Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial.

Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B.

Management and Long-Term Outcomes of Patients With Recurrent Stroke-Like Episodes After Cranial Radiotherapy.

Background: Recurrent Stroke-Like Episodes of transient negative neurologic symptoms are a long-term consequence of cranial radiation therapy (RT) that may lead to significant functional impairment and worsen quality of life. We assessed management patterns and clinical course at our institution to assess optimal management strategy and understand long-term outcomes.

Methods: We conducted a retrospective review of all patients with recurrent negative neurologic symptoms after cranial RT who were treated at Mayo Clinic (Rochester), with follow-up extending through October 2021 with a goal of assessing for clinical change in the setting of medical management.

Marker-based assays for studying gut transit in gnotobiotic and conventional mouse models.

Gastrointestinal motility is regulated by a variety of environmental factors including gut microbes and metabolites. The ability to interrogate mouse models of gut motility has enabled elucidation of these relationships. Here we describe integration of the red carmine dye and fluorescence isothiocyanate-dextran marker-based assays for characterizing gut transit with spatial resolution, along with an optional intracolonic infusion protocol for studying the effects of metabolites on colonic transit.

Microbiome-encoded bile acid metabolism modulates colonic transit times.

Gut motility is regulated by the microbiome via mechanisms that include bile acid metabolism. To localize the effects of microbiome-generated bile acids, we colonized gnotobiotic mice with different synthetic gut bacterial communities that were metabolically phenotyped using a functional screen. Using two different marker-based assays of gut transit, we inferred that bile acids exert effects on colonic transit.

Variability in digestive and respiratory tract Ace2 expression is associated with the microbiome.

COVID-19 (coronavirus disease 2019) patients exhibiting gastrointestinal symptoms are reported to have worse prognosis. Ace2 (angiotensin-converting enzyme 2), the gene encoding the host protein to which SARS-CoV-2 spike proteins bind, is expressed in the gut and therefore may be a target for preventing or reducing severity of COVID-19. Here we test the hypothesis that Ace2 expression in the gastrointestinal and respiratory tracts is modulated by the microbiome.

Generative Adversarial Networks to Synthesize Missing T1 and FLAIR MRI Sequences for Use in a Multisequence Brain Tumor Segmentation Model.

Background Missing MRI sequences represent an obstacle in the development and use of deep learning (DL) models that require multiple inputs. Purpose To determine if synthesizing brain MRI scans using generative adversarial networks (GANs) allows for the use of a DL model for brain lesion segmentation that requires T1-weighted images, postcontrast T1-weighted images, fluid-attenuated inversion recovery (FLAIR) images, and T2-weighted images. Materials and Methods In this retrospective study, brain MRI scans obtained between 2011 and 2019 were collected, and scenarios were simulated in which the T1-weighted images and FLAIR images were missing.

Clinical manifestations of, diagnostic approach to, and treatment of neurolymphomatosis in the rituximab era.

Neurolymphomatosis (NL) is a rare manifestation of lymphoma, with limited evidence for optimal management. The largest patient series, 50 cases of lymphoma and leukemia, was published in 2010 with limited rituximab exposure. This study aims to evaluate the clinical presentation, diagnostic testing, and outcomes of NL in the rituximab era.

Human Tumor-Infiltrating MAIT Cells Display Hallmarks of Bacterial Antigen Recognition in Colorectal Cancer.

Growing evidence indicates a role for the gut microbiota in modulating anti-tumor treatment efficacy in human cancer. Here we study mucosa-associated invariant T (MAIT) cells to look for evidence of bacterial antigen recognition in human colon, lung, and kidney carcinomas. Using mass cytometry and single-cell mRNA sequencing, we identify a tumor-infiltrating MAIT cell subset expressing CD4 and Foxp3 and observe high expression of CD39 on MAIT cells from colorectal cancer (CRC) only, which we show to be expressed specifically after TCR stimulation.

Long-term incidence of glioma in Olmsted County, Minnesota, and disparities in postglioma survival rate: a population-based study.

Background: We assessed glioma incidence and disparities in postglioma survival rate in the Olmsted County, Minnesota, population.

Methods: This population-based study assessed the incidence of pathologically confirmed primary gliomas between January 1, 1995, and December 31, 2014. Age- and sex-adjusted incidence rates per 100 000 person-years were calculated and standardized to the US white 2010 population.

Adult diffuse glioma GWAS by molecular subtype identifies variants in D2HGDH and FAM20C.

Background: Twenty-five germline variants are associated with adult diffuse glioma, and some of these variants have been shown to be associated with particular subtypes of glioma. We hypothesized that additional germline variants could be identified if a genome-wide association study (GWAS) were performed by molecular subtype.

Methods: A total of 1320 glioma cases and 1889 controls were used in the discovery set and 799 glioma cases and 808 controls in the validation set.

Association of Maximal Extent of Resection of Contrast-Enhanced and Non-Contrast-Enhanced Tumor With Survival Within Molecular Subgroups of Patients With Newly Diagnosed Glioblastoma.

Importance: Per the World Health Organization 2016 integrative classification, newly diagnosed glioblastomas are separated into isocitrate dehydrogenase gene 1 or 2 (IDH)-wild-type and IDH-mutant subtypes, with median patient survival of 1.2 and 3.6 years, respectively.

Genomic and Phenotypic Characterization of a Broad Panel of Patient-Derived Xenografts Reflects the Diversity of Glioblastoma.

Purpose: Glioblastoma is the most frequent and lethal primary brain tumor. Development of novel therapies relies on the availability of relevant preclinical models. We have established a panel of 96 glioblastoma patient-derived xenografts (PDX) and undertaken its genomic and phenotypic characterization.

Glial Fibrillary Acidic Protein (GFAP) Autoimmunity in the Setting of Seropositive Rheumatoid Arthritis Treated With Etanercept.

Introduction: Glial fibrillary acidic protein (GFAP) immunoglobulin G is a recently discovered biomarker of an autoimmune central nervous system disorder characterized by a steroid-responsive meningoencephalomyelitis.

Case Report: A 63-year-old man with rheumatoid arthritis on etanercept presented with steroid-responsive subacute encephalopathy and foot drop. Brain and sural nerve biopsies demonstrated a T-cell perivascular infiltrate.

Cerebral blood volume and apparent diffusion coefficient - Valuable predictors of non-response to bevacizumab treatment in patients with recurrent glioblastoma.

Background: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The core of standard of care for newly diagnosed GBM was established in 2005 and includes maximum feasible surgical resection followed by radiation and temozolomide, with subsequent temozolomide with or without tumor-treating fields. Unfortunately, nearly all patients experience a recurrence.

Preliminary exploration of a computerized cognitive battery and comparison with traditional testing in patients with high-grade glioma.

Background: Cognitive function is an important outcome measure in many brain tumor clinical trials, and investigators are interested in employing the most efficient methods of cognitive assessment for this purpose. Computerized testing can be appealing because of the perceived ease of use and electronic data generated. Traditional tests may have the advantage of accumulated validity evidence and comparability across historic trials.

Molecular profiling of long-term IDH-wildtype glioblastoma survivors.

Background: Glioblastoma (GBM) represents an aggressive cancer type with a median survival of only 14 months. With fewer than 5% of patients surviving 5 years, comprehensive profiling of these rare patients could elucidate prognostic biomarkers that may confer better patient outcomes. We utilized multiple molecular approaches to characterize the largest patient cohort of isocitrate dehydrogenase (IDH)-wildtype GBM long-term survivors (LTS) to date.