tbuckley/cabot-search huggingface dataset:
SAT-030-Annual contrast-enhanced MRI is highly effective in the surveillance of hepatocellular carcinoma in cirrhotic patients
Authors: Coskun Ozer Demirtas, feyza gunduz, Davut Tuney, Feyyaz Baltacioglu, Yesim Alahdab, Osman Cavit Ozdogan
Journal: Journal of Hepatology (2019)
PS-002-Persistence of hepatic and adipose tissue alterations in T helper 17 cells, CD8+ cytotoxic T cells and regulatory T cells despite metabolic and histological improvement upon diet reversal in a high-fat high-fructose mouse model of NAFLD
Authors: Mikhail Van Herck, Luisa Vonghia, Peter Michielsen, Chris Bridts, Didier Ebo, Joris De Man, Benedicte De Winter, Sven Francque
Journal: Journal of Hepatology (2019)
SAT-433-Portal venous velocity and platelet count as a simple non-invasive tool to rule out the presence of varices needing treatment in patients with compensated cirrhosis
Authors: Francesco Santopaolo, leonardo baiocchi, Piera Rossi, Alessandra Pecchioli, Alessandra Bosa, Simona Francioso, Arianna Brega, Ilaria Lenci, Chiara Masetti, Martina Milana, Francesca Antenucci, Benedetto Neri, Angelico Mario
Journal: Journal of Hepatology (2019)
Beyond 1000 nm Emission Wavelength: Recent Advances in Organic and Inorganic Emitters for Deep‐Tissue Molecular Imaging
Authors: Feng Ding, Yong Fan, Yao Sun, Fan Zhang
Journal: Advanced Healthcare Materials (2019)

Abstract In vivo second near‐infrared (NIR‐II, 1.0–1.7 µm) bioimaging , a rapidly expanding imaging tool for preclinical diagnosis and prognosis, is of great importance to afford precise dynamic actions in vivo with high spatiotemporal resolution, deeper penetration, and decreasing light absorption and scattering. In the course of preclinical practices, organic and inorganic emitters with NIR‐II signals are indispensable keys to open the invisible biological window. In this review, NIR‐II emitters, including but not limited to organic emitters like organic small molecules and copolymers, and inorganic emitters such as lanthanide‐based nanocrystals, quantum dots like Ag 2 S dots, and carbon nanotubes, are described, especially regarding their unique optical features and noteworthy functions for animal bioimaging. Along with these existing advances, the challenges and potential spaces for further progress are discussed to offer an approximate direction for future researches.
Modulation of asymmetric cell division as a mechanism to boost CD8 <sup>+</sup> T cell memory
Authors: Mariana Borsa, Isabel Barnstorf, Nicolas S. Baumann, Katharina Pallmer, Alexander Yermanos, Fabienne Gräbnitz, Niculò Barandun, Annika Hausmann, Ioana Sandu, Yves Barral, Annette Oxenius
Journal: Science Immunology (2019)

Asymmetric partitioning of fate determinants is a mechanism that contributes to T cell differentiation. However, it remains unclear whether the ability of T cells to divide asymmetrically is influenced by their differentiation state, as well as whether enforcing asymmetric cell division (ACD) rates would have an impact on T cell differentiation and memory formation. Using the murine LCMV infection model, we established a correlation between cell stemness and the ability of CD8+ T cells to undergo ACD. Transient mTOR inhibition was proven to increase ACD rates in naïve and memory cells and to install this ability in exhausted CD8+ T cells. Functionally, enforced ACD correlated with increased memory potential, leading to more efficient recall response and viral control upon acute or chronic LCMV infection. Moreover, transient mTOR inhibition also increased ACD rates in human CD8+ T cells. Transcriptional profiling revealed that progenies emerging from enforced ACD exhibited more pronounced early memory signatures, which functionally endowed these cells with better survival in the absence of antigen exposure and more robust homing to secondary lymphoid organs, providing critical access to survival niches. Our data provide important insights into how ACD can improve long-term survival and function of T cells and open new perspectives for vaccination and adoptive T cell transfer therapies.
THU-296-Hepatic and visceral adipose tissue expression of vitamin D receptor and vitamin D hydroxylases in relation to non-alcoholic fatty liver disease and adipose tissue inflammation
Authors: Ilaria Barchetta, Flavia Agata Cimini, Caterina Chiappetta, Claudio Di Cristofano, Gianfranco Silecchia, Frida Leonetti, Maria Gisella Cavallo
Journal: Journal of Hepatology (2019)
Toxicity-sparing in-tumor profiling of multiple drugs simultaneously in canine patients with sarcoma.
Authors: Jason Frazier, Alicia Moreno-Gonzalez, William Kerwin, Jessica Bertout, Joseph Casalini, Korashon Watts, Sally Ditzler, Thomas Deckwerth, Richard A Klinghoffer
Journal: Journal of Clinical Oncology (2015)

e22177 Background: Cancer drug developers face a fundamental challenge in the way new candidate drugs are evaluated. Early stage compounds are tested in preclinical models that lack important components of the complex tumor microenvironment and poorly reflect disease seen in the clinic. To address this issue we present a technology called CIVO that demonstrates the potential for testing experimental compounds directly in tumors of cancer patients prior to entry into formal clinical trials. Methods: A two-stage feasibility study was performed in canine patients with sarcoma. In the first stage, localized tumor response to a set of four drugs commonly used in the soft-tissue sarcoma clinic including Doxorubicin, Mafosfamide (an active surrogate of the pro-drug Ifosfamide), Gemcitabine, and Docetaxel was evaluated. In the second stage, an additional novel compound (PS-1001) was evaluated and compared to the conventional agents. An eight-needle arrayed microinjection device delivered microdose amounts of each drug or compound to distinct and localized positions of the tumor. Forty-eight hours after injection, tumors were surgically removed and processed for immunohistochemistry-based biomarker analysis. Results: Consistent with the use of doxorubicin as first line therapy in the soft tissue sarcoma clinic, the frequency and extent of response of localized tumor kill induced by Doxorubicin (10/11 patients) exceeded those of all other agents tested. Furthermore, consistent with the ability to induce immunogenic cell death, Doxorubicin induced localized increases in CD3 positive T-cells and in polymorphonuclear neutrophils. None of the other conventional agents induced a consistent immune response. Tumor profiling of PS-1001 revealed unexpected robust increases in localized immune cell infiltrate including NK-cells and polymorphonuclear neutrophils (6/7 patients) that exceeded the immune response induced by Doxorubicin. No toxicity was observed in any patient according to VCOG Conclusions: CIVO technology has the potential for functionally profiling experimental compounds directly in the only truly accurate disease context, the cancer patient.
Diabetes Awareness Among Coronary Artery Disease Patients Is Higher in Women Than in Men
Authors: Christoph H. Saely, Arthur Mader, Christine F. Heinzle, Daniela Zanolin-Purin, Barbara Larcher, Alexander Vonbank, Heinz Drexel
Journal: Diabetes Care (2019)

The risk of diabetes complications can be attenuated by appropriate diabetes management. Unfortunately, many patients with type 2 diabetes mellitus (T2DM) are unaware of their condition (1) and therefore cannot receive appropriate treatment.

Diabetes in various populations is similarly prevalent in men and women, but important sex differences exist with regard to the impact of diabetes on patient outcomes (2). In this context, it appears important to understand how diabetes awareness, i.e., the proportion of patients with diabetes knowing that they have the condition, differs between men and women. Importantly, sex differences in diabetes awareness have not yet been investigated in the extremely high-risk patients with both T2DM and established coronary artery disease (CAD).

We therefore investigated 1,209 unselected consecutive Caucasian patients, 422 women and 787 men, who were referred to coronary angiography for the evaluation of established or suspected stable CAD. Patients with type 1 diabetes (C-peptide negative) were not enrolled. A total of 292 women and 706 men had CAD at angiography and were …
Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures
Authors: Aatur D Singhi, Marina N Nikiforova, Jennifer Chennat, Georgios I Papachristou, Asif Khalid, Mordechai Rabinovitz, Rohit Das, Savreet Sarkaria, M Samir Ayasso, Abigail I Wald, Sara E Monaco, Michael Nalesnik, N Paul Ohori, David Geller, Allan Tsung, Amer H Zureikat, Herbert Zeh, J Wallis Marsh, Melissa Hogg, Kenneth Lee, David L Bartlett, James F Pingpank, Abhinav Humar, Nathan Bahary, Anil K Dasyam, Randall Brand, Kenneth E Fasanella, Kevin McGrath, Adam Slivka
Journal: Gut (2019)

Objective Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. Design We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. Results The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2 -amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. Conclusions The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.
Clinical Application of 18F-AlF-NOTA-Octreotide PET/CT in Combination With 18F-FDG PET/CT for Imaging Neuroendocrine Neoplasms
Authors: Tingting Long, Nengan Yang, Ming Zhou, Dengming Chen, Yulai Li, Jian Li, Yongxiang Tang, Zhaoqian Liu, Zibo Li, Shuo Hu
Journal: Clinical Nuclear Medicine (2019)

The study is to evaluate biodistribution, dosimetry, safety, and clinical usefulness of F-AlF-NOTA-octreotide (F-OC) PET/CT in combination with F-FDG PET/CT for detection of neuroendocrine neoplasms (NENs).The biodistribution, dosimetry, and safety of F-OC were evaluated in 3 healthy volunteers. Twenty-two NEN patients underwent PET/CT at 60 minutes after intravenous injection of 3.7 to 4.44 MBq (0.1-0.12 mCi) per kilogram of body weight of F-OC. This was followed by F-FDG PET/CT within a 2-week period.F-OC was well tolerated by all healthy volunteers and NEN patients. The calculated effective dose of F-OC was 0.023 ± 0.002 mSv/MBq. In NEN patients, we observed prominent F-OC tumor uptake and high tumor-to-background ratios. Tumor uptake of F-OC was greater than that of F-FDG, and this was particularly evident in G2 NENs (median SUVmax, 45.6 vs 4.3; P < 0.015). Tumor uptake of F-OC or F-FDG was significantly correlated with tumor differentiation (P < 0.05). Dual tracer PET/CT detected more lesions and also yielded information on the biological status of tumors.The tracer F-OC exhibited favorable safety and dosimetry profiles. F-OC provided superior imaging of well-differentiated NENs and significantly higher tumor-to-background ratio compared with F-FDG. Combining F-FDG with F-OC PET/CT has the potential to improve NEN staging and management of patient treatment.
PS-112-Endoscopic duodenal mucosal resurfacing improves hepatic fat fraction, glycemic and lipid profiles in type 2 diabetes
Authors: Guruprasad Aithal, Naomi Sakai, Manil Chouhan, David Hopkins, Rachel Batterham, Rehan Haidry, Bu Hayee, Jacques Deviere, Manoel Galvao Neto, Geltrude Mingrone
Journal: Journal of Hepatology (2019)
Safety checklist cuts risk of death after surgery in Scotland
Authors: Bryan Christie
Journal: BMJ (2019)

A simple safety checklist is being credited with reducing the risk of death after surgery in Scotland.

A study published in the British Journal of Surgery analysed the outcomes of 6.8 million operations carried out during 2000-14.1 It found a 36.6% relative reduction in mortality (95% confidence interval –55.2 to –17.9) after Scotland’s nationwide implementation of the World Health …
Prognostic characterization in the terminal phase of cancer: May clinical prediction be improved?
Authors: Paola Ermacora, Micol Mazzer, Giuseppe Aprile, Antonio Orlando, Monica Cattaruzza, Miriam Isola, Giorgia Gregoraci, Gaetano Pascoletti, Alessandra Bin, Fabio Puglisi, Cosimo Sacco, Gianpiero Fasola
Journal: Journal of Clinical Oncology (2015)

e20507 Background: An accurate prediction of survival of advanced cancer patients (pts) is mandatory to avoid inappropriate therapies and tailor appropriate treatments; nonetheless, the Clinical Prediction of Survival (CPS) results often inaccurate. The aim of this prospective study was to assess the role of clinical variables in predicting survival and to compare the accuracy of CPS estimated by two experienced physicians and dedicated nurses. Methods: 336 advanced cancer pts were included in the analysis. Among clinical variables, the need for oxygen therapy, the presence of pain (NRS scale), the presence of anxiety, level of family support (degree of care during hospitalization) and grade of autonomy (ADL score) were evaluated for each patient. Plasma levels of albumin and PCR were also considered. The impact of all these parameters on the 30-day survival was assessed using logistic regression, while the overall survival was estimated with the Cox model. Concordance between CPS and overall survival was studied by using Cohen’s K index. Results: Median survival was 14 days (range 0-544), the estimated survival using the Kaplan-Meier method was 30% at 30 days and 16% at 60 days. ADL score and anxiety significantly influenced the 30-day survival in univariate analysis: OR 0.70, 95%CI 0.62-0.81, p < 0.0001 and OR 4.31, 95%CI 1.65-11.22, p = 0.003. These variables were also associated with overall survival: OR 1.54, 95%CI 1.12-2.11, p = 0.007 and OR 0.86, 95%CI 0.81-0.92, p < 0.0001). The other analysed variables did not show any significant association with survival. In the multivariate analysis only ADL was associated with 30-day and overall survival (OR 0.84, 95%CI0.77-0.91, p < 0.0001 and OR 0.71, 95%CI 0.60-0.84, p < 0.0001). We found a modest correlation between CPS estimated by evaluators and overall survival:K index was 0.43 for physician 1, 0.41 for physician 2 and 0.45 for nurse. All healthcare professionals underestimated the real survival (p = 0.005 for physician 1, p = 0.028 for physician 2, p = 0.020 for nurses). Conclusions: Our data confirm the prognostic value of ADL, a score linked with pts’ performance status. To accurately prognosticate survival of advanced cancer pts, CPS should be used with other prognostic factors.
SAT-268-Non-invasive prediction of gastroesophageal varies by serum wisteria floribunda agglutinin positive Mac-2 binding protein and FIB-4 index in chronic hepatitis C
Authors: Keiya Watakabe, Nobuharu Tamaki, Sakura Kirino, Leona Osawa, Wang Wan, Mao Okada, Takao Shimizu, Mayu Higuchi, Kenta Takaura, Shun Kaneko, Kaoru Tsuchiya, Hiroyuki Nakanishi, Jun Itakura, Masayuki Kurosaki, Namiki Izumi
Journal: Journal of Hepatology (2019)
Leukocyte Adhesion: Reconceptualizing Chemokine Presentation by Glycosaminoglycans
Authors: Gerard J. Graham, Tracy M. Handel, Amanda E.I. Proudfoot
Journal: Trends in Immunology (2019)

Recruitment of immune cells from the vasculature relies on the presentation of glycosaminoglycan-bound chemokines on the luminal side of vascular endothelial cells. However, the current model of chemokine-glycosaminoglycan interactions, and its implications for receptor interactions, remains poorly developed. We propose a refined 'Chemokine Cloud' model, arguing that chemokines are not presented to leukocytes bound to glycosaminoglycans, but rather, in solution while sequestered within the hydrated glycocalyx. We posit that glycosaminoglycans provide an immobilized chemokine depot maintaining a 'cloud' of 'solution-phase' chemokines within the glycocalyx, and that it is this soluble form of any given chemokine that interacts with leukocyte-bound receptors. Our proposition clarifies certain anomalies associated with the current model of chemokine-glycosaminoglycan interactions, with implications for the design of blockers of chemokine function.
FRI-394-Impact of early kidney dysfunction in the incidence of major cardiovascular events after liver transplantation
Authors: Lydia Sastre, Raquel García, Julián Gonzalo Gándara, Julissa Lombardo, Jonathan Aguirre, Pablo Ruiz, Jordi Colmenero, Miquel Navasa, Gonzalo Crespo
Journal: Journal of Hepatology (2019)
Abstract 20504: Comparison of Intensive Care Provision Following the Stage 1 Procedure Among 5 Centers Using Growth Chart-Like 'Care Curves'
Authors: Anjuli Sinha, Sarah van den Bosch, Jesse Davidson, Melissa N Smith-Parrish, Justin Elhoff, Joshua J Blinder, John N Kheir
Journal: Circulation (2017)

Introduction: The variabilities in the care provided to patients in the post-operative period may be important determinants to outcome. We propose a new construct for the comparison of intensive ca...
Criminalisation of unintentional error is not in the public interest
Authors: David J Nicholl
Journal: BMJ (2019)

Ameratunga and colleagues call for legal reform akin to New Zealand.1 I agree, but we should be under no illusion of the huge blocks to progress. The cost of medical negligence claims went up 30% in a year to £2.2bn in 2017-18.2 Spending this staggering sum of money on litigation hinders change.

Criminalisation …
Closing the Gap: Results of the Multicenter Canadian Randomized Controlled Trial of Structured Transition in Young Adults With Type 1 Diabetes
Authors: Tamara Spaic, Tracy Robinson, Ellen Goldbloom, Patricia Gallego, Irene Hramiak, Margaret L. Lawson, Janine Malcolm, Jeffrey Mahon, Deric Morrison, Amish Parikh, Angelo Simone, Robert Stein, Artem Uvarov, Cheril Clarson, T. Spaic, T. Robinson, EB. Goldbloom, P. Gallego, I. Hramiak, ML. Lawson, J. Malcolm, JL. Mahon, D. Morrison, A. Parikh, A. Simone, R. Stein, A. Uvarov, C. L. Clarson, Tamara Spaic, Tracy Robinson, Ellen Goldbloom, Patricia Gallego, Irene Hramiak, Margaret Lawson, Janine Malcolm, Jeffrey Mahon, Deric Morrison, Amish Parikh, Angelo Simone, Robert Stein, Artem Uvarov, Cheril Clarson
Journal: Diabetes Care (2019)

To determine if a structured transition program for young adults with type 1 diabetes improves clinic attendance, glycemic control, diabetes-related distress, quality of life, and satisfaction with care.In this multicenter randomized controlled trial, young adults (17-20 years) with type 1 diabetes were randomly assigned to a transition program with a transition coordinator or to standard care. The intervention lasted 18 months (6 in pediatric and 12 in adult care). The primary outcome was the proportion of participants who failed to attend at least one adult diabetes clinic visit during the 12-month follow-up after completion of the intervention.We randomized 205 participants, 104 to the transition program and 101 to standard care. Clinic attendance was improved in the transition program (mean [SD] number of visits 4.1 [1.1] vs. 3.6 [1.2], P = 0.002), and there was greater satisfaction with care (mean [SD] score 29.0 [2.7] vs. 27.9 [3.4], P = 0.032) and less diabetes-related distress (mean [SD] score 1.9 [0.8] vs. 2.1 [0.8], P = 0.049) reported than in standard care. There was a trend toward improvement in mean HbA1c (8.33% [68 mmol/mol] vs. 8.80% [73 mmol/mol], P = 0.057). During the 12-month follow-up, there was no difference in those failing to attend at least one clinic visit (P = 0.846), and the mean change in HbA1c did not differ between the groups (P = 0.073). At completion of follow-up, the groups did not differ with respect to satisfaction with care or diabetes-related distress and quality of life.Transition support during this 18-month intervention was associated with increased clinic attendance, improved satisfaction with care, and decreased diabetes-related distress, but these benefits were not sustained 12 months after completion of the intervention.
European Union (EU) vs. non-EU (NOEU) countries study compliance: the experience of the phase III FLORENCE study testing febuxostat in the Tumor Lysis Syndrome (TLS) prevention.
Authors: Simone Baldini, Cristina Rossi, Michele Spina, Massimo Federico, Karin Jordan, Igor Aurer, Zsolt Nagy, Josep M. Ribera, Alexander Pristupa, Nataliia L. Glushko, Dusan Ristic, Simona Scartoni, Alessandra Scordari, Mariagiuseppa Matera, Carlo Alberto Maggi, Angela Capriati, Cecilia Simonelli
Journal: Journal of Clinical Oncology (2015)

e20677 Background: Harmonization of clinical practice and standard of care allow multicenter pivotal trials to be successfully run both in EU and NOEU Countries, with patients’ recruitment increasing in favor of NOEU sites. Comparative data on the performance of EU vs. NOEU investigators in terms of compliance to study protocol and data collection are now offered by the FLORENCE study (a pivotal phase III study of Febuxostat vs. Allopurinol for TLS prevention in hematologic malignancies; NCT01724528) that included 75 European sites distributed in both EU (HR, CZ, DE, HU, IT, PL, RO, ES) and NOEU (RU, RS, UA) contributing with 193 and 152 randomized patients (0.35 and 0.44 patients/month/site), respectively. Methods: Compliance of sites to FLORENCE was evaluated by counting all protocol violations (APVs) and major protocol violations (MPVs) weighted for the number of randomized patients grouped by EU and NOEU sites. Distribution of APVs and MPVs was compared using a Chi Square test at 5% significant level. Additionally, distribution of the most affected MPVs subcategories, namely eligibility of randomized patients, errors in treatment intake, use of prohibited medications, compliance to stratification factors/safety data recording (SFSDR), compliance to scheduled Visits/Assessments (SVAs) and timely reporting of serious adverse events (weighted for the number of patients as per APVs and MPVs) was compared using a Fisher’s Exact test at 5% significant level. Results: APVs were 815, 32.4% in NOEU vs. 67.6% in EU sites (p = .0686). MPVs were 68, 17.7% in NOEU vs. 82.3% in EU (p < .0001), however the difference was due to only two MPVs subcategories, namely compliance to SFSDR (12.5% vs. 87.5% for NOEU and EU sites respectively; p = .0056) and to SVAs (4.2% vs. 95.8% for NOEU and EU sites respectively; p = .0001). Conclusions: Overall compliance to FLORENCE study was high with limited MPVs; NOEU sites had less MPVs affecting compliance to SFSDR and to SVAs, which may reflect difference in assigned site resources. The FLORENCE study provides the first evidence that NOEU and EU sites run a multicenter pivotal trial with high and almost comparable study compliance Clinical trial information: NCT01724528.