tbuckley/cabot-search huggingface dataset:
Abstract 14355: Metabolic Dysregulation and Incident Atrial Fibrillation in Older Adults
Authors: Cara N Pellegrini, Petra Buzkova, Adam Oesterle, Joachim H IX, David S Siscovick, Susan R Heckbert, Russell Tracy, Calvin Hirsch, Ken J Mukamal, Luc Djousse, Jorge R Kizer
Journal: Circulation (2021)

Introduction: Obesity and dysmetabolism are major risk factors for atrial fibrillation (AF). Fasting and post-load levels of glucose and non-esterified fatty acids (NEFA) reflect different facets of metabolic regulation, but their contributions to AF risk have not been studied simultaneously in prior studies. We assessed fasting and post-load glucose and NEFA in an older cohort to identify their independent associations with new-onset AF, and secondarily with baseline ECG parameters known to be markers of AF risk. Methods: This study focused on participants from the community-based Cardiovascular Health Study who were free of prevalent AF and had serum collected in the fasting state and after an oral glucose tolerance test. Maximal p wave duration and p wave terminal force in V1 (PTFV1) were measured from 12-lead ECG. Associations were evaluated with linear regression for ECG parameters, and Cox regression for AF. Results: The study included 1,877 participants (age 77.7±4.4). After adjustment, both fasting and post-load glucose, but not NEFA, were positively associated with higher PTFV1. When fasting and post-load glucose were entered together, only the relationship for the latter remained significant (63 μV*ms greater PTFV1 per SD increment in post-load glucose [p=0.028]). During median follow-up of 11.4 years, 717 cases of incident AF occurred. Post-load glucose, but not fasting glucose or either NEFA measure, showed an association with incident AF (adj. HR per SD=1.11 [95% CI=1.02, 1.21], p=0.017). There was significant interaction by sex (p=0.015). The positive relationship of post-load glucose with AF was observed in women (adj. HR per SD=1.21 [1.09, 1.35], p&lt;0.001), but not men (adj. HR per SD=0.97 [0.85, 1.12], p=0.714). Conclusions: Among older adults, post-load glucose, but not fasting glucose or NEFA measures, was positively associated with incident AF, with consistent findings for PTFV1 on baseline ECG. The relationship with AF appeared specific to women. Because post-load glucose is a marker of both pancreatic β-cell insufficiency and skeletal muscle decline, these findings suggest that interventions to address such tissue-organ dysfunction in older women might prevent AF in this high-risk population.
Results of a Single Center Survey on Vaccination Against COVID-19 in Patients with Chronic Myeloid Leukemia
Authors: Ekaterina Yu. Chelysheva, Anna Petrova, Oleg A. Shukhov, Margarita Gurianova, Anastasiya Bykova, Irina Nemchenko, Nikolay Tsyba, Alina V. Kokhno, Anna G. Turkina
Journal: Blood (2021)
Genomic Analysis of <i>NPM1</i> Mutation and <i>KMT2A</i>(<i>MLL</i>)-Rearrangement/Amplification in Japanese Patients with Acute Myeloid Leukemia: Hematologic Malignancies (HM)-Screen-Japan 01
Authors: SungGi Chi, Kentaro Fukushima, Hirohiko Shibayama, Naoko Hosono, Takahiro Yamauchi, Seiichiro Katagiri, Akihiko Gotoh, Motoki Eguchi, Takanobu Morishita, Reiki Ogasawara, Takeshi Kondo, Masamitsu Yanada, Kazuhito Yamamoto, Tsutomu Kobayashi, Junya Kuroda, Yoshimasa Kamoda, Kensuke Usuki, Yoshikazu Utsu, Nobuyuki Aotsuka, Makoto Yoshimitsu, Kenji Ishitsuka, Yasuyuki Nagata, Takaaki Ono, Naohito Fujishima, Naoto Takahashi, Hiroto Horiguchi, Satoshi Iyama, Makoto Nakamura, Kensuke Kojima, Kaoru Yamamoto, Yukinori Nakamura, Suguru Fukuhara, Koji Izutsu, Nobuhiko Yamauchi, Junichiro Yuda, Yosuke Minami
Journal: Blood (2021)
Abstract 13798: Pulmonary Arterial Hypertension Associated With Repaired Congenital Heart Disease in Children: Comparable Survival to Eisenmenger Syndrome
Authors: Andrew Constantine, Konstantinos Dimopoulos, Paul Clift, Robin Condliffe, Katrijn Jansen, Vivek Muthurangu, Shahin Moledina
Journal: Circulation (2021)

Introduction: Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD). Advances in management have altered the demographics of PAH-CHD, with fewer cases of Eisenmenger syndrome (ES) and more patients with PAH after CHD repair, who have worse outcomes than ES patients and an idiopathic PAH (IPAH)-like phenotype. However, pediatric data are limited. Methods: Patients under active follow-up in the National Paediatric Pulmonary Hypertension service UK between 2001 and 2021 were identified. Incident patients were included in survival analysis. Results: Overall, 164 patients with repaired PAH-CHD were included (57.9% female, 53.7% trisomy 21, 3.7[0.1-16.8] years at diagnosis), along with 95 patients with ES and 146 with IPAH. Most repaired PAH-CHD patients had an isolated post-tricuspid (59%), followed by a combined pre/post-tricuspid (28%) and isolated pre-tricuspid shunt (13.4%). Median age at repair was 13.6[5.6-51] months. PAH was diagnosed prior to repair in 24.5%. Symptoms were present in 53.7%, whereas 46.3% were identified during surveillance. PAH therapy was started in 86%; at last follow-up, repaired PAH-CHD patients were less likely to be on combination therapy than IPAH patients (32.9% vs 70.5%, p&lt;0.0001). Resolution of PH occurred in 8.5% patients at 6.4[3.1-9.4] months from diagnosis. Transplant-free survival in repaired PAH-CHD was 91.9% (95%CI: 87.6-96.4%) at 1 year, 86.1% (80.4-92.2%) at 5 years, and 77% (68.2-86.9%) at 10 years. Repaired PAH-CHD diagnosed in infancy had a significantly worse survival ( Fig 1A ). There was no difference in survival between repaired PAH-CHD and ES (p=0.68). IPAH had a worse survival than both groups (HR vs repaired 1.97, 95%CI:1.22-3.2, p=0.006, Fig 1B ). Conclusions: In this national paediatric cohort, patients with PAH after CHD repair had a better prognosis than patients with IPAH and similar to ES, albeit with a 23% mortality at 10 years, worse in patients diagnosed as infants.
Blockade of Tigit on AML-Derived M2 Macrophages Results in Reprograming into the M1 Phenotype and Enhances CD47-Mediated Phagocytosis
Authors: Franziska Brauneck, Brit Fischer, Jasmin Wellbrock, Carsten Bokemeyer, Julian Schulze zur Wiesch, Friedrich Haag, Christin Ackermann, Walter Fiedler
Journal: Blood (2021)
Abstract 100: Integrated Cardiac Metabolism In End-Stage Human Heart Failure
Authors: Emily Flam, Cholsoon Jang, Ken Bedi, Danielle Murashige, Yifan Yang, Michael Morley, Jeff Brandimarto, Ben Prosser, Tom Cappola, Josh Rabinowitz, Ken Margulies, Zolt Arany
Journal: Circulation Research (2021)

Heart failure affects millions of people worldwide with mortality near 50% within five years. This disease is characterized by widespread cardiac and systemic metabolic changes, but a comprehensive evaluation of metabolism in failing human hearts is lacking. Here, we provide a comprehensive depiction of cardiac and systemic metabolic changes in 89 explanted failing and non-failing human hearts through integration of plasma and cardiac tissue metabolomics, genome-wide RNAseq, and proteomic data. The data confirm a profound bioenergetic defect in end-stage human heart failure and demonstrate extensive changes in metabolic homeostasis. The data indicate a substantial defect in fatty acid (FA) use in failing hearts, in particular unsaturated FAs. Reduction of FAs and acyl-carnitines in failing tissue in contrast to concomitant elevations in plasma suggest a defect in import of FAs into the cell, rather than a defect in FA oxidation. Intermediates of glycolysis, the pentose phosphate pathway, and glycogen synthesis are all similarly reduced, as is expression of GLUT1, indicating diminished glucose uptake. However, there was no significant change in tissue pyruvate content, suggesting an increase in lactate utilization. The data suggest increased flux of pyruvate into mitochondria, likely promoting pyruvate oxidation but not pyruvate carboxylation. Blunted anabolic pyruvate flux, in turn, likely leads to insufficient TCA cycle intermediates. Ketone levels were increased in both failing tissue and plasma, as previously reported. The phospholipid content of failing human hearts is greatly increased in both failing tissue and plasma. Nucleotide synthesis pathways also appear to be reprogrammed, with a notable decrease in adenosine metabolism, specifically. Together, these data indicate widespread change in the local cardiac and greater systemic metabolic landscape in severe human heart failure.
Abstract 13579: Serum Neural Biomarkers and Neuroimaging Markers in Neonates With Congenital Heart Disease Undergoing Cardiac Surgery
Authors: Jiuann-huey I Lin, Lauren Lorenzi-Quigley, Tracy Baust, Ashok Panigraphy, Vincent Lee, Joan Sanchez-De-Toledo
Journal: Circulation (2021)

Introduction: Congenital heart disease (CHD) patients requiring neonatal cardiopulmonary bypass (CPB) surgery often experience abnormal neurodevelopment. Open heart surgery and anesthesia induce changes in the developing brain concomitant with an increase in the level of neuromarkers. The aim of this study is to assess the relationship between neuromarkers, brain dysplasia and neurodevelopmental outcomes for CHD patients undergoing neonatal CPB. Hypothesis: Neuromarkers and neuroimaging brain dysplasia can predict the neurodevelopmental outcomes for CHD patients undergoing neonatal CPB. Methods: 42 neonates with CHD requiring CPB were included in this prospective, observational study. Using the Neurology 4-Plex A Assay, serum levels of glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), neurofilament light (NF-L), and Tau protein were measured pre-operatively and at 0 hours, 24 hours, and 48 hours post-operatively. Brain MRIs were obtained in 24 neonates. Neurodevelopment testing was completed at 6 months to 36 months of age using the Bayley-III Scales of infant. Findings of brain MRI were scored using an internally developed scoring system which evaluates the brains structures individually on degrees of dysplasia, hypoplasia, and abnormalities, as well as providing a comprehensive assessment of overall brain development combining the individual structural abnormalities into a composite total brain dysplasia score (TBDS). Results: Bayley-III scales were negatively correlated with NF-L and Tau. For UCH-L1, a positive correlation was seen at immediate postop. Hemorrhage is associated with low language score (P=0.009) and elevated UCH-L1 levels at 24 hours and 48 hours. Infraction (P=0.0375) and lower maturation (P=0.03) are associated with low fine motor scores. Lower maturation is related to more domains below average (P=0.01). Infarction is associated with high postoperative Tau level (P=0.04).TBDS is associated with high levels of GFAP, NFL-1, and decreased language development. Conclusion: A negative correlation of Tau and NF-L to Bayley-III scales was consistent with their known roles as markers of neural injury. High NF-L and GFAP are associated with brain dysplasia.
Abstract 14145: The Ratio Of Hs-ctni/hs-ctnt In Patients With Myocardial Injury Is Associated With Different Clinical Phenotypes
Authors: Ishwar Chuckaree, Samuel McDonald, Deborah B Diercks, Sandeep R Das, James A De Lemos, Rebecca Vigen
Journal: Circulation (2021)

Introduction: Hs-cTnI and hs-cTnT concentrations are poorly correlated with a non-linear relationship. The purpose of this study is to determine whether patients with different ratios of hs-cTnI and hs-cTnT are phenotypically distinct. Methods: The study included a consecutive patient cohort that presented to a single academic institution between June and July 2020. Only the first admission and the first corresponding pair of troponin values obtained was analyzed. Patients with both hs-cTnI and hs-cTnT &gt; 99 th percentile URL (≥ 28 ng/L for hs-cTnI and ≥19 ng/L for hs-cTnT) were categorized based on their hs-cTnT to hs-cTnT ratio (I/T ratio). Patient demographic, clinical characteristics, and adjudicated final diagnoses were compared among tertiles of I/T ratio. Results: Of the 809 unique patient encounters, 137 patients had both hs-cTnI and hs-cTnT &gt; 99% URL. Patients in the lowest I/T tertile were more likely to be male, Black, and have diabetes, hypertension, CKD and CAD. The prevalence of myocardial infarction was 5% with the remaining elevated values secondary to acute or chronic non-ischemic myocardial injury. The adjudicated final diagnosis was more likely to be chronic non-ischemic myocardial injury in the lowest I/T tertile and more likely to be acute non-ischemic myocardial injury in the middle and highest tertiles. Conclusions: In this small, single center study, patients with myocardial injury and lower I/T ratio were more likely to have medical comorbidities and chronic myocardial injury as compared to the highest I/T tertile. This suggests that important phenotypic differences exist among patients with abnormal hs-cTnI and T levels. Table 1. Demographics and clinical characteristics of patient cohort with Hs-cTnI and Hs-cTnT values over 99 th percentile categorized by tertile of I/T ratio #Final adjudicated diagnoses defined as per the Fourth Universal Definition of Myocardial Infarction
Tom Nolan’s research reviews—26 November 2021
Authors: Tom Nolan
Journal: BMJ (2021)

Thiazides and β blockers feel the pressure "5 mm Hg, 11%."I'm trying to commit these numbers to memory for consultations with patients at high risk of developing diabetes: lowering your systolic blood pressure by five points reduces the chances of getting diabetes by about a tenth.This was one of the conclusions of a meta-analysis of individual participant data from 22 studies conducted between 1973 and 2008.
Federated learning for computational pathology on gigapixel whole slide images
Authors: Ming Y. Lu, Richard J. Chen, Dehan Kong, Jana Lipkova, Rajendra Singh, Drew F.K. Williamson, Tiffany Y. Chen, Faisal Mahmood
Journal: Medical Image Analysis (2021)

Deep Learning-based computational pathology algorithms have demonstrated profound ability to excel in a wide array of tasks that range from characterization of well known morphological phenotypes to predicting non human-identifiable features from histology such as molecular alterations. However, the development of robust, adaptable and accurate deep learning-based models often rely on the collection and time-costly curation large high-quality annotated training data that should ideally come from diverse sources and patient populations to cater for the heterogeneity that exists in such datasets. Multi-centric and collaborative integration of medical data across multiple institutions can naturally help overcome this challenge and boost the model performance but is limited by privacy concerns among other difficulties that may arise in the complex data sharing process as models scale towards using hundreds of thousands of gigapixel whole slide images. In this paper, we introduce privacy-preserving federated learning for gigapixel whole slide images in computational pathology using weakly-supervised attention multiple instance learning and differential privacy. We evaluated our approach on two different diagnostic problems using thousands of histology whole slide images with only slide-level labels. Additionally, we present a weakly-supervised learning framework for survival prediction and patient stratification from whole slide images and demonstrate its effectiveness in a federated setting. Our results show that using federated learning, we can effectively develop accurate weakly-supervised deep learning models from distributed data silos without direct data sharing and its associated complexities, while also preserving differential privacy using randomized noise generation. We also make available an easy-to-use federated learning for computational pathology software package: http://github.com/mahmoodlab/HistoFL.
Abstract 12374: Physiologic Changes of COVID-19 Infection Detected by Cardiac Implantable Electronic Device Data
Authors: Meghan Reading Turchioe, Rezwan Ahmed, Ruth M Masterson Creber, Kelly Axsom, Evelyn Horn, Gabriel T Sayer, Nir Uriel, David J Slotwiner
Journal: Circulation (2021)

Background: The trajectory of cardiac physiology throughout a COVID-19 infection remains poorly described. This study aimed to characterize physiologic changes associated with acute COVID-19 infection among patients with cardiac implantable electronic devices (CIEDs). Methods: The study population included 286 patients with a Boston Scientific CIED across a large health system. CIED sensor data from March 2020 - February 2021 were linked to clinical data from electronic health records. Three cohorts were created: COVID-positive (n=20), COVID-negative (n=166), and an untested control (n=100) to account for testing bias as institutional protocols only allowed symptomatic patients to be tested in the early months of the study. The magnitude of sensor changes from baseline (30-60 days before a COVID-19 test) to event (15-day window around a test) was compared between cohorts using one-way ANOVA. A date during the study window was randomly selected to serve as the event for control cases. Results: Comparing COVID-positive vs. COVID-negative vs. control, there was a greater change from baseline to event in respiratory rate (15% vs. 2% vs. 0.6% [p&lt;0.0001]), activity (-44% vs. -12% vs. -6% [p&lt;0.0001]), temperature (1% vs. 0.1% vs. -0.3% [p&lt;0.0001]), and HeartLogic Index, a composite index using multiple sensors (227% vs. -11% vs. 2% [p=0.004]). Average sensor changes show prominent differences surrounding a COVID-19 test for COVID-positive compared to COVID-negative and control cases ( Figure ). Conclusions: Physiologic changes associated with COVID-19 infection are detectable using CIEDs. COVID-positive patients have significant increases in respiratory rate, temperature and HeartLogic index and significant decreases in activity compared to COVID-negative and untested patients. Future studies in a larger population will help characterize the utility of CIEDs in infection surveillance and physiologic worsening that should prompt medical attention.
Abstract 9878: Higher Rates of Cardiac Arrest with Lower Inpatient Mortality Following Hospitalizations for ST-Elevation Myocardial Infarction Among Young Cannabis Users (18-44 Years): A Nationwide Propensity-Matched Analysis
Authors: Rupak Desai, Zainab J Gandhi, Sonali Sachdeva, Nibras Yar Khan, Nilay R Bhatt, Jamila Begum Jabar Ali, Mounika Binkam, Ummul Asfeen, Gautam Kumar, Rajesh Sachdeva
Journal: Circulation (2021)

Introduction: Given the rising use of unmonitored cannabis use in the young population and scarcity of data on the subject, we aimed to compare the outcomes of ST-elevation myocardial infarction (STEMI) admissions in patients with vs without cannabis use disorder (CUD+ vs. CUD-). Methods: The National Inpatient Sample (October2015-2017) was queried to identify STEMI admissions in young patients with CUD vs without CUD using relevant ICD-10 codes. Propensity-matched cohorts were obtained adjusting for sociodemographic, hospital characteristics, cardiovascular/extracardiac comorbidities. Primary endpoints were in-hospital mortality and complications, whereas secondary endpoints were discharge disposition, mean length of stay (LOS) and hospital cost. Results: Matched cohorts, STEMI-CUD+ (n=940) and STEMI-CUD- (n=940) were comparable in terms of age, sex, race and rate of non-elective admissions (Table 1) . The rates of hypertension (52.1% vs. 46.3%) and hyperlipidemia (39.9% vs 34.6%) were higher in the STEMI-CUD+ cohort (p&lt;0.05) with comparable rates of other risk factors (diabetes mellitus, smoking, and obesity). Post-STEMI MACCE was significantly higher (23.9% vs. 19.1%, p=0.012) including cardiac arrest (from ventricular tachyarrhythmias, 14.4% vs 10.6%, p=0.015), though with lower all-cause mortality (2.7% vs 4.8%, p=0.015) compared to CUD- cohort. Although complication rates of cardiogenic shock (9.6% vs 8.5%), arrhythmias (22.3% vs 19.7%), and stroke (3.7% vs. 2.7%) were higher in the CUD+ cohort, the statistical significance was not achieved. Conclusions: This nationwide multicenter analysis demonstrated that CUD+ cohort among young STEMI admissions had higher rates of hypertension, hyperlipidemia and MACCE including cardiac arrest without translating into higher inpatient mortality compared to CUD- cohort. Future large-scale prospective studies are invited to investigate and confirm these findings.
CTNI-59. A MULTICENTER OBSERVATIONAL STUDY OF CS-131 SEEDS EMBEDDED IN A COLLAGEN CARRIER TILE FOR NEWLY DIAGNOSED AND RECURRENT OPERABLE INTRACRANIAL NEOPLASMS – TRIAL IN PROGRESS
Authors: Erin Dunbar, David McCracken, adam nowlan, Clark Chen, Kathryn Dusenbery, Clara Ferreira, Rupesh Kotecha, Michael McDermott, Sivakumar Jaikumar, Colette Shen, David Monyak, John Trusheim, John Wanebo, Samuel Day, Stuart Lee, Zabi Wardak, Toral Patel, Mehee Choi, Lisa Misell, David Brachman
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND For patients with operable intracranial neoplasms, there are opportunities to augment local control beyond traditional methods, such as external beam radiation therapy. Brachytherapy, the implantation of radioactive sources into the resection cavity, can be useful in this setting by providing immediate initiation of radiation and limiting the exposure of surrounding normal tissue to radiation. Traditional intracranial brachytherapy has been limited by uneven dose distributions, complicated workflows, extended procedural times, cost of dedicated equipment, and frequent adverse events. To address these issues, a permanently implanted device with Cs-131 radiation seeds embedded in a bioresorbable collagen carrier tile (GammaTile, GT Medical Technologies, Tempe, AZ USA) was developed. Described as surgically targeted radiation therapy (STaRT), it is FDA-cleared for use in newly-diagnosed malignant intracranial neoplasms and recurrent intracranial tumors, and has demonstrated excellent safety and efficacy in early commercial use. The primary objectives of this multicenter, prospective, observational (phase IV) registry study are to evaluate “real-world” clinical outcomes and patient-reported outcomes that measure the safety and efficacy of STaRT using the GammaTile. METHODS Patients undergoing resection (R) of brain tumors with intra-operative GammaTile placement are eligible for enrollment. Planned sample size is 600 at up to 50 enrolling sites. First subject was enrolled 10/14/2020. Tumor pathology, overall survival, radiation- and surgery-related adverse events, patient- and provider-reported quality of life, serial MRIs, and timing of surgical bed and/or distant recurrence are collected. Powered primary endpoints for recurrent brain metastases, recurrent glioblastoma, and recurrent meningioma (surgical bed-progression free survival (PFS), overall survival, and PFS, respectively), compare STaRT to standard-of-care benchmarks. Results will be used to improve awareness and access to this treatment, benchmark clinical outcomes in the real-world setting, allow for comparisons to existing treatments, facilitate the design of future clinical trials, and contribute to the optimal sequencing of treatments for intracranial neoplasms.