tbuckley/cabot-search huggingface dataset:
Can we trust strong recommendations based on low quality evidence?
Authors: Liang Yao, Gordon H Guyatt, Benjamin Djulbegovic
Journal: BMJ (2021)

A necessary requirement for development of trustworthy guidelines is to respect the relation between the quality (certainty) of evidence and strength of recommendations. Strong recommendations are justified when they are based on high quality evidence, because such recommendations are considered more accurate.1 On the other hand, uncertainty in benefits and harms (that is, low quality evidence) generally leads to weaker recommendations.

The failure to recognise this important principle results in a tendency to issue strong recommendations based on low quality evidence (which we call discordant recommendations), often leading to harm. For instance, based on advice from low quality evidence, women have experienced avoidable adverse effects from hormone replacement therapy prescribed for the prevention of cardiovascular disease; and …
Abstract 9615: Predictors of Impedance During Subcutaneous ICD Defibrillation Testing in Hypertrophic Cardiomyopathy
Authors: Chockalingam A Narayanan, Srijan Shrestha, William Gionfriddo, Benjamin Koethe, Benjamin Katcher, Ann Garlitski, Jonathan Weinstock, Munther Homoud, Barry Maron, Martin S Maron, Ethan J Rowin, Christopher Madias
Journal: Circulation (2021)

Introduction: Defibrillation threshold testing (DFT) is generally reserved for populations with perceived concern for defibrillation failure, including in hypertrophic cardiomyopathy (HCM). Higher shock impedance has been associated with risk of DFT failure with subcutaneous defibrillators (SICD). The PRAETORIAN score is a chest radiograph based tool that evaluates device positioning to predict risk of DFT failure. Objective: We assessed predictors of impedance during DFT in a single center HCM SICD cohort. Methods: Data was collected from HCM patients who underwent SICD implantation from 2013 to 2021. Predictors of impedance were evaluated with linear and logistic regression. Results: Impedance was reported in 75 HCM SICD patients during DFT with 65J. DFT was successful in 74 patients with mean impedance of 72.7 ohm and septal thickness of 20.6 mm. Ten patients had massive HCM (&gt; 30 mm) with mean impedance of 66.4 ohm. Septal thickness was not predictive of impedance (β 0.37, 95% CI 1.24-0.50; P = .40). Independent predictors of impedance were BMI (β 1.41, 95% CI 0.61-2.21; P = .0008) and PRAETORIAN score (β 0.14, 95% CI 0.05-0.22; P = .0015). Multivariable regression revealed BMI no longer significant and PRAETORIAN score remaining significant (β 0.10, 95% CI 0.01-1.66; P = .038). Conclusion: In this HCM SICD cohort BMI and PRAETORIAN score were predictive of impedance. However, in a multivariable model, BMI was no longer predictive, highlighting importance of implant technique to improve impedance and DFT. Additionally, patients with massive hypertrophy all had successful DFT and septal thickness was not predictive of impedance. HCM has historically been portrayed as a high DFT population. Further prospective trials are necessary to establish whether standard DFT practice can be applied in HCM.
Dissecting Richter's Syndrome in a Multiplexed CRISPR-Based Mouse Model Reveals Key Changes in MYC, Interferon and BCR Signaling Underlying Transformation
Authors: Elisa Ten Hacken, Shanye Yin, Tomasz Sewastianik, Livius Penter, Neil Ruthen, Michaela Gruber, Erin Michelle Parry, Romain Guieze, Robert A. Redd, Mohamed Uduman, Shuqiang Li, Jackson Southard, Maria Hernandez-Sanchez, Salma Parvin, Fen Zhu, Gabriela Brunsting Hoffmann, Elizabeth Witten, Kenneth J. Livak, Matthew S. Davids, Anthony G. Letai, Donna S. Neuberg, Ruben D. Carrasco, Catherine J. Wu
Journal: Blood (2021)
TT52CAR19: Phase 1 Trial of CRISPR/Cas9 Edited Allogeneic CAR19 T Cells for Paediatric Relapsed/Refractory B-ALL
Authors: Giorgio Ottaviano, Christos Georgiadis, Farhatullah Syed, Soragia Athina Gkazi, Hong Zhan, Annie Etuk, Jan Chu, Danielle Pinner, Sarah Inglott, Kimberly Gilmour, Stuart Adams, Susanne Kricke, Natalia Izotova, Dariusz Ladon, Agnieszka Kubat, Paul Veys, Ajay Vora, Kanchan Rao, Waseem Qasim
Journal: Blood (2021)
Abstract 10079: Risk of Cardiovascular and All-Cause Mortality in Patients with Myeloproliferative Neoplasms Following Heart Failure Hospitalization
Authors: Orly Leiva, Ankeet Bhatt, Andrew Jenkins, Rachel Rosovsky, Rebecca Karp-Leaf, Katayoon Goodarzi, Gabriela Hobbs
Journal: Circulation (2021)

Introduction: Myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocytosis (ET) and myelofibrosis (MF), are clonal stem cell neoplasms that commonly harbor the JAK2V617F mutation. Recent preclinical studies suggest that the JAK2V617F mutation in hematopoietic stem cells accelerates pathologic cardiac remodeling, potentially contributing to HF. However, the prognostic significance of HF hospitalization in MPNs has not been studied. Methods: Single-center, retrospective cohort study of patients with MPN with ≥ 1 HF hospitalization after MPN diagnosis from 2000-2020 (N = 105, 39 ET, 39 PV, 27 MF). Our outcomes were death (cardiovascular [CV] and all-cause mortality [ACM]) and recurrent HF hospitalization after index hospitalization. To assess predictors of CV death and ACM, we used a multivariable logistic regression using age, sex, LVEF ≥ 50% at index event, cardiology follow-up 3 months after index, pulmonary hypertension (PH) before index, MF, treatment of MPN, NT-proBNP at index, CAD, hypertension, prior stroke, diabetes, and arterial thrombosis (AT) after index (stroke or MI) as co-variables. Results: After median follow-up time of 19 months (IQR 5, 19, full characteristics in Table), CV death, ACM, recurrent HF, AT occurred in 30%, 55%, 54%, 12%, respectively. After multivariable regression, recurrent HF (aOR 5.3, 95% CI 1.7-19.3), PH (aOR 3.2, 95% CI 1.0-10.7) and AT (aOR 4.4, 95% CI 1.1-21.5) were associated with increased odds of CV death. Close cardiologist follow-up (aOR 0.2, 95% CI 0.05-0.7) and LVEF ≥ 50% (aOR 0.3, 95% CI 0.1-0.9) were associated with decreased odds of CV death. Only recurrent HF was associated with increased odds of ACM (aOR 2.5, 95% CI 1.0-6.5). Conclusions: Patients with MPN who have multiple HF hospitalizations have high rates of CV death and ACM. Closer cardiology follow-up pre and post HF hospitalization may improve outcomes in this population and more research is needed to improve cardiovascular outcomes.
Abstract 11864: Ironing Out the Details: Increasing the Screening of Iron Deficiency in Heart Failure Patients and the Promotion of Intravenous Iron Replacement
Authors: Gabriel Ruiz, Zachary Wilson, Mohamed Abdelhabib, Damir Vukomanovic, Vikeen J Patel, Varun Tandon, Shaunak Pandya, Dustin Anderson, JULIE CRAWFORD, ali mehr
Journal: Circulation (2021)

Background: The American College of Cardiology (ACC) recommends intravenous iron replacement (IVIR) in patients with iron deficiency (ID) and heart failure with reduced ejection fraction (HFrEF). IVIR, in patients with HFrEF and ID, is associated with improvement in patient symptoms, functional capacity, 6-minute walk distance, and quality of life. Emerging data demonstrates IVIR can reduce hospital admissions for HFrEF. The purpose of this study is to enhance screening of ID in the HFrEF population and IVIR in the inpatient setting. Methods: This is a single-center, retrospective chart review using ICD 10 codes I50.2 and I50.42 to query the diagnosis of HFrEF in admissions from January 2018 to June 2020. Patients with recent major surgery within the last three months, use of erythropoietin stimulating agents, blood transfusions within a six-week time period, a history of cirrhosis, and/or a diagnosis of end stage renal disease receiving IVIR were excluded. ID in HFrEF is defined as ferritin &lt;100 micrograms/L or a ferritin of 100-299 micrograms/L with transferrin saturation of &lt;20%, per ACC guidelines. Further analysis was performed on 150 of 600 admissions pulled. Results: Of the 150 admissions analyzed, 108 of 150 were due to decompensated HFrEF and only 22 of the 150 had iron studies performed during admission. Approximately 15 of 22 patients with iron studies had a diagnosis of ID and only 1 of the 15 patients was initiated on IVIR. Additionally, 22 of the 150 total patients were on oral iron replacement and were not placed on IVIR. Discussion: Work-up of ID in patients with HFrEF is frequently omitted in the inpatient setting. In patients that have been diagnosed with ID, few receive appropriate treatment. There should be increased efforts to identify and administer IVIR to hospitalized patients with HFrEF and ID once their acute decompensation has been stabilized. This study aims to increase usage of HFrEF order sets on admissions by including iron studies within the workflow. The initiative includes administering first doses of IVIR in the hospital with subsequent transition to the outpatient setting, providing patient/provider education, and offering clinical decision support at time of ordering.
Melphalan-Based Regimen Is a Safe and Effective Conditioning Regimen Prior to Allogeneic Hematopoietic Cell Transplantation in Older Adults (≥70 years) with Hematological Malignancies
Authors: Monzr M. Al Malki, Nitya Nathwani, Dongyun Yang, Karamjeet S. Sandhu, Jaroslava Salman, Michelle Rouse, Sally Mokhtari, Thai Cao, Sanjeet Dadwal, Matthew Mei, Haris Ali, Saro H. Armenian, Pablo Parker, Joseph C. Alvarnas, Eileen P. Smith, Margaret R. O'Donnell, David S. Snyder, Guido Marcucci, Auayporn P. Nademanee, Stephen J. Forman, Anthony S. Stein, Ryotaro Nakamura
Journal: Blood (2017)
Abstract 11703: In-Patient Heart Failure Education Program Associated With Improvement in Patient Reported Knowledge and Decrease in Readmission Rate
Authors: Isata Sesay, Linda Ruppert, Eman A Hamad
Journal: Circulation (2021)

Background: Heart failure (HF) is a progressive syndrome characterized by high mortality, lower quality of life and frequent hospitalizations. A major component of the economic and societal burden imposed by HF remains recurrent hospitalizations, with 30-days readmission rates of 27% nationally. We conducted a quality improvement project at our hospital with the aim to evaluate the impact of a structured nurse-led heart failure education program on patient’s heart failure disease management knowledge, discharge follow-up, and 30-days hospital readmission. Method: Our cohorts included adult patients admitted with Acute Decompensated Heart Failure and successfully completed a structured heart failure education based on the American Heart Association Heart Failure Education guide. Patient also completed a pre-and-posttest to assess their level of understanding of heart disease management which included self-monitoring behaviors. Results: Between March and June 2021, 41 patients participated in the heart failure education session. The mean pre-test and post-test score was 58% versus 74%, with an average improvement of 16% in participants knowledge about heart failure disease management and self-care. Overwhelming majority of the patients (85%) were satisfied with their heart failure education. Eighty-Five percent of the participants had hospital follow-up appointment scheduled within seven days and 76% of them were compliant with follow-up. These patients had a lower 30-day readmission rate at 15% compared to our centers current rate at 21%. Conclusion: This retrospective, single-center observation study found that a structured inpatient heart failure educational program was associated with patients reported improvement in HF disease management knowledge. We observed a reduction in heart failure related hospital readmission compared to our center’s average and the national average. There was also an improvement in 7-day discharge follow up.
Fatty Liver Disease: Diagnosis and Stratification
Authors: Yedidya Saiman, Andres Duarte-Rojo, Mary E. Rinella
Journal: Annual Review of Medicine (2021)

Nonalcoholic fatty liver disease (NAFLD) is a major public health crisis affecting approximately 25% of the world's population. The spectrum of NAFLD ranges from bland steatosis to steatohepatitis with fibrosis; eventual development of cirrhosis in a subgroup of patients now represents the leading indication for liver transplant in women and in individuals older than 65. The development of noninvasive liver disease assessment tools has led to substantial progress in the diagnosis of NAFLD. Patients with NAFLD are at increased risk of cardiometabolic disease, which should therefore be an important part of the therapeutic approach. This review focuses on diagnosis and risk stratification of NAFLD across the full spectrum of disease, including important considerations in the approach to patients with cirrhosis.
Abstract 14036: Post Transcatheter Aortic Valve Replacement (TAVR) Electrophysiologic (EP) Study Trends and Its Implication on Permanent Pacemaker (PPM) Implantation Rate: Insights From National Inpatient Sample Database
Authors: Tawseef A Dar, Shady Abohashem, Diego Celli, Ahmed Hanfy, Ahmed Alnajar, Taimur Abbasi, Imran Mohiuddin, FNU Sibghat Tul Llah, Waqas Qureshi, Michael Dyal
Journal: Circulation (2021)

Introduction: High-risk conduction (HRC) disorders are frequently encountered post transcatheter aortic valve replacement (TAVR). There is a robust expert consensus statement about the management of such patients (e.g.performance of an electrophysiology (EP) study). Yet, it is unclear what the real-world practices are and how they might be influencing outcomes. Hypothesis: Accordingly, we sought to study the trends and implications of EP study post TAVR on the PPM implantation rate. Methods: The National Inpatient Sample (2011-2018) database was queried, using ICD-9 and ICD-10 codes, for individuals who underwent a TAVR procedure. Patients with a history of PPM were excluded. Outcomes of interest were postprocedural EP study, PPM implantation, mortality, and other non-cardiac complications. Logistic and linear regression models were employed to study hospital outcomes. Results: A total of 1,95162 (median age 82 yrs, 47.9% female) underwent TAVR. HRC abnormality and CHB were seen in 19.5% and 11 % of patients, respectively. A total of 12.1% had PPM implantation post-procedure, and 0.77% had an EP study during the same hospitalization. Of all PPM implantations, 2% underwent a prior EP study. Among patients with HRC features (N=33,381), the odds of receiving a PPM were ~3 higher (OR [95% CI] =2.74 [1.92, 3.90], p&lt;0.0001) in those who underwent an EP study (vs. no EP study). Among patients with CHB (N=21,324), there was a 60% (OR [95% CI] =0.39 [0.23, 0.67], p=0.001) decrease in PPM implantation rate in those who underwent an EP study (vs. no EP study). EP study was associated with a longer length of stay (p&lt;0.001) and higher hospital charges (p=0.001) with no difference in mortality rates (p=0.16). The yearly trend of EP study and PPM implantation is shown in figure 1. Conclusions: Depending on the type of conduction disorder, EP study has a significant and variable influence on the rate of PPM implantation post TAVR. The clinical implication of such impact needs further studies.
Abstract P480: Myeloid YAP Inhibition Improves Cardiac Phenotype During Pressure Overload Stress
Authors: Jamie J Francisco, Yu Zhang, Yasuki Nakada, Peiyong Zhai, Dominic Del Re
Journal: Circulation Research (2021)

Inflammation is a component of cardiovascular disease and is thought to contribute to cardiac dysfunction in ischemic and non-ischemic models of heart failure. While ischemia-induced inflammation has been extensively studied in the heart, relatively less is known regarding cardiac inflammation during non-ischemic stress. Recent work has implicated a role for Yes-associated protein (YAP), a transcriptional co-factor, in modulating cardiac inflammation and remodeling after myocardial infarction. We hypothesized that YAP mediates a pro-inflammatory response during pressure overload (PO)-induced non-ischemic injury, and that targeted YAP inhibition is cardioprotective. PO in mice elicits an immune response characterized by infiltration of myeloid cells that precedes cardiac dysfunction. Myeloid cells isolated from the heart after 7d PO showed evidence of increased YAP activity. Myeloid-specific YAP knockout mice (YAP F/F ;LysM Cre ) were subjected to PO stress. After 4 weeks, cardiac hypertrophy was similar between YAP KO mice and controls. However, systolic dysfunction, cardiac fibrosis, and indicators of pathological remodeling were all attenuated in YAP KO mice compared to controls. Additionally, inflammatory gene expression and macrophage infiltration to the myocardium were significantly attenuated in YAP KO mice after PO, indicating reduced inflammation compared to controls. Experiments using RAW264.7 macrophages and primary bone marrow-derived macrophages (BMDMs) from YAP KO and control mice demonstrated that increased YAP expression enhanced, while YAP suppression attenuated, inflammatory gene expression. The inflammasome is a multiprotein complex and important facilitator of cytokine processing that mediates inflammation in the PO heart. We observed attenuated inflammasome priming and function in YAP deficient BMDMs, as well as in YAP KO hearts following PO, indicating disruption of inflammasome induction. Together these data implicate YAP as an important mediator of inflammasome function and cardiac inflammation during PO stress and suggest that selective inhibition of YAP in the myeloid compartment may prove a novel therapeutic target in non-ischemic heart disease.
Abstract 12960: Identifying Gaps in Practice Patterns for Routine Lipid Profiles and High-Intensity Statins in Acute Myocardial Infarction Patients Prior to an Acute Coronary Syndrome Event
Authors: Carlos Nieves La Cruz, Patricia R Holden, Nitza Abreu Vera, Jamessa Scott, Janet Friant, Stacia B Hickey, Anastasia Pargulski
Journal: Circulation (2021)

Introduction: According to the 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction, admitting orders for the patient with STEMI should include a serum lipid profile in laboratory tests. Subsequently, the 2018 Guideline on the Management of Blood Cholesterol guidelines state that in primary prevention statins are recommended for patients with severe hypercholesterolemia and in adults 40 to 75 years of age either with diabetes mellitus or at higher ASCVD risk. Methods: A baseline review of data from Get With The Guidelines® - CAD across 10 pilot sites was conducted. An initial 430 patients were excluded from the Ezetimibe Considered for Very High-Risk Patients measure due to missing data fields. Interviews were conducted with participating sites to determine the root cause of the incomplete data. Results: The root cause analyses resulting from these interviews and case studies revealed that lipid profiles were not consistently performed. Further, only two patients were included in the numerator for the Ezetimibe Considered for Very High-Risk Patients measure. An analysis of 455 eligible patients showed that 70% of AMI patients seen by these hospitals were not presenting on any statin therapy prior to their acute event. Conclusions: Despite the clinical guideline recommendations for lipid management for both acute and secondary prevention, there remains much room for improvement. Preliminary results from this learning collaborative highlight the need for improved lipid profiling practices in the acute setting for STEMI patients and an opportunity for intervention through modifiable risk factor reduction in the form of statin therapy in the outpatient setting. We have identified a gap in AMI patient care, which presents the opportunity to improve long-term patient outcomes through heightened lipid profile collection sensitivity. At a systemic level, further research needs to be conducted to determine why patients are presenting with severe acute coronary events without prior management of their blood cholesterol levels. We hope through continued studies with the pilot sites we will observe a shift in practice patterns and improved non-statin lipid-lowering medication consideration for very high-risk ASCVD patients.
구연 : 간경변 환자에서 수술 후 사망률: Child-Turcotte-Pugh 점수, Model for End Stage Liver Disease 점수 및 Model for End Stage Liver Disease and Serum Sodium Concentration 점수의 비교
Authors: 조현진, 신동현, 정한영, 최문석, 고광철, 백승운, 유병철, 이준혁
Journal: Clinical and Molecular Hepatology (2009)
Abstract P511: Sirtuin 5 Overexpression Protects Against Pressure Overload-Induced Ventricular Dysfunction
Authors: Hanjia Guo, Rachael Baliirra, Mary Skinner, Surinder Kumar, Shaday Michan, Sharlene Day, David Sinclair, Costas Lyssiotis, Adam Stein, David B Lombard
Journal: Circulation Research (2021)

Heart failure (HF) is defined as an inability of the heart to pump blood sufficiently to meet the metabolic demands of the body. HF with systolic dysfunction is caused by a progressive decline in contractile function and chronic hemodynamic overload, and characterized by ventricular hypertrophy and remodeling, neurohormonal compensation mechanisms, and myocardial damage. Transverse aortic constriction (TAC) is a well-established model for inducing hypertrophy and HF in rodents. Mice globally deficient in sirtuin 5 (SIRT5), a NAD + -dependent deacylase, are hypersensitive to cardiac stress and display increased mortality after TAC. Prior studies assessing SIRT5 functions in the heart have all employed loss-of-function approaches. In this study, we generated SIRT5 overexpressing (SIRT5OE) mice, and evaluated their response to chronic pressure overload using TAC. Compared to littermate controls, elevated SIRT5 levels promoted maintenance of cardiac contractile function after 4 weeks of pressure overload, at which point control mice had developed systolic dysfunction, characterized by decreased EF, coupled with ventricular dilation, remodeling and fibrosis. Transcriptomic analysis revealed that SIRT5 suppresses key HF sequelae, including metabolic switch from fatty acid oxidation to glycolysis and immune activation ( i.e., TGFβ, IL6, Renin-Angiotensin, and NFAT, and fibrotic signaling pathways). We conclude that SIRT5 is a limiting factor in the preservation of cardiac function in response to experimental pressure overload.
Abstract 6902: Heart Failure Measurements Using Heartlogic Directly Correlates with Increased Burden of Atrial Fibrillation
Authors: Rezwan Ahmed, Pramodsingh Thakur, Angelo B Biviano, Kevin Clerkin, Hasan Garan, Elaine Y Wan
Journal: Circulation (2021)

Introduction: Atrial Fibrillation (AF) is a risk factor for death in patients with heart failure (HF). Device sensor measurements from ICDs/CRT-Ds can provide detailed data on the impact of AF on HF. HeartLogic index, HF sensor monitoring can detect worsening HF with high sensitivity. Hypothesis: We hypothesize HeartLogic sensors would be able to detect worsening HF with increased AF burden. Methods: AF burden was measured as time greater than atrial tachyarrhythmia rate of 170 bpm. Each patient day was grouped into 7 groups based on daily AF burden: No AF/normal sinus rhythm (NSR), &gt;0min, &gt;6min, &gt;1hr, &gt;5.5hr, &gt;12hr, and 24hr. Total 15,533 US patients from ALTITUDE database with HeartLogic devices and a minimum of 365 days of data were analyzed, 754 patients with all 7 levels of AF burden were included. For each group, mean daily heart sounds (S3, S1), respiratory rate (RR), rapid shallow breathing index (RSBI), thoracic impedance (TI), daily and night heart rate (HR, NHR), patient time active, HeartLogic index, and the percent of in-alert days were evaluated. Sensors were compared during each AF burden and during NSR using paired T-test. Results: AF burden groups above 6min were associated to significant worsening in S1, RR, RSBI, NHR, HR and HeartLogic index (figure). Significant reduction in patient activity occurred above 5.5hr of AF burden. In-alert days (%) increased significantly during AF burden above 6min compared with NSR. Conclusions: This data suggests potential use of HeartLogic sensors to identify patients whose HF status is most impacted by development of AF and those who may benefit most from rhythm control. Additional studies using sensor based AF management may improve clinical outcomes.