tbuckley/cabot-search huggingface dataset:
Association of Electronic Cigarette Use With Incident Respiratory Conditions Among US Adults From 2013 to 2018
Authors: Wubin Xie, Hasmeena Kathuria, Panagis Galiatsatos, Michael J. Blaha, Naomi M. Hamburg, Rose Marie Robertson, Aruni Bhatnagar, Emelia J. Benjamin, Andrew C. Stokes
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Generating robust and timely evidence about the respiratory health risks of electronic cigarettes (e-cigarettes) is critical for informing state and federal regulatory standards for product safety. <h3>Objective</h3> To examine the association of e-cigarette use with incident respiratory conditions, including chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, and asthma. <h3>Design, Setting, and Participants</h3> This prospective cohort study used data from the nationally representative cohort of US adults from the Population Assessment of Tobacco and Health (PATH) study, including wave 1 from 2013 to 2014, wave 2 from 2014 to 2015, wave 3 from 2015 to 2016, and wave 4 from 2016 to 2018. Individuals aged 18 years and older at baseline with no prevalent respiratory conditions were included in the analyses. Analyses were conducted from February to July 2020. <h3>Exposures</h3> e-Cigarette use was assessed by self-reported current use status (never, former, or current) at baseline. <h3>Main Outcomes and Measures</h3> Incident respiratory conditions, including COPD, emphysema, chronic bronchitis, and asthma, as well as a composite respiratory disease encompassing all 4 conditions. <h3>Results</h3> Among 21 618 respondents included in the analyses, 11 017 (491%) were men and 12 969 (65.2%) were non-Hispanic White. A total of 14 213 respondents were never e-cigarette users, 5076 respondents (11.6%) were former e-cigarette users, and 2329 respondents (5.2%) were current e-cigarette users. Adjusted for cigarette and other combustible tobacco product use, demographic characteristics, and chronic health conditions, there was an increased risk of respiratory disease among former e-cigarette uses (incidence rate ratio [IRR], 1.28; 95% CI, 1.09-1.50) and current e-cigarette users (IRR, 1.31; 95% CI, 1.08-1.59). Among respondents with good self-rated health, the IRR for former e-cigarette users was 1.21 (95%CI, 1.00-1.46) and the IRR for current e-cigarette users was 1.43 (95% CI, 1.14-1.79). For specific respiratory diseases among current e-cigarette users, the IRR was 1.33 (95% CI, 1.06-1.67) for chronic bronchitis, 1.69 (95% CI, 1.15-2.49) for emphysema, 1.57 (95% CI, 1.15-2.13) for COPD, and 1.31 (95% CI, 1.01-1.71) for asthma. <h3>Conclusions and Relevance</h3> This cohort study found that e-cigarette use was associated with an increased risk of developing respiratory disease independent of cigarette smoking. These findings add important evidence on the risk profile of novel tobacco products.
Abstract 17169: Endothelium-Specific Reduction in Mitochondrial ROS Induces Coronary Angiogenesis in Ischemic Myocardium via Activation of PI3k/Akt/ERG, ERK1/2, and Jag-1 Signaling
Authors: Rayane Brinck Teixeira, Melissa Pfeiffer, Catherine Karbasiafshar, Giana Blume Corssac, Nagib Ahsan, Frank W Sellke, Ruhul Abid
Journal: Circulation (2020)

Introduction: Global reduction in reactive oxygen species (ROS) failed to improve outcomes in cardiovascular disease patients. Recent reports suggest that subcellular, rather than global ROS, play a crucial role in endothelial cell (EC) health. To that end, we generated a novel transgenic mouse model that overexpresses mitochondrial antioxidant MnSOD in EC-specific manner (MnSODVE-OE). Hypothesis: We hypothesized that decreased EC mitochondrial-ROS will improve post-myocardial infarction (MI) cardiac function by inducing coronary angiogenesis in ischemic myocardium. Methods: MnSODVE mice were assigned to Tet-ON (control) or Tet-OFF (MnSODVE-OE) group. To turn off the transgene, Tetracycline (Tet) (2mg/kg) was added to the drinking water (Tet-ON), while Tet-OFF mice did not receive Tet. Both groups underwent left anterior descending coronary artery (LAD) ligation surgery to mimic acute MI. Echocardiography was done 28 days after LAD ligation. Capillaries, arteriole density, and proliferating ECs were measured in heart sections using anti-CD31, anti-αSMA, and anti-PCNA immunofluorescence. Western blot, proteomic and phosphoproteomic analyses of mouse heart ECs isolated from MnSODVE (Tet-ON and Tet-OFF) animals were performed to study modulation of signaling cascades. Results: MnSODVE-OE mice demonstrated improved cardiac function (EF and FS increased by 16±7.87% and 21.73±10.31%, respectively, p &lt;0.01), increase in capillary and arteriole densities by 4.13±4.10-fold, p&lt;0.05 and 5.48±3.51-fold, p&lt;0.001, respectively, and in EC proliferation by 1.46±0.80-fold, p &lt;0.01, suggesting de novo coronary angiogenesis. Western blots showed activation of Akt (80.46±3.95% increase in p-Akt/ t-Akt ratio, p&lt;0.05) and ERK1/2 (21.05±4.45% increase in p-ERK/ t-ERK 1/2 ratio, p&lt;0.05). Proteome and phosphoproteome analyses showed upregulation of mitochondrial complex I biogenesis, RNA metabolism, and upregulation of Notch-related proteins ERG and Jag-1 (p&lt;0.05). Student’s t-test was used for data analyses. Conclusions: Taken together, these results suggest that decreased mito-ROS in ECs improves post-MI cardiac function by inducing coronary angiogenesis through activation of PI3k/Akt/ERG, ERK1/2, and Jag-1 signaling.
Abstract 14626: Propofol and Dexmedetomidine Related Transient High-grade Symptomatic Av Block
Authors: Usama Talib, Lakshman Sneha, Anneris Estevez
Journal: Circulation (2020)

Introduction: Dexmedetomidine and propofol are both associated with risk of sinus bradycardia and hypotension. High grade AV block has rarely been reported with these medications. We present a case of high grade AV block (Mobitz II) in the setting of co administration of dexmedetomidine and propofol resulting in hypotension, that resolved with discontinuation of propofol. Case: 85 year old female with history significant for hypertension and CLL was admitted to the ICU with ARDS secondary to COVID-19 requiring mechanical ventilation. Along with management of ARDS, dexmedetomidine and propofol were administered for adequate sedation while trying to limit high dose of propofol. On day one of administration of the combination (16 mcg/kg/min propofol and 0.6 mcg/kg/hr dexmedetomidine), patient developed Mobitz II AV block associated with hypotension with systolic pressure in 60s. Propofol was discontinued and AV block and hypotension resolved. Patient continued to improve and was eventually extubated and transferred to the telemetry floor. Her telemetry during hospital course did not reveal any further high grade AV block and thus patient did not require placement of a pacemaker. Discussion: Optimizing sedation in intubated patients and knowledge of associated adverse effects is warranted to minimize mechanical ventilation time and prevent life threatening complications. Dexmedetomidine has been associated with a reduction in mechanical ventilation duration but an increased risk of bradycardia and hypotension as compared to midazolam and propofol. (1) Hypotension is common with propofol but sinus bradycardia and arrythmias have also been reported. (2) Rarely propofol can precipitate high grade AV block that can be life threatening if not promptly addressed. (3) Co administration of dexmedetomidine and propofol can be associated with exaggeration of individual side effects. Mindfulness of such adverse effects can not only help prevent life threatening complications but also decrease chances of unnecessary pacemaker placements. Conclusion: Propofol though associated with sinus bradycardia, may result in high grade AV block when co-administered with dexmedetomidine that is usually reversible with discontinuation of the offending drug.
Abstract 14260: Transcatheter Aortic Valve (tavr) Outcomes Among Hospitalizations for Coronary Artery Disease: An Insight From National Inpatient Sample 2016
Authors: Dinesh C Voruganti, Hafeez Hassan, Sushma Dugyala, Aman M Amanullah
Journal: Circulation (2020)

Background: Trans-catheter Aortic Valve Replacement (TAVR) is an increasingly sought option for aortic stenosis over the open-surgical treatment. Ongoing studies continue to investigate the outcomes of TAVR. However, the outcomes among Coronary Artery Disease (CAD) remain less explored. Aim: Evaluate the hospitalization outcomes for patients with TAVR with and without CAD. Methods: The National Inpatient Sample (NIS) 2016 was used to evaluate the outcomes among hospitalizations related to TAVR. Adult hospitalizations (age &gt;= 18) for TAVR was identified using the ICD 10 procedure code 02RF3. CAD was identified using the ICD 10 codes I25.10, I2511, I25110, I25111, I25118, I25119, I252, I255, and I256. Demographics, In-hospital mortality, Length of stay were abstracted using the variables mentioned in the database. The presence of cardiac tamponade, stroke, acute kidney injury, arrhythmias (AV block, Afib) was identified using Dx codes (ICD 10). All analysis was performed using SAS 9.4 software. Results: During the year 2016, there were a total of 40,000 TAVR related hospitalizations. CAD was present among 28200 hospitalizations. The mean age among both groups was almost identical to ~ 80 years. Among CAD, there were 39.91% females and among non-CAD females constituted 59.8%. No significant differences were noted for Length of stay among both groups (t-test P =0.0588). In-hospital mortality was higher among non-CAD group (2.84% vs. 1.43%, P &lt;0.0001). The prevalence of third-degree AV block was similar in both groups (9.65% vs. 9.66%, P=0.9615). Cardiac tamponade was higher among the non-CAD group (1.61% vs. 0.76%, P&gt;0.0001). Acute kidney injury was slightly higher in the CAD group (12.32% vs. 11.65%, P=0.0611). Atrial fibrillation was higher among the CAD group (18.33% vs. 16.95%, P=0.0010). Stroke was significantly higher among non-CAD group (0.13% vs. 0.04%, P =0.0008) Conclusion: CAD is present in about 70% of TAVR hospitalizations. Fewer females were present in the CAD group. Higher in-hospital mortality, stroke, and cardiac tamponade were noted in the non-CAD group, while AKI and AF were higher in the CAD group. Higher prevalence of death, stroke, and tamponade in the non-CAD group need further study.
Abstract 14620: LncExACT1 Acts as a Pivotal Switch Between Physiological and Pathological Cardiac Growth
Authors: Haobo Li, Lena E Trager, Xiaojun Liu, Margaret H Hastings, CHUNYANG XIAO, Guoping Li, Ashish Yeri, Rodosthenis Rodosthenous, Michael G Silverman, Saumya DAS, Amrut V Ambardekar, Michael R Bristow, Anthony Rosenzweig
Journal: Circulation (2020)

Rationale: Pathological hypertrophy commonly leads to heart failure (HF) and loss of cardiomyocytes, while physiological hypertrophy protects the heart and enhances cardiomyogenesis. The mechanisms underlying these differences remain unclear. While long noncoding RNAs (lncRNAs) are important in cardiac development and disease, their role in physiological hypertrophy is unknown. Objective: To investigate the role of lncRNAs in physiological hypertrophy. Methods and Results: Mice underwent voluntary wheel running for eight weeks or transverse aortic constriction (TAC) for two or ten weeks. RNAseq identified a novel set of lncRNAs altered in exercised hearts, which we termed l ong n on c oding Ex ercise- A ssociated C ardiac T ranscripts (lncExACTs). lncExACT1 was highly conserved and uniquely downregulated in exercised hearts but upregulated in pathological animal models and hearts from HF patients vs controls (1.8-fold; p &lt;0.001, N=24) as well as plasma from HF patients with reduced (2.9-fold; p =0.032, N=16) and preserved ejection fraction (3.4-fold; p =0.006, N=18). In mice, AAV9 lncExACT1 overexpression increased cardiac lncExACT1 7-fold at 16 weeks and increased heart (HW) and lung (LW) weight relative to tibial length (TL), reduced fractional shortening (FS) and increased relative wall thickness (RWT) ( p &lt;0.05 for all). These changes were associated with a pathological gene expression pattern. In contrast, antisense lncExACT1 inhibition reduced cardiac expression 2-fold at 2 weeks and increased HW/TL without an increase in LW/TL, improved cardiac function, and increased RWT ( p &lt;0.05 for all). LncExACT1 inhibition induced a physiological gene expression pattern and increased markers of cardiomyogenesis. LncExACT1 inhibition reduced TAC-induced HW/TL and fibrosis, while increasing FS ( p &lt;0.05 for all). Mechanistic studies revealed that lncExACT1 works by binding miR-222 and as a novel regulator of Hippo/Yap1 signaling through modulation of dachsous cadherin-related 2. Conclusions: lncExACT1 acts as a master switch toggling the heart between physiological and pathological growth and provides a potentially tractable therapeutic target for harnessing the beneficial effects of exercise.
France’s drug regulator is indicted for manslaughter over sodium valproate birth defects
Authors: Owen Dyer
Journal: BMJ (2020)

French judges have indicted the country’s drug regulator, the National Agency for Medicine and Health Product Safety (ANSM), for “injuries and involuntary homicides through negligence,” accusing it of failing to do enough to keep pregnant women from receiving the antiepileptic drug sodium valproate.

Some 17 000 to 30 000 children are estimated to have experienced congenital disease, developmental delay, autism, or behavioural disorders as a result of sodium valproate given to …
Bioscaffolds embedded with regulatory modules for cell growth and tissue formation: A review
Authors: Pengju Wang, Yazhou Sun, Xiaoquan Shi, Huixing Shen, Haohao Ning, Haitao Liu
Journal: Bioactive Materials (2020)

The demand for artificial organs has greatly increased because of various aging-associated diseases and the wide need for organ transplants. A recent trend in tissue engineering is the precise reconstruction of tissues by the growth of cells adhering to bioscaffolds, which are three-dimensional (3D) structures that guide tissue and organ formation. Bioscaffolds used to fabricate bionic tissues should be able to not only guide cell growth but also regulate cell behaviors. Common regulation methods include biophysical and biochemical stimulations. Biophysical stimulation cues include matrix hardness, external stress and strain, surface topology, and electromagnetic field and concentration, whereas biochemical stimulation cues include growth factors, proteins, kinases, and magnetic nanoparticles. This review discusses bioink preparation, 3D bioprinting (including extrusion-based, inkjet, and ultraviolet-assisted 3D bioprinting), and regulation of cell behaviors. In particular, it provides an overview of state-of-the-art methods and devices for regulating cell growth and tissue formation and the effects of biophysical and biochemical stimulations on cell behaviors. In addition, the fabrication of bioscaffolds embedded with regulatory modules for biomimetic tissue preparation is explained. Finally, challenges in cell growth regulation and future research directions are presented.
Enhanced IL-9 secretion by p66Shc-deficient CLL cells modulates the chemokine landscape of the stromal microenvironment
Authors: Laura Patrussi, Noemi Manganaro, Nagaja Capitani, Cristina Ulivieri, Vanessa Tatangelo, Francesca Libonati, Francesca Finetti, Federica Frezzato, Andrea Visentin, Mario Milco D’Elios, Livio Trentin, Gianpietro Semenzato, Cosima T. Baldari
Journal: Blood (2020)
Abstract 16244: Point of Care Ultrasound of the Jugular Venous Pulse in the Upright Position (u <sup>2</sup> Jvp) Predicts Elevated Right Atrial Pressure and Pulmonary Capillary Wedge Pressure on Right Heart Catheterization in Obese and Non-obese Patients
Authors: Libo Wang, Jonathan Harrison, Elizabeth Dranow, Lillian Khor
Journal: Circulation (2020)

Introduction: Accurate intravascular volume status assessment is central to heart failure management, but current non-invasive bedside techniques remain a challenge. The visual inspection of jugular venous pulsation (JVP) in a reclined position and measuring its height from the sternal notch has been used as a surrogate for right atrial pressure (RAP). There are no studies on the predictive value of a visible internal jugular vein (IJV) in the upright position (U 2 JVP). Hypothesis: Point of care ultrasound (POCUS) for volume assessment in the upright position is predictive of clinically significant hypervolemia. Methods: Adult patients undergoing right heart catheterization (RHC) were enrolled prior for IJV imaging with point of care ultrasound (POCUS) device, Butterfly iQ™. The IJV and its size in comparison to the carotid artery was identified on ultrasound with the patient upright. Elevated RAP and PCWP was present if the IJV was still visible and not collapsed throughout the entirety of the respiratory cycle. Valsalva was used to confirm the position of a collapsed IJV. Results: 72 participants underwent U 2 JVP assessment on the same day prior to RHC. Average BMI was 31.9 kg/m2. The area under the curve (AUC) of U 2 JVP predicting RAP greater than 10 mmHg and PCWP of 15 mmhg or higher on RHC was 0.78 (95% CI 0.66-0.9, p&lt;0.001), with AUC of 0.86 and 0.74 for non-obese and obese subgroups respectively, p= 0.38. The finding of a visible U 2 JVP in the upright position was 70.6 % sensitive and 85.5 % specific with a negative predictive value of 90.4% for identifying both RAP greater than 10 mmHg and PCWP equal or greater than 15 mmHg. Conclusions: The U 2 JVP is novel and pragmatic bed-side approach to the assessment of clinically significant elevated intra-cardiac pressures in our increasingly obese heart failure population.
Abstract 16319: Large Weight Loss Improves Left Ventricular Geometry but Not Myocardial Function 6 Months After Bariatric Surgery (the Fatwest Study)
Authors: Lisa M Grymyr, Saied Nadirpour, Eva Gerdts, Johannes Hjertaas, Bjørn Nedrebø, Knut Matre, Dana Cramariuc
Journal: Circulation (2020)

Background: Bariatric surgery causes rapid and large weight loss and improves cardiovascular risk profile, yet the effect on left ventricular (LV) systolic function has been less explored. Methods: In the prospective FatWest (Bariatric Surgery on the West Coast of Norway) study 98 severely obese patients (44±10 years, 72% women, preoperative body mass index [BMI] 41.8±4.8 kg/m 2 , 36% with hypertension) underwent echocardiography before and 5.9 months after gastric bypass surgery. We assessed changes in LV geometry and systolic function by biplane ejection fraction (EF), midwall shortening (MWS) and mitral annular systolic velocity (s′). LV hypertrophy was defined based on LV mass/height 2.7 . Myocardial O 2 demand was derived from the LV mass-wall stress-heart rate product. Results: Patients experienced on average a 10 kg/m 2 reduction in BMI, and a significant drop in heart rate and blood pressure (all p&lt;0.001). LV mass (-12 g) and myocardial O 2 demand improved significantly (all p&lt;0.01). However, LV EF (60 vs. 61%), s’ (8.5 vs. 8.3cm/s) and MWS (16.1 vs. 15.7%) remained unchanged, and 45% of patients had low MWS 6 months after surgery (Figure). In multivariable regression analyses, LV mass reduction was predicted by weight loss and female sex, independent of changes in blood pressure and heart rate (R 2 0.24, p &lt;0.001) while lower myocardial O2 demand was explained by improvement in its three components, particularly lower LV end-systolic wall stress (R 2 0.9, p&lt;0.001). Conclusion: In severely obese patients with normal EF, bariatric surgery induces a significant reduction in BMI, LV mass and myocardial O 2 demand, but no improvement in LV myocardial systolic function 6 months after surgery.
Abstract 15071: Effect of Percutaneous Coronary Intervention on Death and Myocardial Infarction in Patients Withstable Coronary Artery Disease and Inducible Ischemia
Authors: Qais Radaideh, Mohammed Osman, Babikir Kheiri, Ahmad Al-Abdouh, mahmoud Barbarawi, Ghassan Bachuwa, Jacqueline E Tamis-Holland, Nicolas W Shammas, William E Boden
Journal: Circulation (2020)

Introduction: There has been a continuous debate about the survival benefit of percutaneous coronary intervention (PCI) for the management of patients with stable coronary artery disease (CAD) and moderate to severe ischemia. To address this, we performed a meta-analysis of RCTs comparing PCI plus MT vs. MT alone in stable CAD patients to evaluate endpoints of all-cause mortality, cardiovascular (CV) mortality, and MI in a larger cohort of patients with objective evidence of myocardial ischemia. Methods: An electronic database search was conducted for RCTs that compared PCI on top of MT versus MT alone. A random effects model was used to calculate relative risk (RR) and 95% confidence intervals (CIs). Results: A total of 7 RCTs with 10,043 patients with a mean age of 62.54 ± 1.56 years and a median follow up of 3.9 years were identified. Among patients with (CAD) and moderate to severe ischemia by stress testing, PCI didn’t show any benefit for the primary outcome of all-cause mortality compared to MT(RR = 0.85; 95% CI 0.646-1.12; p= 0.639). There was also no benefit in cardiovascular (CV) death (RR = 0.88 ; 95% CI 0.71-1.09; p =0.18) or myocardial infarction (MI) (RR = 0.271 ; 95% CI 0.782-1.087; P =0.327) in the PCI group as compared to MT. Conclusions: Among patients with (CAD) and evidence of moderate to severe ischemia by stress testing, PCI on top of MT appears to add no mortality benefit as compared to with MT alone.
Abstract 14553: Mitochondrial Calcium Uptake via Mitochondrial Calcium Uniporter Suppress Ventricular Arrhythmia in the Ischemic Heart Failure Mice
Authors: Hikaru Hagiwara, Masaya Watanabe, Yoichiro Fujioka,, Taro Koya, Motoki Nakao, Yumi Takahashi, Rui Kamada, Yusuke Ohba, Toshihisa Anzai
Journal: Circulation (2020)

Background: Delayed after depolarization by calcium (Ca 2+ ) leak from sarcoplasmic reticulum (SR) via Ryanodine receptor is one of the causes of ventricular arrhythmias (VAs) in heart failure (HF). Ca 2+ uptake into mitochondria via mitochondrial calcium uniporter (MCU) is participated in Ca 2+ handling, but the relationship between VAs in HF and Ca 2+ uptake into mitochondria is unclear. Purpose: We sought to investigate whether increased Ca 2+ uptake into mitochondria via MCU reduces diastolic Ca 2+ leak and suppresses VAs in ischemic HF mice. Methods: Ten-week-old male C57BL/6J mice were divided into 2 groups; sham operation mice (Sham) or HF mice (HF) in which myocardial infarction was induced by left coronary artery ligation. After 4-6 weeks, cardiomyocyte or mitochondria were isolated respectively from the myocardium of Sham and the non-infarct myocardium of HF. Ca 2+ waves (CaWs) were measured on an epifluorescence microscopy. Calcium transients and calcium sparks were measured on a confocal microscope in linescan mode. Mitochondrial Ca 2+ uptake were measured by estimating the extra-mitochondrial Ca 2+ reduction with Fluo-5N on a spectrofluoro-photometer. VAs was induced in the Langendorff perfused hearts. Left ventricular (LV) pressure was measured using a microtip transducer catheter . Results: HF mice showed left ventricular dysfunction and increased heart and lung weights compared to Sham. Kaempferol, a MCU activator, increased mitochondrial Ca 2+ uptake in the isolated mitochondria both in Sham and HF. CaWs and Ca spark frequency in the presence of isoproterenol was attenuated by 10 μM Kaempferol. Kaempferol did not show significant changes in Ca 2+ transient amplitude, however increased the time to 50% decay significantly. The incidence of induced VAs was suppressed by Kaempferol. In vivo measurements, intravenous administration of Kaempferol (5mg/kg) did not show significant changes in hemodynamic parameters in HF mice. Conclusions: Ca 2+ uptake into mitochondria via MCU suppresses VAs in HF. Despite the adverse influence of the traditional antiarrhythmic drugs for HF condition, a novel strategy that promotes Ca 2+ uptake into mitochondria might be a potential therapeutic approach for VA treatment in HF patients.