bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of pre-course preparation using a serious smartphone game on advanced life support knowledge and skills -A randomized controlled trial
Authors: Kotruchin P , Phungoen P , Mitsungnern T 
Published: November 2020

Abstract

Background
Over the past several years, gamified learning has been growing in popularity in various medical educational contexts including cardiopulmonary resuscitation (CPR) training. Furthermore, prior work in Basic Life Support (BLS) training has demonstrated the benefits of serious games as a method for pre-training among medical students. However, there is little evidence to support these benefits with regard to Advanced Life Support (ALS) training

Objective
We compare the effects of a brief pre-course ALS preparation course using a serious smartphone game on students' knowledge, skills, and perceptions in this area with those of conventional ALS training alone.

Methods
A serious game (Resus Days) was developed by a Thai physician based on global ALS clinical practice guidelines. Fifth-year medical students were enrolled and randomized to either a game group or a control group. Participants in both groups attended a traditional ALS lecture, but the game group was assigned to play Resus Days for 1 hour before attending the lecture and as wished after that. All students underwent conventional ALS training, and their abilities were evaluated using multiple choice questions and with hands-on practice on a mannequin. Subjects' attitudes and perceptions about the game were evaluated using a questionnaire.

Results
A total of 105 students participated in the study and were randomly assigned to either the game group (n=52) or the control group (n=53). Students in the game group performed better on the ALS algorithm knowledge posttest than those in the control group (17.22±1.93 vs 16.60±1.97, P=0.01; adjusted mean difference [AMD] 0.93, 95% CI 0.21–1.66;). The game group's pass rate on the skill test was also higher, but not to a statistically significant extent (79% vs 66%, P=0.09; adjusted odds ratio [AOR] 2.22, 95% CI 0.89–5.51). Students also indicated high satisfaction with the game (9.02±1.11 out of 10).

Conclusions
Engaging in game-based preparation prior to an ALS training course resulted in greater medical students' algorithm knowledge scores than attending the course alone.
A screen shot of Resus Days

Funding Acknowledgement
Type of funding source: None
First clinical experience with the wearable cardiac rhythm long-term monitoring cardioskin device
Authors: Guedeney P , Silvain J , Hidden-Lucet F , Maupain C , Dinanian S , Waintraub X , Gandjbakhch E , Montalescot G 
Published: November 2020

Abstract

Background
There are only limited options for long-term cardiac monitoring devices readily available in clinical practice for outpatients. Holter monitoring devices are limited by the uncomfort of wires and patches, the small number of leads for analysis, the quality of recordings or the monitoring duration while insertable cardiac monitors are costly and exposed to potential local complication.

Purpose
To describe a single center experience with a novel wearable device for cardiac rhythm monitoring.

Methods
The Cardioskin™ system is a patch-free, wire-free, wearable device with rechargeable batteries that provides a high quality 15-lead electrocardiogram monitoring over 1 month (Figure 1). Data are sent using a mobile application downloaded in the patient smartphone to a central Corelab where they can be interpreted by an expert and/or the prescribing physician. An alarm signal is readily available within the Cardioskin™ device, to allow patients to indicate the presence of symptoms. In this single center retrospective registry, we provide a first report of the use of this novel device in real world practice, with indication and duration of cardiac monitoring left at the physicans “discretion”.

Results
From January 2019 to December 2019, the Cardioskin™ system was prescribed in 60 patients for an overall median duration of 26.5 (14–32) days. The mean age of the patients was 45±12.2 years and 24 (40%) were male. Indications for cardiac monitoring were post-Stroke, palpitation, syncope and cardiomyopathy assessment in 56%, 30%, 7% and 7% of the cases, respectively. A sustained (&gt;30 seconds) supraventricular tachycardia was detected in 4 cases, including one case of atrial fibrillation, two case of atrial tachycardia and on case of junctional tachycardia. Unsustained ventricular tachycardia and atrial fibrillation burst were detected in another 2 cases (Figure 1). There was no reported case of skin irritation by the Cardioskin™ system or abrupt interruption of the monitoring by the patients.

Conclusion
The Cardioskin™ system is a novel, discreet and comfortable cardiac rhythm wearable long-term monitoring device which can be used in clinical practice for broad diagnostic indications.
Figure 1. Cardioskin system

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): ACTION coeur
Detection of ST changes by a smartphone-based electrocardiographic monitoring system in patients with ST elevated myocardial infarction
Authors: De La Torre Hernandez J.M , Aritz Gil Ongay A , Borderias Villaroel T , Gonzalez Lizarbe S , Veiga Fernandez G , Catoya Villa S , De Tapia Majado B , Lozano Gonzalez M , Molina San Quirico M , Serrano Lozano D , Cabrera Rubio I , Sanchez Cena J , Garcia Camarero T , Zueco J 
Published: November 2020

Abstract

Background
Recent technological advances have led to several novel electrocardiographic monitoring devices appearing on the market. The pocket sized Kardia Mobile is a monitoring device that requires the patient to trigger the ECG recording through a smartphone-based application. This system is generally aimed to detect alterations in cardiac rhythm and its potential for detection of ST changes remains largely unknown.

Purpose
This study sought to assess the diagnostic sensitivity of the Kardia Mobile system for detection of ST changes in patients with ST elevated myocardial infarction (STEMI).

Methods
Patients admitted with diagnosis of STEMI according to current universal standard definition were consecutively included. Recordings with Kardia were obtained in leads I, II and anterior precordial (prec). All anonymized recordings were submitted for review to a single cardiologist blinded to the 12 leads ECG findings and to all clinical data. A Kardia recording was considered positive if any significant elevation or depression of ST segment was observed.

Results
A total of 102 consecutive patients were included (age 60.6±11.4 years, 27% females, weight 78.6±17.4 kg) admitted with diagnosis of STEMI after a median of 165 (IQR 120–367) minutes of chest pain. STEMI was anterior-lateral in 48% and inferior-posterior in 52%. Values of sensitivity for each lead and for combination of leads are shown in Table for all STEMI and separately for anterior and inferior locations. ST changes in all leads consisted mostly in depression (70–78%). Poor quality recording rates were 8% for lead I, 1% for lead II and 3% for lead prec.

Conclusions
The Kardia Mobile system with single lead use shows a modest sensitivity for detection of ST changes (mostly depression) in STEMI patients. However, the combination of two leads (particularly I+prec or II+prec) or three leads shows a very high sensitivity for both anterior and inferior STEMI.

Funding Acknowledgement
Type of funding source: None
Improved prediction of cardiac, limb and bleeding events in patients with coronary and peripheral arterial disease using machine learning models and artificial intelligence
Authors: Steffel J , Kloss S , Roohi Sefidmazgi N , Chevreux B , Fox K.A.A 
Published: November 2020

Abstract

Background
Coronary artery disease (CAD) and peripheral arterial disease (PAD) represent a significant burden in patients with cardiovascular disease (CVD). However, current antithrombotic therapies are inconsistently used because of clinical concerns about selecting patients with optimal benefit versus risk.

Purpose
We aimed to determine whether complex data engineering, multi-layered machine learning and artificial intelligence could be used to derive and test an improved risk stratification tool to support clinical decision making among CAD/PAD patients at risk of thrombotic events.

Methods
We conducted a retrospective cohort study using claims data from the US Optum Clinformatics dataset, derived from Jan 1, 2010 to Dec 31, 2018. Predictive modeling analytics, including multi-label logistic regression, cox-regression and machine learning techniques (Random Forests and Gradient Boosting Machines) were used to calculate individual patient risks for Major Adverse Cardiac Events (MACE), Major Adverse Limb Events (MALE) and Major Bleeding (MB) events for 1-year and 5-year predictions. To translate findings from black box models into interpretable results, explainable artificial intelligence (AI) techniques based on Shapley additive explanations (SHAP) were applied.

Results
The study cohort consisted of 1,842 million patients with a diagnosis of CAD (mean age: 71±11) and 1,557 million patients with a diagnosis of PAD (mean age: 74±10). 1,017 million patients had a diagnosis of both. Annual event rates for MACE, MALE and Major Bleeding events were 3.5%, 0.7% and 1.6%. 865 variables were extracted from the patient history, including demographics, diagnoses, procedures and prescriptions. For all outcomes, the gradient boosting machines outperformed all other statistical models, including risk scores like CHA2DS2VASc and REACH. The AUCs for the 1-year prediction were 0.75 for MACE, 0.88 for MALE and 0.76 for MB, respectively. For a standard risk score-based approach AUCs were 0.67 for both MACE and Major Bleeding, there was no risk score available for MALE. Linear regression models using all 865 variables showed slightly inferior results compared to the machine learning methods (AUCs: 0.74 for MACE, 0.84 for MALE and 0.75 for MB, respectively).

Conclusion
Our study showed that in a very heterogeneous patient population, machine learning techniques can outperform existing risk scores as well as linear models when assessing individual patient risks. Machine learning and artificial intelligence can be used to shape and evolve evidence generation for personalized healthcare and digital health solutions and support HCPs and payers in understanding most relevant prognostic factors that are associated with patient outcomes.
Figure 1

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Bayer AG
Effect of immortal time bias on the association between atrial fibrillation ablation and incident stroke: a meta-analysis
Authors: Samuel M , Khairy P 
Published: November 2020

Abstract

Background/Introduction
In the era of big data and large observational studies, identification and prevention of immortal time bias (ITB) is essential to attain unbiased effect estimates. Immortal time refers to a period of follow-up in a cohort when the outcome cannot occur. Typically, it results when the exposure is initiated after the start of follow-up. The misclassification of person-time results in a systematic overestimation of the treatment effect. ITB is a common methodological issue in epidemiology studies. We sought to assess the presence and magnitude of bias due to ITB in observational studies evaluating the effectiveness of catheter ablation (CA) for atrial fibrillation.

Purpose
To compare the association between CA and stroke in 1) observational studies that controlled for ITB, 2) observational studies that did not address ITB, and 3) randomized controlled trials (RCT).

Methods
The PUBMED database was screened from inception to January 15, 2020 for publications with the following string of search terms: (“ablation” or “catheter ablation” or “pulmonary vein isolation”) and “atrial fibrillation” and (“stroke” or “thromboembolism”). Observational studies and RCTs comparing CA to medical therapy were eligible. Studies were excluded if: 1) evaluation of the association was limited to a subgroup of AF patients, 2) cryoablation was performed, 3) strokes were not reported, and 4) HRs or 95% CI were not presented. Information on study characteristics, HRs, and the potential for ITB was extracted. Subsequently, articles were classified based on the type of study and whether ITB was addressed. For each group of articles, HRs were logarithmically transformed and pooled using the random effects model.

Results
A total of 10 observational studies and 1 randomized controlled trial were included in the present analysis. Of the 10 observational studies, only 2 studies were designed to prevent ITB. The pooled HR for observational studies without ITB prevention showed a statistically significant reduction in risk of stroke (HR 0.66 (95% CI 0.58–0.74); I2=27.3%) in CA patients compared to non-CA patients. However, pooling the two observational studies that prevented ITB indicated no difference in the incidence of stroke [HR 0.75 (95% CI 0.49–1.02); I2=4.5%] among patients with and without CA, a finding similar to CABANA trial [HR 0.42 (95% CI 0.11–1.21)].

Conclusion
It is important to evaluate the effectiveness of procedures and medications using observational data to determine if the results from RCTs translate to the real-world. However, careful consideration needs to be taken in the design phase to avoid ITB and produce effect estimates that more accurately represent the true association between treatment and outcomes. Examples of design methods to prevent ITB include the use of a time-varying covariate or matching on pre-treatment exposure time.

Funding Acknowledgement
Type of funding source: None
Genome-wide association study identifies 18 new susceptibility variants loci associated with Brugada Syndrome
Authors: Barc J , Trados R , Glinge C , Simonet F , Chiang D , Jouni M , Jurgens S , The Brugada Syndrome Genetic Consortium B.R.S , Tanck M , Dina C , Probst V , Wilde A , Redon R , Schott J.J , Bezzina C 
Published: November 2020

Abstract

The Brugada Syndrome (BrS) is characterized by ST-segment elevation in the right precordial leads and is associated with an increased risk of sudden cardiac death. The disorder was initially described as a monogenic primary cardiac electrical disease. However, mutations in SCN5A, encoding the cardiac sodium channel (NaV1.5), which is the major gene associated with the disorder are found in only around 20% of cases and are associated with low penetrance. Furthermore many cases did not display familial aggregation. Based on a previous GWAS conducted on 312 BrS patients and the discovery of the unexpected strong effect of 3 common variants, we proposed that the BrS may comprise a more complex inheritance model. We conducted a genome-wide association study on 2820 individuals with BrS and 10001 ancestry-matched controls to uncover additional genetic loci that modulate susceptibility to BrS, to characterize further the BrS genetic architecture and to uncover new molecular mechanisms.
We identified 21 susceptibility variants that passed the genome-wide statistical significance threshold (P&lt;5.10–8), of which 18 were novel. Eight were located at the SCN5A-SCN10A locus, illustrating the central role of NaV1.5 in the disease. Interestingly, 9 occur in the vicinity of genes known to play a crucial role in cardiac development (HEY2, TBX20, GATA4, ZFPM2, WT1, TBX5, IRX3, IRX5) and / or control cardiac ion channel expression. Of note, 2 others signals occurred in the vicinity of microtubule / cytoskeleton associated proteins (MAPRE2 and MYO18B). Through studies in zebrafish and in human iPSC-derived cardiomyocytes, we demonstrate a role of MAPRE2 on NaV1.5 function.
We identified 18 new susceptibility variants associated with BrS and uncovered a new pathophysiological molecular mechanism underlying BrS susceptibility. We provided further support for a complex genetic architecture underlying susceptibility for the disorder.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): H2020 - Marie Sklodowska Curie IF grant, Rising star grant from the Pays de la Loire regional council
Intense cardiac-targeted small extracellular vesicles-mediated delivery of RAGE siRNA attenuates inflammation in rat myocarditis model
Authors: Kim H , Mun D , Kang J , Yun N , Joung B 
Published: November 2020

Abstract

Background
Despite advances in the field and new therapeutics being developed, heart disease remains the leading cause of mortality worldwide. Small extracellular vesicles (sEV) are 30–150 nm in diameter and ferry RNA and proteins to cells. sEV are a natural carrier of many signaling molecules and play an important role in heart disease. However, the high probability of off-target effects associated with these carriers is a major barrier to translation into clinical application.

Purpose
Our aim was to evaluate whether sEVs engineered to express potent cardiac targeting peptides (CTPs) could deliver siRNA to the heart and exert a therapeutic effect.

Methods
We use vectors encoding LAMP2B (sEV) or CTP-LAMP2B (PsEV) into HEK 293 cells expressing. sEVs were purified from culture media of HEK 293 cells by serial centrifugation followed by tangential flow filtration (TFF) system. sEV and PsEV were loaded with siRNAs by Exo-Fect™ exosome transfection reagent, and were treated into H9C2 rat cardiomyocyte. TNF-alpha were then added to the cells to induce inflammation. And sEVs were intravenously injected into myocarditis rat. Inflammation factors of in vitro and in vivo inflammation model were identified by western blot. Echocardiographic examination was also performed in rat.

Results
The successful development of PsEVs was analyzed by Western blot and TEM. We observed a 4 fold increase from that of the previously developed sEVs in H9C2 cells and a 200% increase in cardiac-specific delivery without toxicity in rat model. AGE is involved in proinflammatory/pro-apoptotic processes. To block RAGE, we loaded RAGE siRNA (siRAGE) in sEV that had high expression of PsEV. Characteristics of sEVs were maintained despite siRNA load.In inflammatory cell models and rat disease models, PsEV-treated groups significantly reduced molecular levels associated with inflammatory responses such as RAGE, IL-6, TNF-alpha, COX2, HMGB1, and p-p65 / p65.

Conclusions
Our results suggest that PsEV can potentially serve as a treatment delivery vehicle for heart disease.
Scheme

Funding Acknowledgement
Type of funding source: None
Novel regulation of cardiac branched-chain amino acid metabolism through AMP deaminase: a possible therapeutic target for diabetic cardiomyopathy
Authors: Ogawa T , Kouzu H , Tatekoshi Y , Osanami A , Oshima H , Mizuno M , Kuno A , Igaki Y , Sugawara H , Fujita Y , Sato T , Yano T , Tannno M , Miki T , Miura T 
Published: November 2020

Abstract

Background
Dysregulation of branched-chain amino acid (BCAA) metabolism has been shown to be associated with type 2 diabetes mellitus (T2DM) and heart failure. BCAA reportedly protects cells from fatty acid-induced mitochondrial injury via sequestration of fatty acids in intracellular lipid droplets from mitochondria. We previously reported that up-regulation of AMP deaminase 3 (AMPD3) impairs cardiac energetics in T2DM hearts, and AMPD3 was recently shown to participate in regulation of amino acid metabolism in skeletal muscle.

Purpose
We hypothesized that AMPD3 regulates cardiac amino acid metabolism by interaction with branched-chain α-ketoacid dehydrogenase (BCKDH) complex and that cardioprotective effect of sodium glucose cotransporter 2 inhibitors is mediated by modification of BCAA metabolism in diabetic cardiomyocytes.

Methods and results
Proteomic analyses of immunoprecipitates with an anti-AMPD3 antibody in rat hearts revealed that AMPD3 interacted with the E1α component of BCKDH complex. Whereas BCKDH has been reported to localize in mitochondria matrix as a rate-limiting enzyme for BCAA catabolism, immunoblotting using subcellular fractions revealed that BCKDH E1α is present in cytosol and endoplasmic reticulum as well. AMPD3-BCKDH E1α interaction was decreased by 68% in T2DM rats (OLETF) compared to that in control rats (LETO), and significant accumulation of BCAAs was observed in OLETF hearts (317±30 vs. 213±16 nmol/g). Survival rate at 48 hours after myocardial infarction (MI) was significantly lower in OLETF than in LETO (40% vs 84%). Empagliflozin treatment (10 mg/kg/day, 14 days) before MI improved the survival rate in OLETF to 70%, increased BCAAs as the top of 92 detected metabolites (791±187 nmol/g) and significantly preserved tissue ATP in the non-MI remote region. Electron microscopy showed a significantly higher prevalence of myocardium lipid droplets in OLETF, which was further increased by empagliflozin.

Conclusions
Results of the present analyses support the hypotheses that conversion of BCAA-derived branched-chain α-ketoacid to branched-chain acyl-CoA is suppressed by reduced AMPD3-BCKDH interaction in the myocardium of T2DM and that empagliflozin induces compensation of the dysregulated cardiac BCAA metabolism by augmentation of BCAA influx and promotion of fatty acid sequestration in intracellular lipid droplets.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Boehringer Ingelheim
CRISPR-Cas9-based gene editing of human mesenchymal stromal cells to improve the outcome of cell therapy
Authors: Schary Y , Brzezinski R.Y , Teper-Shaihov O , Naftali-Shani N , Leor J 
Published: November 2020

Abstract

Background
The environment of the failing and infarcted myocardium drives resident and transplanted mesenchymal stromal cells (MSCs) toward a pro-inflammatory phenotype, thus restricting their survival and their reparative effects in a mechanism mediated by toll-like receptor 4 (TLR4). Hence, new approaches are needed to improve the efficacy of cell therapy for heart failure. CRISPR is a promising tool for genome editing, which raises the hope for therapeutic genome editing in the clinic.

Purpose
We aimed to provide a new strategy to enhance MSC-based cell therapy to improve cardiac remodeling and function. We hypothesized that ex vivo knockout (KO) of the human TLR4 gene by CRISPR would switch human-cardiac MSCs (hMSCs) to an anti-inflammatory, reparative phenotype that could prevent remodeling of the left ventricle after myocardial infarction (Fig. 1A).

Methods and results
We achieved up to 68% (out of 4x105 cells, R2=0.93) success rate in editing the genome of primary cardiac hMSCs taken from patients with ischemic heart disease. The deletion of TLR4 in hMSCs significantly reduced the secretion of inflammatory and extracellular-matrix (ECM) proteins, compared with unedited hMSCs, by protein mass spectrometry (Fig. 1B) and by multiplex ELISA (Fig. 1C). Additionally, edited cells secreted significantly more extracellular vesicles (EVs) than unedited hMScs (Fig. 1D, p&lt;0.001). These EVs from edited hMSCs stimulated faster migration of hMSCs in a “wound healing” assay (p&lt;0.001).

Conclusions
We show, for the first time, that CRISPR-based deletion of the TLR4 gene in hMSCs inhibits inflammatory and ECM protein secretion and facilitates a reparative response by hMSCs in vitro. This precise and efficient ex vivo gene editing could provide a newly engineered cell line to improve the outcome of hMSC-based cell therapy.
Figure 1

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): The Foundation in Memory of Seymour Fefer, Sheba Medical Center