Impact of corticosteroids on improving lung compliance in a patient with pulmonary microscopic polyangiitis.

Microscopic polyangiitis (MPA) is a small-vessel vasculitis characterised by systemic infiltration, with a primary focus on the renal and pulmonary systems. One of its more lethal pulmonary manifestations is diffuse alveolar haemorrhage (DAH), although the spectrum of lung pathology in MPA is vast and calls for immediate immunosuppressive therapy. Our case looks at an older woman initially presenting with MPA-induced rapid progressive glomerulonephritis.

Genotype-Directed Synthetic Cytotoxicity of ATR Inhibition with Radiotherapy.

Purpose: The importance of the DNA damage response in mediating effects of radiotherapy (RT) has galvanized efforts to target this pathway with radiosensitizers. Yet early clinical trials of this approach have failed to yield a benefit in unselected populations. We hypothesized that ataxia-telangiectasia mutated (Atm)-null tumors would demonstrate genotype-specific synergy between RT and an inhibitor of the DNA damage response protein ataxia-telangiectasia and Rad3-related (ATR) kinase.

Clinical Outcomes and Targeted Genomic Analysis of Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery.

Background: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS).

Objective: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort.

Increased Synthetic Cytotoxicity of Combinatorial Chemoradiation Therapy in Homologous Recombination Deficient Tumors.

Purpose: Homologous recombination deficient (HRD) tumors are exquisitely sensitive to platinum-based chemotherapy and when combined with radiation therapy (RT), leads to improved overall survival in multiple cancer types. Whether a subset of tumors with distinct molecular characteristics demonstrate increased benefit from cisplatin and RT (c-RT) is unclear. We hypothesized that HRD tumors, whether associated with BRCA mutations or genomic scars of HRD, exhibit exquisite sensitivity to c-RT, and that HRD may be a significant driver of c-RT benefit.

Screening for harmful substance use in emergency departments: a systematic review.

Background: Substance use-related emergency department (ED) visits have increased substantially in North America. Screening for substance use in EDs is recommended; best approaches are unclear. This systematic review synthesizes evidence on diagnostic accuracy of ED screening tools to detect harmful substance use.

Artificial-intelligence-driven measurements of brain metastases' response to SRS compare favorably with current manual standards of assessment.

Background: Evaluation of treatment response for brain metastases (BMs) following stereotactic radiosurgery (SRS) becomes complex as the number of treated BMs increases. This study uses artificial intelligence (AI) to track BMs after SRS and validates its output compared with manual measurements.

Methods: Patients with BMs who received at least one course of SRS and followed up with MRI scans were retrospectively identified.

Radiation and Immune Checkpoint Inhibitors: Combination Therapy for Treatment of Hepatocellular Carcinoma.

The liver tumor immune microenvironment has been thought to possess a critical role in the development and progression of hepatocellular carcinoma (HCC). Despite the approval of immune checkpoint inhibitors (ICIs), such as programmed cell death receptor 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitors, for several types of cancers, including HCC, liver metastases have shown evidence of resistance or poor response to immunotherapies. Radiation therapy (RT) has displayed evidence of immunosuppressive effects through the upregulation of immune checkpoint molecules post-treatment.

Quality of Life Before and After Radiation Therapy for Early-Stage Keratinocyte Carcinoma: A Longitudinal Analysis.

Purpose: Little is known about patient-reported quality of life (QOL) before and after radiotherapy (RT) for early keratinocyte carcinoma (KC). The present study tested the hypothesis that QOL is hypothesized to deteriorate soon after RT, with subsequent improvement of a magnitude similar to other KC treatments.

Methods And Materials: This observational study assessed prospectively collected longitudinal patient-reported QOL data at a single center.

Racialization, colonialism, and imperialism: a critical autoethnography on the intersection of forced displacement and race in a settler colonial context.

Migration has been identified as a priority area for policy responses by both the federal and provincial/territorial governments yet, much of our knowledge about migration is not premised on addressing current xenophobic and racist narratives about migrants. The purpose of this research is an interrogation of Canada's colonialism, imperialism, and racialization, which produce specific oppressive policies and practices that have impacted my family. This research is premised on the understanding that in the space between what is known about migration in Canada and what is not, a great deal of narrative and interpretive work is done that makes assumptions about migrants, specifically forcibly displaced people from the Global South.

Ethnic/racial differences in risk factors and clinical outcomes among patients with amyloidosis.

Background: Cardiac amyloidosis is caused by abnormal extracellular deposition of insoluble fibrils in cardiac tissue. It can be fatal when untreated and is often underdiagnosed. Understanding the ethnic/racial differences in risk factors is critical for early diagnosis and treatment to improve clinical outcomes.

Genomic epidemiology of Mycobacterium abscessus in a Canadian cystic fibrosis centre.

The Mycobacterium abscessus complex causes significant morbidity and mortality among patients with Cystic Fibrosis (CF). It has been hypothesized that these organisms are transmitted from patient to patient based on genomics. However, few studies incorporate epidemiologic data to confirm this hypothesis.

The effects of immediate recall and subsequent retrieval strategy on eyewitness memory.

The current study investigated the effects of immediate recall and subsequent interview on mock witnesses' memory of a crime. After watching a video of a crime, 111 participants were randomly allocated to an immediate recall condition (the iWitnessed mobile app, free recall). One week later, participants were randomly allocated to a retrieval condition (timeline aid, category clustering recall, free recall).

Consumer Perspectives on the Use of Artificial Intelligence Technology and Automation in Crisis Support Services: Mixed Methods Study.

Background: Emerging technologies, such as artificial intelligence (AI), have the potential to enhance service responsiveness and quality, improve reach to underserved groups, and help address the lack of workforce capacity in health and mental health care. However, little research has been conducted on the acceptability of AI, particularly in mental health and crisis support, and how this may inform the development of responsible and responsive innovation in the area.

Objective: This study aims to explore the level of support for the use of technology and automation, such as AI, in Lifeline's crisis support services in Australia; the likelihood of service use if technology and automation were implemented; the impact of demographic characteristics on the level of support and likelihood of service use; and reasons for not using Lifeline's crisis support services if technology and automation were implemented in the future.

Emergency department return visits and hospital admissions in trauma team assessed patients initially discharged from the emergency department: A population-based cohort study.

Background: Many injured patients are transported directly to trauma centers, found to be minimally injured, and discharged directly home from the emergency department (ED). Our objectives were to characterize the short-term outcomes in this discharged patient population and to identify patient factors predictive of ED return visits.

Methods: We conducted a retrospective population-based cohort study using linked administrative data sets involving patients assessed at trauma centers in Ontario, Canada between April 1, 2009, and March 31, 2020.

PD-1 and TIGIT downregulation distinctly affect the effector and early memory phenotypes of CD19-targeting CAR T cells.

CD19-targeting chimeric antigen receptor (CAR) T cells have become an important therapeutic option for patients with relapsed and refractory B cell malignancies. However, a significant portion of patients still do not benefit from the therapy owing to various resistance mechanisms, including high expression of multiple inhibitory immune checkpoint receptors. Here, we report a lentiviral two-in-one CAR T approach in which two checkpoint receptors are downregulated simultaneously by a dual short hairpin RNA cassette integrated into a CAR vector.

Associations between Combined Influenza and Pneumococcal Pneumonia Vaccination and Cardiovascular Outcomes.

Background: In 2017, the CDC listed heart disease as the leading cause of death, with pneumonia and influenza being the eighth cause of death. Several studies have suggested the protective effects of influenza vaccination on myocardial infarction (MI). Available evidence supports the use of influenza vaccination in decreasing cardiovascular events, and the Joint Commission considers influenza vaccination a metric of quality care for hospitalized patients.

Community expectations and anticipated outcomes for crisis support services-Lifeline Australia.

Crisis lines provide a critical first line of mental wellbeing support for community members in distress. Given the increasing referral to such services, there is a need to understand what the expectations of the community are around the role of such services in our public health responses. A computer assisted telephone interview was undertaken between 28th October and 30th November 2019.

Microdroplet-based one-step RT-PCR for ultrahigh throughput single-cell multiplex gene expression analysis and rare cell detection.

Gene expression analysis of individual cells enables characterization of heterogeneous and rare cell populations, yet widespread implementation of existing single-cell gene analysis techniques has been hindered due to limitations in scale, ease, and cost. Here, we present a novel microdroplet-based, one-step reverse-transcriptase polymerase chain reaction (RT-PCR) platform and demonstrate the detection of three targets simultaneously in over 100,000 single cells in a single experiment with a rapid read-out. Our customized reagent cocktail incorporates the bacteriophage T7 gene 2.

Phase II trial of sorafenib and doxorubicin in patients with advanced hepatocellular carcinoma after disease progression on sorafenib.

Background: Patients with advanced hepatocellular carcinoma (HCC) who received second line sorafenib plus doxorubicin following disease progression on sorafenib were shown retrospectively to have improved progression free survival (PFS) and overall survival (OS). Sorafenib plus doxorubicin combination may synergistically promote ASK-1 mediated apoptosis in cancer cells through RAF-1 inhibition. Thus, we conducted this phase II study of sorafenib and doxorubicin combination following progression on sorafenib.