tbuckley/cabot-search huggingface dataset:
Abstract P112: Prediction of the Development of Aortopathy in Patients With Bicuspid Aortic Valves
Authors: Bamba Gaye, Hanna M Björck, Magalie Ladouceur, Maxime Vignac, Christian Olsson, Anders F Cereceda, Per Eriksson
Journal: Circulation (2019)

Background: Little is known about the association between bicuspid aortic valves (BAV) and ascending aorta dilatation in the population. We aimed to firstly determine the predictors of aortopathy in BAV patients and secondly to develop a clinical classifier to predict aortopathy in a large group of individuals with bicuspid aortic valve. Method: This study includes 1041 patients (including 545 BAV patients and 506 tricuspid aortic valves (TAV) patients) aged 18 or above with aortic valve disease and/or ascending aorta dilatation but devoid of coronary artery disease and primarily not planned for another concomitant valve surgery. Aortic complications of patients were assessed at baseline. Using automated machine-learning, we applied 10-fold cross-validation logistic regression incorporating multidimensional information (i.e., valvular dysfunction, valves morphology, blood sampling, genetic data, clinical data, family history of cardiovascular diseases, prevalent diseases data, demographic characteristics, lifestyle habits data and medication). Results: Among the 545 BAV subjects (age 64.89 +/- 12 years, 68% men). The prevalence of BAV associated with aneurysm (dilatation) (BAV-D) and without aneurysm (BAV-ND) was 54.9% and 45.1% (p&lt;0.001), respectively. Comparing BAV-D and BAV-ND, significant differences in valvular dysfunction pattern were noted, with aortic stenosis predominating in BAV patients without aneurysm (79.3% vs. 68.7% in BAV with aneurysm; p=0.007), and aortic regurgitation in BAV patients with aneurysm (33.7% vs. 25.1% in BAV patients without aneurysm; p =0.03). No differences in age, prevalence of male sex and BMI were observed between BAV-D and BAV-ND Our descriptive analysis showed several patterns of significantly differently associated traits, between undilated and dilated BAV patients (i.e, blood pressure, hypertension, body surface area, height, high-sensitivity CRP, sibling history of myocardial infarction and mother history of myocardial infarction before 65 years, low density lipoprotein (LDL), prevalent MI, prevalent diabetes and prevalent stroke, BAV phenotype). Our predictive classifier included these traits and showed sensitivity of 80% specificity of 84%, negative predictive value of 76%, and positive predictive value of 82% to predict BAV individuals who are of a high risk of developing aneurysm. All these analyses were also performed in TAV patients and showed different patterns of aneurysm manifestation compared to BAV patients Conclusion: Our findings raise the issue of how to implement prevention of aortopathy in BAV patients in a clinical setting and suggest/demonstrated that cardiovascular risk profiles appear to be more predictive than valve morphology, genetic data and circulating plasma proteins.
Effect of denileukin diftitox (DD) on vaccine-induced T-cell responses and depletion of Tregs in melanoma.
Authors: Jason John Luke, Yuanyuan Zha, Karen Matijevich, Thomas Gajewski
Journal: Journal of Clinical Oncology (2015)

3046 Background: Depletion of CD25+ Tregs improves anti-tumor immunity in preclinical models. DD is a recombinant fusion protein of hIL-2 and diptheria toxin fragment that also kills CD25+ T cells. Prior clinical trials of DD suggested reduction of FoxP3+ Tregs, improved immune responses, and some clinical responses. We evaluated the effect of DD prior to vaccination in patients (pts) with metastatic melanoma. Methods: Pts were randomized to 4-peptide vaccine (250 mcg of Melan-A, gp100, MAGE3 and NA17 with GM-CSF 125 mcg emulsified in Montanide) alone or after single dose of DD (18 mcg/kg). Vaccine was given every 2 weeks for 3 doses and absent progression continued every 2 weeks. Toxicity was evaluated by CTCAE and response by RECIST. Pts were HLA-A2+ with stage IIIC/IV melanoma. Any prior therapy, standard biochemical parameters and no history of autoimmunity were allowed. Blood and tissue biopsy (when possible) were obtained pretreatment and after 3 vaccinations for immunologic assessments. Results: 17 pts were enrolled (7 receiving DD, 41%). Characteristics included (median) age:63, M:14; ECOG:1; cutaneous:mucosal (15:2), M status A:B:C% (6:29:65), pretreated 83%. There were no drug-related G3-4 adverse events. 9 pts (4 DD: 5 vaccine only) showed clinical benefit (1 PR, 8 SD). Time to progression was 4.9 months for DD, 4.4 mo for non-DD. Flow cytometry showed that DD did not affect total Tregs in peripheral blood (p = 0.76). ELISPOT assays revealed that in some pts peptide vaccination augments the number of Ag-specific CD8 T cells in the blood but DD did not increase Ag-specific CD8 T cell response. On-treatment biopsy from DD and non-DD treated pts showed no depletion of intratumoral Foxp3+ T cells by RT-PCR. ELISA for IL2R-alpha demonstrated that outcomes were not impacted by soluble CD25 level (p = 0.13). Conclusions: In contrast with previous studies,DD did not effectively deplete Tregs, augment T cell responses or improve clinical activity in pts with melanoma. Clinical trial information: NCT00515528.
Development of drug cost spreadsheet calculation tool for breast cancer therapy.
Authors: Hiroki Hashimoto, Michiyasu Murakami, Kyoko Shinozaki, Ryota Nakanishi, Hidetoshi Kawaguchi, Takashi Nishizaki, Shozo Senba
Journal: Journal of Clinical Oncology (2015)

e17797 Background: Drug cost is considered an important factor in the continuation of treatment for cancer patients. However, it is difficult to calculate individual drug cost. We were not able to provide enough information on costs to cancer patients starting drug therapy. Therefore, we developed a spreadsheet tool that calculates drug costs for breast cancer treatment. Methods: This software tool runs on every terminal for electronic medical charts in our hospital. We created 10 fictional breast cancer patient sets. Five pharmacists calculated drug costs for 1 regimen using method A (without software) and method B (with software). Next, they calculated drug costs for 3 regimens in the same way. We compared the time to calculate costs using method A and method B. Results: In the 1 regimen case, the mean time for method B (22.6±6.9 s) was 6.4 times shorter than for method A (145.2 ± 28.3s, p < 0.0001). In the 3 regimen case, the mean time for method B (35.5 ± 5.0 s) was significantly shorter (8.9 times) than for method A (315.8 ± 43.1s, p < 0.0001)(Table). Conclusions: By using this software tool, we were able to shorten the calculation time for drug costs, and therefore, alleviate the burden on medical staff. Time to calculate costs with or without software. Method A (without software) B (with software) p-value 1 regimen 145.2±28.3s 22.6±6.9 s p<0.0001 3 regimen 315.8±43.1s 35.5±5.0 s p<0.0001
Reducing overuse of PSA screening in primary care practices.
Authors: Cara B Litvin
Journal: Journal of Clinical Oncology (2019)

37 Background: The United States Preventive Services Task Force and the American Urological Association both recommend against routine PSA-based screening for prostate cancer in men 70 years and older and, for men younger than 70, recommend shared-decision making to discuss the potential benefits and harms of screening before a PSA is ordered. The HIT-OVERUSE study was a 2 year group randomized study from August 2016 thru July 2018 to test a practice-based intervention to reduce overuse in primary care practices, including avoidance of routine PSA screening without shared decision-making. The purpose of this report is present the impact of this intervention on PSA screening. Methods: Twenty one primary care practices in 19 states volunteered to participate in the study. Prior to randomization, all providers received academic detailing on prostate cancer screening recommendations. Eleven practices randomized to the intervention group then received quarterly performance reports, hosted site visits for participatory planning and sent two practice representatives to a one day meeting to share ‘best practices’. The ten control practices only received performance reports. Changes in PSA testing in the past year (excluding patients with prostate cancer) were compared in control and intervention practices. Results: At the patient level, there was a significantly larger unadjusted reduction in PSA screening in men ages 40 to 69 in the past year between intervention practices (28.6 % to 19.0%) and control practices (16.5% to 12.7%) (p&lt;0.0001). There was also a significantly larger unadjusted reduction in PSA screening in men ages 70 and older in the past year between intervention practices (25.7% to 14.7%) and control practices (21.9% to 15.6%) (p&lt;0.0001). Adjusted changes will also be presented. Conclusions: A practice-based intervention to reduce routine PSA-screening performed without shared decision-making resulted in a greater reduction in PSA screening compared to provision of academic detailing alone. Further research could elucidate whether this type of intervention results in increased shared decision-making conversations with patients.
Abstract P175: Association of Midlife Hypertension and a Novel Biomarker of Accelerated Epigenetic Age: Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Yinan Zheng, Sadiya Khan, Tao Gao, Brian Joyce, Sanjiv Shah, Myron Gross, David Jacobs, Kiang Liu, Philip Greenland, Donald Lloyd-Jones, Lifang Hou
Journal: Circulation (2019)

Introduction: Hypertension (HTN) is associated with increased risk of cardiovascular disease (CVD), a hallmark of aging. A new biomarker of epigenetic age using 513 DNA methylation and clinical biomarkers, referred to as phenotypic age, has been derived and validated. Phenotypic age acceleration (PhenoAA) is defined as the residual value of phenotypic age regressed on chronologic age, and is thus independent of chronologic age. Hypothesis: We assessed the hypothesis that higher blood pressure is associated with greater PhenoAA. Methods: A subset of CARDIA cohort participants (ppts) (n=957) underwent genome-wide blood DNA methylation profiling with the Illumina EPIC 850K array at Year 20 (Y20; age 38-54 years) for estimation of PhenoAA. Ppts with adjudicated CVD or cancer history or who were pregnant at Y20 were excluded (n=113). We used robust linear regression models to examine the association of systolic and diastolic blood pressure (SBP and DBP) with PhenoAA at Y20 after adjusting for age, sex, race, education, study center, BMI, smoking status, physical activity, and anti-hypertensive treatment. We also compared mean PhenoAA across three groups: no HTN (BP &lt;130/&lt;80), HTN controlled with treatment (BP &lt;130/&lt;80), and uncontrolled HTN (BP ≥130/≥80). Results: Ppts were 48% female and 40% black with mean chronological age 45±4 years, and mean SBP 116±15 and DBP 73±11 mmHg. Phenotypic age was accelerated by 0.36 years per 10 mmHg higher for SBP (p=0.018, Figure A ) but not for DBP. Compared with ppts with no HTN, those with controlled HTN had 1.8 years greater (P=0.044) and those with uncontrolled HTN had 3.2 years (P=0.0001) greater PhenoAA ( Figure B ); there was no significant difference between controlled and uncontrolled ppts with HTN. Conclusions: PhenoAA is a promising molecular biomarker of aging associated with higher concurrent SBP levels, which reflect greater cumulative SBP exposure. These data suggest that controlling BP after onset of HTN may not fully reverse possible effects of cumulative BP exposure on aging.
Fibrolamellar hepatocellular carcinoma (FHC): Clinicopathologic features and treatment of a cohort of patients attended at Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" (INCMNSZ) from 2002-2014.
Authors: Rosa Luz Luna Palencia, Ignacio García Juárez, Armando Gamboa Dominguez, Eucario Leon Rodriguez
Journal: Journal of Clinical Oncology (2015)

e15136 Background: FHC represents the 0.85% and the less common type of primary liver tumors. Recognized as a unique entity in 1980, it has important differences with classic hepatocellular carcinoma. Methods: Review of the records of patients attended in INNCMSZ at period 2002 to 2014 with the diagnosis of FHC, demographic and tumor characteristics, as well as their primary treatment and prognosis. Results: We analized 9 patients with the diagnosis of FHC. Of them, 6 women with a mean age of 21 years (IQR 17-29) and 3 men with a mean age of 19 years (IQR 19-20). All of them present symptoms at diagnosis, 67% abdominal pain and 67% weight loss. The main sign at diagnosis was a palpable mass in 66% and one patient was evaluated for portal hypertension with the finding at Sugiura procedure of multiple liver tumors. Of the laboratory studies the mean alfa-feto protein was 172 (SD 440.79). Of the 7 patients of whom we can determine the number of tumors, 57% present with an only tumor with a mean size of 16 cm (SD 6.9). Of all patients, 67% of them present with lymph node involvement at image study, 87% were T3 and the remaining T4. Of all the cohort, 67% have metastatic disease, 67% at diagnosis and 33% at the relapse, the main site of metastasis were lung in 67%, 50% mediastinal lymph node, one patient with peritoneal metastasis and one patient with a duodenal metastasis twelve years after the diagnosis of the primary. Only 67% of patients receive treatment, one with surgery of the primary, another with resection of the primary and duodenal metastasis, 67% with chemoembolization, 50% systemic chemotherapy (one as adjuvant treatment) with Doxorubicin alone or with Interferon and 33% with Sorafenib. One patient treated with Doxorubicin and Sorafenib had 5 months with stable disease and at progression began Gemcitabine and Oxaliplatin with 3 months of stable disease. The median survival of the entire cohort was 23.2 months (IQR 1-143), for women 6 months and for men 12 months. Conclusions: This analysis shows a cohort of FLH with advanced stage, the lack of benefit of systemic treatment and poor prognosis of the non-resectable disease.
Short and Long-Term Risk of Major Cardiovascular Events after Ischemic Stroke or Transient Ischemic Attack in Myeloproliferative Neoplasms
Authors: Tiziano Barbui, Valerio De Stefano, Alessandra Carobbio, Vincenzo Di Lazzaro, Paola Guglielmelli, Giuseppe Gaetano Loscocco, Alessandra Iurlo, Daniele Cattaneo, Agostino Cortelezzi, Silvia Betti, Elena Rossi, Maria Chiara Finazzi, Guido Finazzi, Bruno Censori, Mario Cazzola, Elisa Rumi, Marta Bellini, Francisco Cervantes, Eduardo Arellano-Rodrigo, Elena Elli, Maria Luigia Randi, Irene Bertozzi, Martin Griesshammer, Parvis Sadjadian, Francesca Palandri, Nicola Vianelli, Massimiliano Bonifacio, Luigi Scaffidi, Juan Carlos Hernandez-Boluda, Montse Gomez, Emma Cacciola, Rossella Rosari Cacciola, Palova Miroslava, Giuseppe Carli, Eloise Beggiato, Martin H Ellis, Caterina Musolino, Gianluca Gaidano, Davide Rapezzi, Alessia Tieghi, Francesca Lunghi, Alessandro M. Vannucchi
Journal: Blood (2017)
Randomized Trial of Ibrutinib Versus Ibrutinib Plus Rituximab (Ib+R) in Patients with Chronic Lymphocytic Leukemia (CLL)
Authors: Jan A. Burger, Mariela Sivina, Alessandra Ferrajoli, Nitin Jain, Ekaterina Kim, Tapan Kadia, Zeev Estrov, Graciela Nogueras González, Xuelin Huang, Maro Ohanian, Michael Andreeff, Mathew Thomas, Lynette Alexander-Williams, Hagop M. Kantarjian, Susan M. O'Brien, William G Wierda, Michael J. Keating
Journal: Blood (2017)
The “ProPSMA Study” clinical trial protocol: A prospective randomized multi-center study of the impact of Ga-68 PSMA PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy.
Authors: Michael Hofman, Declan G. Murphy, Scott Williams, Tatenda Nzenza, Alan Herschtal, Anetta Matera, Petra Marusic, Richard De Abreu Lourenco, Dale L Bailey, Amir Iravani, Rodney J Hicks, Roslyn J Francis, Nathan Lawrentschuk
Journal: Journal of Clinical Oncology (2019)

TPS138 Background: Disease persistence or relapse following curative-intent surgery or radiotherapy of high-risk prostate cancer is not uncommon. This is attributable, in part, to a failure of accurate staging with diagnostic imaging being insensitive for detection of small volume metastatic disease. Prostate-specific-membrane-antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is a new whole body scanning technique that enables visualisation of prostate cancer with high sensitivity. The hypotheses of this study are that PSMA-PET/CT (a) has improved diagnostic accuracy compared to conventional imaging, (b) should be used as a first-line diagnostic test for staging, (c) the improved diagnostic accuracy will result in significant management impact and (d) provides economic benefits when incorporated into the management algorithm. Methods: This is a 300 patient phase III multi-centre randomized study of patients with untreated high-risk prostate cancer defined by Gleason grade group 3-5, PSA ≥ 20ng/ml or clinical stage ≥ T3. Patients are randomized to Gallium-68-PSMA11 PET/CT or conventional imaging, consisting of computer tomography of the abdomen/pelvis and bone scintigraphy with SPECT/CT. Patients with negative, equivocal or oligometastatic disease cross-over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT to conventional imaging for detecting nodal or distant metastatic disease. Accuracy is defined by a pre-defined “ground truth” scoring system incorporating histopathologic, imaging and clinical follow-up at six months post randomisation. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross-over, health economics, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. 294 of 300 (98%) patients randomised at time of abstract submission. Clinical trial information: 12617000005358.
Abstract 007: Actigraphy-Measured Sleep Regularity and Risk of Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis
Authors: Tianyi Huang, Sara Mariani, Susan Redline
Journal: Circulation (2019)

Background: Prior studies have linked rotating night shift work to increased risk of cardiovascular disease (CVD). Irregular sleep schedules, characterized by high day-to-day variability in sleep duration or timing, represent possibly milder but much more common/chronic disruption of circadian rhythms in the general population. However, no prospective study to date has examined the association between sleep regularity and CVD outcomes. Methods: In the Multi-Ethnic Study of Atherosclerosis, 1,993 participants who were free of CVD completed 7-day wrist actigraphy at home for objective monitoring of sleep duration and quality between 2010 and 2013, and were prospectively followed through 2015. We assessed sleep regularity using the standard deviation (SD) of actigraphy-measured sleep duration and sleep onset timing across 7 days. Incident CVD was defined as total cardiovascular events including coronary heart disease, stroke, congestive heart failure, and cardiovascular death. Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for incident CVD according to SD of sleep duration and timing, adjusted for traditional CVD risk factors (e.g., sociodemographic factors, lifestyles and CVD biomarkers) and other sleep-related factors (e.g., average sleep duration, insomnia symptoms, daytime sleepiness, sleep-disordered breathing, chronotype and work schedules). Results: During a median follow-up of 4.0 years, 95 participants developed CVD events. Compared to participants with a 7-day sleep duration SD ≤60 min, the multivariable-adjusted HR (95% CI) for CVD was 1.12 (0.61, 2.07) for 61-90 min, 1.71 (0.94, 3.09) for 91-120 min, and 2.20 (1.22, 3.96) for &gt;120 min. Every 1-hour increase in sleep duration SD was associated with 23% higher CVD risk (95% CI: 1.05, 1.45; p-trend=0.01). In contrast to this linear association with sleep duration variability, there appeared to be a threshold pattern for the association with SD of sleep onset timing. Compared to participants with a sleep timing SD ≤30 min, the multivariable-adjusted HR (95% CI) for CVD was 1.13 (0.60, 2.13) for 31-60 min, 1.15 (0.58, 2.31) for 61-90 min, and 2.07 (1.09, 3.94) for &gt;90 min. CVD risk was 87% higher comparing sleep timing SD &gt;90 min versus ≤90 min (95% CI: 1.19, 2.96; p=0.007). These associations did not differ significantly by age, sex, race/ethnicity, sleep duration or work schedules. Exclusion of current shift workers yielded similar results. Conclusion: Irregular sleep duration and timing may be novel risk factors for CVD, independent of traditional CVD risk factors and sleep quantity/quality. Given the increased prevalence of irregular sleep (e.g., due to mobile device use), our findings have important public health implications for CVD prevention and suggest value in evaluating the impact of sleep hygiene interventions aimed at improving sleep pattern consistency.
A Microfluidic Tumor‐on‐a‐Chip for Assessing Multifunctional Liposomes' Tumor Targeting and Anticancer Efficacy
Authors: Rui Ran, Hao‐Fei Wang, Fei Hou, Yun Liu, Yue Hui, Nikolai Petrovsky, Fan Zhang, Chun‐Xia Zhao
Journal: Advanced Healthcare Materials (2019)

Abstract Two principal methods for cancer drug testing are widely used, namely, in vitro 2D cell monolayers and in vivo animal models. In vitro 2D culture systems are simple and convenient but are unable to capture the complexity of biological processes. Animal models are costly, time‐consuming, and often fail to replicate human activity. Here a microfluidic tumor‐on‐a‐chip (TOC) model designed for assessing multifunctional liposome cancer targeting and efficacy is presented. The TOC device contains three sets of hemispheric wells with different sizes for tumor spheroid formation and evaluation of liposomes under a controlled flow condition. There is good agreement between time‐elapsed tumor targeting of fluorescent liposomes in the TOC model and in in vivo mouse models. Evaluation of the anticancer efficacy of four PTX‐loaded liposome formulations shows that compared to 2D cell monolayers and 3D tumor spheroid models, the TOC model better predicts the in vivo anticancer efficacy of targeted liposomes. Lastly, the TOC model is used to assess the effects of flow rates and tumor size on treatment outcome. This study demonstrates that the TOC model provides a convenient and powerful platform for rapid and reliable cancer drug evaluation.