tbuckley/cabot-search huggingface dataset:
NIMG-17. SYSTEMATIC REVIEW OF LITERATURE EVALUATING MACHINE LEARNING ALGORITHMS TO DEVELOP OUTCOME PREDICTION MODELS IN GLIOMA USING MOLECULAR IMAGING WITH AMINO ACID PET
Authors: Julia Shatalov, W R Brim, Harry Subramanian, John Bazaar, Michele Johnson, Mariam Aboian
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Machine learning (ML) algorithms demonstrate accurate prediction of tumor segmentation, molecular pathology, and outcomes in gliomas using MRI and recently application of ML tools has expanded into molecular imaging with PET. We performed a systematic review to evaluate the role and applications of ML in characterization of gliomas with PET. METHODS Four databases were searched by medical school librarian and confirmed by an independent librarian: Ovid Embase, Ovid MEDLINE, Cochrane trials (CENTRAL), and Web of Science-Core Collection. The search strategy used keywords and controlled vocabulary combining the terms for: artificial intelligence, machine learning, deep learning, radiomics, magnetic resonance imaging, glioma, and related terms. All articles were reviewed by at least 2 independent reviewers at abstract screening, full text review, data extraction, and bias analysis using TRIPOD. RESULTS An initial 11,727 publications were imported to Covidence for screening. After review, 1135 studies moved to full-text review and 715 articles were included. Twelve publications included PET imaging of gliomas. All publications used single-center databases (3-73 patients) with distribution of tracers being [18F]-FDG (1), [18F]-FET (6), [11C]-MET (3), [18F]-FDOPA (1), and [18F]-AMP (1). All but 2 papers used supervised machine learning algorithms. Number of features ranged from 4-19,284. Nine papers manually extracted semiquantitative features TBRmax, TBRmean, SUV, TTP, in addition to demographics. Study outcomes included prediction of treatment response, survival, molecular subtypes, tumor grade, segmentation, and accuracy of image fusion. Accuracy ranged from 0.64-0.95 with AUC 0.43-0.9. CONCLUSION ML can be used on small datasets of PET imaging of brain tumors. While majority of the clinical scans are performed with FDG-PET, the machine learning approaches are being applied to mostly amino acid tracers. Extending ML approaches to FDG-PET, which is more common in clinical practice, is recommended. Overall, ML has potential as a useful tool for predicting patient outcomes and improving image postprocessing.
NIMG-14. RESTING STATE EXECUTIVE CONTROL AND SALIENCE NETWORK CONNECTIVITY IN CLINICALLY STABLE LOWER GRADE GLIOMA COVARIES WITH COGNITIVE PERFORMANCE
Authors: Tracy Luks, Javier Villanueva-Meyer, Christina Weyer-Jamora, Melissa Brie, Ellen Smith, Steve Braunstein, Paige Bracci, Susan Chang, Shawn Hervey-Jumper, Jennie Taylor
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Survival outcomes for patients with lower grade gliomas (LrGG) are improving. However, injury from tumor growth and consequences of treatment often leads to impaired cognition, particularly in cognitive domains reliant on distributed functional networks and intact white-matter tracts. Resting state functional MRI (rsfMRI) is a method of investigating the integrity of these functional networks. METHODS This study investigated rsfMRI connectivity in 21 patients with clinically stable LrGG compared to age- and gender-matched healthy controls, and associated imaging measures with cognitive outcomes. Data were acquired for 12 cognitive tests administered within one week of imaging. RsfMRI and T1-weighted images for 21 research controls were acquired from OpenNeuro datasets. RsfMRI data were processed and analyzed using the CONN toolbox using CONN’s standard regions of interest (ROI) for the 8 canonical networks as seeds, and cognitive test scores as covariates, with a threshold for T tests of p&amp;lt; .001 uncorrected. RESULTS Median age was 48 years old (range 27-67). There were 6 astrocytomas, IDHmut; 3 astrocytomas IDH-wt, 8 oligodendrogliomas, and 4 NOS. Thirteen had left hemisphere tumors (8 frontal, 3 parietal, 2 temporal), and 6 right (5 frontal, 1 temporal). Fourteen had previously recieved radiotherapy. There was significantly lower connectivity in frontoparietal executive control and the salience networks in LrGG patients versus controls. Within patients, lower executive control network connectivity covaried with worse performance on executive measures (FAS, Tower of London, Trails-A, Animal Naming, FrSBe), and attention and working memory measures (Digit Symbol, HVLT). Lower salience network connectivity covaried with poorer performance on executive measures (FrSBe, FAS) and attention and working memory measures (Digit Span, HVLT, WAIS-WM). CONCLUSION In clinically stable LrGG, rsfMRI measures of network connectivity are potentially useful markers to monitor and track, given the concordance with cognition, and could help guide cognitive assessment and rehabilitation.
Psychotropic medicine consumption in 65 countries and regions, 2008–19: a longitudinal study
Authors: Ruth Brauer, Basmah Alfageh, Joseph E Blais, Esther W Chan, Celine S L Chui, Joseph F Hayes, Kenneth K C Man, Wallis C Y Lau, Vincent K C Yan, Maedeh Y Beykloo, Zixuan Wang, Li Wei, Ian C K Wong
Journal: The Lancet Psychiatry (2021)
PATH-42. PROGNOSTIC FACTORS OF CNS GERM CELL TUMORS; MOLECULAR AND HISTOPATHOLOGICAL ANALYSES ON 154 CASES FROM THE IGCT CONSORTIUM
Authors: Kaishi Satomi, Ryo Nishikawa, Masao Matsutani, Koichi Ichimura, Hirokazu Takami
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Germ cell tumors (GCTs) preferentially occurs in pediatric and young adult age groups. Chemo- and radiation therapies cause long-term sequelae in their later lives. We searched for clinical and histopathological features to predict the prognosis and affect treatment response, with a future goal of treatment stratification. METHODS A total of 154 GCT cases were included in the analysis. Total of 114 germinoma cases underwent measurement of tumor cell content on H-E specimen, and 82 GCT cases underwent 450K methylation analysis. 12p gain was determined on methylation-based copy number computation and FISH. Association with progression-free and overall survival (PFS/OS) was investigated. RESULTS The tumor cell content was widely distributed from &amp;lt; 5% to 90% in the specimens, with a median value of 50%. Patients with a higher tumor cell content (≥50%) showed shorter PFS than those with a lower tumor cell content (&amp;lt; 50 %) (p=0.03). In multivariate analysis with tumor location, tumor cell content was the sole statistically significant prognostic factor (p=0.04). 12p gain was found in 25-out-of-82 cases (30%) and was more frequent in NGGCTs, particularly in cases with malignant components. The presence of 12p gain correlated with shorter PFS and OS, even with histology and tumor markers incorporated in the multivariate analysis. Among NGGCTs, 12p gain still had prognostic significance for PFS and OS. The 12p copy number status was shared among histological components in mixed GCTs. Whole-genome amplification was suggested by FISH. CONCLUSIONS We found that tumor cell content significantly affected the prognosis of germinomas. 12p gain predicts the presence of malignant components of NGGCTs, and poor prognosis of the patients. Furthermore, 12p is likely to be an early event in the tumorigenesis of GCT. These potentially open the possibility of leveraging these pathological and molecular factors in future clinical trials when stratifying the treatment intensity.
Maralixibat: First Approval
Authors: Matt Shirley
Journal: Drugs (2021)

Maralixibat (Livmarli™) is an orally-administered, small-molecule ileal bile acid transporter (IBAT) inhibitor being developed by Mirum Pharmaceuticals for the treatment of rare cholestatic liver diseases including Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC) and biliary atresia. Maralixibat received its first approval on 29 September 2021, in the USA, for use in the treatment of cholestatic pruritus in patients with ALGS 1 year of age and older. Maralixibat is also under regulatory review for ALGS in Europe, and clinical development for cholestatic liver disorders including ALGS in patients under 1 year of age, PFIC and biliary atresia is continuing in several other countries. This article summarises the milestones in the development of maralixibat leading to this first approval for ALGS.
Abstract 11727: Sex Differences in Coronary Endothelial Dysfunction Among Women and Men Living With HIV
Authors: Anum S Minhas, Thorsten M Leucker, Erin Goerlich, Michael Schar, Gabriele V Bonanno, Shashwatee Bagchi, Gary Gerstenblith, Robert G Weiss, Allison Hays
Journal: Circulation (2021)

Introduction: Impaired coronary endothelial function (CEF) is a known predictor of cardiovascular (CV) events and occurs in people living with HIV. HIV+ women compared to men have worse CV outcomes, but prior studies include very few women. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to endothelial cell inflammation and is elevated in HIV+ men. CEF and PCSK9 are not well studied in women with HIV. Hypothesis: We hypothesize that HIV+ women have worse CEF and higher PCSK9 levels compared to risk factor matched HIV- women, and that CEF will be associated with PCSK9 in HIV+ women, similar to prior findings in HIV+ men. Methods: A total of 34 HIV+ women and 75 HIV+ men on stable highly active antiretroviral therapy and 17 HIV- women and 8 HIV- men underwent MRI to measure CEF (%change in coronary artery cross-sectional area (%CSA) and coronary blood flow (CBF) during isometric handgrip exercise, an endothelial dependent stressor). Serum PCSK9 samples were obtained on the day of MRI. Comparisons were performed using student’s t-test for normally distributed and Kruskal-Wallis test for data not normally distributed. Robust regression was used for the association of PCSK9 with CEF. Results: CEF was significantly reduced in HIV+ women compared to age-, race- and BMI-matched HIV- women (p&lt;0.001 for both %CSA and %CBF change Fig. 1A-B). Both HIV+ men and women had similarly impaired CEF. Women with HIV had significantly higher PCSK9 levels than women without HIV (Figure 1C). Further, PCSK9 was significantly inversely associated with %CSA (ß -0.03(-0.06,0.00); p=0.038) in men but not in women (ß -0.02(-0.04,0.01); p=0.26). Conclusions: Coronary endothelial dysfunction is present among HIV+ women as compared to risk factor matched HIV- women. HIV+ women have similarly depressed CEF as HIV+ men. With HIV, PCSK9 is not significantly associated with CEF, suggesting potential alternative mechanisms of impaired CEF in men and women with HIV.
Abstract 14198: Peptide-siRNA Nanoparticles Targeting NF-kB Subunit P50 Suppress Experimental Abdominal Aortic Aneurysm Progression and Prevent Rupture
Authors: Huimin Yan, Ying Hu, Antonina Akk, Hua Pan, Samuel Wickline, Christine Pham
Journal: Circulation (2021)

Rationale: Abdominal aortic aneurysm (AAA) is a progressive vascular condition associated with high risk of mortality due to rupture if left untreated. AAA is an inflammatory process with excessive local production of extracellular matrix degrading enzymes, leading to dilatation, and rupture of the abdominal aorta. We posit that targeting NF-κB, a signaling pathway that controls inflammation, will halt AAA progression and prevent rupture. Methods and Results: In an elastase-induced AAA model we observe that NF-κB activation increases progressively post-elastase perfusion. Unexpectedly, we found that AAA progression is marked by predominant nuclear localization of the NF-κB p50 subunit at the exclusion of p65. Using the amphipathic peptide p5RHH to form nanocomplexes with siRNA, we show that NF-κB p50, but not p65 knockdown mitigates small AAA progression. Since elastase-induced AAA is self-limiting, we turn to an AAA model by topical application of elastase combined with TGF-β inhibition, which leads to rapid aortic diameter expansion and rupture in 50% of experimental animals. Systemic delivery of p5RHH-siRNA nanoparticles suppressing p50 protect 100% of male mice from rupture (and sudden death) in this model but does not significantly mitigate aneurysm expansion. In both models, knockdown of p50 is accompanied by significant decrease in inflammatory infiltrate, release of various cytokines, inducible nitric oxide synthase expression, and cell apoptosis. Conclusions: These results identify NF-κB pathway p50 subunit as a critical key modulator of the inflammatory process in AAA and p50 represents a potential therapeutic target in the medical management of AAA to prevents expansion and rupture. Figure 1. (A) Elastase + anti-TGF-β AAA model. (B) Aortic rupture with hematoma (arrow). (C) Survival curve (n = 6-10 mice per treatment group). p50 knockdown prevents rupture and death (C) but not AAA expansion (D). * P &lt; 0.05, ** P &lt; 0.01, *** P &lt; 0.001. inact.=inactive.
Abstract 14447: Increased Autophagy Flux May Underline Cardiomyocyte Remodeling in Atrial Fibrillation
Authors: Wenwei Zhang, Amy Burrell, Elizabeth Geist, Shin Yoo, Bradley P Knight, Rod S Passman, Rishi Arora
Journal: Circulation (2021)

Atrial fibrillation (AF), the most common progressive tachyarrhythmia, results in structural remodeling that impairs electrical activation of the atria. Studies have shown that mitochondrial dysfunction underlies cardiomyocyte remodeling. Here, we report a 50% reduction in total mitochondrial DNA in the atria tissue of RAP dogs as compared to control dogs, as assessed by qPCR the levels of mitochondrial DNA including mt-NT-1, mt-NT-4, mt-NT 5, mt-NT 6. This reduction in mitochondrial DNA suggests reduced mitochondria number in RAP dogs. Autophagic flux (LC3 II protein levels) was markedly increased in the atria tissue of the AF dog model (vs control dog).Furthermore, we examined autophagy flux in isolated cardiomyocytes. Results showed that LC3II was remarkably activated when subject to electrical stimulation for 6 hours under 3 Hertz condition, suggesting the direct effect of electrical stimulation on increasing autophagy. There was no change in the mRNA levels of autophagosome genes including Belin 1, ATG8, LC3, Lamp1 in the RAP dog tissue as compared to control, however, ATG7 increased by 2 fold and GNG2 increased by 5 fold. In conclusion, our study suggests that electrical stimulation-induced autophagy, and reduced mitochondria number and function, may underlie cardiomyocyte remodeling in AF. Targeting the autophagy pathway may present new therapeutic targets for AF. Ongoing AAV-mediated knockdown experiments in isolated cardiomyocytes will further elucidate the mechanism of electrical stimulation-induced autophagy.
Erratum
Authors: David Hong, Allan Ho, Irene Brana, Robert Haddad, Jessica Bauman, Keith Bible, Sjoukje Oosting, Deborah Wong, Myung-Ju Ahn, ; Val- Entina Boni, Caroline Even, Jerome Fayette, Maria Jos, Kevin Harrington, Sung-Bae Kim, Lisa Licitra, Ioanna Nixon, ; Nabil, F Saba, Stephan Hackenberg, ; Pol Specenier, Francis Worden, Binaifer Balsara, Mollie Leoni, Bridget Martell, Catherine Scholz, Antonio Gualberto, Allan Ho, Valentina Boni, Caroline Even, ; Binaifer Balsara, Alan Ho, Car- Oline Even, Kevin Flor, David Harrington, Ioanna Hong, Nabil Nixon, Stephan Saba, Pol Hack- Enberg, Binaifer Specenier, Mollie Balsara, Bridget Leoni, Antonio Martell, Alan Ho
Journal: Journal of Clinical Oncology (2021)
Abstract 10721: Exposure of Computer-Based Contrast Induced Nephropathy Risk Tool to Operator During Percutaneous Coronary Intervention
Authors: Matthew E Gold, Deyu Sun, Ryan Burkhart, Daniel Gold, Nathan Kong, Lucas Oliveira, John Blair
Journal: Circulation (2021)

Introduction: Contrast induced nephropathy (CIN) is one of the main causes of morbidity, mortality, and increased financial burden in high risk patients undergoing percutaneous coronary intervention (PCI). Although intravenous hydration is routinely used to prevent CIN among patients undergoing PCI, the optimal amount is not defined. Hypothesis: The current trial aims to determine whether a computer-based contrast induced nephropathy (CBCIN) risk tool, in addition to suggested standard hydration strategies exposed to the primary operator, results in lower rates of CIN and improved death and combined death/rehospitalization in patients undergoing PCI. Methods: Patients were recruited prospectively at the cardiac catheterization laboratory at the University of Chicago Medical Center in the inpatient and outpatient setting. Eligible participants were determined to be at-risk for CIN and included adult patients with either a reduced baseline eGFR (&lt;60 ml/min/1.73 m2) or patients with diabetes mellitus, hypertension, heart failure or age &gt;75 years. It is up to the operator’s discretion whether to use this information and hydration strategy. Operators then completed a survey of their experience. Results: There were 21 patients analyzed in this study. The average age was 73 and included 8 (38.1%) women. Operators reported a change in their treatment plan in 12 (57.1%) cases for a change to the contrast plan and 10 (47.6%) cases for a change in IV hydration plan. Use of the CBCIN risk tool led to an increase in the perception of CIN risk in 14 cases (66.7%), decreased time to calculate CIN risk in 16 (76.2%) cases, and increased adoption of CIN risk into the case in 17 (81.0%) cases. Conclusions: This is a preliminary description of an ongoing study showing that the CBCIN tool changed operator behavior, improved perception of CIN risk, and improved workflow. Future randomized studies are needed to determine whether CBCIN use translates into improved renal and clinical outcomes.
A Phase 1 Study of XmAb18968, a CD3-CD38 Bispecific Antibody for the Treatment of Patients with Relapsed/Refractory Acute Leukemia and T Cell Lymphoblastic Lymphoma
Authors: Guru Subramanian Guru Murthy, Tyce J Kearl, Weiguo Cui, Bryon Johnson, Karin Hoffmeister, Aniko Szabo, Kazuhiro Aoki, Alexandra M. Harrington, Karen Carlson, Laura C. Michaelis, Lyndsey Runaas, Sameem Abedin, Adam S Duvall, Wendy Stock, Bijal D. Shah, Jessica Leonard, Keith W. Pratz, Selina M. Luger, Talha Badar, Arielle Baim, Shahriar Yaghoubi, Ehab L. Atallah
Journal: Blood (2021)
Trial in Progress: A Perspective Study of Pan-Oral Triplet Regimen Pomalidomide, Ixazomib and Dexamethasone in Relapsed or Refractory Myeloma Patients
Authors: Miao Chen, Li Bao, Wenming Chen, Rong Fu, Rong Guo, Hongmei Jing, Hui Liu, Qinhua Liu, Yanping Ma, Xiuli SUN, Wei Wang, Yafei Wang, Xiaojing Yan, Jiang Qian, Junling Zhuang
Journal: Blood (2021)
Abstract 10601: Transfusion Strategies in Patients with Acute Coronary Syndrome and Anemia: A Meta-Analysis
Authors: Usama Nasir, Tayyab Ali Waheed, Keerat Ahuja, Charnjeet Sandhu, Muhammad Ameen, Earl J Hope
Journal: Circulation (2021)

Introduction: Anemia is a known risk factor for ischemic heart disease, and serves as an independent predictor of Major Adverse Cardiovascular Events (MACE) in patients with Acute Coronary Syndrome (ACS). Three randomized clinical trials (RCTs) have compared a Liberal Transfusion Strategy (LTS) with a Restrictive Transfusion Strategy (RTS) in ACS. This meta-analysis pools data from these RCTs to better define Hb thresholds for transfusion in this setting. Methods: MEDLINE, EMBASE, and Cochrane databases were searched using the terms “Acute Coronary Syndrome” and “Blood Transfusion” including their synonyms. A total of 3 randomized control trials were included.Restrictive transfusion strategy (RTS) was defined as Hb less than or equal to 8 g/dl with post transfusion goal of 8 to 10 g/dl. Liberal transfusion strategy (LTS) was defined as Hb less than or equal to 10 g/dl with post transfusion goal of at least 11 g/dl. The primary end point was 30-day mortality. Secondary outcomes included recurrent ACS events, new or worsening CHF within 30 days, and MACE. The primary analytic method used was random effects model. Results: Out of 821 patients, 400 were randomized to LTS, and 421 to RTS. Mean age was 70.3 in RTS versus 76.4 in LTS. There was no statistically significant difference for 30-day mortality in LTS compared to RTS (Odds Ratio [OR] 1.69; 95% CI: 0.35 to 8.05). Similarly, there was no significant difference in MACE, (OR 0.74; 95% CI: 0.21 to 2.63), CHF (OR 0.82; 95% CI 0.18 to 3.76), and Acute coronary syndrome (OR 1.21; 95% CI 0.49 to 2.95). Conclusions: In the setting of ACS, there is no difference between LTS and RTS for the outcome of MACE and mortality at 30 days. The ongoing MINT trial (NCT02981407) will provide further evidence in identifying the appropriate transfusion threshold in patients with ACS.
Abstract 12692: Extracorporeal Life Support After Cardiac Intervention Provides Reasonable Survival Even in Patients With Malignancies
Authors: Yota Suzuki, Nicholas Iglesias, Rui-Min D Mao, Abe Deanda, Ravi Radhakrishnan
Journal: Circulation (2021)

Introduction: With an increasingly aging population, cardiac surgery in oncologic patients is no longer rare. In postoperative cardiopulmonary compromise, the use of extracorporeal life support after cardiac intervention (Post-cardiac ECLS) has increased in general but its efficacy in oncologic patients is not clear. Hypothesis: ECLS after cardiac intervention provides reasonable survival in patients with malignancies. Methods: The Extracorporeal Life Support Organization registry was queried for patients older than 18 years with an International Classification of Diseases codes of hematologic and solid malignancy over the last decade (2010-2019). Among them, patients who underwent cardiac surgery or transcatheter valve intervention were selected. Outcomes and clinical data including types of procedure and cancer subtypes were analyzed. Results: One hundred and sixty-two patients met inclusion criteria: 17 pulmonary ECLS, 119 cardiac ECLS, and 26 extracorporeal cardiopulmonary resuscitation. Sixty-two patients (38.3 %) survived to discharge, which was significantly worse than all adult ECLS runs over the same time period (49.0%). Among subtypes, hematologic (p=0.041) and breast cancer (p=0.023) were associated with worse prognosis in comparison with all adult ECLS runs. Coronary artery bypass grafting (n=56) and surgical valve procedure (n=54) were dominant types of the procedure with a survival of 44.6% and 33.3%, respectively. Ventricular assist device procedure (n=48) and cardiac transplant (n=21) were also commonly performed with a survival of 37.5% and 33.3%, respectively. Conclusions: Use of Post-cardiac ECLS in oncologic patients has been increasing. Considering the poor outcomes reported in ECLS for postcardiotomy shock in general, our observed survival rate seems reasonable and should not exclude this population from ECLS consideration, with careful patient selection.