tbuckley/cabot-search huggingface dataset:
Abstract 9579: A History of Multiple Tropical Diseases Increases Risk of Hypertension: A Cross-Sectional Study from the Amazon Basin
Authors: Anna Engell Holm, L. Gomes, K. Lima, Alma Wegener, L. Matos, I. Vieira, Molly D Kaagaard, R. Souza, C Marinho, T B-S, o ms, Philip Brainin
Journal: Circulation (2021)

Introduction: Studies have linked infectious diseases to cardiovascular conditions, however, little is known about tropical disease burden and hypertension. Hypothesis: We hypothesized that a history of multiple tropical infections was associated with greater risk of hypertension. Methods: We examined participants from outpatient clinics in the Amazon Basin, Brazil, who underwent a detailed questionnaire on prior infections with tropical diseases, including dengue, malaria hospitalization and leishmaniasis. Participants were categorized with hypertension if they had a prior diagnosis of hypertension, were treated with anti-hypertensive medication or had systolic/diastolic blood pressure ≥140/≥80mmHg. Results: A total of 556 participants (mean age 41 ± 15 years, 61% women) were enrolled, of which 38% (n=214) had hypertension and 354 (n=64%) had a history of tropical infectious disease. The distribution of tropical diseases was the following: Dengue 76% (n=270), malaria hospitalization 49% (n=104) and leishmaniasis 14% (n=48). In logistic regression models, each increase in prior tropical infections was significantly associated with hypertension (OR 1.50 [95%CI 1.15 to 1.96], P=0.003). The association remained significant after adjusting for age, sex, body mass index, education, income, work status, living area (urban/rural), smoking status, vegetable intake and plasma creatinine (Figure A). Persons with a history of ≥2 tropical infections (n=64) had the greatest risk of hypertension (OR 2.04 [95%CI 1.15 to 3.63], P=0.015) (Figure B). In adjusted models, prior infection with dengue was associated with higher risk of hypertension (P&lt;0.05), but no associations were found for malaria hospitalization or leishmaniasis (P&gt;0.05). Conclusions: A history of multiple tropical infections was associated with hypertension. This finding supports the idea that infectious diseases may be related to cardiovascular conditions.
Evaluation of Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Immunizations in Patients with B-Cell Malignancies
Authors: Mukul Singal, Sanjana Kalvehalli Kashinath, S Shahzad Mustafa, Edward Walsh, Karthik Vadamalai, Saad Jamshed
Journal: Blood (2021)
Abstract 10785: Cardiac Magnetic Resonance Imaging and Optical Coherence Tomography in Patients with a Clinical Diagnosis of Myocardial Infarction with Non-Obstructive Coronary Arteries - A Systematic Review and Meta-Analysis
Authors: Akshay Machanahalli Balakrishna, Mahmoud Ismayl, Abhishek Thandra, Vaishnavi Ganesan, Ryan Walters, Ahmed S Aboeata
Journal: Circulation (2021)

Background: Myocardial Infarction with Non-Obstructive Coronary arteries (MINOCA) is defined as acute Myocardial Infarction (MI) despite the absence of severe coronary artery stenosis on angiography (i.e., stenosis severity &lt;50%) and no specific alternative diagnosis (e.g., sepsis, pulmonary embolism). MINOCA remains a serious diagnostic and therapeutic challenge given the various possible underlying etiologies. Cardiac Magnetic Resonance Imaging (CMR) can distinguish between acute myocarditis (AM), MI, and Takotsubo cardiomyopathy (TCM) which are some of the commonest causes of MINOCA. Hence, The European Society of Cardiology (ESC) recommend CMR in all MINOCA patients with an unclear etiology. Intracoronary Optical coherence tomography (OCT) is a high-resolution imaging modality that allows for assessment of the integrity of the atheroma. We aimed to study the efficacy of CMR and OCT in detecting the etiology in MINOCA patients, which has the potential to guide medical therapy. Methods: A systematic search was made in PubMed, Medline and Cochrane database. Search terms used: Myocardial infarction, Coronary angiography, Normal coronary arteries, CMR, and OCT. Inclusion criteria was fulfilled by 18 studies. Meta-analysis and meta-regression was performed with 14 studies due to increased heterogeneity. Results: A total of 2474 patients were included in the meta-analysis. The mean age of all the patients was 51.5 and 56.4% were men. CMR was able to establish diagnosis in 74% of the patients; 30.4% had AM, 21.3% had true MI and 12% had TCM. Upon meta-regression the demographic variables, cardiovascular risk factors, troponin levels and C-reactive protein levels did not have any association with AM or MI. Incorporation of OCT with CMR was better at finding the etiology than either modalities individually. Conclusion: CMR is integral in finding the cause of MINOCA. Coupling coronary OCT and CMR is better than either techniques alone at identifying the etiology.
Increasing the Impact of Prevention of Depression—New Opportunities
Authors: Pim Cuijpers, Charles F. Reynolds
Journal: JAMA Psychiatry (2021)

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Transcriptional and Metabolic Profiling of Nicotinamide-Enhanced Natural Killer (NAM-NK) Cells (GDA-201)
Authors: Dima Yackoubov, Aviad Pato, Julia Rifman, Sherri Cohen, Astar Hailu, Nurit Persi, Orit Berhani-Zipori, Avishai Edri, Boaz Buhandler, Moshe Shahor, Nathan Dinowitz, Amram Ben David, Avi Izraeli, Vered Caspi, Liron Levin, Amnon Peled, Frank Cichocki, Joshua Rabinowitz, Wenyun Lu, Melanie McReynolds, Tracey Lodie, Julian Adams, Ronit Simantov, Yona Geffen
Journal: Blood (2021)
TAMI-48. THE KETOGENIC DIET IS INEFFECTIVE IN PRECLINICAL MODELS OF IDH1 WILD-TYPE AND IDH1 MUTANT GLIOMA
Authors: Rodrigo Javier, Craig Horbinski
Journal: Neuro-Oncology (2021)

Abstract Despite decades of intensive research, infiltrative gliomas are still usually lethal and challenging to treat. A subset of gliomas contains mutations in isocitrate dehydrogenase 1 (IDH1mut), which disrupts cellular biochemistry; such gliomas are generally less aggressive than their IDH1 wild-type (IDH1wt) counterparts. Some preclinical studies have suggested that a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial against a variety of cancers, including gliomas. However, not all studies have shown promising results, and to date, no study has addressed the sensitivity of glioma cells to KD in the specific context of the endogenous IDH1mut metabolic landscape. The aim of the current study was to compare the effects of KD in preclinical models to IDH1wt versus IDH1mut gliomas. In vitro treatment of patient-derived IDH1wt and IDH1mut glioma cells with the ketone body β-hydroxybutyrate showed no significant effect on cell proliferation in a low glucose culture environment. Likewise, the in vivo flank growth rates of these patient-derived IDH1wt and IDH1mut glioma xenografts showed no significant difference when mice were fed KD versus regular diet (GBM12 p=0.98, GBM164 p=0.4, GBM196 p=0.11). Finally, KD had no effect on the survival of mice engrafted with isogenic Sleeping-Beauty transposase-engineered IDH1wt (median control survival 22 days versus treatment 23 days, p=0.23) or IDH1mut glioma cells (median control survival 26.5 days versus treatment 26 days, p=0.81). These data suggest that IDH1mut gliomas are not more responsive than IDH1wt gliomas to KD, and that clinical trials further exploring KD in this subset of glioma patients are probably not warranted.
Abstract P437: Deep Learning-based Models For Complete Atrioventricular Block Heart Rhythm Analysis
Authors: Dahim Choi, Nam Kyun Kim, Young H Son, Yuming Gao, Christina Sheng, Jeongin Jang, Kihong Lee, Hee C Cho, Sung Jin Park
Journal: Circulation Research (2021)

Atrioventricular block (AVB), caused by impairment in the heart conduction system, presents extreme diversity and is associated with other complications. Only half of AVB patients require a permanent pacemaker, and the process determining the pacemaker implantation is associated with an increase in cost and patient morbidity and mortality. Thus, there is a need for models capable of accurately identifying transient or reversible causes for conduction disturbances and predicting the patient risks and the necessity of a pacemaker. Deep learning (DL) is brought to the forefront due to its prediction accuracy, and the DL-based electrocardiogram (ECG) analysis can be a breakthrough to analyze a massive amount of data. However, the current DL models are unsuitable for AVB-ECG, where the P waves are decoupled from the QRS/T waves, and a black-box nature of the DL-based model lowers the credibility of prediction models to physicians. Here, we present a real-time-capable DL-based algorithm that can identify AVB-ECG waves and automate AVB phenotyping for arrhythmogenic risk assessment. Our algorithm can analyze unformatted ECG records with abnormal patterns by integrating the two representative DL algorithms: convolutional neural networks (CNN) and recurrent neural networks (RNN). This hybrid CNN/RNN network can memorize local patterns, spatial hierarchies, and long-range temporal dependencies of ECG signals. Furthermore, by integrating parameters derived from dimension reduction analysis and heart rate variability into the hybrid layers, the algorithm can capture the P/QRS/T-specific morphological and temporal features in ECG waveforms. We evaluated the algorithm using the six AVB porcine models, where TBX18, a pacemaker transcription factor, was transduced into the ventricular myocardium to form a biological pacemaker, and an additional electronic pacemaker was transplanted as a backup pacemaker. We achieved high sensitivity (95% true positive rate) and quantified the potential risks of various pathological ECG patterns. This study may be a starting point in conducting both retrospective and prospective patient studies and will help physicians understand its decision-making workflow and find the incorrect recommendations for AVB patients.
Recent Updates on Blinatumomab: A Bispecific T-Cell Engaging Antibody in Relapsed and Refractory B-Cell Acute Lymphoblastic Leukemia
Authors: Tabinda Saleem, Abdul Rafae, Ahsan Wahab, Hamid Ehsan, Karun Neupane, Mohammad Ebad Ur Rehman, Pranali Pachika, Rabia Ali, Sundas Ali, Faiz Anwer
Journal: Blood (2021)
Abstract 11865: New Insights Into Optimal Duration of Dual Antiplatelet Therapy After Left Main Coronary Stenting: Findings From the Largest LM PCI Cohort
Authors: Haoyu Wang, Bo Xu, Rui Zhang, Changdong Guan, Kefei Dou
Journal: Circulation (2021)

Background: The optimal duration of dual antiplatelet therapy (DAPT) and the risk-benefit ratio for long-term DAPT in patients with left main coronary artery disease (LMCAD) undergoing PCI remains uncertain. Objectives: The aim of this study was to assess the efficacy and safety of extended duration DAPT (&gt;12-month) versus ≤12-month DAPT in patients who received PCI for LMCAD. Methods: A total of 4,561 consecutive patients undergoing PCI and stenting of LMCAD at a single center from January 2004 to December 2016 were enrolled. The primary outcome was 3-year MACCE (death, myocardial infarction, stent thrombosis, or stroke). The key safety outcome was BARC 2, 3, or 5 bleeding at 3 years. Results: 3,865 patients free of major ischemic or bleeding events in the first 12 months were included in the primary analysis. The distal LM bifurcation disease was involved in 80.5% of cases, in whom 27.0% were treated with a 2-stent strategy. DAPT&gt;12-month (n=1,727) versus ≤12-month DAPT (n=2,138) was associated with a reduced risk of 3-year primary outcome (2.5% vs. 4.5%; adjusted HR [aHR]: 0.592, 95% CI: 0.414-0.948). Similar results were found for the other ischemic end points: all-cause mortality (0.9% vs. 3.0%; aHR: 0.315 [0.179-0.554]), cardiovascular mortality (0.5% vs. 1.6%; aHR: 0.354 [0.169-0.739]), myocardial infarction (0.8% vs. 1.9%; aHR: 0.451 [0.245-0.831]), and stent thrombosis (0.4% vs. 1.1%; aHR: 0.400 [0.171-0.936]). Long-term DAPT showed similar risks of BARC 2, 3, or 5 bleeding compared to short-term DAPT (1.8% vs. 1.6%; aHR: 1.109; 95% CI: 0.681-1.806). The lower risk of a net adverse clinical event (a composite of BARC 2, 3, or 5 bleeding and MACCE) was identified in patients in patients treated with extended-term DAPT (4.1% vs. 5.7%; aHR: 0.729; 95% CI: 0.543-0.980). The effect of DAPT&gt;12-month on the reduction of primary outcome was consistent across clinical presentations (stable CAD vs. ACS), P2Y 12 inhibitor (clopidogrel vs. ticagrelor), and LM bifurcation PCI (1- vs. 2-stent strategy). Conclusions: In a large cohort of consecutive patients undergoing LM PCI, longer DAPT duration (&gt;12 months) could achieve more favorable outcomes by reducing ischemic risk, not significantly offsetting the increases in clinically relevant bleeding events.
Elective care backlog could rise to 12 million patients by 2025, warns watchdog
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The waiting list for elective care in England could reach 12 million by early 2025 without additional staff and bed capacity, the government’s spending watchdog has forecast.

In a report published on 1 December,1 the National Audit Office (NAO) cautioned that tackling the existing backlog and restoring elective and cancer care to the required standards would be a daunting challenge for the NHS.

By September 2021 some 5.83 million patients were on the waiting list for elective care, 1.95 million of whom had waited for more than 18 weeks for treatment and 301 000 for more than a year, it said.

Although cancer activity in the NHS had recovered to pre-pandemic levels by June 2021, the watchdog estimated that 240 000 to 740 000 urgent referrals …
CTNI-47. INTERIM RESULTS OF NCT03011671: A MULTI-INSTITUTIONAL PHASE I STUDY OF ACETAZOLAMIDE WITH TEMOZOLOMIDE IN ADULTS WITH NEWLY DIAGNOSED MGMT-METHYLATED MALIGNANT GLIOMA
Authors: Bakhtiar Yamini, Seán Lyne, Riley Driscoll, Giovanna Bernal, Longtao Wu, Martin NIcholas, Steve Chmura, John Collins, Deric Park, Peter Pytel, Theodore Karrison, Roger Stupp, Sean Grimm, Vinai Gondi, Ryan Merrell, Rimas Lukas
Journal: Neuro-Oncology (2021)

Abstract Preclinical studies indicate that up-regulation of carbonic anhydrase (CA) by temozolomide (TMZ), via a mechanism requiring the proto-oncogene BCL-3, promotes resistance to therapy in glioblastoma (GBM) cells. Moreover, the CA inhibitor, acetazolamide (ACZ), sensitizes patient-derived GBM cells and xenografts to TMZ. These findings led to the current Phase I study investigating the safety and efficacy of adding ACZ to adjuvant TMZ in patients with newly diagnosed, MGMT-methylated malignant glioma. 24 patients were enrolled (23 GBM and one Grade III IDH-mutant astrocytoma), median age was 53.5 and mean KPS 91. ACZ was given on days 1-21 of each adjuvant TMZ cycle (250 mg BID days 1-7, increased to 500 mg BID days 8-21). No patient experienced the primary outcome of regimen limiting toxicity (RLT) and there were only three grade III adverse events deemed likely unrelated to ACZ. For the secondary endpoints of overall and progression free survival (OS and PFS, respectively), only the 23 GBM patients were included (22 IDH-wildtype and 1 IDH-mutant). From diagnosis, median PFS was 18.8 months (95% CI: 10.4-23.0) and median OS was 25.0 months (95% CI: 19.9-28.4). Median time from diagnosis to consent was 2.9 months. As of April 2021, only 7 of 23 deaths had occurred. 2-year OS% was 68.2%. Further analysis of secondary endpoints including 6-month objective response rate (ORR) and biomarker analysis of BCL-3 by IHC will be available in the coming months. In sum, the data indicate that addition of ACZ to TMZ is safe and does not lead to reduced TMZ dosing. Also, compared to historical data, interim outcomes suggest that addition of ACZ may substantially improve PFS and 2-year overall survival. These findings support the hypothesis that ACZ acts as a chemosensitizer of alkylating chemotherapy in GBM and support examination of this regimen in a randomized, placebo-controlled study.
Trends in Obesity Prevalence Among Adults Aged 18 Through 25 Years, 1976-2018
Authors: Alejandra Ellison-Barnes, Sara Johnson, Kimberly Gudzune
Journal: JAMA (2021)

This study uses nationally representative data from the National Health and Nutrition Examination Survey to examine changes in obesity prevalence in the US over the last 4 decades among adults aged 18 through 25 years.
Keynote Session: Reducing Racial Disparities in Oncology—Recommendations for Implementing Guideline-Adherent Cancer Care
Authors: Shonta Chambers, Elizabeth Harrington, Lisa A. Lacasse, Robert Winn, moderated by Alyssa A. Schatz
Journal: Journal of the National Comprehensive Cancer Network (2021)

Research shows that racial disparities exist in the delivery of guideline-adherent cancer care, and that non-White patients are less likely to receive guideline-concordant care than White patients, leading to worse health outcomes. However, these disparities are not often addressed. The Elevating Cancer Equity initiative aims to address these disparities through policy-change recommendations developed by a working group and informed by data from patients/caregivers and oncologists. The hope is that the results of these surveys and the resultant recommendations will be a step toward cancer care equity in the United States.
EPCO-04. RADIOTHERAPY IS ASSOCIATED WITH GLOBAL METHYLATION ALTERATIONS IN PATIENT DERIVED GLIOBLASTOMA CELL LINES
Authors: Aram Modrek, David Byun, Ravesanker Ezhilarasan, Matija Snuderl, Erik Sulman
Journal: Neuro-Oncology (2021)

Abstract PURPOSE/OBJECTIVE(S) In glioblastoma, DNA methylation states are the most predictive marker of overall survival and response to therapy. Our understanding of how epigenetic states, such as DNA methylation, are “mis-repaired” after DNA damage repair is scant, hampering our ability to understand how treatment associated DNA methylation alterations may drive tumor resistance and growth. MATERIALS AND METHODS Three different patient derived IDH wild-type glioma stem cell (GSC) lines, in duplicates, were treated with radiation (20 Gray in 10 fractions vs. sham control) and allowed to recover prior to DNA methylation analysis with 850K methylation arrays. To analyze the methylation array data via bioinformatic methods we used RnBeads (version 2.4.0) and R (version 3.6.1) packages. We further focused our analysis to specific genomic regions, including CpG islands, promoters, gene bodies and CTCF motifs to understand how methylation alterations may differ between these and other genomic contexts following radiation. RESULTS There were widespread differential methylation (pre-treatment vs. radiation treatment) changes among the genomic regions examined. Interestingly, we found differential methylation changes at CTCF motifs, which play important DNA-methylation dependent roles in gene expression and chromatin architecture regulation. Hierarchical clustering, PCA and MDS analysis of DNA methylation status amongst CpG islands, promoters, gene bodies and CTCF domains revealed strong intra-sample differences, but not inter-sample differences (between GSC lines), suggesting radiation associated methylation alterations maybe loci and context dependent. CONCLUSION Radiation treatment is associated with wide-spread alterations of DNA methylation states in this patient derived glioblastoma model. Such alterations may drive gene expression changes or genomic architecture alterations that lead to treatment resistance, warranting further mechanistic investigation of the interplay between radiation induced DNA damage and local epigenetic state restoration following DNA damage repair.
Abstract 13720: Safety Follow Up in Cardiovascular Implantable Electronic Devices After Catheter Based Ablation Procedures
Authors: Muhammad Umer Butt, Faris I Haddadin, Hani Hamade, Adnan Yousaf, ahmad jabri
Journal: Circulation (2021)

Background: Catheter ablation is effective in the treatment of arrhythmias. The effect of ablation on Cardiovascular Implantable Electronic Devices (CIED) in long-term follow-up is unknown. Objectives: To study the impact of radiofrequency catheter ablation on various arrhythmias in patients with pacemakers and implantable cardiac defibrillators. Methods: We studied 119 consecutive patients with pacemakers and defibrillators who underwent various catheter-based procedures from 2011 to 2018. Various generator and lead parameters were compared before and after the procedure using paired sample t-test. Incidence of device-related complications was recorded as a percentage. Results: The mean age was 64.5 years. 88 patients had CHF (73.9 %). 63 Patients had CAD (52.9 %). 8.93 % and 41.3 % of patients had single and dual-chamber ICDs respectively. The rest of the patients had dual-chamber or biventricular pacemakers. 63.2 % of patients had Pulmonary Vein Isolation, Atrial Tachycardia, or Atrial Flutter ablation. 13.5 % of patients had AVNRT ablation and 20.3 % of patients had PVC or VT ablation. The Median follow-up interval was 8 weeks. No changes in before or after the ablation procedure in the atrial sensing ( 3.37± 1.60mV vs 3.40 ± 1.95 mV , P .52) and pacing thresholds ( 0.85mV± 0.46mV vs 0.82± 0.43 mV, P .35) , impedance (471.83± 106 ohm vs 447.57± 88.64 ohm , P .07) was noticed. Similarly, there was no difference in RV lead sensing and pacing threshold, but paradoxically there was a decrease in RV impedance after ablation (549.77± 173ohm vs 507.40 ± 129.0 ohms, p &lt;0.004). There was no difference in the LV lead parameters. There were no complications as lead dislodgement, stroke, hypotension, or death. Conclusion: Any type of catheter-related ablation is safe and efficacious in patients with pacemakers and defibrillators and there was no generator or lead-related complications noticed on interval follow-up.
Characteristics and Outcome of Patients with Acute Myeloid Leukemia and Trisomy 4
Authors: Sabine Kayser, David Martínez-Cuadrón, Maher Hanoun, Friedrich Stölzel, Cristina Gil, H. Christian Reinhardt, Eliana Aguiar, Kerstin Schäfer-Eckart, Juan Miguel Bergua Burgues, Björn Steffen, Teresa Bernal, Stefan W. Krause, Rosalia Riaza, Christoph Schliemann, Jose Cervera, Martin Kaufmann, Laura Torres, Mathias Haenel, Evelyn Acuña-Cruz, Edgar Jost, Jesús Lorenzo Algarra, Martina Crysandt, Lars Fransecky, Javier Cornago Navascués, Sabrina Kraus, Joaquin Martinez-Lopez, Hermann Einsele, Dirk Niemann, Andreas Neubauer, Ruth Seggewiss-Bernhardt, Sebastian Scholl, Stefan Klein, Christoph Schmid, Markus Schaich, Martin Schmidt-Hieber, Anthony D. Ho, Uwe Platzbecker, Claudia D. Baldus, Carsten Müller-Tidow, Christian Thiede, Martin Bornhäuser, Hubert Serve, Mark Levis, Pau Montesinos, Christoph Röllig, Richard F. Schlenk
Journal: Blood (2021)