tbuckley/cabot-search huggingface dataset:
Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial
Authors: Steven Le Gouill, Franck Morschhauser, David Chiron, Krimo Bouabdallah, Guillaume Cartron, Olivier Casasnovas, Caroline Bodet-Milin, Sylviane Ragot, Céline Bossard, Nathalie Nadal, Charles Herbaux, Benoit Tessoulin, Emmanuelle Tchernonog, Cédric Rossi, Rory McCulloch, Thomas Gastinne, Mary B. Callanan, Simon Rule
Journal: Blood (2020)
Abstract 15377: Stabilization of Cardiac Function in Wild-Type Transthyretin Cardiac Amyloidosis With Diflunisal
Authors: Graham Lohrmann, Alexandra Pipilas, Roberta Mussinelli, Deepa M Gopal, John L Berk, Lawreen H Connors, Nirupama Vellanki, Jennifer Hellawell, Omar K Siddiqi, Jonathan Fox, Frederick L Ruberg
Journal: Circulation (2018)

Introduction: Wild-type transthyretin cardiac amyloidosis (ATTRwt) is an underappreciated cause of heart failure with preserved ejection fraction that results from deposition of misfolded TTR prote...
Abstract 15842: Body Mass Index in Covid-19: An Independent Risk Factor for Severe Infections
Authors: Jeanne du Fay de Lavallaz, Setri Fugar, Joanne Michelle M Gomez, Sean Swearingen, Gianna Bosco, Alexander Hlepas, Alan Simmons, Brian Clark, tisha suboc, Annabelle S Volgman, Kim A Williams, Charlotte Bai
Journal: Circulation (2020)

Introduction: The coronavirus disease 2019 (COVID-19) led to a global pandemic. Comorbidities such as hypertension, diabetes mellitus, elevated cholesterol, cardiac/pulmonary diseases, and obesity were postulated as prognostic factors for a worse outcome. Hypothesis: Obese COVID-19 patients have a worse prognosis. Methods: From March to June 2020, we obtained data on all patients ≥18 y.o. who were admitted with a positive COVID-19 test at the Rush System, Chicago. Multivariable logistic regression analysis was performed between predictors and a composite outcome of intubation and in-hospital mortality. Results: Among the 1345 admitted patients, 69 (5%) were underweight (BMI&lt;18.5kg/m2), 365 (27%) of normal weight (BMI 18.5-25kg/m2), 405 (30%) overweight (BMI 25-30kg/m2), 258 (19%) of obesity class I (BMI 30-35kg/m2), 119 (9%) of obesity class II (BMI 35-40kg/m2) and 129 (10%) of obesity class III (BMI &gt;40kg/m2). In a multivariable model assessing the risk for the in-hospital death or intubation, underweight patients showed decreased risk (odds ratio (OR) 0.31) while obesity class III patients showed increased risk (OR 1.68, Figure 1) when compared to normal BMI. When accounting for obesity classes, male sex, atrial fibrillation and coronary artery disease were also independent predictors adverse outcomes. Conclusions: Consistent with previous research, morbidly obese patients had a higher risk for a worse outcome, even when accounting for numerous comorbidities. Underweight patients appeared to be protected. Higher body mass leads to inherent changes in lung function, increased risk of thrombosis, greater viral replication, higher release of adipokines and higher inflammation. Inversely, fewer adipocytes could possibly limit the risk for cytokine storm by reducing the amount of proinflammatory factors released. Figure: Odds ratios with 95% confidence intervals for the outcome of death or intubation in all COVID-19 positive admitted patients.
Abstract 15659: “If at First You Don’t Succeed”: Repeat Ablations in Young Patients With Supraventricular Tachycardia
Authors: Ellis Rochelson, Bradley C Clark, Christopher M Janson, Scott R Ceresnak, Lynn Nappo, Robert H Pass
Journal: Circulation (2018)

Introduction: Success rates for ablation of supraventricular tachycardia (SVT) in the young exceed 90%. While several studies have described reasons for ablation failure, less is known about outcom...
Abstract 17157: The SGLT2 Inhibitor Empagliflozin Ameliorates Interstitial Myocardial Fibrosis and Aortic Stiffness in Non-Diabetic Patients With Heart Failure With Reduced Ejection Fraction: A Secondary Analysis of the EMPATROPISM Trial
Authors: Carlos G Santosgallego, Juan Antonio Requena-Ibanez, Ariana P Vargas, Alvaro Garcia-Ropero, Anderly Rodriguez-Cordero, Donna M MANCINI, Sean Pinney, Anuradha Lala, Johanna P Contreras, Pedro R Moreno, Javier SANZ, Valentin Fuster, Juan J Badimon
Journal: Circulation (2020)

Background: SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on interstitial myocardial fibrosis (IMF) and aortic stiffness has not yet been studied Hypothesis: Empagliflozin ameliorates IMF and aortic stiffness in non-diabetic HFrEF patients Methods: The EMPATROPISM clinical trial (NCT 03485222) investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). IMF was assessed by CMR using extracellular volume (ECV) by T1 mapping. Aortic stiffness was quantified by pulse wave velocity (PWV) by CMR. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in ECV (ΔECV) and PWV (ΔPWV) at 6 months between both arms Results: 80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either ECV or PWV (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p&lt;0.001; and ΔLVEF 6±4 vs 0±4%, p&lt;0.001 for EMPA vs placebo). EMPA-treated patients exhibited a reduction in ECV (ΔECV -1.25±1.5 vs 0.3±1.4% for EMPA vs placebo, p&lt;0.001), which demonstrates IMF regression with SGLT2i. EMPA-treated patients exhibited a reduction in PWV (ΔECV -0.6±1 vs 0.6±1.4 m/s for EMPA vs control, p&lt;0.001), which indicates amelioration of aortic stiffness with SGLT2i Conclusions: In HFrEF patients without diabetes, treatment with empagliflozin ameliorates IMF and aortic stiffness. This may explain the benefits of SGLT2i in HFrEF even in the absence of diabetes
Abstract 14051: Meta-analyses for the Effect of Renin-angiotensin-aldosterone System Inhibitors on Mortality and Testing Positive of Covid-19
Authors: Yujiro Yokoyama, Hisato Takagi, Tadao Aikawa, Toshiki Kuno
Journal: Circulation (2020)

Introduction: Some have hypothesized that the use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) may modify susceptibility to coronavirus disease 2019 (COVID-19) in humans. Thus, we conducted two meta-analyses to compare mortality and susceptibility of COVID-19 between those who were treated with ACEI and/or ARB and those who were not treated with ACEI or ARB. Methods: MEDLINE and EMBASE were searched through June 2020 to identify clinical trials that investigated the mortality and testing positive rates for COVID-19 for those who were treated with ACEI or/and ARB and for those who were not treated with ACEI or ARB. The first analysis investigated the testing positive rate of COVID-19. The second analysis investigated the in-hospital mortality rate for patients with COVID-19. Result: 3 eligible studies for the first analysis and 14 eligible studies for the second analysis were identified. The first analysis demonstrated that the testing positive rates were similar for those who were treated with ACEI and for those who were not treated with ACEI (odds ratio [OR] [confidence interval [CI]] =0.96 [0.88-1.04], p =0.69) and for those who were treated with ARB and for those who were not treated with ARB (OR [CI] =0.99 [0.91-1.08], p =0.35) (Figure 1A,B). The second analysis showed that in-hospital mortality for patients with positive COVID-19 was similar between for those who were on ACEI and/or ARB and for those who were not on ACEI or ARB (hazard ratio [HR] [95% [CI]] =0.88 [0.64-1.20], p =0.42) (Figure 2). The subanalysis by restricting studies only investigating patients with hypertension showed ACEI and/or ARB use was associated with a significant reduction of in-hospital mortality compared with no ACEI or ARB use (HR [CI] =0.65 [0.48-0.87]). Conclusion: Our analysis demonstrated that ACEI and/or ARB use was not associated with positive rates of COVID-19, and not associated with mortality of COVID-19 patients.
Abstract 17161: Type and Intensity of Strategies to Reduce Readmissions Under the Hospital Readmissions Reduction Were Not Associated With Improvements in Readmission Rates
Authors: J Gmerice Hammond, Jonathan Yu, Jose Figueroa, Karen E Joynt Maddox
Journal: Circulation (2020)

Background: Little is known about what strategies are associated with improvements in hospital readmissions under the Hospital Readmissions Reduction Program. Objective: To determine whether the type or intensity of readmission reduction strategies were associated with changes in readmission rates for heart failure, acute myocardial infarction, and pneumonia among acute care hospitals participating in the HRRP. Methods: We surveyed leaders of 1,600 U.S. acute care hospitals participating in the HRRP about their use of 13 specific strategies to reduce readmissions. Strategies were grouped into three domains: transitions of care (TOC, e.g. discharge checklist), quality improvement (QLT, e.g. medication reconciliation), and patient-centered (PC, e.g. patient engagement programs). Intensity of each domain was scored as high or low according to how many strategies were implemented. We calculated hospital-level readmission rates prior to (2011-12) and following (2014-15) HRRP implementation. We used linear regression to determine if there were associations between individual strategies, domains, or overall scope of strategies and a reduction in readmission rates. Results: Of the 1,600 hospitals surveyed, 926 participated (58% response rate). Hospitals reported using 6.1 (SD 2.5) strategies on average. TOC was the most commonly used domain: 69% of hospitals scored high intensity in TOC, compared to only 22% and 14% of hospitals scoring high intensity in QLT and PC domains, respectively. After adjusting for hospital size, type, teaching status, and location, there were no statistically significant associations between any individual strategy and changes in readmission rates, nor between domain intensity and changes in readmission rates. Nearly half of all hospitals, 49%, scored high in only one domain; only 22% scored high in two domains and 5% scored high in all three domains. In fully adjusted models, there was no association between scoring high in multiple domains and reducing readmission rates. Conclusions: Under the HRRP, hospitals focused most on transitions of care strategies. There was no evidence that any of the most commonly employed strategies for reducing readmissions were associated with differential changes in readmission rates.
Abstract 17102: Lower Rate of Device-Related Thrombosis in Watchman Patients Undergoing a Genotype-Tailored Antithrombotic Strategy
Authors: Domenico G Della Rocca, Rodney Horton, Carola Gianni, Luigi Di Biase, CHINTAN G TRIVEDI, Sanghamitra Mohanty, Nicola Tarantino, Mohamed Bassiouny, Amin Al-ahmad, David Burkhardt, G Gallinghouse, Javier Sanchez, Andrea Natale
Journal: Circulation (2020)

Introduction: Loss-of-function (LOF) polymorphisms of the cytochrome P450 2C19 (CYP2C19) gene are associated with reduced hepatic bioactivation of clopidogrel. Hypothesis: To evaluate the prevalence of LOF polymorphisms of CYP2C19 and the incidence of device-related thrombosis (DRT) when clopidogrel is replaced with half dose novel oral anticoagulant (NOAC) in patients with reduced clopidogrel metabolism. Methods: Consecutive Watchman patients were genotyped for CYP2C19 polymorphisms. Patients with reduced clopidogrel metabolism received half dose NOAC plus aspirin during the “dual antiplatelet therapy (DAPT) phase” post-Watchman implantation (between 45 days and 6 months). The incidence of DRT among genotyped patients (Group I, n=401) and a control group without genotypization (Group II, n=357) which received standard DAPT is reported. Results: Overall, 758 Watchman patients were included (mean age: 75±8 yrs, 63% males, CHA 2 DS 2 -VASc: 4.6±1.5; HAS-BLED: 3.2±1.1). Of the 401 Group 1 patients, 25.69% (n=103) were reduced clopidogrel metabolizers. In 87.4% of them, clopidogrel was replaced with half-dose NOAC during the “DAPT phase” post-Watchman implantation whereas 12.6% received ASA plus full-dose NOAC due to the presence of a significant peri-device leak. During the “DAPT phase”, DRT was documented in 1 (0.2%) patient of Group I and 7 (1.96%) patients of Group II (p=0.029). On multivariate analysis, a genotype-tailored antithrombotic strategy was associated with a significant reduction in DRT (odds ratio: 0.11; 95% confidence interval: 0.01 - 0.98; p-value: 0.048). Conclusions: Approximately 25% of our Watchman patients had clopidogrel resistance. Substitution of clopidogrel with half dose NOAC in reduced clopidogrel metabolizers significantly reduced the incidence of DRT.
Abstract 16790: Myocardial Injury is an Independent Predictor of Mortality in Patients With COVID-19
Authors: Matteo Nardin, Davide Cao, Mauro Chiarito, Johny Nicolas, Samantha Sartori, Zhongjie Zhang, George Dangas, Roxana Mehran
Journal: Circulation (2020)

Introduction: Recent reports on COVID-19 patients have shown that elevated troponin (Tn) levels on hospital admission are associated with adverse outcomes. However, no data exists on the predictive role of Tn kinetics parameters in COVID-19 patients. Aim: To analyze the incidence, clinical outcomes and predictors of Tn kinetics parameter, including rise/fall pattern and peak values, in a large cohort of COVID-19 hospitalized patients. Methods: All consecutive patients admitted to an urban tertiary-care health system between February and June 2020 with COVID-19 were included. Patients were grouped according to presence of myocardial injury defined as a high-sensitivity TnI level ≥0.1 ng/ml. A TnI level between 0.4-0.99 was defined as low positive range Tn elevation. Results: We included 5862 COVID-19 patients, 1558 (27%) of whom experienced myocardial injury. Advance age, male sex and higher comorbidity burden, including COPD, hypertension, CAD, atrial fibrillation, HF, CKD, and diabetes were more common in patients with myocardial injury. A total of 828/1558 (53.2%) of patients with myocardial injury died as compared to 634/4304 (14.7%) of those without (OR 6.57, 95% CI 5.76-7.48; p&lt;0.001). After adjustment for baseline imbalances, myocardial injury remained an independent predictor of mortality (Adj.OR 5.26, 95% CI 4.57-6.05; p&lt;0.001). Further stratification of patients into low positive range Tn elevation and myocardial injury groups showed a significant stepwise increase in mortality rates with increasing Tn values (Figure). Secondary endpoints, as shown in the Figure, occurred more frequently in patients with myocardial injury.Data on Tn kinetics parameters,such as rise/fall patterns,and associations with the outcomes will also be presented. Conclusions: Myocardial injury is an independent predictor of all-cause mortality in COVID-19 patients,with a stepwise increase in the risk of mortality reflecting increasing extent of myocardial damage.
Abstract 17117: Prevalence of Systemic AV Valve Regurgitation in Patients With Congenitally Corrected Transposition of the Great Arteries: Anatomic versus Physiologic Repair
Authors: Salima A Bhimani, Aisha ZIA, Paola Barrios, Anabila Moses, Jared Klein, Tara Karamlou, Rukmini R Komarlu
Journal: Circulation (2020)

Background: Congenitally corrected transposition of the great arteries (ccTGA) is a rare anomaly with highly variable time of diagnosis. Depending on time of diagnosis and associated lesions, multiple therapies exist, directed towards surgical correction. Anatomic repair (AR) involving double switch or atrial switch/Rastelli and physiologic repair (PR) leaving the right ventricle as the systemic ventricle are the two main surgical options. A subset of patients without associated lesions exist who can be followed expectantly over time. Systemic atrioventricular valve (SAVV) function is a major anatomic variable, determining eligibility for double switch and durability of physiologic repair or expectant management (medical group). We therefore sought to assess the prevalence of AV valve regurgitation in the different subgroups and its determinants, hypothesizing that SAVV regurgitation (SAVVR) was reduced in the AR group. Methods: Retrospective record review coupled with prospective cross-sectional follow-up of 240 patients with ccTGA treated at our center was performed. Echocardiographic imaging review was conducted to assess SAVV function and systemic ventricular function among the 3 subgroups. Results: Of 240 patients with ccTGA, 162 met inclusion. Median follow up was 10 years (mean +/- SD 11+/- 9 years). In the AR group majority (85%) had none/mild SAVVR. Prior PA band did not influence the severity of SAVVR following double switch. In the PR group, 22% underwent SAVV repair/replacement, and 75% had none/mild SAVVR; as opposed to only 65% with none/mild SAVVR in the medical group. Only 14% of patients were free of systemic ventricle dysfunction in PR group as opposed to 72% in the AR group. Conclusions: SAVV function is preserved in the AR group. In contrast patients in the PR group had higher prevalence of more than mild SAVVR followed by patients who were managed expectantly.
Antibiotic use prior to seeking medical care in patients with persistent fever: a cross-sectional study in four low- and middle-income countries
Authors: Brecht Ingelbeen, Kanika D. Koirala, Kristien Verdonck, Barbara Barbé, Déby Mukendi, Phe Thong, Sayda El Safi, Lukas Van Duffel, Emmanuel Bottieau, Marianne A.B. van der Sande, Marleen Boelaert, François Chappuis, Jan Jacobs
Journal: Clinical Microbiology and Infection (2020)

Community-level antibiotic use contributes to antimicrobial resistance, but is rarely monitored as part of efforts to optimize antibiotic use in low- and middle-income countries (LMICs). We investigated antibiotic use in the 4 weeks before study inclusion for persistent fever.The NIDIAG-Fever (Neglected Infectious diseases DIAGnosis-Fever) study investigated aetiologies of infections in patients ≥5 years old with fever ≥1 week in six healthcare facilities in Cambodia, the Democratic Republic of the Congo (DRC), Nepal, and Sudan. In the present nested cross-sectional study, we describe prevalence and choice of antibiotics before and at study inclusion, applying the Access/Watch/Reserve (AWaRe) classification of the WHO List of Essential Medicines. Factors associated with prior antibiotic use were analysed.Of 1939 participants, 428 (22.1%) reported the prior use of one or more antibiotics, ranging from 6.3% (24/382, Cambodia) to 35.5% (207/583, Nepal). Of 545 reported antibiotics, the most frequent were Watch group antibiotics (351/545, 64.4%), ranging from 23.6% (DRC) to 82.1% (Nepal). Parenteral administration ranged from 5.9% to 69.6% between study sites. Antibiotic use was most frequent among young patients (5-17 years of age; risk ratio 1.42, 95%CI 1.19-1.71) and men (RR 1.29; 95%CI 1.09-1.53). No association was found with specific symptoms. Of 555 antibiotics started before study inclusion, 275 (49.5%) were discontinued at study inclusion.Watch antibiotics were frequently used, and discontinued upon study inclusion. The antibiotic use frequency and choice varied importantly between LMICs. Data on local antibiotic use are essential to guide efforts to optimize antibiotic use in LMICs, should not be restricted to hospitals, and need to take local healthcare utilization into account.
Accuracy and efficacy of pre-dengue vaccination screening for previous dengue infection with five commercially available immunoassays: a retrospective analysis of phase 3 efficacy trials
Authors: Carlos A DiazGranados, Matthew Bonaparte, Hao Wang, Ming Zhu, Yaniv Lustig, Eli Schwartz, Remi Forrat, Gustavo H Dayan, Shekema Hodge, Yasemin Ataman-Önal, Stephen J Savarino
Journal: The Lancet Infectious Diseases (2020)
Machine Learned Cellular Phenotypes in Cardiomyopathy Predict Sudden Death
Authors: Albert J. Rogers, Anojan Selvalingam, Mahmood I. Alhusseini, David E. Krummen, Cesare Corrado, Firas Abuzaid, Tina Baykaner, Christian Meyer, Paul Clopton, Wayne Giles, Peter Bailis, Steven Niederer, Paul J. Wang, Wouter-Jan Rappel, Matei Zaharia, Sanjiv M. Narayan
Journal: Circulation Research (2020)

Susceptibility to VT/VF (ventricular tachycardia/fibrillation) is difficult to predict in patients with ischemic cardiomyopathy either by clinical tools or by attempting to translate cellular mechanisms to the bedside.To develop computational phenotypes of patients with ischemic cardiomyopathy, by training then interpreting machine learning of ventricular monophasic action potentials (MAPs) to reveal phenotypes that predict long-term outcomes.We recorded 5706 ventricular MAPs in 42 patients with coronary artery disease and left ventricular ejection fraction ≤40% during steady-state pacing. Patients were randomly allocated to independent training and testing cohorts in a 70:30 ratio, repeated K=10-fold. Support vector machines and convolutional neural networks were trained to 2 end points: (1) sustained VT/VF or (2) mortality at 3 years. Support vector machines provided superior classification. For patient-level predictions, we computed personalized MAP scores as the proportion of MAP beats predicting each end point. Patient-level predictions in independent test cohorts yielded c-statistics of 0.90 for sustained VT/VF (95% CI, 0.76-1.00) and 0.91 for mortality (95% CI, 0.83-1.00) and were the most significant multivariate predictors. Interpreting trained support vector machine revealed MAP morphologies that, using in silico modeling, revealed higher L-type calcium current or sodium-calcium exchanger as predominant phenotypes for VT/VF.Machine learning of action potential recordings in patients revealed novel phenotypes for long-term outcomes in ischemic cardiomyopathy. Such computational phenotypes provide an approach which may reveal cellular mechanisms for clinical outcomes and could be applied to other conditions.
Plasmonically Modulated Gold Nanostructures for Photothermal Ablation of Bacteria
Authors: Guijian Guan, Khin Yin Win, Xiang Yao, Wensheng Yang, Ming‐Yong Han
Journal: Advanced Healthcare Materials (2020)

Abstract With the wide utilization of antibiotics, antibiotic‐resistant bacteria have been often developed more frequently to cause potential global catastrophic consequences. Emerging photothermal ablation has been attracting extensive research interest for quick/effective eradication of pathogenic bacteria from contaminated surroundings and infected body. In this field, anisotropic gold nanostructures with tunable size/morphologies have been demonstrated to exhibit their outstanding photothermal performance through strong plasmonic absorption of near‐infrared (NIR) light, efficient light to heat conversion, and easy surface modification for targeting bacteria. To this end, this review first introduces thermal treatment of infectious diseases followed by photothermal therapy via heat generation on NIR‐absorbing gold nanostructures. Then, the usual synthesis and spectral features of diversified gold nanostructures and composites are systematically overviewed with the emphasis on the importance of size, shape, and composition to achieve strong plasmonic absorption in NIR region. Further, the innovated photothermal applications of gold nanostructures are comprehensively demonstrated to combat against bacterial infections, and some constructive suggestions are also discussed to improve photothermal technologies for practical applications.