD), metabolic dysfunction-associated fatty liver disease/ metabolic dysfunction-associated steatohepatitis (MAFLD/MASH) and viral hepatitis. While there are many important mediators of these diseases, there is increasing recognition of the importance of the inflammatory immune response in hepatic disease pathogenesis.