tbuckley/cabot-search huggingface dataset:
Use of lipid-lowering drugs in patients with cancer.
Authors: Edgardo G. J. Rivarola, Ernesto Gil Deza, Gabriel Lebersztein, Eduardo L. Morgenfeld, Carlos Fernando Garcia Gerardi, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2014)

e20517 Background: In our population, the use of lipid-lowering drugs is widely spread. The main objective of this paper is to assess cancer patients (Pt) who are being treated with lipid-lowering drugs and compare the indications with the 2013 ACC/AHA Blood Cholesterol Guideline recommendations. Methods: All new Pt admitted between September 26th, 2012 and December 10th, 2013 completed a Past Medical History Form (PMHF) and registered their regularly used medication. All Pt with lipid-lowering medications were identified and medical records were reviewed. Results: Three thousand and thirty-two new cancer Pt filled in the PMHF, and 321 Pt (10.5 %) were receiving lipid-lowering drugs at the time of cancer diagnosis,being the subject of this study. Characteristics of the population (n = 321): Sex F/M: 128/193. Median age 67 y (range 40-97 ) Cancer diagnosis: prostate 65 (20%), breast 62 (19%) , colorectal 33 (10%) , lung 29 (9 %) , kidney 20 (6%), melanoma 6 (2%) and endometrial 4 (1%). Three hundred and forty four lipid lowering drugs were being used in which 10 active principles were identified: Statins (ezetimibe (27), atorvastatin (186), rosuvastatin (55 ), simvastatin (46 ), lovastatin (1) and fluvastatin (1)); Fibrates ( gemfibrozil (13),bezafibrate (6 ), fenofibrate (2) tenofibrate ( 1)) and four dietary supplements. In 91 Pt the indication was for secondary prevention after a cardiovascular event (myocardial infarction in 56 patients, cardiovascular accident in 24 patients and arterial thrombosis in 11 patients). In 241 Pt lowering-lipid drugs were indicated as primary prevention, however,47 Pt in this group had stage IV tumours and, of those Pt with early stages ( stages I- II- III), 51 were older than 75 years old, meaning that 98 out of 241 Pt (40 %) were receiving a futile, costly, and possibly harmful medication at the time of cancer diagnosis. Conclusions: A) In our population, one out of ten Pt used lipid-lowering medication. b) The most frequent indication was for primary prevention , however 40 % of the Pt will probably not benefit from it. c) The evidence of the use of futile , costly and possibly harmful medications at the time of cancer diagnosis in our Pt reinforces the urgency to develop international guidelines for the management of polypharmacy in cancer patients.
Evaluation of In Vivo CAR Transgene Levels in Relapsed/Refractory Pediatric and Young Adult ALL and Adult DLBCL Tisagenlecleucel-Treated Patients
Authors: Rakesh Awasthi, Karen Thudium Mueller, Gregory A. Yanik, Constantine S. Tam, Susana Rives, Joseph P. McGuirk, Michael A. Pulsipher, Michael W. Boyer, Ulrich Jaeger, Andre Baruchel, Gary Douglas Myers, Hyatt Balke-Want, Stephen J. Schuster, Heather Stefanski, Michael R. Bishop, Edward R. Waldron, Özlem Anak, Abhijit Chakraborty, Eric Bleickardt, Stephane Wong, Lida Bubuteishvili Pacaud, Edmund K. Waller, Shannon L. Maude
Journal: Blood (2018)
Reassessing the Mechanisms of Acute Coronary Syndromes
Authors: Peter Libby, Gerard Pasterkamp, Filippo Crea, Ik-Kyung Jang
Journal: Circulation Research (2019)

The mechanisms that underlie superficial erosion, a cause of coronary thrombosis distinct from plaque rupture, have garnered recent interest. In an era of improved control of traditional risk factors, such as LDL (low-density lipoprotein), plaque erosion may assume greater clinical importance. Plaques complicated by erosion tend to be matrix-rich, lipid-poor, and usually lack prominent macrophage collections, unlike plaques that rupture, which characteristically have thin fibrous caps, large lipid pools, and abundant foam cells. Thrombi that complicate superficial erosion seem more platelet-rich than the fibrinous clots precipitated by plaque rupture. The pathogenesis of plaque rupture probably does not pertain to superficial erosion, a process heretofore little understood mechanistically. We review here data that support a substantial shift in the mechanisms of the thrombotic complications of atherosclerosis. We further consider pathophysiologic processes recently implicated in the mechanisms of erosion. Multiple processes likely predispose plaques to superficial erosion, including experiencing disturbed flow, basement membrane breakdown, endothelial cell death, and detachment potentiated by innate immune activation mediated through pattern-recognition receptors and endothelial-to-mesenchymal transition. Monocytes/macrophages predominate in the pathogenesis of plaque rupture and consequent thrombosis, but polymorphonuclear leukocytes likely promote endothelial damage during superficial erosion. The formation of neutrophil extracellular traps probably perpetuates and propagates intimal injury and potentiates thrombosis due to superficial erosion. These considerations have profound clinical implications. Acute coronary syndromes because of erosion may not require immediate invasive therapy. Understanding the biological bases of erosion points to novel therapies for acute coronary syndrome caused by erosion. Future research should probe further the mechanisms of superficial erosion, and develop point-of-care tests to distinguish acute coronary syndromes provoked by erosion versus rupture that may direct more precision management. Future clinical investigations should evaluate intervening on the targets that have emerged from experimental studies and the management strategies that they inform.
Risk of death from cardiovascular disease in long-term breast cancer survivors: A comparison with women from the general population.
Authors: Milada Cvancarova, Kristin V Reinertsen, Marit B Veieroed, Michael Vaeth, Petter Laake, Petter Laake, Grethe S Tell, Sophie D. Fossa
Journal: Journal of Clinical Oncology (2014)

1534 Background: As a result of modern cancer treatment such as surgery, chemotherapy and radiation therapy there is a growing number of cancer survivors. However, it comes at a cost. Cardiovascular disease (CVD) after cancer treatment has gained growing attention in the medical community during the recent decades. Our aim was to compare CVD-related mortality in long term breast cancer (BC) survivors to that in the general population taking into account the competing risk of dying of cancer or other non-CVD causes. We aimed to study the effect of more recent radiotherapy techniques comparing left and right sided BC, and the effect of socioeconomic status measured as the level of income at the time of diagnosis on the risk for dying from CVD. Sosioeconomic status indicators such as low income have been associated with higher prevalence of CVD. Methods: In total, 18614 BC patients diagnosed from 1984 to 2002 who survived at least ten years after their cancer diagnosis were matched with 10 women randomly selected from the general population. Each BC case was matched on date of birth and the selected controls had to be alive and cancer free at the time of their case’s diagnosis. Income at diagnosis was categorized as low, medium and high. The risk of dying of CVD-related cause was modeled using stratified Cox regression. Separate models were fitted for women irradiated on the left and right body side. Results: There was no statistically significant difference in risk of dying due to CVD-related causes between BC cases and their matched controls (HR=1.05, 95%CI[0.98 to 1.12]. However, left-sided irradiated BC survivors had increased risk of CVD-related death compared to their controls (HR=1.17, 95%CI [1.02 to 1.23]. There was no difference between right-sided irradiated cases and their controls (HR=0.99, 95%CI[0.90 to 1.08]. Income at diagnosis was not associated with CVD-related mortality. Conclusions: Recent radiotherapy techniques still imply increased CVD-related mortality among left-sided irradiated BC survivors. Therefore further reduction of cardiac radiation doses should be implemented, particularly in women with left sided breast cancer.
Effect of topical clonidine on the duration and severity of radiation-induced oral mucositis (OM) in a translational hamster model.
Authors: Pierre Attali, Vanessa Roulet, Greg Lyng, Lorraine Zakin, Veronique Trochon-Joseph, Caroline Lemarchand, Stephen T. Sonis
Journal: Journal of Clinical Oncology (2014)

10091 Background: There is currently no effective mechanistically-targeted intervention for radiation-induced OM. Clonidine, a a2 adrenergic agonist, has been shown to impact NF-kappaB with consequent inhibition of the expression and the release of the pro-inflammatory cytokines thought to be involved in OM’s pathogenesis. We assessed the efficacy of a topical formulation of clonidine to mitigate radiation-induced OM in an established translational hamster model. Methods: Two independent studies were performed in which 32 male Syrian Golden hamsters were randomly assigned to four equally-sized groups in each. OM in a saline-treated control was compared to three groups which received clonidine in different concentrations and/or dosing frequency. Study drug was administered topically from the day before radiation (Day -1) until day 20. On study day 0, hamsters were irradiated with a single 40 Gy dose directed to the left buccal cheek pouch. Beginning on day 6 images of the left cheek pouch mucosa were obtained every other day and blindly scored for OM severity using a validated 6-point scale. The number of days of ulcerative OM with scores of ≥ 3 was assessed (Chi-2 test). The individual daily group scores were evaluated (rank sum test). In Study 1 (S1), clonidine was given topically once daily at doses of 30, 100 and 300 μg/kg. In Study 2 (S2), clonidine was given QD at 100 µg/kg and QID at 12.5 and 25 μg/kg. Results: Clonidine consistently reduced the duration and severity of OM. In S1, clonidine dose dependently reduced the % days of score ≥ 3 from 46.9% in controls to 41.7%, (p=0.35), 29.2% (p<0.001) and 30.2% (p<0.001) in clonidine 30, 100 and 300 μg/kg treated animals. In S2, % days was reduced from 35.4% in controls to 21.9% (100 µg/kg, p=0.003), 28.1% (12.5 µg/kg, p=0.12) and 26% (25 µg/kg, p=0.04). OM severity was significantly reduced compared to controls in the clonidine 100 and 300 μg/kg QD groups in S1, and in the clonidine 100 μg/kg QD, 12.5 and 25 μg/kg qid in S2. Clonidine was not shown toxic. Conclusions: Topically administered clonidine mitigated radiation-induced OM in hamsters in a dose-dependent manner. QD administration was as effective as QID dosing. The optimal dose in this model was 100 μg/kg QD.
Incidence and characteristics of depression in cancer patients with chronic hepatitis C infection.
Authors: Anis Rashid, Harrys A. Torres, Leah Jorewicz, Richard De La Garza
Journal: Journal of Clinical Oncology (2014)

e20569 Background: Hepatitis C Virus (HCV) is the most common blood-borne infection in the United States. The prevalence of HCV infection in cancer patients ranges from 1.5% to 32%. At MD Anderson Cancer Center (MDACC), subsets of HCV-infected patients are referred to the Psychiatric Oncology clinic for a variety of mood disorders. We sought to determine the incidence of and group of patients at risk for depression using the Center for Epidemiologic Studies Depression Scale (CES-D). Methods: This study involved extraction of data from charts of HCV-infected patients seen by psychiatry at MDACC for a variety of psychiatric disorders. Basic demographic information, cancer type, psychiatric diagnoses and psychotropic medications were recorded. Depression scores were evaluated using CES-D scale. Results: Charts of199 patients seen between 10/01/2007 -10/31/2011 were reviewed. The average ages was 57 years, most were male (58%), Caucasian (57%), and had solid tumors (54%). About half (47%) were diagnosed with a psychiatric disorder, with depression being the most common mental illness (52%). Among patients with depression, one-way analysis of variance revealed significantly higher CES-D scores in females (21.3 ± 12.3) than males (14.6 ± 11.3) (F1,70=5.7, p=0.019). With regard to age, a significant inverse correlation was shown with older patients having lower CES-D scores (R=0.28, t=-2.4, p=0.019). Among those diagnosed with depression, average CES-D scores during initial assessment was 18.2 ± 12.3 and these significantly decreased at follow-up to 13.7 ± 10.8 (t=2.86, p=0.0065). Patients with psychiatric diagnoses and under psychiatric care did show improvement in their CES-D score. Conclusions: Approximately half of cancer patients with chronic HCV infection have psychiatric disorders, with depression as the most common mental illness. Depression seems to be more common in female patients. CES-D scale seems to be a useful screening tool for depression in cancer patients; however, specialized psychiatric care is warranted to manage these patients.
United States State-Level Variation in the Use of Neuraxial Analgesia During Labor for Pregnant Women
Authors: Alexander J. Butwick, Jason Bentley, Cynthia A. Wong, Jonathan M. Snowden, Eric Sun, Nan Guo
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Neuraxial labor analgesia is recognized as the most effective method of providing pain relief during labor. Little is known about variation in the rates of neuraxial analgesia across US states. Identifying the presence and extent of variation may provide insights into practice variation and may indicate where access to neuraxial analgesia is inadequate. <h3>Objective</h3> To test the hypothesis that variation exists in neuraxial labor analgesia use among US states. <h3>Design, Setting, and Participants</h3> Retrospective, population-based, cross-sectional analysis using US birth certificate data. Participants were 2 625 950 women who underwent labor in 2015. <h3>Main Outcomes and Measures</h3> State-specific prevalence of neuraxial analgesia per 100 women who underwent labor and variability in neuraxial analgesia use among states, assessed using multilevel multivariable regression modeling with the median odds ratio and the intraclass correlation coefficient to evaluate variation by state. <h3>Results</h3> In the study population of 2 625 950 women, 0.1% (n = 2010) were younger than 15 years, 7.0% (n = 183 546) were between the ages of 15 and 19 years, 23.6% (n = 620 118) were between the ages of 20 and 24 years, 29.6% (n = 777 957) were between the ages of 25 and 29 years, 26.0% (n = 683 656) were between the ages of 30 and 34 years, 11.4% (n = 298 237) were between the ages of 35 and 39 years, 2.2% (n = 57 130) were between the ages of 40 and 44 years, and 0.1% (n = 3296) were between the ages of 45 and 54 years. More than 90% were privately insured or insured with Medicaid. Neuraxial analgesia was used by 73.1% (n = 1 920 368) of women. After adjustment for antepartum, obstetric, and intrapartum factors, Maine had the lowest neuraxial analgesia prevalence (36.6%; 95% CI, 33.2%-40.1%) and Nevada the highest (80.1%; 95% CI, 78.3%-81.7%). The adjusted median odds ratio was 1.5 (95% CI, 1.4-1.6), and the intraclass correlation coefficient was 5.4% (95% CI, 4.0%-7.9%). <h3>Conclusions and Relevance</h3> Results of this study suggest that a small portion of the overall variation in neuraxial analgesia use is explained by US states. Unmeasured patient-level and hospital-level factors likely account for a large portion of the variation between states. Efforts should be made to understand what the main reasons are for this variation and whether the variation influences maternal or perinatal outcomes.
Prospective Clinical Trial of Anti-CD19 CAR T Cells in Combination with Ibrutinib for the Treatment of Chronic Lymphocytic Leukemia Shows a High Response Rate
Authors: Saar I. Gill, Vanessa Vides, Noelle V. Frey, Susan Metzger, Megan O'Brien, Elizabeth Hexner, Anthony R. Mato, Simon F Lacey, J. Joseph Melenhorst, Edward Pequignot, Whitney Lynn Gladney, Wei-Ting Hwang, Anne Lamontagne, Megan Davis, John C. Byrd, Stephen J. Schuster, Don L. Siegel, Randi E. Isaacs, Carl H June, David L. Porter
Journal: Blood (2018)
Abstract 20326: Involvement of Neuronal Na+ Channels in Long QT-Associated Ventricular Arrhythmias
Authors: Przemyslaw Radwanski, Megan Koleske, Björn Knollmann, Sandor Gyorke
Journal: Circulation (2017)

Background: Recently we have shown that neuronal Na+ channel (nNav) are an integral part of catecholaminergic polymorphic ventricular tachycardia (CPVT). With the advent of disorders manifesting co...
Results of a Phase 3 Randomised Multicenter Study Comparing Pixantrone + Rituximab with Gemcitabine + Rituximab in Patients with Relapsed Aggressive B-Cell Non-Hodgkin Lymphoma Not Eligible for Stem Cell Transplantation
Authors: Gilles Andre Salles, Wojciech Jurczak, David J. Andorsky, Donald P. Quick, Jack W. Singer, Simran Bedi Singh, Lixia Wang, Anton Egorov, Christine Gabarroca, Ruth Pettengell
Journal: Blood (2018)
Heterotelechelic polymer prodrug nanoparticles: Adaptability to different drug combinations and influence of the dual functionalization on the cytotoxicity
Authors: Daniele Vinciguerra, Merel Jacobs, Stéphanie Denis, Julie Mougin, Yohann Guillaneuf, Gianpiero Lazzari, Chen Zhu, Simona Mura, Patrick Couvreur, Julien Nicolas
Journal: Journal of Controlled Release (2019)

Well-defined, heterotelechelic polymer prodrugs for combination therapy were synthesized by using a combination of the "drug-initiated" nitroxide-mediated polymerization from a gemcitabine-alkoxyamine initiator and the nitroxide exchange reaction using TEMPO-bearing drugs to end-cap the drug-polymer chain-end by a second drug. This methodology was successfully applied to two different clinically relevant combinations, gemcitabine/doxorubicin (Gem/Dox) and gemcitabine/lapatinib (Gem/Lap), showing a certain degree of universality of the synthetic methodology. It also represented the first nanocarrier for the co-delivery of Gem and Lap ever reported. Well-controlled, low molar mass heterotelechelic polymers (Mn = 2100-4090 g.mol-1, Ð = 1.18-1.38) with ~1:1 drug ratios and high overall drug loadings up to 40 wt% were obtained. They were formulated into nanoparticles by nanoprecipitation and exhibited average diameters in the 34-154 nm range, with narrow particle size distributions (PSD = 0.01-0.22) and excellent colloidal stability over time. Their biological evaluation in terms of drug release and cytotoxicity was performed and compared to that of different monofunctional polymer prodrug formulations. We showed that heterobifunctional polymer prodrugs induced cytotoxicity to MCF-7 cells, with IC50 values in the 120-300 nM range depending on the combination tested. Interestingly, whereas Gem/Dox combination did not lead to noticeable improvement over monofunctional therapies, co-nanoprecipitation of Gem/Lap prodrugs led to synergistic effect.
Expression of immune checkpoints (ICs) on circulating tumor cells (CTCs) in men with metastatic prostate cancer (mPC).
Authors: Tian Zhang, Rebecca Garland Austin, Sally E Park, Daniella Runyambo, Rengasamy Boominathan, Chandra Rao, Elizabeth Bronson, Monika Anand, Patrick Healy, Daniel J. George, Megan Ann McNamara, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2018)

5059 Background: Most immune checkpoint inhibitors have shown limited efficacy in unselected men with mPC, and there is limited understanding about which ICs are relevant in mPC. We evaluated ICs on the cell surface of CTCs in patients (pts) with mPC. Methods: Pts were enrolled prospectively at the Duke Cancer Center in three cohorts: A) metastatic castration resistant prostate cancer (mCRPC) starting abiraterone acetate (AA) or enzalutamide (enza), B) mCRPC after AA or enza, and C) metastatic hormone sensitive PC (mHSPC). The Cellsearch platform was used to capture EpCAM- and CK-expressing CTCs and analyzed for PD-L1, PD-L2, B7-H3, and CTLA-4 expression at baseline, 12 weeks, and disease progression. Results: Through December 2017, we enrolled 18 pts (6 in cohort A, 8 in cohort B, and 4 in cohort C). CTCs were detectable in every cohort. At baseline, B7-H3 was the most prevalent IC while the other ICs were detected less frequently (Table 1). PD-L1 expression on CTCs was heterogeneous between and within pts; PD-L1 expression also changed during treatment and upon disease progression (Table 1). Rare CTCs expressed CTLA-4 and PD-L2, mostly in cohort B. Conclusions: Patients with mPC have detectable and heterogeneous ICs on CTCs, particularly PD-L1 and B7-H3, which can be monitored over time. B7-H3 was the most prevalent IC on CTCs, regardless of disease state. Our preliminary data suggest that pts with mCRPC post-enza/AA have higher levels of IC expression on CTCs compared with pts with mHSPC and mCRPC prior to enza/AA. We found evidence for heterogeneous CTC expression of CTLA-4 and PD-L2, particularly in men with mCRPC post-AA/enza. Percentage of CTCs with immune checkpoint over total CTCs at baseline, week 12, and disease progression. Median (range) of CTCs at baseline/week 12/PD PD-L1 (%) baseline/week 12/PD PD-L2 (%) baseline/week 12/PD CTLA-4 (%) baseline/week 12/PD B7-H3 (%) baseline/week 12/PD A: mCRPC pre AA/enza 16 (0-59)/6 (0-50)/31 (16-49) 7/4/8 1/2/1 0/0/0 92/53/66 B: mCRPC post AA/enza 4 (0-54)/1 (0-4)/3 (0-108) 25/17/9 3/50/0 15/50/1 98/80/94 C: mHSPC 3 (0-52)/0 (0-1)/NE 11/100/NE 6/NE/NE 3/NE/NE 68/NE/NE NE: Not evaluable; PD: disease progression
Socioeconomic status and lifestyle behaviors in cancer survivors.
Authors: Hiten Naik, Lawson Eng, Catherine Brown, Xin Qiu, Dan Pringle, Mary Mahler, Henrique Hon, Kyoko Tiessen, Henry Thai, Valerie Ho, Christina Gonos, Rebecca Charow, Vivien Pat, Margaret Irwin, Lindsay Herzog, Anthea Ho, Wei Xu, Jennifer M. Jones, Doris Howell, Geoffrey Liu
Journal: Journal of Clinical Oncology (2014)

6568 Background: Socioeconomic disparities in cancer survival exist even in universal healthcare systems. These disparities may be explained in part by lifestyle behaviors such as smoking and physical activity (PA). We evaluated the associations between socioeconomic variables and changes in smoking and PA after diagnosis in Ontario cancer survivors. Methods: 1,252 adult cancer survivors across diverse disease sites were surveyed about their smoking and exercise habits. Using multivariate logistic regression models, we evaluated the association of income, occupation, and education with each behavior, after adjusting for clinicodemographic and pathological covariates. Results: Cancer survivors were surveyed at a median of 26 months after diagnosis. 16% had breast cancers, 12% gastrointestinal, 26% gynecological/genitourinary, 14% head and neck, 6% lung and 19% hematologic. 15% reported being smokers at diagnosis; 45% reported being physically inactive; after diagnosis, 56% had quit smoking and 18% increased their PA. Survivors with a lower education level were more likely to be current smokers (p<0.0001) and less likely to quit if they were smoking at diagnosis (p=0.02). Similarly, patients with less education were more likely to be physically inactive currently (p<0.0001), and less likely to improve if they were inactive when they were diagnosed (p=0.004). In contrast, household income and occupation were not associated with current engagement or changes in these behaviours. Population-based marginalization indices confirmed that factors related to education level were significantly associated with smoking cessation (p<0.05). Conclusions: Cancer survivors with lower educational levels were more likely to have at baseline, and maintain, after diagnosis, unhealthy lifestyle behaviors. Targeting at-risk survivors by education level should be evaluated as a strategy in cancer survivorship programs.