tbuckley/cabot-search huggingface dataset:
Abstract 226: Statewide Out-of-hospital Cardiac Arrest During the Covid-19 Pandemic
Authors: Lindsey K Rauch, Emily Bergquist, James Pribble, William Fales
Journal: Circulation (2020)

Introduction: Little is known about statewide out-of-hospital cardiac arrests (OOHCA) during a global pandemic. Objective: To characterize the impact of the COVID-19 pandemic on state OOHCA rates. Methods: Data for non-traumatic, OOHCA were obtained and analyzed from a statewide EMS information system from March 1, 2000 to May 31, 2020 (pandemic) and compared to data obtained from the same 3-month period the prior year (control). Analysis occurred using a web-based application designed to analyze state EMS data. OOHCA were identified using a validated data filter applied to 911 calls and limited to transporting EMS units. Shockable OOHCA and arrests occurring in 5 counties with the highest number of COVID-19 deaths during the pandemic were also analyzed. Results: There were 4,665 OOHCAs identified during the pandemic compared to 3,261 OOHCA during the control period, a 43.1% increase (p&lt;0.00001). Bystander AED use (10% vs 10%), bystander CPR (38% vs. 38%), and bystander witnessed arrests (34% and 33%) were similar. Rates of EMS termination of resuscitation (TOR) were higher (59% vs. 47%), while endotracheal intubation (ETI) (12% vs. 31%), and ROSC (5% vs. 8%) were lower during the COVID-19 period. Blacks had a higher rate of OOHCA during the pandemic period (26.6% vs 18.6%, p&lt;0.00001). Overall shockable OOHCA increased by 14.8% (403 vs. 351, p=0.002) during the pandemic. Bystander AED use (10% vs 11%), bystander CPR (55% vs. 51%), and bystander witnessed (71% and 71%) were similar. Rates of field TOR were 33% vs. 24%, ETI were 14% vs. 31%, and ROSC were 16% vs. 17%. Within the 5 highest impact counties total OOHCA increased by 61.4% (2,702 vs. 1,674, p&lt;0.00001) and shockable OOHCAs increased by 21.4% (207 vs 170, p=0.004). Conclusions: OOHCA and shockable OOHCA increased during the COVID-19 pandemic statewide and to a higher degree in the 5 high impact counties. Little change was noted in rates of bystander AED use, CPR, and witnessed arrests. EMS TOR rates increased while ETI rates decreased. ROSC rates decreased in the overall OOHCA group but were not significantly changed in shockable OOHCA. OOHCA involving the black race occurred more frequently. Further research is warranted to understand the causes of these observations.
Target inhibition of galectin-3 by inhaled TD139 in patients with idiopathic pulmonary fibrosis
Authors: Nikhil Hirani, Alison C. MacKinnon, Lisa Nicol, Paul Ford, Hans Schambye, Anders Pedersen, Ulf J. Nilsson, Hakon Leffler, Tariq Sethi, Susan Tantawi, Lise Gravelle, Robert J. Slack, Ross Mills, Utsa Karmakar, Duncan Humphries, Fredrik Zetterberg, Lucy Keeling, Lyn Paul, Philip L. Molyneaux, Feng Li, Wendy Funston, Ian A. Forrest, A. John Simpson, Michael A. Gibbons, Toby M. Maher
Journal: European Respiratory Journal (2020)

Galectin (Gal)-3 is a profibrotic β-galactoside-binding lectin that plays a key role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and IPF exacerbations. TD139 is a novel and potent small-molecule inhibitor of Gal-3. A randomised, double-blind, multicentre, placebo-controlled, phase 1/2a study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of inhaled TD139 in 36 healthy subjects and 24 patients with IPF. Six dose cohorts of six healthy subjects were evaluated (4:2 TD139:placebo ratio) with single doses of TD139 (0.15–50 mg) and three dose cohorts of eight patients with IPF (5:3 TD139:placebo ratio) with once-daily doses of TD139 (0.3–10 mg) for 14 days. Inhaled TD139 was well tolerated with no significant treatment-related side-effects. TD139 was rapidly absorbed, with mean time taken to reach maximum plasma concentration ( C max ) values ranging from 0.6 to 3 h and a plasma half-life ( T 1/2 ) of 8 h. The concentration of TD139 in the lung was &gt;567-fold higher than in the blood, with systemic exposure predicting exposure in the target compartment. Gal-3 expression on alveolar macrophages was reduced in the 3 and 10 mg dose groups compared with placebo, with a concentration-dependent inhibition demonstrated. Inhibition of Gal-3 expression in the lung was associated with reductions in plasma biomarkers centrally relevant to IPF pathobiology (platelet-derived growth factor-BB, plasminogen activator inhibitor-1, Gal-3, CCL18 and YKL-40). TD139 is safe and well tolerated in healthy subjects and IPF patients. It was shown to suppress Gal-3 expression on bronchoalveolar lavage macrophages and, in a concerted fashion, decrease plasma biomarkers associated with IPF progression.
Fluorides and Osteoporosis
Authors: M Kleerekoper, R Balena
Journal: Annual Review of Nutrition (1991)

Sodium fluoride has clearly been shown to have pronounced effects on the skeleton, probably more than any other currently available therapeutic agent. Unfortunately, these effects appear to be both beneficial and potentially toxic at the same time. A more clear understanding is needed of the basic mechanisms whereby these effects (both beneficial and detrimental) are exerted. When such data are forthcoming, it may be possible to modify the therapeutic use of fluoride in osteoporosis and other brittle bone diseases such that the beneficial effects outweigh the toxic effects much more completely than is currently the case. Until such time, and despite thirty years of meaningful clinical investigation, we must conclude that sodium fluoride has no role in clinical medicine outside the confines of properly conducted clinical research studies.
Elevated CXorf67 Expression in PFA Ependymomas Suppresses DNA Repair and Sensitizes to PARP Inhibitors
Authors: Jichang Han, Meng Yu, Yiqin Bai, Jianzhong Yu, Fei Jin, Chen Li, Rong Zeng, Jinghong Peng, Ao Li, Xiaomin Song, Hao Li, Dianqing Wu, Lin Li
Journal: Cancer Cell (2020)
Abstract 13674: Real-world Outcomes Following Fractional Flow Reserve Use
Authors: Cuneyt Sda, Chin Chwan NG, Chris Wong, Martin Ng, Vincent Chow, David Brieger, Leonard Kritharides, William F Fearon, Andy Yong
Journal: Circulation (2020)

Introduction: Fractional flow reserve is an established method for assessing coronary artery stenosis severity. However, long-term outcome data in a real-world population is lacking. Aims: We aim to determine whether FFR use is superior to angiography alone in relation to cardiac death and all-cause death in a real-world population. Methods: Patients undergoing angiography between June-2017 and June-2018 recorded by the Centre-for-Health-Record-Linkage (CHeReL) were included. The CHeReL database captures health data from ≥97% of all healthcare facilities in the state of New South Wales, with a population of 7.5 million people. The cohort was stratified into angiography-FFR group when concomitant FFR was performed, and the angiography-only group which included all patients undergoing angiography without concomitant FFR. The primary and secondary outcomes were cardiac death and all-cause death respectively. Results: The study cohort comprised 34,597 patients, in which 32,863 (95%) patients underwent angiography alone and 1,734 (5%) patients had angiography combined with FFR. At 1-year follow-up, the angiography-FFR group had a lower occurrence of the endpoints of cardiac death (0.8% vs 2.3%, P&lt;0.001) and all-cause death (1.7% vs 4.7%, P&lt;0.001) compared to the angiography-only group. Multivariable Cox regression analysis showed FFR use to be associated with lower rates of both cardiac death (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.32-0.93, P=0.025) and all-cause death (HR 0.55, 95% CI 0.38-0.79, P=0.001) independent of age, sex, facility, country of birth, referral source, marital status, Charlson comorbidity index, valvular heart disease, pre-existing atrial fibrillation (AF), presenting illnesses including AF, congestive heart failure or acute coronary syndrome, planned percutaneous coronary intervention or coronary artery bypass graft surgery, and concomitant or subsequent cardiac valve surgery. Conclusions: FFR use was associated with a reduction in both cardiac death and all-cause death in this real-world study.
Abstract 16213: Short QT Syndrome Case Study
Authors: Lawrenshey Charles, Abdullah Al-Abcha, Tyler Kemnic, Zulfiqar Qutrio Baloch
Journal: Circulation (2020)

Introduction: Short QT syndrome (SQTS) is a very rare genetic disease of the electrical system of the heart which is associated with an increase risk of abnormal cardiac rhythms and sudden cardiac death. First described in 2000 with the first genetic mutation associated with SQTS described in 2004. We present a case of Short QT syndrome in a 53 year old male. Case: A 53 year old male with a PMH of HTN, alcohol abuse, and tobacco dependence presented to the ED with palpitations. Patient endorsed that he was in his usual state of health the day prior to arrival. He went to bed after drinking alcohol and woke up suddenly pale and diaphoretic with dyspnea and a persistent feeling of impending doom. On arrival to the ED, he was tachypneic (26 breaths/min) with a heart rate of 163 bpm and a blood pressure of 100/80 mmHg. EKG showed atrial fibrillation with RVR. The patient converted to normal sinus rhythm after one dose of IV Cardizem 10 mg was administered for rate control. The next day he had multiple episodes of Torsades de Pointe and monomorphic ventricular tachycardia treated with synchronized cardioversion, 2g of magnesium, IV amiodarone and lidocaine drip. He was transferred to the ICU for further evaluation and monitoring. Repeat EKG showed normal sinus rhythm at 75 bpm and short QT (QT= 328). TTE showed normal biventricular size and function (LVEF 60-65%) with no valvular abnormalities. Dual chamber Implantable Cardioverter Defibrillator (ICD) was placed and outpatient genetic testing was scheduled. Discussion: SQTS is very rare with roughly 70 cases identified worldwide since the condition was discovered in 2000. It is a congenital channelopathy related to potassium channels and represented by a normal heart rate with accelerated cardiac repolarization. Normal QT range is 350-440 msec while SQTS range is 210-340 msec. Mutations in the KCNH2, KCNJ2, or KCNQ1 genes lead to enhanced flow of potassium ions across the membrane of cardiac muscle cells. Patients can present at any age with palpitations, syncope, atrial fibrillation, and sudden cardiac death. The cornerstone to diagnosing SQTS is an electrocardiogram. Patients with SQTS can be managed with ICD implantation, quinidine (especially with KCNH2 mutation), and sotalol (with other mutations other than KCNH2).
Severe Hypoglycemia, Cardiac Structure and Function, and Risk of Cardiovascular Events Among Older Adults With Diabetes
Authors: Justin B. Echouffo-Tcheugui, Natalie Daya, Alexandra K. Lee, Olive Tang, Chiadi E. Ndumele, B. Gwen Windham, Amil M. Shah, Elizabeth Selvin
Journal: Diabetes Care (2020)

To assess the association of severe hypoglycemia measured at baseline with cardiovascular disease (CVD) among community-dwelling older individuals with diabetes, a group particularly susceptible to hypoglycemia.
Conduct of Clinical Trials in the Era of COVID-19
Authors: Mitchell A. Psotka, William T. Abraham, Mona Fiuzat, Gerasimos Filippatos, JoAnn Lindenfeld, Tariq Ahmad, Ankeet S. Bhatt, Peter E. Carson, John G.F. Cleland, G. Michael Felker, James L. Januzzi, Dalane W. Kitzman, Eric S. Leifer, Eldrin F. Lewis, John J.V. McMurray, Robert J. Mentz, Scott D. Solomon, Norman Stockbridge, John R. Teerlink, Muthiah Vaduganathan, Orly Vardeny, David J. Whellan, Janet Wittes, Stefan D. Anker, Christopher M. O'Connor
Journal: Journal of the American College of Cardiology (2020)

The coronavirus disease-2019 (COVID-19) pandemic has profoundly changed clinical care and research, including the conduct of clinical trials, and the clinical research ecosystem will need to adapt to this transformed environment. The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory and the Academic Research Consortium, composed of academic investigators from the United States and Europe, patients, the U.S. Food and Drug Administration, the National Institutes of Health, and industry members. A series of meetings were convened to address the challenges caused by the COVID-19 pandemic, review options for maintaining or altering best practices, and establish key recommendations for the conduct and analysis of clinical trials for cardiovascular disease and heart failure. This paper summarizes the discussions and expert consensus recommendations.
Abstract 13527: Inhibition of With-No-Lysine Kinase Improves Right Ventricular Function by Blunting Excess Protein O-GlcNAcylation
Authors: Sasha Z Prisco, Megan Eklund, Kurt W Prins
Journal: Circulation (2020)

Introduction: Pulmonary arterial hypertension (PAH) is caused by obstructive remodeling of the pulmonary arteries which ultimately causes right ventricle (RV) failure and death. Increased expression of the glucose membrane transporters Glut1 and Glut4 occurs in the failing RV, but the upstream regulators of these proteins are unknown. The With-no-Lysine (WNK) kinase-1, a kinase activated in low chloride conditions, promotes expression of Glut1/4 in skeletal muscle, but its regulation in the RV in PAH is unexplored. Furthermore, the relationship between WNK1 and protein O-GlcNAcylation, a glucose based post-translational modification, has not been examined. Methods: Immunoblots quantified the abundance of WNK1, Glut1, Glut4, and total protein O-GlcNAcylation in the RV of control, monocrotaline (MCT) rats, and MCT rats treated with a WNK inhibitor two weeks after MCT injection. Echocardiography and pressure-volume loop analysis assessed RV function and pulmonary vascular disease severity. Results: Treatment with WNK inhibitor improved TAPSE (2.4±0.1 vs 1.8±0.1 mm, p =0.0007), cardiac output (86.0±9.1 vs 52.5±5.6 ml/min, p =0.02), and cardiac output normalized body weight (0.26±0.03 vs 0.15±0.02 ml/min/g, p =0.0032). Importantly, the WNK inhibitor did not alter pulmonary vascular disease severity as there were no differences in pulmonary artery acceleration time (18.2±1.5 vs 14.2±0.9 sec, p =0.22), Ea (0.58±0.07 vs 0.58±0.08 mmHg/μL, p=1.00), or right ventricular systolic pressure (71.8±7.6 vs 72.0±4.0 mmHg, p =1.00) compared to MCT. At the molecular level, WNK1 inhibition decreased expression of WNK1 (MCT: 1.3±0.2 fold increase, MCT-WNK: 3.4±2.2 fold decrease), Glut1 (MCT: 2.7±0.9 fold increase, MCT-WNK: 1.2±0.2 fold increase), Glut4 (MCT: 1.7±0.4 fold increase, MCT-WNK: 1.0±0.2 fold increase), and protein O-GlcNAcylation (MCT: 2.4±0.7 fold increase, MCT-WNK: 1.1±0.1 fold increase). Conclusions: WNK inhibition normalized Glut1/4 expression and protein O-GlcNAcylation in the RV. These molecular changes resulted in improved RV function without a change in pulmonary vascular disease burden.
Abstract 14985: Presence of Repolarization Gradients Reverses Post-infarct Ventricular Tachycardia Exit and Entrance Sites in Personalized Digital Hearts
Authors: Eric Sung, Adityo Prakosa, Natalia Trayanova
Journal: Circulation (2020)

Introduction: Post-infarct ventricular tachycardias (VT) arise due to structural remodeling (scarring). Physiological repolarization gradients (apicobasal and transmural) exist in the human heart, but the effects on post-infarct VT dynamics are unknown. Hypothesis: We hypothesized that incorporation of repolarization gradients in personalized digital hearts of post-infarct patients impacts VT exit sites without altering the location of the VTs. Methods: 3D late-gadolinium enhanced CMR images were acquired from 7 post-infarct patients. Personalized image-based computational heart models (digital hearts) representing scar and infarct border zone distributions were constructed. Apicobasal (AB) and transmural (TM) repolarization gradients were incorporated using a validated method (Fig A). VTs were induced at baseline (no repolarization gradient) via rapid pacing in the right ventricular apex, using two pacing cycle lengths, mimicking non-invasive programmed stimulation. Pacing protocols that induced baseline VTs were repeated under AB and TM conditions. Results: Ten VTs were induced in baseline digital hearts. 8 AB VTs and 8 TM VTs were induced; the remaining 2 VTs for both AB and TM digital hearts could not be induced. 5/8 induced AB VTs had VT exit sites matching baseline VT exit sites; the remaining 3/8 AB VTs had reversed VT exit and entrance sites from the corresponding baseline VTs (Fig B, VT 1 &amp; 2). 4/8 induced TM VTs had exit sites that matched those at baseline; the remaining TM VTs had exit and entrance sites reversed from those of baseline VTs (Fig B, VT 1, 2 &amp; 3). All 8 AB VTs and 8 TM VTs had the same location as corresponding baseline VTs. Conclusion: AB and TM repolarization gradients can act to reverse VT entrance and exit sites without changing VT location. Thus, incorporation of physiological repolarization gradients into personalized digital hearts may not impact VT ablation targeting but may affect accurate prediction of VT exit or entrance sites.
Epigenetic landscape of small cell lung cancer: small image of a giant recalcitrant disease
Authors: Parvez Khan, Jawed Akhtar Siddiqui, Shailendra Kumar Maurya, Imayavaramban Lakshmanan, Maneesh Jain, Apar Kishor Ganti, Ravi Salgia, Surinder Kumar Batra, Mohd Wasim Nasser
Journal: Seminars in Cancer Biology (2020)
Abstract 15459: Impact of Progression From Paroxysmal to Sustained Atrial Fibrillation on Clinical Outcomes in Patients With Obesity: The Fushimi Af Registry
Authors: Akiko Fujino, Hisashi Ogawa, Kenjiro Ishigami, Syuhei Ikeda, KOSUKE DOI, Yasuhiro Hamatani, Yuya Ide, Yoshimori An, MITSURU ISHII, Moritake Iguchi, Nobutoyo Masunaga, Hiromichi Wada, Koji Hasegawa, Mitsuru Abe, Masaharu Akao
Journal: Circulation (2020)

Background: Obesity, which leads to left arterial remodeling, increases the risk for the development of atrial fibrillation (AF). We previously demonstrated the progression from paroxysmal to sustained AF was associated with an increased risk of ischemic stroke or hospitalization for heart failure (HF). However, the risk of progression from paroxysmal to sustained AF in obese patients has not been fully evaluated. Methods: Based on the initial type of AF and whether paroxysmal AF progressed to sustained AF during follow-up (FU), patients enrolled in the Fushimi AF registry were categorized into 3 groups; i) paroxysmal AF without progression, ii) paroxysmal AF with progression, iii) sustained AF. Obesity was defined as BMI at baseline &gt;30. Results: Obese patients (172/3834) had a higher prevalence of sustained AF at baseline as compared with those without obesity (58.7% vs 51.0%, p=0.047), and they had a higher rate of progression from paroxysmal to sustained AF during a median FU of 4.3 years (2.4% vs 1.5% [per person-year], p&lt;0.01). Both obese and non-obese patients had the highest rate of ischemic stroke in the category of paroxysmal AF with progression as compared with other two categories (obese patients: 0.2% [paroxysmal AF without progression] vs 2.6% [paroxysmal AF with progression] vs 0.7% [sustained AF] [per person-year], non-obese patients: 1.2% vs 2.2% vs 1.8%). In contrast, obese patients had the lowest percentage of hospitalization for HF in the category of paroxysmal AF with progression (2.5% vs 1.8% vs 3.8%), but AF progression was associated with a higher incidence of hospitalization for HF in patients without obesity (2.2% vs 3.9% vs 4.2%). Conclusions: Obesity may be the risk of the progression of paroxysmal to sustained AF. The progression may be associated with increased risk of ischemic stroke in both obese and non-obese patients, but the risk of hospitalization for HF might be lower in patients with obesity as compared with those without obesity.
The optimal treatment of stage I nonsmall cell lung cancer in the era of SABR and modern day lung resections
Authors: Eric Vallieres
Journal: European Respiratory Journal (2020)

<b>Both SABR and surgical resection may have a role to play in the treatment of clinical stage I NSCLC, and future studies should focus on the biology of these mostly curable lung cancers to minimise under-and overtreating patients</b>https://bit.ly/2BMlsWm
Abstract 14660: The Ascvd-10 Risk Estimate as a Predictor for True Resistant Hypertension in High-risk Overweight and Obese Hypertensive Subjects: A Cross-sectional Study
Authors: Faris I Haddadin, Claire Huang Lucas, Lingling Wu, Joshua Berookhim, Sananda Moctezuma, Alba Munoz Estrella, Karan Sud, Dipal Patel, Edgar Argulian
Journal: Circulation (2020)

Background: The estimates of 10-year risk for atherosclerotic disease (ASCVD-10) is applicable for individuals who are 40 to 79 years old without prior cardiovascular disease. While multiple components of the risk estimator are shared risk factors for many cardiovascular diseases, the ASCVD-10 does not consider the BMI value and limited studies examined the relationship between the ASCVD-10 risk score and resistant hypertension (RH). Methods: This is a cross-sectional study based on an out-patient primary care practice conducted between Oct 2017 to Oct 2018. Subjects with hypertension with either high-risk overweight (BMI ≥27 &amp; ≤29.9 kg/m2 plus ≥1 obesity-related comorbid conditions) and subjects with obesity (BMI ≥30 kg/m2) were included. Subjects with prior ASCVD were excluded. Apparent treatment-resistant hypertension (ATRH) detected with an average of two blood pressure (BP) readings at the office was confirmed with home BP measurement to exclude pseudoresistance and verify true resistant hypertension (TRH). BP cutoff of &gt;130/80 mmHg was used. Multivariate logistic regression adjusted for significantly different baseline variables among subjects with TRH vs non-TRH was used to examine the performance of ASCVD-10 in predicting TRH. Variables that are part of the ASCVD-10 score were excluded from the adjustment. Results: We identified 595 eligible subjects. Mean age was 60.4 years and 381 (64.1%) were females. ATRH was detected in 69 subjects but only 35 subjects had TRH after home BP measurement confirmation. Subjects with TRH compared to non-TRH were more likely to be of black race (51.4% vs 33.1%, p=0.022), to have chronic kidney disease (34.2% vs 11.3%, p &lt;0.001), higher mean BMI (36.9 vs 33.1 kg/m2, p &lt;0.001), diastolic heart failure (42.9% vs 12.5%, p &lt;0.001), dyslipidemia (60% vs 41.9%, p=0.037) and diabetes mellitus (71.4% vs 36.8%, p &lt;0.001). After adjustment to the variables mentioned previously that are not part of the ASCVD-10 risk calculator components, a higher ASCVD-10 score predicted the presence of TRH (OR 1.04 for each 1% of the ASCVD-10 score, 95% CI 1.01-1.07, p=0.039). Conclusion: The ASCVD-10 risk score can possibly be used as a predictor for the risk of having or developing RH in subjects with obesity or high-risk overweight.