tbuckley/cabot-search huggingface dataset:
Abstract 372: Regional Cerebral Saturation in a Swine Model of Goal-directed Resuscitation of Prolonged Ventricular Fibrillation Cardiac Arrest
Authors: Cornelia Genbrugge, David D Salcido, Allison C Koller, Caelie Kern, James J Menegazzi
Journal: Circulation (2020)

Introduction: The characteristics and limitations of near-infrared spectroscopy (NIRS) measurement of regional cerebral saturation (rSO2) for reflecting key moment-to-moment physiological changes needed to guide cardiopulmonary resuscitation (CPR) have yet to be fully determined. Objective: Examine the impact of NIRS sensor placement and resuscitation process variation on rSO2 measurements during prolonged cardiac arrest. Methods: Thirty mixed-breed domestic pigs (mean weight: 25.0kg+/-2.0) were sedated (ketamine / xylazine), anesthetized (fentanyl), paralyzed (vecuronium) and mechanically ventilated. Micromanometer pressure transducers were placed in the aorta and right atrium via femoral cutdown to measure central pressures, including mean arterial pressure (MAP) and coronary perfusion pressure (CPP). Two NIRS sensors were placed on the cranium: one on the skin surface and one on the bare skull. Ventricular fibrillation was induced electrically and untreated for 8 minutes followed by CPR. Initial BLS phase: 4 minutes of CPR at 100 compressions per minute (CPM) and 2 inches depth with manual ventilations (30:2). Randomized ALS phase: CPR with a pressor-titrated (Group A) or a compression rate/depth-titrated (Group B) strategy targeting 25mmHg CPP. Group A animals received pressor doses q1min and fixed rate/depth CPR. Group B animals received increasing rates and depth of CPR with epinephrine q3min. Defibrillation was attempted at 6min CPR q2min. rSO2 was compared between skin and skull across phases of resuscitation with t-tests and generalized estimating equations (GEE). Results: Mean skin and skull rSO2 differed marginally overall (63.8 vs 62.0, p &lt; 0.001), at baseline (69.9 vs 64.9, p &lt; 0.001), during BLS CPR (56.9 vs 48.7, p &lt; 0.001), during ALS CPR (59.5 vs 51.0, p &lt; 0.001), and following ROSC (70.0 vs 60.5, p&lt;0.001). rSO2 measured on either skull or skin both varied throughout phases of the experiment but not between CPR groups. In GEE models, rSO2 measured on skin or skull was not associated with MAP at baseline, but was directly associated during BLS (coef 0.13; p&lt;0.001) &amp; ALS CPR (coef 0.09; p&lt;0.001), and after ROSC (coef 0.02; p=0.017). Conclusion: rSO2 measures differ between skin and skull though both correlate with MAP.
Association Between Low-Dose Aspirin Use and Colorectal Cancer Incidence in Taiwan
Authors: Hui-Min Diana Lin, Pareen Vora, Montse Soriano-Gabarró, K. Arnold Chan
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Population-based East Asian data have corroborated reports from non-Asian settings on the association between low-dose aspirin and a lower risk of colorectal cancer (CRC). <h3>Objective</h3> To evaluate the association between duration and recency of low-dose aspirin use and CRC risk. <h3>Design, Setting, and Participants</h3> This nested case-control study included individuals who initiated aspirin use and matched individuals who did not use aspirin. Data were collected from Taiwan National Health Insurance and Taiwan Cancer Registry from 2000 through 2015. CRC cases were age- and sex-matched in a 1:4 ratio with individuals in a control group, identified from a cohort of individuals who used and did not use aspirin through risk-set sampling. Data analysis was conducted from June 2018 to July 2019. <h3>Exposures</h3> Low-dose aspirin use was defined as receiving less than 150 mg per day, whereas 100 mg/d was most commonly used. Based on duration and recency of low-dose aspirin use between cohort entry (initiation date of low-dose aspirin for aspirin use group or randomly assigned date for those who did not use aspirin) and index date (CRC diagnosis date for individuals in the case group and the diagnosis date for the 4 corresponding matched individuals in the control group), the 3 following mutually exclusive exposure groups served as the basis for analysis: (1) long-term current low-dose aspirin use, (2) episodic low-dose aspirin use, and (3) no low-dose aspirin use (the reference group). <h3>Main Outcomes and Measures</h3> CRC risk among the 3 exposure groups. <h3>Results</h3> Among 4 710 504 individuals (2 747 830 [51.7%] men; median [interquartile range] age at cohort entry in initiator group, 61 [52-71] years; median [interquartile range] age at cohort entry in nonuse group, 59 [51-68] years), 79 095 CRC cases (1.7% of study cohort) were identified. Compared with no low-dose aspirin use, the adjusted odds ratio (OR) for long-term current low-dose aspirin use and CRC risk was 0.89 (95% CI, 0.85-0.93); for episodic use, 0.88 (95% CI, 0.86-0.89). Adjusted ORs of 0.69 (95% CI, 0.63-0.76) and 0.64 (95% CI, 0.61-0.67) were observed for long-term current use and episodic low-dose aspirin use within the subcohort of individuals who initiated low-dose aspirin between age 40 and 59 years. <h3>Conclusions and Relevance</h3> In this study, low-dose aspirin use was associated with 11% lower CRC risk in an East Asian population, and this association was larger when low-dose aspirin use started before age 60 years.
Abstract 15681: Reduced Left Atrial Strain is Associated With the Development of Atrial Arrhythmias in Hospitalized Patients With COVID-19
Authors: Erin Goerlich, Anum S Minhas, Andreas S Barth, Katherine C Wu, Allison G Hays
Journal: Circulation (2020)

Introduction: Coronavirus Disease 2019 (COVID-19) is a pandemic with frequent cardiovascular (CV) complications, including cardiac arrhythmias. However, little is known about contributing factors to the development of new atrial tachyarrhythmias (ATs) in the inpatient setting. Left atrial strain (LAS) is a novel transthoracic echocardiography (TTE) measure of LA myocardial deformation and predicts arrhythmias. We aimed to compare clinical and echocardiographic variables including LAS in hospitalized patients with COVID-19 who developed new ATs compared to matched controls without arrhythmias. Methods: We retrospectively studied 42 patients hospitalized with COVID-19 who underwent clinical TTE. During admission, 20 patients without prior arrhythmia developed new ATs (including sustained atrial fibrillation/flutter/tachycardia, and undifferentiated supraventricular tachycardia) (cases) and were compared to 22 age and sex-matched COVID-19 patients without arrhythmias (controls). TTEs were analyzed for reservoir (peak longitudinal) LAS using 2D-speckle tracking and LA ejection fraction (LAEF) offline using TomTec software. Comparisons were made using Chi-square and t-tests as appropriate. Results: Mean age was 65±14 years, and 40% were women. There were no significant differences in CV risk factors, BMI, troponin or peak inflammatory markers between cases and controls. LAS was overall lower than normal and significantly lower in cases compared to controls (23.5±7.5% vs 31.0±6.0% respectively, P =0.001; Fig 1). There were no significant differences in left ventricular (LV) ejection fraction (LVEF), LV global longitudinal strain (GLS), LAEF, shock or death. Conclusions: COVID-19 patients who developed new ATs have lower LAS on TTE than patients without atrial arrhythmias. LAS may be a sensitive marker for identifying patients with COVID-19 at risk for ATs compared to LVEF, LV GLS, and LAEF. Larger confirmatory studies are warranted.
Intracellular β <sub>1</sub> -Adrenergic Receptors and Organic Cation Transporter 3 Mediate Phospholamban Phosphorylation to Enhance Cardiac Contractility
Authors: Ying Wang, Qian Shi, Minghui Li, Meimi Zhao, Raghavender Reddy Gopireddy, Jian-Peng Teoh, Bing Xu, Chaoqun Zhu, Kyle E. Ireton, Sanghavi Srinivasan, Shaoliang Chen, Paul J. Gasser, Julie Bossuyt, Johannes W. Hell, Donald M. Bers, Yang K. Xiang
Journal: Circulation Research (2020)

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Abstract 14592: Pregnancy Loss and Cardiovascular Disease Risk Factors in Early Adulthood: Preliminary Findings From Add Health
Authors: Yamnia I Cortes, Shuo Zhang, Diane C Berry, Jon Hussey
Journal: Circulation (2020)

Introduction: Pregnancy loss, including miscarriage and stillbirth, affect 15-20% of pregnancies in the United States annually. Accumulating evidence suggests that pregnancy loss is associated with greater cardiovascular disease (CVD) burden later in life. However, associations between pregnancy loss and CVD risk factors in early adulthood (age&lt;35 years) have not been assessed. Objective: To examine associations between pregnancy loss and CVD risk factors in early adulthood. Methods: We conducted a secondary data analysis using the public-use data set for Wave IV (2007-2009) of the National Longitudinal Study of Adolescent to Adult Health (Add Health). Our sample consisted of women, ages 24-32 years, with a previous pregnancy who completed biological data collection (n=2,968). Pregnancy loss was assessed as any history of miscarriage or stillbirth; and as none, one, or recurrent (≥2) pregnancy loss. Dependent variables included physical measures and blood specimens: body mass index (BMI), blood pressure, diabetes status, and dyslipidemia. Associations between pregnancy loss and each CVD risk factor were tested using linear (for BMI) and logistic regression adjusting for sociodemographic factors, parity, pre-pregnancy BMI, smoking during pregnancy, and depression. Results: Six hundred and ninety-three women (23%) reported a pregnancy loss, of which 21% reported recurrent pregnancy loss. Women with all live births were more likely to identify as non-Hispanic White (73%) and report a higher annual income. After adjusting for sociodemographics (age, race/ethnicity, education, income), pregnancy loss was associated with a greater BMI (ß=0.90; SE,0.39). In fully-adjusted models, women with recurrent pregnancy loss were more likely to have hypertension (AOR, 2.50; 95%CI, 1.04-5.96) and prediabetes (AOR, 1.93; 95%CI. 1.11-3.37) than women with all live births; the association was non-significant for women with one pregnancy loss. Conclusions: Pregnancy loss is associated with a more adverse CVD risk factor profile in early adulthood. Findings suggest the need for CVD risk assessment in young women with a prior pregnancy loss. Further research is necessary to identify underlying risk factors of pregnancy loss that may predispose women to CVD.
Treatment of persistent pain.
Authors: C. E. Pither
Journal: BMJ (1989)

annually.Only a few months ago the international cosmetics firms Avon and Revlon announced that they had found ways to ensure the safety of their products without animal experi- mentation.This was a response to years of pressure from the animal liberation group.It will save thousands of animals every year from painful, often lethal, tests.2Opposition to animal experimentation shows every sign of being with us for many years to come, since its philosophical foundation is clear and difficult to gainsay.Among scientists in the United States, where standards of regulation for animal experimentation lag far behind even those in Britain, there are signs of a reflex defensiveness which can lead only to polarisation and increasing hostility between experimenters and the animal liberation movement.3Doctors and scientists in Britain should resist this tendency to overrespond.Instead they should look for ways in which they can make a radical break with a past in which animal experimentation has been accepted with far too little questioning.
Abstract 16040: High-risk Percutaneous Coronary Intervention Without Mechanical Circulatory Support in Acute Coronary Syndrome
Authors: Nauman Khalid, Hasan Javed, Cheng Zhang, Corey Shea, Evan Shlofmitz, Yuefeng Chen, Anees Musallam, Brian C Case, Charan Yerasi, Brian Forrestal, Chava Chezar Azerrad, Toby Rogers, Hayder Hashim, itsik ben-dor, Nelson L Bernardo, Lowell F Satler, Ron Waksman
Journal: Circulation (2020)

Background: Use of mechanical circulatory support (MCS) for high-risk percutaneous coronary intervention (HRPCI) remains controversial with lack of randomized evidence and associated complication risks from these devices. We investigated whether performing HRPCI without elective MCS in patients with acute coronary syndrome (ACS) is safe and feasible. Methods: A single-center, retrospective analysis was done for patients presenting with ACS meeting HRPCI criteria (defined by Interventional Council of American College of Cardiology) including unprotected left main disease, last remaining conduit, left ventricular ejection fraction&lt;35%, 3-vessel coronary artery disease, severe aortic stenosis or severe mitral regurgitation. Clinical, procedural, major in-hospital and 30-days cardiovascular outcomes were assessed. Results: From 2003-2018, 1992 patients (2887 lesions) with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI) and 920 patients (1328 lesions) with ST-segment elevation myocardial infarction (STEMI) underwent HRPCI. The study population had 64.8% men and 52.9% Caucasians in UA/NSTEMI-group and 64.3% men and 53.7% Caucasians in STEMI-group. Mean age for UA/NSTEMI and STEMI patients were 68.6+/-12.69 and 64.52+/-13.54 years respectively. Procedural success was achieved in 96.5% of UA/NSTEMI and 97.9% of STEMI patients. In-hospital and 30-day all-cause mortality was 2.1% for UA/NSTEMI and 4.7% for STEMI patients. Bailout MCS was required in 2.4% of UA/NSTEMI and 9.9% of STEMI patients. Rates of major complications for UA/NSTEMI and STEMI were low, except for renal failure (Panel A). Panel B provides HRPCI criteria distribution. Conclusions: HRPCI without elective MCS is safe and feasible in majority of ACS patients challenging the current practices of professional societies. A randomized trial comparing unprotected vs. protected HRPCI for ACS patients is warranted to identify patients that would benefit from MCS.
Regulatory T cells engineered with TCR signaling–responsive IL-2 nanogels suppress alloimmunity in sites of antigen encounter
Authors: Siawosh K. Eskandari, Ina Sulkaj, Mariane B. Melo, Na Li, Hazim Allos, Juliano B. Alhaddad, Branislav Kollar, Thiago J. Borges, Arach S. Eskandari, Max A. Zinter, Songjie Cai, Jean Pierre Assaker, John Y. Choi, Basmah S. Al Dulaijan, Amr Mansouri, Yousef Haik, Bakhos A. Tannous, Willem J. van Son, Henri G. D. Leuvenink, Bohdan Pomahac, Leonardo V. Riella, Li Tang, Marc A. J. Seelen, Darrell J. Irvine, Jamil R. Azzi
Journal: Science Translational Medicine (2020)

Adoptive cell transfer of ex vivo expanded regulatory T cells (Tregs) has shown immense potential in animal models of auto- and alloimmunity. However, the effective translation of such Treg therapies to the clinic has been slow. Because Treg homeostasis is known to require continuous T cell receptor (TCR) ligation and exogenous interleukin-2 (IL-2), some investigators have explored the use of low-dose IL-2 injections to increase endogenous Treg responses. Systemic IL-2 immunotherapy, however, can also lead to the activation of cytotoxic T lymphocytes and natural killer cells, causing adverse therapeutic outcomes. Here, we describe a drug delivery platform, which can be engineered to autostimulate Tregs with IL-2 in response to TCR-dependent activation, and thus activate these cells in sites of antigen encounter. To this end, protein nanogels (NGs) were synthesized with cleavable bis(N-hydroxysuccinimide) cross-linkers and IL-2/Fc fusion (IL-2) proteins to form particles that release IL-2 under reducing conditions, as found at the surface of T cells receiving stimulation through the TCR. Tregs surface-conjugated with IL-2 NGs were found to have preferential, allograft-protective effects relative to unmodified Tregs or Tregs stimulated with systemic IL-2. We demonstrate that murine and human NG-modified Tregs carrying an IL-2 cargo perform better than conventional Tregs in suppressing alloimmunity in murine and humanized mouse allotransplantation models. In all, the technology presented in this study has the potential to improve Treg transfer therapy by enabling the regulated spatiotemporal provision of IL-2 to antigen-primed Tregs.
Implementation of Artifact Detection in Critical Care: A Methodological Review
Authors: Shermeen Nizami, James R. Green, Carolyn McGregor
Journal: IEEE Reviews in Biomedical Engineering (2013)

Artifact Detection (AD) techniques minimize the impact of artifacts on physiologic data acquired in Critical Care Units (CCU) by assessing quality of data prior to Clinical Event Detection (CED) and Parameter Derivation (PD). This methodological review introduces unique taxonomies to synthesize over 80 AD algorithms based on these six themes: (1) CCU; (2) Physiologic Data Source; (3) Harvested data; (4) Data Analysis; (5) Clinical Evaluation; and (6) Clinical Implementation. Review results show that most published algorithms: (a) are designed for one specific type of CCU; (b) are validated on data harvested only from one Original Equipment Manufacturer (OEM) monitor; (c) generate Signal Quality Indicators (SQI) that are not yet formalised for useful integration in clinical workflows; (d) operate either in standalone mode or coupled with CED or PD applications; (e) are rarely evaluated in real-time; and (f) are not implemented in clinical practice. In conclusion, it is recommended that AD algorithms conform to generic input and output interfaces with commonly defined data: (1) type; (2) frequency; (3) length; and (4) SQIs. This shall promote (a) reusability of algorithms across different CCU domains; (b) evaluation on different OEM monitor data; (c) fair comparison through formalised SQIs; (d) meaningful integration with other AD, CED and PD algorithms; and (e) real-time implementation in clinical workflows.
Ileal Ulcer Associated With a Large Bezoar Mimicking Malignancy on FDG PET/CT
Authors: Xia Ji, Hui Dong, Aisheng Dong
Journal: Clinical Nuclear Medicine (2020)

Abstract A 34-year-old woman presented with abdominal pain for 2 months. Abdominal CT revealed a large bezoar in the distal ileum with surrounding thickened ileal wall and enlarged mesentery lymph nodes. On FDG PET/CT, the thickened ileal wall and enlarged mesentery lymph nodes showed increased FDG uptake. Ileal malignancy with mesentery lymph node metastasis was suspected. The distal ileum and enlarged mesentery lymph nodes were removed. Benign ileal ulcer and mesentery reactive lymphoid hyperplasia were confirmed by histopathology.
A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis
Authors: Philip N. Newsome, Kristine Buchholtz, Kenneth Cusi, Martin Linder, Takeshi Okanoue, Vlad Ratziu, Arun J. Sanyal, Anne-Sophie Sejling, Stephen A. Harrison
Journal: New England Journal of Medicine (2020)

Nonalcoholic steatohepatitis (NASH) is a common disease that is associated with increased morbidity and mortality, but treatment options are limited. The efficacy and safety of the glucagon-like peptide-1 receptor agonist semaglutide in patients with NASH is not known.We conducted a 72-week, double-blind phase 2 trial involving patients with biopsy-confirmed NASH and liver fibrosis of stage F1, F2, or F3. Patients were randomly assigned, in a 3:3:3:1:1:1 ratio, to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg or corresponding placebo. The primary end point was resolution of NASH with no worsening of fibrosis. The confirmatory secondary end point was an improvement of at least one fibrosis stage with no worsening of NASH. The analyses of these end points were performed only in patients with stage F2 or F3 fibrosis; other analyses were performed in all the patients.In total, 320 patients (of whom 230 had stage F2 or F3 fibrosis) were randomly assigned to receive semaglutide at a dose of 0.1 mg (80 patients), 0.2 mg (78 patients), or 0.4 mg (82 patients) or to receive placebo (80 patients). The percentage of patients in whom NASH resolution was achieved with no worsening of fibrosis was 40% in the 0.1-mg group, 36% in the 0.2-mg group, 59% in the 0.4-mg group, and 17% in the placebo group (P<0.001 for semaglutide 0.4 mg vs. placebo). An improvement in fibrosis stage occurred in 43% of the patients in the 0.4-mg group and in 33% of the patients in the placebo group (P = 0.48). The mean percent weight loss was 13% in the 0.4-mg group and 1% in the placebo group. The incidence of nausea, constipation, and vomiting was higher in the 0.4-mg group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%). Malignant neoplasms were reported in 3 patients who received semaglutide (1%) and in no patients who received placebo. Overall, neoplasms (benign, malignant, or unspecified) were reported in 15% of the patients in the semaglutide groups and in 8% in the placebo group; no pattern of occurrence in specific organs was observed.This phase 2 trial involving patients with NASH showed that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution than placebo. However, the trial did not show a significant between-group difference in the percentage of patients with an improvement in fibrosis stage. (Funded by Novo Nordisk; ClinicalTrials.gov number, NCT02970942.).
Effect of Dapagliflozin on Clinical Outcomes in Patients With Chronic Kidney Disease, With and Without Cardiovascular Disease
Authors: John J.V. McMurray, David C. Wheeler, Bergur V. Stefánsson, Niels Jongs, Douwe Postmus, Ricardo Correa-Rotter, Glenn M. Chertow, Tom Greene, Claes Held, Fan-Fan Hou, Johannes F.E. Mann, Peter Rossing, C. David Sjöström, Roberto D. Toto, Anna Maria Langkilde, Hiddo J.L. Heerspink
Journal: Circulation (2020)

Dapagliflozin reduces the risk of end-stage renal disease in patients with chronic kidney disease. We examined the relative risk of cardiovascular and renal events in these patients and the effect of dapagliflozin on either type of event, taking account of history of cardiovascular disease. In the DAPA-CKD trial (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease), 4304 participants with chronic kidney disease were randomly assigned to dapagliflozin 10 mg once daily or placebo. The primary end point was a composite of sustained decline in estimated glomerular filtration rate ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The secondary end points were a kidney composite outcome (primary end point, minus cardiovascular death), the composite of hospitalization for heart failure or cardiovascular death, and all-cause death. In a prespecified subgroup analysis, we divided patients into primary and secondary prevention subgroups according to history of cardiovascular disease. Secondary prevention patients (n=1610; 37.4%) were older, were more often male, had a higher blood pressure and body mass index, and were more likely to have diabetes. Mean estimated glomerular filtration rate and median urinary albumin-to-creatinine ratio were similar in the primary and secondary prevention groups. The rates of adverse cardiovascular outcomes were higher in the secondary prevention group, but kidney failure occurred at the same rate in the primary and secondary prevention groups. Dapagliflozin reduced the risk of the primary composite outcome to a similar extent in both the primary (hazard ratio, 0.61 [95% CI, 0.48-0.78]) and secondary (0.61 [0.47-0.79]) prevention groups (P-interaction=0.90). This was also true for the composite of heart failure hospitalization or cardiovascular death (0.67 [0.40-1.13] versus 0.70 [0.52-0.94], respectively; P-interaction=0.88), and all-cause mortality (0.63 [0.41-0.98] versus 0.70 [0.51-0.95], respectively; P-interaction=0.71). Rates of adverse events were low overall and did not differ between patients with and without cardiovascular disease. Dapagliflozin reduced the risk of kidney failure, death from cardiovascular causes or hospitalization for heart failure, and prolonged survival in people with chronic kidney disease, with or without type 2 diabetes, independently of the presence of concomitant cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036150.