tbuckley/cabot-search huggingface dataset:
Glucagon-Like Peptide 1 Receptor Agonists and Heart Failure
Authors: Muhammad Shahzeb Khan, Gregg C. Fonarow, Darren K. McGuire, Adrian F. Hernandez, Muthiah Vaduganathan, Julio Rosenstock, Yehuda Handelsman, Subodh Verma, Stefan D. Anker, John J.V. McMurray, Mikhail N. Kosiborod, Javed Butler
Journal: Circulation (2020)

With worsening epidemiological trends for both the incidence and prevalence of type 2 diabetes mellitus (T2DM) and heart failure (HF) worldwide, it is critical to implement optimal prevention and treatment strategies for patients with these comorbidities, either alone or concomitantly. Several guidelines and consensus statements have recommended glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter type 2 inhibitors as add-ons to lifestyle interventions with or without metformin in those at high atherosclerotic cardiovascular disease risk. However, these recommendations are either silent about HF or fail to differentiate between the prevention of HF in those at risk versus the treatment of individuals with manifest HF. Furthermore, these documents do not differentiate among those with different HF phenotypes. This distinction, even though important, may not be critical for sodium-glucose cotransporter type 2 inhibitors in view of the consistent data for benefit for both atherosclerotic cardiovascular disease– and HF-related outcomes that have emerged from the regulatory-mandated cardiovascular outcome trials for all sodium-glucose cotransporter type 2 inhibitors and the recent DAPA-HF trial (Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction)demonstrating the benefit of dapagliflozin on HF-related outcomes in patients with HF with reduced ejection fraction with or without T2DM. However, the distinction may be crucial for glucagon-like peptide-1 receptor agonists and other antihyperglycemic agents. Indeed, in several of the new statements, glucagon-like peptide-1 receptor agonists are suggested treatment not only for patients with T2DM and atherosclerotic cardiovascular disease, but also in those with manifest HF, despite a lack of evidence for the latter recommendation. Although glucagon-like peptide-1 receptor agonists may be appropriate to use in patients at risk for HF, mechanistic insights and observations from randomized trials suggest no clear benefit on HF-related outcomes and even uncertainty regarding the safety in those with HF with reduced ejection fraction. Conversely, theoretical rationales suggest that these agents may benefit patients with HF with preserved ejection fraction. Considering that millions of patients with T2DM have HF, these concerns have public health implications that necessitate the thoughtful use of these therapies. Achieving this aim will require dedicated trials with these drugs in both patients who have HF with reduced ejection fraction and HF with preserved ejection fraction with T2DM to assess their efficacy, safety, and risk-benefit profile.
Retraction: NRH:Quinone Oxidoreductase 2-Deficient Mice Are Highly Susceptible to Radiation-induced B-Cell Lymphomas
Authors: Karim Iskander, Roberto J. Barrios, Anil K. Jaiswal
Journal: Clinical Cancer Research (2018)

This article (1) is being retracted at the request of the editors. Following an institutional review by the University of Maryland (Baltimore, MD), it was determined that the p53 bands in Fig. 4B appeared identical to bands labeled as "Bax" in a previously published article (2). The authors independently contacted the Journal and offered to run repeat experiments; the repeat experiments partially supported the original findings. Because the original data is not available for review and to ensure that the research record is correct, the Clinical Cancer Research editors have decided to retract the article.A copy of this retraction notice was sent to the last known e-mail addresses for all three authors, none of whom responded.
Malignant cell-specific CXCL14 promotes tumor lymphocyte infiltration in oral cavity squamous cell carcinoma
Authors: Anuraag Parikh, JuneHo Shin, William Faquin, Derrick T Lin, Itay Tirosh, John B Sunwoo, Sidharth V Puram
Journal: Journal for ImmunoTherapy of Cancer (2020)

Objectives To explore lymphocyte infiltration as a potential mechanism behind CXCL14-mediated tumor growth suppression in oral cavity squamous cell carcinoma (OSCC). Methods We analyzed single cell RNA-sequencing (scRNA-seq) data from OSCC to identify expression changes among malignant cells in lymph nodes (LN) versus primary tumors. CXCL14 expression in murine OSCC cell lines was quantified using qRT-PCR. Short hairpin RNA knockdown of CXCL14 was performed in mouse oral cavity (MOC)1 cells, and CXCL14 overexpression was performed in MOC2 cells. Cells in each condition were injected into C57BL/6 mice with and without T cell depletion, and tumor volume was measured. At 30 days, tumors were dissociated and analyzed by flow cytometry for CD45 + CD3 + T cells. CXCL14 expression was correlated with gene expression signatures of tumor infiltrating lymphocytes (TIL) in scRNA-seq data, as well as TCGA tumors. Results scRNA-seq revealed CXCL14 as the most significantly downregulated gene among malignant cells in LNs relative to primary tumor, supporting a role in preventing invasion and/or metastasis. In a murine immunocompetent model, CXCL14 expression was higher in indolent MOC1 cells than in more aggressive MOC2 cells. Tumor growth in vivo was significantly increased by CXCL14 knockdown in MOC1 cells relative to control, with a corresponding decrease in TIL. In MOC2 cells, tumor growth was significantly reduced by CXCL14 overexpression relative to control and TIL were increased. Both effects were lost with T cell depletion. In a human tumor scRNA-seq cohort, we found that only malignant cell CXCL14, but not non-malignant cell or fibroblast CXCL14, was associated with TIL. Bulk CXCL14 from the TCGA cohort had no association with TIL. Conclusions Higher CXCL14 expression by tumor cells is associated with reduced tumor growth and increased TIL, supporting immune-mediated suppression of tumor growth in OSCC. Given that CXCL14 is downregulated in LN metastases compared with primary tumors, our data raise the possibility that CXCL14-mediated immune infiltration may discourage invasion and metastasis. In human scRNA-seq data, only malignant cell-specific CXCL14 was associated with TIL, suggesting a critical context-dependent effect of CXCL14 expression.
Plasma <scp>D</scp>‐dimer concentrations predicting stroke risk and rivaroxaban benefit in patients with heart failure and sinus rhythm: an analysis from the <scp>COMMANDER‐HF</scp> trial
Authors: João Pedro Ferreira, Carolyn S.P. Lam, Stefan D. Anker, Mandeep R. Mehra, Dirk J. van Veldhuisen, William M. Byra, David A. La Police, John G.F. Cleland, Barry Greenberg, Faiez Zannad
Journal: European Journal of Heart Failure (2020)
Work and Heart Disease
Authors: AMASA B. FORD, HERMAN K. HELLERSTEIN, DAVID J. TURELL
Journal: Circulation (1959)

Knowledge of the cardiovascular requirements of various types of work is essential in making work recommendations for cardiac patients. In a previous study the stresses of work in a light metal manufacturing plant were shown to be small. The present study is an evaluation of the physiologic requirement of a typical day's work in an open-hearth furnace and other areas in a steel mill. The oxygen consumption, pulmonary ventilation, respiratory rate, and other physiologic responses in cardiac patients are compared to those of normal subjects performing the same tasks.
Abstract 14870: Progression of Paroxysmal to Persistent Af in Patients Awaiting AF Ablation
Authors: Simon Kochhaeuser, Dirk Dechering, Kathleen Trought, Philip Hache, Tanjah Haig-Carter, Yaariv Khaykin, Zaev Wulffhart, Alfredo Pantano, Bernice Tsang, Bernice Tsang, Lars Eckardt, Atul Verma
Journal: Circulation (2015)

Objective: Atrial fibrillation (AF) is a progressive disease for which ablation has become an important treatment option. Success rates have been shown to be significantly higher while AF has not yet progressed to persistent. In a general AF-population the HATCH-score has been proposed to predict the risk of progression to persistent AF. However, little is known about predictors of progression in patients awaiting AF ablation. Methods/Results: We performed a retrospective, single centre investigation of patients with paroxysmal AF at the time they were placed onto our AF ablation waiting list and evaluated possible risk factors for the progression of AF until the time of the actual ablation. Of 564 patients (median age 60.4 (±15.1) years, 194 (34.4%) female) 60 (11%) progressed from paroxysmal to persistent AF during a median waiting time of 291 (±244.3) days. In patients that progressed to persistent AF, ablation took significantly longer (180±99 min vs. 157±85min; p 0.009), had a tendency to require longer RF-energy delivery (68.9±40 min vs. 61.8±44 min; p 0.052) and was associated with a higher rate of recurrence (53.3% vs. 39.1%; p&lt;0.001). Patients that did progress to persistent AF had tied significantly more antiarrhythmic drugs (1 (±2) vs. 1(±1); p 0,048) and more frequently had a history of amiodaron treatment (21.7% vs. 11.9%; p 0.03). The previously proposed HATCH-score was only a poor predictor of AF progression (AUC 0.54). Furthermore, none of the individual HATCH-score parameters was a significantly predicted the progression of AF in our population. However, a left atrial (LA) diameter of more than 45mm (OR 3.46, p&lt; 0.001) and heart failure (OR 3.11, p 0.036) were strong and independent predictors of AF progression in multivariable analysis. Conclusion: Patients with an increased LA-diameter or heart failure have a significantly increased risk to progress to persistent AF. If ablation is considered in such a patient it should be conducted as soon as possible to prevent progression to persistent AF.
Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment
Authors: Elavarasan Subramani, Marina Radoul, Chloe Najac, Georgios Batsios, Abigail R. Molloy, Donghyun Hong, Anne Marie Gillespie, Romelyn Delos Santos, Pavithra Viswanath, Joseph F. Costello, Russell O. Pieper, Sabrina M. Ronen
Journal: Cancer Research (2020)

Abstract Although lower grade gliomas are driven by mutations in the isocitrate dehydrogenase 1 (IDH1) gene and are less aggressive than primary glioblastoma, they nonetheless generally recur. IDH1-mutant patients are increasingly being treated with temozolomide, but early detection of response remains a challenge and there is a need for complementary imaging methods to assess response to therapy prior to tumor shrinkage. The goal of this study was to determine the value of magnetic resonance spectroscopy (MRS)–based metabolic changes for detection of response to temozolomide in both genetically engineered and patient-derived mutant IDH1 models. Using 1H MRS in combination with chemometrics identified several metabolic alterations in temozolomide-treated cells, including a significant increase in steady-state glutamate levels. This was confirmed in vivo, where the observed 1H MRS increase in glutamate/glutamine occurred prior to tumor shrinkage. Cells labeled with [1–13C]glucose and [3–13C]glutamine, the principal sources of cellular glutamate, showed that flux to glutamate both from glucose via the tricarboxylic acid cycle and from glutamine were increased following temozolomide treatment. In line with these results, hyperpolarized [5–13C]glutamate produced from [2–13C]pyruvate and hyperpolarized [1–13C]glutamate produced from [1–13C]α-ketoglutarate were significantly higher in temozolomide-treated cells compared with controls. Collectively, our findings identify 1H MRS-detectable elevation of glutamate and hyperpolarized 13C MRS-detectable glutamate production from either pyruvate or α-ketoglutarate as potential translatable metabolic biomarkers of response to temozolomide treatment in mutant IDH1 glioma. Significance: These findings show that glutamate can be used as a noninvasive, imageable metabolic marker for early assessment of tumor response to temozolomide, with the potential to improve treatment strategies for mutant IDH1 patients.
Clustering and superspreading potential of SARS-CoV-2 infections in Hong Kong
Authors: Dillon C. Adam, Peng Wu, Jessica Y. Wong, Eric H. Y. Lau, Tim K. Tsang, Simon Cauchemez, Gabriel M. Leung, Benjamin J. Cowling
Journal: Nature Medicine (2020)

Superspreading events (SSEs) have characterized previous epidemics of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infections1–6. For SARS-CoV-2, the degree to which SSEs are involved in transmission remains unclear, but there is growing evidence that SSEs might be a typical feature of COVID-197,8. Using contact tracing data from 1,038 SARS-CoV-2 cases confirmed between 23 January and 28 April 2020 in Hong Kong, we identified and characterized all local clusters of infection. We identified 4–7 SSEs across 51 clusters (n = 309 cases) and estimated that 19% (95% confidence interval, 15–24%) of cases seeded 80% of all local transmission. Transmission in social settings was associated with more secondary cases than households when controlling for age (P = 0.002). Decreasing the delay between symptom onset and case confirmation did not result in fewer secondary cases (P = 0.98), although the odds that an individual being quarantined as a contact interrupted transmission was 14.4 (95% CI, 1.9–107.2). Public health authorities should focus on rapidly tracing and quarantining contacts, along with implementing restrictions targeting social settings to reduce the risk of SSEs and suppress SARS-CoV-2 transmission. Cases linked to superspreading events are estimated to account for 80% of all local transmission of SARS-CoV-2 in Hong Kong in a study with implications for public health policies.
Correspondence on ‘classification criteria: time for a rethink ‘by D Porter<i>et al’</i>
Authors: Hasan Yazici, Yusuf Yazici
Journal: Annals of the Rheumatic Diseases (2020)

Correspondence on 'classification criteria: time for a rethink 'by D Porter et al'We take the following three main messages from Porter and colleagues' thoughtful viewpoint article. 1 1.Although disease classification criteria are developed for research purposes, they are commonly used for diagnosis in the clinic.This common practice is wrong since the prior probabilities for the targeted disease are always higher in the research and lower in clinical practice settings.Therefore, the use of the same criteria for diagnosis in general practice would cause an unacceptably high number of false positives in that setting.2. The use of classification criteria for research purposes, the usual setting being enroling patients into clinical trials, is also problematic.Such criteria can not only cause exclusion of patients who would benefit from the drug used in the study, but also the inappropriate inclusion of patients with no disease into the formal study.The authors give suitable examples for both scenarios.3. The authors conclude that since the current disease criteria represent much hard work by experts in the field we should not 'throw the baby out with the water'.The disease criteria could be used 'as a lens through which the study population can be viewed'.First, we must point out the proposal to use the currently available criteria as a lens through which the study population can be viewed and will limit the use of the disease criteria only to better analyse what has already been published.We surely do not think that the authors' suggestion of using disease criteria at hand for future practice or research will be useful after the authors very clearly delineating their shortcomings.We have on repeated occasions tried to highlight the shortcomings and thought barriers in the current classification versus diagnostic criteria discussion/debate. 2 3 Importantly, we had
Liver Injury in Liver Transplant Recipients With Coronavirus Disease 2019 (COVID‐19): U.S. Multicenter Experience
Authors: Atoosa Rabiee, Brett Sadowski, Nia Adeniji, Ponni V. Perumalswami, Veronica Nguyen, Akshata Moghe, Nyan L. Latt, Sonal Kumar, Costica Aloman, Andreea M. Catana, Patricia P. Bloom, Kenneth D. Chavin, Rotonya M. Carr, Winston Dunn, Vincent L. Chen, Elizabeth S. Aby, Jose D. Debes, Renumathy Dhanasekaran
Journal: Hepatology (2020)

Background and Aims Coronavirus disease 2019 (COVID‐19) is associated with liver injury, but the prevalence and patterns of liver injury in liver transplantation (LT) recipients with COVID‐19 are open for study. Approach and Results We conducted a multicenter study in the United States of 112 adult LT recipients with COVID‐19. Median age was 61 years (interquartile range, 20), 54.5% (n = 61) were male, and 39.3% (n = 44) Hispanic. Mortality rate was 22.3% (n = 25); 72.3% (n = 81) were hospitalized and 26.8% (n = 30) admitted to the intensive care unit (ICU). Analysis of peak values of alanine aminotransferase (ALT) during COVID‐19 showed moderate liver injury (ALT 2‐5× upper limit of normal [ULN]) in 22.2% (n = 18) and severe liver injury (ALT &gt; 5× ULN) in 12.3% (n = 10). Compared to age‐ and sex‐matched nontransplant patients with chronic liver disease and COVID‐19 (n = 375), incidence of acute liver injury was lower in LT recipients (47.5% vs. 34.6%; P = 0.037). Variables associated with liver injury in LT recipients were younger age ( P = 0.009; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20‐3.54), Hispanic ethnicity ( P = 0.011; OR, 6.01; 95% CI, 1.51‐23.9), metabolic syndrome ( P = 0.016; OR, 5.87; 95% CI, 1.38‐24.99), vasopressor use ( P = 0.018; OR, 7.34; 95% CI, 1.39‐38.52), and antibiotic use ( P = 0.046; OR, 6.93; 95% CI, 1.04‐46.26). Reduction in immunosuppression (49.4%) was not associated with liver injury ( P = 0.156) or mortality ( P = 0.084). Liver injury during COVID‐19 was significantly associated with mortality ( P = 0.007; OR, 6.91; 95% CI, 1.68‐28.48) and ICU admission ( P = 0.007; OR, 7.93; 95% CI, 1.75‐35.69) in LT recipients. Conclusions Liver injury is associated with higher mortality and ICU admission in LT recipients with COVID‐19. Hence, monitoring liver enzymes closely can help in early identification of patients at risk for adverse outcomes. Reduction of immunosuppression during COVID‐19 did not increase risk for mortality or graft failure.
Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes
Authors: Sonia García-Calzón, Alexander Perfilyev, Mats Martinell, Monta Ustinova, Sebastian Kalamajski, Paul W. Franks, Karl Bacos, Ilze Elbere, Jussi Pihlajamäki, Petr Volkov, Allan Vaag, Leif Groop, Marlena Maziarz, Janis Klovins, Emma Ahlqvist, Charlotte Ling
Journal: Science Translational Medicine (2020)

Blood-based epigenetic markers differentiate metformin responsiveness and tolerance in patients recently diagnosed with type 2 diabetes.
Association of Heart Rate With Troponin Levels Among Patients With Symptomatic Atrial Fibrillation
Authors: Jussi-Pekka Pouru, Samuli Jaakkola, Fausto Biancari, Tuomas O. Kiviniemi, Ilpo Nuotio, K.E. Juhani Airaksinen
Journal: JAMA Network Open (2020)

This cohort study investigates heart rate and cardiac troponin levels in patients admitted to the emergency department with symptomatic atrial fibrillation.
The prognostic value of additional copies of <scp>1q21</scp> in multiple myeloma depends on the primary genetic event
Authors: Maurus Locher, Michael Steurer, Emina Jukic, Markus A. Keller, Friedrich Fresser, Carmen Ruepp, Ewald Wöll, Irmgard Verdorfer, Günther Gastl, Wolfgang Willenbacher, Roman Weger, David Nachbaur, Dominik Wolf, Eberhard Gunsilius, Johannes Zschocke, Normann Steiner
Journal: American Journal of Hematology (2020)

Hyperdiploidy (HRD) and specific immunoglobulin heavy locus (IGH) translocations are primary chromosomal abnormalities (CA) in multiple myeloma (MM). In this retrospective study of 794 MM patients we aimed to investigate clinical features and common CA including gain(1q) in separate subgroups defined by primary CA. In the entire group, we confirmed that gain(1q) was associated with short time to next treatment and adverse overall survival (OS). The impact was worse for four or more copies of 1q21 as compared to three copies. However, in a subgroup of patients with clonal gain(11q) and without known primary IGH translocations (CG11q), already three copies of 1q21 were associated with a poor outcome; in the absence of gain(1q), patients in this subgroup had a remarkably long median OS of more than nine years. These cases were associated with HRD, coexpression of CD56 and CD117, male gender, and IgG subtype. In non-CG11q patients, four or more copies of 1q21 (but not three copies) had a significant adverse impact on outcome. Several associations with CA and clinical findings were observed for the defined subgroups. As an example, we found a predominance of early tetraploidy, plasma cell leukemia, and female gender in the t(14;16) subgroup. Our results underscore the importance of subgrouping in MM.
Comment on Flory et al. Reports of Lactic Acidosis Attributed to Metformin, 2015–2018. Diabetes Care 2020;43:244–246
Authors: Kerstin Brand
Journal: Diabetes Care (2020)

Flory et al. (1) analyzed cases of lactic acidosis (LA) reported to the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) for 2015–2018 to evaluate whether changes to the U.S. metformin label in 2016 altered the reporting rate of LA.

LA is rare, and large electronic databases are useful in studying its incidence. The Originator Pharmacovigilance (PV) Database (Merck KGaA) includes all individual case study reports on all metformin tablets manufactured by Merck, from patients, health care practitioners, health authorities, and the literature. The EudraVigilance Data Analysis System (EVDAS) and FAERS collect cases from marketing authorization holders, health authorities, and the literature in the European Union and U.S., …
Haploinsufficiency of immune checkpoint receptor CTLA4 induces a distinct neuroinflammatory disorder
Authors: Matthew K. Schindler, Stefania Pittaluga, Yoshimi Enose-Akahata, Helen C. Su, V. Koneti Rao, Amy Rump, Steven Jacobson, Irene Cortese, Daniel S. Reich, Gulbu Uzel
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. Cytotoxic T lymphocyte antigen 4 (CTLA4) is essential for immune homeostasis. Genetic mutations causing haploinsufficiency (CTLA4h) lead to a phenotypically heterogenous, immune-mediated disease that can include neuroinflammation. The neurological manifestations of CTLA4h are poorly characterized.