tbuckley/cabot-search huggingface dataset:
Abstract 16602: The Clinical Significance of Mif, Mif-2 and Mif Genotype in Patients Exhibited to Myocardial Ischemia/reperfusion Injury
Authors: Christian Stoppe, Andreas Goetzenich, Sandra Kraemer, Christoph Emontzpohl, Josefin Soppert, Richard Bucala, Christian Weber, Jürgen Bernhagen
Journal: Circulation (2015)

Background: Cardiac surgery is increasingly been performed on an aging patient population with increased numbers of comorbid conditions. These patients are frequently exposed to myocardial ischemia/reperfusion with deleterious consequences and development of organ dysfunctions. The pleiotropic cytokine macrophage migration inhibitory factor (MIF) is an upstream regulator of the immune response and rapidly released from pre-formed cytoplasmatic pools in response to activating stimuli such as hypoxia, infection or inflammation. Yet, its interaction with related mediators such as its homolog, D-dopachrome tautomerase (MIF-2) is largely unknown. Therefore, we aimed to investigate the interaction and clinical significance of MIF and MIF-2 in patients undergoing cardiac surgery with myocardial ischemia/reperfusion. Methods and Results: Circulating levels of MIF and MIF-2 were measured peri-operatively in 100 patients that underwent elective cardiac surgery and showed a rapid increase upon myocardial ischemia. Intra-operative MIF levels reached maximum during myocardial reperfusion and were independently associated with a reduced risk for the development of AF in the post-operative period (odds ratio 0.99 (0.98-1.00); p=0.007), whereas circulating levels of MIF-2 were associated with an increased frequency of organ dysfunction and predicted the occurrence of atrial fibrillation (area under the curve (AUC)=0.663;p=0.041) and pneumonia (AUC=0.708;p=0.040). Known functional MIF allelic variants were analyzed and patients with high-expression MIF-genotype exhibited reduced incidence of organ dysfunction (3 vs. 25; p=0.042). Conclusion: Our findings present the first description of the kinetics and potential clinical relevance of the MIF, MIF-2 and MIF genotype in myocardial ischemia/reperfusion (I/R) in the setting of cardiac surgery. The present study demonstrated that increased intra-operative MIF levels may provide organoprotective effects, whereas elevated serum levels of MIF-2 were associated with the development of organ dysfunctions in patients after cardiac surgery. Patients with a high-expression MIF genotype experienced a significantly lower incidence of organ dysfunctions.
The conundrum of cryptogenic cirrhosis: Adverse outcomes without treatment options
Authors: Zobair Younossi, Maria Stepanova, Arun J. Sanyal, Stephen A. Harrison, Vlad Ratziu, Manal F. Abdelmalek, Anna Mae Diehl, Stephen Caldwell, Mitchell L. Shiffman, Raul Aguilar Schall, Bryan McColgan, G. Mani Subramanian, Robert P. Myers, Andrew Muir, Nezam H. Afdhal, Jaime Bosch, Zachary Goodman
Journal: Journal of Hepatology (2018)
Stem Cell Therapy for Congenital Heart Disease
Authors: Diamantis I. Tsilimigras, Evangelos K. Oikonomou, Demetrios Moris, Dimitrios Schizas, Konstantinos P. Economopoulos, Konstantinos S. Mylonas
Journal: Circulation (2017)

Background: Congenital heart disease (CHD) constitutes the most prevalent and heterogeneous group of congenital anomalies. Although surgery remains the gold standard treatment modality, stem cell therapy has been gaining ground as a complimentary or alternative treatment option in certain types of CHD. The aim of this study was to present the existing published evidence and ongoing research efforts on the implementation of stem cell-based therapeutic strategies in CHD. Methods: A systematic review was conducted by searching Medline, ClinicalTrials.gov, and the Cochrane library, along with reference lists of the included studies through April 23, 2017. Results: Nineteen studies were included in this review (8 preclinical, 6 clinical, and 5 ongoing trials). Various routes of cardiac stem cell delivery have been reported, including intracoronary, intramyocardial, intravenous, and epicardial. Depending on their origin and level of differentiation at which they are harvested, stem cells may exhibit different properties. Preclinical studies have mostly focused on modeling right ventricle dysfunction or failure and pulmonary artery hypertension by using pressure or volume overload in vitro or in vivo. Only a limited number of clinical trials on patients with CHD exist, and these primarily focus on hypoplastic left heart syndrome. Cell-based tissue engineering has recently been introduced, and research currently is focusing on developing cell-seeded grafts and patches that could potentially grow in parallel with whole body growth once implanted in the heart. Conclusions: It seems that stem cell delivery to the diseased heart as an adjunct to surgical palliation may provide some benefits over surgery alone in terms of cardiac function, somatic growth, and quality of life. Despite encouraging preliminary results, stem cell therapies for patients with CHD should only be considered in the setting of well-designed clinical trials. More wet laboratory research experience is needed, and translation of promising findings to large clinical studies is warranted to clearly define the efficacy and safety profile of this alternative and potentially groundbreaking therapeutic approach.
Moving Past Ejection Fraction in Timing of Aortic Stenosis Intervention
Authors: James D. Thomas
Journal: JAMA Cardiology (2018)

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 Cardiology 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 Cardiology journal
SP0121 Tapering in psa – to do or not to do?
Authors: L. Coates
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> This talk will discuss the current evidence regarding tapering or drug withdrawal in patients with psoriatic arthritis. With increasing numbers of patients achieving good outcomes such as remission, the issue of how long to continue treatment for has been raised. Given the cost of some of the newer therapies, this question also has significant cost effectiveness implications. There is a limited amount of evidence but data from randomised and observational studies will be discussed as well as key research questions that remain outstanding. <h3>Disclosure of Interest</h3> None declared
Comparative transcriptomic analyses and single-cell RNA sequencing of the freshwater planarian Schmidtea mediterranea identify major cell types and pathway conservation
Authors: Lakshmipuram Seshadri Swapna, Alyssa M. Molinaro, Nicole Lindsay-Mosher, Bret J. Pearson, John Parkinson
Journal: Genome biology (2018)

In the Lophotrochozoa/Spiralia superphylum, few organisms have as high a capacity for rapid testing of gene function and single-cell transcriptomics as the freshwater planaria. The species Schmidtea mediterranea in particular has become a powerful model to use in studying adult stem cell biology and mechanisms of regeneration. Despite this, systematic attempts to define gene complements and their annotations are lacking, restricting comparative analyses that detail the conservation of biochemical pathways and identify lineage-specific innovations. In this study we compare several transcriptomes and define a robust set of 35,232 transcripts. From this, we perform systematic functional annotations and undertake a genome-scale metabolic reconstruction for S. mediterranea. Cross-species comparisons of gene content identify conserved, lineage-specific, and expanded gene families, which may contribute to the regenerative properties of planarians. In particular, we find that the TRAF gene family has been greatly expanded in planarians. We further provide a single-cell RNA sequencing analysis of 2000 cells, revealing both known and novel cell types defined by unique signatures of gene expression. Among these are a novel mesenchymal cell population as well as a cell type involved in eye regeneration. Integration of our metabolic reconstruction further reveals the extent to which given cell types have adapted energy and nucleotide biosynthetic pathways to support their specialized roles. In general, S. mediterranea displays a high level of gene and pathway conservation compared with other model systems, rendering it a viable model to study the roles of these pathways in stem cell biology and regeneration.
Abstract 20201: Activation of DNA Damage Response and Cellular Senescence in Cardiac Fibroblasts Limit Cardiac Fibrosis After Myocardial Infarction
Authors: Masato Shibamoto, Atsuhiko Naito, Tomoaki Higo, Jong-Kook Lee, Shungo Hikosou, Yasushi Sakata, Issei Komuro
Journal: Circulation (2017)

Introduction: Activation and proliferation of cardiac fibroblasts (CFs) play an important role in the formation of cardiac fibrosis after myocardial infarction (MI). Molecular mechanisms that promo...
Limited Evidence for Parallel Molecular Adaptations Associated with the Subterranean Niche in Mammals: A Comparative Study of Three Superorders
Authors: Kalina T J Davies, Nigel C Bennett, Chris G Faulkes, Stephen J Rossiter
Journal: Molecular Biology and Evolution (2018)

Among mammals, several lineages have independently adapted to a subterranean niche and possess similar phenotypic traits for burrowing (e.g., cylindrical bodies, short limbs, and absent pinnae). Previous research on mole-rats has revealed molecular adaptations for coping with reduced oxygen, elevated carbon dioxide, and the absence of light. In contrast, almost nothing is known regarding molecular adaptations in other subterranean lineages (e.g., true moles and golden moles). Therefore, the extent to which the recurrent phenotypic adaptations of divergent subterranean taxa have arisen via parallel routes of molecular evolution remains untested. To address these issues, we analyzed ∼8,000 loci in 15 representative subterranean taxa of four independent transitions to an underground niche for signatures of positive selection and convergent amino acid substitutions. Complementary analyses were performed in nonsubterranean "control" taxa to assess the biological significance of results. We found comparable numbers of positively selected genes in each of the four subterranean groups; however, correspondence in terms of gene identity between gene sets was low. Furthermore, we did not detect evidence of more convergent amino acids among subterranean species pairs compared with levels found between nonsubterranean controls. Comparisons with nonsubterranean taxa also revealed loci either under positive selection or with convergent substitutions, with similar functional enrichment (e.g., cell adhesion, immune response, and coagulation). Given the limited indication that positive selection and convergence occurred in the same loci, we conclude that selection may have acted on different loci across subterranean mammal lineages to produce similar phenotypes.
Improved Survival for Children and Young Adults With T-Lineage Acute Lymphoblastic Leukemia: Results From the Children’s Oncology Group AALL0434 Methotrexate Randomization
Authors: Stuart S. Winter, Kimberly P. Dunsmore, Meenakshi Devidas, Brent L. Wood, Natia Esiashvili, Zhiguo Chen, Nancy Eisenberg, Nikki Briegel, Robert J. Hayashi, Julie M. Gastier-Foster, Andrew J. Carroll, Nyla A. Heerema, Barbara L. Asselin, Paul S. Gaynon, Michael J. Borowitz, Mignon L. Loh, Karen R. Rabin, Elizabeth A. Raetz, Patrick A. Zweidler-Mckay, Naomi J. Winick, William L. Carroll, Stephen P. Hunger
Journal: Journal of Clinical Oncology (2018)

Early intensification with methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy. Two different approaches to MTX intensification exist but had not been compared in T-cell ALL (T-ALL): the Children's Oncology Group (COG) escalating dose intravenous MTX without leucovorin rescue plus pegaspargase escalating dose, Capizzi-style, intravenous MTX (C-MTX) regimen and the Berlin-Frankfurt-Muenster (BFM) high-dose intravenous MTX (HDMTX) plus leucovorin rescue regimen.COG AALL0434 included a 2 × 2 randomization that compared the COG-augmented BFM (ABFM) regimen with either C-MTX or HDMTX during the 8-week interim maintenance phase. All patients with T-ALL, except for those with low-risk features, received prophylactic (12 Gy) or therapeutic (18 Gy for CNS3) cranial irradiation during either the consolidation (C-MTX; second month of therapy) or delayed intensification (HDMTX; seventh month of therapy) phase.AALL0434 accrued 1,895 patients from 2007 to 2014. The 5-year event-free survival and overall survival rates for all eligible, evaluable patients with T-ALL were 83.8% (95% CI, 81.2% to 86.4%) and 89.5% (95% CI, 87.4% to 91.7%), respectively. The 1,031 patients with T-ALL but without CNS3 disease or testicular leukemia were randomly assigned to receive ABFM with C-MTX (n = 519) or HDMTX (n = 512). The estimated 5-year disease-free survival ( P = .005) and overall survival ( P = .04) rates were 91.5% (95% CI, 88.1% to 94.8%) and 93.7% (95% CI, 90.8% to 96.6%) for C-MTX and 85.3% (95% CI, 81.0%-89.5%) and 89.4% (95% CI, 85.7%-93.2%) for HDMTX. Patients assigned to C-MTX had 32 relapses, six with CNS involvement, whereas those assigned to HDMTX had 59 relapses, 23 with CNS involvement.AALL0434 established that ABFM with C-MTX was superior to ABFM plus HDMTX for T-ALL in approximately 90% of patients who received CRT, with later timing for those receiving HDMTX.
Dysregulated neutrophil responses and neutrophil extracellular trap formation and degradation in PAPA syndrome
Authors: Pragnesh Mistry, Carmelo Carmona-Rivera, Amanda K Ombrello, Patrycja Hoffmann, Nickie L Seto, Anne Jones, Deborah L Stone, Faiza Naz, Philip Carlucci, Stefania Dell'Orso, Gustavo Gutierrez-Cruz, Hong-Wei Sun, Daniel L Kastner, Ivona Aksentijevich, Mariana J Kaplan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is characterised by flares of sterile arthritis with neutrophil infiltrate and the overproduction of interleukin (IL)-1β. The purpose of this study was to elucidate the potential role of neutrophil subsets and neutrophil extracellular traps (NET) in the pathogenesis of PAPA. <h3>Methods</h3> Neutrophils and low-density granulocytes (LDG) were quantified by flow cytometry. Circulating NETs were measured by ELISA and PAPA serum was tested for the ability to degrade NETs. The capacity of NETs from PAPA neutrophils to activate macrophages was assessed. Skin biopsies were analysed for NETs and neutrophil gene signatures. <h3>Results</h3> Circulating LDGs are elevated in PAPA subjects. PAPA neutrophils and LDGs display enhanced NET formation compared with control neutrophils. PAPA sera exhibit impaired NET degradation and this is corrected with exogenous DNase1. Recombinant human IL-1β induces NET formation in PAPA neutrophils but not healthy control neutrophils. NET formation in healthy control neutrophils is induced by PAPA serum and this effect is inhibited by the IL-1 receptor antagonist, anakinra. NETs from PAPA neutrophils and LDGs stimulate IL-6 release in healthy control macrophages. NETs are detected in skin biopsies of patients with PAPA syndrome in association with increased tissue IL-1β, IL-8 and IL-17. Furthermore, LDG gene signatures are detected in PAPA skin. <h3>Conclusions</h3> PAPA syndrome is characterised by an imbalance of NET formation and degradation that may enhance the half-life of these structures in vivo, promoting inflammation. Anakinra ameliorates NET formation in PAPA and this finding supports a role for IL-1 signalling in exacerbated neutrophil responses in this disease. The study also highlights other inflammatory pathways potentially pathogenic in PAPA, including IL-17 and IL-6, and these results may help guide new therapeutic approaches in this severe and often treatment-refractory condition.
Abstract 9796: Transradial versus Transfemoral Approach for Coronary Angiography and Intervention in Elderly: A Systemic Review & Meta-analysis
Authors: Sukhchain Singh, Ankur Sethi, Mukesh Singh, Navsheen Grewal, Sandeep Khosla
Journal: Circulation (2015)

Background: Limited information is available about the safety & efficacy of transradial (TR) versus transfemoral (TF) approach for percutaneous coronary angiography & interventions in the elderly. Objective: The authors Aimed to conduct first ever comprehensive meta-analysis to evaluate the safety & efficacy of TR versus TF approach in the elderly. Methods: The PubMed, Embase & CINAHL were searched for studies evaluating TR versus TF approach in the elderly (age≥75 years). The Stata software package was used to conduct more conservative random effect meta-analysis. Primary end point was access site complications (hematoma, pseudoaneurysm or need for access site surgery). Results: Twelves studies (4 randomized & 8 observational) comprising 5636 patients met inclusion criteria for the review (Figure). The primary end point of access site complications was significantly lower in the TR group versus TF group (RR 0.23, 95% CI 0.15-0.34). The secondary end points of bleeding requiring blood transfusion (RR 0.49...
Abstract 15971: Epigenetic Control of Adult Cardiac Myocyte Proliferation
Authors: Danny El-Nachef, Kyohei Oyama, Yun-Yu Wu, Yonggang Liu, Yiqiang Zhang, W. Robb MacLellan
Journal: Circulation (2016)

Cardiac myocyte (CM) proliferation is required for the heart regeneration seen in lower vertebrates and neonatal mammalian injury models. However, typically mammalian CMs stop proliferating soon af...
Abstract 12975: Cardiac I-123 Metaiodobenzylguanidine Imaging Predicts the Risk of Cardiac Death in Patients With Chronic Heart Failure, Irrespective of Blood Urea Nitrogen to Creatinine Ratio: A Long-Term Follow Up Study
Authors: Hideyuki Hakui, Takahisa Yamada, Takashi Motrita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondou, Masashi Ishimi, Tatsuhisa Ozaki, Yoshihiro Sato, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Masatake Fukunami
Journal: Circulation (2015)

Background: Cardiac I-123 metaiodobenzylguanidine (MIBG) imaging, which reflects cardiac sympathetic activity, provides prognostic information in patients with chronic heart failure (CHF). On the other hand, elevated blood urea nitrogen to creatinine ratio (BUN/Cr), a surrogate for renal neurohumoral activation, is associated with poor outcome in patients with heart failure. However, there is no information available on the prognostic value of cardiac MIBG imaging in patients with CHF, relating to BUN/Cr. Methods: We studied 109 CHF outpatients (NYHA class:2.1±0.6, ischemic origin:52%) with left ventricular ejection fraction &lt;40% (30±8%) in our prospective cohort study. At the enrollment, we measured serum level of BUN and Cr, and performed cardiac MIBG scintigraphy. Elevated BUN/Cr was defined as &gt;20. The cardiac MIBG washout rate (WR) was calculated from the chest anterior view images obtained at 20 and 200 min after isotope injection. Abnormal WR was defined as &gt;27%. Results: Forty patients had elevated BUN/Cr, and 55 patients had abnormal WR. During a follow up period of 7.5±4.2 yrs, 36 of 109 patients had cardiac death. At multivariate Cox analysis, WR was significantly independently associated with cardiac death in group with both elevated BUN/Cr (p=0.02) and normal BUN/Cr (p=0.004). Kaplan-Meier analysis showed that patients with abnormal WR had a higher risk of cardiac death than those with normal WR, in group with both elevated BUN/Cr (48%[11/23] vs 6%[1/17], p=0.02, adjusted hazard ratio 11.8[95%CI 1.5-92.2]) and normal BUN/Cr (55%[18/33] vs 17%[6/36], p=0.001, adjusted hazard ratio 4.6[95%CI 1.8-11.6]). Conclusion: The cardiac MIBG imaging could predict the risk of cardiac death in CHF, irrespective of BUN/Cr.
CAD Is an Independent Risk Factor for Stroke Among Patients With Atrial Fibrillation
Authors: Kamilla Steensig, Kevin K.W. Olesen, Troels Thim, Jens C. Nielsen, Svend E. Jensen, Lisette O. Jensen, Steen D. Kristensen, Hans Erik Bøtker, Gregory Y.H. Lip, Michael Maeng
Journal: Journal of the American College of Cardiology (2018)
Abstract 19592: Management and Outcomes of Sports-Related Cardiac Arrest in Young Adults
Authors: Nicole Karam, Louis Pechmajou, Frankie Beganton, Wulfran Bougouin, Florence Dumas, Daniel Jost, Jean-Philipe Empana, Alain Cariou, Christian Spaulding, Xavier Jouven, Eloi Marijon
Journal: Circulation (2016)

Introduction: Sports-related Out of Hospital Cardiac Arrests (OHCA) have a higher survival rate compared to those occurring outside the context of sports. Hypothesis: Initial management is better in sports-related OHCA than in OHCA occurring outside the context of sports. Methods: Data was taken between May 2011 and February 2016 from the Paris Sudden Cardiac Death Expertise Center prospective registry that includes all adult patients who present OHCA in Paris and its suburbs. Sports-related OHCA was defined as OHCA occurring during sports activities or within 1 hour of sports cessation. OHCA occurring among patients aged below 35 years were included in the study and compared to non-sports related OHCA occurring in the same age range. Results: During the study period, 15,398 OHCA were recorded of which 9087 had a resuscitation attempt. Among them, 361 occurred in patients ≤ 35 years, including 26 (7.2%) during sports activities. Young adults’ sports-related OHCA occurred more frequently in men (92.3% vs 6...