tbuckley/cabot-search huggingface dataset:
Abstract 14270: The Effect of Evinacumab on Apheresis Eligibility in Patients With Homozygous Familial Hypercholesterolemia
Authors: Frederick J Raal, Robert S Rosenson, Laurens F Reeskamp, G. Kees Hovingh, John J Kastelein, Paolo Rubba, Shazia Ali, Poulabi Banerjee, Kuo-Chen Chan, Nagwa Khilla, Jennifer McGinniss, Robert Pordy, Yi Zhang, Daniel Gaudet
Journal: Circulation (2020)

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Evinacumab, a fully human monoclonal antibody against angiopoietin-like protein 3, has demonstrated approximately 50% reductions in LDL-C in HoFH patients when added to maximally tolerated lipid-lowering therapies. Objective: In this post-hoc analysis, we assessed the effect of evinacumab on the eligibility for apheresis using predefined US and EU apheresis criteria. Methods: This was a double-blind, placebo-controlled, 24-week phase 3 trial (NCT03399786) that randomized patients 2:1 to evinacumab 15 mg/kg intravenously every 4 weeks (Q4W; n=43) or placebo (n=22). We assessed the proportion of patients who met per protocol US apheresis criteria (LDL-C ≥300 mg/dL), newer US criteria for FH (LDL-C ≥300 mg/dL or LDL-C ≥160 mg/dL with coronary heart disease or peripheral artery disease) and per protocol EU apheresis criteria (LDL-C &gt;160 mg/dL [primary prevention] or &gt;120 mg/dL [secondary prevention]) at baseline and week 24. Results: Under the newer US criteria (2018), 62.8% (n=27) of evinacumab-treated patients and 54.5% (n=12) placebo-treated patients qualified for apheresis at baseline (Table). Following 24 weeks of treatment, 48.8% of all evinacumab versus 9.1% of all placebo patients no longer qualified for apheresis. Similar results were observed using EU apheresis criteria, where 46.5% of evinacumab-treated patients shifted from qualifying for apheresis at baseline to not qualifying at week 24, compared with 4.5% of placebo-treated patients. The majority of evinacumab (65.1%) and placebo (68.2%) patients did not qualify for per protocol US apheresis at baseline, however a shift of 27.9% and 9.1% was observed, respectively. Conclusions: Evinacumab has the potential to reduce the need for apheresis in patients with HoFH.
Abstract 16053: Impact of COVID-19 Pandemic on Cardiology Fellowship Echocardiography Training
Authors: Merilyn S Varghese, Joseph P Kannam, Marilyn Riley, Warren J Manning
Journal: Circulation (2020)

Introduction: Training in the acquisition and interpretation of echocardiograms is integral to cardiovascular disease fellowship training. The American Society of Echocardiography recommends 150 transthoracic echo (TTE) scans and 300 interpretations for level 2 training. Hypothesis: The COVID-19 pandemic led to the temporary restructuring of many fellowship programs. At our institution, fellows not involved in essential clinical rotations served in a backup capacity or were re-assigned with the onset of the Massachusetts stay-at-home advisory on March 15, 2020. A one-hour mid-day Zoom TTE reading session was offered when fellows were available. We hypothesized that these restrictions would impact fellow education in TTE scanning and interpretation volumes. Methods: We examined the number of TTE performed or interpreted by F1 and F2 fellows between July 2017 and June 2020 as recorded in our echo lab electronic database. Results: In the 21 months prior to the onset of the COVID-19 pandemic, 45 + 1 TTE scans/wk were performed by fellows which was reduced to 9 + 3 scans/wk (-80%, p&lt;0.01) during the pandemic. The average number of F1 and F2 TTE interpretations also fell from 64 + 2/wk to 27 + 5 (-58%, p&lt;0.01). When evaluating scans by year of training (see Table), the 2019-2020 F1s and F2s will have the lowest TTE scan and interpretation volumes compared to prior two academic years (F1: -14% scanning, -28% interpretations, F2: - 33% scanning, -10% interpretations). Conclusions: By recognizing that there has already been an impact on echo education, fellowship programs will need to optimize fellow exposure and instruction in echocardiography so as to maintain adequate training volumes.
Growing vertical aligned mesoporous silica thin film on nanoporous substrate for enhanced degradation, drug delivery and bioactivity
Authors: Zhe Li, Yide He, Lasse Hyldgaard Klausen, Ning Yan, Jing Liu, Fanghao Chen, Wen Song, Mingdong Dong, Yumei Zhang
Journal: Bioactive Materials (2020)

Mesoporous silica thin film has been widely used in various fields, particularly the medical implant coating for drug delivery. However, some drawbacks remain with the films produced by traditional method (evaporation-induced self-assembly, EISA), such as the poor permeability caused by their horizontal aligned mesochannels. In this study, the vertical aligned mesoporous silica thin film (VMSTF) is uniformly grown alongside the walls of titania nanotubes array via a biphase stratification growth method, resulting in a hierarchical two-layered nanotubular structure. Due to the exposure of opened mesopores, VMSTF exhibits more appealing performances, including rapid degradation, efficient small-molecular drug (dexamethasone) loading and release, enhanced early adhesion and osteogenic differentiation of MC3T3-E1 cells. This is the first time successfully depositing VMSTF on nanoporous substrate and our findings suggest that the VMSTF may be a promising candidate for bone implant surface coating to obtain bioactive performances.
Abstract 13206: Blood Pressure Apps: Do They Educate the Lay Public About Risk Factors?
Authors: Arunima Vijay, Gloria Wu
Journal: Circulation (2020)

Introduction: Hypertension affects 108 million Americans. To help track and manage hypertension, there are many free and popular mobile health apps that track BP. Hypothesis: BP tracking mobile health apps have many downloads but do not fully educate the public about hypertension risk factors. Methods: “Blood Pressure” as a search term was used in the Google Play and Apple iOS stores to identify the most popular, free BP tracking apps aimed at the lay public. The top 10 most popular, free apps on each store were evaluated for educating the lay public on hypertension risk factors. Inclusion criteria: top 10 free blood pressure (BP) apps, by highest number of downloads on Google Play and highest rating (out of five stars) on Apple iOS Store (no available data on iOS downloads). Exclusion criteria: non-English, requiring a wearable device, primary purpose other BP tracking. Results: Of top 20 apps: BP log: 19/20, BP ranges: 13/20, height: 5/20, weight: 8/20, BMI: 3/20, race: 1/20, gender: 4/20, age: 6/20, diet: 1/20, exercise: 1/20, medication: 4/20, diabetes: 1/20, FBS: 1/20, goals: 3/20, mood/depression: 1/20. 2 apps mentioned the American Heart Association (AHA). None of the apps had information on cvriskcalculator.com, family history, cholesterol, LDL, triglycerides, HbA1c, and alcohol use. Conclusion: Most free and popular BP apps monitor BP but largely ignore hypertension risk factors such as cholesterol, LDL, triglycerides, alcohol intake, mood/depression, race, and gender. Furthermore, 7/20 apps do not uniformly educate patients that a normal BP is &lt;120/&lt;80, in accordance with the AHA and ACC guidelines. More collaboration may be needed between physicians and software developers to educate and meet the needs of our hypertensive patients in America.
A High-Content Screen Identifies Drugs That Restrict Tumor Cell Extravasation across the Endothelial Barrier
Authors: Georg Hilfenhaus, Ana Mompeón, Jonathan Freshman, Divya P. Prajapati, Gloria Hernandez, Vanessa M. Freitas, Feiyang Ma, Adam D. Langenbacher, Snezana Mirkov, Dana Song, Byoung-Kyu Cho, Young Ah Goo, Matteo Pellegrini, Jau-Nian Chen, Robert Damoiseaux, M. Luisa Iruela-Arispe
Journal: Cancer Research (2020)

Metastases largely rely on hematogenous dissemination of tumor cells via the vascular system and significantly limit prognosis of patients with solid tumors. To colonize distant sites, circulating tumor cells must destabilize the endothelial barrier and transmigrate across the vessel wall. Here we performed a high-content screen to identify drugs that block tumor cell extravasation by testing 3,520 compounds on a transendothelial invasion coculture assay. Hits were further characterized and validated using a series of in vitro assays, a zebrafish model enabling three-dimensional (3D) visualization of tumor cell extravasation, and mouse models of lung metastasis. The initial screen advanced 38 compounds as potential hits, of which, four compounds enhanced endothelial barrier stability while concurrently suppressing tumor cell motility. Two compounds niclosamide and forskolin significantly reduced tumor cell extravasation in zebrafish, and niclosamide drastically impaired metastasis in mice. Because niclosamide had not previously been linked with effects on barrier function, single-cell RNA sequencing uncovered mechanistic effects of the drug on both tumor and endothelial cells. Importantly, niclosamide affected homotypic and heterotypic signaling critical to intercellular junctions, cell-matrix interactions, and cytoskeletal regulation. Proteomic analysis indicated that niclosamide-treated mice also showed reduced levels of kininogen, the precursor to the permeability mediator bradykinin. Our findings designate niclosamide as an effective drug that restricts tumor cell extravasation through modulation of signaling pathways, chemokines, and tumor-endothelial cell interactions. SIGNIFICANCE: A high-content screen identified niclosamide as an effective drug that restricts tumor cell extravasation by enhancing endothelial barrier stability through modulation of molecular signaling, chemokines, and tumor-endothelial cell interactions. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/3/619/F1.large.jpg.
Two-Stage Turnbull-Cutait Pull-Through Coloanal Anastomosis for Low Rectal Cancers
Authors: Wafi Attaallah
Journal: JAMA Surgery (2020)

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Abstract 16422: Lower Mitochondrial-derived Peptide Humanin in Young Adults Born Preterm vs. Term and Association With Left Ventricular Ejection Fraction
Authors: Daniela Ravizzoni Dartora, Adrien Flahualt, Carolina Nobre Pontes, Gabriel Altit, Alyson Deprez, Ying He, Anik Cloutier, Jessica Simoneau, Anie Lapointe, Andréanne Villeneuve, Yan Burelle, Michel White, Jean-Luc Bigras, Thuy-Mai Luu, ANNE MONIQUE NUYT
Journal: Circulation (2020)

Introduction: Preterm (PT) birth is associated with increased risk of cardiovascular diseases (CVD) and heart failure. We previously reported left ventricular (LV) mitochondrial dysfunction in a rat model mimicking the deleterious conditions associated with PT birth. Whether mitochondrial function is altered in humans born PT and associated with LV function changes is unknown. We aimed to determine if serum humanin levels, a mitochondrial-derived peptide with cytoprotective effects, are altered in humans born PT and are associated with impaired myocardial function. Methods: Data were obtained from 55 young adults born PT (&lt;30 weeks of gestational age, GA) compared to 54 full-term (T) controls of the same age. Serum humanin levels were determined by ELISA and LV ejection fraction (LVEF) by echocardiography. Results are shown as median (interquartile range) and comparisons between groups were performed using non-parametric tests. Results: Individuals were evaluated at 23.3 (21.4, 25.3) years, and age and sex distribution were similar between groups. Median GA was 27.5 (26.2, 28.4) weeks in the PT group. Humanin levels (pg/ml) were 132.9 (105.1, 189.3) and 161.1 (123.6, 252) in the PT and the T groups, respectively (p=0.0414). LVEF was within the normal range and similar between groups. Lower LVEF was associated with lower humanin levels (p&lt;0.001), and this association was observed both in the term (p=0.002) and the preterm (p=0.047) groups. Conclusions: Serum humanin levels are lower in adult born PT. Since lower humanin levels are also associated with lower LVEF, our results suggest that mitochondrial alterations could play a role in the long-term adverse cardiovascular consequences of PT birth. Humanin analogs improve LV function in experimental models. Our results pave the way for future studies exploring humanin as a therapeutic avenue for the prevention and treatment of CVD in individuals born PT.
Assisted dying survey: support differs for physician assisted suicide and voluntary euthanasia
Authors: Robert Twycross
Journal: BMJ (2020)

The title of Torjesen’s article, “BMA should drop its opposition to assisting dying, say members in landmark poll,”1 misrepresents the results of the BMA survey, which describes physician assisted dying as both “prescribing drugs for self-administration” (physician assisted suicide) and “administering drugs” (voluntary euthanasia). The space given to voluntary euthanasia—just two paragraphs tagged on at the end—is a travesty.

The survey results show a …
Emergence of carbapenem-resistant ST131 Escherichia coli carrying blaOXA-244 in Germany, 2019 to 2020
Authors: Sybille Welker, Sébastien Boutin, Thomas Miethke, Klaus Heeg, Dennis Nurjadi
Journal: Eurosurveillance (2020)

The dissemination of carbapenem-producing Gram-negative bacteria is a major public health concern. We report the first detection of OXA-244-producing ST131 O16:H5 Escherichia coli in three patients from two tertiary hospitals in the south-west of Germany. OXA-244 is emerging in Europe. Because of detection challenges, OXA-244-producing E. coli may be under-reported. The emergence of carbapenem resistance in a globally circulating high-risk clone, such as ST131 E. coli is of clinical relevance and should be monitored closely.
Abstract 324: Assessment of Optimal Chest Compression Depth to Optimize Cardiopulmonary Resuscitation: A Randomized Controlled Trial
Authors: Marlies Bruckner, Seung Yeun Kim, Gyu Hong Shim, Mattias Neset, Po-yin Cheung, Tze-Fun Lee, Megan O'Reilly, Georg Schmölzer
Journal: Circulation (2020)

Introduction: Neonatal chest compression (CC) should be performed to a 1/3 anterior-posterior (AP) chest diameter depth, however, the optimal AP depth is unknown. Hypothesis: We hypothesized that in asphyxiated neonatal piglets a 40% AP depth compared to 1/3, or 1/4 AP depth will reduce time to achieve return of spontaneously circulation and improve survival. Methods: Newborn piglets (n=8/group) were anesthetized, intubated, instrumented, and exposed to 45-minute normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to four intervention groups (“AP 12.5% depth”, “AP 1/4 depth”, “AP 1/3 depth” or “AP 40% depth“). CCs were performed using an automated CC machine with a rate of 90/min. Hemodynamic and respiratory parameters were continuously measured. Results: Median (IQR) time to return of spontaneously circulation was 70 (60-117), 85 (72-90), 90 (90-130), and 600 (600-600) sec with AP 40% depth, AP 1/3 depth, AP 1/4 depth, AP 12.5% depth, respectively. No piglet in the AP 12.5% depth group achieved ROSC while the short-term survival (1h) in the other groups was 100%. Systolic and diastolic blood pressure, central venous pressure, carotid blood flow, tidal volume, and minute ventilation increased with increasing AP depth. Conclusions: Time to return of spontaneously circulation and survival was similar between 1/4, 1/3, and 40% AP depth, while 12.5% AP depth did not result in return of spontaneously circulation. Hemodynamic and respiratory parameters improved with increasing AP depth suggesting that 40% AP depth might provide improved organ perfusion and oxygen delivery.
Abstract 15824: Safety and Efficacy of Periprocedural Direct Oral Anticoagulant versus Aspirin Use for Reduction of the Risk of Cerebrovascular Events in Patients Undergoing Ventricular Tachycardia Radiofrequency Catheter Ablation (STROKE-VT)
Authors: Dhanunjaya Lakkireddy, Jayaprakash Shenthar, Deepak Padmanabhan, Bharath Banavalikar, Ghulam Murtaza, Krishna Akella, Donita Atkins, Rakesh Gopinathannair, Luigi Di Biase, Andrea Natale
Journal: Circulation (2020)

Background: The STROKE-VT is an ongoing, multicenter, randomized controlled trial that studies the differences in cerebrovascular events between DOAC vs ASA use post procedurally in ischemic and non-ischemic cardiomyopathy patients undergoing left ventricular tachycardia radiofrequency ablation (VT RFA). Methods: 52 Eligible patients scheduled for VT RFA were randomized 1:1 post procedurally to a DOAC (n=26; Dabigatran-11/Rivaroxaban-12 &amp; Apixaban-3) or ASA (n=26, 81mg) for 30 days. VT ablation was performed under moderate sedation or general anesthesia either through retrograde aortic (n=28) or transseptal (n=24) approach. All patients were given IV heparin for ACT&gt;300msec. Study drug was administered 3 hours after hemostasis. A brain MRI was done within 6-12 hours post VTRFA and at 30 days. NIH stroke scale was used to assess for neurological changes before, after and at 30 day follow up. Results: 52 patients (M:F- 4.2:1) with 55% ICM were enrolled. DOAC group was slightly older (65±8 vs 60±6 yrs, p=0.04)), had longer procedural (186±76 vs 150±51, p&lt;0.001) and RF time (45 ± 23 vs 24±23, p=0.01) and greater use of transseptal approach (58 vs 42%, p=0.03) compared to the ASA group. One patient in the ASA group had a TIA in the immediate postop period. 31% (16/52) had acute asymptomatic cerebral embolizations (ACE) (25% vs 5% with Retrograde aortic approach). DOAC group had a significantly lower incidence of ACE at 1 month f/u MRI (8 vs 38%, p&lt;0.001). On multivariate analysis predictors of acute post VTRFA ACE were retrograde aortic approach, prolonged procedure and RFA time, while delayed ACE was ASA therapy. Two patients died of progressive heart failure with one in each group. 1 patient had a TIA during f/u in the ASA group. Conclusions: DOAC decrease the incidence of delayed ACE after VTRFA. However, retrograde aortic approach and prolonged procedural and RFA time can increase the risk of acute ACE.
Targeting the CD146/Galectin-9 axis protects the integrity of the blood–brain barrier in experimental cerebral malaria
Authors: Hongxia Duan, Shuai Zhao, Jianquan Xiang, Chenhui Ju, Xuehui Chen, Irene Gramaglia, Xiyun Yan
Journal: Cellular and Molecular Immunology (2020)

Abstract Cerebral malaria (CM) is a life-threatening diffuse encephalopathy caused by Plasmodium falciparum , in which the destruction of the blood–brain barrier (BBB) is the main cause of death. However, increasing evidence has shown that antimalarial drugs, the current treatment for CM, do little to protect against CM-induced BBB damage. Therefore, a means to alleviate BBB dysfunction would be a promising adjuvant therapy for CM. The adhesion molecule CD146 has been reported to be expressed in both endothelial cells and proinflammatory immune cells and mediates neuroinflammation. Here, we demonstrate that CD146 expressed on BBB endothelial cells but not immune cells is a novel therapeutic target in a mouse model of experimental cerebral malaria (eCM). Endothelial CD146 is upregulated during eCM development and facilitates the sequestration of infected red blood cells (RBCs) and/or proinflammatory lymphocytes in CNS blood vessels, thereby promoting the disruption of BBB integrity. Mechanistic studies showed that the interaction of CD146 and Galectin-9 contributes to the aggregation of infected RBCs and lymphocytes. Deletion of endothelial CD146 or treatment with the anti-CD146 antibody AA98 prevents severe signs of eCM, such as limb paralysis, brain vascular leakage, and death. In addition, AA98 combined with the antiparasitic drug artemether improved the cognition and memory of mice with eCM. Taken together, our findings suggest that endothelial CD146 is a novel and promising target in combination with antiparasitic drugs for future CM therapies.
Abstract 13601: Risk of Coronary Artery Disease Associated With Familial Hypercholesterolemia Genetic Variants is Independent of Historical Low-density Lipoprotein Cholesterol Exposure
Authors: Shoa L Clarke, Catherine Tcheandjieu, Austin Hilliard, Kyung Min Lee, julie lynch, Kyong-Mi Chang, Donald Miller, Christopher J O'Donnell, Philip S Tsao, Daniel J Rader, Peter Wilson, Yan V Sun, Michael Gaziano, Themistocles L Assimes
Journal: Circulation (2020)

Introduction: Familial Hypercholesterolemia (FH) variants confer risk for coronary artery disease (CAD) even after adjusting for a single baseline LDL measure. Hypothesis: We hypothesized that a model incorporating serial LDL measures over many years may account for the risk associated with FH variants. Methods: We analyzed 418,790 participants in the Million Veteran Program with electronic health records (EHR) spanning up to 15 years prior to and 7 years after enrollment. FH variants were defined using ClinVar and standard bioinformatic approaches. Carriers were identified by custom genotype array. CAD cases were identified by chart codes for acute MI and coronary revascularization. We used a nested case-control design conditional on survival to enrollment. Controls were matched on year of first LDL, time between first LDL and the case index date, age, sex, and ancestry. Logistic regression was used to estimate CAD risk among FH carriers while adjusting for CAD risk factors and the first, maximum (max), or mean LDL prior to the index date. Results: We found 53 LDLR , 2 APOB , and 2 PCSK9 variants, and FH prevalence was 1:303. We identified 23,091 cases with ≥1 LDL measure prior to the diagnosis of CAD and matched 10 controls per case. Cases had a median of 6 LDL measures over a median of 49 months prior to the index date. Carriers had an increased risk for CAD compared to non-carriers. Adjusting for the first, max, and mean LDL progressively attenuated risk of CAD associated with FH, but residual FH risk remained substantial ( Figure ). This pattern did not change in the subset of subjects with the most extensive LDL data nor in the subset of incident cases. We additionally found evidence of modifying effects of sex and ancestry, with higher within-group risk for females and subjects of African ancestry ( Figure ). Conclusion: The risk associated with FH variants cannot be fully captured by the LDL data available in the EHR, even when considering multiple LDL measurements spanning several years.