tbuckley/cabot-search huggingface dataset:
Abstract 14961: External Applicability of REDUCE-IT in a Large Diabetes Cardiovascular Outcomes Trial: A Post Hoc Analysis of EMPA-REG OUTCOME
Authors: Subodh Verma, Deepak L Bhatt, Lawrence A Leiter, David H Fitchett, Anne Pernille Ofstad, Christoph Wanner, Jyothis T George, Michaela Mattheus, Bernard Zinman, Patrick R Lawler
Journal: Circulation (2020)

Introduction: In the REDUCE-IT trial, icosapent ethyl (IPE) was shown to reduce major adverse cardiac events (MACE) including cardiovascular (CV) death in patients with elevated triglycerides (TG) and atherosclerotic CV disease (ASCVD) and/or diabetes. There are limited data evaluating the external applicability of REDUCE-IT inclusion criteria in contemporary diabetes trials. In EMPA-REG OUTCOME, empagliflozin (EMPA) reduced the risk of CV death and hospitalization for HF (HHF). We sought to evaluate the benefit of EMPA on CV outcomes across IPE eligibility in the EMPA-REG OUTCOME trial. Methods: In total, 7020 patients with type 2 diabetes and ASCVD were treated with EMPA 10mg, 25 mg, or placebo (PBO). We examined the proportion of patients that had baseline (BL) TG 135 to 499 mg/dl, LDL-C 41 to 100 mg/dl and using a statin (“REDUCE-IT-like patients”). We evaluated the effect of pooled EMPA vs. PBO on CV death, HHF, HHF or CV death (excluding fatal stroke), all-cause death, and 3-point-MACE across the subgroups of patients fulfilling vs not fulfilling the REDUCE-IT criteria at BL using Cox regression. Results: A total of 6935 patients had TG and 6932 had LDL-C available. 1810 patients (25.8%) were REDUCE-IT like with TG 206±69 vs. 158±140 mg/dl, and LDL-C 71±15 vs. 91±39 mg/dl in those who did not meet the criteria. At BL, the former had more often coronary artery disease (84 vs. 73%) and higher BMI (31.7±5.1 kg/m 2 vs. 30.3±5.3) vs. the latter group. CV event rates in PBO were similar in patients who met/did not meet the criteria. Treatment effects of EMPA vs. PBO were consistent in patients who met/did not meet the REDUCE-IT criteria (Fig). Conclusions: In patients with T2D and established ASCVD treated in EMPA-REG OUTCOME, about one-quarter of patients would qualify for IPE according to the REDUCE-IT inclusion criteria. Empagliflozin consistently reduced CV outcomes and mortality in this sub-group, suggesting that IPE and SGLT2 inhibition may be complementary.
Abstract 14610: Renal Dysfunction in Adults With Congenital Heart Disease in Vietnam
Authors: Ngoc Thanh Kim, Thanh Tung Le, Doan Loi Do, Thanh Huong Truong
Journal: Circulation (2020)

Introduction: In Vietnam, knowledge about renal function in adults with congenital heart disease (CHD) is limited. Hypothesis: This study aims to estimate incidence of renal dysfunction in adults with congenital heart disease and risk factors. Methods: This is a cross-sectional study, including 365 CHD patients more than 16 years old. We collected clinical and para-clinical information, estimated glomerular filtration rate (GFR) and calculated the odds ratio (OR) for reduced GFR. Results: Totally, 52.8% patients had GFR &lt; 90 ml/phút/1.73 m 2 . Logistic regression had confirmed the OR for GFR &lt; 90 ml/phút/1.73 m 2 in the group &gt; 60-years-old, the group with atrial fibrillation, the group with heart failure (based on NT-proBNP &gt; 125 pmol/L), and the group with pulmonary arterial hypertension (based on pulmonary artery systolic pressure &gt; 50 mmHg by echocardiography) were 6.46 (95% CI: 1.37 - 30.41), 7.58 (95% CI: 1.66 - 34.56), 2.98 (95% CI: 1.49 - 5.98) and 1.84 (95% CI: 1.02 - 3.33), respectively. Conclusions: Renal dysfunction is common in adults with CHD. Age &gt; 60 years-old, atrial fibrillation, heart failure, and pulmonary arterial hypertension were risk factors for renal dysfunction in adults with CHD.
Assessment of Risk Factors and Outcomes of Severe Ehrlichiosis Infection
Authors: Kevin Kuriakose, April C. Pettit, Jonathan Schmitz, Abelardo Moncayo, Karen C. Bloch
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Ehrlichiosis cases in the US have increased more than 8-fold since 2000. Up to 57% of patients with ehrlichiosis require hospitalization and 11% develop a life-threatening complication; however, risk factors for serious disease are not well documented. <h3>Objective</h3> To examine risk factors associated with severe ehrlichiosis. <h3>Design, Setting, and Participants</h3> An analytic cross-sectional study of patients diagnosed with ehrlichiosis by polymerase chain reaction (PCR) between January 1, 2007, and December 31, 2017, was conducted in a single tertiary-care center in a region endemic for ehrlichiosis. Analysis was performed from February 27, 2018, to September 9, 2020. A total of 407 positive<i>Ehrlichia</i>PCR results were identified from 383 unique patients, with 155 unique patients meeting study criteria. Patients hospitalized at other institutions who had a positive<i>Ehrlichia</i>PCR performed as a reference test (n = 222) were excluded as no clinical data were available. Electronic medical record review was performed to collect demographic, clinical, laboratory, treatment, and outcomes data. Cases were excluded when there were insufficient clinical data to assess the severity of illness (n = 3) and when the clinical illness did not meet the case definition for ehrlichiosis (n = 3). <h3>Exposures</h3> Date of presentation, onset of symptoms, date of PCR testing, date of treatment initiation, site of care, age, birth sex, race/ethnicity, Charlson Comorbidity Index, trimethoprim with sulfamethoxazole use within the prior 2 weeks, and immunosuppression. <h3>Main Outcomes and Measures</h3> Requirement for intensive care unit (ICU) admission. <h3>Results</h3> Of the 155 patients who met inclusion criteria, 99 patients (63.9%) were men, and 145 patients (93.5%) identified as non-Hispanic White; median age was 50 years (interquartile range, 23-64 years). Intensive care unit admission was indicated in 43 patients (27.7%), 94 patients (60.6%) were hospitalized on general medical floors, and 18 patients (11.6%) received care as outpatients. In adjusted analysis, time to treatment initiation was independently associated with an increased risk for ICU admission (adjusted prevalence ratio [aPR], 1.09; 95% CI, 1.04-1.14;<i>P</i> &lt; .001). Documentation of tick exposure was independently associated with a decreased risk for ICU admission (aPR, 0.54; 95% CI, 0.34-0.86;<i>P</i> = .01). There appeared to be a nonsignificant change toward a decreased need for ICU care among immunosuppressed persons (aPR, 0.51; 95% CI, 0.26-1.00;<i>P</i> = .05). <h3>Conclusions and Relevance</h3> This study suggests that delay in initiation of doxycycline therapy is a significant factor associated with severe ehrlichiosis. Increased recognition of infection by front-line clinicians to promote early treatment may improve outcomes associated with this increasingly common and life-threatening infection.
Abstract 15115: Clinical Presentation and Medium-term Outcomes in Anomalous Aortic Origin of the Left Coronary Artery: High-risk Features Beyond Interarterial Course
Authors: J Kevin Wilkes, Tam Doan, Dana Reaves O’Neal, Carlos Bonilla-Ramirez, Shagun Sachdeva, Prakash Masand, Carlos M Mery, Ziyad Binsalamah, Christopher Caldarone, E. Dean McKenzie, Silvana M Molossi
Journal: Circulation (2020)

Background: Anomalous aortic origin of the left coronary artery (AAOLCA) confers a rare, but significant, risk of sudden cardiac death (SCD) in children. Surgical intervention is recommended for AAOLCA with an interarterial course, with other subtypes considered benign. We aimed to determine the clinical characteristics and outcomes of AAOLCA in a prospective cohort following a standardized approach. Methods: All patients with AAOLCA &lt;20 years old were prospectively enrolled. Anatomic details were obtained with coronary computerized tomography angiography (CTA). Myocardial functional studies were obtained under provocative stress, including exercise stress test, stress nuclear perfusion imaging, or dobutamine stress cardiac magnetic resonance. Patients were stratified as high-risk if: 1) episode of aborted SCD, 2) interarterial and/or intramural course, or 3) evidence of myocardial ischemia on functional studies. Results: A total of 47 patients (32 male, 68%) with AAOLCA were enrolled, median age 12 [IQR 6.0;15.0] years. Of these, 20 had exertional symptoms (42.5%) and 5 had aborted SCD (10.5%). Thirty-one patients (79%) were classified high-risk, 28% low-risk, and 3 (6%) work-up is ongoing. Of patients with completed work-up, 16/43 (37%) had inducible ischemia and, of these, 2/16 (13%) presented without symptoms and one with aborted SCD as the first symptom. Two patients in our cohort had AAOLCA arising close to the noncoronary sinus, just above the left and noncoronary commissure, resulting in ostial stenosis: one presented with aborted SCD and another with left ventricular dysfunction. To date, 17 patients have undergone repair, median age 10 years [IQR 6.6;15.7]. Median follow-up was 3.9 [IQR 1.3;6.3] years with no significant symptoms and all but 4 patients are cleared from exercise restrictions. Conclusion: AAOLCA may present with diverse anatomic configuration and risk stratification is essential to determine management. AAOLCA from the noncoronary sinus may also present with myocardial ischemia and, thus, be classified as high-risk. A multimodality imaging approach is necessary to adequately risk stratify this population. All patients are alive at last follow-up and the majority free from exercise restriction.
Abstract 13140: Right Ventricular Remodeling and Changes in Tissue Biomechanics in Healthy Aging
Authors: Danial Sharifikia, Yuanjun Shen, Timothy Bachman, Elena Goncharova, Kang Kim, Marc A Simon
Journal: Circulation (2020)

Introduction: Normal aging in healthy adults has been associated with pulmonary vasculature remodeling and alterations in right ventricular (RV) systolic and diastolic function, which may lead to increased RV afterload and pulmonary hypertension (PH). Previous studies have found a close link between RV biomechanics and function. While current findings suggest a connection between aging and survival rates of PH patients, limited data exist on age-associated differences in the biomechanical properties of RV myocardium. Hypothesis: Aging results in increased RV afterload, hypertrophy, and myocardial stiffening. Methods: Two groups of control (11 weeks) and aging (80 weeks) Sprague-Dawley rats were studied via terminal invasive hemodynamic measurements (n=5/group), quantitative transmural histological analysis (n=3/group; Masson’s trichrome), biaxial mechanical testing (n=6/group) and constitutive modeling (n=6/group) for a comprehensive multi-scale study on the effects of aging on RV biomechanics. Results: Aging increased RV peak pressures by 15% (26.79±0.87 vs. 23.28±0.83 mmHg for aging vs. control; p=0.020). Increased RV wall thickness (0.89±0.06 vs. 0.66±0.04 mm for aging vs. control; p=0.010) and cardiomyocyte width (25.42±0.34 vs. 14.94±0.64 μm for aging vs. control; p&lt;0.001) were observed in the aging group, while not showing any effects on the Fulton index. Histological analyses showed transmural realignment of RV collagen and myofibers towards the apex-to-base direction by 14.6° (p=0.017). This was accompanied by transmural loss of cardiomyocytes (cardiomyocyte area fraction: 88.4%±0.4% vs. 95.3%±0.7% for aging vs. control; p&lt;0.001) and increased myofiber stiffness (169.9±20.6 vs. 65.8±4.7 kPa for aging vs. control; p&lt;0.001). While aging resulted in RV fibrosis (collagen area fraction: 5.1%±0.5% vs. 3.8%±0.1% for aging vs. control; p=0.049), collagen fibers in the aging myocardium showed decreased effective intrinsic stiffness compared to young controls (23.9±3.8 vs. 73.1±15.4 MPa for aging vs. control; p=0.031). Conclusions: Healthy aging has the potential to modulate RV dysfunction via increased myofiber stiffness, fiber reorientation, loss of ventricular cardiomyocytes, RV hypertrophy and fibrosis.
Abstract PO-022: Plasma fatty acid levels in treatment-naïve metastatic pancreatic cancer patients are associated with clinical indicators of cachexia
Authors: Kristyn Gumpper, Phil A. Hart, Martha Belury, Olivia Crowe, Rachel M. Cole, Niharika Badi, Alice Hinton, Mitchell L. Ramsey, Anne Noonan, Darwin L. Conwell, Zobeida Cruz-Monserrate
Journal: Cancer Research (2020)

Abstract Cachexia is a multifactorial syndrome characterized by weight loss and tissue wasting, which is associated with reduced quality of life, responsiveness to chemotherapy, and decreased survival. We aim to determine whether changes in plasma fatty acid content in pancreatic ductal adenocarcinoma (PDAC): 1) are predictive of developing cachexia, and 2) whether these changes are influenced by other clinical parameters, like diabetes, that could contribute to malnutrition. Treatment-naïve metastatic PDAC subjects (n=51) were enrolled in NCT01280058 in which plasma samples and clinical data were collected prior to treatment. Subjects were assigned to either weight stable (&amp;lt;5% relative body weight loss, n=26) or “cachectic” (≥5% weight loss, n=25). Plasma fatty acid composition was analyzed via gas chromatography and reported as a percentage of the total identified fatty acids. Oleic (p=0.004) and adrenic acids (p=0.018) were significantly increased in cachectic subjects, regardless of age, sex, or BMI. Docosapentaenoic n-6 acid was more commonly elevated in older cachectic subjects compared to younger subjects (p=0.048). Adrenic acid levels were higher in subjects with cachexia and diabetes compared to subjects without diabetes with cachexia (p=0.0019) or stable weight (p=0.029). Additionally, linoleic acid was lower in subjects with cachexia and diabetes compared to subjects with cachexia and no diabetes (p=0.015) and subjects with stable weight (p=0.017). Area under the receiver operator curves (AUC) showed that oleic acid (AUC=0.726) and adrenic acid (AUC=0.706) are mildly effective at predicting cachexia, and the combination slightly improved the predictive ability (AUC=0.757). Our pilot study identified several plasma fatty acids that are associated with PDAC-associated cachexia, and are influenced by age and diabetes status. Further studies examining how fatty acids contribute to or arise from the development of cachexia may create opportunities for developing effective therapies for cachexia. Citation Format: Kristyn Gumpper, Phil A. Hart, Martha Belury, Olivia Crowe, Rachel M. Cole, Niharika Badi, Alice Hinton, Mitchell L. Ramsey, Anne Noonan, Darwin L. Conwell, Zobeida Cruz-Monserrate. Plasma fatty acid levels in treatment-naïve metastatic pancreatic cancer patients are associated with clinical indicators of cachexia [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-022.
An endoscopic multimodal approach in a patient with blue rubber bleb nevus syndrome and acute bleeding
Authors: Alejandro Campos-Murguía, Luis Eduardo Zamora-Nava
Journal: Endoscopy (2020)

Blue rubber bleb nevus syndrome is a rare disease characterized by multiple venous malformations found in various organs, among which the gastrointestinal (GI) tract stands out [1]. Patients frequently suffer GI bleeding and iron deficiency anemia. Many endoscopic therapeutic options have been implemented for treatment of this syndrome, such as endoscopic sclerotherapy [2] [3], endoscopic band ligation, detachable snare [4], and even endoscopic submucosal dissection [5].
Abstract 13695: Paracrine-mediated Rejuvenation of Aged Mesenchymal Stem Cells Involves Broad Transcriptional Modulation of Angiogenic Factors
Authors: George Hung, Andreas S Barth, Peter V Johnston, Gary Gerstenblith
Journal: Circulation (2020)

Introduction: Angiogenesis induced by bone marrow mesenchymal stem cells (MSCs) obtained from aged mice is inferior to those obtained from young mice, but is improved following exposure to conditioned media (CM) from young MSCs. To define alterations in gene expression and signaling pathways underlying the observed angiogenic improvement, we characterized differences in cellular mRNA expression between “non-rejuvenated” and “rejuvenated” (exposed to CM from young MSCs) old MSCs. Methods: Replicates of 105 MSCs isolated from old (18-24 months) C57BL mice (n=6) were cultured separately, or in co-culture with MSCs from young (4-6 weeks, n=6) mice using 0.4μm Transwell plates that allow transfer of soluble factors, but not of cells. After 7d in culture, mRNA from old and rejuvenated MSCs was isolated and sequenced. Analysis was performed using open source Galaxy pipeline. Transcription factor (TF) and miRNA target enrichment analyses were performed using ChEA3 and MIENTURNET. Results: Of the 529 unique transcripts involved in angiogenesis (GO-ID 0001525), 98 differentially expressed transcripts (Bonferroni p &lt; 0.0001) were identified. The rejuvenated MSCs showed significantly increased expression of 39 genes. The majority of these involved canonical angiogenic pathways and/or regulation of VEGF: JAK1, LOXL2, KLF4, BMP4, and ADM. Top enriched TFs and miRNAs included EPAS1 and miR-20a, respectively, both directly involved in VEGF signaling, along with SOX18, SNAI1, SOX7, miR-126a, and miR-499 (FDR &lt; 0.05), all of which are known to promote either angiogenesis and/or stemness. Conclusions: Improved angiogenesis by old MSCs exposed to CM from young MSCs is accompanied by significant modulation of angiogenic mediators, crucial in both VEGF and non-VEGF signaling pathways. These changes suggest targets for transcriptional modification to improve angiogenesis and tissue repair in aged patients.
Will coronavirus disease (COVID-19) have an impact on antimicrobial resistance?
Authors: Dominique L Monnet, Stephan Harbarth
Journal: Eurosurveillance (2020)

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Abstract 14168: Hypertension and Clinical Outcomes in Hospitalized Patients With Covid-19; a Multicenter Analysis
Authors: Abdullah Al-Abcha, Ling Wang, manel boumegouas, Baloch Zulfiqar, Steven Do, Randy Ip, george Abela, John Ip
Journal: Circulation (2020)

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia. In nationwide study in China, hypertension was associated with increased in-hospital morbidity and mortality. We performed a similar analysis in a US-based population. Hypothesis: Hypertension is associated with clinical outcomes in patients with COVID-19. Methods: We performed a retrospective analysis of all adult patients with COVID-19 who were admitted to two hospitals in Michigan between 3/1/2020 and 4/30/2020. We divided the patients into two groups according to their pre-admission hypertension status, with hypertension (HTN) and without hypertension (No-HTN). Primary outcome was in-hospital mortality. Secondary outcomes were length of stay (LOS), the risk of intubation, duration of intubation, and the use of vasopressors. Statistical analysis was done using Chi-square tests for binary outcomes and Poisson Regression for count outcomes. Results: A total of 215 patients with COVID-19 were included. Mean age was 62.8 years, mean BMI was 30.9, 119 of them (55%) were males, and 135 (63%) had hypertension. Patients with HTN had significantly higher risk of in-hospital death (N=62/135) when compared to patients without HTN (N=20/80) (p=0.002). Patients with HTN also had higher risk of intubation (HTN=74/135 vs No-HTN=23/80, p&lt;0.001) and higher risk of vasopressors use (HTN=56/136, No HTN=19/80, p=0.007). There was no statistically significant difference in LOS (p=0.295), and duration of intubation (p=0.442). Conclusions: Hypertension is associated with higher risk of in-hospital death, higher risk of intubation, and higher risk of vasopressors use in hospitalized patients with COVID-19. Larger studies are needed to confirm these results with adjusting for confounding factors.
Assessment of Facial Morphologic Features in Patients With Congenital Adrenal Hyperplasia Using Deep Learning
Authors: Wael AbdAlmageed, Hengameh Mirzaalian, Xiao Guo, Linda M. Randolph, Veeraya K. Tanawattanacharoen, Mitchell E. Geffner, Heather M. Ross, Mimi S. Kim
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Congenital adrenal hyperplasia (CAH) is the most common primary adrenal insufficiency in children, involving excess androgens secondary to disrupted steroidogenesis as early as the seventh gestational week of life. Although structural brain abnormalities are seen in CAH, little is known about facial morphology. <h3>Objective</h3> To investigate differences in facial morphologic features between patients with CAH and control individuals with use of machine learning. <h3>Design, Setting, and Participants</h3> This cross-sectional study was performed at a pediatric tertiary center in Southern California, from November 2017 to December 2019. Patients younger than 30 years with a biochemical diagnosis of classical CAH due to 21-hydroxylase deficiency and otherwise healthy controls were recruited from the clinic, and face images were acquired. Additional controls were selected from public face image data sets. <h3>Main Outcomes and Measures</h3> The main outcome was prediction of CAH, as performed by machine learning (linear discriminant analysis, random forests, deep neural networks). Handcrafted features and learned representations were studied for CAH score prediction, and deformation analysis of facial landmarks and regionwise analyses were performed. A 6-fold cross-validation strategy was used to avoid overfitting and bias. <h3>Results</h3> The study included 102 patients with CAH (62 [60.8%] female; mean [SD] age, 11.6 [7.1] years) and 59 controls (30 [50.8%] female; mean [SD] age, 9.0 [5.2] years) from the clinic and 85 controls (48 [60%] female; age, &lt;29 years) from face databases. With use of deep neural networks, a mean (SD) AUC of 92% (3%) was found for accurately predicting CAH over 6 folds. With use of classical machine learning and handcrafted facial features, mean (SD) AUCs of 86% (5%) in linear discriminant analysis and 83% (3%) in random forests were obtained for predicting CAH over 6 folds. There was a deviation of facial features between groups using deformation fields generated from facial landmark templates. Regionwise analysis and class activation maps (deep learning of regions) revealed that the nose and upper face were most contributory (mean [SD] AUC: 69% [17%] and 71% [13%], respectively). <h3>Conclusions and Relevance</h3> The findings suggest that facial morphologic features in patients with CAH is distinct and that deep learning can discover subtle facial features to predict CAH. Longitudinal study of facial morphology as a phenotypic biomarker may help expand understanding of adverse lifespan outcomes for patients with CAH.
Abstract 11232: Derivation and Validation of the Bridge to Transplantation With Left Ventricular Assist Device Score for One Year Mortality After Heart Transplantation. The Btt-lvad-score
Authors: Alexis K Okoh, Setri Fugar, Ebru Ozturk, Molly Schultheis, Mark Russo, Mark Zucker, Margarita Camacho
Journal: Circulation (2019)

Background: The purpose of this study is to derive and validate a risk score that accurately predicts one-year mortality after orthotopic heart transplantation (OHT) in advanced heart failure patie...