Durvalumab Following Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Differences in Survival Based on Age and Post-Progression Systemic Therapy.

Background: Concurrent chemoradiotherapy (cCRT) followed by 1 year of the immune checkpoint inhibitor (ICI) durvalumab is standard of care for patients with unresectable stage III nonsmall cell lung cancer (NSCLC).

Objectives: The purpose of this study was to evaluate survival outcomes of (1) cCRT followed by durvalumab in patients older versus younger than 75 years of age and (2) post-progression treatment with ICI alone versus chemotherapy alone versus combined ICI and chemotherapy.

Patients And Methods: Patients with unresectable stage III NSCLC treated between January 2018 and July 2023 with cCRT followed by durvalumab were identified retrospectively.

Two C. elegans DM domain proteins, DMD-3 and MAB-3, function in late stages of male somatic gonad development.

To bring about sexual dimorphism in form, information from the sex determination pathway must trigger sex-specific modifications in developmental programs. DM-domain encoding genes have been found to be involved in sex determination in a multitude of animals, often at the level of male somatic gonad formation. Here we report our findings that the DM-domain transcription factors MAB-3 and DMD-3 function together in multiple steps during the late stages of C.

Advanced cutaneous squamous cell carcinoma: Impact of age on the safety and efficacy of cemiplimab and the prognostic significance of blood biomarkers.

Introduction: Age-related differences in the safety profile of cemiplimab for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) have not been well described. We investigated the association of increasing age with immune related adverse events (irAE) from cemiplimab, efficacy outcomes, and the prognostic significance of pre-treatment blood biomarkers in contemporary practice.

Materials And Methods: Patients starting first-line cemiplimab for locally advanced or metastatic cSCC at British Columbia Cancer between April 2019 and January 2023 were identified.

Temporal and spatial variation of domoic acid along Canada's coast.

Shellfish poisonings have posed severe risks to human health globally. The Canadian Shellfish Sanitation Program was established in 1948 to monitor the toxin levels at shellfish harvesting sites along the coast of six provinces in Canada. Domoic acid has been a causal toxin for amnesic shellfish poisoning, and a macro-scale analysis of the temporal and spatial variation of domoic acid along Canada's coast was conducted in this study.

Longitudinal study of paralytic shellfish toxins along Canada's coast.

Paralytic shellfish toxins (PST) in shellfish products have led to severe risks to human health. To monitor the risk, the Canadian Shellfish Sanitation Program has been collecting longitudinal PST measurements in blue mussel (Mytilus edulis) and soft-shell clam (Mya arenaria) samples in six coastal provinces of Canada. The spatial distributions of major temporal variation patterns were studied via Functional Principal Component Analysis.

The novel gene, , is expressed downstream of MAB-3 and DMD-3 in the male tail tip at the termination of male tail tip retraction.

The development of the adult male tail involves an extensive remodeling during the last larval stage where the pointed tail of the L4 male is converted into the blunt-ended adult tail with its collection of mechano-sensitive rays. The first step in this remodeling is the retraction of the four hypodermal cells of the tail tip to generate the blunt-ended tail. Male tail tip retraction is an excellent model for characterizing how upstream regulatory networks interact with the downstream cell biological effectors that drive morphogenetic changes in all animals.

First-line osimertinib for patients with EGFR-mutated advanced non-small cell lung cancer: efficacy and safety during the COVID-19 pandemic.

Background: The FLAURA trial demonstrated improved overall survival (OS) with first-line osimertinib for patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). We studied the efficacy and safety of osimertinib in a cohort treated during the coronavirus disease 2019 (COVID-19) pandemic.

Methods: Patients diagnosed with EGFR-mutated advanced NSCLC between 11 March 2020 to 31 December 2021 who received first-line osimertinib in British Columbia, Canada were identified retrospectively.

CD8 + T cell infiltration is associated with improved survival and negatively correlates with hypoxia in clear cell ovarian cancer.

Unlike other histological types of epithelial ovarian carcinoma, clear cell ovarian carcinoma (CCOC) has poor response to therapy. In many other carcinomas, expression of the hypoxia-related enzyme Carbonic anhydrase IX (CAIX) by cancer cells is associated with poor prognosis, while the presence of CD8 + tumor-infiltrating lymphocytes (TIL) is positively prognostic. We employed [F]EF5-PET/CT imaging, transcriptome profiling, and spatially-resolved histological analysis to evaluate relationships between CAIX, CD8, and survival in CCOC.

Improving social justice in observational studies: protocol for the development of a global and Indigenous STROBE-equity reporting guideline.

Background: Addressing persistent and pervasive health inequities is a global moral imperative, which has been highlighted and magnified by the societal and health impacts of the COVID-19 pandemic. Observational studies can aid our understanding of the impact of health and structural oppression based on the intersection of gender, race, ethnicity, age and other factors, as they frequently collect this data. However, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline, does not provide guidance related to reporting of health equity.

Dynamics of fecal coliform bacteria along Canada's coast.

The vast coastline provides Canada with a flourishing seafood industry including bivalve shellfish production. To sustain a healthy bivalve molluscan shellfish production, the Canadian Shellfish Sanitation Program was established to monitor the health of shellfish harvesting habitats, and fecal coliform bacteria data have been collected at nearly 15,000 marine sample sites across six coastal provinces in Canada since 1979. We applied Functional Principal Component Analysis and subsequent correlation analyses to find annual variation patterns of bacteria levels at sites in each province.

Comparison of transcriptome responses of the liver, tail fin, and olfactory epithelium of Rana [Lithobates] catesbeiana tadpoles disrupted by thyroid hormones and estrogen.

Thyroid hormones (THs) are important developmental regulators in vertebrates, including during the metamorphosis of a tadpole into a frog. Metamorphosis is a post-embryonic developmental period initiated by TH production in the tadpole thyroid gland. The two main bioactive forms of TH are L-thyroxine (T) and 3,5,3'-triiodothyronine (T); these hormones have overlapping but distinct mechanisms of action.

Safety and efficacy of pembrolizumab for advanced nonsmall cell lung cancer: before and during the COVID-19 pandemic.

Purpose: The COVID-19 pandemic changed diagnostic and treatment pathways in oncology. We compared the safety and efficacy of pembrolizumab amongst advanced nonsmall cell lung cancer (NSCLC) patients with a PD-L1 tumor proportion score (TPS) ≥ 50% before and during the pandemic.

Methods: Advanced NSCLC patients initiating pembrolizumab between June 2015 and December 2019 ("pre-pandemic cohort") and between March 2020 and March 2021 ("pandemic cohort") at BC Cancer were identified retrospectively.

Anemia and adverse outcomes in pregnancy: subgroup analysis of the CLIP cluster-randomized trial in India.

Background: Iron-deficiency anemia is a known risk factor for several adverse perinatal outcomes, but data on its impact on specific maternal morbidities is less robust. Further, information on associations between anemia in early pregnancy and subsequent outcomes are understudied.

Methods: The study population was derived from the Community Level Interventions for Pre-eclampsia (CLIP) trial in Karnataka State, India (NCT01911494).

Time to Treatment With Nivolumab or Pembrolizumab for Patients With Advanced Melanoma in Everyday Practice.

Background The anti-programmed cell death one antibodies (Anti-PD-1 Ab) pembrolizumab or nivolumab are commonly prescribed to patients with advanced melanoma. The purpose of the current study is to identify baseline clinical characteristics associated with time to treatment initiation (TTI) of pembrolizumab or nivolumab for advanced melanoma and whether treatment delays are associated with differences in survival outcomes. Methods All patients receiving Anti-PD-1 Ab as a first-line treatment for advanced melanoma outside of clinical trials at British Columbia Cancer Agency between 10/2015 and 10/2019 were identified retrospectively.

Immune related adverse events and treatment discontinuation in patients older and younger than 75 years with advanced melanoma receiving nivolumab or pembrolizumab.

Background: Programmed cell-death 1 antibodies (PD-1 Ab) improve overall survival (OS) for patients with advanced melanoma in trials; however, safety data in patients ≥75 years are lacking. The prognostic significance of and risk factors for PD-1 Ab discontinuation due immune related adverse events (irAE) are also uncertain.

Methods: Patients with advanced melanoma receiving frontline PD-1 Ab at British Columbia Cancer outside of clinical trials between 10/2015-10/2019 were retrospectively analyzed.

Survival Outcomes Following Discontinuation of Ipilimumab and Nivolumab for Advanced Melanoma in a Population-based Cohort.

Aims: Induction ipilimumab and nivolumab followed by maintenance nivolumab improve overall survival compared with ipilimumab alone in patients with advanced melanoma, but immune-related adverse events (irAE) occur commonly. The need for induction discontinuation because of irAE and the relationship between irAE and survival in non-trials patients are unclear.

Materials And Methods: Patients with unresectable stage III-IV melanoma receiving first-line combination immunotherapy at one of six centres between December 2017 and February 2020 outside of trials were identified retrospectively.

Synthesis of 16β-derivatives of 3-(2-bromoethyl)-estra-1,3,5(10)-trien-17β-ol as inhibitors of 17β-HSD1 and/or steroid sulfatase for the treatment of estrogen-dependent diseases.

17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) and steroid sulfatase (STS) are involved in the synthesis of the most potent estrogen in the human body, estradiol (E2). These enzymes are known to play a pivotal role in the progression of estrogen-dependent diseases, such as breast cancer and endometriosis. Therefore, the inhibition of 17β-HSD1 and/or STS represents a promising avenue to modulate the growth of estrogen-dependent tumors or lesions.

Prognostic significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for advanced non-small cell lung cancer patients with high PD-L1 tumor expression receiving pembrolizumab.

Background: We investigated the association of peripheral blood inflammatory markers with overall survival (OS) in pembrolizumab treated advanced non-small cell lung cancer (aNSCLC) patients with programmed death ligand 1 (PD-L1) expression ≥50%. Clinical risk factors for development of immune-related adverse events (irAE) were also explored.

Methods: aNSCLC patients with high PD-L1 expression receiving pembrolizumab monotherapy outside of clinical trials were identified retrospectively.

Comparisons of simulation results between passive and active fluid structure interaction models for left ventricle in hypertrophic obstructive cardiomyopathy.

Background: Patient-specific active fluid-structure interactions (FSI) model is a useful approach to non-invasively investigate the hemodynamics in the heart. However, it takes a lot of effort to obtain the proper external force boundary conditions for active models, which heavily restrained the time-sensitive clinical applications of active computational models.

Methods: The simulation results of 12 passive FSI models based on 6 patients' pre-operative and post-operative CT images were compared with corresponding active models to investigate the differences in hemodynamics and cardiac mechanics between these models.

Treatment of non-small-cell lung cancer after progression on nivolumab or pembrolizumab.

Background: Although PD-1 antibodies (PD1 Ab) are the standard of care for advanced non-small-cell lung cancer (ansclc), most patients will progress. We compared survival outcomes for patients with ansclc who received systemic therapy (st) after progression and for those who did not. Additionally, clinical characteristics that predicted receipt of st after PD1 Ab failure were evaluated.

Association of age with differences in immune related adverse events and survival of patients with advanced nonsmall cell lung cancer receiving pembrolizumab or nivolumab.

Objectives: To explore the association of age with development of immune related adverse events (irAE) and survival in patients with advanced nonsmall cell lung cancer (aNSCLC) receiving programmed cell death 1 antibodies (PD-1 Ab) outside of clinical trials.

Methods: A multicenter retrospective study of PD-1 Ab prescription for patients with aNSCLC between 06/2015-11/2018 at BC Cancer. Multivariable (MVA) logistic regression identified baseline variables associated with irAE manifested within 3 months of PD-1 Ab initiation.

White Matter Hyperintensity Volume Influences Symptoms in Patients Presenting With Minor Neurological Deficits.

Background and Purpose- Acute minor neurological deficits are a common complaint in the emergency department and differentiation of transient ischemic attack/minor stroke from a stroke mimic is difficult. We sought to assess the ability of white matter hyperintensity (WMH) volume to aid the diagnosis in such patients. Methods- This is a post hoc analysis of the previously published SpecTRA study (Spectrometry in TIA Rapid Assessment) of adult patients that presented to the emergency department with acute minor neurological deficits between December 2013 and March 2017.

Systolic blood pressure as a predictor of transient ischemic attack/minor stroke in emergency department patients under age 80: a prospective cohort study.

Background: Elevated blood pressure (BP) at emergency department (ED) presentation and advancing age have been associated with risk of ischemic stroke; however, the relationship between BP, age, and transient ischemic attack/minor stroke (TIA/MS) is not clear.

Methods: A multi-site, prospective, observational study of 1084 ED patients screened for suspected TIA/MS (symptom onset < 24 h, NIHSS< 4) between December 2013 and April 2016. Systolic and diastolic BP measurements (SBP, DBP) were taken at ED presentation.

Simultaneous prediction of multiple outcomes using revised stacking algorithms.

Motivation: HIV is difficult to treat because its virus mutates at a high rate and mutated viruses easily develop resistance to existing drugs. If the relationships between mutations and drug resistances can be determined from historical data, patients can be provided personalized treatment according to their own mutation information. The HIV Drug Resistance Database was built to investigate the relationships.

Pembrolizumab for advanced nonsmall cell lung cancer: Efficacy and safety in everyday clinical practice.

Objectives: While pembrolizumab improves overall survival (OS) in a subset of advanced nonsmall cell lung cancer (aNSCLC) patients (pts) in clinical trials, individuals with poor Eastern Cooperative Oncology Group performance status (ECOG PS) were excluded. Furthermore, some studies have identified a potential link between improved pt outcomes and development of immune related adverse events (irAE.) In a large provincial cohort, we studied the efficacy and safety of pembrolizumab for poor ECOG PS pts and whether irAE correlate with improved OS.