Efficacy of BRAF/MEK-inhibitor therapy for epithelioid glioblastoma with a novel BRAFV600 mutation.

Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease.

A summary of the main themes and findings presented at the ASM Intermountain Branch meeting (2024).

The annual meeting for the Intermountain Branch was held in April 2024 on the campus of Brigham Young University. There were 127 branch members from Utah, Idaho, and Nevada who attended the meeting and were composed of undergraduate students, graduate or medical students, and faculty. This report highlights the diversity of, and the emerging trends in, the research conducted by American Society for Microbiology members in the Intermountain Branch.

Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19.

Neurological symptoms, including cognitive impairment and fatigue, can occur in both the acute infection phase of coronavirus disease 2019 (COVID-19) and at later stages, yet the mechanisms that contribute to this remain unclear. Here we profiled single-nucleus transcriptomes and proteomes of brainstem tissue from deceased individuals at various stages of COVID-19. We detected an inflammatory type I interferon response in acute COVID-19 cases, which resolves in the late disease phase.

Deep RNA sequencing of muscle tissue reveals absence of viral signatures in dermatomyositis.

: To explore a possible connection between active viral infections and manifestation of dermatomyositis (DM). Skeletal muscle biopsies were analyzed from patients diagnosed with juvenile (n=10) and adult (n=12) DM. Adult DM patients harbored autoantibodies against either TIF-1γ (n=7) or MDA5 (n=5).

A phase II trial of netupitant/palonosetron for prevention of chemotherapy-induced nausea/vomiting in patients receiving BEAM prior to hematopoietic cell transplantation.

The purpose of this study was to investigate the efficacy and safety of netupitant/palonosetron (NEPA) for the prevention of chemotherapy-induced nausea and vomiting (CINV) for hematopoietic cell transplantation (HCT) patients receiving BEAM therapy. This phase II, prospective, intention-to-treat, single-center, single-arm study involved 43 adult patients who received NEPA and dexamethasone for the prevention of CINV due to BEAM conditioning chemotherapy. An interim analysis, performed after 13 patients, determined utility versus futility, and supported continuation to full enrollment.

Human adenovirus lung disease: outbreaks, models of immune-response-driven acute lung injury and pandemic potential.

Purpose Of Review: An overview of epidemic, human adenovirus (HAdV) lung infections with proposed studies of the viral/host immune response interface to better understand mechanisms of immunopathogenesis, for development of improved responses to a potential HAdV pandemic.

Recent Findings: Emergent HAdV strains 7, 3, 4, 14 are the most common types associated with infection outbreaks. Recent outbreaks have revealed increased community spread, beyond epidemic group settings.

Distinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19.

Prolonged lung pathology has been associated with COVID-19, yet the cellular and molecular mechanisms behind this chronic inflammatory disease are poorly understood. In this study, we combine advanced imaging and spatial transcriptomics to shed light on the local immune response in severe COVID-19. We show that activated adventitial niches are crucial microenvironments contributing to the orchestration of prolonged lung immunopathology.

Long-term follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder: corpus callosum white matter microstructure and neurocognitive outcomes.

Background: Fetal alcohol spectrum disorder (FASD) is a lifelong condition. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood.

Decoding molecular programs in melanoma brain metastases.

Melanoma brain metastases (MBM) variably respond to therapeutic interventions; thus determining patient's prognosis. However, the mechanisms that govern therapy response are poorly understood. Here, we use a multi-OMICS approach and targeted sequencing (TargetSeq) to unravel the programs that potentially control the development of progressive intracranial disease.

An Initial miRNA Profile of Persons With Persisting Neurobehavioral Impairments and States of Disordered Consciousness After Severe Traumatic Brain Injury.

Objective: To examine the merits of using microRNAs (miRNAs) as biomarkers of disorders of consciousness (DoC) due to traumatic brain injury (TBI).

Settings: Acute and subacute beds.

Participants: Patients remaining in vegetative and minimally conscious states (VS, MCS), an average of 1.

Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses.

Background: Autopsy studies have provided valuable insights into the pathophysiology of COVID-19. Controversies remain about whether the clinical presentation is due to direct organ damage by SARS-CoV-2 or secondary effects, such as overshooting immune response. SARS-CoV-2 detection in tissues by RT-qPCR and immunohistochemistry (IHC) or electron microscopy (EM) can help answer these questions, but a comprehensive evaluation of these applications is missing.

Correlation of Tumor Pathology with Fluorescein Uptake and MRI Contrast-Enhancement in Stereotactic Biopsies.

The utilization of fluorescein-guided biopsies has recently been discussed to improve and expedite operative techniques in the detection of tumor-positive tissue, as well as to avoid making sampling errors. In this study, we aimed to report our experience with fluorescein-guided biopsies and elucidate distribution patterns in different histopathological diagnoses in order to develop strategies to increase the efficiency and accuracy of this technique. We report on 45 fluorescence-guided stereotactic biopsies in 44 patients (15 female, 29 male) at our institution from March 2016 to March 2021, including 25 frame-based stereotactic biopsies and 20 frameless image-guided biopsies using VarioGuide.

Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme 2 (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in the alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis is still elusive.

Methods: Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied to infected human lung explants and adult stem cell derived human lung organoids to correlate ACE2 and related host factors with SARS-CoV-2 tropism, propagation, virulence and immune activation compared to SARS-CoV, influenza and Middle East respiratory syndrome coronavirus (MERS-CoV).

Characterization of Viral miRNAs during Adenovirus 14 Infection and Their Differential Expression in the Emergent Strain Adenovirus 14p1.

Human adenoviruses (HAdV) express either one or two virus-associated RNAs (VA RNAI or VA RNAII). The structure of VA RNA resembles human precursor microRNAs (pre-miRNA), and, like human pre-miRNA, VA RNA can be processed by DICER into small RNAs that resemble human miRNA. VA RNA-derived miRNA (mivaRNA) can mimic human miRNA post-transcriptional gene repression by binding to complementary sequences in the 3' UTR of host mRNA.

The genomic and transcriptional landscape of primary central nervous system lymphoma.

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS.

Effectiveness of Immune Checkpoint Inhibition vs Chemotherapy in Combination With Radiation Therapy Among Patients With Non-Small Cell Lung Cancer and Brain Metastasis Undergoing Neurosurgical Resection.

Importance: Patients with brain metastases from non-small cell lung cancer (NSCLC) have regularly been excluded from prospective clinical trials that include therapy with immune checkpoint inhibitors (ICIs). Clinical data demonstrating benefit with ICIs, specifically following neurosurgical brain metastasis resection, are scarce.

Objective: To evaluate and compare the association of radiation therapy with ICIs vs classic therapy involving radiation therapy and chemotherapy regarding overall survival in a cohort of patients who underwent NSCLC brain metastasis resection.

A Fatal Colchicine Ingestion With Antemortem Blood Concentration.

Although there are multiple therapeutic uses for colchicine, it is particularly dangerous in the setting of overdose due to an irreversible mechanism of action combined with a narrow therapeutic window. Colchicine is an antimitotic agent that binds tubulin and inhibits microtubule polymerization. This produces a predictable sequence of toxicity beginning with gastrointestinal effects with progression to multiorgan system dysfunction.