tbuckley/cabot-search huggingface dataset:
Longitudinal tracking of necrotic cell-free DNA in patients with oncological diseases.
Authors: Rajaram Krishnan, Juan Pablo Hinestrosa, George Thomas, Carlos Rosales, Anu Iwanefun, Irina Dobrovolskaia, Mark J. Adler, David Bodkin, Stefanie Sacknoff, David Charlot
Journal: Journal of Clinical Oncology (2015)

e22141 Background: The presence of necrotic cell-free DNA (ncfDNA) has been shown to be elevated in cancer patients when compared to healthy individuals. Tracking the concentration of ncfDNA provides insight into tumor dynamics without the need to perform additional molecular characterizations. Currently, protein biomarkers and imagining are relied upon for monitoring treatment. Biological Dynamics’ AC Electrokinetic (ACE) technology is a rapid streamlined sample-to-answer approach to characterize the presence of ncfDNA in the blood without pre-processing or dilution. Paired with fluorescent microscopy and specific intercalating dyes or antibody labeling, the technology can quantify the isolated ncfDNA. With this approach, a rapid assay has been developed that can track remission, stable, or progressive disease in multiple cancers. Methods: Plasma samples from cancer patients (ovarian, breast, colorectal, lung, and gall bladder) were collected in Heparin tubes and processed according to standard protocols. The concentration of ncfDNA is quantified by loading the samples in the ACE system along with two calibrators. The calibrators are physiological saline solutions with specific concentrations of high molecular weight DNA ( > 500 bp) at a high and a low concentrations. The limit of detection for isolated ncfDNA is around 3 - 6 pg/μL when using specific intercalating fluorescent dyes for dsDNA.Levels of protein biomarkers are measured by sandwich immunoassay. Results: The presence of ncfDNA is confirmed in patients with local, regional or distant diseases while healthy volunteers do not show the presence of the marker. By running the two calibrators in parallel with the sample, the concentration of ncfDNA can be determined. This quantification allows for treatment response monitoring by longitudinal tracking. The quantification of ncfDNA showed direct correlation with levels of protein biomarkers and clinical annotation. Conclusions: Tracking of ncfDNA on a weekly or biweekly basis may be a helpful tool for treatment response / tumor burden monitoring. Doing so will allow for faster assessment of therapy efficacy and can assist medical practitioners in treatment decision making or discover drug resistance patterns.
SAT-115-Fondaparinux vs low molecular weight heparin in the treatment of non malignant portal vein thrombosis in patients with cirrhosis
Authors: Marco Senzolo, Salvatore Piano, David Sacerdoti, Silvia Tonello, Alberto Zanetto, Marta Tonon, Paolo Simioni, Giancarlo Bombonato, Patrizia Burra, Paolo Angeli
Journal: Journal of Hepatology (2019)
Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study
Authors: Jason K. Sicklick, Shumei Kato, Ryosuke Okamura, Maria Schwaederle, Michael E. Hahn, Casey B. Williams, Pradip De, Amy Krie, David E. Piccioni, Vincent A. Miller, Jeffrey S. Ross, Adam Benson, Jennifer Webster, Philip J. Stephens, J. Jack Lee, Paul T. Fanta, Scott M. Lippman, Brian Leyland-Jones, Razelle Kurzrock
Journal: Nature Medicine (2019)
Measles in 2019 — Going Backward
Authors: Catharine I. Paules, Hilary D. Marston, Anthony S. Fauci
Journal: New England Journal of Medicine (2019)

Measles in 2019 — Going Backward Recent increases in measles cases in the United States mirror patterns in other countries that had previously eliminated the virus. This resurgence is all the more frustrating since the disease is entirely preventable through vaccination.
A Proliferation Inducing Ligand (APRIL) Directly Impacts Immune Regulatory Subsets to Regulate Suppressive Multiple Myeloma Bone Marrow Microenvironment
Authors: Yu-Tzu Tai, Liang Lin, Lijie Xing, Kenneth Wen, Phillip Hsieh, An Gang, Lugui Qiu, Nikhil Munshi, Paul G Richardson, Kenneth C Anderson
Journal: Blood (2017)
THU-200-The Real-Eorld Israeli experience of treating mild and severe chronic hepatitis C patients with elbasvir/grazoprevir: A large multi-center cohort study
Authors: Eli Zuckerman, Eyal Ashkenazi, Yulia Kovalev, Oranit Cohen-ezra, Ella Veitsman, Tarek Saadi, Matthias Carlebach, Dr. Rawi Hazzan, Rifaat Safadi, Tova Goldberg, Ran Oren, Yaffa Ashur, Michal Carmiel, Yona Kitay, Ruthy Hadary, Saif Abu-Mouch, Rafael Bruk, Yoram Menachem, Helena Katchman, Oren Shibolet, Orly Sne Arbib, Haim Shirin, Ran Tur-Kaspa, Marius Braun, Michal Cohen-Naftaly, Amir Shlomai
Journal: Journal of Hepatology (2019)
Exosomes in NSCLC: Analysis of its cargo as a source of biomarkers
Authors: E. Durendez-Saez, S. Calabuig Fariñas, C. Suarez, M. Mosqueda, S. Gallach, E. Escorihuela, A. Moreno, N. Dong, A. Herreros Pomares, E. de la Cueva, A. Martinez-Romero, E. Serna, J.M. Paramio, E. Jantus-Lewintre, C. Camps
Journal: Annals of Oncology (2019)

Background: Exosomes are membranous vesicles around 40-130 nm secreted by cells, carrying key information to distant tissues. Exosomes have been detected in different types of clinical samples and may play a key role in NSCLC. They intervene in several processes such as angiogenesis, metastatic niche formation, immunosuppression; being relevant in stem cell differentiation. The main objective of this study was to analyze exosomal cargo from NSCLC cell lines and primary cultures under two conditions: suspension cultures with cancer stem cells features (3D tumorspheres) and adherent cultures (2D). Methods: Cell cultures were established from NSCLC resected patients and cell lines. Exosomes isolation was performed by ultracentrifugation. Characterization was carried out by NTA, electron microscopy, immunoblot and flow cytometry. Exosomal DNA was extracted to determine the mutational status of EGFR and RAS genes by BEAMing dPCR (Sysmex®). Transcriptomic analysis has been carried out from exosomal RNA with Clariom D Human microarrays (Affymetrix®), (p ≤ 0.01). Results: Regarding exosomes characterization, NTA and electron microscopy showed an exosome size from 108-125 nm. Exosomes surface markers were detected by immunoblot and flow cytometry. Mutational analysis of EGFR and RAS genes shown the same pattern displayed by the origin cells. Transcriptomic analysis showed an expression of mRNAs, miRNAs and precursors significantly different between 3D and 2D exosomes. Afterwards, their targets were identified and a pathway enrichment analysis was performed to know in which biological processes (cancer-related) are involved. Significant differential expressions were also found between ADC vs SCC-derived exosomes. Interestingly, 7 exosomal miRNAs (miR-200c, 29a, 339, 224, 31, 21, 33a) had already been identified as overexpressed in NSCLC tissue by our group. Moreover, miR-339 and miR-21 were related to prognosis (p < 0.05) in ADC. Conclusions: Differences in exosomal cargo have been observed between: i) 3D vs 2D cultures and ii) ADC vs SCC. In addition, the same mutational pattern was detected in exosomes as compared with parental cultures. Therefore, exosomes can be a useful source for biomarkers analysis in NSCLC. Legal entity responsible for the study: Fundación de Investigación del Hospital General Universitario de Valencia (FIHGUV). Funding: Supported by grant GV/2018/026 & Asociación Española contra el Cáncer (AECC Valencia). Disclosure: All authors have declared no conflicts of interest.
Screening Colonoscopy Should Be Available to All
Authors: Katerina Wells, James Fleshman
Journal: JAMA Surgery (2019)

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Truth, Trust, and Transparency—The Highly Complex Nature of Patients’ Perceptions of Conflicts of Interest in Medicine
Authors: Kathryn R. Tringale, Jona A. Hattangadi-Gluth
Journal: JAMA Network Open (2019)

Genevieve P. Kanter, PhD; Daniel Carpenter, PhD; Lisa S. Lehmann, MD, PhD; Michelle M. Mello, JD, PhD
SAT-212-Treatment with mTOR inhibitors is an independent risk factor for chronic hepatitis E in transplant patients with increased transaminases levels
Authors: Mar Riveiro-Barciela, Judit Vidal-González, Luisa Roade, Joan Martínez Camprecios, Basilio Rodríguez, Manel Perelló, Guillem Ortí, Virginia Robles, Cristina Berastegui, Jordi Navarro, Fernando Martínez-Valle, Itxarone Bilbao, Lluís Castells, Leonardo Nieto, Francisco Rodríguez-Frías, Maria Buti, Rafael Esteban
Journal: Journal of Hepatology (2019)
Phase II trial of single agent amrubicin (A) in patients (pts) with previously treated advanced thymic malignancies (TM).
Authors: Heather A. Wakelee, Sukhmani Kaur Padda, Matthew Burns, Aaron John Spittler, Jonathan Riess, Melanie San Pedro-Salcedo, Kavitha Ramchandran, Matthew A. Gubens, Joel W. Neal, Patrick J. Loehrer
Journal: Journal of Clinical Oncology (2015)

7580 Background: There are limited treatment options for pts with TM and chemotherapy efficacy is often restricted by cumulative toxicity such as neuropathy (taxanes) and cardiomyopathy (anthracyclines). This trial investigated single agent amrubicin (A), a third generation anthracycline and topoisomerase II inhibitor with minimal cardiac toxicity, in TM pts. Methods: This was an open-label investigator-initiated single drug trial at 2 institutions with overall response rate (RR) as the primary endpoint. Eligible pts had TM (thymoma (T) or thymic carcinoma (TC)) with progressive disease (PD) or relapse after ≥ 1 prior chemotherapy regimen, and adequate organ function including left ventricular ejection fraction (LVEF) of > 50%. The initial treatment plan consisted of A at 40 mg/m2 IV days 1-3 repeated in 21-day cycles with growth factor support. Results: 33 pts (14T/19TC) enrolled from 7/2011 to 4/2014: 14 women/19 men; age 30-81 yo; 9 Asian, 1 African-American, 23 White. A high rate of febrile neutropenia (FN) led to an amended starting dose of 35 mg/m2 days 1-3 of 21-day cycles. In total, 7 pts experienced FN with 1 related death. Other grade 3/4 possibly related events included thrombocytopenia (n = 3), neutropenia (without fever, n = 3), anemia (n = 7), lethargy/fatigue (n = 7), perirectal abscess (n = 2), palmar-plantar erythrodysesthesia (n = 3), syncope (n = 2), venous embolism (n = 2), and 1 pt each with sepsis, oral abscess, pneumonia, UTI, mucositis, chest pain, and epigastric pain. Other toxicities were mild and A was generally well tolerated. No significant changes in LVEF were noted on serial echocardiograms. RR was 18% (n = 6, all partial): 29% (n = 4) in T and 11% (n = 2) in TC. Disease control rate (DCR) at first evaluation was 88% overall (n = 29): 100% (n = 14) in T and 78% (n = 15) in TC. 4 pts had PD or died before first assessment. All but 5 pts received at least 4 cycles, and 17 received 10 or more cycles, with 34 cycles as the highest number to date. 5 pts remain on therapy. Conclusions: Amrubicin, at 35 mg/m2 IV days 1-3 on a 21-day cycle, shows promise as a single agent in pre-treated pts with T and TC with an 18% RR and no unexpected toxicity. Further exploration as a single drug or in combination is warranted. Clinical trial information: NCT01364727.
Immune-related adverse events (irAEs) in advanced non-small cell lung cancer (aNSCLC): Platelet-to-lymphocyte ratio (PLR) predicts the risk of development and relapse
Authors: A. Pavan, L. Calvetti, A. Dal Maso, I. Attili, G. Pasello, G. Aprile, V. Guarneri, P. Conte, L. Bonanno
Journal: Annals of Oncology (2019)

Background: Immune checkpoint inhibitors (ICIs) have radically changed the treatment of aNSCLC patients (pts). IrAEs are mainly reversible but they require timely recognition and management and may be potentially life-threatening. No predictive markers are available to predict the onset of irAEs and their risk of recurrence. Aim of the study was to evaluate the potential role of circulating markers in predicting the development of irAEs. Methods: We retrospectively reviewed clinical data of aNSCLC pts consecutively treated with ICIs at Istituto Oncologico Veneto (Padua, Italy) and at San Bortolo General Hospital (Vicenza, Italy) between August 2013 and August 2018. We collected data on the type, grading (G) and timing of irAEs and calculated NLR and PLR before first ICI administration and at the onset of the irAEs. The values were dichotomized for analysis in two groups: high (H-) and low (L-) NLR and H- and L-PLR using pre-identified cut-offs of 3 and 180, respectively. Results: The analysis included 194 pts. ICIs were administered as first-line treatment in 29 (15%) pts. Median number of ICIs cycles was 6 (range: 1-66). Median PFS and OS were 4.6 months (m) (95% CI: 3.3-5.9) and 8.7m (95% CI: 6.1-11.4). Seventy-two pts (37%) developed irAEs, mainly G1-2 (68%), with permanent discontinuation of ICI in 23 (32%) cases; 15 pts (20.8%) experienced more than one irAE. Median time to irAE onset was 77 days (7-751 days). Pts with baseline L-NLR and L-PLR values had a higher risk of irAE development (OR = 1.98, 95% CI: 1.09-3.61, p = 0.025 and OR = 2.15, 95% CI: 1.16-3.98, p = 0.016). Multivariate analysis confirmed PLR as independent predictive marker (OR = 2.01, 95%CI: 1.02-3.96; p = 0.045). Among pts who experienced irAE, L-PLR at time of irAE onset was associated with the risk of irAE recurrence or second irAE development (OR = 4.5, 95% CI: 1.11-18.16, p = 0.035). Conclusions: Baseline evaluation of NLR and PLR may be a tool to predict the risk of irAE onset and to personalize clinical follow-up during and after treatment with ICIs. The evaluation of PLR at the time of irAE onset might predict the risk of further toxicity. If validated, PLR value may support the clinical decision of re-introducing ICIs after discontinuation. Legal entity responsible for the study: Istituto Oncologico Veneto (IOV), Padua, Italy. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Impact of unbalanced karyotypes at diagnosis on prognosis of CML.
Authors: Ruediger Hehlmann, Lida Kalmanti, Christian Dietz, Michael Lauseker, Claudia Haferlach, Brigitte Schlegelberger, Martine Jotterand, Martin C. Müller, Mathias Haenel, Claus-Henning Köhne, Maria-Elisabeth Goebeler, Michael Pfreundschuh, Leopold Balleisen, Andreas Burchert, Stefan W. Krause, Markus Pfirrmann, Joerg Hasford, Andreas Hochhaus, Susanne Saussele, Alice Fabarius
Journal: Journal of Clinical Oncology (2015)

7041 Background: Major route additional cytogenetic aberrations (ACA) at diagnosis of chronic myeloid leukemia (CML) indicate an increased risk of progression and shorter survival. Since all major route ACA are unbalanced it is unclear whether other unbalanced ACA at diagnosis also confer an unfavourable prognosis. Methods: On the basis of 1348 Philadelphia chromosome positive chronic phase patients of the randomized CML-study IV we examined the impact of unbalanced minor route ACA at diagnosis in comparison to major route ACA on prognosis. Results: At diagnosis, 1175 patients (87%) had a translocation t(9;22)(q34;q11) and 74 (5.5%) a variant translocation t(v;22) only, while a loss of the Y-chromosome (-Y) was present in addition in 44 (3.3%), balanced or unbalanced minor route ACA each in 17 (1.3% each) cases and major route ACA in 21 (1.6%) cases. Patients with unbalanced minor route ACA achieved complete cytogenetic remission, major molecular remission, progression-free survival (PFS) and overall survival (OS) at similar rates as did patients with t(9;22), t(v;22), -Y, and balanced minor route karyotypes. In contrast, patients with major route ACA had a shorter OS and PFS than all other groups (p < 0.005 for all pairwise comparisons with major route). Five year survival probabilities were for t(9;22): 91.4% (95% CI 89.5 – 93.1), t(v; 22): 87% (77.2 – 94.3), - Y: 89.0% (76.7 – 97.0), balanced: 100%, unbalanced minor route: 92.3% (72.4 – 100), major route: 52.2% (28.2 – 75.5). Conclusions: We conclude that only major route, but not unbalanced minor route ACA at diagnosis have a negative impact on prognosis of CML. This observation of the prognostic relevance of specific cytogenetic aberrations for a given malignancy may be of importance also to other cancers. Clinical trial information: NCT00055874.
FRI-387-Risk factors associated with early post-operative acute kidney injury requiring renal replacement therapy following liver transplantation
Authors: Jeremy Nayagam, Oliver Tavabie, Benjamin Norton, Deepak Joshi, Abid Suddle, John O’grady, Wayel Jassem, Krishna Menon, William Bernal, Nigel Heaton, Kosh Agarwal, Michael Heneghan, Varuna Aluvihare
Journal: Journal of Hepatology (2019)
PS-068-The hepatitis C cascade of care and treatment outcomes among people who inject drugs in a Norwegian low-threshold setting: A real life experience
Authors: Havard Midgard, Ulstein Kjersti, Backe Øystein, Tarjei Foshaug, Linda Elise Couëssurel Wüsthoff, Olav Dalgard
Journal: Journal of Hepatology (2019)
Lidocaine and phenylephrine versus saline placebo nasal spray for the pain and distress of nasogastric tube insertion in young children and infants: a randomised, double-blind, controlled trial
Authors: Simon S Craig, Robert W Seith, John A Cheek, Kathryn Wilson, Diana Egerton-Warburton, Eldho Paul, Adam West
Journal: The Lancet Child & Adolescent Health (2019)
Association of immune-related adverse events (irAEs) and immunotherapy (IT) benefit in advanced non-small cell lung cancer (NSCLC)
Authors: C. Saavedra Serrano, A. Barquín García, E. Corral de la Fuente, J.J. Serrano Domingo, V. Albarrán Artahona, R. Martin Huertas, A. Gómez Rueda, M.E. Olmedo García
Journal: Annals of Oncology (2019)

Background: IT has improved outcomes in advanced NSCLC. However, this therapy can yield significant toxicity secondary to immune activation. Several retrospective studies have reported a direct relationship between IT efficacy and the development of irAEs, in Response Rate (RR) and survival. Methods: We retrospective reviewed our experience with anti-PD1/anti-PDL1 as single agent in advanced NSCLC patients treated between February 2014 and August 2018. Patient and tumor features, irAEs, concomitant and subsequent treatments were collected. Stata 14.1 was used for the analysis. Results: 98 patients were included. Mean age was 62 years (41-85). 73.5% were men. 73.5% had > 30 smoked pack-years. 64.3% were adenocarcinoma, of which 41% showed KRAS mutation; PDL1 was known in 50% of patients (11.2% <1%, 13.3% 1-49%, 25.5% >50%). IT was administered mainly as a second line (61%) and third or later (24.5%). Most employed drug was nivolumab (52%). RR was 33% (partial response 28%, complete response 5%). Disease control rate (DCR) was 55% and progression rate 34% as better response, 67% at the moment of the analysis. irAEs were reported in 30.6%. The table summarizes irAEs. We found a significant association between irAEs and RR (OR 3.71 p 0.005 IC 1.49 - 9.23) and DCR (OR 5.06 p 0.002 IC 1.84 - 13.98). An impact of irAEs in progression-free survival (PFS) (1.7 vs 7.7 months (m) HR 0.44 p 0.002 IC 0.26 - 0.73) and overall survival (OS) (6.1 vs 15.7 m HR 0.53, p 0.026, IC 0.31- 0.93) was found too. Most of the patients requiring steroid therapy during IT was due to an irAE. There was not detrimental effect of steroids in RR (OR 3.17 p 0.01 IC 1.3 - 7.76), DCR (OR 6.17 p 0.000 IC 2.33 - 16.34), PFS (1.6 vs 6 m HR 0.36 p 0.000 IC 0.22 - 0.62) or OS (6.2 vs 13.3 m HR 0.61 p 0.057 IC 0.36 - 1.01).Table155PirAEsGrade% (n)Diarrhea1 2 310.2 (10) 40 (4) 30 (3) 30 (3)Pneumonitis2 34.1 (4) 50 (2) 50 (2)Endocrine1 2 312.2 (12) 36.4 (4) 54.6 (6) 9 (1)Skin1 24.1 (4) 50 (2) 50 (2)Hepatitis1 23.1 (3) 33.3 (1) 66.7 (2) Open table in a new tab Conclusions: The development of irAEs appears to be associated with efficacy of IT in our retrospective review. The use of steroids during IT had no negative impact in RR, DCR or survival. Still, we need prospective studies in order to confirm this hypothesis. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
FRI-404-Multicenter experience evaluating outcomes of HCV-seropositive donors to HCV-seronegative recipients liver transplantation
Authors: Karn Wijarnpreecha, Surakit Pungpapong, Aqel Bashar, Kunam Reddy, Burcin Taner, Michael Leise, Rolland Dickson
Journal: Journal of Hepatology (2019)
FDG PET/CT of Spinal Brucellosis
Authors: Alaa Khalid Alduraibi, Sleiman Naddaf, Mohammed Fahad Alzayed
Journal: Clinical Nuclear Medicine (2019)

A 17-year-old adolescent boy's known case of classical seminoma stage IB for which he underwent right radical orchiectomy. At the first-year follow-up, CT abdomen and pelvis was performed and showed lytic vertebral lesion with left paravertebral necrotic mass that warranted further investigation to exclude disease recurrence. FDG PET/CT scan was performed to evaluate the extent of disease and showed high uptake in the same areas. A biopsy was obtained from the hypermetabolic soft tissue lesion and did not reveal malignant cells. Subsequently, serologic tests were suggestive of brucellosis.
Abstract 15888: Low Endothelial Shear Stress Promotes Diffuse Coronary Endothelial Dysfunction in Patients With Early Coronary Atherosclerosis
Authors: Gerasimos Siasos, Jaskanwal Sara, Marina Zaromitidou, Kyoung H Park, Shi-Wei Yang, Ahmet Umit Coskun, Lilach O Lerman, Dimitris Fotiadis, Lampros Michalis, Michail Papafaklis, Kostas Stefanou, Charles Feldman, Amir Lerman, Peter H Stone
Journal: Circulation (2016)

Introduction: Local hemodynamic factors are important determinants of atherosclerotic plaque development and progression. Hypothesis: Low endothelial shear stress (ESS) is associated with epicardia...