tbuckley/cabot-search huggingface dataset:
Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups
Authors: Milou A.M. Stals, Toshihiko Takada, Noémie Kraaijpoel, Nick van Es, Harry R. Büller, D. Mark Courtney, Yonathan Freund, Javier Galipienzo, Grégoire Le Gal, Waleed Ghanima, Menno V. Huisman, Jeffrey A. Kline, Karel G.M. Moons, Sameer Parpia, Arnaud Perrier, Marc Righini, Helia Robert-Ebadi, Pierre-Marie Roy, Maarten van Smeden, Phil S. Wells, Kerstin de Wit, Geert-Jan Geersing, Frederikus A. Klok
Journal: Annals of Internal Medicine (2021)

Background: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. Purpose: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. Data Sources: MEDLINE from 1 January 1995 until 1 January 2021. Study Selection: 16 studies assessing at least 1 diagnostic strategy. Data Extraction: Individual-patient data from 20 553 patients. Data Synthesis: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability–dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups. Limitations: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. Conclusion: Overall, all strategies showed acceptable safety, with pretest probability–dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds. Primary Funding Source: Dutch Research Council. (PROSPERO: CRD42018089366)
Statins for primary prevention among elderly men and women
Authors: Maria Bergami, Edina Cenko, Jinsung Yoon, Guiomar Mendieta, Sasko Kedev, Marija Zdravkovic, Zorana Vasiljevic, Davor Miličić, Olivia Manfrini, Mihaela van der Schaar, Chris P Gale, Lina Badimon, Raffaele Bugiardini
Journal: Cardiovascular Research (2021)

Abstract Aims We undertook a propensity match-weighted cohort study to investigate whether statin treatment recommendations for statins translate into improved cardiovascular (CV) outcomes in the current routine clinical care of the elderly. Methods and results We included in our analysis (ISACS Archives -NCT04008173) a total of 5619 Caucasian patients with no known prior history of CV disease who presented to hospital with a first manifestation of CV disease with age of 65 years or older. The risk of ST-segment elevation myocardial infarction (STEMI) was much lower in statin users than in non-users in both patients aged 65–75 years [14.7% absolute risk reduction; relative risk (RR): 0.55, 95% CI 0.45–0.66] and those aged 76 years and older (13.3% absolute risk reduction; RR: 0.58, 95% CI 0.46–0.72). Estimates were similar in patients with and without history of hypercholesterolaemia (interaction test; P-values = 0.24 and 0.35). Proportional reductions in STEMI diminished with female sex in the old (P for interaction = 0.002), but not in the very old age (P for interaction = 0.26). We also observed a remarkable reduction in the risk of 30 day mortality from STEMI with statin therapy in both age groups (10.2% absolute risk reduction; RR: 0.39; 95% CI 0.23–0.68 for patients aged 76 or over and 3.8% absolute risk reduction; RR 0.37; 95% CI 0.17–0.82 for patients aged 65–75 years old; interaction test, P-value = 0.46). Conclusions Preventive statin therapy in the elderly reduces the risk of STEMI with benefits in mortality from STEMI, irrespective of the presence of a history of hypercholesterolaemia. This effect persists after the age of 76 years. Benefits are less pronounced in women. Randomized clinical trials may contribute to more definitively determine the role of statin therapy in the elderly.
Abstract 12494: The Disparities of Gender-Based Out of Hospital Cardiac Arrest Characteristics and Outcomes: Comparing Rural to Urban Vancouver Island
Authors: Rahaf Al Assil
Journal: Circulation (2021)

Introduction: The relationship between the “chain of survival” metrics of Out of Hospital Cardiac Arrest (OHCA) and survival rates in rural settings has not been fully examined. In previous studies, low survival rate was attributable to the modifiable prehospital metrics and Return Of Spontaneous Circulation (ROSC). We sought to examine the association of the modifiable and non-modifiable OHCA characteristics and patient outcomes with rural settings. Methods: We did a post-hoc analyses of data from the British Columbia cardiac arrest registry, which enrolled all emergency medical system (EMS)-treated OHCAs. All non-EMS-witnessed OHCAs on Vancouver Island from Jan. 2019 to Oct. 2020 were included. The independent variable of interest was rural versus urban settings. Rural areas were defined as all areas outside the urban clusters (population ≥ 1000 and a population density of ≥ 400/km2). Our outcomes were 1. Post resuscitation ROSC, and 2. Survival to hospital discharge. We reported gender-mediated measures and adjusted odds ratios using logistic regression models. Results: We included 1172 OHCA patients, with 23% in rural settings, 33% Female, 30% had ROSC, and 23% survived to hospital discharge. The median EMS response time, from 911-call to first EMS arrival, was prolonged [10.5 mins (IQR 7.5-15)] in rural settings compared to urban settings [6.5 mins (IQR 5-9)] (p value&lt;.001) . Among females, rural settings were associated with higher odds of bystander CPR compared to males [(OR 1.86; 95% CI 1.04-3.35), (OR 1.42; 95% CI 0.95-2.13)], respectively. After adjusting for all covariates, rural settings were associated with lower odds of ROSC among males compared to females [(OR 0.53; 95% CI 0.31-0.90), (OR 0.70; 95% CI 0.34-1.41)], respectively; however, not associated with survival to hospital discharge. Conclusions: There are significant disparities in the modifiable prehospital OHCA characteristics, and post resuscitation ROSC between rural and urban Vancouver Island. An officially integrated rural CPR community-based program, and innovations focused on gender-based implementation may significantly improve OHCA survival rates and subsequent prognostication.
Home mechanical ventilation: the Dutch approach
Authors: R.J.M. van den Biggelaar, A. Hazenberg, N.A.M. Cobben, D.A.M.P.J. Gommers, M.A. Gaytant, P.J. Wijkstra
Journal: Pulmonology (2021)

In the Netherlands we have an unique organisation of only 4 centres being responsible for all patients who need Home Mechanical ventilation(HMV). Nationwide criteria for referral and initiation of HMV are stated in our national guideline and recently a unique national learning management system (LMS) for all caregivers and professionals was developed. A nationwide multi-centric research program is running and every centre is participating. In this paper we provide information about the evolution of HMV in the Netherlands during the last 30 years, including details about the number of patients, different diagnose groups, residence and the type of ventilators.
Abstract 13163: Use of a QR Code Accessed Debrief Tool is Associated With Higher Rates of Debrief After In-Hospital Cardiac Arrest
Authors: Oscar J Mitchell, Karsten Drus, Eugene Yuriditsky, Sam Parnia, Amrita Mukhopadhyay, James Horowitz
Journal: Circulation (2021)

Introduction: In-hospital cardiac arrest (IHCA) affects over 200 000 patients in the US annually. Approximately 20% will survive to hospital discharge, although outcomes vary between hospitals. Debriefing has been shown to improve resuscitation quality and teamwork and has been associated with improved IHCA outcomes. All IHCA at NYU Langone Health are attended by the ALERT team, a dedicated team of critical care nurses who perform active patient surveillance and respond to acute in-hospital emergencies. IHCA debriefs at NYU Langone Health have historically been performed on paper forms but were limited by low rates of compliance. As part of an ongoing quality improvement (QI) initiative, we designed and implemented an electronic debriefing tool for use after IHCA (eDebrief). Methods: The eDebrief tool was developed by the NYU Interdisciplinary Resuscitation Committee. The tool captures cardiopulmonary resuscitation (CPR) quality metrics, teamwork and leadership, use of resuscitation equipment (mechanical CPR, advanced airway adjuncts, and ultrasound), and outcomes. ALERT team nurses received an educational session and ad hoc refresher sessions if required. Data were collected at the conclusion of the event using an electronic device (iPhone, Apple, Cupertino CA). The tool is accessible using a QR code located on every code cart. Rates of IHCA debrief post-implementation (2/13/20-06/10/21) were compared to prior years (01/01/19 - 12/31/19 and 01/01/18-12/31/19). Results: The eDebrief tool was implemented on 2/13/20. During the post-implementation phase, there were 254 IHCA at NYU Langone Health. The eDebrief form was used in 175 events (69%). The debrief rate from previous calendar years were 38% and 42% for 2019 and 2018 respectively. Use of the eDebrief form has identified three targets for ongoing quality improvement and research projects: room overcrowding (identified in 64/175 IHCAs, 37%); ultrasound use (39/175 IHCAs, 22%); and optimization of mechanical CPR. Conclusions: Use of electronic debriefing is feasible at a large academic medical center and has been associated with increased uptake of IHCA debrief. Regular debriefs at our center have identified several targets for further quality improvement and research initiatives.
Error in Title
Authors: Werner Stenzel
Journal: JAMA Neurology (2021)

Marieke P. Hoevenaar-Blom, PhD; Edo Richard, MD; Eric P. Moll van Charante, MD; Lennard L. van Wanrooij, PhD; Wim B. Busschers, PhD; Jan W. van Dalen, PhD; Wim A. van Gool, MD
Barriers and Enablers for Integrating Public Health Cobenefits in Urban Climate Policy
Authors: Maya Negev, Leonardo Zea-Reyes, Livio Caputo, Gudrun Weinmayr, Clive Potter, Audrey de Nazelle
Journal: Annual Review of Public Health (2021)

Urban climate policy offers a significant opportunity to promote improved public health. The evidence around climate and health cobenefits is growing but has yet to translate into widespread integrated policies. This article presents two systematic reviews: first, looking at quantified cobenefits of urban climate policies, where transportation, land use, and buildings emerge as the most studied sectors; and second, looking at review papers exploring the barriers and enablers for integrating these health cobenefits into urban policies. The latter reveals wide agreement concerning the need to improve the evidence base for cobenefits and consensus about the need for greater political will and leadership on this issue. Systems thinking may offer a way forward to help embrace complexity and integrate health cobenefits into decision making. Knowledge coproduction to bring stakeholders together and advance policy-relevant research for urban health will also be required. Action is needed to bring these two important policy agendas together.
Pandemic Provides Rapid Test of Telehealth
Journal: Cancer Discovery (2021)

Access to telehealth in oncology rapidly expanded during the COVID-19 pandemic, and it has been widely touted as a way to alleviate disparities in cancer care. However, researchers have found that higher socioeconomic status correlated with increased use of telehealth in patients diagnosed with cancer during the pandemic, raising questions about how to tailor telehealth to tackle disparities.
NFAT-dependent and -independent exhaustion circuits program maternal CD8 T cell hypofunction in pregnancy
Authors: Emma L. Lewis, Rong Xu, Jean-Christophe Beltra, Shin Foong Ngiow, Jordana Cohen, Rahul Telange, Alexander Crane, Deirdre Sawinski, E. John Wherry, Paige M. Porrett
Journal: The Journal of Experimental Medicine (2021)

Pregnancy is a common immunization event, but the molecular mechanisms and immunological consequences provoked by pregnancy remain largely unknown. We used mouse models and human transplant registry data to reveal that pregnancy induced exhausted CD8 T cells (Preg-TEX), which associated with prolonged allograft survival. Maternal CD8 T cells shared features of exhaustion with CD8 T cells from cancer and chronic infection, including transcriptional down-regulation of ribosomal proteins and up-regulation of TOX and inhibitory receptors. Similar to other models of T cell exhaustion, NFAT-dependent elements of the exhaustion program were induced by fetal antigen in pregnancy, whereas NFAT-independent elements did not require fetal antigen. Despite using conserved molecular circuitry, Preg-TEX cells differed from TEX cells in chronic viral infection with respect to magnitude and dependency of T cell hypofunction on NFAT-independent signals. Altogether, these data reveal the molecular mechanisms and clinical consequences of maternal CD8 T cell hypofunction and identify pregnancy as a previously unappreciated context in which T cell exhaustion may occur.
Abstract 14468: Machine-Learning Identifies Out-of-Hospital Cardiac Arrest Patients With Higher Probability of Survival While Undergoing Extracorporeal Cardiopulmonary Resuscitation
Authors: Ruben Crespo, Solvejg Wastvedt, Julian A Wolfson, Demitris Yannopolous, Jason Bartos
Journal: Circulation (2021)

Introduction: Neurologically favorable survival following OHCA depends on many factors including patient age, presenting rhythm, bystander CPR, CPR duration, and return of spontaneous circulation (ROSC). This study aims to utilize machine learning to construct predictive models of neurologically favorable survival in OHCA patients receiving standard ACLS and extracorporeal cardiopulmonary resuscitation (ECPR). Methods: 3011 patients from the Amiodarone, Lidocaine, Placebo Study (ALPS) were analyzed using supervised and unsupervised machine learning approaches based on several variables available at the time of hospital presentation after OHCA. Machine learning platforms were developed to create real world predictive models of resuscitation. The model was then refined for 180 patients from the UMN-ECPR study with refractory VF/VT cardiac arrest who underwent ECPR. Resuscitative variables were selected and ranked on the likelihood ratio of predicting survival. Results: Machine learning analysis of the ALPS cohort yielded a model of survival with an area under the receiver-operating characteristic curve (AUC) of 0.92. ROSC, CPR duration and age were the highest determinants of neurologically favorable survival. The model was tested on the UMN-ECPR cohort, showing an AUC of 0.74 with a sensitivity and negative predictive value for survival of 12% and 60%, respectively. Machine learning was again used to render a model tailored for the UMN-ECPR group. The ECPR predictive algorithm had an AUC of 0.83, sensitivity and negative predictive value for survival of 70% and 80%, respectively, in which presenting rhythm to the cath lab, ROSC and CPR duration were the main determinants of neurologically favorable survival. Conclusion: Simple and effective predictive algorithms can predict the outcomes of cardiac arrest using only cardiac arrest characteristics. Use of ECPR changes the predictive determinants substantially. While this information is helpful in the appropriate context, the specificity required to withdraw care or halt resuscitation will require further data points and refinement.
Trustworthy AI: Closing the gap between development and integration of AI systems in ophthalmic practice
Authors: Cristina González-Gonzalo, Eric F. Thee, Caroline C.W. Klaver, Aaron Y. Lee, Reinier O. Schlingemann, Adnan Tufail, Frank Verbraak, Clara I. Sánchez
Journal: Progress in Retinal and Eye Research (2021)

An increasing number of artificial intelligence (AI) systems are being proposed in ophthalmology, motivated by the variety and amount of clinical and imaging data, as well as their potential benefits at the different stages of patient care. Despite achieving close or even superior performance to that of experts, there is a critical gap between development and integration of AI systems in ophthalmic practice. This work focuses on the importance of trustworthy AI to close that gap. We identify the main aspects or challenges that need to be considered along the AI design pipeline so as to generate systems that meet the requirements to be deemed trustworthy, including those concerning accuracy, resiliency, reliability, safety, and accountability. We elaborate on mechanisms and considerations to address those aspects or challenges, and define the roles and responsibilities of the different stakeholders involved in AI for ophthalmic care, i.e., AI developers, reading centers, healthcare providers, healthcare institutions, ophthalmological societies and working groups or committees, patients, regulatory bodies, and payers. Generating trustworthy AI is not a responsibility of a sole stakeholder. There is an impending necessity for a collaborative approach where the different stakeholders are represented along the AI design pipeline, from the definition of the intended use to post-market surveillance after regulatory approval. This work contributes to establish such multi-stakeholder interaction and the main action points to be taken so that the potential benefits of AI reach real-world ophthalmic settings.
Abstract 10100: Early Prediction of Neurological Outcome at 30 Days After Return of Spontaneous Circulation From Out-of-Hospital Cardiac Arrest
Authors: Norihiro Nishioka, Daisuke Kobayashi, Takeyuki Kiguchi, Tetsuhisa Kitamura, Taku Iwami
Journal: Circulation (2021)

Aim: To develop and validate a model for early prediction of neurological outcomes in non-traumatic out-hospital cardiac arrest (OHCA) patients. Methods: We analyzed the data of adult non-traumatic cardiac arrest patients who experienced return of spontaneous circulation (ROSC) and were admitted to the intensive care unit between January 2013 and December 2017 from the database of a multicenter registry. We allocated 1329 patients who were admitted from 2013 to 2015 to the derivation set and 1025 patients admitted from 2016 to 2017 to the validation set. The primary outcome was the dichotomized Cerebral Performance Category at 30 days. We developed 2 models: model 1 including variables except for laboratory data and model 2 including all variables with laboratory data immediately available after ROSC. Logistic regression with least absolute shrinkage and selection operator regularization was used for model development. The C-statistics for discrimination, the prognostic ability, and calibration of the prediction model were assessed in the validation set. The reclassification of model 2 compared to model 1 was also evaluated by continuous net reclassification index (NRI). Results: The C-statistics [95% confidence intervals] of model 2 and 1 in validation set was 0.940 [0.921-0.959] and 0.935 [0.914-0.957], respectively (Figure 1). The calibration plot showed that both models were well-calibrated to observed neurological outcomes (Figure 2). The model 2 reclassified patients better than the model 1 (NRI: 0.663, p &lt; 0.001). A web-based calculator based on these models was developed that allows clinicians to input the predictor variables needed for the probability of good or poor neurological outcomes (https://pcas-prediction.shinyapps.io/pcas_lasso/). Conclusion: The prediction tool including detailed in-hospital information showed good performance to predict neurological outcomes at 30 days in patients with ROSC after OHCA.
Alison Paice Hill
Authors: George Freeman
Journal: BMJ (2021)

The relationship was studied between spatial contrast sensitivity function and type of pathology of the visual system. Two characteristics were found to be typical for amblyopia: there is a discrepancy between the high-frequency cut-off (9grating acuity9) and the Snellen acuity; the contrast sensitivity is strongly dependent on the width of the stimulus. In optic nerve degeneration a decrease in contrast sensitivity is found at low spatial frequencies. Decreased contrast sensitivity at high spatial frequencies is atypical but occurs in those disorders associated with decreased Snellen visual acuity. From these findings a relationship is defined which enables spatial contrast sensitivity tests to be used to differentiate between amblyopia and optic nerve degeneration.
TAMI-18. DIFFERENTIAL LIPID METABOLISM IN CANCER MICROENVIRONMENTS LEADS TO A REQUIREMENT FOR FATTY ACID DESATURASES FADS1 AND FADS2 IN GBM CANCER STEM CELL MAINTENANCE
Authors: Sajina Shakya, Anthony D Gromovsky, James S Hale, Arnon M Knudsen, Briana Prager, Lisa Wallace, Luiz O Penalva, H Alex Brown, Bjarne Kristensen, Jeremy N Rich, Justin Lathia, J Mark Brown, Christopher Hubert
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) is marked by cellular heterogeneity through microenvironments of a tumor, including metabolic heterogeneity. While altered cellular metabolism in cancer is well-known, how lipid metabolism is altered in different GBM microenvironmental conditions and cancer stem cell (CSC) states within a tumor remains an open question. We developed 3-dimensional GBM organoid models that mimic the transition zone between nutrient-rich cellular tumor and nutrient-poor psuedopalisading/perinecrotic tumor regions and performed spatially defined RNA-sequencing to investigate lipid metabolism. Spatial analysis revealed striking differences in metabolism between diverse cell populations from the same patient, with lipid enrichment in the hypoxic organoid cores and the pseudopalisading regions of patient tumors. This was accompanied by regionally restricted upregulation of lipid droplets and Hypoxia Inducible Lipid Droplet Associated gene expression in organoid cores and in the pseudopalisading regions of clinical GBM tumors. Using targeted lipidomic analysis, we assessed differences in acutely enriched CSC and non-CSCs from patient-derived models to explore the link between stem cell state and lipid metabolism. CSCs have low lipid droplet accumulation compared to non-CSCs in organoids and xenograft tumors, and prospectively sorted lipid-low GBM cells are functionally enriched for stem cell activity. This suggests lipid metabolism may not be simply a product of the microenvironment but also may be a reflection of cellular state. CSCs had decreased levels of major classes of neutral lipids compared to non-CSCs, but had significantly increased polyunsaturated fatty acid production due to increased expression of fatty acid desaturases FADS1 and FADS2. FADS1 and FADS2 expression are both essential to maintain CSC viability and self-renewal. Our data demonstrate that spatially and hierarchically distinct lipid metabolism phenotypes occur clinically in the majority of patients, can be recapitulated in laboratory models, and these altered lipid metabolic pathways may represent therapeutic targets for GBM.
Tumor microenvironment-responsive Ag2S-PAsp(DOX)-cRGD nanoparticles-mediated photochemotherapy enhances the immune response to tumor therapy
Authors: Ruxia Han, Qingya Liu, Yi Lu, Jinrong Peng, Meng Pan, GuiHua Wang, Wen Chen, Yao Xiao, ChengLi Yang, Zhiyong Qian
Journal: Biomaterials (2021)