tbuckley/cabot-search huggingface dataset:
Abstract 13497: Prognostic Value of the Combination of the Echocardiographic Derived Pulmonary Artery Wedge Pressure and Body Mass Index in Patients With Heart Failure With Preserved Ejection Fraction: Insights From PURSUIT-HFpEF Registry
Authors: Kumpei Ueda, Shungo Hikoso, Daisaku D Nakatani, Shunsuke Tamaki, Masamichi Yano, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Yoshio Yasumura, Takahisa Yamada, Yasushi Sakata
Journal: Circulation (2020)

Background: An elevated pulmonary artery wedge pressure (PAWP), a surrogate of left ventricular filling pressure, is associated with poor outcomes in patients with heart failure (HF). In addition, obesity paradox is well recognized in HF patients and body mass index (BMI) also provides a prognostic information. However, there is little information available on the prognostic value of the combination of the echocardiographic derived PAWP and BMI in patients with HF with preserved ejection fraction (HFpEF). Methods and Results: Patients data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, which is a prospective multicenter observational registry for acute decompensated heart failure (ADHF) patients with HFpEF. We analyzed 548 patients after exclusion of patients undergoing hemodialysis, patients with in-hospital death, missing follow-up data, or missing data to calculate PAWP or BMI. Body weight measurement and echocardiography were performed just before discharge. PAWP was calculated using the Nagueh formula [PAWP = 1.24* (E/e’) + 1.9] with e’ = [(e’ septal + e’ lateral ) /2]. During a mean follow up period of 1.5±0.8 years, 86 patients had all-cause death (ACD). Multivariate Cox analysis showed that both PAWP (p=0.020) and BMI (p=0.0001) were significantly associated with ACD, independently of age and previous history of HF hospitalization, after the adjustment with gender, left ventricular ejection fraction, NT-proBNP and estimated glomerular filtration rate. Kaplan-Meier curve analysis revealed that there was a significant difference in the risk of ACD when patients were stratified into 3 groups based on the median values of PAWP (17.3) and BMI (21.4). Conclusions: The combination of the echocardiographic derived PAWP and BMI might be useful for stratifying ADHF patients with HFpEF at risk for the total mortality.
Abstract 141: Early Cytokine Profile in Selectively Vulnerable Brain Regions, Heart and Serum After Asphyxial Cardiac Arrest vs. Ventricular Fibrillation Cardiac Arrest in Rats
Authors: Abigail A Palmer, Thomas Uray, Cameron Dezfulian, Jason Stezoski, Keri Janesko-Feldman, Patrick M Kochanek, Tomas Drabek
Journal: Circulation (2020)

Background: Currently, post-resuscitative care for survivors of cardiac arrest (CA) is independent of the etiology of CA. We have previously reported that asphyxial CA (ACA) results in different injury pattern vs. ventricular fibrillation CA (VFCA). Exploration of the early inflammatory response could identify insult-specific targets for future therapies. We hypothesized that the early systemic and regional neuroinflammatory cytokine response could differ between ACA vs. VFCA. Methods: Adult male rats were subjected to a 10 min ACA, or 10 min VFCA (n=12/group). Naives (n=12) and shams (n=12) subjected to anesthesia and instrumentation but not CA served as controls. Serum, heart and regional brain cytokine signatures were assessed in selectively vulnerable brain regions: cerebellum, cortex, hippocampus and striatum at 3 h. NSE, S100b and troponin T were also assessed. Results: Asphyxiation produced an ~4 min period of severe hypoxemia followed by a no-flow duration of ~ 6±1 min. VF immediately induced no-flow. Brain cytokines in naïve rats were low or undetectable. Shams had a modest effect on selected cytokines. Both ACA and VFCA resulted in robust selected cytokine responses in serum, heart and brain (Fig. 1) with significant regional differences in brain that identified striatum as a selective neuroinflammatory target. No significant differences in cytokines between CA models were observed. NSE, S100b and troponin T were similarly increased after ACA and VFCA vs. naives and/or shams. Conclusions: Both models of CA resulted in marked systemic, heart and brain cytokine response. Biomarkers of organ injury were also comparable. Contrasting prior studies showing greater oxidative stress and brain injury in ACA, but greater hemodynamic impairment after VFCA, systemic and brain cytokine profiles revealed similar increases across insults, suggesting that the cytokine response may not mediate key secondary injury differences between these two CA phenotypes.
Peptide and peptide-based inhibitors of SARS-CoV-2 entry
Authors: Desiree Schütz, Yasser B. Ruiz-Blanco, Jan Münch, Frank Kirchhoff, Elsa Sanchez-Garcia, Janis A. Müller
Journal: Advanced Drug Delivery Reviews (2020)

To date, no effective vaccines or therapies are available against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pandemic agent of the coronavirus disease 2019 (COVID-19). Due to their safety, efficacy and specificity, peptide inhibitors hold great promise for the treatment of newly emerging viral pathogens. Based on the known structures of viral proteins and their cellular targets, antiviral peptides can be rationally designed and optimized. The resulting peptides may be highly specific for their respective targets and particular viral pathogens or exert broad antiviral activity. Here, we summarize the current status of peptides inhibiting SARS-CoV-2 entry and outline the strategies used to design peptides targeting the ACE2 receptor or the viral spike protein and its activating proteases furin, transmembrane serine protease 2 (TMPRSS2), or cathepsin L. In addition, we present approaches used against related viruses such as SARS-CoV-1 that might be implemented for inhibition of SARS-CoV-2 infection.
Abstract 239: The Relationship Between Duration of Chest Compression and Traumatic Thoracic Injuries in Out-of-hospital Cardiac Arrest Patients
Authors: Aya Katasako, Shoji Kawakami, Takashi Ikee, Yoko Shojima, Akihiro Maezono, Shoichiro Furukawa, Yasuhiro Oga, Yusuke Takahara, Keita Inanaga, Yoshihiro Imamura, Tetsuhisa Yamada, Nobutoshi Miura, Shujiro Inoue
Journal: Circulation (2020)

Background: Recent guidelines emphasized that high-quality chest compression is essential for improving the survival in out-of-hospital cardiac arrest (OHCA) patients. However, it may lead to critical traumatic injuries. Method: Between June. 2018 to Mar. 2019, we collected Utstein-style data on 130 consecutive adult patients with non-traumatic OHCA who were transferred to our hospital without return of spontaneous circulation (ROSC). Patients with aortic dissection and aortic aneurysmal rupture were excluded. Full-body CT scan was performed in all patients and chest compression-induced thoracic injuries were defined as rib fracture, sternum fracture, hemopneumothorax, mediastinal emphysema or intrathoracic hematoma. We identified the possible predictors for thoracic injuries and evaluated the relation between traumatic thoracic injuries and 30-day survival. Results: Patients with thoracic injuries were 105 (81%). The duration of chest compression in patients with thoracic injuries was significantly longer than that in patients without thoracic injuries (30 vs 38min, p&lt;0.01). ROC analysis identified a duration of chest compression of 35 minutes as the optimal cutoff point for predicting thoracic injuries (sensitivity 0.59, specificity 0.83, area under the curve 0.71). Multivariate analysis revealed that age and duration of chest compression were predictors of thoracic injuries (OR 1.05, 1.07, p≦0.01, respectively). The rates of 30-day survival in patients with thoracic injuries was significantly lower than those without thoracic injuries (1 % vs 16 %, p&lt;0.01). Conclusion: The duration of chest compression was one of the independent predictors for thoracic injuries in non-traumatic OHCA patients. Prolonger duration of chest compression are potential candidates for CT scan to diagnose thoracic injuries.
Circuit Determinants of Ventricular Tachycardia Cycle Length
Authors: Takuro Nishimura, Gaurav A. Upadhyay, Zaid A. Aziz, Andrew D. Beaser, Dalise Y. Shatz, Hemal M. Nayak, Roderick Tung
Journal: Circulation (2020)

Background: Fast ventricular tachycardias (VTs) have historically been attributed to shorter path lengths with smaller reentrant circuit dimensions in animal models. The relationship between the dimensions of the reentrant VT circuit and tachycardia cycle length (TCL) has not been examined in humans. This study aimed to analyze the determinants of the rate of human VT with comparison of circuit dimensions and conduction velocity (CV) across a wide range of both stable and unstable VTs delineated by high-resolution mapping. Methods: Fifty-four VTs with complete circuit delineation (&gt;90% TCL) by high-resolution multielectrode mapping were analyzed in 49 patients (men, 88%; age, 65 years [58–71 years]; nonischemic, 47%). Fast VT was defined as TCL &lt;333 milliseconds (rate &gt;180 bpm). Unstable VT was defined by hemodynamic deterioration with an intrinsic mean arterial pressure &lt;60 mm Hg during a sustained episode. Results: The median TCL of VT was 365 milliseconds (306–443 milliseconds), and 24 fast VTs were characterized. A wide range of CVs was observed within the entrance (0.03–0.55 m/s), common pathway (0.03–0.77 m/s), exit (0.03–0.53 m/s), and outer loop (0.17–1.13 m/s). There were no significant differences in the median dimensions of the isthmus and path length between fast and slow VTs and between unstable and stable VTs. The outer loop CV was the only circuit component that correlated with TCL in both ischemic cardiomyopathy ( r =−0.5, P =0.006) and nonischemic cardiomyopathy ( r =−0.45, P =0.028). The duration of the longest diastolic electrogram was inversely correlated with the dimensions of common pathway (length: r =−0.46, P =0.001, width: r =−0.3, P =0.047) and predictive of rapid VT termination by a single radiofrequency application ( r =−0.41, P =0.023). Conclusions: Because of a wide spectrum of CV observed within the reentrant path during human VT, the dimensions of the circuit were not predictive of VT cycle length. For the first time, we demonstrate that the CV of the outer loop, rather than isthmus, is the principal determinant of the rate of VT. The size of the circuit was similar between fast and slow VTs and between unstable and stable VTs. Long, continuous electrograms were indicative of spatially confined isthmus dimensions, confirmed by rapid termination of VT during radiofrequency delivery.
MyD88/CD40 Enhanced CD19-Specific CAR-T Cells Maintain Therapeutic Efficacy Following Resolution of Cytokine-Related Toxicity Using Inducible Caspase-9
Authors: Aaron Foster, Pei-Yi Lin, An Lu, Wei-Chun Chang, Nicholas Shinners, Mariam Khalil, Jeannette Crisostomo, Aruna Mahendravada, Kevin M. Slawin, David M. Spencer
Journal: Blood (2017)
Covid-19: Innova lateral flow test is not fit for “test and release” strategy, say experts
Authors: Elisabeth Mahase
Journal: BMJ (2020)

The government has claimed that rapid lateral flow covid-19 tests, which are being used in mass testing pilots in England and can provide results in 30 minutes, are “accurate and sensitive enough to be used in the community,” after evaluation results were published.1

However, experts warn that the tests may miss as many as half of covid-19 cases, depending on who is using them—making them unsuitable for a “test and release” strategy to enable people to leave lockdown or to allow students to go home from university.

The ongoing assessment, carried out by Public Health England’s Porton Down laboratory and the University of Oxford, tested a number of lateral flow devices in different settings including hospitals, schools, and universities.

The Innova SARS-CoV-2 Antigen Rapid Qualitative Test, which has been used in the Liverpool mass testing pilot to detect infections,2 is the …
Prevalence of different type of valvular heart disease and other cardiac pathologies of the heart in high risk patients with suspicion of heart failure. A retrospective cohort study.
Authors: Madeeha Waleed
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Background: Valvular heart disease and other cardiac pathologies are associated with impending heart failure. An early diagnosis of these can help prevent the disabling ad disastrous effects and improve the prognosis. Aim: The prevalence of various pathologies associated with heart failure is not known. This study helps in recognizing various pathologies that can lead to heart failure, which if diagnosed early can improve the patient’s outcome. Materials and Methods: A total of 4560 patients were included in the study. All the patients were aged greater than 15 years. Patients with suspicion of heart failure on symptoms were ordered echocardiography. Transthoracic echo was done using echocardiography ultrasound machine using the British Society of Echocardiography guidelines. Echocardiography was done by registered sonologists. Echocardiograph were later read by cardiologists. Data was collected on Excel sheet. Echocardiographic results Of 9 690 patients, were admitted to the hospital during the year 2013 to year 2017 with the suspicion of heart failure based on symptoms echocardiogram was ordered. Among these 2448 patients had normal echocardiographic findings were as 4560 had valvular disease. Among the valvular disease patients 2951(64.71%) were females and 1609(35.2%) were males. Among these 2950(64.6%) had mild valvular disease 959(21.0%) had moderate valvular disease and 651(14.2) patients had severe valvular disease. Mitral stenosis occurred in 1200(26.3%) patients, mitral regurgitation in 2953(64.7%) patients, tricuspid stenosis in 40 (0.008%)patients ,tricuspid regurgitation in 1592(34.8%) patients, aortic stenosis in 81 (0.017%) patients and aortic regurgitation in 1957(42.9%) patients. Ischemic cardiomyopathy was present in 24 patients, dilated cardiomyopathy in 14 patients, rheumatic heart disease in 23 patients, ventricular septum defect in 5 patients ,Atrial septum defect in 2 patients , Apical aneurysm formation in 4 patients, Uremic cardiomyopathy on 3 patients, Grade 1 diastolic dysfunction in 2200 patients, Grade 3 diastolic dysfunction in 400 patients, Bicuspid aortic valve in 5 patients and restrictive cardiomyopathy in two patients, 1100 patients had a thin rim of pericardial effusion and were ordered Thyroid function tests. Conclusion: In the community heart failure is a common cause of death. Various pathologies of the heart are predictors of the outcome and hence early diagnosis can help in proper treatment and increased survival
Abstract PO-036: Defining the role of chromatin remodelers in pancreatic cancer
Authors: Lesley Paige Ferguson, Jovylyn Gatchalian, Nikki Lytle, Nirakar Rajbhandari, Matthew McDermott, Kendall Chambers, Sara Brin Rosenthal, Christian Schuerch, Inti Zlobec, Marten Wartenberg, Eva Diamantis, José A. Galván, Sonia Albini, Lorenzo Puri, Benoit Bruneau, Andrew M. Lowy, Diana Hargreaves, Tannishtha Reya
Journal: Cancer Research (2020)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a disease characterized by aggressive metastasis and resistance to therapy, making clinical management a significant challenge. We have focused on understanding how pancreatic cancer may be influenced by developmental and stem cell signals as they are often aberrantly re-activated during cancer progression. Given the central role for epigenetic regulation in development, we hypothesized that epigenetic factors may be required to sustain the self-renewal and aggressive nature of pancreatic cancer cells. To this end, we carried out a functional screen and identified Smarcd3, a component of the SWI/SNF (Baf) nucleosome remodeling complex, as a novel functional dependency in PDAC. SWI/SNF coordinates context-specific gene regulation in development and is frequently dysregulated in cancer. However, Smarcd3 has not been linked to functions in PDAC and represents a new epigenetic mediator of tumorigenesis. We found that Smarcd3 was uniquely up-regulated in PDAC stem cells and was required for the in vivo propagation of mouse and patient-derived tumors. Further using integrated RNA-seq, ChIP-seq, and network analysis we found that Smarcd3 regulates global SWI/SNF binding and histone acetylation, driving the epigenetic regulation of core cell fate and metabolic programs. Specifically, we found that Smarcd3 regulated genes converging on the mevalonate pathway and ultimately cholesterol biosynthesis, which has been directly implicated in stem signaling in PDAC. Collectively, these data identify Smarcd3 as a critical novel dependency and epigenetic regulator of pancreatic cancer metabolism. Citation Format: Lesley Paige Ferguson, Jovylyn Gatchalian, Nikki Lytle, Nirakar Rajbhandari, Matthew McDermott, Kendall Chambers, Sara Brin Rosenthal, Christian Schuerch, Inti Zlobec, Marten Wartenberg, Eva Diamantis, José A. Galván, Sonia Albini, Lorenzo Puri, Benoit Bruneau, Andrew M. Lowy, Diana Hargreaves, Tannishtha Reya. Defining the role of chromatin remodelers in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-036.
Abstract 13512: Sex-related Differences on Valvular Calcifications in Patients With Aortic Stenosis
Authors: Marianne Deslandes, Marine Clisson, Ezequiel Guzzetti, Alexandra Barriault, Erwan Salaun, Marie Annick Clavel
Journal: Circulation (2020)

Introduction: It has been shown that women present lower coronary artery (CAC) and aortic valve calcification (AVC) loads while heavier mitral annular calcification (MAC) than men. However, the sex-specific predictors to these cardiac calcifications remain poorly characterized. Methods: We conducted a cross-sectional study in patients with at least mild AS (indexed aortic valve area: AVAi &lt; 1.5 cm 2 /m 2 , Peak aortic jet velocity: Vpeak &gt; 2.0 m/s, or Mean gradient: MG &gt;15 mmHg). Doppler-echocardiography and non-contrast multidetector compute tomography were performed within 3 months. Ascending aorta calcification (AAC), AVC, CAC and MAC scores were measured using the Agatston method. Descriptive statistical analyses (t-test, Wilcoxon, univariate and multivariate analysis) were performed. Results: We studied 406 patients (71±11 years, 33% women) with AVAi= 0.59±0.21 cm 2 /cm 2 , Vpeak= 3.1±9.8 m/s, MG= 24.7±17.8 mmHg (equivalent between men and women, all p&gt;0.34). Women present less AVC (480[222-1191] vs 1005[485-2364]AU; p&lt;0.0001), and CAC (366[50-914] vs 626[167-1354]AU; p=0.006), but more MAC (60[1-887] vs 48[0-363]AU; p=0.05) and AAC (227[43-863] vs 142[7-493]AU; p=0.03) than men. Even after comprehensive adjustment, sex remained an independent predictor of each cardiac calcification (all p&lt;0.01). In multivariate analysis, correlates with higher AVC or higher MAC were sex dependent (cf. table). Collinearity was avoided with all variance inflating factor &lt;2.5. Conclusion: In AS patients, sex is a powerful and independent predictor of cardiac calcifications. Moreover, predictors of valvular calcification appear to be sex specific.
Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance
Authors: Sreya Bagchi, Robert Yuan, Edgar G. Engleman
Journal: Annual Review of Pathology Mechanisms of Disease (2020)

Immune checkpoint inhibitors (ICIs) have made an indelible mark in the field of cancer immunotherapy. Starting with the approval of anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) for advanced-stage melanoma in 2011, ICIs-which now also include antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1)-quickly gained US Food and Drug Administration approval for the treatment of a wide array of cancer types, demonstrating unprecedented extension of patient survival. However, despite the success of ICIs, resistance to these agents restricts the number of patients able to achieve durable responses, and immune-related adverse events complicate treatment. Thus, a better understanding of the requirements for an effective and safe antitumor immune response following ICI therapy is needed. Studies of both tumoral and systemic changes in the immune system following ICI therapy have yielded insight into the basis for both efficacy and resistance. Ultimately, by building on these insights, researchers should be able to combine ICIs with other agents, or design new immunotherapies, to achieve broader and more durable efficacy as well as greater safety. Here, we review the history and clinical utility of ICIs, the mechanisms of resistance to therapy, and local and systemic immune cell changes associated with outcome.
Abstract 15080: Chronic Mild Sleep Curtailment Increases Markers of Adiposity While Maintained Healthy Sleep Reduces These Measures in Women
Authors: Faris M Zuraikat, Samantha E Scaccia, Arindam RoyChoudhury, Marie-Pierre St-Onge
Journal: Circulation (2020)

Introduction: Over one-third of US adults do not achieve adequate sleep duration of 7 or more h per night. Short sleep is linked to higher odds of cardiometabolic diseases, including obesity. However, whether prolonged insufficient sleep causes increased body weight or adiposity remains unclear. Objective: To compare, in women, changes in body weight and composition in response to prolonged mild sleep restriction (SR) vs maintenance of healthy, habitual sleep (HS). Methods: Women (n=55; age: 35±13 y; BMI: 25.5±3.5 kg/m 2 ) with average adequate sleep duration (total sleep time [TST]=455±23 min) took part in a randomized crossover study with two 6-wk phases: HS and SR. In HS, usual bed and wake times (determined from 2 wk wrist actigraphy and sleep logs) were maintained. In SR, TST was reduced by 1.5 h/night. Sleep was measured continuously and verified weekly for compliance. Body weight and composition were measured at 0 and 6 wk using magnetic resonance imaging (MRI). Linear-mixed models tested interactions of sleep condition with week on outcome measures. Results: Average TST was reduced in SR and unchanged in HS (-87±19 vs -7±26 min, P&lt;0.01). Significant study condition by week interactions were observed for whole-body volume (WBV), waist circumference (WC), and skeletal muscle. In HS, WBV and WC decreased while these measures increased in SR (WBV: -0.47±0.22 vs 0.27±0.05 L, P=0.02; WC: -1.04 ± 0.78 vs 1.16 ± 0.54 cm, P=0.04). Results were similar for skeletal muscle (-0.19 ± 0.07 vs 0.17 ± 0.01 L, P&lt;0.01). A trend for a reduction in weight was observed in HS relative to SR (-0.39±0.31 vs 0.34±0.09 kg, P=0.09). Conclusions: This is the first evidence that prolonged insufficient sleep leads to increased body size in women. Conversely, maintaining adequate sleep may improve body composition. Our data suggest that healthy sleep duration should be a key component of strategies to improve cardiovascular health in women.