Real-World Analysis of Durvalumab after Chemoradiation in Stage III Non-Small-Cell Lung Cancer.

The 2017 PACIFIC trial heralded the incorporation of routine adjuvant durvalumab following curative-intent chemoradiation for stage III non-small-cell lung cancer (NSCLC). However, carefully selected clinical trial populations can differ significantly from real-world populations, which can have implications on treatment toxicities and outcomes, making it difficult to accurately counsel patients. Consequently, we performed a real-world, retrospective analysis of outcomes and toxicities in 118 patients with stage III NSCLC treated with durvalumab after platinum-based chemoradiotherapy. The data were collected from patients who underwent treatment at a single, tertiary-level Canadian cancer centre from May 2018 to October 2020. The variables collected included patient demographics, treatment specifics, progression-free survival, overall survival, and immune-related adverse events (IRAE) from durvalumab. Descriptive statistics were used for toxicity analysis, and progression-free survival and overall survival estimates were calculated using the Kaplan-Meier method. The statistical analyses indicated a 64.4% (n = 76) toxicity rate, with a 21% (n = 25) toxicity rate of grade 3+ IRAEs. The most common documented IRAEs were pneumonitis (n = 44; 40%), followed by rash (n = 20; 18%) and thyroid dysfunction (n = 17; 15%). FEV1 and DLCO were not found to be associated predictors of pneumonitis toxicity. The median PFS and OS were estimated to be >1.7 years and >2.7 years, respectively.

Nationwide Study of Postlegalization Marijuana Use Among Patients With Epilepsy in Canada.

Background and Objectives: Patients with epilepsy have long sought alternatives to conventional antiseizure medications (ASMs) for the treatment of their epilepsy and to improve the significant side effect burden of ASMs and comorbidities. It was established before the legalization of marijuana in Canada in 2018 that many patients with epilepsy use marijuana to treat their seizures or for recreational purposes. However, there exists no current data on the prevalence and habits of marijuana use in the Canadian epilepsy population since legalization. Methods: We conducted a nationwide cross-sectional survey of patients recruited through health care providers or epilepsy organizations to investigate marijuana usage habits and perceptions. Results: From 395 responses obtained through the survey, 221 responses stated that they used marijuana within the past year. A history of seizures for more than 10 years was noted in 50.7% (n = 148) patients with generalized seizures being the most common type (n = 169; 57.1%). Most of them (n = 154; 52.0%) had tried 3 or more ASMs, and 37.2% (n = 110) used various other treatments (ketogenic diet, vagus nerve stimulation, or resective surgery) indicating a proportion with drug-resistant epilepsy. This subgroup was more likely to have started using marijuana for drug-resistant epilepsy (p < 0.001). Current marijuana use for epilepsy management was endorsed by 47.5% (n = 116). Marijuana was "somewhat" to "very" effective at reducing seizure frequency for 60.1% (n = 123). The main side effects of marijuana were impaired thinking (n = 40; 17.17%), anxiety (n = 37; 15.74%), and altered hunger (n = 36; 15.32%). Marijuana was used at least once daily by 70.3% (n = 168) with the median amount per week being 5.0 g (IQR = 1-10), and the preferred method of consumption was smoking (n = 83; 34.7%). The participants expressed concerns regarding financial strain (n = 108; 36.5%), lack of recommendation from a doctor (n = 89; 30.1%), and lack of information (n = 56; 18.9%) surrounding marijuana use. Discussion: This study reveals a high prevalence of marijuana use among patients with epilepsy living in Canada particularly when seizures are drug resistant. A significant proportion of patients reported improvement of seizures with marijuana use, consistent with previous studies. With the increased accessibility of marijuana, it is imperative that physicians are aware of marijuana usage habits among patients with epilepsy.

Mistaken Metastasis: Radiation-Induced Rib Fracture Mimicking Malignancy on Computerized Tomography Case Report.

A 62-year-old woman with a 40-pack-year smoking history and severe chronic obstructive pulmonary disease with early-stage right upper lobe non-small cell lung cancer (NSCLC) was treated with stereotactic ablative radiotherapy (SABR). Two years after treatment, a surveillance computerized tomography scan showed lesions of the posterior 4th and 5th ribs including expansion of the medulla that was unusual and of concern for possible malignant infiltration. A follow-up magnetic resonance imaging (MRI) scan revealed these lesions to be healing fractures post-radiotherapy. Although generally well tolerated, SABR is known to produce inflammatory and fibrotic changes both in-field and in organs at risk, and rib fractures are a well-established adverse event. MRI has high diagnostic accuracy and sensitivity for rib fractures and was able to rule out malignant spread. This case demonstrates the need for regular follow-up following SABR for early-stage NSCLC, as well as the challenge of interpreting indeterminate post-SABR radiography findings.

Developing a Hybrid Four-Prong Approach to Anatomical Education During the COVID-19 Pandemic.

During COVID-19, the anatomy faculty and students at Schulich School of Medicine and Dentistry observed strengths and weaknesses in their transition to online learning. A "four-prong" approach to teaching anatomy was developed. Asynchronous content modules were tailored to specific learning objectives, virtual labs were implemented to work through case-based applications, "live from the lab" review sessions provided the opportunity for interaction and integration, and finally, limited face-to-face laboratory sessions provided an opportunity for supervised consolidation with cadaveric specimens. Our approach may be used by other institutions to enhance anatomical education and student engagement.

Distinct Function-Related Molecular Profile of Adult Human A2B5-Positive Pre-Oligodendrocytes Versus Mature Oligodendrocytes.

Remyelination in the human CNS is ascribed to progenitor cells rather than previously myelinating oligodendrocytes (OLs). The ganglioside-recognizing antibody A2B5 has been used to isolate putative progenitor cells, whose in vitro features resemble cells labeled as "pre-oligodendrocytes." Here, we compare the transcriptional profiles of adult human brain-derived A2B5 antibody-selected cells (A+) after initial isolation (day in vitro (DIV1)) and after DIV6, with nonselected (A-) cells (mature OLs), with regard to their differentiation state and functional properties. While a number of previously recognized progenitor associated genes, specifically PTPRZ1 and PDGFRα, were upregulated in the A2B5+ population, a number of such genes were comparably expressed in the mature OLs, as were mature myelin genes. Additional progenitor-related genes were upregulated in the A+ population. We show that A2B5+ cells have greater capacity to ensheath nanofibers, a model of myelination potential; consistent with this, ingenuity pathway analysis indicated that A+ cells had upregulated expression of genes within cell growth and cell signaling pathways. Differential expression of cell death/survival pathways complements previous functional studies showing their increased susceptibility to metabolic stress. At DIV6, we observed significantly fewer differentially expressed genes; suggestive of cell maturation occurring in vitro, indicating the complexity in comparing in vitro and in situ cell properties.