tbuckley/cabot-search huggingface dataset:
We abandon face-to-face practice at our peril
Authors: Jim Boddington, Aarany Santhakumar, Lucy O'Rourke, Paul Kelland
Journal: BMJ (2021)

With many prominent voices in our profession opposing a return to face-to-face consultations as part of rejecting the GP “rescue plan,”1 we want to express dissent. Now is unequivocally the time to return to face-to-face practice as our dominant model of care. Otherwise, we have much to lose.

The fashionable view that remote consultations (phone, video, or online) can replace most in-person …
Abstract MP249: Mechanistic Basis And Therapeutic Potential Of Targeting The Non-muscle Rbfox2 Isoform In Myotonic Dystrophy
Authors: Chaitali Misra, Ullas V Chembazhi, Sarah Matatov, Sushant Bangru, Auinash Kalsotra
Journal: Circulation Research (2021)

Myotonic Dystrophy type 1 (DM1), the most prevalent form of adult-onset muscular dystrophy, is caused by CTG trinucleotide repeat expansion in the 3’-UTR of the DMPK gene. Heart dysfunctions occur in nearly 80% of DM1 patients, and cardiac arrhythmias or conduction abnormalities are a prominent cause of mortality in affected individuals. Yet, the underlying mechanisms causing such abnormalities are not well understood. We recently demonstrated that aberrant expression of a non-muscle splice isoform of RNA-binding protein RBFOX2 triggers cardiac conduction delay, atrioventricular heart blocks, and spontaneous arrhythmogenesis in DM1 hearts. Here we studied the mechanism(s) by which non-muscle RBFOX2 induces mis-splicing of cardiac conduction genes and tested new therapeutic strategies for treating the lethal cardiac symptoms of this disease. By performing eCLIP and high-resolution RNA-sequencing studies on cardiomyocytes isolated from wild type (expressing the normal muscle-specific RBFOX2 43 isoform), Rbfox2 Δ43/Δ43 (expressing the non-muscle RBFOX2 40 isoform), and RBFOX2 40 overexpressing (OE) mice, we deconstructed the splicing regulatory networks of RBFOX2 43 and RBFOX2 40 isoforms, characterized their respective RNA binding landscapes, and determined the RBFOX2 40 -driven transcriptome alterations in DM1 heart tissue. We acquired induced pluripotent stem cells (iPSC) from healthy, moderate (238 CTG repeats) and severely (1001 CTG repeats) affected DM1 individuals and differentiated them into cardiomyocytes (iPSC-CMs) to generate a human cardiac cell culture model of DM1. Utilizing anti-sense oligonucleotides and RNAi-based approaches, we restored the muscle-specific Rbfox2 splicing pattern and depleted the non-muscle RBFOX2 isoform in the DM1 IPS-CMs. We are currently analyzing the spontaneous electrical phenotypes of normal and DM1 iPSC-CMs. Collectively, our studies provide an in-depth understanding of the molecular basis for DM1-related electrophysiological abnormalities and offer an avenue to test the potential therapeutic utility of targeting the non-muscle RBFOX2 40 isoform in treating cardiac features of DM1.
Abstract 10917: Dna Damage Promotes Atherosclerosis by Enhancing Inflammatory Responses via the DNA Sensing Cgas-Sting Pathway
Authors: CHIEMI SAKAI, Mari Ishida, Keitaro Ueda, Yusuke Kobayashi, Masao Yoshizumi, Takafumi Ishida
Journal: Circulation (2021)

DNA damage is likely a key contributor to atherosclerosis. However, causative links between DNA damage and atherosclerosis are yet to be established. We investigated the role of DNA damage accumulation in atherosclerosis using the DNA repair protein Ku80-deficient apolipoprotein E knockout mice ( Ku80 +/- ApoE -/- ). Ku80 +/- ApoE -/- mice and ApoE -/- mice were fed on high-fat diet for 4 weeks. Oil red O staining showed that plaque area was significantly increased in Ku80 +/- ApoE -/- aortas. Immunohistochemical analysis of lesions from Ku80 +/- ApoE -/- mice revealed enhanced accumulation of DNA double-strand breaks (DSBs). Similar results were obtained from Ku80 +/- ApoE -/- mice fed on high-fat diet for 2 weeks which was considered as the early stages of atherosclerosis. mRNA levels of inflammatory cytokines such as IL-6, MCP-1 and IFN-β in the aorta were significantly elevated in Ku80 +/- ApoE -/- mice than those of ApoE -/- control mice. To further investigate links between DSB accumulation and enhanced proinflammatory responses, vascular smooth muscle cells were isolated from Ku80 WT (WT) and Ku80 +/- mice. mRNA levels of IL-6, MCP-1 and IFN-β were significantly elevated in Ku80 +/- cells compared to those of WT cells. Immunofluorescent analysis revealed DSB accumulation and persistent activation of the DNA repair kinase ATM in Ku80 +/- cells. In addition, senescent markers such as p16 INK4A and senescence-associated β-gal activity were also upregulated in Ku80 +/- cells. Interestingly, the level of cytosolic DNA was elevated in Ku80 +/- cells. Furthermore, phosphorylation of TANK-binding kinase 1 was significantly increased in Ku80 +/- cells, indicating the activation of the cGAS-STING DNA sensing pathway. Thus, we performed cGAS or STING silencing in Ku80 +/- cells using siRNA to test whether cGAS-STING pathway was associated with enhanced proinflammatory responses. cGAS or STING silencing attenuated mRNA level of IL-6 and protein level of IκBα, the NFκB inhibitory protein. Taken together, these results suggested that the accumulation of DSBs promoted atherosclerosis partly through enhanced inflammatory responses via the cGAS-STING activation. Therefore, cGAS-STING may be a promising target for therapeutic intervention of atherosclerosis.
Abstract P434: A Mouse Model To Control Vessel Diameter With Light
Authors: Philip O'Herron, David Hartmann, Andy Y Shih
Journal: Circulation Research (2021)

In diseases such as stroke, hypertension, vascular cognitive impairment, and Alzheimer’s disease, defects in the cerebrovascular system lead to reduced blood flow and vasoreactivity to stimuli. Recently, there has been increased appreciation for the role of small vessels in these vascular pathologies. For example, small vessel dysfunction can cause widespread microinfarcts and capillary stalling, which may underlie cognitive impairment in cases where large scale vascular abnormalities are not readily detected. However, vascular function is difficult to dissociate from concurrent neuronal deficits cause by damage to neuronal circuitry in brain pathology. Thus the ability to directly probe smooth muscle contraction of small, individual vessels in the intact brain would be a valuable tool for increasing our understanding of vascular contributions to cognitive impairment. We developed an experimental paradigm to optically probe the contractile function of arterioles in vivo with high spatiotemporal precision. This was done by expressing the excitatory opsin ReaChR in vascular smooth muscle cells and pericytes. Using a 594 nm light-emitting diode we were able to evoke widespread vasoconstriction across the cranial window. With a 1040 nm focused, pulsed laser for two-photon stimulation, we were able to evoke highly localized constrictions targeted to individual pial artery branches or penetrating arterioles. Our dual light-path imaging system allowed the optogenetic stimulation to be performed with simultaneous two-photon imaging to monitor vessel activity. Using a spatial light modulator, we were also able to constrict vessels both above and below the imaging plane. This is a powerful tool to assay vasoconstrictive function of single arterioles across 3-dimensional vascular networks in vivo. It also presents novel opportunities to study conductance of vascular signals and to modulate dynamics of functional hyperemia.
The Outcome of Autologous Hematopoietic Cell Transplantation in Elderly Patients with Aggressive Non-Hodgkin Lymphoma
Authors: Osman Ilhan, Guldane Cengiz Seval, Sinem Civriz Bozdag, Selami Kocak Toprak, Meltem Kurt Yuksel, Pervin Topcuoglu, Onder Arslan, Muhit Özcan, Taner Demirer, Gunhan Gurman, Meral Beksac
Journal: Blood (2021)
David Oliver: Lessons for NHS staff from the Grenfell inquiry
Authors: David Oliver
Journal: BMJ (2021)

I recently saw a play entitled Value Engineering: Scenes from the Grenfell Inquiry .12 The theatre was within sight of the Grenfell Tower, a 24 storey, 1970s residential tower block in west London, where 72 people lost their lives in 2017 in a completely avoidable blaze that destroyed the building.3

The dramatisation relied entirely on dialogue taken verbatim from transcripts of the public inquiry that followed. Key to the whole tragedy was the use of highly combustible cladding material of a kind that had already led to fatal fires in other tower blocks in London and overseas. The risk was compounded by a small gap left between the cladding and the building, leading to a “flue effect.”

We heard from a …
Abstract 10575: The Effect of Empagliflozin on the Biomarker Growth Differentiation Factor 15 in Patients with Heart Failure and Reduced Ejection Fraction: A Post-Hoc Study of a Randomized, Double-Blind, and Placebo-Controlled Trial
Authors: Massar Omar, Jesper Jensen, Caroline N Kistorp, Kurt Højlund, Julie H Larsen, Camilla Fuchs F Andersen, Lars Videbaek, Christian D Tuxen, Mikael Kjaer K Poulsen, Finn Gustafsson, Lars Kober, Morten Schou, Jacob Moller
Journal: Circulation (2021)

Introduction: Growth differentiation factor 15 (GDF-15) is considered as a biomarker of inflammatory and myocardial tissue injury. However, metformin increases plasma GDF-15, and may be responsible for the metabolic benefits (e.g. weight loss, decrease in Hemoglobin A1c and systolic blood pressure, and improvement in insulin resistance) effects in type 2 diabetes (T2D). Recently, sodium-glucose cotransporter-2 inhibitors (SGLT2i) demonstrated increment in GDF-15 in a proteomic analysis in T2D patients. Hypothesis: To examine SGLT2i’s effect on GDF-15 in HFrEF patients. Methods: This multicenter, randomized, double-blind, placebo-controlled exploratory sub-study enrolled 190 stable HFrEF patients with an ejection fraction of 40% or below. Patients were randomized (1:1) to empagliflozin 10 mg once daily or matching placebo for 12 weeks. Outcome measures were changes from baseline in GDF-15, high sensitive C-reactive protein (hsCRP), and high sensitive troponin T (hsTNT) adjusted for age, sex, BMI, T2D. Results: Mean age was 64 (SD, 11) years; 85% male, 13% with T2D, mean ejection fraction 29 (SD, 8)). Empagliflozin significantly increased GDF-15 compared to placebo [Empagliflozin: baseline, median (interquartile range (IQR)) 1177 (899-1720) pg/mL, follow-up, 1394 (970-1942) pg/mL: Placebo: baseline 1299 (915-1849) pg/mL, follow-up, 1276 (879-1924) pg/mL, adjusted ratio of change (1.10 [95% confidence interval (CI), 1.04-1.17]: p=0.002). There was no significant change in hsCRP (1.13 [95%CI, 0.89-1.43]: p=0.31), nor in hsTNT (1.09 [95%CI, 0.98-1.20]: p=0.12) (Figure 1). Conclusions: Empagliflozin significantly increased GDF-15 in predominantly non-diabetic HFrEF patients regardless of HF etiology, without a concomitant increase in hsCRP, or hsTNT compared to placebo. These results might explain the link between empagliflozin and the metabolic benefits seen in this population.
CNTM-01. Evaluating Traditional and Non-Traditional Eloquent Areas in Patients with Brain Tumors: Large-scale Network Analysis Using a Machine Learning-Based Platform
Authors: Alexis Morell, Daniel Eichberg, Ashish Shah, Evan Luther, Victor Lu, Ricardo Komotar, Michael Ivan
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Developing mapping tools that allow identification of traditional or non-traditional eloquent areas is necessary to minimize the risk of postoperative neurologic deficits. The objective of our study is to evaluate the use of a novel cloud-based platform that uses machine learning to identify cerebral networks in patients with brain tumors. METHODS We retrospectively included all adult patients who underwent surgery for brain tumor resection or thermal ablation at our Institution between the 16th of February and the 15th of May of 2021. Pre and postoperative contrast-enhanced MRI with T1-weighted and high-resolution Diffusion Tensor Imaging (DTI) sequences were uploaded into the Quicktome platform. After processing the data, we categorized the integrity of seven large-scale brain networks: sensorimotor, visual, ventral attention, central executive, default mode, dorsal attention and limbic. Affected networks were correlated with pre and postoperative clinical data, including neurologic deficits. RESULTS Thirty-five (35) patients were included in the study. The average age of the sample was 63.2 years, and 51.4% (n=18) were females. The most affected network was the central executive network (40%), followed by the dorsal attention and default mode networks (31.4%), while the least affected were the visual (11%) and ventral attention networks (17%). Patients with preoperative deficits showed a significantly higher number of altered networks before the surgery (p=0.021), compared to patients without deficits. In addition, we found that patients without neurologic deficits had an average of 2.06 large-scale networks affected, with 75% of them not being related to traditional eloquent areas as the sensorimotor, language or visual circuits. CONCLUSIONS The Quicktome platform is a practical tool that allows automatic visualization of large-scale brain networks in patients with brain tumors. Although further studies are needed, it may assist in the surgical management of traditional and non-traditional eloquent areas.
Abstract 14382: Association of Atherosclerotic Plaque Burden and FFRCT-Serial Cardiac CTA Study
Authors: Kashif Shaikh, April Kinninger, Suraj Dahal, Suvasini Lakshmanan, Ilana Golub, Venkata M Alla, Jonathon Leipsic, Matthew Budoff
Journal: Circulation (2021)

Introduction: Cross-sectional studies have shown the association of atherosclerotic plaque burden and FFRCT. However, the relationship between changes in anatomic CCTA parameters and FFRCT has not ...
Abstract 10402: H <sub>2</sub> FPEF Score as a Prognostic Tool to Predict Mortality and Hospitalization in Adults with Normal Left Ventricular Ejection Fraction and Dyspnea: A Systematic Review and Meta-Analysis
Authors: Gaspar Del Rio-Pertuz, Abel Triana, jose correa, Jackie Rios, Mostafa Abohelwa, Kanak Parmar, Mohamed Elmassry, Erwin E Argueta-Sosa
Journal: Circulation (2021)

Introduction: The score “H2FPEF’’ has been described as a tool to predict heart Failure with Preserved Ejection fraction (HFpEF). The scoring criteria and interpretation are as follows: 0 or 1, exclude HFpEF; 2-5, further examination is needed to confirm the diagnosis; and 6-9, high probability of HFpEF diagnosis. However, predicting the prognosis of patients by using this scoring system is an ongoing topic of interest. Hypothesis: H2FPEF score can be used to predict mortality and heart failure (HF) hospitalization in adults with normal left ventricular ejection fraction (LVEF) and dyspnea. Methods: We systematically searched Pubmed, Embase, and Scopus for abstracts and full-text articles from inception to May 2021. Studies were included if they evaluated the relationship between a high H2FPEF score (defined as ≥6) and mortality or hospitalization due to HF in adults with normal LVEF and/or dyspnea. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using the random-effects model by DerSimonian and Laird. Results: A total of 4 studies were included that had a total of 8071 patients (mean age: 72 years, 49% were females) with an overall mortality of 35%. The relationship between a high H2FPEF score between survivors and non-survivors demonstrated an association with mortality (OR:1.73 CI:1.41-2.11 p&lt;0.01. Figure 1.). The association to mortality persisted in the subgroup analysis of patients who already had the diagnosis of HFpEF and in patients evaluated with unexplained dyspnea, (OR:1.55 CI:1.22-1.96 p&lt;0.01. Figure 2.), (OR:2.02 CI:1.49-2.74 p&lt;0.01 Figure 3.) respectively. In addition, a high H2FPEP was associated with HF related hospitalizations (OR:1.70 CI:1.26-2.29 p&lt;0.01. Figure 4.). Conclusions: A high H2FPEF score is associated with mortality and HF hospitalization irrespective of the presence of a known HFpEF diagnosis. This could help identify a population that may warrant more aggressive monitoring and management strategies.
Abstract 12651: Non-Pharmacological Interventions to Improve Electrical Cardioversion Success in Patients With Atrial Fibrillation: A Scoping Review
Authors: Stephanie T Nguyen, Emilie P Belley-cote, Omar Ibrahim, Kevin J Um, Alexandra Lengyel, Yuan Qiu, Taranah Adli, Serena Sibilio, Michael Wong, Alexander P Benz, Alex Wolf, Whitlock Nicola, J. Gabriel Acosta, Jeff S Healey, Adrian Baranchuk, William F McIntyre
Journal: Circulation (2021)

Introduction: Electrical cardioversion is used commonly in patients with atrial fibrillation (AF). However, success rates vary and practical guidance is limited. Methods: We searched CENTRAL, Medline and EMBASE from inception to present and the grey literature. We included randomized controlled trials (RCTs) comparing any two interventions. Outcomes were initial and cumulative cardioversion success. We pooled data using random effects models. Results: From 13481 citations, we included 52 RCTs. Biphasic as compared to monophasic waveforms resulted in a higher rate of cardioversion for initial (18 studies, risk ratio [RR] 1.45, 95% confidence interval [CI] 1.10-1.90, I 2 =89%) and cumulative success (21 studies, RR 1.07, 95% CI 1.02-1.13, I 2 =75%). Fixed, maximum-energy shocks as compared to low-dose escalating energy protocols had a higher likelihood of initial (4 studies, RR 1.62, 95% CI 1.33-1.98, I 2 =72%) but not cumulative success (3 studies, RR 1.13, 95% CI 0.97-1.32, I 2 =86%). Initial or cumulative cardioversion success did not differ significantly for several other interventions. This included: antero-apical/lateral vs. anteroposterior positioned pads (initial: 10 studies, RR 1.06, 95% CI 0.89-1.27; cumulative: 13 studies, RR 0.99, 95% CI 0.95-1.04); rectilinear/pulsed biphasic vs. biphasic truncated exponential waveform (initial: 3 studies, RR 1.07, 95% CI 0.76-1.50; cumulative: 3 studies, RR 0.95, 95% CI 0.80-1.12); cathodal vs. anodal configuration (cumulative: 2 studies, RR 1.03, 95% CI 0.97-1.09); magnesium pre-treatment vs. none (initial: 2 studies, RR 1.36, 95% CI 0.82-2.24; cumulative: 2 studies, RR 1.05, 95% CI 0.96-1.14); and patches vs. manual pressure/paddles (initial: 2 studies, RR 1.04, 95% CI 0.26-4.12; cumulative: 2 studies, RR 0.87, 95% CI 0.61-1.25). Conclusions: Biphasic shock waveforms and high-energy shocks increase the efficacy of cardioversion of AF. Other interventions, including pad placement, biphasic waveform properties, electrode polarity, electrolyte pre-treatment, and manual pressure require further study.
Abstract 11770: Clinical Outcomes of Optical Coherence Tomography-Guided Compared With Intravascular Ultrasound-Guided in Low-Risk Percutaneous Coronary Intervention: A Meta-Analysis
Authors: Yehia Saleh, Abdullah Al-abcha, Ola Abdelkarim, manel boumegouas, Omar M Abdelfattah, george Abela, Sachin S Goel, Neal S Kleiman
Journal: Circulation (2021)

Background: Axial resolution provided by optical coherence tomography (OCT) is 10 times higher compared with intravascular ultrasound (IVUS), hence OCT could detect fine details such as edge dissections and tissue coverage of stent struts which may be missed by IVUS imaging. Given the lack of robust comparative data, utilization of IVUS or OCT in PCI guidance is mainly based on the operator experience. Recently, multiple studies have compared clinical outcomes between OCT-guided versus IVUS-guided in PCI, thus we performed this meta-analysis. Methods: We conducted a meta-analysis of all studies evaluating the clinical outcomes of OCT-guided versus IVUS-guided in low-risk PCI. Studies that included patients with left main disease, bifurcation lesions, long lesions, in-stent stenosis, and patients with history of coronary artery bypass grafting were all excluded. Our primary outcome was major cardiac adverse events (MACE). Secondary outcomes consisted of all-cause death, myocardial infarction (MI), stent thrombosis (ST), and target lesion revascularization (TLR). Results: Four RCTs and one propensity-matched observational study were included, with a total of 1,544 patients and a median weighted follow-up period of 1.26 years. Out of the total population, 51% were in the OCT arm and 49% in the IVUS arm. Our pooled analysis showed a similar risk of MACE (OCT 5.0% vs IVUS 4.7%, p=0.90), risk of all-cause death (OCT 2.7% vs IVUS 1.7%, p=0.44), MI (OCT 1.5% vs IVUS 1.3%, p=0.76), ST (OCT 0.3% vs IVUS 0.4%, p=0.66) and TLR (OCT 2.2% vs IVUS 2.6%, p=0.58) between the two groups (Figures 1). Heterogeneity was low in all outcomes (I 2 =0). Conclusion: OCT-guided PCI has similar long term clinical outcomes when compared to IVUS-guided PCI in low-risk patients. RCTs with a larger population and longer follow-up periods are needed to confirm these results.
Abstract 6936: American versus Canadian National Funding for Immigrant Cardiovascular Health
Authors: Wassim Bedrouni, Mahdi Bedrouni, Thao HUYNH
Journal: Circulation (2021)

Introduction: The high number of immigrants in North America underscores the need for cardiovascular (CV) health and promotion in these racially and ethnically diverse populations. Although some immigrant races/ethnicities have high cardiovascular mortality, it remains unclear whether there are investments in cardiovascular health promotion and prevention for immigrants for both the United States and America. We aimed to compare American and Canadian national investments cardiovascular health promotion and prevention for immigrants. Methods: We queried the National Institute of Health (NIH) and the Canadian Institute of Health Research (CIHR) databases from 2006 to 2019 for grants supporting projects in diseases prevention and promotion targeting immigrants. We compiled annual funding and normalized the annual data for the number of immigrants and Gross Domestic Product (GDP). We completed normalized descriptive statistics for comparative analysis and presented funding trends over a 14-year period. Results: There were 74 and 50 project grants awarded by the NIH and CIHR, respectively. Between 2007 to 2013, the NIH spent relatively less per immigrant than the CIHR. From 2014 onward, funding trends reversed as the NIH outspent the CIHR. Over the 14-year period, the NIH and the CIHR funded an annual mean of $59.8/1000 immigrants and $79.1/1000 immigrants, respectively. Conclusion: Although the number of immigrants is rising, the relative national funding for CV health promotion and prevention in the USA and Canada is generally decreasing over the last 5 years. Absolute CIHR funding is progressively decreasing since 2008, while NIH grant expenditure has demonstrated an overall pattern of increase over the last 14 years. Policymakers should consider more comprehensive investment in CV health promotion and prevention for immigrants.