tbuckley/cabot-search huggingface dataset:
Acute Effects of Ibrutinib on Ventricular Arrhythmia in Spontaneously Hypertensive Rats
Authors: Beibei Du, Praloy Chakraborty, Mohammed Ali Azam, Stéphane Massé, Patrick F.H. Lai, Ahmed Niri, Daoyuan Si, Paaladinesh Thavendiranathan, Husam Abdel-Qadir, Filio Billia, Kumaraswamy Nanthakumar
Journal: JACC CardioOncology (2020)

The Bruton's Tyrosine Kinase Inhibitor ibrutinib is associated with ventricular arrhythmia (VA) and sudden death. However, the pro-arrhythmic electrophysiological dysregulation that results from ibrutinib with age and cardiovascular disease is unknown.This study sought to investigate the acute effects of ibrutinib on left ventricular (LV) VA vulnerability, cytosolic calcium dynamics, and membrane electrophysiology in old and young spontaneous hypertensive rats (SHRs).Langendorff-perfused hearts of young (10 to 14 weeks) and old (10 to 14 months) SHRs were treated with ibrutinib (0.1 μmol/l) or vehicle for 30 min. Simultaneously, LV epicardial action potential and cytosolic calcium transients were optically mapped following an incremental pacing protocol. Calcium and action potential dynamics parameters were analyzed. VA vulnerability was assessed by electrically inducing ventricular fibrillations (VFs) in each heart. Western blot analysis was performed on LV tissues.Ibrutinib treatment resulted in higher vulnerability to VF in old SHR hearts (27.5 ± 7.5% vs. 5.7 ± 3.7%; p = 0.026) but not in young SHR hearts (8.0 ± 4.9% vs. 0%; p = 0.193). In old SHR hearts, following ibrutinib treatment, action potential duration (APD) alternans (p = 0.008) and APD alternans spatial discordance (p = 0.027) were more prominent. Moreover, calcium transient duration 50 was longer (p = 0.032), calcium amplitude alternans ratio was significantly lower (p = 0.001), and time-to-peak of calcium amplitude was shorter (p = 0.037). In young SHR hearts, there were no differences in calcium and APD dynamics.Ibrutinib-induced VA is associated with old age in SHR. Acute dysregulation of calcium and repolarization dynamics play important roles in ibrutinib-induced VF.
First-Line Lorlatinib or Crizotinib in Advanced <i>ALK</i>-Positive Lung Cancer
Authors: Alice T. Shaw, Todd M. Bauer, Filippo de Marinis, Enriqueta Felip, Yasushi Goto, Geoffrey Liu, Julien Mazieres, Dong-Wan Kim, Tony Mok, Anna Polli, Holger Thurm, Anna M. Calella, Gerson Peltz, Benjamin J. Solomon
Journal: New England Journal of Medicine (2020)

Lorlatinib, a third-generation inhibitor of anaplastic lymphoma kinase (ALK), has antitumor activity in previously treated patients with ALK-positive non–small-cell lung cancer (NSCLC). The efficacy of lorlatinib, as compared with that of crizotinib, as first-line treatment for advanced ALK-positive NSCLC is unclear.
Treatment Patterns of Hypomethylating Agents in Older (≥65 Years) Acute Myeloid Leukemia Patients Who Did Not Receive Intensive Chemotherapy: A Retrospective Claims Database Analysis
Authors: Murali Sundaram, Marie-Hélène Lafeuille, Daniela Hoehn, Bruno Emond, Hela Romdhani, Patrick Lefebvre
Journal: Blood (2017)
Abstract 14368: Artificial Intelligence-Electrocardiography to Predict Time to Atrial Fibrillation: An Analysis of Mayo Clinic Study of Aging
Authors: Georgios Christopoulos, Camden L Lopez, Xiaoxi Yao, Zachi I Attia, Jonathan Graff-radford, Alejandro A Rabinstein, Petersen C Ronald, David Knopman, Michelle M Mielke, Walter Kremers, Paul Friedman, Peter A Noseworthy
Journal: Circulation (2020)

Introduction: An artificial intelligence (AI) algorithm applied to electrocardiography (ECG) during normal sinus rhythm (NSR) has been shown to predict concomitant atrial fibrillation (AF). We sought to characterize the value of AI-ECG as a predictor of future AF and assess its performance compared to other clinical prediction scores in a population-based sample. Methods: We calculated the AI-ECG probability during NSR in patients who enrolled in the population-based Mayo Clinic Study of Aging with at least one ECG in NSR within two years prior and no history of AF at the time of the baseline study visit. The cumulative incidence of AF was estimated for strata defined by AI-ECG probability and CHARGE-AF score. Cox proportional hazards were fit to assess the independent prognostic value and interaction of AI-ECG probability and CHARGE-AF score. Concordance (c) statistics were calculated for AI-ECG probability, CHARGE-AF score and combined AI-ECG and CHARGE-AF score. Results: A total of 1,936 patients with a median age 75.8 (quartile range [QR] 70.4, 81.8) years, median CHARGE-AF score 14.0 (QR 13.2, 14.7) and median CHADS2VASC score 3 (QR 2, 4) were included in the analysis. The cumulative incidence of AF increased in a stepwise fashion across quartiles of AI-ECG probability and CHARGE-AF score (Figure 1). When compared in the same model, both AI-ECG probability (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.51-2.04) and CHARGE-AF score (HR 1.90, 95% CI 1.58-2.28) independently predicted AF without significant interaction (p=0.54). C statistics were 0.69 (95% CI 0.66-0.72) for AI-ECG probability, 0.69 (95% CI 0.66-0.71) for CHARGE-AF and 0.72 (95% CI 0.69-0.75) for combined AI-ECG and CHARGE-AF score. Conclusions: In the Mayo Clinic Study of Aging, both the AI-ECG probability and CHARGE-AF score independently predicted time to AF. The AI-ECG may offer a means to assess risk with a single test without requiring manual or automated clinical data abstraction.
Cerebral Infarction With Increased Uptake on 123I-FP-CIT SPECT
Authors: Satoshi Nakajima, Yasutaka Fushimi, Hirotsugu Kawashima, Toshiya Murai, Yuji Nakamoto
Journal: Clinical Nuclear Medicine (2020)

A 76-year-old woman underwent 123I-FP-CIT brain SPECT due to postural reflex impairment. The transverse slices demonstrated increased uptake in the right middle cerebral artery territory. MR images obtained 2 weeks earlier showed cerebral infarction in the corresponding area. 123I-FP-CIT has high binding affinity for dopamine transporters, especially in the nerve endings of nigrostriatal dopaminergic neurons.
Abstract 17248: The Role of microRNA-21 in Regulating the Coronary Microcirculation in Diabetes
Authors: Cody Juguilon, Zhiyuan Wang, James Gadd, Vahagn A Ohanyan, Anurag Jamaiyar, Molly Enrick, Tao Wang, Chris Kolz, William M Chilian, Liya Yin
Journal: Circulation (2020)

Introduction: Coronary microvascular dysfunction is prevalent among diabetics and intersects with deficits in endothelial-dependent vasodilation. These deficits occur early in the progression of the disease, but the mechanisms remain incompletely understood. Nitric oxide (NO) is the major endothelial-dependent mediator of vasodilation in the healthy coronary circulation, but the mediator switches to hydrogen peroxide (H 2 O 2 ) in coronary artery disease (CAD) patients. Diabetes is a risk factor for CAD, so we hypothesized that a similar switch would occur. Methods: Coronary arteries were isolated and endothelial-dependent vasodilation was assessed using myography. Quantitative polymerase chain reaction (qPCR) was performed for gene expression analysis and myocardial blood flow (MBF) was measured by contrast echocardiography. Results: Nitric oxide synthase inhibitor (L-NAME) inhibited vasodilation in wild type (WT) mice, but the H 2 O 2 scavenger (PEG-catalase) had no effect. In contrast, vasodilation in diabetic mice was blunted by PEG-catalase, but not L-NAME. This suggests that the mediator of coronary vasodilation switched from NO to H 2 O 2 in diabetes. Importantly, we found that microRNA-21 (miR-21) is upregulated in diabetes and the deficiency modulates the mediator switch from NO to H 2 O 2 in diabetic mice. Conclusions: The switch in the mediator of coronary vasodilation from NO to H2O2 contributes to microvascular dysfunction in diabetes and miR-21 regulates this switch. Further genetic profiling will elucidate the pathways and mechanisms converging with miR-21 to regulate microvascular function in diabetes. This is the first mouse model that recapitulates the switch in mediator of coronary vasodilation from NO to H 2 O 2 seen in CAD patients.
Abstract 13910: Importance of Non-invasive Estimates of Left Ventricular Filling Pressures in Critically Ill Patients
Authors: Abdelrahman M Ahmed, Brandon Wiley, Jacob C Jentzer, Nandan S Anavekar, Allan S Jaffe
Journal: Circulation (2020)

Introduction: The presence of cardiac dysfunction predicts adverse outcomes in the intensive care unit (ICU). We explored the relationship of cardiac injury and left ventricular (LV) systolic and diastolic dysfunction (LVDD) to outcomes in critically ill patients. Methods: This is a retrospective analysis of adult medical ICU admissions from May, 2018 through October 2019. Patients with elevated high-sensitivity troponin T (hs-cTnT) and an echocardiogram performed within 72 hours of admission were included. Patients were classified as having normal LV diastolic function, isolated LVDD, concomitant LV diastolic and systolic dysfunction (LVDDSD) or indeterminate LV diastolic function based on American Society of Echocardiography 2016 guidelines. LV systolic dysfunction was defined as an ejection fraction (EF) &lt; 50%. Results: Overall, 222 patients were included. LVDD was seen in 123 patients (55.4%). Thirty patients (13.5%) were classified with indeterminate diastolic function and 56 normal diastolic function (25.2%). Of those with LVDD , 59.3% had LVDDSD while isolated LVDD was seen in 40.7%.Patients with LVDDSD had a higher median hs-cTnT at baseline compared to patients with isolated LVDD [102ng/L IQR (50-257) vs. 77 ng/L (33.5-166); p=0.047]. Medial e’ velocity and tricuspid valve systolic regurgitant velocity were often associated with LV systolic dysfunction (p=0.0172 and 0.0013, respectively). LVDDSD was associated with a longer length of stay than patients with isolated LVDD [2.9 (1.6-4.0) vs.1.8 (1.1-3.3); p-value 0.03].Twenty-nine patients died during their ICU stay (13%). Patients with LVDDSD had 9.6-fold higher odds of dying in the ICU than patients with isolated LVDD (p=0.0048). Reduced medial e’ velocity (OR 0.63, CI 0.4-1.0, p=0.0285) and increased E/e’ (OR 1.08, CI 1.01-1.15, p=0.0192) were associated with ICU mortality. The association between LVEF&lt;50% and ICU mortality was less pronounced (OR 0.95, CI 0.01-0.98; p=0.0023). Conclusions: Concomitant LV systolic and diastolic dysfunction and measures of increased cardiac filling pressures are strong predictors of mortality.
Abstract 16079: The Cusp of Life: Anomalous Origin of All Coronary Arteries From a Single Cusp
Authors: Yuvraj Chowdhury, Karishma Patwa, Mrinali Shetty, Aleksandre Toreli, Shaqueel Sheikh
Journal: Circulation (2020)

Introduction: Anomalous origin of coronary arteries has a prevalence of 1% in the population and is independently associated with a risk of sudden cardiac death. While an anomalous coronary artery arising from the opposite sinus is rare, all three coronary arteries arising from separate ostia in a single cusp is an extremely rare phenomenon. Case: A 48-year-old male with history of hypertension presented with fevers, cough and shortness of breath of 3 days duration. CXR demonstrated multi-lobar pneumonia and serology returned positive for Influenza A. Treatment was initiated with oseltamivir, vancomycin and piperacillin-tazobactam. Subcutaneous heparin was initiated for VTE prophylaxis. On day 3, the patient developed acute hypoxic respiratory failure from flash pulmonary edema necessitating intubation and mechanical ventilation. ECG revealed ST segment elevation in leads II, III, aVF, V5 and V6 (Fig. 1A). He was taken for urgent cardiac catheterization. Coronary angiography revealed anomalous origins of the left circumflex (LCX) and left anterior descending (LAD) arteries arising from the right coronary cusp (RCC) (Fig. 1B &amp; 1C). 99% thrombotic occlusion of the distal right coronary artery was identified as the culprit lesion (Fig 1D). Percutaneous coronary intervention with a 4 x 30 mm drug-eluting stent was performed. Discussion: Absence of the left coronary artery originating from the left coronary sinus should raise suspicion for a coronary anomaly. While an anomalous LCX artery originating from the RCC is seen in 0.7% individuals, the LAD artery arises from the RCC is seen in 0.15% of people. All three coronary arteries arising from the RCC is extremely rare. An abnormal take-off angle, compression between the aorta and the pulmonary trunk, slit-like ostia, coronary hypoplasia and accelerated atherosclerosis are responsible for the increased risk of coronary events in this population.
Abstract 13290: Variation in Coding for Major Cardiac Diagnoses and Procedures in Cardiac Research Using the National Inpatient Sample
Authors: John W Ostrominski, Javier Amione-Guerra, Brian Hernandez, Joel Michalek, Anand Prasad
Journal: Circulation (2020)

Introduction: Code selection is crucial to the accuracy and reproducibility of studies using administrative data, however a comprehensive assessment of coding trends for major cardiac diagnoses and procedures is lacking. Hypothesis: Given the absence of consensus guidelines for administrative code utilization, heterogeneity in code selection for major cardiovascular diagnoses and procedures will be uncovered. Methods: We queried PubMed, CINAHL, Scopus, Medline, and the HCUP Publication Search from inception through March 1st, 2018 for all publications using the National Inpatient Sample (NIS), featuring a primary focus on the heart. ICD-9-CM codes reported for acute myocardial infarction (AMI), heart failure (HF), atrial fibrillation (AF), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG) were collected and analyzed for accuracy and consistency. All studies were also evaluated for adherence to required methodological practices as per previously reported methods. Results: Of 2637 articles identified, 445 were included in the observational analysis. 399 articles (84%) did not adhere to one or more research practices required by the AHRQ, however overall adherence was superior for publications in higher impact journals ( P = 0.0019). Heterogeneity in code utilization was observed for each diagnosis and procedure assessed, with up to 37 unique case definitions reported for HF and PCI. Nonspecific codes were included in 39 (8.8%) studies, and coding heterogeneity increased throughout the study period ( P trend &lt; 0.001 for all cardiac diagnoses and procedures). Coding schema endorsed by national-level clinical guidance documents were infrequently represented, reported in only 8.9% and 1.3% of AMI and HF articles, respectively. Upon reintroduction into the NIS for the period of 2008 to 2012, selected unique case definitions for AMI were found to yield significantly different estimates of AMI incidence. Conclusions: Substantial heterogeneity in code selection exists for major cardiac diagnoses and procedures, with important implications for the accuracy and generalizability of analyses using the NIS. Further efforts are required to establish consensus protocols to ensure consistency in code utilization.
Multiple COVID-19 Outbreaks Linked to a Wedding Reception in Rural Maine — August 7–September 14, 2020
Authors: Parag Mahale, Craig Rothfuss, Sarah Bly, Megan Kelley, Siiri Bennett, Sara L. Huston, Sara Robinson
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Large indoor gatherings pose a high risk for transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 , and have the potential to be super-spreading events (1,2).Such events are associated with explosive growth, followed by sustained transmission (3).During August 7-September 14, 2020, the Maine Center for Disease Control and Prevention (MeCDC) investigated a COVID-19 outbreak linked to a wedding reception attended by 55 persons in a rural Maine town.In addition to the community outbreak, secondary and tertiary transmission led to outbreaks at a longterm care facility 100 miles away and at a correctional facility approximately 200 miles away.Overall, 177 COVID-19 cases were epidemiologically linked to the event, including seven hospitalizations and seven deaths (four in hospitalized persons).Investigation revealed noncompliance with CDC's recommended mitigation measures.To reduce transmission, persons should avoid large gatherings, practice physical distancing, wear masks, stay home when ill, and self-quarantine after exposure to a person with confirmed SARS-CoV-2 infection.Persons can work with local health officials to increase COVID-19 awareness and determine the best policies for organizing social events to prevent outbreaks in their communities.
Influence of the concentration and molecular composition on the LDL and HDL functional characteristics in patients with the metabolic syndrome
Authors: Antonio Casella Filho, Ivani Credidio Trombetta, Lia Casella, Celise A Denardi, Paulo Magno Martins Dourado, Alexandre Segre, Leonardo Roever Borges, C. E Negrão, Raul Cavalcante Maranhão, Antonio Carlos Palandri Chagas
Journal: Circulation (2012)
Abstract PO-047: Lorazepam modifies the pancreatic ductal adenocarcinoma tumor microenvironment
Authors: Abigail C. Cornwell, Abdulrahman A. Alahmari, Arwen A. Tisdale, Michael E. Feigin
Journal: Cancer Research (2020)

Abstract The aim of this work was to determine the role of the benzodiazepine (BZD) lorazepam, an anxiolytic drug, in modifying the pancreatic ductal adenocarcinoma (PDA) tumor microenvironment. PDA is a lethal malignancy. Poor survival rates and tumor intrinsic aspects of the disease, such as altered cytokine pools, promote significant levels of anxiety in patients. Approximately 25% of PDA patients will be prescribed BZDs. Epidemiological evidence suggests BZDs increase the risk of cancer development, but no group has determined the impact of BZDs on the PDA tumor microenvironment. Recent research has established that BZDs promote the signaling of GPR68, a proton-sensing G protein-coupled receptor activated by the acidic tumor microenvironment. GPR68 is expressed on PDA cancer-associated fibroblasts (CAFs) and promotes pro-inflammatory and pro-fibrotic signaling. Additionally, we performed covariate adjusted analyses of pancreatic cancer patients who received chemotherapy at Roswell Park from 2004 to 2020. Patients receiving lorazepam (LOR), an n-unsubstituted BZD that strongly activates GPR68, had shorter progression-free survival (PFS) relative to non-users (HR 3.83 (1.53, 9.57). In contrast, patients receiving alprazolam (ALP), an n-substituted BZD and GPR68 non-activator, had improved PFS relative to non-users (HR 0.38 (0.16-0.92). It is essential that we determine the impact of BZDs and GPR68 activation on the PDA tumor microenvironment and therapeutic response. We hypothesize that BZDs which are strong GPR68 activators will stimulate fibrosis and inflammatory signaling, promoting a more desmoplastic tumor microenvironment, decreasing the efficacy of chemotherapy. Using a subcutaneous KPC allograft mouse model, we found that lorazepam, a strong GPR68-activating BZD, modified the tumor microenvironment by increasing α-SMA (smooth muscle actin) expression, collagen deposition, and ischemic necrosis. Similarly, under acidic conditions, lorazepam-treated primary mouse and human CAFs promoted the mRNA expression of α-SMA and the pro-inflammatory cytokine, interleukin-6. Overall, this research indicates that lorazepam treatment significantly impacts the PDA tumor microenvironment. Significance: This research may guide the development of new clinical recommendations for prescribing anxiolytic drugs to PDA patients. The results of this research will likely be applicable to other cancer types which are reliant on CAFs for growth, such as colon cancer. Citation Format: Abigail C. Cornwell, Abdulrahman A. Alahmari, Arwen A. Tisdale, Michael E. Feigin. Lorazepam modifies the pancreatic ductal adenocarcinoma tumor microenvironment [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-047.
Abstract 16814: Procedural Time in Echocardiogram versus Fluoroscopic Guided Endomyocardial Biopsies: Debunking the Myth
Authors: Mahesh Chandrasekhar, Diego Malaver, Thomas J O'Neill, Barbara A Pisani, Geoffrey Jao
Journal: Circulation (2020)

Introduction: Fluoroscopic-guided endomyocardial biopsy (FGEB) of the right ventricle is the most common method for rejection surveillance among heart transplant recipients. Echocardiogram guided endomyocardial biopsy (EGEB) has been shown to be a safe alternative, but not widely adopted, in part due to perceived longer procedural time. Hypothesis: EGEB is has comparable total procedural and biopsy time compared to FGEB and significantly lowers radiation exposure. Methods: A single center retrospective study was performed on patients who underwent biopsy via right internal jugular vein approach from 1/1/15 to 2/1/19. Biopsy time was time of bioptome insertion to sheath removal. Total procedure time was from physician entrance to exit into procedure lab. Results: 100, patients, 487 biopsies. The mean biopsy time of EGEB was similar to FGEB; 30.0 ± 10.2 min (95% CI: 27.9-32.1 min) to 29.7 ± 9.91 min (95% CI: 28.7 - 30.7 min) respectively, p = 0.73. The mean total procedural time of the EGEB was similar to FGEB; 70.3 ± 18.9 min (95% CI: 34-125 min) to 73.4 ± 18.5 min (95% CI: 21 - 129 min), p = 0.102. Mean fluoroscopy time for EGEB was lower than FGEB; 1.78 min (95% CI: 1.4-2.2 min) vs 5.53 min (95% CI: 5.22-5.83 min) p &lt; 0.0001. A mixed model analysis of mean fluoroscopy time was performed to account for the same patients receiving multiple endomyocardial biopsies, sometimes by different guidance, showed a difference of 1.89 mins less with EGEB than FGEB (p &lt; 0.0001). Conclusions: EGEB has similar biopsy and total procedural time but significantly reduced fluoroscopy time. EGEB should be routinely considered in patients for endomyocardial biopsy.
Abstract 14058: Sex-based Differences in Reported Payments to Cardiologists by Drug and Device Manufacturers
Authors: Kayle Shapero, Qurat-ul-ain Jelani, Peter Kahn
Journal: Circulation (2020)

Introduction: Sex-based disparities in salaries and promotion in cardiovascular medicine are well known, but there is little data on industry compensation by sex. We attempted to explore sex differences in financial ties to industry in the form of drug and device manufacturer payments to cardiologists. Methods: 2018 Open Payments data was obtained from Centers for Medicare and Medicaid Services (CMS). A cross walk was used to link CMS National Plan and Provider Enumeration System National Provider Identifier Data with open payments data. Physician specialty (adult cardiology), sex, state of practice, number and amount of payments, drug and device information were obtained and aggregated for analysis using natural language processing. Results: In 2018, total of 879,119 payments were made to 29246 physicians (10.2% female), totaling $145,556,106. Nationwide, female cardiologists had lower rates of payments (15.5 payments per year vs 25.9 payments), lower average compensation per payment ($113 vs $169) when compared to their male counterparts. Analysis of five drugs/devices with the largest aggregated payments revealed that the female representation in certain categories (consulting, compensation for serving as speaker-non continuing education, and travel and lodging) was far lower than expected (3.8%, 5.4%, and 4.2% respectively). Conclusions: Female cardiologists received fewer payments and lower compensation per payment from drug and device manufacturers as compared to their male counterparts. Further studies are required to determine reasons behind differences in compensation and efforts be made to standardize compensation regardless of sex to promote equal opportunities for all physicians.