tbuckley/cabot-search huggingface dataset:
Abstract 12107: Increased Prehospital Aspirin Use for Myocardial Infarction Patients With Atypical Symptoms Could Reduce Mortality
Authors: Amalie L Moeller, Helene C Rytgaard, Elisabeth H Mills, Helle C Christensen, Stig N Blomberg, Fredrik Folke, Kristian H Kragholm, Gunnar H Gislason, Christian Torp-Pedersen
Journal: Circulation (2021)

Introduction: Myocardial infarction (MI) patients with atypical symptoms receive poor prehospital management and have high mortality. We studied the importance of emergency ambulance response and prehospital aspirin use for survival of these patients. Methods: In Copenhagen, Denmark, citizens can call a 24-h non-urgent medical helpline or an emergency number 1-1-2 (equivalent to 9-1-1) for medical assistance. The primary symptom/purpose of calls is registered at both services. We included calls regarding patients hospitalized with an MI up to 24 h after the call and categorized calls according to primary symptom of chest pain or atypical symptom. Mediation analysis was used to examine the effect of modifying prehospital management. Results: We identified 5,440 calls regarding MI patients, 4,127 (76%) with chest pain and 1,313 (24%) with atypical symptoms. Compared to MI patients with chest pain, patients with atypical symptoms were older (median 73 vs 67 years), more often female (44% vs 31%), and had more often called the medical helpline (46% vs 32%). Among MI patients, 30-day mortality was 2.8% for chest pain and 10.9% for atypical symptoms. In the mediation analysis, mortality increased slightly to 11.3%, an increase of 0.3% CI95% [-1.2%; 1.8%], when changing the probability of receiving emergency ambulances for MI patients with atypical symptoms to the probability for chest pain patients. Emergency ambulances were dispatched to 4.277 (79%) of the MI patients. Among these, 30-day mortality was 2.9% for patients with chest pain and 13.1% for atypical symptoms. Changing the probability of receiving aspirin for patients with atypical symptoms to the probability for patients with chest pain decreased mortality to 10.5%. A reduction of -2.6% CI95% [-5.1%; -0.1%]. Conclusion: MI patients presenting with atypical symptoms have high mortality. Results from the mediation analysis suggest that increased prehospital use of aspirin could improve survival for these patients.
RTID-05. THE MULTI-ARM GLIOBLASTOMA AUSTRALASIA (MAGMA) TRIAL
Authors: Benjamin Kong, Hao-Wen Sim, Eng-Siew Koh, Hui Gan, Elizabeth H Barnes, Sonia Yip, Anna K Nowak, Peter Lau, Katharine Cuff, Eric Khoo, Zarnie Lwin, Adam Cooper, Anthony Dowling, Anthony Linton, Rosemary Harrup, Tracey Dunlop, Elizabeth Hovey, Jonathon Parkinson, Rosalind Jeffree, Merryn Hall, Emily Tu, Diana Andrew, John Simes, Craig Gedye
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Survival outcomes for patients with newly diagnosed glioblastoma have not changed significantly since the introduction of concurrent temozolomide with post-surgical radiation followed by adjuvant temozolomide. METHODS Multi-Arm Glioblastoma Australasia (MAGMA) is a recently initiated phase III multi-arm, multi-centre randomized trial for patients with newly diagnosed glioblastoma, led by the Australian Cooperative Trials Group for Neuro-Oncology (COGNO), that will concurrently test multiple treatment questions. Initially, a partial factorial design will be implemented to compare the current standard of care with either or both of (1) neoadjuvant temozolomide and (2) aduvant temozolomide continued beyond six months until progression. MAGMA will transition to a multi-arm multi-stage (MAMS) design as additional tratment question are introduced. Treatment allocation to each question will be balanced (1:1) using minimisation over several stratification factors, including study site, age, IDH-mutation status, surgical extent and randomization to the prior treatment question(s). The primary outcome is overall survival. Secondary outcomes include progression-free survival (measured by mRANO), time to first non-temozolomide systemic treatment, clinically significant toxicity as measured by Grade 2/4 adverse events, and health-related quality of life measures. Parsimonious data collection and a streamlined assessment schedule have been incorporated to mitigate the burden of data collection (such as low grade toxicity from temozolomide), and to encourage participation in regional and rural settings. A consortium model has been adopted to foster neuro-oncology expertise and infrastructure and share academic credit and future design opportunities. PROGRESS Recruitment commenced in September 2020. To date, 60 patients have been recruited from an initial sample size target of 250 patients for each of these initial two treatment questions. Of these 60 patients, 45 have been randomized in Question 1 (neoadjuvant chemotherapy) whilst 50 randomized in Question 2 (prolonged adjuvant chemotherapy). To date, 14 of the 27 intended sites are open to recruitment.
Abstract 11637: Decline in Stroke Mortality in the United States, 1975-2019: Impact of Obesity Among Women and Men
Authors: Cande V Ananth, Justin S Brandt, Katherine M Keyes, Hillary L Graham, John B Kostis, William J Kostis
Journal: Circulation (2021)

Introduction: The extent to which shifting age distributions, changes in stroke subtypes, and increases in obesity rates have impacted stroke mortality remain uncertain. Hypothesis: We hypothesize strong age and period effects on trends in stroke mortality, with obesity playing an important role in these trends. Methods: We designed a sequential time series analysis of 4,060,259 stroke deaths among women and men aged 18-84 years in the US, 1975-2019. The US annual mortality data, and US mid-year population data were accessed from Our World in Data and the CDC. Mortality rates were examined for overall stroke, and ischemic and hemorrhagic strokes. Trends in stroke mortality based on changes in the distribution of age, period, and birth cohorts (APC) were evaluated from Poisson models. We also aimed to quantify how much of the temporal increase in obesity rates explain the variance in stroke mortality trends. Results: Age-standardized stroke mortality declined for women (87.5 [95% confidence interval , CI, 86.8, 88.1] per 100,000 in 1975 to 30.9 [95% CI, 30.6, 31.2] in 2019) and men (112.1 [95% CI, 111.3, 113.0] per 100,000 in 1975 to 38.7 [95% CI, 38.3, 39.0] in 2019). In an APC analysis, stroke mortality increased sharply with advancing age (Figure). Ischemic and hemorrhagic strokes declined by period. There was a cohort effect for ischemic, but not hemorrhagic stroke. In 2019, the rate ratio (RR) of mortality for men versus women was 1.30 (95% CI, 1.27, 1.33) for ischemic stroke and 1.12 (95% CI, 1.09, 1.15) for hemorrhagic stroke. Increasing rates of obesity accounted for 86% and 80% of the temporal decline in stroke mortality rates among women and men, respectively. Conclusions: In the US, mortality rates from stroke have declined over the last 45 years. While men are more likely to die from stroke, the gender difference has narrowed for ischemic stroke, but widened for hemorrhagic strokes. Obesity appears to have contributed substantially to the decline in stroke mortality.
Different Prognostic Impact of Recurrent Gene Mutations in IGHV-Mutated and IGHV-Unmutated Chronic Lymphocytic Leukemia: A Retrospective, Multi-Center Cohort Study By Eric, the European Research Initiative on CLL, in Harmony
Authors: Larry Mansouri, Birna Thorvaldsdottir, Lesley-Ann Sutton, Manja Meggendorfer, Ferran Nadeu, Christian Brieghel, Helen Parker, Stamatia Laidou, Riccardo Moia, Davide Rossi, Mark Catherwood, Jana Kotaskova, Julio Delgado, Ana E Rodríguez-Vicente, Rocio Benito, Gian Matteo Rigolin, Silvia Bonfiglio, Lydia Scarfo, Mattias Mattsson, Zadie Davis, Ajay Gogia, Lata Rani, Panagiotis Baliakas, Cecilia Jylhä, Aron Skaftason, Inmaculada Rapado, Fatima Miras, Joaquin Martinez-Lopez, Javier de la Serna, Jesús M Hernández Rivas, Patrick Thornton, Maria Jose Larrayoz, María José Calasanz, Zoltán Mátrai, Csaba Bodor, Karin E. Smedby, Blanca Espinet, Anna Puiggros, Ritu Gupta, Lars Bullinger, Francesc Bosch, Bárbara Tazón, Fanny Baran-Marszak, David Oscier, Florence Nguyen-Khac, Thorsten Zenz, María José Terol, Antonio Cuneo, María Hernández-Sánchez, Sarka Pospisilova, Ken I Mills, Gianluca Gaidano, Carsten Utoft Niemann, Elías Campo, Jonathan C Strefford, Paolo Ghia, Kostas Stamatopoulos, Richard Rosenquist
Journal: Blood (2021)
ITVT-05. Intraoperative Ultrasound Guidance Improves Resection In Gliomas – Results From A Single Centre Propensity Matched Comparative Cohort Analysis Of 2D Vs Navigated 3D Ultrasound In 500 Gliomas
Authors: Aliasgar Moiyadi, Prakash Shetty, Vikas Singh
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Intraoperative ultrasound (iUS) is a promising tool for glioma surgery. Navigated 3-D (n3D) iUS has many benefits over standard 2-D iUS. METHODS This was a retrospective comparative cohort study using propensity score matching (PSM). 500 consecutive histologically confirmed gliomas were divided into 2 cohorts – 2DiUS - Cohort A; and n3DiUS -Cohort B. PSM was used to account for known confounders (250 in each group; 1:1 matching). Gross total resection rates (based on iUS findings as well as postoperative MR) and perioperative morbidity were analyzed across the groups as were factors influencing these outcomes (using univariate as well as multivariate regression models). RESULTS Overall, the majority of the patients were adults (94%), males (71%) with hemispheric tumors (96%). 35% had tumors close to eloquent regions and 23% had received some prior treatment. The majority were high-grade gliomas (85%). 2D iUS was employed mainly for localization (80%) whereas n3D was used predominantly for resection control (84%) [p &amp;lt; 0.001]. GTR rate was higher in the n3D cohort (55.2% vs 38.4% in 2D; p = 0.001). The odds of having a complete resection in the n3D cohort was twice that of the 2D. Prior treatment, hemispheric location, and use of fluorescence were also significantly associated with higher GTR rates on univariate analysis. On multivariate analysis, all of these remained significant. There was no difference in the morbidity rates in the two cohorts. N3D iUS had a higher specificity and positive likelihood ratio in detecting tumor residue. CONCLUSION For hemispheric gliomas undergoing resective surgery, the use of navigated 3D ultrasound improves GTR rates, with no added morbidity. It is more likely to be used for resection control mode than is 2DUS and this is probably because n3DUS is more specific and likely to pick up tumor residues contributing to its better accuracy.
Abstract 11575: The Effects of Tlr4 Deletion on Aortic Stiffness and Gut Microbiota Composition in High Fat Diet-Fed Mice
Authors: Chris E Gentile, Satya Raj J Trikha, Grace Stark, Gabriele Brown, Tiffany L Weir, Chris L Gentile
Journal: Circulation (2021)

Introduction: We have previously shown that alterations to the gut microbiota are an important mediator of diet-induced cardiometabolic dysfunction. One potential mechanism by which these microbial alterations may affect cardiometabolic function is via lipopolysaccharide (LPS), a component of gram-negative bacteria that can enter circulation following dysbiosis-related intestinal permeability. Once in circulation, LPS binds to toll-like receptor 4 (TLR4) in various tissues and induces a robust inflammatory response. TLR4 null mice are partially protected from obesity-related metabolic dysfunction, but it’s unclear if this mutation offers protection from vascular dysfunction. Methods: 24 male mice lacking the TLR4 receptor (KO) and 24 C57BL/6 wild type male mice (WT) were fed either a control diet (CON) containing 4% fat or a high fat diet containing 60% fat (HFD) for 6 months, yielding the following four experimental group: WT+CON; WT+HFD; KO+CON; KO+HFD. After 6 months, mice underwent measurement arterial stiffness (via pulse wave velocity), and glucose tolerance (via ip glucose tolerance test). The gut microbiota was analyzed by 16S gene sequencing. Results: Mice fed a high fat diet increased body weight, although the magnitude of weight gain was attenuated in KO+HFD vs WT+HFD (p&lt;0.05). Oral administration of FITC-dextran was used to determine intestinal permeability, HFD fed mice exhibited an increase intestinal permeability, compared to their respective control groups (p&lt;0.05). Circulating LPS binding protein was increased in both HFD groups compared to WT. Aortic pulse wave velocity was increased in WT+HFD but not KO+HFD. Glucose tolerance was higher in WT+CON compared to the other three experimental groups. Microbiota shifts occurred between groups, and surprisingly, genotype was the main driver of these shifts, followed by diet (explaining 27% and 22% respectively). Conclusions: These data indicate that deletion of TLR4 in male mice partially protects from arterial stiffness. These data support the supposition that LPS signaling downstream of gut dysbiosis may be an important factor in diet-induced vascular dysfunction.
Abstract 11962: Applying a Deep-Learning Approach for Automated Quantification of Epicardial Adipose Tissue on Coronary Computed Tomography Angiography in Challenging Clinical Populations
Authors: Henry W West, Muhammad Siddique, Lucrezia Volpe, Ria Desai, Maria Lyasheva, Katerina Dangas, Cheerag Shirodaria, Stefan Neubauer, Keith M Channon, Milind Y Desai, Michelle C Williams, Jonathan C Rodrigues, David Adlam, Nicol D Ed, Charalambos Antoniades
Journal: Circulation (2021)

Introduction: Epicardial adipose tissue (EAT) is a visceral fat deposit within the pericardial sac. The automated quantification of EAT volume is possible from routine CCTA scans via a deep-learning approach. Purpose: To apply a deep-learning approach for automated segmentation of EAT from CCTA scans in challenging clinical populations to assess the real-world viability of automated segmentation. Methods: A deep-learning automated EAT segmentation tool using a 3D Residual-U-Net neural network architecture for 3D volumetric segmentation of CCTA data was created and trained on over 2500 consecutive CCTA scans performed as part of clinical care in patients with stable chest pain from 2015 onwards within the European arm of the Oxford Risk Factors And Non Invasive Imaging (ORFAN) Study. External validation was performed in 817 scans from USA ORFAN sites (Figure 1A demonstrates human vs machine segmented EAT volume for a single case). The network was then applied to sets of unseen CCTAs from the AdipoRedOx Study (UK, n=253) and the SCOTHEART trial (UK, n=1558) to test its ability to perform EAT segmentations in challenging but common patient populations: 1) recent cardiac surgery (&lt;6 weeks post operation), 2) BMI ≥ 40, 3) CAC ≥ 400, 4) significant metallic artefact within the pericardium, and 5) a combined group of recent open-heart surgery, BMI ≥ 30 &amp; CAC ≥ 400. Results: There was excellent correlation between machine and human expert in the within-ORFAN validation cohort (Lin's concordance correlation coefficient (CCC) = 0.972, for both whole pericardial volume and EAT volume). CCC for machine vs human experts for all five challenging but common patient groups were also excellent (range 0.955-0.962) and are presented in Figure 1B-F. Conclusions: A new deep learning network achieves excellent automated segmentation of EAT and can be used to provide this information in a highly accurate and reproducible way, even in challenging common clinical populations.
Abstract 13537: Mortality and Social Vulnerability in the COVID 19 Pandemic
Authors: Andres Felipe Valencia Rendon, Isabela Volschan, Manoella Pereira, Wagner Lima Monteiro, Basilio Bragança Pereira, Emilia Matos do Nascimento, Glaucia Moraes de Oliveira
Journal: Circulation (2021)

Introduction: A disastrous disease, the COVID-19, continues its spread, this, coupled with its severity, led to a initial global lockdown. Early evidence identified Black counties where mortality risk was higher than in white counties, even more evident in Latin America. In Brazil, with multiple forms of social inequalities, where color/race takes high relevance in this debate, it is even more relevant in Rio de Janeiro. We aimed to analyze these socio economic factors and its correlation with COVID 19 mortality. Hypothesis: Patients hospitalized with COVID 19 with a high social vulnerable background would had greater in-hospital mortality Methods: Prospective study of 274 confirmed adult COVID 19 hospitalized patients in the UHCFF. Clinical features/blood chemistry information were obtained from the clinical record. Using the individual address, we correlated it with the Census Code Area (CCA), using a novel methodology, we geoprocessed each home on the Division map. Giving a high relevance to the socio-economic variables for inequity and vulnerability markers, also analyzing the fact to be transferred from another primary care institution, for its delay potential of advanced medical care. We performed a logistic regression, with in-hospital mortality as our primary outcome. Results: Patients living in low adequacy households(p=0.030) with high in-house individual agglomeration markers (p=0.017), and the fact to have been transferred from another primary care institution (p=0.047) presented high in-hospital mortality, with high ICU admission and Mechanical Ventilation rates. Conclusions: In hospital mortality due to COVID 19 was influenced by social individual background characteristics of vulnerability. Among other clinical parameters, these markers should be taken into account to predict the individual likelihood of complications related to the pandemic, prioritizing the attention and vaccination for those at higher risk should be paramount.
Phase II Study of Lower-Intensity Frontline Therapy for Newly Diagnosed Patients with AML Who Are Unfit or Otherwise Not Eligible for Frontline Clinical Trials
Authors: Sangeetha Venugopal, Elias J. Jabbour, Naveen Pemmaraju, Guillermo Montalban-Bravo, Kelly S. Chien, Naval Daver, Nitin Jain, Jan A. Burger, Yesid Alvarado, Abhishek Maiti, Courtney D. DiNardo, Gautam Borthakur, Rashmi Malla, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Tapan M. Kadia
Journal: Blood (2021)
NCMP-10. DYSGRAPHIA AS THE EARLIEST PRESENTING SYMPTOM OF SEVERE CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY NEUROTOXICITY: A SINGLE CENTER EXPERIENCE
Authors: Carlen Yuen, Kourosh Rezania, Thomas Kelly, Michael Bishop
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Chimeric antigen receptor (CAR) T-cell therapy, including axicabtagene ciloleucel (axi-cel; Yescarta®) and tisagenlecleucel (tisa-cel; Kymriah®), are FDA approved for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Neurotoxicity (NT) associated with CAR T-cell therapy (immune effector cell-associated neurotoxicity syndrome [ICANS]) can be fatal. Timely data, in the form of an abbreviated bedside mini-mental status exam, is thought to lead to earlier identification of NT. However, existing literature validating this method is limited. MATERIALS AND METHODS In this retrospective study, patients with R/R DLBCL treated with commercial axi-cel or tisa-cel in our center from December 2017 to September 2018 were assessed for NT with the CTCAE v4 criteria and the CAR-T-cell-therapy-associated TOXicity (CARTOX-10) scoring system. RESULTS Twenty-six patients with R/R DLBCL were treated with CAR T-cell therapy (25 axi-cel/[Yescarta®] and 1 tisagenlecleucel [Kymriah®]). Twenty-three (88%) developed NT with 8 (31%) experiencing severe NT (Grade III-IV). Tremor and dysgraphia occurred in all patients with severe NT. Lower average CARTOX-10 score (p=&amp;lt; 0.01), dysgraphia (p&amp;lt; 0.01), inattention (p=.018), and disorientation (p=.01) were significantly associated in patients with severe NT. A trend towards significance was observed between tremor and severe NT (p=.08). All patients with severe NT had both dysgraphia and tremor 8/8 (100%) and 2/8 (25%) had concurrent dysnomia. Death occurred in 12/26 (46%) of patients due to disease progression (n=11) and cardiac failure due to myositis (n=1). CONCLUSION In our limited cohort, dysgraphia, inattention, and disorientation are heralding symptoms of severe NT in adult R/R DLBCL patients treated with commercial CAR T-cell therapy. Dysgraphia was the earliest presenting symptom in patients with severe CAR T-cell neurotoxicity and was likely a manifestation of motor dysfunction rather than a component of dysphasia. Further studies with a larger cohort are needed to validate our findings.
Abstract 9863: Cannabis Use is Associated with Elevated Atherosclerotic Cardiovascular Disease Risk Score
Authors: Travis M Skipina, Nikhil Patel, Bharathi Upadhya, Elsayed Z Soliman
Journal: Circulation (2021)

Introduction: Cannabis use has been linked to deleterious cardiovascular events including stroke and myocardial infarction in observational studies. However, to date, the association between cannabis use and composite cardiovascular risk has not been studied. Hypothesis: Cannabis use is associated with an elevated atherosclerotic cardiovascular disease risk (ASCVD) score. Methods: This analysis included 7,159 participants (age 37.8±12.4 years, 48.6% male, 61.5% Caucasian) from the National Health and Nutrition Examination Survey years 2011-2018. Cannabis use was defined by self-report. Participants with a history of stroke or myocardial infarction were excluded. ASCVD scores were classified by risk levels: low (&lt;5.0%), borderline (5.0-7.4%), intermediate (7.5-19.9%), and high (≥20.0%). Multinomial logistic regression was used to examine the association between cannabis use and ASCVD risk category using low-risk ASCVD category as the reference level. Results: About 63.9% (n=4,573) of participants had ever used cannabis. Ever cannabis use was associated with 60% increased odds of high-risk ASCVD score [Odds Ratio (95% Confidence Interval): 1.60 (1.04-2.45), p-value=0.03]. Those reporting ≥2 uses per month had 79% increased odds of high-risk ASCVD score [Odds Ratio (95% Confidence Interval): 1.79 (1.10-2.92), p-value=0.02]. Those reporting ≥1 use per day had 87% increased odds of high-risk ASCVD score [Odds Ratio (95% Confidence Interval): 1.87 (1.16-3.01), p-value&lt;0.001]. Conclusions: Cannabis use is associated with elevated cardiovascular risk as evidenced by a positive association with ASCVD score. Patients who use cannabis should be counseled regarding their elevated risk for major cardiovascular events and appropriate risk reduction strategies should be implemented.