tbuckley/cabot-search huggingface dataset:
18F-Fludeoxyglucose PET/CT in SCLC: Analysis of the CONVERT Randomized Controlled Trial
Authors: Prakash Manoharan, Ahmed Salem, Hitesh Mistry, Michael Gornall, Susan Harden, Peter Julyan, Imogen Locke, Jonathan McAleese, Rhona McMenemin, Nazia Mohammed, Michael Snee, Sarah Woods, Thomas Westwood, Corinne Faivre-Finn
Journal: Journal of Thoracic Oncology (2019)

IntroductionWe used phase-3 CONVERT trial data to investigate the impact of fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in SCLC.MethodsCONVERT randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) chemoradiotherapy. Patients were divided into two groups in this unplanned analysis: those staged with conventional imaging (contrast-enhanced thorax and abdomen CT and brain imaging with or without bone scintigraphy) and those staged with 18F-FDG PET/CT in addition.ResultsData on a total of 540 patients were analyzed. Compared with patients who underwent conventional imaging (n = 231), patients also staged with 18F-FDG PET/CT (n = 309) had a smaller gross tumor volume (p = 0.003), were less likely to have an increased pretreatment serum lactate dehydrogenase level (p = 0.035), and received more chemotherapy (p = 0.026). There were no significant differences in overall (hazard ratio = 0.87, 95% confidence interval: 0.70–1.08, p = 0.192) and progression-free survival (hazard ratio = 0.87, 95% confidence interval: 0.71–1.07], p = 0.198) between patients staged with or without 18F-FDG PET/CT. In the conventional imaging group, we found no survival difference between patients staged with or without bone scintigraphy. Although there were no differences in delivered radiotherapy dose, 18F-FDG PET/CT–staged patients received lower normal tissue (lung, heart, and esophagus) radiation doses. Apart from a higher incidence of late esophagitis in patients staged with conventional imaging (for grade ≥1, 19% versus 11%; [p = 0.012]), the incidence of acute and late radiotherapy-related toxicities was not different between the two groups.ConclusionIn CONVERT, survival outcomes were not significantly different in patients staged with or without 18F-FDG PET/CT. However, this analysis cannot support the use or omission of 18F-FDG PET/CT owing to study limitations.
Treatment of Progressive Multifocal Leukoencephalopathy with Nivolumab
Authors: Ondine Walter, Emmanuel Treiner, Fabrice Bonneville, Catherine Mengelle, François Vergez, Fleur Lerebours, Pierre Delobel, Roland Liblau, Guillaume Martin-Blondel
Journal: New England Journal of Medicine (2019)

Treatment of PML with Nivolumab A patient with severe idiopathic lymphopenia and progressive multifocal leukoencephalopathy had T-cell exhaustion and high expression of immune checkpoint markers. T...
Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients (CRISP): a prospective German Registry in stage IV NSCLC AIO-TRK-0315)
Authors: F. Griesinger, W. Eberhardt, N. Marschner, M. Jänicke, A. Fleitz, L. Spring, J. Sahlmann, A. Karatas, A. Hipper, W. Weichert, M. Sebastian, M. Thomas
Journal: Annals of Oncology (2017)
TCTAP C-222 Percutaneous Closure of Ventricular Septal Defect After Myocardial Infarction: Challenges on the Time and the Options
Authors: Imam Kukuh Darmawan, Anggia Chairuddin Lubis, Ali Nafiah Nasution, Zulfikri Mukhtar, Harris Hasan
Journal: Journal of the American College of Cardiology (2019)
THU-453-Dissecting the landscape of (epi-)genetic alterations during sequential evolution of liver cancer
Authors: Carolin Czauderna, Alicia Poplawski, Darko Castven, Stefanie Heilmann-Heimbach, Margarete Odenthal, Wafa Amer, Jesper Andersen, Colm O Rourke, Harald Binder, Dirk Ridder, Beate Straub, Peter Galle, Snorri Thorgeirsson, Young Nyun Park, Jens Marquardt
Journal: Journal of Hepatology (2019)
Abstract P236: The Heritability of Submaximal Exercise Heart Rate Response to Regular Exercise is Accounted for by Nine SNPs
Authors: Tuomo Rankinen, Yun Ju Sung, Mark Sarzynski, Treva K Rice, DC Rao, Claude Bouchard
Journal: Circulation (2012)

Regular physical activity is the most effective non-pharmacological strategy to lower heart rate both at rest and during submaximal physical work. We have previously shown that endurance training-induced changes in heart rate are heritable (h 2 =0.34). However, few genes associated with heart rate training responses have been identified. The purpose of this study was to perform a genome-wide association study (GWAS) to uncover DNA sequence variants associated with submaximal exercise heart rate training responses in the HERITAGE Family Study. Heart rate was measured during steady-state exercise at 50 Watts (HR50) on two separate days both before and after a 20-week endurance training program in 473 white subjects from 99 families. Illumina HumanCNV370-Quad v3.0 BeadChips were genotyped using Illumina BeadStation 500GX platform. After quality control procedures, 320,000 single-nucleotide polymorphisms (SNPs) were available for the GWAS analyses. Associations between HR50 training response (ΔHR50) and the SNPs were tested using the MERLIN software package (single-SNP analyses) and standard regression models (multivariate analyses). Furthermore, conditional heritability analysis (MERLIN) was used to test the contribution of the most significant SNPs to the heritability of ΔHR50. Exercise training induced an average reduction of 11 bpm in HR50 (SD = 9.9 bpm, p&lt;0.0001), while individual training responses ranged from a 12 bpm increase to a 42 bpm decrease. The strongest associations for ΔHR50 (adjusted for age, sex, BMI and baseline HR50) were detected with SNPs at the YWHAQ locus on chromosome 2p25 (p=8.1x10 -7 ), RBPMS locus on 8p12 (p=3.8x10 -6 ) and CREB1 locus on 2q34 (p=1.6x10 -5 ). In addition, 37 other SNPs showed p-values &lt; 9.9x10 -5 . After removing redundant SNPs, the ten most significant SNPs explained 35.9% of the ΔHR50 variance in a multivariate regression model. Conditional heritability test showed that nine of these SNPs (all intragenic) accounted for 100% of the ΔHR50 heritability. Our results indicate that SNPs in nine genes related to cardiomyocyte and neuronal functions as well as cardiac memory formation fully account for the heritability of submaximal exercise heart rate response to regular physical activity in the HERITAGE Family Study.
FRI-177-Association of prophylactic anti-HBV therapy with improved long-term survival in patients with hepatocellular carcionoma undergoing transarterial therapy
Authors: Jeong Won Jang, Sun Hong Yoo, Hee Chul Nam, Pil Soo Sung, Sung Won Lee, Jung Hyun Kwon, Si Hyun Bae, Seung Kew Yoon, Jong Young Choi
Journal: Journal of Hepatology (2019)
SAT-053-Liver stiffness-spleen size-to-platelet ratio risk score detects esophageal varices and HCC risk in HCV- and HBV-related cirrhosis responsive to DAA
Authors: Barbara Imperatrice, Wilma Debernardi Venon, Claudia Chialà, Giorgio Maria Saracco, Alfredo Marzano
Journal: Journal of Hepatology (2019)
Inlaying Radiosensitizer onto the Polypeptide Shell of Drug-Loaded Ferritin for Imaging and Combinational Chemo-Radiotherapy
Authors: Qiuhong Zhang, Jingwen Chen, Jie Shen, Shixiong Chen, Kaicheng Liang, Han Wang, Hangrong Chen
Journal: Theranostics (2019)

Rationale: Ferritin with unique hollow cavity is an emerging protein-based nanoplatform for anticancer-drug delivery, but the in vivo chemotherapeutic effectiveness is still unsatisfactory with such a monotherapy modality, which is urgently in need of improvement.Methods: Here a novel ferritin nanotheranostic with anticancer-drug doxorubicin encapsulated into its hollow interior and nanoradiosensitizer bismuth sulfide nanocrystals inlayed onto its polypeptide shell was synthesized for combinational therapeutic benefits.The formation mechanism of bismuth sulfide nanocrystals based on ferritin has been analyzed.The in vitro and in vivo treatment effects were carried out on HeLa cancer cells and tumor-bearing mice, respectively.The biocompatibility and excretion of the ferritin nanotheranostic have also been evaluated to guarantee their biosafety.Results: The polypeptide shell of ferritin provides nucleation sites for the bismuth sulfide nanocrystals through coordination interaction, and simultaneously inhibits the further growth of bismuth sulfide nanocrystals, rendering the bismuth sulfide nanocrystals like rivets inlaying onto the polypeptide firmly, which can not only strengthen the architectural stability of ferritin to prevent drug burst leakage during systemic circulation, but also act as excellent computed tomography contrast agents and nanoradiosensitizers for in vivo imaging-guided cancer combinational treatments. Conclusions:The design concept of inlaying bismuth sulfide nanocrystals onto the polypeptide shell of doxorubicin-encapsulated ferritin significantly inhibits the tumor growth and simultaneously further broadens the application of ferritin in nanomedicine.
Downregulation of Human DAB2IP Gene Expression in Renal Cell Carcinoma Results in Resistance to Ionizing Radiation
Authors: Eun-Jin Yun, Chun-Jung Lin, Andrew Dang, Elizabeth Hernandez, Jiaming Guo, Wei-Min Chen, Joyce Allison, Nathan Kim, Payal Kapur, James Brugarolas, Kaijie Wu, Dalin He, Chih-Ho Lai, Ho Lin, Debabrata Saha, Seung Tae Baek, Benjamin P.C. Chen, Jer-Tsong Hsieh
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Renal cell carcinoma (RCC) is known to be highly radioresistant but the mechanisms associated with radioresistance have remained elusive. We found DOC-2/DAB2 interactive protein (DAB2IP) frequently downregulated in RCC, is associated with radioresistance. In this study, we investigated the underlying mechanism regulating radioresistance by DAB2IP and developed appropriate treatment. Experimental Design: Several RCC lines with or without DAB2IP expression were irradiated with ionizing radiation (IR) for determining their radiosensitivities based on colony formation assay. To investigate the underlying regulatory mechanism of DAB2IP, immunoprecipitation-mass spectrometry was performed to identify DAB2IP-interactive proteins. PARP-1 expression and enzymatic activity were determined using qRT-PCR, Western blot analysis, and ELISA. In vivo ubiquitination assay was used to test PARP-1 degradation. Furthermore, in vivo mice xenograft model and patient-derived xenograft (PDX) model were used to determine the effect of combination therapy to sensitizing tumors to IR. Results: We notice that DAB2IP-deficient RCC cells acquire IR-resistance. Mechanistically, DAB2IP can form a complex with PARP-1 and E3 ligases that is responsible for degrading PARP-1. Indeed, elevated PARP-1 levels are associated with the IR resistance in RCC cells. Furthermore, PARP-1 inhibitor can enhance the IR response of either RCC xenograft model or PDX model. Conclusions: In this study, we unveil that loss of DAB2IP resulted in elevated PARP-1 protein is associated with IR-resistance in RCC. These results provide a new targeting strategy to improve the efficacy of radiotherapy of RCC.
The Effect of Systolic Variation of Mitral Regurgitation on Discordance Between Noninvasive Imaging Modalities
Authors: Seth Uretsky, Lillian Aldaia, Leo Marcoff, Konstantinos Koulogiannis, Soichiro Hiramatsu, Edgar Argulian, Mark Rosenthal, Linda D. Gillam, Steven D. Wolff
Journal: JACC. Cardiovascular imaging (2019)
Intermittent Versus Continuous PEG-Asparaginase to Reduce Asparaginase-Associated Toxicities: A NOPHO ALL2008 Randomized Study
Authors: Birgitte Klug Albertsen, Kathrine Grell, Jonas Abrahamsson, Bendik Lund, Kim Vettenranta, Ólafur G. Jónsson, Thomas L. Frandsen, Benjamin O. Wolthers, Mats Heyman, Kjeld Schmiegelow
Journal: Journal of Clinical Oncology (2019)

Asparaginase is an essential drug in childhood acute lymphoblastic leukemia (ALL) therapy and is frequently given for months to obtain continuous asparagine depletion. We randomly assigned patients to continuous versus intermittent pegylated-asparaginase (PEG-asp) treatment, hypothesizing there would be decreased toxicity with unchanged efficacy.Children (median age, 4.2 years) treated for non-high-risk ALL according to the Nordic Society for Pediatric Hematology and Oncology ALL2008 protocol received five intramuscular PEG-asp injections (1,000 IU/m2) every two weeks and were then randomly assigned to additional three doses (6-week intervals [experimental arm], n = 309) versus 10 doses (2-week intervals [standard arm], n = 316). The primary end point was noninferior (6% margin) disease-free survival. Toxicity reduction was a secondary end point. Occurrence of asparaginase-associated hypersensitivity, pancreatitis, osteonecrosis, and thromboembolism were prospectively registered.After a median follow-up of 4.1 years, the 5-year disease-free survival was 92.2% (95% CI, 88.6 to 95.8) and 90.8% (95% CI, 87.0 to 94.6) in the experimental and standard arms, respectively. The 3-year cumulative incidence of any first asparaginase-associated toxicity (hypersensitivity [n = 13]; osteonecrosis [n = 29]; pancreatitis [n = 24]; thromboembolism [n = 17]) was 9.3% in the experimental arm and 18.1% in the standard arm (P = .001). Asparaginase-associated toxicity reduction was confirmed in sex- and risk-group-adjusted Cox regression analysis stratified by age (≥ 10 and < 10 years; hazard ratio, 0.48; P = .001). The experimental arm had the lowest incidences of all four toxicities, reaching significance for pancreatitis (6-month risk, 5.8% v 1.3%; P = .002).The excellent cure rates and reduced toxicity risk support the use of intermittent PEG-asp therapy after the first 10 weeks in future childhood ALL trials that apply prolonged PEG-asp therapy.
A novel metric to quantify cell-cycling kinetics and refine the Nottingham Grading System to improve breast cancer patient stratification.
Authors: Sergey Klimov, Vaishali Pannu, Nikita Wright, Remus Osan, Guilherme Henrique Cantuaria, Stephen Wells, Xiaoxian Li, Michelle D. Reid, Padmashree C.G. Rida, Ritu Aneja
Journal: Journal of Clinical Oncology (2015)

e22149 Background: Ki67 Index (KI) and mitotic index (MI) are proliferation markers with established prognostic value in breast carcinomas. While KI is evaluated immunohistochemically and reported as percentage, MI is determined visually and reflects total mitotic cells in 10 high-power fields. Their disparate measurement scales and lack of rational integration diminish prognostic accuracy. Methods: 233 archival paraffin-embedded Nottingham Grade I, II and III (NGI, NGII and NGIII) breast carcinoma tissue slides were stained for Ki67, phosphohistone-H3, α-tubulin and DNA. Using multicolor confocal imaging, Ki67-positive and mitotic cells were counted within the same microscopic field to determine mitosis to proliferation (i.e., M-to-P) ratio. M-to-P ratio reflects cell cycling kinetics of proliferative cells. Patients risk-stratified by Nottingham grading system (NGS), or KI Groups (KG1, 2, 3) using St. Gallen guidelines, were further segmented using an M-to-P classifier. We also pioneered a 2-color immunohistochemical method to enable routine M-to-P profiling of tumors in the clinic. Results: Although both KI and MI increased with tumor grade, M-to-P ratios decreased grade-wise; proliferating cells in high-grade tumors thus spend longer durations (1.435 times) in interphase than those in low-grade tumors. M-to-P classifier “adjusted” tumor grades of 35% of patients graded by NGS, improved their stratification (Hazard ratios (HRs): Adjusted NGII = 1.17 versus original 1.24; HR for NGIII = 1.91 versus original 1.33), model-fit statistics and concordance index. KI Group adjustment using M-to-P classifier “adjusted” 53.3% of patients to new groups yielding better stratification (HRs: Adjusted KG2 = 1.856 versus original 1.674; Adjusted KG3 = 3.58 versus original 1.15), model-fit statistics and concordance index. Conclusions: A novel histological metric, M-to-P ratio, uncovers the yet unrecognized “kinetic element” of cell-cycling that yields clinically-actionable risk-predictive information to improve patient segmentation compared to NGS or KI-based systems. Our facile IHC-based method paves the way for routine M-to-P profiling of tumors in the clinic.
PS-022-Optimal timing of endoscopy is associated with lower 42-day mortality in variceal bleeding
Authors: Stig Borbjerg Laursen, Adrian Stanley, Virginia Hernandez-Gea, Bogdan Procopet, Álvaro Giráldez, Lucio Amitrano, Candid Villanueva, Dominique Thabut, Luis Ibañez-Samaniego, Gilberto Silva-Junior, Javier Martinez, Joan Genescà, Christophe Bureau, Jonel Trebicka, Elba Llop, Wim Laleman, Jm Palazon, Jose Castellote, Susana Rodrigues, Lise L Gluud, Carlos Noronha Ferreira, Rafael Barcelo, Nuria Cañete, Manuel Rodríguez, Arnulf Ferlitsch, Jose Luis Mundi, Henning Gronbaek, Manuel Hernández-Guerra, Romano Sassatelli, Alessandra Dell’Era, Marco Senzolo, Juan G Abraldes, Manuel Romero-Gómez, Alexander Zipprich, Meritxell Casas, Helena Masnou, Massimo Primignani, Frederik Nevens, Jose Luis Calleja, Christian Jansen, Marie Angele Robic, Irene Conejo, Maria-Vega Catalina, Agustin Albillos, Marika Rudler, Edilmar Alvarado, Maria Anna Guardascione, Marcel Tantau, Jaime Bosch, Ferran Torres, Juan Carlos Garcia-Pagán, Aleksander Krag
Journal: Journal of Hepatology (2019)
Abstract 103: Incomplete Kawasaki Disease - Patients With ≦ 5 Days Of Fever Successfully Treated By Antibiotics But Left With Coronary Aneurysms -
Authors: Kenji Suda, Hiroshi Nishino, Yoshiyuki Kudo, Hironaga Yoshimoto, Shintaro Kishimoto, Motofumi Iemura, Jiro Iwamoto, Shigetaka Nishihara, Yoshitaka Gotou, Makoto Nishibatake, Toyojiro Matsuishi
Journal: Circulation (2015)

Objective: We report four patients with incomplete Kawasaki disease (KD) successfully treated by antibiotics without intravenous immunoglobulin (IVIG) treatment with ≦ 5 days of fever but left with coronary artery lesion. Result: The patients were 2 babies and 2 young children age ranged from 2 months to 2 years old and 9 months. They showed fever and other signs of KD, but did not fulfill diagnostic criteria. The numbers of symptoms compatible with KD were 2 or 3 and included conjunctival injection, oral or lip injection, and eruption. Within 5 days, they became afebrile by antibiotics without IVIG treatment. However, they were noted to have coronary artery aneurysm (CAA) on day from 7 to 33 of illness. All patients had been placed on antithrombotic treatment including aspirin or aspirin plus warfarin and, fortunately, showed regression of CAA within 2 years. Conclusions: This case series indicates that there are patients with incomplete KD successfully treated by antibiotics without IVIG but left with CAA. These cases must be underdiagnosed if intentional echocardiographic examination are scheduled and might be left without appropriate treatment, antithrombotic treatment. Further collection of data of these patients is indispensable.
Breast conserving surgery versus mastectomy in Hispanic (Latina) women with breast cancer in the Mexican-Border city of El Paso, TX.
Authors: Zeina A. Nahleh, Alok kumar Dwivedi, Andres Alvarado, Luis Sanchez, Salman Otoukesh
Journal: Journal of Clinical Oncology (2015)

e12064 Background: Socioeconomic and ethnic disparities still exist that preclude patients from receiving breast-conserving therapy. We sought to determine the rate of mastectomy versus breast-conserving surgery (BCS) in Hispanic population at our institution and assess factors that might affect possible disparity in surgical options. Methods: We retrospectively reviewed consecutive cases of Hispanic patients diagnosed with Stages I or II breast cancer between 1/1/2005 and 12/31/2012 in our NAPBC - accredited breast center and determined demographic and clinical characteristics and types of medical insurance and year of diagnosis. We assessed the rates of mastectomy and BCS / lumpectomy determined by treatment code. Data were described using mean, standard deviation (SD), frequency, and proportion. Unpaired and Fisher’s exact tests were used to compare the clinical and demographic characteristics between the two types of surgery. A multiple logistic regression was used to determine the factors associated with lumpectomy as compared with mastectomy. P-values less than 5% were considered as significant results. Results: N = 204 patients. Mean age 60. Insurance information was available for 194 patients: Medicare (18%); Medicaid (8%); Private insurance/3rd part payer (26%) and uninsured receiving the county hospital discount (48%). Most of the patients received BCS. No significant difference was seen based on age, body mass index, stage, Estrogen/Progesterone receptors, Her2 status, or type of insurance. However, we noticed a significant trend toward more mastectomies and less BCS betwen 2005 and 2012 .Conclusions: The recently increasingrates of mastectomies, although consistent with nationwide trends, are particularly concerning in our low-resource patient population. The majority (56%) of whom are underinsured with no ccess to reconstructive surgeries resulting in poorer quality of life. Continuing to raising awareness for early detection and continuing to provide access to BCS and radiation is important for underinsured patients to maintain their quality of life and decrease ethnic disparities in the treatment of breast cancer.
Abstract 15511: Kruppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility
Authors: Marcy Martin, Zhao Li, Jin Zhang, Hsi-Yuan Huang, Liang Bai, Jiao Zhang, Jian Kang, Ming He, Jie Li, Mano Maurya, Shakti Gupta, Guangjin Zhou, Panjamaporn Sangwung, Yong-Jiang Xu, Ting Lei, Hsien-Da Huang, Mohit Jain, Mukesh K Jain, Shankar Subramaniam, John Y Shyy
Journal: Circulation (2017)

Background: Atherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall [e.g., endothelial cells (ECs)] as well as circulating and resident immunogenic cells (e.g., ...