tbuckley/cabot-search huggingface dataset:
Cost-effectiveness of multidisciplinary care in mild to moderate chronic kidney disease in the United States: A modeling study
Authors: Eugene Lin, Glenn M. Chertow, Brandon Yan, Elizabeth Malcolm, Jeremy D. Goldhaber-Fiebert
Journal: PLoS Medicine (2018)

Multidisciplinary care (MDC) programs have been proposed as a way to alleviate the cost and morbidity associated with chronic kidney disease (CKD) in the US.We assessed the cost-effectiveness of a theoretical Medicare-based MDC program for CKD compared to usual CKD care in Medicare beneficiaries with stage 3 and 4 CKD between 45 and 84 years old in the US. The program used nephrologists, advanced practitioners, educators, dieticians, and social workers. From Medicare claims and published literature, we developed a novel deterministic Markov model for CKD progression and calibrated it to long-term risks of mortality and progression to end-stage renal disease. We then used the model to project accrued discounted costs and quality-adjusted life years (QALYs) over patients' remaining lifetime. We estimated the incremental cost-effectiveness ratio (ICER) of MDC, or the cost of the intervention per QALY gained. MDC added 0.23 (95% CI: 0.08, 0.42) QALYs over usual care, costing $51,285 per QALY gained (net monetary benefit of $23,100 at a threshold of $150,000 per QALY gained; 95% CI: $6,252, $44,323). In all subpopulations analyzed, ICERs ranged from $42,663 to $72,432 per QALY gained. MDC was generally more cost-effective in patients with higher urine albumin excretion. Although ICERs were higher in younger patients, MDC could yield greater improvements in health in younger than older patients. MDC remained cost-effective when we decreased its effectiveness to 25% of the base case or increased the cost 5-fold. The program costed less than $70,000 per QALY in 95% of probabilistic sensitivity analyses and less than $87,500 per QALY in 99% of analyses. Limitations of our study include its theoretical nature and being less generalizable to populations at low risk for progression to ESRD. We did not study the potential impact of MDC on hospitalization (cardiovascular or other).Our model estimates that a Medicare-funded MDC program could reduce the need for dialysis, prolong life expectancy, and meet conventional cost-effectiveness thresholds in middle-aged to elderly patients with mild to moderate CKD.
A decade of genome-wide association studies for coronary artery disease: the challenges ahead
Authors: Jeanette Erdmann, Thorsten Kessler, Loreto Munoz Venegas, Heribert Schunkert
Journal: Cardiovascular Research (2018)

In this review, we summarize current knowledge on the genetics of coronary artery disease, based on 10 years of genome-wide association studies. The discoveries began with individual studies using 200K single nucleotide polymorphism arrays and progressed to large-scale collaborative efforts, involving more than a 100 000 people and up to 40 Mio genetic variants. We discuss the challenges ahead, including those involved in identifying causal genes and deciphering the links between risk variants and disease pathology. We also describe novel insights into disease biology based on the findings of genome-wide association studies. Moreover, we discuss the potential for discovery of novel treatment targets through the integration of different layers of 'omics' data and the application of systems genetics approaches. Finally, we provide a brief outlook on the potential for precision medicine to be enhanced by genome-wide association study findings in the cardiovascular field.
Tous les polypes colorectaux réséqués doivent-ils faire l'objet d'un examen anatomopathologique?
Authors: B Denis, J Bottlaender, AM Weiss, A Peter, G Breysacher, P Chiappa, I Gendre, P Perrin
Journal: Endoscopy (2009)

Objectif: L'examen anatomopathologique des polypes colorectaux réséqués par endoscopie représente une charge de travail importante pour les pathologistes ainsi qu'un coût non négligeable. Il a un impact sur la prise en charge lorsqu'il guide le traitement d'un cancer invasif ou la surveillance coloscopique ultérieure. But: évaluer s'il est possible de ne pas faire l'examen anatomo-pathologique de certains polypes colorectaux sans risque pour le patient.
Novel evidence that extracellular nucleotides and purinergic signaling induce innate immunity-mediated mobilization of hematopoietic stem/progenitor cells
Authors: Mateusz Adamiak, Kamila Bujko, Monika Cymer, Monika Plonka, Talita Glaser, Magda Kucia, Janina Ratajczak, Henning Ulrich, Ahmed Abdel-Latif, Mariusz Z. Ratajczak
Journal: Leukemia (2018)

Pharmacological mobilization of hematopoietic stem progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB) is a result of mobilizing agent-induced “sterile inflammation” in the BM microenvironment due to complement cascade (ComC) activation. Here we provide evidence that ATP, as an extracellular nucleotide secreted in a pannexin-1-dependent manner from BM cells, triggers activation of the ComC and initiates the mobilization process. This process is augmented in a P2X7 receptor-dependent manner, and P2X7-KO mice are poor mobilizers. Furthermore, after its release into the extracellular space, ATP is processed by ectonucleotidases: CD39 converts ATP to AMP, and CD73 converts AMP to adenosine. We observed that CD73-deficient mice mobilize more HSPCs than do wild-type mice due to a decrease in adenosine concentration in the extracellular space, indicating a negative role for adenosine in the mobilization process. This finding has been confirmed by injecting mice with adenosine along with pro-mobilizing agents. In sum, we demonstrate for the first time that purinergic signaling involving ATP and its metabolite adenosine regulate the mobilization of HSPCs. Although ATP triggers and promotes this process, adenosine has an inhibitory effect. Thus, administration of ATP together with G-CSF or AMD3100 or inhibition of CD73 by small molecule antagonists may provide the basis for more efficient mobilization strategies.
ROLE OF WIRELESS CAPSULE ENDOSCOPY IN THE DIAGNOSIS OF OBSCURE GASTROINTESTINAL BLEEDING IN VON WILLEBRAND DISEASE: A RETROSPECTIVE CASE SERIES
Authors: F Francesca, F Branchi, S Orlando, SM Siboni, E Biguzzi, M Vecchi, L Elli
Journal: Endoscopy (2018)

Von Willebrand disease (VWD) is the most common inherited bleeding disorder characterized by deficiency/dysfunction of von Willebrand factor. Recurrent gastrointestinal bleeding is a severe manifestation, however the diagnostic and therapeutic approach in obscure bleeding is not standardized. In particular, the role of capsule endoscopy (CE) needs further validation.
M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-β, in patients with heavily pretreated CRC: Preliminary results from a phase I trial.
Authors: Scott Kopetz, Alexander I. Spira, Michael Wertheim, Edward Kim, Benjamin R. Tan, Heinz-Josef Lenz, Petros Nikolinakos, Patricia Rich, David A. Smith, Christoph Helwig, Isabelle Dussault, Laureen Ojalvo, James L. Gulley
Journal: Journal of Clinical Oncology (2018)

764 Background: Inhibiting the transforming growth factor β (TGF-β) pathway, which plays a key role in tumor immunosuppression, may enhance the response to programmed death 1/programmed death ligand 1 (PD-1/PD-L1) monoclonal antibodies (mAbs). M7824 (MSB0011359C) is an innovative first-in-class bifunctional fusion protein composed of a mAb against PD-L1 fused with the extracellular domain of TGF-β receptor II, which serves as a TGF-β “trap.” We report results in patients (pts) with heavily pretreated colorectal cancer (CRC), an area of high unmet need since these pts no longer respond to standard therapies. Methods: In this expansion cohort of the ongoing, phase 1, open-label trial NCT02517398, pts with heavily pretreated (≥3 rd line) advanced CRC receive M7824 1200 mg q2w until confirmed progressive disease (PD), unacceptable toxicity or trial withdrawal. The primary objective is best overall response (BOR) per RECIST v1.1; secondary objectives include safety/tolerability. Results: As of 28 June 2017, 32 heavily pretreated pts with advanced CRC (87.5% had ≥3 prior therapies) received M7824 for a median duration of 7.1 (range: 2-38) weeks; 2 pts remained on treatment. Among the 29 evaluable pts, 1 had a confirmed partial response (PR; ongoing at 8 months), 1 had stable disease (SD) and 27 had PD as BOR per independent read. The pt with a PR had CRC that was microsatellite stable (MSS), consensus molecular subtype (CMS) 4, KRAS mutant (mt) and PD-L1+; this pt had the highest tumor cell PD-L1 expression in our cohort (20%; PD-L1 expression was generally low among the other 24 pts with available results). 4 pts (12.5%) experienced 5 different grade 3 treatment-related adverse events (AEs; adrenal insufficiency, anemia, blood bilirubin increased, enteritis [leading to discontinuation] and fatigue); there were no grade ≥4 treatment-related AEs or treatment-related deaths. Conclusions: In heavily pretreated pts with advanced CRC, 1 pt (MSS, CMS 4, KRAS mt and PD-L1+) had a durable PR, 1 had SD and 27 had PD as BOR. M7824 showed a manageable safety profile. Updated data – including PD-L1, TGF-β and CMS results – will be presented. A study in pts with CMS 4 is in preparation. Clinical trial information: NCT02517398.
NOVEL ENDOSCOPIC TOOL TO PREVENT DELAYED BLEEDING AFTER WIDE ENDOSCOPIC RESECTIONS IN HIGH RISK PATIENTS: AN INITIAL SINGLE-CENTRE EXPERIENCE
Authors: P Soriani, VG Mirante, C Barbera, T Gabbani, L Miglioli, M Manno
Journal: Endoscopy (2018)

High-risk endoscopic procedures, like endoscopic mucosal resection (EMR) and submucosal dissection (ESD) are associated with a potential risk of bleeding requiring further interventions, like hospitalization, transfusion, endoscopic treatment or surgery. The incidence after polypectomy ranges up to 10% and can be displayed until 1 month after the procedure. Many factors are involved, for example polyp size, location, morphology, resection technique type of cautery used and ongoing antiplatelet and/or antithrombotic agents. Self-assembling peptide (SAP, Purastat®, 3D Matrix, Ltd, Tokyo, Japan) forming an hemostatic gel under appropriate conditions of ionization, protecting mucosal defects during the early phase of healing, also preventing stenosis, has been recently available.
A DISTALLY MIGRATED BILIARY STENT RECOVERED WITH OVER-THE-WIRE-ASSISTED GRASPING TRIPOD
Authors: M Hernandez-Tejero, J Santos, M Cimavilla, R Torres, A Carbajo, J García-Alonso, I Peñas, P Gil, C De la Serna, M Pérez-Miranda
Journal: Endoscopy (2018)

A 51-year-old man who was undertaken an orthotopic liver transplantation because of an end-stage liver alcoholic disease. In order to prevent a biliary anastomosis stenosis or leakage in the post-transplatation period was positioned at that point a temporary biliary plastic stent. After four months since the trasplantation, the patient, who had remained asymptomatic, was refered to our unit for an scheduled endoscopic removal. An endoscopic retrograde cholangiopancreatography (ERCP) was performed, procedure in which it was noticed that the biliary stent was distally migrated. Moreover, in the cholangiography we could verify that there was an anastomotic biliary stenosis proximally to the stent.
Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative
Authors: Tamas Constantin, Ivan Foeldvari, Jordi Anton, Joke de Boer, Severine Czitrom -Guillaume, Clive Edelsten, Raz Gepstein, Arnd Heiligenhaus, Clarissa A Pilkington, Gabriele Simonini, Yosef Uziel, Sebastian J Vastert, Nico M Wulffraat, Anne-Mieke Haasnoot, Karoline Walscheid, Annamária Pálinkás, Reshma Pattani, Zoltán Györgyi, Richárd Kozma, Victor Boom, Andrea Ponyi, Angelo Ravelli, Athimalaipet V Ramanan
Journal: Annals of the Rheumatic Diseases (2018)

In 2012, a European initiative called Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is possibly its most devastating extra-articular manifestation. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. Consequently, treatment practices differ widely, within and between nations.To provide recommendations for the diagnosis and treatment of JIA-associated uveitis.Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of nine experienced paediatric rheumatologists and three experts in ophthalmology from Europe. Recommendations derived from a validated systematic literature review were evaluated by an Expert Committee and subsequently discussed at two consensus meetings using nominal group techniques. Recommendations were accepted if >80% agreement was reached (including all three ophthalmologists).In total, 22 recommendations were accepted (with >80% agreement among experts): 3 on diagnosis, 5 on disease activity measurements, 12 on treatment and 2 on future recommendations.The SHARE initiative aims to identify best practices for treatment of patients suffering from JIA-associated uveitis. Within this remit, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated by an evidence-informed consensus process to suggest a standard of care for JIA-associated uveitis patients throughout Europe.
Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer
Authors: Linda S Lindström, Christina Yau, Kamila Czene, Carlie K Thompson, Katherine A Hoadley, Laura J van't Veer, Ron Balassanian, John W Bishop, Philip M Carpenter, Yunn-Yi Chen, Brian Datnow, Farnaz Hasteh, Gregor Krings, Fritz Lin, Yanhong Zhang, Bo Nordenskjöld, Olle Stål, Christopher C Benz, Tommy Fornander, Alexander D Borowsky, Laura J Esserman
Journal: JNCI Journal of the National Cancer Institute (2017)

Breast cancer patients with estrogen receptor (ER)–positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. The STO-3 trial enrolled 1780 postmenopausal lymph node–negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P < .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors.
Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer
Authors: L. Derosa, M.D. Hellmann, M. Spaziano, D. Halpenny, M. Fidelle, H. Rizvi, N. Long, A.J. Plodkowski, K.C. Arbour, J.E. Chaft, J.A. Rouche, L. Zitvogel, G. Zalcman, L. Albiges, B. Escudier, B. Routy
Journal: Annals of Oncology (2018)

The composition of gut microbiota affects antitumor immune responses, preclinical and clinical outcome following immune checkpoint inhibitors (ICI) in cancer. Antibiotics (ATB) alter gut microbiota diversity and composition leading to dysbiosis, which may affect effectiveness of ICI.We examined patients with advanced renal cell carcinoma (RCC) and non-small-cell lung cancer (NSCLC) treated with anti-programmed cell death ligand-1 mAb monotherapy or combination at two academic institutions. Those receiving ATB within 30 days of beginning ICI were compared with those who did not. Objective response, progression-free survival (PFS) determined by RECIST1.1 and overall survival (OS) were assessed.Sixteen of 121 (13%) RCC patients and 48 of 239 (20%) NSCLC patients received ATB. The most common ATB were β-lactam or quinolones for pneumonia or urinary tract infections. In RCC patients, ATB compared with no ATB was associated with increased risk of primary progressive disease (PD) (75% versus 22%, P < 0.01), shorter PFS [median 1.9 versus 7.4 months, hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.4-6.9, P < 0.01], and shorter OS (median 17.3 versus 30.6 months, HR 3.5, 95% CI 1.1-10.8, P = 0.03). In NSCLC patients, ATB was associated with similar rates of primary PD (52% versus 43%, P = 0.26) but decreased PFS (median 1.9 versus 3.8 months, HR 1.5, 95% CI 1.0-2.2, P = 0.03) and OS (median 7.9 versus 24.6 months, HR 4.4, 95% CI 2.6-7.7, P < 0.01). In multivariate analyses, the impact of ATB remained significant for PFS in RCC and for OS in NSCLC.ATB were associated with reduced clinical benefit from ICI in RCC and NSCLC. Modulatation of ATB-related dysbiosis and gut microbiota composition may be a strategy to improve clinical outcomes with ICI.
Caecostomie percutanée endoscopique: résultats d'une étude pilote monocentrique
Authors: E Coron, G Meurette, E Cauchin, M Le Rhun, JP Galmiche, PA Lehur, S Bruley des Varannes
Journal: Endoscopy (2009)

Introduction: Nous avons récemment démontré la faisabilité d'une nouvelle technique de caecostomie percutanée endoscopique (CPE) (1). Cette procédure permet la mise en place d'un dispositif d'irrigations coliques antérogrades (ICA) par une mini-stomie chez les patients ayant une constipation sévère et/ou une incontinence anale. L'objectif de cette étude monocentrique de preuve de concept était d'évaluer l'efficacité thérapeutique des ICA réalisées par la CPE.
Tackling vehicle emissions and physical inactivity. Scottish Government doubles active travel budget
Authors: Aileen Campbell, Humza Yousaf, Roy Brannen, Paul Gray, Graeme Hunter, Nanette Mutrie, Andrew Murray
Journal: British Journal of Sports Medicine (2018)

Increasing greenhouse gas emissions, and physical inactivity are major global challenges of the 21st century.1 Tackling climate change and increasing physical activity are key priorities at local, national and international level. We need to act now to prevent or limit the impacts on our children and future generations (figure 1).



Figure 1 
Best Investments for Physical Activity, includes active travel and suggests “working together to make it happen”.



The Scottish Government has committed to doubling spend on the active travel budget from £40 million per year to £80 million per year from 2018 to 2019 (figure …
OUTCOMES OF GASTRIC ESD IN A EUROPEAN CENTRE – WHAT WE HAVE DONE IN 11 YEARS
Authors: D Libânio, R Castro, I Pita, P Pimentel-Nunes, M Dinis-Ribeiro
Journal: Endoscopy (2018)

Endoscopic submucosal dissection (ESD) was recently recommended as a first-line treatment in patients with gastric superficial neoplasms, although experience with this technique is still limited in Western countries. We aimed to evaluate the outcomes of this technique since the introduction of this technique in our centre.
COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION (CR-ESD), HYBRID ESD (H-ESD) AND RECURRENCE RATE: A WESTERN EUROPEAN EXPERIENCE IN SPAIN
Authors: JC Marín-Gabriel, J Díaz-Tasende, P Cancelas-Navia, S Rodríguez-Muñoz, AJ del Pozo-García, M Alonso-Riaño, Y Rodríguez-Gil, C Ibarrola-Andrés, G Castellano-Tortajada
Journal: Endoscopy (2018)

To compare the recurrence rate after R0 and R1/Rx endoscopic resection (ER), on an ESD “intention-to-treat” basis, in a Western European setting.
OESOPHAGEAL STRICTURES AFTER RADIOFREQUENCY ABLATION (RFA) FOR EARLY BARRETT'S NEOPLASIA: STANDARD VS. SIMPLIFIED PROTOCOL. A RETROSPECTIVE STUDY IN A SINGLE TERTIARY REFERRAL CENTRE
Authors: J Santiago-Garcia, J Ortiz Fernández-Sordo, M Pana, S Beg, K Ragunath
Journal: Endoscopy (2018)

Radiofrequency ablation (RFA) is the ablative treatment of choice for early Barrett's neoplasia without visible lesions. Initial studies were performed under the standard ablation protocol. A new simplified protocol, which omits cleaning the device and ablated mucosa in between ablations, has now been proven to be comparable in efficacy and safety. We aimed to evaluate the stricture rate with the simplified protocol compared to the standard regime.
Risk Factors for Hyperechogenic Pancreas on Endoscopic Ultrasound (EUS). A Case Controlled Study
Authors: M Al-Haddad, S Pungpapong, J Scolapio, K Noh, M Wallace, T Woodward, N Pallotta, M Raimondo
Journal: Endoscopy (2006)

Background: Hyperechogenic pancreas suggestive of fatty replacement is a common finding during EUS. Its clinical significance in the setting of a normal pancreas is unclear.
Ablation of the stress protease OMA1 protects against heart failure in mice
Authors: Rebeca Acin-Perez, Ana Victoria Lechuga-Vieco, Maria del Mar Muñoz, Rocío Nieto-Arellano, Carlos Torroja, Fátima Sánchez-Cabo, Concepción Jiménez, Andrés González-Guerra, Isabel Carrascoso, Cristiane Benincá, Pedro M. Quiros, Carlos López-Otín, José María Castellano, Jesús Ruíz-Cabello, Luis Jesús Jiménez-Borreguero, José Antonio Enríquez
Journal: Science Translational Medicine (2018)

Loss of OMA1 protects cardiomyocytes from death in three murine models of heart failure with diverse etiologies.
LOW CLINICAL EFFICACY OF EMERGENT SIGMOIDOSCOPY IN PATIENTS WITH OVERT LOWER GASTROINTESTINAL BLEEDING: A SINGLE CENTER STUDY
Authors: D Lee, D Kim, SH Hwang, JW Choe, SY Kim, SW Jung, JS Koo, SW Lee
Journal: Endoscopy (2018)

Emergent sigmoidoscopy is commonly used as first diagnostic tool in patients with overt lower gastrointestinal bleeding (LGIB). However, it tis uncommon to find definite bleeding focus in emergent sigmoidoscopy and multiple diagnostic work-up studies are commonly needed after that study. We aimed to compare the clinical efficacy of emergent sigmoidoscopy and colonoscopy with bowel preparation in overt LGIB
De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR− phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel
Authors: U.A. Nitz, O. Gluz, M. Christgen, E. -M. Grischke, D. Augustin, S. Kuemmel, M. Braun, J. Potenberg, A. Kohls, K. Krauss, A. Stefek, C. Schumacher, H. Forstbauer, T. Reimer, H. Fischer, C. Liedtke, R. Wuerstlein, J. Schumacher, R. Kates, H. Kreipe, N. Harbeck
Journal: Annals of Oncology (2017)
ENDOSCOPIC PERORAL MYOTOMY (POEM) VS LAPAROSCOPIC HELLER MYOTOMY WITH FUNDOPLICATION (MHLF) FOR THE TREATMENT OF ACHALASIA IN A TERTIARY MEXICAN CENTER
Authors: G Grajales-Figueroa, LR Valdovinos-Garcia, LE Zamora-Nava, MA Valdovinos-Diaz, E Coss-Adame, G Torres-Villalobos, F Valdovinos-Andraca
Journal: Endoscopy (2018)

To assess the efficacy and safety of POEM vs. Heller laparoscopic myotomy in patients with achalasia in a third level center in Mexico.