tbuckley/cabot-search huggingface dataset:
Utility of early circulating tumour DNA dynamics as a surrogate for progression free survival in the BEECH phase I/II trial in metastatic breast cancer
Authors: S. Hrebien, V. Citi, I. Garcia-Murillas, R. Cutts, I. Kozarewa, J. Ratnayake, E.C. de Bruin, G. Schiavon, A.M. Antunes De Melo e Oliveira, N. Turner
Journal: Annals of Oncology (2019)

Background: Dynamic changes in circulating tumour DNA (ctDNA) levels may predict long-term outcome of therapy. We utilised samples from a phase I/II randomised trial (BEECH) to assess ctDNA dynamics as a surrogate for progression free survival (PFS) and early predictor of drug efficacy. Methods: Patients with oestrogen receptor positive advanced metastatic breast cancer (ER+ mBC) in the BEECH study were randomised to paclitaxel plus placebo versus paclitaxel plus AKT inhibitor capivasertib. Plasma samples were collected for ctDNA analysis at baseline and at multiple timepoints in the development cohort (safety run-in, part A) and validation cohort (randomised, part B). Baseline sample ctDNA sequencing identified mutations for longitudinal analysis, and mutation specific digital droplet PCR (ddPCR) assays were utilised to assess change in ctDNA allele fraction between baseline and 872 on-treatment samples. Early suppression of ctDNA assessment was used to define criteria in the development cohort and independently evaluated in the validation cohort. Results: In the development cohort, suppression of ctDNA was evident after 8 days of treatment (p = 0.014), with cycle 2 day 1 (4 weeks) identified as the optimal timepoint to predict PFS from early ctDNA dynamics. In the validation cohort, median PFS was 11.1 months in patients with suppressed ctDNA at 4 weeks and 6.4 months in patients with high ctDNA (HR = 0.20, 95% CI 0.083 – 0.50, p < 0.0001). No difference in the level of ctDNA suppression was observed between patients randomised to capivasertib or placebo overall (p = 0.904) nor in the PIK3CA mutant subpopulation (p = 0.071). Clonal haematopoiesis of indeterminate potential (CHIP) was evident in 30% (18/59) baseline samples and had no effect on tolerance of chemotherapy nor on PFS. Conclusions: Early on-treatment ctDNA dynamics are a surrogate for PFS. Dynamic ctDNA assessment has the potential to substantially enhance early drug development through targeted therapy and biomarker evaluation. Clinical trial identification: NCT01625286. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: I. Kozarewa, J. Ratnayake, E.C. de Bruin, G. Schiavon: Employee: AstraZeneca. A.M. Antunes De Melo e Oliveira: Grant/research support (to the Institution): AstraZeneca. N. Turner: Advisory board honoraria, research funding: AstraZeneca. All other authors have declared no conflicts of interest.
Abstract 2823: Expression of an Amyloidogenic Polyglutamine (PQ83) Peptide Causes Apoptosis and Heart Failure
Authors: Scott Pattison, Atsushi Sanbe, Raisa Klevitsky, Lisa Martin, Jeffrey Robbins
Journal: Circulation (2006)

Introduction: Pre-amyloid oligomers (PAOs), the entities believed to cause toxicity in Alzheimer’s and other neurodegenerative diseases, are also observed in the cardiomyocytes of many human heart ...
The operationalization of fatigue in frailty scales: a systematic review
Authors: V. Knoop, A. Costenoble, R. Vella Azzopardi, S. Vermeiren, A. Debain, B. Jansen, A. Scafoglieri, I. Bautmans, Ivan Bautmans, Dominque Verté, Ingo Beyer, Mirko Petrovic, Liesbeth De Donder, Tinie Kardol, Gina Rossi, Peter Clarys, Aldo Scafoglieri, Erik Cattrysse, Paul de Hert, Bart Jansen
Journal: Ageing Research Reviews (2019)
Safety of the tau-directed monoclonal antibody BIIB092 in progressive supranuclear palsy: a randomised, placebo-controlled, multiple ascending dose phase 1b trial
Authors: Adam L Boxer, Irfan Qureshi, Michael Ahlijanian, Michael Grundman, Lawrence I Golbe, Irene Litvan, Lawrence S Honig, Paul Tuite, Nikolaus R McFarland, Padraig O'Suilleabhain, Tao Xie, Giridhar S Tirucherai, Clifford Bechtold, Yvette Bordelon, David S Geldmacher, Murray Grossman, Stuart Isaacson, Theresa Zesiewicz, Tina Olsson, Kumar Kandadi Muralidharan, Danielle L Graham, John O'Gorman, Samantha Budd Haeberlein, Tien Dam
Journal: The Lancet Neurology (2019)
SINGLE-SCOPE MONO-RAIL EUS-GUIDED RENDEZVOUS TO SALVAGE FAILED DUODENAL INTUBATION AND FAILED BILIARY CANNULATION
Authors: R Sánchez-Ocaña Hernández, J Tejedor Tejada, AY Carbajo López, M De Benito Sanz, FJ García-Alonso, S Bazaga Pérez De Rozas, C De la Serna-Higuera, M Pérez-Miranda Castillo
Journal: Endoscopy (2019)

All reported variants of EUS-guided rendezvous (EUS-RV) require echoendoscope exchange. Exchanging the echoendoscope is tricky because it entails the risk of guidewire loss (Baron & Levy, PMID: 22622737). We describe a new variant of EUS-RV that does not require echoendoscope exchange. This was combined with the previously reported mono-rail RV, using a home-made sphincterotome.
The Mediterranean Diet and 2-Year Change in Cognitive Function by Status of Type 2 Diabetes and Glycemic Control
Authors: Josiemer Mattei, Sherman J. Bigornia, Mercedes Sotos-Prieto, Tammy Scott, Xiang Gao, Katherine L. Tucker
Journal: Diabetes Care (2019)

To determine associations of a Mediterranean diet score (MeDS) with 2-year change in cognitive function by type 2 diabetes and glycemic control status and contrast it against other diet quality scores.We used data from the longitudinal Boston Puerto Rican Health Study (n = 913; 42.6% with type 2 diabetes at 2 years). Glycemic control at baseline was categorized as uncontrolled (hemoglobin A1c ≥7% [53 mmol/mol]) versus controlled. Two-year change in glycemic control was defined as stable/improved versus poor/declined. We defined MeDS, Healthy Eating Index, Alternate Healthy Eating Index, and Dietary Approaches to Stop Hypertension scores. Adjusted mixed linear models assessed 2-year change in global cognitive function z score, executive and memory function, and nine individual cognitive tests.Higher MeDS, but no other diet quality score, was associated with higher 2-year change in global cognitive function in adults with type 2 diabetes (β ± SE = 0.027 ± 0.011; P = 0.016) but not in those without (P = 0.80). Similar results were noted for Mini-Mental State Examination, word recognition, digit span, and clock drawing tests. Results remained consistent for individuals under glycemic control at baseline (0.062 ± 0.020; P = 0.004) and stable/improved over 2 years (0.053 ± 0.019; P = 0.007), but not for individuals with uncontrolled or poor/declined glycemic control. All diet quality scores were associated with higher 2-year memory function in adults without type 2 diabetes.Both adhering to a Mediterranean diet and effectively managing type 2 diabetes may support optimal cognitive function. Healthy diets, in general, can help improve memory function among adults without type 2 diabetes.
ANTI-REFLUX MUCOSECTOMY (ARMS) IN THE TREATMENT OF REFRACTORY GASTRO-ESOPHAGEAL RELFUX (GERD): PILOT STUDY EVALUATING THE FEASIBILITY AND SAFETY
Authors: JM Gonzalez, R Irarrazaval, P Basile, JP Le Mouel, M Barthet
Journal: Endoscopy (2019)

There is no validated endoscopic treatment of GERD. Esophageal mucosectomy is a reference technique, and induce a tissular shrinking at the eso-gastric junction (EGJ). Thus, we propose a pilot study to evaluate the feasibility and the safety of the ARMS procedure in refractory GERD, and to document its efficacy (disappearance of the main symptom and RDQ score).
ANTIREFLUX MUCOSECTOMY. PRELIMINARY RESULTS OF A PROSPECTIVE STUDY
Authors: A Ortega, P Rosón, F Fernandez, M Angeles Romero, M Angeles Perez Aisa, J Cotta, M Lozano
Journal: Endoscopy (2019)

Gastroesophageal reflux disease (GERD) is very prevalent and has a significant impact on quality of life. Proton pump inhibitors (PPIs) are the mainstay of treatment, but up to 30% of patients do not respond. Several endoscopic treatment systems have been developed, with disparate results. Anti-reflux mucosectomy (ARMS) is based on the resection of the gastric mucosa distal to the cardia, which, after healing, results in a retraction that remodels the cardial valve, and rectifies the angle of Hiss.
Impact of Three-dimensional Printing in Urology: State of the Art and Future Perspectives. A Systematic Review by ESUT-YAUWP Group
Authors: Giovanni E. Cacciamani, Zhamshid Okhunov, Aurus Dourado Meneses, Moises Elias Rodriguez-Socarras, Juan Gomez Rivas, Francesco Porpiglia, Evangelos Liatsikos, Domenico Veneziano
Journal: European Urology (2019)
Abstract 13608: Enhanced Wound Healing by Human Pluripotent Stem Cell-Derived Lymphatic Endothelial Lineage Cells
Authors: Shin-Jeong Lee, Changwon Park, Ji Yoon Lee, Eugine Lee, Young-sup Yoon
Journal: Circulation (2012)

Background: A very common, but not a well investigated lymphatic-related disorder is skin wound. Despite increasing evidence for the importance of lymphatic vessel in wound healing, no studies are ...
FEASIBILITY OF A THREE-DIMENSIONAL SPHEROID CULTURE USING ENDOSCOPIC ULTRASOUND-GUIDED TISSUE SAMPLING IN PANCREATIC CANCER
Authors: CM Cho, SY Nam, GC Kim, AN Seo, HI Bae
Journal: Endoscopy (2019)

Preclinical research is recently advanced for in vitro drug testing using cancer cell lines and xenograft tissues. However, obtaining tumor cells from patients with pancreatic cancer are limited. Recently, methods to culture and/or propagate tumor tissue using specimens obtained from endoscopic ultrasound-guided tissue sampling (EUS-TS) were introduced. The aim of our study was to evaluate the feasibility of a three-dimensional (3D) spheroid culture using EUS-TS in pancreatic cancer.
Unprecedently high targeting specificity toward lung ICAM-1 using 3DNA nanocarriers
Authors: Nikša Roki, Zois Tsinas, Melani Solomon, Jessica Bowers, Robert C. Getts, Silvia Muro
Journal: Journal of Controlled Release (2019)

DNA nanostructures hold great potential for drug delivery. However, their specific targeting is often compromised by recognition by scavenger receptors involved in clearance. In our previous study in cell culture, we showed targeting specificity of a 180 nm, 4-layer DNA-built nanocarrier called 3DNA coupled with antibodies against intercellular adhesion molecule-1 (ICAM-1), a glycoprotein overexpressed in the lungs in many diseases. Here, we examined the biodistribution of various 3DNA formulations in mice. A formulation consisted of 3DNA whose outer-layer arms were hybridized to secondary antibody-oligonucleotide conjugates. Anchoring IgG on this formulation reduced circulation and kidney accumulation vs. non-anchored IgG, while increasing liver and spleen clearance, as expected for a nanocarrier. Anchoring anti-ICAM changed the biodistribution of this antibody similarly, yet this formulation specifically accumulated in the lungs, the main ICAM-1 target. Since lung targeting was modest (2-fold specificity index over IgG formulation), we pursued a second preparation involving direct hybridization of primary antibody-oligonucleotide conjugates to 3DNA. This formulation had prolonged stability in serum and showed a dramatic increase in lung distribution: the specificity index was 424-fold above a matching IgG formulation, 144-fold more specific than observed for PLGA nanoparticles of similar size, polydispersity, ζ-potential and antibody valency, and its lung accumulation increased with the number of anti-ICAM molecules per particle. Immunohistochemistry showed that anti-ICAM and 3DNA components colocalized in the lungs, specifically associating with endothelial markers, without apparent histological changes. The degree of in vivo targeting for anti-ICAM/3DNA-nanocarriers is unprecedented, for which this platform technology holds great potential to develop future therapeutic applications.
OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) DURING LIVE ENDOSCOPY EVENTS – A 12- YEAR FOLLOW-UP
Authors: A Ebigbo, S Freund, A Probst, C Römmele, S Gölder, H Messmann
Journal: Endoscopy (2019)

Live endoscopy events (LEE) have increased considerably in the last 20 years. However, ethical and patient-related issues have been raised, especially concerning complications, patient outcome as well as success rate. There is no data showing the outcome of ESD during LEE. In this study, ESD procedures performed during the Augsburg Endo-Update LEE were compared with matched routine procedures.
HOW WELL DOES POLYP DETECTION RATE CORRELATE WITH ADENOMA DETECTION RATE?
Authors: RN Patel, S Hong, N Gayle, R Poonawala, Z Tariq, K Besherdas
Journal: Endoscopy (2019)

Adenoma detection rate (ADR) is a key performance indictor for colonoscopy as it correlates with diminished risk of interval colorectal cancer (CRC) and mortality. Assessment of the ADR can be time consuming as it requires histological assessment. Polyp detection rate (PDR) is a less cumbersome measure that does not require the linkage of endoscopy and histopathology results. We aim to assess whether PDR was an adequate substitute for ADR.
USEFULNESS OF DEDICATED FORCEPS FOR DIGITAL SINGLE-OPERATOR CHOLANGIOSCOPY FOR THE TREATMENT OF INFLAMMATORY BILIARY STRICTURE
Authors: P Soriani, T Gabbani, S Deiana, VG Mirante, M Manno
Journal: Endoscopy (2019)

Endoscopic treatment of biliary strictures is challenging; moreover, if stenosis is almost complete, dilation can fail for inability to pass over a guidewire dilation devices or stent [1].
Controlled Trial of Budesonide–Formoterol as Needed for Mild Asthma
Authors: Richard Beasley, Mark Holliday, Helen K. Reddel, Irene Braithwaite, Stefan Ebmeier, Robert J. Hancox, Tim Harrison, Claire Houghton, Karen Oldfield, Alberto Papi, Ian D. Pavord, Mathew Williams, Mark Weatherall
Journal: New England Journal of Medicine (2019)

In double-blind, placebo-controlled trials, budesonide–formoterol used on an as-needed basis resulted in a lower risk of severe exacerbation of asthma than as-needed use of a short-acting β2-agonist (SABA); the risk was similar to that of budesonide maintenance therapy plus as-needed SABA. The availability of data from clinical trials designed to better reflect clinical practice would be beneficial.
THE GASTROPACK SYSTEM, A NOVEL METHOD TO ACCESS TO GASTROENTEROLOGICAL CARE: RESULTS OF THE UPPER GASTROINTESTINAL SYMPTOM POPULATION
Authors: L Ceroni, F Lodato, P Tubertini, C Fabbri, F Buonfiglioli, F Ferrara, A Alberani, A Polifemo, C Tosetti, A Lenzi, S Mondini, V Veduti, V Cennamo
Journal: Endoscopy (2019)

Open-access system allows General Practitioners (GP) to directly schedule endoscopic procedures for their patients. A previous Italian multicentric study showed a rate of inappropriate EGD of 22.9% (29.4% with prescriptions from GP and 12.9% from specialists). This study aims to evaluate if the GASTROPACK SYSTEM (GS) may reduce not appropriate EGD.
Robot assisted training for the upper limb after stroke (RATULS): a multicentre randomised controlled trial
Authors: Helen Rodgers, Helen Bosomworth, Hermano I Krebs, Frederike van Wijck, Denise Howel, Nina Wilson, Lydia Aird, Natasha Alvarado, Sreeman Andole, David L Cohen, Jesse Dawson, Cristina Fernandez-Garcia, Tracy Finch, Gary A Ford, Richard Francis, Steven Hogg, Niall Hughes, Christopher I Price, Laura Ternent, Duncan L Turner, Luke Vale, Scott Wilkes, Lisa Shaw
Journal: The Lancet (2019)

Loss of arm function is a common problem after stroke. Robot-assisted training might improve arm function and activities of daily living. We compared the clinical effectiveness of robot-assisted training using the MIT-Manus robotic gym with an enhanced upper limb therapy (EULT) programme based on repetitive functional task practice and with usual care.RATULS was a pragmatic, multicentre, randomised controlled trial done at four UK centres. Stroke patients aged at least 18 years with moderate or severe upper limb functional limitation, between 1 week and 5 years after their first stroke, were randomly assigned (1:1:1) to receive robot-assisted training, EULT, or usual care. Robot-assisted training and EULT were provided for 45 min, three times per week for 12 weeks. Randomisation was internet-based using permuted block sequences. Treatment allocation was masked from outcome assessors but not from participants or therapists. The primary outcome was upper limb function success (defined using the Action Research Arm Test [ARAT]) at 3 months. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN69371850.Between April 14, 2014, and April 30, 2018, 770 participants were enrolled and randomly assigned to either robot-assisted training (n=257), EULT (n=259), or usual care (n=254). The primary outcome of ARAT success was achieved by 103 (44%) of 232 patients in the robot-assisted training group, 118 (50%) of 234 in the EULT group, and 85 (42%) of 203 in the usual care group. Compared with usual care, robot-assisted training (adjusted odds ratio [aOR] 1·17 [98·3% CI 0·70-1·96]) and EULT (aOR 1·51 [0·90-2·51]) did not improve upper limb function; the effects of robot-assisted training did not differ from EULT (aOR 0·78 [0·48-1·27]). More participants in the robot-assisted training group (39 [15%] of 257) and EULT group (33 [13%] of 259) had serious adverse events than in the usual care group (20 [8%] of 254), but none were attributable to the intervention.Robot-assisted training and EULT did not improve upper limb function after stroke compared with usual care for patients with moderate or severe upper limb functional limitation. These results do not support the use of robot-assisted training as provided in this trial in routine clinical practice.National Institute for Health Research Health Technology Assessment Programme.
(Committee for Advanced Therapies (CAT), CAT Scientific Secretariat), Challenges with advanced therapy medicinal products and how to meet them
Authors: C. K. Schneider, N. MacAleenan, A. Samuel, I. G. Reischl, B. Sarkadi, J. Gulbinovic, M. Menezes-Ferreira, R. Maciulaitis, J. L. Robert, J. H. Ovelgönne, G. A. Crosbie, V. Kokkas, P. Celis, F. Bignami, M. Fraczek, S. Lucas, T. VandenDriessche, P. Marinko, L. D'Apote, M. Hystad, S. Ruiz, L. R. Todorova, T. Maimets, A. S. Moraru, E. Flory, M. Schüssler-Lenz, G. Migliaccio, A. Tsiftsoglou, M. Timón, R. Zorec, I. Büttel, T. Methuen, C. Beuneu, J. H. Trouvin, B. Flamion, R. Georgiev, A. Kent, B. S. Lima, N. Meade, N. Vilceanu, D. Niederwieser, A. Paphitou, J. G. Dickson, A. M. Fal, G. Berchem, P. Salmikangas, M. Clausen, A. Pychova, O. Oliver-Diaz, M. Vassiliou, Z. Buzás, A. Linē, I. Haunerova, L. Akerblom, M. C. Galli, K. Gudmundsson, B. Jilma, G. Narayanan, M. O'Donovan, J. Ancāns, M. Hrubisko, P. Turcáni, W. Cheng, M. A. Figuerola-Santos, P. Ljungman, M. L. di Paola
Journal: Nature Reviews Drug Discovery (2010)
Traitement transrectal sous écho-endoscopie de collections pelviennes symptomatiques: Ponction ou drainage? Large étude monocentrique
Authors: M Guingand De Rivery, JM Gonzalez, M Gasmi, M Barthet
Journal: Endoscopy (2019)

Les collections abdomino-pelviennes peuvent survenir après une chirurgie rectale, colique ou gynécologique ou sur des terrains favorisant tel que la maladie de Crohn active. Ces dernières étaient jusque là prises en charge par des méthodes chirurgicales ou radiologiques.
Incidence and Risk Factors of Keratinocyte Carcinoma After First Solid Organ Transplant in Ontario, Canada
Authors: Christina K. Park, Kinwah Fung, Peter C. Austin, S. Joseph Kim, Lianne G. Singer, Nancy N. Baxter, Paula A. Rochon, An-Wen Chan
Journal: JAMA Dermatology (2019)

Keratinocyte carcinoma (KC), also known as nonmelanoma skin cancer, is the most common malignancy after solid organ transplant. Epidemiologic data on posttransplant KC in North America are limited by a lack of KC capture in cancer and transplant registries.To estimate the incidence and identify risk factors for posttransplant KC.This population-based inception cohort study in Ontario, Canada, used linked administrative databases and a health insurance claims-based algorithm. Participants were adult recipients of a first kidney, liver, heart, or lung transplant from January 1, 1994, to December 31, 2012. The cohort (n = 10 198) was followed up to December 31, 2013. Data were analyzed from May 31, 2016, to April 21, 2017.Solid organ transplant with functioning graft.Age- and sex-adjusted standardized incidence ratio for KC in the transplant cohort was compared with that in the general population. Cumulative incidence of posttransplant KC was estimated using cumulative incidence functions, accounting for the competing risks of death or kidney graft loss. The association between KC and patient-, transplant-, and health services-related factors was evaluated with a multivariable cause-specific hazards model.A total of 10 198 transplant recipients were included in the study. The median (interquartile range [IQR]) age at transplant was 51 (41-59) years, with most recipients being male (6608 [64.8%]) and white (5964 [58.5%]). Posttransplant KC was diagnosed in 1690 patients (16.6%) after a median (IQR) of 3.96 (1.94-7.09) years, with an incidence rate of 2.63 per 100 patient-years (95% CI, 2.51-2.76). The rate of KC was significantly higher after transplant compared with the general population (standardized incidence ratio, 6.61; 95% CI, 6.31-6.93). The highest 10-year cumulative incidence was in the subsets of patients with a history of pretransplant skin cancer (66.5%), older than 50 years at transplant (27.5% for 51-65 years; 40.5% for >65 years), and of the white race (24.1%). The strongest independent risk factors for KC included older age at transplant (adjusted hazard ratio [aHR], 9.27; 95% CI, 7.08-12.14 for >65 years vs 18-35 years), white vs black race (aHR, 8.50; 95% CI, 4.03-17.91), pretransplant invasive skin cancer (aHR, 4.30; 95% CI, 3.72-4.98), and posttransplant precancerous skin lesions (aHR, 4.32; 95% CI, 3.77-4.95).The incidence of KC appeared to be substantially increased after transplant, particularly in patients who were older at transplant, were white, and had a history of cancerous or precancerous skin tumors; intensified skin cancer screening, education, and early use of chemopreventive interventions may be warranted for these high-risk patient subsets.