tbuckley/cabot-search huggingface dataset:
Clinical significance of radiotherapy in the treatment of limited stage NK/T cell lymphoma.
Authors: Soo Jung Lee, Yee Soo Chae, Byung Woog Kang, Shinkyo Yoon, Jong Gwang Kim, Joon Ho Moon, Bo-Hee Lee, Young Rok Do, Yong Park, Ho-Young Yhim, Deok-Hwan Yang, Jeong-A Kim, Jooseop Chung, Moo Gon Song, Je-Jung Lee, Jae-Yong Kwak, Shin Young Jeong
Journal: Journal of Clinical Oncology (2015)

8549 Background: For the treatment of limited-stage natural killer (NK)/T-cell lymphoma, combined treatment modality including radiotherapy (RT) is widely recommended. However, the best standard has not been clearly determined. In this study, we analyzed the role and the optimal timing of RT, and the difference of clinical outcome among patients with limited-stage NK/T-cell lymphoma. Methods: We retrospectively analyzed patients with limited-stage NK/T-cell lymphoma, diagnosed between January, 2004 and April, 2013 from six Korean institutes. These patients were categorized into 3 groups, i.e., 1) anthracycline or non-anthracycline-based chemotherapy followed by radiotherapy (CTx/RT), 2) concurrent chemoradiotherapy (CCRT) followed by non-anthracycline-based chemotherapy (CCRT/CTx), and 3) CTx alone group. Results: In total 104 patients, the median age was 52 years (range 28~85). According to therapeutic modalities, 29 (27.9%) and 44 (42.3%) patients were treated by CTx/RT and CCRT/CTx, respectively, and the remaining 31 (29.8%) patients were managed by CTx alone as initial therapy. Overall response (OR) rate was 80.8% including complete response (CR) rate 70.2% after initial therapy. Patients who had CTx/RT or CCRT/CTx achieved high CR rate (76.7%) comparing to those had CTx only group with 54.8% (p = 0.009). With median follow up of 47.6 months, the 5-year progression free survival (PFS) was 44.2% and overall survival was 75.1%. The 5-year PFS of patients with RT containing protocol and those with CTx only group were 52.1% and 25.8%, respectively (p = 0.003). Among patients treated with RT containing protocol, the 5-year PFS was superior in CTx/RT group as 60.6% than CCRT/CTx group as 48.8% (p = 0.001). All patients treated with CTx/RT could finish the planned protocol. Conclusions: Our results show the role of RT for treating limited stage NK/T cell lymphoma. Although CCRT showed a higher CR rate compared CTx followed by RT, the optimal timing of RT should be determined carefully considering the possibility of progression outside RT field prior to systemic chemotherapy or failure to complete planned treatment related with radiotherapy in particular in case of RT at upper aerodigestive tract.
FRI-506-A nationwide multicenter study in Japanese patients treated with lenvatinib in real world practice
Authors: Kaoru Tsuchiya, Masayuki Kurosaki, Shun Kaneko, Toru Kimura, Hiroyuki Marusawa, Hirotaka Arai, Takehiko Abe, Hiroyuki Kimura, Keiji Tsuji, Koichiro Furuta, Chikara Ogawa, Ryoichi Narita, Yuji Kojima, Takehiro Akahane, Yasushi Uchida, Hideo Yoshida, Haruhiko Kobashi, Atsunori Kusakabe, Kouji Joko, Namiki Izumi
Journal: Journal of Hepatology (2019)
Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial
Authors: Cathy Eng, Tae Won Kim, Johanna Bendell, Guillem Argilés, Niall C Tebbutt, Maria Di Bartolomeo, Alfredo Falcone, Marwan Fakih, Mark Kozloff, Neil H Segal, Alberto Sobrero, Yibing Yan, Ilsung Chang, Anne Uyei, Louise Roberts, Fortunato Ciardiello, JB Ahn, J Asselah, S Badarinath, S Baijal, S Begbie, S Berry, JL Canon, RG Carbone, A Cervantes, YJ Cha, K Chang, A Chaudhry, E Chmielowska, SH Cho, D Chu, F Couture, J Cultrera, D Cunningham, E Van Cutsem, PJ Cuyle, J Davies, S Dowden, M Dvorkin, V Ganju, RV Garcia, R Kerr, TY Kim, K King, J Kortmansky, M Kozloff, KO Lam, J Lee, AS Lee, B Lesperance, G Luppi, B Ma, E Maiello, R Mandanas, J Marshall, G Marx, S Mullamitha, M Nechaeva, JO Park, N Pavlakis, CG Ponce, P Potemski, S Raouf, J Reeves, N Segal, S Siena, A Smolin, JO Streb, A Strickland, E Szutowicz-Zielinska, JM Tabernero, B Tan, JS Valera, M Van den Eynde, P Vergauwe, M Vickers, M Womack, M Wroblewska, R Young
Journal: The Lancet Oncology (2019)
Trends and regional variation of end-of-life cancer care in the Medicare program.
Authors: Shi-Yi Wang, Jane Hall, Jessica B. Long, Craig Evan Pollack, Elizabeth Bradley, Kerin B. Adelson, Cary Philip Gross
Journal: Journal of Clinical Oncology (2015)

9526 Background: Although there has been substantial concern of aggressiveness of cancer care near the end-of-life (EOL) in the United States, little is known about recent trends in EOL cancer care and associated regional variation in the Medicare program. Methods: Using the Surveillance, Epidemiology, and End Results–Medicare data, we identified 82,245 beneficiaries who had breast, prostate, lung, colorectal, pancreas, liver, kidney, melanoma, or hematological cancer diagnosed in 2004-2009 and died within 2 years as a result of cancer by December 2009. Aggressiveness of EOL care was measured by 1) chemotherapy received within 14 days of death; 2) > 1 emergency department (ED) visit within 30 days of death; 3) > 1 hospitalization within 30 days of death; 4) ≥ 1 intensive care unit (ICU) admission within 30 days of death; 5) hospital death; and 6) hospice enrollment ≤ 3 days before death. Using hierarchical generalized linear models, we assessed regional variation of EOL care adjusting for patient demographics, tumor characteristics and hospital referral region (HRR)-level market factors. Results: Proportions of receipt of at least one potentially aggressive EOL care increased from 48.3% in 2005 to 48.7% in 2009 (P< .001). From 2005 to 2009, increasing proportions of patients had repeated hospitalization (14.0% vs. 14.8%; P= .0113) or ICU admission (15.2% vs. 19.5%; P< .001), whereas in-hospital death declined (24.1% vs. 22.0%; P< .001). Proportions of receiving chemotherapy (4.4% vs. 4.0%), repeated ED visits (34.0% vs. 32.9%) and very short hospice enrollment (7.2% vs. 8.3%) did not change significantly over time. The proportions of decedents who experienced aggressive EOL care varied substantially across HRRs. After adjusting for patient and HRR-level factors, the difference in the proportion of patients receiving potentially aggressive EOL care between HRRs in the lowest and the highest quintiles was 16.9 percentage point (57.2% vs. 40.3%). Conclusions: Despite growing focus on providing appropriate EOL care, nearly 50% of cancer decedents in the Medicare Program received aggressive EOL care with no evidence of demonstrable improvement in reducing aggressive EOL cancer care.
PS-148-Liver sinusoidal endothelial cells significantly cooperate in the phagocytic immune activities and activation of the adaptive T cell response in a model of experimental cirrhosis by CCl4
Authors: Esther Caparros, Oriol Juanola, Paula Piñero, Isabel Gómez-Hurtado, Raquel Linares, Paula Boix, Rebeca García-Román, Jordi Gracia-Sancho, Rubén Francés
Journal: Journal of Hepatology (2019)
EGFR drives the progression of AKI to CKD through HIPK2 overexpression
Authors: Luyang Xu, Xiaozhou Li, Fei Zhang, Lidong Wu, Zheng Dong, Dongshan Zhang
Journal: Theranostics (2019)

The molecular mechanism underlying the transition of acute kidney injury (AKI) to chronic kidney disease (CKD) induced by vancomycin (VAN) remains largely unknown.
Some characteristics of the major histocompatibility complex influencing neoplastic process in children and adolescents with solid malignant tumors.
Authors: Yuliya Yu. Kozel, Sergei A. Kuznetsov, Maria V. Starzhetskaya, Gulnara A. Mkrtchyan, Zhanna Sergeyevna Supik
Journal: Journal of Clinical Oncology (2015)

e21021 Background: According to modern concepts, the human leukocyte antigen (HLA) system regulates immune response providing interaction between immunocompetent cells, recognition of self and foreign cells (including changed self ones), activation and realization of immune response; it ensures survival of the human species in endogenous and exogenous aggression. The purpose of the study was to analyze effectiveness of treatment for solid malignant tumors in children in dependence on HLA specificity. Methods: The study included 189 patients with solid malignant neoplasms: 41 patients with neuroblastoma (21.6%), 44 – nephroblastoma (23.4%), 27 – osteogenic sarcoma (14.5%), 27 – Ewing's sarcoma (14.5%), 49 – germ cell tumors (26%). HLA class I antigens were typed serologically using typing Trays. Molecular typing of HLA class II antigens was performed by PCR-SSP. The significance of differences was assessed according to the chi-square (χ2) test with Yates’ correction for continuity for small sample size. Results: The study showed the following HLA specificities to be significantly more frequent in the remission group with pronounced clinical effect after complex treatment: А26 – 30.0% (the control group – 5.35%), (р < 0.12) Ewing's sarcoma; А26 – 17.39% (control –5.35%), (р < 0.05); В18 – 21.74 (control –13.5 %), (р < 0.01) – germ cell tumors, В44 – 42.85% (14.07%) (р < 0.01) – osteogenic sarcoma. In tumor progression: А24 – 60.0% (control – 16.46%) (р < 0.05); В13 – 60.0% (control – 11.6%) (р < 0.01); DRB1* – 04 – 80% (control – 18.75%) (р < 0.01) – neuroblastoma; А24 – 50.0% (control – 16.46%) (р < 0.05) – Ewing's sarcoma, В44 – 60.0% (control – 14.07%) (р < 0.001) – germ cell tumors. Conclusions: Carriage of these HLA-specificities in patients of the studied groups was a prognostic factor for the disease course (favorable or unfavorable).
Metabolic and epigenetic reprogramming in the arsenic-induced cancer stem cells
Authors: Lingzhi Li, Zhuoyue Bi, Priya Wadgaonkar, Yongju Lu, Qian Zhang, Yao Fu, Chitra Thakur, Li Wang, Fei Chen
Journal: Seminars in Cancer Biology (2019)

At present, the belief that genetic mutations control every aspect of tumorigenesis is still very popular. Even for the highly debated "bad luck" theory of cancers, it ascertained that random mutation of genes during the self-renewal of somatic stem cells is responsible for cancer initiation. Logically, most of the new therapeutic strategies so far, from molecular targeting to precision medicine or personalized medicine, are genome-obsessed and focused on identifying and targeting these mutated genes. Accordingly, a rather simplified therapeutic regimen was formulated: cancers with the same mutations, e.g., lung cancer, pancreatic cancer, breast cancer, ovarian cancer, etc, were managed with the same chemo or targeting medicine, whereas for a particular cancer, such as breast cancer or lung cancer, with different mutational spectrums was treated with different, so-called personalized medicine. The outcomes of this strategy, however, are mixed with encouraging and disappointing findings. In this review article, we will address the importance of non-genetic factors, the metabolic and epigenetic reprogramming, during the induction of cancer stem cells in response to arsenic, a major environmental human carcinogen. The information provided may not only advance our understanding of carcinogenic mechanism to a new level but also help in designing new strategies through targeting the metabolic and epigenetic signaling pathways for cancer therapy.
THU-215-Association between core mutations and annual decline rate of HBVDNA and HBsAg in chronic hepatitis B patients treated with nucleoside analogue
Authors: Takashi Honda, Masatoshi Ishigami, Takanori Ito, Yoji Ishizu, Teiji Kuzuya, Mitsuhiro Fujishiro
Journal: Journal of Hepatology (2019)
PS-149-Recombinant glutamine synthetase: A novel strategy for the treatment of hyperammonemia and consequent hepatic encephalopathy in rodent model of cirrhosis and urea cycle enzyme deficiency
Authors: Guangjun Song, Annarein Kerbert, Helen Jones, natalia arias, Nathan Davies, Fausto Andreola, tamara nicolson, Rajiv Jalan
Journal: Journal of Hepatology (2019)
One Health approach for West Nile virus surveillance in the European Union: relevance of equine data for blood safety
Authors: Johanna J Young, Denis Coulombier, Dragoslav Domanović, Hervé Zeller, Céline M Gossner
Journal: Eurosurveillance (2019)

West Nile virus (WNV) infection is notifiable in humans and equids in the European Union (EU). An area where a human case is detected is considered affected until the end of the mosquito transmission season (week 48) and blood safety measures have to be implemented. We used human and equine case notifications between 2013 and 2017 to define the WNV distribution in the EU and to investigate the relevance of using equine cases as a complementary trigger for blood safety measures. Adding areas with equine cases to the definition of an affected area would have a major impact on blood safety measures. Adding areas with equine cases where human cases have been reported in the past would increase the timeliness of blood safety measures with only a limited impact. Although the occurrence of human and/or equine cases confirms virus circulation in the EU, no evidence was found that occurrence of equine cases leads to human cases and vice versa. We conclude that information about equine data should contribute to raising awareness among public health experts and trigger enhanced surveillance. Further studies are required before extending the definition of affected areas to areas with human and/or equine cases.
Multimodal and combined multimodal-aerobic therapy in breast cancer survivors with cancer-related fatigue.
Authors: Matthias Kröz, Marcus Reif, Augustina Glinz, Bettina Berger, Andreas Nikolaou, Roland Zerm, Benno Brinkhaus, Matthias Girke, Arndt Büssing, Christoph Gutenbrunner
Journal: Journal of Clinical Oncology (2015)

e20717 Background: Cancer-related fatigue (CRF) and insomnia are major issues in breast cancer survivors (BC). While aerobic training (AT) is the standard therapy in BC with CRF, the effect-size is only minor to moderate. Other evidence-based treatments are cognitive behavioral therapy e.g. sleep education/restriction (SE) or psycho-education (PE) and mindfulness-based therapies. We investigated a 10-week multimodal program (MT) consisting of SE, PE, eurythmy and painting therapy separately or in combination with AT (CT) and compared MT and CT each with AT. Methods: In a comprehensive cohort design study BC with chronic CRF (6-36 months after adjuvant treatment, Fatigue Numerical Scale ≥ 4) were evenly randomized or allocated by patient preference. Primary endpoint was a composite outcome of the Pittsburgh Sleep Quality Index (PSQI) and the Cancer Fatigue Scale (CFS-D) after 10 weeks (T1); a second endpoint included a six months later (T2) follow-up. We tested confirmatively for non-inferiority of MT vs. AT, for superiority of CT and finally MT vs. AT (calculated sample size: 114). A closed testing procedure preserved the global α-level of 5%. The intention-to-treat analysis used 2 propensity scores: the choice of randomization/preference and the preferred treatment. Results: Of 278 candidates 65 BC patients were randomized and 61 allocated by preference to the three treatment arms (AT: n = 22/6, MT: n = 21/23, CT: n = 22/32). Socio-demographic parameters were balanced, however symptom burden was lower in preference AT patients. MT-non-inferiority was confirmed (Δ = -0.048; 95%-CI [-0.081; -0.014], p < 0.05), yet the confirmative analysis stopped at the superiority test of CT vs. AT (Δ = -0.025; 95%-CI [-0.056; 0.006], p = 0.119) at T1. In ensuing explorative analyses MT was significantly better than AT at T1 and T2; and CT better than AT at T2 (all p < 0.05). PSQI and CFS-D contributed nearly equivalently to these findings. Conclusions: In this trial a new multimodal CRF-therapy performed non-inferior to standard therapy and even yielded indications for superiority. Hence, a randomized controlled trial including a large samples size and long-term follow up to evaluate the multimodal CRF-therapy is highly warranted. Clinical trial information: DRKS00003736.
Comparison of 3-Dimensional and Augmented Reality Kidney Models With Conventional Imaging Data in the Preoperative Assessment of Children With Wilms Tumors
Authors: Lianne M. Wellens, Jene Meulstee, Cornelis P. van de Ven, C. E. J. Terwisscha van Scheltinga, Annemieke S. Littooij, Marry M. van den Heuvel-Eibrink, Marta Fiocco, Anne C. Rios, Thomas Maal, Marc H. W. A. Wijnen
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Nephron-sparing surgery can be considered in well-defined cases of unilateral and bilateral Wilms tumors, but the surgical procedure can be very challenging for the pediatric surgeon to perform. <h3>Objective</h3> To assess the added value of personalized 3-dimensional (3-D) kidney models derived from conventional imaging data to enhance preoperative surgical planning. <h3>Design, Setting, and Participants</h3> In a survey study, the conventional imaging data of 10 Dutch children with Wilms tumors were converted to 3-D prints and augmented reality (AR) holograms and a panel of pediatric oncology surgeons (n = 7) assessed the quality of the different imaging methods during preoperative evaluation. Kidney models were created with 3-D printing and AR using a mixed reality headset for visualization. <h3>Main Outcomes and Measures</h3> Differences in the assessment of 4 anatomical structures (tumor, arteries, veins, and urinary collecting structures) using questionnaires. A Likert scale measured differences between the imaging methods, with scores ranging from 1 (completely disagree) to 5 (completely agree). <h3>Results</h3> Of the 10 patients, 7 were girls, and the mean (SD) age was 3.7 (1.7) years. Compared with conventional imaging, the 3-D print and the AR hologram models were evaluated by the surgeons to be superior for all anatomical structures: tumor (median scores for conventional imaging, 4.07; interquartile range [IQR], 3.62-4.15 vs 3-D print, 4.67; IQR, 4.14-4.71;<i>P</i> = .008 and AR hologram, 4.71; IQR, 4.26-4.75;<i>P</i> = .002); arteries (conventional imaging, 3.62; IQR, 3.43-3.93 vs 3-D print, 4.54; IQR, 4.32-4.71;<i>P</i> = .002 and AR hologram, 4.83; IQR, 4.64-4.86;<i>P</i> &lt; .001), veins (conventional imaging, 3.46; IQR 3.39-3.62 vs 3-D print, 4.50; IQR, 4.39-4.68;<i>P</i> &lt; .001 and AR hologram, 4.83; IQR, 4.71-4.86;<i>P</i> &lt; .001), and urinary collecting structures (conventional imaging, 2.76; IQR, 2.42-3.00 vs 3-D print, 3.86; IQR, 3.64-4.39;<i>P</i> &lt; .001 and AR hologram, 4.00; IQR, 3.93-4.58;<i>P</i> &lt; .001). There were no differences in anatomical assessment between the two 3-D techniques (the 3-D print and AR hologram). <h3>Conclusions and Relevance</h3> In this study, the 3-D kidney models were associated with improved anatomical understanding among the surgeons and can be helpful in future preoperative planning of nephron-sparing surgery for Wilms tumors. These models may be considered as a supplementary visualization in clinical care.
PS-061-Non-alcoholic fatty liver disease/Non-alcoholic steatohepatitis patients with advanced liver disease had high burden of comorbidities, healthcare resource utilization and costs: Results from Italian administrative databases
Authors: Salvatore Petta, Jie Ting, Stefania Saragoni, Luca Degli Esposti, Ahmet Burak Ozbay, Giulio Marchesini Reggiani
Journal: Journal of Hepatology (2019)
Cytokine Profiles in Acute Promyelocytic Leukemia Patients at Diagnosis and during the Treatment with Acid All-Trans Retinoic and Anthracyclines
Authors: Luciana Yamamoto Almeida, Priscila S Scheucher, Ana Silvia G de Lima, Sarah C Bassi, Márcia S Baggio, Isabel Weinhäuser, Ana Paula Lange, Diego Antonio Pereira-Martins, Eduardo Magalhães Rego
Journal: Blood (2017)
FRI-284-A combination of fenofibrate with a liver-targeted acetyl-CoA carboxylase inhibitor enhances efficacy while reversing plasma triglyceride increases in a murine model of NASH
Authors: Jamie Bates, Archana Vijayakumar, David Hollenback, Saritha Kusam, Harini Burri, David G. Breckenridge
Journal: Journal of Hepatology (2019)
Synergistic Association of House Endotoxin Exposure and Ambient Air Pollution with Asthma Outcomes
Authors: Angelico Mendy, Jesse Wilkerson, Päivi M. Salo, Charles H. Weir, Lydia Feinstein, Darryl C. Zeldin, Peter S. Thorne
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

House endotoxin and ambient air pollution are risk factors for asthma; however, the effects of their coexposure on asthma are not well characterized.
GMC's Tomorrow's Doctors scheme is well under way
Authors: Nisheeth Rajpa
Journal: BMJ (1999)

Students at Southampton University



Recent visits by members of the GMC education committee to the United Kingdom's 25 medical schools to monitor progress o curricular change and development have proved to be informative.

In 1993 the GMC published Tomorrow's Doctors , a new initiative to improve and update medical undergraduate teaching to the next millennium. With the cooperation of all British medical schools the scheme is presently being implemented. The GMC education committee, led by Professor Charles George, aims to visit all medical …
FRI-320-TM6SF2 silencing impairs lipid metabolism and trafficking in HepG2 cells carrying the I148M PNPLA3 variant and MBOAT7 deletion
Authors: Miriam Longo, Marica Meroni, Raffaela Rametta, Veronica Erconi, Stefano Romeo, Anna Ludovica Fracanzani, Luca Valenti, Paola Dongiovanni
Journal: Journal of Hepatology (2019)
TCTAP A-093 The Prevalence of Leaflet Thrombosis in Intra-annular Versus Supra-annular Transcatheter Aortic Valve Prostheses
Authors: Hashrul Rashid, Nancy Khav, Rob Gooley, Ameera Amiruddin, Arthur Nasis, James Cameron, Adam Brown
Journal: Journal of the American College of Cardiology (2019)
TCTAP A-112 Use of Implantable Cardioverter Defibrillators for Primary Prevention of Sudden Cardiac Death: Results from the Improve SCA Clinical Study
Authors: Seongwook Han, Young-Hoon Kim, Il-Young Oh, Boyoung Joung, Gi-Byoung Nam, Yong Seog Oh
Journal: Journal of the American College of Cardiology (2019)
FRI-055-Failure to normalize ALT and IgG in Autoimmune Hepatitis is associated with more advanced liver disease: Perspectives from a multi-ethnic Canadian AIH registry
Authors: Surain Roberts, Aliya Gulamhusein, Marwa Ismail, Andrew L. Mason, Mark G Swain, Catherine Vincent, Eric Yoshida, Cynthia Tsien, Jennifer Flemming, Harry Janssen, Bettina Hansen, Gideon Hirschfield
Journal: Journal of Hepatology (2019)
Abstract 20437: Predictors of Prosthesis Durability After Mitral Valve Replacement in Children
Authors: Patrick A Upchurch, Sitaram Emani
Journal: Circulation (2016)

Introduction: Limits of successful mitral valve replacement (MVR) in children include patient size, left ventricular (LV) geometry, and lack of small prosthetic valves. Due to its non-fixed diameter, the Melody valve is suited to address these concerns. Methods: A single institution retrospective review of children aged less than 18 years undergoing MVR between 1992 and 2016. Primary outcomes include freedom from structural valve deterioration (SVD) and freedom from re-replacement, which were examined as a function of prosthesis type, patient age, diagnosis of LV hypoplasia, and markers of prosthesis-patient mismatch. A conditional recurrent event Cox proportional hazards regression model assessed association between outcome and predictors. Results: A total of 154 children underwent 213 MVRs: 134 (62.9%) mechanical, 37 (17.4%) porcine, 12 (5.6%) pericardial, and 30 (14.1%) Melody. Median age in years at initial replacement: 8.6 for pericardial valves, 6.0 for mechanical, 3.0 for porcine, and 0.8 for Melod...