tbuckley/cabot-search huggingface dataset:
Diabetic Cardiomiopathy Progression is Triggered by miR122-5p and Involves Extracellular Matrix
Authors: Riccardo Pofi, Elisa Giannetta, Nicola Galea, Marco Francone, Federica Campolo, Federica Barbagallo, Daniele Gianfrilli, Mary Anna Venneri, Tiziana Filardi, Cristiano Cristini, Gabriele Antonini, Roberto Badagliacca, Giacomo Frati, Andrea Lenzi, Iacopo Carbone, Andrea M. Isidori
Journal: JACC. Cardiovascular imaging (2020)

The purpose of this study was to follow the long-term progression of diabetic cardiomyopathy by combining cardiac magnetic resonance (CMR) and molecular analysis.The evolution of diabetic cardiomyopathy to heart failure affects patients'morbidity and mortality. CMR is the gold standard to assess cardiac remodeling, but there is a lack of markers linked to the mechanism of diabetic cardiomyopathy progression.Five-year longitudinal study on patients with type 2 diabetes mellitus (T2DM) enrolled in the CECSID (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes) trial compared with nondiabetic age-matched controls. CMR with tagging together with metabolic and molecular assessments were performed at baseline and 5-year follow-up.A total of 79 men (age 64 ± 8 years) enrolled, comprising 59 men with T2DM compared with 20 nondiabetic age-matched controls. Longitudinal CMR with tagging showed an increase in ventricular mass (ΔLVMi = 13.47 ± 29.66 g/m2; p = 0.014) and a borderline increase in end-diastolic volume (ΔEDVi = 5.16 ± 14.71 ml/m2; p = 0.056) in men with T2DM. Cardiac strain worsened (Δσ = 1.52 ± 3.85%; p = 0.033) whereas torsion was unchanged (Δθ = 0.24 ± 4.04°; p = 0.737), revealing a loss of the adaptive equilibrium between strain and torsion. Contraction dynamics showed a decrease in the systolic time-to-peak (ΔTtP = -35.18 ± 28.81 ms; p < 0.001) and diastolic early recoil-rate (ΔRR = -20.01 ± 19.07 s-1; p < 0.001). The ejection fraction and metabolic parameters were unchanged. Circulating miR microarray revealed an up-regulation of miR122-5p. Network analysis predicted the matrix metalloproteinases (MMPs) MMP-16 and MMP-2 and their regulator (tissue inhibitors of metalloproteinases) as targets. In db/db mice we demonstrated that miR122-5p expression is associated with diabetic cardiomyopathy, that in the diabetic heart is overexpressed, and that, in vitro, it regulates MMP-2. Finally, we demonstrated that miR122-5p overexpression affects the extracellular matrix through MMP-2 modulation.Within 5 years of diabetic cardiomyopathy onset, increasing cardiac hypertrophy is associated with progressive impairment in strain, depletion of the compensatory role of torsion, and changes in viscoelastic contraction dynamics. These changes are independent of glycemic control and paralleled by the up-regulation of specific microRNAs targeting the extracellular matrix. (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes [CECSID]; NCT00692237).
Abstract 15111: Aortic Pulsatility Index Predicts Heart Failure Rehospitalization: A Sub-analysis of the Escape Trial
Authors: Mark N Belkin, Francis J Alenghat, Stephanie Besser, Ann Nguyen, Bow Chung, Bryan Smith, Sara Kalantari, Nitasha Sarswat, John Blair, Gene H Kim, Jonathan Grinstein
Journal: Circulation (2020)

Introduction: Aortic pulsatility index (API), calculated as (systolic blood pressure - diastolic blood pressure)/pulmonary capillary wedge pressure (PCWP), is a novel hemodynamic measurement representing cardiac filling pressures and contractility. Hypothesis: API would predict heart failure hospitalizations in acutely decompensated heart failure participants in the Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness (ESCAPE) trial. Methods: From the ESCAPE trial individual-level data API, cardiac power output (CPO), and pulmonary artery pulsatility index (PAPI) were calculated, as well as reported routine invasive hemodynamics at baseline and after final hemodynamic-monitored optimization. Outcomes assessed were need for any rehospitalization and time to any first rehospitalization. Univariable analysis was conducted to assess rehospitalization. Negative binomial regression was used to analyze duration of time from discharge to first rehospitalization. Results: A total of 433 patients were enrolled in the ESCAPE trial. 189 patients had complete, accurate baseline hemodynamic data and were included in this analysis. No baseline hemodynamic measurements were associated with either outcome, except pulmonary artery (PA) diastolic pressure which predicted rehospitalization (OR 1.05 (95% CI 1.00-1.05, p= 0.02). Final API, OR 0.75 (95% CI 0.60-1.00, p= 0.03) and PAPI, OR 0.90 (95% CI 0.80-1.00, p= 0.03) predicted the need for any rehospitalization. Final API, OR 0.84 (95% CI 0.73-0.97, p= 0.02), and PA diastolic pressure, OR 1.03 (95% CI 1.01-1.06, p= 0.02), were associated with duration of time from discharge to any first hospitalization. Conclusions: The novel hemodynamic measurement API better predicted rehospitalization and time to rehospitalization in the ESCAPE trial when compared to routine, and other advanced invasive hemodynamic measurements.
Association Between Early Severe Cardiovascular Events and Ustekinumab Treatment?
Authors: Joel M. Gelfand, Erica D. Dommasch, Nehal N. Mehta
Journal: JAMA Dermatology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Abstract 14072: Bioenergetic and Metabolic Impairments in Duchenne Muscular Dystrophy (DMD) Patients' Induced Pluripotent Stem Cell-derived Cardiomyocytes (iPSC-CMs)
Authors: Lubna Willi, Jonatan Fernandez-Garcia, Ifat Abramovich, Dov Freimark, Michael Arad, Eyal Gottlieb, Ofer Binah
Journal: Circulation (2020)

Introduction: DMD, an X-linked muscle degenerative fatal disease, is caused by mutations in the dystrophin gene. Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality in DMD patients. Since the DMD DCM treatment is limited, novel therapeutic modalities are urgently needed. Hypothesis: We hypothesized that dystrophin mutations in DMD lead to cardiomyopathy-causing bioenergetic/metabolic impairments, which can be therapeutically targeted for improving cardiac function. Methods: The study included iPSC-CMs from a healthy volunteer and 3 DMD patients (young male, YM; adult male, AM; adult female, AF) and mdx mice. We investigated the bioenergetics, electrophysiology, mitochondrial and metabolic features of iPSC-CMs and heart tissues using the SeaHorse Flux Analyzer, patch clamp, confocal fluorescence microscopy and Liquid Chromatography Mass Spectrometry (LC-MS) technologies, respectively. Results: To test the hypothesis, we measured the iPSC-CM respiration rate using the SeaHorse. Compared to healthy, in both AM and AF DMD, but not in YM DMD cardiomyocytes, ATP production decreased by 75%, and basal respiration decreased by 80% and 45%, respectively. In agreement with impaired oxidative phosphorylation capacity, mitochondrial activity measured by 3D life confocal microscopy was attenuated by 35% in AM, but not in YM. Concurring with the healthy-like bioenergetic status, YM iPSC-CMs fired regularly with no arrhythmias, in contrast to the prominent arrhythmias in AM and AF cardiomyocytes. Further, the LC-MS analysis demonstrated that the levels of 13%, 6% and 7% of the 120 metabolite measured, were lower in AM, AF and YM, while 10%, 18% and 43% were higher, respectively, compared to healthy iPSC-CMs ( p&lt;0.05 ). For example, in AM and AF (but not in YM) the phosphocreatine (PCr) levels were diminished by &gt;80%, compared to healthy iPSC-CMs, indicating a dysfunctional PCr energy system. Finally, the LC-MS analysis of mdx ventricular tissue demonstrated a statistically-significant different metabolic profile in 8 mdx mice vs 8 healthy mice. Conclusion: DMD iPSC-CMs and mdx mice exhibit bioenergetic/metabolic impairments, which constitute novel targets for alleviating the cardiomyopathy in DMD patients.
Deep-LIBRA: An artificial-intelligence method for robust quantification of breast density with independent validation in breast cancer risk assessment
Authors: Omid Haji Maghsoudi, Aimilia Gastounioti, Christopher Scott, Lauren Pantalone, Fang-Fang Wu, Eric A. Cohen, Stacey Winham, Emily F. Conant, Celine Vachon, Despina Kontos
Journal: Medical Image Analysis (2021)

Breast density is an important risk factor for breast cancer that also affects the specificity and sensitivity of screening mammography. Current federal legislation mandates reporting of breast density for all women undergoing breast screening. Clinically, breast density is assessed visually using the American College of Radiology Breast Imaging Reporting And Data System (BI-RADS) scale. Here, we introduce an artificial intelligence (AI) method to estimate breast percentage density (PD) from digital mammograms. Our method leverages deep learning (DL) using two convolutional neural network architectures to accurately segment the breast area. A machine-learning algorithm combining superpixel generation, texture feature analysis, and support vector machine is then applied to differentiate dense from non-dense tissue regions, from which PD is estimated. Our method has been trained and validated on a multi-ethnic, multi-institutional dataset of 15,661 images (4,437 women), and then tested on an independent dataset of 6,368 digital mammograms (1,702 women; cases=414) for both PD estimation and discrimination of breast cancer. On the independent dataset, PD estimates from Deep-LIBRA and an expert reader were strongly correlated (Spearman correlation coefficient = 0.90). Moreover, Deep-LIBRA yielded a higher breast cancer discrimination performance (area under the ROC curve, AUC = 0.611 [95% confidence interval (CI): 0.583, 0.639]) compared to four other widely-used research and commercial PD assessment methods (AUCs = 0.528 to 0.588). Our results suggest a strong agreement of PD estimates between Deep-LIBRA and gold-standard assessment by an expert reader, as well as improved performance in breast cancer risk assessment over state-of-the-art open-source and commercial methods.
Abstract 15934: Comparison of Atrial Fibrillation Burden Reduction in Patients With Paroxysmal and Persistent Atrial Fibrillation Undergoing Cryoballoon Pulmonary Vein Isolation
Authors: Dan L Musat, Nicolle S Milstein, Jacqueline Pimienta, Advay Bhatt, Tina C Sichrovsky, Mark Preminger, Carissa Pistilli, Susan Oliveros, Richard Shaw, Suneet Mittal
Journal: Circulation (2020)

Background: Pulmonary vein isolation (PVI) is a cornerstone of atrial fibrillation (AF) ablation procedures to treat symptomatic AF. Ablation success is defined by absence of AF recurrence &gt;30 seconds. However, reduction in AF burden (AFB) is also an important endpoint. Whether patients with paroxysmal (PAF) and persistent AF (PeAF) have similar reduction in AFB post-ablation is unknown. Objective: To compare the decrease in AFB following cryoballoon (CB) PVI in patients with PAF and PeAF. Methods: We enrolled consecutive pts with an implantable loop recorder (ILR) who subsequently underwent CB PVI. All patients were followed prospectively for at least one year, or until repeat ablation; we compared AFB pre and post-ablation. Results: The cohort included had 47 patients (66 ± 10 years; 32 [68%] male; PAF [n=23, 49%]; CHA 2 DS 2 -VASc 2.7 ± 1.7, 34 [72%] on AAD at the time of ablation). A median of 136 days [IQR 280, 73; minimum of 30 days] of ILR data pre-ablation were available. The median AFB for PAF was 4.7% [IQR 0.9, 14.8] and PeAF was 6.8% [IQR 1.1, 40.4]. After excluding a 3-month post-ablation blanking period, recurrent AF occurred in 12 (52%) PAF and 11 (46%) PeAF patients. The median AFB post-ablation for PAF and PeAF cohorts was 0.03%, [IQR 0, 0.3] and 0.04%, [IQR 0, 1.1], respectively. This represents a &gt;99% reduction in AFB. Conclusion: Although 50% of patients undergoing CB PVI for PAF or PeAF had a recurrence of AF, there was &gt;99% reduction in AFB in both groups. These data highlight the importance of using AFB burden as a marker of therapeutic efficacy post-AF ablation.
Abstract 13869: Inflammatory Changes in the Lungs of Rats Exposed to E-cigarettes Without Marijuana, Vitamin E Oil, or Nicotine
Authors: Jianru Shi, Michael T Kleinman, Rebecca J Arechavala, Dave Herman, Irene Hasen, Amanda Ting, Dai Wangde, Juan Carreno, Jesus Chavez, Lifu Zhao, Robert A Kloner
Journal: Circulation (2020)

Background: Recently, the clinical entity of EVALI (E-cigarette or vaping product use associated lung injury) was described and has similarities to COVID -19 pneumonia. We determined in a quantitative manner the inflammatory changes in the lungs associated with EVALI in a rodent model that does not include use of marijuana, vitamin E oil, or nicotine, which had been implicated as a cause. Methods: Adult Sprague Dawley rats were exposed to either pure air (n=5) or electronic cigarette (eC) vapor (propylene glycol/vegetable glycerin, tobacco flavoring) using a device with a nickel-chromium alloy (NC) heating element at 70 Watts (n=6) for 2 hours. The e-liquid did not contain nicotine, marijuana, or Vitamin E oil. Rats were euthanized within a few days of exposure and H&amp;E-stained lung sections were assessed. Inflammatory cells were counted from 10 random areas per section at 20х magnification. Results: Alveolar structure appeared normal in the air group (Figure, panel C); the eC group using the NC heating element showed alveolar inflammation (D). The numbers of inflammatory cells per high power field in the lung parenchyma were significantly greater in the rats exposed to eC using NC heating element (67.5 ± 44.5) compared to the air group (6.7 ± 0.3; P &lt; 0.001, Kruskal-Wallis test). The predominant cell type was mononuclear and secondary were neutrophils. Other features included accumulation of fibrin and inflammatory cells in the lumen of the trachea (A); thickened alveolar walls; and red blood cell congestion (D). Inflammation of the nasal passages was also observed (B). Exposure of rats to e cigarettes using a stainless steel heating element did not result in EVALI, and the amount of inflammatory cells was closer to air exposed rats (7.2± 0.4). Conclusion: Vaping using a nichrome heating element at high power leads to respiratory tract pathology and a significant increase in the number of inflammatory cells in the alveoli. EVALI occurred without marijuana, vitamin E oil or nicotine.
TRAF2 regulates T cell immunity by maintaining a Tpl2-ERK survival signaling axis in effector and memory CD8 T cells
Authors: Xiaoping Xie, Lele Zhu, Zuliang Jie, Yanchuan Li, Meidi Gu, Xiaofei Zhou, Hui Wang, Jae-Hoon Chang, Chun-Jung Ko, Xuhong Cheng, Shao-Cong Sun
Journal: Cellular and Molecular Immunology (2020)
Abstract 15212: Long-term Outcomes Between Genders Are Similar Despite Gender Disparities in High-intensity Statin Use in a Contemporary Cohort of Patients Diagnosed With Nonobstructive Coronary Artery Disease by Invasive Coronary Angiography
Authors: Edwin Lu, Christopher A Hanson, Saad Sultan Ghumman, George Beller, Jamieson M Bourque
Journal: Circulation (2020)

Introduction: In current practice, high intensity statins are prescribed for patients diagnosed with CAD. However, studies have shown that women are commonly undertreated with statins. We compared long-term outcomes and medication usage patterns related to gender in a contemporary cohort of patients who underwent invasive coronary angiography (ICA) for index evaluation of suspected CAD for an abnormal stress test, stable or unstable angina, following an NSTEMI, or as part of their evaluation for heart failure. Methods: A cohort of 850 consecutive patients who underwent ICA for suspected CAD was classified as having normal/near-normal coronary arteries (≤20% stenosis, n=264), nonobstructive CAD (21-49% stenosis, n=114), or obstructive CAD (≥50% stenosis, n=472). We prospectively determined outcomes (cardiac death, nonfatal MI, and late revascularization) via Kaplan-Meier analysis in these 3 groups. We also obtained baseline and follow up data on statin use, and compared usage in the 3 groups related to gender by Chi-square analysis. Results: Baseline mean LDL values were 103 in men and 113 in women (p&lt;0.001). At a median follow up of 6.0 years, there was an increase in statin use (51.5% at baseline vs 85.0% at follow up in obstructive CAD group; 54.0% vs 67.3% for nonobstructive CAD group). There were no differences in aspirin, beta-blocker, or overall statin usage by gender across all groups (p&gt;0.05 for all medications). No difference in high intensity statin use (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) was seen between genders in patients with obstructive CAD (61.4% of men vs 62.9% of women, p=0.78). Interestingly, there was a significant difference in usage of high intensity statins between genders in patients with nonobstructive CAD (63.9% of men vs 26.8% of women, p =0.001). Yet, outcomes were similar between genders across all stenosis groups (p&gt;0.05 for all groups). Conclusions: Our study shows that fewer women with nonobstructive CAD are treated with high intensity statins compared to their male cohorts. Despite this disparity in treatment, outcomes remained similar between genders. This discrepancy warrants the need for further study and could represent an area for optimization of medical therapy in female patients with nonobstructive CAD.
Myocardial Injury in Severe COVID-19 Compared With Non–COVID-19 Acute Respiratory Distress Syndrome
Authors: Thomas S. Metkus, Lori J. Sokoll, Andreas S. Barth, Matthew J. Czarny, Allison G. Hays, Charles J. Lowenstein, Erin D. Michos, Eric P. Nolley, Wendy S. Post, Jon R. Resar, David R. Thiemann, Jeffrey C. Trost, Rani K. Hasan
Journal: Circulation (2020)

Knowledge gaps remain in the epidemiology and clinical implications of myocardial injury in coronavirus disease 2019 (COVID-19). We aimed to determine the prevalence and outcomes of myocardial injury in severe COVID-19 compared with acute respiratory distress syndrome (ARDS) unrelated to COVID-19.We included intubated patients with COVID-19 from 5 hospitals between March 15 and June 11, 2020, with troponin levels assessed. We compared them with patients from a cohort study of myocardial injury in ARDS and performed survival analysis with primary outcome of in-hospital death associated with myocardial injury. In addition, we performed linear regression to identify clinical factors associated with myocardial injury in COVID-19.Of 243 intubated patients with COVID-19, 51% had troponin levels above the upper limit of normal. Chronic kidney disease, lactate, ferritin, and fibrinogen were associated with myocardial injury. Mortality was 22.7% among patients with COVID-19 with troponin under the upper limit of normal and 61.5% for those with troponin levels >10 times the upper limit of normal (P<0.001). The association of myocardial injury with mortality was not statistically significant after adjusting for age, sex, and multisystem organ dysfunction. Compared with patients with ARDS without COVID-19, patients with COVID-19 were older and had higher creatinine levels and less favorable vital signs. After adjustment, COVID-19-related ARDS was associated with lower odds of myocardial injury compared with non-COVID-19-related ARDS (odds ratio, 0.55 [95% CI, 0.36-0.84]; P=0.005).Myocardial injury in severe COVID-19 is a function of baseline comorbidities, advanced age, and multisystem organ dysfunction, similar to traditional ARDS. The adverse prognosis of myocardial injury in COVID-19 relates largely to multisystem organ involvement and critical illness.
Abstract 14287: Incidence of Atrial Fibrillation on Holter Monitoring After Percutaneous Patent Foramen Ovale Closure in a Prospective Study
Authors: Xavier Odorico, Jean Christophe Macia, Guillaume Cayla, Florence Leclercq
Journal: Circulation (2019)

Introduction: An increased risk of atrial fibrillation (AF) after patent foramen ovale (PFO) closure was observed in randomized studies but systematic screening of AF was not performed in these stu...
Abstract 13941: The Prevalence of Cardiovascular Disease in Patients With Von Willebrand Disease; A Potential Therapeutic Target
Authors: Nawfal Mihyawi, MUHAMMAD AJMAL, Jun Hung, Beeletsega T Yeneneh
Journal: Circulation (2020)

Introduction: Von Willebrand factor (vWF) plays an important role in the coagulation process at the site of vascular injury. It is unclear whether vWF deficiency is protective against cardiovascular disease (CVD) since investigations are limited in this entity. Hypothesis: Our study assessed the hypothesis that the prevalence of CVD is less in patients with than without Von Willebrand disease (vWD). Methods: We queried the National Inpatient Sample (NIS) from 2009-2014. Entire data was used with exclusion of patients below 18 and over 75-year-old. We defined cardiovascular disease as any event of myocardial infarction or a diagnosis of ischemic heart disease using the International Classification of Disease, 9th edition (ICD-9). The primary outcome of interest was to compare the odds ratio of CVD in patients with and without vWD. Results: A total of 224,475,443 weighted hospital discharge samples were identified. Of these, 82,809 carried a diagnosis of vWD. The odds of CVD were less common in vWD patients (OR 0.54; 95% CI 0.52 - 0.56) (table 1). After multivariate logistic regression analysis, with adjustment for age, gender and the most common CVD risk factors including hypertension, smoking, diabetes, hyperlipidemia, family history of CVD, chronic kidney disease and obesity the likelihood of CVD remained lower in vWD patients (OR 0.65; 95% CI 0.63-0.67) (table 2). Conclusions: Our study, the first to involve a large cohort of patients, demonstrated that vWF deficiency is associated with decreased prevalence of CVD. Hence, vWF could potentially be a therapeutic target in CVD management. More investigations are needed for confirmation of these findings and to determine causation.
Association Between Nursing Home Crowding and COVID-19 Infection and Mortality in Ontario, Canada
Authors: Kevin A. Brown, Aaron Jones, Nick Daneman, Adrienne K. Chan, Kevin L. Schwartz, Gary E. Garber, Andrew P. Costa, Nathan M. Stall
Journal: JAMA Internal Medicine (2020)

Nursing home residents have been disproportionately affected by coronavirus disease 2019 (COVID-19). Prevention recommendations emphasize frequent testing of health care personnel and residents, but additional strategies are needed.
Response by Gierula et al to Letter Regarding Article, “Personalized Rate-Response Programming Improves Exercise Tolerance After 6 Months in People With Cardiac Implantable Electronic Devices and Heart Failure: A Phase II Study”
Authors: John Gierula, Judith E. Lowry, Maria F. Paton, Charlotte A. Cole, Rowenna Byrom, Aaron A. Koshy, Hemant Chumun, Lorraine C. Kearney, Sam Straw, T. Scott Bowen, Richard M. Cubbon, Anne-Maree Keenan, Deborah D. Stocken, Mark T. Kearney, Klaus K. Witte
Journal: Circulation (2020)