tbuckley/cabot-search huggingface dataset:
Abstract 14919: Myocardial T <sub>1</sub> Mapping for Prediction of Left Ventricular Reverse Remodeling in Patients With Recent-onset Dilated Cardiomyopathy: a Comparison With Histological Tissue Characterization
Authors: Junko Ishiura, Shiro Nakamori, Kyoko Imanaka-yoshida, Michiaki Hiroe, Kei Nakata, Masaki Ishida, Keishi Moriwaki, Naoki Fujimoto, Hajime Sakuma, Kaoru Dohi
Journal: Circulation (2020)

Background: Accurate prediction of left ventricular reverse remodeling (LVRR) in dilated cardiomyopathy (DCM) remains challenging. The purpose of this study is to assess the potential of cardiovascular magnetic resonance (CMR) T 1 mapping to predict LVRR by histological confirmation. Methods: Twenty-one DCM patients (12 male, mean age 49 ± 13 years) underwent cine, late gadolinium enhancement (LGE) CMR, and triple-slice T 1 mapping using a modified Look-Locker inversion recovery sequence at 3T before receiving optimal medical therapy. LVRR was defined as an absolute increase in LV ejection fraction (LVEF) from ≥10% to a final value of &gt;35%, accompanied by a decrease in LV end-diastolic volume (LVEDV) ≧10% at midterm (mean time 18 months) CMR follow-up. Extra-cellular volume (ECV) was quantified from pre and post-contrast T 1 values of the blood and myocardium with hematocrit correction. Biopsy samples were used for quantification of collagen volume fraction (CVF). Results: LVRR was observed in 11 patients (52%). The mean native T 1 , ECV, and histological CVF were 1395 ± 49 ms, 0.33 ± 0.03, 0.13 ± 0.04, respectively. Native T 1 yielded comparable ability to ECV measurements for detecting histological CVF (r=0.49, 0.52, both p &lt;0.05). While 14 patients (67%) showed focal scar on LGE, there was no significant difference in histological CVF between patients with and without focal scarring (p=0.6). Native T 1, but not ECV and CVF, correlated well with absolute LVEF increase and relative percent decrease of LVEDV and LV end-systolic volume (r=-0.55, 0.55, 0.56, all p &lt;0.05). Native T 1 &lt;1400 ms provided 90% sensitivity and 82% specificity, with the C-statistic of 0.86 (95% CI 0.64-0.97), for predicting LVRR. On the other hand, the C-statistic of ECV, LGE and histological CVF were 0.72 (95% CI 0.48-0.89), 0.53 (95% CI 0.31-0.75) and 0.66 (95% CI 0.43-0.85), respectively. Conclusions: Myocardial native T 1 have the potential to predict LVRR beyond LGE and histological assessment.
Valve Prosthesis–Patient Mismatch, 1978 to 2011: From Original Concept to Compelling Evidence⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology
Authors: Philippe Pibarot, Jean G. Dumesnil
Journal: Journal of the American College of Cardiology (2012)
Abstract 361: The Augmentation of Oxygen-sensitive Generation of Oxygen Radicals in Mitochondria and the Attenuation of Hyperoxia-induced Oxidative Stress After Cardiac Arrest
Authors: Koichiro Shinozaki, Yu Okuma, Tomoaki Aoki, Mitsuaki Nishikimi, Kei Hayashida, Santiago J Miyara, Lance B Becker
Journal: Circulation (2020)

Introduction: Hyperoxia can induce oxidative stress resulting in organ injuries after cardiac arrest (CA). Mitochondrial reactive oxygen species (ROS) are key to understanding its mechanism, however the augmentation of oxygen-sensitive ROS generation caused by CA ( Fig 1 ) has not been well described. Methods: Rats were assigned into: 1) sham with normoxia, 30% O2; 2) sham with hyperoxia, 100% O2; 3) CA with normoxia; and 4) CA with hyperoxia (n=15 for each group). CA was induced by 10-minute asphyxia and CPR was delivered. Neurological deficit score (NDS), histological lung injury score (LIS), survival time were obtained from the CA groups. Carbonyl protein as an oxidative stress indicator was measured at 2 hrs after resuscitation. H2O2 generation from isolated mitochondria were measured ex vivo at a normoxic and hyperoxic condition set up with nitrogen and air saturated medium. Results: Between the CA groups, the normoxia group had a higher 48hr-survival rate (77%), lower NDS (359±140), and lower LIS (4.3±2.9) compared to those (28%, 452±85, 14±2, respectively) of the hyperoxia group (p&lt;0.01, p&lt;0.05, and p&lt;0.01, respectively). In the brain, lung, and kidney, CA augmented the hyperoxia-induced increase in carbonyl protein (absolute change: sham brain, 0.18 nmol/mg protein vs. CA brain, 0.61 nmol/mg protein; sham lung, 0.29 nmol/mg protein vs. CA lung, 0.72 nmol/mg protein; sham kidney, 0.04 nmol/mg protein vs. CA kidney, 0.55 nmol/mg protein, respectively). In the brain and kidney isolated mitochondria, CA augmented the hyperoxia-induced increase in H2O2 (absolute change: sham brain, 18 pmol/mg protein vs. CA brain, 60 pmol/mg protein; sham kidney, 16 pmol/mg protein vs. CA kidney, 45 pmol/mg protein, respectively). Conclusions: The normoxic therapy may attenuate organ damage and improve survival of CA. The reduction of augmented mitochondrial ROS generation, which is oxygen-sensitive, would be an important mechanism and therapeutic target of post-CA care.
Enterobactin induces the chemokine, interleukin-8, from intestinal epithelia by chelating intracellular iron
Authors: Piu Saha, Beng San Yeoh, Xia Xiao, Rachel M. Golonka, Ahmed A. Abokor, Camilla F. Wenceslau, Yatrik M. Shah, Bina Joe, Matam Vijay-Kumar
Journal: Gut Microbes (2020)

Iron is an indispensable nutrient for both mammals and microbes. Bacteria synthesize siderophores to sequester host iron, whereas lipocalin 2 (Lcn2) is the host defense protein that prevent this iron thievery. Enterobactin (Ent) is a catecholate-type siderophore that has one of the strongest known affinities for iron. Intestinal epithelial cells (IECs) are adjacent to large microbial population and are in contact with microbial products, including Ent. We undertook this study to investigate whether a single stimulus of Ent could affect IEC functions. Using three human IEC cell-lines with differential basal levels of Lcn2 (i.e. HT29 < DLD-1 < Caco-2/BBe), we demonstrated that iron-free Ent could induce a dose-dependent secretion of the pro-inflammatory chemokine, interleukin 8 (IL-8), in HT29 and DLD-1 IECs, but not in Caco-2/BBe. Ent-induced IL-8 secretion was dependent on chelation of the labile iron pool and on the levels of intracellular Lcn2. Accordingly, IL-8 secretion by Ent-treated HT29 cells could be substantially inhibited by either saturating Ent with iron or by adding exogenous Lcn2 to the cells. IL-8 production by Ent could be further potentiated when co-stimulated with other microbial products (i.e. flagellin, lipopolysaccharide). Water-soluble microbial siderophores did not induce IL-8 production, which signifies that IECs are specifically responding to the lipid-soluble Ent. Intriguingly, formyl peptide receptor (FPR) antagonists (i.e. Boc2, cyclosporine H) abrogated Ent-induced IL-8, implicating that such IEC response could be, in part, dependent on FPR. Taken together, these results demonstrate that IECs sense Ent as a danger signal, where its recognition results in IL-8 secretion.
Abstract 13594: Adverse Right Ventricular Remodelling, Function and Stress Responses in Obesity: Implications for Severe Acute Respiratory Illness
Authors: Andrew J Lewis, William Watson, Hani Mahmoud-Elsayed, William Moody, Ayisha M Khan-Kheil, Jonathan Senior, Ines ABDESSELAM, Jennifer Rayner, Graham Barker, Claire Colebourn, Razeen Mahroof, Paul Foley, James Byrne, Barry A Borlaug, Stefan Neubauer, Richard P Steeds, Oliver J Rider
Journal: Circulation (2020)

Introduction: The mechanisms linking obesity to increased mortality in patients with coronavirus-disease 2019 (COVID-19) are unclear. Hypothesis: We hypothesised that obesity would be associated with adverse right ventricular (RV) remodelling and function which might be further exacerbated by COVID-19 associated increases in RV afterload/demand. Methods: We used echocardiography and computed tomography to establish links between RV dimensions and function and bodyweight in patients with severe COVID-19. In obese and non-obese participants without COVID-19, we used cardiovascular magnetic resonance to define the effects of obesity upon RV volumes, energetics, systolic function and stress reserve. Results: In patients with severe COVID-19, increasing bodyweight was associated with disproportionate RV dilatation (n=26, echocardiography, R=0.42, P=0.03, CT n=34, R=0.23, P=0.004) and impairment of RV systolic function (fractional area change (FAC) R=-0.45, P=0.04); obesity (BMI &gt;30kg/m2) was associated with a 32% reduction in RV FAC (P=0.03). Similar associations were seen in a validation cohort (n=91, all P&lt;0.05). In participants without COVID-19, class III obesity (n=54, BMI 47±4 kg/m 2 ) was associated with RV remodelling, impaired cardiac energetics (PCr/ATP ratio 23% lower, P&lt;0.001) and reduction in RV systolic function at rest (by 3±1%, P=0.01), which was related to reduced energetics (R=0.3, P=0.04). Participants with class I-II obesity (BMI 35±5 kg/m 2 , n=27) had impaired RV diastolic filling rate at rest (P&lt;0.001) and blunted RV dobutamine stress systolic response (by 68%, P=0.03) and diastolic response (by 78%, P=0.008). Surgical weight loss in patients obesity (n=37, 34±15kg weight loss) was associated with improvement in RV volume (12±26 ml lower, P=0.006) and function (ejection fraction 2±5% higher, P=0.03). Conclusions: Increasing body weight is associated with both significant alterations in RV volumes, systolic function and stress responses which are mitigated with weight loss and also with disproportionate RV dilatation and dysfunction in severe COVID-19. RV dysfunction is a modifiable mechanism which might link obesity to adverse outcomes in patients with COVID-19 and other disorders stressing the right heart.
Perioperative Cardiac Risk Assessment and Management
Authors: Robert Schiff
Journal: Annals of Internal Medicine (1998)

Letters15 April 1998Perioperative Cardiac Risk Assessment and ManagementRobert Schiff, MDRobert Schiff, MDLoyola University Stritch School of Medicine; Maywood, IL 60153Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-8-199804150-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The guidelines for the assessment and management of perioperative risk from coronary artery disease in patients undergoing major noncardiac surgery include a comprehensive review and management recommendations [1, 2]. In their management strategy (Appendix Figure 1), the authors rely heavily on the modified cardiac risk index developed by Detsky and colleagues [3]. I have several concerns about the bedside use of this modified index. One issue is whether the patients in Detsky and coworkers' 1986 study [3] are representative of all patients undergoing noncardiac surgery. I do not think they are representative because the authors “enrolled only ...References1. American College of Physicians. Guidelines for assessing and managing the perioperative risk from coronary artery disease associated with major noncardiac surgery. Ann Intern Med. 1997; 127:309-12. Google Scholar2. Palda VA, Detsky AS. Perioperative assessment and management of risk from coronary artery disease. Ann Intern Med. 1997; 127:313-28. Google Scholar3. Detsky AS, Abrams HB, McLaughlin JR, Drucker DJ, Sasson Z, Johnston N, et al. Predicting cardiac complications in patients undergoing non-cardiac surgery. J Gen Intern Med. 1986; 1:211-9. Google Scholar4. Laupacis A, Sekar N, Stiell IG. Clinical prediction rules: a review and suggested modifications of methodological standards. JAMA. 1997; 277:488-94. Google Scholar5. Goldman L, Caldera DL, Nussbaum SR, Southwick FS, Krogstad D, Murray B, et al. Multifactorial index of cardiac risk in noncardiac surgical procedures. N Engl J Med: 1977; 297:845-50. Google Scholar Author, Article, and Disclosure InformationAuthors: Robert Schiff, MDAffiliations: Loyola University Stritch School of Medicine; Maywood, IL 60153 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 April 1998Volume 128, Issue 8Page: 693KeywordsCardiac surgeryHeart diseasesLikelihood ratioPatient advocacyRisk assessmentsStable coronary artery diseaseSurgery ePublished: 15 August 2000 Issue Published: 15 April 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 327: Asphyxial Cardiac Arrest Induces Dynamic Changes in Dopamine Neurotransmission and Linked Behavioral Deficits
Authors: Aaron R Braverman, David F Fine, Tyler J Shick, Jason P Stezoski, Rehana K Leak, Tomas Drabek, Patrick M Kochanek, Amy K Wagner
Journal: Circulation (2020)

Introduction: Cardiac arrest survival has improved with advances in resuscitation care, but survivors face impairments from the resulting hypoxic-ischemic brain injury (HIBI). Given the popular clinical use of DA modulators, despite limited understanding of disturbances in DA neurotransmission after HIBI, we characterized striatal DA signaling and behavioral deficits in a rat model of asphyxial cardiac arrest (ACA). Hypothesis: ACA-induced HIBI alters DA neurotransmission linked to behavioral deficits. Methods: Adult male Sprague-Dawley rats (n=41) underwent either Sham procedures (n=10) or 5-min no-flow ACA (n=28) insult. Fast-scan cyclic voltammetry (FSCV) and maximal medial forebrain bundle stimulations (60Hz, 10s) were used to characterize presynaptic DA signaling in dorsal striatum (D-Str). FSCV findings were compared with sensorimotor processing [acoustic startle responses (ASR)], open field exploration (total distance &amp; exploratory zone entries), myoclonus, and anhedonia (sucrose preference testing). Results: ACA increased maximum evoked overflow (fig 1) and several DA release-based kinetic metrics. ACA hindered sensorimotor processing via increased ASR %change, elicited myoclonic responses to auditory stimuli, reduced mobility &amp; exploration, and increased anhedonia. Many behavioral measures correlated with D-Str neurotransmission ( fig 2 ). Conclusions: ACA causes early hypodopaminergia that evolves to a hyperdopaminergic state by 2 weeks that is associated with behavioral dysfunction. Future work should further characterize striatal pathology post-ACA and identify treatments to resolve altered DA signaling and behavioral deficits.
From GOLD 0 to Pre-COPD
Authors: MeiLan K. Han, Alvar Agusti, Bartolome R. Celli, Gerard J. Criner, David M. G. Halpin, Nicolas Roche, Alberto Papi, Robert A. Stockley, Jadwiga Wedzicha, Claus F. Vogelmeier
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Currently the diagnosis of chronic obstructive pulmonary disease (COPD) requires the demonstration of airflow limitation, defined as a post-bronchodilator FEV 1 /FVC <0.7, a measurement that remains methodologically robust and widely available.FEV 1 is one of the most powerful predictors of clinically relevant outcomes including symptoms, exacerbations and mortality.However, reliable data suggest that respiratory symptoms, in particular chronic bronchitis, airway abnormality and emphysema detected using modern imaging techniques such as computed tomography (CT), and certain physiologic measures including rapid decline in FEV 1 and DLCO are present among individuals who do not meet spirometric criteria for COPD.These abnormalities may help to identify individuals at increased risk for developing airflow limitation in the future.Here, we review the evidence that support the use of the term "pre-COPD" in individuals with symptoms (e.g., "Non-Obstructive Chronic Bronchitis" (NOCB)), physiologic (e.g., low DLCO) and/or imaging abnormalities (e.g.CT emphysema) but spirometry in the normal range, who are at risk of developing COPD defined by a reduced FEV 1 /FVC ratio.We acknowledge, however, that further research on early disease in young individuals will be critical to develop a clinically operable definition of "pre-COPD" that demonstrates good sensitivity and specificity.
Suppression of Rheumatoid Arthritis by Enhanced Lymph Node Trafficking of Engineered Interleukin‐10 in Murine Models
Authors: Eiji Yuba, Erica Budina, Kiyomitsu Katsumata, Ako Ishihara, Aslan Mansurov, Aaron T. Alpar, Elyse A. Watkins, Peyman Hosseinchi, Joseph W. Reda, Abigail L. Lauterbach, Mindy Nguyen, Ani Solanki, Takahiro Kageyama, Melody A. Swartz, Jun Ishihara, Jeffrey A. Hubbell
Journal: Arthritis & Rheumatology (2020)

Rheumatoid arthritis (RA) is a major autoimmune disease that causes synovitis and joint damage. Although clinical trials have been performed using interleukin-10 (IL-10), an antiinflammatory cytokine, as a potential treatment of RA, the therapeutic effects of IL-10 have been limited, potentially due to insufficient residence in lymphoid organs, where antigen recognition primarily occurs. This study was undertaken to engineer an IL-10-serum albumin (SA) fusion protein and evaluate its effects in 2 murine models of RA.
Estrogen Receptor Alpha Mutations in Breast Cancer Cells Cause Gene Expression Changes through Constant Activity and Secondary Effects
Authors: Spencer Arnesen, Zannel Blanchard, Michelle M. Williams, Kristofer C. Berrett, Zheqi Li, Steffi Oesterreich, Jennifer K. Richer, Jason Gertz
Journal: Cancer Research (2020)

Abstract While breast cancer patients with tumors that express estrogen receptor α (ER) generally respond well to hormone therapies that block ER activity, a significant number of patients relapse. Approximately 30% of these recurrences harbor activating mutations in the ligand binding domain (LBD) of ER, which have been shown to confer ligand-independent function. However, much is still unclear regarding the effect of mutant ER beyond its estrogen independence. To investigate the molecular effects of mutant ER, we developed multiple isogenic ER-mutant cell lines for the most common LBD mutations, Y537S and D538G. These mutations induced differential expression of thousands of genes, the majority of which were mutant allele specific and were not observed upon estrogen treatment of wild-type (WT) cells. These mutant-specific genes showed consistent differential expression across ER-mutant lines developed in other laboratories. WT cells with long-term estrogen exposure only exhibited some of these transcriptional changes, suggesting that mutant ER causes novel regulatory effects that are not simply due to constant activity. While ER mutations exhibited minor effects on ER genomic binding, with the exception of ligand independence, ER mutations conferred substantial differences in chromatin accessibility. Mutant ER was bound to approximately a quarter of mutant-enriched accessible regions that were enriched for other DNA binding factors, including FOXA1, CTCF, and OCT1. Overall, our findings indicate that mutant ER causes several consistent effects on gene expression, both indirectly and through constant activity. Significance: This study demonstrates the multiple roles of mutant ER in breast cancer progression, including constant ER activity and secondary regulatory effects on gene expression and chromatin accessibility.
18F-FDG PET/CT Imaging of Testicular Myeloid Sarcoma in a Pediatric Patient
Authors: Junhao Wu, Guohao Jiang, Ji Wu, Lei Ou, Chunyin Zhang
Journal: Clinical Nuclear Medicine (2020)

Abstract A 5-year-old boy presented with right testicular swelling for 1 week. Ultrasonography revealed a right testicular hypoechoic mass with increased blood flow. A malignant tumor was suspected, and further investigation with 18 F-FDG PET/CT showed a soft tissue mass with increased FDG uptake in the right testis. Biopsy of the mass confirmed a diagnosis of myeloid sarcoma.
Association of Cardiometabolic Multimorbidity and Depression With Cardiovascular Events in Early-Onset Adult Type 2 Diabetes: A Multiethnic Study in the U.S.
Authors: John Epoh Dibato, Olga Montvida, Francesco Zaccardi, Jack Alistair Sargeant, Melanie J. Davies, Kamlesh Khunti, Sanjoy K. Paul
Journal: Diabetes Care (2020)

OBJECTIVE To evaluate the temporal patterns of cardiometabolic multimorbidity (CM) and depression in White Caucasians (WCs) and African Americans (AAs) with early-onset type 2 diabetes and their impact on long-term atherosclerotic cardiovascular disease (ASCVD). RESEARCH DESIGN AND METHODS From U.S. electronic medical records, 101,104 AA and 505,336 WC subjects with type 2 diabetes diagnosed between 2000 and 2017 were identified (mean follow-up 5.3 years). Among those without ASCVD at diagnosis, risk of ASCVD and three-point major adverse cardiovascular events (MACE-3) (heart failure, myocardial infarction, or stroke) was evaluated between ethnicities by age-groups. RESULTS The proportion of patients diagnosed at &amp;lt;50 years of age increased during 2012–2017 (AA 34–38%, WC 26–29%). Depression prevalence increased during 2000–2017 (AA 15–23%, WC 20–34%), with an increasing trend for CM at diagnosis in both groups. Compared with WC, the adjusted MACE-3 risk was significantly higher in AA across all age-groups, more pronounced in the 18–39-year age-group (hazard ratio 95% CI 1.42, 1.88), and in patients with and without depression. AAs had a 17% (1.05, 1.31) significantly higher adjusted ASCVD risk in the 18–39-year age-group only. Depression was independently associated with ASCVD and MACE-3 risk in both ethnic groups across all age-groups. Other comorbidities were independently associated with ASCVD and MACE-3 risk only among WCs. CONCLUSIONS AAs have higher cardiovascular risk compared with WCs, particularly in early-onset type 2 diabetes. CM and depression at diabetes diagnosis have been increasing over the past two decades in both ethnic groups. Strategies for screening and optimal management of CM and depression, particularly in early-onset type 2 diabetes, may result in a lower cardiovascular risk.