tbuckley/cabot-search huggingface dataset:
Evolution of BRAF gene mutation testing and treatment options in BRAF mutation carriers in Canada.
Authors: Snezana Djokic
Journal: Journal of Clinical Oncology (2015)

e20094 Background: Since 2012, four drugs approval in Canada have changed the treatment practice in melanoma – immunotherapy ipilimumab and targeted therapies vemurafenib, dabrafenib and trametinib, all three being indicated for patients who harbor a BRAF mutation. The objective of this study is to show the evolution in BRAF mutation testing usage in Canada since 2012, and to evaluate drug choices in BRAF mutation carriers. Methods: This retrospective observational study utilized IMS Brogan Enhanced Tumor Studies, an anonymised patient database collected through quarterly physician panel survey, which provides comprehensive insight into total cancer care. The inclusion criteria consisted of Canadian patients diagnosed with stage IV melanoma between 2012 and 2014 and entered into the database from October 2013 to September 2014. The carriers of BRAF mutation were then evaluated based on the type of drug treatment: targeted therapy (TT – vemurafenib, dabrafenib and trametinib), immunotherapy (IT – ipilimumab and aldesleukin) or chemotherapy (CT – all other antineoplastic drugs excluding TT and IT). Results: Out of 29, 151 and 125 patients diagnosed in 2012, 2013 and 2014 respectively, BRAF testing was performed in 16 (55%), 124 (82%) and 82 (65%) patients. The number of patients who harbored a BRAF mutation was 13, 76 and 34, with the following anticancer drug treatment: CT (with no exposure to TT or IT) was used in 10 (77%), 32 (41%) and 9 (26%) patients; TT was used in 3 (23%), 32 (41%) and 23 (68%) patients; IT was the option in 14 (18%) and 8 (24%) patients in 2013 and 2014, respectively. The average number of days between the BRAF testing and the first TT were 384, 64 and 25 days in 2012, 2013 and 2014, respectively. Conclusions: The trend for BRAF mutation testing has grown since 2012, but a significant percentage of patients remain untested prior to their first treatment. In BRAF mutation carriers, TT appears to be the treatment of choice, although a surprisingly high percentage of patients continue to be treated with CT. Further studies with longer follow up are needed in order to better understand the uptake of BRAF testing as well as drug utilization in those who carry a BRAF mutation.
TCTAP A-081 Quantitative Assessment of Vulnerable Plaque by NIRS-IVUS Is Helpful for Differentiating Among Plaque Rupture, Plaque Erosion and Calcified Nodule in the Culprit Lesion of ACS.
Authors: Kosei Terada, Takashi Kubo, Yoshiki Matsuo, Yasushi Ino, Hironori Kitabata, Kunihiro Shimamura, Yasutsugu Shiono, Hiroki Emori, Yosuke Katayama, Atsushi Tanaka, Takeshi Hozumi, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2019)
Strength of Association between Pentosan Polysulfate and a Novel Maculopathy
Authors: Adam M. Hanif, Rachel Shah, Jiong Yan, Jithin S. Varghese, Shivani A. Patel, Blaine E. Cribbs, Ghazala O’Keefe, Andrew M. Hendrick, Jessica G. Shantha, G. Baker Hubbard, Purnima S. Patel, Prethy Rao, Steven Yeh, Nieraj Jain
Journal: Ophthalmology (2019)
Abstract 12148: Impact of Multiple Plaque Ruptures and Cavity Area on Intraprocedural Stent Thrombosis: Intravascular Ultrasound Analysis
Authors: Toru Morofuji, Shinji Inaba, Tatsuro Hitsumoto, Kayo Hara, Hiroe Morioka, Haruhiko Higashi, Makoto Saito, Kiyotaka Ohshima, Shuntaro Ikeda, Mareomi Hamada, Takumi Sumimoto
Journal: Circulation (2015)

Objectives: We examined characteristics of lesions in cases of intraprocedural stent thrombosis (IPST) using intravascular ultrasound (IVUS). Background: IPST is a rare complication occurring during percutaneous coronary intervention (PCI) that leads to poor outcomes. However, factors that contribute to IPST remain largely unknown. Methods: We retrospectively analyzed 1,504 consecutive stent-implanted lesions in 1,324 patients [326 with ST-segment elevation myocardial infarction (STEMI), 403 with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), and 595 with stable angina]. IVUS characteristics of plaques that led to IPST were compared with those of a matched control (non-IPST) group (n = 15) without evidence of IPST matched by age; gender; lesion location; or STEMI, NSTE-ACS, or stable angina. Positive remodeling was defined as a lesion greater than the mean reference external elastic membrane cross-sectional area. Continuous variables were displayed as median and 1st and 3rd interquartile range. Results: IPST occurred in 5 (0.4%; 3 with STEMI, 2 with NSTE-ACS) of 1,324 patients during PCI. Plaque burden at the minimum lumen area site was significantly greater in the IPST group than in the non-IPST group (93.0% vs. 87.9%, P = 0.0035). All 5 culprit lesions that led to IPST had ruptured plaques with positive remodeling and attenuation. The maximum cavity area was larger in the IPST group than in the non-IPST group (4.6 [4.3, 6.5] mm2 vs. 0 [0, 1.9] mm2, P = 0.0011), whereas plaque rupture was also observed in 40% of subjects in the non-IPST group. Multiple plaque ruptures in the culprit lesion were far more common in the IPST group (80.0% vs. 6.7%, P = 0.0049). Conclusion: Multiple plaque ruptures and a larger cavity area were associated with IPST occurrence. IVUS assessment may help predict the development of IPST during PCI.
THU-056-Artificial liver support system improves short-term survival of patients with hepatitis B virus-related acute-on-chronic liver failure: A propensity-score matched analysis
Authors: Jun Li, Lingling Yang, Tianzhou Wu, Jiang Li, Jing Jiang, Jiaojiao Xin, Dongyan Shi, Yinyun Lu, Xingping Zhou, Jiaxian Chen, Jiaqi Li, Jianing Zhang, Keke Ren, Beibei Guo, Tan Li, xu xiaowei, Xin Chen
Journal: Journal of Hepatology (2019)
Cardiac care after myocardial infarction in cancer survivors: A population-based study.
Authors: Kelvin K. Chan, Andrew Yan, Winson Y. Cheung, Craig Earle, Dennis Ko
Journal: Journal of Clinical Oncology (2015)

9578 Background: Cancer survivors (CS) may receive suboptimal non-cancer related care, such as lower rates of bypass surgery after myocardial infarction (MI) in the US. Secondary prevention (SP) after MI is an important aspect of survivorship care. We aim to examine the use of medications and interventions for SP after MI in CS vs. non-cancer patients (NCP). Methods: All acute MI patients (pts) hospitalized in Ontario between 1995 and 2012 were identified from the Canadian Institute of Health Information databases, and linked to the Ontario Cancer Registry to determine whether they were CS or NCP. Those who were diagnosed with cancer < 1 year before their MI were excluded. The cohort was linked to other administrative databases to determine demographics, comorbidities, cardiac risk factors, hospital-based interventions and, for those over age 65, outpatient-based medication use. Propensity scores derived from baseline characteristics were used to create a 1:4 (CS:NCP) matched cohort. The use of medications and interventions within the first 90 days of MI, and medication adherence (measured by proportion of days covered (PDC) within the first year of MI) were compared between CS and NCP using matched analyses. Results: We identified 102,415 MI pts (CS = 20,483; NCP = 81,932) with 57% male and 86% > age 65. Slightly fewer CS vs. NCP received angiograms (37.4% vs. 38.6%; p = 0.003) and percutaneous coronary interventions (17.0% vs. 17.8%; p = 0.01), but similar CS and NCP received bypass surgery (2.5% vs. 2.5%). For pts who were > age 65 and active users of the public drug programs with MI < 5 years after cancer diagnosis, fewer CS vs. NCP received ACEi/ARB (67.0% vs. 70.6%; p < 0.001), statins (54.9% vs. 60.0%; p < 0.001), and clopidogrel (27.8% vs. 33.8%; p < 0.001), but the differences for those with MI > 5 years after cancer diagnosis were much less (all interaction p < 0.01). Similar CS and NCP received beta-blockers and nitrates. Both groups had similar degree of medication adherence, except for ACEi/ARB (PDC: 76.0% (CS) vs. 76.9% (NCP), p = 0.03). Conclusions: Slightly fewer CS than NCP received SP after MI, especially for those occurred within 5 years after cancer diagnosis. Further studies are needed to examine the outcome implications of this finding.
PS-127-Analysis of liver infiltrating lymphocytes in primary sclerosing cholangitis by surface antigen and single cell RNAseq
Authors: Kate Lynch, Fabiola Curion, Hing-Yuen Yeung, Eve Fryer, Andrew Slater, Helen Ferry, Moustafa Attar, Hubert Slawinski, Roger W.G. Chapman, Rory Bowden, Calli Dendrou, Paul Klenerman, Satish Keshav
Journal: Journal of Hepatology (2019)
FRI-151-Characterization of regulatory T cells and the role of PD-1 and TNF-alpha in spontaneous hepatitis B surface antigen seroclearance in chronic hepatitis B
Authors: Fen Liu, Saisai Zhang, Fung Yu Huang, Danny Wong, Lung-Yi Mak, Ka-Shing Cheung, Ching Lung Lai, Man-Fung Yuen, Wai-Kay Seto
Journal: Journal of Hepatology (2019)
THU-419-Prevalence of hepatitis B and C virus infections in Mongolian children and adolescents
Authors: Khishigtogtokh Sereenendorj, Maralmaa Enkhbat, Miriam Eichner, Khatantuul Boldbaatar, Bekhbold Dashtseren, Purevjargal Bat-Ulzii, Zulkhuu Genden, Anir Enkhbat, Myagmarjav Budeebazar, Naranjargal Dashdorj, Naranbaatar Dashdorj, Dahgwahdorj Yagaanbuyant
Journal: Journal of Hepatology (2019)
<i>DDX41</i> mutations in myeloid neoplasms are associated with male gender, <i>TP53</i> mutations and high‐risk disease
Authors: Andrés E. Quesada, Mark J. Routbort, Courtney D. DiNardo, Carlos E. Bueso‐Ramos, Rashmi Kanagal‐Shamanna, Joseph D. Khoury, Beenu Thakral, Zhuang Zuo, C. Cameron Yin, Sanam Loghavi, Chi Y. Ok, Sa A. Wang, Zhenya Tang, Sarah A. Bannon, Christopher B. Benton, Guillermo Garcia‐Manero, Hagop Kantarjian, Rajyalakshmi Luthra, L. Jeffrey Medeiros, Keyur P. Patel
Journal: American Journal of Hematology (2019)

Myeloid neoplasms with germline DDX41 mutations have been incorporated into the 2017 WHO classification. Limited studies describing the clinicopathologic features and mutation profile are available. We searched for myeloid neoplasms with a DDX41 gene mutation tested by an 81-gene next-generation sequencing panel over a 7-month period. We identified 34 patients with myeloid neoplasms with DDX41 abnormalities; 26 (76%) men and 8 women (24%) [median age, 70 years], 20 acute myeloid leukemia (AML), 10 myelodysplastic syndrome (MDS), 1 chronic myelomonocytic leukemia (CMML) and 3 myeloproliferative neoplasms (MPN). Fifty-nine DDX41 variants were detected: 27 (46%) appeared somatic and 32 (54%) were presumably germline mutations. The majority of presumed germline mutations were upstream of the Helicase 2 domain (93%) and involved loss of the start codon (30%). The majority of somatic mutations were within the Helicase 2 domain (78%), with the missense mutation p.R525H being most common (67%). There was a significant difference in the location of germline or somatic mutations (P < .0001). Concomitant mutations were detected involving 19 genes, but only TP53 (n = 11, 32%), ASXL1 (n = 8, 24%), and JAK2 (n = 4, 12%) were recurrent. Twenty (59%) patients showed diploid cytogenetics. Twenty-three (68%) patients presented with AML or MDS-EB-2, suggesting an association with high-grade myeloid neoplasm. Patients with myeloid neoplasms carrying DDX41 mutations show male predominance (3:1), higher age at presentation, association with TP53 mutations, and association with high-grade myeloid neoplasms in our cohort at a referral cancer center setting. These findings support the recognition of myeloid neoplasms with DDX41 mutation as unique, need for germline confirmation, and further assessment of family members.
Retinal-detachment repair and vitreous-like-body reformation via a thermogelling polymer endotamponade
Authors: Zengping Liu, Sing Shy Liow, Siew Li Lai, Asfa Alli-Shaik, Graham E. Holder, Bhav Harshad Parikh, Subramanian Krishnakumar, Zibiao Li, Mein Jin Tan, Jayantha Gunaratne, Veluchamy Amutha Barathi, Walter Hunziker, Rajamani Lakshminarayanan, Clement Woon Teck Tan, Caroline K. Chee, Paul Zhao, Gopal Lingam, Xian Jun Loh, Xinyi Su
Journal: Nature Biomedical Engineering (2019)
Cotargeting of BCL2 with Venetoclax and MCL1 with S63845 Is Synthetically Lethal <i>In Vivo</i> in Relapsed Mantle Cell Lymphoma
Authors: Dana Prukova, Ladislav Andera, Zuzana Nahacka, Jana Karolova, Michael Svaton, Magdalena Klanova, Ondrej Havranek, Jan Soukup, Karla Svobodova, Zuzana Zemanova, Diana Tuskova, Eva Pokorna, Karel Helman, Kristina Forsterova, Mariana Pacheco-Blanco, Petra Vockova, Adela Berkova, Eva Fronkova, Marek Trneny, Pavel Klener
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphomas characterized by (over)expression of BCL2. A BCL2-targeting drug, venetoclax, has promising anticancer activity in MCL. We analyzed molecular mechanisms of venetoclax resistance in MCL cells and tested strategies to overcome it. Experimental Design: We confirmed key roles of proapoptotic proteins BIM and NOXA in mediating venetoclax-induced cell death in MCL. Both BIM and NOXA are, however, differentially expressed in cell lines compared with primary cells. First, NOXA protein is significantly overexpressed in most MCL cell lines. Second, deletions of BIM gene harbored by three commonly used MCL cell lines (JEKO-1, MINO, and Z138) were not found by array comparative genomic hybridization using a validation set of 24 primary MCL samples. Results: We demonstrated that MCL1 and NOXA play important roles in mediating resistance to venetoclax. Consequently, we tested an experimental treatment strategy based on cotargeting BCL2 with venetoclax and MCL1 with a highly specific small-molecule MCL1 inhibitor S63845. The combination of venetoclax and S63845 demonstrated synthetic lethality in vivo on a panel of five patient-derived xenografts established from patients with relapsed MCL with adverse cytogenetics. Conclusions: Our data strongly support investigation of venetoclax in combination with S63845 as an innovative treatment strategy for chemoresistant MCL patients with adverse cytogenetics in the clinical grounds.
Surgeon who failed to tell patient that he removed wrong tooth is suspended for eight months
Authors: Clare Dyer
Journal: BMJ (2019)

An oral surgeon who removed the wrong tooth and then misled the patient and attempted to influence a nurse’s testimony during a subsequent trust investigation has been suspended from the UK medical register for eight months.

Michael Winston, who is qualified in both medicine and dentistry, works as an associate specialist in oral surgery one day a week at Liverpool University Dental Hospital. He is also a locum consultant oral surgeon at Blackpool Teaching Hospitals.

In January 2016 at the Liverpool hospital he removed a molar that was not in the patient’s plan for removal. Although he realised his error before the patient left, Winston failed to tell her, and she left unaware that a …
FRI-384-Early cardiovascular mortality following liver transplantation: 30-year temporal trends from the Australian and New Zealand liver transplant registry
Authors: Anoop Koshy, Omar Farouque, Jithin Sajeev, Adam Testro, Matthew Peverelle, Peter Angus, Robert Jones, Mandy Byrne, Benjamin Cailes, Hui-Chen Han, David Clark, Han Lim, Andrew Teh, Paul Gow
Journal: Journal of Hepatology (2019)
WT1 to enhance proliferation and to impede apoptosis in KRAS-mutant NSCLC via targeting cMyc.
Authors: Wu Chen
Journal: Journal of Clinical Oncology (2015)

e22120 Background: A novel link between oncogenic KRAS signalling and WT1 was recently identified. We sought to investigate the role of WT1 and KRAS in proliferation and apoptosis. Methods: KRAS mutations and WT1 (cMyc) were detected using Sanger sequencing and real-time PCR in 77 patients with non-small cell lung cancer (NSCLC). Overexpression and knockdown of WT1 were generated with plasmid and siRNA via transient transfection technology in H1299 and assay for apoptosis evaluation were carried out. Dual luciferase reporter assay and ChIP-PCR were performed to validate the effect of WT1 on cMyc promoter. Results: KRAS mutations showed a negative impact on overall survival (OS). High expressions of WT1 and cMyc were associated with poor OS in KRAS mutant subgroup. The potential mechanisms that WT1 promotes proliferation and impedes apoptosis through affecting multiple apoptosis-related regulators in KRAS mutant NSCLC cells were identified.WT1 could activate cMyc promoter directly in KRAS mutant cells. Conclusions: The results suggest that WT1 and c-MYC expression is important for survival in KRAS mutant tumors as opposed to KRAS wild-type tumors. For treatment of KRAS mutant NSCLC, targeting WT1 and cMyc may provide alternative therapeutic strategies.
New Therapy for Treatment-Resistant Depression
Authors: Feyza Sancar
Journal: JAMA (2019)

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THU-455-Metabolomic analysis by 1H-nuclear magnetic resonance spectroscopy suggest that there are 2 phenotypes of human hepatocellular carcinoma developed in non-alcoholic fatty liver disease according to fibrosis level (F0F1 vs F3F4)
Authors: Camille Teilhet, Christelle Reynes, Robert Sabatier, Anne Sophie Biesse Martin, Marie Paule Vasson, Armand Abergel, Aicha Demidem
Journal: Journal of Hepatology (2019)
Changing epidemiology of meticillin-resistant Staphylococcus aureus in 42 hospitals in the Dutch–German border region, 2012 to 2016: results of the search-and-follow-policy
Authors: Annette Jurke, Inka Daniels-Haardt, Welmoed Silvis, Matthijs S. Berends, Corinna Glasner, Karsten Becker, Robin Köck, Alex W. Friedrich
Journal: Eurosurveillance (2019)

IntroductionMeticillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated infections.AimWe describe MRSA colonisation/infection and bacteraemia rate trends in Dutch-German border region hospitals (NL-DE-BRH) in 2012-16.MethodsAll 42 NL-DE BRH (8 NL-BRH, 34 DE-BRH) within the cross-border network EurSafety Health-net provided surveillance data (on average ca 620,000 annual hospital admissions, of these 68.0% in Germany). Guidelines defining risk for MRSA colonisation/infection were reviewed. MRSA-related parameters and healthcare utilisation indicators were derived. Medians over the study period were compared between NL- and DE-BRH.ResultsMeasures for MRSA cases were similar in both countries, however defining patients at risk for MRSA differed. The rate of nasopharyngeal MRSA screening swabs was 14 times higher in DE-BRH than in NL-BRH (42.3 vs 3.0/100 inpatients; p < 0.0001). The MRSA incidence was over seven times higher in DE-BRH than in NL-BRH (1.04 vs 0.14/100 inpatients; p < 0.0001). The nosocomial MRSA incidence-density was higher in DE-BRH than in NL-BRH (0.09 vs 0.03/1,000 patient days; p = 0.0002) and decreased significantly in DE-BRH (p = 0.0184) during the study. The rate of MRSA isolates from blood per 100,000 patient days was almost six times higher in DE-BRH than in NL-BRH (1.55 vs 0.26; p = 0.0041). The patients had longer hospital stays in DE-BRH than in NL-BRH (6.8 vs 4.9; p < 0.0001). DE-BRH catchment area inhabitants appeared to be more frequently hospitalised than their Dutch counterparts.ConclusionsOngoing IPC efforts allowed MRSA reduction in DE-BRH. Besides IPC, other local factors, including healthcare systems, could influence MRSA epidemiology.
LBP-25-a phase 1 clinical trial of therapeutic vaccine t101 in chronic hepatitis b (chb) patients: a randomized, double-blind, placebo-controlled, single and multiple injections, dose escalation study
Authors: Yue Hu, Xiaomin WANG, zhiming wang, dong gao, lan zhang, min wu, hong zhang, zhongyu hu, shaohui qiu, hong chen, meng wang, xiaojiao li, YANHUA DING, Junqi Niu
Journal: Journal of Hepatology (2019)
Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells
Authors: Tae Jin Yun, Jun Seong Lee, Kawthar Machmach, Dahee Shim, Junhee Choi, Young Jin Wi, Hyung Seok Jang, In-Hyuk Jung, Kyeongdae Kim, Won Kee Yoon, Mohammad Alam Miah, Bin Li, Jinsam Chang, Mariana G. Bego, Tram N.Q. Pham, Jakob Loschko, Jörg Hermann Fritz, Anne B. Krug, Seung-Pyo Lee, Tibor Keler, Jean V. Guimond, Elie Haddad, Eric A. Cohen, Martin G. Sirois, Ismail El-Hamamsy, Marco Colonna, Goo Taeg Oh, Jae-Hoon Choi, Cheolho Cheong
Journal: Cell Metabolism (2016)
Clinical prognostic factors in pediatric osteosarcoma: A single institution study.
Authors: Bilal Ali Abou Ali, Miguel R. Abboud, Raya Hamad Saab
Journal: Journal of Clinical Oncology (2015)

e21011 Background: Treatment of Osteosarcoma necessitates coordinated multi-disciplinary care including chemotherapy and surgery. In developed countries, patients with localized disease have an overall survival of 70-75%, compared to about 30% for those with metastases. Outcome in developing countries has not been adequately described. We analyzed prognostic factors for Osteosarcoma patients treated at a single institution in Lebanon, a developing country with available multidisciplinary treatment modalities. Methods: Characteristics and outcome of 38 patients treated between August 2001 and May 2012 were reviewed. Median follow-up was 61 months (range: 8–142). Common primary sites included long bones around the knee (n = 34, 89%). Nine patients (24%) had metastatic disease, of which three had also multifocal disease. All patients received uniform 3-drug chemotherapy regimen including Cisplatin, Doxorubicin, and Methotrexate as per North American COG protocols. Ifosfamide and Etoposide were added to adjuvant treatment regimen for patients with poor degree of tumor necrosis ( < 90%) and/or patients with metastatic disease. Surgery was performed in all except three patients with multifocal disease. Results: For patients with localized disease, 5-year overall survival and event free survival rates were approximately 78% and 65%, respectively; while for metastatic disease they were approximately 45%. Adverse prognostic factors included non-lower extremity site, metastases, degree of necrosis, and more than 4 weeks delay in local control. In bivariate analysis, only degree of necrosis was a prognostic determinant of outcome. Conclusions: Treatment of childhood Osteosarcoma in a multidisciplinary cancer center in Lebanon results in similar survival to developed countries. Patients with localized Osteosarcoma who have good response to treatment (degree of necrosis ≥ 90%) constitute a favorable prognostic group. Delays in local control were associated with worse outcome, but this factor lost significance in bivariate analysis since most patients with metastatic disease and those with poor response to therapy had delays in local control. Larger studies are needed to further evaluate this possible association.