tbuckley/cabot-search huggingface dataset:
Abstract 18887: The Clinical Implication of New In-hospital Onset Atrial Fibrillation in Patients With Acute Decompensated Heart Failure
Authors: Masashi Kamioka, Akiomi Yoshihisa, Yu Sato, Shunsuke Watanabe, Yoshiyuki Matsumoto, Yuki Kannno, Makiko Tatsumi, Satoshi Abe, Minoru Nodera, Takamasa Sato, Satoshi Suzuki, Takashi Kaneshiro, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2017)

Background: In-hospital atrial fibrillation (AF) often occurs at the acute worsening phase of heart failure (HF). In-hospital AF terminates spontaneously following the recovery of HF in some cases,...
A randomized clinical trial of TrialTALK, a communication tool to facilitate treatment-related shared decision making.
Authors: Toby Christopher Campbell, Mallory Jasicki, Kristine L Kwekkeboom, Margaret L Schwarze, Amy Zelenski, Kimberly Mast
Journal: Journal of Clinical Oncology (2018)

45 Background: Cancer treatment decision making involves timely, high-risk, life altering shared decision-making conversations between patients, their families, and their oncologists. As such, these conversations are a prime target for a carefully designed, easy to interpret approach to facilitate preference-sensitive decision making. Patients need several important pieces of information delivered in a way that is easy to interpret. The TrialTALK approach has two core elements: a verbal approach and a pen and paper (P&amp;P) diagram. The P&amp;P diagram includes the diagnosis with prognostic implications, all available treatment options including best supportive care alone, estimates for efficacy, and anticipated impact on daily life. The verbal conversation corresponds to the diagram and includes a phrase to encourage deliberation, and empathic responses. Our trial is evaluating the effectiveness of TrialTALK to influence decision making, in particular clinical trial participation. Here, we report the results of the initial oncologist training. Methods: 28 oncologists volunteered to participate and were randomly assigned to control (Group A, n=13) or intervention (Group B, n=15). Oncologists in the intervention group each received two hours of training, including simulated conversations with feedback and optional 1:1 follow up for troubleshooting. At the conclusion of training, oncologists completed a video-recorded simulated encounter with an actor. Trainers reviewed P&amp;P diagrams in real time and provided feedback. Results: We used a fidelity checklist to assess effectiveness of the training. We considered ≥ 14 points out of a possible 20 as an acceptable use of TrialTALK. The average score was 14.8 ± 2. Scores ranged 10-18. 12 of 15 intervention oncologists demonstrated adoption of the tool after 2 hours of training. Conclusions: Oncologist can effectively learn to use TrialTALK. The ongoing study will estimate preliminary efficacy of the TrialTALK intervention in regards to patient decision making and participation in clinical trials.
Intraperitoneal management of ovarian cancer using a novel Fas agonist
Authors: Marc Dupuis, Isabelle Bassi, Anne-Lise Etter, Stephane Germain, Jean-Francois Delaloye, Bernard Sordat
Journal: Cancer Research (2007)

1599  MegaFas Ligand (MFL) is a recombinant protein obtained by fusion of the collagen-like domain of human adiponectin (ACRP30) to the extracellular portion of FasL. MFL forms an hexameric structure that efficiently triggers apoptosis after binding to the Fas receptor expressed on target cells. The purpose of this study was to determine the MFL potency in vitro and efficacy in vivo for intraperitoneal management of mice implanted with human ovarian carcinoma cells.  The potency of MFL was compared to that of other Fas agonists including a monoclonal antibody and soluble cross-linked FasL in a cytotoxicity assay on SKOV-3 cells. The potency of MFL was further determined by measuring apoptosis in combination with platinum salts and taxanes. The efficacy of MFL was determined in vivo using peritoneal xenograft models of human ovarian carcinoma.  >In vitro, MFL induced significantly more apoptosis compared to other Fas agonists, and was able to overcome the resistance of the ovarian cancer cell line SKOV-3 to Fas agonist antibody. MFL exerted a cumulative cytotoxic effect when combined with platinum-based drugs or taxanes, leading to significantly more apoptosis than by incubation with MFL or drug alone. Treatment of mice xenografted with SKOV-3 and HOC79 ovarian tumors by intraperitoneal administration of MFL alone or in combination with cisplatin resulted in a significant decrease in peritoneal tumor nodules and ascitic cells, and prolongation of survival as compared to non-treated mice. The beneficial effects of MFL treatment occurred in the absence of severe toxicity.  >In conclusion, MFL is a novel pro-apoptotic molecule that is able to efficiently induce apoptosis in ovarian cancer cells as well as to potentiate the activity of chemotherapeutic agents in vitro and in vivo.
Quality of Life in NSCLC Survivors — A Multicenter Cross-Sectional Study
Authors: Marlene Hechtner, Martin Eichler, Beatrice Wehler, Roland Buhl, Martin Sebastian, Jan Stratmann, Heinz Schmidberger, Bernhard Gohrbandt, Jessica Peuser, Cornelius Kortsik, Ursula Nestle, Sebastian Wiesemann, Hubert Wirtz, Thomas Wehler, Robert Bals, Maria Blettner, Susanne Singer
Journal: Journal of Thoracic Oncology (2018)
AS1411 inhibits the stabilization of bcl-2 mRNA by nucleolin in human breast cancer cells
Authors: Sridharan Soundararajan, Eleanor Spicer, Nigel Courtenay-Luck, Daniel Fernandes
Journal: Cancer Research (2007)

4888  Overexpression of the bcl-2 proto-oncogene in breast cancer cells allows the cells to avoid apoptosis and become resistant to chemotherapeutic drugs. However, the mechanism of bcl-2 upregulation in breast cancer cells has not been elucidated. Studies were carried out to determine whether the mRNA-binding protein nucleolin plays a role in the regulation of bcl-2 mRNA stability in MCF-7 breast carcinoma cells. We have found that cytoplasmic nucleolin is 3.3-fold elevated in MCF-7 cells compared to MCF10A normal mammary epithelial cells. Stable knockdown of nucleolin with a siRNA in MCF-7 cells reduced both nucleolin and bcl-2 protein levels: a 73% decrease was observed for nucleolin protein and an 85% decrease was found for bcl-2 protein relative to cells expressing a scrambled siRNA plasmid. Knockdown of nucleolin with siRNA also decreased the bcl-2 mRNA steady-state levels by 87% and the half-life of bcl-2 mRNA from 10 hr to 5 hr. Further studies were done to evaluate the effect of the nucleolin-targeting aptamer, AS1411, on MCF-7 cells and MCF-10A normal breast epithelial cells. AS1411 at a concentration of 10 µM had no effect on the viability of normal MCF10A cells following exposure times as long as 96 hr. This is consistent with the lower levels of cytoplasmic nucleolin in these cells. In contrast, 10 µM of AS1411 completely inhibited the proliferation of MCF-7 cells. The half-life of bcl-2 mRNA was reduced from 10 hr in untreated MCF-7 cells to 1.5 hr in MCF-7 cells incubated with 10 µM nucleolin for 72 hr. However, 10 µM AS1411 had no effect on the stability of bcl-2 mRNA in MCF-10A cells or β-actin mRNA in either MCF-7 or MCF-10A cells. Taken together, the data show that nucleolin promotes bcl-2 overexpression in MCF-7 cells by increasing bcl-2 mRNA stability and that AS1411 interferes with the stabilization of bcl-2 mRNA by nucleolin. These findings suggest that nucleolin may be a useful target for breast cancer therapy and that AS1411, which has shown promising initial activity in the clinic in renal cancer, could have potential in this context.
Surgical adhesions in mice are derived from mesothelial cells and can be targeted by antibodies against mesothelial markers
Authors: Jonathan M. Tsai, Rahul Sinha, Jun Seita, Nathaniel Fernhoff, Simon Christ, Tim Koopmans, Geoffrey W. Krampitz, Kelly M. McKenna, Liujing Xing, Michael Sandholzer, Jennifer Horatia Sales, Maia Shoham, Melissa McCracken, Lydia-Marie Joubert, Sydney R. Gordon, Nicolas Poux, Gerlinde Wernig, Jeffrey A. Norton, Irving L. Weissman, Yuval Rinkevich
Journal: Science Translational Medicine (2018)

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and are a major cause of postsurgical and infectious morbidity. The primary molecular chain of events leading to the initiation of adhesions has been elusive, chiefly due to the lack of an identifiable cell of origin. Using clonal analysis and lineage tracing, we have identified injured surface mesothelium expressing podoplanin (PDPN) and mesothelin (MSLN) as a primary instigator of peritoneal adhesions after surgery in mice. We demonstrate that an anti-MSLN antibody diminished adhesion formation in a mouse model where adhesions were induced by surgical ligation to form ischemic buttons and subsequent surgical abrasion of the peritoneum. RNA sequencing and bioinformatics analyses of mouse mesothelial cells from injured mesothelium revealed aspects of the pathological mechanism of adhesion development and yielded several potential regulators of this process. Specifically, we show that PDPN+MSLN+ mesothelium responded to hypoxia by early up-regulation of hypoxia-inducible factor 1 alpha (HIF1α) that preceded adhesion development. Inhibition of HIF1α with small molecules ameliorated the injury program in damaged mesothelium and was sufficient to diminish adhesion severity in a mouse model. Analyses of human adhesion tissue suggested that similar surface markers and signaling pathways may contribute to surgical adhesions in human patients.
Predicting outcomes in rheumatoid arthritis related interstitial lung disease
Authors: Joseph Jacob, Nikhil Hirani, Coline H.M. van Moorsel, Srinivasan Rajagopalan, John T. Murchison, Hendrik W. van Es, Brian J. Bartholmai, Frouke T. van Beek, Marjolijn H.L. Struik, Gareth A. Stewart, Maria Kokosi, Ryoko Egashira, Anne Laure Brun, Gary Cross, Joseph Barnett, Anand Devaraj, George Margaritopoulos, Ronald Karwoski, Elisabetta Renzoni, Toby M. Maher, Athol U. Wells
Journal: European Respiratory Journal (2018)

The aim of this study was to compare radiology-based prediction models in rheumatoid arthritis-related interstitial lung disease (RAILD) to identify patients with a progressive fibrosis phenotype.RAILD patients had computed tomography (CT) scans scored visually and using CALIPER and forced vital capacity (FVC) measurements. Outcomes were evaluated using three techniques, as follows. 1) Scleroderma system evaluating visual interstitial lung disease extent and FVC values; 2) Fleischner Society idiopathic pulmonary fibrosis (IPF) diagnostic guidelines applied to RAILD; and 3) CALIPER scores of vessel-related structures (VRS). Outcomes were compared to IPF patients.On univariable Cox analysis, all three staging systems strongly predicted outcome (scleroderma system hazard ratio (HR) 3.78, p=9×10-5; Fleischner system HR 1.98, p=2×10-3; and 4.4% VRS threshold HR 3.10, p=4×10-4). When the scleroderma and Fleischner systems were combined, termed the progressive fibrotic system (C-statistic 0.71), they identified a patient subset (n=36) with a progressive fibrotic phenotype and similar 4-year survival to IPF. On multivariable analysis, with adjustment for patient age, sex and smoking status, when analysed alongside the progressive fibrotic system, the VRS threshold of 4.4% independently predicted outcome (model C-statistic 0.77).The combination of two visual CT-based staging systems identified 23% of an RAILD cohort with an IPF-like progressive fibrotic phenotype. The addition of a computer-derived VRS threshold further improved outcome prediction and model fit, beyond that encompassed by RAILD measures of disease severity and extent.
Diagnostic heuristics: metacognition and other fixes
Authors: E.J. Lowenstein, R. Sidlow
Journal: British Journal of Dermatology (2018)

The shortcuts in thinking that humans use to solve problems (‘heuristics’, covered in an earlier review) are not always perfect, and in medicine this can lead to errors in diagnosis. So, how to recognize what is happening and try to combat it? In this review (part 2 of 2) the authors from the USA suggest ways of getting doctors ‘to think about the way they think’ (an approach known as metacognition) during the process of diagnosis. A number of strategies are considered: for instance, learning to pay more attention to – and acting more readily on – gut feelings of uncertainty, and being more aware of when to take time out to look at possibly uncertain diagnoses from different angles (‘What else could it be?’ ‘Why does this not fit?’ ‘Let's discuss it with a colleague.’). Even being more consciously aware of when the work environment is too demanding or distracting (the phone never stops ringing, emails are constantly coming in, fatigue is kicking in, etc.) is an important skill. Reflecting on personal errors in diagnosis is another simple, practical example, as is asking for feedback from patients about what worked and what didn't. High risk professions have used checklists for a long time: does medicine need to catch up? Finally, the authors comment that experience can be a two‐edged sword: although experienced doctors generally use heuristics more effectively in diagnosis than inexperienced ones (see part 1), this can be undermined if they also ‘become less likely to seek outside opinions or use reference materials’.
Trends in First Gabapentin and Pregabalin Prescriptions in Primary Care in the United Kingdom, 1993-2017
Authors: François Montastruc, Simone Y. Loo, Christel Renoux
Journal: JAMA (2018)

This study examined the rates of patients in the United Kingdom treated with gabapentin and pregabalin for the first time, and the rates of these patients with an off-label indication or a coprescription of opioids or benzodiazepines.
Delivery of miR-146a to Ly6C<sup>high</sup> Monocytes Inhibits Pathogenic Bone Erosion in Inflammatory Arthritis
Authors: Meryem Ammari, Jessy Presumey, Clara Ponsolles, Gautier Roussignol, Christine Roubert, Virginie Escriou, Karine Toupet, Anne-Laure Mausset-Bonnefont, Maïlys Cren, Maxime Robin, Philippe Georgel, Ramzi Nehmar, Leonie Taams, Joachim Grün, Andrea Grützkau, Thomas Häupl, Yves-Marie Pers, Christian Jorgensen, Isabelle Duroux-Richard, Gabriel Courties, Florence Apparailly
Journal: Theranostics (2018)

teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Improving the Affordability of Prescription Medications for People with Chronic Respiratory Disease. An Official American Thoracic Society Policy Statement
Authors: Minal R. Patel, Valerie G. Press, Lynn B. Gerald, Teresa Barnes, Kathryn Blake, Lee K. Brown, Richard W. Costello, Courtney Crim, Mark Forshag, Andrea S. Gershon, Christopher H. Goss, MeiLan K. Han, Todd A. Lee, Stuart Sweet, Joe K. Gerald
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Mounting evidence indicates that out-of-pocket costs for prescription medications, particularly among low- and middle-income patients with chronic diseases, are imposing financial burden, reducing medication adherence, and worsening health outcomes. This problem is exacerbated by a paucity of generic alternatives for prevalent lung diseases, such as asthma and chronic obstructive pulmonary disease, as well as high-cost medicines for rare diseases, such as cystic fibrosis. Affordability and access challenges are especially salient in the United States, as citizens of many other countries pay lower prices for and have greater access to prescription medications.The American Thoracic Society convened a multidisciplinary committee comprising experts in health policy pharmacoeconomics, behavioral sciences, and clinical care, along with individuals providing industry and patient perspectives. The report and its recommendation were iteratively developed over a year of in-person, telephonic, and electronic deliberation.The committee unanimously recommended the establishment of a publicly funded, politically independent, impartial entity to systematically draft evidence-based pharmaceutical policy recommendations. The goal of this entity would be to generate evidence and action steps to ensure people have equitable and affordable access to prescription medications, to maximize the value of public and private pharmaceutical expenditures on health, to support novel drug development within a market-based economy, and to preserve clinician and patient choice regarding personalized treatment. An immediate priority is to examine the evidence and make recommendations regarding the need to have essential medicines with established clinical benefit from each drug class in all Tier 1 formularies and propose recommendations to reduce barriers to timely generic drug availability.By making explicit, evidence-based recommendations, the entity can support the establishment of coherent national policies that expand access to affordable medications, improve the health of patients with chronic disease, and optimize the use of public and private resources.
Abstract 213: Retrieval of Plaque Debris by Aspiration Thrombectomy is the Sign of High Risk for Distal Embolization in Acute Coronary Syndrome Patients
Authors: Koshi Matsuo, Yasunori Ueda
Journal: Circulation (2013)

Background: Slow flow or no re-flow phenomenon during coronary intervention is mainly caused by distal embolization of thrombus and plaque debris, and is associated with unfavorable long-term clinical outcomes. However, its high-risk patients are not well understood. Aspiration thrombectomy in the patients with acute coronary syndrome (ACS) often retrieves thrombus but sometimes plaque debris. Therefore, we examined if the ACS patients in whom plaque debris was retrieved by aspiration thrombectomy were high-risk of distal embolization. Methods: Consecutive patients with ACS (n=151) who received aspiration thrombectomy and coronary intervention with filter-type distal protection device (Filtrap) were prospectively enrolled. We classified them into two groups according to whether (Group A, n=29) or not (Group B, n=122) the plaque debris was retrieved by aspiration thrombectomy. We compared between the groups the frequency of filter slow flow/ no-reflow phenomenon and the frequency of distal embolization captured by filter device. Results: Distal embolization of plaque debris was detected more frequently in Group A than in Group B (90% vs. 30%, P&lt;0.0001). Filter slow flow/ no-reflow phenomenon occurred more frequently in Group A than in Group B (93% vs. 29%, P&lt;0.0001). Conclusion: Retrieval of plaque debris by aspiration thrombectomy is the sign of high risk for distal embolization in ACS patients. Distal protection may potentially be useful for those high-risk patients.
Autologous Dendritic Cell-Cytokine Induced Killer Cell Immunotherapy Combined with S-1 Plus Cisplatin in Patients with Advanced Gastric Cancer: A Prospective Study
Authors: Guoliang Qiao, Xiaoli Wang, Lei Zhou, Xinna Zhou, Yuguang Song, Shuo Wang, Lei Zhao, Michael A. Morse, Amy Hobeika, Jin Song, Xin Yi, Xuefeng Xia, Jun Ren, Herbert Kim Lyerly
Journal: Clinical Cancer Research (2018)

We have assessed the combination of DC-CIK with S-1 plus cisplatin chemotherapy in advanced gastric cancer (AGC) and the role of mutational analysis of circulating tumor DNA (ctDNA) and T-cell receptor (TCR) repertoire in predicting clinical outcomes.Consecutive patients (n = 63) with AGC were allocated to treatment with S-1 alone, S-1 plus cisplatin, DC-CIK combined with S-1 or DC-CIK combined with S-1 plus cisplatin. The primary endpoints were progression-free survival (PFS) and overall survival (OS) at 1 year; the secondary endpoints were disease control rate and analysis of ctDNA and TCR repertoire.The DC-CIK infusions were well tolerated with no serious adverse events. The disease control rates (CR+PR+SD) were 5.6%, 33.3%, 47.1%, and 76.9% in the S-1 alone, the S-1 plus cisplatin, DC-CIK combined with S-1 and DC-CIK combined with the S-1 plus cisplatin groups, respectively (P = 0.001). After adjusting for competing risk factors, treatment with DC-CIK combined with S-1 plus cisplatin was confirmed to be an independent predictor of PFS and OS (P = 0.001). A decrease in the frequency and number of mutations in ctDNA was observed in 19 patients (63.3%) following the DC-CIK infusions. Decreased ctDNA mutational frequency and restored TCR repertoire were associated with improved PFS and OS (P = 0.001).DC-CIK combined with S-1 plus cisplatin provided a favorable PFS and OS in patients with AGC and the combination therapy was safe with tolerable toxicities. Clinical efficacy correlated with decreases in ctDNA mutational profiles and restored TCR repertoire.
AB1407-HPR Adverse drug reactions in patients with rheumatoid arthritis
Authors: J. Urrego, K Mendez, P. Santos-Moreno
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> adverse drug reactions (ADRs) are events that may seriously affect the health of people who use drugs for therapeutic purposes.<sup>1</sup> In the case of patients with rheumatic diseases the existence of comorbidities, the use of DMARDs, or polymedication may increase the risk of developing any type of adverse drug reaction.<sup>2</sup> <h3>Objectives</h3> We aim to describe the adverse drug reactions in patients with rheumatoid arthritis. <h3>Methods</h3> A cross sectional study was performed during 2017; we collected data from the patients who reported an adverse drug reaction in the consult with a multidisciplinary health care team. We collected the ADR characteristics, medication group and severity. Descriptive epidemiology was done. <h3>Results</h3> A total of 6793 patients were diagnosed with rheumatoid arthritis and comorbidities in our specialised centre where 1.8% (123) patients reported any adverse drug reaction, 82% were women. The main diagnosis was rheumatoid arthritis 88% followed by rheumatoid arthritis plus osteoarthritis 12%; less than 1% was other diagnoses. The drug that had a higher proportion of ADRs was methotrexate 33% followed by leflunomide 14%, Certolizumab 7% and acetaminophen combined with hydrocodone 6%; see table 1. The dermatological adverse events were the most common followed by gastrointestinal events and errors in self-medication 11%, these adverse events were classified as mild or moderate; see <h3>Conclusions</h3> The proportion of adverse events in our centre is low; other studies had shown, the frequency of patients with ADRs is common, mainly in patients who use anti rheumatic medications. This real life data can support the evidence for future studies in order to prevent ADRs. <h3>References</h3> [1] Machado-Alba JE, Ruiz AF, Machado-Duque ME. Adverse drug reactions associated with the use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis. Rev Panam Salud Publica. 2014;36(6):396–401. [2] Tragulpiankit P, Chulavatnatol S, Rerkpattanapipat T, Janwityanujit S, Somjarit S, Sirikhedgon U. Adverse drug events in rheumatoid arthritis and osteoarthritis ambulatory patients. International journal of rheumatic diseases. 2012;15(3):315–21. <h3>Disclosure of Interest</h3> None declared