Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells.

Therapy-resistant leukemia stem and progenitor cells (LSC) are a main cause of acute myeloid leukemia (AML) relapse. LSC-targeting therapies may thus improve outcome of patients with AML. Here we demonstrate that LSCs present HLA-restricted antigens that induce T-cell responses allowing for immune surveillance of AML. Using a mass spectrometry-based immunopeptidomics approach, we characterized the antigenic landscape of patient LSCs and identified AML- and AML/LSC-associated HLA-presented antigens absent from normal tissues comprising nonmutated peptides, cryptic neoepitopes, and neoepitopes of common AML driver mutations of NPM1 and IDH2. Functional relevance of shared AML/LSC antigens is illustrated by presence of their cognizant memory T cells in patients. Antigen-specific T-cell recognition and HLA class II immunopeptidome diversity correlated with clinical outcome. Together, these antigens shared among AML and LSCs represent prime targets for T cell-based therapies with potential of eliminating residual LSCs in patients with AML. SIGNIFICANCE: The elimination of therapy-resistant leukemia stem and progenitor cells (LSC) remains a major challenge in the treatment of AML. This study identifies and functionally validates LSC-associated HLA class I and HLA class II-presented antigens, paving the way to the development of LSC-directed T cell-based immunotherapeutic approaches for patients with AML. See related commentary by Ritz, p. 430 . This article is featured in Selected Articles from This Issue, p. 419.

Burnout and work-work imbalance in radiology- wicked problems on a global scale. A baseline pre-COVID-19 survey of US neuroradiologists compared to international radiologists and adjacent staff.

PURPOSE: Worldwide, radiologists are experiencing increasing clinical workloads with associated increased burnout. This paper will review burnout definitions, prevalence, and causes. We will also share data from a survey of US neuroradiologists as an example of the impact of work-work imbalances from clinical overload. This article examines the impact on several key job indicators and upon the quality of the neuroradiology work environment in one nation. Finally, we will review proposals for ameliorating and preventing radiologist burnout. METHOD: A survey was sent to members of the American Society of Neuroradiology (ASNR) practicing in the US. Selected measures included workhours and volume, burnout symptoms, subjectively reported errors, participation in non-clinical activities, perceived interpretation quality, results communication, and consideration of early retirement. RESULTS: Survey respondents (n = 412) included 57.5% with teaching responsibilities. Cutbacks in teaching, mentoring, research and/or practice building were reported by 86.2% of respondents. Subjective errors were reported as occurring sometimes or more frequently in the majority of respondents (56.9%) and were increased with faster than optimal speeds of interpretation (P < 0.001) and signing (P < 0.001). At least one burnout measure was reported by 85.2% of respondents. CONCLUSIONS: Increasing clinical demands in conjunction with a more challenging work environment impacts the ability of radiologists to perform core non-interpretive duties that are critical for success in both private and academic practice and is associated with burnout symptoms and adverse effects on quality. While this survey does not prove causation, the trends and findings are concerning and warrant both close monitoring and appropriate intervention.

Identification of the minimum requirements for successful haematopoietic stem cell transplantation.

Historically, defining haematopoietic subsets, including self-renewal, differentiation and lineage restriction, has been elucidated by transplanting a small number of candidate cells with many supporting bone marrow (BM) cells. While this approach has been invaluable in characterising numerous distinct subsets in haematopoiesis, this approach is arguably flawed. The haematopoietic stem cell (HSC) has been proposed as the critical haematopoietic subset necessary for transplantation. However, due to the presence of supporting cells, the HSC has never demonstrated sufficiency. Utilising the homeobox B5 (Hoxb5)-reporter system, we found that neither long-term (LT) HSCs nor short-term (ST) HSCs alone were sufficient for long-term haematopoietic reconstitution. Critically, reconstitution can be rescued by transplanting combined LT- and ST-HSCs, without supporting cells; a fraction we term the 'Minimum Subset for Transplantation' (MST). The MST accounts for only 0·005% of nucleated cells within mouse BM, and this MST can be cultured, expanded and genetically modified while preserving its rapid haematopoietic engraftment potential. These results support the consideration of an MST approach for clinical translation, especially for gene therapy approaches that require HSC compartment modification.

Joint Modeling of RNAseq and Radiomics Data for Glioma Molecular Characterization and Prediction.

RNA sequencing (RNAseq) is a recent technology that profiles gene expression by measuring the relative frequency of the RNAseq reads. RNAseq read counts data is increasingly used in oncologic care and while radiology features (radiomics) have also been gaining utility in radiology practice such as disease diagnosis, monitoring, and treatment planning. However, contemporary literature lacks appropriate RNA-radiomics (henceforth, radiogenomics ) joint modeling where RNAseq distribution is adaptive and also preserves the nature of RNAseq read counts data for glioma grading and prediction. The Negative Binomial (NB) distribution may be useful to model RNAseq read counts data that addresses potential shortcomings. In this study, we propose a novel radiogenomics-NB model for glioma grading and prediction. Our radiogenomics-NB model is developed based on differentially expressed RNAseq and selected radiomics/volumetric features which characterize tumor volume and sub-regions. The NB distribution is fitted to RNAseq counts data, and a log-linear regression model is assumed to link between the estimated NB mean and radiomics. Three radiogenomics-NB molecular mutation models (e.g., IDH mutation, 1p/19q codeletion, and ATRX mutation) are investigated. Additionally, we explore gender-specific effects on the radiogenomics-NB models. Finally, we compare the performance of the proposed three mutation prediction radiogenomics-NB models with different well-known methods in the literature: Negative Binomial Linear Discriminant Analysis (NBLDA), differentially expressed RNAseq with Random Forest (RF-genomics), radiomics and differentially expressed RNAseq with Random Forest (RF-radiogenomics), and Voom-based count transformation combined with the nearest shrinkage classifier (VoomNSC). Our analysis shows that the proposed radiogenomics-NB model significantly outperforms (ANOVA test, p < 0.05) for prediction of IDH and ATRX mutations and offers similar performance for prediction of 1p/19q codeletion, when compared to the competing models in the literature, respectively.

Accuracy of a rapid glial fibrillary acidic protein/ubiquitin carboxyl-terminal hydrolase L1 test for the prediction of intracranial injuries on head computed tomography after mild traumatic brain injury.

OBJECTIVE: The objective was to determine the accuracy of a new, rapid blood test combining measurements of both glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) for predicting acute traumatic intracranial injury (TII) on head CT scan after mild traumatic brain injury (mTBI). METHODS: Analysis of banked venous plasma samples from subjects completing the Prospective Clinical Evaluation of Biomarkers of Traumatic Brain Injury (ALERT-TBI) trial, enrolled 2012-2014 at 22 investigational sites in the United States and Europe. All subjects were ≥18 years old, presented to an emergency department (ED) with a nonpenetrating head injury and Glasgow Coma Scale score (GCS) 9-15 (mild to moderate TBI), underwent head CT scanning as part of their clinical care, and had blood sampling within 12 h of injury. Plasma concentrations of GFAP and UCH-L1 were measured using i-STAT Alinity and TBI plasma cartridge and compared to acute TII on head CT scan. RESULTS: Of the 2011 subjects enrolled in ALERT-TBI, 1918 had valid CT scans and plasma specimens for testing and 1901 (99.1%) had GCS 13-15 (mTBI), for which the rapid test was intended. Among these subjects, the rapid test had a sensitivity of 0.958 (95% confidence interval [CI] = 0.906 to 0.982), specificity of 0.404 (95% CI = 0.382 to 0.427), negative predictive value of 0.993 (95% CI = 0.985 to 0.997), and positive predictive value of 0.098 (95% CI = 0.082 to 0.116) for acute TII. CONCLUSIONS: A rapid i-STAT-based test had high sensitivity for prediction of acute TII, comparable to lab-based platforms. The speed, portability, and high accuracy of this test may facilitate clinical adoption of brain biomarker testing as an aid to head CT decision making in EDs.

Deep Neural Network Analysis of Pathology Images With Integrated Molecular Data for Enhanced Glioma Classification and Grading.

Gliomas are primary brain tumors that originate from glial cells. Classification and grading of these tumors is critical to prognosis and treatment planning. The current criteria for glioma classification in central nervous system (CNS) was introduced by World Health Organization (WHO) in 2016. This criteria for glioma classification requires the integration of histology with genomics. In 2017, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) was established to provide up-to-date recommendations for CNS tumor classification, which in turn the WHO is expected to adopt in its upcoming edition. In this work, we propose a novel glioma analytical method that, for the first time in the literature, integrates a cellularity feature derived from the digital analysis of brain histopathology images integrated with molecular features following the latest WHO criteria. We first propose a novel over-segmentation strategy for region-of-interest (ROI) selection in large histopathology whole slide images (WSIs). A Deep Neural Network (DNN)-based classification method then fuses molecular features with cellularity features to improve tumor classification performance. We evaluate the proposed method with 549 patient cases from The Cancer Genome Atlas (TCGA) dataset for evaluation. The cross validated classification accuracies are 93.81% for lower-grade glioma (LGG) and high-grade glioma (HGG) using a regular DNN, and 73.95% for LGG II and LGG III using a residual neural network (ResNet) DNN, respectively. Our experiments suggest that the type of deep learning has a significant impact on tumor subtype discrimination between LGG II vs. LGG III. These results outperform state-of-the-art methods in classifying LGG II vs. LGG III and offer competitive performance in distinguishing LGG vs. HGG in the literature. In addition, we also investigate molecular subtype classification using pathology images and cellularity information. Finally, for the first time in literature this work shows promise for cellularity quantification to predict brain tumor grading for LGGs with IDH mutations.

Hoxb5 defines the heterogeneity of self-renewal capacity in the hematopoietic stem cell compartment.

Self-renewal and multipotency are essential functions of hematopoietic stem cells (HSCs). To maintain homeostatic hematopoiesis, functionally uniform HSCs have been thought to be an ideal cell-of-origin. Recent technological advances in the field have allowed us to analyze HSCs with single cell resolution and implicate that functional heterogeneity may exist even within the highly purified HSC compartment. However, due in part to the technical limitations of analyzing extremely rare populations and our incomplete understanding of HSC biology, neither the biological meaning of why heterogeneity exists nor the precise mechanism of how heterogeneity is determined within the HSC compartment is entirely known. Here we show the first evidence that self-renewal capacity varies with the degree of replication stress dose and results in heterogeneity within the HSC compartment. Using the Hoxb5-reporter mouse line which enables us to distinguish between long-term (LT)-HSCs and short-term (ST)-HSCs, we have found that ST-HSCs quickly lose self-renewal capacity under high stress environments but can maintain self-renewal under low stress environments for long periods of time. Critically, exogeneous Hoxb5 expression confers protection against loss of self-renewal to Hoxb5-negative HSCs and can partially alter the cell fate of ST-HSCs to that of LT-HSCs. Our results demonstrate that Hoxb5 imparts functional heterogeneity in the HSC compartment by regulating self-renewal capacity. Additionally, Hoxb5-positive HSCs may exist as fail-safe system to protect from the exhaustion of HSCs throughout an organism's lifespan.

All About Shoulder Arthroplasty: What Radiologists Should Know.

Over the last decade, the number of shoulder arthroplasty procedures has been increasing and evolving. The types of prostheses have also been evolving, and familiarity with the various design types will assist in postoperative assessment for hardware complications. New preoperative planning tools are available that have radically changed the protocol of preoperative image studies performed. This article reviews the main types of shoulder prostheses, discusses radiologic studies required before surgery, and describes the common complications of shoulder arthroplasty.

First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With Advanced Cancers.

PURPOSE: To evaluate the safety, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 (5F9), a humanized IgG4 antibody that targets CD47 to enable phagocytosis. PATIENTS AND METHODS: Adult patients with solid tumors were treated in four cohorts: part A, to determine a priming dose; part B, to determine a weekly maintenance dose; part C, to study a loading dose in week 2; and a tumor biopsy cohort. RESULTS: Sixty-two patients were treated: 11 in part A, 14 in B, 22 in C, and 15 in the biopsy cohort. Part A used doses that ranged from 0.1 to 3 mg/kg. On the basis of tolerability and receptor occupancy studies that showed 100% CD47 saturation on RBCs, 1 mg/kg was selected as the priming dose. In subsequent groups, patients were treated with maintenance doses that ranged from 3 to 45 mg/kg, and most toxicities were mild to moderate. These included transient anemia (57% of patients), hemagglutination on peripheral blood smear (36%), fatigue (64%), headaches (50%), fever (45%), chills (45%), hyperbilirubinemia (34%), lymphopenia (34%), infusion-related reactions (34%), and arthralgias (18%). No maximum tolerated dose was reached with maintenance doses up to 45 mg/kg. At doses of 10 mg/kg or more, the CD47 antigen sink was saturated by 5F9, and a 5F9 half-life of approximately 13 days was observed. Strong antibody staining of tumor tissue was observed in a patient at 30 mg/kg. Two patients with ovarian/fallopian tube cancers had partial remissions for 5.2 and 9.2 months. CONCLUSION: 5F9 is well tolerated using a priming dose at 1 mg/kg on day 1 followed by maintenance doses of up to 45 mg/kg weekly.

CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin's Lymphoma.

BACKGROUND: The Hu5F9-G4 (hereafter, 5F9) antibody is a macrophage immune checkpoint inhibitor blocking CD47 that induces tumor-cell phagocytosis. 5F9 synergizes with rituximab to eliminate B-cell non-Hodgkin's lymphoma cells by enhancing macrophage-mediated antibody-dependent cellular phagocytosis. This combination was evaluated clinically. METHODS: We conducted a phase 1b study involving patients with relapsed or refractory non-Hodgkin's lymphoma. Patients may have had diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma. 5F9 (at a priming dose of 1 mg per kilogram of body weight, administered intravenously, with weekly maintenance doses of 10 to 30 mg per kilogram) was given with rituximab to determine safety and efficacy and to suggest a phase 2 dose. RESULTS: A total of 22 patients (15 with DLBCL and 7 with follicular lymphoma) were enrolled. Patients had received a median of 4 (range, 2 to 10) previous therapies, and 95% of the patients had disease that was refractory to rituximab. Adverse events were predominantly of grade 1 or 2. The most common adverse events were anemia and infusion-related reactions. Anemia (an expected on-target effect) was mitigated by the strategy of 5F9 prime and maintenance dosing. Dose-limiting side effects were rare. A selected phase 2 dose of 30 mg of 5F9 per kilogram led to an approximate 100% CD47-receptor occupancy on circulating white and red cells. A total of 50% of the patients had an objective (i.e., complete or partial) response, with 36% having a complete response. The rates of objective response and complete response were 40% and 33%, respectively, among patients with DLBCL and 71% and 43%, respectively, among those with follicular lymphoma. At a median follow-up of 6.2 months among patients with DLBCL and 8.1 months among those with follicular lymphoma, 91% of the responses were ongoing. CONCLUSIONS: The macrophage checkpoint inhibitor 5F9 combined with rituximab showed promising activity in patients with aggressive and indolent lymphoma. No clinically significant safety events were observed in this initial study. (Funded by Forty Seven and the Leukemia and Lymphoma Society; ClinicalTrials.gov number, NCT02953509 .).

Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study.

BACKGROUND: More than 50 million people worldwide sustain a traumatic brain injury (TBI) annually. Detection of intracranial injuries relies on head CT, which is overused and resource intensive. Blood-based brain biomarkers hold the potential to predict absence of intracranial injury and thus reduce unnecessary head CT scanning. We sought to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI. METHODS: This prospective, multicentre observational trial included adults (≥18 years) presenting to participating emergency departments with suspected, non-penetrating TBI and a Glasgow Coma Scale score of 9-15. Patients were eligible if they had undergone head CT as part of standard emergency care and blood collection within 12 h of injury. UCH-L1 and GFAP were measured in serum and analysed using prespecified cutoff values of 327 pg/mL and 22 pg/mL, respectively. UCH-L1 and GFAP assay results were combined into a single test result that was compared with head CT results. The primary study outcomes were the sensitivity and the negative predictive value (NPV) of the test result for the detection of traumatic intracranial injury on head CT. FINDINGS: Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analysable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries. 1288 (66%) patients had a positive UCH-L1 and GFAP test result and 671 (34%) had a negative test result. For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931-0·995) and an NPV of 0·996 (0·987-0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative. INTERPRETATION: These results show the high sensitivity and NPV of the UCH-L1 and GFAP test. This supports its potential clinical role for ruling out the need for a CT scan among patients with TBI presenting at emergency departments in whom a head CT is felt to be clinically indicated. Future studies to determine the value added by this biomarker test to head CT clinical decision rules could be warranted. FUNDING: Banyan Biomarkers and US Army Medical Research and Materiel Command.

Post-operative imaging assessment of non-functioning pituitary adenomas.

BACKGROUND: Non-functioning pituitary adenomas (NFAs) are the most common pituitary tumors. There is significant variability in clinical practice in terms of post-operative imaging evaluation. The objective of this manuscript is to provide an exhaustive review of published articles pertaining to the post-operative imaging evaluation of NFAs. METHODS: The MEDLINE database was queried for studies investigating imaging for the post-operative evaluation of pituitary adenomas. From an initial search of 5589 articles, 37 articles were evaluated in detail and included in this review. RESULTS: Magnetic resonance imaging (MRI) is the gold standard for post-operative monitoring of NFAs, although functional imaging modalities may improve identification of residual tumor in conjunction with MRI. The residual tumor can be distinguished from post-operative changes by experienced practitioners using high-resolution MRI in the immediate post-operative setting (within 1 week of surgery). However, continued imaging evolution in the appearance of residual tumor or resection cavity is expected up to 3 months post-operatively. CONCLUSIONS: Post-operative imaging appearance of the pituitary gland, optic apparatus, and pneumocephalus patterns, correlated with the clinical outcomes. Long-term, lifetime follow-up is warranted for NFA patients who underwent surgical resection.

Intraoperative Magnetic Resonance Imaging-Guided Biopsy in the Diagnosis of Suprasellar Langerhans Cell Histiocytosis.

BACKGROUND: Magnetic resonance imaging (MRI)-guided biopsy is an emerging diagnostic technique that holds great promise for otherwise difficult to access neuroanatomy. CASE DESCRIPTION: Here we describe MRI-guided biopsy of a suprasellar lesion located posterior and superior to the pituitary stalk. The approach was implemented successfully in a 38-year-old woman who had developed progressive visual deterioration. CONCLUSION: Intraoperative MRI revealed the need for trajectory adjustment due to an unintended, minor deviation in the burr hole entry point, demonstrating the benefit of an MRI-guided approach. Langerhans cell histiocytosis was diagnosed after biopsy, and the lesion regressed after cladribine treatment. Technical nuances of the case are reviewed in the context of the available literature.

Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy.

Exciting progress in the field of cancer immunotherapy has renewed the urgency of the need for basic studies of immunoregulation in both adaptive cell lineages and innate cell lineages. Here we found a central role for major histocompatibility complex (MHC) class I in controlling the phagocytic function of macrophages. Our results demonstrated that expression of the common MHC class I component ß2-microglobulin (ß2M) by cancer cells directly protected them from phagocytosis. We further showed that this protection was mediated by the inhibitory receptor LILRB1, whose expression was upregulated on the surface of macrophages, including tumor-associated macrophages. Disruption of either MHC class I or LILRB1 potentiated phagocytosis of tumor cells both in vitro and in vivo, which defines the MHC class I-LILRB1 signaling axis as an important regulator of the effector function of innate immune cells, a potential biomarker for therapeutic response to agents directed against the signal-regulatory protein CD47 and a potential target of anti-cancer immunotherapy.

Web-Based Tools and Mobile Applications To Mitigate Burnout, Depression, and Suicidality Among Healthcare Students and Professionals: a Systematic Review.

OBJECTIVE: Being a healthcare professional can be a uniquely rewarding calling. However, the demands of training and practice can lead to chronic distress and serious psychological, interpersonal, and personal health burdens. Although higher burnout, depression, and suicide rates have been reported in healthcare professionals, only a minority receive treatment. Concerns regarding confidentiality, stigma, potential career implications, and cost and time constraints are cited as key barriers. Web-based and mobile applications have been shown to mitigate stress, burnout, depression, and suicidal ideation among several populations and may circumvent these barriers. Here, we reviewed published data on such resources and selected a small sample that readily can be used by healthcare providers. METHODS: We searched PubMed for articles evaluating stress, burnout, depression, and suicide prevention or intervention for healthcare students or providers and identified five categories of programs with significant effectiveness: Cognitive Behavioral Therapy (online), meditation, mindfulness, breathing, and relaxation techniques. Using these categories, we searched for Web-based (through Google and beacon.anu.edu.au -a wellness resource website) and mobile applications (Apple and mobile. va.gov/appstore ) for stress, burnout, depression, and suicide prevention and identified 36 resources to further evaluate based on relevance, applicability to healthcare providers (confidentiality, convenience, and cost), and the strength of findings supporting their effectiveness. RESULTS: We selected seven resources under five general categories designed to foster wellness and reduce burnout, depression, and suicide risk among healthcare workers: breathing (Breath2Relax), meditation (Headspace, guided meditation audios), Web-based Cognitive Behavioral Therapy (MoodGYM, Stress Gym), and suicide prevention apps (Stay Alive, Virtual Hope Box). CONCLUSIONS: This list serves as a starting point to enhance coping with stressors as a healthcare student or professional in order to help mitigate burnout, depression, and suicidality. The next steps include adapting digital health strategies to specifically fit the needs of healthcare providers, with the ultimate goal of facilitating in-person care when warranted.

Where Hematopoietic Stem Cells Live: The Bone Marrow Niche.

SIGNIFICANCE: Hematopoietic stem cells (HSCs) can sustain the production of blood throughout one's lifetime. However, for proper self-renewal of its own population and differentiation to blood, the HSC requires a specialized microenvironment called the "niche." Recent Advances: Recent studies using novel mouse models have shed new light on the cellular architecture and function of the HSC niche. Here, we review the different cells that constitute the HSC niche and the molecular mechanisms that underlie HSC and niche interaction. We discuss the evidence and potential features that distinguish the HSC niche from other microenvironments in the bone marrow. The relevance of the niche in malignant transformation of the HSCs and harboring cancer metastasis to the bone is also outlined. In addition, we address how the niche may regulate reactive oxygen species levels surrounding the HSCs. Critical Issues and Future Directions: We propose future directions and remaining challenges in investigating the niche of HSCs. We discuss how a better understanding of the HSC niche may help in restoring an aged hematopoietic system, fighting against malignancies, and transplanting purified HSCs safely and effectively into patients. Antioxid. Redox Signal. 00, 000-000.

Enabling the Next-Generation Radiology Report: Description of Two New System Standards.

Currently, most radiology reports are highly variable and consist of unconstrained narrative text. This variability limits the ability to extract information from the report to guide clinical care, populate a data registry, or support quality improvement. This article introduces two newly available standards that pertain to radiology reports. Management of Radiology Reporting Templates (MRRT) is an integration profile that defines the format and exchange mechanisms for radiology report templates. Digital Imaging and Communications in Medicine Part 20 defines how reports built using MRRT-based templates can be transmitted into an electronic health record (EHR). Together, these two standards enable new ways to improve report consistency and completeness, ensure proper clinical action, and improve the quality of patient care. Commercial and open-source developers are beginning to incorporate these standards into clinical systems. The authors use an example of a patient with an incidentally detected lung nodule to illustrate how these standards improve the exchange of information. The clinical scenario follows the use of the appropriate template through the completion of the radiology report, with the incidental finding structured and coded to enable automated follow-up in the EHR. ©RSNA, 2017.

Multiple-response regression analysis links magnetic resonance imaging features to de-regulated protein expression and pathway activity in lower grade glioma.

BACKGROUND AND PURPOSE: Lower grade gliomas (LGGs), lesions of WHO grades II and III, comprise 10-15% of primary brain tumors. In this first-of-a-kind study, we aim to carry out a radioproteomic characterization of LGGs using proteomics data from the TCGA and imaging data from the TCIA cohorts, to obtain an association between tumor MRI characteristics and protein measurements. The availability of linked imaging and molecular data permits the assessment of relationships between tumor genomic/proteomic measurements with phenotypic features. MATERIALS AND METHODS: Multiple-response regression of the image-derived, radiologist scored features with reverse-phase protein array (RPPA) expression levels generated correlation coefficients for each combination of image-feature and protein or phospho-protein in the RPPA dataset. Significantly-associated proteins for VASARI features were analyzed with Ingenuity Pathway Analysis software. Hierarchical clustering of the results of the pathway analysis was used to determine which feature groups were most strongly correlated with pathway activity and cellular functions. RESULTS: The multiple-response regression approach identified multiple proteins associated with each VASARI imaging feature. VASARI features were found to be correlated with expression of IL8, PTEN, PI3K/Akt, Neuregulin, ERK/MAPK, p70S6K and EGF signaling pathways. CONCLUSION: Radioproteomics analysis might enable an insight into the phenotypic consequences of molecular aberrations in LGGs.

Tumefactive demyelination associated with developmental venous anomaly: Report of two cases.

We present two cases of tumefactive demyelination (TD) occurring in close association with a developmental venous anomaly (DVA). Our purpose is to describe the association between demyelinating lesions and venous anomalies, as only one case of TD associated with a DVA has been published in the literature. Appropriate recognition of this "do not touch" lesion may avoid invasive and potentially harmful procedures such as biopsy or resection.

Ruptured Dural Arteriovenous Fistula/Malformation.

When "common things are common," the discovery of a subdural hemorrhage in an adult is most likely to be due to trauma. When the subdural hemorrhage is associated with an intraparenchymal hematoma, statistically speaking, the subdural hemorrhage is likely the result of a hypertensive hemorrhage that has ruptured into the subdural space or trauma that resulted from a collapse to the ground following hypertensive intra-axial bleeding. However, "common things" do not always explain the source of a subdural hemorrhage or intraparenchymal hematoma. In this case, an adult woman presented to the hospital obtunded and was diagnosed with a subdural hemorrhage (with mass effect) and intraparenchymal hematoma as the result of a ruptured dural arteriovenous fistula/malformation. This case highlights an unusual source of intracranial bleeding that resulted in death.