Evaluation of the impact of artificial intelligence-assisted image interpretation on the diagnostic performance of clinicians in identifying pneumothoraces on plain chest X-ray: a multi-case multi-reader study.

Background: Artificial intelligence (AI)-assisted image interpretation is a fast-developing area of clinical innovation. Most research to date has focused on the performance of AI-assisted algorithms in comparison with that of radiologists rather than evaluating the algorithms' impact on the clinicians who often undertake initial image interpretation in routine clinical practice. This study assessed the impact of AI-assisted image interpretation on the diagnostic performance of frontline acute care clinicians for the detection of pneumothoraces (PTX).

Retinal microglia express more MHC class I and promote greater T-cell-driven inflammation than brain microglia.

Introduction: Macrophage function is determined by microenvironment and origin. Brain and retinal microglia are both derived from yolk sac progenitors, yet their microenvironments differ. Utilizing single-cell RNA sequencing (scRNA-seq) data from mice, we tested the hypothesis that retinal and brain microglia exhibit distinct transcriptional profiles due to their unique microenvironments.

Getting our ducks in a row: The need for data utility comparisons of healthcare systems data for clinical trials.

Background: Better use of healthcare systems data, collected as part of interactions between patients and the healthcare system, could transform planning and conduct of randomised controlled trials. Multiple challenges to widespread use include whether healthcare systems data captures sufficiently well the data traditionally captured on case report forms. "Data Utility Comparison Studies" (DUCkS) assess the utility of healthcare systems data for RCTs by comparison to data collected by the trial.

Tocilizumab Treatment in COVID-19 Patients: Comparing Cutaneous Disease and Adverse Drug Effects.

Actemra (tocilizumab) received emergency use authorization for the treatment of coronavirus disease 2019 (COVID-19) in June 2021. Literature has linked numerous cutaneous adverse effects to tocilizumab. In this current survey, investigators reviewed and compared these adverse effects to the common cutaneous manifestations of COVID-19.

No Dramas: Using applied theatre to explore youth health issues in regional Central Queensland.

Introduction: Young people in a regional Central Queensland community identified concerns related to their health and health behaviours, but have limited access to health information.

Objective: To explore the youth health perspectives and priorities of young people in regional Queensland and identify how young people prefer to access health information.

Design: A participatory action research approach, using applied theatre methods and technology.

Towards nationally curated data archives for clinical radiology image analysis at scale: Learnings from national data collection in response to a pandemic.

The prevalence of the coronavirus SARS-CoV-2 disease has resulted in the unprecedented collection of health data to support research. Historically, coordinating the collation of such datasets on a national scale has been challenging to execute for several reasons, including issues with data privacy, the lack of data reporting standards, interoperable technologies, and distribution methods. The coronavirus SARS-CoV-2 disease pandemic has highlighted the importance of collaboration between government bodies, healthcare institutions, academic researchers and commercial companies in overcoming these issues during times of urgency.

The age of the bone marrow microenvironment influences B-cell acute lymphoblastic leukemia progression via CXCR5-CXCL13.

B-cell acute lymphoblastic leukemia (B-ALL) occurs most commonly in children, whereas chronic myeloid leukemia is more frequent in adults. The myeloid bias of hematopoiesis in elderly individuals has been considered causative, but the age of the bone marrow microenvironment (BMM) may be contributory. Using various murine models of B-ALL in young vs old mice, we recapitulated B-ALL preponderance in children vs adults.

Molecular landscape and prognostic impact of FLT3-ITD insertion site in acute myeloid leukemia: RATIFY study results.

In acute myeloid leukemia (AML) internal tandem duplications of the FLT3 gene (FLT3-ITD) are associated with poor prognosis. Retrospectively, we investigated the prognostic and predictive impact of FLT3-ITD insertion site (IS) in 452 patients randomized within the RATIFY trial, which evaluated midostaurin additionally to intensive chemotherapy. Next-generation sequencing identified 908 ITDs, with 643 IS in the juxtamembrane domain (JMD) and 265 IS in the tyrosine kinase domain-1 (TKD1).

Clinical and molecular relevance of genetic variants in the non-coding transcriptome of patients with cytogenetically normal acute myeloid leukemia.

Expression levels of long non-coding RNA (lncRNA) have been shown to associate with clinical outcome of patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, the frequency and clinical significance of genetic variants in the nucleotide sequences of lncRNA in AML patients is unknown. Herein, we analyzed total RNA sequencing data of 377 younger adults (aged <60 years) with CN-AML, who were comprehensively characterized with regard to clinical outcome.

Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance).

Overexpression of B-cell leukemia/lymphoma 2 (BCL2) renders acute myeloid leukemia (AML) cells resistant to chemotherapy and has been associated with unfavorable outcomes. Oblimersen (G3139) is a phosphorothioate 18-mer antisense oligonucleotide directed against the first 6 BCL2 codons. In a phase 1 study of AML patients treated with G3139, cytarabine, and daunorubicin induction with cytarabine consolidation, no antisense-related toxicity was reported, and BCL2 downregulation occurred in patients achieving complete remission.

Precision oncology in AML: validation of the prognostic value of the knowledge bank approach and suggestions for improvement.

Recently, a novel knowledge bank (KB) approach to predict outcomes of individual patients with acute myeloid leukemia (AML) was developed using unbiased machine learning. To validate its prognostic value, we analyzed 1612 adults with de novo AML treated on Cancer and Leukemia Group B front-line trials who had pretreatment clinical, cytogenetics, and mutation data on 81 leukemia/cancer-associated genes available. We used receiver operating characteristic (ROC) curves and the area under the curve (AUC) to evaluate the predictive values of the KB algorithm and other risk classifications.

A precision medicine classification for treatment of acute myeloid leukemia in older patients.

Background: Older patients (≥ 60 years) with acute myeloid leukemia (AML) often have multiple, sequentially acquired, somatic mutations that drive leukemogenesis and are associated with poor outcome. Beat AML is a Leukemia and Lymphoma Society-sponsored, multicenter umbrella study that algorithmically segregates AML patients based upon cytogenetic and dominant molecular abnormalities (variant allele frequencies (VAF) ≥ 0.2) into different cohorts to select for targeted therapies.

Genomic analysis of cellular hierarchy in acute myeloid leukemia using ultrasensitive LC-FACSeq.

Hematopoiesis is hierarchical, and it has been postulated that acute myeloid leukemia (AML) is organized similarly with leukemia stem cells (LSCs) residing at the apex. Limited cells acquired by fluorescence activated cell sorting in tandem with targeted amplicon-based sequencing (LC-FACSeq) enables identification of mutations in small subpopulations of cells, such as LSCs. Leveraging this, we studied clonal compositions of immunophenotypically-defined compartments in AML through genomic and functional analyses at diagnosis, remission and relapse in 88 AML patients.

DNA methylation epitypes highlight underlying developmental and disease pathways in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a molecularly complex disease characterized by heterogeneous tumor genetic profiles and involving numerous pathogenic mechanisms and pathways. Integration of molecular data types across multiple patient cohorts may advance current genetic approaches for improved subclassification and understanding of the biology of the disease. Here, we analyzed genome-wide DNA methylation in 649 AML patients using Illumina arrays and identified a configuration of 13 subtypes (termed "epitypes") using unbiased clustering.

Gene expression signature predicts relapse in adult patients with cytogenetically normal acute myeloid leukemia.

Although ∼80% of adult patients with cytogenetically normal acute myeloid leukemia (CN-AML) achieve a complete remission (CR), more than half of them relapse. Better identification of patients who are likely to relapse can help to inform clinical decisions. We performed RNA sequencing on pretreatment samples from 268 adults with de novo CN-AML who were younger than 60 years of age and achieved a CR after induction treatment with standard "7+3" chemotherapy.

Midostaurin reduces relapse in FLT3-mutant acute myeloid leukemia: the Alliance CALGB 10603/RATIFY trial.

The prospective randomized, placebo-controlled CALGB 10603/RATIFY trial (Alliance) demonstrated a statistically significant overall survival benefit from the addition of midostaurin to standard frontline chemotherapy in a genotypically-defined subgroup of 717 patients with FLT3-mutant acute myeloid leukemia (AML). The risk of death was reduced by 22% on the midostaurin-containing arm. In this post hoc analysis, we analyzed the cumulative incidence of relapse (CIR) on this study and also evaluated the impact of 12 4-week cycles of maintenance therapy.

Clonal evolution of acute myeloid leukemia with FLT3-ITD mutation under treatment with midostaurin.

In the international randomized phase 3 RATIFY (Randomized AML Trial In FLT3 in patients less than 60 Years old) trial, the multikinase inhibitor midostaurin significantly improved overall and event-free survival in patients 18 to 59 years of age with FLT3-mutated acute myeloid leukemia (AML). However, only 59% of patients in the midostaurin arm achieved protocol-specified complete remission (CR), and almost half of patients achieving CR relapsed. To explore underlying mechanisms of resistance, we studied patterns of clonal evolution in patients with FLT3-internal tandem duplications (ITD)-positive AML who were entered in the RATIFY or German-Austrian Acute Myeloid Leukemia Study Group 16-10 trial and received treatment with midostaurin.

Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial.

The results from the RATIFY trial (ClinicalTrials.gov: NCT00651261; CALGB 10603) showed that midostaurin combined with standard chemotherapy significantly improved outcomes in patients with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML), compared with placebo. In this post hoc subgroup analysis from the trial, we evaluated the impact of midostaurin in 163 patients with FLT3-tyrosine kinase domain (TKD) mutations.

Mutational landscape and clinical outcome of patients with de novo acute myeloid leukemia and rearrangements involving 11q23/.

Balanced rearrangements involving the gene, located at 11q23, are among the most frequent chromosome aberrations in acute myeloid leukemia (AML). Because of numerous fusion partners, the mutational landscape and prognostic impact of specific 11q23/ rearrangements are not fully understood. We analyzed clinical features of 172 adults with AML and recurrent 11q23/ rearrangements, 141 of whom had outcome data available.