tbuckley/cabot-search huggingface dataset:
Use of Confidence Intervals in Interpreting Nonstatistically Significant Results
Authors: Alexander T. Hawkins, Lauren R. Samuels
Journal: JAMA (2021)

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Abstract 13703: Outpatient Cardiac Rehabilitation Reduces Heart Failure Re-Hospitalization in Patient With Heart Failure With Reduced Ejection Fraction When Compared to Patients With Heart Failure With Preserved Ejection Fraction
Authors: KELECHI EMMANUEL, Halimat Lawal, Guillermo Valenzuela, Yijin Wert
Journal: Circulation (2021)

Introduction: Cardiac rehabilitation has been increasingly recognized as an integral part in the management of patients with congestive heart failure. It has been shown to improve the quality of life in this patient population. However, It is unknown how much cardiac rehabilitation reduces heart failure hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF). Hypothesis: We hypothesize that outpatient cardiac rehabilitation is associated with reduced re-hospitalization for heart failure symptoms in patients with heart failure with HFrEF when compared with patients with HFpEF. Methods: We retrospectively analyzed data from 128 heart failure patients enrolled in an outpatient cardiac rehabilitation center from January 2015 to December 2020. The number of heart failure re-hospitalizations was measured in each of these patients. A Student t-test was used to analyze the difference between the two groups, while fisher’s test or chi square was used to analyze categorical variables. Results: Among the 128 patients enrolled in the outpatient cardiac rehabilitation center, age 68.1+-14 years, 63 (57.1%) were males. There were 70 patients (54.6%) in the HFrEF group and 58 (55.28%) in the HFpEF group. Hospitalization for acute exacerbation of heart failure symptoms was lower in the patients with HFrEF when compared with patients with HFpEF (41.3% vs 70.69% p value &lt;0.0009). Conclusion: Outpatient cardiac rehabilitation program is associated with reduced hospitalization for heart failure symptoms in patients with HFrEF when compared to patients with HFpEF.
Abstract 9904: Association of History of Bariatric Surgery and Outcomes of Primary Atrial Fibrillation Hospitalizations: Insights from National Inpatient Sample 2016-2018
Authors: Abdul Minhas, Shakeel Jamal, Waqas Ullah, Sardar H Ijaz, Muhammad Hisham Khan Wazir, Marat Fudim
Journal: Circulation (2021)

Background: Atrial fibrillation (AF) is the most prevalent arrhythmia in the United Sates. Obesity is a known adverse prognostic factor for several cardiovascular diseases. We aimed to evaluate clinical outcomes in patients hospitalized with AF with history of bariatric surgery versus morbid obesity. Methods: We conducted a retrospective analysis of adult discharges from the National Inpatient Sample (NIS) between 2016 and 2018. ICD Codes were used to identify primary AF hospitalizations. These were further divided into two groups 1. Body mass index (BMI) &gt;/= 35; 2. History of bariatric surgery with BMI &lt; 35. Prevalence estimates were weighted using NIS-provided discharge-level weights to reflect national estimates. Weighted multivariable logistic regression was used to assess the association of history of bariatric surgery vs morbid obesity on various other clinical outcomes in primary AF hospitalizations. These models were adjusted for several patient-level and hospital-level characteristics. Results: There were 7,340 primary AF related hospitalizations with history of bariatric surgery and 159,105 primary AF hospitalizations with morbid obesity. There was no significant difference in adjusted all-cause mortality, use of mechanical circulatory support, cardiac arrest, cardiogenic shock, invasive mechanical ventilation, pressors use or inflation-adjusted cost between the two groups. However, admissions with morbid obesity (in comparison to history of bariatric surgery) were associated with higher rates of acute kidney injury, disposition to short/long term care and length of stay. Conclusion: Our study did not show any difference in mortality and various other outcomes between the two groups. However acute kidney injury, disposition to short/long term care and length of stay were significantly higher for the admissions with morbid obesity.
EPID-06. ASSOCIATIONS BETWEEN GERMLINE GENETIC VARIANTS AND OVERALL SURVIVAL IN PATIENTS WITH GLIOMA
Authors: Kunal Potnis, Quinn Ostrom, Elizabeth Claus
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND In addition to somatic genetic variation in tumors, germline genetic variation can better define cancer susceptibility risk, guide therapy, and predict survival. Most prior research into associations between germline genetic variants and survival outcomes in patients with glioma has been limited by small sample sizes and to high-grade glioma only. This study is the first to use data from Brigham and Women’s Hospital (BWH) and to include both low-grade and high-grade glioma cases to explore associations between germline genetic variants and overall survival. METHODS This study included 211 patients enrolled at BWH from April 2010 to January 2020. Ninety-two candidate germline genetic variants were identified via literature review. Fifty-five variants with minor allele frequency &amp;gt;0.05 were included preliminarily, for which bivariate Cox proportional hazards regression models were employed. Twenty-two variants with P&amp;lt; 0.5 were included in the final multivariable model, adjusted for patient sex, age, race, and glioma grade. Stratified sub-analyses were also conducted by sex. Associations were considered statistically significant at P&amp;lt; 0.05. RESULTS Among all patients, homozygous C/C genotype at rs17655 (ERCC5 gene) was significantly associated with worse overall survival (hazard ratio=2.61, P=0.0095). Among females only, worse survival was associated with homozygous T/T genotype at rs1381057 (POLQ, hazard ratio=2.58, P=0.046). Among males only, heterozygous status for the A genotype at rs487848 (POLQ, hazard ratio=0.31, P=0.018) and the A genotype at rs1468923 variant (PIK3CA, hazard ratio=0.51, P=0.016) were associated with improved survival. CONCLUSION We identified statistically significant associations between overall survival and four variants in genes involved in DNA repair and the PIK3 pathway, three of which were sex-specific. Our results contribute to improving patient stratification in glioma and may lead to increased targeting of treatment strategies.
Abstract 12098: A Physics-Based Machine Learning Approach for Instantaneous Classification of Myocardial Infarct Size
Authors: Rashid Alavi, Wangde Dai, Robert A Kloner, Niema M Pahlevan
Journal: Circulation (2021)

Introduction: Intrinsic frequency (IF) method is a novel systems-based approach that uses a single uncalibrated arterial waveform for the analysis of the left ventricle (LV) and arterial function. In a recent Framingham Heart Study, it was shown that IFs derived from carotid waveforms predict incident of heart failure and composite cardiovascular disease events (Hypertension. 2021, 77(2):338-346). The predictive and diagnostic values of IF for acute events such as myocardial infarction (MI) is not fully known. Here, we propose a hybrid IF-machine learning (ML) method to classify the MI size (mass percentage of necrosis over total LV). Methods: We used standard MI rat models (Sprague Dawley; n =27). Necrosis was ensured by occluding proximal left coronary artery for 30 minutes, followed by 3 hours of reperfusion. IFs were computed from carotid waveforms 2 hours after the reperfusion. MI sizes were obtained via histopathology (white areas of LV slices are the necrotic areas in Fig.1). The range of rats’ MI size was from 10.9% to 59.9%. MI sizes of 18% and 36% were considered as the cut-offs for ML classification. A 8-split decision tree was trained as the classifier model using the IFs as predictors. The k -fold cross-validation ( k =3) was used to avoid overfitting. Gini’s diversity index was considered as the split criterion. Results: Our ML model showed accuracies of 86.7%, 85.7%, and 60% for predicting the true class of MI sizes (i.e., large, mid-sized, and small, respectively) (Fig.1). The accuracy was particularly strong (86.7%) for detecting large MI sizes. Conclusions: The results suggest that an IF-based ML model (a physics-based approach) can instantaneously classify the severity of the anatomic infarct size using a single arterial waveform without advanced imaging. Since IFs can be measured noninvasively and remotely (i.e., using a smartphone or wearable devices), our proposed method can have potential clinical impact in management and treatment of patients post MI.
Whole blood versus red cell concentrates for children with severe anaemia: a secondary analysis of the Transfusion and Treatment of African Children (TRACT) trial
Authors: EC George, S Uyoga, B M'baya, D Kyeyune Byabazair, S Kiguli, P Olupot-Olupot, R Opoka, G Chagaluka, F Alaroker, TN Williams, I Bates, D Mbanya, DM Gibb, AS Walker, K Maitland
Journal: The Lancet Global Health (2021)
CTNI-57. MATRix REGIMEN FOR NEWLY DIAGNOSED PRIMARY DIFFUSE B-CELL LYMPHOMA OF THE CENTRAL NERVOUS SYSTEM
Authors: Richard Green, Ruben Guzman-Marin, Keng Lam, Colleen Thornton
Journal: Neuro-Oncology (2021)

Abstract We report our experience treating 20 patients with newly diagnosed primary diffuse B-cell lymphoma of the central nervous system with the MATRix regimen as reported by Ferreri, et al in 2016. The median age was 65 y; 8 patients were men and 12 were women. Eighteen had cerebral mass lesions, 1 had a paraspinal mass, and 1 leptomeningeal disease. Treatment consisted of 4 cycles of rituximab 375 mg/sq m (Days 1, 6); methotrexate 3.5 g/sq m (Day 2); cytarabine 2 g/sq m every 12 h (Days 3, 4); and thiotepa 30 mg/sq m (Day 5). Patients without disease progression received carmustine 400 mg/sq m and thiotepa 5 mg/kg followed by autologous bone marrow transplantation. Four patients were switched to MATRix after 6 cycles of methotrexate and rituximab and received only 2 initial cycles including cytarabine and thiotepa. Overall, 14 patients completed initial chemotherapy. Twelve of these 14 went on to transplantation; one patient had early disease progression, and in one no stem cells could be collected. All 4 patients over 70 y died early after 1-2 cycles; the median age of these was 80 y, and the causes of early death were neutropenic fever, septic thrombophlebitis, and cardiac arrest. One patient who completed the entire regimen including transplantation died of fungal pneumonia; the other 13 experienced no serious acute toxicity. One patient had late disease progression; one developed symptomatic leukoencephalopathy. Thirteen of the 20 patients remain alive. Median OS for the cohort is 698 days. These preliminary data suggest that the MATRix regimen in safe and highly effective in the newly diagnosed setting. However, the high incidence of early death in patients over 70 y suggests that the regimen may be too toxic for elderly individuals.
Non-Intensive Continuous Treatment with a Tyrosine Kinase Inhibitor (TKI) Followed By Allo-HSCT Is an Effective Therapeutic Strategy for Adult Ph-Positive Acute Lymphoblastic Leukemia: Outcomes of the Russian Prospective Multicenter RALL Study
Authors: Olga A. Gavrilina, Elena N. Parovichnikova, Vera V. Troitskaya, Zalina Kh. Akhmerzaeva, Sergey N. Bondarenko, Valery A. Lapin, Maria E. Grishunina, Olga S. Samoylova, Tatiana S. Konstantinova, Larisa A. Kuzmina, Julia A. Chabaeva, Valery G. Savchenko
Journal: Blood (2021)
Validation of New International Prognostic Scores, Including Baseline Peripheral Blood Variables, in Patients with Diffuse Large B-Cell Lymphoma and HIV Infection Treated with R-CHOP and Combined Antiretroviral Therapy. Retrospective Study from Spanish Lymphoma Group Geltamo
Authors: Maria Huguet, Mireia Morgades, Armando Lopez-Guillermo, Alfredo Rivas-Delgado, Mariana Bastos-Oreiro, Teresa Aldamiz-Echevarría, Antonio Salar, Fátima de la Cruz Vicente, Miguel Alcoceba, Blanca Ferrer Lores, Ana Jimenez-Ubieto, Antonio Gutierrez, Maria Stefania Infante, Sofia Huerga, Pau Abrisqueta, David Cruz, Carlos Montalban, Ana Muntañola Prat, Sonia González de Villambrosia, Míriam Verdú, Juan-Manuel Sancho, Josep-Maria Ribera, José-Tomás Navarro
Journal: Blood (2021)
Abstract 10390: Transcatheter and Surgical Aortic Valve Replacement in Children with Congenital Heart Disease: An Institutional Experience
Authors: Dwight M Robertson, Marlayna Despres, Dana Boucek, Mary Hunt Martin, Robert G Gray, Eric Griffiths, Aaron Eckhauser, Zhining Ou, Linda M Lambert, Richard V Williams, Adil Husain
Journal: Circulation (2021)

Introduction: Surgical approaches have historically been the mainstay for aortic valve replacement in children and adults, while transcatheter approaches have been increasingly utilized in adults with rare use in children. We hypothesized that short-term outcomes for native aortic valve replacement are comparable between the surgical (SAVR) or transcatheter (TAVR) approach in children. Methods: Patients &lt; 21 years who had native SAVR or TAVR between January 2010 to April 2020 at our institution were included. Analysis focused on short-term outcomes for ages 10-21. SAVR and TAVR were compared using a composite outcome score (stroke within 6 months, readmission within 30 days, death). Pre- and post-procedural characteristics were compared using chi-squared test or Wilcox rank sum test as appropriate. Results: Of 77 patients included, 46 were 10-21 yrs (30 SAVR, 16 TAVR). Mean follow-up was 3.7 yrs for the SAVR group and 1.7 yrs for the TAVR group. There was no significant difference in the composite score between groups (3 SAVR, 2 TAVR; p = 1). Patients in the SAVR group were more likely to have undergone concomitant surgical intervention (e.g., Konno procedure, mitral valve repair/replacement, etc.) and have longer hospital stays (Table 1). Death in the SAVR group was secondary to patient non-compliance with recommended medications and follow-up, resulting in severe aortic stenosis with cardiogenic shock and respiratory failure. Death in the TAVR group was secondary to endocarditis of the valve and associated stroke, which converted from ischemic to hemorrhagic following surgical intervention. Conclusion: Our study suggests similar short-term outcomes for TAVR and SAVR in children and young adults &gt; 10 years of age. Long-term studies are essential in the pediatric population to fully explore the option of transcatheter aortic valve replacement as an alternative to surgical aortic valve replacement.
Abstract 10743: Overexpression of GLUT4 Induces Pulmonary Hypertension
Authors: Joel James, Mathews Valuparampil Varghes, Olga Rafikova, Ruslan Rafikov
Journal: Circulation (2021)

Introduction: Pulmonary arterial hypertension (PAH) induces significantly elevated glucose uptake in the patient lungs and right ventricles (RV), which correlates with the severity of the disease. However, the mechanisms responsible for the increased glucose uptake and its contribution to the PAH pathobiology remain unclear. We discovered that Sugen/hypoxia-induced PAH is associated with a marked overexpression of glucose transporter, GLUT4, starting from the early stage of the disease. Hypothesis: We investigated the role of GLUT4 overexpression in triggering PAH and evaluated the downstream mechanisms responsible for the PAH phenotype. Methods: In this study, we used the mouse model overexpressing human GLUT4 (hGLUT4). RV hemodynamics and function were assessed in hGLUT4 mice treated or not with IMPA1 inhibitor (L690,330, i.p., 22 mg/kg BW, daily for 6 weeks). Isolated pulmonary artery smooth muscle cells (PASMC) were used to perform glucose uptake assays and bioenergetics measurements. Results: hGLUT4 mice showed significantly increased RV systolic pressure (RVSP, 28.98±0.72, p&lt;0.001, N=7-9) and RV hypertrophy (0.319±0.006, p&lt;0.0001, N=7-9) compared to WTs and non-transgenic controls. GLUT4 overexpression significantly increased the glucose uptake in PASMC (~30% increase to control, p&lt;0.01) and induced severe mitochondrial dysfunction in unstimulated and insulin-stimulated cells. Previously, we discovered that an increase in glucose uptake elevates the levels of glucose 6-phosphate (G6P) and activates the G6P metabolizing enzyme, myo-inositol monophosphatase 1 (IMPA1). We confirmed the increased expression of IMPA1, a critical activator of the inositol synthesis and inositol-dependent proliferative pathways in hGLUT4 mice. Notably, treatment with the IMPA1 inhibitor completely reversed PAH by reducing RVSP and RV hypertrophy. Conclusions: We conclude that increased GLUT4 expression is sufficient to induce spontaneous PAH through increased glucose uptake, initiation of mitochondrial dysfunction, and upregulation of IMPA1. This discovery introduces a novel potential target, IMPA1, that connects dysregulated glucose metabolism with activation of the proliferative signaling.
Abstract P407: Role Of Cyclic AMP During The Intracellular Infection Cycle Of <i>Trypanosoma Cruzi</i>
Authors: Daniel E Velez-Ramirez, Michelle Shimogawa, Kent Hill
Journal: Circulation Research (2021)

Trypanosoma cruzi is the causative agent of Chagas disease, a vector-borne disease. In the 1990s the distribution of the vector, a hematophagous triatomine, and consequently the parasite, was from the southeast tropical regions of Mexico to South America. Now, global warming is causing this distribution to expand to northern territories in Mexico, reaching southern parts of US, in which up to 300,000 people are affected. Furthermore, an increase in chronically-infected immigrants to the US makes Chagas disease a matter of Pan-American public health that it should be addressed by all the America countries. Chagas disease manifests clinically as cardiovascular disease, characterized by hypertrophy of heart, esophagus and colon. Congestive heart failure is the main cause of death (58%) in Chagas patients, whereas cardiac arrhythmias and unexpected deaths add another 36%. A major cause of heart pathology in Chagas disease damage is caused by the host immune system, as it attacks chronically infected tissue. Therefore, pathology of the disease is a direct consequence of the ability of the parasite to invade host cells, so it can establish chronic infection. To achieve this, T. cruzi must sense and adapt to the host environment, but the underlying mechanisms are poorly understood. In particular, parasite signaling pathways used to sense and transduce signals from the host environment are most completely unknown. Our lab studies cAMP signaling in trypanosome parasites and several lines of evidence suggest T. cruzi cAMP signaling is important for host cell invasion, differentiation and persistent infection, which in turn underlies heart tissue pathology of Chagas disease. A transcriptome analysis revealed that mRNA of proteins involved in cAMP metabolism, i.e. adenylate cyclases and phosphodiesterases, are either upregulated or downregulated during the intracellular infection cycle. In fact, the phosphodiesterases have flagellar homologs with known cAMP signaling functions in a related parasite. This suggests that cAMP might fluctuate during as T. cruzi invades, differentiates, and multiplies inside the host cells. We have implemented a cAMP FRET sensor to monitor cAMP levels in trypanosomes to understand the role of cAMP in T. cruzi pathogenesis.
Abstract 12952: Endothelial Cell Specific Deletion of mTOR Ameliorates Age-Related Arterial and Metabolic Dysfunction
Authors: Torikul Islam, Shelby A Hall, Samuel I Bloom, R Colton C Bramwell, Tavia Dutson, Jordan R Tucker, John Kim, Daniel R Machin, Anthony J Donato, Lisa A Lesniewski
Journal: Circulation (2021)

Background: Systemic inhibition of mammalian target of rapamycin (mTOR) improves age-related arterial and metabolic dysfunction. Although the mechanisms and tissues involved in this amelioration remain unknown, endothelial cells (ECs), key regulators of arterial and metabolic function, may be responsible for these effects. Hypothesis: The beneficial effects of systemic mTOR inhibition will be recapitulated after EC specific mTOR deletion in old mice. Methods: We studied 22-24 mo old wildtype (WT) and EC specific tamoxifen-inducible mTOR knockout (KO) mice. The arterial function was determined by assessing aortic stiffness by measuring pulse wave velocity (PWV) using Doppler ultrasound as well as endothelium-dependent dilation (EDD) and nitric oxide (NO) bioavailability using pressure myography. Carotid artery superoxide production was measured using electric paramagnetic resonance. Glucose (2g/kg, ip) and lipid (3mL/kg, oral) tolerance tests were performed to examine metabolic function. Results: Two weeks after tamoxifen administration (4mg/day, 4 days, oral), we found a ~ 60% reduction in EC mTOR protein (p=0.04). Aortic PWV was lower in KO compared to WT mice (Fig A), indicating lower aortic stiffness. EDD to acetylcholine (ACh) was higher in mesenteric arteries from KO compared to WT mice (Fig B) due to an increase in NO bioavailability (31.6 ± 8.6 vs 8.4 ± 2.3; p=0.01). Superoxide scavenger, TEMPOL, increased EDD in both WT and KO mice (Fig C), eliminating differences between groups. Superoxide was lower in carotid arteries of KO compared to WT (Fig D), suggesting that oxidative stress impairs EDD in WT mice and ablation of EC selective mTOR ameliorates this effect. Aged KO mice demonstrated greater glucose and lipid tolerance compared to WT (Fig E, F). Conclusions: Our findings demonstrate that EC specific deletion of mTOR provides beneficial effects on arterial function via reductions in oxidative stress and prevents metabolic dysfunction in old mice.