tbuckley/cabot-search huggingface dataset:
Assessment of Treatment With Sorafenib Plus Doxorubicin vs Sorafenib Alone in Patients With Advanced Hepatocellular Carcinoma
Authors: Ghassan K. Abou-Alfa, Qian Shi, Jennifer J. Knox, Andreas Kaubisch, Donna Niedzwiecki, James Posey, Benjamin R. Tan, Petr Kavan, Rakesh Goel, Philip E. Lammers, Tanios S. Bekaii-Saab, Vincent C. Tam, Lakshmi Rajdev, Robin K. Kelley, Imane El Dika, Tyler Zemla, Ryan I. Potaracke, Jennifer Balletti, Anthony B. El-Khoueiry, James J. Harding, Jennifer M. Suga, Lawrence H. Schwartz, Richard M. Goldberg, Monica M. Bertagnolli, Jeffrey Meyerhardt, Eileen M. O’Reilly, Alan P. Venook
Journal: JAMA Oncology (2019)

Previous communication has reported significant improvement in overall survival (OS) when using doxorubicin plus sorafenib in the treatment of advanced hepatocellular cancer (HCC).To determine if doxorubicin added to sorafenib therapy improves OS, with stratification for locally advanced and metastatic disease.This unblinded randomized phase 3 clinical trial was led by Alliance in collaboration with Eastern Cooperative Oncology Group-American College of Radiology Imaging Network, Canadian Cancer Trials Group, and Southwest Oncology Group. It was launched in February 2010 and completed in May 2015; data were also analyzed during this time frame. Patients with histologically proven advanced HCC, no prior systemic therapy, Child-Pugh grade A score, Eastern Cooperative Oncology Group performance status of 0 to 2 (later amended to 0-1), and adequate hematologic, hepatic, renal, and cardiac function were eligible. The OS primary end point had a final analysis planned with 364 events observed among 480 total patients with 90% power to detect a 37% increase in median OS.Patients received either 60 mg/m2 of doxorubicin every 21 days plus 400 mg of sorafenib orally twice daily or the sorafenib alone, adjusted to half doses for patients with bilirubin levels of 1.3 to 3.0 mg/dL.The primary end point was OS, and progression-free survival (PFS) was a secondary end point.Of 356 patients included in the study, the mean (SD) age was 62 (10.1) years, and 306 (86.0%) were men. Although it was planned to include 480 patients, the study was halted after accrual of 356 patients (180 patients treated with doxorubicin plus sorafenib and 176 with sorafenib alone) with a futility boundary crossed at a planned interim analysis. Median OS was 9.3 months (95% CI, 7.3-10.8 months) in the doxorubicin plus sorafenib arm and 9.4 months (95% CI, 7.3-12.9 months) in the sorafenib alone arm (hazard ratio, 1.05; 95% CI, 0.83-1.31). The median PFS was 4.0 months (95% CI, 3.4-4.9 months) in the doxorubicin plus sorafenib arm and 3.7 months (95% CI, 2.9-4.5 months) in the sorafenib alone arm (hazard ratio, 0.93; 95% CI, 0.75-1.16). Grade 3 or 4 neutropenia and thrombocytopenia adverse events occurred in 61 (36.8%) and 29 (17.5%) patients, respectively, being treated with doxorubicin plus sorafenib vs 1 (0.6%) and 4 (2.4%) patients treated with sorafenib.This multigroup study of the addition of doxorubicin to sorafenib therapy did not show improvement of OS or PFS in patients with HCC.ClinicalTrials.gov identifier: NCT01015833.
Temporal Trends and Patterns in Mortality After Incident Heart Failure
Authors: Nathalie Conrad, Andrew Judge, Dexter Canoy, Jenny Tran, Ana-Catarina Pinho-Gomes, Elizabeth R. C. Millett, Gholamreza Salimi-Khorshidi, John G. Cleland, John J. V. McMurray, Kazem Rahimi
Journal: JAMA Cardiology (2019)

Despite considerable improvements in heart failure care, mortality rates among patients in high-income countries have changed little since the early 2000s. Understanding the reasons underlying these trends may provide valuable clues for developing more targeted therapies and public health strategies.To investigate mortality rates following a new diagnosis of heart failure and examine changes over time and by cause of death and important patient features.This population-based retrospective cohort study analyzed anonymized electronic health records of individuals who received a new diagnosis of heart failure between January 2002 and December 2013 who were followed up until December 2014 from the Clinical Practice Research Datalink, which links information from primary care, secondary care, and the national death registry from a subset of the UK population. The data were analyzed from January 2018 to February 2019.All-cause and cause-specific mortality rates at 1 year following diagnosis. Poisson regression models were used to calculate rate ratios (RRs) and 95% confidence intervals comparing 2013 with 2002, adjusting for age, sex, region, socioeconomic status, and 17 major comorbidities.Of 86 833 participants, 42 581 (49%) were women, 51 215 (88%) were white, and the mean (SD) age was 76.6 (12.6) years. While all-cause mortality rates declined only modestly over time (RR comparing 2013 with 2002, 0.94; 95% CI, 0.88-1.00), underlying patterns presented explicit trends. A decline in cardiovascular mortality (RR, 0.73; 95% CI, 0.67-0.80) was offset by an increase in noncardiovascular deaths (RR, 1.22; 95% CI, 1.11-1.33). Subgroup analyses further showed that overall mortality rates declined among patients younger than 80 years (RR, 0.79; 95% CI, 0.71-0.88) but not among those older than 80 years (RR, 0.97; 95% CI, 0.90-1.06). After cardiovascular causes (898 [43%]), the major causes of death in 2013 were neoplasms (311 [15%]), respiratory conditions (243 [12%]), and infections (13%), the latter 2 explaining most of the observed increase in noncardiovascular mortality.Among patients with a new heart failure diagnosis, considerable progress has been achieved in reducing mortality in young and middle-aged patients and cardiovascular mortality across all age groups. Improvements to overall mortality are hindered by high and increasing rates of noncardiovascular events. These findings challenge current research priorities and management strategies and call for a greater emphasis on associated comorbidities. Specifically, infection prevention presents as a major opportunity to improve prognosis.
Bilirubin-Related Differential Striatal [18F]FP-CIT Uptake in Parkinson Disease
Authors: Dong Yun Lee, Minyoung Oh, Soo-Jong Kim, Jungsu S. Oh, Sun Ju Chung, Jae Seung Kim
Journal: Clinical Nuclear Medicine (2019)

Purpose of the Report Oxidative stress is a leading factor in the pathogenesis of idiopathic Parkinson disease (IPD). Two intrinsic antioxidative molecules, bilirubin and uric acid, are known to protect dopaminergic neurons from oxidative stress in IPD. The objective of this study was to determine the relationship between basal serum levels of 2 molecules and dopaminergic deficit assessed by dopamine transporter imaging with 18 F-fluorinated- N -3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane ([ 18 F]FP-CIT) PET/CT in patients with early-stage drug-naive IPD. Methods Cases of IPD patients who possess the levels of uric acid and bilirubin within a month from [ 18 F]FP-CIT PET/CT from January 2011 to December 2016 were retrospectively reviewed. As a control, the same criteria applied to patients with essential tremor (ET). PET images were analyzed using volume-of-interest templates for 12 striatal subregions and 1 occipital area, and the specific-to-nonspecific binding ratio (SNBR) was calculated. Results One hundred five patients with drug-naive, early-stage IPD and 62 patients with ET were finally included. Levels of bilirubin were significantly higher in the IPD group than in controls ( P = 0.026), and bilirubin level was the factor showing the most correlations with SNBR in IPD ( P &lt; 0.001), whereas uric acid showed no such difference or relationship. Furthermore, levels of bilirubin showed a positive correlation with SNBR in more affected posterior putamen in the IPD group (Pearson correlation coefficient, ρ = 0.456; P &lt; 0.001), but a negative one in the ET group ( ρ = −0.440, P &lt; 0.001). Conclusions Bilirubin, not uric acid, was the most significant antioxidant marker for dopaminergic deficit in early-stage drug-naive IPD assessed by [ 18 F]FP-CIT PET/CT.
OS3.5 Prescription medications in glioma patients and the prevalence of depression, anxiety and subjective cognitive impairment
Authors: P B van der Meer, M J B Taphoorn, M J van den Bent, L Dirven, J Koekkoek
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Several medications prescribed for the management of symptoms in glioma patients, such as antiepileptic drugs and corticosteroids, have been associated with depression, anxiety and cognitive impairment in glioma patients. However, no previous study has incorporated all prescription medications instead of only one class of medications. The aim of this observational study was to assess the prevalence of depression, anxiety and subjective cognitive impairment associated with prescription medications, that have a potential for such adverse drug effects, in glioma patients. MATERIAL AND METHODS Use of prescription medications with a &gt;1% risk of potential depressive, anxiety or cognitive adverse effects was defined as a categorical variable (0, 1 or ≥2), separately for each adverse drug effect. Depression and anxiety were measured with the Hospital Anxiety and Depression Scale, while subjective cognitive impairment was measured with the Medical Outcomes Study-Cognitive Functioning Scale. Hierarchical multivariable logistic regression analyses were performed for each outcome separately. Besides use of medications with a &gt;1% risk of adverse effects (depression, anxiety or cognitive adverse effects, depending on the outcome analysed), other confounding variables such as seizure severity and Karnofsky Performance Status score were included. RESULTS A total of 272 grade II-IV glioma patients were included in the study. Prevalence of depression increased significantly from 9% for patients taking 0 medications with &gt;1% risk of depressive adverse effects, to 18% taking 1 medication and 29% (adjusted Odds Ratio [aOR]=3.3 [95% Confidence Interval {CI}=1.3–8.4]) taking ≥2 medications. Prevalence of subjective cognitive impairment also increased significantly, from 14% for patients using 0 medications with a &gt;1% risk of cognitive adverse effects to 25% using 1 and 29% using ≥2 medications, but association was not independent (aOR=2.1 [95%CI=0.8–5.6]). While prevalence of anxiety increased from 18% for patients using 0 medications with &gt;1% risk of anxiety adverse effects to 25% using 1 and 33% (aOR=1.7 [95%CI=0.7–4.1]) using ≥2 medications, this was not significant. CONCLUSION Higher number of medications with depressive or cognitive adverse effects used by a glioma patient corresponds with a higher prevalence of depression and subjective cognitive impairment. However, after adjustment of potential confounders the association is only independent for depression.
Outcomes and prognostic factors in African American and black patients with mycosis fungoides/Sézary syndrome: Retrospective analysis of 157 patients from a referral cancer center
Authors: Shamir Geller, Emily Lebowitz, Melissa P. Pulitzer, Steven M. Horwitz, Alison J. Moskowitz, Steve Dusza, Patricia L. Myskowski
Journal: Journal of the American Academy of Dermatology (2019)
Activity anorexia: Biological, behavioral, and neural levels of selection
Authors: W. David Pierce
Journal: Behavioral and Brain Sciences (2001)

Activity anorexia illustrates selection of behavior at the biological, behavioral, and neural levels. Based on evolutionary history, food depletion increases the reinforcement value of physical activity that, in turn, decreases the reinforcement effectiveness of eating – resulting in activity anorexia. Neural opiates participate in the selection of physical activity during periods of food depletion.
P03.09 Real world management and prognosis of glioma patients:SYSUCC report from China
Authors: D Li, Y Chen, C Guo, Q Yang, S Wu, Y Xia, J Zeng, X zhang, C Ke, K Sai, J Wang, Y Mou, Z Chen
Journal: Neuro-Oncology (2019)

Abstract Background: The conventional way of patient treatment should be following guidelines. While in clinical practice, patients received treatments very often away from suggested guideline. In this report, we reviewed glioma patients received real world treatment at Sun Yat-sen University Cancer Center (SYSUCC) and results of this patient series. Methods: Total of 1215 glioma patients received surgery at SYSUCC from 2000 to 2017 were enclosed for analysis. The pathologic diagnosis of patients has followed WHO classification (initially 2007 standard, than 2016 standard). Results: A total of 1001 newly diagnosed brain glioma patients were analyzed, including 90 cases WHO grade I, 307 grade II, 239 grade III and 365 grade IV. The median age of onset was 14 (1–75), 35 (2–69), 41 (8–82) and 50 (2–86) years old, respectively, for grade I, II, III and IV glioma patients. Tumor total resection was achieved in 567 patients (57.5%). Among all patients, 331 high-grade gliomas (54.8%) and 159 low-grade glioma (40.1%) received radiotherapy, whereas 285 high-grade gliomas (47.1%) and 80 low-grade tumors (20.2%) received chemotherapy. Among high-grade gliomas, the median OS of glioblastoma, anaplastic astrocytoma and anaplastic oligodendroglial tumors were 17.7 months (15.7–19.7 months), 33.7 months (24.0–43.4 months) and 110.6 months (43.5–177.7 months), respectively, whereas the median OS of low-grade gliomas was not reach. The 5-year survival rate of grade I, II, III and IV gliomas was 94.7%, 73.7%, 45.1% and 18.6%, respectively. Multivariate analysis identified that onset age, Karnofsky performance status, tumor location, preoperative seizure, pathological subtype, resection extent and post-surgical treatment were independent predictors of OS for patients with high-grade gliomas. Patients received post-surgical radiotherapy and (or) chemotherapy had better survival than those without adjuvant treatment (grade III: 53.3 vs. 20.6 months, p =0.012; grade IV: 22.9 vs. 12.3 months, p &lt; 0.001). For low-grade gliomas, patients’ age, Ki-67 index, tumor subtype and resection extent were associated with clinical outcomes. Conclusions: Glioma patients received treatments do not always following guidelines in clinical practice. Although standard care for patients may beneficial for prognosis, personalized treatment may more acceptable for patients and even resulting better outcome which should keep in mind in routine clinical practice.
Preoperative radiotherapy and docetaxel in resectable pancreatic adenocarcinoma: A phase II trial
Authors: F. Viret, M. Ychou, V. Moutardier, V. Magnin, P. Rouanet, G. Monges, D. Azria, O. Turrini, A. Gonçalves, M. Giovannini, J. R. Delpero
Journal: Journal of Clinical Oncology (2006)

4099 Background: We previously reported results a phase I trial of weekly docetaxel concurrently with radiation therapy in patients (pts) with locally advanced pancreatic adenocarcinoma (Pancreas, Vol 27, N°3, 2003). We prospectively explored this regimen in 34 pts with biopsy proven potentially resectable pancreatic adenocarcinoma. Methods: Treatment consisted of concomitant radiotherapy (45 Gy within 5 weeks directed at the pancreatic tumor and regional lymphatics) with 5 weekly doses of docetaxel (30 mg/m 2 /week) by 1-hour infusion, followed by a complete staging evaluation 3–4 weeks after chemo-radiation. Pts without disease progression underwent surgery. Results: From May, 2003 to July, 2005, this study enrolled 34 pts (59% men) with median age 62 years (range 45–72). Median tumor size was 3 cm. Pretreatment Endoscopic Ultrasound (EUS) staging was uT1 (7 pts), uT2 (25 pts), uT3 (2pts), uN0 (26 pts) and uN1 (8 pts). Median pretreatment CA 19.9 levels was 114 (range 1–9432). All pts (97%) but one completed radiation and 91% (31 pts) received the 5 weekly doses of docetaxel. Adverse events included grade 3/4 asthenia (28%), grade 3/4 nausea/vomiting (10%), grade 3/4 anemia (7%) and grade 3/4 neutropenia (7%). Median time between diagnosis and surgery was 3.7 months (range 2.8–8.7). Ten pts (29%) presented progressive disease after chemo-radiation and one additional patient (pt) voluntary stopped treatment procedure. Twenty three pts (68%) underwent surgical procedure, which was with curative intent in 17 pts (50%). One pt died within the 30-day post operative period. Pathological response was observed in 7 pts (30%), including 2 complete response. The median Disease Free Survival (DFS) was 11 months and the 2-year DFS was 21%. The median overall survival (OS) was 14 months. The 2-year DFS for the 17 pts resected with a curative intent was 50.4%. In this subgroup, median overall survival was not reached. Conclusions: Pre-operative combination of radiotherapy and docetaxel is feasible with tolerable toxicity and with promising pathological response. A randomized phase III study comparing this regimen (radiotherapy and docetaxel) and surgery versus surgery alone is starting. Supported in part by Sanofi Aventis, France. No significant financial relationships to disclose.
P10.01 Anti-migration and anti-invasion effects of curcumin via suppression of fascin expression in glioblastoma cells
Authors: P Ki-Su, S Yoon, J Hwang, H Ahn
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The natural compound Curcumin was known to inhibit migration and invasion of glioblastoma (GBM) cells. Fascin, a kind of actin-binding proteins, is correlated with migration and invasion of GBM cells. The purpose of this study was to investigate anti-migration and anti-invasion effects of Curcumin via suppression of fascin expression in GBM cells. MATERIAL AND METHODS U87 cell line was used as an experimental model of GBM. Fascin was quantified by Western blot analysis. And, the signal transducer and activator of transcription 3 (STAT3), known to play an important role in migration and invasion of tumor cells, were analyzed by sandwich-ELISA. Migration and invasion capacities were assessed by attachment, migration and invasion assays. Cellular morphology was demonstrated by immunofluorescence. RESULTS At various concentrations of curcumin and exposure times, fascin expression decreased. After temporarily exposure to 10μM/L Curcumin during 6 hours as less invasive concentration and time, fascin expression temporarily decreased at 12 hours (18.4%, p=0.024), and since then recovered. And, the change of phosphrylated STAT3 level also reflected the temporarily decreased pattern of fascin expression at 12 hours (19.7%, p=0.010). Attachment, migration, and invasion capacities consistently decreased at 6, 12, and 24 hours. And, immunofluorescence showed the change of shape and the reduction of filopodia formation in cells. CONCLUSION Curcumin is likely to suppress the fascin expression in GBM cells, and this might be a possible mechanism for anti-migration and anti-invasion effects of Curcumin via inhibition of STAT3 phosphorylation.
Randomized phase II trials (RP2T): Selection design or poor man's phase III?
Authors: R. Riechelmann, E. Sasse, G. Borghesi, V. Miranda, A. Fede, L. Saad, V. Oliveira, E. Barros, M. P. Campos, A. Del Giglio, E. D. Saad
Journal: Journal of Clinical Oncology (2009)

6595 Background: With the increasing number of new anticancer agents, RP2Ts have been used more often, aiming to select active agents to be tested further. RP2Ts are typically underpowered for statistical comparisons of endpoints between treatment arms. We sought to investigate how frequently formal statistical testing (as opposed to “picking the winner”) has been used in RP2Ts. Methods: We systematically searched PubMed for RP2Ts on systemic cancer therapy, using the medical subject headings “drug therapy” and “neoplasms,” and limiting the search to years 1995/1996 and 2005/2006, and to publication type “randomized controlled trials.” For each study, relevant data that were collected independently by two investigators included reporting of P values and confidence intervals (CIs) for primary (PE) and other endpoint(s) results. Results: 288 articles were retrieved and 107 were eligible: 22 were published in 1995/96 and 85 in 2005/06. Median number of arms and patients per RP2Ts were 2 and 94, respectively. PE was response rate in 71 (66.4%), a control arm was present in 55 (51.4%) and 48 (45%) were partially or entirely sponsored by for-profit organizations. For the PE, P values were reported in 50 (47%), and CIs in 69 (65%) RP2Ts. Either P values or CIs for the PE were reported in 85 (79.4%; 95% CI: 70.8% - 86.1%) cases. No temporal trend was identified in such practice (17 of 22 RP2Ts from 1995/1996 and 68 of 85 RP2Ts from 2005/2006). Likewise, source of funding and use of a control group were not associated with reporting P values/CIs for PE. Conclusions: Our study suggests that formal statistical comparisons are frequently performed between arms of RP2Ts. Further studies are needed in order to identify factors that are associated with such practice. [Table: see text]
Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine
Authors: Matthew C. Madison, Cameron T. Landers, Bon-Hee Gu, Cheng-Yen Chang, Hui-Ying Tung, Ran You, Monica J. Hong, Nima Baghaei, Li-Zhen Song, Paul Porter, Nagireddy Putluri, Ramiro Salas, Brian E. Gilbert, Ilya Levental, Matthew J. Campen, David B. Corry, Farrah Kheradmand
Journal: Journal of Clinical Investigation (2019)

Electronic nicotine delivery systems (ENDS) or e-cigarettes have emerged as a popular recreational tool among adolescents and adults. Although the use of ENDS is often promoted as a safer alternative to conventional cigarettes, few comprehensive studies have assessed the long-term effects of vaporized nicotine and its associated solvents, propylene glycol (PG) and vegetable glycerin (VG). Here, we show that compared with smoke exposure, mice receiving ENDS vapor for 4 months failed to develop pulmonary inflammation or emphysema. However, ENDS exposure, independent of nicotine, altered lung lipid homeostasis in alveolar macrophages and epithelial cells. Comprehensive lipidomic and structural analyses of the lungs revealed aberrant phospholipids in alveolar macrophages and increased surfactant-associated phospholipids in the airway. In addition to ENDS-induced lipid deposition, chronic ENDS vapor exposure downregulated innate immunity against viral pathogens in resident macrophages. Moreover, independent of nicotine, ENDS-exposed mice infected with influenza demonstrated enhanced lung inflammation and tissue damage. Together, our findings reveal that chronic e-cigarette vapor aberrantly alters the physiology of lung epithelial cells and resident immune cells and promotes poor response to infectious challenge. Notably, alterations in lipid homeostasis and immune impairment are independent of nicotine, thereby warranting more extensive investigations of the vehicle solvents used in e-cigarettes.
Comparison of Molecular Kinetics after the First and Second Imatinib Discontinuation: Results from the KID Study
Authors: Dae Young Zang, Sung-Eun Lee, Soo Young Choi, Soo-Hyun Kim, So-Young Park, Joon Seong Park, Hyeoung-Joon Kim, Sung-Hyun Kim, Suk Joong Oh, Hawk Kim, Young Rok Do, Jae-Yong Kwak, Jeong-A Kim, Yeung-Chul Mun, Won-Sik Lee, Myung Hee Chang, Jinny Park, Jihyun Kwon, Dong-Wook Kim
Journal: Blood (2016)
Off-Label Prescription of Hydroxycarbamide (Hydroxyurea, HU) for Severe Anemia: Preliminary Results from European Non-Interventional, Multicentric, Prospective Escort-HU Study
Authors: Mariane De Montalembert, Gylna Loko, Jerome Clouzeau, Valentine Brousse, Frederic Galacteros, Corinne Charneau, Marie Belloy, Malika Benkerrou
Journal: Blood (2017)