tbuckley/cabot-search huggingface dataset:
Abstract 11042: Serum Ceramides and Type 2 Diabetes Are Mutually Independent Predictors of Cardiovascular Events in Patients With Peripheral Artery Disease
Authors: Andreas Leiherer, Axel Muendlein, Christoph H Saely, Reijo Laaksonen, Mitja Lääperi, Alexander Vonbank, Arthur Mader, Peter Fraunberger, Iris Baumgartner, Joern F Dopheide, Heinz Drexel
Journal: Circulation (2019)

Introduction: Ceramides are enriched in atherosclerotic plaques, and a set of circulating ceramides including Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1), and Cer(d18:1/24:0) has recently eme...
TCT CONNECT-79 Is Surgical Cut Down Still an Option in Patients Undergoing Transcatheter Aortic Valve Replacement? A System-Wide Analysis With Second-Generation Valves
Authors: Puneet Gandotra, Dillon Gurciullo, Azhar Supariwala, Sridhar Uttara, Saurav Chatterjee, Robert Kalimi, Rajiv Jauhar, Efstathia Mihelis, Luis Gruberg
Journal: Journal of the American College of Cardiology (2020)
Fresh <i>vs.</i> frozen allogeneic peripheral blood stem cell grafts: A successful timely option
Authors: Ahmad S. Alotaibi, Shruti Prem, Shiyi Chen, Jeffrey H. Lipton, Dennis D. Kim, Auro Viswabandya, Rajat Kumar, Wilson Lam, Arjun D. Law, Jonas Mattsson, Fotios V. Michelis
Journal: American Journal of Hematology (2020)

Abstract Cryopreservation of grafts has been established in autologous and cord blood transplantation, yet there is little experience regarding the effect of cryopreservation with sibling and unrelated grafts. We evaluated the effect of cryopreservation of grafts on allogeneic transplant outcomes using related, unrelated and haploidentical donors, including 958 patients, age 18‐74 years (median 55) and using PBSC for various hematologic malignancies. Fresh grafts were received by 648 (68%) patients, 310 (32%) received cryopreserved. There was no difference between fresh vs cryopreserved grafts for neutrophil engraftment ( P = .09), platelet engraftment ( P = .11), graft failure (5.6% vs 6.8%, P = .46) and grade II‐IV acute graft‐vs‐host disease (GVHD) ( P = .71), moderate/severe chronic GVHD was observed in 176 (27%) vs 123 (40%) patients, respectively ( P &lt; .001). Multivariable analysis demonstrated no difference between fresh vs cryopreserved for OS ( P = .39) and CIR ( P = .08) while fresh grafts demonstrated borderline increased NRM (HR 1.27, 95% CI 1.02‐1.59, P = .04). Of note, for patients with no or mild chronic GVHD, CIR was less for fresh compared to cryopreserved (HR = 0.67 for fresh, 95% CI 0.48‐0.92, P = .01). We conclude there were no differences in engraftment and survival between fresh and cryopreserved grafts for allogeneic HCT, thus establishing cryopreservation to be a safe option for allogeneic HCT.
Ibrutinib-Mediated Atrial Fibrillation Attributable to Inhibition of C-Terminal Src Kinase
Authors: Ling Xiao, Joe-Elie Salem, Sebastian Clauss, Alan Hanley, Aneesh Bapat, Maarten Hulsmans, Yoshiko Iwamoto, Gregory Wojtkiewicz, Murat Cetinbas, Maximilian J. Schloss, Justin Tedeschi, Bénédicte Lebrun-Vignes, Alicia Lundby, Ruslan I. Sadreyev, Javid Moslehi, Matthias Nahrendorf, Patrick T. Ellinor, David J Milan
Journal: Circulation (2020)

Background: Ibrutinib is a Bruton tyrosine kinase inhibitor with remarkable efficacy against B-cell cancers. Ibrutinib also increases the risk of atrial fibrillation (AF), which remains poorly understood. Methods: We performed electrophysiology studies on mice treated with ibrutinib to assess inducibility of AF. Chemoproteomic analysis of cardiac lysates identified candidate ibrutinib targets, which were further evaluated in genetic mouse models and additional pharmacological experiments. The pharmacovigilance database, VigiBase, was queried to determine whether drug inhibition of an identified candidate kinase was associated with increased reporting of AF. Results: We demonstrate that treatment of mice with ibrutinib for 4 weeks results in inducible AF, left atrial enlargement, myocardial fibrosis, and inflammation. This effect was reproduced in mice lacking Bruton tyrosine kinase, but not in mice treated with 4 weeks of acalabrutinib, a more specific Bruton tyrosine kinase inhibitor, demonstrating that AF is an off-target side effect. Chemoproteomic profiling identified a short list of candidate kinases that was narrowed by additional experimentation leaving CSK (C-terminal Src kinase) as the strongest candidate for ibrutinib-induced AF. Cardiac-specific Csk knockout in mice led to increased AF, left atrial enlargement, fibrosis, and inflammation, phenocopying ibrutinib treatment. Disproportionality analyses in VigiBase confirmed increased reporting of AF associated with kinase inhibitors blocking Csk versus non-Csk inhibitors, with a reporting odds ratio of 8.0 (95% CI, 7.3–8.7; P &lt;0.0001). Conclusions: These data identify Csk inhibition as the mechanism through which ibrutinib leads to AF. Registration: URL: https://ww.clinicaltrials.gov ; Unique identifier: NCT03530215.
Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection
Authors: Chi-Jen Chu, Munira Hussain, Anna S. F. Lok
Journal: Hepatology (2002)

The goals of this retrospective study were to determine whether there is a threshold hepatitis B virus (HBV) DNA value associated with spontaneous or antiviral therapy—related hepatitis B e antigen (HBeAg) clearance. We also investigated whether there is an HBV DNA value that can be used for differentiating inactive carriers from patients with HBeAg-negative chronic hepatitis B. HBV DNA levels in sequential serum samples of 165 Chinese patients with different stages of chronic HBV infection were quantified by a polymerase chain reaction (PCR)—based assay. Our results showed that almost all of the patients (89%) who remained HBeAg-positive had HBV DNA levels that were persistently above 10 5 copies/mL. Serum HBV DNA levels decreased by a mean of 3 log 10 in patients with HBeAg loss, but 51% had levels above 10 5 copies/mL at the time HBeAg first became undetectable. Mean serum HBV DNA levels were significantly lower in HBeAg-negative patients. HBV DNA value above 10 5 copies/mL would exclude all inactive carriers, but 45% of patients with HBeAg-negative chronic hepatitis would also be excluded if testing were only performed at presentation and 30% would be excluded if testing were performed on 3 occasions. In conclusion, serum HBV DNA levels decreased significantly in patients with HBeAg loss, but there was no threshold HBV DNA level associated with HBeAg clearance. Given the fluctuating course of HBeAg-negative chronic hepatitis, it is not possible to define a single cutoff HBV DNA value for differentiating inactive carriers from patients with HBeAg-negative chronic hepatitis. (Hepatology2002;36:1408-1415).
Reversible pulmonary hypertension associated with multivisceral Whipple's disease
Authors: Alice Camboulive, Etienne-Marie Jutant, Laurent Savale, Xavier Jaïs, Olivier Sitbon, Charlotte Mussini, Jérémie Bénichou, Jean-Christophe Lagier, Marc Humbert, David Montani
Journal: European Respiratory Journal (2020)

<b>A report of multivisceral Whipple9s disease with severe precapillary pulmonary hypertension cured by doxycycline and hydroxychloroquine therapy associated with initial oral combination of bosentan and tadalafil.</b>https://bit.ly/2SECU3L
Where Is the Level of Atrioventricular Block?
Authors: Raghav Bansal, Chetan Rathi, Yash Lokhandwala
Journal: Circulation (2020)

ECG CHALLENGEA 66-year-old woman presented to the clinic with complaints of New York Heart Association Class II exertional dyspnea and easy fatiguability for 3 months.General physical and cardiac examination were normal.The baseline ECG and echocardiography were also unremarkable.A treadmill stress ECG test with the Bruce protocol revealed the development of 2:1 atrioventricular block in Stage III, with narrow QRS complexes (Figure 1).The patient further underwent electrophysiology study for evaluation of conduction system disease.The 12-lead ECG at baseline during the study is demonstrated in Figure 2. How do we reconcile these findings?What is the level of atrioventricular block?Please turn the page to read the diagnosis.
del(17p) without <i>TP53</i> mutation confers a poor prognosis in intensively treated newly diagnosed patients with multiple myeloma
Authors: Jill Corre, Aurore Perrot, Denis Caillot, Karim Belhadj, Cyrille Hulin, Xavier Leleu, Mohamad Mohty, Thierry Facon, Laure Buisson, Laura Do Souto, Romain Lannes, Stephanie Dufrechou, Naïs Prade, Frederique Orsini-Piocelle, Laurent Voillat, Arnaud Jaccard, Lionel Karlin, Margaret Macro, Sabine Brechignac, Mamoun Dib, Laurence Sanhes, Jean Fontan, Lauriane Clement-Filliatre, Jean-Pierre Marolleau, Stephane Minvielle, Philippe Moreau, Hervé Avet-Loiseau
Journal: Blood (2020)
TCT CONNECT-98 Impact of Flow on the Incidence and Prognosis of Prosthesis-Patient Mismatch Following Aortic Valve Replacement in the PARTNER 2 Study and Registry
Authors: Amr Abbas, Philippe Pibarot, Rebecca Hahn, Julien Ternacle, Jeroen Bax, Ke Xu, Maria Alu, Erin Rogers, Michael Mack, Martin Leon, Vinod Thourani
Journal: Journal of the American College of Cardiology (2020)
Abstract 21401: Mitofusin 2 Gene Therapy Increases PGC-1α Expression in Pulmonary Artery Smooth Muscle Cells but Does Not Alter Mitochondrial Oxygen Consumption
Authors: Glenn Marsboom, Peter T Toth, Hannah J Zhang, Jalees Rehman, Stephen L Archer
Journal: Circulation (2010)

Introduction: Vasoconstriction and proliferation of pulmonary artery smooth muscle cells (PASMCs) is important in the development of pulmonary arterial hypertension. Mitochondrial morphology is ver...
PCI-31523: An irreversible inhibitor of Bruton’s tyrosine kinase (Btk) that disrupts B cell receptor (BCR) signaling, is cytotoxic to B cell lymphomas, and is active in an animal arthritis model
Authors: Lee Honigberg, Ashley Smith, Jun Chen, Erik Verner, Richard Miller, Joseph Buggy
Journal: Cancer Research (2007)

5398  Many lymphomas require an intact BCR for survival and, therefore, should be uniquely sensitive to drugs that target the BCR pathway. The kinase Btk is activated by stimulation of the BCR and it in turn phosphorylates and activates Phospholipase C-gamma (PLCg) to transmit BCR signaling further downstream. We have designed PCI-31523, a selective and irreversible inhibitor that covalently binds to Cys-481 in the active site of Btk. In purified enzyme assays, PCI-31523 inhibits Btk with an IC50 of  200-fold selectivity over the structurally related kinase Lck. In normal human B cells, PCI-31523 inhibits anti-IgM induced signaling and proliferation at concentrations as low as 10nM. To confirm that PCI-31523 acts as a selective inhibitor in cells, we used phospho-specific antibodies that detect known phosphorylation events downstream of BCR stimulation. We found that PCI-31523 does not significantly inhibit the Src-family proximal kinases that trans-phosphorylate Btk at Tyr-551. In contrast, at 10nM, PCI-31523 completely blocks the Btk-dependent phosphorylation of PLCg. In addition, PCI-31523 leads to a significant decrease in Ca++ flux and phosphorylation of Erk. Lastly, PCI-31523 has no effect on PMA/Ionomycin induced phosphorylation of Erk. Thus, as predicted for a selective Btk inhibitor, PCI-31523 acts downstream of the Src-family kinases and upstream of PLCg.  We tested the effects of PCI-31523 on a variety of BCR expressing lymphoma cell lines. The diffuse large B cell lymphoma lines DHL-4 and DHL-6 as well as the follicular lymphoma line DoHH2 are sensitive to PCI-31523, with growth arrest and apoptosis occurring at concentrations as low as 0.5uM. In contrast, the lymphoma cell lines Ramos, Raji, and DB are resistant to PCI-31523 cytotoxicity. To investigate this differential sensitivity, we used phospho-flow cytometry to quantitate basal and anti-IgM-induced phosphorylation of Erk. PCI-31523 is more potent at reducing phospho-Erk in a sensitive cell line (DHL-6) than in a resistant cell line (Ramos). Thus the amount of inhibition of phospho-Erk appears to be correlated with the degree of cytotoxicity and this biomarker may function as a predictor of clinical responsiveness.  PCI-31523 has been tested in vivo in a mouse collagen antibody arthritis model. Oral dosing of PCI-31523 (10mg/kg qd) results in almost complete inhibition of inflammation, indicating that this compound may be effective in both autoimmune disease and lymphoma.
TCT CONNECT-492 Tricuspid Anatomic Regurgitant Orifice Area Assessment by Functional DSCT: Reproducibility and Comparison With 3D TEE
Authors: Bernardo Lopes, Go Hashimoto, Miho Fukui, Yu Du, Robert Schwartz, Richard Bae, Larissa Stanberry, Maurice Sarano, John Lesser, Paul Sorajja, Joao Cavalcante-Dupe
Journal: Journal of the American College of Cardiology (2020)
Part 4: Pediatric Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Authors: Alexis A. Topjian, Tia T. Raymond, Dianne Atkins, Melissa Chan, Jonathan P. Duff, Benny L. Joyner, Javier J. Lasa, Eric J. Lavonas, Arielle Levy, Melissa Mahgoub, Garth D. Meckler, Kathryn E. Roberts, Robert M. Sutton, Stephen M. Schexnayder, Ronald A. Bronicki, Allan R. de Caen, Anne Marie Guerguerian, Kelly D. Kadlec, Monica E. Kleinman, Lynda J. Knight, Taylor N. McCormick, Ryan W. Morgan, Joan S. Roberts, Barnaby R. Scholefield, Sarah Tabbutt, Ravi Thiagarajan, Janice Tijssen, Brian Walsh, Arno Zaritsky
Journal: Circulation (2020)
The Anatomy and Physiology of Teaming in Cancer Care Delivery: A Conceptual Framework
Authors: Dana C Verhoeven, Veronica Chollette, Elizabeth H Lazzara, Marissa L Shuffler, Raymond U Osarogiagbon, Sallie J Weaver
Journal: JNCI Journal of the National Cancer Institute (2020)

Care coordination challenges for patients with cancer continue to grow as expanding treatment options, multimodality treatment regimens, and an aging population with comorbid conditions intensify demands for multidisciplinary cancer care. Effective teamwork is a critical yet understudied cornerstone of coordinated cancer care delivery. For example, comprehensive lung cancer care involves a clinical "team of teams"-or clinical multiteam system (MTS)-coordinating decisions and care across specialties, providers, and settings. The teamwork processes within and between these teams lay the foundation for coordinated care. Although the need to work as a team and coordinate across disciplinary, organizational, and geographic boundaries increases, evidence identifying and improving the teamwork processes underlying care coordination and delivery among the multiple teams involved remains sparse. This commentary synthesizes MTS structure characteristics and teamwork processes into a conceptual framework called the cancer MTS framework to advance future cancer care delivery research addressing evidence gaps in care coordination. Included constructs were identified from published frameworks, discussions at the 2016 National Cancer Institute-American Society of Clinical Oncology Teams in Cancer Care Workshop, and expert input. A case example in lung cancer provided practical grounding for framework refinement. The cancer MTS framework identifies team structure variables and teamwork processes affecting cancer care delivery, related outcomes, and contextual variables hypothesized to influence coordination within and between the multiple clinical teams involved. We discuss how the framework might be used to identify care delivery research gaps, develop hypothesis-driven research examining clinical team functioning, and support conceptual coherence across studies examining teamwork and care coordination and their impact on cancer outcomes.
TCT CONNECT-123 Cardiac Amyloidosis Is Underdiagnosed in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Michael Megaly, Paul Sorajja, Santiago Garcia, John Lesser, Mario Goessl, Thomas Treibel, Mathew Maurer, Joao Cavalcante - DUPE
Journal: Journal of the American College of Cardiology (2020)
Systemic Therapy and Sequencing Options in Advanced Hepatocellular Carcinoma
Authors: Mohamad Bassam Sonbol, Irbaz Bin Riaz, Syed Arsalan Ahmed Naqvi, Daniel R. Almquist, Syeda Mina, Jehad Almasri, Shiv Shah, Diana Almader-Douglas, Pedro Luiz Serrano Uson Junior, Amit Mahipal, Wen Wee, Zhaohui Jin, Kabir Mody, Jason Starr, Mitesh J. Borad, Daniel H. Ahn, M. Hassan Murad, Tanios Bekaii-Saab
Journal: JAMA Oncology (2020)

The treatment landscape for advanced hepatocellular carcinoma (HCC) has recently changed and become relatively confusing. Head-to-head comparisons between most of the available agents have not been performed and are less likely to be examined in a prospective fashion in the future. Therefore, a network meta-analysis (NMA) is helpful to compare different agents from across different trials.To evaluate comparative effectiveness of different systemic treatments in advanced patients with HCC across lines of therapy.We searched various databases for abstracts and full-text articles published from database inception through March 2020.We included phase 3 trials evaluating different vascular endothelial growth factor inhibitors (VEGFis), checkpoint inhibitors (CPIs), or their combinations in advanced HCC, in the first-line or refractory setting.The reporting of this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The overall effect was pooled using the random effects model.Outcomes of interest included overall (OS) and progression-free survival (PFS).Fourteen trials (8 in the first-line setting and 6 in the second-line setting) at low risk of bias were included. The 8 trials in the first-line setting encompassed a total of 6290 patients, with an age range of 18 to 89 years. The 5 trials included in the second-line analysis encompassed a total of 2653 patients, with an age range of 18 to 91 years. Network meta-analysis showed the combination of atezolizumab and bevacizumab was superior in patients with HCC treated in the first-line setting compared with lenvatinib (HR, 0.63; 95% CI, 0.44-0.89), sorafenib (HR, 0.58; 95% CI, 0.42-0.80), and nivolumab (HR, 0.68; 95% CI, 0.48-0.98). In the refractory setting, NMA showed that all studied drugs had PFS benefit compared with placebo. However, this only translated into OS benefit with regorafenib (HR, 0.62; 95% CI, 0.51-0.75) and cabozantinib (HR, 0.76; 95% CI, 0.63-0.92) compared with placebo. In the NMA of patients with α-fetoprotein (AFP) levels of 400 ng/mL or greater, regorafenib, cabozantinib, and ramucirumab showed PFS and OS benefit compared with placebo with no superiority of an active drug compared with any others.This systematic review and NMA of 14 trials found that atezolizumab and bevacizumab in combination is now considered the standard of care in the first-line setting in patients with advanced HCC. Regorafenib and cabozantinib are preferred options in refractory patients, with ramucirumab as an additional option in those with levels of AFP of 400 ng/mL or higher. Future trials should focus on other potential combinations and best treatment strategy in patients with prior VEGFi/CPI exposure.
TCT CONNECT-322 Discordance Between Coronary Flow Reserve and the Index of Microcirculatory Resistance Post Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction
Authors: Klio Konstantinou, Thomas Keeble, John Davies, Reto Gamma, Kare Tang, Osama Alsanjari, Rohan Jagathesan, Jeremy Sayer, Paul Kelly, Gerald Clesham, Grigoris Karamasis
Journal: Journal of the American College of Cardiology (2020)
Everything I Could Buy on eBay about Malaria
Authors: Claire McKenna
Journal: BMJ (2002)

Rating:![Graphic][1] ![Graphic][2] ![Graphic][3] 

Short of cash? Then why not sell your soul? The going rate for souls, almost new, in good condition, is £11.61 on eBay, the world's largest online auction house. So diverse are the items on sale that NASA has recently admitted to searching eBay for replacement computer parts for the space shuttle programme. Now Canadian artist Bill Burns has joined the devotees of the auction house and has amassed an eclectic and eccentric cornucopia of items relating to malaria for this Wellcome Trust exhibition.

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Henry Wellcome's model floating Nile laboratory

The items on display amount to a veritable pocket history of malaria and malaria prevention and treatment programmes in the 20th century. One can see model crop dusters designed to spray DDT (dichlorodiphenyltrichloromethane), stamps from around the world featuring malaria themes, maps circa 1960 of …

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TCT CONNECT-309 Three-Year Follow-up of PCI in Patients With True Left Main Bifurcation Lesions
Authors: Zaurbek Shugushev, Olga Safonova, Alexandr Chepurnoi, Ekaterina Gitelzon, Vladislav Baranovich, Galina Veretnik, Daniil Maximkin
Journal: Journal of the American College of Cardiology (2020)
Selection of Oncogenic Mutant Clones in Normal Human Skin Varies with Body Site
Authors: Joanna C. Fowler, Charlotte King, Christopher Bryant, Michael W.J. Hall, Roshan Sood, Swee Hoe Ong, Eleanor Earp, David Fernandez-Antoran, Jonas Koeppel, Stefan C. Dentro, David Shorthouse, Amer Durrani, Kate Fife, Edward Rytina, Doreen Milne, Amit Roshan, Krishnaa Mahububani, Kourosh Saeb-Parsy, Benjamin A. Hall, Moritz Gerstung, Philip H. Jones
Journal: Cancer Discovery (2020)

Abstract Skin cancer risk varies substantially across the body, yet how this relates to the mutations found in normal skin is unknown. Here we mapped mutant clones in skin from high- and low-risk sites. The density of mutations varied by location. The prevalence of NOTCH1 and FAT1 mutations in forearm, trunk, and leg skin was similar to that in keratinocyte cancers. Most mutations were caused by ultraviolet light, but mutational signature analysis suggested differences in DNA-repair processes between sites. Eleven mutant genes were under positive selection, with TP53 preferentially selected in the head and FAT1 in the leg. Fine-scale mapping revealed 10% of clones had copy-number alterations. Analysis of hair follicles showed mutations in the upper follicle resembled adjacent skin, but the lower follicle was sparsely mutated. Normal skin is a dense patchwork of mutant clones arising from competitive selection that varies by location. Significance: Mapping mutant clones across the body reveals normal skin is a dense patchwork of mutant cells. The variation in cancer risk between sites substantially exceeds that in mutant clone density. More generally, mutant genes cannot be assigned as cancer drivers until their prevalence in normal tissue is known. See related commentary by De Dominici and DeGregori, p. 227. This article is highlighted in the In This Issue feature, p. 211
Neuromuscular blockade in patients with ARDS: a rapid practice guideline
Authors: Waleed Alhazzani, E. Belley-Cote, M. H. Møller, D. C. Angus, L. Papazian, Y. M. Arabi, G. Citerio, B. Connolly, L. Denehy, A. Fox-Robichaud, C. L. Hough, J. H. Laake, F. R. Machado, M. Ostermann, T. Piraino, S. Sharif, W. Szczeklik, P. J. Young, A. Gouskos, K. Kiedrowski, K. E. A. Burns
Journal: Intensive Care Medicine (2020)
TCT CONNECT-366 Role of Embolic Protection Devices in Reducing Major Adverse Limb Events in Femoropopliteal Arterial Interventions in a Matched Cohort of Patients With Critical Limb Ischemia: Results From the XLPAD Registry
Authors: Ehrin Armstrong, Emmanouil Brilakis, Subhash Banerjee, Nicolas Shammas, Qais Radaideh
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-213 Clinical Characteristics and Outcomes of Patients With COVID-19 and STEMI Treated With Fibrinolytic Therapy
Authors: Anas Hamadeh, Ali Aldujeli, Kasparas Briedis, Kristen Tecson, Jorge Sanz Sanchez, Montazar Al Dujeili, Ammar Al-Obeidi, Jose L. Diez-Gil, Remigijus Zaliunas, Robert Stoler, Peter McCullough
Journal: Journal of the American College of Cardiology (2020)