Cost-Utility Analysis of Durvalumab and Tremelimumab Versus Best Supportive Care in Refractory Metastatic Colorectal Cancer.

Objectives: To determine the cost-effectiveness of combined durvalumab and tremelimumab in patients with metastatic colorectal cancer in the intention-to-treat (ITT) and biomarker-enriched populations using direct CCTG CO.26 phase-2 trial data.

Methods: A 4-state microsimulation model was used to evaluate the expected health outcomes in quality-adjusted life years (QALYs) and costs (2023 Canadian Dollars) over a lifetime horizon (5 years) from the Canadian public-payer perspective.

Development and evaluation of an integrated multispecialty clinic for people with multiple long-term conditions.

Introduction: The number of people with multiple long-term conditions (MLTC) is increasing. People with MLTC experience fragmentation of care due to single-disease-orientated healthcare organisation and have increased morbidity and mortality. We developed an innovative clinic model whereby people with MLTC are assessed by a team of specialists together in one appointment to form a consensus management plan in real time.

Machine Learning Models of Early Longitudinal Toxicity Trajectories Predict Cetuximab Concentration and Metastatic Colorectal Cancer Survival in the Canadian Cancer Trials Group/AGITG CO.17/20 Trials.

Purpose: Cetuximab (CET), targeting the epidermal growth factor receptor, is a systemic treatment option for patients with colorectal cancer. One known predictive factor for CET efficacy is the presence of CET-related rash; other putative toxicity factors include fatigue and nausea. Analysis of early CET-associated toxicities may reveal patient subpopulations that clinically benefit from long-term CET treatment.

Effects of cannabinoids on immune checkpoint inhibitor response: CCTG pooled analysis of individual patient data.

Background: Immune checkpoint inhibitors (ICIs) benefit patients across various tumor types. ICIs block cancer and T-cell interactions whereas cannabinoids may inhibit T-cell activation, reducing lysis of tumor cells. Interactions between cannabinoid use and dual ICI treatment remain unknown.

Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2): study protocol for a phase 2, prospective, multicentre, open-label, multiarm, biomarker-directed, signal-seeking, umbrella, clinical trial for recurrent IDH mutant, grade 2/3 glioma.

Introduction: All grade 2/3 gliomas are incurable and at the time of inevitable relapse, patients have significant unmet needs with few effective treatments. This study aims to improve outcomes by molecular profiling of patients at relapse, then matching them with the best available drug based on their molecular profile, maximising the chances of patient benefit while simultaneously testing multiple novel drugs.

Methods And Analysis: Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2) will be an international, phase 2, multicentre, open-label, biomarker-directed, umbrella clinical trial for recurrent isocitrate dehydrogenase mutant, histologically grade 2/3 gliomas.

Prognostic factors for overall survival in elderly patients with glioblastoma: Analysis of the pooled NOA-08 and Nordic trials with the CCTG-EORTC (CE.6) trial.

Background: The majority of patients diagnosed with glioblastoma are >60 years. Three randomized trials addressed the roles of radiotherapy (RT) and temozolomide (TMZ) for elderly patients. NORDIC and NOA-08 compared RT versus TMZ, while CE.

Plasma arginine as a predictive biomarker for outcomes with immune checkpoint inhibition in metastatic colorectal cancer: a correlative analysis of the CCTG CO.26 trial.

Background: Nutritional stress is a mechanism that allows tumor cells to evade the immune system. Arginine (ARG), an amino acid involved in immunomodulation, aids in regulating T-lymphocyte cell activity and the antitumor response. ARG deficiency in the tumor microenvironment can impair T-cell response while ARG supplementation may promote antitumor immune activity.

The association of health-care contact days with physical function and survival in CCTG/AGITG CO.17.

Introduction: Although contact days-days with health-care contact outside home-are increasingly adopted as a measure of time toxicity and treatment burden, they could also serve as a surrogate of treatment-related harm. We sought to assess the association between contact days and patient-reported outcomes and the prognostic ability of contact days.

Methods: We conducted a secondary analysis of CO.

Dietary salt intake in chronic kidney disease: recent studies and their practical implications.

Epidemiologic studies in the general population show that the level of dietary salt intake is associated with increases in blood pressure (BP), cardiovascular events, and mortality. According to trial data, reducing salt intake lowers the incidence of these 3 outcomes. On the basis of this evidence, the World Health Organization and other bodies recommend restricting salt intake.

Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids.

Isolation of tissue-specific fetal stem cells and derivation of primary organoids is limited to samples obtained from termination of pregnancies, hampering prenatal investigation of fetal development and congenital diseases. Therefore, new patient-specific in vitro models are needed. To this aim, isolation and expansion of fetal stem cells during pregnancy, without the need for tissue samples or reprogramming, would be advantageous.

Lentiviral expression of wild-type LAMA3A restores cell adhesion in airway basal cells from children with epidermolysis bullosa.

The hallmark of epidermolysis bullosa (EB) is fragile attachment of epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated in the ear, nose, and throat department of a tertiary pediatric hospital linked to the United Kingdom's national EB unit between 1992 and 2023. Patients suffered a high degree of morbidity and mortality from laryngotracheal stenosis.

NEMA NU 2-2018 evaluation and image quality optimization of a new generation digital 32-cm axial field-of-view Omni Legend PET-CT using a genetic evolutionary algorithm.

A performance evaluation was conducted on the new General Electric (GE) digital Omni Legend PET-CT system with 32 cm extended field of view. The first commercially available clinical digital bismuth germanate system. The system does not use time of flight (ToF).

Molecular and functional correction of a deep intronic splicing mutation in by CRISPR-Cas9 gene editing.

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene. The 10th most common mutation, c.3178-2477C>T (3849+10kb C>T), involves a cryptic, intronic splice site.

Eyeglasses and risk of COVID-19 transmission-analysis of the Virus Watch Community Cohort study.

Objectives: The importance of SARS-CoV-2 transmission via the eyes is unknown, with previous studies mainly focusing on protective eyewear in healthcare settings. This study aimed to test the hypothesis that wearing eyeglasses is associated with a lower risk of COVID-19.

Methods: Participants from the Virus Watch prospective community cohort study responded to a questionnaire on the use of eyeglasses and contact lenses.

High-Speed Video Microscopy of Ependymal Cilia in Brain Organotypic and Cell Culture Models.

The wall of the ventricular system within the neuraxis is lined almost entirely by E1 ependymal cells, each of which projects multiple motile cilia from their apical surface into the cerebrospinal fluid (CSF). This specialized layer of E1 cells constitutes the border between the CSF and the brain interstitial fluid (BIF), and by controlling influx and efflux across the CSF to BIF interface, it is increasingly recognized to play an integral role in modulating and maintaining the brain microenvironment. The motile cilia have been shown to be responsive to changes in the CSF microenvironment, and while the physiological role of this mechanism remains incompletely understood, manipulating this control mechanism may influence the brain microenvironment potentially opening a new frontier in therapeutic intervention.

Axonemal structures reveal mechanoregulatory and disease mechanisms.

Motile cilia and flagella beat rhythmically on the surface of cells to power the flow of fluid and to enable spermatozoa and unicellular eukaryotes to swim. In humans, defective ciliary motility can lead to male infertility and a congenital disorder called primary ciliary dyskinesia (PCD), in which impaired clearance of mucus by the cilia causes chronic respiratory infections. Ciliary movement is generated by the axoneme, a molecular machine consisting of microtubules, ATP-powered dynein motors and regulatory complexes.

Evaluation of a Simple Low-cost Intervention to Empower People with CKD to Reduce Their Dietary Salt Intake: OxCKD1, a Multicenter Randomized Controlled Trial.

Key Points: A randomized controlled trial demonstrates that a simple and cheap 1-month intervention empowers people with CKD to lower their dietary salt intake. The effect of the intervention persisted after the intervention finished.

Background: To evaluate the efficacy of a simple low-cost intervention to empower people with CKD to reduce their dietary salt intake.

Evaluating the Time Toxicity of Cancer Treatment in the CCTG CO.17 Trial.

Purpose: The time spent in pursuing treatments for advanced cancer can be substantial. We have previously proposed a pragmatic and patient-centered metric of these time costs-which we term time toxicity-as any day with physical health care system contact. This includes outpatient visits (eg, bloodwork, scans, etc), emergency department visits, and overnight stays in a health care facility.

INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG).

Background: Advanced gastro-oesophageal cancer (AGOC) carries a poor prognosis. No standard of care treatment options are available after first and second-line therapies. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine kinases.

Cell-intrinsic differences between human airway epithelial cells from children and adults.

The airway epithelium is a protective barrier that is maintained by the self-renewal and differentiation of basal stem cells. Increasing age is a principle risk factor for chronic lung diseases, but few studies have explored age-related molecular or functional changes in the airway epithelium. We retrieved epithelial biopsies from histologically normal tracheobronchial sites from pediatric and adult donors and compared their cellular composition and gene expression profile (in laser capture-microdissected whole epithelium, fluorescence-activated cell-sorted basal cells, and basal cells in cell culture).

Functional Evaluation and Genetic Landscape of Children and Young Adults Referred for Assessment of Bronchiectasis.

Bronchiectasis is the abnormal dilation of the airway which may be caused by various etiologies in children. Beyond the more recognized cause of bacterial and viral infections and primary immunodeficiencies, other genetic conditions such as cystic fibrosis and primary ciliary dyskinesia (PCD) can also contribute to the disease. Currently, there is still debate on whether genome sequencing (GS) or exome sequencing reanalysis (rES) would be beneficial if the initial targeted testing results returned negative.