tbuckley/cabot-search huggingface dataset:
Abstract 13767: Cardiac MRI Predictors of Good Long-term Outcomes in Patients With Repaired TOF
Authors: Amara Majeed, Tal Geva, Julia Graf, Minmin Lu, Sonya Babu-Narayan, Barbara Mulder, Rachel Wald, Lynn A Sleeper, Anne M Valente
Journal: Circulation (2020)

Introduction: Good outcomes in adults with repaired tetralogy of Fallot (rTOF) are not well explored. Identifying markers of a benign clinical course late after TOF repair can guide resource utilization in this growing population. Methods: Clinical and CMR data were analyzed from the International Multicenter TOF Registry (INDICATOR). The clinical outcome was a composite of death, aborted sudden death, sustained ventricular and atrial arrhythmia, non-sustained ventricular tachycardia, and New York Heart Association functional class&gt;II. Multinomial regression explored predictors of the 3-category outcome-Good and intermediate outcomes; defined as freedom from clinical outcome at 50 and &lt;50 years respectively; and bad outcome; defined as having an adverse event at &lt;50 years. Results: The cohort had 1088 patients-good outcome, n=96; intermediate, n=747; bad, n=245 with median age at last CMR 44 (40, 47); 21 (15, 28); 31 (20, 39) years respectively. Median follow-up was 8 (5, 11) years after CMR in event-free patients. Right ventricular (RV) parameters associated with a good outcome were smaller RV end-systolic volume index, higher RV ejection fraction (EF), lower RV mass index, and lower RV mass/volume ratio. Left ventricular (LV) parameters associated with a good outcome were lower LV mass index and LV mass/volume ratio. Multivariable models showed RV EF (OR 1.56 per 10% increase, p=.009) and RV mass index (OR 1.51, per 10 g/m 2 decrease, p=.002) as independently associated with good outcome after adjusting for age at CMR. Important thresholds identified in older patients (age ≥37 years) were RVEF ≥42% and RV mass index &lt;39 g/m 2 . Combined, this subgroup had a 56% likelihood of a good outcome. Conclusions: Adults with rTOF and CMR findings of adequate RV systolic function and no significant ventricular hypertrophy are likely to have a benign clinical course by age 50 years. Frequency of cardiac testing in such patients may be lower than in those not fulfilling these criteria.
Abstract 15858: Efficacy of Hypertension Self-management Classes Among Low-Income Patients of a Federally Qualified Health Center
Authors: Cameron Eck, Holly Biola, Dominique Bulgin, Colette A Whitney, Melanie Bakovic, Tiffany M Hayes, Jennifer Deyo, Awanya Caesar, Rosa Becerra-Soberan, Howard Eisenson, Bradi B Granger
Journal: Circulation (2020)

Introduction: Racial and socioeconomic disparities in hypertension prevalence and treatment have been observed over numerous decades. There is opportunity to close racial disparities by focusing resources on patient education, skill-building, and self-management. Methods: A hypertension-reduction program was established between an academic-affiliated FQHC in the southeast, the American Heart Association, the Centers for Disease Control, and the American College of Preventive Medicine using a multidisciplinary outreach model in the community setting. Participants included 265 high-risk patients from the FQHC with severe hypertension (&gt;160/90 mm HG). Program activities included a weekly class where participants learned about hypertension, were trained to take their blood pressure (BP), and received cuffs to use at home. A prospective pre-post cohort design was used to evaluate this portion of the program. Participants’ attendance at the self-management classes was tracked along with BP measurements at every class attended. Results: Over the program’s first 6 months, 93 of the 265 recruited participants attended at least one of 28 BP management classes. The 29 participants who attended multiple classes achieved an average 19 mm HG reduction in systolic BP ( p =0.004) and an average 14 mm HG reduction in diastolic BP ( p =0.002). Patients who were Black were significantly more likely to attend multiple classes than patients who were Hispanic ( p =0.004). Also, patients who were self-monitoring their BP prior to class attendance were significantly more likely to attend multiple classes than those who were not previously self-monitoring ( p =0.014). Multiple class attendance was also associated with higher baseline BP ( p =0.038 for systolic and p =0.018 for diastolic). Conclusions: Implementation of blood pressure self-management classes showed success in reducing hypertension among many of the high-risk participants. Hispanic patients were much less likely to attend multiple classes, underscoring the need for culturally and linguistically appropriate class content. The low proportion of Hispanic patients previously monitoring their BP points to an opportunity to improve patient awareness about hypertension among Hispanic populations generally.
Engineering Silk Fibroin‐Based Nerve Conduit with Neurotrophic Factors for Proximal Protection after Peripheral Nerve Injury
Authors: Cristiana R. Carvalho, Wei Chang, Joana Silva‐Correia, Rui L. Reis, Joaquim M. Oliveira, Joachim Kohn
Journal: Advanced Healthcare Materials (2020)

Abstract Artificial nerve conduits capable of adequately releasing neurotrophic factors are extensively studied to bridge nerve defects. However, the lack of neurotrophic factors in the proximal area and their visible effects in axonal retrograde transport following nerve injury is one of the factors causing an incomplete nerve regeneration. Herein, an advanced conduit made of silk fibroin is produced, which can incorporate growth factors and promote an effective regeneration after injury. For that, enzymatically crosslinked silk fibroin‐based conduits are developed to be used as a platform for the controlled delivery of neurotrophic factors. Nerve growth factor and glial‐cell line derived neurotrophic factor (GDNF) are incorporated using two different methodologies: i) crosslinking and ii) absorption method. The release profile is measured by ELISA technique. The bioactivity of the neurotrophic factors is evaluated in vitro by using primary dorsal root ganglia. When implanted in a 10 mm sciatic nerve defect in rats, GDNF‐loaded silk fibroin conduits reveal retrograde neuroprotection as compared to autografts and plain silk fibroin conduit. Therefore, the novel design presents a substantial improvement of retrograde trafficking, neurons’ protection, and motor nerve reinnervation.
Risk factors for severe and critically ill COVID‐19 patients: A review
Authors: Ya‐dong Gao, Mei Ding, Xiang Dong, Jin‐jin Zhang, Ahmet Kursat Azkur, Dilek Azkur, Hui Gan, Yuan‐li Sun, Wei Fu, Wei Li, Hui‐ling Liang, Yi‐yuan Cao, Qi Yan, Can Cao, Hong‐yu Gao, Marie‐Charlotte Brüggen, Willem van de Veen, Milena Sokolowska, Mübeccel Akdis, Cezmi A. Akdis
Journal: Allergy (2020)

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1β, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.
Abstract 278: A Novel Resuscitative Agent, Centhaquine (Lyfaquin®), has the Potential to Treat Acute Kidney Injury Following Hemorrhagic Shock
Authors: Amaresh Ranjan, Seema Briyal, Zhong Zhang, Anil Gulati
Journal: Circulation (2020)

Introduction: Centhaquine (CQ) is being developed as a first-in-class resuscitative agent to treat hemorrhagic shock. Its safety, tolerability and efficacy have been demonstrated through pre-clinical studies and phase I, II and III clinical trials (NCT02408731, NCT04056065 and NCT04045327). Shock is often complicated with acute kidney injury (AKI). Hypothesis: CQ will increase renal blood flow (RBF) and attenuate hypoxia related damage after hemorrhagic shock. We investigated whether CQ improves RBF and provides protection after hemorrhagic shock. Methods: Rats were anesthetized, and carotid artery, femoral artery and femoral vein were catheterized. Renal arteries were clamped, hemorrhage was induced and mean arterial pressure (MAP) was maintained between 35-40 mmHg for 30 min. After 20 min of hemorrhage, renal arteries were de-clamped and hemorrhage continued for 10 more min. Resuscitation was performed with either normal saline (NS) or CQ (0.02 mg/kg) infusion for 10 min. MAP, heart rate and RBF were monitored for 120 min after which rats were sacrificed, kidneys were collected and analyzed with western blots and immunofluorescence. Results: Resuscitation with CQ produced a significant improvement in RBF (at 30 min 257.03±21.2 vs 199.81±42.32, p=0.002 sustained till 120 min 211.76±27.47 vs 148.24±42.39, p=0.002 of infusion) compared to NS. A non-significant increase in MAP was observed in CQ compared to NS. Western blots showed significantly higher expression HIF1-A (1.13±0.19 vs 0.86±0.16) and lower expression of early kidney damage marker, NGAL (0.35±0.16 vs 0.82±0.31) in CQ vs NS. Immunofluorescence showed significantly higher expression of HIF1-A and lower expression of Bax in cortex (HIF1-A 11.19±0.31 vs 8.43±0.39, p=0.03689, Bax 18.09±0.47 vs 24.80±2.01, p=0.0010) of CQ than NS and similar change was observed in medulla. Expression of PHD3 and Cytochrome C was higher in the cortex (PHD3 5.38±0.38 vs 4.05±0.12, p=0.0348, Cytochrome C 24.95±0.65 vs 29.24±1.87, p=0.01429) of CQ than NS. HIF1-B expression was similar in CQ and NS groups. Conclusions: CQ (Lyfaquin®) is a frontline resuscitative agent with a potential to treat hemorrhagic shock related AKI by improving kidney blood flow and decreasing hypoxia related tissue damage.
Abstract 113: Effects of Anticoagulation and Thrombolytic Therapy in a Porcine Model of Prolonged Out-of-hospital Cardiac Arrest Treated with ECPR
Authors: Stephen L Harvey, Joseph E Hill, Jensyn J VanZalen, Pavel Hala, Emre Gok, Anne G Phillips, Olivia L Pak, Noah Willett, Tasneem Ali, Joshua H Jung, Joshua Mergos, Robert H Bartlett, Alvaro Rojas-Peña, Robert W Neumar
Journal: Circulation (2020)

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) has been used in patients with refractory out-of-hospital cardiac arrest (OHCA). However, recovery of organ function and survival are potentially impaired due to microvascular coagulation causing a “no-reflow” phenomenon. Hypothesis: Early anticoagulant therapy (argatroban) during CPR and/or thrombolytic therapy (streptokinase) at ECPR onset improves recovery of organ function in an OHCA porcine model. Methods: In a blinded and randomized study, 48 swine (40±5kg) were subjected to 8min of ventricular fibrillation cardiac arrest (CA) followed by 30min of goal directed CPR (gdCPR), and 8h of ECPR (33°C) with heparin anticoagulation during ECPR. Animals (n=12) were randomized to one of 4 groups with 350mg/kg argatroban (Arg) or placebo (20mL NSS) given 12min after CA onset and 1.5 MU streptokinase (STK) or placebo (50mL NSS) given at ECPR initiation: Group 1 (placebo and placebo); Group 2 (Arg and placebo); Group 3 (placebo and STK); and Group 4 (Arg and STK). Recovery of cardiac function measured by a cardiac resuscitablity score (CRS), see Table. Recovery of neurologic function measured by amplitude recovery of cortical somatosensory evoked potentials (cSSEP). Data analysis: Kruskal Wallis and single factor ANOVA tests with ( p &lt;0.05 significant). Results: Average CRS and cSSEP recovery were not significantly different between groups. However, the combined average CRS of the argatroban groups (2&amp;4) was 3.2±2.1 compared to 2.0±1.6 for the groups without it (1&amp;3), p =0.03 single factor ANOVA. Furthermore, more animals in groups 2&amp;4 (n=8) achieved a robust recovery in cSSEP amplitude (≥30% amplitude return) than in groups 1&amp;3 (n=4). Discussion: These results provide evidence that argatroban given early during CPR potentially improves early recovery of cardiac and neurological function in a porcine model of OHCA. However, the impact of these therapies on long term recovery remains to be determined.
Abstract 12895: Tissue Sodium Content Increases With Severity of Chronic Heart Failure
Authors: Julie Kolwelter, Armin Nagel, Dennis Kannenkeril, Agnes Bosch, Kristina Striepe, Peter R Linz, Christian Ott, Peter Bramlage, Michael Uder, Stephan Achenbach, Roland E Schmieder
Journal: Circulation (2020)

Introduction: Heart failure is strongly linked to renal sodium and water retention as well as intravascular and interstitial fluid shifts. Experimental studies demonstrated a non-osmotic sodium storage, bound to proteoglycans, in the extravascular space. New sodium magnetic resonance imaging ( 23 Na-MRI) enables us to quantify tissue (muscle and skin) sodium content in a reliable and accurate way. Hypothesis: We hypothesised that the increase of tissue sodium content is dependent on the severity of chronic heart failure (CHF). Methods: We investigated patients with stable CHF before initiating treatment with an SGLT2-inhibitor within a prospective, placebo-controlled study. We here report the baseline data of 64 patients with CHF, defined as patients with reduced (HFrEF) or mid-range ejection fraction (HFmEF). In each patient, tissue sodium content of the lower leg was assessed non-invasively by a clinical 3.0T 23 Na-MRI. The median NT-proBNP plasma level at baseline was 493.3pg/ml (IQR: 225.8-1122.0pg/ml) and was used as cut off value of CHF severity. Results: Our patients (men: n=54) were 66.9±8.9 years old and had NYHA class II-III; mean muscle sodium content was 19.1±3.8mmol/l and mean skin sodium content was 22.5±5.9mmol/l. Our reference for young healthy subjects are 18.7±2.0 mmol/l for muscle sodium content and 19.6±3.1 mmol/l for skin sodium content. Patients with CHF and NT-proBNP levels above the median showed higher muscle (20.2±3.5 vs 17.9±3.7mmol/l, p=0.008) and skin sodium content (24.1±6.8 vs 20.8±4.4mmol/l, p=0.005) than patients with CHF and NT-proBNP levels below the median. No difference in plasma sodium levels between the two groups (138.0±3.7 vs 138.8±2.1mmol/l, p=0.527) was observed, but patients with NT-proBNP levels above the median had lower urinary sodium excretion over 24 hours (167.0±78.8 vs 172.3±63.4mmol/l, p=0.009). Age was different in the two groups (69.88±8.2 vs 63.8±8.7, p&lt;0.001) with no difference in gender. The number of diagnosed coronary heart disease was similar in the two groups (62.5% vs 59.4%, p=0.802). Conclusion: Concluding, tissue sodium content in patients with stable CHF as assessed by 23 Na-MRI increases with the severity of CHF. A decrease of tissue sodium content might be a future therapeutic goal.
Abstract 12527: Serum Amyloid A, Inflammasome Activation and Stroke
Authors: Mark S Kindy
Journal: Circulation (2020)

Serum amyloid A (SAA) proteins are critical to the regulation of inflammation in systemic as well as neurological diseases. Studies have shown that during an acute phase response (APR), SAA levels increase 1000-fold and can stimulate the inflammasome, trigger the recruitment of immune cells to inflammatory sites, and elicit the induction of enzymes that degrade extracellular matrix. Our long-term goal is to dissect the mechanisms regulating SAA function, particularly the contribution to stroke related damage. Recent studies have demonstrated that activation of the inflammasome is a critical event in stroke progression in mice. The central hypothesis is that SAA activates the NLRP3 inflammasome, and amplifying the local inflammatory responses that enhance neuronal cell death and stroke progression. We show that activation of the NLRP3 inflammasome by SAA exacerbates stroke in mice. Using mice deficient in SAA, RAGE and various inflammasome components (cathepsin B, NLRP3, ASC, caspase-1 and IL-1beta) or IL-1R mice, we demonstrated that SAA-mediated stroke outcomes are dependent on the NLRP3 inflammasome. In addition, using microglial cell cultures, we determined the impact of SAA on RAGE mediated pathologies (ROS generation, etc.) as well as the influence of SAA-HDL on SAA-mediated NLRP3 activation. We tested the hypothesis that systemic SAA exacerbates the progression of neuronal cell death and inflammation in stroke. We showed that SAA deficient mice determined the impact on stroke infarct volume and outcomes. In addition, using viral vectors to express SAA as well as an inducible transgene help us determine the role of SAA with specific expression of SAA. The impact of SAA on inflammation, neuronal cell death, matrix remodeling, etc. was attenuated in SAA deficient mice. In addition, we demonstrated the role of SAA and the inflammasome in human stroke, and the relationship between plasma SAA, IL-1beta and the impact on stroke outcomes.
Abstract 13895: Machine Learning-based Prediction Model With Contribute the Optimal Recipient Selection for the Regenerative Therapy in ICM and Non-ICM Patients
Authors: Yuji Sakashita, Hidetsugu Asanoi, Shigeru Miyagawa, Satoshi Kainuma, Ai Kawamura, Noriyuki Kashiyama, Takuji Kawamura, Daisuke Yoshioka, Takayoshi Ueno, Koichi Toda, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2020)

Background: Although transplantation of patch-shaped autologous skeletal muscle-derived cells has been introduced to ischemic cardiomyopathy (ICM) or non-ICM patients, we found responders or non-responders to this treatment exist and how to predict the responsiveness to this treatment is crucial for the improvement of the effectiveness. In this study, we revealed the clinical features associated with the responders using a machine learning based-model, which was discriminated between the responder and the non-responders in this treatment. Methods and Results: We used the retrospective databases of 23 ICM patients and 23 non-ICM patients undergoing autologous myoblast patch transplantation to develop machine learning models to discriminate 3-year VAD free survival. Sixty-nine pre-transplantation clinical futures were selected to train the models. In ICM models, there were 4 VADs or deaths, and in non-ICM models, there were 10 VADs or deaths during the 3-year follow-up periods. Using these databases, we trained multiple machine learning models and evaluated the models with the leave-one-out method. In ICM, k nearest neighbor demonstrated the best performance, showing the accuracy was 95.7%, and the AUC was 0.95. The features associated with 3-year VAD free survival in ICM were NYHA classification, cardiac index, and left ventricular ejection fraction. In non-ICM, k nearest neighbor demonstrated the best performance among the trained classifiers, demonstrating the accuracy was 95.7%, and the AUC was 0.93. The features associated with 3-year VAD free survival in non-ICM were pulmonary capillary wedge pressure, pulmonary vascular resistance, and albumin. Conclusion: We found the features associated with 3-year VAD free survival in autologous myoblast patch transplantation in ICM and non-ICM. Focusing on these features may facilitate optimal candidate selection in ICM and non-ICM for regenerative therapy.
Interleukin-15 and cancer: some solved and many unsolved questions
Authors: Piera Filomena Fiore, Sabina Di Matteo, Nicola Tumino, Francesca Romana Mariotti, Gabriella Pietra, Selene Ottonello, Simone Negrini, Barbara Bottazzi, Lorenzo Moretta, Erwan Mortier, Bruno Azzarone
Journal: Journal for ImmunoTherapy of Cancer (2020)

Soluble interleukin (IL)-15 exists under two forms: as monomer (sIL-15) or as heterodimeric complex in association with sIL-15Rα (sIL-15/IL-15Rα). Both forms have been successfully tested in experimental tumor murine models and are currently undergoing investigation in phase I/II clinical trials. Despite more than 20 years research on IL-15, some controversial issues remain to be addressed. A first point concerns the detection of the sIL-15/IL-15Rα in plasma of healthy donors or patients with cancer and its biological significance. The second and third unsolved question regards the protumorigenic role of the IL-15/IL-15Rα complex in human cancer and the detrimental immunological consequences associated to prolonged exposure of natural killer (NK) cells to both forms of soluble IL-15, respectively. Data suggest that in vivo prolonged or repeated exposure to monomeric sIL-15 or the soluble complex may lead to NK hypo-responsiveness through the expansion of the CD8 + /CD44 + T cell subset that would suppress NK cell functions. In vitro experiments indicate that soluble complex and monomeric IL-15 may cause NK hyporesponsiveness through a direct effect caused by their prolonged stimulation, suggesting that this mechanism could also be effective in vivo. Therefore, a better knowledge of IL-15 and a more appropriate use of both its soluble forms, in terms of concentrations and time of exposure, are essential in order to improve their therapeutic use. In cancer, the overproduction of sIL-15/IL-15Rα could represent a novel mechanism of immune escape. The soluble complex may act as a decoy cytokine unable to efficiently foster NK cells, or could induce NK hyporesponsiveness through an excessive and prolonged stimulation depending on the type of IL-15Rα isoforms associated. All these unsolved questions are not merely limited to the knowledge of IL-15 pathophysiology, but are crucial also for the therapeutic use of this cytokine. Therefore, in this review, we will discuss key unanswered issues on the heterogeneity and biological significance of IL-15 isoforms, analyzing both their cancer-related biological functions and their therapeutic implications.