Real-world impact of pembrolizumab availability for deficient mismatch repair metastatic colorectal cancer.

Background: Immunotherapy has emerged as a standard treatment for deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). Pembrolizumab became widely available as a first-line (1L) option in Australia following the Pharmaceutical Benefits Scheme (PBS) listing in August 2021. The uptake of new treatment options can be lengthy.

Causes of Intracranial Hypotension: Spontaneous, Traumatic, and Iatrogenic Cerebrospinal Fluid Leaks.

Cerebrospinal fluid leaks are important to recognize because they can cause debilitating symptoms for patients and have life-threatening complications. Leakage of cerebrospinal fluid (CSF) from the subarachnoid space can occur at the cranial or spinal level, with distinct clinical presentations, diagnostic evaluations, and treatment modalities depending on the type and location of the leak. Spontaneous, traumatic, and iatrogenic spinal CSF leaks cause reduced intracranial CSF volume and the clinicoradiologic syndrome commonly called "intracranial hypotension".

5-HT1F agonists.

5-Hydroxytryptamine (HT)/serotonin receptor agonism has been a long-recognized property of triptan medications, and more recently, the study and development of medications with selective binding to the 1F receptor subtype have been explored. While the exact mechanism contributing to decreased symptoms of an acute migraine attack remains unclear, selective 5-HT1F agonists have demonstrated clinical efficacy with lasmiditan as the only approved medication from this class to date. Lasmiditan lacks vasoconstrictive properties, giving it utility in specific patient populations in whom triptans should be avoided.

Relatively undervalued: Comparing the work relative value units of neuropsychological evaluation to other services.

: We examined work relative value units (wRVUs) and associated revenue of current procedural terminology (CPT) codes for evaluation and management (E&M) services, neuropsychological evaluation (NPE), psychological evaluation (PE), and psychotherapy. : CPT code wRVUs were aggregated for E&M (99202-99215), NPE (96116, 96132, 96133, 96136, and 96137), PE (90791, 96130, 96131, 96136, and 96137), and psychotherapy (90791 and 90832-90837 with and without the complexity modifier, 90785). Per minute wRVUs were calculated for each CPT code.

Improving Neurology Inpatient Fall Rate: Effect of a Collaborative Interdisciplinary Quality Improvement Initiative.

Objective: To reduce unwitnessed inpatient falls on the neurology services floor at an academic medical center by 20% over 15 months.

Patients And Methods: A 9-item preintervention survey was administered to neurology nurses, resident physicians, and support staff. Based on survey data, interventions targeting fall prevention were implemented.

Changing patterns of care for pancreas cancer in Victoria: the 2022 Pancreas Tumour Summit.

Background: The Victorian Government convened the second Pancreas Cancer Summit in 2021 to identify unwarranted variation in care 2016-2019, and to assess trends compared with the first Summit 2017 (reporting 2011-2015). State-wide administrative data were assessed at population level in alignment with optimal care pathways across all stages of the cancer care continuum.

Methods: Data linkage performed by Centre for Victorian Data Linkage combined data from Victorian Cancer Registry with other administrative data sets including Victorian Admitted Episodes Dataset, Victorian Radiotherapy Minimum Data Set, Victorian Emergency Minimum Dataset and Victorian Death Index.

Item Response Theory Modeling of the Verb Naming Test.

Purpose: Item response theory (IRT) is a modern psychometric framework with several advantageous properties as compared with classical test theory. IRT has been successfully used to model performance on anomia tests in individuals with aphasia; however, all efforts to date have focused on noun production accuracy. The purpose of this study is to evaluate whether the Verb Naming Test (VNT), a prominent test of action naming, can be successfully modeled under IRT and evaluate its reliability.

Areas of Law: Three Questions in Special Jurisprudence.

This article addresses three fundamental questions about a key phenomenon in special jurisprudence, 'areas of law': (i) what is an area of law; (ii) what are the consequences of dividing law into distinct areas; and (iii) what constitutes the foundations of an area of law. It claims that (i) 'an area of law' is a set of legal norms that are intersubjectively recognised by the legal complex as a subset of legal norms in a given jurisdiction; (ii) the sub-division of law into multiple areas matters to the content and scope of legal doctrine, to law's perceived legitimacy and possibly to its effectiveness; and (iii) the search for the normative foundations of an area of law is typically an inquiry into its 'aims' or 'functions'. This article systematically articulates, explains and answers these three questions , ie in relation to areas of law .

Detection and targeting of splicing deregulation in pediatric acute myeloid leukemia stem cells.

Pediatric acute myeloid leukemia (pAML) is typified by high relapse rates and a relative paucity of somatic DNA mutations. Although seminal studies show that splicing factor mutations and mis-splicing fuel therapy-resistant leukemia stem cell (LSC) generation in adults, splicing deregulation has not been extensively studied in pAML. Herein, we describe single-cell proteogenomics analyses, transcriptome-wide analyses of FACS-purified hematopoietic stem and progenitor cells followed by differential splicing analyses, dual-fluorescence lentiviral splicing reporter assays, and the potential of a selective splicing modulator, Rebecsinib, in pAML.

Reversal of malignant ADAR1 splice isoform switching with Rebecsinib.

Adenosine deaminase acting on RNA1 (ADAR1) preserves genomic integrity by preventing retroviral integration and retrotransposition during stress responses. However, inflammatory-microenvironment-induced ADAR1p110 to p150 splice isoform switching drives cancer stem cell (CSC) generation and therapeutic resistance in 20 malignancies. Previously, predicting and preventing ADAR1p150-mediated malignant RNA editing represented a significant challenge.

Deciphering the Role of miR-200c-3p in Type 1 Diabetes (Subclinical Cardiovascular Disease) and Its Correlation with Inflammation and Vascular Health.

Uncomplicated type 1 diabetes (T1DM) displays all features of subclinical cardiovascular disease (CVD) as is associated with inflammation, endothelial dysfunction and low endothelial progenitor cells. MiR-200c-3p has been shown in animal tissues to be pro-atherogenic. We aimed to explore the role of miR-200c-3p in T1DM, a model of subclinical CVD.

Saliva as a sample type for SARS-CoV-2 detection: implementation successes and opportunities around the globe.

Introduction: Symptomatic testing and asymptomatic screening for SARS-CoV-2 continue to be essential tools for mitigating virus transmission. Though COVID-19 diagnostics initially defaulted to oropharyngeal or nasopharyngeal sampling, the worldwide urgency to expand testing efforts spurred innovative approaches and increased diversity of detection methods. Strengthening innovation and facilitating widespread testing remains critical for global health, especially as additional variants emerge and other mitigation strategies are recalibrated.

The relationship between the pH value of a hydration solution and the biomechanical properties of Crosado-embalmed human iliotibial bands.

Determining the biomechanical properties of human tissues commonly involves the immersion or spraying of the tissues to maintain them in a hydrated state. However, the influence of the pH value of these solutions on the biomechanical properties of the tissues is not well understood. This study investigated the effects of the pH value on the biomechanical properties of the collagen-rich human iliotibial band (ITB).

Current Understanding of the Pathophysiology and Approach to Tension-Type Headache.

Purpose Of Review: Description of headache dates back thousands of years, and to date, tension-type headache (TTH) remains the most common form of headache. We will review the history and current understanding of the pathophysiology of TTH and discuss the recommended clinical evaluation and management for this syndrome.

Recent Findings: Despite being the most prevalent headache disorder, TTH pathophysiology remains poorly understood.

Interstitial amyloidosis in sporadic inclusion body myositis.

Introduction/aims: Intracellular congophilic inclusions within muscle fibers, although nonspecific, are one of the pathological hallmarks of sporadic inclusion body myositis (sIBM). Extracellular amyloid deposits in muscle, on the other hand, are the canonical findings of amyloid myopathies, which occur with or without systemic amyloidosis.

Methods: We reviewed the muscle biopsy database (1998-2020) to identify sIBM patients with extracellular amyloid deposits.

First Bite Syndrome: What Neurologists Need to Know.

Purpose Of Review: Though first bite syndrome is well known in surgical settings, it is not commonly included in the differential for sharp paroxysmal facial pain in the neurology literature. This paper will highlight the clinical features and relevant anatomy of first bite syndrome, with the goal of helping clinicians differentiate this from other similar facial pain disorders.

Recent Findings: First bite syndrome is severe sharp or cramping pain in the parotid region occurring with the first bite of each meal and improving with subsequent bites.

BRAFV600E Mutations Arising from a Left-Side Primary in Metastatic Colorectal Cancer: Are They a Distinct Subset?

Background: B-Raf proto-oncogene (BRAF)-V600E mutations (BRAFmt) in colorectal cancer (CRC) predominantly occur in right-side (RS) primaries. In metastatic CRC (mCRC), there is substantial overlap between the reported features of BRAFmt and of an RS primary.

Objectives: To explore the significance of BRAFmt in a left-side (LS) primary, we analysed data from a multi-site mCRC registry.

Right versus left sided metastatic colorectal cancer: Teasing out clinicopathologic drivers of disparity in survival.

Background: Metastatic colorectal cancer (mCRC) patients with a right-sided primary (RC) have an inferior survival to mCRC arising from a left-sided primary (LC). Previous analyses have suggested multiple factors contribute.

Methods: The Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry prospectively captured data on consecutive mCRC patients.

Previous Bevacizumab and Efficacy of Later Anti-Epidermal Growth Factor Receptor Antibodies in Metastatic Colorectal Cancer: Results From a Large International Registry.

Background: The FIRE-3 [5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment colorectal cancer (CRC)] study reported that first-line FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab resulted in similar progression-free survival (PFS) but improved overall survival (OS). A potential explanation is that the initial biologic agent administered in metastatic CRC (mCRC) affects later line efficacy of the other treatments. We sought to test this hypothesis.

Malocclusion model of temporomandibular joint osteoarthritis in mice with and without receptor for advanced glycation end products.

Objective: This study has two aims: 1. Validate a non-invasive malocclusion model of mouse temporomandibular joint (TMJ) osteoarthritis (OA) that we developed and 2. Confirm role of inflammation in TMJ OA by comparing the disease in the presence and absence of the receptor for advanced glycation end products (RAGE).