tbuckley/cabot-search huggingface dataset:
Abstract 11835: Increased Incidence of Heart Failure in Patients with Depression Among 479,000 Patients Followed at a Tertiary Care Center
Authors: Jamie L Pfaff, Shi Huang, Jeffrey Annis, Evan Brittain
Journal: Circulation (2021)

Introduction: Depressive disorders are associated with development and progression of heart failure (HF). Though these patients have demonstrated worse outcomes, the subpopulations at greatest risk remain under-recognized. We sought to identify patients at risk for HF and depression. Hypothesis: Depression is associated with increased risk of incident HF among outpatients followed at a tertiary care center. Methods: We used the Vanderbilt de-identified electronic medical record (EMR) to identify patients free of HF who met a medical home definition (at least 3 outpatient visits over 5 years). We defined incident HF and depression as occurrence of one inpatient or two outpatient ICD codes. We report HF incidence rate by sex, self-identified race, and depression status. Risk of incident HF was assessed by a Cox proportional hazard model adjusted for fourteen relevant covariates (see Table footnote). Results: Among 2.8 million patients in the EMR, 479,490 met inclusion criteria (50±17 years, 60% women) and were followed for incident HF over median 10.3 years (IQR 7.5, 14.3). Rates of HF were significantly higher in men vs. women (0.56/100PY vs. 0.36/100PY; p&lt;0.001), self-identified black race vs. white (0.54/100PY vs. 0.47/100PY; p&lt;0.001), and among those with co-morbid depression (0.61/100PY vs. 0.41/100PY; p&lt;0.001). When adjusted for confounders, male sex, self-identified black race, and depression were independent risk factors for incident HF (see Table 1; all p&lt;0.001). The highest risk for incident HF was among self-identified black males with depression (HR 1.81, 95%CI 1.70-1.93; p&lt;0.001). Conclusions: Among outpatients followed at a tertiary care center, male sex, self-identified black race, and co-morbid depression are associated with increased risk of HF. Self-identified black males appear particularly vulnerable to develop HF. Further study is warranted to determine whether treatment of depression modifies risk of incident HF.
Abstract 12601: Higher Arterial Stiffness Predicts Chronic Kidney Disease in the ELSA-Brasil Cohort Study
Authors: Julia Sosa Antunes Candido, Luisa C Brant, Sandhi Maria Barreto, JOSE GERALDO MILL, Lidyane Camelo
Journal: Circulation (2021)

Introduction: Arterial stiffening can directly affect the kidneys, which are passively perfused by a high flow. However, whether the relation between arterial stiffness and renal function is completely mediated by diabetes and hypertension (HTN) is a matter of debate. Objective: To investigate the relationship between arterial stiffness and the incidence of chronic kidney disease (CKD) in individuals without cardiovascular disease, and verify whether this association is mediated by HTN and diabetes. Methods: Baseline data of 13,068 adults from the ELSA-Brasil cohort (2008-2010, mean age 51 ± 9 years, 55% female) with validated carotid-to-femoral pulse wave velocity (cfPWV), estimated glomerular filtration rate (eGFR) estimated by the CKD-EPI equation, and albumin-to-creatinine ratio (ACR) were followed for 4 years (3.8 ± 0.42 years) to investigate the incidence of CKD. Arterial stiffness was measured by cfPWV, per quartile. CKD was defined as eGFR &lt; 60ml/min/1.73m 2 and/or RAC ≥ 30mg/g. Logistic regression models were adjusted for age, sex, race, schooling, smoking, cholesterol/HDL, body mass index (BMI), diabetes, use of antihypertensive, mean arterial pressure, and heart rate. The same analyses were performed in the subsample free of HTN and diabetes at baseline. Results: In individuals in the upper quartile of cfPWV (10.1 to 27.9 m/s), the chance of incident CKD increased by 79% (CI 95%: 1.20; 2.68) and by 60% (CI 95% 1.01;2.52) when ACR was used. In the group free of HTN and diabetes, there was twice the chance of eGFR&lt;60ml/min/1.73m 2 (OR 2.08 95%CI 1.17;3.69) and no association when CKD was measured by ACR. Conclusion: Our data indicate that higher values of cf-PWV is associated with incident CKD in adults, independent of diabetes or HTN.
Abstract 11986: A Safety Study of Intermittent versus Continuous Inhaled NO Therapy in Spontaneously Breathing COVID-19 Patients: A Randomized Controlled Trial
Authors: Nikolay O Kamenshchikov, Boris N Kozlov, Andrey Y Dish, Yuri K Podoksenov, Nina D Anfinogenova, Alla A Boshchenko, Bijan Safaee, Lorenzo Berra
Journal: Circulation (2021)

Introduction: Nitric oxide (NO) inhalation (iNO) therapy has been approved as a salvage therapy in patients with acute respiratory distress syndrome. However, the optimal patterns of therapeutic administration and iNO efficacy in COVID-19 patients with hypoxemia have not been studied so far. Hypothesis: A combination of high-concentration intermittent iNO treatment with continuous low-concentration NO gas supplementation between therapeutic high-dose iNO sessions may be a safe approach in COVID-19 patients with hypoxemia compared with the high-dose spike therapy alone. Methods: A single-center randomized controlled trial examined the safety of administration of intermittent high-dose iNO therapy versus the intermittent therapy in the presence of continuous low-dose iNO in spontaneously breathing COVID-19 patients (www.clinicaltrials.gov #NCT04476992). The study comprised adult patients tested positive for the COVID-19 by RT-PCR, who required oxygen and was admitted to the respiratory hospital. After attrition, a total of 20 patients were enrolled and randomized to the group of intermittent high-dose iNO treatment combined with continuous low-dose NO supplementation (group 1) or the group of intermittent high-dose iNO treatment(group 2). Control group (group 3) comprised retrospective patients who received conventional treatment for COVID-19 in hospital. Results: Administration of intermittent high-dose iNO therapy combined with continuous low-dose NO supplementation significantly improved physiological interactions in the heart-lung blood circulation system and was not associated with the extrapulmonary organ dysfunction. Safety parameters are presented in Table 1. Conclusions: High-dose intermittent iNO therapy combined with continuous low-dose NO gas supplementation may be considered a safe adjuvant modality of treatment for COVID-19 in spontaneously breathing hypoxemic patients.
Abstract P343: Physiologic Mechanical Stress In An Induced Pluripotent Stem Cell Derived Cardiomyocyte Model Of Duchene Muscular Dystrophy-related Cardiomyopathy Treated With A Membrane Resealant
Authors: Dominic E Fullenkamp, Jodi L Curtin, Ansel P Amaral, Sloane I Harris, Paul W Burridge, Alexis R Demonbreun, Elizabeth M McNally
Journal: Circulation Research (2021)

Heart failure is leading cause of morbidity and mortality in the X-linked disease Duchenne muscular dystrophy (DMD). DMD is due to mutations the gene encoding dystrophin. Dystrophin localizes to the costamere in skeletal and cardiac muscle and is part of the larger dystrophin complex, which forms a critical connection linking the sarcomere to extracellular matrix. Disruptions in this complex lead to membrane fragility and multiple forms of muscular dystrophy, most of which have significant cardiac involvement. Therapeutic strategies for DMD include FDA-approved agents for exon skipping, as well as micro-dystrophins gene therapy, which is currently in clinical trials. Despite this progress, there is inadequate information as to how these and other novel agents will affect the DMD heart. Given the critical importance of cardiac muscle efficacy for any therapeutic for DMD and importance of membrane fragility in the disease phenotype, we assessed the susceptibility of patient-derived induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) harboring an out-of-frame exon 46-47 DMD deletion. iPSC-CMs were reprogrammed via a standard approach and differentiated, expanded, and purified by published methods. Troponin T flow cytometry was performed to and a minimum troponin T positivity &gt;85% positivity was set for inclusion. DMD and control cells were plated onto flexible silicone membranes and subjected to equibiaxial strain as physiologic mechanical stressor, consistent with the inciting pathologic insult in DMD. Troponin and LDH release were assessed as clinically-relevant biomarkers of injury. Physiologic stress parameters were defined using troponin and LDH release relative to unstressed conditions. A membrane resealant being developed for treating DMD was shown to reduce troponin and LDH release in DMD iPSC-CMs, and also showed benefit in control cells. This work provides a ready platform for assessing therapeutics that target not only DMD-related cardiomyopathy, but other forms of cardiomyopathy and myocardial injury.
Abstract 13620: Comparison of Endothelial Shear Stress (ESS) Computation Utilizing Non-Invasive Coronary Computed Tomography Angiography (CCTA) vs Invasive Intravascular Ultrasound (IVUS) Imaging
Authors: Diaa Hakim, Ahmet Coskun, Chuck Maynard, zhongyue pu, Deborah Rupert, Nicholas Cefalo, Michelle Cormier, Kevin Croce, james K min, James Earls, Rob Jennings, Daniele Andreini, Saima Mushtaq, Edoardo Conte, Peter H Stone
Journal: Circulation (2021)

Introduction: Risk-stratification of individual coronary plaques is an important goal to detect high-risk plaques likely to progress/destabilize, which could inform preemptive intervention to prevent adverse cardiac events. IVUS imaging, the current gold standard to assess plaque risk, has shown that biomechanical variables, particularly local ESS, contributes critical synergistic prognostic insight when combined with anatomic high-risk plaque features. Non-invasive risk assessment of coronary plaques with CCTA would be invaluable to enable broad population risk screening, but it is unknown whether CCTA, which has less spatial resolution than IVUS, can adequately measure the critical local biomechanical and anatomic variables. Aim: To compare the accuracy of ESS computation of local ESS metrics by non-invasive CCTA vs invasive IVUS imaging. Methods: We analyzed 30 arteries (22 LAD, 4 LCx,4 RCA) from 30 patients selected from a registry of patients who underwent both IVUS and CCTA of the same artery for suspected CAD. CCTA images were acquired using a CCTA with either 64 or 256 detector rows. We segmented lumen, vessel, and plaque areas with both IVUS (manual segmentation) and CCTA (AI based software; Cleerly Inc, NY). Co-registration of IVUS and CCTA Images was performed using fiduciary anatomic landmarks. Images from IVUS and CCTA were used to generate a 3-D arterial reconstruction, and local ESS distribution was assessed by computational fluid dynamics and reported in consecutive 3-mm segments. Results: Table Conclusion: Compared to IVUS values, 256-slice is more accurate than 64-slice CCTA to measure lumen and vessel areas, but computation of detailed local ESS (average, low and high) is similar by both CCTA methods. Local ESS evaluation using non-invasive CCTA is feasible and comparable to invasive gold standard IVUS and is suitable to characterize the local flow patterns that play an important role in plaque development, progression, and destabilization
Improving infant feeding, care, and dental hygiene practices in South Asian infants aged younger than 2 years in east London through women's group participatory learning and action cycles (NEON): a behaviour intervention trial
Authors: Logan Manikam, Shereen Allaham, Zhen Ling Ong, Michelle Heys, Clare Llewellyn, Neha Batura, Andrew Hayward, Rajalakshmi Lakshman, Jenny Gilmour, Kelley Webb Martin, Carol Irish, Mfon Archibong, Corinne Clarkson, Mary Marsh, Delceta Daley, Monica Lakhanpaul, Amanda Nutkins
Journal: The Lancet (2021)
Abstract P445: A Combinatorial Approach Comprehensively Improves The Maturation Of Human Induced Pluripotent Stem Cell Derived Atrial Cardiomyocytes
Authors: Olivia T Ly, Grace Brown, Hanna Chen, Liang Hong, Xinge Wang, Yong Duk Han, Mahmud Arif Pavel, Arvind Sridhar, Mark Maienschein-Cline, Seock Won Youn, Brandon Chalazan, Malek G Massad, khaled Abdelhady, Joseph C Wu, Jalees Rehman, SALMAN KHETANI, Dawood Darbar
Journal: Circulation Research (2021)

Introduction: The limited success of pharmacological approaches to atrial fibrillation ( AF ) is due to limitations of in vitro and in vivo models and inaccessibility of human atrial tissue. Patient-specific induced pluripotent stem cell-derived atrial cardiomyocytes (iPSC-aCMs) are a robust platform to model the heterogeneous myocardial substrate of AF, but their immaturity limits their fidelity. Objective: We hypothesized that a combinatorial approach of biochemical (triiodothyronine [ T3 ], insulin-like growth factor-1 [ IGF-1 ], and dexamethasone; collectively TID ), bioenergetic (fatty acids [ FA ]), and electrical stimulation ( ES ) will enhance electrophysiological ( EP ), structural, and metabolic maturity of iPSC- a CMs. Methods: We assessed maturation with whole cell patch clamping, calcium transients, immunofluorescence (IF), Seahorse Analyzer, contractility assay, RT-PCR, Western Blotting, and RNA sequencing (RNAseq). Using a time series with RNAseq we identified signaling pathways and transcriptional regulation that drive EP, structural, and metabolic atrial development and compared iPSC-aCM maturity with human aCMs (haCMs) obtained from the same patient. Results: TID+FA+ES significantly improved structural organization and cell morphology ( Fig. 1a ), enhanced membrane potential stability and improved depolarization ( Fig. 1b ), improved Ca 2+ kinetics with faster and increased Ca 2+ release from sarcoplasmic reticulum ( Fig. 1c ), and increased expression of Na + , Ca 2+ , and K + channels, markers of structural maturity, FA metabolism, and oxidative phosphorylation ( Fig. 1d ). There was no difference in each parameter between TID+FA+ES iPSC-aCMs and haCMs from the same patient. Conclusion: Our optimized, combinatorial TID+FA+ES approach markedly enhanced EP, structural, and metabolic maturity of human iPSC-aCMs, which will be useful for elucidating the genetic basis of AF developing precision drug therapies.
CTNI-06. TRAM-01: A PHASE 2 STUDY OF TRAMETINIB FOR PATIENTS WITH PEDIATRIC GLIOMA WITH ACTIVATION OF THE MAPK/ERK PATHWAY
Authors: Sébastien Perreault, Valérie Larouche, uri tabori, Cynthia Hawkins, sarah Lippe, Benjamin Ellezam, Jean-Claude decarie, Luis H Ospina, yves theoret, Leandra Desjardins, Marie-Elaine Metras, serge Sultan, Edith Cantin, Marie-Eve Routhier, Maxime Caru, Stephanie Vairy, Geneviève Legault, Eric Bouffet, Lucie Lafay-Cousin, Juliette Hukin, Craig Erker, Nada Jabado
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children. It is known that the majority of PLGG have activation of the MAPK/ERK pathway. METHODS This ongoing multicenter phase II trial includes three progressing/refractory PLGG groups: NF1 patients, KIAA1549-BRAF fusion patients and patients with other activation of the MAPK/ERK pathway (excluding V600E). The primary objective was to evaluate the overall response rate based on RANO criteria after daily oral trametinib administration for 18 cycles, lasting 28 days each. Secondary objectives include the assessment of progression-free survival, tolerability of trametinib, serum levels of trametinib and quality of life evaluation during treatment. RESULTS As of February 12 2021, 50 patients have been enrolled (NF1: n=10; KIAA1549-BRAF fusion: n=31; other: n=9 including 5 patients with FGFR1 alterations). Median age is 8.8 years (range 2.4-25.5). Median follow-up is 17.5 months (range 4.7-28.5). Forty-three patients are evaluable. The overall response includes: 4 partial response (PR) (9%), 18 minor response (MR) (42%), 17 stable disease (40%), 4 progressive disease (9%). Median time to response is 5.5 months (range 2.4-13.8). Median duration of response is 6.1 months (range 0.6-26.5). Progression free survival at 12 months is 79.9% (95% CI 68.5-93.6%) and median progression free survival has not yet been reached. Treatment was discontinued for 30 patients: 16 after completing 18 cycles as planned, 5 for progressive disease, 5 for adverse events, 4 for other reasons. A total of 8 patients progressed after discontinuation of treatment including 6 patients (37.5%) that completed 18 cycles. Five of these patients had achieved minor response prior to discontinuation. CONCLUSION Trametinib is a potentially effective targeted therapy for patients with recurrent/refractory PLGG. Treatment was overall well tolerated. This ongoing trial will continue to gather data on response rate, duration of response and safety of trametinib for PLGG.
David Oliver: Dismissing unwell people to argue for pandemic freedoms is abhorrent and unrealistic
Authors: David Oliver
Journal: BMJ (2021)

On 12 November the Daily Telegraph headlined with “Six healthy children died of covid in a year, but lockdowns fuel youth health time bomb.” It explained that, of 3100 child deaths in the 12 months since March 2020, only 61 were “with covid,” 24 were “from covid,” and six were in children with no underlying health conditions.1 The Daily Mail ran a similar piece, emphasising that mortality from covid in children had been around one in 500 000.2

Although the stories centred on the serious issue of worsening access to care and worse outcomes in children with serious conditions other than covid, the headlines and graphics were clearly designed to push a message that our focus on covid protection measures had been …
Abstract 12474: Acute Myocardial Infarction Following Hospitalizations for Gastrointestinal Bleeding: Incidence, Predictors, Management, and Outcomes
Authors: Gregory Rubinfeld, Jeffrey Berger, Nathaniel Smilowitz
Journal: Circulation (2021)

Introduction: Patients hospitalized with gastrointestinal bleeding (GIB) are at risk for acute myocardial infarction (AMI). Clinical characteristics of patients with AMI after a GIB are poorly characterized. We sought to evaluate the incidence, management and outcomes of AMI following hospitalization for GIB. Methods: Patients admitted with a diagnosis of GIB were identified in the 2014 United States Nationwide Readmission Database using ICD-9 diagnosis codes. Hospital readmissions for AMI within 90 days of GIB were identified. Patients with AMI after GIB were compared to those without a prior GIB to determine differences in management and in-hospital outcomes. Invasive management of AMI was defined as invasive angiography or coronary revascularization. Logistic regression models were used to estimate odds of invasive management and all-cause, in-hospital morality after adjustment for clinical covariates. Results: A total of 644,622 patients with GIB were identified, of which 7,523 (1.2%) were readmitted for AMI within 90 days. Older age, diabetes mellitus, chronic kidney disease, coronary and peripheral artery disease, unknown GIB source, and AMI during the index GIB hospitalization were associated with 90-day AMI readmission. Compared to AMI patients without a recent GIB, patients with AMI within 90 days after GIB were older (74.4 vs. 68.4 years, p&lt;0.01), more likely to be women (47% vs. 41.1%, p&lt;0.01), have kidney disease (43.2% vs. 22.4%, p&lt;0.01), present with non-ST segment elevation MI (82% vs. 73%, p&lt;0.01), and were less likely to undergo invasive management of AMI (28% vs 63%, P&lt;0.01; adjusted odds ratio [aOR] 0.40, 95% CI 0.37-0.44). Recent hospitalization for GIB within 90 days was associated with higher all-cause in-hospital AMI mortality (22% vs 9%, P&lt;0.01; aOR 1.86 [1.68-2.06]). Conclusion: In the first 3 months after hospitalization for GIB, 1 of every 83 patients was readmitted with AMI. Patients with AMI after GIB were less likely to undergo invasive management of AMI and had higher mortality than those without recent GIB. Strategies to reduce morbidity and mortality of GIB-associated thrombosis are needed.
BAIAP2L1 enables cancer cell migration and facilitates phospho‐Cofilin asymmetry localization in the border cells
Authors: Nut Pipatpanyanugoon, Nicha Wareesawetsuwan, Sunisa Prasopporn, Wannapan Poolex, Trairak Pisitkun, Worasak Kaewkong, Somponnat Sampattavanich, Siwanon Jirawatnotai
Journal: Cancer Communications (2021)
Peripheral Levels of Monocytic Myeloid-Derived Suppressive Cells at Diagnosis Predict Survivals in AML Patients Eligible for Intensive Chemotherapy
Authors: Pierre Peterlin, Camille Debord, Alice Garnier, Amandine Le Bourgeois, Thierry Guillaume, Marion Eveillard, Yannick Le Bris, Béatrice Mahé, Viviane Dubruille, Nicolas Blin, Anne Lok, Cyrille Touzeau, Thomas Gastinne, Benoit Tessoulin, Soraya Wuillème, Catherine Godon, Olivier Theisen, Maxime Jullien, Sophie Vantyghem, Philippe Moreau, Steven Le Gouill, Marie C Bene, Patrice Chevallier
Journal: Blood (2021)
Liposome-Encapsulated Cytarabine and Daunorubicin (CPX-351) Induces Remission in Newly Diagnosed Pediatric Secondary Myeloid Malignancies
Authors: Kenneth J Caldwell, Yixin Hu, Mihaela Onciu, Sara M Federico, Marta Salek, Sara Lewis, Shaohua Lei, Jinghui Zhang, Kim E. Nichols, Clifford M Takemoto, Brandon M Triplett, Jason E Farrar, Jeffrey E. Rubnitz, Raul C Ribeiro, Marcin W. Wlodarski
Journal: Blood (2021)
Abstract 11610: Characteristics and Predictors of Effective Height of the Aortic Valve Assessed by Electrocardiography-Gated Cardiac Computed Tomography
Authors: Keiichi Ishida, Takashi Igarashi, Hitoshi Yokoyama
Journal: Circulation (2021)

Introduction: Effective height of the aortic valve has been used as an index for durable aortic valve repair. This study aimed to analyze the relationship between effective height and the other morphological parameters of aortic valve complex when aortic valve is closed. Methods: We retrospectively analyzed 100 patients (70.7±10.2 years) without diseased aortic valve, root or ascending aorta, who had electrocardiography-gated cardiac computed tomography as a screening test of coronary artery, from August 2014 to December 2018. Parameters of the configuration of aortic valve complex (effective height ; geometric height ; aortic annular diameter ; sinus of Valsalva diameter ; sinotubular junction diameter ; commissure height) in diastole were measured using the software Ziostation2 (Ziosoft, Tokyo, Japan). Pearson correlation was used to evaluate the association between effective height and the other parameters. In addition, multiple regression analysis was performed to determine which variables predict effective height. Results: Significant correlations were shown between effective height and geometric height (r = 0.704 ; P &lt; 0.001), sinus of Valsalva diameter (r = 0.433 ; P &lt; 0.001), sinotubular junction diameter (r = 0.547 ; P &lt; 0.001) and commissure height (r = 0.396 ; P &lt; 0.001). There was no significant correlation between effective height and aortic annular diameter (r = 0.111 ; P = 0.27). Multivariable analysis showed that geometric height (regression coefficients β = 0.853 ; 95% confidence intervals, CI, 0.647 to 0.923 ; P &lt; 0.001), aortic annular diameter (β = -0.574 ; 95% CI, -0.467 to -0.284 ; P &lt; 0.001) and sinotubular junction diameter (β = 0.327 ; 95% CI, 0.085 to 0.211 ; p &lt; 0.001) were significant predictors of effective height. The overall model fit was R 2 = 0.716. Conclusions: This study demonstrated that effective height was strongly correlated with geometric height, and predicted by geometric height, aortic annular diameter and sinotubular junction diameter. These findings may help heart surgeon to decide an appropriate effective height for individual aortic valve complex during aortic valve repair surgery.