tbuckley/cabot-search huggingface dataset:
A phase II study of the histone deacetylase inhibitor panobinostat (LBH589) in low-grade neuroendocrine tumors.
Authors: Saurabh Rajguru, Sam Joseph Lubner, Daniel Mulkerin, William R. Schelman, Natalie Winterle, Kyle D. Holen, Glen Leverson, Herbert Chen, Noelle K. LoConte
Journal: Journal of Clinical Oncology (2012)

e14554 Background: Neuroendocrine tumors (NETs) are a diverse and rare group of neoplasms arising from the neuroendocrine system. The most common subtypes are pancreatic islet cell tumors and carcinoid tumors. Although they represent only 2% of all gastrointestinal malignancies, given their overall favorable prognosis, the prevalence is much higher. Histone deacetylase (HDAC) inhibitors have already been shown to suppress tumor growth and induce apoptosis in a variety of solid tumors in preclinical data. We have previously shown that in NET cells, HDAC inhibitors have resulted in increased Notch1 expression and subsequent inhibition of growth. Methods: A single arm phase II study was performed. Adult patients with histologically confirmed, metastatic, low-grade NETs and an ECOG performance status of ≤ 2 were treated with the oral HDAC inhibitor panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. Results: 15 patients were accrued and 13 were evaluable for response (66.7% male, age range 40-80 years old (mean 59.4 years old), 66.7% carcinoid, 33.3% pancreatic NET). The median number of prior therapies was 1 (range 0-2) and no patient had previously received everolimus. The response rate was 0%. The stable disease rate was 92.3% as defined by stability seen on the first CT scan. Median progression-free survival was 11.8 months. The 1 year PFS was 42%. Thrombocytopenia and fatigue were the most common treatment-related grade 3 toxicities. There was one grade 4 toxicity of thrombocytopenia. The study was stopped early at the planned interim analysis based on lack of meaningful clinical efficacy outlined in the Simon two-stage design. Conclusions: The HDAC inhibitor panobinostat had infrequent grade 3 and 4 events in this patient population and resulted in a large percentage of subjects with disease control. The disease control rate, however, needs to be considered in the context of the typical slow growth rate of NETs. These data alone do not support continued evaluation of HDAC inhibitors in low-grade NETs. This study was supported by Novartis.
Aversive state processing in the posterior insular cortex
Authors: Daniel A. Gehrlach, Nate Dolensek, Alexandra S. Klein, Ritu Roy Chowdhury, Arthur Matthys, Michaela Junghänel, Thomas N. Gaitanos, Alja Podgornik, Thomas D. Black, Narasimha Reddy Vaka, Karl-Klaus Conzelmann, Nadine Gogolla
Journal: Nature Neuroscience (2019)
Biologically Effective Dose in Stereotactic Body Radiotherapy and Survival for Patients With Early-Stage NSCLC
Authors: Amy C. Moreno, Bryan Fellman, Brian P. Hobbs, Zhongxing Liao, Daniel R. Gomez, Aileen Chen, Stephen M. Hahn, Joe Y. Chang, Steven H. Lin
Journal: Journal of Thoracic Oncology (2019)
Selective deployment of transcription factor paralogs with submaximal strength facilitates gene regulation in the immune system
Authors: Ludovica Bruno, Vijendra Ramlall, Romain A. Studer, Stephan Sauer, David Bradley, Gopuraja Dharmalingam, Thomas Carroll, Mohamed Ghoneim, Michaël Chopin, Stephen L. Nutt, Sarah Elderkin, David S. Rueda, Amanda G. Fisher, Trevor Siggers, Pedro Beltrao, Matthias Merkenschlager
Journal: Nature Immunology (2019)
P156/O08 Systemic inflammation originating from the skin or the intestine combined with biomechanical stress has different effects on the joints in an in vivo mouse model
Authors: GR Gulino, M Van Mechelen, R Lories
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> Psoriasis (PsO) and inflammatory bowel disease (IBD) share a wide range of comorbidities, including psoriatic arthritis (PsA). Entheses, the attachment sites of tendons and ligaments into the bones, spread the mechanical forces generated by movement onto the bone and are considered as a primary disease localization in PsA. Increasing evidence supports the hypothesis that biomechanical stress, together with inflammatory triggers from distant sites, such as the skin or the intestine, can contribute to the onset of PsA by inducing microdamage in the entheses. <h3>Objectives</h3> In this study, we aimed to investigate the role of biomechanical stress together with cutaneous or intestinal inflammation in initiating joint disease. <h3>Methods</h3> Eight-week-old male C57/Bl6 mice were treated with imiquimod cream (IMQ) on a shaved area of the back skin or with dextran sodium sulphate (DSS) dissolved in the drinking water to induce PsO-like skin or IBD-like gut inflammation. Control mice were left untreated. Afterwards, half of the mice were subject to a forced treadmill running protocol to increase biomechanical stress. Control mice with or without IMQ or DSS treatment did not run. Severity of cutaneous or intestinal inflammation was assessed clinically and by histology; knees and paws were analyzed by microCT, histology and immunohistochemistry. <h3>Results</h3> Local induction of cutaneous or intestinal inflammation led to a systemic response, as detected by splenomegaly, trabecular subchondral bone loss and bone marrow hypercellularity. On a background of PsO- but not of IBD-like inflammation, discrete signs of synovitis determined by the presence of CD45+ cells and overexpression of IL-17 were detected, with no significant impact of the running protocol. The CD45+ cells in the IMQ non-running condition were identified as F4/80+cells, in contrast to the running condition where the CD45+ cells could not be further identified, showing negative results for F4/80, CD3, MPO and MCSF-R stainings. Furthermore, forced exercise and PsO-like inflammation both induced overexpression of IL-17 at the entheses and acted synergistically when combined. <h3>Conclusions</h3> Local induction of PsO- or IBD-like inflammation triggers a systemic response with inflammation-associated bone loss and discrete signs of joint disease. PsO-like inflammation in combination with biomechanical stress increased the degree of synovitis and enthesitis, showing that systemic inflammation combined with biomechanical stress may contribute to disease manifestations in PsA. <h3>Disclosure of Interest</h3> G. Gulino: None declared, M. Van Mechelen: None declared, R. Lories Consultant for: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer, UCB.
Uncovering the Blind Spot of Clinical Trials: First Report of Baseline Characteristics of Newly Diagnosed (ND) and Relapsed/Refractory (RR) Multiple Myeloma (MM) Patients (Pts) in Insight-MM, a Global, Prospective, Observational Study
Authors: Evangelos Terpos, Ajai Chari, Robert M Rifkin, Rafat Abonour, Jesus G. Berdeja, Mario Boccadoro, Gordon Cook, Caitlin Costello, Saulius Girnius, Hartmut Goldschmidt, Roman Hájek, Vania T M Hungria, Hans C. Lee, Xavier Leleu, Jim Omel, Andrew Spencer, Michael A Thompson, Saad Z Usmani, Jorge Vela-Ojeda, Jeffrey A Zonder, Liviu Niculescu, Stephen Noga, Tomas Skacel, Roxanne Cacioppo, Brittany Sickler, Shawn Yu, Kaili Ren, Katarina Luptakova, Dawn Marie Stull, Faith E. Davies
Journal: Blood (2017)
Drug Interactions with Coumarin Anticoagulants
Authors: Jan Koch-Weser, Edward M. Sellers
Journal: New England Journal of Medicine (1971)

Interactions of Individual Drugs with CoumarinsA very large number of drugs have been suspected of interacting with coumarin anticoagulants. Often, this suspicion has stemmed from the interpretation of a single clinical event, and one of the many other factors that influence the relation between coumarin dose and hypoprothrombinemic response may actually have been responsible. Reports of such clinical impressions are useful, but they should be considered mere leads and should be followed up by controlled investigations. Unfortunately, some such anecdotal reports, even when invalidated by subsequent careful studies, have gradually developed into "facts" and are endlessly repeated in the . . .
ASCO Direct GU: A multistakeholder blended-learning project to make global education local.
Authors: Kurt Miller, Suneil Singh Malhotra, Daina Nanchanatt, Eva Thalmann, Robert A. Van Der Zwart, Steven Joniau
Journal: Journal of Clinical Oncology (2019)

10515 Background: International clinicians (HCPs) often find it difficult to attend North American congresses due to time out of the clinic, institutional travel restrictions, &amp; individual financial burden. HCPs continue to highlight the value of peer to peer scientific exchange at international meetings &amp; peer reviewed journals. Coupled with the dramatic increase of new scientific &amp; clinical data that are rapidly changing clinical paradigms, there is a need for an effective &amp; efficient digital solution to reach as many HCPs as possible. ASCO GU Direct sought to develop an educational program that culled the latest clinical &amp; scientific data from ASCO GU in real time to global HCPs. ASCO GU Direct is a partnership between ASCO, MEDtalks Netherlands, Bayer &amp; Janssen to drive global education locally since 2016. The live connection was broadcast in real time to local digital hubs in Europe, Middle East &amp; Asia, where an expert panel from ASCO GU reviewed key scientific data with local HCPs in real time. HCPs were able to view ASCO presentations &amp; ask questions to the panel despite time zone &amp; geography. Methods: We present results from the surveys done with participating HCPs to understand the effectiveness of this blended program by examining the quality &amp; objectivity of the content, impact on their clinical treatment, &amp; the Net Promotor Score (NPS). Results: To measure quality &amp; objectivity, NPS was calculated based on HCP responses to: “Would you recommend ASCO GU Direct to a colleague.” The NPS was 59 in 17 &amp; 72 in 18 (scale: -100 to +100), showing willingness to recommend the educational program. Conclusions: Providing digital access can effectively &amp; efficiently bridge gaps that would otherwise exist for international HCPs who did not attend ASCO GU. Digital access through this collaboration with live access to experts provides an excellent solution for HCPs who want to remain updated on clinical &amp; scientific data.
Price hike makes access to patient data unaffordable, say researchers
Authors: Jacqui Wise
Journal: BMJ (2019)

The Clinical Practice Research Datalink (CPRD)—a valuable source of patient care data—is now unaffordable for many non-industry funded UK researchers after the introduction of a new pricing structure, a group of academics has said.

The CPRD, a not-for-profit service to which 1600 general practices contribute data, is now managed by the Medicines and Healthcare Products Regulatory Agency (https://www.cprd.com/). The MHRA argued that the costs for accessing the data services had not changed since 2009, despite rising operating costs and a threefold increase in data volumes.

In a rapid response to The BMJ , Tom Macdonald, professor of clinical pharmacology at the University of Dundee, and nine other academics said that the cost of using CPRD has risen “very substantially” resulting in “many academic …
Anticoagulation After Surgical or Transcatheter Bioprosthetic Aortic Valve Replacement
Authors: Tarun Chakravarty, Akshar Patel, Samir Kapadia, Matthias Raschpichler, Richard W. Smalling, Wilson Y. Szeto, Yigal Abramowitz, Wen Cheng, Pamela S. Douglas, Rebecca T. Hahn, Howard C. Herrmann, Dean Kereiakes, Lars Svensson, Sung-Han Yoon, Vasilis C. Babaliaros, Susheel Kodali, Vinod H. Thourani, Maria C. Alu, Yangbo Liu, Thomas McAndrew, Michael Mack, Martin B. Leon, Raj R. Makkar
Journal: Journal of the American College of Cardiology (2019)
A new 'treatment-response score' for AUTO immune hepatitis is predictive of LONG-TERM event-free survival and overall survival : a multicenter Belgian cohort study
Authors: Cedric Simoen, Jeoffrey Schouten, Isabelle Colle, Christophe van Steenkiste, Filip Sermon, Anne Hoorens, Anja Geerts, Hans Van Vlierberghe, Xavier Verhelst
Journal: Hepatology (2018)
Phase II trial of bevacizumab plus docetaxel in patients with previously treated nonsquamous non-small cell lung cancer.
Authors: Fumiyoshi Ohyanagi, Azusa Tanimoto, Toshio Sakatani, Yuko Kawano, Ryota Saito, Kyohei Kaburaki, Noriko Yanagitani, Keita Kudo, Atsushi Horiike, Sachiko Hagiwara, Takeshi Horai, Makoto Nishio
Journal: Journal of Clinical Oncology (2012)

e18004 Background: The additional effects of bevacizumab (B) as first line chemotherapy for non-squamous (Nsq) non-small cell lung cancer (NSCLC) have been established. However, the efficacy of bevacizumab as a second- or more line chemotherapeutic agent has not been well examined. Docetaxel (D) is a standard second line treatment for NSCLC, a synergistic effect of the combination of D and B being shown in preclinical models. Therefore, this phase II study was conducted to evaluate the efficacy and safety of DB in patients with previously treated Nsq NSCLC. Methods: Patients with histologically or cytologically confirmed Nsq NSCLC, 20 to 74 years of age, ECOG performance status 0-2, with at least one prior chemotherapy, were eligible for the study. Patients were treated with D (60 mg/m²) and B (15 mg/kg) on day 1, repeated every 3 weeks until progressive disease (PD)or unacceptable toxicity occurred. The primary endpoint was the response rate (RR), and planned sample size was 28 patients. Results: Between May 2010 and July 2011, 28 patients (16 males/12 females; median age 65 years; PS 0/1/2: 19/9/0; ad/other: 22/6, no. of prior chemotherapy 1/2/3/4/5: 16/5/2/1/4) were enrolled in the study. Among these patients, 28 were included in analysis of toxicities and 27 patients were evaluated for response. Objective response was observed in 18 patients (PR; 18, SD; 8, PD 1), the response rate and disease control rate being 66.7% and 96%, respectively. With a median follow-up of 12.7 months, the median progression free survival was 7.9 months and overall survival did not reach median. Main toxicities of this regimen were myelosuppression (G3/4 neutropenia 85.7% and febrile neutropenia 21%). Mild non-hematological toxicity with no severe bleeding was also observed. Conclusions: The combination of D plus B is a very active regimen in previously treated Nsq NSCLC, warranting further study.
Use of “Doctor” Badges for Physician Role Identification During Clinical Training
Authors: Michael B. Foote, Ersilia M. DeFilippis, Benjamin N. Rome, Sanjay Divakaran, Maria A. Yialamas
Journal: JAMA Internal Medicine (2019)

This survey-based pilot study explores the frequency and implications of role misidentification experienced by residents at a large academic medical center and evaluates the use of a simple, low-cost method for distinguishing physicians from other members of the health care team.
Validation of the HFA‐PEFF score for the diagnosis of heart failure with preserved ejection fraction
Authors: Arantxa Barandiarán Aizpurua, Sandra Sanders‐van Wijk, Hans‐Peter Brunner‐La Rocca, Michiel Henkens, Stephane Heymans, Lauren Beussink‐Nelson, Sanjiv J. Shah, Vanessa P.M. van Empel
Journal: European Journal of Heart Failure (2019)
TeamX integrative oncology scholars: Harnessing the potentials of students in shaping oncological care.
Authors: Kin Wai (Tony) Hung, Ka-Kit Hui, Irene S. Kim, Silvia Orvietani Busch
Journal: Journal of Clinical Oncology (2019)

10516 Background: Teams are critical in delivering patient-centered care amid the challenge of health care workforce shortages. While conventional team-based collaborative care model involves physician and non-physician professionals, roles for pre-professional students in teams are largely educational and arguably underutilized. Methods: In a collaborative effort with the University of California Los Angeles (UCLA) Center for East West Medicine (CEWM), TeamX Health, a 501(c)3 nonprofit organization, designed an innovative, team-based curriculum for pre-professional students with our aims to harness the potentials of students in shaping the present and future delivery of oncological care. Over a 10-week academic quarter, students are challenged to explore the evolving evidence-based specialty of integrative oncology, and delivered as a “capstone project”, a creative solution to problems facing cancer patients today. Results: From April 2018 through October 2018, two 6-student cohorts have completed the curriculum. 10 participants (83%) were undergraduates and 2 (17%) were post-graduate alumni. Participants were selected based on a competitive application process with commitment to engage in the 2-hour weekly learning session. Sessions were taught in team-based learning format, covering topics ranging from cancer prevention, survivorship, symptoms management, nutrition, complementary therapies, integrative medicine models, and informatics. At completion of the curriculum, cohort one launched a health promotion YouTube channel addressing the physical and emotional burden for cancer survivors, and cohort two published a website for patients and caregivers to share their cancer journey serving as a greater social support platform. Conclusions: Redesigning the educational experience for pre-professional students may unlock unexpected possibilities to shape how we learned from and care for our patients. Harnessing the potentials for all levels of stakeholders ought to be part of defining team-based collaborative care.
Neoadjuvant chemoradiotherapy with 5-fluorouracil-cisplatin combined with cetuximab in patients with resectable locally advanced esophageal carcinoma: A prospective phase I/II trial (FFCD-PRODIGE 3)—Preliminary phase II results.
Authors: Laetitia Dahan, Christophe Mariette, Marc Ychou, Tan Dat Nguyen, Rosine Guimbaud, Thomas Aparicio, Veronique Vendrely, Xavier d'Journo, Fabien Subtil, Franck Bonnetain, Antoine Adenis, Jean Francois Seitz
Journal: Journal of Clinical Oncology (2012)

4091 Background: Chemoradiotherapy (CRT) for locally advanced esophageal cancer is based on 5FU combined with cisplatin. The anti-EGFR antibody cetuximab increases the efficacy of RT-based regimen for patients (pts) with cancer of the head and neck. This phase I/II trial was evaluating MTD, safety and pathologic complete response (pCR) rate of the combination of cetuximab with platinum-based CRT in esophageal cancer. Methods: Inclusion criteria: squamous cell carcinoma or adenocarcinoma of the esophagus, stage II-III, WHO PS 0-1. A radiotherapy of 45 grays (1.8 Gy/25F) was given over 5 weeks. During phase I, four patients experienced limited toxicity to dose level 0, and treatment was desescalated to dose level -1: weekly cetuximab (400 mg/m 2 one week before start of radiotherapy and 250 mg/m 2 during radiotherapy), and 5 FU (500 mg/m 2 per day D1-D4) combined with cisplatin (40 mg/m 2 D1) on week 1 and 5. Nine pCR over 27 resections were needed to show a pCR rate&gt;20% (α=5%, power = 90% ). Thirty three patients were included in the phase II. Results: From 07-2007 to 01-2011, 33 pts were enrolled, 20 squamous cell carcinoma (60.6%), 13 adenocarcinoma (39.4%), 25 (75.8%) stage III and 8 (24.2%) stage II. Among 32 pts who received CRT, the main grade 3-4 toxicities were esophagitis (4 pts), leucopenia (1 pt), anaphylaxis reaction (1 pt), rash (1 pt). Resection was achieved in 27 pts (25 R0)/31 who underwent surgery. Complete or near complete pathologic response (TRG grades 1 and 2 to Mandard) was achieved respectively in 5 (18.5%) and 6 (22.2%) pts. There were 4 deaths at 30 days post surgery. Severe postoperative complications were pulmonary complications (8), anastomotic stricture (4), gastric necrosis (1) and infection (7). The median overall survival was 15.7 months [11.01-.], and the median relapse free survival was 13.7 months [5.47-.]. Conclusions: Adding cetuximab to preoperative chemoradiotherapy including 5FU and cisplatin did not increase pCR. The recommended dose level of chemotherapy determined during phase I could explain those disappointing results. We won’t initiate a phase III trial.
Epidemiology of Clostridioides difficile infections, France, 2010 to 2017
Authors: Mélanie Colomb-Cotinat, Laetitia Assouvie, Julien Durand, Côme Daniau, Lucie Leon, Sylvie Maugat, Sophan Soing-Altrach, Cécile Gateau, Jeanne Couturier, Isabelle Arnaud, Pascal Astagneau, Anne Berger-Carbonne, Frédéric Barbut
Journal: Eurosurveillance (2019)

BackgroundClostridioides difficile is a leading cause of healthcare-associated diarrhoea in middle and high-income countries. Up to 2018, there has been no systematic, annual surveillance for C. difficile infections (CDI) in France.AimsTo provide an updated overview of the epidemiology of CDI in France between 2010 and 2017 based on five different data sources.MethodsThis is a descriptive study of retrospective surveillance and alerts data. Incidence of CDI cases was estimated through the CDI incidence survey (2016) and data from the French National Uniform Hospital Discharge Database (PMSI; 2010-16). Testing frequency for CDI was estimated through the CDI incidence survey and point prevalence studies on healthcare-associated infections (HAI; 2012 and 2017). The national early warning response system for HAI (HAI-EWRS, 2012-17) and National Reference Laboratory data (2012-17) were used to follow the number of severe CDI cases and/or outbreaks.ResultsIn 2016, CDI incidence in acute care was 3.6 cases per 10,000 patient days (PD). There was a statistically significant increase in CDI incidence between 2010 and 2016 (+ 14% annually) and testing frequency was 47.4 per 10,000 PD. The number of CDI HAI-EWRS notifications decreased between 2015 and 2017 with only a few large outbreaks reported.ConclusionThe CDI incidence estimate increased from 2010, but remained below the European average of 7 per 10,000 PD in 2014; there were fewer severe cases or clusters reported in France. The consistency between PMSI and laboratory-based estimated CDI incidence could allow for more routine monitoring of CDI incidence.