tbuckley/cabot-search huggingface dataset:
Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis
Authors: Tamara Pérez-Jeldres, Manuel Alvarez-Lobos, Jesús Rivera-Nieves
Journal: Drugs (2021)

Sphingosine-1-phosphate (S1P) is a bioactive lipid metabolite that exerts its actions by engaging 5 G-protein-coupled receptors (S1PR1-S1PR5). S1P receptors are involved in several cellular and physiological events, including lymphocyte/hematopoietic cell trafficking. An S1P gradient (low in tissues, high in blood), maintained by synthetic and degradative enzymes, regulates lymphocyte trafficking. Because lymphocytes live long (which is critical for adaptive immunity) and recirculate thousands of times, the S1P-S1PR pathway is involved in the pathogenesis of immune-mediated diseases. The S1PR1 modulators lead to receptor internalization, subsequent ubiquitination, and proteasome degradation, which renders lymphocytes incapable of following the S1P gradient and prevents their access to inflammation sites. These drugs might also block lymphocyte egress from lymph nodes by inhibiting transendothelial migration. Targeting S1PRs as a therapeutic strategy was first employed for multiple sclerosis (MS), and four S1P modulators (fingolimod, siponimod, ozanimod, and ponesimod) are currently approved for its treatment. New S1PR modulators are under clinical development for MS, and their uses are being evaluated to treat other immune-mediated diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis. A clinical trial in patients with COVID-19 treated with ozanimod is ongoing. Ozanimod and etrasimod have shown promising results in IBD; while in phase 2 clinical trials, ponesimod has shown improvement in 77% of the patients with psoriasis. Cenerimod and amiselimod have been tested in SLE patients. Fingolimod, etrasimod, and IMMH001 have shown efficacy in RA preclinical studies. Concerns relating to S1PR modulators are leukopenia, anemia, transaminase elevation, macular edema, teratogenicity, pulmonary disorders, infections, and cardiovascular events. Furthermore, S1PR modulators exhibit different pharmacokinetics; a well-established first-dose event associated with S1PR modulators can be mitigated by gradual up-titration. In conclusion, S1P modulators represent a novel and promising therapeutic strategy for immune-mediated diseases.
Abstract MP56: Specific Nutrients Associate Better Than Dietary Approaches To Stop Hypertension Score With Adult Cardiovascular Risk Factors Over 25 Years: The Princeton Lipid Study
Authors: Leah Beck, Jessica G Woo
Journal: Circulation (2021)

Introduction: Diet is a contributing factor to cardiovascular disease risk and is the basis for dietary guidelines such as the Dietary Approaches to Stop Hypertension (DASH) eating plan. However, little is known about how childhood dietary habits are maintained into adulthood or how child to adult, or adult to adult changes in diet may influence disease risk. Hypothesis: Our goal was to examine the relationship between diet quality, cardiovascular disease risk, and changes in diet quality over time. We hypothesized that diets lacking in nutrients for ideal cardiovascular health would be conserved from childhood to adulthood. This would be reflected as increased rates of hypertension, diabetes, dyslipidemia, and obesity. Methods: Diet data was analyzed from the Princeton Lipid Research study (24 hour recall in the 70’s; Block Food Frequency Questionnaire in 1998). Diet quality at each visit was assessed as a ranking of 15 different macro/micronutrients and by a modified DASH index based on 9 nutrient targets and adapted for children. Outcomes in both childhood and adulthood included: glucose intolerance/diabetes, high blood pressure/hypertension, dyslipidemia/hyperlipidemia, and obesity. Linear and logistic regression models were performed with adjustment for age, race, sex, BMI, occupation and education of self or head of household, and marital status. Results: Analysis included 221 total individuals in Generation 1 (parents at initial visit; 39% (86 of 221) male, mean age 38.9 ± 6.5 followed up at 66.6 ± 6.6 years) and 606 individuals in Generation 2 (45% (271 of 606) male, mean age 11.9 ± 3.23 at initial visit and 38.5 ± 3.6 years at follow up). Generation 1 increased in total DASH score from initial visit to follow-up (1.74 ± 0.95 → 2.11 ± 1.33) while Generation 2 decreased (1.91 ± 0.80 → 1.64 ± 1.13). Overall DASH score was not significantly associated with baseline or follow up outcomes in childhood or adulthood. However, in Generation 2 at follow-up, fiber, potassium, iron, niacin, and vitamin A were associated with hypertension; fiber and sugar with hyperlipidemia; cholesterol with obesity; and saturated fat with diabetes in Generation 1. Conclusions: Overall diet quality was poor in both generations and changed little over time. In conclusion, no relationship was detected between DASH diet accordance and disease outcomes, however certain nutrients are associated with higher cardiovascular disease risk.
Assessing the Risk of SARS-CoV-2 Transmission via Surgical Electrocautery Plume
Authors: Leigh J. Sowerby, Anthony C. Nichols, Richard Gibson, Doron D. Sommer, Corey Moore, Douglas D. Fraser, Eric Arts
Journal: JAMA Surgery (2021)

This quality improvement study used a nonhuman subject research approach to examine whether SARS-CoV-2 from aerosolized virus is present in and potentially transmissible from a electrocautery plume in surgery.
Neuromatch Academy: Teaching Computational Neuroscience with Global Accessibility
Authors: Tara van Viegen, Athena Akrami, Kathryn Bonnen, Eric DeWitt, Alexandre Hyafil, Helena Ledmyr, Grace W. Lindsay, Patrick Mineault, John D. Murray, Xaq Pitkow, Aina Puce, Madineh Sedigh-Sarvestani, Carsen Stringer, Titipat Achakulvisut, Elnaz Alikarami, Melvin Selim Atay, Eleanor Batty, Jeffrey C. Erlich, Byron V. Galbraith, Yueqi Guo, Ashley L. Juavinett, Matthew R. Krause, Songting Li, Marius Pachitariu, Elizabeth Straley, Davide Valeriani, Emma Vaughan, Maryam Vaziri-Pashkam, Michael L. Waskom, Gunnar Blohm, Konrad Kording, Paul Schrater, Brad Wyble, Sean Escola, Megan A.K. Peters
Journal: Trends in Cognitive Sciences (2021)
Abstract 17400: Using Electronic Health Records for Predicting Hospitalization of COVID-19 Patients in Massachusetts
Authors: Hesam Dashti, Elise C. Roche, David W. Bates, Nancy R Cook, Samia Mora, Olga Demler
Journal: Circulation (2020)

Introduction: The electronic health record (EHR) provides a platform to design models for predicting the severity of illness in COVID-19 patients. We used the Mass General Brigham (MGB) EHR that contains records mostly from greater Boston, Massachusetts. The objective of this research is to predict risk of hospitalization in patients who tested positive for COVID-19. Methods: Between 01/01/2020 to 05/11/2020 the MGB EHR contained 8,213 laboratory- confirmed COVID-19 patients. We queried the EHR for medical records of these patients from 12/31/2015 to 05/11/2020. To examine pre-COVID-19 medical history, we considered latest records prior to 21 days before the first COVID-19 positive test. To consider patients who were hospitalized before their test results become available, we analyzed admission records from 7 days before the first positive test. We used patients with no missing medical records to construct our dataset (N=2,783) and conducted a forward feature selection on 51 variables to identify markers that minimized the Akaike information criterion for predicting hospitalization. These markers then were used to train a generalized linear model on a subset of the dataset of MGB non-employees (N=2,367; 56% hospitalized). The trained predictive model was then tested on the remaining subset of the dataset that contains MGB employees (N=416; 17% hospitalized). Results: The model based on EHR data predicted risk of hospitalization well, with area under the curve (AUC, DeLong method) of 0.76 [95% CI: 0.7002-0.8206], Figure. Significant determinants of hospitalization risk included demographic variables (age, sex, race), prior medication use (heparin, erythropoietin, and beta blockers), and lab tests (albumin and white blood cell counts). Conclusions: EHR data of COVID-19 patients can be leveraged to predict risk of hospitalization among COVID-19 patients. Further validation of the predictive model on other cohorts is needed.
Abstract 16970: Prognostic Utility of High-Sensitivity Troponin I Among Hospitalized COVID-19 Positive Patients in Michigan - A Retrospective Analysis
Authors: Ahmed M Altibi, Radhika Sheth, Allison LeDuc, Lama Al Jebbawi, Ahmad Masri, Alexander Slota, Hassan Liaqat, Matthew George, Saniya Jain, Enas Abdallah, Luke Russell, Narine Shirvanian, Brijesh D Patel, Pallavi Bhargava, Vivek Kak
Journal: Circulation (2020)

Introduction: Cardiac injury, evidenced by elevated troponin levels, had been proposed as a prognostic marker in COVID-19 patients. Hypothesis: We conducted a retrospective analysis to investigate whether high-sensitivity troponin I (hs-TNI) predicts mortality in hospitalized COVID-19 patients. Methods: Medical records for all COVID-19 positive patients hospitalized between March 1 and May 10, 2020 were reviewed retrospectively (n= 708). Patients with no available hs-TNI data (n=22) were excluded. Elevated hs-TNI was defined as values &gt;18 ng/L. Multivariate logistic regression and Cox proportional-hazard model were used to investigate association between hs-TNI and in-hospital and 30-day mortality. Adjustment in both models was for age, gender, and race. Kaplan-Meier curve was plotted to compare mortality in patients with and without cardiac injury. Results: In 684 included patients, mean age was 66.9±15.6, 57.6% were males, and 47.7% were Caucasians. Prevalence of comorbidities: hypertension 74.3%, dyslipidemia 57.8%, type 2 diabetes 33.9%, coronary artery disease 19.6%, prior myocardial infarction 9.2%, and heart failure 16.2%. hs-TNI was elevated in 36.6% of included patients. 30-day mortality was higher in patients with elevated hs-TIN (46.8% vs. 14.3%). Unadjusted OR of in-hospital death was 5.0 (95% CI: 3.36-7.31, p-value &lt;0.001) and adjusted OR was 2.97 (95% CI: 1.93-4.55, p-value &lt;0.001). Unadjusted HR of 30-day mortality was 4.1 (95% CI 3.0-5.6, p-value &lt;0.001), and adjusted HR was 2.10 (95% CI: 1.49-2.95, p-value &lt;0.001). Conclusions: Elevated troponin levels in hospitalized COVID-19 patients is associated with significant increase in risk of in-hospital and 30-day mortality.
Abstract 17076: Empowering Telemetry Technicians to Call Code Blue
Authors: Cody McCoy, Neil Keshvani, Maryam Warsi, Eugene Chu, Anita Hegde
Journal: Circulation (2020)

Background: Delays in treatment of in-hospital cardiac arrest (IHCA) events are associated with lower survival and poor neurologic outcomes. With centralized telemetry, telemetry technicians need to notify nursing staff of life-threatening arrhythmias immediately for nursing to verify a patient's clinical status and determine whether code blue activation is necessary. Delays in this verification lead to delays in code activation, which can in turn lead to increased morbidity and mortality. Objective: We sought to assess the impact of empowering telemetry technicians to activate code blues on IHCA code survival, survival to discharge, time to cardiopulmonary resuscitation (CPR), and inappropriate code activation. Methods: We implemented a quality improvement protocol September 1, 2016 at Parkland Memorial Hospital, a 900-bed, urban, safety-net hospital, in Dallas, Texas to empower telemetry technicians to call code blue directly for the following life-threatening arrhythmias: ventricular fibrillation, sustained ventricular tachycardia of greater than 30 seconds, asystole, or bradycardia less than 30 beats/minute. We performed a retrospective chart review of all IHCA in patients on centralized telemetry at Parkland for one year prior to the intervention and three years post intervention to look at code survival and survival to discharge. Secondary outcomes were time to CPR and inappropriate code activation. Results: The pre intervention code survival was 12/20 (60.0%) and the post intervention code survival was 46/55 (83.6%) (p=0.03). The pre intervention survival to discharge was 3/20 (15.0%) and the post intervention survival to discharge was 21/55 (38.2%), (p=0.0585). The time to CPR, in seconds, was 180 versus 120 (p=0.58) for pre and post intervention non-PEA codes. There were 0 inappropriate code activations post intervention. Conclusions: Empowering telemetry technicians to activate code blue for general ward patients on centralized telemetry showed a significant improvement in code survival and a trend in survival to discharge. Importantly, there were no inappropriate code activations by telemetry technicians, highlighting the safety of this intervention.
Abstract 17305: Frequency, Predictors and Outcomes of Unplanned Coronary Angiography Following Successful Primary Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction Patients
Authors: Mehmet Yildiz, Christian Schmidt, Santiago Garcia, Ross Garberich, Larissa I Stanberry, Scott W Sharkey, Frank V Aguirre, Mark Tannenbaum, Daniel Shivapour, Roberto Coronado-Pacheco, Timothy Smith, Jenny Chambers, Heather Rohm, Teresa Coulson, Timothy D Henry
Journal: Circulation (2020)

Introduction: There is limited data regarding the frequency, predictors and impact of repeat, unplanned coronary angiography following successful reperfusion with primary PCI in STEMI pts. Methods: We used the prospective, multicenter Midwest STEMI Consortium database, which was created by unique consolidation of 4 large STEMI systems of care: Iowa Heart Center, Minneapolis Heart Institute Foundation, Prairie Cardiovascular, and The Christ Hospital. Each center has similar, well-established standardized STEMI protocols with collaboration over 100 non-PCI-capable hospitals in Midwest. We included all consecutive STEMI pts who underwent repeat, unplanned coronary angiography within 48-hour of successful primary PCI. We excluded pts who underwent a planned or staged coronary angiography. We compared pts with repeat, unplanned coronary angiography to a propensity-score matched (1:2) pts without repeat coronary angiography within 48-hour. Results: Among 6507 STEMI pts treated with primary PCI from 03/2003 to 01/2020, only 136 (2.1%) underwent repeat, unplanned coronary angiography. These pts had higher rates of LAD culprit, history of prior MI, poor pre-PCI TIMI flow (0 or 1) and lower EF. Nearly half of the repeat, unplanned coronary angiographies revealed patent stent (63/136). There were only 32 (24%) in-stent thrombosis and 30 (22%) new occlusions. Compare to the control group, pts with repeat, unplanned coronary angiography were more likely to have major bleeding and longer LOS (p=&lt;0.001) but similar MI, stroke, CV- or all-cause mortality up to 1-year follow-up. Of note, in-hospital MI, which was significantly higher reported in pts with repeat, unplanned coronary angiography, occurred basically prior to repeat coronary angiography (Table). Conclusions: Repeat, unplanned coronary angiography is relatively uncommon after contemporary primary PCI for STEMI pts and is more common with larger, anterior MIs.
Dynamic regulation of Z-DNA in the mouse prefrontal cortex by the RNA-editing enzyme Adar1 is required for fear extinction (vol 41, pg 891, 2020)
Authors: Paul R Marshall, Qiongyi Zhao, Xiang Li, Wei Wei, Ambika Periyakaruppiah, Esmi L Zajaczkowski, Laura J Leighton, Sachithrani U Madugalle, Dean Basic, Ziqi Wang, Jiayu Yin, Wei-Siang Liau, Ankita Gupte, Carl R Walkley, Timothy W Bredy
Journal: Nature Neuroscience (2020)
Audio Interview: Vaccination and Variants in the U.S. and South Africa
Authors: Eric J. Rubin, Lindsey R. Baden, Glenda E. Gray, Stephen Morrissey
Journal: New England Journal of Medicine (2021)

Vaccination and Variants in the U.S. and South Africa In this audio interview conducted on May 11, 2021, the editors are joined by Glenda Gray, head of the South African Medical Research Council, t...
Abstract 15241: Implantable Cardioverter Defibrillator Monotherapy and Congenital Long QT Syndrome: A Single Center’s Experience
Authors: Ciorsti J Macintyre, John Giudicessi, Johan M Bos, Michael J Ackerman
Journal: Circulation (2019)

Background: In contrast to symptomatic Brugada syndrome where an implantable cardioverter defibrillator (ICD) as monotherapy is a class I recommendation, most patients with congenital long QT syndr...
Exploring the feasibility of using real-world data from a large clinical data research network to simulate clinical trials of Alzheimer’s disease
Authors: Zhaoyi Chen, Hansi Zhang, Yi Guo, Thomas J. George, Mattia Prosperi, William R. Hogan, Zhe He, Elizabeth A. Shenkman, Fei Wang, Jiang Bian
Journal: npj Digital Medicine (2021)

Abstract In this study, we explored the feasibility of using real-world data (RWD) from a large clinical research network to simulate real-world clinical trials of Alzheimer’s disease (AD). The target trial (i.e., NCT00478205) is a Phase III double-blind, parallel-group trial that compared the 23 mg donepezil sustained release with the 10 mg donepezil immediate release formulation in patients with moderate to severe AD. We followed the target trial’s study protocol to identify the study population, treatment regimen assignments and outcome assessments, and to set up a number of different simulation scenarios and parameters. We considered two main scenarios: (1) a one-arm simulation: simulating a standard-of-care (SOC) arm that can serve as an external control arm; and (2) a two-arm simulation: simulating both intervention and control arms with proper patient matching algorithms for comparative effectiveness analysis. In the two-arm simulation scenario, we used propensity score matching controlling for baseline characteristics to simulate the randomization process. In the two-arm simulation, higher serious adverse event (SAE) rates were observed in the simulated trials than the rates reported in original trial, and a higher SAE rate was observed in the 23 mg arm than in the 10 mg SOC arm. In the one-arm simulation scenario, similar estimates of SAE rates were observed when proportional sampling was used to control demographic variables. In conclusion, trial simulation using RWD is feasible in this example of AD trial in terms of safety evaluation. Trial simulation using RWD could be a valuable tool for post-market comparative effectiveness studies and for informing future trials’ design. Nevertheless, such an approach may be limited, for example, by the availability of RWD that matches the target trials of interest, and further investigations are warranted.
Abstract 16208: Safety and Efficacy of Arterio-venous Extracorporeal Membrane Oxygenation (SAVE Study) Cannulation by Interventional Cardiologists for Pediatric Population: Results of a Single Center Pilot Study
Authors: Cihangir Buyukgoz, Hitesh Sandhu, Katherine Rower, Benjamin Waller, Umar Boston, Samir H Shah, Shyam K Sathanandam
Journal: Circulation (2020)

Introduction: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) cannulations have been successfully performed in adults by interventional cardiologists (IC) for cardiopulmonary resuscitation (CPR) but little data exists in children. Hypothesis: This study aimed to describe the safety and efficacy of ultrasound-guided percutaneous VA-ECMO cannulation performed by IC for cardiopulmonary resuscitation. Methods: VA-ECMO cannulation performed by IC for CPR between January 2018 - June 2020 in a tertiary care children’s hospital were reviewed. Efficacy was defined as successful initiation of VA-ECMO following CPR without a surgical cut-down. Safety was defined as the absence of the need for additional procedures related to the cannulation event. Results: Eight VA-ECMO cannulations were attempted on 7 patients with 100% success; 1 patient was cannulated twice at 2 separate CPR events. Patients had congenital heart disease (n=3), idiopathic pulmonary hypertension (n=1), T-cell lymphoma (n=1) and dilated cardiomyopathy (n=2). Median age was 15 (6-18) years, median weight was 74 (16-109) kg. Uninterrupted CPR occurred during all cannulations. All cannulations were performed from left femoral artery and right femoral vein, 4 (50%) cannulations included additional internal jugular vein access. Reperfusion cannulation for distal limb circulation was also performed percutaneously by IC for 5 cannulations. Median venous cannula size was 22 (15-25) Fr and median arterial cannula size was 17 (15-17) Fr. Median cannulation start time to ECMO flow was 34.5 (18-112) min. Median ECMO duration was 3 (0.3-50) days. Survival at ECMO decannulation was 75% with a 30-day survival of 87.5%. The overall complication rate was 12.5%. One patient developed hematoma at cannulation site that was conservatively managed, and 1 patient (16 kg) developed avulsion of the intima of the left common femoral artery that needed repair. A cardiovascular surgeon was available or present during all ECMO cannulations. Conclusions: Pediatric VA-ECMO cannulation for CPR can be performed safely and efficiently by IC without interruption. Larger studies and further investigations are necessary especially in smaller children before advocating for its routine practice.
Getting Out of the Game
Authors: Donald Venes
Journal: Annals of Internal Medicine (2021)

Ad LibitumMay 2021Getting Out of the GameDonald Venes, MDDonald Venes, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-0116 Audio Reading - “Getting Out of the Game” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “Getting out of the Game” by Donald Venes, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Ten days out from Hospital Bayand the outlines of its hectic shoreare already vanishingThe only fibrillationthat of whitecap on wave.The emergent sirensThe alarms in sterile corridorsthe worries,the weightAll fall asternAheada broad expanse too great to fathomA nearly infinite sky, thick with cloudsandBefore heaving waters carry everything awaya chance to redraw the mapPracticed eyesso used to making sense of small thingsare sightless now, unable to focuson anything butthe tranquil horizon, serene as a graveBalancing on legsLong accustomed to strainI am weightlessThe waves of a titanic seabreak over the bow of my ConcernDecks awashThirty-six years ... Author, Article, and Disclosure InformationAffiliations: Current Author Address: Donald Venes, MD, PO Box 7799, Brookings, OR 97415; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Getting Out of the Game” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “Getting out of the Game” by Donald Venes, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics May 2021Volume 174, Issue 5Page: 715 ePublished: 18 May 2021 Issue Published: May 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...