tbuckley/cabot-search huggingface dataset:
SAT-351-Biomarkers and clinical characteristics associated with nonalcoholic steatohepatitis fibrosis progression in the CENTAUR study
Authors: Nicolas Lanthier, Johannes Kluwe, Andrew Fowell, Maciej Jablkowski, Vincent Wai-Sun Wong, Jiacheng Yuan, Sean Muthian, Jean Paul Nicandro, Star Seyedkazemi, Eduardo Bruno Martins, Laurent Fischer, Rohit Loomba
Journal: Journal of Hepatology (2019)
FRI-266-Saccharomyces boulardii modulates the colonic microbiota towards a more favourable composition in patients with non-alcoholic fatty liver disease (simple steatosis)
Authors: Pavel Seliverstov, Stanislav Sitkin, Elena Avalueva, Timur Vakhitov, Elena Demyanova, Maria Suvorova, Valeriy Radchenko
Journal: Journal of Hepatology (2019)
With equal access, African American patients have superior survival compared to white patients with multiple myeloma: a VA study
Authors: Nathanael R. Fillmore, Sarvari V. Yellapragada, Chizoba Ifeorah, Ansh Mehta, Diana Cirstea, Paul S. White, Gustavo Rivero, Andrew Zimolzak, Saiju Pyarajan, Nhan Do, Mary Brophy, Nikhil C. Munshi
Journal: Blood (2019)
Autophagy modulation in bone metastatic breast cancer: A potential therapeutic targeting strategy.
Authors: Ahmad Hasan Othman, Manish Tandon, Jitesh Pratap
Journal: Journal of Clinical Oncology (2015)

e22009 Background: Metastasis to bone is a frequent complication associated with breast cancer; with no curative therapy currently available. While the mechanisms of metastasis are not entirely clear, aberrant expression of the transcription factor Runx2 has been shown to promote metastasis and osteolysis associated with breast cancer. Autophagy is a process where cells degrade defective organelles and proteins into their subunits with the flux representing the rate of degradation of Cancer cells undergo autophagy to cope with metabolic stress imposed during tumor metastasis. Autophagy has been shown to be highly up regulated in cancers with Mitogen Activated Protein Kinase (MAPK) mutations; however a link between Runx2 and autophagy is unknown. Methods: To examine the contributions of Runx2 and autophagy to bone metastasis experiments were conducted using MDA-231 cells, a cellular model of breast cancer metastasis, which aberrantly expresses Runx2 along with several MAPK mutations. Cells were serum starved for 24hr followed by treatment with flux inhibitors Chloroquinine and Bafilomycin A1 and MEK inhibitor PD184161. Lysates were probed for the autophagosome marker Microtubule Associated Light Chain 3 Protein (LC3) which is degraded via flux. To visualize flux, cells were transfected with plasmid encoding RFP labeled LC3 protein followed by Chloroquinine and Bafilomycin A1 treatment for 24hrs. Results: Western blot analysis of LC3 showed a loss of flux in Runx2 null cells compared to control cells. Fluorescent microscopy analysis of RFP-LC3 further validated increased build-up of LC3 in Runx2 null cells. Treatment with flux inhibitors or MEK inhibitor PD184161 resulted in build-up of LC3 in control cells while no increase was observed in Runx2 null cells. These results suggest that Runx2 promotes flux, which may contribute to tumor metastasis to bone. Conclusions: Our studies highlight Runx2 as a positive regulator of flux suggesting autophagy may help potentiate the metastatic and osteolytic effects of Runx2. Furthermore, our results suggest that survival of cancer cells with MAPK mutations which are addicted to autophagy can be targeted by combination of FDA approved MAPK and flux inhibitors.
Hadiza Bawa-Garba can return to practice under close supervision
Authors: Clare Dyer
Journal: BMJ (2019)

Hadiza Bawa-Garba, the trainee paediatrician convicted of manslaughter over the death of 6 year old Jack Adcock in 2011, will be allowed to return to practice under close supervision, after a medical practitioners tribunal deemed her to be a low risk to patients.

The tribunal found “extensive and substantial” mitigating factors in her case, including remorse, insight, and remediation, as well as the support of her employers and the East Midlands Deanery. It imposed a range of conditions on her practice for a period of two years, beginning in July 2019, when her current suspension ends.

Bawa-Garba, 43, who recently had …
Comparative effectiveness of second-line treatment for non-small cell lung cancer (NSCLC) among patients ≥ 70 versus &lt; 70 years of age.
Authors: Lisa M. Hess, Robert Goodloe, Zhanglin Lin Cui, Gebra Cuyun Carter, Julie Beyrer, Joseph Treat
Journal: Journal of Clinical Oncology (2015)

e19018 Background: Until 2014 guidelines for the second-line treatment of NSCLC included pemetrexed, docetaxel, gemcitabine, and erlotinib. Outcomes among patients (pts) ≥ 70 years are not well understood. This retrospective study describes second-line treatments and compares their outcomes in real-world clinical settings by age in the US. Methods: IMS Oncology patient-level EMR data (1/2007-6/2014) were used for this study. Eligible pts were those with a diagnosis of lung cancer (ICD-9-CM 162.2-162.9) from 1/2007-6/2013 who received at least 2 lines of treatment. Baseline demographic and treatment data were analyzed using descriptive statistics. Survival analyses by age cohort were adjusted using propensity-score matching. Pts alive at the end of the database were censored in the survival analyses. Results: There were 10,634 eligible pts: the mean age was 66.4 (SD = 9.9), 54% were male and 86% of the 40% with stage data were initially diagnosed with stage III-IV disease. Of all eligible pts, 4,418 (41.5%) were age ≥ 70 and survived a median of 6.8 months (95% CI: 6.7-6.9); pts < 70 survived a median of 6.9 months (95% CI: not estimable). The most common initial second-line treatments used in the ≥ 70 versus < 70 groups were pemetrexed (16.6% vs 16.7%, p = 0.82), carboplatin + paclitaxel (11.6% vs 11.7%, p = 0.92), erlotinib (10.2% vs 7.1%, p < 0.001), gemcitabine (6.5% vs 4.6%, p < 0.001) and docetaxel (6.4% vs 7.3%, p = 0.09). There were significantly better survival outcomes in the < 70 cohort for docetaxel (p ≤ 0.001), carboplatin + gemcitabine (p = 0.03) and bevacizumab + pemetrexed (p < 0.001) compared to patients ≥ 70 based on the log-rank test. Other regimens (e.g. gemcitabine, carboplatin + taxane) were not significantly different. Conclusions: There is great variation in treatment for NSCLC in the second line, with no single regimen accounting for more than 20% of the 2nd line population. Pts ≥ 70 were more likely to receive erlotinib or gemcitabine than those < 70. Survival outcomes were comparable between age groups; however, there were statistically significant differences in survival among several treatment regimens received by age group.
SAT-168-HBV splice DNA forms detected in serum in majority of patients with chronic HBV infection
Authors: Charlotte Hedskog, Silvia Chang, Bandita Parhy, Dara Burdette, Ondrej Podlaha, Wan-Long Chuang, Kosh Agarwal, Edward Gane, Anuj Gaggar, Simon Fletcher, Hongmei Mo, Evguenia S Svarovskaia
Journal: Journal of Hepatology (2019)
HDAC6 Suppresses Let‐7i‐5p to Elicit TSP1/CD47‐Mediated Anti‐Tumorigenesis and Phagocytosis of Hepatocellular Carcinoma
Authors: Hee Doo Yang, Hyung Seok Kim, Sang Yean Kim, Min Jeong Na, Gyeongdeok Yang, Jung Woo Eun, Hee Jung Wang, Jae Youn Cheong, Won Sang Park, Suk Woo Nam
Journal: Hepatology (2019)

Histone deacetylase 6 (HDAC6) uniquely serves as a tumor suppressor in hepatocellular carcinogenesis, but the underlying mechanisms leading to tumor suppression are not fully understood. To identify comprehensive microRNAs (miRNAs) regulated by HDAC6 in hepatocellular carcinogenesis, differential miRNA expression analysis of HDAC6 ‐transfected Hep3B cells was performed. Using integrative analyses of publicly available transcriptome data and miRNA target prediction, we selected five candidate miRNAs and, through in vitro functional validation, showed that let‐7i‐5p specifically suppressed thrombospondin‐1 (TSP1) in hepatocellular carcinoma (HCC). Ectopic expression of antisense let‐7i‐5p (AS‐let‐7i‐5p) inhibited in vitro tumorigenesis of HCC cells. In addition, treatments of partially purified TSP1 from culture cell media (ppTSP1) and recombinant TSP1 (rTSP1) exhibited similar effects with AS‐let‐7i‐5p treatment on the same HCC cells, whereas TSP1 neutralizing antibody treatment significantly attenuated these effects. Notably, treatments of HDAC6 plasmid, AS‐let‐7i‐5p, ppTSP1, and rTSP1 significantly suppressed in vitro angiogenesis and metastatic potential of HCC cells, but the co‐treatment of TSP1 antibody specific to cluster of differentiation 47 (CD47) binding domain successfully blocked these effects in the same cells. Furthermore, we demonstrated that recovery of HDAC6 elicited let‐7i‐5p suppression to de‐repress TSP1 expression; therefore, it occupied the CD47 receptor to block CD47‐SIRPα‐mediated anti‐phagocytosis of macrophage in HCC. We also observed that HCC‐derived exosomal let‐7i‐5p suppressed TSP1 of recipient hepatocyte cells. Treatments of HDAC6 plasmid, AS‐let‐7i‐5p, and rTSP1 suppressed tumor incidence as well as tumor growth rates in a spontaneous mouse HCC model. Conclusion : Our findings suggest that the HDAC6–let‐7i‐5p–TSP1 regulatory pathway suppresses neoplastic and antiphagocytic behaviors of HCC by interacting with cell surface receptor CD47 in HCC and neighboring cells of tumor microenvironment, providing a therapeutic target for the treatment of liver malignancy and metastasis.
Use of Opioid Overdose Deaths Reported in One State’s Criminal Justice, Hospital, and Prescription Databases to Identify Risk of Opioid Fatalities
Authors: Matthew D. Eisenberg, Brendan Saloner, Noa Krawczyk, Lindsey Ferris, Kristin E. Schneider, B. Casey Lyons, Jonathan P. Weiner
Journal: JAMA Internal Medicine (2019)
68Ga CXCR-4 PET/CT Imaging in an Atypical Case of Extramedullary Plasmacytoma Mimicking as Renal Cell Carcinoma
Authors: Rajender Kumar, Bhagwant Rai Mittal, Apurva Sood, Harmandeep Singh, Jaya Shukla, Ritambra Nada, Manish Rathi
Journal: Clinical Nuclear Medicine (2019)

Abstract Multiple-myeloma (MM) is a malignant plasma cell proliferation disorder and the second most common blood malignancy after non-Hodgkin lymphoma. The chemokine (CXCR-4) receptor analogues are the newer agents being postulated for myeloma imaging and have shown good diagnostic performance. We report a case of plasmacytoma with suspicious renal cell carcinoma, in whom 68 Ga CXCR-4 PET/CT revealed tracer-avid lesion in the left perinephric region. PET/CT-guided biopsy from the tracer-avid lesion revealed plasmacytoma. PET/CT-imaging and guided biopsy using 68 Ga CXCR4 receptor ligand, proved its usefulness for accurate localization of the culprit lesion and helped in definitive management of the patient.
SAT-271-Genetic risk factors for advanced alcoholic and non-alcoholic liver disease in the general population
Authors: Fredrik Åberg, Pauli Puukka, Perttu Sahlman, Markku Nissinen, Veikko Salomaa, Satu Männistö, Annamari Lundqvist, Markus Perola, Antti Jula, Martti Färkkilä
Journal: Journal of Hepatology (2019)
Hedgehog pathway activation might mediate pemetrexed resistance in NSCLC cells
Authors: Y. Liu, R. Kiefl, R.M. Huber, A. Tufman, D. Kauffmann-Guerrero
Journal: Annals of Oncology (2019)

Background: Lung cancer is the leading cause of death among all other malignancies. Despite the wide use and the high efficacy of immunotherapy, most patients with advanced or metastatic disease need chemotherapeutic treatment. Primary and acquired resistance to chemotherapeutic agents are the main cause of reduced overall survival. The Hedgehog (HH) pathway has been shown to be crucial in cell development and survival. Activated in several types of cancer it might be a potent bypass mechanism mediating chemo resistance. Thus, this study aims at investigating the role of HH signalling in chemo resistant NSCLC cells. Methods: HCC827 NSCLC cells were treated with increasing sub-lethal doses of pemetrexed and vinorelbine to produce pemetrexed and vinorelbine resistant cells. RNA was isolated from both chemo resistant and naive cells. RT-qPCR was performed to evaluated mRNA gene expression. To measure cell growth capacity we used a MTT assay to evaluate the impact of the HH-inhibitor vismodegib in naïve and chemo resistant cell lines. Results: Pemetrexed resistant cells showed clearly increased expression levels of most of HH signalling genes. The HH transcription factors GLI1, GLI2 and GLI3 were increased 3.7, 4.3 and 3.5 fold compared to non-resistant cells. The trans-membrane HH receptor PTCH1 showed to be elevated 2.4 fold and the ligand of HH signalling SSH revealed to be expressed 5.9 fold compared to naïve cells. However, vinorelbine resistant cells did not show a significant activation of HH signalling. Supporting these results pemetrexed resistant cells treated with the HH inhibitor vismodegib showed reduced proliferation compared to naïve cells treated with vismodegib. Conclusions: These are the first results of our study investigating the impact of HH signalling on chemo resistant NSCLC cells. In the case of pemetrexed resistance activation of HH pathway could play an important role to mediate this resistance. However, further investigation is needed to clarify the role of the HH pathway in NSCLC treatment. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Treatment of venous thromboembolism in ambulatory cancer patients in Germany: A prospective noninterventional study.
Authors: Axel Matzdorff, Bettina Ledig
Journal: Journal of Clinical Oncology (2015)

e20666 Background: Within the last 20 years cancer management has shifted from in-hospital to ambulatory chemotherapy. Accordingly, most cancer-related venous thromboembolisms (VTEs) occur in out-patients (pts). VTE in cancer pts carries a particularly high morbidity and mortality. This study was aimed to assess VTE treatment of cancer pts in the ambulatory care setting in Germany. Methods: We conducted a prospective non-interventional study in ambulatory cancer pts from office-based oncologists with objectively confirmed VTE. A standardized case-report form was used to obtain data on pts characteristics, treatment regimen, duration of treatment, and side effects. Results: From 2/2012-12/2013 76 pts from 34 centers were documented. Median age was 62y (33-81 y). The four most common cancer types were breast (32%), colorectal (18%), lymphoma and lung cancer (each 8%). 40% of pts had T1-2, 39% had cM0, 72% were ECOG 0-1. Diagnosis of DVT was based on clinical symptoms and ultrasound in 100%, no specialist used a risk score (e.g. Wells Score). 19% of acute VTEs were treated as in-pts, 81% as out-pts, and 99% with low molecular weight heparin (LMWH), unfractionated heparin, or fondaparinux. LMWH was planned for secondary prophylaxis in 61% of pts, switching to vitamin K antagonists or rivaroxaban in 39%. Secondary prophylaxis was administered for a median of 166 d and terminated earlier than intended in 25% of pts (death 20%, pt’s request 3%, other 2%). During acute phase treatment and secondary prophylaxis no recurrent VTE occured. 4 pts (5%) experienced minor bleedings, mostly bleedings at injection site, one nose bleed, and one urethral bleed. Conclusions: This study though limited by the small number of pts reveals that many ambulatory cancer pts with VTE have early tumors, no metastases, and an excellent performance score. Most pts receive LMWHs as recommended by national and international guidelines but a relevant percentage is also switched to vitamin k antagonists. These results were the starting point for a more detailed survey on VTE prophylaxis and treatment in both hospitalized and ambulatory cancer pts in Germany.
PS-073-Preclinical profile of HBV core protein inhibitor, ABI-H, a potent inhibitor of cccDNA generation in HBV infected cells
Authors: Qi Huang, Simon Haydar, Yi Zhou, Dawei Cai, Xiang Xu, Ran Yan, Lida Guo, Esteban Carabajal, Xuman Tang, Michael Walker, Roopa Rai, Mark Bures, Leping Li, Richard Colonno
Journal: Journal of Hepatology (2019)
PS-207-Molecular classifier for T-cell-mediated and antibody-mediated rejection after liver transplantation
Authors: Anne Höfer, Danny Jonigk, Björn Hartleben, Robert Geffers, Frank Klawonn, Murielle Verboom, Michael Hallensleben, Stefan G. Hübscher, Michael P. Manns, Elmar Jaeckel, Richard Taubert
Journal: Journal of Hepatology (2019)
PS-200-The combination of HEPAmet fibrosis score and transient elastography shows a high diagnostic accuracy in predicting advanced fibrosis in NAFLD
Authors: Javier Ampuero, Rocío Aller, Rocío Gallego-Durán, José Luis Calleja Panero, Jerome Boursier, Salvatore Petta, Salvador Benlloch, Javier Crespo, Zheng Ming-Hua, Judith Gómez-Camarero, Salvador Augustin, Desamparados Escudero-García, Agustin Albillos, Moises Diago, Oreste Lo Iacono, Juan Caballería, Juan Turnés, Rubén Francés, Manuel Romero Gomez
Journal: Journal of Hepatology (2019)
Abstract 21009: Outcomes of Pregnancy in Young Women With Valvular Dysfunction, 2005-2015
Authors: Jaya Batra, Joanna Chikwe, Shinobu Itagaki, Timothy Lee, Nana Toyoda, Natalia N Egorova
Journal: Circulation (2017)

Background: For young women who require cardiac valve replacement, the optimum prosthetic type for successful future pregnancy is not well established. Current data is limited to single-center studies and guidelines offer weak or no recommendations on valve selection. This study compares outcomes of pregnancy in women with mechanical valves (MHVs), bioprosthetic valves (BHVs), and valve repair. Methods: This was a retrospective analysis of 268 pregnancies in 222 women with a history of cardiac valve replacement or repair in California and New Jersey between 2005 and 2015. Each pregnancy was treated as a unique event. Patients were identified using state-run mandatory administrative databases which capture all inpatient, emergency department, and ambulatory surgery discharges. A multivariable logistic regression model with clustering by patient was used to identify factors associated with pregnancy loss, defined as spontaneous or induced abortion, fetal death, or maternal death prior to delivery. Covariates included maternal demographic characteristics and baseline comorbidities, time between most recent valve operation and pregnancy, year of pregnancy, and valve characteristics. Results: There were 64 pregnancies with MHVs present, 107 with BHVs, and 97 with repair only. Mean age at the time of first valve operation was 27.5 years (SD, 7.9 years; range, 11.2-53.7 years). Mean maternal age was 30.3 years (SD, 6.4 years; range, 15.6-54.9), with no significant difference between the three groups. Rates of spontaneous abortion for MHVs, BHVs, and repair were 32.8%, 8.4%, and 13.4%, respectively (p&lt;0.0001), and rates of total pregnancy loss were 57.8%, 15.0%, and 22.7% (p&lt;0.0001). After adjustment for covariates, the odds ratio for pregnancy loss with MHVs compared to BHVs was 5.3 (95% CI, 3.9-28.3) and 1.2 (95% CI, 0.9-6.2) with repair compared to BHVs. Other risk factors for pregnancy loss included maternal age ≥35 years and maternal hypertension. Conclusion: For women in the United States with mechanical heart valves, the risk of pregnancy loss is significant, with less than half of all pregnancies successfully progressing to delivery.
Improved CoChR Variants Restore Visual Acuity and Contrast Sensitivity in a Mouse Model of Blindness under Ambient Light Conditions
Authors: Tushar H. Ganjawala, Qi Lu, Mitchell D. Fenner, Gary W. Abrams, Zhuo-Hua Pan
Journal: Molecular Therapy (2019)

Severe photoreceptor cell death in retinal degenerative diseases leads to partial or complete blindness. Optogenetics is a promising strategy to treat blindness. The feasibility of this strategy has been demonstrated through the ectopic expression of microbial channelrhodopsins (ChRs) and other genetically encoded light sensors in surviving retinal neurons in animal models. A major drawback for ChR-based visual restoration is low light sensitivity. Here, we report the development of highly operational light-sensitive ChRs by optimizing the kinetics of a recently reported ChR variant, Chloromonas oogama (CoChR). In particular, we identified two CoChR mutants, CoChR-L112C and CoChR-H94E/L112C/K264T, with markedly enhanced light sensitivity. The improved light sensitivity of the CoChR mutants was confirmed by ex vivo electrophysiological recordings in the retina. Furthermore, the CoChR mutants restored the vision of a blind mouse model under ambient light conditions with remarkably good contrast sensitivity and visual acuity, as evidenced by the results of behavioral assays. The ability to restore functional vision under normal light conditions with the improved CoChR variants removed a major obstacle for ChR-based optogenetic vision restoration.
Outcomes of curative treatment for non-small cell lung cancer (NSCLC) with synchronous brain metastasis: A single-institutional experience.
Authors: Jonathan Rogozinski, William J. Fulp, Alberto Chiappori, Tawee Tanvetyanon
Journal: Journal of Clinical Oncology (2015)

e19009 Background: Patients with NSCLC and brain metastasis typically have poor prognosis. Nevertheless, previous studies have shown that rare patients with isolated brain metastasis may be treated curatively with surgery to both lung and brain. Over the years, this has been extrapolated to include patients with an unresectable or inoperable lung primary. To date, it remains unknown whether aggressive chemoradiation to lung primary plus definitive brain treatment can lead to a curative result. Methods: We retrospectively identified patients with NSCLC who presented with synchronous brain metastasis at diagnosis during 1997-2006. Included patients were those who received definitive treatment to both brain and lung site. This entailed surgical resections or definitive radiotherapy to all disease sites. For those with unresectable or inoperable lung primary, thoracic radiation ( ≥ 5000 cGy) was required. Patients with metastasis to sites other than brain known at the time of treatment were excluded. Results: There were 34 patients eligible for analysis: 22 patients (65%) received lung surgery (resected group) and 12 patients (35%) received thoracic chemoradiation (unresected group). Resection of brain metastasis occurred in 28 patients (82%), comparable between groups. Median age was 56.1 years in the resected group vs. 50.7 years in the unresected group. In the resected group, 14% of patients had N2/N3 disease, compared with 27% in the unresected group. The median overall survival was 17.7 months. This was 20.3 months in the resected group and 12.9 months in the unresected group (p= 0.030). The overall 5-year survival rate was 17.6%. This was 27.0% in the resected group and 0% in the unresected group. Multivariable model adjusting age, sex, and comorbidity index indicated that unresected lung primary significantly increased the risk of death with HR 1.59 (95% CI: 1.05, 2.42), p= 0.027. Conclusions: Based on our limited experience, no long-term survivor was observed among patients with NSCLC with isolated brain metastasis and with unresectable or inoperable lung primary. Given the toxicity and resource utilization, thoracic chemoradiation for such patients should be avoided.
THU-329-Opioid use is common in patients with non-alcoholic fatty liver disease and associated with severity of liver disease, hepatic encephalopathy and psychiatric comorbidities
Authors: Andrew Moon, Roberto J Firpi, Vandana Khungar, Justin Kupec, Anna LOK, Laura Malahias, Cheryl Schoen, Huy N. Trinh, A. Sidney Barritt
Journal: Journal of Hepatology (2019)
SAT-349-Improvement of hepatic inflammation and fibrosis independently of weight loss from a short, individualized, web-based exercise program in patients with NAFLD
Authors: Yvonne Huber, Daniel Pfirrmann, Christian Labenz, Eva Kalliga, Nadine Gehrke, Beate Straub, Diana Leeming, Heike Bantel, Peter Galle, Perikles Simon, PD Dr. Schattenberg Jörn
Journal: Journal of Hepatology (2019)