tbuckley/cabot-search huggingface dataset:
Impact of MET variants on PD-L1 expression in pleomorphic lung carcinoma
Authors: A. Januszewski, Y.Z. Zhang, W.-C. Chang, U. Laggner, A. Bowman, T. Adefila-Ideozu, I. Vivanco, M.F. Moffatt, W.O. Cookson, N.P. Gupta, A.G. Nicholson, A. Bowcock, S. Popat
Journal: Annals of Oncology (2019)

Background: Pleomorphic Lung Carcinoma (PC) is a rare subtype of NSCLCs poorly responsive to systemic therapy. It is a heterogenous tumour with both epithelial and sarcomatoid components. MET variants are targetable aberrations and have recently been reported to be more frequent in PCs. The relationship between MET and PD-L1 expression is not well understood. We determined PD-L1 expression in PCs and its relationship with MET variants. Methods: 80 cases of pleomorphic carcinoma were identified from the biobank and diagnostic archives of Royal Brompton Hospital and Imperial College Healthcare NHS trust. DNA was isolated for determination of a. MET copy number by digital droplet PCR (ddPCR) and b. Genomic MET aberrations by NGS. IHC of PD-L1 (28-8) with % positive cells were scored by two pathologists independently and >49% tumour staining was defined as high. Results: 78 cases were evaluated for PD-L1 status with a median score of 44%. 23/63 (36%) cases had MET CN of > 2.2. METex14 splice variants were identified in 5/73 (7.2%) cases. 2/73 (2.7%) cases had deleterious MET mutations. By MET CN status: low/normal MET CN (<2.3) median PDL1 expression was higher (50%) than in high MET CN (> =2.3: 37.5%; p = 0.18). This translates into a significantly fewer number of high PD-L1 expressors (>49%) in cases with high MET CN (>2.2; p = 0.06; Table). There was no significant difference in PDL1 expression between MET mutation vs. wild-type (p = 0.9).Table1O MET copy number and PDL-1 expressionPD-L1 ExpressionMET CN < 2.3MET CN > =2.3TotalPD-L1<50%20 (50%)17 (74%)37PD-L1 >50%20 (50%)6 (26%)26 Open table in a new tab Conclusions: PCs have high levels of PD-L1 expression. There is an inverse relationship between MET CN and PD-L1 expression. This has implications when using checkpoint inhibitors for cases with MET copy number gain in NSCLC. Further evaluation is needed to better understand response to checkpoint inhibitors of PC cases with MET CN gain. Legal entity responsible for the study: The Royal Marsden Foundation NHS Trust. Funding: National Institute for Health Research (NIHR) and British Lung Foundation. Disclosure: All authors have declared no conflicts of interest.
The Meniscus in Normal and Osteoarthritic Tissues: Facing the Structure Property Challenges and Current Treatment Trends
Authors: Caroline A. Murphy, Atul K. Garg, Joana Silva-Correia, Rui L. Reis, Joaquim M. Oliveira, Maurice N. Collins
Journal: Annual Review of Biomedical Engineering (2019)

The treatment of meniscus injuries has recently been facing a paradigm shift toward the field of tissue engineering, with the aim of regenerating damaged and diseased menisci as opposed to current treatment techniques. This review focuses on the structure and mechanics associated with the meniscus. The meniscus is defined in terms of its biological structure and composition. Biomechanics of the meniscus are discussed in detail, as an understanding of the mechanics is fundamental for the development of new meniscal treatment strategies. Key meniscal characteristics such as biological function, damage (tears), and disease are critically analyzed. The latest technologies behind meniscal repair and regeneration are assessed.
SAT-215-Cryoglobulinemia in asymptomatic, symptomatic acute and chronical HEV infections
Authors: Dirk Westholter, Rabea Lubke, Susanne Polywka, Marc Lutgehetmann, Karoline Rutter, Peine Sven, Julian Schulze zur Wiesch, Ansgar Lohse, Sven Pischke, Thomas Horvatits
Journal: Journal of Hepatology (2019)
FRI-210-Establishment of high rates of functional cure of HBeAg negative chronic HBV infection with REP 2139-Mg based combination therapy: Ongoing follow-up results from the REP 401 study
Authors: Michel Bazinet, Victor Pantea, Gheorghe Placinta, Iurie Moscalu, Valentin Cebotarescu, Lilia Cojuhari, Pavlina Jimbei, Liviu Iarovoi, Valentina Smesnoi, Tatiana Musteata, Alina Jucov, Adalbert Krawczyk, Andrew Vaillant
Journal: Journal of Hepatology (2019)
A Versatile Biocompatible Antibiotic Delivery System Based on Self‐Assembling Peptides with Antimicrobial and Regenerative Potential
Authors: Franziska Koch, Katharina Ekat, David Kilian, Timm Hettich, Oliver Germershaus, Herrmann Lang, Kirsten Peters, Bernd Kreikemeyer
Journal: Advanced Healthcare Materials (2019)

Abstract Periodontitis is a chronic inflammatory and tissue‐destructive disease. Since the polymicrobiome in the oral cavity makes it difficult to treat, novel therapeutic strategies are required. Hydrogels based on self‐assembling peptides (SAP) can be suitable candidates for periodontal therapy due to their injectability, biocompatibility, cargo‐loading capacity, and tunable physicochemical and mechanical properties. In this study, two SAP hydrogels (P11‐4 and P11‐28/29) are examined for their intrinsic antimicrobial activity, regenerative potential, and antibiotic delivery capacity. A significant antibacterial effect of P11‐28/29 hydrogels on the periodontal pathogen Porphyromonas gingivalis and a less pronounced effect for P11‐4 hydrogels is demonstrated. The metabolic activity rates of human dental follicle stem cells (DFSCs), which reflect cell viability and may thus indicate the regenerative capacity, are similar on tissue culture polystyrene (TCPS) and on P11‐4 hydrogels after 14 days of culture. Noticeably, both SAP hydrogels strengthen the osteogenic differentiation of DFSCs compared with TCPS. The incorporation of tetracycline, ciprofloxacin, and doxycycline does not affect fibril formation of either SAP hydrogel and results in favorable release kinetics up to 120 h. In summary, this study reveals that P11‐SAP hydrogels combine many favorable properties required to make them applicable as prospective novel treatment strategy for periodontal therapy.
Abstract 15155: Nonsteroidal Anti-Inflammatory Drug Use in Acute Myopericarditis is Associated With Decreased Late Gadolinium Enhancement at 3 Months Follow-Up
Authors: Marina Lovrinovic, Nora Baltensperger, Jan Berg, Christine K Kissel, Jan Kottwitz, Robert Manka, Frank Scherff, Christian Schmied, Dimitri Patriki, Thomas F Lüscher, Bettina Heidecker
Journal: Circulation (2017)

Introduction: Current scientific statements recommend against the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in myocarditis based on animal research. However, the impact of NSAIDs in pati...
Oncogenic kinase inhibition limits Batf3-dependent dendritic cell development and antitumor immunity
Authors: Benjamin D. Medina, Mengyuan Liu, Gerardo A. Vitiello, Adrian M. Seifert, Shan Zeng, Timothy Bowler, Jennifer Q. Zhang, Michael J. Cavnar, Jennifer K. Loo, Nesteene J. Param, Joanna H. Maltbaek, Ferdinand Rossi, Vinod Balachandran, Ronald P. DeMatteo
Journal: The Journal of Experimental Medicine (2019)

Gastrointestinal stromal tumor (GIST) is driven by an activating mutation in the KIT proto-oncogene. Using a mouse model of GIST and human specimens, we show that intratumoral murine CD103+CD11b− dendritic cells (DCs) and human CD141+ DCs are associated with CD8+ T cell infiltration and differentiation. In mice, the antitumor effect of the Kit inhibitor imatinib is partially mediated by CD103+CD11b− DCs, and effector CD8+ T cells initially proliferate. However, in both mice and humans, chronic imatinib therapy decreases intratumoral DCs and effector CD8+ T cells. The mechanism in our mouse model depends on Kit inhibition, which reduces intratumoral GM-CSF, leading to the accumulation of Batf3-lineage DC progenitors. GM-CSF is produced by γδ T cells via macrophage IL-1β. Stimulants that expand and mature DCs during imatinib treatment improve antitumor immunity. Our findings identify the importance of tumor cell oncogene activity in modulating the Batf3-dependent DC lineage and reveal therapeutic limitations for combined checkpoint blockade and tyrosine kinase inhibition.
Monitoring of blood serum amyloid (SAA) to predict outcome of first-line pembrolizumab (P) in patients (pts) with advanced non-small cell lung cancer (ANSCLC)
Authors: V. Di Noia, E. D’Argento, E. Vita, M. Ferrara, P. Damiano, M. Ribelli, A. Cannella, A. Virtuoso, G. Tortora, E. Bria
Journal: Annals of Oncology (2019)

Background: In melanoma pts, SAA inhibits the anti-tumor immune response by the expansion of IL-10-secreting neutrophils. We previously found that baseline high SAA was associated with early progressive disease (PD) in small cohort of ANSCLC pts receiving up-front P. Here we explored the relationship between dynamic monitoring of SAA and survival outcomes in an enlarged cohort. Methods: Pts with ANSCLC (PD-L1 ≥50%) receiving upfront P at our institution, were prospectively evaluated for blood SAA and radiological response at baseline and every 9 weeks during the treatment. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS) and PD rate. The most accurate SAA cut-off to predict PFS was established with a ROC-analysis. Results: We enrolled 37 consecutive pts. Pts characteristics: male/female (70/30%), number of sites <3/≥ 3 (30/70%), ECOG PS 0/≥ 1 (38/62%); never/former or current smokers (54/46%); median age 72.5 (range 59-86) years. Baseline SAA was > the ROC-derived cut-off (73.9 mg/L, AUC 0.77, 95% CI 0.6-0.9,p=0.002) in 11 (30%) pts. After a median follow-up of 11.5 months (m), pts with pre-treatment high SAA achieved worse PFS (1.4 vs not reached [NR], HR 0.11, 95%CI 0.03-0-41, p < 0.0001) andOS(7.2 vs NR, HR 0.07, 95%CI 0.01-0.37, p < 0.0001) compared with those having lower level. Baseline high SAA was also related to PD (p < 0.05). Combining SAA at baseline and the dynamic monitoring, the median PFS was 1.4 m (95%CI 0.6-4.4) when SAA remained high (n = 10) while was not reached at-12 m when SAA remained low (n = 12) or changed (n = 7)(p < 0.0001).The SAA monitoring was also associated with OS (p = 0.0003);the worst prognosis (median 7.2 m, 95%CI 5.4-13.6) was observed in pts maintaining high SAA. Conclusions: Baseline high SAA predicts poor outcome in ANSCLC pts receiving 1stline P, supporting the potential immunosuppressive role. Considering the strong relationship between SAA monitoring and survival outcomes, the acquired resistance to P could be early and easily detected with a simple blood test. This prospective study is currently ongoing to increase the power and to confirm the predictive role of SAA including a control group. Legal entity responsible for the study: Catholic University of Sacred Heart. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
THU-390-Results of a birth cohort hepatitis C screening program in an academic emergency department in Canada
Authors: Camelia Capraru, Steven M. Friedman, Kathy Bates, Tony Mazzulli, Danielle Porplycia, Bentley McCormack, Aaron Vanderhoff, Hemant A Shah, Harry Janssen, Jordan Feld
Journal: Journal of Hepatology (2019)
Antitumor response to microscopic melanoma in the gastric mucosa mimicking ipilimumab-induced gastritis
Authors: Elisa Bello, Justine V. Cohen, Mari Mino-Kenudson, Michael Dougan
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Alongside its clinical success, checkpoint blockade has also given rise to a set of immune-related adverse events (irAEs). In addition to causing considerable morbidity and even mortality, irAEs may limit the success and scope of immunotherapy. Most irAEs arise at mucosal barriers, including the gastrointestinal mucosa, leading most commonly to colitis, though both gastritis and enteritis can result from checkpoint blockade. While guidelines generally recommend confirmatory testing for suspected severe irAEs, the role of endoscopy in diagnosing more moderate irAEs is less clear. Many patients with suspected gastrointestinal irAEs are treated empirically with glucocorticoids based on typical symptoms. Although efficient, this approach may miss less common underlying etiologies, and may expose patients unnecessarily to an increased risk of infection, and a potentially dampened antitumor response. <h3>Case presentation</h3> We report a case of ipilimumab-induced antitumor immunity targeting microscopic gastric melanoma metastases, mimicking checkpoint blockade induced gastritis. Immune suppression was avoided and the immunotherapy was continued. <h3>Conclusion</h3> Checkpoint blockade can induce rapid inflammatory responses to tumor tissue present throughout the body. These responses are desirable, but may also lead to local tissue injury, causing symptoms that may mimic adverse events. This is particularly important to consider in organs where metastatic disease may be unappreciated at the time of treatment, and where irAEs are otherwise common, such as the gastrointestinal tract. In this setting, empiric immune suppression may inhibit antitumor responses, improving symptoms but at a potential cost to therapeutic efficacy.
Gene Expression Profile in Patients with Classical Hodgkin Lymphoma in Brazil: Results from a Pilot Study
Authors: Priscilla Brito Silva, Juliana Monte Real, Ludmila Rodrigues Pinto Ferreira, Gustavo Henrique Esteves, Joao Garibaldi Junior, Adriana M. Damasco Penna, Fabio Nascimento Brito, Egyla Cavalcante, Otavio C. G. Baiocchi
Journal: Blood (2016)
FRI-459-Prognostic performance of ten non-invasive liver function tests in patients with hepatocellular carcinoma submitted to transarterial chemoembolization
Authors: Pedro Costa-Moreira, Joel Silva, Emanuel Dias, Rui Morais, Marco Silva, Patricia Andrade, Helder Cardoso, Pedro Pereira, Margarida Marques, Rosa Coelho, Rodrigo Liberal, Rui Gaspar, Susana Lopes, Guilherme Macedo
Journal: Journal of Hepatology (2019)
SAT-418-Splenic stiffness measurement using the ultrasound-fusion method
Authors: Masashi Hirooka, Yohei Koizumi, Takaaki Tanaka, Kotaro Sunago, Atsushi Yukimoto, Yusuke Imai, Takao Watanabe, Osamu Yoshida, Masanori Abe, Yoichi Hiasa
Journal: Journal of Hepatology (2019)
Advance Care Planning Improves Psychological Symptoms But Not Quality of Life and Preferred End-of-Life Care of Patients With Cancer
Authors: Siew Tzuh Tang, Jen-Shi Chen, Fur-Hsing Wen, Wen-Chi Chou, John Wen-Cheng Chang, Chia-Hsun Hsieh, Chen Hsiu Chen
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: This study was conducted to examine whether a longitudinal advance care planning (ACP) intervention facilitates concordance between the preferred and received life-sustaining treatments (LSTs) of terminally ill patients with cancer and improves quality of life (QoL), anxiety symptoms, and depressive symptoms during the dying process. Patients and Methods: Of 795 terminally ill patients with cancer from a medical center in Taiwan, 460 were recruited and randomly assigned 1:1 to the experimental and control arms. The experimental arm received an interactive ACP intervention tailored to participants’ readiness to engage in this process. The control arm received symptom management education. Group allocation was concealed, data collectors were blinded, and treatment fidelity was monitored. Outcome measures included 6 preferred and received LSTs, QoL, anxiety symptoms, and depressive symptoms. Intervention effectiveness was evaluated by intention-to-treat analysis. Results: Participants providing data had died through December 2017. The 2 study arms did not differ significantly in concordance between the 6 preferred and received LSTs examined (odds ratios, 0.966 [95% CI, 0.653–1.428] and 1.107 [95% CI, 0.690–1.775]). Participants who received the ACP intervention had significantly fewer anxiety symptoms (β, −0.583; 95% CI, −0.977 to −0.189; P = .004) and depressive symptoms (β, −0.533; 95% CI, −1.036 to −0.030; P = .038) compared with those in the control arm, but QoL did not differ. Conclusions: Our ACP intervention facilitated participants’ psychological adjustment to the end-of-life (EoL) care decision-making process, but neither improved QoL nor facilitated EoL care honoring their wishes. The inability of our intervention to improve concordance may have been due to the family power to override patients’ wishes in deeply Confucian doctrine–influenced societies such as Taiwan. Nevertheless, our findings reassure healthcare professionals that such an ACP intervention does not harm but improves the psychological well-being of terminally ill patients with cancer, thereby encouraging physicians to discuss EoL care preferences with patients and involve family caregivers in EoL care decision-making to eventually lead to patient value–concordant EoL cancer care.
FRI-392-Sarcopenia associated with worse pre-transplant psychosocial status and predicted post-transplant diabetes
Authors: Yael Milgrom, Samir Abu Gazala, Abed Khaliala, Reem Gawi, Yusef Azraq, Mina Rowe, Mohamad Masarwah, David Hakimian, Hadar Merhav, Rifaat Safadi
Journal: Journal of Hepatology (2019)
Prognostic importance of pretreatment sodium levels in patients of NSCLC treated with pemetrexed-platinum doublet chemotherapy.
Authors: Kartik Doshi, Manjunath Nookala, Bharati Shriyan, Vikram Gota, Amit Joshi, Vanita Noronha, Kumar Prabhash
Journal: Journal of Clinical Oncology (2015)

e18510 Background: A recent study has shown pretreatment sodium level to be a predictive and prognostic marker in NSCLC patients treated with erlotinib. Low serum sodium (LSS) has been associated with poor outcome in other conditions such as hepatocellular carcinoma, gastric cancer and small cell lung cancer. The objective of this study was to evaluate the prognostic impact of pretreatment sodium levels on progression free survival (PFS) and overall survival (OS) in patients of NSCLC treated with pemetrexed-platinum doublet chemotherapy. Methods: Stage IIIB/IV NSCLC patients aged ≥ 18 years treated between January 2011 to November 2014 at our centre were included in this retrospective study. Patients received pemetrexed 500 mg/m2 with either cisplatin 75 mg/m2or carboplatin (AUC 5) on day 1 of a 21 day cycle for 6 cycles followed by maintenance pemetrexed till progression. Electronic medical record (EMR) database of our hospital was used to retrieve demographic data, pretreatment sodium levels, PFS and OS data. LSS was defined as serum sodium < 136mEq/L. Survival analysis was performed using Kaplan-meier curves and compared between LSS and normal serum sodium (NSS) groups using Log-Rank test. Results: Data was available for 256 patients (M/F = 172/84) with median age of 53 (25-79) yrs. Majority had EGOG PS of 1 (0 = 34, 1 = 172, 2 = 44, 3 = 6). Stage IIIb = 24 (9%), stage IV = 232 (91%). Pretreatment LSS was observed in 75(29%) patients while 181(71%) had NSS. Baseline characteristics were comparable between LSS and NSS groups. Median duration of follow-up was 17 months. Patients with NSS had significantly longer PFS (10.7 vs. 7.4 months; P < 0.05) and OS (17.6 vs. 13.4 months; P < 0.05) compared to LSS group. Conclusions: Pretreatment serum sodium levels is an important prognostic marker in stage IIIB/IV NSCLC patients. The simple possibility of testing coupled with low cost makes it an attractive marker to implement in clinical practice.
The prognostic significance of the cancer stem cells marker (aldehyde dehydrogenase type I [ALDH1]) expression with breast cancer patients.
Authors: Elizaveta Maslyukova, Sergey I. Zabroda, Luiza Korytova, Kazimir Pozharisskiy, Grigoriy Raskin, Oleg Korytov, Razifa Zhabina, Vladimir Sergeev, Evgenii Obuhov
Journal: Journal of Clinical Oncology (2015)

e22051 Background: High ALDH1 expression correlates with more aggressive breast cancer subtypes. The works of several authors have proven that a higher ALDH1 expression corresponds to chemotherapy resistance and lower survival rate. Ginestier et al. have demonstrated that ALDH1 (aldehyde dehydrogenase type I) can be a better marker for the breast cancer stem cells profile, the high quantity of which in the tumor is a bad prognosis predictor. Methods: In the present research we have analyzed the ALDH1 expression with BC patients. Besides we have studied the correlation between the presence of this marker and clinicopathologic properties of BC. The research has been carried out over 83 patients with locally advanced BC (T1-4N0-3M0), who had received treatment from 2005 till 2009. The criteria for including these patients in the research were as follows: histologically confirmed invasive breast cancer diagnosis, age older than 18 years, ECOG 0 or 1. All the necessary clinical data have been obtained through detailed studies of medical documentation and through dynamic monitoring of the patients. Results: The analysis of dependence of time period till the development of metastases on the ALDH1 expression has statistically proved the decrease of time period till the advance of the disease at high expression (ALDH1(high)) with BC patients as compared to the patients with low expression (ALDH1(low)). Similar regularity has been observed during studies of general survival rate. The survival rate of the patients whose cancer cells had the ALDH1 expression less than 1 % was statistically higher than in the group of patients with high ALDH1 expression (higher than 1%). The plausibility of the differences between the survival curves was proved by the Gehan's Wilcoxon and Cox's F-Test. Conclusions: The present research shows the importance of ALDH1 status in the studies of the cancer stem cells and defines the ALDH1 as potential prognostic marker and possibly a therapeutic target for treating BC patients in the future.
FRI-016-Validation of the PREsTo machine learning algorithm for the prediction of disease progression in patients with primary sclerosing cholangitis
Authors: John Eaton, Konstantinos Lazaridis, Pietro Invernizzi, Olivier Chazouillères, Gideon Hirschfield, Herold Metselaar, Henning Grønbæk, Xiaomin Lu, Chuhan Chung, Mani Subramanian, Robert Myers, Bryan Mccauley, Elizabeth Atkinson, Brian Juran, Zachary Goodman, Michael P. Manns, Christopher Bowlus, Cynthia Levy, Andrew Muir
Journal: Journal of Hepatology (2019)
Single Lesion on Prostate-specific Membrane Antigen-ligand Positron Emission Tomography and Low Prostate-specific Antigen Are Prognostic Factors for a Favorable Biochemical Response to Prostate-specific Membrane Antigen-targeted Radioguided Surgery in Recurrent Prostate Cancer
Authors: Thomas Horn, Markus Krönke, Isabel Rauscher, Bernhard Haller, Stephanie Robu, Hans-Jürgen Wester, Margret Schottelius, Fijs W.B. van Leeuwen, Henk G. van der Poel, Matthias Heck, Jürgen E. Gschwend, Wolfgang Weber, Matthias Eiber, Tobias Maurer
Journal: European Urology (2019)
FRI-137-l-carnitine impedes hepatitis B surface antigen loss through immunosuppressive effect in chronic hepatitis B virus infection
Authors: Shuqin Gu, Ling Guo, Chengcong Chen, Shihong Zhong, Weibin Wang, Libo Tang, Jinlin Hou, Yongyin Li
Journal: Journal of Hepatology (2019)
Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted helminths in Kenya: a cluster-randomised controlled trial
Authors: Rachel L Pullan, Katherine E Halliday, William E Oswald, Carlos Mcharo, Emma Beaumont, Stella Kepha, Stefan Witek-McManus, Paul M Gichuki, Elizabeth Allen, Tom Drake, Catherine Pitt, Sultani H Matendechero, Marie-Claire Gwayi-Chore, Roy M Anderson, Sammy M Njenga, Simon J Brooker, Charles S Mwandawiro
Journal: The Lancet (2019)

School-based deworming programmes can reduce morbidity attributable to soil-transmitted helminths in children but do not interrupt transmission in the wider community. We assessed the effects of alternative mass treatment strategies on community soil-transmitted helminth infection.